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The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [ 111 In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.

Skin diseases are a common health problem affecting millions of people worldwide. Effective treatment often depends on the precise delivery of drugs to the affected areas. One promising approach is currently the transdermal drug delivery system (TDDS), whose significant challenge is the poor penetration of many compounds into the skin due to the stratum corneum (SC), which acts as a formidable barrier. To overcome this limitation, nanocarriers have emerged as a highly effective alternative. This review discusses the use of liposomes and ethosomes for transdermal drug delivery. Liposomes are micro- or nanostructures consisting of a lipid bilayer surrounding an aqueous core. They facilitate transdermal drug penetration and may be advantageous for site-specific targeting. Some methods of treating skin diseases involve incorporating drugs such as acyclovir, dithranol, and tretinoin or bioactive compounds such as fluconazole, melanin, glycolic acid, kojic acid, and CoQ10 into nanocarriers. The inability of liposomes to pass through the narrowed intercellular channels of the stratum corneum led to the invention of lipid-based vesicular systems such as ethosomes. They are structurally similar to conventional liposomes, as they are prepared from phospholipids, but they contain a high ethanol concentration. Ethosomes are noninvasive carriers that allow drugs to reach the deep layers of the skin. Examples of commonly used substances and drugs combined with ethosomes in cosmetics include methotrexate, ascorbic acid, vitamin A and E, and colchicine. A significant development in this area is the use of rutin-loaded ethosomes. Encapsulating rutin in ethosomes significantly improves its stability and enhances skin penetration, allowing more efficient delivery to deeper skin layers. In cosmetics, rutin–ethosome formulations are used to protect the skin from oxidative stress, reduce redness, and improve capillary strength, making it a valuable formulation in anti-aging and anti-inflammatory products. The results of the first clinical trial of the acyclovir–ethosome formulation confirm that ethosomes require further investigation. The work provides an update on recent advances in pharmaceutical and cosmetic applications, mentioning the essential points of commercially available formulations, clinical trials, and patents in the recent past. [ABSTRACT FROM AUTHOR]

Simple Summary: Visceral pain due to abdominal malignancies or pancreatitis is common in both people and animals. In human medicine, the celiac plexus block or neurolysis are performed in subjects with intractable visceral pain. Ultrasonographic-guided percutaneous techniques for block and/or neurolysis have been described in people. The aim of this study is to describe a percutaneous ultrasound-guided technique to localize the celiac plexus in a pig cadaveric model. The described technique was effective in localizing the celiac plexus in all subjects. Following anatomical and clinical studies, its role in veterinary analgesia should be assessed. Celiac plexus (CP) block (CPB) and neurolysis (CPN) are interventional techniques employed in human analgesia to control visceral pain originating from the upper abdomen. Visceral pain is common in animals and its treatment is challenging. A percutaneous ultrasound (US)-guided approach to the CP has been reported in people but not in veterinary species. The objective of this study is to describe a US-guided percutaneous approach to the CP in a porcine cadaveric model. Cadavers were positioned in right lateral recumbency. The vertebral body of the last thoracic vertebra (T15) was identified (in transverse view) with a left cranial abdominal US scan. Under US guidance, an 18 G Tuohy needle was inserted parallel and ventral to the transverse process of T15. The transducer was gently slid and tilted to have an in-plane view while introducing the needle through the epaxial muscle layer. Once the T15 body was contacted, the needle was advanced towards the ventral surface of the vertebra, and if loss of resistance was present, 2 mL of dye (China Ink) was injected. A laparotomy was performed, and the dyed tissue dissected for histological preparation from 14 cadavers. In all samples submitted for histological study, tissue belonging to the CP was found. The percutaneous ultrasound-guided approach to the CP was effective in localizing the CP in all subjects. Future studies are warranted to identify the clinical utility of this technique in veterinary species. [ABSTRACT FROM AUTHOR]

Simple Summary: The mortality rate in horses undergoing general anaesthesia (GA) is 1%, which is higher than in small animals. This mortality rate is impacted by complications that occur during the recovery period, making it the riskiest phase in equine anaesthesia. It has been shown that using a postanaesthetic intravenous bolus dose of an α2-agonist improves recovery quality and increases its time. However, recovery time should not be prolonged as complications such as neuro/myopathy or hypoxaemia can occur. The objective of this study was to compare the recovery quality and time after administering two different doses of medetomidine at the end of the anaesthesia (0.5 or 1 µg/kg IV). There were no significant differences between the groups for recovery quality, recovery time, or the number of attempts to return to the standing position. It can be concluded that the low dose medetomidine postanaesthetic bolus (0.5 µg/kg IV) did not decrease the recovery time but maintained recovery quality when compared to the high dose medetomidine (1 µg/kg IV). Further research is necessary to optimise the quality–time ratio of recovery. A 50% reduction in the post-anaesthetic bolus dose of medetomidine was not enough to reduce the recovery time. Further studies using lower doses to reduce the time and maintain quality could be postulated. Recovery from general anaesthesia is risky in horses. Alpha2-agonist administration after anaesthesia enhances the quality of recovery but may prolong this phase. Recovery time and quality were investigated after medetomidine administration at the end of general anaesthesia in a prospective, randomised, masked and clinical study. Horses underwent medetomidine–isoflurane partial intravenous anaesthesia. Medetomidine (0.5 or 1 µg/kg) IV was administered just after isoflurane was discontinued. The duration of different recovery phases and the number of attempts were recorded. A composite scale (from 1—excellent to 6—accident) was used for quality assessment. Mann—Whitney U-test was performed (p < 0.05). Twenty-seven horses per group were included. Results for 0.5 and 1 µg/kg groups were as follows: lateral recumbency time: 35 (24–45) and 43 (35–55) minutes; sternal recumbency time: 6 (3–15) and 5 (2–15) minutes; total recovery time: 47 (40–59) and 49 (42–62) minutes; number of attempts to sternal: 1 (1–1) and 1 (1–2) and to standing: 1 (1–3) and 1 (1–2); and, quality: 2 (1–2) and 2 (1–2), respectively. No significant differences between the groups were found. Medetomidine 0.5 µg/kg dose did not decrease the recovery time but maintained the recovery quality. [ABSTRACT FROM AUTHOR]

Simple Summary: In human medicine, catheter implantation for local anesthetic administration in the quadratus lumborum (QL) inter-fascial plane (IFP) has been reported to extend the duration of a single-shot block's effect in the postoperative period of patients undergoing abdominal surgeries. In the first phase of this study, we described an ultrasound-guided technique for placing catheters in the QL IFP in canine cadavers and assessed the spread of 0.3 versus 0.6 mL kg−1 per side of contrast media solution injected through the catheters using computed tomography (CT). The second phase described the outcomes of five dogs undergoing open cholecystectomy or adrenalectomy, in which QL catheters were used for postoperative pain management. CT scan images showed that using a higher volume of injectate resulted in a significantly higher number of vertebral bodies stained by the contrast solution between the QL and psoas minor muscles. Results of the second phase of the study suggest that ropivacaine 0.5% injected uni- or bilaterally every eight hours through QL catheters could be safely implemented in a multimodal analgesic approach during the postoperative period in dogs subjected to abdominal surgeries. This study aimed to describe an ultrasound-guided technique for implanting catheters for local anesthetic administration into the quadratus lumborum (QL) inter-fascial plane in canine cadavers and assessing the spread along the vertebral bodies (VBs) by computed tomography (CT). Phase 1: eight canine cadavers received one catheter per hemiabdomen, followed by injection of contrast media solution [low volume (LV) 0.3 mL kg−1 or high volume (HV) 0.6 mL kg−1]. Phase 2: postoperative pain of five dogs was managed by injecting 0.3 mL kg−1 of ropivacaine 0.5% through QL catheters every eight hours, up to 72 h after abdominal surgery. Pain was assessed using the Short Form of the Glasgow Composite Measure Pain Scale, and methadone 0.2 mg kg−1 was administered intravenously when the pain score was ≥6. The number of VBs stained by the contrast solution between the QL and psoas minor muscles was significantly higher in group HV than group LV. The catheter tip was visualized in the retroperitoneal space in 1/16 and 2/10 hemiabdomens in phases 1 and 2, respectively. Rescue analgesia was required in 3/5 dogs during the postoperative period. The QL catheter placement technique appears feasible and may be included in a multimodal analgesic approach for dogs undergoing abdominal surgeries. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in pain research challenge the concept that animals lack pain senses, showing that they have similar neural pathways to humans and experience pain similarly. Understanding brain circuits for effective pain control is crucial for adjusting pain control to individual patient responses and conditions. Pain management in oncological patients aims to lessen the impact of tumor cell development and its consequences on the immune system. Researchers have focused on improving algological approaches to better respond to patient needs, which requires a deeper understanding of how analgesics work, interact with other drugs, and affect patients' conditions. Opioids, although linked to tumor progression, remain the mainstay for managing oncologic pain. Advancements in understanding pain physiopathology have historically challenged animals' absence of pain senses. Studies have demonstrated that animals have comparable neural pain pathways, suggesting that cats and dogs likely experience pain similarly to humans. Understanding brain circuits for effective pain control has been crucial to adjusting pain management to the patient's individual responses and current condition. The refinement of analgesic strategies is necessary to better cater to the patient's demands. Cancer pain management searches to ascertain analgesic protocols that enhance patient well-being by minimizing or abolishing pain and reducing its impact on the immune system and cancer cells. Due to their ability to reduce nerve sensitivity, opioids are the mainstay for managing moderate and severe acute pain; however, despite their association with tumor progression, specific opioid agents have immune-protective properties and are considered safe alternatives to analgesia for cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Pain scoring in dogs can be challenging, particularly in a busy clinical setting and when staff with diverse training and veterinary students are involved. Consequently, concerns about dogs receiving inadequate analgesia were raised at this institution. This study was performed to investigate if veterinary students, veterinary nurses, veterinary surgeons with no specific training in anaesthesia, and diplomates in veterinary anaesthesia and analgesia perform pain scoring using the short form of the canine Glasgow Composite Measure Pain Scale (CMPS-SF) in a similar manner. The results obtained indicated good to excellent pain assessment agreement between groups. Nevertheless, the overall agreement amongst all assessors was poor and the intra-group agreement was poor to moderate, suggesting significant individual differences when pain scoring dogs. Veterinary students tend to pain score higher than more experienced assessors. Several pain scoring systems have been validated to measure pain in dogs. However, pain may not be adequately assessed since these tools are associated with high-level inter-observer variation. The aim of this study is to evaluate the agreement of pain assessment using the CMPS-SF between veterinary students, veterinary nurses, veterinary surgeons, and European College of Veterinary Anaesthesia and Analgesia (ECVAA) diplomates. Forty-five client-owned dogs presented to a teaching hospital were enrolled in this prospective, observational study. All dogs were pain-scored in vivo, while a video of the assessment was recorded and subsequently evaluated by twenty assessors, with five per group. Mean scores between groups were compared, and agreement within groups and agreement of the average scores between groups were assessed by calculating the intraclass correlation coefficient (ICC). The intervention point at which dogs were deemed to require additional analgesia was also evaluated. Overall agreement of pain assessment was poor (ICC = 0.494). Nurses had the best inter-observer agreement (ICC = 0.656), followed by ECVAA diplomates (ICC = 0.540), veterinary surgeons (ICC = 0.478), and veterinary students (ICC = 0.432). The best inter-group agreement was between veterinary surgeons and nurses (ICC = 0.951) and between ECVAA diplomates and nurses (ICC = 0.951). Students were more likely to determine that additional analgesia was required compared to other groups. Pain assessment is key for animal welfare, and training in this area should be reinforced to improve consistency. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated how dexmedetomidine, a sedative, works when given to healthy cats via intramuscular injection at a dose of 10 μg/kg. Nine adult cats were observed before and after receiving the drug, with blood samples taken at various times to measure drug levels. Dexmedetomidine acted quickly, causing sedation that lasted for at least an hour, with peak effects between 20 and 30 min and a half-life of about 70 min. Significant decreases in heart rate, respiratory rate, and blood pressure were observed in the first hour, along with an increase in blood sugar levels after 60 min. Overall, dexmedetomidine proved to be effective and safe for sedation in healthy cats, providing valuable information for veterinarians to ensure its safe and effective use in feline patients. This study investigated the pharmacokinetic profile of and pharmacodynamic response to dexmedetomidine administered intramuscularly (IM) at a dose of 10 μg/kg in healthy cats. Nine adult cats were evaluated before and after administration of the drug, with serial collections of plasma samples. Dexmedetomidine induced deep sedation, with a rapid onset of action and a duration of one hour, reaching a peak between 20 and 30 min after administration. The half-life (T½) was 70.2 ± 48 min, with a maximum concentration (Cmax) of 2.2 ± 1.9 ng/mL and time to reach maximum concentration (Tmax) of 26.4 ± 19.8 min. The area under the curve (AUC) was 167.1 ± 149.1 ng/mL*min, with a volume of distribution (Vd) of 2159.9 ± 3237.8 mL/kg and clearance (Cl) of 25.8 ± 33.0 mL/min/kg. There was a reduction in heart rate (HR) and respiratory rate (RR) in relation to the baseline, with a slight decrease in systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure in the first hour. Blood glucose increased after 60 min. Dexmedetomidine proved to be effective and safe, with rapid absorption, metabolization, and elimination, promoting good sedation with minimal adverse effects after IM administration in healthy cats. [ABSTRACT FROM AUTHOR]

Simple Summary: The GIN-TONIC block is an interfascial ultrasound-guided regional anesthesia technique that desensitizes the lumbosacral plexus and provides analgesia to the pelvic limb. Different methods have been attempted previously, such as blocking specific plexuses (e.g., lumbar and sacral plexuses) and nerves (e.g., femoral and sciatic). However, these approaches either resulted in excessive motor block or failed to encompass all the required areas for surgery. This study assessed the efficacy of the GIN-TONIC block in dogs premedicated with either acepromazine or dexmedetomidine for surgeries on the hip and stifles. It also checked how well the dogs could move after the surgery. The results showed that the GIN-TONIC block provided adequate perioperative analgesia, independently of the drug used in premedication. During recovery, dogs showed minimal motor block, suggesting that GIN-TONIC block provides a motor-protective analgesic effect. However, more research is needed to fully understand how effective the GIN-TONIC block is during surgery. This study assessed the analgesic and motor effects of the GIN-TONIC block, a combination of the greater ischiatic notch plane block and the caudal lateral quadratus lumborum block, in 24 dogs undergoing pelvic limb surgery. Dogs were randomly divided into two equal groups: GA received acepromazine [(20 µg kg−1 intravenously (IV)] as premedication, and GD received dexmedetomidine (2 µg kg−1 IV). General anesthesia was maintained with isoflurane, and both groups received a GIN-TONIC block using 2% lidocaine. Nociception during surgery and postoperative pain [assessed using the Glasgow Composite Measure Pain Score (GCMPS-SF)] were assessed. Fentanyl (2 µg kg−1 IV) was administered if nociception was noted and morphine (0.5 mg kg−1 IV) was administered during recovery if the pain scores exceeded the predefined threshold. Motor function was assessed during the recovery period using descriptors previously reported. All dogs received analgesics at the 4 h mark before being discharged. Three and two dogs in GD and GA required fentanyl once. Postoperative pain scores remained ≤4/20 for all dogs except one. Dogs achieved non-ataxic ambulation within 38.9 ± 10.3 and 35.1 ± 11.1 min after extubation in GD and GA, respectively. This study highlighted the potential of the GIN-TONIC block as a feasible regional anesthesia method for delivering perioperative analgesia in dogs undergoing pelvic limb orthopedic surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Periorbital surgeries are painful procedures that require effective pain management, and regional anaesthesia is an essential tool used to achieve it. To desensitise the area of the head involved, blockade of the branches of the trigeminal nerve (ophthalmic, maxillary, and mandibular nerves) is warranted. This technique is well described and employed in human medicine, but the literature on veterinary medicine (dogs) is scarce. This study aims to assess and compare two ultrasound-guided approaches for trigeminal nerve block. Thirteen dog heads were utilised, and following a preliminary anatomical assessment, procedures were conducted using temporal and coronoid approaches. The needle was advanced under ultrasonographic guidance from the dorsal aspect of the temporal area or ventral to the zygomatic arch, respectively. A computed tomography scan was performed with the needles in place and repeated after injection of a contrast medium/tissue dye mixture. Dissection of the heads was immediately performed thereafter. Needle position, contrast distribution, and nerve staining were evaluated and compared between the two techniques. Results indicate no significant difference between both techniques. Both methods demonstrate adequate distribution, with minimal intracranial spread of the injectate. Both techniques are promising, although further studies in live animals are required. The trigeminal nerve is responsible for innervating the periorbita. Ultrasound-guided trigeminal block is employed in humans for trigeminal neuralgia or periorbital surgery. There are no studies evaluating this block in dogs. This study aims to evaluate and compare two approaches (coronoid and temporal) of the trigeminal nerve block. We hypothesised superior staining with the coronoid approach. Thirteen dog heads were used. After a preliminary anatomical study, two ultrasound-guided injections per head (right and left, coronoid and temporal approach, randomly assigned), with an injectate volume of 0.15 mL cm−1 of cranial length, were performed (iodinated contrast and tissue dye mixture). The ultrasound probe was placed over the temporal region, visualising the pterygopalatine fossa. For the temporal approach, the needle was advanced from the medial aspect of the temporal region in a dorsoventral direction. For the coronoid approach, it was advanced ventral to the zygomatic arch in a lateromedial direction. CT scans and dissections were conducted to assess and compare the position of the needle, the spread of the injectate, and nerve staining. No significant differences were found. Both approaches demonstrated the effective interfascial distribution of the injectate, with some minimal intracranial spread. Although the coronoid approach did not yield superior staining as hypothesised, it presents a viable alternative to the temporal approach. Studies in live animals are warranted to evaluate clinical efficacy and safety. [ABSTRACT FROM AUTHOR]

Simple Summary: The celiac plexus (CP) is a dense network of ganglia and sensitive fibres receiving nociceptive inputs from most abdominal viscera. In human medicine, the CP is a therapeutic target to control pain originating from pancreatic tumours and chronic pancreatitis. The fluoroscopic-guided block and neurolysis of the CP are commonly used in human analgesia but they have not been described in animals. We describe a fluoroscopically guided transcutaneous approach to the CP in swine cadavers to assess the feasibility of the technique in veterinary species. This technique is shown to be feasible, and its application in veterinary subjects suffering abdominal pain should be assessed. Celiac plexus block (CPB) and neurolysis (CPN) are used for pain management in people suffering from abdominal tumours or chronic pancreatitis. The fluoroscopically guided approach common in human medicine has not been described in veterinary settings. The aim of this study was to describe a fluoroscopic approach to the celiac plexus (CP) in fresh pig cadavers. Twelve animals were included in the procedure. Cadavers were positioned in sternal position and, under fluoroscopic guidance, a Chiba needle was inserted parasagittal at 6 cm from the spinal midline at the level of the last thoracic vertebra. From the left side, the needle was directed medio-ventrally with a 45° angle towards the T15 vertebral body; once the vertebral body was contacted, the needle was advanced 1 cm ventrally towards the midline. Iodinated contrast was injected to confirm the location. Following this, 2 mL of dye (China ink) was injected. A laparotomy was performed, and dyed tissue was dissected and prepared for both histochemical and immunohistochemical techniques. In 10 out of 12 samples submitted for histological evaluation, nervous tissue belonging to CP was observed. Fluoroscopy guidance allows for feasible access to the CP in swine cadavers in this study. Further studies are warranted to determine the efficacy of this technique in swine and other veterinary species. [ABSTRACT FROM AUTHOR]

Simple Summary: Dexmedetomidine is a frequently used sedative; however, in some cases, its administration may prove insufficient; therefore, an additional dose or another drug is required to achieve the desired sedative outcome. The present study investigated the sedative effects of commonly used anaesthetics when administered after an inadequate initial dose of dexmedetomidine. Six healthy adult cats were included in the study, and each cat participated seven times. The initial dose of dexmedetomidine was followed by the administration of a second dose of dexmedetomidine, butorphanol, buprenorphine, tramadol, ketamine, midazolam, or saline NS 0.9%. Additionally, atipamezole was administered to all animals to elicit recovery. To assess the sedative effect of each treatment, a sedation scale was used, and recovery quality was evaluated using two recovery scales. The results suggested that the two consecutive doses of dexmedetomidine produced deeper sedation compared to the administration of a single dose of dexmedetomidine. Sedation levels were also enhanced by the administration of dexmedetomidine, butorphanol, or ketamine following the administration of an initial dose of dexmedetomidine, and the recovery quality was good. On the contrary, administration of midazolam following dexmedetomidine administration resulted in inferior sedation and recovery quality. Dexmedetomidine is an a2-agonist commonly used in veterinary practice. Occasionally, the administered dose of dexmedetomidine may result in insufficient sedation, and an additional dose or drug may be required. The sedative effects of seven different drugs administered at subsequent time points after an initial, insufficient dose of dexmedetomidine were evaluated. Seven adult cats participated in this crossover, blind, randomised study. The groups consisted of two consecutive doses of dexmedetomidine (15 + 10 μg/kg) (DD) or a dose of dexmedetomidine (15 μg/kg) followed by either NS 0.9% (DC-control group), tramadol 2 mg/kg (DT), butorphanol 0.2 mg/kg (DBT), buprenorphine 20 μg/kg (DBP), ketamine 2 mg/kg (DK), or midazolam 0.1 mg/kg (DM). Sedation was evaluated using the Grint sedation scale. In all groups, atipamezole was administered at the end of the evaluation, and recovery was assessed using the Lozano and Sams recovery scales. The DC and DM groups exhibited minimal sedative effects. The maximum sedative effect was observed in the DD and DK groups, while sedation in the DD and DK groups was significantly higher compared to the DC group. Recovery in all groups was uneventful, except in the DM group, where it was prolonged and difficult, although no statistically significant difference was detected. Therefore, insufficient sedation with dexmedetomidine can be enhanced by a subsequent dose of dexmedetomidine, ketamine, or butorphanol, whereas the addition of midazolam reduces sedation and prolongs recovery. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxidative stress is a metabolic state in which the organism possesses more oxidative compounds than antioxidant ones. This imbalance contributes to the formation of multiple pathologies and can be caused by different methods of drug administration, surgery, and anesthesia. The aim of the current study was to evaluate the effect of two different anesthetic protocols on oxidative stress and vital parameters. Ten dogs were randomly assigned into two groups and received different anesthetic agents during anesthesia for female spaying procedures. It was noted and concluded that the administration of medetomidine–butorphanol contributed to higher values of oxidative stress markers during different time frames when compared to the medetomidine–buprenorphine group. Even though the cardiorespiratory parameters were stable throughout the study in all dogs, the medetomidine–butorphanol group experienced greater alterations in vital parameters during anesthesia. Therefore, this study suggests that medetomidine–buprenorphine might be a superior anesthetic combination in comparison to medetomidine–butorphanol. Oxidative stress (OS) is caused by an imbalance between the production of oxygen-containing free radicals and their elimination. General anesthesia increases the production of reactive oxygen species (ROS) and therefore causes oxidative stress. Our objective was to determine the effects of medetomidine–butorphanol (MEDBUT) and medetomidine–buprenorphine (MEDBUP) on oxidative stress and cardiorespiratory parameters in dogs undergoing ovariohysterectomy (OHE). Ten healthy female dogs were randomly assigned to two groups: the MEDBUT group (n = 5) received medetomidine and butorphanol, while the MEDBUP group (n = 5) received medetomidine and buprenorphine. OS was evaluated by measuring total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) during five different time points (from the administration of anesthetic drugs to 2 h after surgery). The observed vital cardiorespiratory parameters included heart rate (HR), respiratory rate (fR), noninvasive systolic (SAP) and diastolic (DAP) arterial blood pressures, oxygen saturation (SpO2), end-tidal CO2 (EtCO2), and body temperature (BT). Cardiorespiratory parameters were altered at a significantly greater degree in animals sedated with MEDBUT (p < 0.05). The administration of medetomidine–butorphanol was more likely to increase OS parameters, while medetomidine–buprenorphine showed decreased levels of oxidative stress throughout the study. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic has found the whole world unprepared for its correct management. Italy was the first European country to experience the spread of the SARS-CoV-2 virus at the end of February 2020. As a result of hospital overcrowding, the quality of care delivered was not always optimal. A substantial number of patients admitted to non-ICU units could have been treated at home. It would have been extremely useful to have a score that, based on personal and clinical characteristics and simple blood tests, could have predicted with sufficient reliability the probability that a patient had or did not have a disease that could have led to their death. This study aims to develop a scoring system to identify which patients with COVID-19 are at high mortality risk upon hospital admission, to expedite and enhance clinical decision making. Methods: A retrospective analysis was performed to develop a multivariable prognostic prediction model. Results: Derivation and external validation cohorts were obtained from two Italian University Hospital databases, including 388 (10.31% deceased) and 1357 (7.68% deceased) patients with confirmed COVID-19, respectively. A multivariable logistic model was used to select seven variables associated with in-hospital death (age, baseline oxygen saturation, hemoglobin value, white blood cell count, percentage of neutrophils, platelet count, and creatinine value). Calibration and discrimination were satisfactory with a cumulative AUC for prediction mortality of 0.924 (95% CI: 0.893–0.944) in derivation cohorts and 0.808 (95% CI: 0.886–0.828) in external validation cohorts. The risk score obtained was compared with the ISARIC 4C Mortality Score, and with all the other most important scores considered so far, to evaluate the risk of death of patients with COVID-19. It performed better than all the above scores to evaluate the predictability of dying. Its sensitivity, specificity, and AUC were higher than the other COVID-19 scoring systems when the latter were calculated for the 388 patients in our derivation cohort. Conclusions: In conclusion, the CZ-COVID-19 Score may help all physicians by identifying those COVID-19 patients who require more attention to provide better therapeutic regimens or, on the contrary, by identifying those patients for whom hospitalization is not necessary and who could therefore be sent home without overcrowding healthcare facilities. We developed and validated a new risk score based on seven variables for upon-hospital admission of COVID-19 patients. It is very simple to calculate and performs better than all the other similar scores to evaluate the predictability of dying. [ABSTRACT FROM AUTHOR]

Simple Summary: The combination of an opioid compound with a nonsteroidal anti-inflammatory drug can lead to additive or enhanced effects while minimizing adverse reactions. Recently, we reported the pharmacokinetic profiles of metamizole and tramadol in donkeys at single doses and without association. However, no studies have reported on the pharmacokinetic profile of the combination of tramadol and metamizole. The objective of this research was to assess pharmacokinetic profile of metamizole co-administered with tramadol at single dose. Behavioral changes in the animals were observed, and at specific intervals, blood samples were taken for subsequent analysis. Analyses were performed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The findings indicate that tramadol and its metabolite presented modified profiles, implying that metamizole and tramadol interact and affect each other's metabolic processes at the dosages used in this study. Clinical researches are necessary to determine the optimal that effectively addresses the pain relief requirements of the species. Our objective was to assess the pharmacokinetic characteristics of metamizole when administered together with tramadol in a single intravenous dose to donkeys. Ten male animals received 10 mg∙kg−1 of dipyrone associated with 2 mg∙kg−1 of tramadol (T2M10) and 25 mg∙kg−1 of dipyrone with 2 mg∙kg−1 of tramadol (T2M25). Venous blood samples were taken from groups to determine the pharmacokinetics after drug administration, using initial brief intervals that were followed by extended periods until 48 h. Restlessness and ataxia were observed in two animals in the T2M25 group. Analysis revealed prolonged detectability of tramadol, 4-methylamine antipyrine, 4-aminoantipyrine (up to 24 h), and O-desmethyltramadol (up to 12 h) after administration. Although metamizole and its metabolites showed no significant pharmacokinetic changes, tramadol and O-desmethyltramadol exhibited altered profiles, likely because of competition for the active sites of CYP450 enzymes. Importantly, the co-administration of metamizole increased the bioavailability of tramadol and O-desmethyltramadol in a dose-dependent manner, highlighting their potential interactions and emphasizing the need for further dose optimization in donkey analgesic therapies. In conclusion, metamizole co-administered with tramadol interferes with metabolism and this interference can change the frequency of drug administration and its analgesic efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: The study evaluated the intraoperative isoflurane end-tidal concentration (isoflurane-sparing effect), clinical parameters, intraoperative antinociceptive effect, and postoperative analgesia in cats undergoing ovariohysterectomy treated with fentanyl, tramadol, or a combination of both. A reduction in the end-tidal isoflurane fraction and better analgesia were observed during fentanyl/tramadol infusion while no differences were found between the two drugs used alone. The results of this study suggest that the combination of fentanyl and tramadol could be proposed as a viable alternative anesthetic protocol in cats undergoing ovariohysterectomy. The aim of this study was to evaluate the end-tidal concentration of isoflurane required, clinical parameters, intraoperative antinociceptive effect, and postoperative analgesia in cats undergoing ovariohysterectomy, receiving fentanyl, tramadol, or fentanyl/tramadol. Sixty-six cats in three groups, were premedicated with dexmedetomidine and infused with one of the following treatments: fentanyl, tramadol, or fentanyl/tramadol combination. Anesthesia was induced with alfaxolone and maintained with isoflurane, titrated to keep heart rate, respiratory rate and systolic arterial pressure within target values recorded at endotracheal intubation. An intraoperative cumulative scale was performed. Postoperatively, a short form of the Glasgow Composite Measure Pain Scale Feline was used at 2, 12, and 24 h. The groups were similar for age, weight, dose of dexmedetomidine, and alfaxalone administered. A greater reduction in the end-tidal isoflurane fraction was observed with the combined fentanyl/tramadol infusion than with either fentanyl or tramadol alone. No differences in the end-tidal isoflurane fraction were found between fentanyl or tramadol alone. Hemodynamic stability associated with minimal cardiopulmonary changes, low response to noxious intraoperative stimulation, and low postoperative pain scores were also observed with the fentanyl/tramadol combination. The fentanyl/tramadol combination provided a reduction in the end-tidal isoflurane fraction compared with fentanyl or tramadol alone. [ABSTRACT FROM AUTHOR]

The skin's protective mechanisms, in some cases, are not able to counteract the destructive effects induced by UV radiations, resulting in dermatological diseases, as well as skin aging. Nutlin-3, a potent drug with antiproliferative activity in keratinocytes, can block UV-induced apoptosis by activation of p53. In the present investigation, ethosomes and transethosomes were designed as delivery systems for nutlin-3, with the aim to protect the skin against UV damage. Vesicle size distribution was evaluated by photon correlation spectroscopy and morphology was investigated by cryogenic transmission electron microscopy, while nutlin-3 entrapment capacity was evaluated by ultrafiltration and HPLC. The in vitro diffusion kinetic of nutlin-3 from ethosomes and transethosomes was studied by Franz cell. Moreover, the efficiency of ethosomes and transethosomes in delivering nutlin-3 and its protective role were evaluated in ex vivo skin explants exposed to UV radiations. The results indicate that ethosomes and transethosomes efficaciously entrapped nutlin-3 (0.3% w/w). The ethosome vesicles were spherical and oligolamellar, with a 224 nm mean diameter, while in transethosome the presence of polysorbate 80 resulted in unilamellar vesicles with a 146 nm mean diameter. The fastest nutlin-3 kinetic was detected in the case of transethosomes, with permeability coefficients 7.4-fold higher, with respect to ethosomes and diffusion values 250-fold higher, with respect to the drug in solution. Ex vivo data suggest a better efficacy of transethosomes to promote nutlin-3 delivery within the skin, with respect to ethosomes. Indeed, nutlin-3 loaded transethosomes could prevent UV effect on cutaneous metalloproteinase activation and cell proliferative response. [ABSTRACT FROM AUTHOR]

Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure. [ABSTRACT FROM AUTHOR]

Simple Summary: Locoregional anaesthesia plays a fundamental role in the correct management of surgical interventions. Veterinary ultrasound-guided techniques are in continuous evolution to obtain adequate analgesia with minimal motor impact. We hypothesized that the block of the obturator nerve in the inguinal compartment, combined with the block of the saphenous and the sciatic nerves, without the block of the femoral nerve, could produce analgesia with less motor function impairment for tibial-plateau-levelling-osteotomy (TPLO) surgery. Having easily identified a window during the anatomical study that included an inguinal approach, we could correctly perform this new ultrasound-guided obturator-nerve-block technique. Patients that received three blocks with ropivacaine had statistically significantly less need for rescue analgesia during surgery than those that received saline solution at the level of the obturator nerve. In the group that did not receive ropivacaine for the obturator nerve block, nociception occurred in almost all patients at the time of incision of the joint capsule, showing the obturator nerve role in the innervation of the knee joint. The use of this new technique in association with the block of the sciatic and saphenous nerves represents an improvement in locoregional techniques in knee surgery, as the patient not only has a reduction in intraoperative nociception but also has better postoperative mobility, resulting from the fact that the femoral nerve, which is responsible for the innervation of the quadriceps muscles, was not blocked. The objective of our study was to compare the efficacy of sciatic and saphenous ultrasound nerve blocks with and without US-guided obturator nerve block in dogs undergoing tibial-plateau-levelling-osteotomy (TPLO) surgery. This study was developed in two phases: identification of an ultrasound window in the inguinal region for obturator nerve block and utilization of it in dogs undergoing TPLO. Dogs were assigned randomly to one of two groups: one received the three blocks with 0.5% ropivacaine (ON group) and the second one (NoON group) with NaCl instead of ropivacaine for the obturator block. In phase 1, the obturator nerve was visible between the pectineus and the abductor muscles and was approached using an in-plane technique. It was possible to use the ultrasound window for phase two. The number of dogs that received at least one bolus of intraoperative rescue analgesia in the NoON group (12/15 dogs) was significantly higher (p = 0.003) in comparison with the ON group (4/15). An ultrasound window to block the obturator nerve in the inguinal compartment with an in-plane technique was found. The use of this approach could produce adequate analgesia with less motor function impairment in dogs for TPLO surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Laparoscopic ovariectomy is currently considered the gold standard for neutering female dogs thanks to the reduced surgical trauma, lower perioperative pain, and decreased hospitalization stays. Perioperative analgesic management becomes crucial to reduce the occurrence of uncontrolled post-surgery stress response. The quadratus lumborum block is an ultrasound-guided block capable of providing somatic and visceral analgesia to the abdomen. The aims of this study were (I) to evaluate the efficacy of the transversal quadratus lumborum block performed with two different concentrations of ropivacaine (0.5% and 0.33%) in prolonging the time to the first postoperative rescue analgesia in dogs undergoing laparoscopic ovariectomy, in comparison with a fentanyl-based protocol, and (II) to investigate the cardiovascular impact of the block on the arterial blood pressure. The results of this study showed a significantly longer time to the first postoperative rescue analgesia in groups receiving the block, in comparison with the group receiving a fentanyl-based protocol. Surprisingly, ropivacaine 0.33% produce a more important reduction in the arterial blood pressure than ropivacaine 0.5%. Further studies are needed to better assess the intraoperative efficacy of the quadratus lumborum block. The aim of this study was to evaluate the effect of the transverse quadratus lumborum block (QLBLQL-T) on time to the first postoperative rescue analgesia in dogs submitted to laparoscopic ovariectomy. A total of twenty-three female dogs were included. Dogs were randomly assigned to receive a bilateral QLBLQL-T, performed either with 0.3 mL kg−1 ropivacaine 0.5% [group QLB0.5% (n = 8)] or with ropivacaine 0.33% [group QLB0.33% (n = 8)] or a fentanyl-based protocol [group No-QLB (n = 7)]. Dogs were premedicated intravenously (IV) with fentanyl 5 mcg kg−1, general anesthesia was induced IV with propofol and maintained with sevoflurane. Invasive mean arterial pressure (MAP) values were recorded five minutes before and five minutes after performing the QLBLQL-T. The short-form of the Glasgow composite measure pain scale was used every hour after extubation, and methadone 0.2 mg kg−1 was administered IV when pain score was ≥5/24. Kolmogorov–Smirnov test, ANOVA test combined with Tukey post hoc test, Student's T-test and Chi-square test were used to analyze data; p < 0.05. Time from QLBLQL-T to the first rescue analgesia was significantly longer in QLB0.5% than in group QLB0.33% and No-QLB. MAP pre- and post-block decreased significantly only in group QLB0.33%. [ABSTRACT FROM AUTHOR]

As many natural origin antioxidants, resveratrol is characterized by non-suitable physicochemical properties for its topical application. To allow its benefits to manifest on human skin, resveratrol has been entrapped within liquid crystal nanocarriers (LCNs) made up of glyceryl monooleate, a penetration enhancer, and DSPE-PEG 750. The nanosystems have been more deeply characterized by using dynamic light scattering and Turbiscan Lab® Expert optical analyzer, and they have been tested in vitro on NCTC 2544. The improved antioxidant activity of entrapped resveratrol was evaluated on keratinocyte cells as a function of its concentration. Finally, to really propose the resveratrol-loaded LCNs for topical use, the systems were gelled by using two different gelling agents, poloxamer P407 and carboxymethyl cellulose, to improve the contact time between skin and formulation. The rheological features of obtained gels were evaluated using two important methods (microrheology at rest and dynamic rheology), before testing their safety profile on human healthy volunteers. The obtained results showed the ability of LCNs to improve antioxidant activity of RSV and the gelled LCNs showed good rheological profiles. In conclusion, the results confirmed the potentiality of gelled resveratrol-loaded nanosystems for skin disease, mainly related to their antioxidant effects. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, loco-regional anesthesia has become a common practice in both human and veterinary medicine. In particular, it is widely used in the treatment of perioperative analgesia for neurological and orthopedic surgery. The advantage of successfully applying loco-regional anesthesia is better perioperative pain relief with a lesser need for systemic analgesic drugs. This case series aims to show how the practice of loco-regional anesthesia (retrobulbar block) has allowed good management of perioperative analgesia without the use of systemic opioids in 13 out of 14 dogs. A multimodal approach to perioperative analgesia focused on the use of a retrobulbar ultrasound-guided block with a supra-temporal approach was used in 14 dogs undergoing elective unilateral enucleation. A total of 2 out of 14 patients received rescue analgesia intraoperatively, while no patients required rescue analgesia during the postoperative period. No complications were recorded during the perioperative period, and all patients were discharged within the same day. The objective of this retrospective case series is to report the outcomes of an opioid-free anesthetic plan in dogs undergoing enucleation surgery. A total of 14 dogs were admitted for enucleation between March and December 2020. A multimodal approach to perioperative analgesia was used, with a focus on retrobulbar anesthesia. A combination of an ultrasound-guided retrobulbblock with a supratemporal approach in association with ketamine, dexmedetomidine and non-steroidal anti-inflammatory drugs was used in the reported cases. Intraoperative nociception was defined as an increase of 20% from the baseline in one or more of the following parameters: heart rate, respiratory rate or mean arterial pressure. An ultrasound-guided retrobulbar block in an opioid-free anesthesia regime was effective at managing the perioperative analgesia of 13 out of 14 dogs. In only one case, a bolus of fentanyl was administered to treat intraoperative nociception. Recovery was uneventful in all the dogs, and the postoperative pain scores remained below the intervention threshold at all time points. To the authors' knowledge, this is the first reported case series of opioid-free anesthesia for enucleation in dogs. [ABSTRACT FROM AUTHOR]

The interest in silver radioisotopes of medical appeal (silver-103, silver-104m,g and silver-111) has been recently awakened by the versatile nature of their nuclear decays, which combine emissions potentially suitable for non-invasive imaging with emissions suited for cancer treatment. However, to trigger their in vivo application, the production of silver radioisotopes in adequate amounts, and with high radionuclidic purity and molar activity, is a key prerequisite. This review examines the different production routes of silver-111, silver-103 and silver-104m,g providing a comprehensive critical overview of the separation and purification strategies developed so far. Aspects of quality (radiochemical, chemical and radionuclidic purity) are also emphasized and compared with the aim of pushing towards the future implementation of this theranostic triplet in preclinical and clinical contexts. [ABSTRACT FROM AUTHOR]

Simple Summary: Gabapentin is an anticonvulsant drug effective in humans to control neuropathic pain. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are not effective, when drugs are toxic, or for neuropathic pain treatment and anxiety. This review aimed to clarify gabapentin use and pharmacokinetic aspects to promote conscious use in dogs, cats, and horses. In dogs, gabapentin was useful in the treatment of epilepsy, as well as chronic, neuropathic, and post-operative pain and anxiety. In cats, it was effective in post-ovariohysterectomy-related pain and in the management of anxiety. In horses, it has been administered as an analgesic for chronic pain. In conclusion, when used in combination with other drugs, gabapentin is an interesting therapeutic option for the treatment of neuropathic diseases and analgesia. Despite its beneficial use in different clinical settings, further trials and pharmacokinetic studies are needed for the definition of an effective dosage regimen through proper pharmacokinetic/pharmacodynamic correlation in dogs, cats, and horses. Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood–brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatment and anxiety. This review aimed to clarify gabapentin use and pharmacokinetic aspects to promote conscious use in dogs, cats, and horses. In dogs, gabapentin was beneficial in the treatment of epilepsy, as well as chronic, neuropathic, and post-operative pain, as well as anxiety. In cats, it showed efficacy in post-ovariohysterectomy-related pain and in anxiety management. In horses, gabapentin has been administered as an analgesic for chronic pain management. In conclusion, when used in combination with other drugs, gabapentin can be considered an interesting therapeutic option for the treatment of neuropathic diseases and analgesia in postoperative and chronic pain. However, despite its beneficial use in different clinical settings, further trials and pharmacokinetic studies are needed for the definition of an effective dosage regimen through proper pharmacokinetic/pharmacodynamic correlation in dogs, cats, and horses. [ABSTRACT FROM AUTHOR]

Simple Summary: Pain in animals is an important problem as a lack of verbal communication might underestimate their perception and thus lead to undertreatment. Abdominal surgery is frequently performed in dogs, be it elective or for curative reasons. Recommendations to administer a local anaesthetic agent (i.e., a drug that inhibits pain at the site where it is administered) into the abdomen are existing without knowing how good they really work to prevent pain after surgery. In this study, pain, sedation level, the heart rate and opioid requirements were assessed in dogs that underwent abdominal surgery for an underlying disease. Half of the dogs received the investigated drug ropivacaine, while the other half received saline. Pain and sedation level were assessed using scientifically established scores. Rescue analgesia was provided if necessary. Sedation, pain on one score, and sensitivity to pressure next to the surgical wound were not different between both groups. Another pain score achieved slightly higher scores in dogs treated with ropivacaine, and the heart rate was lower in this group. These findings lead to the conclusion that the dosage and concentration used in this study should not be investigated further and cannot be promoted for clinical use. Recommendations for intraperitoneal (IP) and incisional (INC) administration of local anaesthetics after visceral surgery exist, but evidence is scarce. This prospective, randomized, blinded, controlled, clinical trial compared postoperative pain in dogs undergoing major abdominal surgery. Sixteen client-owned dogs were anaesthetized with a standardized balanced protocol including opioids and received either 2 mg/kg ropivacaine IP (0.27 mL/kg) and a 1 mg/kg INC splash (0.13 mL/kg) or equal volumes of saline. Influence of the treatment on heart rate (HR) and postoperative pain was assessed using the Short Form of the Glasgow Composite Pain Scale (GCPS-SF), a dynamic interactive visual analogue scale (DIVAS) and mechanical nociceptive threshold testing (MNT). Data was tested with mixed ordinal regression and log linear mixed models for 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 h after extubation. Rescue analgesia was given to 3/8 dogs after ropivacaine and 0/8 dogs after saline. GCPS-SF and MNT were not different between groups. DIVAS was slightly higher after ropivacaine (odds increased by 5.44 (confidence interval (CI) 1.17–9.96, p = 0.012)), and HR after ropivacaine was 0.76 * that after saline (CI 0.61–0.96, p = 0.02) with no effect of time (p = 0.1). Undiluted ropivacaine IP and INC was not beneficial for postoperative analgesia. [ABSTRACT FROM AUTHOR]

The clinical success of radiolabeled somatostatin analogs in the diagnosis and therapy—"theranostics"—of tumors expressing the somatostatin subtype 2 receptor (SST2R) has paved the way for the development of a broader panel of peptide radioligands targeting different human tumors. This approach relies on the overexpression of other receptor-targets in different cancer types. In recent years, a shift in paradigm from internalizing agonists to antagonists has occurred. Thus, SST2R-antagonist radioligands were first shown to accumulate more efficiently in tumor lesions and clear faster from the background in animal models and patients. The switch to receptor antagonists was soon adopted in the field of radiolabeled bombesin (BBN). Unlike the stable cyclic octapeptides used in the case of somatostatin, BBN-like peptides are linear, fast to biodegradable and elicit adverse effects in the body. Thus, the advent of BBN-like antagonists provided an elegant way to obtain effective and safe radiotheranostics. Likewise, the pursuit of gastrin and exendin antagonist-based radioligands is advancing with exciting new outcomes on the horizon. In the present review, we discuss these developments with a focus on clinical results, commenting on challenges and opportunities for personalized treatment of cancer patients by means of state-of-the-art antagonist-based radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Another radionuclide of great interest is the PET radionuclide zirconium-89 ( SP 89 sp Zr) and the increased interest in immunoPET imaging probes for preclinical and clinical studies has led to a rising demand for this radionuclide. The work by Da Silva et al. [[18]] has been dedicated to developing new biomedical cyclotron irradiation and radiochemical isolation methods to produce SP 165 sp Er suitable for targeted radionuclide therapeutic studies and characterize a new agent targeting prostate-specific membrane antigen. The field of radiopharmaceuticals is constantly evolving thanks to the great contribution of specialists coming from different disciplines such as inorganic chemistry, radiochemistry, organic and biochemistry, pharmacology, nuclear medicine, physics, etc. 30304795 12 Borgna F., Ballan M., Favaretto C., Verona M., Tosato M., Caeran M., Corradetti S., Andrighetto A., Di Marco V., Marzaro G. Early Evaluation of Copper Radioisotope Production at ISOLPHARM. [Extracted from the article]

The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on size distribution and dimensional stability of ethosomes by photon correlation spectroscopy. Ethosome morphology was investigated by cryogenic transmission electron microscopy, while the interaction between dimethyl fumarate and vesicles, and the drug entrapment capacity were respectively evaluated by FTIR and HPLC. To favor the topical application of ethosomes on mucosa and skin, different semisolid forms, based on xanthan gum or poloxamer 407, were designed and compared for spreadability and leakage. Dimethyl fumarate release and diffusion kinetics were evaluated in vitro by Franz cells. The antiviral activity against HSV-1 was tested by plaque reduction assay in Vero and HRPE monolayer cells, while skin irritation effect was evaluated by patch test on 20 healthy volunteers. The lower drug concentration was selected, resulting in smaller and longer stable vesicles, mainly characterized by a multilamellar organization. Dimethyl fumarate entrapment in ethosome was 91% w/w, suggesting an almost total recovery of the drug in the lipid phase. Xanthan gum 0.5%, selected to thicken the ethosome dispersion, allowed to control drug release and diffusion. The antiviral effect of dimethyl fumarate loaded in ethosome gel was demonstrated by a reduction in viral growth both 1 h and 4 h post-infection. Moreover, the patch test demonstrated the safety of the ethosomal gel applied on the skin. [ABSTRACT FROM AUTHOR]

Skin fungal infection is still a serious public health problem due to the high number of cases. Even though medicines are available for this disease, drug resistance among patients has increased. Moreover, access to medicine is restricted in some areas. One of the therapeutic options is herbal medicine. This study aims to develop an ethosome formulation loaded with Zingiber zerumbet (L.) Smith. rhizome extract for enhanced antifungal activity in deep layer skin, which is difficult to cure. Ethosomes were successfully prepared by the cold method, and the optimized formulation was composed of 1% (w/v) phosphatidylcholine and 40% (v/v) ethanol. Transmission electron microscope (TEM) images revealed that the ethosomes had a vesicle shape with a diameter of 205.6–368.5 nm. The entrapment of ethosomes was 31.58% and could inhibit the growth of Candida albicans at a concentration of 312.5 μg/mL. Finally, the ethosome system significantly enhanced the skin penetration and retention of the active compound (zerumbone) compared with the liquid extract. This study showed that Z. zerumbet (L.) rhizome extract could be loaded into ethosomes. The findings could be carried over to the next step for clinical application by conducting further in vivo penetration and permeation tests. [ABSTRACT FROM AUTHOR]

In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9% w/w and transethosomes based on phosphatidylcholine 0.9 or 2.7% w/w plus polysorbate 80 0.3% w/w as an edge activator were prepared and characterized. The vesicle mean size, morphology and deformability were influenced by both phosphatidylcholine and polysorbate 80. Indeed, the mean diameters of ethosome were around 200 nm, while transethosome's mean diameters were 146 or 350 nm in the case of phosphatidylcholine 0.9 or 2.7%, w/w, respectively. The highest deformability was achieved by transethosomes based on phosphatidylcholine 0.9%, w/w. The three types of vesicular nanosystems were applied on explanted human skin maintained in a bioreactor. Transmission electron microscopy demonstrated that all vesicles were able to enter the skin, keeping their structural integrity. Notably, the vesicle penetration capability was influenced by their physical-chemical features. Indeed, ethosomes reached keratinocytes and even the dermis, phosphatidylcholine 0.9% transethosomes were found in keratinocytes and phosphatidylcholine 2.7% transethosomes were found only in corneocytes of the outer layer. These findings open interesting perspectives for a differentiated application of these vesicles for transdermal drug delivery as a function of the cutaneous pathology to be addressed. [ABSTRACT FROM AUTHOR]

Simple Summary: A pain assessment is essential to provide appropriate pain relief. The Feline Grimace Scale© (FGS) is a facial expression-based acute pain scale used in feline medicine; increased FGS scores could indicate acute pain in cats requiring analgesia. However, it is unknown if some sedatives and/or anesthetics can bias pain assessment using the FGS. This study aimed to investigate the effects of sedation with dexmedetomidine-butorphanol followed by anesthesia with propofol-isoflurane on the FGS scores of healthy cats. The cats were video-recorded before and up to 24 h after sedation and general anesthesia. Images collected from the videos were randomized and scored independently by four raters who were masked to the treatments. Dexmedetomidine and butorphanol significantly increased the FGS scores at 20 min after administration. General anesthesia with propofol and isoflurane significantly increased the FGS scores at 0.5 h post-anesthesia, but not after. There were no other statistically significant findings. In conclusion, sedation with dexmedetomidine and butorphanol and general anesthesia with propofol and isoflurane increase FGS scores and may bias clinical pain assessment. Although the effects were short-lived, they should be taken into account during acute pain assessment. This study aimed to evaluate the effects of sedation and anesthesia on Feline Grimace Scale© (FGS) scores. Twelve healthy cats were included in a prospective, blinded and randomized, cross-over study with a 14 day wash-out. Saline or dexmedetomidine-butorphanol (Dex-But) was administered intramuscularly before an anesthetic induction with propofol and maintenance with isoflurane. Saline or atipamezole (Dex-But) was administered at the end of the general anesthesia. Video-filming/image capturing was performed before and up to 24 h post-anesthesia. A total of 125 images were evaluated by four raters blinded to the treatment groups using the FGS (ear position/orbital tightening/muzzle tension/whiskers change/head position; action units (AU); scores 0–2 for each AU). The effects of the sedation/anesthesia were analyzed (p < 0.05). The total FGS and each AU scores were significantly higher with Dex-But than with saline 20 min post-sedation. In the saline group, the total FGS, orbital tightening, and whiskers and head position scores were significantly higher than baseline at 0.5 h post-anesthesia. In the Dex-But group, the total FGS and each AU scores were significantly higher after sedation, whereas the orbital tightening scores were significantly higher at 0.5 h post-anesthesia when compared with the baseline. None of the other comparisons between or within the groups was significantly different. The sedation with dexmedetomidine-butorphanol and anesthesia with propofol-isoflurane changed the FGS scores on a short-term basis; consequently, they may bias acute pain assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: C-reactive protein is a major positive acute phase protein in dogs. It is commonly used as a marker of inflammation that, although nonspecific, is highly sensitive. The high clinical value lies in its rapid response and relatively short half-life time; these qualities make the C-reactive protein a good therapeutic guide; among others, it can be used to determine when an antimicrobial therapy could be ceased. Various tests are available on the market and the measurement is becoming a part of routine biochemistry blood panels in many countries. Although it is very useful, especially in conjunction with white blood cell count or other acute phase response proteins measurements, it does not allow a complete evaluation as a single parameter. Acute phase response is a nonspecific reaction to disturbances in homeostasis during which the production of some Acute Phase Proteins (APPs) is stimulated; they are sensitive but nonspecific markers of systemic inflammatory processes. The major positive APP in dogs is the C-reactive protein (CRP). The dynamic of its concentration changes fast, rising and decreasing rapidly with the onset and removal of the inflammatory stimulus. It increases within the first 4–24 h after the stimulus and reaches up to a 50–100-fold increase of the baseline level. It has been documented that this APP's concentration is elevated during several diseases, such as pyometra, panniculitis, acute pancreatitis, polyarthritis, sepsis, immune-mediated hemolytic anemia, and neoplasia in dogs. In clinical practice, canine CRP is mostly measured to detect and monitor systemic inflammatory activity and the efficacy of treatments, because it is a more sensitive marker than shifts in leukocyte counts. Blood serum CRP concentration is becoming a part of routine biochemistry panels in many countries. In this article, changes in CRP concentration and its clinical application in healthy and diseased dogs are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Nonhuman primates (NHPs) mimic most aspects of the human and play a critical role in translational research of neurological diseases. Functional connectivity is frequently examined using resting-state functional MRI (rsfMRI) to assess the functional abnormality in the anesthetized animal brain. As anesthetics show different effects on physiology and neural activity in a dose-dependent manner, specific and safe anesthesia procedures must be considered and applied to keep the animal from stress and motion during rsfMRI scanning. In this review, typical anesthesia protocols and rsfMRI techniques for NHPs are summarized. An optimal anesthesia protocol and rsfMRI scanning protocol for NHPs are introduced. Nonhuman primates (NHPs) are the closest living relatives of humans and play a critical and unique role in neuroscience research and pharmaceutical development. General anesthesia is usually required in neuroimaging studies of NHPs to keep the animal from stress and motion. However, the adverse effects of anesthesia on cerebral physiology and neural activity are pronounced and can compromise the data collection and interpretation. Functional connectivity is frequently examined using resting-state functional MRI (rsfMRI) to assess the functional abnormality in the animal brain under anesthesia. The fMRI signal can be dramatically suppressed by most anesthetics in a dose-dependent manner. In addition, rsfMRI studies may be further compromised by inter-subject variations when the sample size is small (as seen in most neuroscience studies of NHPs). Therefore, proper use of anesthesia is strongly demanded to ensure steady and consistent physiology maintained during rsfMRI data collection of each subject. The aim of this review is to summarize typical anesthesia used in rsfMRI scans of NHPs and the effects of anesthetics on cerebral physiology and functional connectivity. Moreover, the protocols with optimal rsfMRI data acquisition and anesthesia procedures for functional connectivity study of macaque monkeys are introduced. [ABSTRACT FROM AUTHOR]

Simple Summary: Many analgesic protocols are described to manage pain during ovariohysterectomy. Over the past few years, loco-regional anaesthesia techniques have been introduced in veterinary anaesthesia. Therefore, students should be aware of these techniques and trained on them. This retrospective study assessed four different methods of providing analgesia for ovariohysterectomy (i.e., epidural analgesia (EPIDURAL), quadratus lumborum block (QLB), transversus abdominis plane (TAP) block, or systemic analgesia (GENERAL). Undergraduate students performed all the loco-regional anaesthesia procedures under the direct supervision of a qualified anaesthetist. Considering the inclusion criteria, 120 dogs were included in this study (22 EPIDURAL, 32 QLB, 39 TAP, 27 GENERAL). Based on our study results, we can conclude that all these four analgesic protocols are suitable for controlling nociception during ovariohysterectomy. All of them required a similar number of analgesic rescues and showed a very low rate of complications. No matter the technique, loco-regional anaesthesia showed better quality of recovery than just systemic analgesia. A significatively lower dose of methadone was used for premedication in the loco-regional anaesthesia groups compared with the systemic analgesia group. Epidural analgesia was the only technique in which the concentration of the volatile agent was lower than in the other groups. No complications related to loco-regional anaesthesia techniques were recorded; therefore, this indicates that it would be safe for students to perform when the procedure is conducted under direct supervision. This study compared four methods to provide intraoperative analgesia during canine ovariohysterectomy in a veterinary teaching hospital. A retrospective study was designed to assess the nociceptive response, cardiorespiratory stability, quality of recovery and complications of four analgesic protocols: epidural analgesia (EPIDURAL group), Quadratus Lumborum block (QLB group), Transversus Abdominis Plane block (TAP group), and just systemic analgesia (GENERAL group). Undergraduate students carried out all the loco-regional techniques under the direct supervision of a qualified anaesthetist. A total of 120 cases met the inclusion criteria and were included in the study and were distributed as follows: 22, 27, 32 and 39 cases with EPIDURAL, GENERAL, QLB and TAP groups, respectively. Data were analysed with statistical software R using different statistical methods. Significant differences among groups were defined as p < 0.05. Based on our results, all the groups needed the same number of rescue analgesia during the intra-operative period. The use of loco-regional techniques anticipated a better quality of recovery compared with the general group. The EPIDURAL group showed a statistically lower expired fraction of sevoflurane. No differences were found regarding complications. In conclusion, these four analgesic methods are suitable and safe to be performed for canine ovariohysterectomy, although loco-regional techniques might have some advantages. [ABSTRACT FROM AUTHOR]

In this study, transethosomes were investigated as potential delivery systems for dimethyl fumarate. A formulative study was performed investigating the effect of the composition of transethosomes on the morphology and size of vesicles, as well as drug entrapment capacity, using cryogenic transmission electron microscopy, photon correlation spectroscopy, and HPLC. The stability of vesicles was evaluated, both for size increase and capability to control the drug degradation. Drug release kinetics and permeability profiles were evaluated in vitro using Franz cells, associated with different synthetic membranes. The in vitro viability, as well as the capacity to improve wound healing, were evaluated in human keratinocytes. Transmission electron microscopy enabled the evaluation of transethosome uptake and intracellular fate. Based on the obtained results, a transethosome gel was further formulated for the cutaneous application of dimethyl fumarate, the safety of which was evaluated in vivo with a patch test. It was found that the phosphatidylcholine concentration affected vesicle size and lamellarity, influencing the capacity to control dimethyl fumarate's chemical stability and release kinetics. Indeed, phosphatidylcholine 2.7% w/w led to multivesicular vesicles with 344 nm mean size, controlling the drug's chemical stability for at least 90 days. Conversely, phosphatidylcholine 0.9% w/w resulted in 130 nm sized unilamellar vesicles, which maintained 55% of the drug over 3 months. These latest kinds of transethosomes were able to improve wound healing in vitro and were easily internalised by keratinocytes. The selected transethosome gel, loading 25 mg/mL dimethyl fumarate, was not irritant after cutaneous application under occlusion, suggesting its possible suitability in the treatment of wounds caused by diabetes mellitus or peripheral vascular diseases. [ABSTRACT FROM AUTHOR]

(1) Background: The double pelvic osteotomy (DPO) is a prophylactic surgical procedure associated with 0.4% incidence of sciatic nerve injury. The piezoelectric cutting tool is a surgical device able to involve only mineralized tissue avoiding neurovascular tissue and other soft tissue. This study aimed to evaluate the sciatic nerve injury observed in dogs underwent iliac osteotomy performed using the piezoelectric cutting tool. (2) Methods: Dogs underwent DPO performed with piezoelectric cutting tool were included. Neurological assessment was performed 6 and 24 h after surgery and then repeated 12 days, 4 and 8 weeks after surgery. Temporary and or permanent sciatic nerve injury were recorded. (3) Results: 84 DPOs performed in fifty dogs were included. No temporary/permanent neurological disease associated with iatrogenic damage of the sciatic nerve were observed. (4) Conclusions: The iliac osteotomy performed with piezoelectric cutting tool was not associated to iatrogenic sciatic nerve injury. [ABSTRACT FROM AUTHOR]

The present study is aimed to design ethosomes and transethosomes for topical administration of quercetin. To overcome quercetin low bioavailability, scarce solubility and poor permeability that hamper its pharmaceutical use, the drug was loaded in ethosomes and transethosomes based on different concentrations of phosphatidylcholine. Vesicle morphology was studied by cryogenic transmission electron microscopy, while size distribution and quercetin entrapment capacity were evaluated up to 3 months, respectively, by photon correlation spectroscopy and high-performance liquid chromatography. The antioxidant property was studied by photochemiluminescence test. Quercetin release and permeation was investigated in vitro, using Franz cells associated to different membranes. In vitro assays were conducted on human keratinocytes and melanoma cells to study the behavior of quercetin-loaded nano-vesicular forms with respect to cell migration and proliferation. The results evidenced that both phosphatidylcholine concentration and quercetin affected the vesicle size. Quercetin entrapment capacity, antioxidant activity and size stability were controlled using transethosomes produced by the highest amount of phosphatidylcholine. In vitro permeation studies revealed an enhancement of quercetin permeation in the case of transethosomes with respect to ethosomes. Notably, scratch wound and migration assays suggested the potential of quercetin loaded-transethosomes as adjuvant strategy for skin conditions. [ABSTRACT FROM AUTHOR]

(1) Background: Theranostic approaches in the management of cholecystokinin subtype 2 receptor (CCK2R)-positive tumors include radiolabeled gastrin and CCK motifs. Moving toward antagonist-based CCK2R-radioligands instead, we herein present three analogs of the nonpeptidic CCK2R-antagonist Z360, GAS1/2/3. Each was conjugated to a different chelator (DOTA, NODAGA or DOTAGA) for labeling with medically relevant trivalent radiometals (e.g., Ga-68, In-111, Lu-177) for potential use as anti-CCK2R cancer agents; (2) Methods: The in vitro properties of the thee analogs were compared in stably transfected HEK293-CCK2R cells. Biodistribution profiles were compared in SCID mice bearing twin HEK293-CCK2R and wtHEK293 tumors; (3) Results: The GAS1/2/3 analogs displayed high CCK2R-affinity (lower nM-range). The radioligands were fairly stable in vivo and selectively targeted the HEK293-CCK2R, but not the CCK2R-negative wtHEK293 tumors in mice. Their overall pharmacokinetic profile was found strongly dependent on the radiometal-chelate. Results could be visualized by SPECT/CT for the [111In]In-analogs; (4) Conclusions: The present study highlighted the high impact of the radiometal-chelate on the end-pharmacokinetics of a new series of Z360-based radioligands, revealing candidates with promising properties for clinical translation. It also provided the impetus for the development of a new class of nonpeptidic radioligands for CCK2R-targeted theranostics of human cancer. [ABSTRACT FROM AUTHOR]

To evaluate the use of ketamine-medetomidine-midazolam total intravenous infusion as part of a balanced anaesthetic technique for surgical castration in horses. Five healthy Standardbred cross colts were premedicated with IV acepromazine (0.01-0.02 mg/kg), medetomidine (7 μg/kg) and methadone (0.1 mg/kg) and anaesthesia induced with IV ketamine (2.2 mg/kg) and midazolam (0.06 mg/kg). Horses were anaesthetised for 40 min with an IV infusion of ketamine (3 mg/kg/h), medetomidine (5 μg/kg/h) and midazolam (0.1 mg/kg/h) while routine surgical castration was performed. Cardiorespiratory variables, arterial blood gases, and anaesthetic depth were assessed at 5 to 10 min intervals. Post-anaesthesia recovery times were recorded, and the quality of the recovery period was assessed. The anaesthetic period and surgical conditions were acceptable with good muscle relaxation and no additional anaesthetic required. The median (range) time from cessation of the infusion to endotracheal tube extubation, head lift and sternal recumbency were 17.2 (7-35) min, 25 (18.9-53) min and 28.1 (23-54) min, respectively. The quality of anaesthetic recovery was good, with horses standing 31.9 (28-61) min after the infusion was ceased. During anaesthesia, physiological variables, presented as a range of median values for each time point were: heart rate 37-44 beats/min, mean arterial pressure 107-119 mmHg, respiratory rate 6-13 breaths/min, arterial partial pressure of oxygen 88-126 mmHg, arterial partial pressure of carbon dioxide 52-57 mmHg and pH 7.36-7.39. In conclusion, the co-administration of midazolam, ketamine and medetomidine as in IV infusion, when used as part of a balanced anaesthetic technique, was suitable for short term anaesthesia in horses undergoing castration. [ABSTRACT FROM AUTHOR]

A continuous demand for assistance and an overcrowded emergency department (ED) require early and safe discharge of low-risk severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. We developed (n = 128) and validated (n = 330) the acute PNeumonia early assessment (aPNea) score in a tertiary hospital and preliminarily tested the score on an external secondary hospital (n = 97). The score's performance was compared to that of the National Early Warning Score 2 (NEWS2). The composite outcome of either death or oral intubation within 30 days from admission occurred in 101 and 28 patients in the two hospitals, respectively. The area under the receiver operating characteristic (AUROC) curve of the aPNea model was 0.86 (95% confidence interval (CI), 0.78–0.93) and 0.79 (95% CI, 0.73–0.89) for the development and validation cohorts, respectively. The aPNea score discriminated low-risk patients better than NEWS2 at a 10% outcome probability, corresponding to five cut-off points and one cut-off point, respectively. aPNea's cut-off reduced the number of unnecessary hospitalizations without missing outcomes by 27% (95% CI, 9–41) in the validation cohort. NEWS2 was not significant. In the external cohort, aPNea's cut-off had 93% sensitivity (95% CI, 83–102) and a 94% negative predictive value (95% CI, 87–102). In conclusion, the aPNea score appears to be appropriate for discharging low-risk SARS-CoV-2-infected patients from the ED. [ABSTRACT FROM AUTHOR]

Rutin is a natural compound with several pharmacological effects. Among these, antioxidant activity is one of the best known. Despite its numerous benefits, its topical application is severely limited by its physicochemical properties. For this reason, the use of suitable systems could be necessary to improve its delivery through skin, thus enhancing its pharmacological effects. In this regard, the aim of this work is to optimize the ethosomal dispersion modifying both lipid and ethanol concentrations and encapsulating different amounts of rutin. Characterization studies performed on the realized systems highlighted their great stability properties. Studies of encapsulation efficiency and loading degree allowed us to identify a better formulation (EE% 67.5 ± 5.2%, DL% 27 ± 1.7%), which was used for further analyses. The data recorded from in vitro studies showed that the encapsulation into these nanosystems allowed us to overcome the photosensitivity limitation of rutin. Indeed, a markable photostability of the loaded formulation was recorded, compared with that reported from the free rutin solution. The efficacy of the nanosystems was finally evaluated both in vitro on keratinocyte cells and in vivo on human healthy volunteers. The results confirmed the potentiality of rutin-loaded nanosystems for skin disease, mainly related to their anti-inflammatory and antioxidant effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Acetaminophen is the most commonly used pain relief (analgesic) agent in humans worldwide and its use is becoming more frequent in dogs. However, limited evidence supports this use. This study aimed to investigate the analgesic effect of acetaminophen when administered as an intravenous injection post-operatively in female dogs. A total of 34 dogs were randomly divided into two groups and either administered acetaminophen or saline intravenously immediately after desexing. The dogs had their pain levels evaluated at 10, 20, 40, 60, 120, and 180 min after awakening from general anesthesia and the pain levels between groups were compared. Concurrently, the dogs had blood collected at 2, 5, 10, 40, and 80 min following injection of the acetaminophen. The blood was analyzed to quantify the levels of acetaminophen in the body. This study found that acetaminophen was no better than saline in providing analgesia in dogs following surgery. This study suggests that acetaminophen used alone may not be an appropriate post-operative analgesic agent for desexing procedures. (1) Objective: To investigate the analgesic effects of intravenous acetaminophen after intravenous administration in dogs presenting for ovariohysterectomy. (2) Methods: 14 ASA I client-owned female entire dogs. In this randomized, blinded, clinical study, dogs were given meperidine and acepromazine intramuscularly before induction of anesthesia with intravenous propofol. Anesthesia was maintained with isoflurane in oxygen. Intravenous acetaminophen 20 mg/kg or 0.9% NaCl was administered postoperatively. Pain assessments were conducted using the Glasgow Pain Scale short form before premedication and at 10, 20, 60, 120, and 180 min post-extubation or until rescue analgesia was given. The pain scores, times, and incidences of rescue analgesia between the groups was compared. Blood was collected before and 2, 5, 10, 20, 40, and 80 min after acetaminophen administration. Acetaminophen plasma concentration was quantified by liquid chromatography-mass spectrometry. The acetaminophen plasma concentration at the time of each pain score evaluation was subsequently calculated. (3) Results: There was no significant difference in pain scores at 10 min, highest pain scores, or time of rescue analgesia between groups. In each group, 3 dogs (43%) received rescue analgesia within 20 min. (4) Conclusions: Following ovariohysterectomy in dogs, there was no detectable analgesic effect of a 20 mg/kg dosage of intravenous acetaminophen administered at the end of surgery. [ABSTRACT FROM AUTHOR]

This review focuses on the improved topical treatment of various medical skin conditions by the use of drugs delivered from carriers containing phospholipid soft vesicles. Topical drug delivery has many advantages over other ways of administration, having increased patient compliance, avoiding the first-pass effect following oral drug administration or not requesting multiple doses administration. However, the skin barrier prevents the access of the applied drug, affecting its therapeutic activity. Carriers containing phospholipid soft vesicles are a new approach to enhance drug delivery into the skin and to improve the treatment outcome. These vesicles contain molecules that have the property to fluidize the phospholipid bilayers generating the soft vesicle and allowing it to penetrate into the deep skin layers. Ethosomes, glycerosomes and transethosomes are soft vesicles containing ethanol, glycerol or a mixture of ethanol and a surfactant, respectively. We review a large number of publications on the research carried out in vitro, in vivo in animal models and in humans in clinical studies, with compositions containing various active molecules for treatment of skin medical conditions including skin infections, skin inflammation, psoriasis, skin cancer, acne vulgaris, hair loss, psoriasis and skin aging. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide analogs, derived from the natural peptide hormone gastrin, are promising candidates for improving the visualization and treatment of tumors. Gastrin specifically binds to the cholecystokinin-2 receptor, a G-protein-coupled receptor expressed on the cell surface of different tumors. This enables specific targeting of tumor cells using gastrin analogs, labeled with radioisotopes. The receptor is expressed at high incidence in medullary thyroid carcinoma, a rare form of thyroid cancer lacking effective treatments at an advanced stage. Different radiolabeled gastrin analogs as well as nonpeptidic compounds targeting CCK2R have been developed. Specific modifications have been introduced in order to safely deliver the radiation to the tumor site. In this review, recent strategies applied to improve the targeting properties are described. These developments enabled the introduction of new radiolabeled peptide analogs for imaging and therapy in cancer patients. In addition to highlighting the current clinical trials, the perspectives for future applications are given. The cholecystokinin-2 receptor (CCK2R) has been a target of interest for molecular imaging and targeted radionuclide therapy for two decades. However, so far CCK2R targeted imaging and therapy has not been introduced in clinical practice. Within this review the recent radiopharmaceutical development of CCK2R targeting compounds and the ongoing clinical trials are presented. Currently, new gastrin derivatives as well as nonpeptidic substances are being developed to improve the properties for clinical use. A team of specialists from the field of radiopharmacy and nuclear medicine reviewed the available literature and summarized their own experiences in the development and clinical testing of CCK2R targeting radiopharmaceuticals. The recent clinical trials with novel radiolabeled minigastrin analogs demonstrate the potential for both applications, imaging as well as targeted radiotherapy, and reinforce the clinical applicability within a theranostic concept. The intense efforts in optimizing CCK2R targeting radiopharmaceuticals has led to new substances for clinical use, as shown in first imaging studies in patients with advanced medullary thyroid cancer. The first clinical results suggest that the wider clinical implication of CCK2R-targeted radiopharmaceuticals is reasonable. [ABSTRACT FROM AUTHOR]

The multifunctional role of the human skin is well known. It acts as a sensory and immune organ that protects the human body from harmful environmental impacts such as chemical, mechanical, and physical threats, reduces UV radiation effects, prevents moisture loss, and helps thermoregulation. In this regard, skin disorders related to skin integrity require adequate treatment. Lipid nanoparticles (LN) are recognized as promising drug delivery systems (DDS) in treating skin disorders. Solid lipid nanoparticles (SLN) together with nanostructured lipid carriers (NLC) exhibit excellent tolerability as these are produced from physiological and biodegradable lipids. Moreover, LN applied to the skin can improve stability, drug targeting, occlusion, penetration enhancement, and increased skin hydration compared with other drug nanocarriers. Furthermore, the features of LN can be enhanced by inclusion in suitable bases such as creams, ointments, gels (i.e., hydrogel, emulgel, bigel), lotions, etc. This review focuses on recent developments in lipid nanoparticle systems and their application to treating skin diseases. We point out and consider the reasons for their creation, pay attention to their advantages and disadvantages, list the main production techniques for obtaining them, and examine the place assigned to them in solving the problems caused by skin disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: Many human diseases are not yet fully understood. Tests in animals can support the evaluation of new techniques meant to be applied in humans. Such animal experiments can only be justified with continuous improvements of the analgesic protocols during and after surgery. This study was designed to test the efficacy and feasibility of a technique aiming to desensitize the large nerves of one hind limb in experimental sheep undergoing invasive surgery on one hind limb. This technique was compared to epidural analgesia, a technique known to be effective in alleviating pain but leading to stress due to an inability to move both hind limbs in the early post-operative phase. Nerve blocks of peripheral nerves are widely used in human and veterinary medicine and can improve peri-operative pain therapy. The following study demonstrated that peripheral nerve block provided comparable analgesia to epidural anesthesia. Peripheral nerve blocks of the sciatic and femoral nerves can be used as an alternative to epidural analgesia in experimental sheep. Peripheral nerve blocks are commonly used in human and veterinary medicine. The aim of the study was to compare the analgesic efficacy of a combined block of the femoral and sciatic nerves with an epidural injection of ropivacaine in experimental sheep undergoing orthopaedic hind limb surgery. Twenty-five sheep were assigned to two groups (peripheral nerve block; sciatic and femoral nerves (P); epidural analgesia (E)). In group P 10 mL ropivacaine 0.5% was injected around the sciatic and the femoral nerves under sonographic guidance and 10 mL NaCl 0.9% into the epidural space while in group E 10 mL ropivacaine 0.5% was injected into the epidural space and 10 mL NaCl 0.9% to the sciatic and the femoral nerves. During surgery, heart rate, respiratory rate and mean blood pressure were used as indicators of nociception. In the postoperative phase, nociception was evaluated every hour by use of a purposefully adapted pain score until the animal showed painful sensation at the surgical site. The mean duration of analgesia at the surgical wound was 6 h in group P and 8 h in group E. Mean time to standing was 4 h in group P and 7 h in group E. In conclusion time to standing was significantly shorter in group P while the duration of nociception was comparable in both groups. The peripheral nerve block can be used as an alternative to epidural analgesia in experimental sheep. [ABSTRACT FROM AUTHOR]

Simple Summary: Recovery from general anaesthesia poses the most critical phase of equine anaesthesia and is the main cause for the relatively high anaesthetic mortality rate compared to other species. It is, therefore, essential to identify anaesthetic protocols that promote safe recoveries. This retrospective study compared the quality of 470 recoveries following general anaesthesia with the anaesthetic gas isoflurane combined with a constant rate infusion of two different alpha-2 adrenergic agonists (xylazine or medetomidine). On the basis of video recordings, recovery quality was scored by two observers unaware of animal details, procedure, or drugs used. Additionally, factors that may affect recovery (e.g., breed, age, procedure, duration of anaesthesia, and intraoperative complications) were taken into consideration. Horses needing higher doses of xylazine to sedate prior to anaesthesia, the intraoperative use of tetrastarch for cardiovascular support, and the use of salbutamol to improve inadequate blood oxygenation during general anaesthesia were related to poorer recovery scores. Whilst recoveries of horses treated with medetomidine took significantly longer compared to xylazine, the attempts to stand and the overall quality of recovery were similar for both groups, indicating that both anaesthetic protocols promote similarly safe recoveries. Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was used: sedation with 7 µg·kg−1 medetomidine or 1.1 mg·kg−1 xylazine, anaesthesia induction with ketamine/diazepam, maintenance with isoflurane and 3.5 µg·kg−1·h−1 medetomidine or 0.7 mg·kg−1·h−1 xylazine, and sedation after anaesthesia with 2 µg·kg−1 medetomidine or 0.3 mg·kg−1 xylazine. Recovery was timed and, using video recordings, numerically scored by two blinded observers. Influence of demographics, procedure, peri-anaesthetic drugs, and intraoperative complications (hypotension, hypoxemia, and tachycardia) on recovery were analysed using regression analysis (p < 0.05). A total of 470 recoveries (medetomidine 279, xylazine 191) were finally included. Following medetomidine, recoveries were significantly longer (median (interquartile range): 57 (43–71) min) than xylazine (43 (32–59) min) (p < 0.001). However, the number of attempts to stand was similar (medetomidine and xylazine: 2 (1–3)). Poorer scores were seen with increased pre-anaesthetic dose of xylazine, intraoperative tetrastarch, or salbutamol. However, use of medetomidine or xylazine did not influence recovery score, concluding that, following medetomidine–isoflurane PIVA, recovery is longer, but of similar quality compared to xylazine. [ABSTRACT FROM AUTHOR]

Human skin is dramatically exposed to toxic pollutants such as ozone. To counteract the skin disorders induced by the air pollution, natural antioxidants such as mangiferin could be employed. A formulative study for the development of vesicular systems for mangiferin based on phosphatidylcholine and the block copolymer pluronic is described. Plurethosomes were designed for mangiferin transdermal administration and compared to ethosome and transethosome. Particularly, the effect of vesicle composition was investigated on size distribution, inner and outer morphology by photon correlation spectroscopy, small angle X-ray diffraction, and transmission electron microscopy. The potential of selected formulations as vehicles for mangiferin was studied, evaluating encapsulation efficiency and in vitro diffusion parameters by Franz cells. The mangiferin antioxidant capacity was verified by the 2,2-diphenyl-1-picrylhydrazyl assay. Vesicle size spanned between 200 and 550 nm, being influenced by phosphatidylcholine concentration and by the presence of polysorbate or pluronic. The vesicle supramolecular structure was multilamellar in the case of ethosome or plurethosome and unilamellar in the case of transethosome. A linear diffusion of mangiferin in the case of ethosome and transethosomes and a biphasic profile in the case of plurethosomes indicated the capability of multilamellar vesicles to retain the drug more efficaciously than the unilamellar ones. The antioxidant and anti-inflammatory potential effect of mangiferin against pollutants was evaluated on 3D human skin models exposed to O3. The protective effect exerted by plurethosomes and transethosomes suggests their possible application to enhance the cutaneous antioxidant defense status. [ABSTRACT FROM AUTHOR]

Skin may be affected by many disorders that can be treated by topical applications of drugs on the action site. With the advent of nanotechnologies, new efficient delivery systems have been developed. Particularly, lipid-based nanosystems such as liposomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers, cubosomes, and monoolein aqueous dispersions have been proposed for cutaneous application, reaching in some cases the market or clinical trials. This review aims to provide an overview of the different lipid-based nanosystems, focusing on their use for topical application. Particularly, biocompatible nanosystems able to dissolve lipophilic compounds and to control the release of carried drug, possibly reducing side effects, are described. Notably, the rationale to topically administer antioxidant molecules by lipid nanocarriers is described. Indeed, the structural similarity between the nanosystem lipid matrix and the skin lipids allows the achievement of a transdermal effect. Surely, more research is required to better understand the mechanism of interaction between lipid-based nanosystems and skin. However, this attempt to summarize and highlight the possibilities offered by lipid-based nanosystems could help the scientific community to take advantage of the benefits derived from this kind of nanosystem. [ABSTRACT FROM AUTHOR]

Simple Summary: Recovery is the most dangerous phase of general anaesthesia in horses. Numerous publications have reported about this phase, but structured reviews that try to reduce the risk of bias of narrative reviews/expert opinions, focussing on the topic are missing. Therefore, the aim of the present article was to publish the first structured review as a summary of the literature focussing on the recovery phase after general anaesthesia in horses. The objective was to summarise the available literature, taking into account the scientific evidence of the individual studies. A structured approach was followed with two experts in the field independently deciding on article inclusion and its level of scientific evidence. A total number of 444 articles, sorted by topics and classified based on their levels of evidence, were finally included into the present summary. The most important findings were summarised and discussed. The present structured review can be used as a compilation of the publications that, to date, focus on the recovery phase after general anaesthesia in adult horses. This type of review tries to minimise the risk of bias inherent to narrative reviews/expert opinions. Recovery remains the most dangerous phase of general anaesthesia in horses. The objective of this publication was to perform a structured literature review including levels of evidence (LoE) of each study with the keywords "recovery anaesthesia horse", entered at once, in the search browsers PubMed and Web of Science. The two authors independently evaluated each candidate article. A final list with 444 articles was obtained on 5 April 2021, classified as: 41 "narrative reviews/expert opinions", 16 "retrospective outcome studies", 5 "surveys", 59 "premedication/sedation and induction drugs", 27 "maintenance with inhalant agents", 55 "maintenance with total intravenous anaesthesia (TIVA)", 3 "TIVA versus inhalants", 56 "maintenance with partial intravenous anaesthesia (PIVA)", 27 "other drugs used during maintenance", 18 "drugs before/during recovery", 18 "recovery systems", 21 "respiratory system in recovery", 41 "other factors", 51 "case series/reports" and 6 "systems to score recoveries". Of them, 167 were LoE 1, 36 LoE 2, 33 LoE 3, 110 LoE 4, 90 LoE 5 and 8 could not be classified based on the available abstract. This review can be used as an up-to-date compilation of the literature about recovery after general anaesthesia in adult horses that tried to minimise the bias inherent to narrative reviews. [ABSTRACT FROM AUTHOR]