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Background and Objectives: A degenerative joint disease that primarily affects elderly individuals, osteoarthritis (OA) causes pain, decreased mobility, and a lower quality of life. Procaine is regarded as a "veteran" medicine due to its extensive clinical use, although it remains a molecule of interest, as researchers are uncovering new biological and pharmacological effects through innovative experimental methods. This study evaluates the efficacy of the "procaine complex", developed in our country, in alleviating pain and improving functionality in elderly individuals with osteoarthritis of the knee and hip. Materials and Methods: We conducted an assessment of a longitudinal short-term study involving 177 patients aged 65 and older, who were randomly divided into two groups. One group received physical therapy and "procaine complex" periarticular injections (n = 101), while the other group received just physical therapy (n = 76). We assessed pain using a visual analog scale (VAS), in addition to functional evaluations using the Lequesne Index, Activities of Daily Living (ADL), and Instrumental ADL (IADL) scores. We evaluated these through a CGA (complex geriatric assessment), the walk test, "Up and Go" test, Mini Mental State (MMSE) and Geriatric Depression Scale (GDS) for cognitive status. We analyzed all the data from this study using PSPP v3 software. Results: The procaine complex treatment group exhibited a significant reduction in pain (p < 0.001) and improvement in daily activities (p < 0.001) relative to the control group. However, there was no notable difference in walking test scores (p = 0.171). No substantial detrimental effects were identified. The procaine complex did not surpass physical therapy in reducing depressive disorders, but both groups showed some enhancement in this regard. Conclusions: This study demonstrates an innovative approach to pain management by integrating periarticular "procaine complex" injections with physical therapy. This provides elderly individuals experiencing osteoarthritis pain and functional limitations with a secure and efficacious alternative to surgery, or may diminish years of disability. [ABSTRACT FROM AUTHOR]

The present work reports the development, optimization, and validation, of a methodology to determine lidocaine, procaine, tetracaine, and benzocaine in urine matrices. Two extractive preconcentration techniques, solid-phase microextraction (SPME) LC Tips and bar adsorptive microextraction (BAμE), were studied and applied to the four target anesthetics, followed by gas chromatography-mass spectrometry (GC-MS) analysis. Several parameters that could affect microextraction and back-extraction were optimized using two different designs of experiments (Box–Behnken and full-factorial) to maximize extraction efficiency from aqueous media. Under optimized experimental conditions, the BAμE technique showed better performance than SPME LC Tips and was chosen for validation assays and urine sample analysis. In blank urine, the BAµE/GC-MS methodology revealed suitable sensitivity (LOD between 2 and 18 ng/mL), good linearity (r2 ≥ 0.9945) between 0.5 and 30.0 µg/mL and recovery yields of 30.3–97.9%. Good precision (%RSD ≤ 8.8%) and accuracy (bias % between −15.9 and 15.0%) values were achieved. The developed methodology was successfully applied to the target anesthetics analysis of volunteers' urine matrices and proved to be an environmentally friendly alternative to monitor trace levels of local anesthetics in complex matrices compared to other extraction techniques. [ABSTRACT FROM AUTHOR]

Chloroprocaine is favored in anesthesia for its effectiveness and safety but is produced through complex, environmentally harmful processes. There is a growing interest in developing greener, more cost‐effective methods for producing chloroprocaine. Here, we establish a green and cost‐effective photoelectrochemical (PEC) approach for synthesizing chloroprocaine from procaine using a WO3 photoanode with oxygen vacancies. Achieving a high yield of 18.8 μmol cm−2 h−1 with selectivity of 92% and FE of 99%, this method leverages a free radical chain mechanism initiated by Cl· radicals formed over the WO3. The incorporation of oxygen vacancies enhances light absorption and charge separation, facilitating Cl· and Cl2 generation critical for its synthesis. We successfully produced 37.4 mg of chloroprocaine and 5.4 mL of hydrogen using a self‐powered PEC device, demonstrating the method effectiveness and environmental friendliness for chloroprocaine synthesis and hydrogen production. [ABSTRACT FROM AUTHOR]

ABSTRACT Within the European Union, the use of lidocaine in food‐producing animals is restricted due to concerns over human safety. This study compared the clinical effectiveness of procaine, with and without epinephrine, against lidocaine in pain alleviation during thermocautery disbudding in xylazine‐sedated calves. The efficacy of local blocks was assessed through needle pricks, and the behavioral reactions to disbudding were scored. Post‐disbudding pain was subjectively evaluated, and pressure pain threshold and tactile sensitivity around the horn bud were assessed at intervals. Blood was collected at intervals for plasma cortisol analysis. No significant differences were found between the groups in the needle prick test (p = 0.329) and the disbudding score (p = 0.855). Pain scores and quantitative sensory tests showed no significant differences between the lidocaine and procaine‐epinephrine groups. Conversely, tactile sensitivity and pain scores were significantly higher, and pressure pain thresholds were significantly lower with procaine alone than in other groups. Elevated cortisol concentrations were observed in all groups before disbudding compared to the baselines. The results suggest that procaine combined with epinephrine appears to be a safe and effective alternative to lidocaine for calf disbudding. Cortisol concentrations as an indicator of pain in xylazine‐sedated calves appear inadequate. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we applied translational informatics for intelligent medicine of acute myeloid leukemia, a type of cancer characterized by disease relapses even after seemingly successful treatments. Treatment failure is associated, at least in part, with the fact that targeting individual proteins often promotes rewiring of relevant networks and re-organization of interactions of, among others, non-targeted proteins to eventually evade single-target therapies. To develop efficient therapies, these dynamics should be taken into account and target whole network modules instead of singleton genes in order to prevent the establishment of compensating signaling circuits. Therefore, we integrated network-based methods, structural pharmacology, and molecular modeling to establish two complementary multitargeting strategies, one in the form of repurposable drug combinations and the other as a de novo synthesized triple-targeting agent. Of note, our study exploits, for the first time, a greedy algorithm to identify optimal combinations of drugs and therapeutic protein targets. Background/Objectives: Acute myeloid leukemia (AML) is characterized by therapeutic failure and long-term risk for disease relapses. As several therapeutic targets participate in networks, they can rewire to eventually evade single-target drugs. Hence, multi-targeting approaches are considered on the expectation that interference with many different components could synergistically hinder activation of alternative pathways and demolish the network one-off, leading to complete disease remission. Methods: Herein, we established a network-based, computer-aided approach for the rational design of drug combinations and de novo agents that interact with many AML network components simultaneously. Results: A reconstructed AML network guided the selection of suitable protein hubs and corresponding multi-targeting strategies. For proteins responsive to existing drugs, a greedy algorithm identified the minimum amount of compounds targeting the maximum number of hubs. We predicted permissible combinations of amiodarone, artenimol, fostamatinib, ponatinib, procaine, and vismodegib that interfere with 3–8 hubs, and we elucidated the pharmacological mode of action of procaine on DNMT3A. For proteins that do not respond to any approved drugs, namely cyclins A1, D2, and E1, we used structure-based de novo drug design to generate a novel triple-targeting compound of the chemical formula C15H15NO5, with favorable pharmacological and drug-like properties. Conclusions: Overall, by integrating network and structural pharmacology with molecular modeling, we determined two complementary strategies with the potential to annihilate the AML network, one in the form of repurposable drug combinations and the other as a de novo synthesized triple-targeting agent. These target–drug interactions could be prioritized for preclinical and clinical testing toward precision medicine for AML. [ABSTRACT FROM AUTHOR]

Introduction: Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant Aspergillus strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine. Methods: Conidia of different A. fumigatus strains, A. flavus and A. terreus were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca2+ distribution during treatment of A. fumigatus with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during in vitro coinfection of lung epithelial cells with A. fumigatus and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay. Results: Both substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant A. fumigatus strains. However, the addition of CaCl2 reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca2+ homeostasis. Furthermore, in vitro studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and A. fumigatus during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication. Discussion: This research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens. [ABSTRACT FROM AUTHOR]

Introduction: The Sydney Medically Supervised Injecting Centre provides a safe, non‐judgemental space where people can inject pre‐obtained substances under the supervision of trained staff. This article describes an unusual incident occurring at the Medically Supervised Injecting Centre in January 2023. Case Presentation: Two regular male clients attending the Medically Supervised Injecting Centre injected a substance they believed to be cocaine. Both clients experienced adverse reactions; one was transported to hospital, while the other became extremely distressed and agitated. Paraphernalia sent for testing returned a result of tiletamine (a dissociative used in veterinary medicine) and no cocaine, 30 h after the incident. Discussion and Conclusions: Where substances are novel or unknown, adverse events are often unexpected and may be more difficult to prepare for. Substance‐induced acute agitation can be alarming and hazardous for people consuming drugs and those around them and may pose challenges for staff. There is a substantial evidence base for the benefits of on‐site drug analysis and drug checking in reducing harms related to drug use, and in enhancing drug market monitoring. This incident was successfully managed by Medically Supervised Injecting Centre and hospital staff, with no major consequence, however clinical management could have been improved using point of care drug testing. [ABSTRACT FROM AUTHOR]

Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time measurements of drug concentrations in the brains of freely moving rats. Specifically, using such sensors, we achieve 1.5 hours. These results demonstrate the utility of such sensors in (i) the determination of the site-specific, seconds-resolved neuropharmacokinetics, (ii) enabling the study of individual subject neuropharmacokinetics and concentration-response relations, and (iii) performing high-precision control over intracranial drug levels.

Introduction: Treatment of influenza A virus infections is currently limited to few direct acting antiviral substances. Repurposing other established pharmaceuticals as antivirals could aid in improving treatment options. Methods: This study investigates the antiviral properties of ProcCluster® and procaine hydrochloride, two derivatives of the local anesthetic procaine, in influenza A virus infection of A549, Calu-3 and MDCK cells. Results: Both substances inhibit replication in all three of these cell lines in multi-cycle experiments. However, cell line-dependent differences in the effects of the substances on viral RNA replication and subsequent protein synthesis, as well as release of progeny viruses in single-cycle experiments can be observed. Both ProcCluster® and procaine hydrochloride delay endosome fusion of the virus early in the replication cycle, possibly due to the alkaline nature of the active component procaine. In A549 and Calu-3 cells an additional effect of the substances can be observed at late stages in the first replication cycle. Interestingly, this effect is absent in MDCK cells. We demonstrate that ProcCluster® and procaine hydrochloride inhibit phospholipase A2 (PLA2) enzymes from A549 but not MDCK cells and confirm that specific inhibition of calcium independent PLA2 but not cytosolic PLA2 has antiviral effects. Discussion: We show that ProcCluster® and procaine hydrochloride inhibit influenza A virus infection at several stages of the replication cycle and have potential as antiviral substances. [ABSTRACT FROM AUTHOR]

Background: 3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women. Methods: We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level. Results: There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed. Conclusions: Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Clinical trial number and registry URL: The registration number: ChiCTR2200065201; http://www.chictr.org.cn, Principal investigator: MEN, Date of registration: 31/10/2022. [ABSTRACT FROM AUTHOR]

IntroductionInfluenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant Aspergillus strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine.MethodsConidia of different A. fumigatus strains, A. flavus and A. terreus were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca2+ distribution during treatment of A. fumigatus with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during in vitro coinfection of lung epithelial cells with A. fumigatus and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay.ResultsBoth substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant A. fumigatus strains. However, the addition of CaCl2 reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca2+ homeostasis. Furthermore, in vitro studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and A. fumigatus during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication.DiscussionThis research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens.

Chemical epigenetic modifiers could optimize the compound biosynthesis of endophytes by activating the silent genes. Treatment of procaine, an epigenetic modifier, on endophytic fungus Talaromyces wortmannii isolated from Morus Cathayana Hemsl., was evaluated with NMR spectroscopy analysis combined with multivariate data analysis and antibacterial assay. In total, 29 compounds were successfully annotated in the T. wortmannii extracts and most of them are primary metabolites. Semi-quantitative 1H NMR analysis revealed that the concentrations of some annotated compounds increased in the treated endophyte, including wortmin, mannitol, and choline. Meanwhile, the contents of glucose and skyrin decreased in the treated T. wortmannii. Multivariate data analysis successfully distinguished the metabolite profile of the treated T. wortmannii from that of the control endophyte. This analysis revealed that procaine treatment on T. wortmannii possibly induced the biosynthesis of mannitol, choline, lactic acid, and phosphocholine and repressed the contents of fatty acids, including palmitic, stearic, linoleic, and oleic acids. The antibacterial assay revealed chloroform extracts of the treated endophyte, and its control possessed potent antibacterial activity against the tested pathogenic bacteria. Meanwhile, the antibacterial activity of water-methanol extract of the treated T. wortmannii increased against Enterococcus faecalis and Salmonella enterica. In this report, the procaine treatment altered the metabolite profiles of the endophytic fungus T. wortmannii. Here we also demonstrated that 1H NMR-based metabolomics was the effective method to study the effect of the epigenetic modifier on endophytic fungi. [Display omitted] • Procaine treatment modified the metabolite profiles of Talaromyces wortmannii. • Wortmin biosynthesis was induced by the procaine treatment. • Mannitol concentration increased significantly on the treated T. wortmannii. [ABSTRACT FROM AUTHOR]

IntroductionTreatment of influenza A virus infections is currently limited to few direct acting antiviral substances. Repurposing other established pharmaceuticals as antivirals could aid in improving treatment options.MethodsThis study investigates the antiviral properties of ProcCluster® and procaine hydrochloride, two derivatives of the local anesthetic procaine, in influenza A virus infection of A549, Calu-3 and MDCK cells.ResultsBoth substances inhibit replication in all three of these cell lines in multi-cycle experiments. However, cell line-dependent differences in the effects of the substances on viral RNA replication and subsequent protein synthesis, as well as release of progeny viruses in single-cycle experiments can be observed. Both ProcCluster® and procaine hydrochloride delay endosome fusion of the virus early in the replication cycle, possibly due to the alkaline nature of the active component procaine. In A549 and Calu-3 cells an additional effect of the substances can be observed at late stages in the first replication cycle. Interestingly, this effect is absent in MDCK cells. We demonstrate that ProcCluster® and procaine hydrochloride inhibit phospholipase A2 (PLA2) enzymes from A549 but not MDCK cells and confirm that specific inhibition of calcium independent PLA2 but not cytosolic PLA2 has antiviral effects.DiscussionWe show that ProcCluster® and procaine hydrochloride inhibit influenza A virus infection at several stages of the replication cycle and have potential as antiviral substances.

To explore the action of procaine on ovarian cancer cell oncogenic phenotypes and its molecular mechanism. Ovarian cancer cells were divided into control group, procaine low, medium and high dose group, microRNA-204 group, microRNA-NC group, high dose group+anti-microRNA-ovarian cancer group, high dose group+anti-microRNA-204 group; 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, clone formation and transwell assays detected cell proliferation, migration and invasion, Western blotting and quantitative reverse transcription polymerase chain reaction detected protein and ribonucleic acid expression. Procaine treatment dose-dependently impaired the proliferation, migration, invasion and epithelialmesenchymal transition progression in ovarian cancer cells. Moreover, microRNA-204 levels were observed to be dose-dependently increased by procaine treatment. MicroRNA-204 overexpression suppressed the oncogenic phenotypes mentioned above in ovarian cancer cells. Importantly, the inhibition of microRNA-204 abolished the anticancer effects of procaine on ovarian cancer cells. In conclusion, procaine up-regulated microRNA-204 to ovarian cancer cell oncogenic phenotypes. [ABSTRACT FROM AUTHOR]

Background: The use of Procaine hydrochloride in cardioplegia has been discontinued due to challenges importing the product from outside the country despite its crucial role in preserving myocardium during heart surgery. However, Lidocaine hydrochloride, an anti-arrhythmic medication, functions similarly to Procaine hydrochloride. Both medications are compared regarding their effectiveness in preventing ventricular fibrillation, the most common type of heart arrhythmia, after releasing the aortic cross-clamp in cardiac surgery. Materials and Methods: This is a retrospective study in which data was collected from medical records of patients who were operated on with coronary artery bypass grafts between May 2017 and August 2023. Patient demographics and early outcomes between the two groups were analyzed. Results: A total of 328 patients who underwent CABG were divided into 2 groups, respectively. Group "P" received cardioplegia solutions with Procaine hydrochloride, whilst group "L" received cardioplegia solutions with Lidocaine hydrochloride. The average age of the participants was 64.19 years old in group P and 64.24 years old in group L. The duration of the aortic cross-clamp was significantly different between the two groups, with durations of 76.06 minutes and 87.79 minutes, respectively, showing a p-value of less than 0.01 in statistical analysis. Following the release of aortic cross-clamping, the occurrence of ventricular fibrillation was observed in 37 patients (43%) in the first group and 49 patients (56.9%) in the second group, with no significant difference noted. After defibrillation at 10 joules, there were 21 patients (24.4%) in the first group and 13 patients (15.1%) in the second group, indicating a significant difference. Additionally, no significant difference was observed in the duration of the CCU stay between both groups. Conclusion: Cardioplegic solution containing Lidocaine hydrochloride provides the same clinical result as Procaine hydrochloride in coronary artery bypass grafting surgery. [ABSTRACT FROM AUTHOR]

The multifunctionality of an A3B mixed-substituted porphyrin, namely 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin (5-COOH-3MPP), was proven due to its capacity to detect procaine by different methods, depending on the polymer matrix in which it is incorporated. The hybrid nanomaterial containing k-carrageenan and AuNPs (5-COOH-3MPP-k-carrageenan-AuNPs) was able to optically detect procaine in the concentration range from 5.76 × 10−6 M to 2.75 × 10−7 M, with a limit of detection (LOD) of 1.33 × 10−7 M. This method for the detection of procaine gave complementary results to the potentiometric one, which uses 5-COOH-3MPP as an electroactive material incorporated in a polyvinylchloride (PVC) membrane plasticized with o-NPOE. The detected concentration range by this ion-selective membrane electrode is wider (enlarged in the field of higher concentrations from 10−2 to 10−6 M), linearly dependent with a 53.88 mV/decade slope, possesses a detection limit of 7 × 10−7 M, a response time of 60 s, and has a certified stability for a working period of six weeks. [ABSTRACT FROM AUTHOR]

The use of low-dose local anesthetics (LAs) has significantly transformed patient care by providing rapid and effective relief of pain and other clinical conditions while minimizing recovery time. This study aims to identify and describe the existing scientific evidence on the therapeutic use of low-dose LAs in various conditions and to identify gaps in the current literature in order to prioritize future research. This systematic scoping review adhered to the methodological guidelines outlined in the Arksey and O'Malley framework, which includes five distinct stages. Of the 129 studies included, 37.98% (n = 49) were clinical trials, 55.03% (n = 71) were observational studies, and 6.97% (n = 9) were systematic reviews. The most commonly reported indication for the use of low-dose LAs was chronic pain management (72.86%), followed by acute pain management (13.17%). Additionally, non-pain-related indications were also identified (13.95%). Overall, the administration of low-dose, short-acting LAs demonstrated favorable outcomes in terms of pain management and reduction in anxiety and depression scales, thereby having a positive impact on the patients' quality of life. This review represents the first systematic scoping review regarding the therapeutic role of LAs. To substantiate the reported positive effects on efficacy and safety, further rigorous research comprising larger, well-designed randomized controlled trials (RCTs) and long-term outcome monitoring is imperative. [ABSTRACT FROM AUTHOR]

The article titled "Procaine inhibits proliferation and migration and promotes cell apoptosis in osteosarcoma cells by upregulation of microRNA-133b" has been retracted from Oncology Research due to concerns about the accuracy of the data. The western blots in the article contained protein bands that were atypical and possibly anomalous. The authors were given the opportunity to address these concerns but did not respond. The Editors-in-Chief have retracted the article due to a lack of confidence in the integrity of the data. The publisher regrets any inconvenience caused by this situation. [Extracted from the article]

As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster® and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed. [ABSTRACT FROM AUTHOR]

Anesthetic residues in fish represent a potential risk to human health. Therefore, it is important to develop a sensitive and broad-specific method for the detection of anesthetics. In this study, we developed a colloidal gold-based quadruplex immunochromatographic (Qua-ICS) assay using four highly sensitive monoclonal antibody immunotherapy (mAbs) that simultaneously detected 11 anesthetic residues in fish within 10 min. The colorimetric and cut-off values (COVs) for procaines, eugenols, bupivacaines, and tricaine (TMS) were 0.37–1.1 and 3.3–10, 11–222 and 100–2000, 0.37 and 3.3, and 111 and 10,000 µg/kg, respectively. Quantitative analysis was achieved with a portable strip-reader, and the detection ranges were 0.15–2.6, 6.3–677, 0.13–2.8, and 83–1245 µg/kg for procaines, eugenols, bupivacaines, and tricaine, respectively. Our developed method was reliable and accurate according to the recovery test results and analyses of real samples. Therefore, the strip can be used as an alternative method for the rapid detection of anesthetic residues in fish. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a serious devastating disease. However, the current clinical options to treat DN are not adequate. Thus, in the present study, we intend to develop novel series of procaine‐embedded thiazole‐pyrazoles as protective agent against DN. The compounds were tested for inhibition of dipeptidyl peptidase (DPP)‐4, −8, and − 9 enzyme subtypes, where they selectively and potently inhibit DPP‐4 as compared to other subtypes. The top three ranked DPP‐4 inhibitors (8i, 8e and 8k) were further screened for inhibitory activity against NF‐ĸB transcription. Among these three, compound 8i was identified as the most potent NF‐ĸB inhibitor. The pharmacological benefit of compound 8i was further established in streptozotocin‐induced diabetic nephropathy in rats. Compound 8i showed marked improvements in blood glucose, ALP, ALT, total protein, serum lipid profile such as total cholesterol, triglyceride, HDL levels and renal functions such as urine volume, urinary protein excretion, serum creatinine, blood urea nitrogen and creatinine clearance as compared to nontreated diabetic control group. It also reduces oxidative stress (MDA, SOD and GPx) and inflammation (TNF‐α, IL‐1β and IL‐6) in the rats as compared to disease control group rats. This study demonstrated the discovery of procaine‐embedded thiazole‐pyrazole compounds as a novel class of agent against diabetic nephropathy. [ABSTRACT FROM AUTHOR]

In dentistry, local anesthesia is needed, especially for oral and maxillofacial surgery to reduce the sensation of pain. Besides its use as an analgesic, local anesthetics also have antibacterial activity which inhibits the growth of various bacteria. The purpose of this study was to determine the antibacterial activity of procaine and mepivacaine in inhibiting the growth of Porphyromonas gingivalis. In this study, the antibacterial activity test was carried out using the Kirby-Bauer diffusion method for ten repetitions and four treatment groups tested, 2% procaine, 3% mepivacaine, metronidazole as a positive control, and aquadest as a negative control dripped on paper discs and incubated for 24 hours. The results showed that procaine and mepivacaine had antibacterial activity with inhibition zone diameters of 9.36 mm and 8.47 mm, metronidazole 11.80 mm, and aquadest showed no inhibition diameter. The results of the research data were analyzed using the One-way ANOVA test. There was a significant difference in the diameter of the inhibition zone (p <0.05) between the four treatment. Two percent procaine and 3% mepivacaine have antibacterial activity against the growth of Porphyromonas gingivalis which is classified as a moderate inhibitory response according to David and Stout. [ABSTRACT FROM AUTHOR]

Aim To explore the effect and molecular mechanism of procaine on hypoxia induced injury of N9 and PC12 cells. Methods N9 cells and PC12 cells were divided into control group, hypoxia group, low, medium and high dose (hypoxia+2, 6, 18 mg/L procaine) procaine group, anti-miR-con group, anti-miR-369-3p group, miR-con+ high dose procaine group (transfection miR-con+hypoxia+18 mg/L procaine), miR-369-3p+high dose procaine group (transfection miR-369-3p+hypoxia+18 mg/L procaine). Flow cytometry was used to detect apoptosis, reagent kit was used to detect the content of reactive oxygen species (ROS) and malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), ELISA was used to detect the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). RT-qPCR was used to detect the expression of miR-369-3p. Results Compared with the control group, the apoptosis rate of N9 cells and PC12 cells in the hypoxia group increased, the content of MDA and ROS increased, the activity of SOD decreased, the levels of TNF-α, IL-1β and IL-6 increased, the expression of miR-369-3p increased (P<0. 05). Compared with the hypoxia group, the apoptosis rate of N9 cells and PC12 cells in the low, medium and high dose procaine groups decreased, the content of MDA and ROS decreased, the activity of SOD increased, the levels of TNF-α, IL-1β and IL-6 decreased, the expression of miR-369-3p decreased in a concentration dependent manner (P <0. 05). Compared with the anti-miR-con group, the apoptosis rate of N9 cells and PC12 cells in the anti-miR-369-3p group decreased, the content of ROS and MDA decreased, the activity of SOD increased, the levels of TNF-α, IL-1β and IL-6 decreased (P<0. 05). Compared with miR-con+high dose procaine group, the apoptosis rate of N9 cells and PC12 cells in miR-369-3p+high dose procaine group increased, the expression of cleaved Caspase-3 protein increased, the content of MDA and ROS increased, the activity of SOD decreased, the levels of TNF-α, IL-1β and IL-6 increased (P <0. 05). Conclusion Procaine can reduce hypoxia induced injury to N9 and PC12 cells, and its mechanism may be related to inhibiting the expression of miR-369-3p. [ABSTRACT FROM AUTHOR]

Myocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor agonist), caused a graded increase in mean arterial pressure in rats with sinoaortic denervation and vagotomy. This effect of α,β-meATP was abolished by blockade of cardiac neural transmission with intrapericardial procaine treatment and eliminated by intrapericardial A-317491, a selective P2X2/3 and P2X3 receptor antagonist. Intrapericardial α,β-meATP also evoked CSR response in vagus-intact rats. Furthermore, the P2X receptor-mediated CSR responses were enhanced by intrapericardial naloxone, a specific opioid receptor antagonist. These data suggest that stimulation of cardiac P2X2/3 and P2X3, but not P2Y receptors, powerfully evokes CSR responses through activation of cardiac spinal afferents, and that endogenous opioids suppress the P2X receptor-mediated CSR responses.

Myocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents' activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor agonist), caused a graded increase in mean arterial pressure in rats with sinoaortic denervation and vagotomy. This effect of α,β-meATP was abolished by blockade of cardiac neural transmission with intrapericardial procaine treatment and eliminated by intrapericardial A-317491, a selective P2X2/3 and P2X3 receptor antagonist. Intrapericardial α,β-meATP also evoked CSR response in vagus-intact rats. Furthermore, the P2X receptor-mediated CSR responses were enhanced by intrapericardial naloxone, a specific opioid receptor antagonist. These data suggest that stimulation of cardiac P2X2/3 and P2X3, but not P2Y receptors, powerfully evokes CSR responses through activation of cardiac spinal afferents, and that endogenous opioids suppress the P2X receptor-mediated CSR responses.

Author(s): T. A. Sokolova [sup.1], S. Yu. Doronin [sup.1] Author Affiliations: (1) grid.446088.6, 0000 0001 2179 0417, Institute of Chemistry, Chernyshevskii Saratov State University, , 410012, Saratov, Russia Novocaine is [...], The work deals with the extraction and preconcentration of novocaine using mixed surfactants of nonionic (Triton X-114) and anionic (sodium dodecyl sulfate) types with the photometric registration of an analytical signal. The method is based on the condensation reaction of novocaine with p-dimethylaminobenzaldehyde (pH 2.5-3.5) and the subsequent micellar extraction of the colored analytical form, the Schiff base. For the effective extraction of this form, the parameters of micellar extraction (concentrations of reagents: Ñ.sub.NaCl = 0.5-1 Ð, c.sub.Triton X-114 = 2 x 10.sup.-3-1 x 10.sup.-2 M; conditions: centrifugation time 5 min at 3000 rpm) are optimized. The proposed method makes it possible to determine novocaine in the concentration range 38-4800 ng/mL (RSD [less than or equal to] 7%, limit of detection 19 ng/mL), which is several orders of magnitude lower than in the known spectrophotometric versions. The Bouguer-Lambert-Beer law is obeyed in the range 8 x 10.sup.-7-4 x 10.sup.-5 M. The developed extraction-photometric method was tested in the determination of novocaine in 0.5% ampoule solutions for injection.

The present study was designed to synthesize and characterize calcium oxide nanoparticles (using mangrove oyster shell as a precursor) and apply the synthesized nanoparticles as a photocatalyst to degrade procaine penicillin in an aqueous solution. The photocatalyst exhibited an average band gap of 4.42 eV, showed a maximum wavelength of absorbance in the UV region (i.e., 280 nm), and is a microporous nanoparticle with a particle diameter of 50 nm. The photocatalyzed degradation of the drug was conducted under natural sunlight, and the influence of parameters such as the period of contact, catalyst load, pH, initial drug concentration, and ionic strength was investigated concerning the degradation profile. The results obtained from response surface analysis indicated that an optimum degradation efficiency of about 93% can be obtained at a concentration, pH, and catalyst dosage of 0.125 M, 2, and 0.20 g respectively, at 0.902 desirabilities. The Langmuir–Hinshelwood, modified Freundlich, parabolic diffusion, pseudo-first-/second-order, and zero-, first-, and second-order kinetic parameters were tested to ascertain the best model that best described the experimental data. Consequently, the Langmuir–Hinshelwood, modified Freundlich, and pseudo-second-order models were accepted based on the minimum error and higher R2 values. Based on the Langmuir–Hinshelwood rate constants for adsorption and photodegradation as well as the evaluated valence bond potential, the degradation of the drug first proceeded through the mechanism of adsorption and followed by the oxidation of the drug by superoxide (generated from the interaction of electrons that generated by through the absorption of UV radiation). The quantum chemical calculation gave evidence that pointed towards the establishment of strong agreement with experimental data and also showed that the carboxyl functional group in the drug is the target site for adsorption and subsequent degradation. [ABSTRACT FROM AUTHOR]

In this study, a new potentiometric sensor was developed for the determination of the local anesthetic drug procaine in pharmaceutical samples. Procaine (Pr)–Tetraphenlyborate (TPB) ion–pair was synthesized and used as a sensor material. Potentiometric sensors using the synthesized ion pair (Pr–TPB), poly(vinyl chloride) (PVC) and o –nitrophenyloctyl ether (o –NPOE) in different proportions were prepared and their performance properties were tested. Among the prepared sensors, the best potentiometric response characteristics were obtained with the sensor composition Pr–TPB:PVC: o –NPOE in the ratio of 6.0:32.0:62.0 (w/w %). The new procaine sensor developed in the present study had a near–Nernstian behavior of 54.1 ± 3.3 mV/per decade and a low detection limit of 3.18 × 10−5 mol L−1 in the concentration range of 1.0 × 10−1–1.0 × 10−4 mol L−1. Additionally, the sensor had a response time of less than 10 s and could work in a wide pH range for two different concentration values without being affected by pH changes. Finally, the new procaine potentiometric sensor was used to detect procaine in injection samples and successfully determined procaine concentrations with high recoveries. [Display omitted] • A rapid and selective method for the accurate determination of procaine in injection samples. • Solid contact potentiometric sensors based on procaine–tetraphenylborate ion–pair. • Fast, economical, simple and repeatable sensors for the detection of procaine. [ABSTRACT FROM AUTHOR]

Procaine is one of the most popular local anesthetics of all time and represented a revolutionary discovery both for human medicine (and here we are mainly referring to the practice of general surgery) and pharmacy, as well as for dentistry (stomatology or dental medicine). Thus, in this material, we will try to present a biography as succinct as possible of Professor Alfred Einhorn, discoverer of procaine. [ABSTRACT FROM AUTHOR]

Lateral epicondylitis is an inflammatory disease that affects the attachment site of the wrist extensor tendons. It mostly occurs in middle ages after repetitive grasping and turning movements. In this disease, there is significant pain and loss of function in the elbow and forearm. It can be treated with conservative treatment options such as medical treatment, rest, epicondylitis orthosis, physical therapy and exercise regimens, and injection methods. In this case, treatment with neural therapy for lateral epicondylitis in a patient who was unresponsive to conservative treatment was included. All symptoms of a 62-year-old female patient regressed after 6 sessions of neural therapy and there was no recurrence of symptoms during follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical castration of piglets is generally recognized as a painful procedure. Thus, for animal welfare reasons, the German Animal Welfare Act stipulates the use of effective anesthesia during castration. However, whether local anesthesia provides adequate analgesia has been an ongoing debate in Germany. In the present study, we compared the behavior of 178 piglets allocated to various test groups in an observation arena before any of the applied procedures, after administration of the local anesthetic, and 0, 2 and 24 h after surgical castration. The local anesthetic and the injection techniques were evaluated and optimized in three sequential study parts. Overall, the results revealed that when local anesthesia was used, piglets less frequently showed pain-associated behaviors—such as changes in tail position—than piglets of the control group that had been castrated without local anesthesia. Non-castrated piglets showed the fewest pain-associated behaviors in the observation arena. In several test groups, the piglets showed changes in tail position, tail wagging, or hunched-back posture on the day following the procedure. These behaviors differed significantly from those shown before the procedure. The administration of local anesthetics in the present study considerably reduced castration-related pain. However, because local anesthesia has a limited duration of effect, adverse effects due to castration-related pain were still observable one day after castration. Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness of local anesthetics. In this study, we investigated the efficacy of four local anesthetics in terms of pain relief during and after surgical castration in three sequential study parts. To do so, we filmed 178 piglets before the applied procedures, after injection of the local anesthetic, and up to 24 h after castration (five observation times in total) in an observation arena and compared their behavior before and after castration and between treatments and control groups. The results showed significant differences in the behavior of the piglets before and after castration and between the sham-castrated control group and the control group castrated without anesthesia. The different local anesthesia treatment groups showed diverging differences to the control groups. The most frequently shown pain-associated behaviors of the piglets were changes in tail position and hunched back posture. We observed a reduction but no complete elimination of the expressed pain-associated behaviors after local anesthesia. Several behavioral changes—such as changes in tail position, hunched back posture or tail wagging—persisted until the day after castration. Owing to the limited duration of the effects of the local anesthetics, local anesthesia did not influence long-term pain. [ABSTRACT FROM AUTHOR]

The response of agricultural crops to the application of biostimulators depends on the climatic conditions, the type of soil and cultivated variety. While knowing the role of biostimulators on the growth and development of crops, as well as on quantitative and qualitative increases in the scientific field, the aim of this research is to follow the influence of procaine treatments on the level of production and quality of two potato varieties (Armonia and Gared), depending on planting density (55 X 103 and 70 X 103 tubers/ha). The tubers were treated with procaine by immersion, for two hours, prior to planting, in a 10 mg/l solution. The research was carried out in the period 2019-2022, in the pedoclimatic conditions of the Almaj Depression, on a semi carbonate eutric alluvial type soil, located in the meadow area, with loamy-sandy texture, slightly alkaline soil reaction, pH 7.67, and a medium humus content (2.72%). The researched area has a moderate continental temperate climate, with Mediterranean and oceanic influences, which give a special nuance to the depression, with multiannual average of atmospheric precipitation varying between 670-750 mm. Fertilization of the crop was achieved by incorporating under ploughing 25 t/ha of manure and 600 kg/ha of 15:15:15 complex fertilizers. The results obtained highlight the positive effect of the treatment with procaine on the tubers before planting, on average on the two tested varieties and the two densities, expressed in production increases of 7%. [ABSTRACT FROM AUTHOR]

This single cell study aimed to clarify whether an elevated incidence of sperm with a retained cytoplasmic droplet (CD) can be compensated by a higher sperm number in boar semen doses to maintain fertility. Cluster analysis of motile spermatozoa (ten boars) revealed that spermatozoa with a CD are underrepresented in the fast, linearly moving sperm cohort compared to morphologically normal sperm. Nonetheless, the response to the motility stimulator procaine was barely affected in spermatozoa with distal CD (Cramer's V = 0.14), but moderately affected in sperm with proximal CD (V = 0.28). Viability was lower in sperm with distal CD (p < 0.05) but not with proximal CD compared to normal sperm during 168 h storage of extended semen samples (n = 11) and subsequent thermic stress. Morphologically normal sperm from normospermic samples (n = 10) or samples with a high incidence (≥ 15%) of sperm with CD (n = 9) had similar motility patterns and responses to procaine. The origin of morphologically normal sperm had no effect on sperm viability (p > 0.05; n = 26). In conclusion, a moderately enhanced prevalence of sperm with CD seems to be compensable by an increase in sperm numbers in boar semen doses. [ABSTRACT FROM AUTHOR]