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The transdermal route is one of the effective routes for delivering drugs. It also overcomes many limitations associated with oral delivery. One of the limitations of this route is the drug's poor skin permeability—stratum corneum, the skin's outermost layer that also acts as a barrier for the drug to penetrate. Traditional liposomal formulation is utilized to overcome these limitations. However, these liposomes also have certain difficulty in delivering drugs across the barriers. Ultra-deformable vesicles are novel vesicular structures that are flexible and stable, they can easily bypass the skin barriers more efficiently and thus enhance bioavailability. These vesicles consist of ethosomes, transethosomes, and transferosomes. Transethosomes are more advanced than other vesicular systems because they contain ethanol, phospholipids, and edge activators, making them more deformable and easier to penetrate deeper skin membranes. These vesicular systems can be prepared by various methods, such as cold, hot, and thin film hydration. Characterization of transethosomes includes vesicular size, zeta potential, polydispersity index and encapsulation efficiency, stability, and drug release studies. These vesicular systems can be utilized to deliver a variety of medications transdermally, including analgesics, antibiotics, and arthritis medications. Despite their promising potential, ethanol-based formulations present several problems requiring additional study. This review aims to describe various vesicular structures that have been used to overcome the barrier for the transdermal delivery of drugs and also describe brief composition, method of preparation, characterization, mechanism of penetration of transethosomes, as well as highlighted various applications of transethosomes in medicine, clinical trials and patents. [ABSTRACT FROM AUTHOR]

Background: Silver-111 is a promising β−-emitting radioisotope with ideal characteristics for targeted radionuclide therapy and associated single photon emission tomography imaging. Its decay properties closely resemble the clinically established lutetium-177, making it an attractive candidate for therapeutic applications. In addition, the clinical value of silver-111 is further enhanced by the existence of the positron-emitting counterpart silver-103, thus imparting a truly theranostic potential to this element. A so-fitting matching pair could potentially overcome the current limitations associated with the forced use of chemically different isotopes as imaging surrogates of lutetium-177, leading to more accurate and efficient diagnosis and treatment. However, the use of silver-111-based radiopharmaceuticals in vivo has faced obstacles due to the challenges related to its production and radiochemical separation from the target material. To address these issues, this study aims to implement a chromatographic separation methodology for the purification of reactor-produced silver-111. The ultimate goal is to achieve a ready-to-use formulation for the direct radiolabeling of tumour-seeking biomolecules. Results: A two-step sequence chromatographic process was validated for cold Ag-Pd separation and then translated to the radioactive counterpart. Silver-111 was produced via the 110Pd(n,γ)111Pd nuclear reaction on a natural palladium target and the subsequent β−-decay of palladium-111. Silver-111 was chemically separated from the metallic target via the implemented chromatographic process by using commercially available LN and TK200 resins. The effectiveness of the separations was assessed by inductively coupled plasma optical emission spectroscopy and γ-spectrometry, respectively, and the Ag+ retrieval was afforded in pure water. Recovery of silver-111 was > 90% with a radionuclidic purity > 99% and a separation factor of around 4.21·10−4. Conclusions: The developed separation method was suitable to obtain silver-111 with high molar activity in a ready-to-use water-based formulation that can be directly employed for the labeling of radiotracers. By successfully establishing a robust and efficient production and purification method for silver-111, this research paves the way for its wider application in targeted radionuclide therapy and precision imaging. [ABSTRACT FROM AUTHOR]

Biofilm formation by Propionibacterium acnes is known to cause failure of anti-acne treatment. Conventional therapies for acne are typically inadequate. Accordingly, in this study, we evaluated the therapeutic potential of photodynamic therapy (PDT) using hexyl-aminolevulinate (HAL)-loaded ethosomes (ESs) against the biofilms of P. acnes in vitro and P. acnes–induced inflammatory acne model in vivo. The antibacterial effects of HAL ESs were evaluated using XTT colorimetric assays and scanning electron microscopic observations of morphological changes. P. acnes was intradermally injected into the ears of Sprague-Dawley rats, and the anti-inflammatory effects of HAL ESs were measured by determining changes in appearance, histology, and the antibacterial effects by P. acnes abundance in ear tissues compared with blank control ESs, HAL alone, and 5-aminolevulinic acid (ALA) alone. The highest reduction in viability in P. acnes biofilms was observed after treatment with 5 mg/mL HAL ESs. Notably, blank control ESs also showed significant inhibitory effects. Furthermore, HAL ESs had superior therapeutic effects in the rat model compared with HAL or ALA solutions. The observed therapeutic effects of HAL ESs against P. acnes biofilms and P. acnes–induced inflammation suggest that PDT with HAL-loaded ESs may have potential applications in the treatment of acne. [ABSTRACT FROM AUTHOR]

The paper presents the distribution of natural radionuclides in soils with various clay minerals of Davanagere district. The activity concentration of natural radionuclides in soil were measured using NaI(TI) gamma spectrometry and the minerals present in the soils were identified using Fourier–transform infrared spectroscopy. The normality of the frequency distribution curve of 226Ra, 232Th and 40K concentration was verified using Kolmogorov–Smirnov test. The major trace minerals observed in the soils were determined based on the intensity of corresponding peaks. The soil with clay minerals Quartz and Hematite showed higher radionuclide content. [ABSTRACT FROM AUTHOR]

Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in small and medium-sized animal models, anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select survival agents (dexmedetomidine, alfaxalone, and propofol) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [∆HR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. The urodynamic parameters under isoflurane and α-chloralose were also examined in terminal procedures for four cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices. [ABSTRACT FROM AUTHOR]

Spontaneous animal models of Alzheimer's disease (AD) offer the potential to bridge the translational gulf between promising rodent studies and failed human clinical trials. In this review, the relationship between cell biology, neuropathology, clinical phenotype and biomarker progression in human AD is summarized. Genetically altered animals have provided key insights into the cell biology of AD and, together with emerging stem cell systems, remain the most effective means to disentangle the entwined mechanisms that underlie AD. Translating therapeutic success from these models of familial AD to late onset human AD has been challenging. Spontaneous models of AD do not harbor AD-associated mutations and could potentially be used to demonstrate greater generalizability of new therapies to late onset AD. The value of such models has been advanced primarily on the basis of similar amyloid (and far less frequent, tangle) neuropathology. While these models are promising, this alone is insufficient for use of these models to assess efficacy of potential therapies. The correlation between progression of neuropathology and cognitive phenotype and the association of these with biomarker progression in these models is discussed, with an emphasis on the dog and non-human primates. Currently, interventional studies using these models are hampered by use of a variety of outcomes that are not easily comparable with those used in human trials and do not permit longitudinal assessment. Additional studies aimed at closing the gap between neuropathology and usable outcome measures would support more accurate subject selection, assessment of target engagement and evaluation of therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Tramadol hydrochloride (an opioid-like analgesic) and ketoprofen (a non-steroidal anti-inflammatory drug) are routinely used in human and veterinary medicine for the management of post-surgical pain. However, data on the safety of constant rate infusion tramadol as an adjunct to ketoprofen for peri-operative analgesia is lacking. This study evaluated changes in haematology and serum biochemistry associated with constant rate infusion (CRI) tramadol hydrochloride as an adjunct to ketoprofen for analgesia in adult female dogs following laparotomy (LP) and ovariohysterectomy (OVH). Thirty (30) adult female dogs randomly assigned into six groups of five dogs each were used in studies 1 and 2. In both studies, group 3 served as the control which received normal saline while groups 1 and 2 were given 1.0 and 2.0 mg/kg/h of tramadol Hcl, respectively. Dogs in study 1 were laparotomized while OVH was performed on dogs in study 2. Ketoprofen (4 mg/kg) was given subcutaneously for 3 days post-surgery (PS) to all the groups. There was no significant difference in the haematological parameters of treated and control groups. There was a transient significant rise in some serum biochemical parameters of the treated groups but these decreased to baseline values by day 7 post-surgery. Based on the findings in this study, it was concluded that constant rate infusion of 1 and 2 mg/kg/h of tramadol hydrochloride as an adjunct to ketoprofen caused no clinically observable deleterious effect on haematology and serum biochemistry of dogs post-laparotomy and ovariohysterectomy. [ABSTRACT FROM AUTHOR]

Purpose: First, to determine whether scoliosis development could be limited or reversed by growth when a novel modular hinged implant was fixed to the convexity of a scoliosis created by contralateral rib and laminar tethering and unilateral rib resection in a sheep model. Second, to assess the effect and performance of the implant in normal non-tethered sheep. Methods: At 5 weeks, 20 Scottish Blackface lambs underwent surgery to create a right sided scoliosis by (i) tethering the left lamina of T5-L1 and the left lower six ribs and (ii) resecting a segment of their right lower six ribs [, ]. Twelve weeks later, through an antero-lateral thoracotomy, a mobile bi-planar hinged implant was inserted onto the right side of the spine of eight animals (group 1). For comparison, 12 sheep were tethered only but had no implant insertion (group 2). In addition, seven had no tethering but were implanted (group 3) and normal growth patterns were observed in five that had no surgery (group 4). Curve progression was assessed by plain radiography and CT over a 1-year period. Results: Before implant insertion the trial animals had a scoliosis of 35º ± 16º and a lordosis of 44º ± 20º ( n = 8, mean ± SD). Surgery immediately reduced these values to 25º ± 14º, p < 0.01 and 35º ± 18º, p < 0.001, with scoliosis continuing to decrease during the next three months. Spinal flexibility was retained. In the un-tethered sheep, a scoliosis of 10º ± 6º was created on the opposite side to the implant ( p < 0.05) with no significant change in alignment in the sagittal plane (1º ± 6º). The implant did not cause any adverse effect on growth or affect neurological function. Conclusions: In the un-tethered animals the effect of the implant was to create a scoliotic deformity and in the tethered to improve deformity while maintaining spinal motion. We believe that the results are promising and that devices of similar construct may be of use in children with scoliosis, potentially changing current methods of clinical care. [ABSTRACT FROM AUTHOR]

Four cases of Tinea Nigra by Exophiala werneckii, observed in Porto Alegre, RS, during the period 1981-1992 were related. A boy presented bilateral palmar lesions, one girl had plantar lesions and the remaining two girls had lesions on the palms. Three cases were autochthonous and the remaining patient was infected during a trip to Chile. A review of Brazilian literature and comments on the epidemiology and clinical aspects of the mycosis is presented. [ABSTRACT FROM AUTHOR]