Animal Studies Research Articles

Cannabinoids and General Anesthetics: Revisiting Molecular Mechanisms of Their Pharmacological Interactions.

Cannabis has been used for recreation and medical purposes for more than a millennium across the world; however, its use's consequences remain poorly understood. Although a growing number of surgical patients are regular cannabis consumers, little is known regarding the pharmacological interactions between cannabis and general anesthetics; consequently, there is not a solid consensus among anesthesiologists on the perioperative management of these patients. The existing evidence about the molecular mechanisms underlying pharmacological interactions between cannabinoids and anesthetic agents, both in animal models and in humans, shows divergent results. While some animal studies have demonstrated that phytocannabinoids (tetrahydrocannabinol [THC], cannabidiol [CBD], and cannabinol [CBN]) potentiate the anesthetic effects of inhalation and intravenous anesthetics, while others have found effects comparable with what has been described in humans so far. Clinical studies and case reports have consistently shown increased requirements of GABAergic anesthetic drugs (isoflurane, sevoflurane, propofol, midazolam) to achieve adequate levels of clinical anesthesia. Several potential molecular mechanisms have been proposed to explain the effects of these interactions. However, it is interesting to mention that in humans, it has been observed that the ingestion of THC enhances the hypnotic effect of ketamine. Animal studies have reported that cannabinoids enhance the analgesic effect of opioids due to a synergistic interaction of the endogenous cannabinoid system (ECS) with the endogenous opioid system (EOS) at the spinal cord level and in the central nervous system. However, human data reveals that cannabis users show higher scores of postoperative pain intensity as well as increased requirements of opioid medication for analgesia. This review aims to improve understanding of the molecular mechanisms and pharmacological interactions between cannabis and anesthetic drugs and the clinical outcomes that occur when these substances are used together.

Cognitive decline in Cushing's syndrome: A systematic review.

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.

Amphiphilic Gelator-Based Shear-Thinning Hydrogel for Minimally Invasive Delivery via Endoscopy Catheter to Remove Gastrointestinal Polyps.

Injectable polymeric hydrogels delivered via endoscopic catheter have emerged as promising submucosal agents, offering durable, long-lasting cushions to enhance the efficacy of endoscopic submucosal dissection (ESD) for the removal of small, flat polyps from the gastrointestinal tract (GIT). However, polymer-based injections do not meet the easy-injectability criteria via catheter because their high viscosity tends to clog the catheter needle. To the best of knowledge, for the first time, report the fabrication of an amphiphile-based small molecule hydrogel of diglycerol monostearate (DGMS)thatself-assembles to form hydrogel (DGMSH) for delivery via an endoscopic catheter. Physicochemical characterization of the hydrogel reveals its fibrous morphology, shear-thinning behaviour, and easy injectability, along with its scalability and long shelf-life (6 months). Ex vivo studies on the goat's stomach and intestine demonstrate the ease of injectability through the catheters and the development of visible submucosal cushion depots with the desired height. Moreover, the hydrogel can encapsulate both hydrophobic and hydrophilic drugs/dyes. In vivo studies in small animals have found that the hydrogel depot is durable, biocompatible, non-immunogenic, and has a hemostatic effect. Endoscopic studies in the porcine model demonstrate a safe injection and endoscopic excision of GI polyps acting as a suitable agent for ESD.

Disordered eating in anorexia nervosa: give me heat, not just food

The recommendation to apply external heat to patients with anorexia nervosa (AN) was first documented by William Gull in 1874. Gull encountered this practice during his tenure as a consultant physician, responsible for issuing medical certifications for wealthy clients seeking admission to Ticehurst Asylum, one of the most successful and reputable private asylums in England. Gull attributed the origins of this practice to the studies by Charles Chossat (1796–1875), a physiologist, physician, and politician from Geneva, who discovered the therapeutic effects of heat on starved animals by chance. In the 20th century, further evidence of the beneficial effects of heat on starved animals emerged serendipitously when anomalies were observed following a malfunction in laboratory thermostats controlling animal temperatures. Moving into the 21st century, experimental research has empirically substantiated the crucial role of ambient temperature (AT) in the animal model of activity-based anorexia (ABA). Recent translational studies have shown that a warmed environment significantly reduces anxiety around mealtime in AN patients, a method shown to be more effective than exposure-based procedures. Despite the overwhelming evidence from both animal and patient studies, it is difficult to comprehend how the impact of providing a warm environment to AN patients, particularly around mealtimes, continues to be a neglected area of research.

The emerging role of alternatively activated macrophages to treat acute liver injury.

Acute liver injury (ALI) has a clear requirement for novel therapies. One emerging option is the use of alternatively activated macrophages (AAMs); a distinct subtype of macrophage with a role in liver injury control and repair. In this comprehensive review, we provide an overview of the current limited options for ALI, and the potential advantages offered by AAMs. We describe the evidence supporting their use from in vitro studies, pre-clinical animal studies, and human clinical trials. We suggest why the first evidence for the clinical use of AAMs is likely to be found in acetaminophen toxicity, and discuss the specific evidence for AAM use in this population, as well as potential applications for AAMs in other patient populations. The key domains by which the performance of AAMs for the treatment of ALI will be assessed are identified, and remaining challenges to the successful delivery of AAMs to clinic are explored.

DeepCt: Predicting Pharmacokinetic Concentration-Time Curves and Compartmental Models from Chemical Structure Using Deep Learning.

After initial triaging using in vitro absorption, distribution, metabolism, and excretion (ADME) assays, pharmacokinetic (PK) studies are the first application of promising drug candidates in living mammals. Preclinical PK studies characterize the evolution of the compound's concentration over time, typically in rodents' blood or plasma. From this concentration-time (C-t) profiles, PK parameters such as total exposure or maximum concentration can be subsequently derived. An early estimation of compounds' PK offers the promise of reducing animal studies and cycle times by selecting and designing molecules with increased chances of success at the PK stage. Even though C-t curves are the major readout from a PK study, most machine learning-based prediction efforts have focused on the derived PK parameters instead of C-t profiles, likely due to the lack of approaches to model the underlying ADME mechanisms. Herein, a novel deep learning approach termed DeepCt is proposed for the prediction of C-t curves from the compound structure. Our methodology is based on the prediction of an underlying mechanistic compartmental PK model, which enables further simulations, and predictions of single- and multiple-dose C-t profiles.

Development and validation of a controlled heating apparatus for long‐term MRI of 3D microfluidic tumor models

AbstractConventional testing of novel contrast agents for magnetic resonance imaging (MRI) involves cell and animal studies. However, 2D cultures lack dynamic flow and in vivo MRI is limited by regulatory approval of long‐term anesthesia use. Microfluidic tumor models (MTMs) offer a cost‐effective, reproducible, and high throughput platform for bridging cell and animal models. Yet, MRI of microfluidic devices is challenging, due to small fluid volumes generating low sensitivity. For the first time, an MRI of MTMs was performed at low field strength (1 T) using conventional imaging equipment without microcoils. To enable longitudinal MRI, we developed (1) CHAMP‐3 (controlled heating apparatus for microfluidics and portability) which heats MTMs during MRI scans and (2) an MRI‐compatible temperature monitoring system. CHAMP‐3 maintained chip surface temperature at ~37°C and the media inside at ~35.5°C. Enhanced T1‐weighted MRI contrast was achieved in 3D MTMs with free manganese (Mn2+) solutions and Mn2+ labeled tumor cells.

Deep learning based highly accurate transplanted bioengineered corneal equivalent thickness measurement using optical coherence tomography

Corneal transplantation is the primary treatment for irreversible corneal diseases, but due to limited donor availability, bioengineered corneal equivalents are being developed as a solution, with biocompatibility, structural integrity, and physical function considered key factors. Since conventional evaluation methods may not fully capture the complex properties of the cornea, there is a need for advanced imaging and assessment techniques. In this study, we proposed a deep learning-based automatic segmentation method for transplanted bioengineered corneal equivalents using optical coherence tomography to achieve a highly accurate evaluation of graft integrity and biocompatibility. Our method provides quantitative individual thickness values, detailed maps, and volume measurements of the bioengineered corneal equivalents, and has been validated through 14 days of monitoring. Based on the results, it is expected to have high clinical utility as a quantitative assessment method for human keratoplasties, including automatic opacity area segmentation and implanted graft part extraction, beyond animal studies.

Early subclinical stages of the inflammatory bowel diseases - insights from human and animal studies.

The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals that mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. The natural history of IBD progression begins with early subclinical stages of disease that occur before clinical diagnosis. Improved understanding of those early subclinical stages could lead to new or improved strategies for IBD diagnosis, prognostication or prevention. Here we review our current understanding of the early subclinical stages of IBD in humans including studies from first-degree relatives of IBD patients and members of the general population who go on to develop IBD. We also discuss representative mouse models of IBD that can be used to investigate disease dynamics and host-microbiota relationships during these early stages. In particular, we underscore how mouse models of IBD that develop disease later in life with variable penetrance may present valuable opportunities to discern early subclinical mechanisms of disease before histological inflammation and other severe symptoms become apparent.

UBE2C, targeted by miR-140-3p, promotes the progression of osteosarcoma via PI3K/AKT signaling pathway.

UBE2C was reported to play carcinogenic effects in diverse cancers. However, the role of UBE2C in osteosarcoma was poorly understood, and its functional mechanisms were not fully clarified. RT-qPCR was used to assess the expression of UBE2C mRNA and miR-140-3p, and western blot technique was used to examine the UBE2C protein and PI3K/AKT pathway-associated proteins. CCK-8 test was applied to measure cell proliferation, and wound healing assay were used to measure migration. Using animal studies, the function of UBE2C invivo was evaluated. Dual-luciferase reporter assay was used to confirm the potential interaction among UBE2C and miR-140-3p. In osteosarcoma cells as well as tumor samples, UBE2C was strongly expressed. Osteosarcoma cell proliferation as well as cell migration were inhibited by UBE2C knockdown, and PI3K/AKT signaling activity was diminished. In addition, UBE2C knockdown impeded tumor growth in animal models. UBE2C expression was lessened by miR-140-3p as miR-140-3p targets it. UBE2C is overexpressed which promote osteosarcoma proliferation as well as migration, and strengthened the PI3K/AKT signaling activity, while forced miR-140-3p expression partially abolished these effects. UBE2C, targeted by miR-140-3p, drove carcinogenic effects in osteosarcoma through activating the PI3K/AKT pathway.

Glucagon‐like Peptide-1 Agonists and Smoking Cessation: A Brief Review

The glucagon‐like peptide 1 (GLP-1) agonists such as semaglutide (Ozempic®, Wegovy®) and tirzepatide (Mounjaro®) have shown efficacy inducing weight loss in both diabetics and non-diabetics. According to the incentive sensitization theory of addiction, these drugs may prove useful in addictive disorders such as nicotine addiction. Animal data has been suggestive of a potential positive effect but early human studies have been mixed. This manuscript reviews the theory of addiction as well as the few animal and human studies available. Further human studies are needed to show GLP-1 agonist efficacy in smoking cessation.

Ocular biometric responses to simulated polychromatic defocus.

Evidence from human studies of ocular accommodation and studies of animals reared in monochromatic conditions suggest that chromatic signals can guide ocular growth. We hypothesized that ocular biometric response in humans can be manipulated by simulating the chromatic contrast differences associated with imposition of optical defocus. The red, green, and blue (RGB) channels of an RGB movie of the natural world were individually incorporated with computational defocus to create two different movie stimuli. The magnitude of defocus incorporated in the red and blue layers was chosen such that, in one case, it simulated +3 D defocus, referred to as color-signed myopic (CSM) defocus, and in another case it simulated -3 D defocus, referred to as color-signed hyperopic (CSH) defocus. Seventeen subjects viewed the reference stimulus (unaltered movie) and at least one of the two color-signed defocus stimuli for ∼1 hour. Axial length (AL) and choroidal thickness (ChT) were measured immediately before and after each session. AL and subfoveal ChT showed no significant change under any of the three conditions. A significant increase in vitreous chamber depth (VCD) was observed following viewing of the CSH stimulus compared with the reference stimulus (0.034 ± 0.03 mm and 0 ± 0.02 mm, respectively; p = 0.018). A significant thinning of the crystalline lens was observed following viewing of the CSH stimulus relative to the CSM stimulus (-0.033 ± 0.03 mm and 0.001 ± 0.03 mm, respectively; p = 0.015). Differences in the effects of CSM and CSH conditions on VCD and lens thickness suggest a directional, modulatory influence of chromatic defocus. On the other hand, ChT responses showed large variability, rendering it an unreliable biomarker for chromatic defocus-driven responses, at least for the conditions of this study.

Gelatin-Modified Bioactive Glass for Treatment of Dentin Hypersensitivity

When dentin is directly exposed to the oral cavity for various reasons, such as a lack of enamel on the tooth surface, external stimuli to the dentin often cause transient discomfort known as dentin hypersensitivity. In order to block the incoming stimulus signal, an ideal treatment is to induce the production of minerals to block the dentinal tubules. In this work, a dentin-desensitizing plugging material was prepared by modifying mesoporous bioactive glass with gelatin, the mineralization and desensitization effects of which were compared with Gluma in in vitro experiments. These experiments confirmed that gelatin-modified bioactive glass (MBG@PDA@Gel) is more effective than traditional desensitizing agents at blocking dentin tubules. Following the successful synthesis of MBG@PDA@Gel, as confirmed by scanning electron microscopy, transmission electron microscopy, and other tests, the treatment of demineralized dentin with MBG@PDA@Gel demonstrated that the dentinal tubules were tightly blocked under scanning electron microscopy. MBG@PDA@Gel induces minerals in deeper layers of dentinal tubules, promoting remineralization and forming a unified structure with the tubule blockage. Animal studies showed that MBG@PDA@Gel can remineralize demineralized dentin, and it is stable in the oral cavity and does not fall out. MBG@PDA@Gel not only enhances the biocompatibility of the nanoparticle but also results in an overall uniform and rapid remineralization of the demineralized dentin.

Muscle structure assessment using synchrotron radiation X-ray micro-computed tomography in murine with cerebral ischemia.

Muscles are crucial for balance and walking, activities which depend specifically on the lower extremity muscles. Therefore, the evaluation of stroke induced atrophy and paralysis is essential; however, determining the extent of damage in the days after its occurrence remains challenging. In this study, we evaluated ischemic stroke-induced soleus muscle damage in gerbils using synchrotron radiation X-ray micro-computed tomography (SR-µCT), comparing a control group (n = 3), animals 7 days after stroke (7 d, n = 3), and animals 14 days after stroke (14 d, n = 3). The left muscle was paralyzed, whereas the right muscle was not. Subsequently, we quantified the assessment by segmenting the soleus muscle based on the extracellular space/matrix and fiber region to determine the degree of damage. The muscle fiber-to-extracellular space/matrix ratio were significantly damaged due to paralysis on the left side (control vs. 14 d, P = 0.040). Muscle area was significantly different at 14 d between the left and right sides (P = 0.010). Additionally, the left local fascicle surface area, thickness, global pennation angle, and local fascicle angle were significantly different between the control and 14 d groups (P = 0.002, P = 0.007, P = 0.005, and P = 0.014 respectively). These findings underscore the potential of post-stroke animal studies in improving rehabilitation treatment for the central nervous system by assessing the degree of muscle recovery.

The role of immunity in comorbid pain and depression

The narrative review aims to shed light on the influence of inflammation in the comorbid chronic pain and major depressive disorder (MDD). This connection is known to be multifactorial, with a dynamic interaction between genetic and epigenetic factors. However, a growing body of evidence has shown that the co-presence of MDD and pain is underlain by immune mechanisms involved in the persistence of the inflammatory process. In particular, the cytokines released following activation of the innate immune system during inflammation cause changes at the endocrine level that result in glucocorticoid resistance, as well as altering the synthesis and metabolism of some central nervous system (CNS) mediators. Cytokines appear to generate neuroinflammation by activating normally protective microglia. Various other mechanisms, including changes in the function of the glutamatergic, GABAergic, and serotonergic systems are also implicated, but inflammation-induced reduction of BDNF (brain-derived neurotrophic factor) appears to be the deciding factor. In turn, neuroinflammation leads to sickness behavior, which is characterized by anhedonia and social withdrawal. This review explored these mechanisms, which may be at the root of comorbid pain and MDD. Although intriguing, however, most available evidence comes from animal studies, and rigorous clinical exploration is warranted.

Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundIrinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We designed this clinical trial to supply more evidences on the use of SXD as prophylaxis for irinotecan-induced diarrhea, especially for high-risk population predicted by gene testing of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1).MethodsIn this clinical trial, 120 patients with SCLC were recruited from six hospitals in China. They received two cycles of chemotherapy, meanwhile they were randomized to receive SXD or placebo for 14 days of oral administration in each cycle of chemotherapy. The primary outcome is the incidence of diarrhea. And secondary outcomes include the the degree of diarrhea and neutropenia, the number of chemotherapy cycles with diarrhea, first occurrence time and duration of diarrhea. To evaluate the effect of SXD on the intestine, a rat model with delayed-onset diarrhea induced by irinotecan was established, and the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, anti-inflammatory factors including IL-10, TGF- β in jejunal tissue was detected by ELISA.Results101 patients (53 in SXD group, 48 in placebo group) completed the trial. The incidence of diarrhea in SXD group and placebo group were 26.42% (14/53) and 52.08% (25/48), respectively (P < 0.05), and the degree of diarrhea also had significant differences (P < 0.05). In UGT1A1 high-risk population, the incidence of diarrhea in two groups were 9.09% and 66.67% (P < 0.05), but there was no significant differences in UGT1A1 low-risk population. The incidence of neutropenia with degree 1–3 between two groups was 20.75% vs 20.83%, 13.21% vs 18.57%, 9.43% vs 20.83% (P < 0.05). No severe adverse events were reported in any group. And animal studies had shown SXD reduced content of IL-1β, IL-6, TNF-α, increased content of IL-10, TGF-β in jejunum tissue.ConclusionsSXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors.Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250. The preliminary protocol of this clinical study has been published in the journal “Trials” in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).

Inhibition of Small Extracellular Vesicles by GW4869 Does not Disrupt the Paracrine Regulation of Adipose-Derived Mesenchymal Stem Cells Over Keloid Fibroblasts.

Keloid, scar caused by atypical wound repair, represents a significant difficulty for specialists in plastic surgery and dermatology. Adipose-derived mesenchymal stem cells (ADSCs) can regulate fibrotic phenotypes of keloid fibroblasts (KFs) in a paracrine fashion, but whether small extracellular vesicles (SEVs) are the key functional carrier in ADSC paracrine regulation of KFs remains unknown. This study aims to explore whether the regulatory effects of conditioned medium (CM) obtained from ADSCs on KFs can be impaired by decreased SEV content in the ADSC-CM. Clinical specimens were utilized to extract keloid fibroblasts (KFs), normal fibroblasts (NFs), and adipose-derived stem cells (ADSCs). Fibroblasts were cultured with CM obtained from ADSCs untreated or treated with the sphingomyelinase inhibitor GW4869. The features of SEVs derived from ADSC-CM were characterized, and fibroblast proliferation, migration, apoptosis, and expression of ECM proteins were analyzed. The sphingomyelinase inhibitor GW4869 successfully reduced the SEV content in ADSC-CM, and both control ADSC-CM and ADSC-CM with reduced SEV content significantly inhibited KF proliferation, migration, and α-SMA synthesis but not KF apoptosis, whereas only NF proliferation was inhibited by ADSC-CM. The reduced SEV content only affected the inhibition of KF proliferation induced by ADSC-CM. ADSC-CM inhibits various fibrotic phenotypes of KFs, but decreasing the SEV content in ADSC-CM did not significantly alter the antifibrotic effects of ADSC-CM. Thus, SEVs may not be the key mediator of ADSCs paracrine regulation of KFs. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors . www.springer.com/00266 .

Activation of Irrigants in Root Canals with Open Apices: A Narrative Review

Performing endodontic treatment on a tooth with an immature apex can be challenging due to the risk of irrigant extrusion beyond the apex. This narrative review investigates the over-apex extrusion of activated irrigants in teeth with open and immature apices and aims to provide crucial insights for practice and research. Two hundred fifty-two results were found from the electronic search. Sixteen duplicates were removed before selection, and 24 were excluded. Of the 212 remaining results, the full text was evaluated for eligibility. One hundred ninety-four results were excluded: in one hundred sixty-five, irrigant activation was not performed; twenty-nine were animal studies; in seven, irrigant activation was not performed to disinfect the canal. Finally, 13 studies were included. They cover a range of topics, from the types of irrigants used to the techniques of activation, and their findings contribute to our understanding of the risks and consequences of irrigant extrusion. All the activation techniques investigated can, to varying degrees, cause the irrigant to extrude beyond the apex. Extrusion may not always be clinically relevant; however, the consequences of excessive irrigant leakage from the apex are dangerous, so try to assess all the variables that may cause it and adopt techniques to reduce it.

Evaluation of Antifungal Activity of Somaraji Taila Extract &amp; Taila in Dadru Kushta (Tinea Infections) - An Experimental Study

Dermatophytosis has become a significant health problem affecting children, adolescents, and adults worldwide. In India 5 out of 1000 people suffer from Tinea infections. The present study evaluated the antifungal activity of Somaraji Taila in Tinea (Dermatophytosis) in Invitro &amp; Invivo model. Cultures were brought from MTCC a government body and inoculated in SDA media under aseptic condition. Later it was subjected to microscopic and macroscopic examination to identify the organism. A sensitivity test was done using SDA media by well diffusion method, with 4 different concentrations of Hydro-Methanolic extraction of Somaraji Taila ingredients. After the incubation period, the zone of inhibition was checked and was measured in mm. As the next phase of the study, animal study was also conducted to check antifungal properties &amp; anti dermal toxicity on albino rat skin.

Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.