Experimental Animal Studies Research Articles

Modeling of local and systemic exposure to metals and metalloids after inhalation exposure: Recommended update to the USEPA metals framework.

The USEPA issued the "Framework for Metal Risk Assessment" in 2007, recognizing that human and environmental exposure to metals and metalloids (MMEs) poses challenges risk assessment. Inhalation of aerosols containing MMEs is a primary pathway for exposure in the occupational setting, for consumer exposure, and to general population exposure associated with point-source emissions or ambient sources. The impacts of inhalation can be at the point of deposition (local exposure) or may manifest after uptake into the body (systemic exposure). Both local and systemic exposure can vary with factors that determine the regional deposition of MME-containing aerosols. Aerosol characteristics such as particle size combine with species-specific characteristics of airway morphology and lung function to modulate the deposition and clearance of MME particulates. In contrast to oral exposure, often monitored by measuring MME levels in blood or urine, inhalation exposure can produce local pulmonary impacts in the absence of significant systemic distribution. Exposure assessment for nutritionally essential MMEs can be further complicated by homeostatic controls that regulate systemic MME levels. Predictions of local exposure can be facilitated by computer models that estimate regional patterns of aerosol deposition, permitting calculation of exposure intensity in different regions of the respiratory tract. The utility of deposition modeling has been demonstrated in assessments of nutritionally essential MMEs regulated by homeostatic controls and in the comparison of results from inhalation studies in experimental animals. This facilitates extrapolation from animal data to humans and comparisons of exposures possessing mechanistic linkages to pulmonary toxicity and carcinogenesis. Pulmonary deposition models have significantly advanced and have been applied by USEPA in evaluations of particulate matter. However, regional deposition modeling has yet to be incorporated into the general guidance offered by the agency for evaluating inhalation exposure. Integr Environ Assess Manag 2024;20:952-964. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: An animal experimental study.

Early assessment of the severity of acute kidney injury (AKI) is critical to the prognosis of patients. Renal microcirculation hemodynamic changes and inflammatory response are the essential links of AKI induced by ischemia-reperfusion injury (IRI). This study aims to explore the value of contrast-enhanced ultrasound (CEUS) based on vascular cell adhesion molecule-1 (VCAM-1) targeted microbubbles (TM) in evaluating the renal microcirculation hemodynamics and inflammatory response of different severity of AKI. Eighteen male C57BL/6J mice were randomly divided into three groups (n = 6): sham operation (sham) group, mild IRI-AKI (m-AKI) group, and severe IRI-AKI (s-AKI) group. CEUS based on VCAM-1 TM was used to evaluate renal microcirculation perfusion and inflammatory response. Pearson's correlation was used to analyze the correlation between ultrasonic variables and pro-inflammatory factors. Compared with the sham group, AUC in m-AKI and s-AKI groups was significantly decreased, and s-AKI group was lower than m-AKI group (P < 0.05). NID of m-AKI and s-AKI groups was significantly higher than that of the sham group, and s-AKI group was higher than that of m-AKI group (P < 0.05). There was a linear positive correlation between NID and VCAM-1 protein expression (r = 0.7384, P < 0.05). NID and AUC were correlated with TNF-α and IL-6 levels (P < 0.05). Compared with early AKI biomarkers, CEUS based on VCAM-1 TM has higher sensitivity in evaluating the severity of AKI. CEUS based on VCAM-1 TM can evaluate renal microcirculation perfusion and inflammatory response in mild and severe AKI, which may provide helpful information for assessing the severity of AKI.

Tacrolimus Pharmacotherapy: Infectious Complications and Toxicity in Organ Transplant Recipients; An Updated Review.

After allogeneic organ transplantation, in order to reduce the risk of rejection, tacrolimus is given. In fact, infection is reported as one of the most common side effects of tacrolimus that might be associated with graft failure. This study aims to review the association between the occurrence of infections due to toxicity following the administration of tacrolimus in organ transplant recipients. Scientific literature on the pharmacotherapy of tacrolimus after organ transplantation, infections, and neurotoxicity were searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus (n=108). All articles were screened, and the data associated with the topic of interest was extracted. The primary outcome was infection and neurotoxicity. Total area under the curve exposure, the ratio of parent drug/metabolites of tacrolimus was reported to be correlated with aggressive events such as infection episodes. A trough/dose ratio may demonstrate the net state of immunosuppression and drug-related events. The most frequent infectious complication of tacrolimus after organ transplantation was reported as urinary tract infections (UTIs). Virulent strains of recombinant Listeria monocytogenes, in addition to an increase in bacterial burden in the liver and spleen tissues, were reported in experimental animal studies. Patient survival was significantly lower in recipients with UTIs in the first post-transplant month. A higher degree of immunosuppression was associated with recurrent UTIs and drug-resistant organisms. By inhibiting the cerebral immune system, tacrolimus could cause neurodegeneration. Transplant type, gut dysmotility, acute or chronic condition before transplant surgery, use of azole, antifungal, hematocrit, tacrolimus methods of detection, the total area under the curve, and duration of hospital stay could define the risk of infection through the first month of transplant surgery. In addition, neurological and infectious complications could be associated with the higher amounts of tacrolimus trough levels (C0). Polypharmacy based on tacrolimus, antiviral, and antifungal drugs, in addition to neurotoxicity, could increase the risk of opportunistic infections such as cytomegalovirus within the first year of organ transplantation.

Choline - a scoping review for Nordic Nutrition Recommendations 2023.

Choline is an essential nutrient with metabolic roles as a methyl donor in one carbon metabolism and as a precursor for membrane phospholipids and the neurotransmitter acetylcholine. Choline content is particularly high in liver, eggs, and wheat germ, although it is present in a variety of foods. The main dietary sources of choline in the Nordic and Baltic countries are meat, dairy, eggs, and grain. A diet that is devoid of choline causes liver and muscle dysfunction within 3 weeks. Choline requirements are higher during pregnancy and lactation than in non-pregnant women. Although no randomized controlled trials are available, observational studies in human, supported by coherence from interventional studies with neurodevelopmental outcomes and experimental studies in animals, strongly suggest that sufficient intake of choline during pregnancy is necessary for normal brain development and function in the child. Observational studies suggested that adequate intake of choline could have positive effects on cognitive function in older people. However, prospective data are lacking, and no intervention studies are available in the elderly.

Assessing neurotropic effects of new antiepileptic nitrogen-containing drugs

Objective: to evaluate an effectiveness of new nitrogen-containing compounds for alleviating epileptiform conditions in animal experimental study, and conduct molecular modeling of a new neurotropic drug.Material and methods. The anticonvulsant and psychotropic effects of six new heterocyclic compounds synthesized at the Institute of Fine Organic Chemistry were analyzed: № 1 (tetrahydrobenzothienopyrimidine), № 2 (pyridopyrimidine), № 3 (pyranotriazolopyridine), № 4 (thioalkylpyranotriazolopyridine), № 5 (pyrazolyltetrahydrothienoisoquinoline), and № 6 (thioxopyranopyridine). Experiments were carried out with 300 white outbred male mice weighing 18–24 g and 48 male rats weighing 120–150 g. The anticonvulsant spectrum of action was assessed in mice using the following tests: maximum electric shock, corazole-induced seizure. The psychotropic compound-related properties were analyzed using the following tests: elevated plus maze, open field, conflict situation. The neurotoxic compound-related effects were evaluated by incoordination of movements in rotating rod test. Comparison was performed with pufemide (3-(p-isopropoxyphenyl)succinimide), ethosuximide and diazepam.Results. The new nitrogen-containing drugs were revealed to exhibit high anticonvulsant activity, especially observed in corazoleinduced seizure test. All select compounds have anticonvulsant, anxiolytic, psychosedative or behavior-activating effects. Compound № 1 (N3212) is the most effective (median effective dose is 16 mg/kg) in antagonism to corazole action and is significantly superior to ethosuximide and pufemide exceeding by 10- and 5-fold, respectively. The compound shows least toxic (median lethal dose is 2300 mg/kg) and low neurotoxic (median toxic dose is 660 mg/kg) effects. Therapeutic and protective indices for Compound No. 1 exceeds that of ethosuximide by 17- and 13-fold, and of pufemide by 6- and 8-fold, respectively.Conclusion. The select compounds are superior to the approved drugs used in medical practice, pufemide and ethosuximide. A Compound N3212 selected among them may find application as an anticonvulsant drug with psychotropic effects.

Use of bee venom in preventive medicine: An experimental hepatic encephalopathy study in rats.

Bee venom is used for medicinal purposes, including the treatment of neurological and liver diseases, but its use as a primary health care approach for preventive purposes requires further exploration. The aim of this study was to provide the first investigation into the possible protective effects of bee venom against hepatic encephalopathy, a serious neurodegenerative disease. An experimental animal study was conducted in which healthy albino Sprague-Dawley rats were randomized into three groups: healthy, control and bee venom groups. All rats were tested for locomotor activity at the beginning and end of the study. No intervention was made in the healthy group, whereas hepatic encephalopathy was induced in the control and bee venom groups by the administration of thioacetamide (TAA) (200mg/kg/day). The bee venom group also received bee venom (5mg/kg/day) subcutaneously every day for 14 days prior to the TAA administration. The results for the final locomotor activity tests were statistically better in the bee venom group than in the control group, supporting a beneficial effect of prophylactic bee venom application. Blood ammonia levels and liver weights, determined as indicators of inflammation, were lower in the bee venom group than in the control group and were close to levels in the healthy group, but not statistically significant. Bee venom administration has protective effects against the development of hepatic encephalopathy and offers a promising therapeutic opportunity in preventive medicine.

The protective effects of betanin on titanium dioxide (TiO2) nanoparticle exposure in rats

The aim of this study was to investigate the protective properties of betanin in rats exposed to Titanium dioxide (TiO2) nanoparticles. An experimental animal study was conducted on 40 Spraque Dawley rats. The rats were studied in 4 groups (n = 10). Group I: Control group, Group II: TiO2 group (250 mg/kg/bw), Group III: TiO2 + Betanin group (250 mg/kg/bw TiO2 + Betanin; 100 µg/ml), Group IV: Betanin group (100 µg/ml). After 28 days of application, blood and liver tissue samples of the rats were collected. Total Antioxidant Status (TAS, mmol Trolox Eq/L), Total Oxidant Status (TOS, µmol H2O2 Eq/L), Paraoxonase (PON, U/L), Total thiol (μmol/L), Nitric oxide (NO, µmol/L), Malondialdehyde (MDA, nM/ml) and Catalase (CAT, U/mg protein) activity levels in the blood and liver tissue measured. Liver tissue samples were evaluated by immunohistochemical methods (Caspase-3 and 8-Hydroxy-2'-deoxyguanosine) and hematoxylin-eosin staining. As a result, a significant (p < 0.001) increase in the mean oxidant parameters and a significant (p < 0.001) decrease in the antioxidant parameters were determined in the TiO2 group when compared to the control group. Caspaze-3 and 8-OHdG histopathological results findings indicated a similar situation. However, it was determined that TiO2 damage was significantly reduced (p < 0.001) in rats to which TiO2 and betanin were administered together. In addition, the highest antioxidant levels and low histopathological damage were determined among all groups in the betanin-only group. Betanin (C24H26N2O13) shows protective activity in oxidative tissue damage caused by TiO2 nanoparticles.

Sildenafil as a Salvage Treatment for Ovarian Torsion: A Rat Model

OBJECTIVE: In this study, we aimed to investigate the effect of sildenafil, acting as an anti-oxidant on the ischemic rat ovarian torsion model by pointing out ovarian reserve via AMH levels which is the best marker for oocyte pool.STUDY DESIGN: This study is an experimental animal study conducted according to the principles of the Declaration of Helsinki. Twenty-seven rats were assigned into three groups, each consisting of nine individuals. Group 1: Sham operation (laparotomy only) was performed. Group 2: The torsion group had bilateral torsion and detorsion of the ovaries. Group 3: In Sildenafil and torsion group the rats received 0.7 mg/kg sildenafil (Viagra, Pfizer, New York, ABD) intraperitoneally one hour before torsion and detorsion operation. One month after the initial operation, blood was drawn via the intra-cardiac route, and serum antimullerian hormone (AMH) concentrations were studied.RESULTS: The mean weights of the rats were similar 224 g, 229 g, and 222 g for groups 1, 2, and 3 respectively. Only one rat from Group 2(T/D) died during the experiment leaving eight rats for analysis. The mean value for AMH was 24.9227±12.19124 ng/ml and the mean value for weight was 226.22±19.200. The differences in AMH groups were not statistically significant (p=0.873)CONCLUSIONS: As a result, as is shown in our study, the ovarian reserve may not be influenced by ischemia developed by ovarian torsion or any influences could not change AMH levels. Sildenafil which was given to the rats before detorsion to protect against reperfusion ischemia was found to be ineffective on ovary reserve according to AMH assessment.

An in-silico porcine model of phosgene-induced lung injury predicts clinically relevant benefits from application of continuous positive airway pressure up to 8 h post exposure

We present the first computational model of the pathophysiological consequences of phosgene-induced lung injury in porcine subjects. Data from experiments previously performed in several cohorts of large healthy juvenile female pigs (111 data points from 37 subjects), including individual arterial blood gas readings, respiratory rate and heart rate, were used to develop the computational model. Close matches are observed between model outputs (PaO2 and PaCO2) and the experimental data, for both terminally anaesthetised and conscious subjects. The model was applied to investigate the effectiveness of continuous positive airway pressure (CPAP) as a pre-hospital treatment method when treatment is initiated at different time points post exposure. The model predicts that clinically relevant benefits are obtained when 10 cmH2O CPAP is initiated within approximately 8 h after exposure. Supplying low-flow oxygen (40%) rather than medical air produced larger clinical benefits than applying higher CPAP pressure levels. This new model can be used as a tool for conducting investigations into ventilation strategies and pharmaceutical treatments for chemical lung injury of diverse aetiology, and for helping to refine and reduce the use of animals in future experimental studies.

A synthetic retinoic acid receptor γ antagonist (7C)-loaded nanoparticle enhances bone morphogenetic protein-induced bone regeneration in a rat spinal fusion model

BACKGROUND CONTEXTBone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced. PURPOSETo address this problem, we synthesized 7C, a retinoic acid receptor γ antagonist-loaded nanoparticle (NP), and investigated its potential application in BMP-based bone regeneration therapy using a rat spinal fusion model. STUDY DESIGNAn experimental animal study. METHODSFifty-three male 8-week-old Sprague–Dawley rats underwent posterolateral spinal fusion and were divided into the following five treatment groups: (1) no recombinant human (rh)BMP-2 and blank-NP (Control), (2) no rhBMP-2 and 1 μg 7C-NP (7C group), (3) low-dose rhBMP-2 (0.5 μg) and 1 μg blank-NP (L-BMP group), (4) low-dose rhBMP-2 (0.5 μg) and 1 μg 7C-NP (L-BMP + 7C group), and (5) high-dose rhBMP-2 (5.0 μg) and 1 μg blank-NP (H-BMP group). Micro-computed tomography and histologic analysis were performed 2 and 6 weeks after the surgery. RESULTSThe spinal fusion rates of the Control and 7C groups were both 0%, and those of the L-BMP, L-BMP + 7C, and H-BMP groups were 55.6%, 94.4%, and 100%, respectively. The L-BMP + 7C group markedly promoted cartilaginous tissue formation during BMP-induced endochondral bone formation that resulted in a significantly better spinal fusion rate and bone formation than in the L-BMP group. Although spinal fusion was slower in the L-BMP + 7C group, the L-BMP + 7C group formed a spinal fusion mass with better bone quality than the spinal fusion mass in the H-BMP group. CONCLUSIONSThe combined use of 7C-NP with rhBMP-2 in a rat posterolateral lumbar fusion model increased spinal fusion rate and new bone volume without deteriorating the quality of newly formed bone. CLINICAL SIGNIFICANCE7C-NP potentiates BMP-2-induced bone regeneration and has the potential for efficient bone regeneration with low-dose BMP-2, which can reduce the dose-dependent side effects of BMP-2 in clinical settings.

A systematic review and meta-analysis of animal and human studies demonstrates the beneficial effects of Kaempferia parviflora on metabolic syndrome and erectile dysfunction

Kaempferia parviflora (KP) has traditionally been used for centuries to promote health and well-being. Scant evidence is available to explain the relationship between KP and metabolic syndrome and impotence. We sought to test the hypothesis that administration of KP extract enriched with active ingredients, such as polymethoxyflavone, could improve metabolic syndrome, erectile dysfunction, and related outcomes in in vivo. We performed a systematic review and meta-analysis to evaluate the in vivo effects of KP extract on metabolic syndrome, erectile dysfunction, and related outcomes. Studies from 4 databases (i.e., PubMed, Scopus, Embase, and Cochrane Library) were searched from inception up to December 2022. Animal experiment studies and randomized controlled trials comparing KP extract to a placebo control were retrieved and analyzed using RevMan 5.4.1 software. The effect estimate was presented as the standardized mean difference along with its 95% confidence interval (CI). Of 664 articles, a total of 57 articles met our prespecified criteria. KP extract significantly decreased fasting blood glucose in both animal and human studies with standardized mean difference of –0.88 (95% CI, –1.63 to –0.14) and –0.51 (95% CI, –0.98 to –0.05), respectively. Furthermore, KP extract also markedly improved sexual function and physical performance. In sum, KP extract is shown to have effects beneficial to metabolic syndrome, erectile dysfunction, and physical performance.

Post-operative Dressing for Paediatric Hypospadias Repair

The optimal dressing is still unclear, despite hypospadias being one of the most prevalent surgical operations. Children’s dressing for hypospadias surgery was searched on PubMed as “dressing for hypospadias,” “postoperative dressing for pediatric hypospadias,” and “dressing AND hypospadias.” Experimental studies, animal studies, reviews, letters, and repetitive publications were excluded from the study. By evaluating these reviewed publications, factors affecting hypospadias dressing, such as surgeon, country, dressing type, characteristics, and why it is preferred, will be revealed. As a result, 17 articles were examined, and the advantages of each were established by examining the results. The type of hypospadias, the surgeon’s choice, and its ease of removal stand out as the crucial factors in treating hypospadias in children, along with the degree of development of the nation.

Feasibility study of a novel robotic system for transperitoneal partial nephrectomy: An in vivo experimental animal study.

To evaluate the safety and feasibility of partial nephrectomy with the use of the novel robotic system in an in vivo animal model. Right partial nephrectomy was performed in female pigs by a surgical team consisting of one surgeon and one bedside assistant. Both were experienced in laparoscopic surgery and trained in the use of the novel robotic system. The partial nephrectomies were performed using four trocars (three trocars for the robotic arms and one as an assistant trocar). The completion of the operations, set-up time, operation time, warm ischemia time (WIT) and complication events were recorded. The decrease in all variables between the first and last operation was calculated. In total, eight partial nephrectomies were performed in eight female pigs. All operations were successfully completed. The median set-up time was 19.5 (range, 15-30) minutes, while the estimated median operative time was 80.5 minutes (range, 59-114). The median WIT was 23.5 minutes (range, 17-32) and intra- or postoperative complications were not observed. All variables decreased in consecutive operations. More precisely, the decrease in the set-up time was calculated to 15 minutes between the first and third attempts. The operative time was reduced by 55 minutes between the first and last operation, while the WIT was decreased by 15 minutes during the consecutive attempts. No complications were noticed in any operation. Using the newly introduced robotic system, all the advantages of robotic surgery are optimized and incorporated, and partial nephrectomies can be performed in a safe and effective manner.

Effectiveness of Cages Inducing Nasopharyngeal Dysplasia in Wistar Rats (Rattus norvegicus)

The cage is a place used to put experimental animals in experimental studies to study the mechanism of the disease and its response to therapy. Formaldehyde as a carcinogenic compound can increase the occurrence of chronic inflammation which has the potential to increase the growth of cancer cells in experimental animals due to the stress experienced while in the cage. Therefore, the purpose of this study was to compare the effectiveness of large and small cages induced by formaldehyde 30 ppm against nasopharyngeal dysplasia in Wistar rats. This research is an experimental study with a true experimental design with the type of post-test only control group design. This study used 12 male Wistar rats (Rattus norvegicus) which were divided into two groups, namely the group of Wistar rats which were placed in large cages measuring (30 x 24 x 11.5) cm3 of 6 individuals, and in small cages (27 .5 x 21.5 x 9) cm3 of 6 individuals induced by 30 ppm formaldehyde with a span of 6 hours per day for 16 weeks. The rats were terminated and retro-orbital blood samples were taken to measure MDA levels and nasopharyngeal tissue to assess the degree of dysplasia. The results of this study showed that there was a statistically significant difference (p &lt;0.05) between the degrees of nasopharyngeal dysplasia (p=0.003) and MDA levels (p=0.003) in Wistar rats in small cages and large cages. In this study the effectiveness of small cages was greater than large cages in causing dysplasia in the nasopharyngeal tissue of Wistar rats.

Transcriptional response of the heart to vagus nerve stimulation.

Heart failure is a major clinical problem, with treatments involving medication, devices, and emerging neuromodulation therapies such as vagus nerve stimulation (VNS). Considering the ongoing interest in using VNS to treat cardiovascular disease, it is important to understand the genetic and molecular changes developing in the heart in response to this form of autonomic neuromodulation. This experimental animal (rat) study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity using an optogenetic approach. Vagal preganglionic neurons in the dorsal motor nucleus of the vagus nerve were genetically targeted to express light-sensitive chimeric channelrhodopsin variant ChIEF and stimulated using light. RNA sequencing of the left ventricular myocardium identified 294 differentially expressed genes (false discovery rate < 0.05). Qiagen Ingenuity Pathway Analysis (IPA) highlighted 118 canonical pathways that were significantly modulated by vagal activity, of which 14 had a z score of ≥2/≤-2, including EIF-2, IL-2, integrin, and NFAT-regulated cardiac hypertrophy. IPA revealed the effect of efferent vagus stimulation on protein synthesis, autophagy, fibrosis, autonomic signaling, inflammation, and hypertrophy. IPA further predicted that the identified differentially expressed genes were the targets of 50 upstream regulators, including transcription factors (e.g., MYC and NRF1) and microRNAs (e.g., miR-335-3p and miR-338-3p). These data demonstrate that the vagus nerve has a major impact on the myocardial expression of genes involved in the regulation of key biological pathways. The transcriptional response of the ventricular myocardium induced by stimulation of vagal efferents is consistent with the beneficial effect of maintained/increased vagal activity on the heart.NEW & NOTEWORTHY This experimental animal study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity. Vagal stimulation induced significant transcriptional changes in the heart involving the pathways controlling autonomic signaling, inflammation, fibrosis, and hypertrophy. This study provides the first direct evidence that myocardial gene expression is modulated by the activity of the autonomic nervous system.

A prospective randomized comparison of functional and cosmetic outcomes of a coronal zigzag incision versus a conventional straight incision pattern for craniotomy.

Wound healing problems after neurosurgical procedures can lead to serious complications and may require complex revision or even reconstructive surgery. Therefore, optimal surgical management is critical to prevent complications. In a recent experimental study in animals, the authors demonstrated the superiority of a zigzag skin incision over a straight incision pattern. In this study, the authors applied these findings to clinical situations of neurosurgical patients with an indication for a coronal skin incision. The aim of this study was to objectively assess the functional and cosmetic outcomes between straight coronal and zigzag incisions in neurosurgical procedures. This prospective, randomized, controlled, single-center trial included adult patients undergoing frontal craniotomy for cerebrovascular or tumor pathologies. The study primarily included patients who were not expected to receive adjuvant radiation or chemotherapy. The zigzag incision was standardized using a template. A common straight skin incision behind the hairline served as a control. Complication rates, functional (2-point discrimination, width of the wound, Vancouver Scar Scale [VSS], and Patient and Observer Scar Assessment Scale [POSAS]), and cosmetic outcomes were assessed postoperatively and at 3-month follow-up evaluations. Additionally, all patients answered a wound-specific questionnaire and the SF-36 questionnaire. Twenty-eight patients were randomized to the zigzag and 29 to the straight incision groups. Indications for surgery were cerebrovascular in 16 cases and tumors in 41 cases. Risk factors for wound healing were equally distributed in both groups. One patient in the zigzag group with poor postoperative compliance required surgery for secondary wound healing problems. Overall, the width of the scar was significantly smaller (p = 0.001) and local 2-point discrimination better (p = 0.005) in the zigzag group. Scores on the VSS (p = 0.003) and POSAS (p = 0.005) proved to be significantly superior in the zigzag group as well. A zigzag coronal skin incision pattern leads to significantly superior functional and cosmetic outcome scores. For certain patient groups, these findings may prove to be practice-changing.

Branched chain amino acids harbor distinct and often opposing effects on health and disease.

The branched chain amino acids (BCAA) leucine, isoleucine, and valine are essential nutrients that have been associated with diabetes, cancers, and cardiovascular diseases. Observational studies suggest that BCAAs exert homogeneous phenotypic effects, but these findings are inconsistent with results from experimental human and animal studies. Hypothesizing that inconsistencies between observational and experimental BCAA studies reflect bias from shared lifestyle and genetic factors in observational studies, we used data from the UK Biobank and applied multivariable Mendelian randomization causal inference methods designed to address these biases. In n = 97,469 participants of European ancestry (mean age = 56.7 years; 54.1% female), we estimate distinct and often opposing total causal effects for each BCAA. For example, of the 117 phenotypes with evidence of a statistically significant total causal effect for at least one BCAA, almost half (44%, n = 52) are associated with only one BCAA. These 52 associations include total causal effects of valine on diabetic eye disease [odds ratio = 1.51, 95% confidence interval (CI) = 1.31, 1.76], valine on albuminuria (odds ratio = 1.14, 95% CI = 1.08, 1.20), and isoleucine on angina (odds ratio = 1.17, 95% CI = 1.31, 1.76). Our results suggest that the observational literature provides a flawed picture of BCAA phenotypic effects that is inconsistent with experimental studies and could mislead efforts developing novel therapeutics. More broadly, these findings motivate the development and application of causal inference approaches that enable 'omics studies conducted in observational settings to account for the biasing effects of shared genetic and lifestyle factors.

Therapeutic effects of garlic (Allium sativum) on female reproductive system: A systematic review

Complementary and alternative medicine, including Persian medicine (PM), offers a variety of disease prevention and treatment methods, including the application of medicinal plants. The health of the reproductive system is an important issue for women, and understanding the potential effect of garlic (Allium sativum) for preventive and therapeutic purposes in this field is of interest. This systematic review focused on the effects of garlic on the female reproductive system. The method involved a comprehensive search of relevant literature on experimental animal studies using electronic databases from January 2010 to September 2023, followed by selection of eligible studies and data extraction. A total of 18 studies met the inclusion criteria and were included in the review. This review reported that garlic may have positive effects on women's reproductive health, such as improving hormonal balance, relieving PMS symptoms, and potentially supporting fertility outcomes. This review revealed that garlic compounds such as allicin and ajoene can modulate various aspects of the female reproductive system, including regulation of the menstrual cycle, hormonal balance, fertility, and reproductive disorders. This review determined that further research is needed to elucidate the molecular pathways and direct effects of garlic on the female reproductive system. Although garlic has many potential health benefits, it should not be used as a substitute for medications.

Evaluation of degeneration retinal ganglion cell loss in acute glaucoma model rats using syringe pump technique

Link of Video Abstract: https://youtu.be/vaGQXY-i4KE Introduction: Glaucoma is a neurodegenerative disorder marked by the gradual decline in function and degeneration of the retinal ganglion cells (RGCs) and their axons. The elevated intraocular pressure (IOP) is a predominant contributing factor to its onset. Employing laboratory animals to model glaucoma is a well-established strategy that serves the dual purpose of identifying disease mechanisms and developing novel neuroprotective approaches. The aim of this study was to develop a preclinical acute model of glaucoma based on controllable intraocular pressure with a syringe pump in rat Rattus norvegicus. Methods: This research was an animal-experimental study in animal model adult male Wistar rat (Rattus norvegicus), taken in May - October 2023 in an integrated laboratory Faculty of Veterinary Medicine Universitas Syiah Kuala. Total samples used in this research were 10 rats, divided into two categories which are control group (A) and treatment group (B) were given a pressure of 250 mmHg pressure in the right eye for 60 minutes. Apoptosis and degeneration of retinal ganglion cells after 8 weeks of elevated intraocular a pressure of 250 mmHg in the right eye for 60 minutes were observed by the HE staining. Result: A significant difference in IOP was noted between control group rat and treatment group rat. All rats that received treatment experienced an increase in IOP (100%). The RGC density decreased significantly in the treatment group rat (mean: 11.72 cell/field of view or lower 46.88%) compared with the control group (p =0.005). Conclusion: A pressure of 250 mmHg for 60 minutes has been proven to cause degeneration of the RGCs up to nearly 50% within a week. We tried a technique to induce increased IOP in rats as a model of acute glaucoma. Syringe pump technique can effectively induce acute ocular hypertension in rats, which causes progressive loss of retinal ganglion cells.

Intestinal microbiota protects against methylmercury-induced neurotoxicity.

Methylmercury (MeHg) remains a global public health issue because of its frequent presence in human food sources obtained from the water. The excretion of MeHg in humans occurs slowly with a biological half-time of 32-47 days. Short-term MeHg exposure may cause long-lasting neurotoxicity. The excretion through feces is a major route in the demethylation of MeHg. Accumulating evidence suggests that the intestinal microbiota plays an important role in the demethylation of MeHg, thereby protecting the host from neurotoxic effects. Here, we discuss recent developments on the role of intestinal microbiota in MeHg metabolism, based on in vitro cell culture experiments, experimental animal studies and human investigations. Demethylation by intestinal bacteria is the rate-limiting step in MeHg metabolism and elimination. The identity of bacteria strains responsible for this biotransformation is currently unknown; however, the non-homogenous distribution of intestinal microbiota may lead to different demethylation rates in the intestinal tract. The maintenance of intestinal barrier function by intestinal microbiota may afford protection against MeHg-induced neurotoxicity, which warrant future investigations. We also discuss studies investigating the effects of MeHg exposure on the population structural stability of intestinal microbiota in several host species. Although this is an emerging area in metal toxicity, current research suggests that a change in certain phyla in the intestinal microbiota may indicate MeHg overexposure.