Simultaneous Intranasal Codelivery of Donepezil and Memantine in a Nanocolloidal Carrier: Optimization, Pharmacokinetics, and Pharmacodynamics Studies.

This work focuses on developing nanoemulsions using a low-energy emulsification method for the codelivery of donepezil and memantine in one dosage form intended to be administered via the intranasal route for enhanced brain delivery. The nanoemulsion formulation was prepared using a low emulsification technique and characterized using various microscopy and nasal ciliotoxicity studies. The safe nanoemulsion was intended for preclinical pharmacokinetics with brain distribution and pharmacodynamics in a scopolamine-induced murine model. The formulated nanoemulsion was 16 nm in size, with a zeta potential of -7.22 mV, and exhibited a spherical shape. The brain concentration of IN-administered NE for DPZ and MEM was ∼678 and 249 ng/mL after 15 min. This concentration is more than 2 times higher in amount when compared with NE administered via PO, free drug solution administered via IN and PO route both. However, the plasma concentration of IN-administered NE for DPZ and MEM was ∼3 and 28 ng/mL after 15 min. In pharmacodynamic studies, the efficacy of NE administered via the IN route was higher when compared with other groups in neurobehavioral, biochemical estimation, and gene expression studies. The results suggest that the IN route can be explored in the future for the delivery of actives via nanocolloidal carriers in the brain for neurological disorders and can serve as promising alternatives for conventional dosage forms and routes.

Short-term trivalent arsenic and hexavalent chromium exposures induce gut dysbiosis and transcriptional alteration in adipose tissue of mice.

BACKGROUND: Inorganic arsenic [As(III)] and hexavalent chromium [Cr(VI)] can potentially affect metabolic functions. These heavy metal(s)/metalloids can also affect the gut microbial architecture which affects metabolic health. Here, we assessed the effects of short-term exposure of As(III) and Cr(VI) on key transcription factors in adipose tissues and on selected gut microbial abundances to understand the possible modulatory role of these toxicants on host metabolic health. METHODS AND RESULTS: qRT-PCR based relative bacterial abundance studies in cecal samples, gene expression analysis for gut wall integrity in ileum and colon and adipogenesis, lipolysis, and thermogenic genes in gonadal white and brown adipose tissue (gWAT and BAT), along with tissue oxidative stress parameters have been performed. As(III) and Cr(VI) exposure reduced beneficial Lactobacilli, Bifidobacteria, Akkermansia, Lachenospiraceae, Fecalibacterium, Eubacterium, and clostridium coccoid group while increasing lipopolysaccharides producing Enterobacteriaceae abundances. It also impaired structural features and expression of key tight junction and mucin production genes in ileum and colon (Cld-2, Cld-4, ZO-1, ZO-2, MUC-2 and - 4). In gWAT it inhibited adipogenesis (PPARγ, FASN, SREBP1a), lipolysis (HSL, ACOX-1), and thermogenesis (UCP-1, PGC1a, PRDM-16, PPARa) related genes expression, whereas in BAT, it enhanced adipogenesis and reduced thermogenesis. These exposures also reduces the endogenous antioxidants levels in these tissues and promote pro-inflammatory cytokines genes expression (TLRs, IL-6, MCP-1). The combinatorial exposure appears to have more deleterious effects. CONCLUSION: These effects of As(III) and Cr(VI) may not directly be linked to their known toxicological effects, instead, more intriguing crosstalk with gut microbial ecosystem hold the key.

Occupation-Related Biological Health Hazards and Infection Control Practices among Indian Veterinarians.

Veterinarians experience different types of health hazards from their occupation. Studies on the prevalence and occurrence of biological health hazards in veterinary medicine in India are scant and probably underreported. Thus, we sought to assess the biological health hazards and infection control practices (ICPs) among veterinarians from the states of Gujarat and Maharashtra, India. A cross-sectional survey was conducted among veterinarians (n = 562) from Gujarat and Maharashtra states in India to identify biological health hazards and ICPs for the prevention of occupational health hazards during 2016-2017 by personally contacting them. Responses regarding a biological hazard and ICPs were recorded. Descriptive analysis was attempted, and continuous variables are presented as the mean ± SD. Categorical variables are reported as counts and percentages (%). Most of the veterinarians (49.3%) worked in the field and were continuously exposed to different types of biological health hazards, especially zoonoses, ranging from mild and self-limiting to fatal diseases (e.g., brucellosis (subclinical and clinical form) and rabies (fatal)) without common prophylactic vaccinations, such as rabies and tetanus. While inquiring medical health status of the veterinarians, only 35.8% of the total respondents underwent a routine medical health checkup within the past year, and 56.9% did not receive a routine dose of an anthelmintic for deworming. Forty-nine percent of the respondents took all necessary precautions, including wearing an apron, facemask, and gloves. In contrast, 10.2% of the respondents wore only an apron, and 8.4% of respondents did not take any precautions while performing their day-to-day work. In total, 40.2% of the respondents followed the proper method of handwashing, that is, washing hands between patient examinations. In contrast, 27.9% of the respondents washed their hands once after completing the work. The majority of the respondents (87.7%) reported an urgent need for occupational hazards and safety (OHS) training in continued veterinary education (CVE) programs. The present study demonstrates that veterinarians in the states of Gujarat and Maharashtra in India pay less attention to their own health that may increase the risk of occupation-related biological health hazards. These results suggest that safety and ICPs are not prioritized, which are serious concerns. These findings may be useful for developing policies to prevent occupationally related biological health hazards among veterinarians in India.

Evaluation of recombinant leptospiral surface antigen (Lsa27) lipoprotein for serodiagnosis of human leptospirosis by latex agglutination test.

PURPOSE: Leptospirosis has wide clinical presentations often mimicking other illnesses, thus rapid and simple diagnostics will have facilitated the initial patient management and therapy compared to other inaccessible and laborious tests/assays. METHOD: In this study, the sensitized latex beads coated with purified recombinant outer membrane (OM)-leptospiral surface antigen (Lsa27) lipoprotein of pathogenic Leptospira was evaluated as a diagnostic antigen in latex agglutination test (LAT) for the detection of anti-leptospiral antibodies in the human sera. The prepared rLsa27 latex beads were evaluated with the confirmed microscopic agglutination test (MAT) reactive (at 1:50) Leptospira-specific positive (n = 42) and non-reactive negative (n = 80) sera from human cases suspected of leptospirosis with the history of pyrexia of unknown origin. RESULT: The results revealed the relative diagnostic sensitivity of 90.48 % (confidence interval (CI) at 95 % : 77.4-97.3 %) and diagnostic specificity of 91.35 % (CI at 95 %: 82.8-96.4 %), with an accuracy of 90.98 % (CI at 95 %: 84.44-95.41 %), and the kappa value of 0.8036 ±â€¯0.056 SE (CI at 95 %: 0.69-0.91) with a substantial agreement against gold standard serological MAT. CONCLUSION: The findings suggest that the rLsa27 protein-based LAT can be useful as a simple rapid screening diagnostic test for the detection of anti-leptospiral antibodies in the sera of humans. This rapid test can be complemented by other confirmatory diagnostics for the early detection of Leptospira antibodies which may in turn help in the prompt treatment and mitigates the public health problem at primary health care level.

Risk factors and prevalence of work-related injuries and accidents among veterinarians in India.

BACKGROUND AND AIM: Veterinary medicine is a high-risk occupation and imparts a risk of physical injuries due to the unpredictable nature of the animals and workplace conditions. This study aimed to identify the associated risk factors and prevalence of work-related injuries, and automobile accidents among veterinarians in India. MATERIALS AND METHODS: A cross-sectional study was carried out among veterinarians (n=565). The responses were recorded using a self-administered questionnaire on work-related injuries, automobile accidents, and physical hazards. RESULTS: Work-related injuries due to animals in the past 2 years were reported by more than half of veterinarians (prevalence=54.7%, 95% confidence interval [CI]=50.58-58.79), while two-thirds experienced workplace injuries due to animals during any time of their career. The risk for injury was 1.1 times higher (odds ratio=1.1, 95% CI=0.611, 1.981) for veterinarians with a long job duration (>10 years). Large animal practicing veterinarians faced a higher (2.03 times) risk of injury. Workplace absenteeism due to animal-related injury (up to 15 or more days) was reported by 25.9% (95% CI=22.44-29.68) of respondents, including hospitalizations for 7.8% of veterinarians. More than half of veterinarians suffered from automobile injuries (prevalence=60.9%, 95% CI=6.8-64.8) due to work-related travel in the past 2 years, resulting in workplace absenteeism for 56.2% (95% CI=51.46-60.97) of subjects. The prevalence of needlestick injury among veterinarians was very high and reported as 80.9% (95% CI=77.49-83.99). Recapping of needles significantly increased the risk of needlestick injury by 1.67 times. CONCLUSION: Veterinarians are at risk of work-related injuries, including automobile accidents. Kicking by animals and needlestick injuries were the most frequent physical hazards. Recapping of needles and responding to emergency calls at night were significant risk factors for needlestick injury and automobile accidents, respectively.

Poisoning Cases Reported to Poison Information Centre, Ahmedabad, India: A Three Year Observational Study.

Introduction: Morbidity and mortality associated with pesticide poisoning is a major public health issue, especially in lower and middle income countries, including India. Timely understanding of poisoning trends is required for improved prevention. The objective of the present study was to analyze the trend of poisoning cases in Ahmedabad, India in the period of 2015-2017. Methods: Detailed history, including demographic data, risk factors, poisoning history, agents involved, and occupational influence were collected for poisoning cases reported to the Poison Information Centre in Ahmedabad. Cholinesterase activity and HPTLC method for detection of sanguinarine in urine were used to investigate the agents of poisoning. Non-parametric tests, such as Chi-square test and Mann-Whitney U Test were applied to test statistical significance between the groups. All statistical analysis was carried out using IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. Results: A total 1373 poisoning cases were investigated. The incidence and fatality rate was found to be higher in males compared to females (M/F ratio 1.89:1). About 91.62% of the poisoning were through the oral route. Erythrocyte cholinesterase activity assay results indicated that 41.29% of the cases were due to organophosphorus/carbamate poisoning. Insecticides were found to be the agent of poisoning in 26.29% cases, and 11.07% of all the cases were agricultural workers. Poisoning with medications, household pesticides and chemicals were also reported. Few cases of food poisoning with sanguinarine were detected. Conclusions: The data presented here suggest that pesticides used for agriculture are the major source of poisonings. Implementation of usage guidelines, educating farmers and vulnerable population, and finding novel alternatives for highly toxic chemicals may be helpful in decreasing the number of poisoning cases.

Acute oral toxicity of pesticide combination (acephate 50% and imidacloprid 1.8% as active ingredients) in Sprague-Dawley rats.

AIM: The aim of this study was to assess the acute toxic interaction and lethal dose (LD50) of pesticide combination product (acephate 50% and imidacloprid 1.8% as active ingredients) available in the market in Sprague-Dawley female rats by oral route. MATERIALS AND METHODS: A total of 10 Sprague-Dawley female rats were divided into two groups, comprising five rats in each dose group. Both groups were identified as control and test groups, respectively. Control group received sterile water as vehicle and test group received pesticide combination (acephate 50% and imidacloprid 1.8% as active ingredients) at a dose of 0 and 2000 mg/kg body weight. As per the Organization for Economic Cooperation and Development Guideline 420, initially one animal each from both the control and test groups were dosed with 0 and 2000 mg/kg, respectively, as sighting study. Based on the results of sighting study, additionally, four animals each from both groups were dosed with the same dose to make a total of five animals in each group. Dose volume was constant as 10 mL/kg. All animals were observed daily twice for clinical signs and mortality. Body weight was recorded on day 0 and weekly thereafter during 14 days' observation period; last body weight (fasted) was recorded on day 15. All the rats of both the groups were humanely sacrificed on day 15 for gross pathology, collection of organs for histopathology, organ weighing, and morphometry. Organ weights were taken as absolute values, and relative organ weights to last fasted body weights were calculated. RESULTS: Pesticide combination (acephate 50% and imidacloprid 1.8% as active ingredients) treated rats showed cholinergic signs with one mortality in the test group. No significant difference was observed in body weight, relative organ weights, and organ morphometry between pesticide combination exposed and non-exposed groups. Gross pathology of the treated rats was also comparable with respect to control group. Histopathological changes in the liver, kidneys, heart, lung, adrenaline, spleen, and ovaries of test group rats were found to be comparable with control group rats. CONCLUSION: The present study demonstrated the LD50 of one of the combination products available in the market having acephate 50% and imidacloprid 1.8% as active ingredients in Sprague-Dawley female rats which is >2000 mg/kg body weight. Furthermore, gross, histopathology and histoarchitectural alterations of all the vital organs of the test group were comparable to the control.