Potential acetylcholinesterase inhibitors to treat Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is identified by neuropathological symptoms, and there is now no effective treatment for the condition. A lack of the brain neurotransmitter acetylcholine has been related to the etiology of Alzheimer's disease. Acetylcholinesterase is an enzyme that breaks down acetylcholine to an inactive form and causes the death of cholinergic neurons. Conventional treatments were used but had less effectiveness. Therefore, there is a crucial need to identify alternative compounds with potential anti-cholinesterase agents and minimal undesirable effects. MATERIALS AND METHODS: Fluoroquinolones and benzimidazole-benzothiazole derivatives offer antimicrobial, anti-inflammatory, anti-oxidant, anti-diabetic, and anti-Alzheimer activities. To enhance the chemical portfolio of cholinesterase inhibitors, a variety of fluoroquinolones and benzimidazole-benzothiazole compounds were evaluated against acetylcholinesterase (AChE) butyrylcholinesterase (BChE) enzymes. For this purpose, molecular docking and adsorption, distribution, metabolism, excretion, and toxicology ADMET models were used for in-silico studies for both AChE and BChE enzymes to investigate possible binding mechanisms and drug-likeness of the compounds. The inhibitory effect of docked heterocyclic compounds was also verified in vitro against AChE and BChE enzymes. Fluoroquinolones (Z, Z3, Z4, Z6, Z8, Z12, Z15, and Z9) and benzimidazole-benzothiazole compounds (TBIS-16, TBAF-1 to 9) passed through the AChE inhibition assay and their IC50 values were calculated. RESULTS: The compound 1-ethyl-6-fluoro-7-(4-(2-(4-nitrophenylamino)-2-oxoethyl)piperazin-1-yl) -4-oxo-1,4 di-hydroquinoline-3-carboxylic acid and 2-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(3-bromobenzyl)-4-hydroxy-2H-thiochromene-3-carbohydrazide 1,1-dioxide (Z-9 and TBAF-6) showed the lowest IC50 values against AChE/BChE (0.37±0.02/2.93±0.03 µM and 0.638±0.001/1.31±0.01 µM, respectively) than the standard drug, donepezil (3.9±0.01/4.9±0.05 µM). During the in-vivo investigation, behavioral trials were performed to analyze the neuroprotective impact of Z-9 and TBAF-6 compounds on AD mouse models. The groups treated with Z-9 and TBAF-6 compounds had better cognitive behavior than the standard drug. CONCLUSIONS: This study found that Z-9 (Fluoroquinolones) and TBAF-6 (benzimidazole-benzothiazole) compounds improve behavioral and biochemical parameters, thus treating neurodegenerative disorders effectively.

Effect of Nutrition and Behavior Modification Program (NBMP) on maternal and neonatal outcomes among hyperglycemic mothers.

OBJECTIVE: Hyperglycemic mothers and their offspring are at increased risk of various maternal and neonatal complications such as macrosomia, future type 2 diabetes, and metabolic abnormalities. Early diagnosis and individualized dietary management, exercise, and emotional well-being are expected to reduce these risks. The study aims to identify the effect of the Nutrition and Behavior Modification Program (NBMP) on maternal and neonatal outcomes of hyperglycemic mothers. PATIENTS AND METHODS: A pre-experimental study was performed among 89 hyperglycemic mothers. Glycemic control at 28 and 36 weeks, weight gain during pregnancy, pre-eclampsia, pregnancy-induced hypertension (PIH), mode of delivery, duration of exercise, emotional well-being, neonates' birth weight, incidence of hypoglycemia, and NICU admission were compared among the study and control groups. The intervention group received an individualized NBMP from their diagnosis of hyperglycemia until delivery. RESULTS: The results showed a significant difference in blood glucose between the study periods and groups at p<0.05 as per repeated ANOVA. Also, diet scores had a significant influence on BMI and glycemic control at p<0.05. Logistic regression models, adjusted for potential confounders including baseline blood glucose, age, economic status, previous GDM, family history of DM as well as baseline BMI, diet score, physical activity, and maternal well-being score, indicated that the NBMP reduced the blood glucose and BMI significantly at p<0.05 in the study group. NBMP also reduced the risk of SGA/LGA and preterm/post-mature birth, as well as increased the exercise duration and emotional well-being of mothers. CONCLUSIONS: The study's conclusions draw attention to the possible roles that maternal wellness, physical activity, and diet may have in reducing risks for both hyperglycemic mothers and their newborns. The NBMP resulted in higher adherence to lifestyle changes. Further research on a larger sample of hyperglycemic mothers is recommended to expand the generalizability of the findings.

The wake of the triple epidemic (Tripledemic): does it emphasizes the COVID-19 vaccine as a routine immunization for children? - A cross-sectional study.

OBJECTIVE: Many countries, including the USA, are currently confronting a triple epidemic in children as COVID-19 cases increase and new strains emerge which urge COVID-19 vaccination for children. The Advisory Committee on Immunization Practices (ACIP) for the CDC unanimously approved the inclusion of the COVID-19 vaccine (C19V) in the recommended immunizations. As healthcare professionals (HCPs) and parents are significant players in changing the trend of the triple epidemic by giving the C19V, the present study was done to determine awareness and perception of HCPs and parents on the tripledemic and the need for inclusion of C19V in vaccination schedules for children. PATIENTS AND METHODS: A cross-sectional study was conducted among 400 HCPs and 200 parents to assess their knowledge and perception of tripledemic and the need for the inclusion of C19V. RESULTS: Noticeably, half of the participants had either recent personal (36.2%) or family (21.8%) exposure to some of the tripledemic like RSV, Flu, or COVID-19. On perceived awareness, 42% were concerned about tripledemic, and 35% thought that regular C19V may prevent or reduce tripledemic. Ironically, 11% were not willing to give C19V to their children. The logistic regression model for positive perception of tripledemic and regular C19V identified significant relationships with education (OR 2.19, CI 1.48-3.81), gender (OR 0.9, CI 01.02-2.63), recent personal or family exposure to any of the tripledemic (OR 0.239, CI 0.87-1.63) and presence of children in the family (OR 0.71, CI 1.4-1.96). The reason for favorable perception was preventing self and family from tripledemic. CONCLUSIONS: The findings may give insight to the policymakers for a strategic plan to include C19V in the routine schedule to combat the pandemic and tripledemic by improving herd immunity.

The complexity of basophobia and aging: covariates and consequences.

OBJECTIVE: The study aim is to determine the drug-induced incidence of basophobia, falls, its' related variables and the consequences among older adults. PATIENTS AND METHODS: A descriptive, cross-sectional study was adopted with 210 older adult samples. The tool consisted of 6 sections: a standardized, semi-structured questionnaire and physical examination. Descriptive and inferential statistics were used to analyze the data. RESULTS: Among the study participants, 49% had falls or near falls and 51% had basophobia in the past 6 months. As per final simultaneous regression analysis model of the study, the covariates to activity avoidance were age (ß=-0.129, CI=-0.087 to -0.019), having >5 chronic diseases (ß=-0.086, CI=-1.41 to -1.182), depressive symptoms (ß=-0.09, CI=-0.089 to -0.189), vision impairment (ß=-0.075, CI=-1.28 to -1.56), basophobia (ß=-0.26, CI=-0.059 to -0.415), taking regular antihypertensives (ß=-0.096, CI= -1.21 to -1.56), oral hypoglycemics and insulin (ß=-0.17, CI=-0.442 to -0.971) and sedatives and tranquilizers (ß=-0.37, CI=-1.32 to -1.73). Use of antihypertensives (p<0.001), oral hypoglycemics and insulin (p<0.01), sedatives and tranquilizers (p<0.001) were strongly associated with fall related to activity avoidance. CONCLUSIONS: The result of this current study suggests that the falls, basophobia and its related activity avoidance among elderly may set in a "vicious cycle" of falls, basophobia, and the numerous negative outcomes such as functional impairment, a decrease in quality of life, and hospitalization. Preventive strategies such as tittering dosage, home- and community -based exercises, cognitive behavioral therapy, yoga, meditation and sleep hygiene may be the choice to break this vicious cycle.

Beneficial effects of Naringin against lopinavir/ ritonavir-induced hyperlipidemia and reproductive toxicity in male albino rats.

OBJECTIVE: This research work was planned to determine whether Naringin (NG) had any protective effects against lopinavir/ritonavir (LR)-induced alterations in blood lipid levels, hepatotoxicity, and testicular toxicity. MATERIALS AND METHODS: Four groups of six rats each were used for the study: Control (1% ethanol), naringin (80 mg/kg), lopinavir (80 mg/kg)/ritonavir (20 mg/kg), and lopinavir (80 mg/kg)/ritonavir (20 mg/kg) + naringin (80 mg/kg). The drug treatment was continued for 30 days. On the last day, the serum lipid fractions, liver biochemical parameters, testicular antioxidants (enzymatic and non-enzymatic), and the histopathology of the liver and testis tissue were assessed for all rats. RESULTS: Treatment with NG decreased significantly (p<0.05), the baseline serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C). But these parameters were significantly (p<0.05) increased in LR-treated animals. Naringin, co-administered with LR, restored the liver and testicular biochemical, morphological, and histological balance. CONCLUSIONS: This study shows that NG can be used as a treatment for LR-induced biochemical and histological changes in the liver and testes and changes in serum lipid levels.

Evaluation of Anti-diarrheal Potential of Hydro-alcoholic Extracts of Leaves of Murraya koenigii in Experimental Animals.

BACKGROUND: The indigenous medical system of India mentions the use of Murraya koenigii leaves for the treatment of different types of diarrheas over ages. OBJECTIVE: To evaluate the anti-diarrheal activity of hydro-alcoholic extracts of leaves of Murraya koenigii and to check its effects on intestinal transits in experimental rat model. MATERIALS AND METHODS: The hydro-alcoholic extract of Murraya koenigii leaves was obtained with Soxhlet extraction method. Animals were divided into four groups (n = 6) receiving daily for three consecutive days: vehicle, standard drug atropine (3mg/kg, i.p.), leaf extracts 200 & 400 mg/kg respectively in oral route. Effects of the drugs on normal defecation were noted and then castor oil induced diarrhea was used to measure the effects of leaf extract on stool frequency and consistency. Finally, charcoal meal test was used to evaluate the effect of the extract on intestinal transit. Statistical evaluation was done using SPSS version 17, one way ANOVA followed by Dunnett's t-test was done and P< 0.001 was considered as significant. RESULTS: Murraya koenigii leaf extracts in 200 and 400 mg/kg dose reduced stool frequency, increased stool consistency and increased small intestinal transit time. CONCLUSION: Hydro-alcoholic extract of Murraya koenigii leaves possesses significant anti-diarrheal activity due to its inhibitory effect on gastrointestinal motility, making it useful for a wide number of gastrointestinal diseases.