Punicalagin improves inflammation and oxidative stress in rat model of pelvic inflammatory disease.

Pelvic inflammatory disease (PID) is one of the major public health concerns accounting for 30% of infertility and 50% of ectopic pregnancy cases due to severe inflammation and fibrosis. Punicalagin® are known to exhibit potent anti-inflammatory activity. The aim of this study was to demonstrate the anti-inflammatory and antioxidant effects of Punicalagin®, against pelvic inflammatory disease in rats. Female Sprague Dawley rats (n = 24) were divided into 6 groups (n = 4) as control, PID, prophylactic (low dose and high dose) and therapeutic group (low dose and high dose). PID model was constructed by implanting the rat cervix with mixed microbe (Escherichia Coli and Staphylococcus Aureus) solution. Prophylactic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting one day before PID induction and therapeutic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting 1 day after confirmation of PID model. Rats were sacrificed at the end of experiment and samples from upper genital tract were collected for ELISA, antioxidant assay and histopathological examination. According to results, obvious signs of inflammation and oxidative stress including infiltration of neutrophils and significantly raised levels of cytokines, and oxidative stress markers were observed in PID group when compared to control group. Punicalagin® significantly decreased the levels of IL-1ß, catalase and lipid peroxidation in both prophylactic and therapeutic groups when compared to PID group. Punicalagin® also decreased the infiltration of leucocytes in uterus of prophylactic and therapeutic group when compared to PID group, as determined by histological examination. On basis of these results, we concluded that Punicalagin® showed anti-inflammatory and antioxidant potential in rat model of pelvic inflammatory disease and could be used as possible therapeutic agent in treatment of PID.

Salivary Oxidative Stress and Antioxidant Capacity in Smokeless Tobacco (Naswar) Users.

Background: Naswar, a smokeless tobacco product, commonly consumed in Pakistan, is associated with a 10-fold increase in the risk of oral cancer. However, little is known about Naswar's underlying toxicity mechanisms. Objective: The current study aimed to investigate the effects of Naswar use on oral health and salivary parameters. Methods: A case-control study was conducted among Naswar users (n=42) and age-matched healthy controls (n=42) in Pakistan in 2019. Participant data were collected using questionnaires. Decayed, missing, and filled teeth (DMFT) scores were computed during clinical examinations. Unstimulated whole saliva was collected to assess salivary flow rate, pH, and salivary total oxidative stress (TOS)/total antioxidant capacity (TAC) using commercially available kits. Participants' oral health parameters were compared between cases and controls using ANOVA. Results: No significant differences were observed between the two groups in terms of age, oral health, and hygiene practices and mean DMFT score. Mean salivary pH and the salivary flow rate was significantly (p<0.001) higher in Naswar users (7.7 and 0.71 mL/minute, respectively) than in non-users (6.95 and 0.52 mL/minute, respectively). Although TOS and TAC were not significantly different between the groups, Naswar users generally had a higher TOS (51.6±42 µmol/L) and lower TAC (0.55±0.18 mmol/L) than non-users (TOS 45.5±38.2 µmol/L and TAC 0.57±0.17 mmol/L). Correlational analysis also revealed a significant positive correlation between DMFT score and Naswar use duration (r=0.796, p<0.001) and the number of dips/units consumed each day (r=0.515; p<0.001). Conclusion: Habitual Naswar use is associated with increased salivary flow rate, pH, and TOS, and reduced TAC levels in Pakistani adults compared to non-users. The pro-oxidant changes may contribute toward deleterious effects of Naswar use including oral cancer.

The effects of tobacco and cannabis use on semen and endocrine parameters in infertile males.

Substances such as tobacco and cannabis can negatively modulate seminal parameters and sex hormones and lead to fertility problems in males. The present study aimed to determine the effect of cigarettes, dipping tobacco, and cannabis on semen parameters and sex hormones in infertile males. A total of 160 infertile healthy participants (cigarette smokers n = 40, dipping tobacco users n = 40, cannabis users n = 40 and infertile controls n = 40) were included in the study. Fasting blood samples were collected from all the participants using the aseptic technique, and semen samples were collected by masturbation following sexual abstinence of 2-7 days. The levels of serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined using ELISA. The serum level of FSH was significantly higher in cannabis users relative to the control group (p = 0.043). A mild non-significant decrease in sperm count, serum LH and testosterone levels were observed in all drug users compared to controls. In conclusion, chronic use of tobacco and cannabis mildly modulates semen and hormonal parameters in infertile males.

Outcomes of Endoscopic Third Ventriculostomy in Pediatric Patients With Hydrocephalus.

Background Endoscopic third ventriculostomy (ETV) is used to treat patients with obstructive hydrocephalus in infants. This study evaluated the postoperative outcomes of ETV among pediatric patients. Methodology A retrospective study was undertaken at the Mardan Medical Complex between June 2018 and June 2021. All pediatric patients who underwent the procedure of ETV in both the absence and presence of choroid plexus cauterization (CPC) at our center were included in the study. Using medical history data, a comprehensive survey questionnaire was designed. The findings and effects were evaluated either as a success or failure. Results A total of 90 cases were reviewed during the study. The rate of in-hospital mortality was 1.1% while the most commonly identified causes of hydrocephalus were myelomeningocele and aqueductal stenosis. A total of 39 (43.33%) patients had a successful surgery. In patients where hydrocephalus was secondary to aqueductal stenosis, the success rate was the highest, while the success rate was quite low for post-infectious hydrocephalus and intraventricular hemorrhage (p < 0.0001). The postoperative complication rate was 55.56% in our study. The rate of in-hospital mortality was 1.1%. Conclusions We found that the success rate of ETV was dependent upon factors such as the cause of hydrocephalus, type of hydrocephalus, and the age of the patient. Therefore, ETV is not suitable for all patients, and vigilance must be undertaken in selecting patients for the procedure. The rate of postoperative infections in our institution was alarmingly high which is a concerning matter for the institution.

Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder and the main cause of infertility in women of reproductive age. Affected women suffer from insulin resistance and present with an intense stress response. Treatment with insulin sensitizers alone and in combination is used to ameliorate the signs and symptoms associated with the disease. This study was designed to compare the endocrine and metabolic parameters as well as subjective and objective measures of stress in women with PCOS before and after treatment with acetyl-L-carnitine (ALC) and metformin plus pioglitazone. METHODS: A total of 147 women with PCOS were randomly assigned into two groups: the combo group (n = 72) received a combination of metformin, pioglitazone, and ALC (500 mg, 15 mg, and 1500 mg, respectively), twice daily; the Met + Pio group (n = 75) received metformin plus pioglitazone (500 mg, 15 mg, respectively) and placebo (citric acid plus calcium carbonate), twice daily for 12 weeks. Medications were discontinued when pregnancy was confirmed. The Perceived Stress Scale (PSS14) and Profile of Mood States (POMS) were employed as subjective measures of stress. The endocrine and metabolic functions of women with PCOS were assessed by measuring insulin, leutinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and adiponectin levels in fasting blood samples. Insulin resistance was calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: Women at baseline had significantly elevated circulating concentration of insulin and low level of adiponectin. Treatment decreased insulin in both groups; however, the combo group showed a significant decrease (p = 0.001). Serum adiponectin level was raised significantly after treatment in both groups (p < 0.001). HOMA-IR also decreased in both groups (both p < 0.001). Testosterone, FSH, and LH significantly improved in both groups. LH also decreased in both groups; however, the change was significant only in the combo (metformin plus pioglitazone plus ALC) group (p = 0.013). Interestingly, there was a significant improvement in body circumference (p < 0.001) in the combo group. The PSS scores of the patients improved significantly (p < 0.001) in the combo group. Interestingly, regular menstrual cycles were found (97.2%) in the carnitine group, but in only 12.9% of the other group. CONCLUSION: We conclude that addition of ALC therapy is superior to metformin plus pioglitazone in ameliorating insulin resistance, polycystic ovaries, menstrual irregularities, and hypoadiponectinemia in women with PCOS. TRIAL REGISTRATION: Trial registration: clinicalTrial.gov NCT04113889. Registered 3 October, 2019. https://clinicaltrials.gov/ct2/show/NCT04113889 .

Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts.

Infantile and childhood-onset cataracts form a heterogeneous group of disorders; among the many genetic causes, numerous pathogenic variants in additional genes associated with autosomal-recessive infantile cataracts remain to be discovered. We identified three consanguineous families affected by bilateral infantile cataracts. Using exome sequencing, we found homozygous loss-of-function variants in DNMBP: nonsense variant c.811C>T (p.Arg271∗) in large family F385 (nine affected individuals; LOD score = 5.18 at θ = 0), frameshift deletion c.2947_2948del (p.Asp983∗) in family F372 (two affected individuals), and frameshift variant c.2852_2855del (p.Thr951Metfs∗41) in family F3 (one affected individual). The phenotypes of all affected individuals include infantile-onset cataracts. RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells, and leads to a ∼50% reduction in electroretinography amplitudes in young flies. DNMBP regulates the shape of tight junctions, which correspond to the septate junctions in invertebrates, as well as the assembly pattern of E-cadherin in human epithelial cells. E-cadherin has an important role in lens vesicle separation and lens epithelial cell survival in humans. We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans.

Endostatin Concentration In Plasma Of Healthy Human Volunteers.

BACKGROUND: Angiogenesis is involved in many cardiovascular and cancerous diseases, including atherosclerosis and is controlled by a fine balance between angiogenic and angiostatic mediators. Endostatin is one of the main angiostatic mediators, and inhibits angiogenesis and prevents progression of atherosclerosis. The available literature shows a broad range of concentrations in relatively small samples of healthy controls and is calculated by using different techniques. This study was aimed to determine the basal endostatin concentration in plasma of healthy volunteers, to fully understand its physiological role. METHODS: Fifty healthy adult volunteers were recruited to the study. Participants were advised not to participate in any physical activity on the day before the blood sampling. The volunteers' physical activity, height, weight, heart rate and blood pressure were recorded. The samples were analysed for plasma endostatin concentration, using ELISA. The participants were divided by gender and ethnic groups to calculate any difference. RESULTS: Endostatin and other variables were normally distributed. Most of the participants had a moderate level of physical activity with no gender related difference (p=0.370). The mean value for plasma endostatin in all samples was 105±12 ng/ml with range of 81-132 ng/ml. For males, it was 107±13 ng/ml, while for females; 102±12 ng/ml. There were no significant gender or ethnicity related differences in endostatin concentration. Moreover, endostatin was not significantly related with any anthropometric and physical variable. CONCLUSIONS: This study gives endostatin levels in normal healthy people and show no gender and ethnicity related differences in endostatin levels. Endostatin was not related with any anthropometric and physical variable.