Insulin-euglycemia therapy in acute aluminum phosphide poisoning: a randomized clinical trial.

Introduction: Aluminum phosphide is a pesticide that is used in developing countries. Aluminum phosphide poisoning has a high mortality rate and there is no known antidote. This study aimed to evaluate the safety and efficacy of insulin-euglycemia therapy in the management of patients with acute aluminum phosphide poisoning.Methods: This trial was prospectively registered in the Pan African Clinical Trials Registry (PACTR202008534546951). A total of 108 patients were randomly allocated to two groups. The intervention group received insulin-euglycemia therapy in addition to standard treatment (norepinephrine and supportive care); the control group received standard treatment plus placebo. The main outcome measures were survival, blood pressure, and laboratory investigations.Results: The two groups had similar baseline parameters. Insulin-euglycemia therapy was associated with a significant reduction in mortality compared with that in the control group (64.8 percent and 96.3 percent, respectively; P value <0.001). Patients randomized to insulin-euglycemia also required lower doses of vasopressors (median was 7 mg versus 26 mg in control group; P value 0.006) and fewer patients needed intubation (61.1 percent versus 81.5 percent in the control group; P value 0.019). Insulin-euglycemia therapy significantly improved blood pressure (systolic, diastolic, and mean arterial pressure) (median at 6h post-admission was 80 mmHg, 55 mmHg and 65 mmHg compared with 20 mmHg, 10 mmHg and 13 mmHg in the control group respectively; P value <0.001) and bicarbonate and lactate concentrations.Conclusion: Insulin-euglycemia therapy appears to be a safe and effective treatment option for patients with aluminum phosphide poisoning. Vasopressor only therapy was associated with very poor outcomes in acute aluminum phosphide poisoning.

Ameliorative effect of sesame oil on experimentally induced polycystic ovary syndrome: A cross-link between XBP-1/PPAR-1, regulatory proteins for lipogenesis/steroids.

Polycystic ovary syndrome (PCOS) is a mixed endocrine/metabolic/reproductive disorder in women of reproductive age. Sesame oil (SO) contains sesame lignans & vitamin E with broad-spectrum antioxidant and anti-inflammatory effects. This study investigates the ameliorative effect of SO on experimentally induced PCOS and elucidates the possible molecular mechanisms with a deeper focus on the different signaling pathways involved. The study was carried out on 28 nonpregnant female Wister albino rats that were divided into four equal groups; Group I (control group) received oral 0.5% wt/vol carboxymethyl cellulose daily. Group II (SO group): orally administered SO (2 mL/kg body wt./day) for 21 days. Group III (PCOS group) received letrozole daily, 1 mg/kg, for 21 days. Group IV (PCOS + SO group): concomitantly administered letrozole and SO for 21 days. The serum hormonal and metabolic panel and the homogenate ATF-1, StAR, MAPK, PKA, and PI3K levels of the ovarian tissue were calorimetrically evaluated. However, endoplasmic reticulum (ER) stress was evaluated by ovarian XBP1 and PPAR-γ messenger RNA expression level using the qRT-PCR technique. Ovarian COX-2 was detected immunohistochemically. The results suggest that SO-treated PCOS rats showed a significantly improved hormonal, metabolic panel, inflammatory, and ER stress status with concomitant decreases in ATF-1, StAR, MAPK, PKA, and PI3K in ovarian rats compared to the correspondent values in PCOS without treatment. CONCLUSIONS: The protective effects of SO against PCOS are triggered by ameliorating regulatory proteins of ER stress, lipogenesis, and steroidogenesis through the PI3K/PKA and MAPK/ERK2 signaling cascades. SIGNIFICANCE STATEMENT: Polycystic ovary syndrome (PCOS) is the most common mixed endocrine-metabolic dysfunction among women within the reproductive period, with an estimated prevalence of 5%-26% worldwide. Doctors traditionally recommend metformin for PCOS patients. However, metformin is known to be associated with significant adverse effects and contraindications. This work aimed at shedding light on the ameliorative effect of sesame oil (SO), natural polyunsaturated fatty acids-rich oil, on the induced PCOS model. SO proved to have a marvelous effect on the metabolic and endocrine derangements in the PCOS rat model. We hoped to provide a valuable alternative treatment for PCOS patients to avoid the side effects of metformin and to help PCOS patients for whom metformin is contraindicated.

Simvastatin and non-segmental vitiligo: A new potential treatment option?

There is a paucity of data about the impact of systemic statins on vitiliginous lesions in non-segmental vitiligo (NSV) patients. To the best of our knowledge, no other studies have considered the correlation between lipid disturbances in vitiligo and vitiligo disease activity (VIDA) score. We sought in this study to evaluate the influence of simvastatin on vitiliginous lesions in NSV patients with dyslipidemia and study the correlation between VIDA score and lipid profile. This clinical trial started with 120 patients with NSV, 79 patients had dyslipidemia and received simvastatin 80 mg daily (till normalization of lipid profile or for 4 months, which came first) and only 63 patients continued till the end of the study. Lipid profile, vitiligo area severity index and VIDA were assessed before and 6 months after the end of simvastatin use. Serum total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein, and LDL/HDL ratio showed statistically significant increases in the NSV than in the control group (p Ë‚ 0.001). There was a statistically significant positive correlation between VIDA and serum levels of TC and LDL and with LDL/HDL ratio. Simvastatin significantly improved the lipid profile and significantly decreased VIDA (p < 0.011). Negative moderate correlation was found between the decrease in VIDA and duration of disease (r = -0.562, p < 0.001). Simvastatin 80 mg daily could be a helpful treatment for NSV patients with dyslipidemia, controlling the vitiligo activity and protecting against the hazardous effects of dyslipidemia. Better results can be obtained in patients with short duration of the disease.

Evaluation of admission levels of P, E and L selectins as predictors for thrombosis in hospitalized COVID-19 patients.

Thromboembolic complications are the most reported cause of death in coronavirus disease-2019 (COVID-19). Hypercoagulability, platelets activation and endotheliopathy are well-recognized features in COVID-19 patients. The aim of this work was to evaluate circulating soluble selectins P, E and L at the time of hospital admission as predictors for upcoming thrombosis. This retrospective study included 103 hospitalized COVID-19 patients and 50 healthy volunteer controls. COVID-19 patients were categorized into two groups; group 1 who developed thrombosis during hospitalization and group 2 who did not. Soluble selectins were quantitated using ELISA technique. Higher levels of sP-selectin, sE-selectin and sL-selectin were detected in COVID-19 patients compared to controls. Furthermore, significantly higher levels were found in group 1 compared to group 2. Their means were [5.86 ± 1.72 ng/mL vs. 2.51 ± 0.81 ng/mL]; [50 ± 8.57 ng/mL vs. 23.96 ± 6.31 ng/mL] and [4.66 ± 0.83 ng/mL vs. 2.95 ± 0.66 ng/mL] for sP-selectin, sE-selectin and sL-selectin respectively. The elevated selectins correlated with the currently used laboratory biomarkers of disease severity. After adjustment of other factors, sP-selectin, sE-selectin and sL-selectin were independent predictors for thrombosis. At sP-selectin ≥ 3.2 ng/mL, sE-selectin ≥ 32.5 ng/mL and sL-selectin ≥ 3.6 ng/mL thrombosis could be predicted with 97.1%, 97.6% and 96.5% sensitivity. A panel of the three selectins provided 100% clinical sensitivity. Admission levels of circulating soluble selectins P, E and L can predict thrombosis in COVID-19 patients and could be used to identify patients who need prophylactic anticoagulants. E-selectin showed a superior clinical performance, as thrombo-inflammation biomarker, to the most commonly studied P-selectin.