Background This Phase I, two-part, first-in-human study assessed safety/tolerability and pharmacokinetics/pharmacodynamics of single-ascending doses (SAD) and multiple doses (MD) of the oral toll-like receptor-7 agonist, JNJ-64794964 (JNJ-4964) in healthy adults. Methods In the SAD phase, participants received JNJ-4964 0.2 ( N = 6), 0.6 ( N = 6), 1.25 ( N = 8) or 1.8 mg ( N = 6) or placebo ( N = 2/dose cohort) in a fasted state. Food effect was evaluated for the 1.25 mg cohort following ≥6 weeks washout. In the MD phase, participants received JNJ-4964 1.25 mg ( N = 6) or placebo ( N = 2) weekly (fasted) for 4 weeks. Participants were followed-up for 4 weeks. Results No serious adverse events (AEs) occurred. 10/34 (SAD) and 5/8 (MD) participants reported mild-to-moderate (≤Grade 2), transient, reversible AEs possibly related to JNJ-4964. Five (SAD) participants had fever/flu-like AEs, coinciding with interferon-α serum levels ≥100 pg/mL and lymphopenia (<1 × 109/L), between 24–48 h after dosing and resolving approximately 96 h after dosing. One participant (MD) had an asymptomatic Grade 1 AE of retinal exudates (cotton wool spots) during follow-up, resolving 6 weeks after observation. JNJ-4964 exhibited dose-proportional pharmacokinetics, with rapid absorption (tmax 0.5–0.75 h) and distribution, and a long terminal half-life (150–591 h). Overall, no significant differences in JNJ-4964 pharmacokinetic parameters were observed in the fed versus fasted state. JNJ-4964 dose-dependently and transiently induced cytokines with potential anti-HBV activity, including interferon-α, IP-10, IL-1 RA, and/or MCP-1, and interferon-stimulated genes (ISG15, MX1, and OAS1) in serum. Conclusions In healthy adults, JNJ-4964 was generally well-tolerated, exhibited dose-proportional pharmacokinetics and induced cytokines/ISGs, with possible anti-HBV activity.

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Objective: To determine the anti-hyperglycemic effects of interleukin-1 inhibitor (diacerein) in alloxan induced diabetic albino wistar rats. This experimental study was performed at the Department of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University, Tando Jam within 6 months from April 2016 to September 2016. Total of 160 adult Albino Wistar Rats having an average of 200 to 300 grams body weights were selected. Animals were categorized into 4 groups as; Group A (n=15): Control rats – receive 0.9% normal saline as placebo Experimental Groups Group B (n=15): Experimental Control (Diabetic rats) - Alloxan50 mg/kg body weight intraperitoneal. Group C (n=15): Diabetic rats + Diacerein (30 mg/kg/day) orally daily. Group D (n=15): Diabetic rats + Diacerein (50 mg/kg/day) orally daily. Animals were kept and treated as per the NIH Guideline for Use and Care of Laboratory Animals. Diabetes mellitus was induced via a single intraperitoneal injection of 50 milligram/kg alloxan monohydrated dissolved in aseptic 0.9% saline. After 72 hours, blood specimens were taken from the caudal vein of the rats and glucose level>200 mg/dL was taken as diabetes. Experimental rats were given diacerein approximately 30 and 50 mg orally for 6 weeks. At the completion of experiment the body weight was measured of each animal by electronic measuring balance and blood sample was taken from each animal of all groups to assess the blood glucose level and HbA1c level. Data were recorded via self-made proforma and analysis was done by using SPSS version 20. Results: Average body weight of Diabetic control (Group B) was 193.33±22.50 grams, which was lower in contrast to Diacerein treated group C 202.47±25.70 grams and significantly lower as compared to Diacerein treated group D as  212.6±23.43 grams. A significant increase in blood glucose levels 182.07±10.63 mg/dl was noted in the Diabetic control (Group B) compared to Diacerein treated group C (110.13± 8.54 mg/dl) and group D (85.87±8.41 mg/dl) (P=0.001). HbA1c was markedly raised in the Group B- diabetic controls, while diacerein treated diabetic rats (groups C and D) showed a significant decrease in HbA1c (P=0.001). Conclusion: It was concluded that Diacerein achieves the Euglycemic state by reducing the levels of blood glucose and glycated hemoglobin (HbA1c) in Alloxan-Induced diabetes mellitus in Wistar Albino Rats.

Background: Pregnancy-induced hypertension is a leading cause of deleterious changes in the placenta resulting in decreased blood supply towards the placenta. The objective of the current study was to analyze the histo-morphometric variations in the placenta of women with or without known pregnancy-induced hypertension. Methods: Cross-sectional study was carried out in the Gynecology and obstetrics section of Nazeer Hussain Medical Complex, Hyderabad in collaboration with Isra University, Hyderabad from March 2019 to August 2019. A total of 100 placentae were selected and divided into two groups (control and study groups) based on the presence or absence of hypertension in pregnancy. The observations of the control group placenta were compared with the study group placentas. All placentae were observed for morphometric and histological changes. SPSS ver. 22 was used to analyze the collected data. Results: There was an increase in the mean weight of placentae among the control group as compared to the group having known hypertension cases and the difference was statistically significant (p-value <0.05). The fetoplacental weight ratio was increased among the hypertension group when compared to the statistically insignificant control group (p-value <0.05). Various gross (infarction, calcification) and histological changes (hyalinised villi, intervillous hemorrhage, decreased villous vascularity) were observed in the placentae of the hypertensive group as compared to the normal group. Conclusion: The findings of the study concluded that Preeclampsia/PIH poses harmful and serious histo-morphometric variations in the placental tissues that affect fetal outcome.