Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat.

Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100 µg/kg/day) for 5 days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated (p < 0.05) mRNA and protein of AT1R within the PVN and lowered (p < 0.05) circulating angiotensin II in rats. RUPP increased neural and microglial activation. Cellular localization assessment revealed that AT1R was primarily expressed in neurons and slightly in microglia and astrocytes. Infusion of 100 ng/kg as bolus increased the mean arterial pressure (MAP in mmHg) in both RUPP and Sham. ICV losartan infusion attenuated RUPP-increased MAP (113.6 ± 6.22 in RUPP vs. 92.16 ± 5.30 in RUPP + Los, p = 0.021) and the expression of nuclear transcription factor NF-κB, tyrosine hydroxylase (TH), NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) in the PVN. Our data suggest that centrally expressed AT1R, within the PVN, contributes to placental ischemia-induced hypertension in RUPP rats highlighting its therapeutic potential in PE.

Clinical Characteristics and the Long-Term Post-recovery Manifestations of the COVID-19 Patients-A Prospective Multicenter Cross-Sectional Study.

Objective: Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global issue. In addition to managing acute cases, post-COVID-19 persisting symptoms/complaints and different hematological values are of great concern. These have an impact on the patient's well-being and are yet to be evaluated. Therefore, clinical and primary diagnosis based on routine laboratory findings bears high importance during the initial period of COVID-19, especially in regions with fewer diagnostic facilities. Methods: Clinical information and associated complaints of the COVID-19 illness confirmed by reverse transcription-polymerase chain reaction (RT-PCR) were collected directly from the patients. Regular follow-ups were obtained on the phone every 2 weeks following recovery for 20 weeks. Initial hematological and radiology findings of the hospitalized patients except for intensive care unit (ICU) and high dependency units (HDUs) and a follow-up evaluation after 4 weeks following recovery were analyzed. Results: The post-COVID-19 persisting symptoms/complaints were found among 21.4% of symptomatic patients, which persisted for ≥20 weeks and had a significant relationship with the duration of COVID-19 illness and the existing comorbidity (p < 0.05). Post-COVID-19 primary type 2 diabetes mellitus (DM, 0.64%) and hypertension (HTN, 1.28%) and unstable DM (54.55%) and HTN (34.78%) to the pre-existing diabetic and hypertensive patients were observed. Post-recovery remarkable changes in the laboratory values included leukocytosis (16.1%), lymphocytosis (14.5%), and an increased prothrombin time (PT, 25.8%). Abnormalities in the D-dimer, serum ferritin, hemoglobin, and erythrocyte sedimentation rate (ESR) levels were present to an extent. Laboratory findings like chest X-ray, ESR, white blood cell (WBC) count, lymphocyte count, C-reactive protein (CRP), serum glutamic pyruvic transaminase (SGPT), serum ferritin, PT, D-dimer, and serum creatinine are important markers for the diagnosis and prognosis of COVID-19 illness (p < 0.05). Conclusion: Post-COVID-19 persisting symptoms and the changes in the laboratory values need to be considered with importance and as a routine clinical measure. Post-COVID-19 periodic follow-up for evaluating the patient's physical condition and the biochemical values should be scheduled with care and managed accordingly to prevent future comorbidity in patients with the post-COVID-19 syndrome.

Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-α synthetsis and antagonizing tumour necrosis factor-α-related effects.

OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. METHODS: The expression of tumour necrosis factor (TNF)-α was evaluated in normal and preeclampsia pregnant women. PYR (20 mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-α (150 ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-α-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. RESULTS: Preeclampsia women had higher placental TNF-α expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-α-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-α decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. CONCLUSION: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-α but also by acting against TNF-α-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management.

Emerging Hand Foot Mouth Disease in Bangladeshi Children- First Report of Rapid Appraisal on Pocket Outbreak: Clinico-epidemiological Perspective Implicating Public Health Emergency.

Background: Hand, foot and mouth disease (HFMD) is a common contagious disease among children under 5 years, particularly in the Asia-Pacific-region. We report a localized outbreak of childhood HFMD for the first time from Bangladesh, diagnosed only based on clinical features due to gross lack of in laboratory-diagnostic facilities. Methods: Following the World Health Organization's case-definition, we conducted a rapid-appraisal of HFMD among 143 children attending Pabna Medical College and General Hospital with fever, mouth ulcers and rash. Data were collected between September and November 2017 using a preset syndromic approach and stringent differential diagnostic-protocols. Results: The mean age of children was 2.9±2.3 years. Age did not differ with sex (P=0.98), first sibling being more likely to (62%) belong to middle-income families. Younger children (<5 years) were more likely to suffer with moderate-to-high (38.5°C) fever (P<0.04), painful oral ulcers (P<0.03) and painful/itchy rash (P<0.01). Sex did not differ with other symptoms, but boys had less painful oral ulcers than girls (P<0.04). Fever (63%) and chicken-pox-like-rash (62%) was observed more in mid-October to mid-November than September to mid-October (P<0.01 and P<0.03, respectively). No differences in symptoms (fever, oral ulcers and extremity rash) were observed with precipitation, nor with ambient temperature. Children <5 years (85%) had quicker recovery (within 5 days) than those ≥5 years (69%), (P<0.04), with marginal differences in sex (P<0.05). Conclusions: Our findings highlight the potential usefulness in diagnosing HFMD based on clinical parameters, although stringent differential diagnosis remains indispensable. It is particularly applicable for resource-constrained countries who lack appropriate virology laboratory equipment. Since no specific treatment or effective vaccination is available for this disease, supportive therapy and preventive measures remain the primary methods to circumvent transmission augmented by climate-related factors. Standardized virology laboratory warrants appropriate diagnosis and globally representative multivalent vaccine is deemed essential towards preventing HFMD.