Effects of Moxonidine Administration on Serum Neuropeptide Y Levels in Hypertensive Individuals: A Prospective Observational Study

Moxonidine is a centrally acting, anti-hypertensive medication that exerts additional metabolic properties. It is unknown whether its effects are mediated by neurotransmitters or sympathetic tone regulators, including Neuropeptide Y (NPY). In this study, we evaluated the effects of moxonidine administration on serum NPY in humans. Methods: Ninety individuals with mild or moderate arterial hypertension that required monotherapy were categorized in three age and gender-matched groups according to their Body Mass Index (BMI) as normal weight (n = 30), overweight (n = 30), and obese (n = 30). Moxonidine was administered in therapeutic doses of up to 0.6 mg daily for 12 weeks, and clinical, biochemical and hormonal parameters were recorded. Results: In all three groups, a decrease in systolic and diastolic blood pressure and heart rate was shown. After treatment, BMI, 24 h urine catecholamines and catecholamines’ metabolites, and serum total cholesterol were also reduced. Most importantly, we found a decrease in serum NPY levels in all study groups, with the largest mean decrease in the group of obese and overweight participants compared to normal weight. Conclusions: Moxonidine administration results in improvement in cardio-metabolic parameters, as well as a decrease in serum NPY levels, which therefore represents it being a potent agent against obesity-associated hypertension. Its involvement in energy balance regulation warrants further investigation.

Anticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 ± 128 and 5689 ± 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1–2 h after administration and were still detectable 24 h later (120 ± 12 and 904 ± 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 hour after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined.

Heparin and SARS-CoV-2: Multiple Pathophysiological Links

Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.

Controlling Hyperglycaemia Diabetes Mellitus Type-II: Bromocriptine Alone or in Combination with Metformin

Background: Diabetes Mellitus is one of the leading cause of morbidity and mortality globally. According to WHO there is a steady increase in the number of diabetic patients annually. Maintenance of good glycaemic control in type 2 diabetic patients typically becomes progressively more difficult as the duration of disease lengthens due to decline in the capacity of the pancreatic beta cells for glucose stimulated insulin release, in the presence of insulin resistance. This study is conducted to observe the effect of metformin and bromocriptine individually and sub-therapeutic doses of these drugs when used as a combination therapy. Objective: The objective of this study is to primarily investigate and then compare the antihyperglycemic effects of bromocriptine with metformin, also to see the combined effect of sub therapeutic doses of both these drugs. Methodology: Random allotment of 24 albino male rats was done in four groups. Group 1 was kept as control. Alloxan monohydrate was given to group 2, 3 and 4 and diabetes was induced. Group 2 and 3 were treated with metformin (1.5mg/kg body weight) and bromocriptine (3 mg/kg body weight) respectively while group 4 was treated with sub therapeutic doses of metformin (1 mg/kg body weight) and bromocriptine (1.5 mg/kg body weight)both. Serum glucose levels were estimated at 1, 10, 20 and 30 days. Results: Results showed that metformin reduces blood glucose level significantly where as bromocriptine also showed reduction of blood glucose level but not as significantly as metformin. However, the combination of metformin and bromocriptine showed much reduction in blood glucose level than metformin and bromocriptine used alone. Conclusion: Bromocriptine and metformin when combined ameliorated blood guclose efficiently than given alone Keywords: Diabetes mellitus, bromocriptine, metformin

The effect of serial administration of doxorubicin at the level of main female sex hormones in the experiment

Annotation. The article presents the results of an experimental study of the dynamics of changes in the main female sex hormones with serial use of doxorubicin. The experiments were performed on 45 adult female white rats. The levels of antimullerian hormone, estradiol and follicle-stimulating hormone were studied. In total, 4 courses of chemotherapy were performed with an interval of 3 weeks. After each course of chemotherapy, the hormonal status of the experimental animals was studied twice: during the first proestrus after the course (to determine the acute ovarian toxicity of the drug) and during the last proestrus before the next course of chemotherapy (to study ovarian function restoration). The obtained data were processed using the statistical software package SPSS 20.0 for Windows. The dynamics of the levels of studied sex hormones with serial administration of doxorubicin is characterized by wavy dynamics with deterioration immediately after chemotherapy and partial recovery during the period between adjacent courses. Ovariotoxicity of doxorubicin when serial administration in therapeutic doses in the experiment is manifested by significant changes in the levels of major female sex hormones after the second course of chemotherapy.

Failure to Eliminate Persistent Anaplasma marginale Infection from Cattle Using Labeled Doses of Chlortetracycline and Oxytetracycline Antimicrobials

Bovine anaplasmosis, caused by the intracellular rickettsial pathogen Anaplasma marginale, is the most prevalent tick-transmitted disease of cattle worldwide. In the U.S., tetracycline antimicrobials are commonly used to treat and control anaplasmosis. Oxytetracycline, administered by injection, is indicated for treatment of clinical anaplasmosis in beef and dairy cattle and calves. Chlortetracycline, administered orally, is indicated for control of active anaplasmosis infection in beef and nonlactating dairy cattle. Tetracyclines have been demonstrated to be effective for treating active anaplasmosis, but their ability to eliminate A. marginale at currently approved therapeutic doses or dosing regimens remains unclear. In the absence of approved dosing regimens for A. marginale clearance, a study was conducted to determine the effect of approved oxytetracycline and chlortetracycline indications on A. marginale bacteremia. Fifteen animals with persistent anaplasmosis were enrolled and divided into three treatment groups. Group 1 (n = 6) received oral chlortetracycline (1.1 mg/kg bodyweight) administered via hand-fed medicated feed for 60 consecutive days. Group 2 (n = 6) received injectable oxytetracycline administered subcutaneously at 19.8 mg/kg bodyweight three times in 3-week intervals. Group 3 (n = 3) served as an untreated control. After 60 days, bacteremia failed to permanently decrease in response to treatment. This result indicates that clearance of A. marginale is unlikely to be reliably achieved using currently approved tetracycline-based regimens to manage anaplasmosis.

Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding

Introduction: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. Methods: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. Results: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68–0.79) for major bleeding, 0.73 (95% CI: 0.67–0.78) for non-major bleeding and 0.82 (95% CI: 0.76–0.87) for bleeding-related death. Conclusions: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.