Elderly rats fed with a high-fat high-sucrose diet developed sex-dependent metabolic syndrome regardless of long-term metformin and liraglutide treatment.

Aim/Introduction: The study aimed to determine the effectiveness of early antidiabetic therapy in reversing metabolic changes caused by high-fat and high-sucrose diet (HFHSD) in both sexes. Methods: Elderly Sprague-Dawley rats, 45 weeks old, were randomized into four groups: a control group fed on the standard diet (STD), one group fed the HFHSD, and two groups fed the HFHSD along with long-term treatment of either metformin (HFHSD+M) or liraglutide (HFHSD+L). Antidiabetic treatment started 5 weeks after the introduction of the diet and lasted 13 weeks until the animals were 64 weeks old. Results: Unexpectedly, HFHSD-fed animals did not gain weight but underwent significant metabolic changes. Both antidiabetic treatments produced sex-specific effects, but neither prevented the onset of prediabetes nor diabetes. Conclusion: Liraglutide vested benefits to liver and skeletal muscle tissue in males but induced signs of insulin resistance in females.

Increased cerebral vascular resistance underlies preserved cerebral blood flow in response to orthostasis in humans on a high-salt diet.

Cerebral blood flow autoregulation protects brain tissue from blood pressure variations and maintains cerebral perfusion pressure by changes in vascular resistance. High salt (HS) diet impairs endothelium-dependent vasodilation in many vascular beds, including cerebral microcirculation, and may affect vascular resistance. The aim of present study was to determine if 7-day HS diet affected the reactivity of middle cerebral artery (MCA) to orthostatic challenge in healthy human individuals, and if autoregulatory mechanisms and sympathetic neural regulation were involved in this phenomenon.Twenty-seven persons participated in study (F:21, M:6, age range 19-24). Participants consumed 7-day low-salt (LS) diet (< 2.3 g kitchen salt/day) and afterwards 7-day HS diet (> 11.2 g kitchen salt/day). Blood and urine analysis and anthropometric measurements were performed after each diet. Arterial blood pressure, heart rate and heart rate variability, and cerebral and systemic hemodynamic parameters were recorded simultaneously with transcranial Doppler ultrasound and The Task Force® Monitor in response to orthostatic test.Participants remained normotensive during HS diet. Following both, the LS and HS dietary protocols, mean cerebral blood flow (CBF), as well as the velocity time integral and diastolic blood pressure decreased, and cerebral pulsatility index increased after rising up. Importantly, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Urine concentration of noradrenaline and vanillylmandelic acid, baroreflex sensitivity (BRS), and sympathetic neural control was significantly decreased in HS diet.Results suggest that CBF in response to orthostatic test was preserved in HS condition due to altered vascular reactivity of MCA, with increased cerebrovascular resistance and blunted BRS and sympathetic activity.

A method for forecasting the number of hospitalized and deceased based on the number of newly infected during a pandemic.

In this paper we propose a phenomenological model for forecasting the numbers of deaths and of hospitalized persons in a pandemic wave, assuming that these numbers linearly depend, with certain delays [Formula: see text] for deaths and [Formula: see text] for hospitalized, on the number of new cases. We illustrate the application of our method using data from the third wave of the COVID-19 pandemic in Croatia, but the method can be applied to any new wave of the COVID-19 pandemic, as well as to any other possible pandemic. We also supply freely available Mathematica modules to implement the method.

A mathematical model reveals sex-specific changes in glucose and insulin tolerance during rat puberty and maturation.

AIM: To evaluate the effects of maturation and sex on glucose metabolism during glucose tolerance (GTT) and insulin tolerance tests (ITT) in young and adult male and female rats by using two different approaches - the conventional, which uses area under the curve and glucose curve, and mathematical modeling that identifies parameters necessary for determining the function that models glucose metabolism. METHODS: Male and female rats at 3.5 and 12 months of age underwent standard GTT and ITT after overnight fasting. The parameters were identified by using Mathematica-module NonlinearModelFit [] for experimentally obtained data. RESULTS: When data were statistically analyzed, both sexes and age groups had similar glucose and insulin tolerance. In the mathematical model of GTT, parameters describing the rate of glucose concentration increase G'(0) and decrease G'I multiplied with maturation, with a concomitant decrease in the time point (tmax, tI) of reaching maximum and minimum glucose concentration (Gmax, G0). The mathematical model of ITT for males was independent of age, unlike of that for females, which had increased G'(0) and G'I, and more quickly recovered from hypoglycemia after maturation. CONCLUSION: The mathematical model revealed female susceptibility to large glucose excursions, which are better reflected by ITT in young animals and by GTT in adults.