High Vitamin D Level in Female Mice Increases the Number of Live Fetuses.

Little is known about the impact of high-normal range of 25-hydroxyvitamin D [25(OH)D] on reproductive function. The aim of this study was to investigate the effect of different dose vitamin D supplementation in female mice on the pregnancy outcomes. Three groups of female mice were fed with fodder containing different dose of vitamin D at both pre-gestational and gestational stages. Serum 25(OH)D and calcium concentrations were monitored. The expression levels of vitamin D receptor (VDR) mRNA and protein in placenta were determined by real-time RT-PCR and western blot. Pregnancy outcomes were evaluated and compared among the three groups. Compared with the medium and low dose groups, serum 25(OH)D concentration was significantly increased and approximated to high-normal range in the high dose group (pre-gestational: 81.3±5.75 vs 52.8±6.24 and 25.0±3.99 ng/mL; gestational: 86.8±5.99 vs 52.6±9.29 and 27.9±4.96 ng/mL, respectively; all p<0.001). Interestingly, the average number of live fetuses per litter was much larger in the high dose group than in other two groups (19.8±5.31 vs 13.8±1.30 and 12.8±3.55 respectively, both p<0.05). However, no significant differences of the expression levels of VDR mRNA and protein in placenta were identified among the three groups. Supplementation of high dose vitamin D can enhance the female mice reproductive function. Further study is warranted to explore the mechanism by which high level of 25(OH)D in female mice increases the number of fetuses.

A Single Large Dose of Vitamin D Could be Used as a Means of Coronavirus Disease 2019 Prevention and Treatment.

There is no specific and effective medication for coronavirus disease 2019 (COVID-19), and avaccine is not available in recent months. Here, we hypothesize that a single large dose of vitamin D (Vit D) could be an option for trial in COVID-19. Vit D deficiency or insufficiency is very common in the general population as well as in patients with COVID-19. It has been shown that low Vit D level is associated with viral infection, and Vit D supplementation is beneficial for people infected with viruses, such as HIV and hepatitis C virus. Although COVID-19 is a respiratory disease, the morbidity and mortality of this disease are driven by coagulopathy. Clinical studies have shown that Vit D can exert anticoagulant effects. Vit D, a lipid-soluble vitamin, can be administered as a draught. Vit D supplementation is safe and has rare toxic events. In addition, the cost of Vit D is fairly low. Based on these observations, we speculate that a single dose of 300,000 IU Vit D may have a role in the prevention and treatment of COVID-19.

Myopathy after rapid correction of hyperthyroidism: A case report and review of literature.

RATIONALE: Myalgia and elevated creatine kinase (CK) have been reported during the treatment of hyperthyroid patients. The causes of these symptoms are usually considered to be treatments of antithyroid drugs (ATDs), thyroidectomy or radio-iodine (131-I). However, the underlying cause may be the rapid correction of thyrotoxicosis (or relative hypothyroidism), which was usually neglected in clinical practice. PATIENT CONCERNS: This report describes a case of a 25-year-old female with typical symptoms and laboratory test results of Grave hyperthyroidism. The patient complained about fatigue and myalgia 7 weeks after receiving methimazole (MMI) treatment. Blood tests showed dramatically elevated serum CK level, although free triiodothyronine (FT3) and free thyroxine (FT4) level had returned to the normal reference range. MMI was; therefore, discontinued and the patient's muscular symptoms disappeared quickly with the normalization of CK level and the relapse of hyperthyroidism. Later she received 131-I treatment and suffered similar muscular symptoms when FT3 and FT4 decreased to the normal range. This time, her symptoms were quickly relieved by levothyroxine (L-T4) replacement treatment. DIAGNOSES: Myopathy induced by rapid correction of hyperthyroidism (or relative hypothyroidism). INTERVENTIONS: MMI was discontinued after the patient's first episode of muscular symptoms. And for her second episode of muscular injury after 131-I treatment, we initiated L-T4 supplementation. OUTCOMES: For the 2 episodes of muscular injury after ATDs or 131-I treatment, both of the interventions mentioned above brought a rapid relief of symptoms accompanied with normalization of CK level and restoration of thyroid hormone level. LESSONS: Myopathy can be caused by a rapid reduction of thyroid hormone during the treatment of hyperthyroidism. This relative hypothyroidism syndrome should be considered if patients make complaints about fatigue and myalgia, even when thyroid hormone level is within the normal range during the antithyroid treatments. Serum CK level and thyroid function should be closely monitored post antithyroid treatments. Reduction of ATD dosage or replacement of thyroid hormone is suggested to relieve muscular symptoms.

Liraglutide restores angiogenesis in palmitate-impaired human endothelial cells through PI3K/Akt-Foxo1-GTPCH1 pathway.

Glucagon-like peptide-1 (GLP-1) and its analogues have a beneficial role in cardiovascular system. Here, we aimed to investigate whether liraglutide, a GLP-1 analogue, modulated angiogenesis impaired by palmitic acid (PA) in cultured human umbilical vein endothelial cells (HUVECs). Cells were incubated with liraglutide (3-100 nmol/L) in the presence of PA (0.5mmol/L), and endothelial tube formation was observed and quantified. The protein levels of signaling molecules were analyzed and the specific inhibitors were used to identify the signaling pathways through which liraglutide affected angiogenesis. Results showed that liraglutide ameliorated endothelial tube formation impaired by PA in HUVECs in a dose-dependent manner. Meanwhile, liraglutide increased the phosphorylation of Akt and forkhead box O1 (Foxo1), and upregulated the levels of guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1) and endothelial nitric oxide synthase (eNOS) in PA-impaired HUVECs. Notably, addition of the PI3K inhibitor LY294002, Foxo1 nuclear export inhibitor trifluoperazine dihydrochloride (TFP), GTPCH1 inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP) or NOS inhibitor N-nitro-l-arginine-methyl ester (L-NAME) eliminated the angiogenic effect of liraglutide. Moreover, either LY294002 or TFP abolished the liraglutide-induced upregulation of GTPCH1 and eNOS protein levels. In conclusion, liraglutide restores angiogenesis in PA-impaired HUVECs. The effect is mediated via upregulation of GTPCH1 and eNOS levels in a PI3K/Akt-Foxo1-dependent mechanism.

Beneficial metabolic effects of nateglinide versus acarbose in patients with newly-diagnosed type 2 diabetes.

AIM: To investigate the acute and chronic effects of nateglinide versus acarbose on plasma asymmetric dimethylarginine (ADMA) levels and lipid profiles in patients with newly-diagnosed type 2 diabetes. METHODS: A crossover trial of nateglinide and acarbose was conducted on 16 drug-naïve patients with newly-diagnosed type 2 diabetes during a total period of 9 weeks. Plasma glucose, serum insulin, free fatty acids (FFA), lipids and lipoproteins, and plasma ADMA were measured. RESULTS: The efficiencies of a single dose of nateglinide (120 mg) and acarbose (50 mg) for lowering postprandial hyperglycemia were similar. Compared to acarbose, nateglinide significantly increased postprandial insulin release after a standard meal test in patients with type 2 diabetes. Nateglinide acutely decreased postprandial 120 min FFA concentrations and 240 min ADMA levels more significantly than acarbose. The fasting high-density lipoprotein cholesterol level increased and the low-density lipoprotein cholesterol level decreased significantly, but the fasting levels of triglycerides, total cholesterol, and ADMA were unchanged after 4 weeks of treatment with nateglinide. Acarbose did not affect fasting lipid profiles or the ADMA levels after 4 weeks of treatment. CONCLUSION: These results suggest that the reduction of postprandial FFA and ADMA concentrations induced by nateglinide may be associated with the partial restoration of early-phase insulin secretion and may impart a cardiovascular advantage in comparison with acarbose.