Hyperprolactinemia in Adults with Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioural challenges, cognitive dysfunction, and hypogonadism. Psychotic illness is common, particularly in patients with maternal uniparental disomy (mUPD), and antipsychotic medications can result in hyperprolactinemia. Information about hyperprolactinemia and its potential clinical consequences in PWS is sparse. Here, we present data from an international, observational study of 45 adults with PWS and hyperprolactinemia. Estimated prevalence of hyperprolactinemia in a subset of centres with available data was 22%, with 66% of those related to medication and 55% due to antipsychotics. Thirty-three patients were men, 12 women. Median age was 29 years, median BMI 29.8 kg/m2, 13 had mUPD. Median prolactin was 680 mIU/L (range 329–5702). Prolactin levels were higher in women and patients with mUPD, with only 3 patients having severe hyperprolactinemia. Thyroid function tests were normal, 24 were treated with growth hormone, 29 with sex steroids, and 20 with antipsychotic medications. One patient had kidney insufficiency, and one a microprolactinoma. In conclusion, severe hyperprolactinemia was rare, and the most common aetiology of hyperprolactinemia was treatment with antipsychotic medications. Although significant clinical consequences could not be determined, potential negative long-term effects of moderate or severe hyperprolactinemia cannot be excluded. Our results suggest including measurements of prolactin in the follow-up of adults with PWS, especially in those on treatment with antipsychotics.

Potential natural immunization against atherosclerosis in hibernating bears

Brown bears (Ursus arctos) hibernate for 5–6 months during winter, but despite kidney insufficiency, dyslipidemia and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) are associated with less atherosclerosis, CVD and mortality in uremia in humans and have anti-inflammatory and other potentially protective properties. PC but not MDA is exposed on different types of microorganisms. We determine anti-PC and anti-MDA in brown bears in summer and winter. Paired serum samples from 12 free ranging Swedish brown bears were collected during hibernation in winter and during active state in summer and analyzed for IgM, IgG, IgG1/2 and IgA anti-PC and anti-MDA by enzyme linked immunosorbent assay (ELISA). When determined as arbitrary units (median set at 100 for summer samples), significantly raised levels were observed in winter for anti-PC subclasses and isotypes, and for IgA anti-PC the difference was striking; 100 IQR (85.9–107.9) vs 782.3, IQR (422.8–1586.0; p < 0.001). In contrast, subclasses and isotypes of anti-MDA were significantly lower in winter except IgA anti-MDA, which was not detectable. Anti-PCs are significantly raised during hibernation in brown bears; especially IgA anti-PC was strikingly high. In contrast, anti-MDA titers was decreased during hibernation. Our observation may represent natural immunization with microorganisms during a vulnerable period and could have therapeutic implications for prevention of atherosclerosis.

MO439NATURAL IMMUNISATION AGAINST ATHEROSCLEROSIS IN BEARS DURING HIBERNATION*

Background and Aims Brown bears (Ursus arctos) hibernate for 5-6 months during winter, but in spite of kidney insufficiency, dyslipidemia, insulin resistance and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). Antibodies against phosphorylcholine (anti-PC) are associated with protection in atherosclerosis, CVD and uremia. Potential underlying protective mechanisms include anti-inflammatory effects, inhibition of cell death, promotion of T regulatory cells, clearance of dead cells and inhibition of oxidized Low density lipoprotein (OxLDL)-uptake in macrophages in atherosclerotic plaques. PC is an important antigen on nematodes, parasites, some bacteria, dead and dying cells and OxLDL. Method Paired serum from 12 brown bears sampled during winter and summer were analyzed for metabolic parameters and for IgM, IgG, IgG1/2 and IgA anti-PC by enzyme linked immunosorbent assay (ELISA). Differences in antibody levels between winter and summer were determined by paired Student´s t test or Wilcoxon´s signed rank test (when not normally distributed). Results As expected, marked differences in metabolic parameters were found comparing median summer vs winter values; Cholesterol 5.9 vs 11.3 mmol/L; p&lt;0.001, triglycerides 1.9 vs 3.7 mmol/L; p&lt;0.001, glucose 5.4 vs 7.7 mmol/L; p&lt;0.05, S-creatinine 76 vs 203 µmol/L; p&lt;0.001, urea 12.1 vs 2.9 mmol/L; p&lt;0.002. When determined as arbitrary units (AU; median set at 100 at summer), marked and significant differences were observed between summer and winter. Conclusion Anti-PC (strikingly so for IgA and IgG1) are significantly raised during hibernation as compared to levels during summer. We hypothesize that these changes contribute to the protection of arteries, but also kidneys and other organs, during the metabolic vulnerable hibernation period. Our observation may represent a natural immunization with microorganisms, preventing atherosclerosis during a period of severe kidney insufficiency and could have therapeutic implications for patients with chronic kidney disease.

Renalase in Haemodialysis Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is an inflammatory disease leading to kidney insufficiency and uremia. Renalase is a novel flavoprotein with enzymatic activities. Previous studies have shown that chronic kidney disease may influence renalase serum levels. Renalase metabolises catecholamines and therefore may be involved in the pathogenesis of hypertension and other diseases of the circulatory system. In this study, we examined renalase levels in serum, erythrocytes and urine from haemodialysis CKD patients. The study enrolled 77 haemodialysis CKD patients and 30 healthy subjects with normal kidney function as the control group. Renalase serum and urine concentrations in CKD patients were significantly increased when compared with control subjects (185.5 ± 64.3 vs. 19.6 ± 5.0 ng/mL; p < 0.00001 and 207.1 ± 60.5 vs. 141.6 ± 41.3 ng/mL; p = 0.00040, respectively). In contrast, renalase levels in erythrocytes were significantly lower in CKD patients when compared with control subjects (176.5 ± 60.9 vs. 233.2 ± 83.1 ng/mL; p = 0.00096). Plasma levels of dopamine, adrenaline and noradrenaline were also significantly lower in CKD patients when compared with controls. Conclusions: Increased serum and urine concentrations of renalase in haemodialysis CKD patients are likely related to compensatory production in extrarenal organs as a result of changes in the cardiovascular system and hypertension. The decreased plasma concentrations of catecholamines may be due to their increased degradation by plasma renalase. Decreased renalase levels in erythrocytes may be probably due to lower renalase synthesis by the kidneys in CKD. The results indicate the presence of renalase in erythrocytes.

The Current and Potential Therapeutic Use of Metformin—The Good Old Drug

Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical studies showed that metformin has a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). Moreover, there are numerous studies, meta-analyses and population studies indicating that metformin is safe and well tolerated and may be associated with cardioprotective and nephroprotective effect. Recently, it has also been reported in some studies, but not all, that metformin, besides improvement of glucose homeostasis, may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease and prolong the lifespan. This paper presents some arguments supporting the initiation of metformin in patients with newly diagnosed T2DM, especially those without cardiovascular risk factors or without established cardiovascular disease or advanced kidney insufficiency at the time of new guidelines favoring new drugs with pleotropic effects complimentary to glucose control. Moreover, it focuses on the potential beneficial effects of metformin in patients with T2DM and coexisting chronic diseases.

Determination of Groups of Risks at the Diseases COVID-19

Introduction. In the group of risk at people with COVID-19 there are persons with the such chronic diseases: heart-vessel system; respiratory system; endocrine system; oncologic diseases; immune-deficit states; patients with kidney insufficiency. For every disease there is the concrete set of genes the mutations of which multiply the risk of development of illness. Determination of DNA of sick and healthy people resulted in determination of the genes, related to the diseases which arise up at COVID-19. At persons having by had COVID-19 with the certain disease, with the high stake of probability took place points mutations in certain genes. These people can be brought in a teaching sampling «sick», in a class «healthy» persons are brought in with the negative result of PCR. Purpose of the article. On the basis of teaching selections to develop the effective methods of determination of groups of risks of diseases which COVID-19 accompanies. Results. We consider that genes in a left table column are signs for Bayesian procedure. Work of procedure is executed on the basis of count of amount of mutations or their absence in the teaching selections of classes «sick» and «healthy». We correlate the explored person in that class «sick» and «healthy», for which result of procedure higher. Conclusions. Determination of DNA of sick and healthy people resulted in determination of the genes related to the concrete diseases, including with the diseases which arise up at COVID-19. It is shown that the presence of points mutations in the genes of DNA of man results in the certain disease. On the basis of Bayesian procedure of recognition it is possible effectively to determine the groups of risks of diseases which COVID-19 accompanies. Keywords: determination of DNA, the points mutations, Bayesian procedure of recognition.

Two Lithuanian Cases of Classical Galactosemia with a Literature Review: A Novel GALT Gene Mutation Identified

Galactosemia is a rare autosomal recessive genetic disorder that causes impaired metabolism of the carbohydrate galactose. This leads to severe liver and kidney insufficiency, central nervous system damage and long-term complications in newborns. We present two clinical cases of classical galactosemia diagnosed at the Lithuanian University of Health Sciences (LUHS) Kaunas Clinics hospital and we compare these cases in terms of clinical symptoms and genetic variation in the GALT gene. The main clinical symptoms were jaundice and hepatomegaly, significant weight loss, and lethargy. The clinical presentation of the disease in Patient 1 was more severe than that in Patient 2 due to liver failure and E. coli-induced sepsis. A novel, likely pathogenic GALT variant NM_000155.4:c.305T>C (p.Leu102Pro) was identified and we believe it could be responsible for a more severe course of the disease, although further study is needed to confirm this. It is very important to suspect and diagnose galactosemia as early in its course as possible, and introduce lactose-free formula into the patient’s diet. Wide-scale newborn screening and genetic testing are particularly crucial for the early detection of the disease.