Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability.

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Perspectives on Post-COVID-19 Pulmonary Fibrosis Treatment.

Pulmonary fibrosis, a critical outcome of chronic inflammatory diseases, has gained prominence in the context of post-coronavirus (post-COVID-19) complications. This review delves into the multifaceted landscape of post-COVID-19 pulmonary fibrosis, elucidating the intricate molecular mechanisms underlying its pathogenesis and highlighting promising therapeutic avenues. Examining the aftermath of severe acute respiratory syndrome-2 (SARS-CoV-2) infection, the review reveals key signaling pathways implicated in the fibrotic cascade. Drawing parallels with previous coronavirus outbreaks enhances our understanding of the distinctive features of post-COVID-19 fibrosis. Antifibrotic drugs, like pirfenidone and nintedanib, take center stage; their mechanisms of action and potential applications in post-COVID-19 cases are thoroughly explored. Beyond the established treatments, this review investigates emerging therapeutic modalities, including anti-interleukin agents, immunosuppressants, and experimental compounds, like buloxybutide, saracatinib, sirolimus, and resveratrol. Emphasizing the critical importance of early intervention, this review highlights the dynamic nature of post-COVID-19 pulmonary fibrosis research. In conclusion, the synthesis of current knowledge offers a foundation for advancing our approaches to the prevention and treatment of these consequential sequelae of COVID-19.

The Role of Phytosterols in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, ß-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.

Protective role of selenium on thyroid morphology in iodine-induced autoimmune thyroiditis in Wistar rats.

Excess iodine may induce and exacerbate autoimmune thyroiditis (AIT) in humans and animals. In order to assess the potential protective mechanisms of selenium (Se) in thyroid autoimmunity, the effects of inorganic Se (sodium selenite) administration on thyroid morphology and follicular cytology were investigated in adult Wistar rats with iodine-induced AIT. A total of 48 adult Wistar rats (24 females, 24 males) were allocated to one of four dietary regimens: C0, control; C1, only potassium iodine (KI); C2, concomitant KI and Se; C3, only KI initially, followed by Se administration. For AIT induction the rats were fed with 0.05% KI for 56 days. Se-treated rats received 0.3 mg/l sodium selenite in drinking water. Thyroid tissues were collected for pathologic diagnosis after 7 days in C0 group, 56 days in C1 and C2 groups, and 112 days in C3 group. In C1 group, moderate to severe thyroiditis was observed in 83% of males and 50% of female rats (P=0.223). In C3 group 16.7% of male rats developed moderate thyroiditis and none in C2 group, whereas no females were identified with moderate to severe thyroiditis in C2 or C3 group. Thus, the administration of Se was proven to have protective effects against thyroiditis cytology in both male and female Wistar rats.

IMPLICATIONS OF GHRELIN AXIS IN BREAST CANCER--REVIEW.

Breast cancer is, by far, the most frequent cancer among women and many factors influence the physiological and pathological growth and development of the mammary gland. There is developing evidence that the hormone ghrelin, known for the growth hormone releasing effect and food intake modulator, could also play a role in the pathogenesis of breast cancer and may represent a new diagnostic marker and a potential therapeutic target. We performed a PubMed Database search of relevant studies and ten papers were included in our systematic review. Ghrelin axis seems to be definitely involved in the pathogenesis of breast cancer, although a precise role has not been yet established. In order to verify the precise role of ghrelin axis in breast cancer further studies with larger populations are necessary that should include the analysis of metabolic, genetic and environmental factors which are expected to influence the results.

SELENIUM STATUS IN AUTOIMMUNE THYROIDITIS.

UNLABELLED: Selenium (Se) is an important element that exerts its effects through selenoproteins. The thyroid gland has the highest Se concentration and specific selenoprotein enzymes families are crucial in the thyroid hormone metabolism. There is little evidence on the link between Se and thyroid autoimmune disease, therefore future studies are required to elucidate the nature of this associ ation. AIM: To evaluate the Se status in euthyroid subjects with autoimmune thyroiditis. MATERIAL AND METHODS: From January 2014 to January 2015 we recruited 100 consecutive euthyroid subjects with autoimmune thyroiditis, living in the same region and with normal iodine intake. Serum concentrations of Se, thyroid antibodies (antithyroperoxidase--TPOAb--and antithyroglobulin--TgAb), thyroid-stimulating hormone (TSH), and thyroid ultrasound were performed in all patients. RESULTS: Mean age of the study group was 48.87 ± 12.83 years, range: 18-82 years. Since thyroid pathology is more frequent in the 5th - 6th decades of life we selected the age of 50 for the comparative analysis of the results (51% of patients were under 50). No statistical age-group differences in antibody levels were found: mean TPOAb = 420.95 IU/ml, p = 0.840; mean TgAb = 327.98 IU/ml, p = 0.977. TSH mean was 2.14 [µIU/ml, with no significant age-group differences (p = 0.176). Se levels ranged between 8.05 - 998.50 µg/ with a mean value of 294.96 µg/L and no significant differences between age groups (p = 0.158). Thyroid ultrasound showed inhomogeneity in 89%, nodules in 35% of patients, and a mean thyroid volume of 11.72ml, with no significant age-group differences (p = 0.366). The low TSH levels were associated with low Se levels in 11.6% of cases, but the direct correlation was statistically insignificant (r = 0.116; R2 = 0.0161; p = 0.371). Depend ing on TSH percentiles, mean Selevels showed no significant differences, however pointing out the highest mean value at the 25th percentile (F = 0.441, df = 61, p = 0.646). A negative correlation trend was found between Se and TPOAb (r = -0.2276) or TgAb (r = -0.2190) but lacking statistical significance (p=0.099). CONCLUSION: Our results showed a weak negative correlation between Se and antithyroid antibodies, suggesting that selenium supplementation may improve the course of thyroid autoimmunity.