Balkan Medical Journal最新文献

Background: Fabry disease is characterized by the accumulation of globotriaosylceramide. Substrate accumulation in lysosomes is thought to trigger an inflammatory response and is responsible for progressive organ damage through the induction of autoimmunity. The levels of pteridine and kynurenine pathway metabolites increase when immune activation is observed and are employed to monitor several diseases and determine prognosis.

Aims: To elucidate the effects of immune activation on the pathophysiology of Fabry disease and to investigate the potential utility of pteridine and kynurenine metabolites.

Study design: A prospective case-control study.

Methods: In this study, 33 patients with Fabry disease and 33 age-and sex-matched healthy controls were included. Blood pteridine and kynurenine metabolites were studied in both groups. Organ involvement in Fabry disease and its correlation with the pteridine and kynurenine pathways were also investigated.

Results: The patients’ neopterin and biopterin levels and the tryptophan/kynurenine ratio were statistically higher than those of the healthy control group (p < 0.05). A statistically significant association was found between neopterin levels and hypertrophic cardiomyopathy, cardiac arrhythmias, and GFR values (p = 0.044, p = 0.021, and p = 0.030, respectively), tryptophan and corneal verticillate, hearing loss and tinnitus (p = 0.010, p = 0.009 and p = 0.046, respectively), and kynurenine levels and valvular heart disease (p = 0.020).

Conclusion: From the onset of the disease, patients with Fabry disease exhibited elevated levels of inflammation and immune activation. Furthermore, inflammation and immune activation markers can be used as early disease biomarkers.

The testis develops in the abdominal cavity and descends into the scrotum. Although numerous theories have been proposed, the mechanism of descent and the reason for its inhibition remain unknown. Furthermore, none of the explanations account for the other occurrences related to the descent, such as failed obliteration of the processus vaginalis, or the reasons for the decrease in fertility and increase in the risk of malignancy associated with an undescended testis. The gubernaculum is a primitive mesenchymal tissue that was first described in 1786. However, the role of the gubernaculum in the descent process remains obscure. The testis descends through the processus vaginalis. Although the processus vaginalis (PV) is usually defined as a simple peritoneal protrusion, it actively develops into the gubernaculum. The gubernaculum gives rise to the smooth muscles that surround the processus vaginalis. The striated cremaster muscle (CM) is also derived from the gubernaculum. Because the testis descends through the processus vaginalis, the muscles develop to propel the testis. After propelling the testis, the smooth muscle (SM) undergoes programmed cell death. The initiation of programmed cell death through the intrinsic pathway requires activation of phospholipase C. A transient shift in the autonomic balance via a decrease in the sympathetic tonus and an increase in the parasympathetic tonus is essential for initiating this programmed cell death. Programmed cell death in the SM is the physiological pathway for the obliteration of the processus vaginalis. Differences in the timing, intensity, or duration of this physiological pathway result in pathological conditions. A shift before testicular descent diminishes the SM content that is required to propel the testis, and thus inhibits descent. The early shift persists throughout childhood and results in the decrease in fertility and increase in the risk of malignancy because of the differences in signal transduction. Despite a successful descent, persistence of the shift alters the contractility of the CM by increasing the cytosolic calcium levels. Contracted CMs retracts or even ascends the testis. Inadequate intensity or duration of the shift of autonomic tonus causes failure of the programmed cell death. Persistence of the SM hinders the obliteration of PV and gives rise to hydroceles or inguinal hernias depending on the amount of residual smooth muscles. Similar findings from different countries support these explanations. Thus, our proposed mechanism satisfactorily explains the process of descent while considering all the factors related to the process of testicular descent.

Background: Previous studies have mainly focused on individual mental disorders, and there is no study addressing the total burden of mental disorders in the Middle East and North Africa (MENA).

Aims: To evaluate the burden of mental disorders in the MENA region from 1990 to 2019.

Study design: A cross-sectional study.

Methods: We utilized global burden of disease data to examine the burden of 12 mental disorders from 1990 to 2019 across age groups, genders, and the 21 MENA countries. We collected data on prevalence, incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years (DALY), including both crude and age-standardized rates per 100,000 people.

Results: The DALY rate of mental disorders in MENA countries increased by 13.88% from 1,747.92 per 100,000 people in 1990 to 1990.5 per 100,000 people in 2019. The highest percentage increases in the DALY rates of mental disorders were observed for bulimia nervosa (35.69%), other mental health disorders (34.58%), and schizophrenia (33.02%) from 1990 to 2019. However, the DALY rates for idiopathic developmental intellectual disability (-26.48%), conduct disorder (-23.91%), attentiondeficit/ hyperactivity disorder (-16.46%), and autism spectrum disorders (-4.12%) decreased in the MENA region from 1990 to 2019. In 2019, the highest DALY rates for idiopathic developmental intellectual disability, anxiety disorders, and major depressive disorder were observed in age groups ≤ 4 years, 5-19 years, and ≥ 20 years, respectively. The age-standardized DALY rate of mental disorders was the highest in Palestine (2,396.9 per 100,000), Iran (2,295.8 per 100,000), and Lebanon (2,126.0 per 100,000) compared with other MENA countries in 2019.

Conclusion: There has been a slight increase in the burden of mental disorders in the MENA region between 1990 and 2019. National policies should prioritize evidence-based preventive measures and ensure accessible treatment options for mental health disorders in the population, especially in the MENA region.

Background: The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LIRA) is a potential hypoglycemic drug with anti-atherosclerosis (AS) effects. Autophagy in the vascular smooth muscle cells (VSMCs) facilitates AS. However, the role of autophagy in the anti-AS mechanism of LIRA remains unclear.

Aims: To examine the role and mechanisms of autophagy in LIRA’s improvement of the biological characteristics of VSMCs in high glucose conditions.

Study design: Experimental animal study.

Methods: VSMCs isolated from the thoracic aorta of male SD rats were subjected to a high glucose (HG) condition (25 mM) in Dulbecco’s Modified Eagle’s Medium with or without LIRA, the GLP-1 receptor antagonist exendin9-39 (Exe9-39), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), and autophagy inhibitors (3-methyladenine [3-MA] and bafilomycin A1 [Baf A1]). Acridine orange staining, western blotting, transmission electron microscopy, and mCherry-GFP-LC3 transfection were performed to evaluate the autophagy flux. Additionally, VSMC migration, calcification, proliferation, and apoptosis in HG conditions were observed.

Results: Addition of LIRA alone or in combination with autophagy inhibitors significantly downregulated Beclin, increased the LC3-II/LC3-I ratio, and upregulated p62 in VSMCs in HG conditions. Furthermore, autophagolysosome formation was markedly curbed after treatment with LIRA and/or autophagy inhibitors. Inhibition of autophagy by LIRA and/or the autophagy inhibitors attenuated VSMC phenotype conversion, proliferation, migration, and calcification and promoted VSMC apoptosis in HG conditions. This protective role of LIRA was augmented by LY294002, but inhibited by Exe9-39.

Conclusion: LIRA plays a significant role in the improvement of the biological features of VSMCs in HG conditions.