The Role of Mineralocorticoid Receptors in Pathogenesis of Hypertension

Mineralokortykoidy, których głównym przedstawicielem jest aldosteron, mają znaczny wpływ na układ naczyniowo-sercowy — regulują transport jonów w cewkach dystalnych nerek, powodując retencję sodu i chloru oraz wydalanie potasu i kationów wodorowych, a także stabilizują ciśnienie krwi. Zwiększają siłę skurczu mięśnia sercowego oraz powodują włóknienie serca. Mechanizm działania aldosteronu i innych mineralokortykoidów związany jest z obecnością receptorów mineralokortykoidowych, zarówno wewnątrzkomórkowych MR, jak i błonowych. Mineralokortykoidy regulują więc transkrypcję genów, a także działają poprzez przekaz wewnątrzkomórkowy (HSP, kalcyneuryna, cAMP, trójfosfatydyloinozytol). Jednym z czynników decydujących o selektywności przyłączania aldosteronu do MR jest obecność enzymu-11-b-dehydrogenazy hydroksysteroidowej (11-b-HSD). Przypuszcza się, że niektóre postacie nadciśnienia tętniczego mogą mieć związek z zaburzeniami układu MR i zmianą aktywności 11-b-HSD. Budzi to nadzieje lekarzy klinicystów na możliwość ingerencji na poziomie receptorowym, w celu leczenia chorób zależnych od działania aldosteronu, stąd zainteresowanie selektywnymi antagonistami MR, powodującymi obniżenie ciśnienia tętniczego krwi.Mineralocorticoids, among which aldosterone is the most important factor, have great influence on cardio-vascular system: they regulate ion transport in renal distal tubules causing chloride and sodium retention and potassium and hydrogen secretion. They maintain proper blood pressure, have positive inotropic effect and may cause heart-fibrosis. Aldosterone and other mineralocorticoids act through intracellular and membrane receptors (MRs). Thus mineralocorticoids regulate genes’ transciption and have their own intracellular mediators (HSP, calcineurin, cAMP, inositol-1,4,5-trisphosphate). One of the most important factors determining aldosterone selectivity for MRs is the presence of 11-b-hydroxysteroid dehydrogenase (11-b-HSD). It is supposed that some manifestations of arterial blood pressure can be connected with MRs system disturbance and some changes in 11-b-HSD activity. Mediation on the receptor level appears to be very promising way of treatment of many aldosterone-related diseases, that is why a general interest in selective antagonists of MRs lowering the arterial blood pressure is taken

Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families

Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families

Human Alveolar Echinococcosis in Poland: 1990–2011

<div><h3>Background</h3><p>Alveolar echinococcosis (AE) caused by <em>Echinococcus multilocularis</em> infections is a dangerous old disease in the Northern Hemisphere. The aim of the paper was to collect and analyze data on human AE in Poland in the last two decades.</p> <h3>Methodology/Principal Findings</h3><p>The sources of data were both the cases officially registered and detected by an active field and laboratory surveillance. The cases were verified by clinical, epidemiological, and laboratory criteria. Altogether 121 human cases of AE were detected. Among these 83 (68,6%) cases were classified as confirmed, 16 as probable and 22 as possible. During the two decades a continuous increase in detection rate was noticed. The cases were 6–82 years old at the time of diagnosis (mean - 47.7 years). Sex ratio M/F was 0.86/1.0. The AE was fatal in 23 (19%) patients (mean age at death - 54.1 years). Family agglomeration of AE was found in 4 foci, involving 9 patients. Seventy six of the cases were diagnosed in an advanced stage of disease. In all cases the liver was the primary location of AE. In 30 (24.8%) patients a spread to other organs was observed. Ninety four of the patients were treated with albendazole. In 73 (60%) patients a surgical operation was performed, including 15 liver transplantations.</p> <h3>Conclusions/Significance</h3><p>The studies confirmed that AE is an emerging disease in Poland, which is the fourth country in Europe with over 120 cases detected. The results also indicate the need of a wider national programme for implementation of screening in the highest AE risk areas (north-eastern Poland) with an effort to increase the public awareness of the possibility of contracting <em>E. multilocularis</em>, and above all, training of the primary care physicians in the recognition of the risk of AE to allow for an early detection of this dangerous disease.</p> </div

Impact of the COVID-19 pandemic on pulmonary hypertension patients : insights from the BNP-PL national database

We aimed to evaluate the clinical course and impact of the SARS-CoV-2 pandemic on the rate of diagnosis and therapy in the complete Polish population of patients (pts) with pulmonary arterial hypertension (PAH-1134) and CTEPH (570 pts) treated within the National Health Fund program and reported in the national BNP-PL database. Updated records of 1704 BNP-PL pts collected between March and December 2020 were analyzed with regard to incidence, clinical course and mortality associated with COVID-19. Clinical characteristics of the infected pts and COVID-19 decedents were analyzed. The rates of new diagnoses and treatment intensification in this period were studied and collated to the proper intervals of the previous year. The incidence of COVID-19 was 3.8% (n = 65) (PAH, 4.1%; CTEPH, 3.2%). COVID-19-related mortality was 28% (18/65 pts). Those who died were substantially older and had a more advanced functional WHO class and more cardiovascular comorbidities (comorbidity score, 4.0 ± 2.1 vs. 2.7 ± 1.8; p = 0.01). During the pandemic, annualized new diagnoses of PH diminished by 25–30% as compared to 2019. A relevant increase in total mortality was also observed among the PH pts (9.7% vs. 5.9% pre-pandemic, p = 0.006), whereas escalation of specific PAH/CTEPH therapies occurred less frequently (14.7% vs. 21.6% pre-pandemic). The COVID-19 pandemic has affected the diagnosis and treatment of PH by decreasing the number of new diagnoses, escalating therapy and enhancing overall mortality. Pulmonary hypertension is a risk factor for worsened course of COVID-19 and elevated mortality

Geographical distribution of human AE cases in Poland.

<p><b>A – Number of AE cases in each province.</b> Localizations of three patients could not be determined. A – Pomorskie Province; B – Varmia-Masuria Province; C- Podlaskie Province. <b>B – Distribution of 65 AE cases in the Varmia - Masuria Province.</b> Global area amounts to 24 173 km², and population 1 426 155 (2008). a – Elbląski district; b – Lidzbarski district; c – Kętrzyński district; d – Węgorzewski district; e – Iławski district.</p

Age of 117 patients in the year of AE diagnosis and death of 21 persons.

<p>Age of 117 patients in the year of AE diagnosis and death of 21 persons.</p