Sleep disorders and hypertension

Badania nad patogenezą chorób układu krążenia oraz powikłań sercowo-naczyniowych innych schorzeń, przede wszystkim cukrzycy oraz innych składowych zespołu metabolicznego, dostarczają nowych informacji na temat potencjalnych czynników ryzyka sercowo-naczyniowego, mogących mieć znaczenie w praktyce klinicznej. Szczególnie intensywne badania dotyczą nadciśnienia tętniczego oraz cukrzycy typu 2. Postulowany jest wpływ zaburzeń snu na rozwój oraz występowanie powikłań sercowo-naczyniowych w tych chorobach. Do najczęściej występujących w tych populacjach zaburzeń snu należą obturacyjny bezdech podczas snu oraz bezsenność. Podkreśla się również znaczenie ograniczenia czasu snu związanego ze stylem życia. Obturacyjny bezdech podczas snu jest silnym i niezależnym czynnikiem rozwoju nadciśnienia tętniczego wtórnego, stanowiąc jednocześnie jego potencjalnie odwracalną przyczynę. Współistnieje on również często z otyłością i zespołem metabolicznym. Udowodniono wpływ bezsenności na rozwój nadciśnienia tętniczego oraz jego powikłań narządowych. Wydaje się, że cechą łączącą patogenetycznie wpływ zaburzeń snu na rozwój nadciśnienia tętniczego, cukrzycy, otyłości i zespołu metabolicznego jest nadmierna aktywacja układu współczulnego. Konieczne są jednak dalsze badania kliniczne dla uzasadanienia tej hipotezy. Nadciśnienie Tętnicze 2010, tom 14, nr 5, strony 411-419.Research on pathogenesis of cardiovascular diseases and cardiovascular complications of other pathologies, mainly diabetes mellitus and other components of metabolic syndrome, deliver new data on potential cardiovascular risk factors which may be relevant in clinical practice. Particularly intensive research is focused on hypertension and diabetes mellitus type 2. It is postulated that sleep disorders might be significant in development of these diseases as well as their cardiovascular complications. One of the most frequent sleep disorders in general population are: obstructive sleep apnea, insomnia and sleep time reduction. Obstructive sleep apnea is a strong and independent risk factor for secondary hypertension, however it is a potentially reversible pathology. Obstructive sleep apnea also co-exists with obesity and metabolic syndrome. Reduction of total sleep time below 7 hours is strongly correlated with the risk for obesity, diabetes mellitus and hypertension. It is worth to be noticed that the same relation has been observed for elongation of total sleep time over 8 hours. It has been also proven that insomnia is correlated with hypertension and its organic complications. Hyperactivation of symphatetic system seems to be a pathogenetic link between sleep disorders and development of hypertension, diabetes mellitus, obesity and metabolic syndrome. These issues need further research to explain existing ambiguities and confirm pathogenetic relations already shown. Arterial Hypertension 2010, vol. 14, no 5, pages 411-419

Patient with bilateral, adrenal pheochromocytoma and neurofibromatosis type 1 - case report

Nerwiakowłókniakowatość typu 1 (NF1, neurofibromatosis type 1) jest stosunkowo często występującym zaburzeniem o charakterze autosomalnym dominującym, występującym u około 1 na 3000 osób. Do najbardziej charakterystycznych objawów NF1 należą przebarwienia skórne typu "kawa z mlekiem", piegi w okolicach pach i pachwin, nerwiakowłókniaki oraz guzki Lischa zlokalizowane w tęczówkach. U chorych z NF1 częściej niż w populacji ogólnej obserwuje się nowotwory łagodne i złośliwe. Częstość występowania guza chromochłonnego u tych osób ocenia się na 1-10%. Przebieg kliniczny pheochromocytoma w NF1 jest podobny do przypadków sporadycznych. W niniejszej pracy przedstawiono przypadek 48-letniego chorego przyjętego do Kliniki Nadciśnienia Tętniczego Instytutu Kardiologii w Warszawie w celu diagnostyki ciężkiego nadciśnienia tętniczego. W badaniu przedmiotowym stwierdzono obecność plam cafe au lait, piegi w okolicy pach i pachwin, liczne nerwiakowłókniaki skóry oraz guzki Lischa widoczne w lampie szczelinowej. Dobowe wydalanie katecholamin z moczem było podwyższone. W tomografii komputerowej odnotowano obustronne guzy nadnerczy, potwierdzone w scyntygrafii znakowanej 131I-metajodobenzylguanidyną (131I-MIBG, 131I-metaiodobenzylguanidine). Po 2-tygodniowym przygotowaniu chorego skojarzonym leczeniem fenoksybenzaminą i metoprololem wykonano laparoskopową obustronną adrenalektomię. Badanie histopatologiczne potwierdziło rozpoznanie pheochromocytoma. W dyskusji omówiono patogenezę i obraz kliniczny nerwiakowłókniakowatości typu 1 oraz diagnostykę i sposób postępowania.Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders in man, affecting 1 in 3000 people. Café au lait spots, axillary freckling, dermal neurofibromas and Lisch nodules of the iris are the most frequent manifestations of the disease. Affected persons are also at risk of developing benign and malignant tumors. The association between NF1 and pheochromocytoma is present in 1-10% of cases. Clinical features of pheochromocytoma in neurofibromatosis 1 patients are similar to those in patients with sporadic pheochromocytomas, unlike pheochromocytomas associated with other hereditary syndromes. Here we report a case of pheochromocytoma associated with NF1. 48-year-old man with NF1 was admitted to our hospital because of uncontrolled hypertension. On physical examination, cafe-au-lait spots and neurofibromas were observed. Lisch nodules were visible in split lamp. 24-hour urine catecholamine excretion was elevated. Computed tomography revealed two small tumors in both adrenal glands which was confirmed by 131I-MIBG scintigraphy. After diagnosis of pheochromocytoma had been established, medical management was initiated using phenoxybenzamine with concomitant using of metoprolol and was continued for two weeks preoperatively. Bilateral laparoscopic adrenalectomy was performed. Histopathological examination confirmed diagnosis of pheochromocytoma. The authors discuss the pathogenetic aspects of this rare pathological association and clinical manifestation of NF1

Capecitabine-induced-coronary-vasospasm leading to polymorphic ventricular tachycardia and cardiac arrest

Abstract Capecitabine, a pro-drug of 5-fluorouracil, is commonly used in the treatment of breast and colorectal cancer. Its side effects, including nausea, vomiting, diarrhea, fatigue, loss of appetite, and bone marrow suppression, are well recognized. However, coronary vasospasm represents a less commonly recognized but significant complication of fluoropyrimidine-based therapies such as capecitabine. Proposed mechanisms for this adverse effect complication include direct endothelium-independent vasoconstriction, activation of protein kinase C, and activation of the cyclooxygenase pathway. In this report, we present a case of capecitabine-induced coronary vasospasm leading to progressive, focal ST-elevations, myocardial ischemia, and subsequently polymorphic ventricular tachycardia. These events were captured on telemetry, in a male in his early 40s, diagnosed with stage IIIB sigmoid colon cancer. Notably, the patient had no pre-existing coronary artery disease or other cardiovascular risk factors. Upon diagnosis, the patient was initiated on a calcium channel blocker, verapamil, to mitigate further coronary vasospasm events. After thorough discussions that prioritized the patient’s input and values, an implantable cardioverter-defibrillator was placed subcutaneously. Following discharge, the patient restarted capecitabine therapy along with verapamil prophylaxis and did not experience any subsequent shocks from his ICD as assessed during his outpatient follow-up visits. This case emphasizes the need to involve patients in decision-making processes, especially when managing unexpected and serious complications, to ensure treatments align with their quality of life and personal preferences

Anti-Inflammatory Effects of Encapsulated Human Mesenchymal Stromal/Stem Cells and a Method to Scale-Up Cell Encapsulation

Mesenchymal stem/stromal cells (MSC) promote recovery in a wide range of animal models of injury and disease. They can act in vivo by differentiating and integrating into tissues, secreting factors that promote cell growth and control inflammation, and interacting directly with host effector cells. We focus here on MSC secreted factors by encapsulating the cells in alginate microspheres, which restrict cells from migrating out while allowing diffusion of factors including cytokines across the capsules. One week after intrathecal lumbar injection of human bone marrow MSC encapsulated in alginate (eMSC), rat IL-10 expression was upregulated in distant rat spinal cord injury sites. Detection of human IL-10 protein in rostrally derived cerebrospinal fluid (CSF) indicated distribution of this human MSC-secreted cytokine throughout rat spinal cord CSF. Intraperitoneal (IP) injection of eMSC in a rat model for endotoxemia reduced serum levels of inflammatory cytokines within 5 h. Detection of human IL-6 in sera after injection of human eMSC indicates rapid systemic distribution of this human MSC-secreted cytokine. Despite proof of concept for eMSC in various disorders using animal models, translation of encapsulation technology has not been feasible primarily because methods for scale-up are not available. To scale-up production of eMSC, we developed a rapid, semi-continuous, capsule collection system coupled to an electrosprayer. This system can produce doses of encapsulated cells sufficient for use in clinical translation

The effect of immunosuppressive therapy on renal cell apoptosis in native rat kidneys

Aim: To analyse the impact of the most commonly used immunosuppressive drugs on the occurrence of apoptosis in the native kidneys of Wistar rats. Method: The study involved 36 rats. The animals grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The medication dose was adjusted based on available literature data. No drugs were administered to the control group. The rats were then killed. Autopsies of all animals were performed and the kidneys were isolated for histopathology (HE + PAS). To assess cell apoptosis the TUNEL reaction was performed. Blood trough levels of immunosuppressive drugs as well as the parameters of peripheral blood were determined. Results: 1. In rats treated with cyclosporine A distal nephron tubules were characterised by more pronounced apoptosis. 2. In tacrolimus-treated rats a lower intensity of apoptosis was found in the distal tubules. 3. In rapamycin-treated rats the apoptosis was inhibited both in the distal and proximal nephron tubules. 4. In MMF treated rats intense apoptosis was observed in the proximal nephron tubules. 5. There were no significant changes in renal histopathology (HE + PAS). Conclusions: The apoptosis in nephron tubules caused by immunosuppressive therapy is not accompanied by any histopathological changes (eg fibrosis, inflammation, tubular atrophy, vacuolation of the tubular cells) in light microscop