Miopatia nemalinowa u noworodka – opis rzadkiej choroby

Nemaline myopathy (NM) is a genetically and clinically heterogeneous muscle disorder, defined by the presence of characteristic nemaline bodies on muscle biopsy. The disease has a wide spectrum of phenotypes, ranging from forms with neonatal onset and fatal outcome to asymptomatic forms. The neonatal form is severe and usually fatal. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis difficult during infancy. There is no curative treatment. L-tyrosine may prevent aspiration by reducing pharyngeal secretions and drooling. Most of the patients die from respiratory and cardiac failure. This article discusses a newborn infant who presented with generalized weakness and respiratory failure. Partial response to L-tyrosine treatment was noted. The case is worth presenting to remind clinicians of congenital myopathies in the differential diagnosis of floppy infant during neonatal period and to emphasize the importance of muscle biopsy in diagnosis.Miopatia nemalinowa jest schorzeniem mięśni, niejednorodnym pod względem genetycznym i klinicznym. Chorobę cechuje obecność charakterystycznych struktur nemalino-wych w bioptacie mięśnia. Fenotyp jest bardzo zróżnicowany i obejmuje zarówno postacie noworodkowe prowadzące do zgonu, jak i postacie bezobjawowe. Postać noworodkowa przebiega ciężko i zwykle kończy się śmiercią. Zmienność kliniczna, łącznie ze zróżnicowanym wiekiem w chwili wystąpienia objawów i z różnym ich nasileniem, może utrudniać rozpoznanie w wieku niemowlęcym. Choroba jest nieuleczalna. Podawanie L-tyrozyny może zapobiec zachłyśnięciu poprzez zmniejszenie produkcji wydzieliny w gardle i śliny. Większość chorych umiera z powodu niewydolności oddechowej i krążenia. W artykule omówiono przypadek noworodka z uogólnionym niedowładem i niewydolnością oddechową. Reakcja na podawanie L-tyrozyny była częściowa. Przedstawiony opis przypadku ma na celu przypomnienie klinicystom o miopatiach wrodzonych, które należy uwzględniać w rozpoznaniu różnicowym zespołu wiotkiego dziecka w okresie noworodkowym, oraz podkreślenie znaczenia biopsji mięśnia w ustalaniu rozpoznania

Fenofibrate Treatment Enhances Antioxidant Status and Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Rats

Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-α activator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg−1 day−1) for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-α level in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity

Controlled release of 5-fluorouracil from biocompatible polymeric beads

Primidin analoğu olan 5-Fluorourasil (5-FU) çok çeşitli kanserlerin (meme, kolorektal, gastrointestinal vb.) tedavisinde kullanılan bir kemoterapi ajanıdır. Ancak, plazma yarı ömrünün kısa olması, kanser hücrelerine karşı düşük seçiciliği ve ciddi yan etkilere sebep olması klinik kullanımını sınırlandırmıştır. Bu çalışmada 5-FU’nun kontrollü salım teknolojisi ile olumsuz özelliklerinin en aza indirilmesi hedeflendi. Bu amaçla 5-FU yüklü poli (vinil alkol)/sodyum aljinat (PVA/NaAlg) küreleri FeCl3 kullanılarak iyonik çapraz bağlanma yöntemiyle hazırlandı ve Fourier transform infrared spektroskopi (FTIR), taramalı elektron mikroskopi (SEM) ve diferansiyel taramalı kalorimetri (DSC) ile karakterize edildi. İn vitro salım çalışmaları 2’şer saat süre ile 3 farklı pH (1.2, 6.8 ve 7.4) değerinde toplam 6 saat olacak şekilde gerçekleştirildi. PVA/NaAlg (m/m) oranı, ilaç/polimer (m/m) oranı, çapraz bağlama süresi ve çapraz bağlayıcı derişiminin 5-FU salımı üzerine etkisi araştırıldı. Kürelerde PVA miktarının artmasıyla 5- FU salımının arttığı buna karşın çapraz bağlama süresinin ve çapraz bağlayıcı derişimin artmasıyla 5-FU salımının azaldığı belirlendi.5-Fluorouracil (5-FU), a pyrimidine analog, is a chemotherapy agent used in the treatment of a wide variety of cancers (breast, colorectal, gastrointestinal, etc.). However, its short plasma half-life, low selectivity against cancer cells and serious side effects limited its clinical use. In this study, it was aimed to minimize the negative properties of 5-FU with controlled release technology. For this purpose, 5-FU loaded poly(vinyl alcohol)/sodium alginate (PVA/NaAlg) beads were prepared by ionic crosslinking method using FeCl3 and beads were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). In vitro release studies were carried out for 2 hours at 3 different pH values (1.2, 6.8 and 7.4) for a total of 6 hours. The effects of PVA/NaAlg (w/w) ratio, drug/polymer (w/w) ratio, crosslinking time and crosslinker concentration on 5-FU release were investigated. It was determined that 5-FU release increased with increasing PVA amount in the beads, whereas 5-FU release decreased with increasing crosslinking time and crosslinker concentration

A Histologically Diagnosed Case with Infantile Osteopetrosis Complicated by Hypopituitarism

Malignant infantile osteopetrosis is a rarely seen severe disorder which appears early in life with general sclerosis of the skeleton. It is caused by functionally defective osteoclasts which fail to resorb bone. Affected infants can exhibit a wide spectrum of clinical manifestations including impaired hematopoiesis, hepatosplenomegaly, visual impairment, and hypocalcemia. With the exception of secondary hyperparathyroidism, involvement of the endocrine system seems to be quite rare. Hypopituitarism is defined as underproduction of the growth hormone in combination with deficiencies of other pituitary hormones. Any lesion that damages hypothalamus, pituitary stalk, or anterior pituitary can cause secondary hypopituitarism. In this report, we presented a rare combination of malignant infantile osteopetrosis and secondary hypopituitarism in a newborn who presented predominantly with endocrinological symptoms. This is the first case report of malignant infantile osteopetrosis accompanied by hypopituitarism secondary to sclerosis of the sella turcica. On the other hand, this is a very interesting case which was diagnosed based on histological examination of bone marrow biopsy specimens despite lack of any clinical suspicion

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

<p>Abstract</p> <p>Background</p> <p>Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.</p> <p>In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.</p> <p>Results</p> <p>In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p> <p>Conclusions</p> <p>We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p

Effects of N-Acetylcysteine on Nicotinamide Dinucleotide Phosphate Oxidase Activation and Antioxidant Status in Heart, Lung, Liver and Kidney in Streptozotocin-Induced Diabetic Rats

Purpose: Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress plays a key role in the pathogenesis of diabetic complications. Nicotinamide dinucleotide phosphate (NADPH) oxidase is one of the major sources of ROS production in diabetes. We, therefore, examined the possibility that NADPH oxidase activation is increased in various tissues, and that the antioxidant N-acetylcysteine (NAC) may have tissue specifc effects on NADPH oxidase and tissue antioxidant status in diabetes. Materials and Methods: Control (C) and streptozotocin-induced diabetic (D) rats were treated either with NAC (1.5 g/kg/ day) orally or placebo for 4 weeks. The plasma, heart, lung, liver, kidney were harvested immediately and stored for biochemical or immunoblot analysis. Results: levels of free 15-F 2t-isoprostane were increased in plasma, heart, lung, liver and kidney tissues in diabetic rats, accompanied with significantly increased membrane translocation of the NADPH oxidase subunit p67phox in all tissues and increased expression of the membrane-bound subunit p22phox in heart, lung and kidney. The tissue antioxidant activity in lung, liver and kidney was decreased in diabetic rats, while it was increased in heart tissue. NAC reduced the expression of p22phox and p67phox, suppressed p67phox membrane translocation, and reduced free 15-F 2t-isoprostane levels in all tissues. NAC increased antioxidant activity in liver and lung, but did not signifcantly affect antioxidant activity in heart and kidney. Conclusion: The current study shows that NAC inhibits NADPH oxidase activation in diabetes and attenuates tissue oxidative damage in all organs, even though its effects on antioxidant activity are tissue specifc. © Yonsei University College of Medicine 2012.link_to_OA_fulltex

In vivo Bioimaging as a Novel Strategy to Detect Doxorubicin-Induced Damage to Gonadal Blood Vessels

INTRODUCTION: Chemotherapy may induce deleterious effects in normal tissues, leading to organ damage. Direct vascular injury is the least characterized side effect. Our aim was to establish a real-time, in vivo molecular imaging platform for evaluating the potential vascular toxicity of doxorubicin in mice. METHODS: Mice gonads served as reference organs. Mouse ovarian or testicular blood volume and femoral arterial blood flow were measured in real-time during and after doxorubicin (8 mg/kg intravenously) or paclitaxel (1.2 mg/kg) administration. Ovarian blood volume was imaged by ultrasound biomicroscopy (Vevo2100) with microbubbles as a contrast agent whereas testicular blood volume and blood flow as well as femoral arterial blood flow was imaged by pulse wave Doppler ultrasound. Visualization of ovarian and femoral microvasculature was obtained by fluorescence optical imaging system, equipped with a confocal fiber microscope (Cell-viZio). RESULTS: Using microbubbles as a contrast agent revealed a 33% (P<0.01) decrease in ovarian blood volume already 3 minutes after doxorubicin injection. Doppler ultrasound depicted the same phenomenon in testicular blood volume and blood flow. The femoral arterial blood flow was impaired in the same fashion. Cell-viZio imaging depicted a pattern of vessels' injury at around the same time after doxorubicin injection: the wall of the blood vessels became irregular and the fluorescence signal displayed in the small vessels was gradually diminished. Paclitaxel had no vascular effect. CONCLUSION: We have established a platform of innovative high-resolution molecular imaging, suitable for in vivo imaging of vessels' characteristics, arterial blood flow and organs blood volume that enable prolonged real-time detection of chemotherapy-induced effects in the same individuals. The acute reduction in gonadal and femoral blood flow and the impairment of the blood vessels wall may represent an acute universal doxorubicin-related vascular toxicity, an initial event in organ injury

Cationic cyclodextrin/alginate chitosan nanoflowers as 5-fluorouracil drug delivery system

Cyclodextrins (CDs) have widely been used as component of drug delivery systems. However unmodified cyclodextrins are associated with cytotoxicity and poor water solubility thus limiting their use in pharmaceutical industry. The cationic-β-cyclodextrin (Cat-β-CD) polymer cores were synthesized using β-CD, epichlorohydrin and choline chloride via a one-step polycondensation process. The main aim of this study was to synthesize hierarchical nanoflowers composed of cationic-β-CD as polymeric core along with alginate and chitosan “petals” (Cat-β-CD/Alg-Chi nanoflowers) as carriers for oral delivery of 5-Fluorouracil (5-FU) via an ionic-gelation technique. The drug loading capacity, particle size, zeta potential and surface morphology of the synthesized nanoflowers were determined. The prepared nanoflowers were formed with an average size of 300 nm and a zeta potential of + 9.90 mV with good encapsulation efficiency of up to 77.3%. In vitro release of 5-FU from the loaded nanoflowers showed controlled and sustained release compared to the inclusion complex alone. Cat-β-CD/Alg-Chi nanoflowers were assessed against L929 cells and found to be effectively inhibiting the growth of L929 cells in a concentration dependent manner