Chronic cyanidin-3-glucoside administration improves short-term spatial recognition memory but not passive avoidance learning and memory in streptozotocin-diabetic rats

This research study was conducted to evaluate the efficacy of chronic cyanidin‐3‐glucoside (C3G) on alleviation of learning and memory deficits in diabetic rats as a result of the observed antidiabetic and antioxidant activity of C3G. Male Wistar rats were divided into control, diabetic, C3G‐treated‐control and ‐diabetic groups. The C3G was administered i.p. at a dose of 10 mg/kg on alternate days for eight weeks. For evaluation of learning and memory, initial latency (IL) and step‐through latency (STL) were determined at the end of study using passive avoidance test. Meanwhile, spatial recognition memory was assessed as alternation in the Y‐maze task. Oxidative stress markers in brain tissue were also measured. It was found that the alternation score of the diabetic rats was lower than that of control (p < 0.01) and C3G‐treated diabetic rats showed a higher alternation score as compared to diabetic group (p < 0.05). Diabetic rats also developed a significant impairment in retention and recall in passive avoidance test (p < 0.01) and C3G treatment of diabetic rats did not produce any significant improvement. Meanwhile, increased level of malondialdehyde (MDA) in diabetic rats was significantly reduced following C3G treatment (p < 0.05). Taken together, chronic C3G could improve short‐term spatial recognition memory disturbance in the Y‐maze test but not retention and recall capability in passive avoidance test in STZ‐diabetic rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Comparative characterization of cellular and molecular anti-restenotic profiles of paclitaxel and sirolimus. Implications for local drug delivery

Pleiotropic anti-restenotic properties of drugs that are eluted from coated stents are critical for efficacy and safety. Little is known about comparative drug properties in appropriate human coronary target cell lines for the two compounds that are utilized on FDA-approved drug-eluting stent (DES) platforms, paclitaxel (PTX) and sirolimus (SRL). Target cell lines that play a pivotal role for the pathogenesis of restenosis and vascular healing include human coronary artery smooth muscle (CASMC) and endothelial cells (CAEC). PTX and SRL inhibited CASMC and CAEC proliferation and migration efficiently. However, there was a differential effect on proliferation and migration in CAEC with a more profound inhibition of both parameters by PTX, even at low dosages. Induction of cytotoxicity and apoptosis was pronounced in PTX- and very modest in SRL-treated CASMC and CAEC. PTX increased eNOS activity and nitric oxide (NO) release from CAEC. Neutrophilic leukocyte activation and transmigration, which should be avoided since it may precipitate adverse coronary events such as restenosis and stent thrombosis, was suppressed by SRL, whereas PTX tended to increase neutrophilic leucocyte activity. Therefore, although the primary drug target, inhibition of mitogen-mediated CASMC proliferation, is effectively accomplished by both drugs, auxiliary pharmacological properties that are crucial for the anti-restenotic drug effect and vascular healing are considerably different between PTX and SRL. In comparison with PTX, SRL shows minor interference with endothelial cell proliferation and migration, lower levels of cytotoxicity and apoptosis, a broader therapeutic range and distinctive immunosuppressive properties.     

Direct effects of leptin on size and extracellular matrix components of human pediatric ventricular myocytes

OBJECTIVE: There is a well-documented association between obesity and heart failure although the mechanistic basis for this correlation is unclear. Both extracellular matrix remodeling and left ventricular hypertrophy are well-defined components of remodeling in heart failure, and here we further investigate the role of leptin, the obese gene product, on these parameters. METHODS: We used primary human pediatric ventricular cardiomyocytes combined with gelatin zymography, quantitative PCR analysis, proline and leucine incorporation assays, and investigation of kinase activation by Western blotting. RESULTS: We show using gelatin zymography that leptin dose-dependently (0-60 nM) increased proteolytic activity at approximately 72 kDa. Accordingly, upon quantitative PCR analysis we found that leptin increased expression of matrix metalloproteinase-2 (MMP-2). Leptin also caused an increase in collagen type III and IV mRNA expression and a decrease in collagen type I mRNA expression. This was reflected in no significant change in total collagen synthesis, measured by [3H]proline incorporation, in response to leptin. A statistically significant increase in cell size, [3H]leucine incorporation, and expression of well-characterized markers of cardiac hypertrophy, namely cardiac alpha-actin and myosin light chain, were observed in response to leptin. We demonstrate activation of Janus-activated kinase and mitogen-activated protein kinase pathways by leptin, and using pharmacological inhibitors we show that these signaling pathways play a role in mediating the effects of leptin. CONCLUSIONS: Our findings show that leptin regulates cell size, stimulates MMP-2 expression, and alters the profile, but not the total content, of collagen in human cardiomyocytes. This indicates the potential for altered leptin sensitivity to directly regulate cardiac remodeling in obesity.     

Congenital superior sternal cleft—An unusual age of diagnosis with review of the literature

Sternal cleft is a rare congenital anomaly which is generally observed at birth and stays asymptomatic in most cases. The aetiology remains obscure. Surgery is recommended not only to protect the heart and other mediastinal contents from trauma but also to improve respiratory dynamics.We report the case of a 23-year-old young woman with a failure of the upper two thirds of the sternum, causing pain in lateral decubitus position and an aesthetic appearance problem.Through this case report we will show the chest computed tomography (CT) aspects regarding this malformation and we will give a review of the literature.     

Corticosteroids usage in pediatric liver transplantation: To be or not to be!

Abstract:  The theoretical risks of early SW, <3 months post-LT, and complete elimination (steroid-free LT) lie in mainly three areas, namely the risks of AGR, CGR, and the development of d-AIH that has been described in SW post-LT in children. These should be balanced against the benefits of early SW mainly manifested as effects on growth post-LT. In this paper, we focused on the clinical trials that included CS therapy risks and benefits in pediatric LT. Focusing mainly on CGR and d-AIH as risks, and the beneficial effects on growth post-LT with either low-dose CS, SW, or steroid-free regimens. Main conclusions from comparing a large number of studies are: early SW or elimination from immunosuppression protocols was neither harmful to the patient nor to the graft survival rate in the short term, the overall impression is that steroids negatively affect growth in LT recipients when used in high doses and prolonged course, and that development of d-AIH is not associated with CS therapy with evidence that chronic low dose steroids post-LT have no preventative role against d-AIH.     

New paradigms in anticancer therapy: targeting multiple signaling pathways with kinase inhibitors

Signal transduction in cancer cells is a sophisticated process that involves receptor tyrosine kinases (RTKs) that eventually trigger multiple cytoplasmic kinases, which are often serine/threonine kinases. A number of tumor models have identified several key cellular signaling pathways that work independently, in parallel, and/or through interconnections to promote cancer development. Three major signaling pathways that have been identified as playing important roles in cancer include the phosphatidyl inositol-3-kinase (PI3K)/AKT, protein kinase C (PKC) family, and mitogen-activated protein kinase (MAPK)/Ras signaling cascades. In clinical trials, highly selective or specific blocking of only one of the kinases involved in these signaling pathways has been associated with limited or sporadic responses. Improved understanding of the complexity of signal transduction processes and their roles in cancer has suggested that simultaneous inhibition of several key kinases at the level of receptors and/or downstream serine/threonine kinases may help to optimize the overall therapeutic benefit associated with molecularly targeted anticancer agents. Using targeted agents to inhibit multiple signaling pathways has emerged as a new paradigm for anticancer treatment based on preclinical and clinical data showing potent anti-tumor activity of single drugs inhibiting multiple molecular targets or combination therapies involving multiple drugs with selective or narrow target specificity. Preclinical and clinical studies point to molecules on vascular endothelial cells and pericytes as being important targets for anticancer therapies, as well as molecules on or within tumor cells themselves. This suggests that optimal therapeutic approaches to cancer may involve targeting multiple molecules found in both the tumor and supportive tissues. In this review, we will use the most recent preclinical and clinical data to describe this emerging paradigm for anticancer therapy involving targeting multiple signaling pathways with tyrosine or serine/threonine kinase inhibitors.     

A study of neonatal morbidity and mortality at Damanhour Teaching Hospital Newborn Unit

Newborns in Behira governorate represented 2.5% of total Behira population in 2000. In Damanhour teaching hospital 4040 live births were delivered during one year from 1st January 1995 to 31st December 1995. During this period an observational study of morbidity and mortality of the newborn unit (NBU) attendants was performed. The total number of admitted neonates to the newborn unit were 557, of those 307 were borne in hospital (representing 7.6% of total hospital deliveries) and 250 were admitted from outside the hospital. The number of eligible neonates for the study were 544, they spent 2355 days in the unit, thirteen neonates were excluded from the analysis. The low birth weight (< 2500 gm) were 218 (40% of studied cases). According to Dubowitz score, Infants were classified as appropriate for gestational age (AGA) 60.7%, small for gestational age (SGA) 27.6% and large for gestational age (LGA) 11.8%. Neonates with birth weight < 1500 gm and gestational age < 28 weeks had the worst prognosis with a mortality rate of 60.3% and 65.1% respectively. All neonates had 738 morbid conditions, the major causes were prematurity 262 (35.5%), respiratory distress (RD) 200 (27%) hyperbilirubinaemia 115 (15.6%) and sepsis 58 (7.9%). Most of the cases (73.9%) were admitted on the day of birth. The mortality rate was 28.5%. The leading causes of mortality were, RD ( 34.8% of all deaths), prematurity (32.9%) and sepsis (15.5%). Neonatal convulsions and congenital anomalies had highest case fatality rates (50% for each). Most of deaths (51%) occurred on the first day of admission. "The early results of this work was presented at the 6th international conference of the General Organization of "Teaching Hospitals and Institutes (GOTHI) "Health Services.....Present and future" 7-9 November 2001".