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Dabet Rynga, Malini R Capoor, Swati Varshney, Mayuresh Naik, V Gupta
Scedosporium apiospermum is a rare cause of infection but is increasingly being reported among immunocompromised individuals around the world. We report two cases of S. apiospermum, one of keratitis and the other of nasal polyp both from immunocompetent patients. The two cases were successfully treated with voriconazole. It is important to diagnose such infections as their antifungal susceptibility to amphotericin B is variable.
October 2017: Indian Journal of Pathology & Microbiology
Sumra Nazir, Ihsan Gadi, Moh'd Mohanad Al-Dabet, Ahmed Elwakiel, Shrey Kohli, Sanchita Ghosh, Jayakumar Manoharan, Satish Ranjan, Fabian Bock, Ruediger C Braun-Dullaeus, Charles T Esmon, Tobias B Huber, Eric Camerer, Chris Dockendorff, John H Griffin, Berend Isermann, Khurrum Shahzad
Cytoprotection by activated protein C (aPC) after ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation, and hence, cell-death forms disjunct from immunologically silent apoptosis are, in theory, more likely to be relevant. Because pyroptosis (ie, cell death resulting from inflammasome activation) is typically observed in IRI, we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRIs...
December 14, 2017: Blood
Andi Marquardt, Moh'd Mohanad Al-Dabet, Sanchita Ghosh, Shrey Kohli, Jayakumar Manoharan, Ahmed ElWakiel, Ihsan Gadi, Fabian Bock, Sumra Nazir, Hongjie Wang, Jonathan A Lindquist, Peter Paul Nawroth, Thati Madhusudhan, Peter R Mertens, Khurrum Shahzad, Berend Isermann
Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells...
November 2017: Journal of the American Society of Nephrology: JASN
Thati Madhusudhan, Hongjie Wang, Sanchita Ghosh, Wei Dong, Varun Kumar, Moh'd Mohanad Al-Dabet, Jayakumar Manoharan, Sumra Nazir, Ahmed Elwakiel, Fabian Bock, Shrey Kohli, Andi Marquardt, Ibrahim Sögüt, Khurrum Shahzad, Andreas J Müller, Charles T Esmon, Peter P Nawroth, Jochen Reiser, Triantafyllos Chavakis, Wolfram Ruf, Berend Isermann
Coagulation proteases have increasingly recognized functions beyond hemostasis and thrombosis. Disruption of activated protein C (aPC) or insulin signaling impair function of podocytes and ultimately cause dysfunction of the glomerular filtration barrier and diabetic kidney disease (DKD). We here show that insulin and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling pathway to maintain endoplasmic reticulum (ER) homeostasis. Analogous to insulin, physiological levels of aPC maintain ER proteostasis in DKD...
September 21, 2017: Blood
Shrey Kohli, Juliane Hoffmann, Franziska Lochmann, Paulina Markmeyer, Hanna Huebner, Fabian B Fahlbusch, Moh'd Mohanad Al-Dabet, Ihsan Gadi, Jayakumar Manoharan, Michael Löttge, Ana C Zenclussen, Anat Aharon, Benjamin Brenner, Khurrum Shahzad, Matthias Ruebner, Berend Isermann
Placental insufficiency jeopardizes prenatal development, potentially leading to intrauterine growth restriction (IUGR) and stillbirth. Surviving fetuses are at an increased risk for chronic diseases later in life. IUGR is closely linked with altered trophoblast and placental differentiation. However, due to a paucity of mechanistic insights, suitable biomarkers and specific therapies for IUGR are lacking. The transcription factor p45 NF-E2 (nuclear factor erythroid derived 2) has been recently found to regulate trophoblast differentiation in mice...
April 6, 2017: Cell Death & Disease
Zhao-Yang Lu, Rui-Lin Li, Hong-Sheng Zhou, Jing-Juan Huang, Zhi-Xiao Su, Jia Qi, Lan Zhang, Yue Li, Yi-Qin Shi, Chang-Ning Hao, Jun-Li Duan
Therapeutic ultrasound (TUS) has been demonstrated to improve endothelial nitric oxide synthase (eNOS) activity, which played a crucial role in the regulation of angiogenesis. Diabetes Mellitus (DM) impairs eNOS activity. We tested the hypothesis that DM may retard unilateral hindlimb ischemia-induced angiogenesis by inhibiting eNOS in high-fat diet (HFD)/streptozocin (STZ) induced diabetic mice, and that TUS may reverse DM-related impairment of angiogenesis. C57BL/6 mice were allocated to four groups: (A) mice were fed standard diet (control); (B) mice were fed standard diet and treated with TUS (control+TUS); (C) type-2 DM mice were induced by HFD/STZ (diabetic); and (D) type-2 DM mice and treated with TUS (dabetic+TUS)...
2016: American Journal of Translational Research
Khurrum Shahzad, Fabian Bock, Moh'd Mohanad Al-Dabet, Ihsan Gadi, Sumra Nazir, Hongjie Wang, Shrey Kohli, Satish Ranjan, Peter R Mertens, Peter P Nawroth, Berend Isermann
While a plethora of studies support a therapeutic benefit of Nrf2 activation and ROS inhibition in diabetic nephropathy (dNP), the Nrf2 activator bardoxolone failed in clinical studies in type 2 diabetic patients due to cardiovascular side effects. Hence, alternative approaches to target Nrf2 are required. Intriguingly, the tetracycline antibiotic minocycline, which has been in clinical use for decades, has been shown to convey anti-inflammatory effects in diabetic patients and nephroprotection in rodent models of dNP...
October 10, 2016: Scientific Reports
J Wolter, L Schild, F Bock, A Hellwig, I Gadi, M M Al-Dabet, S Ranjan, R Rönicke, P P Nawroth, K-U Petersen, C Mawrin, K Shahzad, B Isermann
Essentials The role of protein C (PC) activation in experimental autoimmune encephalitis (EAE) is unknown. PC activation is required for mitochondrial function in the central nervous system. Impaired PC activation aggravates EAE, which can be compensated for by soluble thrombomodulin. Protection of myelin by activated PC or solulin is partially independent of immune-modulation. SUMMARY: Background Studies with human samples and in rodents established a function of coagulation proteases in neuro-inflammatory demyelinating diseases (e...
November 2016: Journal of Thrombosis and Haemostasis: JTH
Shrey Kohli, Satish Ranjan, Juliane Hoffmann, Muhammed Kashif, Evelyn A Daniel, Moh'd Mohanad Al-Dabet, Fabian Bock, Sumra Nazir, Hanna Huebner, Peter R Mertens, Klaus-Dieter Fischer, Ana C Zenclussen, Stefan Offermanns, Anat Aharon, Benjamin Brenner, Khurrum Shahzad, Matthias Ruebner, Berend Isermann
Preeclampsia (PE) is a placenta-induced inflammatory disease associated with maternal and fetal morbidity and mortality. The mechanisms underlying PE remain enigmatic and delivery of the placenta is the only known remedy. PE is associated with coagulation and platelet activation and increased extracellular vesicle (EV) formation. However, thrombotic occlusion of the placental vascular bed is rarely observed and the mechanistic relevance of EV and platelet activation remains unknown. Here we show that EVs induce a thromboinflammatory response specifically in the placenta...
October 27, 2016: Blood
Michelle Woods, Giuliana Murfet
No abstract text is available yet for this article.
April 2016: Australian Nursing & Midwifery Journal
Meidong Yao, Yanhui Wu, Qingxiao Fang, Lulu Sun, Tingting Li, Hong Qiao
AIMS/INTRODUCTION: To investigate the association between two single nucleotide polymorphisms (SNPs; rs3774261 and rs822393) in the ADIPOQ gene and type 2 diabetes mellitus in Han Chinese from northeast China. MATERIALS AND METHODS: The present study comprised 993 type 2 diabetes mellitus patients and 966 unrelated controls from northeastern China. Two SNPs were sequenced using SNPscan. The distribution of genotype frequencies of the two SNPs in ADIPOQ between cases and controls, and in subgroups stratified based on body mass index, were compared using logistic regression analysis...
November 2016: Journal of Diabetes Investigation
Khurrum Shahzad, Fabian Bock, Moh'd Mohanad Al-Dabet, Ihsan Gadi, Shrey Kohli, Sumra Nazir, Sanchita Ghosh, Satish Ranjan, Hongjie Wang, Thati Madhusudhan, Peter P Nawroth, Berend Isermann
Glomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old diabetic (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) and CIX (inhibiting caspase-3, -6, -7, -8, and -10). Notably, despite reduction in glomerular cell death and caspase-3 activity by both inhibitors, only M-920 ameliorated dNP. Nephroprotection by M-920 was associated with reduced renal caspase-1 and inflammasome activity...
August 2016: Journal of the American Society of Nephrology: JASN
Allison Tsai
No abstract text is available yet for this article.
September 2015: Diabetes Forecast
Dabet Rynga, Malini Shariff, Monorama Deb
BACKGROUND: Acinetobacter has gained importance as a multi-drug resistant and hence a difficult to treat pathogen. This study was done to characterize our isolates with respect to drug resistance and presence of beta-lactamases which is a major mechanism of resistance and to type using RAPD and MLST so that comparison of our clones can be made with the existing international clones. METHODS: 100 isolates recovered from clinical samples from two hospitals in Delhi were tested for their susceptibility against major groups of antimicrobials...
September 4, 2015: Annals of Clinical Microbiology and Antimicrobials
M M Iversen, G Nefs, G S Tell, B Espehaug, K Midthjell, M Graue, F Pouwer
BACKGROUND: Depression and anxiety have been found to be predictors of poor health outcomes in diabetes, but mechanisms are still unclear. AIMS: To examine whether symptoms of anxiety and depression were associated with timing of initiating insulin therapy. METHODS: A cohort study of insulin-naive particpants with type 2 dabetes completed the Hospital Anxiey and Depression Scale, HADS-A (n = 731) and/or the HADS-D (n = 768) in the communy-based Nord-Trøndelag Health Study (1995-1997)...
October 2015: Journal of Psychosomatic Research
Wei Dong, Hongjie Wang, Khurrum Shahzad, Fabian Bock, Moh'd Mohanad Al-Dabet, Satish Ranjan, Juliane Wolter, Shrey Kohli, Juliane Hoffmann, Vishnu Mukund Dhople, Cheng Zhu, Jonathan A Lindquist, Charles T Esmon, Elisabeth Gröne, Herman-Josef Gröne, Thati Madhusudhan, Peter R Mertens, Dirk Schlüter, Berend Isermann
Ischemia-reperfusion injury (IRI) is the leading cause of ARF. A pathophysiologic role of the coagulation system in renal IRI has been established, but the functional relevance of thrombomodulin (TM)-dependent activated protein C (aPC) generation and the intracellular targets of aPC remain undefined. Here, we investigated the role of TM-dependent aPC generation and therapeutic aPC application in a murine renal IRI model and in an in vitro hypoxia and reoxygenation (HR) model using proximal tubular cells. In renal IRI, endogenous aPC levels were reduced...
November 2015: Journal of the American Society of Nephrology: JASN
S F Haghighi, Z Salehi, M R Sabouri, N Abbasi
Dabetic retinopatny Is the most common microvascular complication of diabetes and a leading cause of blindness in industrialized countries. Oxidative stress plays an important role in the development of microangiopathic complications in diabetes. Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme in the cellular defense against agents that induce oxidative stress. The aim of the present study was to assess whether the MnSODA16V (C47T) polymorphism is associated with Diabetic retinopathy in northern Iran...
January 2015: Molekuliarnaia Biologiia
Khurrum Shahzad, Fabian Bock, Wei Dong, Hongjie Wang, Stefan Kopf, Shrey Kohli, Moh'd Mohanad Al-Dabet, Satish Ranjan, Juliane Wolter, Christian Wacker, Ronald Biemann, Stoyan Stoyanov, Klaus Reymann, Peter Söderkvist, Olaf Groß, Vedat Schwenger, Sascha Pahernik, Peter P Nawroth, Herman-Josef Gröne, Thati Madhusudhan, Berend Isermann
Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro...
January 2015: Kidney International
Tim S Poulsen, Maiken L M Espersen, Vibeke Kofoed, Tanja Dabetic, Estrid Høgdall, Eva Balslev
The purpose was to evaluate and compare 5 different HER2 genetic assays with different characteristics that could affect the performance to analyze the human epidermal growth factor 2 (HER2) gene copy number under low and high throughput conditions. The study included 108 tissue samples from breast cancer patients with HER2 immunohistochemistry (IHC) results scored as 0/1+, 2+, and 3+. HER2 genetic status was analysed using chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH)...
2013: International Journal of Breast Cancer
G Mahendran, G Thamotharan, S Sengottuvelu, V Narmatha Bai
ETHNOPHARMACOLOGICALS RELEVANCE: Swertia corymbosa locally called as Shirattakuchi have a long history of use in Ayurveda herbal preparations in Indian traditional system of medicine. It has been used in folklore medicine for the treatment of diabetes. AIM OF THE STUDY: The present study aimed to investigate the effect of the methanolic extract of Swertia corymbosa (SC) in diabetic and to analyze its chemical composition by HPLC-ESI/MS that may correlate with their pharmacological activities...
February 12, 2014: Journal of Ethnopharmacology
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