Losartan Induced Angioedema, a Rare Case Report and the Dilemma of Using Angiotensin II Receptor Blockers in Patients with Previous Angioedema with Angiotensin Converting Enzyme Inhibitors

Angiotensin Receptor Blockers (ARB) are used as an alternative of Angiotensin Converting Enzyme Inhibitors (ACEI) in patients where ACEIs cannot be used because of their known adverse effects, cough and angioedema. Thus ARB induced angioedema is considered to be a rare phenomenon and it is continued to be used as an alternatives of ACEIs. In this case report, we reported a case of 78-year-old gentleman who presented to emergency department with losartan, an ARB induced angioedema, who did not have history of any previous use of ACEIs. He was given steroids and antihistamine as a treatment. His angioedema resolved rapidly and he was discharged after six hours of emergency department (ED) observation with stable hemodynamically. We, the authors by reporting this case, wants to make clinicians aware ARB, however rarely, can cause angioedema, which can be life threatening if clinicians are not aware of it and diagnose and stop the offending drug promptly and treat it early.

Role of corticotrophin releasing hormone in cerebral infarction-related gastrointestinal barrier dysfunction

BACKGROUND： Corticotrophin releasing hormone （CRH） is believed to mediate stress-induced behaviors, implying a broader, integrative role for the hormone in the psychological stress response, and studies on CRH in physical stress are few. This study was undertaken to investigate whether CRH plays an important role in cerebral infarction-related gastrointestinal barrier dysfunction.METHODS： Thirty male Wistar rats were randomly divided into a pseudo-operation group （group C, n=10）, a cerebral infarction group （group I, n=10）, and a cerebral infarction ＋ ic α-helical-CRH （9-41） group （group Aic, n=10）. Urine samples were collected to determine the levels of epinephrine, norepinephrine, cortisol, and sucrose. At 24 hours after establishment of the models, blood samples were taken to determine the activity of diamine oxidase （DAO） and the concentration of D-lactic acid （D-lac）. The stomach was taken to determine gastric Guth score, and the hypothalamus was also taken to determine tissue CRH protein expression using Western blotting.RESULTS： The hypothalamus CRH protein, the indicators of stress, the plasma DAO activity and plasma D-lac, urine sucrose exertion and gastric Guth score in group I were higher than those in groups Aic and C.CONCLUSIONS： After cerebral infarction, CRH in the hypothalamus was increased, the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system were activated, gastrointestinal permeability was increased, and gastrointestinal barrier function was destroyed. CRH receptor antagonist alleviated the gastrointestinal barrier function.

A Case Report of Pediatric Cerebral Venous Thrombosis with Undiagnosed Complex Congenital Heart Disease: Tetralogy of Fallot with OS ASD: A Cataclysmic Ending

Cerebral Venous Sinus Thrombosis (CVST/CSVT) is occlusion of cerebral veins and venous sinuses of brain secondary to blood clot formation resulting in hindrance in the blood drainage system in brain, leading to disturbances the internal homeostasis of brain, raised intracranial pressure, cerebral edema, and 50% of cases will have venous infarction or venous hemorrhage (stroke). CVST although being a Rare disorder but may be more common in children than adults with greater risk in neonatal period i.e. first 28 days of life. Here we are discussing a case of Pediatric CVST in a 7-month-old baby boy who presented to Emergency Room (ER) with recurrent discrete episodes of vomiting, fever, seizures, drowsiness and respiratory distress. The fatal outcome in our child was attributed to delayed presentation in a tertiary care center, hence missed early diagnosis and treatment. In this child the CVST could be result of amalgamation of complex underlying ongoing multiple pathological processes: an acute systemic illness like sepsis, severe dehydration, undiagnosed and untreated complex congenital heart disease, tetralogy of fallot with osteum secondum atrial septal defect, worsening the coagulopathy. It takes this case even more unique. This discussion is to bring focus on the importance of knowledge about CVST amongst emergency physicians and primary care physicians, specially managing this rare disorder with flummox presentation mimicking other more common disorders, especially in pediatric and neonatal population where definitive history and chief complaints are often vague and difficult to obtain, making it more difficult to diagnose. We the authors hence reporting this case with intent to spread awareness of CVST, how to doubt it, detect it and then manage it, especially in places like Chhattisgarh, India, where CVST is not so uncommon. We believe early diagnosis, early presentation to tertiary care center with aggressive early treatment can significantly reduce the mortality. Should the parents brought the baby early to any tertiary care center owing to his complex deteriorating symptoms like high grade fever progressed to drowsiness and seizure episodes, could there be a different outcome for this child as well as his parents.

Reduction of mitomycin C resistance in human bladder cancer T24 cells by knocking-down ras oncogene

Aim:Mitomycin C(MMC)is a commonly used as intravesical treatment for superficial bladder cancer.However,its role in combination with ras inhibition has not been investigated.The aim of this study was to explore the role of ras in MMC-induced apoptosis in T24 bladder cancer cells and to determine the efficacy of combination therapy in vitro.Methods:We measured the effects of various doses of MMC on apoptosis induction as well as on ras,ERK and Ki-67 protein expression by T24 cell line using immunocytochemistry,flow cytometry and Western blotting.We also tested the effect of siRNA on ras employed singly or in combination with MMC.Results:T24 cells expressed high level of ras protein.MMC treatment increased the level of ras and ERK protein expression after 24 h,and decreased these levels after 72 h.Ras siRNA(100 nmol/L)caused massive apoptosis associated with a marked decrease in ras expression in T24 cells.When combined with low doses of MMC,ras siRNA(50 nmol/L)sensitized T24 cells to apoptosis and decreased their expression of ras.The effect of combined therapy was higher than that of either compound used alone.Expression levels of ERK,a downstream target of ras,declined following combination therapy.Conclusion:Ras siRNA in combination with low dose MMC is a possible treatment strategy for patients with ras-positive bladder tumors.

Implication of the LINGO2 gene in the predisposition to movement disorders

Previous reports on the pathogenesis of age-related movement disorders,such as Parkinson’s disease(PD)and essential tremor(ET),have demonstrated the potential implications of LINGO1(leucine-rich repeat and immunoglobulin domain-containing protein)gene.Although LINGO2 has a high degree of homology with LINGO1,but it is less characterized and the role of LINGO2 in the development of PD/ET remains unreported.Hence,this metaanalysis was conducted to evaluate the role of LINGO2 in PD/ET pathogenesis.A total of 4 studies,which complied with the Hardy-Weinberg equilibrium,were included in the meta-analysis.Analysis of the pooled odds ratio and confidence interval of the studies were performed for five genetic models,namely:allelic,dominant,recessive,homozygous,and heterozygous.No significant association was observed between the LINGO2 polymorphism and PD/ET,although subgroup analysis through conventional metaanalysis indicated that the recessive models of rs7033345 and rs10812774 are significantly associated with predisposition to ET in the Asian population.However,trial sequential analyses for both polymorphisms were unlikely to reveal any robust effect.Hence,studies with larger samples on this association are needed in the future to corroborate our results.