Renin angiotensin system modulates mTOR pathway through AT2R in HIVAN

Mammalian target of rapamycin (mTOR) has been reported to contribute to the development of HIV-associated nephropathy (HIVAN). We hypothesized that HIV may be activating renal tissue mTOR pathway through renin angiotensin system (RAS) via Angiotensin Receptor Type II receptor (AT2R). Renal tissues of Vpr transgenic and Tg26 (HIVAN) mice displayed enhanced phosphorylation of mTOR and p70S6K. Aliskiren, a renin inhibitor attenuated phosphorylation of both mTOR and p70S6K in renal tissues of HIVAN mice. Interestingly, Angiotensin Receptor Type I (AT1R) blockade did not modulate renal tissue phosphorylation of mTOR in HIVAN mice; on the other hand, AT2R blockade attenuated renal tissue phosphorylation of mTOR in HIVAN mice. In vitro studies, both renin and Ang II displayed enhanced mouse tubular cell (MTC) phosphorylation of p70S6K in a dose dependent manner. HIV/MTC also displayed enhanced phosphorylation of both mTOR and p70S6K; interestingly this effect of HIV was further enhanced by losartan (an AT1R blocker). On the other hand, AT2R blockade attenuated HIV-induced tubular cell phosphorylation of mTOR and p70S6K, whereas, AT2R agonist enhanced phosphorylation of mTOR and p70S6K. These findings indicate that HIV stimulates mTOR pathway in HIVAN through the activation of renin angiotensin system via AT2R.     

Echocardiography for Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy. The prevalence of phenotypic expression, in the absence of another systemic or cardiac disease causing increased left ventricular (LV) wall thickness, is estimated to be 1:500. The frequency of clinical presentation is far less, highlighting the need for a non-invasive diagnostic imaging tool. Echocardiography is readily available and allows for structural characterization and hemodynamic assessment of the hypertrophic heart and to screen patients at-risk for HCM, such as first degree relatives of affected individuals, and differentiate HCM from the athletic heart. Echocardiography can also be used to assess for anatomic abnormalities of the mitral valve apparatus that may exacerbate LV outflow track obstruction and to further risk stratify patients during exercise. Finally, echocardiography plays an integral role in guiding alcohol septal ablation procedures.     

A study of clinical presentation and delays in management of acute myocardial infarction in community

To assess the medico social demographics of acute myocardial infarction (AMI) in our community we studied 609 patients presenting between January 2008 to December 2008 with a detailed questionnaire in four centres of UP. Medical attention was sought late (> 6 hours) in 316 (51.6%), thrombolysis was obtained in 45.2% (275) and presentation was atypical in 16.3% (99). 36.2% (221) had pre-monitory symptoms of which 68% (150) ignored the same while of 32% (71) who did seek medical attention 47.9% (37) were brushed away as non-cardiac in origin. 20.3% (46/226) of hypertension, 23.2% (43/185) of diabetes and 83.4% (91/109) of hyperlipidaemia was diagnosed post event. We conclude that at least half of patients with AMI do not get definitive therapy, at least one in 10 patients do not have the classical symptoms, reasonable proportion are unaware of their risk factors, and a good majority have pre-monitory symptoms which get overlooked.     

The adenylyltransferase domain of bacterial Pnkp defines a unique RNA ligase family

Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from ten different phyla. To gain insight to the mechanism and evolution of this repair system, we determined the crystal structures of the ligase domain of Clostridium thermocellum Pnkp in three functional states along the reaction pathway: apoenzyme, ligase•ATP substrate complex, and covalent ligase-AMP intermediate. The tertiary structure is composed of a classical ligase nucleotidyltransferase module that is embellished by a unique α-helical insert module and a unique C-terminal α-helical module. Structure-guided mutational analysis identified active site residues essential for ligase adenylylation. Pnkp defines a new RNA ligase family with signature structural and functional properties.     

Transcatheter Retrieval of Embolized AMPLATZER Septal Occluder

In selected patients, transcatheter closure of atrial septal defects with the AMPLATZER Septal Occluder has yielded excellent results. However, there is a slight risk of device embolization after deployment. We report the case of a 26-year-old woman in whom an embolized AMPLATZER device was retrieved percutaneously from the right pulmonary artery. We also discuss important technical principles for managing this uncommon but potentially severe complication.Key words: Device removal/methods, embolization, therapeutic/instrumentation, heart catheterization/instrumentation, heart septal defects, atrial/ultrasonography, patient selection, prosthesis implantation/adverse effects, prostheses and implants, septal occluder device/adverse effects, treatment outcomeTranscatheter closure of atrial septal defects (ASDs) with use of the AMPLATZER® Septal Occluder (St. Jude Medical, Inc.; St. Paul, Minn) has yielded excellent results in properly selected patients.^1,2 The major advantage of the AMPLATZER occluder is its easy retrieval at all stages of deployment before its final release from the delivery cable. Although embolization of AMPLATZER ASD occluders is rare, it can occur even when interventional cardiologists are experienced. Despite an earlier belief that the transcatheter retrieval of embolized AMPLATZER devices would be difficult, success rates from 50% to 75% have been reported.^3,4 We describe the retrieval of an embolized AMPLATZER device in a young woman. In addition, we present some technical principles with which operators practicing device closure should be familiar.     

Intraocular endoscopy: A review

Optimal visualization is one of the most challenging aspects of performing vitreoretinal surgery. In situations where conventional microscopic techniques provide poor posterior visualization, the adjunctive skill set of endoscopic visualization may be needed. This allows for by-passing the opaque anterior segment media and getting access to the posterior segment pathology. Endoscopic vitrectomy is a useful and unique adjunct to microincision vitreoretinal surgery. The optical set-up of endoscopy allows for clinical approaches that are impossible with regular microscope viewing systems. These include the ability to observe across optically significant anterior segment opacities and directly visualize the posterior segment of the eye. It also allows for visualizing the difficult-to-access retroirideal, retrolental, and anterior retinal structures. Surgical access to anatomic spaces like the pars plana, pars plicata, ciliary sulcus, ciliary body, and peripheral lens is tedious. This is made simpler by endoscopy. In this review, we summarize and review the usage of the intraocular endoscope as a diagnostic and therapeutic armamentarium across a wide spectrum of ocular pathologies.