Inflammation and oxidative stress induced by cigarette smoke in Lewis rat brains

Exposure to cigarette smoke has been associated with an increased risk of neurological diseases such as stroke, Alzheimer's disease and multiple sclerosis. In these studies, serum and brain sections from Lewis rats or those exposed to cigarette smoke and control rats were examined for evidence of increased inflammation and oxidative stress. Immunocytochemical staining of brain sections from CS-exposed rats showed increased expression of class II MHC and, in ELISA, levels of IFN-gamma and TNF-α were higher than for non-exposed rats. In polymerase chain reaction assays there was increased interferon-gamma, TNF-α, IL-1α, IL-1β, IL-23, IL-6, IL-23, IL-17, IL-10, TGF-β, T-bet and FoxP3 gene expression with CS exposure. There was also markedly elevated MIP-1α/CCL3, less prominent MCP-1/CCL2 and no elevation of SDF-1α gene expression. Analysis of samples from CS-exposed and control rats for anti-oxidant expression showed no significant difference in serum levels of glutathione and, in brain, similar levels of superoxide dismutase and decreased thioredoxin gene expression. In contrast, there was increased brain gene expression for the pro-oxidants iNOS and the NADPH components NOX4, dual oxidase 1 and p22^phox. Nrf2 expression, which is typically triggered as a secondary response to oxidative stress, was also increased in brains from CS-exposed rats with nuclear translocation of this protein from cytoplasm demonstrated in astrocytes in association with increased expression of the aryl hydrocarbon receptor gene, an Nrf2 target. These studies, therefore, demonstrate that CS exposure in these animals can trigger multiple immune and oxidative responses that may have important roles in the pathogenesis of CNS inflammatory neurological diseases.     

Teleophthalmology in Diabetic Retinopathy

Over the past decade, there have been rapid strides in progress in the fields of telecommunication and medical imaging. There is growing evidence regarding use of teleophthalmology for screening of diabetic retinopathy. This article highlights some pertinent questions regarding use of telescreening for diabetic retinopathy. It deals with evidence regarding accuracy of diagnosis, patients satisfaction and cost-effectiveness. The American Telemedicine Association have given certain guidelines for teleheath practices for diabetic retinopathy. The article discusses regarding these guidelines. Finally, a working model for diabetic retinopathy screening through teleophthalmology has been described. Telescreening for diabetic retinopathy seems to be a cost-effective, accurate, and reliable method for screening for diabetic retinopathy. The American Telemedicine Association has set up guidelines for telescreening that should be adhered to provide quality screening services to people with diabetes.     

Multimodality Imaging of Submitral Left Ventricular Aneurysm

Submitral left ventricular aneurysms are a rare nonischemic aneurysm thought to be developmental in origin. These aneurysms invariably occur at the site of posterior mitral annulus and lead to mitral valve incompetence. We hereby describe a case of a 30‐year‐old adult with a rare form of submitral left ventricular aneurysm involving whole of the posterior mitral annulus. Multimodality imaging with two‐dimensional echocardiography, three‐dimensional echocardiography, computed tomography and invasive left ventriculography helped the patient to undergo successful resection of the aneurysm along with mitral valve replacement.     

Comparative study of pulsatile and nonpulsatile flow during cardio-pulmonary bypass

The use of nonpulsatile flow during extracorporeal circulation remains popular despite theoretical advantages of pulsatile cardiopulmonary bypass (CPB). Pulsatile CPB is considered to be more physiological than nonpulsatile flow as the pulsatile energy ensures the patency of the vascular bed and mechanical motion of tissue fluid around the cell membrane, improves microcirculation and enhances diffusion. The purpose of this study was to compare the effect of pulsatile and nonpulsatile flow on the coagulation profile, liver and kidney function and also on the haemodynamics in patients undergoing coronary artery bypass grafting on CPB. One hundred patients between 35 and 65 years of age with normal left ventricular function were randomly divided into two equal groups: Pulsatile (P) and nonpulsatile (NP). Haematological parameters, clotting profile, renal parameters, hepatic function tests and haemodynamic variables were measured preoperatively and postoperatively at specific intervals. Surgical, anaesthetic and CPB regimen was standard in all cases. There was a decrease in platelet count during and after CPB in both groups. Coagulation profile and renal function parameters remained similar in both groups except that creatinine clearance was better in group P on the first postoperative day. Urine output was also better in group P. There was no change in liver function tests in both groups. The haemodynamic variables were comparable in both groups. The systemic vascular resistance was higher in group NP postoperatively and oxygen consumption was higher in group P post CPB. In conclusion we did not find any significant difference between pulsatile and nonpulsatile flow during CPB except the creatinine clearance and urine output were better in pulsatile group.     

Typhoid and paratyphoid fever

Typhoid fever is estimated to have caused 21.6 million illnesses and 216,500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings.     

Novel Therapies and Treatment Strategies for Patients with Inflammatory Bowel Disease

Purpose of review

This article reviews current treatment options and strategies and provides an update on the status of drug development programs of new therapeutic agents for inflammatory bowel diseases (IBD).

Recent findings

In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e.g., caused by immunogenicity), side effects, or other poorly characterized mechanisms. Recently, additional therapies, such as vedolizumab, an integrin blocker that prevents T cell trafficking to the gut, and ustekinumab, an antibody blocking the common p40 subunit of interleukin (IL)-12 and 23, were introduced to the market. In addition, other agents including novel anti-trafficking therapies (e.g., anti-β7 and sphingosine-1-phosphate receptor modulators), antibodies against p19 (unique to IL-23), and small molecules including Janus kinase inhibitors are under investigation in phase II and III trials.Furthermore, the management of IBD has evolved from targeting control of symptoms to suppression of mucosal inflammation. This shift in thinking has been accompanied by the early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation and utilization of a treat to target paradigm approach, and adoption of therapeutic drug monitoring.

Summary

The treatment landscape for IBD is rapidly evolving with the recent approval of novel biologics as well as several other agents in late phase of clinical development. Moreover, we have started to use agents more intelligently with a focus on risk stratification and early use of highly effective therapy in high-risk patients, treat to target using patient-reported outcomes (PROs), biomarkers, endoscopy, and therapeutic drug monitoring.