Isolated diastolic hypertension and its risk factors in semi-rural population of South India

BackgroundIsolated diastolic hypertension (IDH) has been actively discussed for the last two decades because of its prevalence in a younger population and its association with cardiovascular disease. Furthermore, the association of IDH is significant in South Asian Countries such as India because relatively younger populations are known to have a higher risk of cardiovascular events.ObjectiveThe objective of this study is to find prevalence of IDH and its risk correlates in a semiurban population of South Indian state of Andhra Pradesh.MethodsData were collected using the modified World Health Organization - STEPwise approach to Surveillance (WHO STEPS) questionnaire for 16,636 individuals from a group of villages under Thavanampalle Mandal. Collated data were analyzed for prevalence and risk factors of IDH.ResultsPrevalence of IDH was found to be 4.0% with mean age of 46.0 (±SD 13.6) years and a relatively higher prevalence in men (5.3%) as compared with women (3.2%). The prevalence of IDH peaked in the fifth decade of life (40–49 years of age) and declined thereafter. Among various risk factors that were analyzed for their association with IDH, only age, body weight, and body mass index retained their significance in multivariate binary logistic regression analysis.ConclusionThere is a significant prevalence of IDH below 50 years of age in the semiurban population of South India. As IDH in young and middle age is known to be associated with increased risk of cardiovascular events and end organ involvement, it highlights need for study and development of effective IDH management strategies to reduce associated morbidity and mortality.     

Cooperative role of caveolin-1 and C-terminal Src kinase binding protein in C-terminal Src kinase-mediated negative regulation of c-Src

In the present study, we assessed the cooperative roles of C-terminal Src kinase (Csk) binding protein (Cbp) and Caveolin-1 (Cav-1) in the mechanism of Src family tyrosine kinase (SFK) inhibition by Csk. SFKs are inactivated by phosphorylation of their C-terminal tyrosine by Csk. Whereas SFKs are membrane-associated, Csk is a cytoplasmic protein and therefore requires membrane adaptors such as Cbp or Cav-1 for recruitment to the plasma membrane to mediate SFK inhibition. To determine the specific role of Cav-1 and Cbp in SFK inhibition, we measured c-Src activity in the absence of each membrane adaptor. It is noteworthy that in lungs and fibroblasts from Cav-1(-/-) mice, we observed increased expression of Cbp compared with wild-type (WT) controls. However, both c-Src activity and Csk localization at the membrane were similar between Cav-1(-/-) fibroblasts and WT cells. Likewise, Cbp depletion by small interfering RNA (siRNA) treatment of WT cells had no effect on basal c-Src activity, but it increased the phosphorylation state of Cav-1. Immunoprecipitation then confirmed increased association of Csk with phosphomimicking Cav-1. Knockdown of Cbp by siRNA in Cav-1(-/-) cells revealed increased basal c-Src activity, and re-expression of WT Cav-1 in the same cells reduced basal c-Src activity. Taken together, these results indicate that Cav-1 and Cbp cooperatively regulate c-Src activity by recruiting Csk to the membrane where it phosphorylates c-Src inhibitory tyrosine 529. Furthermore, when either Cav-1 or Cbp expression is reduced or absent, there is a compensatory increase in the phosphorylation state or expression level of the other membrane-associated Csk adaptor to maintain SFK inhibition.     

Hepatitis B virus reactivation in a Juvenile Rheumatoid arthritis patient under treatment and its successful management: a complicated case

Juvenile rheumatoid arthritis is a common chronic inflammatory disease in the childhood and it can differentiate rarely into spondiloarthropaties. It is one of the important causes of chronic pain and disability. Some of the drugs used for the treatment have immunosupressive activity. One of the serious side-effects of immunosupressive treatment is activation of opportunistic pathogens. Hepatitis B virus (HBV) is one of these pathogens, and the rate of carriers in the population is considerably high. It can cause liver damage and death if reactivated. Thus, the management of oppotunistic pathogens becomes a complex issue when treating rheumatic diseases with immunosupressive drugs. In this case report, we present a juvenile rheumatoid arthritis patient whose liver enzymes raised while he was under treatment and afterwards HBV reactivation was determined as the cause. When reactivation was detected, we started controlled antiviral therapy. We achieved successful clinical and laboratory results after adding biological agents to the treatment. Careful evaluation of the patients who have indication for immunosuppressive agents and regular follow-up in case of infection may be protective from severe morbidity and/or mortality.     

Ipilimumab in treatment-naive and previously treated patients with metastatic melanoma: retrospective analysis of efficacy and safety data from a phase II trial

Ipilimumab is a fully human, monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to potentiate antitumor T-cell responses. In a phase III trial, ipilimumab monotherapy at 3 mg/kg demonstrated an improvement in overall survival (OS) in patients with previously treated, metastatic melanoma. Here, we conducted a retrospective analysis of efficacy and safety data from a phase II clinical trial in which treatment-naive and previously treated patients with metastatic melanoma received ipilimumab at an investigational dose of 10 mg/kg. Patients were randomized 1:1 to receive oral budesonide or placebo, and ipilimumab at 10 mg/kg every 3 weeks for 4 doses, to determine whether prophylactic budesonide affected the rate of grade ≥2 diarrhea. One hundred fifteen patients were randomized and treated: 62 had received prior systemic therapy for metastatic disease and 53 had not. No efficacy endpoint was affected by budesonide therapy, and the efficacy data were therefore pooled for budesonide and placebo subgroups. Median OS was 30.5 months for treatment-naive patients who received ipilimumab, with survival rates of 69.4%, 62.9%, and 56.9% at 12, 18, and 24 months. In previously treated patients who received ipilimumab, median OS was 13.6 months, with survival rates of 50.0%, 37.7%, and 28.5% at 12, 18, and 24 months. There were no meaningful differences in the number of objective responses or rate of grade ≥2 diarrhea between groups. These retrospective analyses are the first to provide survival data for ipilimumab in treatment-naive and previously treated patients within the same clinical trial.     

Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.     

MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury

Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10⁶ hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood–brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.