Signaling Mechanisms Regulating Fibroblast Activation, Phenoconversion and Fibrosis in the Heart.

Cardiac fibroblasts (CFs) maintain the cardiac extracellular matrix (ECM) through myocardial remodelling. The remodelling process can become dysregulated during various forms of heart disease  which leads to an overall accumulation of ECM. This results in cardiac fibrosis which increases the risk of heart failure in many patients. During heart disease, quiescent CFs undergo phenoconversion to an activated cell type called cardiac myofibroblasts (CMFs). Factors influencing phenoconversion include transforming growth factor β (TGF-β) which via SMADs (small mothers against decapentaplegic) activates the myofibroblast marker gene αSMA (α smooth muscle actin). Signaling molecules as diverse as NAD(P)H oxidase 4 (Nox4) and Wnt have been found to interact with TGF-β signalling via SMADs. Pathways, including FAK/TAK/JNK and PI3K/Akt/rac have also been implicated in activating phenoconversion of fibroblasts. Another major contributor is mechanical stress exerted on CFs by ECM changes, which involves activation of ERK and subsequent αSMA expression. Other factors, such as the mast cell protease tryptase and the seeding density also affect the phenoconversion of fibroblast cultures in vitro. Further, reversal of myofibroblast phenotype has been reported by a negative regulator of TGF-β, Ski, as well as the hormone relaxin and the second messenger cAMP. Targeting the signaling molecules involved in promoting phenoconversion of CFs to CMFs presents a possible method of controlling cardiac fibrosis. Here, we provide a brief review of signaling mechanisms responsible for phenoconversion and identify critical targets for the treatment of cardiac fibrosis.

A Study of Renal Calyces by Using Barium Contrast.

Objectives: To know the pelvicalyceal anatomy by radiological method that helps in localizing the calculi or tumors in kidneys. Materials and method: The study was conducted in Sri Devaraj Urs Medical College, Tamaka, Kolar from 2011 to 2013. Forty four adult, formalin embalmed cadaveric kidneys (20 right and 24 left) were injected with 8 to 10 ml of 10% radio opaque barium sulphate solution into the renal pelvis and calyces and radiographs were taken in anteroposterior view. Results: The observations were statistically analyzed. There were 14 extra renal pelves and 30 intra renal pelves. The major calyces were classified into three categories [Double (D), Three (T) and Multiple (M) divisions]. Out of 44 kidneys 20 were right and 24 left.. 23 kidneys presented multiple (more than 4) calyces, 12 had two major calyces and only 9 presented with three major calyces). Typical ‘Y’ arrangement in 03 out of 12 and typical multiple in 03 out of 23 kidneys. There were 14 kidneys (31.8%) presented with extra renal pelvis whereas 30 kidneys (68.2%) presented intrarenal formation of the renal pelvis. Conclusion: Due to the variation in the number of major and minor calyces, position of renal pelvis (intrarenal and extra renal), the knowledge of pelvicalyceal anatomy will help the urologist and nephrologists to pin point the position of renal calyceal calculi or malignant growth for the surgery to be carried out.

Analysis of autosomal dominant spinocerebellar ataxia type 1 in an extended family of central India.

Background: Spinocerebeller ataxia type 1 (SCA1) is a specific type of ataxia among a group of inherited diseases of the central nervous system. In SCA1, genetic defects lead to impairment of specific nerve fibers carrying messages to and from the brain, resulting in the degeneration of the cerebellum, the coordination center of the brain. We investigated 24 members of an extended family in Gwalior city, India, some of which were earlier clinically diagnosed to be suffering from yet unconfirmed type of SCA neurodegenerative disorder. Materials and Methods: All the family members from each age group were screened clinically and the characteristics of those resembling with ataxia were recorded for diagnosis by MRI. The confirmed patients of the family were genetically tested by PCR based molecular testing to identify the type of SCA (i.e., SCA 1, 2, 3, 4, 6 or 7). Family tree of the disease inheritance was constructed by pedigree based method. Result and Conclusion: We found the clinical (symptoms and MRI) and genetic (Pedigree and PCR) results to be correlated. The PCR result revealed the disease to be of SCA 1 type being inherited in the family.

An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of fixed duration therapy.

The present study was carried out involving 25 patients with paucibacillary leprosy who attended the outpatient department of dermatology of Father Muller's Medical College Hospital during the period January 2001 to March 2002. All the patients were examined clinically and histopathologically at the beginning and at the end of six months of MDT and relevant data recorded. Clinicopathological correlation with histopathological classification before MDT was 72% and 68% at the end of MDT in our study. At the end of treatment 4 (16%) cases were clinically active and 8 (32%) were histopathologlcally active. The study showed that active cases were significantly reduced as a result of MDT, both clinically and histopathologically. The histopathological activity that outlasts MDT may be due to the bacillary fragments that persist; but clinical activity coupled with histopathological activity seen in 2 patients at the end of 6 months of MDT was possibly an indicator of relapse and these patients and similar others need to be followed up for a longer duration. In this study, resolution of granuloma and clinical activity after completion of MDT were assessed.

Impact of MDT on leprosy with a special reference to monolesions and smear positivity among the new cases.

The impact of MDT on the prevalence and incidence rate of leprosy was studied in a project area of 130,000 population over a period of 14 years, with a special reference to new monolesional cases and those presenting as smear positive cases. The prevalence rate showed a fall from 23 per 10,000 in 1986-87 to 1.33 per 10,000 in 1999-2000. The number of cases presenting with single lesion however showed a downward trend from 63.69% in 1986-87 to 26.09% in 1999-2000. The cases showing smear positivity among the new cases detected showed an ascent from 3.91% in 1986-87 to 4.35% in 1999-2000 with a peak of 25% in 1995-96. A similar trend was seen in the analysed figures of the 4 general surveys done.

Bacterial clearance with WHO--recommended multidrug regimen for multibacillary leprosy.

Sixty multibacillary leprosy patients with an average initial bacteriological index (BI) of 2.5 were followed up after they had completed the WHO--recommended multidrug therapy regularly till attaining bacteriological negativity. The minimum duration of treatment was two years as stipulated by WHO and the maximum duration for reaching negativity was seven years (mean 4.25 years). The minimum time for the attainment of bacteriological negativity was one year and the maximum was 6.75 years (mean 3.75 years). The higher the initial BI the longer was the time taken for the attainment of bacteriological negativity. The average fall of BI per year was 0.67. Dapsone monotherapy received before the commencement of MDT, prednisolone received during therapy and the type of leprosy did not have any effect on the time taken for bacteriological clearance. There was no relapse during the period of observation (mean 2.83 years). The site to attain negativity last was the ear lobe, in 95% of the cases.