Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

The number of cardiac myocytes in the hypertrophic and hypotrophic left ventricle of the obese and calorie-restricted mouse heart

Changes in body mass due to varying amounts of calorie intake occur frequently with obesity and anorexia/cachexia being at opposite sides of the scale. Here, we tested whether a high-fat diet or calorie restriction (CR) decreases the number of cardiac myocytes and affects their volume. Ten 6–8-week-old mice were randomly assigned to a normal (control group, n = 5) or high-fat diet (obesity group, n = 5) for 28 weeks. Ten 8-week-old mice were randomly assigned to a normal (control group, n = 5) or CR diet (CR group, n = 5) for 7 days. The left ventricles of the hearts were prepared for light and electron microscopy, and analysed by design-based stereology. In CR, neither the number of cardiac myocytes, the relationship between one- and multinucleate myocytes nor their mean volume were significantly different between the groups. In contrast, in the obese mice we observed a significant increase in cell size combined with a lower number of cardiomyocytes (P < 0.05 in the one-sided U-test) and an increase in the mean number of nuclei per myocyte. The mean volume of myofibrils and mitochondria per cardiac myocyte reflected the hypertrophic and hypotrophic remodelling in obesity and CR, respectively, but were only significant in the obese mice, indicating a more profound effect of the obesity protocol than in the CR experiments. Taken together, our data indicate that long-lasting obesity is associated with a loss of cardiomyocytes of the left ventricle, but that short-term CR does not alter the number of cardiomyocytes.     

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles

Background

Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.

Results

PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.

Conclusion

PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.     

Oxidized-LDL through LOX-1 increases the expression of angiotensin converting enzyme in human coronary artery endothelial cells

BACKGROUND AND OBJECTIVES: Our previous studies have shown that oxidized low-density lipoprotein (ox-LDL) and angiotensin II (Ang II) influence each other's action in endothelial cells. This study was designed to examine the regulation by ox-LDL of the expression of angiotensin converting enzyme (ACE) gene in human coronary artery endothelial cells (HCAECs). In addition, we studied the effect of the HMG CoA reductase inhibitor simvastatin on this interaction. METHODS AND RESULTS: Cultured HCAECs were incubated with ox-LDL (10-80 microg/ml) for 1-24 h. Ox-LDL increased the expression of ACE in a concentration- and time-dependent fashion. The upregulation of ACE expression in response to ox-LDL was mediated by its endothelial receptor LOX-1, since pretreatment of HCAECs with a blocking antibody to LOX-1 prevented the expression of ACE (P<0.01). Native-LDL had no significant effect on ACE expression. In this process, ox-LDL-induced activation of mitogen-activated protein kinase (MAPK p42/44) played an important role, since pretreatment of HCAECs with the MAPK p42/44 inhibitor (PD98059, 10 microM) inhibited MAPK activation and subsequently attenuated the expression of ACE (P<0.01 vs. ox-LDL alone). In other experiments, we pretreated HCAECs with simvastatin (10 microM) and then exposed the cells to ox-LDL. Simvastatin markedly attenuated ox-LDL-induced MAPK activation, and concurrently reduced ACE expression (P<0.01 vs. ox-LDL alone). CONCLUSIONS: Our observations provide direct evidence that ox-LDL via LOX-1 activation induces ACE gene expression in HCAECs, and MAPK activation plays a signal transduction role in this process. Simvastatin, which inhibits MAPK activation, also blocks ox-LDL-mediated upregulation of ACE.     

Tumor angiogenesis in keratocystic odontogenic tumor assessed by using CD‐105 antigen

J Oral Pathol Med (2011) 40 : 263–269 Background: The purpose of this study was to assess and compare angiogenesis with proliferative activity in Keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC) by using monoclonal mouse anti‐human antibody against CD105 (endoglin). Material and Methods: Angiogenesis was assessed in 38 KCOT, 27 DCs and 19 Normal Oral Mucosa (NOM) by measuring the Mean Vascular Density (MVD), Total Vascular Area (TVA) and Mean Vascular Area (MVA). Cell proliferation was assessed by obtaining Ki‐67 Labeling Index (Ki‐67LI) in all the groups. Results: Statistically significant difference was observed in MVD, TVA, MVA and Ki‐67 LI between the KCOT, DC and NOM (P = 0.000). The MVD, TVA, MVA and Ki‐67 LI were significantly higher in KCOT than in DC and NOM (P = 0.000). The Ki‐67 LI was significantly higher in NOM than in DC (P = 0.000). MVD (P = 0.032) and TVA (P = 0.038) were significantly higher in NOM than in DC. There was significant positive correlation between Ki‐67 LI and MVD, Ki‐67 and TVA and Ki‐67 and MVA. Conclusion: The result suggests that CD105 (endoglin) is strongly expressed in microvessels of KCOT compared with that in Dentigerous cyst and Normal oral mucosa. Thus, it suggests that angiogenesis may be associated with locally aggressive biological behavior of KCOT. These findings further stress on the hypothesis that the stroma of KCOT could be regarded not just as a structural support of the cyst wall, but as playing a part in the neoplastic behavior of cyst.     

Clinical presentation of the "depression-executive dysfunction syndrome" of late life.

It has been proposed that a "depression-executive dysfunction (DED) syndrome" occurs in late life. This assertion was based on clinical, neuropathological, and neuroimaging findings suggesting that frontostriatal dysfunctions contribute to the development of both depression and executive dysfunction and influence the course of depression. The authors describe the clinical presentation of DED and its relationship to disability, studying 126 elderly subjects with major depression and evaluating depressive symptoms, cognitive functioning, disability, and personality dimensions. Patients with the DED syndrome had reduced fluency, impaired visual naming, paranoia, loss of interest in activities, and psychomotor retardation, but showed a rather mild vegetative syndrome. Depressive symptomatology, and especially psychomotor retardation and loss of interest in activities, contributed to disability in DED patients, whereas paranoia was associated with disability independently of executive dysfunction. These findings may aid clinicians in identifying patients needing vigilant follow-up, because depression with executive dysfunction was found to be associated with disability, poor treatment response, relapse, and recurrence.