Diagnostic significance of estimation of serum apolipoprotein A along with alpha-fetoprotein in alcoholic cirrhosis and hepatocellular carcinoma patients

The serum apolipoprotein A (Apo A) and alpha-fetoprotein (AFP) were evaluated in histologically verified 30 cases of alcoholic cirrhosis and 18 cases of hepatocellular carcinoma (HCC). The latter were also divided into subgroups depending on the presence or absence of associated cirrhosis. Serum Apo A levels were found to be significantly decreased in cirrhotics (p less than 0.001) compared to controls and non-cirrhotic HCC patients. In 22 cases of alcoholic cirrhosis (AFP less than 10 ng/ml) and 12 cases of HCC (AFP greater than 600 ng/ml), the AFP levels itself were diagnostic, but in the remaining cases, AFP levels (100-600 ng/ml) were not able to differentiate between cirrhosis and malignancy. In this later group of patients with low pathological range of AFP, serum Apo A levels found to be significantly decreased in alcoholic cirrhotic patients (p less than 0.001) compared to HCC patients. Thus, estimation of Apo A levels may be helpful to interpret the AFP values at lower pathological range due to suspected liver pathology.     

Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.

PURPOSE: This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were randomly assigned to 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated. RESULTS: Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients. CONCLUSION: The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.     

Sinonasal T Cell Lymphoma: A Case Report

Sinonasal lymphomas are aggressive locally destructive midfacial necrotizing lesions. Most of them initially diagnosed as lethal midline granulomas, a term which is slowly replaced by sinonasal lymphoma. Here is one such case report of sinonasal T cell lymphoma where there was a difficulty in diagnosis and required an incisional biopsy.     

Epigenetic histone modifications in a clinically relevant rat model of chronic ethanol-binge-mediated liver injury

Purpose

Ethanol binge augments liver injury after chronic ethanol consumption in humans, but the mechanism behind the enhanced liver injury by ethanol binge is not known. In this study we used a clinically relevant rat model in which liver injury is amplified by binge after chronic ethanol treatment and investigated the importance of histone modifications.

Methods

Eight-week-old Sprague-Dawley rats were fed ethanol in a liquid diet for 4 weeks. Control rats were fed an isocaloric liquid diet. This was followed by three binge administrations of ethanol (intragastric 5 g/kg body weight, 12 h apart). In the control, ethanol was replaced by water. Four hours after the last binge administration, liver samples were analyzed for histone modifications and parameters of liver injury.

Results

Chronic ethanol administration alone caused an increase in histone H3 ser10 and ser28 (H3S10 or S28) phosphorylation, and binge ethanol reduced their levels. Levels of dually modified phosphoacetylated histone H3 (H3AcK9/PS10) increased after acute binge ethanol and remained same after chronic ethanol binge. In contrast, histone H3 lysine-9 acetylation (H3AcK9) was not increased after chronic ethanol but increased significantly after acute binge and chronic ethanol binge. Increase in histone acetylation was accompanied by increased phospho-ERK1/2 in the nuclear extracts. Increased acetylation after chronic ethanol binge was also accompanied by increased protein levels of GCN5 histone acetyl transferase and a modest increase in HDAC3 in the nucleus. Histone lysine-9 dimethylation was significantly increased after chronic ethanol binge. Chronic ethanol binge also resulted in a decrease in the SAM:SAH ratio with a relative decrease of SAM levels and a corresponding increase in SAH levels.

Conclusions

Ethanol binge after chronic ethanol altered the profile of site-specific histone modifications and may underlie the mechanism of augmented liver injury by chronic-ethanol-binge-treated rats.

     

Temporal activation of p42/44 mitogen-activated protein kinase and c-Jun N-terminal kinase by acetaldehyde in rat hepatocytes and its loss after chronic ethanol exposure

Several cell-damaging effects of ethanol are due to its major metabolite acetaldehyde but its mechanisms are not known. We have studied the effect of acetaldehyde on p42/44 mitogen-activated protein kinase (MAPK) and p46/p54 c-Jun N-terminal kinase (JNK 1/2) in rat hepatocytes. Acetaldehyde caused peak activation of p42/44 MAPK at 10 min followed by JNK activation at 1 h. These responses were acetaldehyde dose-dependent (0.2-5 mM). There was a consistently higher activation of p46 JNK than p54 JNK. Ethanol also activated both p42/44 MAPK and p46/p54 JNK. The activation of JNK by ethanol, however, was not significantly affected by treatment of hepatocytes with 4-methylpyrazole, an alcohol dehydrogenase inhibitor. Cells treated with 200 mM ethanol for 1 h accumulated 0.35 +/- 0.02 mM acetaldehyde, but the magnitude of JNK activation was greater than that expected with 0.35 mM acetaldehyde. Thus, ethanol-activated JNK may be both acetaldehyde-dependent and -independent. The activation of JNK by ethanol or acetaldehyde was insensitive to the treatment of hepatocytes with genistein (tyrosine kinase inhibitor) and 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide (GF109203X) (protein kinase C inhibitor). Remarkably, in contrast to the above-mentioned effects on normal hepatocytes, acetaldehyde was unable to increase JNK activity in hepatocytes isolated from rats chronically fed ethanol for 6 weeks and indicated a loss of this acetaldehyde response. Thus, temporal activation of the p42/44 MAPK and p46/p54 JNK, the greater activation of p46 JNK than p54 JNK, and loss of JNK activation after chronic ethanol exposure indicate that these kinases are differentially affected by ethanol metabolite acetaldehyde.     

Salt loading exacerbates diastolic dysfunction and cardiac remodeling in young female Ren2 rats

ObjectiveRecent data would suggest pre-menopausal insulin resistant women are more prone to diastolic dysfunction than men, yet it is unclear why. We and others have reported that transgenic (mRen2)27 (Ren2) rats overexpressing the murine renin transgene are insulin resistant due to oxidative stress in insulin sensitive tissues. As increased salt intake promotes inflammation and oxidative stress, we hypothesized that excess dietary salt would promote diastolic dysfunction in transgenic females under conditions of excess tissue Ang II and circulating aldosterone levels.Materials/methodsFor this purpose we evaluated cardiac function in young female Ren2 rats or age-matched Sprague–Dawley (SD) littermates exposed to a high (4%) salt or normal rat chow intake for three weeks.ResultsCompared to SD littermates, at 10 weeks of age, female Ren2 rats fed normal chow showed elevations in left ventricular (LV) systolic pressures, LV and cardiomyocyte hypertrophy, and displayed reductions in LV initial filling rate accompanied by increases in 3-nitrotyrosine content as a marker of oxidant stress. Following 3 weeks of a salt diet, female Ren2 rats exhibited no further changes in LV systolic pressure, insulin resistance, or markers of hypertrophy but exaggerated increases in type 1 collagen, 3-nitrotryosine content, and diastolic dysfunction. These findings occurred in parallel with ultrastructural findings of pericapillary fibrosis, increased LV remodeling, and mitochondrial biogenesis.ConclusionThese data suggest that a diet high in salt in hypertensive female Ren2 rats promotes greater oxidative stress, maladaptive LV remodeling, fibrosis, and associated diastolic dysfunction without further changes in LV systolic pressure or hypertrophy.     

Elevation of serum ceruloplasmin levels in brain tumours

Serum ceruloplasmin levels have been estimated in 80 patients with various intracranial space occupying lesions and in 30 controls. The ceruloplasmin levels were significantly increased in all brain tumours except in meningiomas. After therapy, the ceruloplasmin levels were still significantly increased when compared to controls and their respective preoperative values. However, the rise in levels of ceruloplasmin in malignant tumours compared to benign was statistically not significant. It is concluded that ceruloplasmin may have a role to play as an acute phase reactant protein in brain tumours.