Endothelial dysfunction and hypertension in 5/6 nephrectomized rats are mediated by vascular superoxide

BACKGROUND: Nitric oxide inactivation by superoxide impairs endothelium-dependent vasodilation and plays a role in various forms of hypertension. Almost no data exist regarding hypertension secondary to chronic renal failure. Previous studies have shown that endothelium-related relaxations, secondary to decreased nitric oxide bioactivity, are impaired in resistance vessels from rats 3 to 10 days after renal mass reduction (RMR). METHODS: The membrane-permeable superoxide dismutase (SOD)-mimetic (tempol) was administered IP (1.5 mmol/kg/day for 10 days) to RMR rats and sham-operated controls (SN). Systolic blood pressure (SBP) was measured by tail cuff manometry at days 0, 3, 6 and 10. The increase of flow induced by acetylcholine (10-6 mol/L) was measured in isolated perfused mesenteric arteries from RMR and SN rats pre-contracted with noradrenaline (1 to 5 micromol/L), with or without exogenous SOD. Plasma levels of advanced oxidative protein products (AOPPs; chloramine-T equivalents) were measured in SN and RMR rats. RESULTS: Tempol prevented the increase of SBP: 118 +/- 2.2 mm Hg at baseline and 122 +/- 1.6 mm Hg at 10 days in tempol-treated vs 118.14 +/- 1.65 mm Hg at baseline and 145 +/- 7.69 mm Hg at 10 days in untreated RMR rats (P < 0.01). Responsiveness to acetylcholine was reduced in RMR rats (peak flow increase: 139 +/- 7.8% vs. 176 +/- 11% in SN, P=0.028 at 3 days and 140 +/- 6.4% vs. 187 +/- 16.9% in SN at 10 days, P=0.007). In arteries pre-incubated with SOD (200 U/mL) the peak flows were 175 +/- 9.4% at 3 days and 157 +/- 5.8% at 10 days (P=0.007 and P=0.051, respectively, vs. control RMR vessels). AOPP values were significantly increased in plasma from RMR rats 3 days after 5/6 nephrectomy (747 +/- 107 vs. 481 +/- 77 micromol/L, P < 0.05) but returned to normal by day 10. AOPP levels were not significantly reduced by tempol. CONCLUSIONS: Increased vascular superoxide production plays a central role in the development of vascular endothelial dysfunction and hypertension early after 5/6 nephrectomy.     

Surgical management of thyroid diseases--a study on 78 cases

A total of 78 cases with thyroid diseases were treated surgically in the Department of ENTD, Mymensingh Medical College Hospital during the period from 2000-2001. The different types of surgery were done according to the diagnosis being presented here. Out of 78 cases, 60 (76.9%) were female and 18 (23.1%) were male having female to male ratio of 3.3:1. The highest number, 47 cases (60.3%) belongs to 21-40 year age group. The study revealed the incidence of thyroid diseases as follows: 53 (67.9%) Benign cold single nodular goitre. 17(21.8%) Benign cold multinodular goitre and 08 (10.3%) Papillary carcinoma of thyroid. Regarding surgical management 40 (51.3%) patients underwent hemithyroidectomy. Lobectomy were done for 13 (16.7%), subtotal thyroidectomy for 15 (19.2%), total thyroidectomy for 5 (6.4%) patients and total thyroidectomy with functional neck dissection were performed for 5 (6.4%) patients. The study showed that females were the mostly affected group having benign single cold nodular goitre who were treated surgically by hemithyroidectomy.     

Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations.

The major risk factors for hepatocellular carcinomas (HCC) in high incidence areas include infection with hepatitis B and C viruses (HBV, HCV) and exposure to aflatoxin. Genetic alterations in 24 liver resection specimens from Shanghai and Qidong were studied. Hepatitis B virus was integrated in all patient samples, and a null phenotype for the GSTM1 enzyme was present in 63% of patients. Alteration of p53 was present in 95% (23/24) of cases: mutations of the p53 gene in 12 HCC, p53 overexpression in 13 and loss of heterozygosity (LOH) of chromosome 17p in 17. All seven HCCs with a p53 mutation from Qidong and three of five from Shanghai had the aflatoxin-associated point mutation with a G to T transversion at codon 249, position 3. No HCC had microsatellite instability. LOH of chromosome 4q, 1p, 16q and 13q was present in 50%, 46%, 42% and 38%, respectively, and 4q was preferentially lost in HCCs containing a p53 mutation: LOH of 4q was present in 75% (9/12) of HCC with, but only 25% (3/12) of HCC without, a p53 gene mutation (P = 0.01). These data indicate a possible interaction between p53 gene mutation and 4q loss in the pathogenesis of HCC.     

Loss of heterozygosity at D14S62 and metastatic potential of breast cancer.

BACKGROUND: In breast cancer progression, the prevalence of damage at specific genetic loci often increases with the stage of the lesion (i.e., from noninvasive to invasive to metastatic). By use of genetic markers and analysis of allelic imbalances (loss of heterozygosity [LOH]) to compare DNA samples from paired normal and breast tumor tissues, we examined whether specific genetic changes in primary breast cancers can serve as biomarkers of metastatic potential. METHODS: DNA samples from 76 patients with primary breast cancer (42 with axillary lymph node-negative disease and 34 with axillary lymph node-positive disease) were genotyped with four genetic markers spanning chromosome 14q31-q32. The intensity ratios of the two genetic alleles in normal-tumor DNA pairs were examined in genetically informative individuals. LOH was scored when the tumor allele intensity ratio (tumor allele 1/tumor allele 2) divided by the normal allele intensity ratio (normal allele 1/normal allele 2) was either less than 0.71 (tumor allele 1 LOH) or greater than 1. 4 (tumor allele 2 LOH). RESULTS/CONCLUSIONS: Contrary to our expectations, we found statistically significantly more LOH events at markers D14S62 (two-sided P =.001) and D14S51 (two-sided P =.02) in primary breast cancers from patients with lymph node-negative disease versus lymph node-positive disease, suggesting the presence of a gene in this region that affects metastatic potential. Analysis of small interstitial or terminal deletions in the tumors of six especially informative patients with lymph node-negative disease places the putative metastasis-related gene in a 1490-kilobase region near D14S62. IMPLICATIONS: LOH in the D14S62 region may impede the process of metastasis. Therefore, the D14S62 region LOH profile may have prognostic implications, and the isolation of the metastasis-related gene(s) in this region may lead to better diagnosis and treatment of breast cancer.     

Alterations in Liver ATP Homeostasis in Human Nonalcoholic Steatohepatitis: A Pilot Study

Context  The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved. Objective  To determine if patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion. Design  Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998. Setting  University hospital. Patients  Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age- and sex-matched controls. Main Outcome Measure  Level of ATP 1 hour after fructose infusion in patients vs controls. Results  In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (P<.02 vs minimum ATP) but patients did not. Hence, patients' hepatic ATP levels were lower than those of controls at the end of the study (P = .04). Body mass index (BMI) correlated inversely with ATP recovery, even in controls (R = -0.768; P = .07). Although BMI was greater in patients than controls (P = .02) and correlated strongly with fatty liver and serum aminotransferase elevations, neither of the latter 2 parameters nor the histologic severity of fibrosis strongly predicted hepatic ATP recovery. Conclusions  These data suggest that recovery from hepatic ATP depletion becomes progressively less efficient as body mass increases in healthy controls and is severely impaired in patients with obesity-related nonalcoholic steatohepatitis.      

Thoracoscopic (upper thoracic) sympathectomy for primary palmar hyperhidrosis in children

Primary palmar hyperhidrosis is a disabling disorder that starts in childhood and causes physical and psychological inconvenience. Conservative treatment is not effective in severe cases. Thoracoscopic sympathectomy is the treatment of choice. It is a safe minimally invasive procedure with good results. There are few reports in the UK regarding surgical treatment in children. Post-operative compensatory hyperhidrosis of the trunk and thighs occurs in up to 50% of cases. We report on three cases involving six procedures.     

Structural studies of bioactivity in sol-gel-derived glasses by X-ray spectroscopy

Extended X-ray absorption fine structure spectroscopy and X-ray absorption near edge structure, X-ray fluorescence spectroscopy, and X-ray powder diffraction have been used to study the local calcium environment in four sol-gel-derived bioactive calcium silicate glasses of the general formula (CaO)(x)(SiO(2))(1-x). The formation of a hydroxyapatite layer on the composition with the highest bioactivity (x = 0.3) with time has been studied, in an in vitro environment, by immersion in simulated body fluid (SBF) at 37 degrees C. The calcium oxygen environment in the four compositions has been shown to be six-coordinate in character. Both the extended X-ray absorption fine structure spectroscopy and X-ray absorption near edge structure show a gradual increase in coordination number and Ca--O bond distance with longer exposure to SBF. X-ray fluorescence show that calcium is quickly lost from the samples on exposure to SBF and the calcium concentration then recovers with time. There is clear evidence that the recovery of calcium content is due to the formation of a CaO-P(2)O(5)-rich layer. Annealing of samples at 650 degrees C shows the presence of what, on the length scales probed by X-ray diffraction, appears to be noncrystalline calcium phosphate after 1 h of exposure to an SBF solution, which becomes more crystalline on longer exposure.