Vitamin E-based therapy is effective in ameliorating transaminasemia in nonalcoholic fatty liver disease.

BACKGROUND: Comparative trials of ursodeoxycholic acid (UDCA), vitamin E and weight management programs among patients with nonalcoholic fatty liver disease (NAFLD) are lacking. AIM: To find an effective single agent or combination of agents for management of NAFLD. METHODS: In this retrospective study, consecutive patient with histologically confirmed NAFLD with raised ALT were included. The patients received either weight management (exercise and therapeutic lifestyle changes [TLC] diet with a target to reduce body weight 10% in 6 months) (group I) ; weight management + UDCA (300 mg BID) (group II); or weight management + UDCA + vitamin E (400 mg OD) (group III). Outcome measure was normalization of ALT. RESULTS: 42 patients (18, 12 and 12 in groups I, II and III, respectively) were included between 1996 and 2004. All patients in group III normalized their ALT levels, which was significantly higher than numbers in group I (8/18) and group II (5/12); (p=0.003). Post treatment ALT was significantly lower in group III (28.6 [9.3]) as compared to group I (59.3 [32.2]) and group II (49.0[31.8]); (p=0.01). Type of therapy received was the only factor predictive of ALT normalization. CONCLUSION: Combination regimen containing vitamin E appears to be effective in normalizing ALT among NAFLD patients.     

Normative MDCT Cross-Sectional Data Estimation of Superior Vena Cava and Innominate Vein in Growing Children Using Age as a Predictor

This retrospective study aimed to determine the superior vena cava (SVC) and left innominate vein (INV) normative cross-sectional area in children noninvasively using age as a predictor and also to compare the correlation of the area measured with the diameter on multidetector computed tomography (MDCT). Analysis of the SVC-INV cross-sectional area was performed for 73 consecutive patients. The cross-sectional area of the SVC-INV was manually estimated. A regression analysis was performed for the cross-sectional area and age separately, and regression equations were compared. One-way analysis of variance (ANOVA) was performed to evaluate significant differences in the area means according to age groups. Regression analysis showed that age can be a predictor for the area of the SVC (50.6 mm² + 1.01 × age), te INV (48.3 mm² + 0.93 × age), and the left SVC-INV junction (47.2 mm² + 0.92 × age), with respective R ² values of 93, 88 and 94 %. The comparative evaluation of the cross-sectional area and the diameter measurement of SVC showed that the cross-sectional area was more closely associated with the increasing age of the cohort (R ² of 68 vs. 61 %) than the measured diameter. For a cohort of patients without congenital or acquired heart disease, MDCT can be used as a complementary test for a normative cross-sectional normogram area database of SVC-INV using age as a predictor.     

Inhibition of tumorigenic potential and prostate-specific antigen expression in LNCaP human prostate cancer cell line by 13-cis-retinoic acid

Prostate-specific antigen (PSA) is a member of the kallikrein family and has been an important biological marker for prostate cancer. The mechanisms regulating PSA expression in prostatic cancer cells are unclear. The present study was designed to elucidate the role of 13-cis-retinoic acid (RA) in regulation of PSA and the tumorigenic potential of the human prostate cancer cell line LNCaP. The growth regulation of LNCaP cells was examined by DNA synthesis and doubling time. The tumorigenic potential of prostate cancer cells was analyzed by soft agar colony-forming assay, in vitro invasion assay, type IV collagenase assay and binding to extracellular matrix assay. The nuclear receptors for retinoic acid (RARα, -β, -γ and RXRα, -β,-γ) as well as PSA mRNA were determined by Northern blot using specific oligonucleotide probes. Our results suggest that 13-cis-RA significantly inhibits PSA secretion and expression both at the mRNA and protein levels compared with untreated cells. Electron microscopic studies suggest that after 13-cis-RA treatment, cells become more differentiated as they contain lumina, lined by plasma membrane and microvilli. Prostate cancer cell growth and tumorigenic potential after 13-cis-RA treatment was significantly decreased compared with controls. Nude mice tumorigenicity studies showed that 13-cis-RA-treated cells produced significantly smaller tumors compared with untreated cell tumors. There was also a significant increase in the expression of RXRa mRNA after 13-cis-RA treatment compared with untreated cells.     

Homologous acellular matrix graft for vaginal repair in rats: a pilot study for a new reconstructive approach

The purpose of this paper is to investigate using an acellular matrix graft of vagina (VAMG) or bladder (BAMG) in vaginal reconstruction. In 18 rats, vaginal length was measured and a hysterectomy performed. In three control animals, the vaginal stump was closed. In eight rats, the vagina was augmented with a VAMG; in seven, a BAMG was used. After 2-12 weeks, the animals were sacrificed, the vaginal length was reevaluated, and the vaginas were prepared for histologic evaluation. In the controls, the vagina was markedly shorter postoperatively. In the grafted animals, vaginal length was not significantly less than preoperative values with either matrix. Epithelialization, vascularization, and alpha-actin expression in the grafts were consistently observed. Regeneration appeared to be slightly greater in the organ-specific vagina matrix. With either matrix, however, although the vaginal stump remained open, the grafts lost most of the lumen. Vaginal reconstruction with a vagina acellular matrix graft is technically feasible. If further experiments can address the problem of luminal collapse - with, for instance, tissue expanders in the matrix - this technique may offer an alternative to the complex therapeutic options currently available.     

Catechol-O-methyltransferase gene polymorphisms in benign prostatic hyperplasia and sporadic prostate cancer.

Various carcinogenic metabolites, including catechol estrogens, play a role in malignant transformation. An enzyme that is capable of neutralizing the genotoxic effects of these compounds is catechol-O-methyltransferase (COMT). A variant form of this enzyme has been shown to reduce its activity by up to 4-fold; thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for benign prostatic hyperplasia (BPH) and prostate cancer. To test this hypothesis, the genetic distribution of three different COMT polymorphisms at codon 62 (C-->T), codon 72 (G-->T), and codon 158 (G-->A) were analyzed in 131 normal healthy subjects, 134 BPH, and 178 sporadic prostate cancer samples from a Japanese population. Results of these experiments show that the variant genotype at codon 62 (P = 0.060) and codon 158 (P = 0.047) are risk factors for prostate cancer but not BPH when compared with normal controls. Odds ratio (OR) and 95% confidence interval (95% CI) for cancer were 3.24 and 1.38 to 7.61, respectively, for codon 62 T/T genotype when compared with wild type. At codon 158, the A/A variant for cancer had an OR of 3.00 with a 95% CI of 1.38 to 6.54 compared with wild type. Codons 62 and 158 were in linkage disequilibrium (LD), and when compared with the C-G haplotype, other types (C-A, T-G, T-A) were observed to be associated with prostate cancer (P = 0.040) but not BPH. Codon 72 on the other hand, was not in LD with either codon 62 or 158. The homozygous variant on codon 72 was rare in this Japanese population, and the heterozygous G/T at this codon was not associated with either prostate cancer or BPH. When evaluating the risk of COMT polymorphisms with stage or grade of cancer, no associations were observed for any of the genotypes with the exception of a tendency (P = 0.096) for the variant A allele on codon 158 to be correlated with higher stages (> or = T3) of cancer. This is the first report that shows the polymorphisms of COMT to be associated with sporadic prostatic carcinogenesis. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of prostate cancer.     

Vascular endothelial growth factor restores erectile function through inhibition of apoptosis in diabetic rat penile crura

PURPOSE: Vascular endothelial growth factor (VEGF) is known as a multifunctional protein with roles in angiogenesis stimulation and apoptosis inhibition. We hypothesized that intracavernous administration of VEGF would recover erectile dysfunction due to diabetes by protection from apoptosis in the penile cavernosum. MATERIALS AND METHODS: A total of 30, 6-month-old male Sprague-Dawley rats were divided into 2 large groups, namely 20 with diabetes and 10 healthy controls. The diabetic group received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Intracavernous injection of VEGF was administered to randomly selected STZ diabetic rats 6 weeks after STZ injections. Erectile functional studies were performed in 10 STZ and 10 STZ plus VEGF rats at 12 weeks. After completion of the functional study the penile crura were collected for molecular and immunohistochemical studies. RESULTS: Mean intracavernous pressure in the diabetic group was significantly lower than in controls and low pressure was significantly recovered by VEGF treatment. Gene expression of pro-apoptotic and anti-apoptotic factors were present in the control, diabetic and VEGF treated groups. However, anti-apoptotic protein expression was lacking in the diabetic group and it was recovered by VEGF treatment. The apoptotic index in the diabetic group was significantly higher than in controls and this index was significantly decreased in the VEGF treated group. CONCLUSIONS: The decrease in and recovery of intracavernous pressure correlated significantly with a variation in anti-apoptotic protein expression in the diabetic and VEGF treated groups. To our knowledge this is the first study to show that intracavernous injection of VEGF restores erectile dysfunction through the inhibition of apoptosis in diabetic rats.