Dual role of VEGF in pretreated experimental ePTFE arterial grafts

BACKGROUND: Lack of endothelialization and abnormal smooth muscle cell (SMC) growth adversely affect the outcome of vascular synthetic grafts. The aims of our study were to investigate how a coating of extracellular matrix (ECM) and vascular endothelial growth factor (VEGF) might affect the endothelialization rate, smooth muscle cells (SMC) proliferation, and myointimal hyperplasia in experimental arterial ePTFE grafts. METHODS: In each of 30 male Lewis rats, a 1-cm-long ePTFE graft was inserted at the level of the abdominal aorta. Animals were randomized in five groups (six animals each): groups A and A1 received ePTFE grafts coated with a synthetic extracellular matrix (growth factor-reduced matrigel) containing VEGF; groups B and B1 received ePTFE grafts coated with synthetic ECM; and group C received ePTFE grafts alone. The grafts were explanted at 30 days from surgery for immunohistochemical analysis. RESULTS: Both endothelialization rate and myointimal hyperplasia were augmented in group A versus groups B and C, and these findings were statistically significant. SMC density resulted significantly higher in group A versus groups B and C, and this was associated with an altered expression of bFGF and TGFbeta. CONCLUSIONS: Pretreating ePTFE grafts with synthetic ECM and VEGF results in better endothelialization, but also in undesired higher SMC density and myointimal hyperplasia.     

Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh

BACKGROUND: Indian Asian men residing in the United Kingdom have a higher prevalence of hyperhomocysteinemia than do their European counterparts. This has been largely attributed to dietary deficiencies in cobalamin associated with vegetarianism among these Indian Asians. OBJECTIVE: We aimed to ascertain the prevalence of folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. DESIGN: Plasma concentrations of homocysteine, folate, and cobalamin and urinary concentrations of creatinine were assessed in 1650 adults in Bangladesh. RESULTS: The prevalence of hyperhomocysteinemia (men: >11.4 micromol/L; women: >10.4 micromol/L) was markedly (P < 0.0001) greater among men (63%; x +/- SD: 15.3 +/- 9.5 micromol/L) than among women (26%; 9.5 +/- 4.7 micromol/L). Folate was lower (9.8 +/- 6.5 and 12.3 +/- 7.6 nmol/L, respectively), whereas cobalamin was higher (281 +/- 115 and 256 +/- 118 pmol/L, respectively) (P < 0.0001 for both) among men than among women. Folate explained 15% and cobalamin explained 5% of the variation in homocysteine concentrations. For men, folate (P = 0.005) and cobalamin (P = 0.03) were positively correlated with urinary creatinine. Smoking (P < 0.0003) and betelnut use (P < 0.0002) were independent negative predictors of folate. CONCLUSIONS: Bangladeshi men have a high prevalence of hyperhomocysteinemia, which is more closely associated with folate than with cobalamin, although other factors, eg, smoking and betelnut use, may also contribute to its cause. The positive correlations between urinary creatinine and plasma folate and cobalamin were unanticipated and could suggest that, in marginal nutrition, these vitamins may be limiting for creatine biosynthesis.     

The pharmacology of 2,3-dimercaptosuccinic acid and its potential use in arsenic poisoning.

Arsenic (As2O3)-poisoned rats were treated with either 2,3-dimercaptosuccinic acid (DMS) or dimercaptopropanol (BAL) at doses of 30 mg/kg/day. A control group received no treatment. The total quantity of arsenic excreted was not significantly different in response to 4 days of treatment with either DMS or BAL. In addition, there was no difference between the two drug treatment groups in the residual arsenic content of brain, liver, kidney and spleen after treatment. Both drugs reduced the arsenic content of each tissue to approximately 40% of that of untreated controls. Previous studies have shown that DMS is orally effective for the treatment of lead poisoning. The LD50 of DMS was determined to be in excess of 3 g/kg in rats and mice, approximately 30 times the LD50 of BAL. No gross, histopathological or biochemical evidence of toxicity was observed in mice, rats or dogs which received DMS 5 days per week for 6 months. DMS did not affect the excretion of zinc, iron, calcium or magnesium. Urinary copper excretion was significantly elevated in response to 30 mg/kg of DMS, suggesting that the drug might also be useful for the treatment of Wilson's disease.     

Alpha-actin gene mutations and polymorphisms in Italian patients with nemaline myopathy

Nemaline myopathy is a rare neuromuscular disorder, showing striking clinical and genetic heterogeneity. Patients can show a spectrum of disease ranging from severe congenital to an adult-onset mild form. Disease-causing mutations have been reported in five genes encoding sarcomeric thin filament proteins, and inheritance can be either autosomal recessive or dominant. No phenotype-genotype correlation is apparent at the moment. alpha-actin gene mutations are responsible for about 20% of cases. We have collected 18 patients from 17 families. Our patients exhibit an overall marked clinical variability, but 10 out of 18 show typical features of nemaline myopathy (slowly progressive congenital form). We have identified disease-causing mutations in the alpha-actin gene in 5 out of 17 families, through direct sequencing of its whole coding sequence. One patient carried two mutations, thus we describe a total of 6 mutations, all arising de novo. We also describe some intronic polymorphisms which constitute two common alpha-actin gene haplotypes; we show that haplotype characterisation may have a strong impact in mutation detection due to preferential amplification of a chromosome in subjects carrying both haplotypes. Screening of the alpha-actin gene coding sequence may account for the identification of disease-causing mutations in 20-30% of nemaline myopathy patients. Since the chance to identify mutations is independent of the clinical picture, we suggest that it is appropriate to check for mutations in all patients. Demonstration of a de novo origin of the mutation is of great relevance for families seeking genetic counselling.     

A prospective study of prenatal and childhood lead exposure and erythropoietin production

We test the hypothesis that chronic lead (Pb) exposure may be associated with an inability to maintain an adequate serum erythropoietin (EPO) concentration. From a longitudinal study of Pb exposure and infant and childhood development, we measured blood Pb (BPb) and serum EPO concentrations serially at ages 4.5, 6.5, 9.5, and 12 and tibia (cortical) Pb concentration at age 12. Pb-exposed children aged 4.5 and 6.5 produced increased concentrations of EPO to maintain normal Hgb concentrations. EPO production declined between ages 4.5 and 6.5. At ages 9.5 and 12, further diminution of the association was found. No association was found between tibia Pb and EPO. The continued decline in the slope of the relationship between EPO and BPb with age, after adjustment for hemoglobin, implies a gradually decreasing capacity to produce EPO.     

An update of the leukotriene modulators for the treatment of asthma

Bronchial asthma is a chronic inflammatory airway disease involving many cells and mediators. Chronic inflammation constitutes an important predisposing condition for airway remodelling with secondary irreversible airflow obstruction. Current approaches for asthma treatment involve many classes of drugs, adequate patient education for their correct use, environmental exposure control and daily monitoring of pulmonary function. Unfortunately, the use of multiple therapies complicates treatment regimens, thus leading to a reduced compliance to therapy. Available evidence from randomised clinical trials and real-word experience derived from managing patients with asthma justifies a broader role for leukotriene receptor antagonist drugs in asthma management than that recommended in the National Asthma Education and Prevention Programme and National Health Lung and Blood Institute Treatment Guidelines. While a low dose of inhaled corticosteroids remains the reference drug as a controller in mild-to-moderate persistent asthma, oral therapy with an leukotriene-receptor antagonist drug represents a good option providing the clinical efficacy requested in common clinical practice. For this reason the recent Global Initiative for Asthma Guidelines allocate this drug to the second and third steps of asthma treatment.     

High curative resection rate with weekly cisplatin, 5-fluorouracil, epidoxorubicin, 6S-leucovorin, glutathione, and filgastrim in patients with locally advanced, unresectable gastric cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS 相似文献   

Growth and aging of facial soft tissues: A computerized three-dimensional mesh diagram analysis

The normal growth, development, and aging of facial soft tissues was studied by three-dimensional (3D) computerized mesh diagram analysis. The 3D coordinates of 50 soft-tissue landmarks were collected from 591 healthy white northern Italians (351 males, 240 females) 6-40 years of age. For each gender and age class, mean values were computed, and a standardized mesh of equidistant horizontal, vertical, and anterior-posterior lines was constructed. Within each age group, male meshes were superimposed on female meshes. For each gender, the 6-year-old reference mesh was superimposed on the reference mesh of each age group. The global (size plus shape) difference was evaluated by calculating the relevant displacement vectors for each landmark. Consequently, a size normalization was carried out and the shape difference was evaluated by calculating new relevant displacement vectors for each landmark. Growth and development were different along the three spatial planes: the largest increment was observed in the vertical dimension, with major modifications in the soft-tissue profile. The vertical dimension in males increased even after 30 years of age: ear dimensions increased, trichion moved superiorly and posteriorly, and pogonion, menton, and gonion moved anteriorly and inferiorly. In all age groups, size-standardized shape differences were found in the forehead, lower-third facial profile, eyes, cheeks, and ears. In each age class, male dimensions were larger than female dimensions. During childhood, gender differences in size were limited; shape differences were even less manifest. Overall, the profile was more anterior and inferior, the gonia were more inferior and more lateral, the forehead was more anterior, and the ears were larger in males than in females of corresponding age.