Effect of resveratrol on angiogenesis and platelet/fibrin-accelerated tumor growth in the chick chorioallantoic membrane model

We carried out this investigation to examine the effects on angiogenesis-mediated processes and to define anti-angiogenesis mechanisms for flavonoids. We examined the effects and mechanisms of the flavonoid resveratrol on angiogenesis and tumor growth using the chick chorioallantoic membrane (CAM) model of angiogenesis, the CAM tumor growth model, and the effect on p53 in fibroblast growth factor-2 (FGF2) stimulated human endothelial cells using immunoassay. Resveratrol demonstrated potent inhibition (effective dose50=0.7+/-0.1 microM) of FGF2-induced angiogenesis and tumor growth. Furthermore, resveratrol significantly (P<0.01) inhibited platelet/fibrin clot-promoted human colon and fibrosarcoma tumor growth in the CAM tumor model. Resveratrol in a concentration-dependent (1-3 microM) manner significantly promoted apoptosis in FGF2-stimulated endothelial cells by increasing p53 protein production. These data indicated potent anti-angiogenesis efficacy, inhibition of tumor growth, and clot-mediated enhanced tumor growth. These data suggest potential anticancer benefits as a chemopreventive and chemotherapeutic for the flavonoid resveratrol.     

Periodontal diseases and the risk of coronary heart and cerebrovascular diseases: a meta-analysis

BACKGROUND: This meta-analysis was conducted to examine the relationship between periodontal diseases and coronary heart diseases (CHD) and cerebrovascular diseases (CVD) in observational studies. METHODS: This study was based on seven cohort studies and four studies of other designs that met prestated inclusion criteria. Information on study design, year of publication, study location, sample size, study population, participant characteristics, measurement of risk factors, exposure and outcome measures, matching, controlling for confounders, and risk estimates was abstracted independently by two investigators using a standard protocol. RESULTS: Subjects with periodontitis had an overall adjusted risk of CHD that was 1.15 times (95% confidence interval [CI]: 1.06 to 1.25; P = 0.001) the risk for healthy subjects. There was no heterogeneity among the studies in the overall relative risk estimate (P = 0.472). As compared to healthy subjects, those with periodontitis had an overall adjusted relative risk of CVD of 1.13 (95% CI: 1.01 to 1.27; P = 0.032). CONCLUSIONS: Findings indicated that periodontal infection increases the risk of CHD and CVD. However, this meta-analysis provided no evidence for the existence of strong associations between periodontitis and CHD and CVD. Larger and better-controlled studies involving socially homogeneous populations and measuring specific periodontal pathogens are required to identify a definite association between periodontal disease and the risk of coronary heart disease and cerebrovascular disease.     

Alpha-interferon with ribavirin in the treatment of hemodialysis patients with hepatitis C

INTRODUCTION: Hepatitis C Viral (HCV) infection is the leading cause of chronic liver disease in end-stage renal disease patients (ESRD). The impact of HCV on patient and graft survival posttransplantation is controversial. The most successful approach is to eliminate the virus while the patient is on dialysis prior to transplantation. The main aim of this pilot study was to assess the efficacy of combined alpha-interferon (alpha-IFN) and ribavirin treatment of HCV hemodialysis (HDx) patients, by comparing the sustained virological response to that obtained by local historical data on treatment with alpha-IFN alone. A secondary aim was to establish the optimal therapeutic dose of ribavirin in this regimen. METHODS: Twenty HCV-HDx patients who were histologically (liver biopsy) and virologically (HCV-PCR)-positive were selected randomly. They received combination therapy with 3 million units (MU) of alpha-IFN and 200 mg of ribavirin three times a week. Initially nine patients were treated for 24 weeks. Later, another 11 patients were randomly selected to give the combination for 48 weeks. RESULTS: Six of the nine patients who were treated for 24 weeks (66%) became HCV-PCR-negative by the end of the treatment period. They continued to have a sustain virologic response at 6 months after the cessation of therapy. Six of the 11 patients (55%) who were treated for 48 weeks became HCV-PCR-negative at the end, and at 6 months after cessation of treatment. Of the first six responders, 4 (66%) maintained a sustained virologic response at 1 year postcessation of therapy. Nine of the 11 patients had genotype 4 and 1. No side effects were reported for a ribavirin dose of 200 mg three times a week. CONCLUSION: This pilot study suggests that combination treatment for 24 weeks and 48 weeks with 3 MU alpha-IFN and 200 mg ribavirin three times a week, elicited a sustained virologic response in HDx patients with HCV infection better than IFN alone with minimal side effects. A prospective, double-blind, controlled study using pegylated INF plus ribavirin is currently underway.     

The value of penile duplex in the prediction of intracavernous drug-induced priapism

The aim of this work is to assess the value of penile duplex in the prediction of intracavernous drug-induced ischemic priapism. A total of 400 patients with erectile dysfunction were evaluated before and after diagnostic intracavernous injection of a trimix solution (papaverine+phentolamine+PGE1) using color Doppler sonography. In all, 29 patients experienced sustained rigid erections for more than an hour. Patients were further divided into two groups. Group A included patients with spontaneous resolution of their rigid erection within 3 h (10/29) and group B included patients with priapism (19/29) that did not resolve within 3 h. In group A, patients had minimal cavernous artery blood flow within the first hour postinjection, that increased with relief of their erection. Group B patients had no blood flow in their cavernous artery an hour after intracavernous injection and for 6 h later. The disappearance of blood flow in the cavernous artery after an hour of sustained rigid erection predicted priapism with 100% specificity and sensitivity. The persistent absence of cavernous artery blood flow for more than an hour, as detected by color Doppler ultrasound, is an objective predictor of priapism. This may guide early intervention to resolve the prolonged erection.     

Two cases of adreno-hepatic fusion in cynomolgus monkeys (Macaca fascicularis)

In this report we describe 2 cases of adreno-hepatic fusion (AHF) in Cynomolgus monkeys (Macaca fascicularis) used in short-term toxicity studies. AHF is defined as the union of hepatic tissue with the adrenal gland with close intermingling of the respective parenchymal cells. In this condition, a continuous intervening connective tissue septum is lacking. AHF is believed to be a congenital anomaly caused by a defect or delay in the formation of the organ capsules from the intermediate primitive mesenchymal stroma. To our knowledge, this is the first time this anomaly is described in the monkey.     

Rupture of excluded popliteal artery aneurysm: implications for type II endoleaks--a case report

The fate of popliteal artery aneurysms after ligation and bypass is believed to be relatively innocuous. The patient presented in this report, however, experienced spontaneous rupture of a popliteal aneurysm 11 years after ligation and bypass. Magnetic resonance angiography was used to establish the diagnosis of rupture, which was subsequently confirmed at surgery. Intraoperative arteriography demonstrated persistent collateral arterial perfusion of the excluded popliteal aneurysm sac. The collateral arterial flow originated from the superior and inferior lateral genicular arteries. The persistent arterial perfusion resulted in growth of the aneurysm from 4.2 to 7.0 cm over the 11-year period. The ruptured aneurysm was successfully treated by direct arterial exposure and suture ligation of the collateral vessels performed from within the aneurysm sac. The development of popliteal aneurysm expansion and rupture as a result of collateral arterial perfusion suggests that persistent collateral perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) may lead to aneurysm rupture. Therefore, close observation and intervention for aneurysm expansion to prevent rupture of the excluded aneurysm are warranted.     

Assessing the impact of nutrition education on growth indices of Iranian nomadic children: an application of a modified beliefs, attitudes, subjective-norms and enabling-factors model

In order to teach suitable feeding and hygiene practices to a group of randomly selected Qashqa'i tribe families with 406 children aged 0-59 months, a culturally appropriate community-based education intervention approach was used. To assess the impact of the intervention on the study group, another group of families with 405 children were randomly selected to serve as the controls. At the beginning of the intervention programme both groups of children had access to a similar diet, consisting of cereals, beans, oil, sugar, milk and yoghurt. Baseline data, age, gender, weight, height and mean arm circumference (MAC), were obtained before the intervention. Using Hubley's behavioural change model, the components of which deal with beliefs, attitudes, subjective norms and enabling factors, the research team studied the behaviour of the family members and tried to change their nutritional behaviour. This was achieved by designing a suitable education programme to be carried out for 12 months. During the programme, families were instructed to follow different methods of food preparation and cooking practices. The final data were collected 3 months after the end of the intervention programme. The results indicated that the children in the study group gained: 1.16 (sd 1.2) kg body weight, 0.033 (sd 0.05) m in height, 0.0067 (sd 0.015) m in MAC, 0.8 (sd 1) in weight-for-age Z-score, 0.97 (sd 1.7) in height-for-age Z-score and 0.28 (sd 1.8) in weight-for-height Z-score by the end of the study. The corresponding values for the control group were 0.42 (sd 1.0), 0.0167 (sd 0.047), 0.0017 (sd 0.012), 0.35 (sd 1.1), 0.56 (sd 1.5) and 0.014 (sd 1.6) respectively and the differences were statistically significant (P<0.05). These findings suggest that educational interventions involving parents and/or other family members who might play a role in the care behaviour and care resources are important in feeding the children energy- and protein-enriched, hygienic, simple and cheap foods. Such practices could improve child growth even under conditions of poverty.     

Selectins and integrins but not platelet-endothelial cell adhesion molecule-1 regulate opioid inhibition of inflammatory pain

1.Control of inflammatory pain can result from activation of opioid receptors on peripheral sensory nerves by opioid peptides secreted from leukocytes in response to stress (e.g. experimental swim stress or surgery). The extravasation of immunocytes to injured tissues involves rolling, adhesion and transmigration through the vessel wall, orchestrated by various adhesion molecules. 2. Here we evaluate the relative contribution of selectins, integrins alpha(4) and beta(2), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) to the opioid-mediated inhibition of inflammatory pain. 3. We use flow cytometry, double immunofluorescence and nociceptive (paw pressure) testing in rats with unilateral hind paw inflammation induced by complete Freund's adjuvant. 4. In inflamed tissue, 43-58% of hematopoietic cells (CD45(+)) expressed opioid peptides. L-selectin and beta(2) were coexpressed by 7 and 98% of opioid-containing leukocytes, respectively. Alpha(4) integrin was expressed in low levels by the majority of leukocytes. Opioid-containing cells, vascular P- and E-selectin and PECAM-1 were simultaneously upregulated. 5. Swim stress produced potent opioid-mediated antinociception in inflamed tissue, unaffected by blockade of PECAM-1. However, blockade of L- and P-selectins by fucoidin, or of alpha(4) and beta(2) by monoclonal antibodies completely abolished peripheral stress-induced antinociception. This coincided with a 40% decrease in the migration of opioid-containing leukocytes to inflamed tissue. 6. These findings establish selectins and integrins alpha(4) and beta(2), but not PECAM-1, as important molecules involved in stress-induced opioid-mediated antinociception in inflammation. They point to a cautious use of anti-inflammatory treatments applying anti-selectin, anti-alpha(4) and anti-beta(2) strategies because they may impair intrinsic pain inhibition.