Isolation of cDNA clones encoding putative odourant binding proteins from the antennae of the malaria-transmitting mosquito, Anopheles gambiae

One way of controlling disease transmission by blood-feeding mosquitoes is to reduce the frequency of insect-host interaction, thus reducing the probability of parasite transmission and re-infection. A better understanding of the olfactory processes responsible for allowing mosquitoes to identify human hosts is required in order to develop methods that will interfere with host seeking. We have therefore initiated a molecular approach to isolate and characterize the genes and their products that are involved in the olfactory recognition pathway of the mosquito Anopheles gambiae, which is the main malaria vector in sub-Saharan Africa. We report here the isolation and preliminary characterization of several cDNAs from male and female A. gambiae antennal libraries that encode putative odourant binding proteins. Their conceptual translation products show extensive sequence similarity to known insect odourant binding proteins (OBPs)/pheromone binding proteins (PBPs), especially to those of D. melanogaster. The A. gambiae OBPs described here are expressed in the antennae of both genders, and some of the A. gambiae OBP genes are well conserved in other disease-transmitting mosquito species, such as Aedes aegypti and Culex quinquefasciatus.     

Operative treatment of rectal endometriosis

27 patients with rectal endometriosis were operated upon in Turku University Central Hospital in 1967-1976. The main symptom was defecation pain especially during menstruation. Eighteen patients had had previous surgery for endometriosis of the pelvic area. A palpable tumor was found on gynaecological examination in every patient. The tumors did not grow through the rectal wall. Three kinds of operative procedures were applied (a simple excision method, a so called "window" operation, and resection of rectum) and the results were good.     

A mouse model of cerebral oligemia: relation to brain histopathology, cerebral blood flow, and energy state

An animal model involving stepwise occlusion of the common carotid arteries (sCCAO) in DBA/2 mice is presented in which the right and left carotid arteries were permanently ligated within a time interval of four weeks. Thereafter, cerebral functional and structural parameters were determined at acute (15 min) and subchronic (1 day; 3, 7, and 14 days) time points after sCCAO. Quantitative changes in regional cerebral blood flow (rCBF) as determined by the [14C]iodoantipyrine method, energy state (ATP, phosphocreatine, ADP, AMP, adenosine) as shown by HPLC, brain histopathology, and neuronal densities were measured in both hemispheres. Acute sCCAO was accompanied by a drastic reduction in cerebral energy-rich phosphate concentrations, ATP and phosphocreatine, and in rCBF of more than 50%. In contrast, cortical adenosine increased around five-fold. Subchronic sCCAO, however, was associated with normalization in brain energy metabolites and near-complete restoration of rCBF, except in the caudate nucleus (–40%). No marked signs of necrotic or apoptotic cell destruction were detected. Thus, during the subchronic period, compensatory mechanisms are induced to counteract the drastic changes seen after acute vessel occlusion. In conclusion, this sCCAO mouse model may be useful for long-lasting investigations of stepwise deterioration contributing to chronic cerebrovascular disorders.     

Toxic metals and the menopause

Toxicity of chemicals and environmental pollutants may be expressed differently in women than in men. Until recently, most research involved men. With the initiation of studies on the effects of environmental pollutants in women, there is increasing evidence of effects at specific periods in a woman's life; however, accrual of data is slow. This review focuses on the kinetics and effects of the toxic metals lead and cadmium related to menopause. Data on other metals are extremely limited. One of the few well described examples of menopausal-related effects of metals is the very painful disease called Itai-itai, which is a combination of osteoporosis, osteomalacia and renal damage caused by consumption of cadmium-polluted rice. Recent data demonstrate mild effects of cadmium on both kidney and bone with present environmental exposure levels. Women may be at greater risk than men, because of increased gastrointestinal uptake of cadmium at low iron stores, which is common in women of childbearing age. Thus, improvement of iron status, which often occurs at menopause, has a positive effect on cadmium exposure in the sense that its absorption decreases. Cadmium accumulates in the kidney with a half-life of 10-30 years. The health effects appear around menopause, concurrent with the peak in renal cadmium concentrations. About 90% of body lead is localised to bone. There is a significant release of bone lead after the menopause, in association with the acceleration of bone resorption. Thus, postmenopausal women may be at increased risk of adverse effects of lead.     

Interaction between matrix metalloproteinase 3 and the epsilon4 allele of apolipoprotein E increases the risk of Alzheimer's disease in Finns

Polymorphisms affecting the expression of matrix metalloproteinases (MMPs), i.e. proteolytic enzymes that degrade intercellular material, have been found at position -1607 (1G/2G) in MMP1 and at -1171 (5A/6A) in MMP3. Interestingly, elevated levels of MMP1 and MMP3 have been observed in the brains of Alzheimer's disease (AD) patients and those of tissue inhibitors of MMPs in the cerebrospinal fluid of AD and Parkinson's disease (PD) patients, suggesting a role for MMPs in these disorders. The aim was to investigate a possible association between the afore-mentioned MMP1 and MMP3 polymorphisms and the risk of developing AD or PD. The polymorphisms were genotyped in 97 AD, 52 PD and 101 control patients. We found an interaction between MMP3*5A and APOE 4 alleles (P < 0.0001) which increases the risk of AD (OR: 23.7, 95% CI: 5.8-144.9, P < 0.0001) compared to those who possess neither MMP3*5A nor APOE 4. In conclusion, our finding suggests that the MMP3 gene, especially together with APOE 4, may contribute to the development of AD.     

Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton

The role of 5-lipoxygenase (5-LOX) in the pathophysiology of the organ injury/dysfunction caused by endotoxin is not known. Here, we investigate the effects of treatment with 5-LOX inhibitor zileuton in rats and targeted disruption of the 5-LOX gene in mice (5-LOX(-/-)) on multiple organ injury/dysfunction caused by severe endotoxemia. We also investigate the expression of beta2-integrins CD11a/CD18 and CD11b/CD18 on rat leukocytes by flow cytometry. Zileuton [3 mg/kg intravenously (i.v.)] or vehicle (10% dimethyl sulfoxide) was administered to rats 15 min prior to lipopolysaccharide (LPS; Escherichia coli, 6 mg/kg i.v.) or vehicle (saline). 5-LOX(-/-) mice and wild-type littermate controls were treated with LPS (E. coli, 20 mg/kg intraperitoneally) or vehicle (saline). Endotoxemia for 6 h in rats or 16 h in mice resulted in liver injury/dysfunction (increase in the serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin), renal dysfunction (creatinine), and pancreatic injury (lipase, amylase). Absence of functional 5-LOX (zileuton treatment or targeted disruption of the 5-LOX gene) reduced the multiple organ injury/dysfunction caused by endotoxemia. Polymorphonuclear leukocyte infiltration (myeloperoxidase activity) in the lung and ileum as well as pulmonary injury (histology) were markedly reduced in 5-LOX(-/-) mice. Zileuton also reduced the LPS-induced expression of CD11b/CD18 on rat leukocytes. We propose that endogenous 5-LOX metabolites enhance the degree of multiple organ injury/dysfunction caused by severe endotoxemia by promoting the expression of the adhesion molecule CD11b/CD18 and that inhibitors of 5-LOX may be useful in the therapy of the organ injury/dysfunction associated with endotoxic shock.     

Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease

OBJECTIVE: To evaluate and synthesize the evidence on the effect of supplements of vitamin E on the prevention and treatment of cardiovascular disease. DESIGN: Systematic review of placebo-controlled randomized controlled trials; meta-analysis where justified. MEASUREMENTS AND MAIN RESULTS: Eighty-four eligible trials were identified. For the outcomes of all-cause mortality, cardiovascular mortality, fatal or nonfatal myocardial infarction, and blood lipids, neither supplements of vitamin E alone nor vitamin E given with other agents yielded a statistically significant beneficial or adverse pooled relative risk (for example, pooled relative risk of vitamin E alone = 0.96 [95% confidence interval (CI), 0.84 to 1.10]; 0.97 [95% CI, 0.80 to 1.90]; and 0.72 [95% CI, 0.51 to 1.02] for all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction, respectively. CONCLUSIONS: There is good evidence that vitamin E supplementation does not beneficially or adversely affect cardiovascular outcomes.     

The diagnostic value of endoscopy and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> tests for peptic ulcer patients in late post-treatment setting

Background  

Guidelines for management of peptic ulcer patients after the treatment are largely directed to detection of H. pylori infection using only non-invasive tests. We compared the diagnostic value of non-invasive and endoscopy based H. pylori tests in a late post-treatment setting.     

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production

BACKGROUND: Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. OBJECTIVE: Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ERbeta (AluI) and ERbeta[cx] (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. DESIGN: One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. RESULTS: Isoflavones improved CRP concentrations [odds ratio (95% CI) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ERbeta AluI genotypes. CONCLUSION: Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.