Ex vivo cytokine production by whole mid-trimester amniotic fluid

We hypothesized that ex vivo measurement of intraamniotic production of immune mediators differed from analysis of these mediators within unincubated amniotic fluid. Mid-trimester amniotic fluid from 72 women were incubated ex vivo with or without 50 ng/ml lipopolysaccharide (LPS). Supernatants and the corresponding unincubated amniotic fluids were tested for interleukin (IL)-6, IL-1 receptor antagonist (IL-1ra), IL-10 and nitric oxide. Ex vivo culture resulted in increased release of IL-6, IL-10 and nitric oxide; IL-1ra levels were decreased following the incubation. A spontaneous preterm birth (SPTB) occurred in 12 (16.7%) of the subjects. Women with a subsequent SPTB had decreased IL-6 and increased IL-10 production following ex vivo culture compared to women with a term delivery. This association was not evident with unincubated amniotic fluids. Conversely, IL-1ra concentrations were elevated in women with subsequent SPTB only in unincubated amniotic fluids. Immune mediator production by ex vivo amniotic fluid culture differs from that present in amniotic fluid supernatants and may provide a more accurate indication of the immune potential of the intraamniotic environment.     

Serum dehydroepiandrosterone sulfate and osteoarthritis in older people: the Pro.V.A. study

Clinical Rheumatology - Although osteoarthritis (OA) and low levels of dehydroepiandrosterone sulfate (DHEAS) are common in the elderly, no studies on human beings are available concerning the...     

The impact of unfractionated heparin or bivalirudin on patients with stable coronary artery disease undergoing percutaneous coronary intervention

Objectives

To compare bleeding and clinical events of patients with stable angina or silent ischemia undergoing percutaneous coronary intervention (PCI) treated with unfractionated heparin (UFH) or bivalirudin.

Background

Few direct comparisons between UFH monotherapy versus bivalirudin exist for patients with stable ischemic heart disease undergoing PCI.

Methods

A prospective, investigator‐initiated, single‐center, single‐blinded, randomized trial of UFH versus bivalirudin was conducted. The primary endpoint was all bleeding (major and minor) from index‐hospitalization to 30 days post discharge. Secondary endpoints included major adverse cerebral and cardiovascular events (MACCE) and net adverse clinical events (NACE).

Results

Two‐hundred‐sixty patients were randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137) (53%) There were no significant differences in baseline clinical and angiographic characteristics between the two groups. Primary endpoint was similar in both groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs 0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI: 1.00‐13.3.6). Death and stent thrombosis rates were low and similar in both groups. Radial access was associated with fewer bleeding events compared to femoral access but not statistically significant (P = 0.29).

Conclusions

Among patients with stable angina or silent ischemia, there was no difference between UFH and bivalirudin in bleeding rates up to 30‐days post‐PCI. MACCE and NACE were higher among the bivalirudin group. Radial access was associated with a numerically lower rate of bleeding compared with femoral access.     

Mannan-binding lectin and ficolin deposition in skin lesions of pemphigus

Pemphigus is characterized by circulating autoantibodies directed against desmossomal antigens that, once bound to target antigens, induce disruption in the cell–cell adhesion of the epidermis and mucosal epithelium, leading to blister formation. Evidence has indicated a role for complement in the physiopathology of pemphigus, with complement deposition in intercellular spaces of skin and mucous membrane lesions. Mannan-binding lectin (MBL) and Ficolin-2 are recognition proteins of innate immunity, which by binding to specific molecular patterns on pathogens surfaces trigger the activation of complement, leading to phagocytosis and lyses of target cells and inflammation. In this study we report for the first time the deposition of MBL and ficolins in pemphigus lesions. Eight biopsies of skin lesions of pemphigus vulgaris were studied for in situ deposition of IgG and the complement components MBL, Ficolin 1, Ficolin-2, C1q, C3 and membrane attack complex C5b-9. All biopsies presented deposition of IgG and C3 in the intercellular spaces (ICS) of epidermis. MBL deposition was found in the ICS and basal membrane zone (BMZ) of all specimens, whereas C5b-9 showed deposition only in the ICS, with irregular distribution. Ficolin-2 were positive in 50% (4/8) of biopsies showing deposition in the BMZ. On the other hand, ficolin-1 and C1q were negative in all specimens. Our study suggest that MBL and to a lesser extend Ficolin-2 may bind to altered intercellular structures in the skin and lead to the activation of complement in situ, contributing to tissue damage in pemphigus.     

Health-promoting substances and heavy metal content in tomatoes grown with different farming techniques

BACKGROUND: Organic farming is a production technique that imposes major restrictions on the use of fertilizers, pesticides, feed additives and veterinary drugs and for this reason consumers perceive organic foods to be healthier. The content of health-promoting molecules such as ascorbic acid, beta-carotene, lycopene and salicylic acid are important aspects of the nutritional quality of organic foods. AIM: To evaluate health promoting substances and the heavy metal content of tomato berries grown using conventional, integrated pest management (IPM) and organic farming techniques. METHODS: Moisture was determined by drying, crude protein by the Kjeldhal method, and ashes by incineration at 550 degrees C. Ergosterol, ascorbic acid, beta-carotene, lycopene and salicylic acid were determined by HPLC. The levels of heavy metals were measured by atomic absorption spectroscopy. RESULTS: Compared to crops grown using conventional and IPM methods, organic tomatoes contained more salicylic acid but less vitamin C and lycopene. Organic tomatoes had higher Cd and Pb levels but a lower Cu content. Organic fruits had a slightly higher protein content than conventionally cultivated fruits, but the difference was minimal and consequently the nutritive significance was poor. CONCLUSIONS: Farming techniques may have an impact on the quality of tomatoes. Their higher salicylate content supports the notion that organic foodstuffs are more wholesome. However, the lower lycopene and ascorbic acid levels of organic tomatoes are not to be regarded as positive. No residues of pesticides and ergosterol were detected.     

Effects of Combined Ezetimibe and Simvastatin Therapy as Compared With Simvastatin Alone in Patients With Type 2 Diabetes: A prospective randomized double-blind clinical trial

OBJECTIVE

To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients.

RESEARCH DESIGN AND METHODS

In a multicenter prospective randomized double-blind placebo-controlled trial, we primarily compared by ANCOVA the effect of 2-month ezetimibe (10 mg/day) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria <200 μg/min and total cholesterol concentrations >135 mg/dl despite simvastatin treatment (40 mg/day).

RESULTS

Unlike placebo, ezetimibe decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl, total cholesterol from 162 ± 36 to 124 ± 30 mg/dl, and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl (P < 0.0001 for all changes versus placebo). A total of 72 and 17% of patients on ezetimibe or placebo achieved LDL levels <70 mg/dl, respectively (P < 0.0001). Treatment was well tolerated.

CONCLUSIONS

Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone.Inhibited gastrointestinal cholesterol absorption by add-on ezetimibe therapy (1) reduced cholesterol levels in patients with persistent dyslipidemia despite statin therapy (1–6). Advantages of dual- versus single-drug lipid-lowering therapy, however, could not be definitely established, since the effects of ezetimibe combined with a given dosage of a statin were compared with those of monotherapy with another competitor statin (4,5) or even with the same statin but given at higher dosages (2). To address this issue, the Ezetimibe and Simvastatin in Dyslipidemia of Diabetes (ESD) study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00157482","term_id":"NCT00157482"}}NCT00157482) compared the lipid-lowering effects of ezetimibe or placebo added on the same background statin therapy in type 2 diabetic patients with persistent hypercholesterolemia despite HMG-CoA reductase inhibition.     

Non-steroidal anti-inflammatory drug (NSAID) use and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study

Objective

Chronic inflammation is suspected to have a role in breast carcinogenesis. Results of studies of non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer have been inconsistent. Timing of exposure and analysis of individual NSAIDs should be considered.

Methods

We conducted a population-based case–control study in western New York State between 1996 and 2001. Cases, 35–79 years, had incident, primary, histologically confirmed breast cancer (n = 1,170). Controls (n = 2,115) were randomly selected from NY Department of Motor Vehicles records (<65 years) or Medicare rolls (≥65 years). Participants were queried on use of aspirin, ibuprofen, and acetaminophen in the year prior and on aspirin during adulthood. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).

Results

Recent aspirin use was inversely associated with breast cancer risk (adjusted OR 0.80, 95% CI: 0.68–0.94); the strongest reduction in risk was observed among those who took ≥2 pills/day on days that aspirin was taken (OR 0.74, 95% CI: 0.61–0. 90). Adult lifetime use was also associated with breast cancer risk (>10 days/month, adjusted OR 0.68, 95% CI: 0.46–1.00). Use of ibuprofen or acetaminophen was not associated with breast cancer.

Conclusions

This is the first study to investigate the association of adult lifetime aspirin intake with breast cancer risk. Our findings provide evidence that aspirin use throughout a woman’s life may confer some benefit.