Effects of acetaminophen and nonsteroidal anti-inflammatory drugs on progesterone production by porcine granulosa cells in vitro

We investigated the effects of a group of pharmaceutical agents commonly ingested by reproductive-aged women, acetaminophen and the nonsteroidal anti-inflammatory drugs (NSAID), on progesterone (P) production by cultures of highly differentiated porcine granulosa cells. These compounds were added to cultures over a dose range of 10(-8) to 10(-5) M and P, and cell protein was measured after 24 hours. P production was suppressed by acetaminophen, fenoprofen, and sulindac to a maximum of 81%, 76%, and 71% of control, respectively. P production was enhanced by butazolidin at all doses tested to a maximum of 140% of control. Granulosa cell protein was suppressed by butazolidin and salicylic acid to a maximum of 81% of controls. These data imply that acetaminophen and several NSAID have the potential for clinical reproductive toxicity with differing individual effects on reproductive tract tissues, suggesting further selective testing in vivo.     

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion The relationship between acute otitis media and otitis media with effusion (OME) is uncertain and the aetiology of OME is multifactorial. Otitis media with effusion may be an inflammatory condition; both bacteria and viral infections could play a part in this inflammation. The four bacteria Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus and Branhamella catarrhalis cause 60% of the infections whereas S. pneumoniae accounts for up to 35%. IgA provides the dominant surface response to polysaccharide and lipopolysaccharide antigens, of which IgA₂ is the main subclass. Once the mucosa has been breached, most protection is provided by IgG. IgG₂ acts mainly against bacterial capsular antigens. This study looked at two groups of 50 children with and without OME who were aged between 3 and 10 years. The aims were to determine if, firstly, the levels of the serum immunoglobulins were different in the two groups, secondly whether these children made the appropriate antibody response to the capsular antigen to S. pneumoniae (PCP), and finally if there was a delay in the maturity of the IgA response. The total IgG, IgA and all subclass levels were measured using radial immunodiffusion. Levels of functional IgA and IgG were measured using ELISAs (25 patients in each group). The results were analysed with non‐parametric tests. The immunoglobulin levels were within the normal levels for both groups. There were very good correlations between the IgG total anti‐PCP and the IgG₂ anti‐PCP (R > 0.9, p = 0.001). There was a good correlation between the levels of both IgG total and IgG₂ anti‐PCP against IgA total anti‐PCP in both groups (R > 0.85, p > 0.01). This confirms a normal antibody response between both groups of patients. The ages of the controls and patients (50 samples) were correlated with increasing titres of circulating functional antibodies (P = 0.001). This is highly suggestive of a normal age‐related response. In conclusion, the findings were contradictory to our original hypothesis that there is a subtle difference in surface protection between children with and without OME. We believe that a previous history of recurrent acute otitis media is unrelated to the development of OME after 3 years of age.     

Start Talking About Risks: Development of a Motivational Interviewing-Based Safer Sex Program for People Living with HIV

The epidemiology of HIV infection in the US in general, and in the southeast, in particular, has shifted dramatically over the past two decades, increasingly affecting women and minorities. The site for our intervention was an infectious diseases clinic based at a university hospital serving over 1,300 HIV-infected patients in North Carolina. Our patient population is diverse and reflects the trends seen more broadly in the epidemic in the southeast and in North Carolina. Practicing safer sex is a complex behavior with multiple determinants that vary by individual and social context. A comprehensive intervention that is client-centered and can be tailored to each individual’s circumstances is more likely to be effective at reducing risky behaviors among clients such as ours than are more confrontational or standardized prevention messages. One potential approach to improving safer sex practices among people living with HIV/AIDS (PLWHA) is Motivational Interviewing (MI), a non-judgmental, client-centered but directive counseling style. Below, we describe: (1) the development of the Start Talking About Risks (STAR) MI-based safer sex counseling program for PLWHA at our clinic site; (2) the intervention itself; and (3) lessons learned from implementing the intervention.     

The effects of diet on inflammation: emphasis on the metabolic syndrome.

Reducing the incidence of coronary heart disease with diet is possible. The main dietary strategies include adequate omega-3 fatty acids intake, reduction of saturated and trans-fats, and consumption of a diet high in fruits, vegetables, nuts, and whole grains and low in refined grains. Each of these strategies may be associated with lower generation of inflammation. This review examines the epidemiologic and clinical evidence concerning diet and inflammation. Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by an excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. The whole diet approach seems particularly promising to reduce the inflammation associated with the metabolic syndrome. The choice of healthy sources of carbohydrate, fat, and protein, associated with regular physical activity and avoidance of smoking, is critical to fighting the war against chronic disease. Western dietary patterns warm up inflammation, while prudent dietary patterns cool it down.     

Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers.

BACKGROUND & AIMS: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment-insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk, and none have reported associations on the basis of HOMA-IR. METHODS: We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n=29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin x fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. RESULTS: Median (interquartile range) values for serum insulin, glucose, and HOMA-IR were 4.1 (2.9-7.2) mIU/L, 101 (94-108) mg/dL, and 0.99 (0.69-1.98) for case subjects and 4.1 (2.7-6.1) mIU/L, 99 (93-107) mg/dL, and 1.02 (0.69-1.53) for non-case subjects, respectively. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03-3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06-3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92-3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend=.12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates. CONCLUSIONS: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors.     

Effect of pregnancy on the pharmacokinetics of metformin.

AIMS: To determine the effects of pregnancy on metformin pharmacokinetics. METHODS: Seven women with Type 2 diabetes mellitus taking metformin throughout pregnancy were studied on two occasions, once at 28-36 weeks gestation and once at least 8 weeks postpartum. Serum metformin concentrations were determined across a dosing interval using high-performance liquid chromatography. The areas under the serum concentration-time curve from 0 to 4 h post-dose (AUC0-4) and 0 to 8 h post-dose (AUC0-8) where possible, were compared in the pregnant and non-pregnant state. RESULTS: Metformin concentrations were lower in pregnancy in six subjects, with a mean (95% CI) AUC0-4 that was 69% (53.6, 84.8) of the postpartum value. The AUC0-4 of one subject was higher in pregnancy at 142% of the postpartum value. Overall, the mean (95% CI) AUC0-4 during pregnancy for all seven subjects was 80% (51.3, 107.8) of the postpartum value (P = 0.053, two-tailed t-test; P = 0.027, one-tailed t-test). CONCLUSION: These results are consistent with our hypothesis that the clearance of metformin increases in pregnancy as a result of enhanced renal elimination. A larger study is required to establish whether metformin dose adjustments are required in late pregnancy to maintain therapeutic effect.     

Screening for major depression in persons with HIV infection: the concurrent predictive validity of the Profile of Mood States Depression‐Dejection Scale

Major Depressive Disorder (MDD) is among the most prevalent but underdiagnosed psychiatric disorders in persons with HIV infection. Given the known adverse impact of comorbid MDD on HIV disease progression and health‐related quality of life, it is important both for research and for efficient, effective clinical care, to validate existing screening measures that may discriminate between MDD and the somatic symptoms of HIV (such as fatigue). In the current study, we evaluated the concurrent predictive validity of the Profile of Mood States (POMS) Depression‐Dejection scale in detecting current MDD in 310 persons with HIV infection. The Structured Clinical Interview for DSM‐IV (SCID) diagnosis of MDD and the Cognitive‐Affective scale from the Beck Depression Inventory (BDI‐CA) served as comparative diagnostic and severity measures of depression, respectively. Results demonstrated that the POMS Depression‐Dejection scale accurately classified persons with and without MDD SCID diagnoses, with an overall hit rate of 80%, sensitivity of 55%, specificity of 84%, and negative predictive power of 91% using a recommended cutpoint of 1.5 standard deviations above the normative mean. Moreover, the POMS performed comparably to the BDI‐CA in classifying MDD. Findings support the predictive validity of the POMS Depression‐Dejection scale as a screening instrument for MDD in persons with HIV disease. Copyright © 2006 John Wiley & Sons, Ltd.