7-hydroperoxycholesterol and oxysterols as indices of oxidative stress: chronic ethanol feeding and rat skeletal muscle

The present study is undertaken to determine if ethanol affects 7-hydroperoxycholesterol or oxysterols in rat skeletal muscle after chronic ethanol feeding. Wistar rats were fed a liquid diet containing ethanol as 35% of total calories. After 6 weeks, soleus (Type I fibre-predominant) and plantaris (Type II fibre-predominant) skeletal muscles were dissected out. We measured 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH) and 3beta-hydroxycholest-5-en-7-one (7-keto). We found that in response to chronic alcohol feeding, there were significant increases in soleus 7alpha-OH (P=0.0005), 7beta-OH (P=0.0005) and 7-keto (P=0.0007), but in the plantaris, 7beta-OH increased (P=0.0418). Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.     

Population-based patterns of human immunodeficiency virus-related Hodgkin lymphoma in the Greater San Francisco Bay Area, 1988-1998

BACKGROUND: Epidemiologic characteristics of human immunodeficiency virus (HIV)-related Hodgkin lymphoma (HL) have not been examined in the Greater San Francisco Bay Area, a center of the HIV/acquired immunodeficiency syndrome (AIDS) epidemic, for a decade, despite changes in AIDS-associated diseases after the availability of highly active antiretroviral therapies (HAART). METHODS: With population-based cancer registry data for 1988-1998, the authors examined risk factors, Epstein-Barr virus (EBV) association, incidence rates, and survival probabilities for 1752 patients with HL who were classified as HIV-positive or HIV-negative by a cancer registry-based method. RESULTS: One hundred twenty-eight patients with HL (7%) were classified with HIV/AIDS; 95% were male. Among males, multivariate analysis (n=514 patients) found that HIV-related HL was associated strongly at diagnosis with ages 30-49 years, San Francisco residence, late-stage disease, lymphocyte depletion and unspecified histologic subtypes, and tumor cell EBV but not with other clinical features or mixed cellularity histology. Survival among patients with HIV-related HL, although it was poor, did not differ by race/ethnicity but was worse for patients with the nonnodular sclerosis histologic subtypes. Patients who were HIV-positive with HAART era (1996-1998) diagnoses were slightly older, were less likely to live in San Francisco, and were much more likely to be Hispanic compared with HIV-positive patients who were diagnosed before the HAART era; they had somewhat less aggressive disease and better survival. Incidence rates were higher for patients with HL overall compared with patients who had HIV-unrelated HL by 11% for white patients, 22% for black patients, and by 14% for Hispanic patients; excesses were greater in young adults. CONCLUSIONS: Among males in the San Francisco Bay Area, HIV-related HL had distinctive demographic features, more aggressive clinical characteristics, stronger EBV association, and poorer survival and contributed to elevated regional HL incidence rates, particularly in young adults. Patients with HIV-related HL who were diagnosed after HAART was introduced appeared to have less aggressive disease and better survival.     

Pharmacokinetic/pharmacodynamic analysis of anti-hyperprolactinemic effect of terguride based on dopamine D2 receptor occupancy

Terguride has been widely used for the treatment of hyperprolactinemia via partial agonistic action on dopamine D2 receptors in the pituitary. The present study analyzed retrospectively the dopamine D2 receptor binding occupancy (phi) of terguride. The average phi value was estimated to be 14.1% after oral administration of the average/standard therapeutic dose of terguride. Taking the intrinsic activity (alpha) into consideration, the value of alpha. phi was 2.33%. These results suggest that the antihyperprolactinemic effect of terguride was elicited despite the low receptor occupancy. Furthermore, we developed a pharmacokinetic/pharmacodynamic model for ascertaining the serum prolactin-lowering effect of terguride, considering both the reversible binding to D2 receptors and the effect on the increase rate in the prolactin level. The developed model fit well with the actual data. Although this model could be improved, it could explain the long duration of the antihyperprolactinemic activity of terguride and might be useful for designing its rational dosage regimen.     

Effects of abstinence and smoking on information processing in adolescent smokers

RATIONALE: Although adolescent smokers appear to display some of the hallmark features of dependence, the biological and behavioral effects of smoking in this population are poorly understood. OBJECTIVES: This study aimed to define empirically the effects of abstinence and smoking in adolescent smokers, using indices validated in adult smokers. METHODS: Subjects were 16 young novice smokers (five male, 11 female), ages 14-18 years. A modified Stroop task measured the ability to inhibit attention to smoking-related cues; the classic Stroop task measured the ability to inhibit a pre-potent response (i.e. reading a word); a rapid information processing (RIP) task measured vigilance. RESULTS: Abstinence increased and smoking decreased the intrusiveness of smoking cues. Parallel effects were seen in commission errors on the RIP task. These effects were restricted to heavier smokers (>11 cigarettes/day). Subjective withdrawal effects predicted the intrusiveness of smoking words during abstinence. The number of cigarettes smoked per day predicted the beneficial effect of smoking on the classic as well as modified Stroop tasks. The physiological effects of abstinence and smoking predicted RIP performance. CONCLUSIONS: Abstinence impairs and smoking improves inhibitory information processing in young novice smokers in a manner similar to adult smokers. Daily frequency of smoking is a critical moderator of these effects.     

Staphylococcus aureus rectal carriage and its association with infections in patients in a surgical intensive care unit and a liver transplant unit.

BACKGROUND: The role of rectal carriage of Staphylococcus aureus as a risk factor for nosocomial S. aureus infections in critically ill patients has not been fully discerned. METHODS: Nasal and rectal swabs for S. aureus were obtained on admission and weekly thereafter until discharge or death from 204 consecutive patients admitted to the surgical intensive care unit and liver transplant unit RESULTS: Overall, 49.5% (101 of 204) of the patients never harbored S. aureus, 21.6% (44 of 204) were nasal carriers only, 3.4% (7 of 204) were rectal carriers only, and 25.5% (52 of 204) were both nasal and rectal carriers. Infections due to S. aureus developed in 15.7% (32 of 204) of the patients; these included 3% (3 of 101) of the non-carriers, 18.2% (8 of 44) of the nasal carriers only, 0% (0 of 7) of the rectal carriers only, and 40.4% (21 of 52) of the patients who were both nasal and rectal carriers (P - .001). Patients with both rectal and nasal carriage were significantly more likely to develop S. aureus infection than were those with nasal carriage only (odds ratio, 3.9; 95% confidence interval, 1.18 to 7.85; P= .025). By pulsed-field gel electrophoresis, the infecting rectal and nasal isolates were clonally identical in 82% (14 of 17) of the patients with S. aureus infections. CONCLUSIONS: Rectal carriage represents an underappreciated reservoir for S. aureus in patients in the intensive care unit and liver transplant recipients. Rectal plus nasal carriage may portend a greater risk for S. aureus infections in these patients than currently realized.     

Low plasma adiponectin level, white blood cell count and Helicobacter pylori titre independently predict abnormal pancreatic β-cell function

Adiponectin is an adipocytokine with insulin sensitizing effect while chronic inflammation damages pancreatic β-cells leading to reduced insulin response. We aimed to prove the hypothesis that adiponectin levels and inflammatory markers (white blood cell counts [WCC], Helicobacter pylori [HP] titers, high sensitivity C-reactive protein [hs-CRP]) may interact to affect risk of diabetes. We studied 288 Chinese men (age-median: 41.0 years, IQR: 35.3–46.0 years) being recruited from the community in Hong Kong. The mean adiponectin level was 5.39 ± 2.81 μg/ml and 40.9% (n = 107) had low adiponectin level (<4 μg/ml). On multiple regression analysis, adiponectin was negatively associated with diabetes, HOMA insulin resistance top quartile, plasma glucose (PG) and 2 h insulin; and positively associated with HOMA insulin sensitivity index. WCC was independently associated with PG and 15′ insulin, and negatively associated with HOMA insulin sensitivity top quartile. HP titre was associated with 30′ PG level and diabetes. hs-CRP did not enter the multivariable model. In conclusion, adiponectin, WCC and HP titer are independent predictors for hyperglycemia and reduced insulin sensitivity in Chinese men. These findings may explain the high risk for diabetes in Chinese population despite their relatively low adiposity.     

Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. INTRODUCTION: The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in once-weekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N = 520) or risedronate 35 mg (N = 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. RESULTS: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had > or =0% (p < 0.001) and > or =3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. CONCLUSIONS: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.