Influence of lecithin on mitochondrial DNA and age-related hearing loss.

OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA(4834)) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging.     

Comorbidities in head and neck cancer: agreement between self-report and chart review.

OBJECTIVES: To determine the accuracy of self-reported comorbidities compared with medical record review and the clinical and sociodemographic characteristics associated with accuracy of self-reported comorbidities. STUDY DESIGN: We conducted a prospective study of 458 newly diagnosed head and neck cancer patients using self-administered questionnaire and medical chart review data. Overall and itemwise consistency between self-report and chart review was evaluated. Social, clinical, and demographic characteristics of consistent versus inconsistent responders were analyzed. RESULTS: Seventy-four percent of patients had at least one comorbidity. There was good overall consistency between self-report and chart review (kappa = 0.50). Compared with consistent responders, inconsistent responders were found to be older (P < 0.05), have lower sleep (P < 0.05) and physical activity scores (P < 0.05), be more depressed (P < 0.05), and have more severe comorbidities (P < 0.05). CONCLUSIONS AND SIGNIFICANCE: Self-report may be considered as an alternative to chart review for comorbidity assessment in head and neck cancer patients. Younger patients, those with good general health, fewer depressive symptoms, and mild comorbidities, are more likely to give responses consistent with chart review.     

Enzyme immunoassay compared with cell culture and immunofluorescence for detecting genital chlamydia.

A novel enzyme immunoassay test (Pharmacia EIA) was evaluated against cell culture for the detection of chlamydial genital infection. Specimens were obtained from 525 patients (257 men and 268 women). Sensitivity, specificity, predictive value of positive (PVP) and predictive value of negative (PVN) for the new test were, respectively, 83.6, 98.5, 94.4 and 95.1% for men and 86, 97.2, 87.8 and 96.8% for women. Discrepancies were further evaluated by repeating the EIA, and by direct immunofluorescence on the EIA transport buffer. The sensitivity, specificity, PVP and PVN of the EIA against the combination of cell culture and direct immunofluorescence were, respectively 85.9, 100, 100, and 95.5% for men, and 90.5, 98.1, 92.3 and 97.7% for women. Overall agreement between the EIA and the combination of cell culture and direct immunofluorescence was 97%. The Pharmacia EIA is rapid and simple to perform and does not require elaborate equipment.     

Improving the teaching skills of residents as tutors/facilitators and addressing the shortage of faculty facilitators for PBL modules

Background  

Residents play an important role in teaching of medical undergraduate students. Despite their importance in teaching undergraduates they are not involved in any formal training in teaching and leadership skills. We aimed to compare the teaching skills of residents with faculty in facilitating small group Problem Based Learning (PBL) sessions.     

Cross-regulation of CD86 by CD80 differentially regulates T helper responses from Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets

We report that stimulation of Mycobacterium tuberculosis secretory antigen- and tumor necrosis factor alpha-matured BALB/c mouse bone marrow dendritic cells (BMDCs) with anti-CD80 monoclonal antibody up-regulated CD86 levels on the cell surface. Coculture of these BMDCs with na?ve, allogeneic T cells now down-regulated T helper cell type 1 (Th1) responses and up-regulated suppressor responses. Similar results were obtained with splenic CD11c(+)/CD8a(-) DCs but not to the same extent with CD11c(+)/CD8a(+) DCs. Following coculture with T cells, only BMDCs and CD11c(+)/CD8a(-) DCs and not CD11c(+)/CD8a(+) DCs displayed increased levels of surface CD86, and further, coculturing these DCs with a fresh set of T cells attenuated Th1 responses and increased suppressor responses. Not only na?ve but even antigen-specific recall responses of the Th1-committed cells were modulated by DCs expressing up-regulated surface CD86. Further analyses showed that stimulation with anti-CD80 increased interleukin (IL)-10 and transforming growth factor-beta-1 levels with a concomitant reduction in IL-12p40 and interferon-gamma levels from BMDCs and CD11c(+)/CD8a(-) DCs and to a lesser extent, from CD11c(+)/CD8a(+) DCs. These results suggest that cross-talk between costimulatory molecules differentially regulates their relative surface densities leading to modulation of Th responses initiated from some DC subsets, and Th1-committed DCs such as CD11c(+)/CD8a(+) DCs may not allow for such modulation. Cognate antigen-presenting cell (APC):T cell interactions then impart a level of polarization on APCs mediated via cross-regulation of costimulatory molecules, which govern the nature of subsequent Th responses.     

Tissue repair plays pivotal role in final outcome of liver injury following chloroform and allyl alcohol binary mixture.

The objective of this study was to evaluate the interaction profile of chloroform (CHCl(3))+allyl alcohol (AA) binary mixture (BM)-induced acute hepatotoxic response. Plasma alanine aminotransferase (ALT) was measured to assess liver injury, and 3H-thymidine (3H-T) incorporation into hepatonuclear DNA was measured as an index of liver regeneration over a time course of 0-72 h. Male Sprague-Dawley (S-D) rats received single ip injection of 5-fold dose range of CHCl(3) (74, 185 and 370 mg/kg) in corn oil (maximum 0.5 ml/kg) and 7-fold dose range of AA (5, 20 and 35 mg/kg) in distilled water simultaneously. The doses for BM were selected from individual toxicity studies of CHCl(3) alone [Int. J. Toxicol. 22 (2003) 25], and AA alone [Reg. Pharmacol. Toxicol. 19 (1999) 165]. Since the highest dose of each treatment (CHCl(3)- 740 and AA- 50 mg/kg) yielded mortality due to the suppressed tissue repair followed by liver failure, this dose was omitted for BM. The levels of CHCl(3) (30-360 min) and AA (5-60 min) were quantified in blood and liver by gas chromatography (GC). The liver injury was more than additive after BM compared to CHCl(3) alone or AA alone at highest dose combination (370+35 mg/kg), which peaked at 24 h. The augmented liver injury observed with BM was consistent with the quantitation data. Though the liver injury was higher, the greater stimulation of tissue repair kept injury from progressing, and rescued the rats from hepatic failure and death. At lower dose combinations, the liver injury was no more than additive. Results of the present study suggest that liver tissue repair, in which liver tissue lost to injury is promptly replaced, plays a pivotal role in the final outcome of liver injury after exposure to BM of CHCl(3) and AA.     

Possible role of endothelin-1 in the rabbit urinary bladder hyperplasia secondary to partial bladder outlet obstruction

OBJECTIVES: Urinary bladder hypertrophy and hyperplasia are common features of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1), which is a potent vasoconstrictor peptide with mitogenic properties. Using an animal model of partial BOO, we investigated the potential role of ET-1 and its receptor subtypes (ET(A) and ET(B)) in bladder smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Partial BOO was produced in adult male New Zealand White rabbits. After 3 weeks, the bladder was removed and SMCs from the dome and bladder neck were grown using standard explant methodology. At passage 2, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or partial BOO serum (BRS) in the presence or absence of ET(A)-antagonist (BQ123) or ET(B)-antagonist (BQ788). SMC proliferation was then measured 24 h later with 5-bromo-2'deoxy-uracil and by cell counting using a haemocytometer at 48 h. Immunostaining for alpha-actin was performed on detrusor and bladder neck cells to confirm the presence of smooth muscle cells. RESULTS: BQ123 and BQ788 did not influence detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of BRS, BQ123 and BQ788 (100 nmol/L) significantly (p = 0.008) inhibited detrusor and bladder neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with BQ123 and BQ788, respectively) and bladder neck (p = 0.01 for both BQ123 and BQ78). CONCLUSIONS: These results suggest that ET antagonists may have a role in preventing SMC hyperplasia associated with partial BOO.     

Sclerosing polycystic adenosis of the oral cavity

Minor salivary glands are ubiquitous in the oral cavity, and related diseases are often indolent and asymptomatic. We describe the unusual features of sclerosing polycystic adenosis, and its similarities to more sinister conditions of the minor salivary glands. Its importance is currently uncertain and research points to a pathogenesis that is neoplastic, which can create ambiguity. Sclerosing polycystic adenosis is a newly-discovered condition that merits further discussion and research to evaluate its full impact.