Uptake of dehydroascorbic acid in high-GSH and normal-GSH dog erythrocytes

Uptake of dehydroascorbic acid (DHA) was studied in two types of dog erythrocytes with high GSH and normal GSH levels. Compared with ascorbic acid uptake, DHA produced a much greater ascorbic acid accumulation in dog erythrocytes. Both dog erythrocytes showed a concentration dependence of DHA uptake, and cellular ascorbic acid concentrations were significantly higher in high-GSH cells than in normal-GSH cells. Glucose and cytochalasin B inhibited DHA uptake. This suggests that DHA enters dog erythrocytes predominantly by the facilitated glucose transporter, particularly by the Glut 1 glucose transporter. The rate of glucose uptake was quite similar in the two types of cells. Compared with normal-GSH cells, high-GSH cells were more resistant to oxidative stress induced by high concentration of DHA. As a rapid entry of DHA inflicts on cells a heavy demand for GSH for its reduction to ascorbic acid, high-GSH cells containing a larger reserve of GSH have an advantage over normal-GSH cells in both ascorbic acid accumulation and resisting oxidative stress produced by DHA.     

Cerebral Effects in Superior Vena Caval Cannula Obstruction: The Role of Brain Monitoring

A pediatric cardiac case of transient obstruction of the superior vena cava by the venous cannula before cardiopulmonary bypass is presented. With venous obstruction and increase in central venous pressure, reduced cerebral blood flow velocities and absence of diastolic Doppler flow were detected. This was followed by regional cerebral venous oxygen desaturation and global electroencephalographic slowing. Reposition of the venous cannula led to the recovery of these physiologic indicators and a noncomplicated clinical outcome.     

Defective Acidification in Human Breast Tumor Cells and Implications for Chemotherapy

Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. This report presents a quantification of the pH for identified compartments of the MCF-7 human breast tumor cell line and demonstrates that (a) the chemotherapeutic Adriamycin concentrates in acidified organelles of drug-resistant but not drug-sensitive cells; (b) the lysosomes and recycling endosomes are not acidified in drug-sensitive cells; (c) the cytosol of drug-sensitive cells is 0.4 pH units more acidic than the cytosol of resistant cells; and (d) disrupting the acidification of the organelles of resistant cells with monensin, bafilomycin A1, or concanamycin A is sufficient to change the Adriamycin distribution to that found in drug-sensitive cells, rendering the cell vulnerable once again to chemotherapy. These results suggest that acidification of organelles is causally related to drug resistance and is consistent with the hypothesis that sequestration of drugs in acidic organelles and subsequent extrusion from the cell through the secretory pathways contribute to chemotherapeutic resistance.     

The determinants of bronchial hyperresponsiveness in patients with allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis and bronchial hyperresponsiveness (BHR) may be at higher risk of developing asthma. OBJECTIVE: To investigate whether reactivity to aeroallergens in skin prick testing (SPT) and serum eosinophil cationic protein levels can be used to predict BHR in allergic rhinitis patients. METHODS: Fifty-nine consecutive patients with allergic rhinitis underwent SPTs using grass, tree, weed, parietaria, Alternaria, Aspergillus, mites, and cat and dog dander extracts. Methacholine challenge tests were performed using spirometry. RESULTS: Methacholine-induced BHR was detected in 23 patients (39%). Of 59 patients, 14 had 1 positive SPT response, 35 had 2 to 4 positive responses, and 10 had more than 4 positive responses. There was a significant inverse correlation between methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) and the number of positive SPT responses (r = -0.28; P = .03). The BHR-positive patients had a mean of 4 positive SPT responses, whereas BHR-negative patients had a mean of 2.6 (P = .04). Nine BHR-positive patients (39%) and only 1 BHR-negative patient (3%) had more than 4 positive SPT responses (P < .001). There was no correlation between serum eosinophil cationic protein levels and methacholine PC20 doses. There was a strong association between hyperresponsiveness to methacholine and both cat and dog dander sensitivity (P < .001 and P = .001, respectively). CONCLUSIONS: Allergic rhinitis patients with SPT responses to a higher number of allergens are more likely to have BHR. Whether the number of positive SPT responses correlates with the risk of developing asthma in allergic rhinitis patients remains to be determined.     

Satisfaction among women: differences between current users of barrier (male condom) and non-barrier methods.

OBJECTIVES: To determine the differences in and factors related to satisfaction between barrier (male condom) and non-barrier method users. METHODS: A semi-structured questionnaire was used for collecting data for this cross-sectional survey. The questionnaires were completed via one-on-one interviews by the researchers. The study group was selected using stratified random sampling. Exclusion criteria were, being unmarried, pregnant, in postmenopausal status and using traditional methods. A total of 434 currently married women using modern contraceptive methods participated in the study. Contraceptive users were dichotomized into two groups as non-barrier method users and barrier method users. RESULTS: About half of the participants (n = 191, 44%) were barrier method users. Their mean age was 33.7 +/- 7.3 years, 66.6% (n = 131) were well educated and reported significantly less pregnancies, given births, living children and abortions (reproductive history events) than non-barrier users. Barrier method users were significantly more likely to be satisfied with their contraceptive method of choice (OR: 2.4; 95% CI 1.2-5.2). Among barrier method users, deciding the type of the contraceptive method themselves had significant effect on satisfaction.CONCLUSION: In our study, satisfaction was mostly affected by heavy side effects and health risks of the methods resulting in less satisfaction with the contraceptive method among non-barrier method users. Other factors which may influence satisfaction deserve further investigation.     

Prognostic significance of metastasis-associated protein S100A4 (Mts1) in prostate cancer progression and chemoprevention regimens in an autochthonous mouse model.

PURPOSE: We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen. EXPERIMENTAL DESIGN: Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study. RESULTS: With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin. CONCLUSIONS: S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.     

Clinical and biochemical spectrum of metabolic cardiomyopathy in Egyptian children

BackgroundInborn errors of metabolism (IEMs) commonly present with pediatric cardiomyopathy. Identification of the underlying cause is necessary as it may lead to improved outcomes.ObjectivesWe aimed to investigate the diagnostic rate, the clinical, and biochemical spectra of IEMs among Egyptian pediatric patients presenting with cardiomyopathy, and their outcome measures.MethodsWe retrospectively analyzed the clinical, biochemical, and radiological data of 1512 children diagnosed with cardiomyopathy at Cairo University Children''s Hospital over a 5-year duration.ResultsTwo hundred twenty-nine children were clinically suspected as IEMs and underwent metabolic workup. Nineteen different IEMs were confirmed in 57 (24.4%) of the suspected children. Their median age at presentation was 2.6 years and the majority had extra-cardiac manifestations. Hypertrophic cardiomyopathy represented 43/57 (75.4%) of confirmed cases, while dilated cardiomyopathy represented 13/57 (22.8%), and one patient presented with a mixed phenotype. Twenty- six patients (45.6%) survived, while 31 patients (54%) either died or were lost to follow up and assumed deceased.ConclusionsWe developed for the first time a database and a diagnostic scheme for metabolic cardiomyopathies in Egyptian children. With the recent introduction of enzyme replacement therapy, many metabolic disorders became treatable, thus establishing an early and accurate diagnosis is extremely important.     

Acknowledging the use of human cadaveric tissues in research papers: Recommendations from anatomical journal editors

Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors‐in‐chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.