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.     

Evidence for reduced cerebellar volumes in trichotillomania.

BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups.     

Calcium mass transfer in peritoneal dialysis patients using 2.5 mEq/l calcium dialysate.

Standard peritoneal dialysate has a relatively high calcium concentration of 3.5 mEq/l. Peritoneal dialysis patients thus gain calcium from the dialysate which contributes to the risk of hypercalcemia. Dialysate with 2.5 mEq/l calcium is now available. Theoretically, using dialysate with this calcium content, calcium transfer should be negative (from the patient into the dialysate) when the patient is hypercalcemic, and positive when the patient is normocalcemic or hypercalcemic. Thus, 2.5 mEq/l calcium dialysate may allow larger doses of calcium carbonate to be prescribed. We compared calcium mass transfer (CMT) in 17 stable peritoneal dialysis patients using 3.5 and 2.5 mEq/l calcium dialysate. A solution of 2.05 l, 1.5 g/dl dextrose was dwelled for 4 hours. Calcium was measured in the drained dialysate and serum (total and ionized). Mean CMT was 0.7 +/- 0.5 mEq/exchange using 3.5 mEq/l calcium dialysate and -0.9 +/- 0.9 mEq/exchange using 2.5 mEq/l calcium dialysate (p less than 0.0001). At the time of the CMT studies, the mean serum ionized calcium levels were identical for the two groups (2.6 mEq/l). CMT correlated inversely with serum total calcium, serum ionized calcium, and drained dialysate volume. During hypercalcemia calcium transfer was from the dialysate to the patient when 3.5 mEq/l calcium dialysate was used, but from the patient to the dialysate when 2.5 mEq/l calcium dialysate was used. We conclude that 2.5 mEq/l calcium dialysate is effective in removing calcium and will be helpful in preventing hypercalcemia when large doses of oral calcium compounds are prescribed as a phosphate binder.     

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.     

Are sex offenders treatable? A research overview

OBJECTIVE: Recent legislation in several states providing for civil commitment and preventive detention of sexually violent persons has stirred legal, clinical, and public policy controversies. The mandate for psychiatric evaluation and treatment has an impact on public mental health systems, requiring clinicians and public administrators to direct attention to treatment options. It is a common view that no treatments work for disorders involving sexual aggression. The authors examine this assumption by reviewing research on the effectiveness of treatment for adult male sex offenders. METHODS: MEDLINE was searched for key reviews and papers published during the years 1970 through 1998 that presented outcome data for sex offenders in treatment programs, individual case reports, and other clinically and theoretically important information. RESULTS: Although rigorous research designs are difficult to achieve, studies comparing treated and untreated sex offenders have been done. Measurement of outcome is flawed, with recidivism rates underestimating actual recurrence of the pathological behavior. Outcome research suggests a reduction in recidivism of 30 percent over seven years, with comparable effectiveness for hormonal and cognitive-behavioral treatments. Institutionally based treatment is associated with poorer outcome than outpatient treatment, and the nature of the offender's criminal record is an important prognostic factor. CONCLUSIONS: Although treatment does not eliminate sexual crime, research supports the view that treatment can decrease sex offense and protect potential victims. However, given the limitations in scientific knowledge and accuracy of outcome data, as well as the potential high human costs of prognostic uncertainty, any commitment to a social project substituting treatment for imprisonment of sexual aggressors must be accompanied by vigorous research.     

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.     

Quiescent Volcano—Chest Wall Hemangioma

Chest wall hemangiomas are rare tumors that may originate within the soft tissue or from the ribs. Intramuscular hemangioma is infrequent, representing less than 1 % of all hemangiomas, and the localization in the chest wall is even less frequent. They are typically cutaneous in location, large, and poorly circumscribed and can be locally destructive. We present a case of a 34-year-old lady presented with firm lump 3 × 3 cm in left upper and inner quadrant of left breast well defined borders, non-pulsatile and restricted mobility. Sono-mammogram was suggestive of ill-defined lesion at 10 o’clock position. CT chest was conclusive of chest wall hemangioma. The patient underwent excision of the lump. HPE was suggestive of cavernous hemangioma. Cavernous hemangioma typically manifest at birth or before the age of 30 years. CT is more sensitive than plain radiography in detecting phleboliths, which are present in approximately 30 % of cavernous hemangiomas. Surgical excision would be treatment of choice. In this case, the site of the lesion was in the breast clinically mimicking that of a fibroadenoma which warrants hemangioma as a differential diagnosis.