Non-clastogenicity in mouse bone marrow of fructose/lysine and other sugar/amino acid browning products with in vitro genotoxicity

Heated sugar/amino acid reaction mixtures, known to contain products that are clastogenic and/or mutagenic to cells in vitro, were evaluated for clastogenic activity in mouse bone marrow using the erythrocyte micronucleus assay. Heated (i.e. browned) fructose/lysine reaction mixtures were also evaluated in the Salmonella his-reversion assay and the Chinese hamster ovary (CHO) cell chromosomal aberration assay to confirm and extend previous in vitro observations. Significant mutagenicity of fructose/lysine mixtures was observed in Salmonella typhimurium strains TA100, TA2637, TA98 and TA102, with greater activity in mixtures heated at pH 10 than at pH 7. S-9 decreased the activity in strains TA100, TA2637 and TA98, but increased the activity in strain TA102. Both pH 7 and pH 10 reaction mixtures of the fructose/lysine browning reaction were highly clastogenic in CHO cells. Heated mixtures of fructose and lysine, and of glucose or ribose with lysine, histidine, tryptophan or cysteine, did not increase the frequency of micronucleated erythrocytes in mice when administered by the oral route. This indicates the absence of chromosomal aberrations in erythrocyte precursor cells, and indicates that the genotoxic components of the browned mixtures are not absorbed and distributed to bone marrow cells in amounts sufficient to induce micronuclei when given orally. Because sugar/amino acid browning reactions occur commonly in heated foods, it is important to evaluate further the in vivo genotoxicity of browning products in cell populations other than bone marrow.     

Cerebral glucose metabolism in patients with summer seasonal affective disorder.

Positron emission tomography scans of nine patients diagnosed with summer seasonal affective disorder (SSAD) were compared with scans of 45 normal control subjects to investigate differences in brain glucose metabolism. All subjects performed an auditory discrimination task beginning several minutes before injection of F-18-deoxyglucose and continuing for 30 minutes after injection. Regional glucose metabolic rates were extracted from 60 rectangular regions of interest measured in five planes selected as atlas matches from 28 total slices. Statistically significant differences between patients with SSAD and normal control subjects were found in cerebral glucose metabolic rate and also in normalized regional glucose metabolic rates in the orbital frontal cortex and in the left inferior parietal lobule.     

Neuroendocrine response to 5-hydroxytryptophan in seasonal affective disorder

A double-blind random-ordered comparison of the effects of placebo and 5-hydroxytryptophan (200 mg, orally) in ten depressed patients with seasonal affective disorder (SAD) and ten controls disclosed slightly but significantly higher basal levels of serum prolactin and a trend toward higher basal levels of serum cortisol in the patients with SAD compared with controls. After administration of 5-HTP, the cortisol level significantly increased and the prolactin level significantly decreased in both patients and controls. No differences in the melatonin level, growth hormone level, blood pressure, or pulse rate and no side effects were noted between patients and controls in the two study conditions; the timing of basal and 5-hydroxytryptophan-stimulated hormonal secretions was similar for both groups. These results are discussed with reference to current hypotheses of the cause of SAD.     

Longitudinal in vivo effects of growth hormone overexpression on bone in transgenic mice.

In this study we examined the effect of systemic overexpression of GH on bone in transgenic mice longitudinally in vivo over a period of 9 months. We observed substantially increased BMC in GH transgenic mice and a significant reduction in serum osteocalcin. GH effects on bone were strongly dependent on gender and developmental stage. INTRODUCTION: State-of-the-art bone marker and microimaging technology was applied in this longitudinal study to examine bone metabolism, BMC, bone density, and cortical bone structure over the life span of growth hormone (GH) transgenic (tg) mice. MATERIALS AND METHODS: Thirty-eight mice from four genetic groups (male, female, tg, and controls) were examined with DXA, and their femur and tibia were examined with peripheral QCT (pQCT). Osteocalcin (formation) and collagen cross-links (resorption) from serum and urine were also measured at postnatal weeks 3, 6, 9, 12, 18, 26, and 38. RESULTS: GH tg mice displayed a significant increase in body weight (up to 50%) and BMC (up to 90%), but serum osteocalcin was significantly reduced compared with controls. GH tg females (but not males) displayed increased trabecular density over controls up to week 12. In contrast, male (but not female) GH tg mice displayed a higher cortical cross-sectional area than controls. Cortical density was significantly lower in both male and female GH tg mice compared with control mice. CONCLUSIONS: The increase in BMC in GH tg mice is associated with reduced serum osteocalcin levels, indicating that bone turnover may be lower than in the control mice. On a structural level, bone responds to GH excess in a gender-specific manner, with alterations varying substantially between different developmental stages.     

Epidemiological findings of seasonal changes in mood and behavior. A telephone survey of Montgomery County, Maryland

Patterns of seasonal changes in mood and behavior in Montgomery County, Maryland, were evaluated in randomly selected household samples by lay interviewers using a telephone version of the Seasonal Pattern Assessment Questionnaire. The method for selecting the sample unit was random-digit dialing. We found that 92% of the survey subjects noticed seasonal changes of mood and behavior to varying degrees. For 27% of the sample seasonal changes were a problem and 4.3% to 10% of subjects, depending on the case-finding definition, rated a degree of seasonal impairment equivalent to that of patients with seasonal affective disorder. The seasonal pattern of "feeling worst" exhibited a bimodal distribution with a greater winter and a substantially lower summer peak (ratio, 4.5:1). Younger women who have a problem with seasonal changes and who feel worse on short days tended to exhibit the highest seasonality scores. It is apparent from our study that seasonal affective disorder represents the extreme end of the spectrum of seasonality that affects a large percentage of the general population. The influence of environmental factors on mood disorders and mood changes in the general population might provide valuable insight into pathogenesis, treatment, and prevention of affective illness.     

Considerations in selecting a moisturizer

The symptoms of xerosis (dry skin) can be ameliorated by increasing the hydration state of the stratum corneum through a humectant or occlusive effect, smoothing the rough surface with an emollient, replenishing natural moisturizing factors, and normalizing the stratum corneum. We present the primary and secondary functions of various "active" and vehicle ingredients and include precautions regarding certain classes of materials. Recommendations on selecting moisturizing systems are made based on ingredient functionality and the severity of the dry skin condition.     

The durations of human melatonin secretion and sleep respond to changes in daylength (photoperiod)

Seasonal changes in daylength (photoperiod) modify the duration of nocturnal melatonin (MT) secretion in many vertebrates. In some cases the changes in MT act as chemical signals that trigger photoperiodic induction of breeding and other seasonal phenomena. It is unclear whether, and to what extent changes in daylength modify the duration of human MT secretion. To address this question, I investigated whether the duration of human MT secretion could be altered by artificial photoperiods. I exposed eight healthy volunteers to a conventional "summer" photoperiod of 16 h light and 8 h darkness for 1 week and to a "winter" photoperiod of 10 h light and 14 h darkness for 4 weeks. As occurs in animals, the duration of nocturnal MT secretion in human beings was longer after exposure to the short photoperiod (12.5 +/- 1.8 vs. 10.3 +/- 0.8 h, t = 3.778, P less than 0.01). The duration of the sleep-phase (recorded by electroencephalogram) was also longer (11.0 +/- 0.8 vs. 7.7 +/- 0.2 h, t = 11.754, P less than 0.001). Whether such changes would lead to significant seasonal changes in human physiology and behavior under natural lighting conditions may be worthy of further investigation.     

Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy: A propensity score–matched cohort

Objectives

In patients with hypertrophic cardiomyopathy, obstruction of the left ventricular outflow tract can be relieved by surgical septal myectomy or alcohol septal ablation, but uncertainty remains regarding long-term results and comparative effectiveness of alcohol septal ablation. This study aims to compare short- and long-term outcomes of the 2 procedures.

Novel Steerable Telescoping Catheter System for Implantation of Left Ventricular Pacing Leads

Advances in left ventricular transvenous lead delivery systems for biventricular pacing are leading to more refined techniques, shorter procedure times and higher implant success rates. Despite these advances, the inability to successfully cannulate the coronary sinus and deliver a lead to a distal location are still major causes of prolonged procedures times and implant failures. The pathophysiologic process of heart failure results in dilatation of the right atrium as well as other morphological changes in cardiac anatomy. Additionally, cannulation can be further complicated by congenital anomalous cardiac anatomy. This report describes the implant of a biventricular pacing system using a novel, steerable 7 French catheter system developed to aid in the cannulation of the coronary sinus ostium and its venous branches. The steerable catheter is used in conjunction with a 9 French braided sheath and guide-wire to create a telescoping system. The use of new tools and methods as described provides insight into available options for left ventricular transvenous lead implantation and dealing with difficult anatomy.Additional Notes This case, in part, was presented at Cardiostim 2004 (June 16–19, 2004, Nice Acropolis, Nice).     

Synthesis of different glutathione–sulfur mustard adducts of verified and potential biomarkers

Sulfur Mustard (SM) is a blistering agent used as a chemical weapon. Glutathione (GSH) is involved in the β-lyase degradation pathway of SM and recently, bioadducts between SM and GSH were observed in vitro. While these bioadducts have never been isolated from in vivo tests or real poisoning with SM, they could be of interest as potential future biomarkers for the retrospective validation of exposure. We herein report the synthesis of different observed and new potential GSH–SM bioadducts as reference materials for analytical investigation. Two distinct approaches were investigated: a building-block pathway and the direct reaction with GSH. The availability of these references will aid future studies and may lead to the discovery of new GSH–SM biomarkers.

Recently, several adducts between the chemical agent sulfur mustard (SM) and glutathione (GSH) were observed in vitro. We report the synthesis of different observed and potential GSH–SM bioadducts as reference materials for analytical investigation.