Cell cycle progression kinetics of regenerating mouse epidermal cells: an in vivo study combining DNA flow cytometry, cell sorting, and [3H]dThd autoradiography

Cantharidin application to mouse skin induces cell injury followed by a regenerative wave of cells entering S phase in partial synchrony about 16 h after application. After pulse labeling with [3H]dThd the synchronized cohort of cells was traced through subsequent cell cycles during regeneration. This was accomplished by DNA flow cytometry of isolated basal cells combined with sorting from G1, S, and G2 phases followed by autoradiography at intervals after pulse labeling. Successive peaks of labeled cells in S phase at about 12-h intervals, followed by subsequent peaks in G2 and G1 phases were seen. This shows that the peaks of S-phase cells seen at 16 and 28 h after cantharidin application represent mother and daughter cells, respectively, the latter still cycling in partial synchrony. These 2 peaks of S-phase cells, therefore, are not keratinocyte subpopulations with different time lags between the stimulus to regeneration and the subsequent response. It is further shown that the mean cell cycle time is reduced from about 55 h in normal epidermis to 12 h during early regeneration. This is mainly due to a considerably reduced G1 phase duration, but the S and G2 phase durations are also reduced, although still within the range of circadian variations seen in normal animals. It is reasonable to assume a causal relationship between the considerably reduced G1 duration and loss of growth restriction. Cells with a slow progression rate through G2 phase (70% of all G2 cells) in normal mouse epidermis seem to maintain a slow progression rate during regeneration. Normal growth homeostasis seems to be gradually reestablished during the second day of regeneration.     

Effect of calcium deficiency on vitamin B12 absorption in rats

The influence of calcium on vitamin B12 absorption was investigated in two experiments. In the first we investigated whether B12 malabsorption in rats with biliary diversion through choledochocolic fistula is caused by deficiency of calcium in the small intestine. Calcium concentrations were measured in 10 fistula- and 10 sham-operated rats. Fistula rats had steatorrhea, but the concentration of calcium in the intestinal lumen was increased. In the second experiment we studied the effect of calcium deficiency on B12 absorption. Ten young rats were fed a low-calcium diet and 10 rats a control diet for 4 weeks. Rats on the low-calcium diet had moderately reduced calcium concentration in the blood and in the intestinal juice but unaltered calcium concentration in the cytosol fraction of intestinal mucosal scrapings. The absorption of 57CoB12 was unimpaired. This suggests that moderate calcium deficiency does not influence the intestinal absorption of vitamin B12 in the rat.     

Local disodium cromoglycate is ineffective in ulcerative proctosigmoiditis

Conflicting results have emerged from studies using oral and rectal disodium cromoglycate (DSCG) in inflammatory bowel disease. In the present double-blind study, 43 patients with active ulcerative proctosigmoiditis received either placebo (n = 22) or 600 mg DSCG (n = 21) rectally as enemas for eight weeks. Assessment was made from clinical investigations, endoscopy, laboratory tests, biopsies, and diary cards. No statistically significant differences in bowel frequency, rectal bleeding, general well-being, abdominal pain, and severity and extent of the disease were found between the groups during the study. There was no significant change in the histologic parameters. No side-effect was encountered. It is concluded that DSCG did not improve symptoms or inflammatory changes in ulcerative proctosigmoiditis.     

Über den Einfluss des Vitamin A auf die Weisse Maus

Ohne Zusammenfassung     

Role of Marginal Vitamin C Deficiency in Atherogenesis: In Vivo Models and Clinical Studies

Abstract: Vitamin C is a pivotal redox modulater in many biological reactions of which several remain poorly understood. Naturally, vitamin C has been the subject of many investigations over the past decades in relation to its possible beneficial effects on cardiovascular disease primarily based on its powerful yet general antioxidant properties. However, growing epidemiological, clinical and experimental evidence now suggests a more specific role of ascorbate in vasomotion and in the prevention of atherosclerosis. For example, in contrast to most other biological antioxidants, administration of vitamin C can apparently induce vasodilation. Millions of people worldwide can be diagnosed with vitamin C deficiency according to accepted definitions. In this perspective, the present review examines the evidence for a specific link between vitamin C deficiency and increased risk of atherosclerosis as well as the possible mechanisms by which vitamin C may exert its protective function.     

A presynaptic role for the ADP ribosylation factor (ARF)-specific GDP/GTP exchange factor msec7-1

ADP ribosylation factors (ARFs) represent a family of small monomeric G proteins that switch from an inactive, GDP-bound state to an active, GTP-bound state. One member of this family, ARF6, translocates on activation from intracellular compartments to the plasma membrane and has been implicated in regulated exocytosis in neuroendocrine cells. Because GDP release in vivo is rather slow, ARF activation is facilitated by specific guanine nucleotide exchange factors like cytohesin-1 or ARNO. Here we show that msec7-1, a rat homologue of cytohesin-1, translocates ARF6 to the plasma membrane in living cells. Overexpression of msec7-1 leads to an increase in basal synaptic transmission at the Xenopus neuromuscular junction. msec7-1-containing synapses have a 5-fold higher frequency of spontaneous synaptic currents than control synapses. On stimulation, the amplitudes of the resulting evoked postsynaptic currents of msec7-1-overexpressing neurons are increased as well. However, further stimulation leads to a decline in amplitudes approaching the values of control synapses. This transient effect on amplitude is strongly reduced on overexpression of msec7-1E157K, a mutant incapable of translocating ARFs. Our results provide evidence that small G proteins of the ARF family and activating factors like msec7-1 play an important role in synaptic transmission, most likely by making more vesicles available for fusion at the plasma membrane.     

Calcium-Mobilizing Effect of Large Doses of 25-Hydroxycholecalciferol in Anephric Rats

The effect of high doses of 25-hydroxycholecalciferol on plasma calcium concentration was studied in rats receiving a low-calcium normal vitamin D diet. In bilaterally nephrectomized animals, as in sham-operated controls, 62.5 nmol of 25-hyroxycholecalciferol did not produce a rise of plasma calcium concentration. In contrast, the administration of 125 or 625 nmol, doses 1,000-5,000 times the minimal active dose in D-deficient rats, was followed in both groups of animals by a significant increase of plasma calcium concentration. Removal of either parathyroids alone or parathyroid and thyroid glands did not suppress this effect. These data suggest that when large doses are used in vivo, the renal conversion of 25-hydroxycholecalciferol to more polar metabolites is not an obligatory step for its calcium-mobilizing action. The present study does not elucidate, however, the exact mechanism(s) of this effect.     

Quality of life in nonorganic and organic sleep disorders: I. Comparison with normative data

Subjective health-related quality of life (HRQoL) was investigated in 100 patients with disturbed sleep (39 women aged 52 +/- 13 years and 61 men aged 53 +/- 10 years) referred to the sleep laboratory and compared with HRQoL in 100 normal healthy adults. Measurements included the Quality of Life Index (QLI) (Mezzich and Cohen), and objective (polysomnographic) and subjective (psychometric) quality of sleep and awakening. Statistical analysis (Mann-Whitney U-test) showed HRQoL to be significantly reduced in sleep disorders (SDs), with a more pronounced reduction in nonorganic than in organic SDs. Patients with nonorganic hypersomnia were more disturbed than those with nonorganic insomnia. Within organic SDs, patients with apnea were more disturbed than those with obstructive snoring. Out of ten elementary HRQoL components, seven were disturbed in SDs: physical well-being, psychological well-being, self-care and independent functioning, occupational functioning, interpersonal functioning, personal fulfillment, and overall quality of life. No differences between patients and normal healthy subjects where found in the components social support, community and services support or spiritual fulfillment. Patients suffering from nonorganic SDs had significantly worse scores in physical and psychological well-being and overall quality of life than those with organic SDs. Patients with both SDs and additional diagnoses of affective disorders had more profoundly reduced HRQoL than those with anxiety disorders. Follow-up of 51 patients (31 with nonorganic SDs and 20 with organic SDs) one year after sleep laboratory investigation and subsequent treatment found significantly improved HRQoL compared with pre-treatment. Moreover, patients diagnosed and treated in the sleep laboratory showed lower re-hospitalization rats.     

Evaluation of indicators of cobalamin deficiency defined as cobalamin-induced reduction in increased serum methylmalonic acid

BACKGROUND: Early detection of cobalamin deficiency is clinically important, and there is evidence that such deficiency occurs more frequently than previously anticipated. However, serum cobalamin and other commonly used tests have limited ability to diagnose a deficiency state. METHODS: We investigated the ability of hematological variables, serum cobalamin, plasma total homocysteine (tHcy), serum and erythrocyte folate, gastroscopy, age, and gender to predict cobalamin deficiency. Patients (n = 196; age range, 17-87 years) who had been referred from general practice for determination of serum cobalamin were studied. Cobalamin deficiency was defined as serum methylmalonic acid (MMA) >0.26 micromol/L with at least 50% reduction after cobalamin supplementation. ROC and logistic regression analyses were used. RESULTS: Serum cobalamin and tHcy were the best predictors, with areas under the ROC curve (SE) of 0. 810 (0.034) and 0.768 (0.037), respectively, but age, intrinsic factor antibodies, and gastroscopy gave additional information. CONCLUSIONS: When cobalamin deficiency is suspected in general practice, serum cobalamin should be the first diagnostic test, and the result should be interpreted in relation to the age of the patient. When a definite diagnosis cannot be reached, MMA and tHcy determination will provide additional discriminative information, but MMA, being more specific, is preferable for assessment of cobalamin status.     

Cancer nursing research priorities: a Norwegian perspective

The purpose of the study was to determine research priorities among Norwegian nurses in cancer care, and to investigate implications that these priorities might have for future planning of nursing research. Differences between specialists in cancer nursing and other nurses working in cancer care, and between the current results and earlier findings in this area also were evaluated. Half the members of The Norwegian Society of Nurses in Cancer Care (n = 197) were mailed a questionnaire used in a similar Canadian study. The nurses were asked to select the five topics they perceived as most important from a list of 80 items, and to rank them in order of research priority. The response rate was 43% (197/464), and 75 respondents were specialists in cancer nursing. Quality of life was given the highest research priority in the total sample. Psychosocial support/counseling, communication between patient and nurse, patient participation in decision making, nurse burnout, and ethics also were ranked highly. In contrast to the others, cancer nursing specialists ranked ethics as their number one priority. Except for symptom management, the priorities given in Norway and other Western countries were found to be similar. These results might suggest topics for future research tailored to the needs of cancer nursing.