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Biomedical subjects

A Malan

Publications and source records attributed to A Malan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Single-dose benzathine penicillin in infants at risk of congenital syphilis--results of a randomised study.

OBJECTIVE: To determine the efficacy of single-dose benzathine penicillin G in infants at high risk of congenital syphilis. DESIGN: Randomised study comparing benzathine penicillin with no therapy. SETTING: Peninsula Maternal and Neonatal Service, Cape Town. SUBJECTS: Asymptomatic infants born to mothers with untreated syphilis whose VDRL titre was 32 or more. OUTCOME MEASURES: The number of cases of congenital syphilis was determined by results of IgM Western blots and follow-up VDRL titres. RESULTS AND CONCLUSIONS: Of 8 patients followed up in the non-treatment group, 4 had congenital syphilis while 0/11 had the disease (P = 0.035) in the group receiving benzathine penicillin. Although the exact failure rate is unknown, benzathine penicillin is effective in preventing symptomatic congenital syphilis when administered to high-risk newborns.

Blotting, Western↗
PubMed1996

Intergeniculate leaflet lesion and daily rhythms in food-restricted rats fed during daytime.

In control rats kept under light/dark cycle (LD) and fed during daytime 50% of ad lib food intake, the acrophase of temperature rhythm was 5 h phase-advanced, and plateaued close to the light/dark transition. The nocturnal pattern of locomotor activity rhythm was 6 h phase-advanced. By contrast, in food-restricted rats with electrolytic lesion of intergeniculate leaflet (IGL: IGLX group), there was only a 1 h phase-advance of the acrophase of temperature rhythm. Furthermore, except for a feeding-associated activity, the nocturnal pattern of activity of food-restricted IGLX rats remained unchanged. This demonstrates the involvement of IGL in the phase-advancing properties of a timed caloric restriction in LD.

Animals↗
PubMed1996

Daily hypocaloric feeding entrains circadian rhythms of wheel-running and body temperature in rats kept in constant darkness.

Since high levels of physical activity are known to interact with the circadian system, we tested whether hyperactivity induced by hypocaloric feeding may facilitate the synchronizing effect of periodic feeding in rats in constant darkness. Wheel-running (WRR) and body temperature (BTR) rhythms were analyzed in rats fed daily 50% of ad libitum food intake. In addition to a feeding-associated component (FAC) expressed for both rhythms, WRR and BTR were phase-shifted towards the feeding time by 12.1 +/- 0.4 and 12.4 +/- 0.4 h, respectively. BTR and FAC of temperature merged into a single cosine-wave food-entrained rhythm (FER) of temperature. Similarly, WRR and FAC of activity merged into a unimodal FER of wheel-running. This indicates that daily hypocaloric feeding may synchronize circadian rhythms in rats.

Animals↗
PubMed1996

Ventromedial hypothalamic lesions prevent the fasting-induced changes in day-night pattern of locomotor activity.

The time-course of day-night organization of running wheel activity during prolonged fasting was studied in rats, with or without electrolytic lesions in the ventromedial hypothalamus (VMH). For each individual, dates were referenced to the metabolic transition from lipid to protein utilization in late fasting; this was estimated by daily weighing. In fasted sham-operated controls, daytime activity increased progressively over the fast. This fasting-induced rise in diurnal activity was not due to daily handling, since it was observed also in non-handled (fasted) controls. The pattern of the increase in sham-operated rats differed between 2-hour periods (8-10 h to 18-20 h). The distribution of nocturnal activity was also modified during food deprivation: nocturnal activity in late fasting increased in the 20-22 h period and concomitantly decreased in the two 4-6 h and 6-8 h periods. By contrast, VMH lesions markedly limited and delayed the rise in diurnal running activity, irrespective of the 2-hour period. They prevented any significant change in nocturnal activity pattern over the fast. In fasted sham-operated rats, the data may be interpreted as a phase-advance of the nocturnal pattern of locomotor activity, concomitant with the increase of activity during daytime. These changes were suppressed by the VMH lesions. This suggests that the fasting-induced changes in the day-night pattern of locomotor activity are centrally mediated by a neuronal circuit involving the ventromedial hypothalamus.

Animals↗
PubMed1995

Locomotor activity and utilization of energy reserves during fasting after ventromedial hypothalamic lesions.

The ventromedial hypothalamus (VMH) is known to be involved in the regulation of energy metabolism but it may also modulate locomotor activity. Since prolonged fasting is marked by a succession of changes in energy utilization and locomotor activity, it was hypothesized that VMH may be a critical link controlling mobilization of energy stores and/or behavioral changes in response to fasting. To test this, the changes in rate of body mass loss, body content in lipid and protein, and wheel-running activity were studied in fasted nonobese rats with VMH electrolytic lesions. Secondary effects of VMH obesity were ruled out by postoperative restricted feeding. During fasting, VMH lesions impaired neither the overall lipid mobilization nor the late rise in daily body mass loss, concomitant with the increase in net proteolysis. Despite that the onset of this late stage of fasting was significantly delayed in VMH vs. sham-operated rats (13 +/- 1 vs. 8 +/- 1 days, respectively), the final amount of reserve lipids (3 g) was closely similar in both groups: this is the first experimental evidence of the hypothesis of a lipidic set-point. These results indicate that VMH is not a critical link controlling the time-course of utilization of energy reserves. The increase in diurnal (and total) daily wheel-running observed in fasted sham-operated rats still occurred in fasted VMH rats but was significantly reduced and delayed. VMH nuclei and/or associated fibers are therefore involved in the fasting-induced rise in diurnal activity.

Animals↗
PubMed1995

Involvement of corticosterone in the fasting-induced rise in protein utilization and locomotor activity.

During fasting, most of the energy is derived from lipids whereas proteins are efficiently spared. However, there is a late rise in net protein utilization. Fasting is also associated with an increase in locomotor activity. Because the plasma corticosterone level increases concomitantly with these metabolic and behavioral changes, the involvement of corticosterone has been hypothesized. To test this, the net protein utilization and locomotor activity were investigated in fasted adrenalectomized (Adx) rats, with or without replacement with corticosterone, and in fasted intact rats treated with RU486, an antagonist of type II glucocorticoid receptors. During the phase of fasting characterized by protein sparing, urine nitrogen loss was further reduced in Adx rats and in RU486-treated controls compared with intact rats and with Adx rats with corticosterone replacement: this indicates a catabolic effect of corticosterone through type II receptors. In the last phase of fasting, the rise in net protein breakdown was suppressed in Adx rats and restored by corticosterone replacement. The increase in locomotor activity induced by fasting in controls was suppressed in Adx and restored by corticosterone replacement. This rise in running activity was still present in RU486-treated rats. In conclusion, this study shows that corticosterone plays a critical role in the changes of both protein catabolism and locomotor activity during prolonged fasting.

Adipose Tissue↗
PubMed1995

Stimulation of brown adipose tissue activity in tumor-bearing rats.

Despite anorexia, cancer development is frequently accompanied by an increase of energy expenditure. Considering the pivotal role played by brown adipose tissue (BAT) in the energy metabolism of small mammals, we investigated the functional and compositional modification in BAT of anorexic tumor-bearing (Yoshida sarcoma) and pair-fed control rats. BAT thermogenic activity (assessed by maximal mitochondrial GDP binding) was 1.8-fold greater in tumor-bearing rats than in controls, while the thermogenic capacity (assessed by measurement of uncoupling protein) was unchanged. This suggests that tumor bearing had induced an unmasking of uncoupling protein sites. BAT hypertrophy and hyperplasia, characteristic of full-fledged BAT activation, did not occur. The mitochondrial oxidative capacity of BAT (assessed by cytochrome c oxidase activity) was 1.6-fold lower in tumor-bearing than in control rats. The main compositional modification observed in BAT of tumor-bearing rats was an increase in the saturation of cardiolipin fatty acids. These results suggest that the BAT stimulation induced by tumor bearing after 10 days is almost exclusively functional and that the tissue development is limited, probably by anorexia. However, a suppressive effect of anorexia inhibition by tumor bearing cannot be excluded.

Adipose Tissue, Brown↗
PubMed1994

Search for rhythmicity during hibernation in the European hamster.

Temporal patterns of hibernation were studied by continuous monitoring of body temperature by radiotelemetry over 6 months in European hamsters, Cricetus cricetus, at constant temperature and photoperiod. Entrances into hibernation occurred mostly at the end of the night (0000-0800 hours), while arousals were randomly distributed between day and night. This is at variance with a control of bout duration by a clock with a period of 24 h. Consequently, the timing of entrances implies a phase-resetting of the circadian clock on each arousal. Persistence of circadian rhythmicity with a period different from 24 h during deep hibernation was investigated examining whether the durations of torpor bouts were integer multiples of a constant period. A non-parametric version of the classical contingency test of periodicity was developed for this purpose. Periods ranging from 21 to 29 h were tested. Nine animals out of ten showed at least one significant period in this range (P < 0.01), either below 24 h (21.8 +/- 0.5 h, n = 4) or above (27.3 +/- 0.5 h, n = 7). However, we have found a theoretical model of bout durations for which the contingency test of periodicity sometimes gives false significant results. This indicates that the power of the test is weak. With this reservation our results suggest that a circadian oscillator controls the duration of a bout of hibernation, which would occur after an integer, but variable and possibly temperature-dependent number of cycles.

Animals↗
PubMed1993

Body protein and lipid deficit in tumour-bearing rats in relation to age.

Cancer cachexia is among the most dramatic situations of depletion in body energy reserves. To ascertain whether the pattern of body composition alteration during tumour development is influenced by aging as in uncomplicated starvation, we compared the difference of body composition between Yoshida sarcoma bearing rats and young (200 g, 7 weeks) and adult (400 g, 13 weeks) control rats. After the same duration of tumour bearing, mass and composition of tumours were similar in adult and young rats, indicating that they are independent of host age. Food intake decreased to a remarkably similar value in both young and adults. Body water content was elevated in hosts of both ages. The relative deficit of body lipid vs controls was similar for both, the absolute lipid deficit being therefore larger in adult than in young tumour-bearing rats (14.3 +/- 4.4 g vs 6.8 +/- 0.9 g; P < 0.01). In contrast, there was a relatively larger deficit of body protein in young rats. Paradoxically, these rats still maintained a positive nitrogen balance whereas this balance was negative in adult tumour-bearing rats. In conclusion, as previously shown in uncomplicated undernutrition, the anorexia induced by Yoshida sarcoma development is still associated with some protein accretion in young rats whereas cachexia develops in adults.

Aging↗
PubMed1992

Early insulin response after food intake in geese.

Plasma glucose and insulin levels were measured in chronically catheterized, freely moving, undisturbed geese, which were offered a free standard meal after an overnight fast. The insulin level markedly rose within the first minute after the start of food ingestion, whereas plasma glucose did not increase. This early insulin response was not correlated with the size of the meal. In contrast, both postabsorptive insulin response and plasma glucose changes were dependent on meal size. When a small amount of food (2-6 g) was eaten, insulin returned to basal level within 30 min, whereas plasma glucose remained unchanged. Larger meals (15-20 g) maintained plasma insulin at a higher level and induced a sustained rise of plasma glucose. These results indicate that there is a cephalic phase of insulin secretion at the beginning of the meal in birds as previously described in mammals.

Animals↗
PubMed1988

pH-temperature interactions on protein function and hibernation: GDP binding to brown adipose tissue mitochondria.

1. [3H]GDP binding to the uncoupling protein of brown adipose tissue was determined on mitochondria isolated from hibernating European hamsters, at two temperatures, 35 and 15 degrees C, and four values of 25pH (pH corrected to 25 degrees C): 6.4, 6.8, 7.2 and 7.6, encompassing the physiological range of pH. Buffer composition was adjusted to get the same pH-temperature relationship as for mammalian blood, in which this relationship is mainly determined by protein imidazole buffers. 2. The maximal binding capacity was independent both of temperature and pH. The dissociation constant KD was highly pH-dependent, but was independent of temperature when 25pH was held constant. Under these conditions, the uncoupling protein thus fully conserves its regulatory properties over the temperature range studied (eurythermal adaptation). 3. The temperature coefficient of the apparent pK' for the pH effect (-0.012 +/- 0.004) differed significantly from that of GDP terminal phosphoryl group, but not from that of blood protein imidazole buffer groups, in good agreement with the imidazole alphastat theory. 4. The results indicate that GDP reaction with the protein involves an electrostatic binding with a titratable group of the protein, probably a sulfhydryl. 5. pH modulation of the uncoupling of brown adipose tissue mitochondria probably permits a reversible control of thermogenesis in the hibernation cycle, heat dissipation being inhibited by respiratory acidosis in deep hibernation, but facilitated by the hyperventilation of arousal.

Adipose Tissue, Brown↗
PubMed1988

Time-course of blood acid-base state during arousal from hibernation in the European hamster.

1. Arterial blood was sampled at 15 min-intervals in European hamsters Cricetus cricetus fitted with indwelling catheters, from deep hibernation to full arousal. Temperature-corrected pH and PCO2, respectively pH* and P*CO2, were directly measured at 37 degrees C. 2. Deep hibernation corresponded to a respiratory acidosis: pH* = 7.01 +/- 0.01 (mean +/- SE), P*CO2 = 160 +/- 4 Torr (n = 9 animals). 3. Three periods could be distinguished in the arousal: (i) a period of hyperventilation (28 +/- 5 min), in which P*CO2 was reduced to 79 +/- 4 Torr, while cheek pouch temperature increased only by 0.9 +/- 0.2 degrees C; (ii) a period of metabolic acidification by lactate accumulation (84 +/- 6 min), corresponding to the period of peak thermogenesis; (iii) a progressive return to euthermic conditions (104 +/- 10 min), by simultaneous respiratory and metabolic alkalinization. 4. Over 60% of the blood CO2 stores accumulated at the beginning of the hibernation bout were released by hyperventilation during the first period, prior to the full development of thermogenesis. This is in agreement with the hypothesis of an inhibitory role of the respiratory acidosis in hibernation.

Acid-Base Equilibrium↗
PubMed1985

Intracellular pH in hibernation and respiratory acidosis in the European hamster.

Intracellular pH was determined (DMO method) in European hamsters, in the spontaneously-occurring respiratory acidosis of hibernation, in hypercapnia due to breathing 12% CO2 in air in euthermy in spring, and in euthermicnormocapnic controls. From euthermy to hibernation, the temperature coefficient of pH was lowest in blood plasma and brain, intermediate in striated muscles (thigh muscles and diaphragm), and highest in heart and liver (Fig. 1). Correspondingly, the estimated dissociation ratio of the protein imidazole buffer groups, alpha Im, decreased markedly in plasma and brain, denoting an acid titration, but varied little in liver and heart. Striated muscles were intermediate (Fig. 2). Like in other mammals, intracellular responses to short-term euthermic respiratory acidosis were characterized by a partial metabolic compensation in the brain and a small metabolic acidification in striated muscles. In hibernation, a powerful metabolic compensation took place in liver and heart, nearly restoring alpha Im, but none occurred in brain (Figs. 3 to 5). The existence of an intracellular acidosis in brain and striated muscles during hibernation is in keeping with an inhibitory role of acidosis, whereas the homeostasis of intracellular alpha Im in liver and heart would subserve the eurythermal functioning of metabolic regulations in these organs, like in most organs of ectotherms.

Acidosis, Respiratory↗
PubMed1981

An O2-CO2 mixing system for studies on water-breathing animals.

A simple system based on single-stage gas-stream mixing produces accurate O2-CO2 mixtures suitable for studies on water-breath-ing animals. CO2 fractions as low as 0.05% can be obtained, with an output pressure up to 25 kPa and a full range accuracy of +/- 1%.

Animals↗