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Biomedical subjects

J J Taljaard

Publications and source records attributed to J J Taljaard.

At least 19 recordsLinked to original sources

Central effects of the preservative, methylparaben. In vivo activation of cAMP-specific phosphodiesterase and reduction of cortical cAMP.

The phenolic preservative, methylparaben (MPB), has in the past been demonstrated to harbour definite pharmacological effects. In an attempt to examine the possible central effects of MPB, notably on cyclic nucleotides and cyclic nucleotide phosphodiesterase (PDE; EC 3.1.4.17), rats were orally treated with the drug (0.4% in rat food) for 3 weeks with cortex extracts being used for the various determinations. Three isozymes were identified by DEAE-cellulose anion exchange chromatography, namely the calmodulin/calcium-stimulated form or PDE I (peak I), the cGMP-stimulated form or PDE II (peak II), and an independent form not affected by either calmodulin or cGMP also known as PDE IV (peak III). The presence of MPB induced a significant decrease in cortical cAMP, as well as strongly stimulating the activity of PDE IV (peak III). In addition, a small, yet significant, increase in cGMP levels was observed. Since no increase in cGMP hydrolysis was observed, we conclude that chronic ingestion of MPB induces a preference for cAMP hydrolysis, which was confirmed by the increase in PDE IV (peak III) activity. PDE IV is a membrane-bound, low Km PDE exhibiting high selectivity for cAMP hydrolysis. While there was an increase in cGMP, we failed to observe an increase in the activity of the cGMP-stimulated PDE (PDE II). These data are discussed with reference to the possible membrane effects of MPB allowing it to alter both the kinetic properties of PDE IV with the resultant effects on cAMP, as well as a means whereby it may activate guanyl cyclase and increase cGMP.

3',5'-Cyclic-AMP Phosphodiesterases

Measurement of micro-albuminuria in patients with diabetes mellitus.

Persistent micro-albuminuria (MA) in patients with diabetes mellitus identifies a high-risk group for the development of vascular complications. Since the methodology involved in measuring MA has not been standardised, MA in 40 diabetic patients was measured in order to compare nephelometry with radio-immunoassay (RIA). The effect of storage (7 days), the influence of freezing and thawing on MA levels, and possible differences between glass and plastic containers were also assessed. An excellent correlation (r = 0.971) was found between RIA and nephelometry. Urine could be safely stored at 4 degrees C in either plastic or glass containers without any significant influence on MA concentrations. It is concluded that nephelometry is an excellent method for accurately measuring MA.

Albumins

Rat brain hypothalamic and hippocampal monoamine and hippocampal beta-adrenergic receptor changes during pregnancy.

The concentration of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites was measured in hypothalamic and hippocampal brain tissue obtained from non-pregnant, 15- or 20-day pregnant and 4-day postpartum rats. At 20 days of pregnancy, hypothalamic NA and DA concentrations were significantly decreased and their turnover increased relative to postpartum and estrous values, respectively. Hippocampal 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels were significantly decreased at 15 days of pregnancy and 4 days postpartum compared to estrous and 20-day pregnant levels and the MHPG/NA ratio was significantly reduced at 4 days postpartum relative to the estrous value. Hippocampal 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) levels were significantly decreased at 15 days of pregnancy while 5-HIAA levels and the 5-HIAA/5-HT ratio were significantly decreased at 20 days of pregnancy. Hippocampal beta-adrenergic receptor density was significantly lower at 4 days postpartum than at 15 days of pregnancy. A positive correlation was observed between plasma progesterone and hippocampal beta-adrenoceptor Kd values, suggesting a possible causal relationship between these two variables. The monoamine and beta-adrenoceptor changes which occur during pregnancy may be an important contributing factor in determining the mood changes which occur during pregnancy and postpartum.

Animals

Effect of corticosterone on noradrenergic nuclei in the pons-medulla and [3H]NA release from terminals in hippocampal slices.

The aim of the present study was to investigate possible membrane and genomic effects of corticosterone on the noradrenergic system of the rat brain. Corticosterone effects were studied in vivo by treating rats s.c. with 10 mg/kg corticosterone for 7 or 14 days. In the first two experiments corticosterone significantly decreased the noradrenaline (NA) and dopamine (DA) levels in the pons-medulla, an area which contains the A1-A7 noradrenergic cell groups, while the NA and DA levels in the dorsal hippocampus remained unchanged. In a third experiment where the locus coeruleus (LC) and the A1 and A2 nuclei (A1,A2) were analysed separately, NA levels were unchanged but total MHPG levels and the total MHPG/NA ratio were decreased in the A1,A2 area. Chronic corticosterone treatment (14 days) did not alter the alpha 2-adrenoceptor-mediated modulation of [3H]NA release from dorsal hippocampal slices. Neither the spontaneous outflow nor the electrically stimulated release of [3H]NA from dorsal hippocampal slices of untreated rats was affected by exposure of the slices to corticosterone (10(-7) M - 10(-4) M) in the superfusion buffer. Thus, chronic corticosterone treatment of rats altered the noradrenergic system of the pons-medulla, but did not change the alpha 2-adrenoceptor-mediated modulation of NA release in the dorsal hippocampus, a major terminal area of the LC neurons. Corticosterone also did not appear to have a direct membrane effect on the NA terminals in the dorsal hippocampus of the rat.

Animals

Regional effects of neurotensin on the electrically stimulated release of [3H]dopamine and [14C]acetylcholine in the rat nucleus accumbens.

This study has shown that neurotensin (NT) increases the electrically stimulated release of [3H]DA to a similar extent in all but the extreme caudolateral area of the rat nucleus accumbens and appears to modulate DA release equally in the medial and lateral zones of this brain area. The simultaneous release of ACh was not significantly affected by NT.

Acetylcholine

Effects of alpha 2- and beta-adrenoceptor agonists on growth hormone secretion following lesion of the noradrenergic system of the rat.

The aim of the present investigation was to lesion the noradrenergic system and to measure the effect on growth hormone (GH) secretion following peripheral administration of alpha 2- and beta-adrenoceptor agonists. Direct injection of these agonists into the paraventricular nucleus of the hypothalamus (PVN) and its effect on GH secretion were also investigated. Systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4, 60 mg/kg, injected i.p. 10 days prior to experimentation) significantly decreased the noradrenaline (NA) content of the hippocampus, frontal cortex and hypothalamus but had no effect on the dopamine (DA) or serotonin (5-HT) content of these areas. Bilateral injection of 6-hydroxydopamine (6-OHDA, 10 micrograms/microliters, 14 days prior to experimentation) into the medial forebrain bundle (MFB) caused a greater reduction of NA and also decreased the DA and 5-HT content of the hypothalamus. Analysis of the PVN of the hypothalami of rats following 6-OHDA lesion of the MFB showed significantly decreased NA and 5-HT content. Neither DSP4 treatment nor 6-OHDA lesion of the MFB affected the clonidine (250 micrograms/kg, i.p.) induced stimulation of GH secretion. Injection of isoproterenol (1 mg/kg, i.p.) had varying effects on GH secretion. It stimulated GH release in control rats but not in DSP4 or MFB lesioned rats. Direct injection of clonidine (0.1 microgram/microliters) into the PVN significantly stimulated GH secretion, whereas injection of isoproterenol (2.5 micrograms/microliters) into the PVN did not affect GH levels when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists

Membrane fluidity of platelets and erythrocytes in patients with Alzheimer's disease and the effect of small amounts of aluminium on platelet and erythrocyte membranes.

The membrane fluidity of platelet and erythrocyte membranes in 10 Alzheimer's disease patients and 9 age-matched controls was studied. The platelet membranes of patients with Alzheimer's disease were found to be significantly more fluid than those of controls (p less than 0.02). However, erythrocyte membranes of Alzheimer patients were less fluid (more viscous) than those of controls (p less than 0.05). On further investigation of platelet and erythrocyte membranes obtained from healthy volunteers, the fluidity was found to change with increasing aluminium concentrations. When aluminium ammonium sulphate (0.01-10 microM) was added to membrane suspensions, the fluidity of platelet membranes was increased, whereas the fluidity of erythrocyte membranes was decreased (i.e. the microviscosity was increased).

Aluminum

Regional distribution of monoamines and dopamine D1- and D2-receptors in the striatum of the rat.

Dopamine (DA) D1- and D2-receptor densities were determined in 18 discrete areas of the caudate-putamen-globus pallidus of male Wistar rats and compared to local DA concentrations. All three parameters were found to decrease caudally. The globus pallidus was distinguished by the low concentration of DA and its receptors and high noradrenaline (NA) content. While there were no mediolateral differences in DA or DA D1-receptors, a clear mediolateral gradient was observed for DA D2-receptors which extended over several sections of the brain. The ratio of DA D1- to D2-receptors was significantly higher in the dorsal than in the ventral areas of the mediolateral and caudal striatum. This is the first report of clear dorsoventral differences in parameters relating to DA activity in the striatum. These findings may be of particular significance in understanding the functional dichotomy between the dorsal and ventral striatum.

Animals

Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet.

Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non-primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins.

Animals

Dietary patterns and nutritional status in free-living older white men with established vascular disease.

Thirty-nine white men aged 51-84 years with established vascular disease were studied to investigate the effect of fish oil capsules on the regression of these lesions. This article deals with the baseline data of the study. The subjects completed a 7-day dietary record, weight and height were measured and a fasting blood sample was analysed for proteins, haematological values and certain vitamins. Dietary analysis indicated that the mean energy intake was 8,552 kJ (SD = 2,095). The energy distribution was 15.5% protein, 33.6% fat and 46.4% carbohydrate. In the light of the recommended dietary allowances the diet was lacking in zinc, vitamin B6 and folic acid, which suggests that the subjects might be deficient in these micronutrients. Although the diets were lacking in these nutrients, no clinical stigmata were observed. The subjects averaged a body mass index of 26.1 and could therefore be classified as overweight. The mean haematological values as well as the plasma vitamins were within the normal range. In conclusion it can be said that the men consumed a diet that was too high in fat and that the diet lacked certain micronutrients.

Aged

The effect of medial forebrain bundle lesion on thyrotropin secretion in the rat.

The medial forebrain bundle (MFB) was partially lesioned with 6-hydroxydopamine (6-OHDA) in order to investigate the effect of deficient central noradrenergic regulation on thyrotropin (TSH) secretion in the rat. 6-OHDA injection into the MFB significantly reduced the noradrenaline (NA), dopamine (DA) and serotonin (5-HT) content of the whole hypothalamus. NA and 5-HT concentrations were also significantly decreased in the paraventricular nucleus (PVN). The MFB lesion did not affect the clonidine (250 micrograms/kg, i.p.) induced stimulation of TSH release or the isoproterenol (1 mg/kg i.p.) induced decrease in TSH levels. Thyrotropin releasing hormone (TRH, 5 micrograms/kg i.v.) caused a similar significant stimulation of TSH secretion in lesioned and non-lesioned rats. The present results do not support the hypothesis that the blunted TSH response to TRH observed in depressed patients results from a deficiency in noradrenergic neurotransmission.

Animals

Mycotoxic peripheral myelinopathy, myopathy, and hepatitis caused by Diplodia maydis in vervet monkeys.

During recent historical times many Africans changed their diet to one based on maize. The grain is regularly contaminated by fungi which are toxigenic to domestic animals and birds. After one of the fungi, Diplodia maydis, in pure culture on maize, was added to the food of omnivorous primates there was demyelination of nerves, atrophy, degeneration and necrosis of muscle, and hepatitis. These preliminary results are applicable to veterinary and laboratory animal sciences. They may also be medically significant since neuromuscular syndromes of unknown cause are prevalent among Africans. Nerve conduction velocities and organ weights are defined for vervet monkeys.

Animals

Hormonal vaginal cytology of vervet monkeys.

The cellular proliferation and maturation of the vaginal epithelium of adult female Vervet monkeys was examined during their menstrual cycles. At the same time the serum contents of estrogen and progesterone were analysed. Gradual but distinct patterns demarcated the phases of the menstrual cycle cytologically. The karyopyknotic index paralleled the estrogen concentration. Mid-cycle peak maturation produced many anucleate squames, which exfoliated, forming a diagnostic vaginal discharge.

Animals

Evidence that the stimulatory effect of neurotensin on dopamine release in rat nucleus accumbens slices is independent of dopamine D2-receptor activation.

Neurotensin (NT, 10(-9) M and 10(-7) M) increased the electrically stimulated release of [3H]dopamine (DA) in rat nucleus accumbens slices. This effect was not altered by activation of DA D2-receptors with high or low concentrations of quinpirole (10(-6) M and 10(-8) M) or blockade of DA D2-receptors with near maximal concentrations of sulpiride (10(-6) M and 10(-5) M). The sulpiride-mediated increase in [3H]DA release and the release induced by NT were additive. These results suggest that NT functions independently of DA D2-receptor activation to modulate DA release in the nucleus accumbens. NT did not modulate the simultaneous release of [14C]acetylcholine.

Acetylcholine

The beta-adrenoceptor and endocrine abnormalities in juvenile depression.

Neuro-endocrine disturbances were determined in juvenile depressives and possible correlations with biochemical abnormalities investigated. It was established that, as in adult depressives, the young also showed a high incidence of cortisol non-suppression after dexamethasone administration. In addition, a positive correlation observed between lymphocyte beta-adrenoceptor maximal number of binding sites and basal cortisol levels stresses the involvement of the noradrenergic neurotransmission system.

Adolescent

Inappropriate antidiuretic state in long-term psychiatric inpatients.

To investigate the occurrence of an inappropriate antidiuretic state in a long-term psychiatric inpatient population, 690 patients underwent serum sodium determination. Forty-four patients (6.4%) had levels less than 133 mmol/l. Fifteen of these patients could be investigated further and the biochemical findings in all were consistent with an inappropriate antidiuretic state. Evidence of previous episodes of water intoxication was found in 80% of these patients. Although more than one possible cause was present in most patients, the two factors most strongly incriminated in the pathogenesis of the inappropriate antidiuretic state were the drugs carbamazepine and hydrochlorothiazide.

Adult

Rat brain monoamine and Serotonin S2 receptor changes during pregnancy.

The concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites were determined in 5 brain areas of non-pregnant, 15 and 20 day pregnant and 4 day post-partum rats. Striatal 5-HT content was significantly lower in 15 and 20 day pregnant rats than in estrous controls. A significant decrease in striatal and frontal cortex 5-hydroxyindole-3-acetic acid (5-HIAA) concentration was observed in 15 day pregnant rats. Significant increases in hypothalamic and hippocampal NA levels were observed at 4 days post-partum. Frontal cortex serotonin S2 receptor KD was reduced in 4 day post-partum rats. There was no significant change in S2 receptor Bmax during pregnancy. Levels of progesterone were negatively correlated with striatal DA, homovanillic acid (HVA), 5-HT, and 5-HIAA levels, hypothalamic DA, hippocampal 5-HT, and frontal cortex 5-HIAA values as well as striatal HVA to DA, and HVA to 3,4-dihydroxyphenylacetic acid (DOPAC) ratios and amygdaloid HVA to DOPAC ratios. The limbic neurotransmitter changes might possibly contribute to mood changes which occur during pregnancy and post-partum.

3,4-Dihydroxyphenylacetic Acid

The effect of intrahippocampal injection of kainic acid on corticosterone release in rats.

The aim of the present study was to investigate whether the hippocampus exerts a modulatory effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Kainic acid was stereotaxically injected into the CA1 pyramidal cell layer of the dorsal hippocampus, causing histological and behavioural changes typical of kainic acid toxicity. The CA3 pyramidal cells of the dorsal hippocampus were selectively lesioned. Rats treated with kainic acid were hyperactive, executed clockwise rotatory movements and displayed epileptic seizures. The acute excitatory effect of kainic acid on glutamatergic receptors in the hippocampus resulted in an elevation in plasma corticosterone levels, suggesting a stimulation of HPA axis activity. Direct or indirect stimulation of the CA1 pyramidal cells of the dorsal hippocampus appeared to have caused the increase in corticosterone secretion.

Adrenal Glands