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Biomedical subjects

G Van Dijk

Publications and source records attributed to G Van Dijk.

12 recordsLinked to original sources

Effects of repetitive hypoglycemia on neuroendocrine response and brain tyrosine hydroxylase activity in the rat.

Hypoglycemia-associated autonomic failure (HAAF) is a syndrome of acute adaptation to a metabolic stressor, in which neuroendocrine responses to repetitive hypoglycemic bouts are blunted. The CNS mechanisms that contribute to HAAF are unknown. In the present study, we modeled HAAF in the rat and measured the activity of tyrosine hydroxylase (TH) as an index of acute noradrenergic activation, to test the hypothesis that noradrenergic activation of the hypothalamus might be impaired. In association with a significant counter-regulatory response to a single bout of hypoglycemia (elevated corticosterone, catecholamines, and glucagon), TH activity was elevated overall in brainstem NE cell body areas and hypothalamus. With multiple hypoglycemic episodes in a 24 h period, the counter-regulatory response was blunted, and hypothalamic TH activity was comparable to that of saline-infused controls. In a similar paradigm, multiple bouts of CNS neuroglucopenia did not blunt the hyperglycemic or corticosterone responses, and were required for elevation of TH activity. This alternate response pattern suggests that insulin-induced hypoglycemia and cerebral neuroglucopenia represent somewhat different metabolic stressors at the CNS.

Animals↗

Comparison of two enzyme-linked immunosorbent assays and one rapid immunoblot assay for detection of herpes simplex virus type 2-specific antibodies in serum.

The sensitivities and specificities of three immunoassays for the detection of herpes simplex virus type 2 (HSV-2)-specific immunoglobulin G antibodies in serum, including the one-strip rapid immunoblot assay (RIBA; Chiron Corporation) and two indirect enzyme immunosorbent assays (EIA; Gull Laboratories and Centocor), were compared by testing a panel of 1,250 serum samples from individuals attending an outpatient clinic for sexually transmitted diseases. A qualitative agreement among the three assays was observed with 1,080 serum samples (86.4%); 291 of the serum samples (23.3%) were positive, 789 samples (63.1%) were negative, and 170 serum samples (13.6%) gave a discordant result. Results were considered conclusive when a concordant result was obtained with two of three assays. The sensitivities and specificities of the RIBA, the Gull EIA, and the Centocor EIA proved to be 99.2, 99.7, and 89.9% and 97.1, 96.7, and 99.3%, respectively. These results indicate that the Chiron RIBA and the Gull EIA are especially useful and reliable for the detection of HSV-2-specific antibodies in serum.

Adolescent↗

[PhysioFlex: a target-controlled self-regulating closed-circuit inhalation anesthesia regulator].

Physi Flex is the first commercially available apparatus capable for quantitative, or self-regulating target controlled inhalational anaesthesia, with a totally closed circuit, in adults and children. The fresh gas supply to the circuit is intermittent, automatically regulated by continuous monitoring of the volume and composition of the gas mixture in the breathing circuit. The circle system includes, instead of the two conventional one way valves, a blower creating a continuous unidirectional flow at 70 L.min-1. In addition to the CO2-absorber it contains an absorber with carbon, absorbing the anaesthetic vapour when switched into the circuit. The ventilator consists of four ventilating chambers, each one with a membrane separating the patient and the motor compartments. The displacement of the membranes generates and measures the tidal volume. Automatic ventilation is achieved by electric valves and motor gas, and manual ventilation using a bag. Spontaneous ventilation is also possible. The machine is operated via a computer with selects the number of ventilating chambers (one, two or four), and the tidal volume between 50 and 2,000 mL, depending on age, gender and weight of the patient. The computer maintains the gas volume and the gas and vapour concentrations at their preset values. The O2-flow and consumption, the N2O flow and uptake, FICO2 and FETCO2, FI and FET of the volatile anaesthetic, all other important data are displayed in a numerical and graphical form on a color screen and registered for a delayed analysis. The end tidal concentration of the volatile anaesthetic drives a stepmotor with a syringe containing the selected volatile anaesthetic agent with is directly injected into the breathing circuit where it is vaporized. Therefore the concentration of the anaesthetic vapour can be instantaneously increased with this injector at induction and lowered at end of anaesthesia with the carbon absorber, and the fresh gas consumption is significantly decreased.

Adult↗

45-hour continuous quintuple-site actimetry: relations between trunk and limb movements and effects of circadian sleep-wake rhythmicity.

Diurnal and nocturnal trunk and limb motor activity of 20 healthy individuals was evaluated by actimetry for 45 consecutive hours. Sleep was assessed by sleep logs. Overall, motor activity significantly (p < .05) decreased in the order wrist, ankle, and trunk. There was significantly more motor activity in the dominant wrist during the diurnal period. Motor activity was significantly affected by the 24-hr sleep-wake cycle, with lower levels and prolonged immobility during the night. Time series analyses revealed different but significant correlations between motor activity at all sites. These data imply that (a) motor activity should be recorded at the dominant wrist when the highest level of motor activity is of importance, (b) recordings at the nondominant wrist are better indicators of trunk movement than are dominant wrist recordings, and (c) sites other than the conventional nondominant wrist recording site should be evaluated to improve the validity of motor activity-based sleep-wake scoring.

Adult↗

Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats.

Leptin (ob protein) and glucagon-like peptide-1-(7-36) amide (GLP-1) are peptides recently proposed to be involved in the regulation of food intake. Although the ability of exogenous leptin and GLP-1 to modulate consummatory behavior is consistent with the suggestion that these peptides are endogenous regulatory agents, central administration of these peptides may have aversive side effects, which could explain the anorexia. In the present experiment, exposure to a saccharine taste was immediately followed by central administration of leptin or GLP-1 to determine if these drugs could produce a conditioned taste aversion (CTA) in rats. At doses equated for producing comparable reductions in short-term food intake, GLP-1, but not leptin, generated a robust CTA. Although leptin caused no aversion, this peptide was the only drug to cause relatively long-term reductions in food consumption (16 h) and body weight (24 h). Hence, the results indicate that central GLP-1 produces aversive side effects, and it is argued that these nonspecific effects may explain the anorectic actions of GLP-1.

Animals↗

Effects of glucagon-like peptide-I on glucose turnover in rats.

The influences of glucagon-like peptide-I-(7-36) amide (GLP-I; 15 mumol. kg-1.min-1) on glucose turnover were studied in freely moving Wistar rats. In fed rats, GLP-1 reduced plasma glucose (from 7.3 +/- 0.2 to 5.6 +/- 0.3 mmol/l; P = 0.017), increased plasma insulin (from 20 +/- 3 to 89 +/- 11 mU/l; P = 0.002), and reduced plasma glucagon (from 44 +/- 1 to 35 +/- 2 pg/ml; P = 0.009) and glucose appearance rate (Ra; from 3.9 +/- 0.2 to 1.7 +/- 0.7 micromol.min-1. 100 g-1 after 30 min; P = 0.049) without affecting glucose disappearance rate (Rd). The glucose clearance rate (MCR) was increased (P = 0.048). In 48-h-fasted rats, GLP-I reduced plasma glucose (from 5.0 +/- 0.2 to 4.4 +/- 0.3 mmol/l; P = 0.035) and increased plasma insulin (from 4 +/- 1 to 25 +/- 10 mU/l; P = 0.042) and plasma glucagon (from 43 +/- 3 to 61 +/- 7 pg/ml; P = 0.046). Ra and Rd were not significantly affected, although Ra was lower than Rd after 15-30 min (P = 0.005) and MCR was increased (P = 0.049). Thus GLP-I reduces Ra in fed rats and increases MCR in fed and fasted rats. The reduced Ra seems mediated by an increased insulin-to-glucagon ratio; the increased glucose clearance seems dependent on insulin and a peripheral effect of GLP-I.

Animals↗

Central insulin and macronutrient intake in the rat.

When rats are maintained on a standard laboratory diet, the infusion of low doses of insulin into the cerebroventricular system causes a reduction of food intake and body weight. It was recently reported that, if rats are maintained on a high-fat diet (56% calories as fat), they are insensitive to this action of insulin. To investigate further the effect of dietary composition on responsiveness to central insulin, we carried out two experiments. In experiment 1, rats were maintained on one of four equicaloric diets (providing 7, 22, 39, or 54% of calories as fat) before and during a 6-day third-ventricular infusion (i3vt) of insulin (10 mU/day) or saline. Rats consuming 7 or 22% of calories as fat had a significant reduction of both food intake (-17.2 +/- 2.9 and -14.6 +/- 3.3 g, respectively) and body weight (-50 +/- 5 and -41 +/- 5 g, respectively) from baseline over the insulin-infusion infusion period. Rats consuming 39 or 54% calories as fat did not reliably alter food intake (-4.0 +/- 3.9 and -1.9 +/- 3.7 g, respectively) or body weight (-10 +/- 6 and -6 +/- 4 g, respectively) in response to i3vt of insulin. In experiment 2, rats were offered a choice of three macronutrients (carbohydrates, fats, and proteins) in separate jars in their home cages. After they had adapted to the diets, they were infused i3vt with insulin or saline. Insulin caused a significant reduction of body weight relative to saline-infused controls (body wt: -23.1 +/- 4 g) and a reduction in food intake that was selective for dietary fat. These data suggest that the effects of central insulin administration are highly dependent on the macronutrient content of the diet as well as the ability of rats to select their own diets.

Animals↗

Central infusions of leptin and GLP-1-(7-36) amide differentially stimulate c-FLI in the rat brain.

Recently, glucagon-like peptide-1-(7-36) amide (GLP-1) and leptin have been implicated in the regulation of food intake. In the present study, we compared the effects of third ventricular administration (i3vt) of leptin (3.5 micrograms) and GLP-1 (10.0 micrograms) on short-term food intake and c-Fos-like immunoreactivity (c-FLI) in hypothalamic, limbic, and hindbrain areas in the rat. Relative to controls, infusion of leptin or GLP-1 (3 h before lights off) significantly reduced food intake over the first 2 h in the dark phase (53 and 63%, respectively). In different rats, infusion of leptin or GLP-1 elevated c-FLI in the paraventricular hypothalamus and central amygdala. Furthermore, leptin selectively elevated c-FLI in the dorsomedial hypothalamus, whereas GLP-1 selectively elevated c-FLI in the nucleus of the solitary tract, area postrema, lateral parabrachial nucleus, and arcuate hypothalamic nucleus. The fact that most of the c-FLI after leptin or GLP-1 administration was observed in separate regions within the central nervous system (CNS) suggests different roles for leptin and GLP-1 in the CNS regulation of food intake and body weight.

Animals↗

Contribution of liver nerves, glucagon, and adrenaline to the glycaemic response to exercise in rats.

The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of somatostatin in combination with adrenodemedullation. Blood samples were taken for measurements of blood glucose, plasma free fatty acids (FFA), adrenaline (A), noradrenaline (NA), insulin and glucagon. Liver denervation by itself did not influence glucose levels during exercise. Infusion of somatostatin in SHAM animals, which inhibited the exercise-induced glucagon response, led to enhanced sympathoadrenal outflow (measured as plasma A and NA) and a reduced blood glucose during exercise, suggesting that glucagon serves as a powerful mediator of the glycaemic response during swimming. Infusion of somatostatin in LDX animals failed to enhance plasma NA levels and led to a more pronounced reduction in blood glucose levels. This indicates that liver nerves do contribute to the glycaemic response to exercise when glucagon secretion is suppressed. Reduced blood glucose levels after adrenodemedullation revealed that adrenal A is another important mediator of the glucose response to exercise. Infusion of somatostatin in adrenodemedullated SHAM or LDX animals was not accompanied with increased NA outflow, suggesting that adrenal A is necessary to allow the compensatory increased outflow of NA from sympathetic nerves. In conclusion, the study shows that pancreatic glucagon and adrenal A are the predominant factors influencing the glycaemic response to exercise, whereas a role of the sympathetic liver nerves becomes evident when glucagon secretion is suppressed.

Adrenal Medulla↗

High flow closed circuit anaesthesia.

We present an automatic closed circuit anaesthesia ventilator designed for routine clinical use. The ventilator combines the benefits of high flow systems and true closed circuits, without their disadvantages. The system can be used with any FiO2, with air or nitrous oxide as carrier gas. Servo controlled delivery of modern volatile anaesthetics is regulated on end-tidal value. The time constant for increase or decrease of concentrations is only a few minutes. There is no need to open the system at any time, nor is it necessary to increase the fresh gas flow. An automatic flush procedure prevents accumulation of unwanted gases. Operation is as easy as contemporary non-closed circuit ventilators. With this machine, closed circuit anaesthesia is possible from the beginning to the end of the procedure.

Absorption↗

Exercise-induced sympathetic FFA mobilization in VMH-lesioned rats is normalized by fasting.

This study investigates whether reduced sympathetic responses during physical exercise in ventromedial hypothalamus (VMH)-lesioned obese rats are the direct result of damage to hypothalamic circuits or a secondary effect of the altered metabolism in obesity. Obese, VMH-lesioned rats and lean controls were deprived of food for 48 h and submitted to 15 min of swimming. Food-deprived lean and obese rats displayed increased free fatty acid mobilization and utilization, whereas blood glucose concentrations were decreased. Basal plasma insulin levels were reduced by fasting in both groups, when compared with the ad libitum situation, but remained higher in the obese animals. Fasting augmented the norepinephrine response of the obese rats, resulting in equal profiles in lean and obese animals. These results indicate that VMH-lesioned animals are able to increase the sympathetic activation of adipose tissue during exercise to overcome an energy deficiency. Therefore, the function of the VMH in the regulation of the sympathetic nervous system controlling metabolism can be taken over by redundant mechanisms. The reduced sympathetic activity in ad libitum fed VMH-lesioned animals is therefore likely to be the result of the altered metabolism.

Animals↗

Anti-Mycobacterium leprae monoclonal antibodies cross-react with human skin: an alternative explanation for the immune responses in leprosy.

A panel of 17 mouse monoclonal antibodies (MoAb) raised against Mycobacterium leprae (M. leprae) antigens was used to detect antigenic determinants in normal human skin. An indirect immunoperoxidase technique was used. Eight of the MoAb detected epidermal antigens similar to patterns well known for human sera. Five of these MoAb detected determinants in the dermis, too. These observations may indicate a certain degree of similarity between the antigenic determinants occurring in M. leprae and in the human host. We propose that such a similarity on the one hand may facilitate the survival of M. leprae in the human host when the antigens are not recognized as "non-self," a situation which seems to occur in lepromatous leprosy, when the patients' tissues are loaded with bacteria virtually without any immune response. On the other hand, M. leprae antigens which mimic host antigens may induce an auto-immune reaction against the host's own antigens, which could explain the immune reaction in tuberculoid leprosy and during a "reversal reaction" when M. leprae is not observed in the host tissues, but extensive granuloma formation occurs.

Animals↗