[Determination of insulin, leptin and neuropeptide y by radioimmunoanalysis in patients with morbid obesity and anorexia nervosa after therapeutic intervention]. / Determinación por radioinmunoanálisis de insulina, leptina y neuropéptido Y en pacientes con obesidad mórbida y anorexia nerviosa después de intervención terapéutica.

The present study was conducted in order to analyze the relationship existing between leptin, insulin and neuropeptide Y (NPY) levels in massive weight loss and weight recovery. Twenty-three patients with severe obesity, 23 patients with anorexia nervosa and 28 healthy control subjects were studied. Patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet during 16 weeks, with evaluation taking place before (Body mass index, BMI, 52,1 8 Kg/m2) and after the drastic weight loss (BMI 39,2 6,2 Kg/m2). Patients with anorexia nervosa were treated with nutritional therapy exclusively during 16 weeks, and they were evaluated in the low weight situation (BMI 15,3 1,7 Kg/m2) and after weight recovery (BMI 18,9 2,8 Kg/m2). Normal subjects had a normal BMI from 20 to 27 (average 21,8 2 Kg/m2). BMI, percentage of body fat, and serum levels of leptin, insulin, and NPY, were determined in each patient and normal subjects. In severe obese patients serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 48,8 19,2 to 24,3 9,8 ng/ml; insulin: from 26,2 10,8 to 18 6 U/ml). In patients with anorexia nervosa serum leptin mean levels were significantly higher after weight recovery (3,7 1,9 vs 9,2 5,1 ng/ml). In subjects with morbid obesity NPY levels decreased after weight loss below those of control group (43,5 16,1 vs 57,3 12,8 pmol/l). On the other hand, patients with anorexia nervosa had NPY levels superior to those of control group. In subjects with anorexia, NPY levels decreased after weight recovery (69,1 16,7 a 59,1 20,3 pmol/l). In the whole population, Leptin and NPY plasma levels were correlated with body fat percentage. Leptin was positively correlated with BMI and body fat percentage in obese and anorectic subjects after weight loss or recovery, respectively. NPY was inversely correlated with body fat percentage in controls and obese subjects before treatment. These data reveal that the concentration of serum leptin and NPY correlates significantly with the total adiposity in subjects with a wide weight range and caloric intake. Leptin plasma levels are proportional to fat stores in patients with severe obesity and anorexia nervosa after drastic weight loss or recovery, respectively. NPY serum levels are negatively correlated with de total body fat in normal weight subjects and obese patients in their initial weight.

Determinación por radioinmunoanálisis de insulina, leptina y neuropéptido y en pacientes con obesidad mórbida y anorexia nerviosa después de intervención terapéutica / Determination of insulin, leptin and neuropeptide by radioimmunoanalysis in patients with morbid obesity and anorexia nervosa after therapeutic intervention

El objetivo del presente estudio fue analizar la relación existente entre los niveles de insulina, leptina y neuropéptido Y (NPY) durante la pérdida masiva de peso o la recuperación del mismo. Fueron estudiados 23 pacientes con obesidad severa, 23 con anorexia nerviosa y 28 sujetos control normopesos. Los pacientes con obesidad severa fueron sometidos a una gastroplastia vertical anillada seguida de dieta hipocalórica (800 Kcal/día) durante dieciséis semanas, las evaluaciones tuvieron lugar antes (Índice de masa corporal, I.M.C. 52,1 ñ 8 Kg/m2) y tras conseguir una pérdida drástica de peso (I.M.C. 39,2 ñ 6,2 Kg/m2). Los pacientes con anorexia nerviosa se trataron con soporte nutricional exclusivamente durante dieciséis semanas, siendo evaluados en la situación de peso más bajo (I.M.C. 15,3 ñ 1,7 Kg/m2) y tras recuperar peso (I.M.C. 18,9 ñ 2,8 Kg/m2). Los sujetos normales poseían un I.M.C. normal en rango de 20 a 27 Kg/m2 (media 21,8 ñ 2 Kg/m2). En cada paciente y sujeto normal se determinó el I.M.C., porcentaje de grasa corporal, y los niveles séricos de leptina, insulina y NPY. En los pacientes con obesidad severa los niveles de leptina e insulina disminuyeron significativamente tras la reducción drástica de peso (leptina de 48,8 ñ 19,2 a 24,3 ñ 9,8 ng/ml; insulina de 26,2 ñ 10,8 a 18 ñ 6 µU/ml). En los pacientes con anorexia nerviosa los niveles medios de leptina fueron significativamente mayores tras la ganancia de peso (3,7 ñ 1,9 vs 9,2 ñ 5,1 ng/ml). En sujetos con obesidad mórbida el NPY se redujo cuando perdieron peso, estando por debajo de los niveles del grupo de sujetos controles (43,5 ñ 16,1 vs 57,3 ñ 12,8 pmol/l). Por su parte en los sujetos con anorexia nerviosa los niveles de NPY fueron superiores a los controles y disminuyeron cuando ganaron peso (69,1 ñ 16,7 a 59,1 ñ 20,3 pmol/l). Los niveles plasmáticos de leptina y NPY se correlacionaban positiva y negativamente con el porcentaje de grasa corporal al analizar la muestra completa. La leptinemia se correlaciona linearmente con el I.M.C. y porcentaje de grasa corporal en los sujetos obesos y anoréxicos tras pérdida y ganancia de peso, respectivamente. El NPY mostraba una correlación inversa con el porcentaje de grasa corporal en los grupos de sujetos obesos en situación basal y controles. Los datos obtenidos revelan que la concentración de leptina y NPY se correlaciona significativamente con el contenido graso del organismo en sujetos con un amplio rango de peso e ingesta calórica. Los niveles de leptina van con relación al tamaño de los depósitos grasos en pacientes obesos tras una pérdida drástica de peso y en pacientes anoréxicos después de recuperar peso. El NPY circulante se relaciona inversamente al contenido graso del organismo en sujetos con normopeso y obesos en el peso inicial (AU)

[Plasma levels of insulin and leptin in patients with morbid obesity and anorexia nervosa after weight loss or gain, respectively]. / Niveles plasmáticos de insulina y leptina en pacientes con obesidad mórbida y anorexia nerviosa después de pérdida o ganancia de peso, respectivamente.

The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese patients after drastic weight loss; 3) in anorexic patients after weight gain; and that hyper- or normoinsulinemia do not seem to have any influence on the leptin changes caused by weight loss or gain.

The effects of different monoaminergic antidepressants on the analgesia induced by spinal cord adrenal medullary transplants in the formalin test in rats.

We studied the effects of chronic intraperitoneal administration of antidepressants on the antinociception induced by adrenal medullary transplants into the subarachnoid space in rats using the formalin test. Administration of drugs started 28 days after operation and the formalin test was performed on Day 56. When amitriptyline (AMT; 15 mg x kg(-1) x day(-1)) was administered to sham-operated rats, it decreased the licking time and increased the transplant-induced analgesia in Phase 1 when administered to transplanted rats. Chronic treatment with fluvoxamine (FVX, 10 mg x kg(-1) x day(-1)) had no influence on the licking response in sham rats, nor did it modify the transplant-induced analgesia when administered to transplanted rats. When desipramine (DMI; 10 mg x kg(-1) x day(-1)) was administered to sham rats, it significantly reduced the licking response in Phase 1, but when administered to transplanted rats it did not increase the transplant-induced analgesia. None of the drugs administered showed any effect on Phase 2 of the formalin test. These results suggest that adrenal medullary transplants into the spinal cord induce analgesia as determined by the formalin test. This effect is more pronounced when AMT (a nonselective noradrenaline-serotonin reuptake inhibitor) is chronically administered, but not when FVX or DMI are chronically administered.

Effect on nociception of intracerebroventricular administration of low doses of neuropeptide Y in mice.

The present study shows further evidence about the implication of neuropeptide Y (NPY) in nociception. The effect of NPY (1-36), when intracerebroventricularly administered, has been studied using two physical models of acute pain (hot plate test and electrical tail stimulation) and the formalin test. The animal response to these three pain models has been shown to be integrated at different levels in the CNS. A decrease in pain threshold was exhibited in both the hot plate test (10, 30, 60, 120 and 480 pmol of NPY i.c.v.) and the electrical tail simulation test (10, 30 and 60 pmol of NPY i.c.v.), while in the formalin test (10, 30, 60 and 120 pmol of NPY icv) the licking response decreased in phase I but not in phase 2. In these three tests NPY showed hyperalgesic or analgesic effects when administered at low doses, while at high doses it failed to induce any effect. Results show that the effect of NPY on nociception is clearly test-dependent and is only observed at low doses.

Test-dependent relationship of the antidepressant and analgesic effects of amitriptyline.

Antidepressants have been found to be of value in the treatment of pain of various etiologies. Nevertheless, the data are conflicting as it is often difficult to distinguish between the analgesic and antidepressant action. The analgesic effect of acutely administered amitriptyline at doses of 2.5, 5, 10, 20 and 40 mg/kg was investigated in four nociceptive tests involving physical (hot plate and tail flick tests), or noxious chemical stimuli (acetic acid and formalin tests). Relationships were established between the analgesic actions and the antidepressant effect of acutely administered amitriptyline at doses of 2.5, 5, 10 and 20 mg/kg in the forced swimming test. The results demonstrated a relationship between the antidepressant effect and the analgesic action in the tail flick test, but not in the hot plate, acetic acid and formalin tests. Thus, the type of noxious stimulus may be a determining factor in the relationship between these two pharmacological actions.

Effect of amitriptyline on the analgesia induced by adrenal medullary tissue transplanted in the rat spinal subarachnoid space as measured by an experimental model of acute pain.

The effect of short and long term amitriptyline (AMI) treatment on the analgesia induced by adrenal medullary autotransplant into the subarachnoid space was investigated in rats. For this purpose, two experiments were carried out. In the first one, the rats were chronically treated for 28 days after transplantation. In the second experiment, rats were treated for 28 days starting 28 days after surgery. Before starting the experiments, basal levels were tested. Tail-flick latencies were checked at Day 4 and Day 28 in the first experiment and at Day 28 and Day 56 in the second. AMI itself did not induce any tail-flick modification after 28 or 56 days. However, it increased the transplantation-induced analgesia at Day 28 in the first experiment and at Day 56 in the second. These results are interpreted in the sense of the ability of AMI to enhance the effects of both monoamine and opioids previously released by the transplantation.

D1 dopamine receptors in the nucleus accumbens modulate cocaine self-administration in the rat.

Previous work using systemic injections of dopamine receptor antagonists has established that dopamine D1 receptors may have a role in cocaine self-administration. The purpose of the present study was to test the hypothesis that these effects were mediated by dopamine D1 receptors in the region of the nucleus accumbens. Animals were trained to perform operant responses to self-administer cocaine via an IV catheter on a fixed-ratio 5 (FR 5) schedule of reinforcement. SCH23390, a selective D1 dopamine antagonist, significantly increased the self-administration of cocaine when injected into the nucleus accumbens. This increase in self-administration is thought to reflect decreases in the magnitude of the reinforcer, similar to the increase observed when the dose of cocaine is reduced. Similar doses of SCH23390 injected into the posterior caudate nucleus failed to alter cocaine self-administration. These data suggest that D1 receptors in the nucleus accumbens are important for the reinforcing properties of cocaine.

Central administration of neuropeptide Y induces hypothermia in mice. Possible interaction with central noradrenergic systems.

Neuropeptide Y (0.24 and 1.17 nmol icv) and clonidine (0.025, 0.05 and 0.1 mg/Kg ip) induced a slight decrease of short duration of the rectal temperature in mice in a dose-dependent manner. While pretreatment with yohimbine (0.5 mg/Kg sc), was without effect on neuropeptide Y-induced hypothermia, it attenuated the hypothermic effect of clonidine. The association of neuropeptide Y (0.05 and 0.24 nmol icv) with clonidine (0.0125, 0.025, 0.05 and 0.1 mg/Kg ip) induced a synergistic effect, but it only was significant when neuropeptide Y 0.05 and 0.24 nmol icv was associated with clonidine 0.1 mg/Kg ip and when neuropeptide Y 0.05 nmol icv was associated with clonidine 0.05 mg/Kg ip. These results suggest that the effect of neuropeptide Y is not mediated by an interaction on alpha 2-adrenoceptor, but in accordance with these results, the existence of a collaborative mechanism between both neuropeptide Yergic and noradrenergic systems cannot be ruled out.