Sedación y analeesia con bolos de xilazina y mofina en infusión continua en unna yegua criolla Colombiana sometida a ovarioectomía en estación / Sedation and analgesia with xylazine bolus and morphine in continuous infusion in a mare standing subjected to ovariectomy: case report

En el acto quirúrgico la anestesia es un proceso que siempre conlleva riesgos. Un procedimiento común en equinos es realizar cirugías en estación para disminuir el riesgo de la anestesia general. Para los procedimientos anestésicos en estación en equinos se han utilizado las combinaciones de bolos de xilazina y anestesia local; sin embargo, la analgesia irregular y la marcada ataxia son complicaciones frecuentes. En el presente caso clínico se evaluó un protocolo de bolos de xilazina 0,6 mg/kg I.V. y morfina en infusión I.V. continua a 30 µg/kg/hora, con aplicación de anestesia local para la extraccción de un tumor de células de la granulosa en una yegua. Durante el procedimiento quirúrgico se observó una buena analgesia, sedación moderada y ataxia leve, sin alteraciones cardiovasculares o respiratorias, lo que favoreció el procedimiento quirúrgico; solamente se observó un corto periodo de amotilidad intestinal el cual fue superado espontáneamente. La yegua se recuperó totalmente del procedimiento quirúrgico y presentó evidencia de estro en dos ocasiones dentro del año siguiente a la intervención. Los procedimeintos anestésico y quirúrgico empleados en esta yegua fueron apropiados y la llevaron a su normalidad reproductiva.

Anesthesia is always a procedure that leads many risks in the quirurgical act. A common procedure in horses is to make standing surgeries to decrease the general anesthesia risks. For standing anesthetic procedures in horses there have been used combinations of xilazine bolus and local anesthesia; however, irregular analgesia and marked ataxia are frequent complications. In this clinical case it was evaluate a protocol of xilazine bolus 0,6 mg/kg I.V. and a constant rate infusion of morphine 30 µg/kg/h I.V., with local anesthesia for the extraction of a granulosa cell tumor in one mare. In general, during the surgical procedure it was observed good analgesia, moderate sedation and slight ataxia, without cardiovascular or respiratory problems which favored the surgical procedure; it was observed only a short period without intestinal motility that returned to normality spontaneously. The mare recovered fully from the surgical procedure and presented evidence of estrus twice within one year after the intervention. The anesthetic and surgical procedures used in this case were appropriate and lead recovery of the normal reproductive behavior of this mare.

G allele of the -930A>G polymorphism of the CYBA gene is associated with insulin resistance in obese subjects.

It has been shown that NADPH oxidase plays a role in oxidative stress which has been involved in the development of metabolic syndrome. The -930A/G polymorphism of the CYBA gene (that codes p22phox, a major component of the NADPH oxidase) has been associated with human hypertension and with a reduction in NADPH oxidase activity. In this work, we have examined the influence of the -930A/G polymorphism on obesity risk and insulin resistance in a case-control study of Spanish subjects (n=313). In the obese group (n=159), there was a statistically significant association between the GG genotype of the -930A/G polymorphism of the CYBA gene and fasting insulin levels and HOMA index. This outcome agrees with previous findings concerning functional analyses of this polymorphism and reinforces the hypothesis that insulin resistance is associated with oxidative stress. In conclusion, a protective effect in carriers of the -930A/G polymorphism of the p22phox gene against insulin resistance in a population of Spanish obese adults has been found.

Treatment of obesity in children and adolescents. How nutrition can work?

Overweight appears when persistent positive energy imbalances occur for long periods of time. Knowledge of dietary risk factors during childhood and adolescence is needed in order to design preventive measures against the increase in the prevalence of obesity and its consequences but is, however, largely missing. Longitudinal studies in children have not found clear causal associations between energy intake or diet composition and overweight development. Research has been ongoing to develop effective intervention studies for obese children but it is not clear which intervention is the most effective in assisting overweight/obese children to improve body composition without affecting growth rates. The objective of this article is to review the available knowledge on dietary risk factors for the development of childhood obesity, to discuss different dietary treatment strategies, and to propose an evidence-based approach to treat obese adolescents.

A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population.

OBJECTIVE: The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation. METHODS: The study was composed of 451 Spanish children and adolescents (49% boys), aged 5-18 year. According to the International Obesity Task Force (IOTF) criteria, the groups included 160 obese, 132 overweight and 159 normal-weight control subjects. RESULTS: One novel (Thr162Arg) and three known nonsynonymous mutations in the MC4R gene (Ser30Phe, Thr150Ile, Ala244Glu) were detected heterozygously. The MC4R mutations were found in three male (one obese and two overweight) and two female subjects (one obese and one overweight). The novel mutation did not appear to lead to an impaired receptor function. An unequivocal relationship of MC4R mutations with obesity in pedigrees together with an impaired function of the encoded receptor could not be established for any of the mutations. CONCLUSIONS: The presence of heterozygous MC4R mutations in obese and overweight subjects indicates that these mutations may be a susceptibility factor for obesity development, but lifestyle factors, such as exercise or sedentary activities, may modify their effect.

[Influence of the -866G/A polymorphism of the UCP2 gene on an obese pediatric population]. / Influencia del polimorfismo -866G/A del gen de la UCP2 en población infantil obesa.

OBJECTIVE: In the present study, our objectives were to evaluate the prevalence of -866G/A mutation of UCP2 gene and to study its influence on the phenotype of obese children (11-12 years old) from Navarra. BACKGROUND AND STUDY SETTING: Obesity is a disease with a multifactorial origin that may related be to the presence of mutations and polymorphisms in several candidate genes. The gene of the uncoupling protein UCP2 is one of the most studied ones in relation to obesity because it seems to participate in body composition and several metabolic processes control. Three polymorphisms have been described for this gene: an insertion/deletion of 45 nucleotides, a nucleotide change of guanine for adenine in -866 position, an another change that replaces alanine for valine at amino acid position 55. According to several studies, the -866G allele is related to an increased risk of developing obesity, although the results are contradictory about this association in the literature. SUBJECTS: The study was carried out on 125 obese children (52% male), aged 11-12 years, selected through the Pediatric Endocrinology Departments of Clínica Universitaria and Hospital Virgen del Camino of Pamplona (Spain), the reported results on this association are contradictory. INTERVENTIONS: After checking the inclusion criteria, anthropometrical data (weight, height, BMI, tricipital and subscapular skinfolds) were taken, and the percentage of fat mass was measured by bioelectrical impedance. Besides, plasma levels of total cholesterol, glucose, insulin, and leptin were measured. DNA was extracted from white blood cells to determine the genotype by PCR technique followed by BstUI digestion and further visualization in agarose gel with 2% ethidium bromide. RESULTS: The genetic analysis revealed a 0.404 frequency of the allele A, with a percentage of individuals G/G, G/A, and A/A of 40.0%, 39.2%, and 20.8%, respectively. Carriers of the A allele had a significantly higher sum of tricipital and subscapular folds (p = 0.034). No significant differences between mutant and non-mutant subjects with regard to the studied biochemical variables were observed. CONCLUSIONS: Subjects carrying the polymorphism present higher values of tricipital and subscapular skinfolds as compared to non-mutant subjects, which may indicate a relationship between the presence of the A allele in obese children and higher amounts of subcutaneous fat.

TV watching modifies obesity risk linked to the 27Glu polymorphism of the ADRB2 gene in girls.

OBJECTIVE: A matched case-control study was conducted in a population of Spanish children and adolescents (5-18 years old), to assess the interaction between the Gln27Glu polymorphism of the ADRB2 and television (TV) watching on obesity risk. PATIENTS: Obese (n=165) and control subjects (n=165) matched by sex and age were recruited and classified according to Spanish reference data. Results. Using conditional logistic regression, we calculated the obesity risk linked to the polymorphism. A statistically significant association was found for 27Glu carrier allele girls (OR = 1.95; 95% CI = 1.02-3.70), but no association was apparent among boys. In the fully adjusted model, the odds ratio for obesity linked to the genotype Glu27Glu in the female population rose to 4.84 (95% CI = 1.37-17.10). Moreover, we found a significant negative interaction between hours of TV watching and the Gln27Glu polymorphism for obesity risk in girls. Surprisingly, among 27Glu carrier subjects, even girls with a low level of TV watching ( < 12.5 h/week) had a high obesity risk (OR = 4.60; 95% CI = 1.01-20.02), which was not very different to the odds ratio values for sedentary girls carrying the 27 Glu allele watching TV more than 12.5 h/week (OR = 6.05; 95% CI = 1.31-27.71). Conclusion. A higher risk of obesity was found for girls carrying the 27Glu allele of the ADRB2 gene even when they spent less than 12.5 h/week watching TV. In addition, our results suggest that the effect of sedentary lifestyle on obesity risk may depend on the genotype of the subject.

No evidence of association between the serotonin 2A receptor--1438G/A promoter polymorphism and childhood obesity in a Spanish population: A case-parent study and a matched case-control study.

Serotonin has been related to feeding behaviour and body weight control through its suppressive effect on appetite. Conflicting results have been published in the literature regarding the association between the - 1438 G/A promoter polymorphism of the 5HT2A gene with obesity-related variables. The aim of this study was to assess the association between the--1438 G/A polymorphism of the 5HT2A gene with childhood obesity in a Spanish population. A total of 136 cases aged 6-16 years with BMI above the 97th percentile of the Spanish BMI reference data for age and gender were matched by gender and age (+/- 6 months) with 136 controls. Additionally, 43 obese children and their parents were selected for a family-based association study (case-parent study). Genotyping was carried out by polymerase chain reaction and restriction enzyme analysis. Conditional logistic regression and transmission/disequilibrium test were used to assess genotype-obesity association. In the matched case-control study, the crude and adjusted odds ratios for the association between 5HT2A--1438 G/A genotypes were nonsignificant. Likewise, no association is suggested by the case-parent study. In conclusion, it is unlikely that the--1438 G/A polymorphism of 5HT2A gene may influence obesity in a Spanish children population.

Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents.

AIMS: Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene to obesity risk in a Spanish children and adolescent population. METHODS: We designed a sex- and age-matched case-control study. Participants were 185 obese and 185 control children (aged 5-18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPAR gamma 2 mutation and BstNI for ADR beta 3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls. RESULTS: Carriers of the polymorphism Pro12Ala of the PPAR gamma 2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09-4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17-5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPAR gamma 2 and ADR beta 3) was 5.30 (95% CI=1.08-25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43-146.8). CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene for obesity risk was found in a case-control study including children and adolescents.

Chronopharmacokinetics and calcium in the prevention of gentamicin-induced nephrotoxicity in rabbits.

The study used 36 New Zealand white rabbits organized into three groups of 12 animals each. Group I received gentamicin; Group II received joint administration of gentamicin and calcium chloride and Group III received gentamicin, calcium chloride and verapamil. All the drugs were administered over 16 day periods. Groups I and II were divided in two subgroups, one subgroup receiving the treatment in winter and the other in summer. The results obtained for Group I indicate that there is an influence of the seasonal period on the gentamicin elimination and/or distribution. Mean plasma levels of the antibiotic at steady-state as well as the amounts of gentamicin accumulated in renal tissue are higher in winter than in summer. On the other hand, when calcium was administrated with the antibiotic, no significant circannual variations were observed in the renal toxicity of gentamicin. Under our study conditions the presence of calcium diminishes gentamicin plasma levels and the amount accumulated in kidney. Calcium, probably, generated a diminution in renal damage and consequently gentamicin renal excretion increases. The differences between Group II and Group III are due to the effect of verapamil. This agent blocks the calcium channels reducing the calcium protective effect on the nephrotoxicity of gentamicin.

Effect of the anticonvulsant U-54494A on cortical neuron excitability: comparison to the kappa agonist U-50488H.

U-54494A, a 1,2-diamine anticonvulsant, and U-50488H, a structurally related agonist for opiate kappa receptors, were tested for effects on spontaneous and glutamate-evoked firing rates in cerebral cortex of urethane-anesthetized male Sprague-Dawley rats. Iontophoretic application of 1,2-diamines, glutamate diethyl ether (GDEE), or procaine depressed spontaneous and amino acid-induced firing of cortical neurones. With continued ejection of 1,2-diamines or procaine, firing was silenced completely, but GDEE could maintain a partial suppression. A rapid rebound of excitation followed cessation of procaine ejections, but not of other agents. Procaine, but not U-54494A, blocked axonal conduction of rabbit sciatic nerve. Intravenous U-54494A and U-50488H significantly depressed spontaneous firing rates of cortical neurones, but only the U-50488H effects were antagonized by naloxone. It is concluded that U-54494A inhibits neuronal excitability by a mechanism independent of the analgesic kappa receptor. Biochemical and physiological studies have demonstrated that U-54494A and the kappa opioid agonist U-50488H (a structurally related diamine) (1) have anticonvulsant activity (2, 3). U-54494A lacks kappa analgesic and sedative properties, and it has been suggested that the mechanism of action of this compound may be mediated by a subtype of kappa opioid receptor (3). The effects of kappa analgesics on neuronal firing in nociceptive pathways have been described (4, 5). However, no previous electrophysiological studies on U-54494A have been done. Since U-54494A antagonizes amino acid-induced seizures (3), the interactions of this compound with glutamate are of interest. In the present study, the antagonist efficacies of U-54494A and U-50488H for inhibiting spontaneous and 1-glutamate stimulated neurons of the rat prefrontal cerebral cortex were assessed after i.v. and microiontophoretic administration of the compounds. Effects observed with these routes of administration allow the observation of neuronal changes occurring immediately after administration and take advantage of the high temporal resolution provided by the electrophysiological recording techniques of single cells. A preliminary account of portions of this work have been previously disclosed (6).

Preliminary pharmacokinetics of a new pyridopyrimidine derivative.

This paper describes the preliminary pharmacokinetic studies of 4-anilino-2-methylthiopyrido[2,3-d]pyrimidine (MD-39-AM) following a single administration of the compound to male rats via different routes (intravenous and oral) in the dose range of 6-24 mg.kg-1. The plasma level versus time plots after intravenous and oral administration to male rats can well be described by an open two-compartment model. The product was rapidly absorbed and peak concentrations in plasma were reached before 1 h after a single oral administration whatever the dose studied. The absolute bioavailability calculated on the basis of AUC0-infinity after intravenous and oral administration was estimated to be about 90%. Plasma levels found at higher doses than 6 mg/kg suggest that the product kinetics is dose dependent.

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidine derivatives as diuretics.

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidines 1 and 6,10-dihydro-5H-pyrido[3',2':5,6]pyrimido[2,1-c] [1,2,4]triazines 4 with 5-one, 5-thione or 5-hydrazono substituents and in some cases 1,2,3,4 or 8,9 hydrogenated are synthetized. The diuretic, natriuretic and kaliuretic activities of these compounds in Wistar rats at a dose of 24 mg/kg were estimated. A series of 24 possible derivatives of 1 and 4 possessing diuretic and saliuretic activities are investigated for structure-activity relationships in light of Fujita-Ban model. The Fujita-Ban group contributions have been calculated for different structural variations on the parent ring 1a. It is observed that the hydrogenation of pyridine, [1,3]thiazole or [1,2,4]triazine rings on 1 or 4 decrease the diuretic and saliuretic activities.

Diuretic and hypotensive activities of 4-anilino derivatives of 2-methylthiopyrido[2,3-d]pyrimidines.

The synthesis of a series of 12 compounds referring to 4-anilino-2-methylthiopyrido [2,3-d]pyrimidines (1-12), and the results of a study of their diuretic, saliuretic and antihypertensive activities are reported. Most of this compounds showed significant diuretic activity at the dosage of 3-24 mg/kg. The 4-Anilino-2-methylthiopirido[2,3-d]pyrimidine 1 remained active to a dosage of 1 mg/kg. The diuretic activity of these compounds implied an increase in the Na+ excretion. Some of the most active diuretics have been studied for antihypertensive effect.

U-54494A: a unique anticonvulsant related to kappa opioid agonists.

The benzamide U-54494A was compared to U-50488H (a structurally related kappa opioid agonist), phenytoin and phenobarbital in a variety of tests of anticonvulsant and sedative activities. In electroshock convulsion antagonism studies in mice and rats, U-54494A was generally similar to the standards in regard to milligrams of potency, threshold elevation, p.o. activity and duration of action. In contrast to phenytoin and phenobarbital, both U-54494A and U-50488H were effective antagonists of the convulsions induced by the excitatory amino acid agonists (kainic, N-methyl-aspartic and quisqualic acids) and the Ca++ channel agonist (Bay K 8644). They were not, however, effective antagonists of the gamma-aminobutyric acid-related convulsants (bicuculline and pentylenetetrazole), but all four blocked audiogenic convulsions in genetically epileptic mice. U-54494A in contrast to U-50488H lacks the kappa receptor-mediated sedative and analgesic activities but the anticonvulsant properties of both compounds are antagonized by high doses of naltrexone. Further investigations of the mechanism of action of these compounds revealed that both caused a dose-related suppression of post-tetanic repetitive discharge in cats soleus nerve-muscle preparations as measured by an abolition of the obligatory potentiation of soleus muscle contractile tension. On a biochemical level, both U-54494A and U-50488H attenuate the depolarization induced uptake of 45Ca++ into forebrain synaptosomes and block the enhancement of [3H]kainic acid binding induced by CaCl2. Together these results suggest that U-54494A is a unique and selective anticonvulsant agent acting by a Ca++-related mechanism possibly through a subclass of kappa receptors.

Biochemical and functional interactions of a selective kappa opioid agonist with calcium.

The discovery of the selective kappa opioid receptor agonist, U-50488H, has provided a tool for the study of the mechanisms and function of the kappa receptor-effector. We have investigated the interactions of this compound with calcium in several biochemical and functional studies to assess the involvement of calcium mechanisms in the kappa receptor-linked effector. In rat brain synaptosomes, U-50488H attenuated the uptake of 45Ca++ induced by K+ (40 mM) depolarization. This effect was concentration-related (U-50488H 10(-5) to 10(-7) M), was apparent in short (8-second) but not longer (1-minute) term incubations, and did not occur in the presence of a non-polarizing concentration (5.6 mM) of K+. Naloxone (10(-7) M) did not block this effect of U-50488H (10(-6) M), and higher concentrations (10(-5) M) alone blocked calcium uptake. We have found that the binding of the depolarizing amino acid analog, kainic acid, is enhanced by CaCl2. U-50488H (10(-4) to 10(-6) M) blocks this enhancement of 3H-kainic acid binding in vitro and also blocks the in vivo effects of kainic acid. In mice, intravenous injection of kainic acid causes scratching, convulsions, and death, depending on the dose administered. U-50488H blocks all of these effects (ED50 = 4.5 mg/kg for antagonism of convulsions induced by 27.5 mg/kg kainic acid). The convulsions induced by intracerebroventricularly administered kainic acid are also blocked by U-50488H as are those induced by similarly administered Bay K 8644, a calcium channel activator. All of these anticonvulsant effects of U-50488H were antagonized by naltrexone. Together these data indicate that the kappa agonist U-50488H has functionally relevant interactions with depolarization-related Ca++ mechanisms in the central nervous system.

Effects of the administration of artroglobina suppositories in healthy volunteers.

Forty-nine healthy volunteers were treated daily with Artroglobina suppositories (anticartilage antiparathyroid immunoglobulins) for twelve days, in order to prove the absence of side effects. Volunteers were examined daily. Blood and urine samples were taken before the treatment, twelve days, twenty-four days and six months after the beginning of the treatment. Slight changes were noted in some parameters though remaining in the normal range and disappearing six months later. No symptoms of intolerance, toxicity or side effects were registered.