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Biomedical subjects

J Perrin

Publications and source records attributed to J Perrin.

At least 19 recordsLinked to original sources

Neuronal responses to cannabinoid receptor ligands in the solitary tract nucleus.

Our previous study showed many neurons in the subpostremal division of the nucleus tractus solitarii to be cannabinoid-sensitive. In order to further investigate this sensitivity, single unit activity was recorded extracellularly in rat hindbrain slices, and the effects of bath application of delta9-tetrahydrocannabinol and of two synthetic cannabinoid receptor agonists were analysed and compared to each other. Approximately half the recorded neurons responded to agonists, and most of the neurons exposed to two of the agonists reacted similarly to both. The involvement of cannabinoid CB receptors in neuronal sensitivity to delta9-tetrahydrocannabinol is supported by these data and by the effects of N-piperidin-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-p yrazole-carboxamide, hydrochloride (SR 141716A), a compound which is considered to be a selective antagonist and/or a selective inverse agonist of this receptor type.

Animals

Characteristics of glycemia-sensitive neurons in the nucleus tractus solitarii: possible involvement in nutritional regulation.

Single unit responses to moderate glycemic variations were extracellularly recorded in the caudal division of the nucleus tractus solitarii of rats anesthetized by i.v. infusion of ketamine. As previously observed, a majority of recorded neurons (70%) were either activated or depressed by moderate hyperglycemia. Responses were consistently reproducible and amplitude was dependent on the maximum level of hyperglycemia. All glycemia-sensitive neurons responded in opposite directions to induced hyperglycemia and hypoglycemia, and almost all displayed the same type of response to local and i.v. glucose administration. Most glycemia-sensitive neurons were depressed by iontophoresis of clonidine, suggesting that they were adrenergic or noradrenergic. Based on these findings, we speculate that glycemia-sensitive neurons in the caudal nucleus tractus solitarii may act as glucose sensors that transmit glycemic information corresponding to different nutritional states, as well as other relevant signals toward hypothalamic structures involved in feeding and metabolic regulation via ascending adrenergic and noradrenergic pathways.

Animals

Neuronal responses to systemic nicotine in the solitary tract nucleus: origin and possible relation with nutritional effects of nicotine.

Single-unit activity was recorded extracellularly in the caudal part of the solitary tract nucleus of anesthetized rats. Of 60 recorded neurons, 44 (73.3%) responded to intravenous (I.V.) nicotine. The incidence of response was significantly greater in the cells sensitive to moderate changes in blood glucose level, suggesting that the effects of nicotine on food intake and body weight are partly mediated by the glycemia-sensitive neurons in the caudal nucleus tractus solitarius. Only one-fourth of the neurons affected by I.V. nicotine responded in the same direction to iontophoretic nicotine application, suggesting that sensitivity to systemic nicotine results mainly from an indirect mechanism. Based on the observed effects of nicotinic agonists and antagonists unable to cross the blood-brain barrier, a majority of indirect unit responses to I.V. nicotine might be mediated by peripheral receptors, while the remaining ones might involve central or both central and peripheral receptors.

Animals

Neuronal responses to delta 9-tetrahydrocannabinol in the solitary tract nucleus.

The effects of delta 9-tetrahydrocannabinol on single-unit activity in the subpostremal division of the nucleus tractus solitarii were investigated by extracellular recording in rat brain slices. The spontaneous firing rate of 54.8% of the recorded neurons was significantly changed after bath applications of delta 9-tetrahydrocannabinol. Putative nutrition-related neurons responding to a moderate increase in glucose concentration were selectively sensitive to delta 9-tetrahydrocannabinol. The delta 9-tetrahydrocannabinol-sensitive neurons were depressed by clonidine and are therefore likely to be adrenergic or noradrenergic. These observations suggest that some catecholaminergic, glucose-responsive neurons in the subpostremal nucleus tractus solitarii might mediate the influence of cannabinoids on feeding behaviour. Furthermore, most delta 9-tetrahydrocannabinol-sensitive neurons in the nucleus tractus solitarii showed opposite responses to delta 9-tetrahydrocannabinol and the 5-HT3 receptor agonist 1-phenylbiguanide, and might therefore be involved in the nausea-reducing effects of cannabinoids.

Animals

A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders.

BACKGROUND: Previous cross-sectional data showed that children and adolescents with attention-deficit hyperactivity disorder (ADHD) are at increased risk of comorbid conduct, mood, and anxiety disorders as well as impairments in cognitive, social, family, and school functioning. However, longitudinal data were needed to confirm these initial impressions. METHODS: Using DSM-III-R structured diagnostic interviews and raters blinded as to diagnosis, we reexamined psychiatric diagnoses at 1- and 4-year follow-ups in children with ADHD and controls. In addition, subjects were evaluated for cognitive, achievement, social, school and family functioning. RESULTS: Analyses of follow-up findings revealed significant differences between children with ADHD and controls in rates of behavioral, mood, and anxiety disorders, with these disorders increasing markedly from baseline to follow-up assessments. In addition, children with ADHD had significantly more impaired cognitive, family, school, and psychosocial functioning than did controls. Baseline diagnosis of conduct disorder predicted major depression and bipolar disorder at follow-up, and anxiety disorders at baseline predicted anxiety disorders at follow-up. CONCLUSION: These results confirm and extend previous retrospective results indicating that children with ADHD are at high risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning. These findings provide further support for the value of considering psychiatric comorbidity in both clinical assessment and research protocols involving children with ADHD.

Achievement

Antimutagenic effects of amifostine: clinical implications.

The radioprotector S-2-(3-aminopropylamino) ethylphosphorothioic acid (amifostine; WR-2721) was evaluated for its ability to protect against cyclophosphamide-induced mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in mouse splenocytes under conditions that do not interfere with cyclophosphamide's therapeutic effectiveness against fibrosarcoma lung tumors. Mutations at the HPRT locus increase in frequency as a function of the dose of cyclophosphamide used. With a spontaneous mutation frequency in C3H mice of 1.5 x 10(-6), mutation frequencies increased from 6.2 x 10(-6) to 2.0 x 10(-5) as the cyclophosphamide dose increased from 50 to 200 mg/kg. C3H male mice had 3.5 x 10(5) viable fibrosarcoma cells injected into their tail veins. This resulted in an average of 68 tumor colonies per mouse. Four days following injection, animals received cyclophosphamide 100 mg/kg, which provided significant tumor cell killing and a reduction in tumor colony number to an average of less than one per animal. Amifostine at a concentration of 100 mg/kg did not affect cyclophosphamide's therapeutic efficacy. However, amifostine 100 mg/kg was effective in reducing cyclophosphamide-induced HPRT mutation frequency in mice from 160 to 35 per 10(5) viable cells regardless of whether it was administered 30 minutes before or 2 hours after the cyclophosphamide.

Amifostine

Sensitivity of nucleus tractus solitarius neurons to induced moderate hyperglycemia, with special reference to catecholaminergic regions.

Extracellular single-unit recordings have been carried out in the caudal part of the nucleus tractus solitarius of male rats anesthetized by i.v. infusion with Ketamine. The sensitivity of 38 cells to 0.2 ml of 0.55 M glucose i.v. administration has been studied. The spike frequency of 75% of these cells was affected by the induced moderate hyperglycemia and a majority of them was activated. Immunohistochemical data on 9 glycemia-sensitive neurons showed that all recording sites were within TH-immunoreactive regions of the caudal part of the nucleus (either in the A2 noradrenergic group, or the C2 adrenergic group). These results confirm the existence of glycemia-sensitive neurons in the nucleus tractus solitarius, and suggest that these cells might mediate the effects of physiological fluctuations in blood glucose level on the control of food intake and metabolic regulations. The localization of these cells in catecholaminergic regions suggests that adrenaline and/or noradrenaline efferents might convey feeding relevant information concerning glycemic level or satiety signal from the nucleus tractus solitarius to forebrain structures involved in food intake, such as the perifornical lateral hypothalamic area and the paraventricular nucleus.

Animals

Evaluation of cryopreservation techniques for goat embryos.

A total of 410 goat embryos were divided at random into 9 groups. Cryoprotectants (glycerol, ethylene glycol or dimethylsulfoxide) were added by a 3-step procedure using increasing concentrations of cryoprotectant (0.5 M; 1 M; 1.5 M) in PBS at 10 min intervals. After freezing and thawing, each cryoprotectant was removed by 3 methods: the classic 3-step procedure (cryoprotectant 1 M-10 min; 0.5 M-10 min; PBS alone-10 min); the same procedure, but with sucrose added to the first 2 steps (sucrose 0.25 M and cryoprotectant 1 M-10 min; sucrose 0.25 M and cryoprotectant 0.5 M-10 min; PBS alone-10 min); and a 2-step procedure with sucrose alone (sucrose 0.25 M-10 min; PBS alone-10 min). Each removal protocol was performed for embryos in each cryoprotectant. The viability of the embryo was evaluated by its capacity to subsequently develop during 48 h in vitro culture. For morulae the development rate of the embryos was significantly higher when they were frozen with ethylene glycol than when dimethylsulfoxide or glycerol was used (P < 0.05). For blastocysts the development rate was the same whether they had been frozen with ethylene glycol or dimethylsulfoxide, and was significantly lower when they were frozen with glycerol (P < 0.05). Among the 3 removal procedures tested, the 3-step procedure with sucrose gave the best development rate and differed significantly from the classic 3-step procedure (P < 0.05).

Animals

Clinical correlates of enuresis in ADHD and non-ADHD children.

Enuresis and attention deficit hyperactivity disorder (ADHD) are common childhood disorders that often co-occur. Although each has been linked to neurodevelopmental immaturity and increased risk for psychopathology, the clinical correlates of enuresis remain unclear. Subjects were 140 6-17-year-old boys with DSM-III-R ADHD and 120 non-ADHD controls. Information on enuresis and psychiatric diagnoses was obtained in a standardized manner blind to the child's clinical status. Our results show that (1) enuresis did not increase the risk for psychopathology in children with or without ADHD; (2) enuresis was not associated with psychosocial adversity or developmental immaturity; (3) enuresis was associated with increased risk for learning disability, impaired intellectual functioning, and impaired school achievement in normal control children but not in children with ADHD; and (4) the same pattern of findings was obtained after stratifying children with enuresis by primary versus secondary and by nocturnal versus diurnal subtypes. These results suggest that the clinical implications of enuresis may differ for ADHD and non-ADHD children.

Adolescent

[Presence of Campylobacter spp., Clostridium difficile, C. perfringens and salmonellae in litters of puppies and in adult dogs in a shelter].

In order to ascertain the importance of Campylobacter spp., C.difficile, C.perfringens and Salmonella as agents of bacterial gastroenteritis in dogs, two groups of animals were studied prospectively. The first group consisted of 77 puppies in 14 litters, with fecal cultures performed weekly for 10 weeks, starting at birth. The second group consisted of a kennel population with every dog cultured at entry, and at two-month intervals thereafter. Incidence of Campylobacter spp. was 32 and 31 per 100 dog-month of observation for healthy pups and healthy adult dogs respectively, 46 and 0 for C.difficile, 51 and 36 for C.perfringens and 6.5 and 1.3 for Salmonella. The incidence of Campylobacter spp. in pups peaked at 8 weeks of age. This incidence (43 per 100 dog-months) was higher in pups reared together with older dogs than in pups reared without contact to other dogs (0 per 100 dog-months). Toxigenic strains of C.difficile were found in 61.5% of the healthy neonate dogs. None of the cases of non-watery and non-inflammatory diarrhea we observed was associated with any of the pathogens studied. Furthermore newly acquired colonization with Campylobacter spp. or Salmonella was never associated with episodes of diarrhea. No conclusions could be drawn about the role of bacterial pathogens for causation of watery or inflammatory diarrhea which were not observed in our study.

Animals

Metabolism and pharmacokinetics of N1,N11-diethylnorspermine.

The pharmacokinetics and metabolism of N1,N11-diethylnorspermine (DENSPM) is described. When administered to dogs as an intravenous bolus, DENSPM was shown to have a plasma half-life of 72.8 +/- 11.8 min, with an early distribution phase half-life of approximately 4 min and an apparent volume of distribution of 0.216 +/- 0.032 liter/kg. The renal clearance half-life was 59.7 +/- 7.6 min, with 48.8 +/- 12.5% of the drug recovered in the urine between 0-4 hr unchanged. In three other experiments, the drug was administered to dogs by constant rate intravenous infusion over periods ranging from 10 min to 2 hr. Analysis of plasma concentration-time data and urinary excretion data yielded pharmacokinetic parameters in general agreement with the intravenous bolus experiments. DENSPM metabolites were identified in both beagle dog and mouse tissues. Tissues were sampled from a single beagle 24 hr posttreatment, and rodent samples were examined at 12, 24, 48, and 96 hr posttreatment. Both the concentration of DENSPM and the metabolic profile were shown to vary in the lung, liver, spleen, and kidney. Although all the tissues examined contained DENSPM and its metabolites, the liver and kidney had the highest level of metabolites that included N1-ethylnorspermine, N1-ethylnorspermidine, N1-ethyl-1,3-diaminopropane, and norspermidine. These data suggest that DENSPM is metabolized by N-deethylation and step-wise removal of aminopropyl equivalents by spermine/spermidine N1-acetyltransferase/polyamine oxidase, a metabolic pathway unique to the polyamines.

Animals

Catecholaminergic projections from the solitary tract nucleus to the perifornical hypothalamus.

The source of adrenergic and other catecholaminergic fibers innervating the perifornical lateral hypothalamus was localized in the medulla after combination of Fluoro-Gold retrograde tracing and immunohistochemistry for either tyrosine-hydroxylase or phenylethanolamine-N-methyltransferase. Following perifornical injections, Fluoro-Gold-labeled neurons were observed mainly in regions including the noradrenergic and adrenergic cell groups. In the caudal solitary tract nucleus, two kinds of doubly labeled neurons were found: a) numerous noradrenergic neurons in the A2 group at the level of, or caudal to the area postrema; b) some adrenergic neurons in the C2 group at a level immediately rostral to the area postrema. These catecholaminergic neurons connecting the caudal solitary tract nucleus to the perifornical hypothalamus might convey feeding relevant information such as glycemic level or satiety signals.

Animals

[Infection with Mycoplasma mycoides ssp. mycoides LC (large colony type) in bezoar goat kids (Capra aegagrus cretica) in the Bern (Switzerland) Zoo].

Mycoplasma mycoides ssp. mycoides LC (large colony type) (MML) was isolated from three 2 to 6 weeks old wild goat kids (Capra aegagrus cretica) dead of septicemia in a Swiss zoo. Necropsy revealed peritonitis, pneumonia and enteritis. MML was isolated out of the ear canal of most of the healthy animals in the flock. The high density of the animals, the presence of concomitant diseases and the carriage among healthy animals seem to have been important predisposing factors for the MML-infection.

Animals