Role of alpha2A-adrenoceptors in the effects of MDMA on body temperature in the mouse

3,4-Methylenedioxymetamphetamine (MDMA) produces complex effects on body temperature, including hypo- and hyperthermic components that vary with ambient temperature and strain of rat. We have previously reported that MDMA is an alpha(2)-adrenoceptor agonist, and alpha(2)-adrenoceptor agonists such as clonidine produce hypothermia. The purpose of this study was to investigate the effects of MDMA on core body temperature measured by radiotelemetry in conscious wild-type (WT) and alpha(2A)-knockout (alpha(2A)-KO) mice. Clonidine (0.1 mg kg(-1), subcutaneously (s.c.)) produced a hypothermic response in WT mice, but did not significantly affect temperature in alpha(2)-KO mice. MDMA (20 mg kg(-1), s.c.) produced a significant hyperthermia in WT mice beginning at approximately 100 min after injection, recovering by 300 min, but produced a biphasic response, hypothermia followed by hyperthermia, in alpha(2)-KO mice. In WT mice, following the alpha(2A)-adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (1 mg kg(-1), s.c.), MDMA (20 mg kg(-1)) produced an initial hypothermia. Hence, alpha(2)-adrenoceptor agonist actions of MDMA contribute to its effects on body temperature, but in a surprising way. Although selective alpha(2A)-adrenoceptor agonism produces hypothermia, the alpha(2A)-adrenoceptor actions of MDMA alter the body temperature response to MDMA from biphasic (hypothermia followed by hyperthermia) to monophasic hyperthemia.     

Effect of sodium valproate monotherapy on serum uric acid concentrations in ambulatory epileptic children: A prospective long-term study

PURPOSE: Hyperuricemia has been shown to be related to cardiovascular morbidity and mortality. There is controversial data about the effect of sodium valproate (VPA) monotherapy on serum uric acid concentrations. The purpose of this study was to investigate by a long-term, prospective method, whether treatment with VPA monotherapy may alter serum uric acid concentrations and liver function tests in ambulatory epileptic children. MATERIAL AND METHODS: Serum uric acid concentrations were determined in 28 ambulatory epileptic children before and at 6, 12 and 24 months of VPA monotherapy. Serum concentrations of biochemical markers of liver and renal function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (gamma-GT) and creatinine (Cr) were also measured before and at 6, 12 and 24 months of VPA monotherapy. Serum VPA concentrations remained within the therapeutic range (50-100 mg/L) during the period of study. RESULTS: No statistically significant changes in serum uric acid concentrations were found at 6, 12 or 24 months of treatment. Serum ALT concentrations were significantly increased at 6 and 12 months of treatment, AST concentrations at 6 and 12 months of treatment and LDH concentrations at 12 months of treatment. CONCLUSIONS: VPA monotherapy does not have a significant effect on serum uric acid concentrations in ambulatory epileptic children. Further studies are needed to definitively address whether it would be useful for physicians to routinely check for elevated serum uric acid levels in children treated with VPA.     

"Absent" pulmonary artery in one adult and five pediatric patients: imaging,embryology, and therapeutic implications

OBJECTIVE: The purpose of this article is to present serial clinical and imaging findings for the "absent" pulmonary artery. Data from six patients with this condition (five unilateral cases and one bilateral case) provide evidence concerning its embryology and illustrate the therapeutic implications of surgical intervention. CONCLUSION: In our series, we found the anatomy of the absent pulmonary artery to be consistent with a distal ductal origin and involution of the proximal sixth aortic arch. The absent pulmonary artery is a distinct embryologic entity that requires early detection and detailed investigation. Early surgical intervention may be justified in selected patients.     

Invasive balantidiasis presented as chronic colitis and lung involvement

Summary A unique case of chronic balantidiasis is described, presenting with chronic colitis and inflammatory polyposis of the rectum and sigmoid colon and an intrapulmonary mass. Histology of the colonic polyps showedBalantidium coli, and bothAspergillus andBalantidium coli were found in the aspirate of the pulmonary mass. The patient was treated with doxycycline HC1 100 mg/day for 10 days with complete clinical recovery and marked improvement of the endoscopic appearance of the colonic mucosa.     

Relaxations to beta-adrenoceptor subtype selective agonists in wild-type and NOS-3-KO mouse mesenteric arteries

We have investigated the role of nitric oxide (NO) in relaxations to beta-adrenoceptor agonists in mesenteric artery from wild-type (WT) and NO synthase-3 knockout (NOS-3-KO) mice. Isoprenaline, formoterol and BRL 37344 ((R(),R())-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid) were chosen as non-selective and beta(2)- and beta(3)-adrenoceptor agonists, respectively. Atenolol, ICI 118,551 ((+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) and SR59230A (1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol hydrochloride) were chosen as selective beta(1)-, beta(2)- and beta(3)-adrenoceptor antagonists, respectively. Experiments employing isoprenaline were carried out in the presence of prazosin (0.1 microM). Isoprenaline produced relaxations with a potency of 5.68+/-0.36 (-log M, n=6) in WT mice. Relaxations to isoprenaline were blocked by atenolol (10 microM) and were absent in vessels from NOS-3-KO animals. Formoterol produced relaxations with two components. ICI 118,551 (1 microM) abolished relaxations to low concentrations of formoterol (0.1-10 microM), but failed to affect relaxations to formoterol (100 microM). In NOS-3-KO mice only the highest concentration of formoterol (100 microM) produced relaxations: the relaxation was resistant to all of the beta-adrenoceptor antagonists employed. BRL 37344 (5.75+/-0.28, n=9) was approximately equipotent with isoprenaline but produced a smaller degree of relaxation, in WT mice. SR59230A (1 microM) abolished relaxations to BRL 37344 in WT mice. In NOS-3-KO mice, BRL 37344 produced concentration-dependent relaxations which were abolished by SR59230A. It is concluded that the predominant beta-adrenoceptor mediating relaxations in mouse mesenteric artery is beta(1), and relaxations involve NOS-3. In addition, beta(3)-adrenoceptors mediate smaller relaxations at least partly independent of NOS-3, and beta(2)-adrenoceptors may mediate smaller relaxations dependent on NOS-3.     

Oral hygiene in 12-year-old disabled children in Flanders, Belgium, related to manual dexterity

As part of a larger epidemiological survey of a stratified sample of 12-year-old handicapped children in Flanders, Belgium, the present study describes gingival health, gingival hypertrophy, oral cleanliness and the presence of calculus. Statistical analysis was performed with motor skills, brushing help, the use of chemical agents, the use of anti-epileptic drugs, the knowledge of parents and educators (or caregivers) and their opinion of the oral hygiene of their children/ pupils as response variables. From this study, it became clear that mildly mentally retarded and learning-impaired children had significantly better manual dexterity skills than moderately and severely mentally retarded and physically impaired children. However, this was not reflected in improved oral hygiene. The use of chemical plaque controlling agents was found to be extremely low and, with the exception of children with gingival hyperplasia, the users of these agents did not have better oral hygiene. No difference was found between subtypes in the opinion of parents and educators on oral status. There was, however, a difference between their assessment and the clinical picture. It was concluded that there was a need for in-service training programmes in oral health care for educators as well as for parents.     

Neurological outcome at 6 and 12 months corrected age in hospitalised late preterm infants -a prospective study

Late preterm infants (34-0/7 to 36-6/7 weeks“ gestation) account for 10–20% of NICU admissions and are at increased risk for morbidity and mortality. Although they are prone to developmental delays, reports on neurological outcome during the first 2 years of life are scarce.The aim of the study was to assess neurological/neuromotor outcome in high risk late preterm infants at 6 and 12 months corrected age and the change in neurological scores over time, and to identify factors associated with the neurological outcome.The Hammersmith Infant Neurological Examination was performed in a cohort of 157 late preterm infants admitted in the NICU. The infants were examined at 6 and 12 months corrected age respectively and scored with the optimality score system including 26 items assessing cranial nerve function, posture, movements, tone and reflexes. Also parents reported neurological milestones in the follow up visit.Infants at 6 months had a global score of 59 (47–76) and optimal scores achieved in 25.4%. At 12 months they had a global score of 70 (58–78) and achieved optimal scores in 63.2%. The subscores of posture, tone and reflexes gradually increased from 6 to 12 months corrected age. Being born small for gestational age was the only factor that adversely influenced HINE score at 6 and 12 months. At 12 months 58.5% achieved independent walking. High risk late preterm infants have suboptimal HINE scores at 6 and 12 months of age, suggesting a need for closer follow up and early intervention programs.