A study of the neurotoxic effect of MDMA (‘ecstasy') on 5-HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy

1. It is well established that 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy'') is neurotoxic and produces long term degeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals in many species. Since MDMA is used extensively as a recreational drug by young people, it is being ingested by many women of child bearing age. We have therefore examined the effect of administering high doses of MDMA to rats during pregnancy on the cerebral content of both the dams and the neonates.
2. MDMA (20 mg kg⁻¹, s.c.) was injected twice daily on days 14–17 of the gestation period. The initial dose produced a marked hyperthermic response in the dam which was progressively attenuated in both peak height and area under the curve following further doses of the drug. The body weight of the dams decreased during the period of treatment.
3. There was a modest decrease in litter size (−20%) of the MDMA-treated dams.
4. The concentration of 5-HT and its metabolite 5-HIAA was decreased by over 65% in the hippocampus and striatum and 40% in the cortex of the dams 1 week after parturition. In contrast, the content of 5-HT and 5-HIAA in the dorsal telencephalon of the pups of the MDMA-treated dams was the same as that seen in tissue from pups born to control animals.
5. Administration of MDMA (40 mg kg⁻¹, s.c.) to adult rats increased thiobarbituric acid reacting substances (TBARS) in cortical tissue 3 h and 6 h later, indicating increased lipid peroxidation. No increase in TBARS was seen in the cortical tissue of 7–10 day neonates injected with this dose of MDMA 3 h or 6 h earlier.
6. The data suggest that exposure to MDMA in utero during the maturation phase does not produce damage to 5-HT nerve terminals in the foetal rat brain, in contrast to the damage seen in the brains of the mothers. This may be due to MDMA being metabolized to free radical producing entities in the adult brain but not in the immature brain or, alternatively, to more effective or more active free radical scavenging mechanisms being present in the immature brain.

     

Subjective versus statistical model assessment of mortality risk in open heart surgical procedures

BACKGROUND: The aim of this study was to compare the predictive accuracy for open heart surgical mortality between a statistical model based on collection of clinical data and surgeons' subjective risk assessment. METHODS: Predictive discrimination of both risk assessments (surgeons' and model) was compared through the area under the receiver operating characteristic curve. Logistic regression analysis was used to assess the relation between surgeons' and model predictions to actual outcomes. Calibration of the subjective estimates was evaluated with a chi2 test. RESULTS: Overall, the area under the receiver operating characteristic curve was 0.76 for the statistical model and 0.70 for the subjective assessment. Logistic regression analysis showed that the statistical model remained significant after accounting for the subjective assessment. Calibration of subjective mortality predictions was poor. CONCLUSIONS: Surgeons' risk assessment tends to cluster in the middle ranges of risk. Subjective assessment seems accurate in identifying the two extremes of risk but is inaccurate for intermediate risk levels. A multivariate statistical model improves the accuracy of subjective predictions.     

Independent Associations of the HLA-B27 Antigen and the Complement Haplotype SC21 in Chronic Anterior Uveitis

There is evidence of an association between major histocompatibility complex (MHC) genes and acute anterior uveitis; here the authors report the frequency of class I and class III MHC phenotypes in 32 Mexican mestizo patients with chronic anterior uveitis and compared them to those present in 100 ethnically matched healthy controls. Results showed in patients statistically significant increased frequencies of HLA-B(27) antigen (pC=0.02, OR=6.33, 95+ CI:1.63-26.47) and the complotype SC(21) (pC=0.04, OR=4.5, 95+ CI:1.40-14.67); the authors found a decreased frequency of HLA-B(35) (p=0.006, OR=0.10, 95+ CI: 0.00-0.65) as compared to normal controls. None of the individuals bearing the SC(21) complotype were positive for HLA-B(27), suggesting independent roles of the class I and class III antigens in the genetic susceptibility to chronic anterior uveitis.     

Parents' reports of barriers to care for children with special health care needs: development and validation of the barriers to care questionnaire.

OBJECTIVE: To describe the development and validation of the Barriers to Care Questionnaire (BCQ). METHODS: The 39-item BCQ was developed through review of the literature, focus groups, and cognitive interviews of Spanish- and English-speaking parents of children with chronic health conditions. Barriers to care are conceptualized as a multidimensional construct consisting of pragmatics, health knowledge and beliefs, expectations about care, skills, and marginalization. The BCQ was field tested in 3 samples of children with special health care needs (CSHCN). RESULTS: Response rate for the field test was 77.2%. There were minimal missing data (0.08%), no floor effects, and minimal ceiling effects (3.8%, total scale). Internal consistency reliability (alpha) for the BCQ total scale was.95 and subscale alpha ranged from.75 to.91. The BCQ total scale and subscales correlated in the expected direction with validated measures of primary care characteristics and health-related quality of life. BCQ scores were higher (fewer barriers) for children with a primary care physician and for those who reported no problems getting care or foregone care. CONCLUSION: The BCQ is a feasible, reliable, and valid instrument for measuring barriers to care for CSHCN. Its use may inform efforts to support consumer choice, enhance provider accountability, and spur quality improvement.     

Synergistic antinociceptive interaction between acetaminophen or metamizol and B vitamins in the formalin test

There is evidence that B vitamins produce antinociception in animals. However, potentiation of NSAID‐induced antinociception by B vitamins is unclear. The current study was designed to investigate the antinociceptive interaction between a mixture of B vitamins and either acetaminophen or metamizol. Acetaminophen (56–316 mg/kg), metamizol (32–178 mg/kg), and the mixture of B vitamins (32–178 mg/kg of thiamine, pyridoxine, and cyanocobalamin in a 100:100:1 proportion, respectively) or a combination of each drug with the B vitamins mixture was administered orally to female Wistar rats, and the antinociceptive effect determined in the formalin test. Isobolographic analyses were used to define the nature of the interaction between NSAIDs and B vitamins. Oral administration of either drug produced a dose‐related antinociceptive effect. Isobolographic analyses revealed that both acetaminophen or metamizol and the B vitamins mixture interacted synergistically in the formalin test, suggesting that these two combinations could be useful in treating inflammatory pain states. Drug Dev. Res. 66:286–294, 2006. © 2006 Wiley‐Liss, Inc.     

Subacute and acute fasciolosis in sheep in southern Brazil

Eight outbreaks of acute and subacute fasciolosis are reported in sheep in the municipality of Santa Vitória do Palmar, southern Brazil, in areas used for irrigated rice cultivation, which are subject to frequent flooding. Two outbreaks occurred mid-winter during July and August, and six occurred during spring and early summer. Morbidity ranged from 3 to 66.7 %, and mortality ranged from 3 to 50 %. Clinical signs included weight loss, mucosal pallor, apathy, depression, muscle tremors, and drooling; these were followed by death within approximately 24 h. Some sheep were found dead. Gross lesions were characterized by an irregular liver capsule with fibrin deposition and hemorrhages. The liver parenchyma contained hemorrhagic tracts or irregular clear areas alternated with dark hemorrhagic areas. Histologically, hemorrhagic dark red tracts of necrotic liver parenchyma and an inflammatory infiltrate were noted; these lesions coincided with the presence of immature flukes. Langhans-type giant cells, fibrous tissue, and bile duct cell proliferation were observed in subacute cases. Chronic fasciolosis is a well-known disease to farmers in southern Brazil; nevertheless, acute and subacute fasciolosis, which are more difficult to diagnose and treat, may cause important economic losses. Efficient control of fasciolosis requires integration of measures to treat infections in the definitive host, to reduce the population of snails of the genus Lymnaea, and to avoid contact between the parasite and host by appropriate pasture management.     

Effects of High-Fat Diet and Maternal Binge-Like Alcohol Consumption and Their Influence on Cocaine Response in Female Mice Offspring

BackgroundPrenatal alcohol exposure is a leading cause of neurobehavioral and neurocognitive deficits collectively known as fetal alcohol spectrum disorders, including eating disorders and increased risk for substance abuse as very common issues. In this context, the present study aimed to assess the interaction between prenatal and lactation alcohol exposure (PLAE) and a high-fat diet (HFD) during childhood and adolescence.MethodsPregnant C57BL/6 mice underwent a procedure for alcohol binge drinking during gestation and lactation periods. Subsequently, PLAE female offspring were fed with an HFD for 8 weeks, and thereafter, nutrition-related parameters as well as their response to cocaine were assessed.ResultsIn our model, feeding young females with an HFD increased their triglyceride blood levels but did not induce overweight compared with those fed with a standard diet. Moreover, PLAE affected how females responded to the fatty diet as they consumed less food than water-exposed offspring, consistent with a lower gain of body weight. HFD increased the psychostimulant effects of cocaine. Surprisingly, PLAE reduced the locomotor responses to cocaine without modifying cocaine-induced reward. Moreover, PLAE prevented the striatal overexpression of cannabinoid 1 receptors induced by an HFD and induced an alteration of myelin damage biomarker in the prefrontal cortex, an effect that was mitigated by an HFD-based feeding.ConclusionTherefore, in female offspring, some effects triggered by one of these factors, PLAE or an HFD, were blunted by the other, suggesting a close interaction between the involved mechanisms.