Dopamine and serotonin release-regulating autoreceptor sensitivity in A9/A10 cell body and terminal areas after withdrawal of rats from continuous infusion of cocaine

The effects of dopamine (DA) and 5-hydroxytryptamine (5-HT) autoreceptor agents on electrically induced [3H]DA and [3H]5-HT release from superfused slices of striatum, nucleus accumbens and ventral mesencephalon (VM) containing A9 and A10 neurons were investigated in rats made tolerant to the stimulatory effect of cocaine on locomotor behavior by a 14-day continuous infusion of cocaine (29 mg/kg/day) by s.c. implanted osmotic minipumps followed by a 7-day drug-free period. In VM, electrically induced [3H]DA was increased, the ability of pergolide to inhibit this release was abolished, but the ability of sulpiride to facilitate the release was potentiated, implicating a higher concentration of synaptic DA modifying the responsiveness of somatodendritic D2 autoreceptors to D2 agents. Both electrically induced [3H]5-HT release from VM and the stimulatory effect of in vitro cocaine on this release were enhanced whereas the effects of both 5-methoxytryptamine and methiothepin were attenuated, indicating that subsensitivity of 5-HT autoreceptors developed in DA cell body regions. In striatum and nucleus accumbens, no significant changes were observed in [3H]DA and [3H]5-HT release, except for a modest reduction in the effects of both pergolide and sulpiride on electrically induced [3H]DA release from striatum. These results emphasize the importance of pretreatment-induced changes in DA cell body regions, rather than terminal areas, under the present conditions. The observed increase in DA autoinhibitory tone and subsensitivity of 5-HT release-regulating autoreceptors in the VM may contribute to the locomotor tolerance upon cocaine challenge after continuous cocaine.     

Social validity of support group and behavior therapy interventions for families of adolescents with insulin-dependent diabetes mellitus

Compared the social validity of behavior therapy vs. support group interventions for reduction of parent-adolescent conflict among families of adolescents with diabetes. Families were randomized to 10 sessions of an Education and Support group (ES) or 10 sessions of Behavioral Family Systems Therapy (BFST). We compared participants' social validity ratings of BFST and ES using the Treatment Evaluation Questionnaire (TEQ). Mean TEQ scores were significantly more positive for BFST than ES and, for 13 of 20 items, BFST was rated significantly more positively by parents and/or adolescents. Adolescents rated ES less positively than did parents. Fathers' responses reflected fewer differences between ES and BFST. Results extend previous research on BFST and confirm its superiority over ES for targeting family conflict.     

Effect of cytochalasin B and cycloheximide on the activation rate, chromosome constituent and in vitro development of porcine oocytes following parthenogenetic stimulation

Activation rate, chromosome constituent and developmental pattern of porcine oocytes was examined in the presence and absence of cytochalasin B and cycloheximide following parthenogenetic stimulation. Treatment with cycloheximide after ethanol or Ca2+ ionophore treatment increased the incidence of activation. The percentage of oocytes with two or more female pronuclei was higher (P < 0.05) in oocytes treated with cytochalasin B than in control or cycloheximide-treated oocytes. Treatment with both electrical stimulation and cytochalasin B increased the incidence of diploid chromosome spreads, and accelerated development to the morula and blastocyst stage compared with the control and cycloheximide-treated groups, suggesting a role of ploidy in the development of parthenote.     

Intranigral iron infusion in the rat. Acute elevations in nigral lipid peroxidation and striatal dopaminergic markers with ensuing nigral degeneration

Iron is known to induce lipid peroxidation and recent evidence indicates that both iron and lipid peroxidation are elevated in the substantia nigra in Parkinson's disease (PD). To test whether excess intranigral iron induces lipid peroxidation, we infused an iron citrate solution (0.63 nmol in 0.25 microL) into the rat substantia nigra and measured nigral thiobarbituric acid reactive products at 1-h, 1-d, 1-wk, and 1-mo postinfusion. In a separate group of iron-infused animals, histologic analysis within the substantia nigra through 1-mo postinfusion was accomplished by thionine- and iron-staining, with concurrent assessment of striatal neurochemical markers. Concentrations of nigral thiobarbituric acid reactive products were significantly elevated at 1 h and 1 d in iron-infused animals compared to vehicle-infused and unoperated animals, with a return to control values by 1 wk. Similarly, striatal dopamine turnover was acutely elevated, suggesting damage to dopaminergic neurons, which was confirmed histologically. Although iron-staining within the iron diffusionary area was increased through the postinfusion month, there was an apparent progression of the cellular character of staining from predominantly neuronal to reactive glial and finally to oligodendroglial by 1 mo postinfusion. This progression of cellular iron-staining may indicate a shifting of infused iron to a more bound unreactive form, thus explaining only an acute elevation in lipid peroxidation through 1 d following intranigral iron infusion. The data indicate that damage to nigral neurons induced by iron infusion is transciently associated with a marker of oxidative damage and supports the possibility that iron-induced oxidative stress contributes to the pathogenesis of PD.     

Sources of sporadic Yersinia enterocolitica infections in Norway: a prospective case-control study

Yersinia enterocolitica is a recognized cause of gastroenteritis in northern Europe. During October 1988-January 1990, a prospective case-control study was performed to address risk factors associated with sporadic Y. enterocolitica infections in southeastern Norway. Sixty-seven case-patients (mean age 23.4 years, range 8 months-88 years) and 132 age-, sex- and geographically-matched controls were enrolled in the study. Multivariate analysis of the data showed that persons with Y. enterocolitica infection reported having eaten significantly more pork items (3.79 v. 2.30 meals, P = 0.02) and sausage (2.84 v. 2.20 meals, P = 0.03) in the 2 weeks before illness onset than their matched controls; only one patient had eaten raw pork. Patients were also more likely than controls to report a preference for eating meat prepared raw or rare (47 v. 27%, P = 0.01), and to report drinking untreated water (39 v. 25%, P = 0.01) in the 2 weeks before illness onset. Each of these factors was independently associated with disease, suggesting a link between yersiniosis and consumption of undercooked pork and sausage products and untreated water. Efforts should be directed towards developing techniques to reduce Y. enterocolitica contamination of pork and educating consumers about (1) proper handling and preparation of pork items and (2) the hazards of drinking untreated water.     

Risk factors and multiple failures in posterior resin-bonded bridges in a 5-year multi-practice clinical trial

OBJECTIVES: A randomized controlled clinical trial was undertaken, to study the influence of some patient- and operator-dependent variables on the survival of posterior resin-bonded bridges (PRBBs) and to assess the survival of replacement' PRBBs. This report contains some of the results of the 5-year analysis. METHODS: Survival was defined at three levels: (1) complete survival (without any debonding), (2) functional survival (i.e. survival after one loss of retention) and (3) replacement survival (survival of 'replacement' PRBBs, inserted after rebonded bridges suffered a second dislodgement). Potential risk factors were analysed with Cox's proportional hazards model and differences were tested for significance with the Breslow test. Observed effects are expressed as conditional-relative-risk (CRR). Survival of 'replacement' PRBBs was assessed with the Kaplan-Meier method. RESULTS: Factors showing significant influences on complete survival were: 'location' (highest risk for mandibular PRBBs: CRR = 2.2), 'aetiology' (higher risk in treatment of aplasia: CRR = 2.9), and 'time of existence' (open spaces existing less than 2 years before insertion of PRBB: CRR: 2.0). The factor 'large open spaces in the mandible' was a risk for both complete and functional survival (CCR values 3.1 and 3.5, respectively). The survival of mandibular and maxillary 'replacement' PRBBs after 5 years was 19 +/- 7% and 31 +/- 18%, respectively. CONCLUSIONS: Risk factors for PRBBs were: 'location', 'aetiology', 'time of existence', 'isolation method' and 'large open spaces in the mandible'. Mandibular 'replacement' PRBBs showed such an unacceptably low survival rate that fabrication is not recommended.     

Pharmacokinetic interaction of fluconazole and zidovudine in HIV-positive patients

To investigate the interaction of fluconazole and zidovudine in HIV-positive non-smoking male patients with AIDS categorized as CDC group IV we studied two groups, each consisting of 10 male, non-smoking, HIV-positive patients with CDC group IV disease, with the patients in the first group additionally suffering from candida esophagitis. In the first group, the pharmacokinetics of 500 mg oral zidovudine were determined both before and after 7 days of treatment with fluconazole 400 mg/d. In the second group, the pharmacokinetics of 200 mg oral fluconazole were determined before and after 14 days of treatment with zidovudine 4 x 250 mg/d. In order to determine the microsomal enzyme activity, the 6-beta-hydroxycortisol/17-hydroxycorticosteroid ratio and antipyrine pharmacokinetic parameters were determined. 6-beta-hydroxycortisol was quantitated by RIA. The 17-hydroxycorticosteroids were determined by a colorimetric method. Zidovudine (ZDV) and zidovudine glucuronide (GZDV), and the fluconazole and antipyrine plasma and urine concentrations were measured by HPLC. Administration of fluconazole resulted in a significant increase in the half-life of zidovudine and antipyrine (0.97 +/- 0.17 h prior to vs. 1.11 +/- 0. 14 h after fluconazole administration and 11.9 +/- 1.9 h prior to vs. 13.7 +/- 3.0 h after fluconazole, respectively) while the 6-beta-hydroxycortisol excretion decreased significantly (472.3 +/- 80.6 microg/24 h before and 340.6 +/- 82.1 microg/24 h after administration of fluconazole). No changes were found in the GZDV plasma kinetics and the ZDV and GZDV urinary excretion. Treatment with ZDV did not have any impact on the half-life of fluconazole. Administration of zidovudine did, however, result in a significant reduction in antipyrine half-life (11.7 +/- 2.0 h before vs. 9.9 +/- 2.3h after ZDV) and a significant increase in 6-beta-hydroxycortisol excretion (438,7 +/- 138.2 microg/24 h before and 684.6 +/- 157.3 microg/24 h after ZDV). Since the antipyrine clearance is altered after administration of ZDV, it is assumed that zidovudine induces cytochrome P450 enzymes. This effect, however, does not alter the pharmacokinetics of fluconazole. High doses of fluconazole can inhibit the plasma elimination of both antipyrine and zidovudine, but the extent of this inhibitory effect is so small that no clinically relevant accumulation is to be expected.