A comparison of the discriminative stimulus effects of delta(9)-tetrahydrocannabinol and O-1812, a potent and metabolically stable anandamide analog, in rats

Efforts to determine whether Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and anandamide elicit similar discriminative stimulus effects have yielded conflicting results. The difficulty in establishing a discriminative cue to anandamide may be due to its metabolic instability. Rats were trained to discriminate either Delta(9)-THC or O-1812, a metabolically stable anandamide analog, from vehicle to avoid this issue. O-1812 and Delta(9)-THC substituted for each other; however, both drugs were more potent in the O-1812-trained rats. Further, O-1812 only substituted for Delta(9)-THC at response rate decreasing doses. The CB(1) antagonist, SR141716A, blocked the discriminative stimulus effects of both drugs but augmented their rate effects. O-1839, a VR(1) agonist, failed to substitute for either cannabinoid. These results suggest that the discriminative stimulus effects of Delta(9)-THC and O-1812 are similar, but subtle differences also exist.     

Distal spinal muscular atrophy of upper limb (Hirayama disease) associated with high serum lead levels

Hirayama disease causes unilateral or asymmetrical bilateral distal weakness and atrophy of upper limbs. We report a 6 1/2-year-old female with Hirayama disease and associated high serum lead levels. This report highlights the occurrence of this condition in younger children and the need to further study the role of lead in its pathophysiology.     

The influence of prematurity and long chain polyunsaturate supplementation in 4-week adjusted age baboon neonate brain and related tissues

Clinical studies show that docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplemented formula improve visual function in preterm infants, however improved fatty acid status is known only for plasma and red blood cells (RBC) since target organs cannot be sampled from humans. Baboons were randomized to one of four groups: Term breast-fed (B); Term formula-fed (T-); Preterm formula-fed (P-); and Preterm DHA/ARA-supplemented formula-fed (P+). The P+ contained 0.61 +/- 0.03% DHA and 1.21 +/- 0.09% ARA, and breast milk had 0.68 +/- 0.22% and 0.62 +/- 0.12% as DHA and ARA, respectively. The B and P+ groups had significantly higher DHA concentration in all tissues than T- and P-. The P- group showed dramatically lower DHA content of 35%, 27%, 66%, and 75% in the brain, retina, liver, and plasma, respectively, compared with B. Supplementation prevented declines in DHA levels in the retina, and liver, and attenuated the decline in brain, plasma and RBC of preterm animals. In contrast, ARA was not significantly lower compared with B in any group in any tissue but was significantly elevated in liver and brain. RBC and plasma DHA were correlated with DHA in tissues; RBC/plasma ARA were uncorrelated with tissue ARA. We conclude that 1) DHA drops precipitously in term and preterm primates consuming formula without long chain polyunsaturates, while 22:5n-6 concentration rises; 2) tissue ARA levels are insensitive to dietary LCP supplementation or prematurity, 3) plasma and RBC levels of ARA are uncorrelated with total ARA levels; 4) DHA levels are correlated with group effects and are uncorrelated within groups.     

Antibody response to pneumococcal capsular polysaccharides in children with acute otitis media

BACKGROUND: To describe the antibody response to pneumococcal capsular polysaccharides in children <2 years of age with pneumococcal acute otitis media (AOM) caused by serotypes 6A, 6B, 11A, 14, 19F or 23F. These serotypes were commonly found in both nasopharyngeal carriage and AOM in children of the study population in Finland. METHODS: Serum antibody concentrations to pneumococcal capsular polysaccharides of types 6B, 11A, 14, 19F and 23F were measured by enzyme immunoassay in acute and convalescent sera from children with AOM. RESULTS: Responses (at least 2-fold increase of antibody concentration) were relatively infrequent and varied with both the age of the child and the serotype of the Streptococcus pneumoniae isolated from the middle ear fluid. Children older than 12 months were more likely to have antibody responses than were younger children. Responses were seen only infrequently to types 6A, 6B or 19F (1 of 14, 1 of 9 and 2 of 25, respectively), more often to types 11A and 14 (2 of 8 and 3 of 8) and relatively frequently to type 23F (8 of 18). However, the convalescent antibody concentrations to type 23F were low and usually declined after the infection, whereas responders to 14 AOM had antibodies that persisted at a high concentration through the follow-up. CONCLUSIONS: The results emphasize the differences between Streptococcus pneumoniae serotypes in their immunogenicity and quantitative and qualitative differences of antibodies produced after infection.     

Selection of a thiazole urea-resistant variant of bovine viral diarrhoea virus that maps to the RNA-dependent RNA polymerase

By passing wild type bovine viral diarrhoea virus (BVDV) in increasing concentrations of DPC-A69280-29, a thiazole urea class compound that inhibits BVDV replication, we were able to select several variants of BVDV that exhibited decreased susceptibility to this compound. When the non-structural genes of these variants were sequenced and compared with wild type, only one change was common to all the variants that also exhibited resistance to DPC-A69280-29 (>10-fold increase in IC50). This change was a T-to-A transversion at position 11198 of the BVDV genome, which would cause a predicted substitution of isoleucine for phenylalanine at amino acid 78 of the RNA-dependent RNA polymerase (RdRp). This substitution would occur in a region of the BVDV RdRp which has been proposed to be important for the formation of the RdRp homodimer that is essential for the activity of the enzyme. However, since DPC-69280-29 inhibits BVDV replication by interfering with the initiation of viral RNA synthesis, we discuss the possibility that this region of the BVDV RdRp also may play a role in the initiation process. Furthermore, since this region is located fairly close to the template RNA, we also propose that the role it plays may involve either template selection, stabilization or processivity.     

Social representations of HIV/AIDS in Central and Eastern Europe

Although a relatively recent epidemic, HIV is now increasing in Eastern Europe faster than anywhere else in the world. In the study reported in this paper, we interviewed 511 business people and health professionals in five Central and Eastern European nations: Estonia, Georgia, Hungary, Poland and Russia, deriving our questions primarily from a Social Representations perspective. Respondents also freely completed their associations with the stimulus word 'AIDS'. Our findings indicate that, although there is considerable agreement about the threat posed by the epidemic, there are also notable cultural differences in attributions about the origin and spread of the virus and the nature of those groups at risk of infection. These findings are interpreted in the light of the historical legacies of the Communist era, as well as the real economic and social challenges faced by the population of this region.     

Mites in facilities for laboratory animals

OBJECTIVES: Two laboratory animal facilities were examined for storage and house-dust mites. METHODS: Samples of settled dust or material were investigated microscopically, and all of the found mites were identified. RESULTS: Every fourth sample contained mites. On the average, 86 mites were found in a gram of dust. Measurement with a two-way enzyme-linked immunosorbent assay revealed only one sample containing a minor amount of allergen from Dermatophagoides pteronyssinus. CONCLUSIONS: It seems that, in addition to house-dust mites, other mites may be important occupational contaminants in animal facilities.     

The contribution of lifestyle factors to socioeconomic differences in obesity in men and women--a population-based study in Sweden

BACKGROUND: The objective was to investigate whether and to what extent the association between socioeconomic status and obesity can be explained by lifestyle factors. METHODS: The relationship between socioeconomic status (SES) and obesity, and the role of lifestyle factors such as smoking, physical activity, heavy alcohol use, avoidance of dietary fat and propensity to eat fiber-rich food, was studied in a cross-sectional population-based study consisting of 6394 men and women aged 25-74 years in V?rmland County in Sweden. Educational level was used for measuring SES. The contribution of the measured lifestyle factors was assessed using logistic regression models. RESULTs: 12% of men and 14% of women were obese. Subjects with high education were leaner than subjects with low education, except among elderly women (65-74 years). Although many lifestyle factors were related to obesity and SES in this study, only a part (18-29%) of the association between educational level and obesity could be explained by the measured lifestyle factors. Physical inactivity and heavy alcohol use were the main factors contributing to this association, whereas smoking and the measured dietary attitudes towards fat and fiber had little additional effect. CONCLUSIONS: The findings of this study are consistent with the view that socioeconomic differences in obesity and its consequences can only partly be reduced by changes in lifestyle. Longitudinal studies, a more detailed investigation of the role of dietary factors and more studies including elderly subjects are, however, recommended to further elucidate the association between SES and obesity.     

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease

The endothelial nitric oxide synthase (eNOS) gene is responsible for constitutive nitric oxide synthesis and arterial vasodilatation. Recently two polymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substitution in exon 7 of the eNOS gene have been reported to be related to coronary heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients with type 2 diabetes with CHD, and in 110 randomly selected healthy subjects without CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabetic patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Among type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean arterial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in statistical analysis the 4a allele of the eNOS gene was associated with elevated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even after adjustment for confounding factors. We conclude that the 4a allele of the eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabetic patients with CHD.     

Stability of buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9 % sodium chloride solution

Combinations of opioids and adjuvant drug solutions are often used in clinical practice while little information is available on their microbiological or chemical stability. Currently there are no commercially available, prepacked, readytouse epidural or subcutaneous mixtures. Thus, epidural and subcutaneous analgesic mixtures must be prepared in the pharmacy on an asneeded basis. Such mixtures are typically used for the treatment of severe pain in cancer patients. The aim of this study was to investigate the microbiological and chemical stability of a buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9% sodium chloride solution. A high performance liquid chromatographic (HPLC) method and pHmeter were used to conduct the analyses. Antimicrobial activity of each component was studied by an agar dilution method. According to the results from the chemical and microbiological stability studies, this mixture can be stored in polypropylene (PP) syringes and polyvinyl chloride (PVC) medication cassettes for at least 30 days at either 21 °C or 4 °C, and for 16 days in PP syringes at 36 °C, and for 9 days in PVC medication cassettes at 36 °C.