The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations

Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome, affecting human infants and adolescents. Two main behavioural features are reported: (1). impaired attention and (2). an impulsive-hyperactive behavioural trait. The latter has been studied in a series of experiments, using the spontaneously hypertensive-rat (SHR) strain (which is regarded as a validated animal model for ADHD) in operant tasks. Food-restricted SHRs and their Wistar-Kyoto (WKY) controls were tested during adolescence (i.e. post-natal days 30-45), in operant chambers provided with two nose-poking holes. Nose-poking in one hole (H1) resulted in the immediate delivery of a small amount of food, whereas nose-poking in the other hole (H5) delivered a larger amount of food after a delay, which was increased progressively each day (0-100 s). As expected, all animals showed a shift in preference from the large (H5) to the immediate (H1) reinforcer as the delay length increased. Impulsivity can be measured by the steepness of this preference-delay curve. The two strains differed in home-cage circadian activity, SHRs being more active than WKYs at several time-points. During the test for impulsivity, inter-individual differences were completely absent in the WKY strain, whereas a huge inter-individual variability was evident for SHRs. On the basis of the median value of average hole-preference, we found an 'impulsive' SHR subgroup, with a very quick shift towards the H1 hole, and a flat-slope ('non-impulsive') SHR subgroup, with little or no shift. The impulsive subpopulation also presented reduced noradrenaline levels in both cingulated and medial-frontal cortex, as well as reduced serotonin turnover in the latter. Also, cannabinoid CB1 receptor density resulted significantly lower in the prefrontal cortex of impulsive SHRs, when compared to both the non-impulsive subgroup and control WKYs. Interestingly, acute administration of a cannabinoid agonist (WIN 55,212, 2 mg/kg s.c.) normalized the impulsive behavioural profile, without any effect on WKY rats. Thus, two distinct subpopulations, differing for impulsive behaviour and specific neurochemical parameters, were evidenced within adolescent SHRs. These results support the notion that a reduced cortical density of cannabinoid CB1 receptors is associated with enhanced impulsivity. This behavioural trait can be positively modulated by administration of a cannabinoid agonist. Present results confirm and extend previous literature, indicating that adolescent SHRs represent a suitable animal model for the preclinical investigation of the early-onset ADHD syndrome.     

Behavior of sunbed users in Switzerland

OBJECTIVES: A constant rise in the number of skin cancer cases has been observed during the last few years. An important reason for this trend is that exposure of the population to UV radiation is higher. Although natural UV radiation is the major source, exposure due to use of sunbeds must be considered from the point of view of prevention. METHODS: 151 sunbed users in Bern and Basel were questioned on their reasons for visiting a solarium, their behaviour when using a sunbed and their awareness of risks resulting from UV radiation. RESULTS: It was shown that young women are the most frequent sunbed users. Also, sunbeds are often used regularly, not only for cosmetic reasons but also from a desire for relaxing and well-being in the warmth and light. Although most of the persons questioned were aware of certain health risks resulting from UV radiation, this knowledge hardly influenced their behaviour. Thus, more than half the people questioned use sunbeds longer and more often than advised by international recommendations. CONCLUSIONS: In view of a continuing increase in the number of skin cancer cases the improvement of preventive strategies for sunbed users is of major importance. Another urgent requirement is informing the public and increasing the general awareness of possible adverse health effects caused by UV radiation.     

Aminopeptidase inhibitors bestatin and actinonin inhibit cell proliferation of myeloma cells predominantly by intracellular interactions

Dimethylarsinic acid (DMA), a major metabolite of inorganic arsenics, and arsenic exposure is associated with tumor development in a wide variety of human tissues. In the present study, we examined whether DMA has tumor-promoting activity on rat lung carcinogenesis initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male, 8-week-old, F344 rats were treated with DHPN at a concentration of 0.1% in drinking water for 1 week, and starting 1 week thereafter, DMA was administered at concentrations of 0, 100, 200 or 400 ppm in the drinking water for 30 weeks. Induction of epithelial lesions, classified as alveolar epithelial hyperplasia, adenoma, and adenocarcinoma was evident in the lungs of DHPN-initiated animals, but no significant differences were found between DMA-treated groups and control groups. Furthermore, no significant differences in 5-bromo-2'-deoxyuridine labeling indices, as a marker of cell proliferation were observed among the groups. An additional group treated with DMA at concentrations of 200 ppm alone, without prior DHPN initiation was found to develop no epithelial lesions in the lung. There was no significant gain in 8-hydroxydeoxyguanosine formation, as a marker of oxidative stress, in the lungs of rats treated with DMA in their drinking water. In conclusion, oral-administered DMA does not exert promoting effects on rat lung carcinogenesis initiated with DHPN.     

Effect of neuropeptide Y on inflammatory paw edema in the rat: involvement of peripheral NPY Y1 and Y5 receptors and interaction with dipeptidyl-peptidase IV (CD26)

Several lines of evidence suggest that neuropeptide Y (NPY) may exert regulatory effects in local inflammatory responses. Here, we show that intraplantarly (i.pl.) applied NPY, peptide YY (PYY), and an NPY Y5 receptor-selective agonist dose-dependently potentiate concanavalin A (Con A)-induced paw edema in the rat. The NPY Y1 receptor antagonist BIBO 3304 abolishes the pro-inflammatory action of both NPY and PYY while the dipeptidyl-peptidase IV (CD26) inhibitor Ile-thiazolidide exerted synergistic and potentiating effects in vivo. Taken together, the present data reveal an NPY Y1/Y5 receptor interplay and an involvement of CD26 in the NPY-induced potentiation of paw edema in the rat.     

Rabies treatment of health care staff

This article deals with post-exposure treatment of contacts of human cases of rabies. Experience suggests that rabies is hardly ever transmitted from person to person if at all. With the modern generation of vaccines against rabies, the use of post-exposure treatment is more widespread. A lot of contacts of patients with rabies in developed countries are treated, most of them being health care workers. This treatment is however not practised so often in developing countries where the supply of highly protective vaccines with a few side effects is low. According to reports good hygienic practice in nursing these patients is well established.     

Successful early pyeloplasty in infants

BACKGROUND: Early pyeloplasty for the treatment of congenital ureteropelvic junction obstruction to maximize nephron salvage is justified only if potential hazards of operating on small infants are avoided. METHODS: The records were analyzed of all infants who underwent pyeloplasty over a 5-year period. Open pyeloplasty was performed if collecting systems had deteriorated or were demonstrated to be obstructed; it was also performed for severe cases of hydronephrosis. Outcome of surgery in the younger infant (patients <2 months of age) was compared with the older infant group (patients >2 months of age). Preoperative evaluation in case of mild or moderate hydronephrosis was directed toward ruling out a non-obstructed collection system and included voiding cystourethrography, and serial ultrasonography and/or dual isotope diuretic renography. Postoperative assessment consisted of serial ultrasonography and/or nuclear imaging to confirm decompression and relief of obstruction. RESULTS: A total of 24 pyeloplasties were performed on 22 patients in the younger infant group (two bilateral) and 30 were performed on 27 infants in the older infant group (three bilateral). The only significant differences between the groups were as follows: patients in the younger infant group were likely to present in utero (75%, p = 2.69), whereas those in the older infant group were more likely to present with a urinary tract infection (48%, p = 4.12). During follow-up examination, 23 renal units in the younger infant group and 24 in the older infant group were judged to be stable or improved. Four kidneys were not salvaged after pyeloplasty, one in the younger infant group and three in the older infant group. CONCLUSIONS: Good results of pyeloplasties performed in the infants in this series support early correction of ureteropelvic junction obstruction in infants.     

Experience with caspofungin in the treatment of persistent fungemia in neonates.

OBJECTIVE: To review our experience of caspofungin in the treatment of persistent candidemia in the neonatal intensive care unit. STUDY DESIGN: This was a retrospective chart review on 13 infants in whom caspofungin was added to conventional antifungals (amphotericin B and/or fluconazole or flucytosine) for the treatment of refractory candidemia. RESULTS: A total of 12 infants were preterm (gestational age, 24 to 28 weeks) and one was term; the median birth weight was 800 g (range, 530 to 5600 g). Candidemia (Candida albicans in five, C. parapsilosis in six, C. albicans and C. parapsilosis in one and C. tropicalis in one) persisted despite 6 to 30 days of conventional antifungal therapy. After the addition of caspofungin, sterilization of blood cultures was achieved in 11 infants at the median time of 3 days (range, 1 to 21 days). Adverse events included thrombophlebitis (one patient), hypokalemia (two patients) and elevation of liver enzymes (four patients). Three infants had a second episode of candidemia and seven patients died. CONCLUSION: Caspofungin may be an efficacious addition for treatment of candidemia refractory to conventional antifungal therapy. This drug should be further investigated in neonates.     

Hemotherapy in kidney transplantation

A total of 40 kidney transplantations (37 males and 3 females) from living donors (Group I) and 10 kidney transplantations (6 males and 4 females) from cadavers (Group II) were performed in the period 1996-October 1999 at the Military Medical Academy (MMA). Lymphocytotoxic crossmatching was done before each kidney transplantation and results from all tests were negative for all recipients. All donors had the same blood group in ABO system as the recipients. In perioperative transfusion treatment (hemotherapy) determined quantity of filtered red blood cells (F-RBCs) and/or filtered platelets (F-PLT) were given to recipients according to intraoperative blood loss and their clinical state. Leukoreduction filters were used to prevent HLA alloimmunization. In only 4 (8%) recipients in group I transfusion therapy was not applied perioperatively. An average of 3.27 units of F-RBCs (929.44 mL) was used intraoperatively in 36 (72%) recipients in group I, an average of 1.9 units of F-RBCs (521 mL) was used before kidney transplantation in 10 (20%) recipients in group I and an average of 2.65 units of F-RBCs (739.23 mL) was used postoperatively in 26 (52%) recipients. In all recipients from group II transfusion therapy was applied perioperatively. An average of 3.4 units of F-RBCs (953 mL) was used intraoperatively. An average of 4.9 units (1.328 mL) and an average of 1.4 units of F-PLT were used postoperatively. All recipients well tolerated the therapy and no adverse effects of the therapy were observed. The need for transfusion therapy intraoperatively was approximatively same in both recipient groups, while in recipients from cadavers need for transfusion support in posttransplantation period was much higher.     

Are Serbian gynaecologists in line with modern family planning?

OBJECTIVES: In Serbia, gynaecologists could play an important role in achieving the transition from an abortion-based family planning culture to a modern contraception-based one. Exploring their knowledge, attitudes and practice regarding birth control is of particular importance for ensuring the quality of contraceptive counselling. METHODS: A questionnaire was sent to all the 1,139 members of the Gynaecology and Obstetrics Section of the Serbian Medical Society. The response rate was 27%. RESULTS: Of the respondents, 61.8% reported that either they or their partner had had one or more induced abortions; 37.6% stated that they usually used either coitus interruptus or no contraceptive method at all; 51.0% were unwilling to prescribe combined oral contraceptives (COCs) to girls younger than 18 years, and 76.5% advised women against the use of COCs for more than two years. Irrational concerns about the health risks of contraception were identified. The contraceptive needs of women aged 20 + were particularly hampered by the fact that 75.5% of respondents thought that intrauterine device use was unsafe for women with benign, non infectious cervicitis. CONCLUSIONS: The results indicate that a significant number of Serbian gynaecologists neither use modern methods of contraception themselves nor have adequate knowledge to advise their patients. Thus, education and training of gynaecologists in all methods of available contraception is a priority in Serbia.