Reduced H3 histamine receptor binding densities in the upper layers of motor cortex in rats prone to audiogenic convulsive seizures.

Fits of audiogenic seizures in rodents are considered as a model for generalized convulsive epilepsies in humans. The laminar distribution of the H3 histamine receptor binding densities was quantified in the motor cortex of two strains of rats with genetically determined generalized epilepsies, namely KM rats with audiogenic seizures only, and WAGRij rats with both audiogenic seizures and absence seizures. It was found that H3 histamine receptor binding densities in layer 2/3d of the primary and secondary motor cortices of the rats that experienced audiogenic seizure fits were significantly lower than in the cortices of control rats. Possible explanations are discussed.

Effect of drinking water temperature on water intake and performance of dairy calves.

Very limited information is available on the effects of drinking water temperature on dairy calves. Therefore, the present experiment was designed to study the effects on performance, health, and water consumption of dairy calves offered drinking water either warm (16 to 18 °C) or cold (6 to 8 °C). The calves (60 calves/treatment) were housed in an insulated barn in pens (3.0 × 3.5m; 5 calves in each) providing 2.1m(2)/calf. During the experimental period (20 to 195 d of age), the calves had free access to water from an open water bowl (depth 80 mm, diameter 220 mm, 2-L capacity, 1 bowl/pen). During the preweaning period (20 to 75 d of age), all calves received milk replacer (7.5L/calf daily) and had free access to commercial starter, grass silage, and hay. During the postweaning period (75 to 195 d), the weaned calves had free access to grass silage and hay and were given 3 kg/d (air-dry basis) of a commercial concentrate mixture. During the preweaning period, the water intake of the calves offered warm water was 47% higher than that of the calves offered cold water. Water intake in both treatments increased rapidly during weaning and for a few days following weaning. At 180 to 195 d of age, the calves consumed approximately 18 to 20 L of water daily. Calves offered warm water drank 7 and 8% more water during the postweaning period and overall during the experimental period, respectively, compared with those offered cold water. No treatment differences were observed in dry matter or energy intakes, body weight gains, or feed conversion rates. Furthermore, total serum IgG concentrations of the calves did not differ during the preweaning or postweaning periods. Dairy calves consumed more warm than cold water, but the increase in water intake did not influence feed intake, body weight gain, or health parameters.

Asthma Programme in Finland: Did the use of secondary care resources become more rational?

OBJECTIVES: The aims were to evaluate the profile of newly diagnosed adult asthma cases and the approach adopted to the secondary care management at the launch of the Finnish asthma programme in 1994 and seven years later, in 2001. METHODS: A retrospective medical record audit was made of non-acutely referred patients with asthma in 1994 (n=165) and in 2001 (n=133). Clinical profile data, numbers of out-patient visits and periods of in-patient care before and after asthma diagnosis were gathered from referral letters and secondary care records. RESULTS: The newly diagnosed asthma patients in 2001 were older, more obese and had more co-morbidities. The main asthma symptoms, such as dyspnoea, wheezing and cough, occurred equally in both years but were more often periodic than daily in 2001. Wheezing during auscultation was significantly less common in 2001. The diagnostic process was associated to a history of asthma in first-degree relatives (OR 5.34, 95% CI 1.12-24.49) in 1994 and a visit to a nurse prior to that to a physician (OR 3.13, 95% CI 1.17-8.37) in 2001. Secondary care visits per new case of asthma (7.3 in 1994 vs. 5.4 in 2001) and days in hospital (3.6 in 1994 vs. 0.95 in 2001) decreased significantly. CONCLUSIONS: The profile of asthma diagnosed in secondary care indicates milder disease with more co-morbidities in 2001 than in 1994.Trends towards assigning a more active role on the part of primary care physicians and more rational use of secondary care resources in the management of asthma were found.

A 10 year asthma programme in Finland: major change for the better.

BACKGROUND: A National Asthma Programme was undertaken in Finland from 1994 to 2004 to improve asthma care and prevent an increase in costs. The main goal was to lessen the burden of asthma to individuals and society. METHODS: The action programme focused on implementation of new knowledge, especially for primary care. The main premise underpinning the campaign was that asthma is an inflammatory disease and requires anti-inflammatory treatment from the outset. The key for implementation was an effective network of asthma-responsible professionals and development of a post hoc evaluation strategy. In 1997 Finnish pharmacies were included in the Pharmacy Programme and in 2002 a Childhood Asthma mini-Programme was launched. RESULTS: The incidence of asthma is still increasing, but the burden of asthma has decreased considerably. The number of hospital days has fallen by 54% from 110 000 in 1993 to 51 000 in 2003, 69% in relation to the number of asthmatics (n = 135 363 and 207 757, respectively), with the trend still downwards. In 1993, 7212 patients of working age (9% of 80 133 asthmatics) received a disability pension from the Social Insurance Institution compared with 1741 in 2003 (1.5% of 116 067 asthmatics). The absolute decrease was 76%, and 83% in relation to the number of asthmatics. The increase in the cost of asthma (compensation for disability, drugs, hospital care, and outpatient doctor visits) ended: in 1993 the costs were 218 million euro which had fallen to 213.5 million euro in 2003. Costs per patient per year have decreased 36% (from 1611 euro to 1031 euro). CONCLUSION: It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society. Improvements would have taken place without the programme, but not of this magnitude.

The brain 5HTergic response to an acute sound stress in rats with generalized (absence and audiogenic) epilepsy.

The brain serotoninergic (5HTergic) system of epileptic subjects can influence their vulnerability to stress. We studied the putative dependency of 5HT neurotransmission parameters on emotional stress, and the presence, types and severity of seizures using rats with genetic generalized (absence and/or audiogenic) epilepsy, of WAG/Rij and Wistar strains. The animals were stressed by exposure to a short aversive noise or left without sound stimulation. Tissue concentrations of 5HT, tryptophan (TRT) and 5-hydroxyindolacetic acid (5HIAA) were assessed by HPLC. The stressor activated the 5HTergic system within thalamus (5HIAA elevated), frontal cortex (5HT, TRT elevated), hypothalamus (increased TRT) in all rats. However, the normal (non-epileptic) rats displayed the highest response in the frontal cortex and the lowest one in the thalamus, as compared to the epileptic rats. Absence-epileptic rats exhibited higher thalamic 5HIAA increase than their controls. Significant correlations existed between propensity of absence epilepsy and 5HTergic parameters measured in the cortex and hypothalamus of absence-epileptic rats. No major difference was found between groups with and without audiogenic epilepsy. The results imply that the stress response depends on the presence of epileptic pathology and the seizure type and severity. The brain 5HT may be involved in the control of the paroxysms and behaviour in absence-epileptic subjects.

Convulsive and nonconvulsive epilepsy in rats: effects on behavioral response to novelty stress.

Behavioral response to a new environment of Wistar and WAG/Rij rats with absence and/or audiogenic seizures (AGSs) was investigated. Behavior was observed in open-field (OF) and light-dark choice (LD) tests. Correlations of test performance with seizure parameters were evaluated. AGS-susceptible Wistar rats exhibited reduced exploration (rearing) in both tests and a tendency toward hyperlocomotion in the OF test. Genetically absence-epileptic WAG/Rij rats demonstrated agitation (increased vertical/horizontal locomotion, enhanced defecation/urination) in the LD test, whereas they exhibited reduced exploration, increased grooming, and hyperlocomotion in the OF test. Anxiety level, as estimated by grooming time in the OF test and latency to first "risk assessment" in the LD test, correlated positively with the propensity for absence seizures in WAG/Rij rats not susceptible to AGSs. It can be concluded that the behavioral response to novelty stress in epileptic subjects depends on the type and severity of seizures.

Distribution of D1-like and D2-like dopamine receptors in the brain of genetic epileptic WAG/Rij rats.

The densities of the dopamine (DA) D1-like and D2-like receptors were studied by autoradiography in brain regions of rats with (WAG/Rij strain) and without (ACI strain) genetic absence epilepsy. The core of the nucleus accumbens in WAG/Rij rats had a lower density of D1-like receptors than in ACI rats, a reduction of both D1-like and D2-like DA receptors was also found for the dorsal striatum (dorsal caudate-putamen). On the other hand, the density of D2-like receptors was higher in cortical (frontal and parietal) regions and lower in the CA3 region of the hippocampus of WAG/Rij, as compared to ACI rats. These results give new information about possible malfunction of the brain dopaminergic system in the WAG/Rij rat model of absence epilepsy. It seems that there are differences between WAG/Rij and other models of absence epilepsy, especially concerning the role of striatum.

[The interstrain differences in the effects of D-amphetamine and raclopride on dorsal striatum dopaminergic system in KM and Wistar rats (microdialysis study)]. / Mezhlineinye razlichiia v éffekta amfetamina i rakloprida na aktivnost' dofaminergicheskoi sistemy v dorzal'nom striatume u krys linii KM i Vistar (mikrodializnoe issledovanie).

The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05). A single amphetamine injection (1 mg/kg body weight, intraperitoneously) caused a significant increase in the DA basal level up to 250-260% in animals of both genotypes. However, in Wistar rats, the level of DA reached maximum as soon as 20 min after amphetamine administration, whereas in KM rats, this happened only after 120 min. After a single injection of the antagonist of D2 and D3 dopamine receptors raclopride (1.2 mg/kg of body weight, intraperitoneously), an increase in the level of DA was similar in amplitude in rats of both genotypes (up to about 210%); however, this occurred 20-30 and 100 min after raclopride administration to Wistar and KM rats, respectively. This evidence suggests that the genetic defect of KM rats, namely, the high level of audiogenic epilepsy, is caused by abnormalities of the neuromediator brain systems and presumably accompanied by the regulatory gene dysfunction.

Increased brain histamine levels in Parkinson's disease but not in multiple system atrophy.

We investigated histamine concentration in post-mortem brain samples of patients with Parkinson's disease (PD, n = 24), multiple system atrophy (MSA, n = 8) and age-matched controls (n = 27). Histamine concentrations were significantly increased in the putamen (to 159% of the control mean), substantia nigra pars compacta (to 201%), internal globus pallidus (to 234%) and external globus pallidus (to 200%), i.e. in areas which play a crucial role in the motor behaviour and which show typical functional alterations in PD. In MSA no significant differences were seen. Tele-methylhistamine (histamine metabolite) concentrations were unchanged in PD. These results indicate that histamine concentration, but not its metabolism is increased in PD, but not in MSA. This finding may have implications in developing new drug therapies for PD and in differential diagnosis between PD and MSA.