Serotonergic modulation of pain and analgesic responses: a study in rats with constitutionally altered serotonin transporters.

BACKGROUND: A role of the serotonin (5HT) transporter, a key regulator of serotonergic transmission, in the physiology, pharmacology and genetics of pain responses has been proposed recently. The present study aimed to explore the impact of constitutive differences in the activity of the serotonin transporter, and 5HT homeostasis in general, on the modulation on pain sensitivity and analgesic responses to drugs that utilize 5HT mechanisms. METHODS: A novel genetic animal model, Wistar-Zagreb 5HT rats, obtained by selective breeding of animals for extreme activity of the platelet serotonin transporter was used. As a consequence of breeding, two sublines of this model, termed high-5HT and low-5HT, differ in both central and peripheral serotonin homeostasis. Thermal pain sensitivity of 5HT sublines was assessed at baseline and following administration of analgesic drugs, as determined by paw withdrawal latency to radiant heat stimulation. RESULTS: Animals from 5HT sublines show differences in both basal pain sensitivity and analgesic responses. Rats with the low-5HT phenotype displayed decreased baseline paw withdrawal latencies (hyperalgesia) in comparison to their high-5HT counterpart (25%; p < 0.001). They also showed better analgesic response to acute and prolonged treatment with tramadol (p = 0.027) and clomipramine (p = 0.019), respectively, whereas administration of fluvoxamine did not produce an analgesic effect in either 5HT subline. CONCLUSIONS: These findings support the idea that functionality of the serotonin transporter is one of the physiological/genetic determinants of individual differences in pain responses and modulation. They also validate Wistar-Zagreb 5HT rats, with constitutionally up-regulated/down-regulated serotonin transporter, as a potential new genetic model for studying serotonergic modulation of pain responses.

Vitamin E, γ-tocopherol, diminishes ex vivo basophil response to dust mite allergen.

Epidemiologic studies suggest that dietary vitamin E is a candidate intervention for atopic disease. We used in vitro and ex vivo exposures to test the hypothesis that the most common dietary isoform of vitamin E, γ-tocopherol (γT), could suppress FcεRI-mediated basophil activation. Rat basophilic leukemia (RBL)-SX38 cells that express human FcεRI were treated with or without γT, followed by stimulation with α-IgE. In the ex vivo study, 20 Der f 1-allergic volunteers consumed a γT-enriched supplement for 7 days. Their basophils were challenged ex vivo with α-IgE and graded doses of Der f 1 before and after the supplementation period. γt treatment of RBL-SX38 cells significantly reduced basophil degranulation and de novo TH2 cytokine production. Daily consumption of a γT-rich supplement by dust mite-allergic volunteers reduced basophil activation after ex vivo dust mite challenge. Vitamin E supplements rich in γT may be useful adjuncts in decreasing atopic disease.

Emergence patterns and ecological associations of some haematophagous blackfly species along an oligotrophic hydrosystem.

Emergence patterns of blackflies (Diptera: Simuliidae) were investigated for 2 years at nine sites in the Plitvice Lakes area of Croatia, using pyramid-type traps. A total of 38 012 specimens representing 10 haematophagous species were collected. The dominant species was Simulium angustipes Edwards, 1915, a vector transmitting avian trypanosomes. Water temperature, alkalinity, conductivity and habitat type represented the factors with the greatest degree of influence on blackfly species composition, structure and distribution along a longitudinal gradient of this oligotrophic karstic hydrosystem. Simulium angustipes was highly associated with lake outlets. The blackfly communities at all sites were dominated by species typical of the rhithral zone, but there was a shift in species composition along a longitudinal gradient from the hypocrenal-epirhithral to the epirhithral-metarhithral zone. Multiple generations per year were detected in S. angustipes, whereas in Simulium costatum Friederichs, 1920, the number of generations differed between sites with constant and those with variable water temperature.

Perception of stroke in Croatia--knowledge of stroke signs and risk factors amongst neurological outpatients.

BACKGROUND AND PURPOSE: The aim of this hospital-based survey was to determine baseline stroke knowledge in Croatian population attending the outpatient services at the Department of Neurology. METHODS: A multiple choice questionnaire was designed, divided into three sections: (i) demographic data, (ii) knowledge of stroke risk factors and stroke signs and (iii) actions the patients would undertake if confronted with risk of stroke and information resources regarding health. RESULTS: The analysis included 720 respondents (54.9% women). The respondents most frequently indicated stroke symptoms as following: speech disorder 82%, paresthesiae on one side of the body 71%, weakness of arm or leg 55%, unsteady gait 55%, malaise 53%, monocular loss of vision 44%. The risk factors most frequently identified were hypertension 64%, stress 61%, smoking 59%, elevated lipids 53%, obesity 52%, coagulation disorder 47%, alcoholism 45%, low-physical activity 42%, elderly age 39%, cardiac diseases 38%, weather changes 34%, drugs 33% and diabetes 32%. If confronted with stroke signs 37% of respondents would consult the general practitioner and 31% would call 911 or go to a neurologist. Amongst patients with a risk factor, only diabetics were aware that their risk factor might cause stroke (P < 0.001). Respondents with lowest education had the least knowledge regarding stroke signs (P < 0.01). DISCUSSION: The results of this study indicate that respondents showed a fair knowledge about stroke signs and risk factors for stroke. The results of our study will help to create and plan programmes for improvement of public health in Croatia.