Citrus fruit and fabacea secondary metabolites potently and selectively block TRPM3.

BACKGROUND AND PURPOSE: The melastatin-related transient receptor potential TRPM3 is a calcium-permeable nonselective cation channel that can be activated by the neurosteroid pregnenolone sulphate (PregS) and heat. TRPM3-deficient mice show an impaired perception of noxious heat. Hence, drugs inhibiting TRPM3 possibly get in focus of analgesic therapy. EXPERIMENTAL APPROACH: Fluorometric methods were used to identify novel TRPM3-blocking compounds and to characterize their potency and selectivity to block TRPM3 but not other sensory TRP channels. Biophysical properties of the block were assessed using electrophysiological methods. Single cell calcium measurements confirmed the block of endogenously expressed TRPM3 channels in rat and mouse dorsal root ganglion (DRG) neurones. KEY RESULTS: By screening a compound library, we identified three natural compounds as potent blockers of TRPM3. Naringenin and hesperetin belong to the citrus fruit flavanones, and ononetin is a deoxybenzoin. Eriodictyol, a metabolite of naringenin and hesperetin, was still biologically active as a TRPM3 blocker. The compounds exhibited a marked specificity for recombinant TRPM3 and blocked PregS-induced [Ca(2+)]i signals in freshly isolated DRG neurones. CONCLUSION AND IMPLICATIONS: The data indicate that citrus fruit flavonoids are potent and selective blockers of TRPM3. Their potencies ranged from upper nanomolar to lower micromolar concentrations. Since physiological functions of TRPM3 channels are still poorly defined, the development and validation of potent and selective blockers is expected to contribute to clarifying the role of TRPM3 in vivo. Considering the involvement of TRPM3 in nociception, TRPM3 blockers may represent a novel concept for analgesic treatment.

Tick-borne encephalitis and its prevention in Hungary.

Tick-borne encephalitis (TBE) has been registered in Hungary since 1977. In the last four years a moderate decrease of cases was observed. Most cases belong to the age group of 30-39 years, and the number of males is twice as high as that of the females among the TBE cases. The efficacy of TBE vaccination was proven also in field trials. The use of the specific hyperimmune gamma-globulins for postexposure prophylaxis is effective. The need to create an international standard for TBE vaccine is discussed.

The 1988-1989 measles epidemic in Hungary: assessment of vaccine failure.

Hungary has had a successful measles vaccination programme, achieving over 93% coverage in targeted groups. However, from September 1988 until December 1989, 17,938 measles cases were reported among the civilian population (attack rate [AR] = 169 per 100,000 population) with the majority of cases occurring in vaccinated people. National surveillance data were analysed to determine reasons for the outbreak and risk factors for vaccine failure. People born during 1971 and 1972 had been targeted for vaccination during campaigns in April and September of 1973 and had the highest AR (1332 and 1632 per 100,000, respectively). Epidemiological studies of vaccine efficacy conducted among secondary school students corroborated these findings. Among 754 secondary school students, those vaccinated during the April 1973 campaign were at highest risk compared with those vaccinated at routine health care after 1974 (relative risk = 10.9, 95% confidence interval [Cl]: 2.5-47.9). Among 341 primary school students, one-dose recipients were at higher risk compared with two-dose recipients controlling for age at and time elapsed since vaccination (P = 0.04).

Salmonella and shigella surveillance in Hungary, 1972-1976. II. Shigella surveillance.

Shigellae were isolated from 32 399 persons in the bacteriological laboratories of the Public Health Stations between 1972-1976. The number of isolations ranged between 5325 and 8237 yearly. As S. dysenteriae and S. boydii serotypes occurred only in about 1.5% of all isolations, the epidemiological situation was determined by the incidence of S. flexneri and S. sonnei. Except in 1973, S. sonnei constituted the majority in every year. S. sonnei predominance, observed first in the western regions of the country, showed a gradual eastward spread and became characteristic of all localities in 1975-1976. The July-September peak of shigella isolations was associated with S. sonnei, as S. flexneri was distributed practically evenly in every season. The incidence of shigella isolations per 100 000 inhabitants was the lowest in the middle and the highest in the northern parts of the country. Sporadic cases were somewhat more frequent than epidemic outbreaks. Shigellae were isolated in 64.1% from patients and in 35.9% from asymptomatic excreters. The patient : excreter ratio was higher for S. sonnei (70.2 : 29.8) than for S. flexneri (54.6 : 45.4). In the survey period, 14 692 isolations were made in the course of 3278 epidemics; out of these, 11 171 cases were involved in 574 extensive outbreaks. S. sonnei was responsible mainly for school and nursery outbreaks, whereas S. flexneri dysentery predominated in mental wards and in homes for the aged and for mentally retarded children. The prevalent types of S. flexneri were (serological/phage type): 2a/69, 3a/5, 3a/19, 4a/81, 4a/89d and 6/85. The prevalent epidemiological subunits of S. sonnei were (phage/colicin type): 2/0, 2/6, 2/12, 3/12, 6/0, 7/0, 65/0, 65/6 and 65/12.