Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study.

BACKGROUND: Bullous pemphigoid (BP), pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune bullous diseases characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Although rare, these diseases run a chronic course and are associated with significant morbidity and mortality. There are few prospective data on gender- and age-specific incidence of these disorders. OBJECTIVES: Our aims were: (i) to evaluate the incidence of BP and PV/PF in Swiss patients, as the primary endpoint; and (ii) to assess the profile of the patients, particularly for comorbidities and medications, as the secondary endpoint. METHODS: The protocol of the study was distributed to all dermatology clinics, immunopathology laboratories and practising dermatologists in Switzerland. All newly diagnosed cases of BP and pemphigus occurring between 1 January 2001 and 31 December 2002 were collected. In total, 168 patients (73 men and 95 women) with these autoimmune bullous diseases, with a diagnosis based on clinical, histological and immunopathological criteria, were finally included. RESULTS: BP showed a mean incidence of 12.1 new cases per million people per year. Its incidence increased significantly after the age of 70 years, with a maximal value after the age of 90 years. The female/male ratio was 1.3. The age-standardized incidence of BP using the European population as reference was, however, lower, with 6.8 new cases per million people per year, reflecting the ageing of the Swiss population. In contrast, both PV and PF were less frequent. Their combined mean incidence was 0.6 new cases per million people per year. CONCLUSIONS; This is the first comprehensive prospective study analysing the incidence of autoimmune bullous diseases in an entire country. Our patient cohort is large enough to establish BP as the most frequent autoimmune bullous disease. Its incidence rate appears higher compared with other previous studies, most likely because of the demographic characteristics of the Swiss population. Nevertheless, based on its potentially misleading presentations, it is possible that the real incidence rate of BP is still underestimated. Based on its significant incidence in the elderly population, BP should deserve more public health concern.

Comparative effects on TXA2 biosynthesis of products extracted from Lippia multiflora Moldenke leaves.

The effects of the total phenolic extract (TPLi) from Lippia multiflora leaves and of its 2 main components i.e. Verbascoside (VLi) and Lil on TXA2 biosynthesis were studied. TXA2 biosynthesis was induced by incubation of arachidonic acid with horse platelet microsomes (HPM), TXB2, a stable metabolite of TXA2, was determined by using RIA. Under the experimental conditions adopted, Verbascoside did not significantly modify TXA2 biosynthesis. On the contrary, the total phenolic extract and Lil both inhibited TXA2 biosynthesis. Their action was dose-related, Lil being the more potent. The ID50 were 1.19 +/- 0.08 mg/ml and 10.64 +/- 0.64 mg/ml for Lil and total phenolic extract respectively. The study of regression curves representing the hypotensive action and the anti-thromboxane synthetase activity versus log(dose) of TPLi and Lil suggested that Lil would likely be responsible for the TPLi hypotensive action. Its antithromboxane synthetase activity could be considered as a major contributor to the mechanism of this effect.

Comparative effects of some 3-amino 4,6-diarylpyridazines on the biosynthesis in vitro of TXA2 and PGI2- and on the TXA2- and PGI2-synthesizing activities of cardiac tissue.

Some 3-amino 4,6-diarylpyridazine derivatives were tested for their effects on TXA2 and PGI2 biosyntheses in vitro and on the TXA2- and PGI2-synthesizing activities of cardiac tissue. Horse platelet and aorta microsomes were used as sources of thromboxane and prostacyclin synthetases respectively. The TXA2- and PGI2-synthesizing activities of cardiac tissue were studied on isolated perfused rabbit hearts (the heart microsomes being used both as TXA2 synthetase and PGI2 synthetase sources). TXB2 and 6-keto PGF1 alpha were determined by RIA. Among the compounds under study, 3-morpholino 4,6-diphenylpyridazine (III) was shown to inhibit specifically the TXA2 synthetase. Substitution of the morpholino group by a dimethylamino one (I) reinforced the inhibiting effects on TXA2 synthetase but it also revealed a slight anti-prostacyclin synthetase action of the molecule. Replacement of 3-morpholino moieties by either a 3-hydrazino (IV), or a 2-dimethylaminoethylamino (V), or a 2-morpholinoethylamino group (VI) abolished completely the effects of the molecule on TXA2 and PGI2 synthetases. Likewise the addition of chlorine on the para-position on the phenyl ring of I neutralized all its inhibitory effects both on TXA2 and PGI2 synthetases in vitro. None of the 3-amino 4,6-diarylpyridazine derivatives was active on either the TXA2- or PGI2-synthesizing activities of cardiac tissue.

Toxicological studies of deltamethrin.

Deltamethrin [( S]-alpha-cyano-3-phenoxybenzyl-cis-(1R,3R)-3-(2,2-dibromovinyl+ ++) (2,2-dimethyl-cyclopropane-carboxylate], is the most potent insecticide known at the present time. But it is also one of the most toxic pyrethroids for vertebrates. The toxicity study of deltamethrin was performed on mice and rats, and on anaesthetized dogs, the administration route being either oral or intravenous. The oral LD50 of deltamethrin suspended in 10% gum-arabic solution was 5.54 +/- 1.29 g/kg p.o. in male mice and 3.45 +/- 1.27 g/kg p.o. in female mice. In rats and anaesthetized dogs, deltamethrin at high concentrations by the oral route engendered neither mortality nor signs of intoxication. When dissolved in glycerol formal and given intravenously, the LD50 of deltamethrin was as low as 3.44 +/- 0.67 mg/kg in anaesthetized dogs. Values obtained for the toxicity of deltamethrin varied not only with the animal species and sex involved, but also with the administration routes and solvents used. Administered orally, it was 100 times less toxic when suspended in gum-arabic solution than dissolved in oil or organic solvent. Whatever the animal species, sex, administration routes and solvents employed, the poisoning symptoms of deltamethrin are identical, i.e. salivation, ataxia and choreoathetotic movements with rolling convulsions, appearing within 7 h after administration. No cellular alteration was detectable by means of optical microscopy of excised organs.

Effect of a deproteinized blood extract on respiratory and haemodynamic modifications induced by hypoxia in the anaesthetized animal.

The effects of a deproteinized blood extract on the modifications of respiration, general metabolism and systemic haemodynamics induced by hypoxia were studied. Under the experimental conditions adopted, the deproteinized blood extract moderated the reactions of the organism which are exacerbated by hypoxia, that is increase in oxygen consumption and stimulation of the cardiac performances. The mechanism of action of the deproteinized blood extract has been discussed.

Taurine and icosanoids in the heart.

Experiments were carried out on non-working isolated rabbit hearts perfused by Tyrode solution: the effects of Taurine introduced into the coronary circulation were studied on the biosynthesis of the anti-thromboxane synthetase factor ("FATS") and on the TXA2 and PGI2 synthetase activities of cardiac tissue. The effects of Taurine were simultaneously studied on the biosynthesis of TXA2 and PGI2 in vitro. Experiments performed under the adopted conditions have shown that in vitro Taurine did not significantly modify the biosynthesis of TXA2 and PGI2; ex vivo Taurine did not change the biosynthesis of "FATS" but inhibited both TXA2 and PGI2 synthetase activities of the cardiac tissue: Taurine was more active on the TXA2 synthetase activity than on the PGI2 one. Thus Taurine promoted the formation of vasodilator and antiaggregating PGI2 at the expenses of vasoconstrictor and proaggregating TXA2. This could at least partly explain the beneficial effects of Taurine in the physiopathology of the heart.

Low amyloid (Abeta) plaque load and relative predominance of diffuse plaques distinguish argyrophilic grain disease from Alzheimer's disease.

Argyrophilic grain disease constitutes one cause of late-onset dementia. Its classification among dementia disorders is still unclear because most of the reported argyrophilic grain disease cases are associated with neurofibrillary lesions (e.g. neurofibrillary tangles) which are also typical of Alzheimer's disease. In the present study we determine whether argyrophilic grain disease is associated with the senile plaques of Alzheimer's disease. The distribution and density of senile plaques was systematically investigated in 11 demented argyrophilic grain disease cases using Abeta immunohistochemistry and stereological techniques, and the results were compared with 11 Alzheimer's disease cases. All subjects with argyrophilic grain disease exhibited neurofibrillary changes corresponding to Braak stages I-III. Three of the 11 argyrophilic grain disease cases (27%) were completely devoid of Abeta deposits. In argyrophilic grain disease cases with senile plaques, the average total plaque-load was significantly lower (1%) than in Alzheimer's disease (3.1%) (P<0. 005). The regional distribution of the senile plaques and the proportion of diffuse vs. primitive or mature plaques in argyrophilic grain disease resembled values of senile plaques reported in non-demented elderly subjects, and was significantly different from Alzheimer's disease. Similarly the immunocytochemical profile of the Abeta deposition in argyrophilic grain disease resembled that of non-demented elderly subjects rather than that of subjects with Alzheimer's disease. As all argyrophilic grain disease cases under investigation were demented, including those devoid of senile plaques, the present study further supports the thesis that dementia in argyrophilic grain disease correlates more with the density and distribution of argyrophilic grains than with associated lesions of the Alzheimer-type.

Enhanced prostacyclin biosynthesis and decreased thromboxane formation by 3-dimethylamino 5-(2',6'-dichlorobenzylidene) 6-methyl (4H)-pyridazine (PC 89).

The effects of 3-dimethylamino 5-(2',6'-dichlorobenzylidene) 6-methyl (4H)-pyridazine (PC 89) on the biosynthesis of PG I2 and TX A2 using horse aorta and horse platelet microsomes as sources of enzymes and arachidonic acid as substrate, were investigated. PC 89 (1.10(-6) M- 1.10(-3) M) dose-dependently - enhanced the biosynthesis of PG I2: the AD50 was 6.8 X 10(-6) M +/- 1.2 X 10(-9) M, the Vmax did not vary significantly with concentrations: PC 89 increased the affinity of enzyme for substrate - but inhibited TX A2 biosynthesis (ID50 = 3.31 X 10(-3) M +/- 4.8 X 10(-7) M): this inhibiting action was not of competitive type. Owing to this dual activity of preventing TX A2 formation and stimulating PG I2 biosynthesis, PC 89 could be a valuable drug for myocardial ischemia and atherosclerosis therapeutics.