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Biomedical subjects

D Hofer

Publications and source records attributed to D Hofer.

At least 19 recordsLinked to original sources

Chemistry and biology of thiamethoxam: a second generation neonicotinoid.

Thiamethoxam is the first commercial neonicotinoid insecticide from the thianicotinyl subclass. It was discovered in the course of our optimisation program on neonicotinoids started in 1985. Novel variations of the nitroimino-heterocycle of imidacloprid led to 4-nitroimino-1,3,5-oxadiazinanes exhibiting high insecticidal activity. Among these, thiamethoxam (CGA 293433) was identified as the best compound and selected for worldwide development. The compound can be synthesised in only a few steps and high yield from easily accessible starting materials. Thiamethoxam acts by binding to nicotinic acetylcholine receptors. It exhibits exceptional systemic characteristics and provides excellent control of a broad range of commercially important pests, such as aphids, jassids, whiteflies, thrips, rice hoppers, Colorado potato beetle, flea beetles and wireworms, as well as some lepidopteran species. In addition, a strong preventative effect on some virus transmissions has been demonstrated. Thiamethoxam is developed both for foliar/soil applications and as a seed treatment for use in most agricultural crops all over the world. Low use rates, flexible application methods, excellent efficacy, long-lasting residual activity and favourable safety profile make this new insecticide well-suited for modern integrated pest management programmes in many cropping systems.

Animals↗

[Marginal fit of dental restorations and the periodontium in Swiss army recruits].

The present study analyzed the relationship between periodontal health adjacent to filled and unfilled tooth sites in young men (recruits). The status of oral health of 419 Swiss army recruits, aged 19 to 20 years was assessed by determining Plaque Index (PI), Retention Index (RI) and Gingival Index (GI) as well as Pocket Probing Depth (PPD) and Probing Attachment Loss (PAL). In addition, the level of alveolar bone was measured using digitized bite-wing radiographs with an enlargement of 4.5x. Filling margins were assessed and the distance between the alveolar bone crest and the cemento-enamel junction (CEJ) measured to the nearest one tenth of a millimeter. These data were compared with the clinical parameters. A total of 8'050 sites were examined. 765 or 9.5 of the sites in the posterior area were filled. 119 of them showed filling overhangs larger than 0.2 mm. Thus, 1.5 % of the examined sites had a significant overhanging margin. All clinical parameters had greater values at filled than at unfilled sites. The differences were statistically not significant. Even the sites with margins overhanging more than 0.8 mm (n=14) did not show significantly different parameters compared to unfilled sites. The comparison with a similar study involving recruits 11 years earlier assessed that the recruits of 1996 had less and smaller filling overhangs. This, in turn, means that, in Switzerland restorative dentistry in young males has been markedly improved during the 1980's and 1990's.

Adult↗

The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat.

OBJECTIVE: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. DESIGN: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h after the administration of CGP-12177 or NE. METHODS: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500 g for 10 min at 4 degrees C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 microCi [(125)I]T4. Aliquots were chromatographed on paper for the measurement of [(125)I]T4 and its deiodinated subproducts. RESULTS: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. CONCLUSIONS: The results indicate that CGP-12177 stimulated the in vivo activation of 5'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.

Adipose Tissue, Brown↗

Prevalence and infection risks of zoonotic enteropathogenic bacteria in Swiss cow-calf farms.

A longitudinal study was performed in 67 larger Swiss cow-calf farms from September 1996 through November 1997. The objectives of the study were to estimate prevalence and risk factors for colonization with potentially zoonotic enteropathogenic bacteria in younger calves and in calves at weaning age. The study included data from 395 calves with three to four fecal samples each. Fecal samples were analyzed for Campylobacter spp., verotoxin producing E. coli (VTEC), Yersinia spp. and Salmonella sp. Possible environmental and individual factors associated with colonization of these agents were examined. The calves were housed indoor during the first 3 months of life (winter 1996/1997). The prevalences within this time period were: C. coli 3.4%, C. fetus 15.5%, C. hyointestinalis 9.6%, C. jejuni 38.5%, VTEC 44.3% and Yersinia spp. 2%. At the end of the grazing season the prevalences at weaning (8-10 months of age) were: C. coli 1.7%, C. fetus 4.0%, C. hyointestinalis 25.9%, C. jejuni 13.3%, VTEC 38.2% and Yersinia spp. 0%. No salmonellae were present at any time of the study. The prevalences of C. jejuni and VTEC increased significantly within the first 3 months of life, whereas C. hyointestinalis decreased. None of the environmental factors such as housing or feeding had any consistent influences on colonization by the bacteria studied. VTEC, Campylobacter spp. and Yersinia spp. should probably be considered as normal inhabitants of the bovine intestinal tract. However, as they represent a source of gastrointestinal infections in humans, management factors limiting intestinal colonization of these bacteria should be considered in cow-calf operations.

Agglutination Tests↗

Leishmania major: histone H1 gene expression from the sw3 locus.

Histone H1 in the parasitic protozoan Leishmania is a developmentally regulated protein encoded by the sw3 gene. Here we report that histone H1 variants exist in different Leishmania species and strains of L. major and that they are encoded by polymorphic genes. Amplification of the sw3 gene from the genome of three strains of L. major gave rise to different products in each strain, suggesting the presence of a multicopy gene family. In L. major, these genes were all restricted to a 50-kb Bg/II fragment found on a chromosomal band of 1.3 Mb (chromosome 27). The detection of RFLPs in this locus demonstrated its heterogeneity within several species and strains of Leishmania. Two different copies of sw3 (sw3.0 and sw3.1) were identified after screening a cosmid library containing L. major strain Friedlin genomic DNA. They were identical in their 5' UTRs and open reading frames, but differed in their 3' UTRs. With respect to the originally cloned copy of sw3 from L. major strain LV39, their open reading frames lacked a repeat unit of 9 amino acids. Immunoblots of L. guyanensis parasites transfected with these cosmids revealed that both copies could give rise to the histone H1 protein. The characterization of this locus will now make possible a detailed analysis of the function of histone H1 in Leishmania, as well as permit the dissection of the molecular mechanisms governing the developmental regulation of the sw3 gene.

Amino Acid Sequence↗

[Prevalence and importance of endoparasites in calves raised in Swiss cow-calf farms].

A longitudinal study was performed to establish estimates of prevalence of selected endoparasites in Swiss cow-calf operations and to investigate the importance of an infection with endoparasites on diarrhea and weight gain until weaning. Three hundred and eighty-six calves raised in 67 larger cow-calf herds were included in the study. Faecal samples were collected during the first three months of life and at weaning. Parasitological analyses were performed according to standard procedures including specifically the detection of Eimeria spp., Cryptosporidium parvum, Strongyloides papillosus and Trichostrongylida. The effects of an infection with endoparasites on weight gain were analyzed with a linear model accounting for effects of farm, breed, sex, calving month and weight at birth. The average prevalences of endoparasites within the first three months of life were: E. bovis 36%, E. zuernii, 19%, C. parvum 16.8%, S. papillosus 22.3% and Trichostrogylida 1.5%. The prevalence of diarrhea within the same time period was 13%. Prevalences at weaning (at the end of the grazing period) were: E. bovis 56.5%, E. zuernii 4.6%, C. parvum 3.7%, S. papillosus 14.4% and Trichostrogylida 84.5%. With the exception of E. zuernii, endoparasites were more frequently observed in healthy calves than in diarrheic calves. Weaning weights were available from 190 calves (33 herds). Statistical analyses of weaning weights revealed no evidence that an infection with helminths and/or protozoa within the first three months of life or at weaning had a negative influence on individual weight gain.

Animals↗

A case control study of potential enteric pathogens for calves raised in cow-calf herds.

A matched case control study was performed to describe the epidemiological features of potential enteric pathogens for calves reared in 53 cow-calf herds located in western Switzerland. A total of 106 diarrhoeic calves and 126 healthy control calves were collected, all calves were less than 4 months old. Faecal samples were analysed for presence of infectious agents related to calf diarrhoea including enterotoxigenic E. coli, Verotoxin producing E. coli (VTEC), Campylobacter sp., Yersinia sp., Salmonella sp., rotavirus, coronavirus, helminths and coccidian protozoa. Multivariate logistic models were used to analyse the relationship between presence of infection and onset of diarrhoea. The study provided evidence of significant associations between diarrhoea and infection with rotavirus, Campylobacter coli and the presence of Verotoxin in faecal samples. With the exception of Cryptosporidium parvum intestinal parasites including Strongylidae and Eimeria sp. were found to be less prevalent in cases than in controls. Control calves were significantly more frequently infected with Strongyloides papillosus than case animals.

Animals↗

Adrenergic/cholinergic immunomodulation in the rat model--in vivo veritas?

For several years, our group has been studying the in vivo role of adrenergic and cholinergic mechanisms in the immune-neuroendocrine dialogue in the rat model. The main results of these studies can be summarized as follows: (1) exogenous or endogenous catecholamines suppress PBL functions through alpha-2-receptor-mediated mechanisms, lymphocytes of the spleen are resistant to adrenergic in vivo stimulation, (2) direct or indirect cholinergic treatment leads to enhanced ex vivo functions of splenic and thymic lymphocytes leaving PBL unaffected, (3) cholinergic pathways play a critical role in the "talking back" of the immune system to the brain, (4) acetylcholine inhibits apoptosis of thymocytes possibly via direct effects on thymic epithelial cells, and may thereby influence T-cell maturation, (5) lymphocytes of the various immunological compartments were found to be equipped with the key enzymes for the synthesis of both acetylcholine and norepinephrine, and to secrete these neurotransmitters in culture supernatants.

Acetylcholine↗

Melatonin and the immune system.

In recent years, melatonin, i.e. the major endocrine product of the pineal gland, was investigated as to its possible regulatory role in the communication between the neuroendocrine and the immune systems. First indications that melatonin may be an endocrine immunomodulator came from early reports about antitumor effects in animals and humans. Since then evidence has accumulated suggesting that melatonin-as a well-preserved molecule during evolution-is indeed involved in the feedback between neuroendocrine and immune functions. At present we begin to discover molecular mechanisms, by which melatonin affects cellular functions in general, and from the variety of possible direct and indirect interactions it appears that melatonin may play a complex physiological role in neuroimmunomodulation. In this article we want to give a critical review of the numerous reports on melatonin influencing immune functions, and to discuss the possible different mechanisms of action, which were suggested recently.

Animals↗

Effect of inhaled magnesium sulfate on sodium metabisulfite-induced bronchoconstriction in asthma.

BACKGROUND: Inhaled magnesium (Mg) seemed to have a mild protective (nonbronchodilator) effect against histamine and methacholine. Inhaled sodium metabisulfite (MBS) causes bronchoconstriction in asthma through indirect mechanisms that involve sensory nerve stimulation, and it is extensively used to study airway hyperresponsiveness. We designed this double-blind, randomized, crossover, and placebo-controlled study to test the effect of nebulized Mg sulfate against indirect challenge with MBS. METHODS: Ten asthmatic subjects (three male) aged 38.8 (3.29, SEM) years came on three occasions to perform MBS challenges 5 min after inhalation of either normal saline solution as placebo or Mg sulfate (4 mL; 286 mOsm). Doubling increasing concentrations of MBS were administered by continuous nebulization at tidal breathing during 1 min starting at 0.3 to 80 mg/mL until a >20% fall in FEV1 (PC20) from post saline solution baseline value was achieved. PC20 values were logarithmically transformed before analysis. RESULTS: The mean baseline FEV1 at control day was 2.52 (0.14) L and 88.46 (4.28) percentage predicted, while the geometric mean MBS PC20 was 1.95 (1.38, geometric SEM) mg/mL. After placebo, the geometric mean PC20 was 2.26 (1.26) mg/mL. Inhaled Mg increased significantly the PC20 to 5.06 (1.52) mg/mL; p<0.05. Mg diminished the bronchoconstrictor response to MBS by 1.3 doubling doses (p=0.08). CONCLUSIONS: Inhaled Mg attenuates MBS-induced bronchoconstriction in these asthmatic subjects. This new feature of Mg, even modest in magnitude, emphasizes the necessity of studying the potential role of this cation in modulating airway response.

Administration, Inhalation↗

Trauma-related disorders in psychiatrists' and general practitioners' private practice in Switzerland.

A questionnaire addressing traumatic stress related issues was mailed to every third psychiatrist in private practice and to every fifth general practitioner in Switzerland (N = 1406, number of returns 517 (37%). Trauma-related disorders seem to be underdiagnosed. Patients suffering from rape, accidents and war related trauma were most often mentioned. Psychiatrists knew more about specific treatment possibilities than general practitioners. Only 14% of the responding clinicians were satisfied with the existing therapeutic services for trauma victims; more psychiatrists voiced a need for their improvement. A majority suggested interdisciplinarity and the cooperation of institutions and therapists in private practice for the treatment of trauma-related disorders. It is proposed that further education should be tailored according to the target professional group.

Adult↗

Beta-blockade enhances adrenergic immunosuppression in rats via inhibition of melatonin release.

We have recently shown in rats that an in vivo treatment with catecholamines via alpha 2-receptors leads to a pronounced suppression of T- and B-cell mitogen responses of peripheral blood lymphocytes (PBL), provided that a beta-blocker is administered concomitantly. Since melatonin (MEL) reportedly has stress-protective effects on several immune functions, and since the release of MEL from the pineal gland is inhibited by beta-blockade, we tested the effect of MEL substitution on T- and B-cell mitogen responses of PBL in rats treated with two s.c. implanted retard tablets containing noradrenaline (NA) and propranolol. It was found that an oral treatment with MEL (about 40 micrograms/animal) abolished the adrenergic immunosuppression. Furthermore, functional pinealectomy induced by constant light had a similar enhancing effect on the alpha 2-adrenergic immunosuppression as observed with beta-blockers, whereas PBL from animals kept at the regular light/dark interval were resistant to the treatment with the selective alpha 2-agonist clonidine. It is concluded that endogenous MEL effectively protects rat PBL from adrenergic immunosuppression, and that beta-blockers enhance the immunosuppressive property of alpha 2-adrenergic agents via blocking the night-time release of MEL.

Adrenergic alpha-Agonists↗

The effect of a single mechanical treatment on the subgingival microflora in patients with HIV-associated gingivitis.

The purpose of the present study was to investigate the effect of a single episode of scaling and root planing on clinical periodontal parameters and on the subgingival microflora in human immunodeficiency virus (HIV)-positive and HIV-negative subjects. 13 subjects participated and were clinically scored at days -7, 7, 30 and 90. 7 subjects were infected with HIV and presented an HIV-associated gingivitis. 6 subjects were HIV-negative with at least 12 teeth affected by conventional gingivitis. No significant differences were seen between both groups regarding the presence of P. gingivalis, P. intermedia and A. actinomycetemcomitans. The mean plaque index (PlI) was 1.79 in the HIV-negative and 1.29 in the HIV-positive group. The mean gingival index (GI) was higher in the HIV-positive group (HIV-positive: 1.55; HIV-negative: 1.47). Whereas, the PlI decreased significantly in the HIV-negative group during the course of the study, no change was observed in the HIV-positive group. GI as well as bleeding upon sampling decreased significantly in both patient groups during the same period. The bacterial counts decreased from day -7 to day 7 and generally remained on a lower level until day 90. Small differences were seen in the microbiological flora of the HIV-positive and the HIV-negative subjects following mechanical treatment.

AIDS-Related Opportunistic Infections↗

Characterization of the spontaneous apoptosis of rat thymocytes in vitro.

Unlike splenic or blood lymphocytes, rat thymocytes spontaneously undergo continuously increasing apoptosis during culture. In this study we characterized apoptotic thymus cells of rats according to cell size, nuclear dye binding and surface marker expression. Furthermore, the effects of cell density in culture, the age of the donor animals, glucocorticoids, and inhibition of protein synthesis were studied. It was found that: (1) apoptotic rat thymocytes are recognized in flow cytometry as small, acridine orange low, CD4low, CD8high cells; (2) the rate of apoptosis is dependent on the cell density in the culture in a biphasic manner; (3) thymic apoptosis increases with age of the donor animal in fresh, as well as in 24-hour cultivated cell suspensions; (4) neither adrenalectomy nor in vivo or in vitro treatment with the glucocorticoid antagonist RU 38486 influenced spontaneous apoptosis of thymocytes, and (5) inhibition of protein synthesis, which decreases apoptosis induced by corticosterone, had no effect on spontaneous apoptosis of thymocytes.

Acridine Orange↗

Adrenergic suppression of peripheral blood T cell reactivity in the rat is due to activation of peripheral alpha 2-receptors.

A 20-h treatment of rats with catecholamines using s.c.implantable retard tablets markedly suppresses the in vitro reactivity of peripheral blood (PBL) T lymphocytes, provided that beta-receptors are blocked with propranolol (Felsner et al., 1992). The results can be summarized as follows: (i) the suppressive effect of noradrenaline+propranolol to the concanavalin A (ConA) response of PBL was abolished by the simultaneous application of the alpha-blocker phentolamine. Using selective agonists, the relevant receptor was identified to belong to the alpha 2-subtype. (ii) The alpha-adrenergic suppression of the PBL T cell response was likewise observed in adrenalectomized animals, which rules out the participation of secondarily induced glucocorticoids. Furthermore, the combination of noradrenaline with the watersoluble beta-blocker nadolol was equally effective to suppress the ConA response of PBL. (iii) An analogous alpha-mediated suppression of T cell function of PBL, but not spleen cells, was observed 1 h after i.p. treatment with tyramine, which leads to the release of endogenous noradrenaline. From these results it is concluded that the adrenergic suppression of PBL T cell functions is primarily due to the activation of peripheral alpha 2-receptors and that it is likewise observed under acute indirect sympathomimetic treatment.

Animals↗