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Biomedical subjects

R Giger

Publications and source records attributed to R Giger.

15 recordsLinked to original sources

Somato-sympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide.

AIM: Patients suffering from non-allergic chronic rhinosinusitis (NACRS) increasingly use intranasal saline sprays. They report better nasal comfort. METHODS: In order to better understand this phenomenon, we studied intranasal laser Doppler flowmetry (LDF) and nasal nitric oxide (NO) variations evoked by local administration of saline, histamine, N-acetylcysteine (NAC) and lidocaine at room temperature (22 degrees C). RESULTS: There was a significant (P < 0.05) 14 +/- 3.8% decrease in LDF signal after 30 s, which lasted for 60-90 s, for all the substances applied at 22 degrees C. This pharmaco-independent vasoconstriction was further studied in patients under general anaesthesia (GA), with saline at 37 degrees C and after intranasal adrenaline treatment. While GA did not influence the vasoconstriction, saline at 37 degrees C and adrenaline pre-treatment abolished it. Nasal NO is influenced by vasoconstriction. Therefore we investigated, whether the observed vasoconstriction also changes nasal NO. A significant (P < 0.001) 8.03 +/- 0.59% decrease in nasal NO was recorded 60 s after administration of all the substances, and under GA after 22 degrees C saline application. This NO decrease was absent after intranasal adrenaline pre-treatment. An additional experiment tested the effect of nose blowing on nasal NO concentration. We registered an NO decrease with a similar pattern than observed with the other substances. CONCLUSIONS: Intranasal fluid nebulization at 22 degrees C induces a sympathetic mediated, transient vasoconstrictor reflex response. This somato-sympathetic vasoconstriction induces a decrease in nasal NO. Both could be related to the subjective comfort experienced by NACRS patients using intranasal saline sprays.

Acetylcysteine↗

Comparison of once- versus twice-daily use of beclomethasone dipropionate aqueous nasal spray in the treatment of allergic and non-allergic chronic rhinosinusitis.

The aim of the study was to assess the efficacy and safety of nasal aqueous beclomethasone dipropionate (BDP), 400 micro g/day, given via a metered pump in a once-daily or twice-daily regimen following a double-blind, parallel group design over a 12-week period. Adult patients (n=112) with allergic or non-allergic chronic rhinosinusitis recorded their nasal and ocular symptoms for the 7-day run-in period and for the first 4 weeks of treatment. At baseline and after 4 weeks the airways' resistance via active anterior rhinomanometry and the volume and area section via acoustic rhinometry were measured. Morning serum cortisol was measured at baseline and at week 12. Adverse events were to be reported at each visit. Of the 112 randomised patients, three did not enter the ITT analysis and another 13 in total discontinued the treatment. Significant improvements over the baseline were reported in both groups for the primary variable sum of nasal scores (-53.7% in the once-daily group and -59.7 in the twice-daily group), as well as for each nasal and ocular symptoms, without differences between the groups. Because of a wider variability than expected, the 95% confidence interval (C.I.) for the difference between the least square means exceeded the pre-defined limit of +/-10% of the reference mean. Similar improvements in both groups were also reported for the nasal airway patency's parameters. The total number of drug-related adverse events was 26 in the once-daily group and 32 in the twice-daily group, with most of the events consisting of local effects at the site of application. No signs of adrenal suppression were observed, and serum morning cortisol values did not significantly change. The once-daily BDP dosing (400 micro g/day) therefore has a similar efficacy and safety profile as the same daily dose given in a twice-daily regimen.

Administration, Intranasal↗

[Correlation between objective criteria and subjective evaluation of symptoms in chronic rhinosinusitis].

INTRODUCTION: We evaluated the possible correlations between the extent of inflammatory infiltration of the nasal mucosa caused by mechanical irritation (septal deviation and hypertrophy of the middle turbinate) and nasal airway resistance measured by rhinomanometry and acoustic rhinometry. Subjective evaluation of the nasal obstruction, rhinorrhoea and headache was done by visual analogic scale and compared with the inflammation. PATIENTS AND METHODS: 40 patients with a more than 18 months' history of chronic rhinosinusitis associated with septal deviation and/or hypertrophy of the middle turbinate were included in the study. The density of inflammatory cells (graded from + to +3, where + means few and +3 abundant inflammatory cells) in the mucosa of the middle turbinate was evaluated histopathologically. RESULTS: We found a significant correlation between subjective intensity of nasal obstruction and inflammation (mainly lymphocytes) of the middle turbinate mucosa and the value of nasal airway resistance measured by rhinomanometry. No correlation was found between the other parameters studied. CONCLUSION: Mechanical stimulation at the level of turbinoseptal contact causes inflammation in the mucosa which correlates with both subjective nasal airway resistance and rhinomanometry values.

Adolescent↗

[Study of the enzyme peptidyl peptidase IV in nasal mucosa].

INTRODUCTION: The endothelial serine protease dipeptidyl peptidase IV (DPP IV) cleaves the tyrosin-prolin dipeptide of several inflammatory mediators and neuropeptides, including neuropeptide Y (NPY), yielding the endogenous Y2-receptor agonist NPY (3-36) which modulates sensory and parasympathetic nerve activity. The aims of the study were to investigate the localisation of DPP IV in human nasal mucosa and to measure in vitro activity of DPP IV in nasal mucosa biopsies from patients suffering from chronic rhinosinusitis. PATIENTS AND METHODS: Using immunohistochemistry we have studied the localisation of DPP IV in human nasal biopsies. The activity of DPP IV was measured in vitro in nasal mucosa samples obtained from 45 patients suffering from chronic rhinosinusitis and compared with the density of inflammatory cell infiltration. RESULTS: Positive immunoreactivity for DPP IV was observed in the human nasal mucosa. Low activity of DPP IV was associated with high density of inflammatory cells in the mucosa of patients suffering from chronic rhinosinusitis. The regressive correlation was statistically significant (p < 0.001). CONCLUSION: Low level DPP IV activity is associated with inflammation of the nasal mucosa. This enzyme may be involved in the pathophysiological mechanism of nasal hyperreactivity and chronic rhinosinusitis.

Adolescent↗

[Length of gestation of Freiberger mares with mule and horse foals].

In a retrospective study the gestation lengths of two groups, each consisting of 193 "Freiberger" mares, were compared. The mares of the first group were bred by a donkey, those of the second group by a stallion of the "Freiberger" breed. On average, the gestation length of mares with "Freiberger" foals lasted 336.5 days, and that of mares with mule foals 343.1 days. The difference between both groups was significant (p < 0.001). The shortest and longest observed gestation length of mares with "Freiberger" foals was 307 and 361 days, and that of mares with mule foals 315 and 369 days, respectively. Additionally, we examined if the stallion, the mare, the age of the mare, the sex of the foal and the time of mating during the breeding season influenced gestation length of mares with mule foals and if the age of the mare, the sex of the foal and the time of breeding influenced gestation length of mares with "Freiberger" foals. The time of breeding and the mare had a significant (p < 0.05) influence on gestation length.

Age Factors↗

Differential expression of the mRNAs of the axonal glycoproteins axonin-1 and NgCAM in the developing chick retina.

Cell adhesion molecules expressed on the axonal membrane have been thought to be involved in the guidance of axons to their target area. In the chick, axonin-1 and NgCAM have been shown to promote, through reciprocal interactions, neurite outgrowth in vitro. We have recently shown that chick retinal ganglion cells (RGC) express both proteins as early as the axonal elongation begins. Their expression continues throughout the development of the retinotectal system synchronously with the chronotopic spread of axons. To further investigate the spatiotemporal distribution of axonin-1 and NgCAM in the retina, we have analysed the expression of their mRNAs in the present study. From stage 36 (E10) until hatching photoreceptors express axonin-1 but not NgCAM. In the inner nuclear layer groups of amacrine cells were strongly labelled with both probes but they seemed to belong to different subgroups. These patterns of expression might indicate a differential influence of the two proteins on the development of the local neural circuits of the retina.

Animals↗

The serotonin 5-HT4 receptor. 1. Design of a new class of agonists and receptor map of the agonist recognition site.

The design and synthesis of a new class of potent and selective 5-HT4 receptor agonists containing an indole nucleus linked to a carbazimidamide are presented. A conformational study of the 5-HT4 receptor agonists serotonin and zacopride led to the identification of an initial pharmacophore and to the definition of a three-dimensional map of the 5-HT4 agonist recognition site. 1, a representative member of our new class of 5-HT4 receptor agonists, incorporates all reference structural features and matched perfectly with these models. 1 is a highly potent, full agonist at 5-HT4 receptors present in the isolated electrically stimulated guinea pig ileum preparation, with a pD2 value of 8.8, displaying selectivity (ranging from 40- to over 10,000-fold) versus other members of the serotonin receptor family.

Animals↗

The serotonin 5-HT4 receptor. 2. Structure-activity studies of the indole carbazimidamide class of agonists.

A number of substituted indole carbazimidamides were prepared and evaluated as 5-HT4 receptor agonists by using the isolated field-stimulated guinea pig ileum preparation. Their selectivity for the 5-HT4 receptor was established by examining their affinity for other 5-HT receptors using radioligand-binding techniques. Several selective and highly potent full as well as partial agonists emerged from this study. For example, 1b,d were found to be the most potent, full 5-HT4 receptor agonist described so far (EC50 = 0.5 and 0.8 nM, respectively), being 6 and 4 times more potent than serotonin itself. On the other hand, 5b and 1h appeared as partial 5-HT4 receptor agonists in the nonstimulated guinea pig ileum preparation with potencies, evaluated against serotonin action, respectively similar (5b, Ki = 12 nM) to and 300-fold higher (1h, Ki = 0.04 nM) than serotonin.

Amides↗

A survey of veterinarian and producer perceptions of herd health services in the Saskatoon milkshed.

A cross-sectional survey was conducted to determine the availability, rates of adoption, and producer perceptions of veterinary services in five areas of dairy production medicine: reproduction, milk quality, nutritional consulting, infectious disease control, and heifer rearing. Questionnaires were completed by all veterinary clinics and 86% of the dairy producers in the Saskatoon milkshed. Veterinary perceptions of services offered were compared with farmer perceptions of services received. The veterinary clinics appeared to overestimate their services in the areas of nutritional consulting and heifer rearing. The primary determinant of a producer's perception of being on a herd health program was the occurrence of regularly scheduled reproduction visits. Producers who perceived themselves as being on a herd health program also believed that they received more services in the other four main areas of production medicine. Grouping of producers, based on whether or not herd records were analyzed by their veterinarian, showed a clustering of adopters of more comprehensive herd health services as clients of two practices. This suggests that comprehensive herd health services are not readily available from all veterinary clinics in the Saskatoon milkshed.

Animals↗

Hepatic branch vagotomy enhances glucoprivic feeding in food-deprived old rats.

Glucoprivic feeding induced by intraperitoneal (IP) injection of 2-deoxy-D-glucose (2-DG, 250 mg/kg body weight) in the middle of the light phase was investigated in old (age: 15-16 months) and young (age; 2.5-3.5 months) hepatic branch-vagotomized (HBV) and sham-vagotomized (SV) rats. Rats were fed either a carbohydrate-rich diet or a fat-enriched diet with a moderate carbohydrate content. The glucoprivic feeding response was greater in 13-h food-deprived old HBV rats than in 13-h food-deprived old SV rats on both diets. 2-Deoxy-D-glucose produced a greater feeding response when rats were fed the fat-enriched diet. Independent of the diet, the transient hyperphagia induced by 2-DG was followed by a long-term hypophagia in old SV rats, but not in old HBV rats. In 13-h food-deprived young rats, hepatic branch vagotomy did not affect the changes in food intake induced by 2-DG. In undeprived old and young rats, the feeding response to 2-DG, exceeding that of deprived rats, was also not affected by HBV. It is concluded that under certain conditions hepatic branch vagotomy eliminates a 2-DG-induced signal inhibiting food intake and thus enhances glucoprivic feeding. The feeding response to 2-DG therefore seems to depend on stimuli affecting food intake in an antagonistic manner.

Afferent Pathways↗

Mutants of human insulin-like growth factor II with altered affinities for the type 1 and type 2 insulin-like growth factor receptor.

With the aim to produce insulin-like growth factors (IGF) with enhanced specificity for the type 1 or type 2 IGF receptors, three mutants of IGF II have been prepared and expressed in NIH-3T3 cells. IGF II mutated at Tyr27 to Leu and Glu showed a 25- and 54-fold decrease in affinity for the type 1 IGF receptor and a 3.4- and 9.2-fold decrease in affinity for the type 2 IGF receptor. IGF II mutated at Phe48 to Glu showed a 18-fold decrease in affinity for the type 2 IGF receptor and a 2.8-fold decrease in affinity for the type 1 IGF receptor. These affinities were measured in radioreceptor assays using type 1 or 2 IGF receptor overexpressing cells. Data obtained on receptor cross-linking and thymidine incorporation assays confirmed the results of the radioreceptor assays. It is concluded that mutations of Tyr27 preferentially decrease binding to the type 1 IGF receptor and of Phe48 to the type 2 IGF receptor, either by the loss of a residue involved in receptor binding or by preferentially destabilizing the region involved in receptor binding.

Amino Acid Sequence↗