Vitamin D Increases Glucose Stimulated Insulin Secretion from Insulin Producing Beta Cells (INS1E).

BACKGROUND: Vitamin D affects the pancreatic beta cell function and in vitro studies have shown that vitamin D may influence insulin secretion, apoptosis, and gene regulation. However, the outcomes have differed and there has been uncertainty regarding the effect of different vitamin D metabolites on insulin secretion. OBJECTIVES: We hypothesized that vitamin D could increase insulin secretion in insulin producing beta cells and investigated the effect of 25(OH) vitamin D and 1,25(OH)2 vitamin D on insulin secretion. METHODS: The study was conducted in INS1E cells, an established insulinoma cell line from rat. The cells were divided into three groups; a control group, a group with 1,25(OH)2 vitamin D enriched medium (10 nM), and a group with 25(OH) vitamin D (10 nM) supplemented medium. After 72 hours of treatment, the cells underwent glucose stimulation at different concentrations (0, 5, 11, and 22 mM) for 60 minutes. RESULTS: INS1E cells treated with 1,25(OH)2 vitamin D showed a trend towards increased insulin secretion at all glucose concentrations compared to control cells and at 22 mM glucose, the difference was significant (18.40 +/- 1.97 vs 12.90 +/- 2.22 nmol/L, P < 0.05). However, pretreatment with 25(OH) vitamin D did not show any significant increase in insulin secretion compared to cells without vitamin D treatment. There was no difference in insulin secretion in cells not stimulated with glucose. CONCLUSIONS: Treatment with 1,25(OH)2 vitamin D combined with high levels of glucose increased insulin secretion in INS1E cells, whereas 25(OH) vitamin D had no effect. This suggests that glucose stimulated insulin secretion in INS1E beta cells appears to be related to the type of vitamin D metabolite treatment.

Pharmacology of neurotransmitter transport into secretory vesicles.

Many neuropsychiatric disorders appear to involve a disturbance of chemical neurotransmission, and the mechanism of available therapeutic agents supports this impression. Postsynaptic receptors have received considerable attention as drug targets, but some of the most successful agents influence presynaptic processes, in particular neurotransmitter reuptake. The pharmacological potential of many other presynaptic elements, and in particular the machinery responsible for loading transmitter into vesicles, has received only limited attention. The similarity of vesicular transporters to bacterial drug resistance proteins and the increasing evidence for regulation of vesicle filling and recycling suggest that the pharmacological potential of vesicular transporters has been underestimated. In this review, we discuss the pharmacological effects of psychostimulants and therapeutic agents on transmitter release.

IL-8 inhibits isoproterenol-stimulated ciliary beat frequency in bovine bronchial epithelial cells.

Mucociliary clearance is a critical host defense that protects the lung. The mechanisms by which mucociliary function is altered by inflammation are poorly defined. Chronic exposure to cigarette smoke decreases ciliary beating and interferes with proper airway clearance. Bronchoalveolar lavage (BAL) fluid from smokers and ex-smokers has increased amounts of IL-8, which has played a critical role in airway inflammation. We hypothesized that IL-8 might interfere with stimulated ciliary beating in airway epithelium. To test this hypothesis, we stimulated bovine ciliated bronchial epithelial cells (BBECs) with a known activator of ciliary beat frequency (CBF), isoproterenol (ISO; 100 microM), in the presence or absence of IL-8 (100 pg/mL). We measured CBF digitally using the Sisson-Ammons Video Analysis (SAVA) system. CBF increased in untreated cells exposed to ISO (approximately 3 Hz) over baseline. In contrast, cells pre-incubated with IL-8 failed to respond to ISO. Pretreatment with IL-8 also blocked ISO-stimulated cAMP-dependent kinase (PKA) activation, which is known to control ISO-stimulated CBF. In addition, IL-8 pretreated cells revealed a marked decrease in PKA activity when cells were stimulated with forskolin (FSK; 10 microM). Cells were assayed specifically for cAMP-phosphodiesterase (PDE) activity. ISO-stimulated cells demonstrated an increase in PDE activity as compared to control. Pretreatment with IL-8 had no effect on ISO-stimulated PDE activity. Collectively, these data suggest that IL-8 appears to mediate its effect at the level of adenylyl cyclase. It is also possible that IL-8 may not only act as a chemotactic agent, but also as a potential autocrine/paracrine inhibitor of PKA-mediated stimulation of ciliary motility. In conclusion, IL-8 inhibits beta-agonist dependent ciliostimulation and such inhibition of stimulated ciliary activity may contribute to the impaired mucociliary clearance seen in airway diseases. Furthermore, since IL-8 levels are increased in the airway of cigarette smokers, it is likely they may be more resistant to the cilio and muco-ciliostimulating effects of beta-agonists.

Death certificates in asthma and COPD patients (survey of statistical data in Warsaw).

UNLABELLED: Mortality statistics regarding asthma and COPD (in the older age groups) are probably lower due to the misplacement of underlying and additional causes of death in the death certificates. To check this possibility, all death certificates over one year were reviewed(20.881) in Warsaw. In 1,431 cases (6.85%) the medical diagnoses were missing. Asthma, COPD and Pulmonary Heart Disease (PHD) (excluding any other cause of PHD) were mentioned at some point in 315 cases (on one of the three items cards). 212 deaths occurred in hospital, 103 at home (22 were regarded as sudden deaths). After reviewing records from 16 hospitals and patients' local clinics, the existence of long-standing asthma and/or COPD was confirmed in all cases. Considering all the three items (underlying, secondary, direct causes) in the death certificates the mortality rates (for 100,000 all-age inhabitants) were established for asthma--4.51 for COPD--10.54, for PHD--3.23 (different from official statistics). PRINCIPAL CONCLUSIONS: The main sources of underestimation in mortality from asthma and/or COPD (in official statistics) are: 1) disregarding the "additional" and "immediate" causes of death, 2) regarding PHD as an underlying cause of death, 3) the lack of medical diagnoses in great number of death certificates.

[Asthma caused by allergy to cat fur]. / Astma spowodowana uczuleniem na siersc kota.

Sensitivity to cats fur alergen, Fel. d. 1 is presented as the second most important cause, after allergy to mites, of perennial atopic asthma. The authors collected the data from literature concerning the concentrations of Fel. d. 1 in homes and public places. Further the structure and production of Fel d. 1 also its cross reactivity and the methods of it's elimination from the environment are described and discussed. Authors own observations of 20 cases of cats fur asthma and atopic dermatitis support the opinion that only half of the patients suspect cats as the cause of their illness and cats fur sensitivity is always accompanied by inhalant or food allergy.

[Sensitivity to birch pollen--under-appreciated etiology of atopic asthma in towns]. / Uczulenie na pylek brzozy--niedoceniana etiologia astmy atopowej w miastach.

Author presents some epidemiological data of birch pollen allergy. Pathogenesis and also crossreactivity of such allergy is discussed, especially concerning allergy to fruits. Some data about various phenotypes of birch tree are presented. Finally author gives some clinical data of 30 observed cases of young adults whose birch pollen allergy in 63% manifested itself as bronchial asthma.

Arnold's nerve reflex among pollinosis patients: sign of predictable asthma?

Examination of the external auditory canals in a group of 53 asymptomatic (before the season) grass pollen-sensitive patients was performed by means of fiberoptic otoscope. The mechanical irritation of the walls of the auditory canals resulted in a cough reflex in 11 patients. An analysis of the lack or presence of any bronchial symptoms, during or out of season, in the whole group was performed. It was concluded that otorespiratory (or otocough) reflex may be a predictive measure for bronchial symptoms among pollinosis patients. In this aspect, the sensitivity of the test was 50 percent, but its specificity was 92 percent.

[Oto-respiratory reflex in patients with pollinosis]. / Odruch uszno-kaszlowy u chorych z alergia pylkowa.

The examinations of the external auditory canals among the group of 53 asymptomatic (before the season) grass pollen sensitive patients have been performed by means of fiberoptic otoscope. The mechanical irritation of the walls of the auditory canals resulted in the cough reflex in 11 patients. The analysis of the lack or presence of any bronchial symptoms (during or out of the season) among the whole group has been made. The conclusion was, that oto-respiratory (or oto-cough) reflex may be the predictive measure of any bronchial symptoms among pollinosis patients. In the aspect, the sensitivity of the was 50%, but its specificity--92%.

Immunotherapy of asthma.

A questionnaire in 1965 indicated that immunotherapy (IT) was accepted for pollen and house-dust induced allergy. There was less agreement over its use for food and drug induced allergy, as well as acute reactions to bacteria. In spite of this there is renewed controversy at the present time. A special risk of side effects has always been accepted, which seems to vary in intensity with the country in which the procedure is performed. In France deaths are rare, but in Great Britain and USA there have been many serious reactions, including deaths from anaphylactic shock. Expression of side effects seems to depend at least partly, on the schedule of injections used. The clearest results of IT are to be found in young adult (teenage) patients, but chronic infections decrease its efficacy. Good compliance by patients is essential.

[Sensitivity to mugwort pollen allergens (Artemisia vulgaris)]. / Uczulenie na bylice (Artemisia vulgaris).

The author has found that 42% of patients with pollinosis had positive skin reactions with mugwort (Artemisia vulgaris) pollen allergens. The majority of tested patients (139 out of 187) were also allergic to grass pollens. However, hypersensitivity to mugwort pollen allergens was isolated and did not accompany grass pollen allergy. The symptoms of pollinosis appeared in this group later than in patients sensitive to grass pollen allergens only (over 21 years of age in 71%). Bronchial asthma was diagnosed in 40% of these patients and allergic skin reactions in 25%. Sensitivity to mugwort pollen allergens was accompanied by the sensitivity to pollen allergens of Graminae family of plants in 80% of cases. The author suggests that sensitivity to mugwort pollen allergens is the second most frequent cause of the pollinosis and is diagnosed too rarely. Failures of desensitization in patients sensitive to pollen allergens of Graminae family of plants may often result from coexisting sensitivity to mugwort pollen allergens as this sensitivity produces not only season but perennial clinical symptoms in nearly 50% of patients. The author discusses also botanical relations and cross-reactions in allergy to mugwort and ragweed pollen allergens.

Allergy to Artemisia vulgaris in the region of Warsaw.

From 446 pollinic patients, 398 of them (89%) were sensitive to the pollen of graminae and 187 (42%) to Artemisia Vulgaris. Sensitivity to the antigens of both increased the possibility of bronchial symptoms among pollinosis patients from 38% when only the allergy to graminae was present (up to 51%). Seventy eight percent of patients allergic exclusively to the pollen of grasses become symptomatic below the age of 20, whereas among 48 patients sensitive only to artemisia, in 71% the clinical symptoms appeared much later-after the age of 20. In half of these patients, the clinical symptoms were not only seasonal but also perennial. Almost 25% of these suffered from allergic skin reactions and 1/3 also from asthma. Eighty percent of Artemisia sensitive pollinic patients were also sensitive to the pollen of other plants from the family of compositae. The possible causes of the apparent increase of the prevalence of allergy to Artemisia Vulgaris are discussed.

Meteorological and climatic factors in bronchial asthma. A clinical dilemma.

In this work a review is made of the importance of climatic and meteorological factors together with other factors in bronchial asthma. The temperature and atmospheric humidity are two important parameters to be taken into account in the stimulation phenomena of bronchial hyperreactivity.

Allergy to cereals and dairy products in adult, uncomplicated asthma: an epidemiological survey.

From a representative group from the adult population (34.958) of a town of 77.384 inhabitants, 99 persons were selected who: a) claimed to be periodically dyspneic independently with respect to respiratory tract infections. b) had normal chest x-rays and normal PE flow values. Approximately one year later, a history of atopic diseases was taken from 79 of them, and intradermal skin tests were performed with some inhalants and food allergens. At this time, 15 persons failed to report their previous complaints of dyspnea. Only 5 persons reported that various vegetables and pickles were responsible for their urticaria or eczema. Only 2 persons admitted various gastrointestinal symptoms, but non mentioned milk, eggs or cereals as possible causative agents of their bronchial, nasal, skin or circulatory symptoms. Distinctly positive immediate type skin reactions to the mixed milk and egg allergen were recorded in 19 patients (24%), and to cereals in 11 persons (14%). They all reacted strongly also to the house dust allergen, but they did not differ from all the remaining subjects in the intensity of their skin response to the control solution of histamine. People with positive skin reactions to cereals or dairy products complained of chronic or recurrent rhinitis much more often than the others (73% and 63% compared with 35%). Forty-five (47%) of them had a positive personal history of urticaria or eczema. These "food reactors" did not differ from "non reactors" in the frequency of the elevated serum IgE level which was raised in 66% of the whole group (of 79). The results suggest that allergy to cereals and dairy products may often be underestimated in adult asthmatics especially when positive reactions to inhalants are also present. The problems of reliability of the skin tests and history taking in food allergy are briefly discussed.