Effect of canine mesenchymal stromal cells loaded with paclitaxel on growth of canine glioma and human glioblastoma cell lines.

This study investigated whether canine mesenchymal stromal cells (cMSCs) are able to take up and release paclitaxel (PTX) in active form, and therefore whether they have potential as a tool for therapeutic delivery of this drug. cMSCs from bone marrow and adipose tissue were isolated, expanded and characterised phenotypically. cMSCs were loaded with PTX (cMSCs-PTX) and their capacity for release of PTX was determined by their effect on proliferation of cancer cells. cMSCs-PTX derived from bone marrow and adipose tissue were able to take up and then release active PTX. cMSCs-PTC inhibited proliferation of the canine glioma cell line J3T, and the human glioblastoma cell lines T98G and U87MG. The potential of canine cMSCs-PTX for treatment of canine gliomas should be investigated further.

Effects of aging and cyclosporin a on collagen turnover in human gingiva.

BACKGROUND: WE AIMED AT CHARACTERIZING THE AGING GINGIVA ANALYZING: i) collagen content and turnover in human gingival tissues and fibroblasts obtained from healthy young and aging subjects. ii) the effect of cyclosporin A administration in human cultured gingival fibroblasts obtained from aging compared to young subjects. METHODS: Morphological analysis was performed on haematoxylin-eosin and Sirius red stained paraffin-embedded gingival biopsies from young and aging healthy subjects. The expression of the main genes and proteins involved in collagen turnover were determined by real time PCR, dot blot and SDS-zymography on cultured young and aging gingival fibroblasts, and after cyclosporin A administration. RESULTS: Our results suggest that in healthy aged people, gingival connective tissue is characterized by a similar collagen content and turnover. Collagen turnover pathways are similarly affected by cyclosporin A treatment in young and aging gingival fibroblasts. CONCLUSIONS: Cyclosporin A administration affects gingival collagen turnover pathways in young and aging fibroblasts at the same extent, suggesting that during aging cyclosporin A administration is not related to relevant collagen turnover modifications.

A therapeutic dose of FK506 does not affect collagen turnover pathways in healthy human gingival fibroblasts.

We previously demonstrated that a high dose of tacrolimus (1 mumol/L) induced expression of matrix metalloproteinase (MMP) proteins in human cultured gingival fibroblasts, suggesting a molecular mechanism maintaining gingival collagen homeostasis in tacrolimus-treated patients. Herein we have analyzed whether the effect on collagen turnover might be influenced by a therapeutic tacrolimus dose. Human gingival fibroblasts were incubated for 72 hours with 10 nmol/L, 100 nmol/L, and 1 mumol/L tacrolimus, or left untreated (CT). Collagen type I and III (COL-I, COL-III), lysyl hydroxylase 2b (LH2b), MMP-1 and -2, tissue inhibitor of MMP-1 and transforming growth factor-beta1 (TGF-beta1) mRNA levels were assayed by reverse-transcriptase polymerase chain reaction, collagen protein levels by dot blot, and MMP activity by sodium dodecyl sulfate zymography. Tacrolimus did not affect COL-I, COL-III, or MMP gene expression, while LH2b and TGF-beta1 tended to be down-regulated after 1 mumol/L FK506. Conversely, protein levels of MMP-1 (P = NS) and MMP-2 (P < .05 vs CT, 10 nmol/L, 100 nmol/L) were up-regulated after 1 mumol/L tacrolimus. Our findings confirmed that a high dose of tacrolimus does not induce interstitial collagen overexpression by gingival fibroblasts and induces up-regulation of MMPs protein levels. Interestingly, at doses corresponding to whole blood trough levels, tacrolimus did not exert any evident effect on collagen turnover pathways, suggesting that tacrolimus is likely to not affect collagen homeostasis in the gingival connective tissue compartment of FK506-immunosuppressed subjects. This effect did not seem to be dose-dependent.

Prevalence of occupational allergy due to live fish bait.

BACKGROUND: Larvae of insects and worms, used as live fish bait (LFB), are a common source of allergy in anglers and occupationally exposed workers, but the prevalence and predictors have not yet been investigated. OBJECTIVE: This study assessed the prevalence and associated factors of occupational allergy in workers exposed to LFB. METHODS: We assessed the prevalence of sensitization to LFB and work-related symptoms (WRS) in 76 workers occupationally exposed to it. All workers completed a case history questionnaire and underwent skin prick tests (SPT) for common aeroallergens and bluebottle (Calliphora vomitoria), bee moth (Galleria mellonella), mealworm (Tenebrio molitor), and gusano rojo (Cilecomadia moorei). Specific IgE were tested in 64 subjects. Two-thirds of the workers had a high level of LFB exposure. RESULTS: Sensitization to LFB was found in 24 workers (31.6%). Seven subjects (9.2%) reported WRS (asthma in 3, rhinoconjunctivitis in 5, and contact urticaria in 1), and 5 were positive for SPT and serum IgE to one or more LFB extracts. One was also exposed to LFB while fishing. Sensitization to LFB extracts and WRS were strongly associated (Odds Ratio = 6.6, P < 0.05). The 7 subjects with WRS had been exposed longer than asymptomatic subjects with positive skin tests to LFB (P < 0.05). No differences in sex, age, smoking habit, duration or level of exposure, and atopy were detected in symptomatic or in sensitized subjects, compared with normal workers. CONCLUSION: Sensitization to LFB and WRS are relatively frequent in occupationally exposed workers. No associated factors of occupational allergy to LFB could be detected.

Short-term effectiveness of an asthma educational program: results of a randomized controlled trial.

Asthma educational programs have been shown to reduce the use of emergency room, frequency of severe asthma attacks and hospitalization. However, its effectiveness in other morbidity parameters and on quality of life has yet to be fully understood. This prospective randomized control trial evaluated the effectiveness of a patient education program in 77 asthmatics according to "Teach Your Patients About Asthma: A Clinicians Guide" (1992). Forty asthmatic patientswere randomly allocated to Group A (usual treatment) and 37 to Group B (usual treatment plus a patient education program). The effectiveness of the educational program was evaluated by comparing morbidity outcomes at baseline and 3 months after initial evaluation. At enrolment, the two groups were not different with regard to age, sex, smoking, asthma severity atopy, FEV1, symptom-free days, use of rescue salbutamol and quality of life. Three months later, subjects in Group B showed a significant improvement in the overall quality of life (p < 0.01) and in the "Symptoms"domain (p < 0.01). None of the other parameters (use of rescue salbutamol, symptom-free days, days absent from work or school, FEV1) showed any significant change. After stratification for asthma severity, only subjects with moderate-to-severe asthma showed a significant improvement inthe overall qualityof life (p < 0.05) and in the "Symptoms" (p < 0.01) and 'Activities" (< 0.05) domains. Moreover, in subjects with moderate-to-severe asthma FEV1 value at the 3rd month of follow-up was higher in Group B than in Group A (p < 0.05). In conclusion, the educational program improved the quality of life in asthratic subjects, mainly in patients with moderate-to-severe asthma.

Reported diagnosis of previous asthma in a sample of the Italian general population.

In this cross-sectional study we describe the prevalence and characteristics of subjects who self-reported a diagnosis of previous asthma in a sample of the Italian general population. We chose a wide age range (3-69 yrs) in order to obtain data over a large spectrum of the population. Interviews were conducted in 1,038 subjects by trained physicians using a modified version of the American Thoracic Society and National Heart & Lung Institute--Division of Lung Disease questionnaire proposed in 1978 (ATS-DLD-78). 791 subjects underwent skin prick tests for 7 common aeroallergens; 422 subjects underwent spirometry and 212 methacholine challenge tests. Cumulative prevalence of asthma was 7.9% (82/1038). Previous asthma (PA) was reported by 29 (35.4%) of the subjects, who said they had been but were no longer asthmatic; 65.5% of these claimed that PA had developed at or before the age of 14 yrs. No significant differences emerged in sex, age, family and personal history of atopy, and size of skin test reaction in subjects with PA compared to those with current asthma (CA). Although the difference was not statistically significant, the latter tended to be lifetime nonsmokers while subjects with PA were more often current smokers. Age at onset of asthma was significantly higher in subjects with CA than in subjects with PA (24.6 +/- 20 yrs vs. 12.0 +/- 15.0 yrs, p = 0.005). Bronchial hyperreactivity was present in 37.5% of subjects with PA, while forced expiratory volume in 1 sec (FEV1) was within normal limits in all. In conclusion, in this sample of the Italian population, PA was reported by about 1/3 of the asthmatic subjects, most of whom were atopic. Lung function was within normal limits in all, but bronchial hyperreactivity persisted in 1/3 subjects.

Prevalence of asthma and rhinitis in Perugia, Italy.

This cross-sectional study evaluated the prevalence of, and risk factors for, asthma and rhinitis in a randomized sample of males and females, aged 0-69 yrs, in Perugia, Italy. To determine the prevalence of asthma and rhinitis, 824 subjects were interviewed by trained physicians using a modified American Thoracic Society and National Heart and Lung Institute-Division of Lung Disease questionnaire proposed in 1978 (ATS-DLD-78). Skin-prick tests were carried out in 667 subjects > or = 3 yrs of age. Age, sex, atopy, smoking, and household pets were considered potential risk factors for the development of asthma and rhinitis. Cumulative prevalences of: asthma was 8.1%; current asthma 5.0%; and rhinitis 15.2%. Positive skin tests were observed in 21.3% of subjects: in 63.4% of the cases of current asthma and in 68.7% of rhinitis cases. The prevalence of asthma and rhinitis was similar in both sexes. Prevalence of current asthma was almost three times higher in childhood than after the age of 10 yrs. Positive skin tests for pollens and house dust mite were the most prevalent risk factors for asthma. Current smoking was inversely associated with prevalence of current asthma possibly because of a self-selecting effect. Household pets were found not to be major risk factors for asthma or rhinitis. In conclusion, prevalence of asthma and rhinitis is a common health problem in the Perugia area, and atopy, particularly pollen sensitivity, is the most important risk factor for the development of asthma and rhinitis.