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Biomedical subjects

J Sastre

Publications and source records attributed to J Sastre.

At least 19 recordsLinked to original sources

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats.

BACKGROUND AND PURPOSE: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor alpha production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. EXPERIMENTAL APPROACH: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. KEY RESULTS: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. CONCLUSIONS AND IMPLICATIONS: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans.

Acute Disease↗

Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens.

Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevity-associated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes. Estrogen administration, however, has serious undesirable effects and of course, cannot be administered to males because of its powerful feminizing effects. Thus, we tested the effect of genistein, a phytoestrogen of high nutritional importance whose structure is similar to estradiol, on the regulation of the expression of antioxidant, longevity-related genes and consequently on oxidant levels in mammary gland tumour cells in culture. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed.

Animals↗

Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma.

BACKGROUND: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.

Administration, Inhalation↗

IgE reactivity to latex allergens among sensitized healthcare workers before and after immunotherapy with latex.

BACKGROUND: New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen-specific immunotherapy (IT). METHODS: Twenty-four healthcare workers (HCWs) -- patients included in a latex IT study -- were analysed, 16 in active treatment and eight in placebo. Sera were obtained at baseline and after 6 months of IT and analysed with immunoblotting and CAP System with eight single recombinant latex allergens (rHev b 1, 3, 5, 6.01, 8, 9, 10, 11, and a mix of rHev b1, 5, 6.01 and 8). RESULTS: After IT with latex, three patients in the active treatment group had new IgE sensitizations, one to Hev b 5, one to Hev b 11 and another to Hev b 6.01. No other significant variation in mean of specific IgE to latex or recombinant allergens were observed in patients who received placebo or active treatment. A significant (P = 0.012) negative correlation (-0.72) was observed between maximal tolerated dose and specific IgE to Hev b 6.01 at baseline. After IT, immunoblot analysis demonstrated a significant increase in IgE binding in a band of approximately 22 kDa (P = 0.032) that may correspond to Hev b 6.01. New or more intense bands appeared in seven patients of the active group, while in three subjects a reduction was observed. CONCLUSIONS: Hev b 6.01 seems to be the most relevant latex allergen in HCWs. New or more intense IgE binding to latex allergenic components occurs during latex immunotherapy. However, the levels of specific IgE against these new components are low and do not seem to have clinical relevance.

Allergens↗

Bronchial responsiveness to bakery-derived allergens is strongly dependent on specific skin sensitivity.

BACKGROUND: Quantitative relationships between immunological reactivity, non-specific bronchial responsiveness and bronchial responsiveness to allergens have scarcely been investigated in occupational asthma. METHODS: We assessed the above relationships in 24 subjects with baker's asthma. The skin endpoint titration to bakery allergens as a measure of immunological reactivity, together with the methacholine PC20 and allergen PC20 during early asthmatic reaction were determined. RESULTS: All patients had positive skin tests to some bakery allergens (wheat and rye flour, soybean flour, fungal enzymes and egg white proteins) and bronchial hyperresponsiveness to methacholine. Specific inhalation challenge (SIC) tests were performed with aqueous allergen extracts of cereal flour (n = 14), soybean (n = 8), baking enzymes (n = 12), and egg white proteins (n = 8) in sensitized workers. A positive asthmatic reaction was observed in 84% of the inhalation challenges. SIC elicited isolated early asthmatic reactions in 62%, dual reactions in 32% and isolated late reactions in 5%. Multiple linear regression analysis showed allergen PC20 as a function of skin sensitivity to allergen and methacholine PC20, yielding the following highly significant regression formula: log-allergen PC20 = 0.18 + 0.99 log(skin sensitivity) + 0.343 log(methacholine PC20) (r = 0.89, P < 0.001). This formula predicted allergen PC20 to within one double concentration in 67%, to within two double concentrations in 85% and within three double concentrations in 97%. CONCLUSION: The main determinant of bronchial responsiveness to allergen in patients with baker's asthma is the degree of sensitization to occupational allergens as determined by skin reactivity, modulated to a lesser extent by non-specific bronchial hyperresponsiveness.

Adult↗

Occupational asthma due to piperazine citrate.

BACKGROUND: Piperazine is a secondary heterocyclic amine that may give rise to occupational asthma of uncertain mechanism. METHODS: We report on a 42-year-old woman, a process operator in a chemical factory, who developed work-related symptoms of rhinitis and asthma upon exposure to piperazine citrate. She remained symptom free during holidays and days off work. RESULTS: Skin prick test with piperazine citrate was positive. Specific inhalation challenge with piperazine citrate at a concentration of 5 mg/m3 for 30 minutes elicited an isolated late asthmatic response. Airway hyperresponsiveness to methacholine significantly increased 3 hours after the piperazine challenge, preceding the late asthmatic response. CONCLUSION: This patient had developed occupational asthma caused by piperazine, as confirmed by the specific inhalation challenge test, possibly due to an immunological mechanism.

Adult↗

Effect of the cationic composition of sorption solution on the quantification of sorption-desorption parameters of heavy metals in soils.

We obtained the sorption isotherms of Cd, Cu, Pb and Zn in clay, clay saline and organic soils. The distribution coefficients (K(d)) were determined in 0.02 eq l(-1) CaCl(2) and in a solution that simulated the soil solution cationic composition. The K(d) values greatly varied with the composition of the sorption solution and the initial metal concentration. The sorption experiments were complemented with the quantification of the extractable metal, to estimate the reversibility of metal sorption. The extraction yields depended on the metal-soil combination, and the initial metal concentration, showing no correlation with previous K(d) values. The effect of the solution composition in mobility predictions was estimated through a Retention Factor, defined as the ratio of the K(d) versus the extraction yield. Results showed that risk was over- or underestimated using the CaCl(2) medium in soils with a markedly different soil solution composition.

Aluminum↗

Double-blind study of tolerability and antibody production of unmodified and chemically modified allergen vaccines of Phleum pratense.

BACKGROUND: The physicochemical modification of allergen extracts provides a chance for administering higher doses of allergen vaccines. OBJECTIVE: To evaluate the safety of a chemically modified (depigmented-glutaraldehyde polymerized) therapeutic vaccine of Phleum pratense administered at doses that are 10 times higher than those used in clinical practice, in comparison with conventional doses of the corresponding non-modified alum-adsorbed vaccine. MATERIALS AND METHODS: The design of the study was randomized, double-blind, parallel and included two groups of patients. Twenty-three patients were treated weekly during nine visits for the build-up phase, followed by two weekly maintenance doses (a total of 11 injections per patient). Twelve patients received a vaccine containing the standardized unmodified extract, at a maximum concentration of 308.5 mcg of freeze dried material/mL (Group A). Eleven patients received a standardized modified allergen extract (Group B). The maximum dose used was 2400 mcg/mL. Safety was evaluated recording all adverse events. Skin test results and specific antibody levels were evaluated at the beginning and at the end of the study. RESULTS: Group A patients experienced three local immediate (two clinically irrelevant and one with a diameter>5 cm) and 18 delayed reactions (15 irrelevant and three with a diameter>10 cm), while Group B experienced six local immediate and 12 delayed reactions (all clinically irrelevant). Nine Group A patients experienced 12 systemic reactions (one immediate of grade 1, one of grade 2; and one delayed of grade 1; four of grade 2 and three of grade 3), while Group B patients experienced one immediate systemic reaction of grades 1, and 1 delayed reaction of grade 1. CONCLUSIONS: The modified extract of P. pratense is safe to treat sensitive patients, even at concentrations that are 10 times higher than those regularly administered in clinical practice. The majority of the local reactions were clinically irrelevant. No systemic reactions of grade 2, 3 or 4 were reported using the modified extract.

Adult↗

Isolation, cloning and allergenic reactivity of natural profilin Cit s 2, a major orange allergen.

BACKGROUND: Orange is among the most widely consumed fruits, and among the plant food sources causing allergic reactions according to popular perception. However, its relevant allergenic components are virtually unknown. Profilin is a well-defined minor plant panallergen, showing prevalences around 30% in fruits and vegetables. METHODS: Twenty-three orange-allergic patients were studied. Natural orange profilin, named Cit s 2, was purified by affinity chromatography and characterized by N-terminal amino acid sequencing, matrix-assisted laser desorption/ionization mass spectrometry analysis and isolation of its coding cDNA. Reactivity to Cit s 2 was analyzed in vivo by skin prick tests (SPT) and in vitro by IgE immunodetection, specific IgE determination in individual sera and enzyme-linked immunosorbent assay-inhibition assays. RESULTS: The N-terminal amino acid sequence and molecular mass of natural Cit s 2, both fully in agreement with the complete amino acid sequence deduced from its coding cDNA, demonstrated its profilin nature. An unexpectedly high reactivity to Cit s 2 was found in vivo (78% of positive SPT responses) and in vitro (87% of sera from orange allergic patients had specific IgE to Cit s 2). The purified allergen inhibited around 50% of the IgE binding to an orange pulp extract. CONCLUSION: Orange profilin Cit s 2, unlike other plant food profilins, is a major and highly prevalent allergen.

Adolescent↗

Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis.

BACKGROUND: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). AIM: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren's syndrome (SS). SUBJECTS: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). METHODS: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. RESULTS: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. CONCLUSIONS: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

Adolescent↗

Anaphylaxis caused by cauliflower.

BACKGROUND: Cauliflower is a vegetable belonging to the family Cruciferae, genus Brassica, var. Botrytis. METHODS: We report the case of a 70 year-old man who suffered an acute episode consisting of oropharyngeal itching, facial and hand swelling, dyspnea and severe bronchospasm within a few minutes after eating vegetable paella containing cauliflower, green beans, red and green pepper. Due to the severity of the reaction he needed treatment in the emergency room. RESULTS: Skin prick tests with common aeroallergens were positive to Cupressus, Platanus and grass pollen. A strong skin prick test response was obtained with cauliflower and peach lipid transfer protein. Skin prick test with rice, green beans and pepper were negative. Specific IgE determinations were positive to cabbage and cauliflower, and negative to mustard. CONCLUSIONS: The clinical history and the results of the allergologic work-up point out to this patient having experienced an IgE-mediated anaphylactic reaction to cauliflower. To the best of our knowledge, this is the first case report of anaphylaxis due to cauliflower.

Aged↗

Immunological studies in a case of hydrochlorothiazide-induced pulmonary edema.

A case of acute onset non-cardiogenic pulmonary edema induced by hydrochlorothiazide (HCT) is presented. Rapid recovery was obtained with supportive therapy. Leukopenia was evident during the acute phase, with rapid recovery parallel to the clinical improvement, suggesting pulmonary sequestration of granulocytes. Immunological studies including lymphocyte stimulation test with HCT and measurement of specific IgG and IgE to HCT elicited negative results. The pathogenesis of this type of reaction remains to be elucidated.

Antihypertensive Agents↗