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Biomedical subjects

A Martinelli

Publications and source records attributed to A Martinelli.

At least 19 recordsLinked to original sources
PubMed2006

Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy.

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800 mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.

Adult↗
PubMed2006

Glass transition and the origin of poly(p-phenylene sulfide) secondary crystallization.

The effect of low temperature cold-crystallization on quenched poly(p-phenylene sulfide) (PPS) amorphous phase behaviour was systematically investigated by differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMTA) over the entire range of the process, from its early stage to the end. For the first time a well resolved double glass transition of partially cold-crystallized samples was evidenced. A T(g) steady increase was observed during the primary crystallization process, due to the reduction of amorphous chain segmental mobility imposed by the growing rigid phase. A shift of the relaxation temperature of about 10 degrees C was recorded at the end of the primary crystallization process. As the secondary crystallization takes place a new glass transition appears at higher temperature. For longer annealing time the lower T(g) disappears while the intensity of the upper one increases. The upper temperature glass transition of semi-crystalline PPS is explained as a consequence of the PPS secondary cold-crystallization process. In the light of the thermal and dynamic mechanical results, an interpretation is given of step-wise double crystallization, evidenced in non-isothermal cold-crystallization experiments carried out at low heating rate and followed by means of FT-IR techniques.

Journal Article↗
PubMed2006

Search for low-allergenic apple cultivars for birch-pollen-allergic patients: is there a correlation between in vitro assays and patient response?

BACKGROUND: Due to the cross-reactivity between Bet v 1 and proteins present in vegetable foods, birch pollen allergic patients frequently develop allergy to fruits and vegetables, mostly apples. Since many apple cultivars exist some of them might contain sufficiently low amounts of Mal d 1 to be tolerated by most allergic patients. OBJECTIVE: To assess whether apple cultivars containing low amounts of Mal d 1 are better tolerated by apple-allergic patients. METHODS: Mal d 1 content was determined in many apple cultivars by ELISA. Selected cultivars containing high (Golden Delicious) or low (Orim, G 198 and Vienna) amounts of Mal d 1 were compared in apple allergic patients both by SPT and oral challenges. RESULTS: The 3 different apple cultivars induced wheals of similar size in most patients. Upon oral challenges no patient reported the total absence of oral symptoms following the ingestion of either high or low allergenic apples. Golden Delicious and G-198 elicited OAS of similar severity 3/7 cases. The 2 cultivars induced significantly more severe symptoms in 2 cases each. CONCLUSION: Allergy to Mal d 1 is characterized by significant inter-patient variability. Moreover, marked inter-apple and intra-apple variability exists. As a consequence, the amount of Mal d 1 in apples classified as containing low concentrations of allergen may be sufficient to induce both clinical symptoms and skin reactivity in birch pollen-allergic patients. The search for low allergenic apples therefore should be continued and extended to other germplasm accessions, be it cultivars, breeding lines or wild species.

Administration, Oral↗
PubMed2006

Peach fuzz contains large amounts of lipid transfer protein: is this the cause of the high prevalence of sensitization to LTP in Mediterranean countries?

BACKGROUND: Allergy to lipid transfer protein (LTP) is quite common in the Mediterranean countries but virtually absent in Northern Europe. The reasons for this latitude-dependent distribution are unclear. One hypothesis is that peach, the primary sensitizer to LTP, may lose in part its allergenicity as a consequence of treatments (handling, brushing, washing, and packaging) preceding marketing in Northern European. Peach surface fuzz might represent a potential vehicle of LTP. OBJECTIVE: To detect LTP in peach fuzz, and compare IgE reactivity to peach fuzz and peel of sera from LTP-allergic patients. METHODS: IgE reactivity to peach peel and peach fuzz extract was measured by ELISA using sera from 2 LTP-allergic PATIENTS. Purified peach LTP was used in inhibition studies. RESULTS: Both sera strongly reacted both to peach peel and fuzz but reactivity to fuzz was stronger than to peel. Pre-absorption of one serum with peach LTP caused an 87% reduction of IgE reactivity to peach fuzz extract. CONCLUSION: Peach fuzz contains large amounts of LTP and might be a potential vehicle of this allergen causing sensitization in genetically predisposed subjects. Fuzz loss during pre-marketing handling of peaches might be at the basis of the geographic differences that characterize allergy to LTP.

Antigens, Plant↗
PubMed2004

Severe immune haemolysis after standard doses of Penicillin.

Summary Penicillin causes immune haemolytic anaemia by the 'drug-adsorption' mechanism and typically occurs after prolonged exposure to large doses of the drug. Withdrawal of the drug is associated with improved red cell survival and gradual cessation of haemolysis. Although this complication is uncommon, it can be potentially serious. An unusual case is described herein. The patient was exposed to a short course (9 days) of standard dose penicillin but suffered acute severe haemolysis about 1 week after cessation of therapy. A high titre anti-penicillin antibody (1 : 512) not cross-reacting with cephalosporins, was demonstrated. The delay in the development of immune haemolysis vis-à-vis penicillin therapy may be due to the patient being immunologically naive to the drug. Penicillin may persist for weeks in circulation, coating red cells and providing continued antigenic stimulation for the development of anti-penicillin antibody.

Aged↗
PubMed2003

3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot) in advanced prostate cancer: results from an Italian, open, multicenter trial.

OBJECTIVES: To determine the endocrine effects, efficacy and tolerability of the 3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot; 'Zoladex' is a trade mark of the AstraZeneca group of companies) in the treatment of patients with advanced prostate cancer. METHODS: Between February 1996 and October 1997, this open, multicentre study enrolled 120 patients with locally advanced (T3/4) or metastatic (N+ or M1) disease, or an increase in prostate-specific antigen (PSA) level after radical prostatectomy. Patients received goserelin acetate 10.8-mg depot every 12 weeks until clinical progression or interruption for adverse events or other reasons. RESULTS: The mean testosterone concentrations were suppressed to the castration range (< or =2 nmol/l) after 4 weeks of treatment and remained suppressed throughout the study. In total, 99/115 (86%) patients had a serum PSA response, and the mean PSA value decreased significantly during treatment (p = 0.006). The mean PSA level at baseline was significantly lower in patients without disease progression compared to those who experienced disease progression (p = 0.0002). Goserelin acetate 10.8-mg depot was well tolerated and there were no injection site reactions. CONCLUSIONS: The goserelin acetate 10.8-mg depot is well tolerated with no injection site reactions. It produces PSA responses and provides reliable suppression of serum testosterone.

Aged↗
PubMed2001

T wave alternans detection during exercise stress test and during dobutamine stress. A comparative study in patients with a recent myocardial infarction.

BACKGROUND: Beat to beat electrical alternans of the T wave (TWA) on the electrocardiogram is a risk marker for the occurrence of life-threatening ventricular tachyarrhythmias. Atrial pacing or exercise are commonly used to increase heart rate to the critical level for TWA detection. However, atrial pacing requires invasive procedures while exercise may cause significant noise on the electrocardiographic recording or may be not performed by a number of patients with cardiac diseases. Dobutamine stress testing is routinely used in post-myocardial infarction patients and may represent an alternative means to detect TWA. However, the comparability of data obtained with exercise and dobutamine needs to be proven. METHODS: We measured TWA during exercise and/or dobutamine stress in 42 patients with a recent myocardial infarction. TWA was detected using a commercially available software while the heart rate was increased to the target range of 105-130 b/min. Each patient performed the two tests in random order with an adequate recovery time in between. RESULTS: The mean level of noise during data acquisition for TWA detection was significantly lower during the dobutamine test than during exercise (1.003 +/- 0.67 vs 1.46 +/- 1.20 microV, p < 0.01). With exercise, 32 (78%) patients had a determinable TWA. Of these, 9 (27%) were TWA positive and 23 TWA negative. In the other patients noise (n = 8) or exercise-induced arrhythmias (n = 1) prevented an appropriate TWA determination. One patient could not exercise. With dobutamine stress, 38 (87%) of the 42 patients studied had a determinable TWA. Arrhythmias prevented TWA determination in the remaining 4 patients. Dobutamine and exercise testing provided comparable proportions of TWA determinability. However, by combining exercise and dobutamine testing, a greater (p = 0.0071) proportion of the patients (41/42, 98% vs 32/42, 76%) had a determinable TWA when compared with exercise alone. A comparative TWA study could be performed in 29 patients who completed both the dobutamine and the exercise stress tests. All 22 patients TWA negative at exercise were so at dobutamine testing also. On the other hand, 5 of the 7 patients TWA positive at exercise were so at dobutamine testing also. Overall, 27 (93%) of the 29 patients in whom internal comparison could be performed showed a concordant result. CONCLUSIONS: Dobutamine testing allows TWA detection with results comparable to those obtained at exercise testing. Combining exercise and dobutamine stress allows TWA determination in most of post-myocardial infarction patients. The present study provides the evidence for a safe and effective TWA determination for risk stratification after myocardial infarction.

Adult↗
PubMed2000

Selective inhibition of human erythrocyte Na+/K+ ATPase by cardiac glycosides and by a mammalian digitalis like factor.

Na+/K+ATPase is a transport membrane protein which contains the functional receptor for digitalis compounds. In this work we compare the inhibition curves of Na+/K+ATPase measured by the inhibition of 86Rb uptake in human red blood cells by cardiac glycosides and by an endogenous digitalis like factor (EDLF) extracted from human newborn cord blood. The curves of Na+/K+TPase inhibition show a monophasic shape for ouabain, strophantidin, digitoxin, proscillaridin and EDLF whereas a biphasic shape for ouabagenin, digoxin, digoxigenin and digitoxigenin. All the drugs are potent inhibitors of erythrocyte Na+/K+ATPase with an IC50 ranging from 1.8 x 10(-9) M to 1.4 x 10(-11) M for the higher affinity binding site and from 1.8 x 10(-6) M to 5.5 x 10(-9) M for the lower affinity site. Digitoxigenin is the most active showing the higher active site at 1.4 x 10(-11) M. Ouabain and digoxin have higher affinity compared with their corresponding genins, while digitoxigenin shows a binding site with higher affinity than the respective cardiac glycosides. The increased affinity of the drugs to Na+/K+ATPase may be related to a lipophilic region in correspondence of the carbons 10, 9, 11, 12, 13 of the steroid nucleus, situated in the opposite side with respect of the C-OH-14. The comparison of the inhibition curves and the HPLC profile of newborn EDLF and of the investigated cardenolides suggest that EDLF may be a compound identical or very similar to ouabain.

Cardiac Glycosides↗
PubMed2000

A novel class of highly potent and selective A1 adenosine antagonists: structure-affinity profile of a series of 1,8-naphthyridine derivatives.

A series of 1,8-naphthyridine derivatives (12-36), bearing a phenyl group in position 2 and various substituents in positions 4 and 7, were synthesized in an attempt to obtain potent, selective antagonists for the A1 adenosine receptor subtype. The compounds were tested to evaluate their affinity for A1 compared with A2A and A3 adenosine receptor subtypes. In binding studies in bovine brain cortical membranes, most of the compounds showed an affinity for A1 receptors in the low nanomolar range and two in the subnanomolar range with an interesting degree of A1 versus A2A and A3 selectivity. Comparison of the 4-substituted derivatives indicated that 4-OH substitution, with a 4-quinoid structure, causes an increase in the A1 and A2A affinity and generally also in A1 selectivity. The kind of substitution in position 7 can greatly modulate the affinity: the most interesting substituents in this position seemed to be electron-withdrawing groups; in particular the 7-chloronaphthyridine 25d showed a remarkable selectivity (A2A/A1 ratio of 670, A3/A1 ratio of 14,000) associated with a higher A1 affinity (Ki = 0.15 nM). NMR studies on these compounds 12-36 indicated that the 4-OH-substituted ones prefer the tautomer in which the oxygen in position 4 is in the quinoid form and the nitrogen in position 1 is protonated. Theoretical calculations are in agreement with the NMR data.

Adenylyl Cyclases↗
PubMed2000

Synthesis, inhibitory activity towards human leukocyte elastase and molecular modelling studies of 1-carbamoyl-4-methyleneaminoxyazetidinones.

Some monocyclic beta-lactam derivatives of type 3 (MAOAs) in which the leaving group (LG) on the C(4) is a methyleneaminoxy moiety, were synthesised and tested in vitro and in vivo for their inhibitory activity towards human leukocyte elastase (HLE). Some compounds showed an appreciable in vitro inhibitory activity against this enzyme. Effects on the anti-HLE activity due to the nature of the substituents R and R(1) present on their LG were observed and rationalised by means of molecular modelling techniques. The results of in vivo pharmacological tests indicated that MAOAs, while showing an inhibitory activity on the haemorrhage induced by HLE, did not exhibit any effects due to the R and R(1) substituents.

Animals↗
PubMed2000

Synthesis and beta-blocking activity of (R,S)-(E)-oximeethers of 2, 3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2, 3-b]pyridine:potential antihypertensive agents - part IX.

The synthesis of oximeethers of 2,3-dihydro-1,8-naphthyridine and 2, 3-dihydrothiopyrano[2,3-b]pyridine is described. These compounds exhibit a selective beta-blocking activity, with a selectivity towards beta(2)-receptors. Groups in the N(1) position giving rise to a considerable steric hindrance led to a higher beta(2)-blocking selectivity, whereas groups creating a moderate hindrance caused a weak but significant decrease in beta(2)-antagonist potency. Substitution of the N(1)-R group with a sulfur atom led to compounds possessing beta(1)-, beta(2)- and beta(3)-blocking properties. Compounds 9c(1) and 10a(1) showed a beta(3)-antagonist activity slightly lower than that of propranolol.

Adipose Tissue↗
PubMed1999

Thermodynamics of the alkaline transition of cytochrome c.

The apparent equilibrium constant (Kapp) of the alkaline transition (AT) of beef heart cytochrome c, obtained from pH titrations of the current intensities in cyclic voltammetry experiments, has been measured as a function of the temperature from 5 to 65 degrees C, at different ionic strength (I = 0.01-0.2 M). The temperature profile of the pKapp values is biphasic and yields two distinct sets of DeltaH degrees 'AT and DeltaS degrees 'AT values below and above approximately 40 degrees C. In the low-temperature range, the process is endothermic and is accompanied by a small positive entropy change, while at higher temperatures it becomes less endothermic and involves a pronounced entropy loss. The temperature dependence of the transition thermodynamics is most likely the result of the thermal transition of native ferricytochrome c from a low-T to an high-T conformer which occurs at alkaline pH values at a temperature comparable with above (Ikeshoji, T., Taniguchi, I., and Hawkridge, F. M. (1989) J. Electroanal. Chem. 270, 297-308; Battistuzzi, G., Borsari, M., Sola, M., and Francia, F. (1997) Biochemistry 36, 16247-16258). Thus, it is apparent that the transitions of the two native conformers to the corresponding alkaline form(s) are thermodynamically distinct processes. It is suggested that this difference arises from either peculiar transition-induced changes in the hydration sphere of the protein or to the preferential binding of different lysines to the heme iron in the two temperature ranges. Extrapolation of the Kapp values at null ionic strength allowed the determination of the thermodynamic equilibrium constants (Ka) at each temperature, hence of the "true" standard thermodynamic parameters of the transition. The pKa value at 25 degrees C was found to be 8.0. A pKapp value of 14.4 was calculated for the alkaline transition of ferrocytochrome c at 25 degrees C and I = 0.1 M. The much greater relative stabilization of the native state in the reduced as compared to the oxidized form turns out to be almost entirely enthalpic in origin, and is most likely due to the greater affinity of the methionine sulfur for the Fe(II) ion. Finally, it is found that the Debye-Hückel theory fits the ionic strength dependence of the pKapp values, at least qualitatively, as observed previously for the ionic strength dependence of the reduction potential of this protein class. It is apparent that the increase in the pKapp values with increasing ionic strength is for the most part an entropic effect.

Animals↗
PubMed1999

Synthesis and HIV-1 inhibitory properties of new tetrahydrobenzoquinazolinedione and tetrahydrobenzocycloheptenuracil derivatives and of their thioxo analogues.

Some new tetrahydrobenzoquinazolinediones 2a-4a, tetrahydrobenzocycloheptenuracils 5a, 6a and their thioxo analogues 2b-6b were synthesized within a project aimed at obtaining new HIV-1 tricyclic inhibitors whose scaffold includes a pyrimidine and a phenyl ring, which are present in various HIV-1 non-nucleoside inhibitors. Among the tetrahydrobenzoquinazolinediones 2a-4a, compounds 3a and 4a, in which the tricyclic system is respectively in an angular or linear arrangement, proved to possess a HIV-1 inhibitory activity which was in the micromolar range, while compound 2a, in which the tricyclic system is in the angular arrangement opposite to that of 3a, was found to be completely inactive. As regards the tetrahydrobenzocycloheptenuracil derivatives (5a and 6a), only 5a showed an inhibitory activity similar to that of 3a and 4a. Furthermore, all thioxo analogues 2b-6b were found to be devoid of any activity.

Anti-HIV Agents↗
PubMed1998

N-n-Propyl-substituted 3-(dimethylphenyl)piperidines display novel discriminative properties between dopamine receptor subtypes: synthesis and receptor binding studies.

3-Phenylpiperidines (PPEs) have been thoroughly investigated in view of their interesting dopaminergic activity, and the N-n-propyl substitution has been suggested as the most effective among several PPEs differently substituted on the phenyl ring. In previous studies, we found that the dimethyl substitution on the phenyl ring of N-unsubstituted PPEs provided compounds active toward alpha2-adrenergic receptors (alpha2-ARs), which proved to possess interesting selectivity properties. The high degree of homology between the binding domains of alpha2-ARs and D4-dopaminergic receptors (D4-DARs) prompted us to verify whether this kind of substitution on the aromatic ring might prove to be active against retinal DARs of the D4 subtype. On the basis of these premises, we synthesized the dimethylphenyl-substituted PPEs 4a-f, in which an n-propyl chain is present on the aminic nitrogen. Radioligand binding assays on bovine retina and striatum membranes for D1-like and D2-like DARs indicated that PPEs 4a, 4b, and 4f possess a high affinity and selectivity for the D4-DAR subtype of bovine retina.

Animals↗
PubMed1998

Synthesis and aldose reductase inhibitory activity of new N-(benzyloxy) glycine derivatives.

This paper reports the synthesis and aldose reductase (AR) inhibitory properties of some N-(benzyloxy) glycine derivatives (compounds 2-6), structurally related to the previously described N-(aroyl)-N-(arylmethyloxy) glycines A which had proved to possess an appreciable AR inhibitory activity. In compounds 2-5, spacers of different lengths and degrees of rigidity were inserted between the phenyl ring and the carbonyl group of type A derivatives; compound 6 differs from the most active type A derivative (compound 1) in the replacement of the methoxy moiety in the para position of the benzoyl side-chain with a group with different electronic characteristics, such as the trifluoromethyl moiety. Biological results indicated that among compounds 2-5 only derivative 3, which presents a CH2CH2 spacer between the phenyl and the carbonyl moiety, proved the possess AR inhibitory properties analogous to those of 1, while all the other compounds proved to be devoid of any significant activity. Furthermore, compound 6 showed an inhibitory activity about 3 times lower than that of 1.

Aldehyde Reductase↗
PubMed1998

Radiological findings when very small lung volumes are irradiated in breast and chest wall treatment.

Acute pneumonitis following breast irradiation is a rare and transient phenomenon that can be easily managed by drugs. The aim of this study is to evaluate late sequelae on lung, after postoperative radiotherapy (RT) for breast cancer. We were concerned with investigating late radiological findings when very small lung volumes are involved in the irradiated volume. We studied 28 consecutive patients. They underwent clinical examination and all staging procedures before surgery, evaluation of pulmonary function with spirometry, postoperative chest x-ray and high resolution computed tomography (HRCT) of the lung before RT. Clinical examinations were usually performed every 3 months after RT. A second chest x-ray, HRCT and spirometry were carried out after nearly 7 months from the end of RT. We estimated the irradiated lung volume by measuring the area of the lung surface enclosed by the 50% isodose (LA50) in each profile. We found a significant correlation between LA50 and the score of radiological findings after RT. No correlations were found between other factors (i.e., adjuvant chemotherapy, age, weight, smoking) and lung fibrosis. No woman developed radiation pneumonitis syndrome or respiratory symptoms. Our results indicate that irradiation of the breast and/or chest wall is well tolerated if treatment planning is done accurately. The fibrosis likelihood is strongly correlated to the irradiated lung volume. The use of tangential fields limits radiological changes that can be detected only by HRCT examination and are not associated with clinical symptoms.

Adult↗
PubMed1998

Synthesis and beta-adrenergic properties of (Z)-N-[3-(alkylamino)-2-hydroxypropylidene](aryl-methyloxy)amines: effects of the configuration around the methyloxyiminomethyl (MOIM) double bond on the biopharmacological properties of MOIM-type beta-blocking agents.

The N-isopropyl- (3a-g) and N-tert-butyl-substituted (4a-g) (Z)-N-(3-(amino)-2-hydroxypropylidene)-(arylmethyloxy)amines were synthesized in order to compare their beta 1- and beta 2-adrenergic properties with those of their previously studied corresponding analogues with the E configuration (1a-g and 2a-g). Compounds 3 and 4 were tested for their affinity for beta 1-a and beta 2-adrenoceptors by radioligand binding experiments, and the compounds with the highest affinity were also assayed for their activity towards the same types of beta-adrenoceptors by functional tests on isolated preparations. The Z-methyloxyiminomethyl (Z-MOIM) compounds 3 and 4 proved to possess, on the whole, affinity (Ki) and activity (PIC50) indices similar to those of the E isomers 1 and 2, thus indicating that for the MOIM-type beta-adrenergic antagonists 1-4, the type of configuration around the MOIM double bond does not have any appreciable effect either on the affinity or on the activity towards beta-adrenoceptors. These results are rationalized on the basis of the steric and electronic analogies existing between the MOIM groups of 1-4 in the two types of configurations (E and Z).

Adrenergic beta-Antagonists↗