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Biomedical subjects

D Giordano

Publications and source records attributed to D Giordano.

At least 19 recordsLinked to original sources

Airborne pollen concentrations and the incidence of allergic asthma and rhinoconjunctivitis in northern Italy from 1992 to 2003.

BACKGROUND: Aeroallergens and the environment play an important role in the pathogenesis of respiratory allergies. In a 12-year study carried out in Northern Italy (geographic area of Parma), the effects of airborne pollen and meteorological conditions on the incidence of allergic asthma and rhinoconjunctivitis were evaluated. PATIENTS AND METHODS: Among 9,060 subjects examined for respiratory pathologies at our Allergy Unit, Parma Hospital, Italy, from 1992 to 2003, only 1,054 positive to only one type of inhalant allergen in the skin prick test were studied, to avoid bias of cross-reactivity. Allergy and clinical aspects were compared with the duration of the pollination period, and peaks and total concentrations of airborne pollen. RESULTS: Our data showed a significantly growing trend of allergy to mites, pets and birch pollen and a significant increase in asthma, and a significantly decreasing trend of positive reactions to grasses and a decrease in rhinoconjunctivitis. At the same time, there was a significant decrease in total pollen counts, concentration peaks and pollination period of grasses. A significant increase was only observed in ragweed and ash-olive total and peak pollen concentrations. CONCLUSIONS: Significant correlations between the increasing incidence in asthma and allergy to mites, pets and birch pollen are shown. The decrease in the total pollen count and concentration peaks of grass pollen was correlated to the decreasing trend of rhinoconjunctivitis. The trend of increasing concentrations of ash-olive and ragweed pollen was not accompanied by an increase in the related allergy.

Adult↗

Adiponectin and insulin resistance in early- and late-onset pre-eclampsia.

OBJECTIVE: To evaluate the importance of adiponectin and insulin resistance in early- and late-onset pre-eclampsia. DESIGN: A nested case-control study in 72 pregnant women who participated in the first-trimester Down-syndrome-screening programme and who delivered at our hospital. SETTING: University Hospital, Department of Obstetrics and Gynecology. POPULATION: Pregnant women: 36 women with pre-eclampsia of which 20 late onset and 16 early onset were compared with 36 uncomplicated pregnancies who delivered at term. METHODS: In all the women, insulin resistance was calculated by the homeostasis model assessment ratio (HOMA-IR) and plasma adiponectin was determined using an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Insulin resistance and adiponectin concentration. RESULTS: First-trimester plasma adiponectin mean levels in the whole pre-eclampsia group were significantly lower than that in the control group (8.4 +/- 3.3 versus 14.8 +/- 4.6 microgram/ml; P < 0.001), whereas first-trimester mean HOMA-IR values were significantly higher in the pre-eclampsia group than that in the control group (2.0 +/- 1.1 versus 1.0 +/- 0.4; P= 0.01). Plasma adiponectin concentrations at delivery in the pre-eclampsia group were significantly higher than that in the control group (9.2 +/- 3.7 versus 7.8 +/- 2.6 microgram/ml; P= 0.04). First-trimester plasma adiponectin mean concentrations in the late-onset subgroup were significantly lower compared with the concentrations in early-onset subgroup (6.2 +/- 1.4 microgram/ml versus 11.1 +/- 3.2 microgram/ml; P < 0.001), and there was a significant difference in adiponectin plasma values only between women in the late-onset pre-eclampsia group versus those in the control group (P < 0.001). First-trimester mean HOMA-IR values were significantly higher in the late-onset subgroup compared with that of the early-onset subgroup (2.5 +/- 1.3 versus 1.3 +/- 0.3; P= 0.02), and there was a significant difference only between the control group versus the late-onset subgroup (P= 0.001). CONCLUSIONS: First-trimester adiponectin and HOMA-IR values seem to select two completely different populations: early- and late-onset pre-eclampsia, which might suggest a different pathogenesis.

Adiponectin↗

An endogastric capsule for measuring tumor markers in gastric juice: an evaluation of the safety and efficacy of a new diagnostic tool.

BACKGROUND: In gastric juice, high levels of the carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9) have been found to correlate with precancerous lesions and gastric cancer. So far, sampling of gastric juice has required upper endoscopy. In place of this invasive procedure, we investigated a new tool for the quantitation of tumor markers in gastric juice. MATERIALS AND METHODS: The study population consisted of healthy controls and consecutive subjects with suspected gastric cancer or dyspepsia/epigastric distress. Patients were asked to swallow a small gelatine capsule (14 mm in length and 5 mm in diameter) containing a pierced plastic cover and surrounding a piece of absorbent paper. The capsule was left in the gastric cavity for 60 min to allow saturation of the absorbent paper with gastric juice. A 45-50 cm length of nylon thread connected to the inner capsule was used to remove the device from the gastric cavity. After processing the absorbent paper for radioimmunoassay, CEA and CA 19-9 levels were correlated to the findings of upper endoscopy and biopsies of gastric mucosa or suspected lesions. RESULTS: The endogastric capsule did not cause any side-effects and 62 participants were fully compliant to the procedure. Assessable gastric juice samples were taken from 23 patients with gastric cancer, 15 patients with intestinal metaplasia or dysplasia, 12 patients with gastritis and 12 controls without gastric diseases. In the 12 samples of gastric juice from control patients, mean values of CEA and CA 19-9 were 1.1 +/- 0.9 ng/ml and 16 +/- 7.5 ng/ml, respectively. The mean levels of both markers were found to increase according to the severity of gastric lesions and in patients with cancer, mean CEA and CA 19-9 levels were 513 +/- 627 ng/ml and 545 +/- 510 ng/ml, respectively. Patients with precancerous lesions and cancer showed higher levels of CEA and CA 19-9 than patients with normal findings or gastritis (P <0.001). CONCLUSIONS: The endogastric capsule is a simple, non-invasive tool for the measurement of CEA and CA 19-9 levels in gastric juice. These values may discriminate between normal or minor pathologic changes and precancerous lesions or carcinomas. Further investigations are warranted, since this may represent a new method for gastric cancer screening.

Adolescent↗

Computing DIT from energy expenditure measures in a respiratory chamber: a direct modeling method.

The possibility of computing Diet Induced Thermogenesis (DIT) is an important feature of metabolic investigations. However, methodological problems have affected the determination of DIT in the indirect calorimetric chamber. DIT has been commonly estimated by regressing energy expenditure on a measure of physical activity. Although used for many years as the only feasible approach to calculate DIT in a respiratory chamber, this traditional method has been criticized because of an apparent underestimation of the DIT, but no alternative method has been suggested so far. The present work proposes to estimate DIT directly by means of a mathematical model. This approach also allows to simultaneously estimate other parameters, namely resting energy expenditure (REE), physical activity (PA) and physical exercise (PE).

Adult↗

Safety of inhalant allergen immunotherapy with mass units-standardized extracts.

BACKGROUND: Allergen-specific immunotherapy (SIT) is an effective treatment for patients with respiratory allergies. However, subcutaneous injection of allergens can provoke systemic side-effects. OBJECTIVE: This study was carried out to determine the incidence and risk factors o fsystemic reactions caused by SIT treatment, using extracts of different inhalant allergens, adsorbed in aluminium hydroxide and biologically standardized with the major allergens quantified in mass units. METHODS: Five hundred and fifty-five subjects with allergic rhinitis and/or asthma were evaluated on clinical history and skin prick test (SPT) reactions to common inhalant allergens. Subcutaneous SIT was administered to all patients, according to the suggested precautionary guidelines and administration schedule. Patients were treated with house dust mite, grass pollen, Parietaria judaica pollen and olive pollen extracts, each receiving one or two extracts. RESULTS: A total of 36,359 injections were administered in the 555 patients. We observed 34 episodes of serious systemic side-effects (0.093% of all injections), in 29 patients (5.2% of all patients), and no fatalities. About 55% of patients reported mild rhinitis and asthma. The majority (59%) of the serious systemic reactions (SSR), and all the anaphylactic reactions, were immediate (i.e. occurred within 30 min after the injection). Asthmatic subjects were at higher risk of SSR than patients with rhinitis (P = 0.01). Most of the side-effects observed occurred during the dose-increase phase (P < 0.05). There was no association of SSR with age, gender, SPT reactivity or allergen type. CONCLUSION: SIT performed in patients with respiratory allergies by specialized staff with the allergen extracts studied, standardized in mass units, provoked a low rate of SSR. The significant risk factors for systemic reactions were asthma and the build-up period.

Adolescent↗

Nonuniqueness of the two-temperature Saha equation and related considerations.

The present paper contains considerations relative to the long debated thermodynamic derivation of two-temperature Saha equations. The main focus of our discourse is on the dependence of the multitemperature equilibrium conditions on the constraints imposed on the thermodynamic system. We also examine the following key issues related to that dependence: correspondence between constraints and equilibrium-equation forms that have appeared in the literature; presumed dominance of the free-electron translational temperature in the two-temperature expression of the equilibrium constant of the ionization reaction A <--> A++e(-); disagreement between the derivation methods based on, respectively, the extended second law of classical thermodynamics and axiomatic thermodynamics; and plausibility of the existence of entropic constraints.

Journal Article↗

Expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in mouse tissues and cell lines using an antibody against the enzyme amino-terminal domain.

We have produced a polyclonal antibody that specifically recognizes cGMP-binding cGMP-specific phosphodiesterase (PDE5). The antibody was raised in rabbit using as immunogen a fusion protein, in which glutathione S-transferase was coupled to a 171 amino acid polypeptide of the N-terminal region of bovine PDE5. The antibody is able to immunoprecipitate PDE5 activity from mouse tissues and neuroblastoma extracts while it has no effect on all other PDE isoforms present in the extracts. PDE5 activity recovered in the immunoprecipitates retains its sensitivity to specific inhibitors such as zaprinast (IC(50)=0.6 microM) and sildenafil (IC(50)=3.5 nM). Bands of the expected molecular mass were revealed when solubilized immunoprecipitates were analysed in Western blots. The antibody selectively stained cerebellar Purkinje neurones, which are known to express high levels of PDE5 mRNA. Western blot analysis of mouse tissues revealed the highest expression signal in mouse lung, followed by heart and cerebellum, while a lower signal was evident in brain, kidney and a very low signal was present in the liver. In the hybrid neuroblastoma-glioma NG108-15 cells the antibody revealed a high PDE5 induction after dibutyryl-cAMP treatment.

3',5'-Cyclic-GMP Phosphodiesterases↗

Replacement of an NH(3) by an iminoether in transplatin makes an antitumor drug from an inactive compound.

To investigate the modifications of antitumor activity and DNA binding mode of transplatin after replacement of one nonleaving group NH(3) by an iminoether group, trans-[PtCl(2)(Z-HN=C(OMe)Me)(NH(3)] and trans-[PtCl(2)(E-HN=C(OMe)Me)(NH(3)] complexes (differing in the Z or E configuration of iminoether, and abbreviated mixed Z and mixed E, respectively), have been synthesized. In a panel of human tumor cell lines, both mixed Z and mixed E show a cytotoxic potency higher than that of transplatin, the mean IC(50) values being 103, 37, and 215 microM, respectively. In vivo mixed Z is more active and less toxic than mixed E in murine P388 leukemia and retains its efficacy against SK-OV-3 human cancer cell xenograft in nude mice. In the reaction with naked DNA, mixed Z forms monofunctional adducts that do not evolve into intrastrand cross-links but close slowly into interstrand cross-links between complementary guanine and cytosine residues. The monofunctional mixed Z adducts are removed by thiourea and glutathione. The interstrand cross-links behave as hinge joints, increasing the flexibility of DNA double helix. The mixed Z, transplatin, and cisplatin interstrand cross-links, as well as mixed Z monofunctional adducts are not specifically recognized by HMG1 protein, which was confirmed to be able to specifically recognize cisplatin d(GpG) intrastrand cross-links. These data demonstrate that the DNA interaction properties of the antitumor-active mixed Z are very similar to those of transplatin, thus suggesting that clinical inactivity of transplatin could not depend upon its peculiar DNA binding mode.

Animals↗

[Traumatic rupture of the aortic isthmus. Our experience with 23 cases].

BACKGROUND: Traumatic rupture of the aortic isthmus is a highly lethal lesion. Controversy currently exists regarding the best management of the lower body circulation system during repair of an acute aortic transsection. The aim of this study was to evaluate our results using different methods of distal aorta perfusion in order to prevent ischemia of the spinal cord. METHODS: Between October 1987 and October 1999, 23 patients (20 males, 3 females, mean age 28 years) with rupture of the thoracic aorta underwent surgical repair; 18 of these were acute ruptures and 5 post-traumatic pseudoaneurysms. RESULTS: All cases of rupture were associated with violent, sudden deceleration and in all but one subject it was due to a traffic accident. Twenty patients had severe associated lesions involving the cranium, abdomen, thorax or leg fractures. The operation was performed with a left postero-lateral thoracotomy in all but one case which underwent sternotomy (the patient with an associated lesion of the distal part of the arch). In 1 patient repair was accomplished using simple aortic cross-clamping, in another with total cardiopulmonary bypass, deep hypothermia and cardiac arrest and in 4 cases with partial cardiopulmonary bypass (1 left atrium-femoral artery and 3 femoro-femoral bypass). Seventeen patients were treated using the centrifugal pump (Bio-Medicus) for left atrium-femoral artery bypass. The perioperative mortality was 8.6%, including 2 patients operated in cardiogenic shock. In the 21 surviving patients the postoperative period was free from any cardiovascular complications, with no cases of paraplegia. There were no late deaths (mean follow-up 4 years) and all patients are in good clinical conditions. CONCLUSIONS: These results indicate that the outcome mainly depends on preoperative clinical conditions, associated lesions and the timing of the operation. We conclude that the Bio-Medicus centrifugal pump is a simple and safe means of perfusing the lower body, kidney, and spinal cord without heparinization in a patient with multiple injuries.

Adolescent↗

cAMP-dependent induction of PDE5 expression in murine neuroblastoma cell differentiation.

The present study demonstrates, in both hybrid NG108-15 and mouse neuroblastoma N18TG2 cells, the presence and regulation of PDE5 mRNA during cell differentiation. PDE5 cDNA probes in Northern blot analysis recognize a approximately 9 kb transcript in bovine lung as well as in mouse neuroblastoma cells. Hybridization on total RNA extracted from dibutyryl-cAMP-treated NG108-15 cells shows a 5-fold increase of PDE5 9 kb mRNA: such an increase is not observed in N18TG2 although we observed a similar increase in the enzymatic activity of both cell lines. Our data demonstrate that PDE5 gene expression can be regulated by cAMP and suggest the existence of a complex regulatory system for PDE5 activity.

3',5'-Cyclic-GMP Phosphodiesterases↗

In vitro and in vivo antitumour activity and cellular pharmacological properties of new platinum-iminoether complexes with different configuration at the iminoether ligands.

In order to widen our knowledge on antitumour trans-[PtCl2(iminoether)2] complexes, we have synthesised two new derivatives, trans-[PtCl2¿E-HN = C(OEt)Me¿2] (1) and trans-[PtCl2¿Z-HN = C(OEt)Me¿2] (2), which differ in the configuration of the iminoether ligands. Isomer 1 showed an in vitro cytotoxicity similar to that of cisplatin in a panel of human tumour cell lines (mean IC50 = 8 and 7.7 microM, respectively), whereas isomer 2 showed a lower activity (IC50 = 14.3 microM). Both 1 and 2 isomers overcame cisplatin resistance of ovarian cancer cell line A2780/Cp8. In agreement with the n-octanol/saline partition ratios, intracellular platinum content (and DNA platination) after a 2-h exposure to equimolar drug concentrations was in the order 1 > 2 >> cisplatin, thus indicating that substitution of imminoethers for ammines determines a major lipophilicity and cellular uptake of the platinum drug. Both 1 and 2 showed a major toxic effect towards an excision repair-defective Drosophila strain, thus indicating cellular DNA as cytotoxic target. Finally, both 1 and 2 were active in vivo against the murine P388 system, but, contrary to the in vitro activity, isomer 2 was slightly more active than 1. On the whole, the results confirm the antitumour activity of trans-[PtCl2(iminoether)2] complexes, and indicate that the configuration of the iminoether ligands may affect the pharmacological properties of this class of complexes.

Animals↗

In vitro antitumour activity and cellular pharmacological properties of the platinum-iminoether complex trans-[PtCl2[E-HN=C(OMe)Me]2].

The platinum complex trans-[PtCl2¿E-HN=C(OMe)Me¿2] was compared to cisplatin for cytotoxicity towards tumour cells, and for cellular pharmacological properties in A2780 and cisplatin-resistant A2780/Cp8 ovarian cancer cells. Trans-[PtCl2¿E-HN=C(OMe)Me¿2] was comparably cytotoxic to cisplatin (mean IC50 after 72 h exposure = 6. 1 microM and 7 microM, respectively) and did not show cross-resistance in A2780/Cp8 cells (resistance factor = 0.9). Cellular accumulation measurements after treatment with equimolar drug concentrations showed that trans-[PtCl2¿E-HN=C(OMe)Me¿2] entered both A2780 and A2780/Cp8 cells much more efficiently than cisplatin, whose accumulation was reduced in A2780/Cp8 cells. Unlike cisplatin, trans-[PtCl2¿E-HN=C(OMe)Me¿2] induced rapidly cell death and cell cycle modifications of treated cells, thus indicating substantially different mechanistic properties.

Antineoplastic Agents↗

Tobacco smoke is a source of toxic reactive glycation products.

Smokers have a significantly higher risk for developing coronary and cerebrovascular disease than nonsmokers. Advanced glycation end products (AGEs) are reactive, cross-linking moieties that form from the reaction of reducing sugars and the amino groups of proteins, lipids, and nucleic acids. AGEs circulate in high concentrations in the plasma of patients with diabetes or renal insufficiency and have been linked to the accelerated vasculopathy seen in patients with these diseases. Because the curing of tobacco takes place under conditions that could lead to the formation of glycation products, we examined whether tobacco and tobacco smoke could generate these reactive species that would increase AGE formation in vivo. Our findings show that reactive glycation products are present in aqueous extracts of tobacco and in tobacco smoke in a form that can rapidly react with proteins to form AGEs. This reaction can be inhibited by aminoguanidine, a known inhibitor of AGE formation. We have named these glycation products "glycotoxins." Like other known reducing sugars and reactive glycation products, glycotoxins form smoke, react with protein, exhibit a specific fluorescence when cross-linked to proteins, and are mutagenic. Glycotoxins are transferred to the serum proteins of human smokers. AGE-apolipoprotein B and serum AGE levels in cigarette smokers were significantly higher than those in nonsmokers. These results suggest that increased glycotoxin exposure may contribute to the increased incidence of atherosclerosis and high prevalence of cancer in smokers.

Animals↗

Induction of cyclic AMP and cyclic GMP 3':5'-cyclic nucleotide phosphodiesterase activities in neuroblastoma lines under differentiating conditions.

It is now widely accepted that cyclic nucleotide phosphodiesterases (PDEs) play fundamental roles in signal transduction pathways; they show a remarkable molecular complexity, different tissue distribution and complex regulatory mechanisms. Here we report PDE isoforms expression in two dibutyryl cyclic AMP differentiated murine cell lines: the hybrid neuroblastoma-glioma 108CC15 and the parental neuroblastoma N18TG2. They differ in the ability to establish functional synapses, a feature present only in the former. Ionic exchange chromatography elution profiles of N18TG2 and 108CC15 undifferentiated cell extracts show two main peaks of activity. The first one hydrolyzes cyclic GMP and is specifically inhibited by Zaprinast, thus representing a member of the PDE5 family. The second peak hydrolyzes cyclic AMP and is significantly inhibited by rolipram, as all the PDE4 family members. The induction of differentiation by dibutyryl cyclic AMP in both clonal lines results in an increase of PDE activities only after 3 hr of treatment, suggesting that protein neosynthesis is involved. Interestingly in both clones, besides the increase in cyclic AMP hydrolyzing specific activity (3.1-fold in 108CC15 and 2.5-fold in N18TG2), we also observed an increase in cyclic GMP hydrolyzing activity (1.7-fold in 108CC15 and 4.3-fold in N18TG2). While the induction of PDE4, previously reported also in other cellular systems, could be considered as a feedback response to the higher cyclic AMP levels, this is not true for the isoform that hydrolyzes cyclic GMP. These data suggest that the induction of PDE isoforms in neuroblastoma cells could be related to the activation of neuronal differentiative pathway.

3',5'-Cyclic-AMP Phosphodiesterases↗