PubMed Health⌕ Search

Biomedical subjects

A Podestà

Publications and source records attributed to A Podestà.

At least 37 records · Page 2Linked to original sources
PubMed1999

Protection against doxorubicin-induced cardiotoxicity in weanling rats by dexrazoxane.

PURPOSE: Dexrazoxane (DZR) protects against anthracycline-induced cardiotoxicity in several laboratory animal species and in patients with breast cancer. Encouraging results have also been obtained in a limited number of pediatric oncology patients. We conducted studies to determine the safety and cardioprotective activity of DZR in the doxorubicin (DOX)-treated weanling rat simulating the rapidly growing immature child. METHODS: Male weanling rats and young adult rats, 20 days old and 7 weeks old, respectively, were given 1 mg/kg DOX i.v., either alone or with 20 mg/kg DZR, once weekly for 7 weeks. Rats were sacrificed at weeks 8, 12 or 26 following blood collection for hematology and serum chemistry. Hearts were weighed and examined histologically. RESULTS: DOX, either alone or with DZR, inhibited growth, and body weight remained below that of controls throughout the 26 weeks of study. There were no biologically significant hematologic changes in either the DOX- or DZR + DOX-treated young rats. DOX caused a slight increase in liver and kidney weights relative to body weight and a slight increase in serum cholesterol and triglycerides in the young rats. These effects were ameliorated or delayed by DZR. DOX, either alone or with DZR, caused a marked atrophy of the testes in the young rats which had recovered by week 26. In the mature rats, DOX caused a significant decrease in the WBC 1 week after the last treatment, and the WBC was significantly lower in the rats given DZR + DOX compared to those given DOX alone. There were marked increases in liver and kidney weight, serum cholesterol and triglycerides in the mature rats given DOX alone but not in those given DZR + DOX. There was also a marked testicular atrophy in the mature rats given either DOX or DZR + DOX but, unlike that observed in the young rats, this had not returned to normal by week 26. DOX-induced cardiotoxicity was less severe in the younger rats than in the mature rats but in both age groups, the lesion progressed rapidly until week 12, 5 weeks after the last dose, and remained relatively stable or progressed slightly thereafter. DZR provided significant cardioprotection in both age groups at all time points examined. Moreover, in both age groups, the severity of the cardiomyopathy in the DZR-treated rats was somewhat less at week 26 than it was at week 12. CONCLUSIONS: The results indicate that the pharmacologic effects of DZR, including its ability to protect against cardiotoxicity, are similar in immature and adult male animals treated with DOX.

Aging↗
PubMed1999

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel.

PURPOSE: Results of several clinical studies suggest that the combination of doxorubicin (DOX) and paclitaxel (PTX) is highly active against solid tumors. Both drugs are known to cause adverse cardiac effects, cardiomyopathy in the case of DOX and acute changes in cardiac rhythm in the case of PTX. It has been suggested that the addition of dexrazoxane (DZR) to this regimen may reduce the risk of cardiotoxicity. A model of chronic cardiomyopathy in the rat was used to determine whether DZR was tolerated and cardioprotective in a DOX + PTX combination. METHODS: Male rats were treated once weekly for 7 weeks with one of the following vehicle and/or drug sequences: Group A, M/6 sodium lactate/saline/Cremophor EL (CEL); Group B, lactate/DOX/CEL; Group C, DZR/DOX/CEL; Group D, lactate/DOX/PTX; and Group E, DZR/DOX/PTX. DZR and DOX or their respective vehicles were given i.v. whilst PTX or CEL were given i.p. DZR, DOX and PTX were administered at 16 mg/kg, 0.8 mg/kg and 2.4 mg/kg, respectively, doses which caused minimal noncardiac toxicities. The hearts were examined histologically 5 weeks following the last treatment. RESULTS: There were no deaths and no signs of overt toxicity during the 12 weeks of study. There was a significant decrease (P < 0.01) in white blood cell count in rats treated with DZR + DOX, DOX + PTX or DZR + DOX + PTX but not in those given DOX alone. Liver and kidney weights were increased in rats given DOX (P < 0.05) but not in those given DZR + DOX. PTX had no effect on the DOX-induced liver and kidney changes and did not interfere with the protective effect of DZR on the kidney. The severity and extent of cardiomyopathy expressed as the mean total score (MTS) for each treatment group, was similar for DOX and DOX + PTX (4.6 and 4.2, respectively). DZR provided significant cardioprotection (P < 0.01) when added to either DOX (MTS 2.0) or to DOX + PTX (MTS 2.1). CONCLUSIONS: The results suggest that PTX does not exacerbate the chronic cardiomyopathy caused by DOX and when added to the DOX + PTX combination, DZR retains its protective activity against DOX-induced cardiotoxicity without increasing noncardiac toxicity.

Animals↗
PubMed1998

In vitro effects of different formulations of bovine collagen on cultured human skin.

Irritant effects and cytotoxicity of three different products based on collagen were investigated: a sponge formulation and a thin film composed by Type I collagen from bovine Achille's tendon, and a membrane prepared from bovine derma. The test system was a three-dimensional human skin model, developed by Advanced Tissue Science, La Jolla, CA, USA. Squares of dermal tissue (11 x 11 mm) were cultured in suitable media and exposed to the products under study. Dimethyl sulphoxide was used as the chemical control of tissue responsiveness to irritating substances. After 24 and 48 h the prostaglandin E2 (PGE2) concentration and the lactate dehydrogenase (LDH) activity in the culture medium were measured, as indexes of early inflammatory response and cell membrane breakdown, respectively. In addition, cell morphology was examined by light microscopy. The highest PGE2 concentrations were observed after cell exposure to the collagen sponges. The intensity of the inflammatory response changed accordingly to the collagen dose in use. However, it was never followed by an increased rate of cell death, as revealed by LDH activity measurement and microscopy. These findings suggest that hydrolysis of exogenous collagen starts shortly after it is kept in contact with tissues and evokes a local inflammatory response whose intensity depends on the pharmaceutical formulation in use.

Achilles Tendon↗
PubMed1998

A source of false-negative results in clenbuterol analysis in tissues of veal calves.

The possibility of false-negative results in clenbuterol analysis was investigated in bovine tissues. An extraction procedure currently in use was adapted to process 100 specimens of different tissues each time. Its efficiency and accuracy were investigated radiometrically by means of a series of different molar concentration of the tritiated drug. In samples not submitted to extensive delipidation, unreliability of the analysis was evident. The measurement of tissue clenbuterol content, by a competitive ELISA, gave results numerically similar to those existing in literature, but with an accuracy high enough to minimize the frequency of false-negative results.

Adrenergic beta-Agonists↗
PubMed1997

Developmental changes in DNA methylation of the two tobacco pollen nuclei during maturation.

Changes in DNA methylation during tobacco pollen development have been studied by confocal fluorescence microscopy using a monoclonal anti-5-methylcytosine (anti-m5C) antibody and a polyclonal anti-histone H1 (anti-histone) antibody as an internal standard. The specificity of the anti-m5C antibody was demonstrated by a titration series against both single-stranded DNA and double-stranded DNA substrates in either the methylated or unmethylated forms. The antibody was found to show similar kinetics against both double- and single-stranded DNA, and the fluorescence was proportional to the amount of DNA used. No signal was observed with unmethylated substrates. The extent of methylation of the two pollen nuclei remained approximately constant after the mitotic division that gave rise to the vegetative and generative nuclei. However, during the subsequent development of the pollen, the staining of the generative nucleus decreased until it reached a normalized value of (1)/(5) of that of the vegetative nucleus. The use of a confocal microscope makes these data independent of possible focusing artefacts. The anti-histone antibody was used as a control to show that, while the antibody staining directed against 5-methylcytosine changed dramatically during pollen maturation, the histone signal did not. We observed the existence of structural dimorphism amongst tobacco pollen grains, the majority having three pollen apertures and the rest with four. However, the methylation changes observed occurred to the same extent in both subclasses.

5-Methylcytosine↗
PubMed1996

Dose-response relationship of dexrazoxane for prevention of doxorubicin-induced cardiotoxicity in mice, rats, and dogs.

Dexrazoxane [(DZR), ADR 529, ICRF-187] ameliorates doxorubicin (DOX)-induced cardiotoxicity in animals, and is recommended as a cardioprotectant in patients receiving cumulative doses of DOX above 300 mg/m2. A DZR:DOX dose ratio of 10:1 is recommended based on studies in patients receiving 50 mg/m2. Since DOX may be used at much higher doses in certain clinical settings, we evaluated the ability of DZR to protect against cardiomyopathy in animals given bolus doses of DOX at varying dose levels. The severity and extent of the cardiomyopathy were evaluated histologically and expressed as the mean total score (MTS). Mice were given 10 doses of DOX (2 or 4 mg/kg) over a 7-week period. Without DZR, the MTS 4 weeks after the last treatment was 3.7 with 4 mg/kg DOX and 1.3 with 2 mg/kg DOX. DZR at 5:1, 10:1, and 20:1 dose ratios caused a dose-dependent decrease in the MTS but was less efficacious with the higher, more cardiotoxic dose of DOX. Rats were given DOX at 0.2, 0.4, and 0.8 mg/kg with a 20:1 ratio of DZR weekly for 13 weeks. Cardiomyopathy was most severe with the highest dose of DOX in the absence of DZR, especially in males, and progressed during the 6 weeks following the last treatment. DZR reduced the MTS in both sexes but in the males given the highest dose of DOX, there was still a significant amount of cardiac damage compared to vehicle-treated controls. Dogs were given 0.1, 0.3, and 0.8 mg/kg DOX with 20:1 DZR for 13 weeks. DZR reduced the MTS significantly (P < 0.05) in males and females but cardiac lesions were still present in each of the DZR-treated dogs. The results indicate that although DZR is highly effective in attenuating the cardiomyopathy caused by DOX, dose ratios of DZR:DOX capable of providing total or nearly complete cardioprotection at low doses of DOX are less efficacious at higher doses of DOX. One possible explanation for this effect is the marked pharmacokinetic difference between DZR and DOX, with DZR undergoing a much more rapid rate of elimination from the body compared to DOX. These findings point to the need for further studies to optimize the dose scheduling of DZR before using it clinically with bolus doses of DOX above those currently recommended.

Animals↗
PubMed1996

Shared reaction in solid-phase immunoassay for estriol determination.

In the search of factors responsible for the experimental difficulties in developing accurate and sensitive solid-phase immunoassay of steroids, an experimental model has been set up for the study of nonspecific interaction of the steroid analyte with the coating protein. Along with the development of a highly sensitive enzyme-linked, solid-phase immunoassay for estriol measurement, we observed evidence of shared reactions. This property, to our knowledge not previously described for monomeric, low-molecular-weight antigens like estrogens, has been attributed to the presence of bovine serum albumin, which is capable of binding estrogens through hydrophobic interactions. The addition of estriol in solution in large excess did not reach a complete inhibition of the binding, so the possibility was excluded that the antibody simply binds to the adsorbed estrogen. The simplest explanation for the occurrence of the reaction is the hypothesis that a family of antigen determinants arises when the estriol is conjugated to a protein carrier. The corresponding antibodies are revealed only when the estrogen participates to the actual analytical system in the form of a steroid-protein conjugate. In the experiment, the estriol has been recognized as being coupled with one or more amino acid side chains present around its site of covalent linkage to the immunogen protein. The discussed results may be of help in developing a solid-phase immunoassay of small antigens as steroids, but also in applying the hybridoma and phage display technologies, the screening methods of which are based on sensitized solid phases.

Antigen-Antibody Reactions↗
PubMed1994

Specificity in protein-ligand interactions: a model from estrone-antiserum binding.

The specificity of protein-ligand interactions has been investigated using the binding of structurally related steroids to a polyclonal anti-estrone antiserum as a model. The cross-reaction profile of the native antiserum was compared with profiles obtained for the same antiserum preparation following affinity separation on stationary phases carrying structures which mimic parts of the antigen molecule: the coupling bridge, the A ring of the estrogen and the carrier protein. This fractionation produced antibody mixtures with different specificities from that observed for the pre-affinity antiserum. The changes in specificity observed and, more importantly, the direction of each variation detected, suggested the basis for a description of the nature of molecular recognition of small ligands by a protein as discrete rather than continuous. This methodology has revealed some recognition mechanisms.

Animals↗
PubMed1993

Molecular geometry of antigen binding by a monoclonal antibody against 5-methylcytidine.

1. The specificity of a monoclonal IgG1 raised against a 5-methylcytidine-keyhole limpet hemocyanin conjugate was investigated by inhibition experiments with soluble competing antigens. 2. A competitive enzyme immunoassay has been set up, with the antigen immobilized on polystyrene microtitration wells. 3. The analysis of the cross-reaction profile allowed the topography of the antigen-antibody interaction to be described. 4. The binding properties of the monoclonal antibody are discussed in terms of both analytical applications and working limitations in the immunochemical study of gene methylation.

Animals↗
PubMed1990

[Our experience with recurrent biliary calculosis after cholecystectomy].

Recurrent calculi of the main bile way may be recurrent or residual. Recurrent stones are yellow-brown, crumbly and earthy and contain high quantities of calcium palmitate; residual stones, on the other hand, are firmer, round or berry-like, usually faceted and contain cholesterol, bilirubinate and carbonate of calcium (aragonite, vaterite, etc.) but never palmitate. Residual stones at times also present a peripheral "shell" presenting palmitate and this shows that a new component determined by bile changes is added to the cholesterol stone, which represents the central core, because of stasis and biliary infection. The distinction of calculi into residual and recurrent is also made on the basis of the classic morphologic and clinical criteria described in the literature, also and above all on the basis of specific, objective scientific criteria deriving from in-depth clinical study of the patient, the chemical study of the bile, morphological, mineralogical and structural study of the stone. The following are considered in particular: instrumental examinations made during hospitalisation and operation; pH, enzymatic activity (phospholipase, trypsin and amylase) and examination of bile cultures; morphological, microscopic examination (electronic scan microscopy) and mineralogical examination (X-ray diffractometry and infrared spectroscopy) of the calculus. A personal series of recurrent calculosis of the main biliary way is considered, special attention being paid to a case that was particularly interesting in relation to the fact lithiasic recurrence occurred just 10 months after the previous operation and the fact that biliary stasis was not determined by stenosis of the papilla which proved fully patent.

Aged↗
PubMed1990

[Our experience concerning acute phase proteins (A.P.P.) in the monitoring of surgical patients at risk of infection].

Continuing researches on the monitoring of acute phase proteins (A.P.P.) as markers of septic risk in the surgery patient, a series of 50 patients suffering from pathological processes classifiable as follows has been examined: 1) acute biliary pancreatitis 18 cases; 2) acute hepatobiliary pathology without pancreatic impairment 26 cases; 3) burn 2 cases; 4) particularly serious sepsis in immunodepressed subjects 4 cases. The constant finding of increased values of PCR, fibrin, cerul, alpha 1-Trip in the surgery patient at septic risk and their normalisation after treatment is, in single cases, particularly significant and perfectly consistent with the clinical entity of the infectious process. In immunodepressed surgery patients showing deficiency in nitrogen balance and suffering from endotoxin shock a marked, persistent decrease in alpha 2-Macro, Tranfs, Albu and Prealbu parameters was noted. The reduction in these four A.P.P. can, in the Authors' experience, be considered a diagnostic indicator of sepsis of extreme gravity and an unfavourable prognosis finding regarding the course of the disease process.

Acute-Phase Proteins↗
PubMed1990

[On lymph node excision in malignant neoplasms of the splenocolic fold].

The latest findings on lymphatic draining of the splenocolic flexure are recalled in a discussion of lymphadenectomy in the surgical treatment of cancer of the left corner of the colon. The main features of the lymphatic down flow ways of this colon segment justify extended exeresis operations as described by Madden and Welti: they also mention colon resection, removal in one block of the spleen and the caudal corporal portion of the pancreas with the lymph node stations of the pancreatico-lienal group invaded by cancer. Some observations are made regarding experience of twenty-five years at various Hospital Surgeries and twenty operated patients: stress is laid on the importance of intraoperative biopsy of the pancreatico-lineal lymph nodes for the purposes of correct staging and for programming extended surgical exeresis.

Colon↗
PubMed1989

[The so-called spontaneous hematoma of the anterior rectus abdominis reproducing syndromes of acute surgical abdomen].

Personal experience of spontaneous haematoma on the anterior straight muscles of the abdomen over 15 years is reported. True spontaneous haematoma on the anterior straight muscles of the abdomen are extremely rare, even exceptional and must be distinguished from those haematomas, improperly called spontaneous that are, in fact, clearly traumatic in origin. Personal observation suggests that true spontaneous haematoma is the expression of a pathological rupture of the muscle and/or the epigastric blood vessels that in its turn reflects a serious basic pathology.

Abdomen, Acute↗
PubMed1989

Treatment of complicated benign prostatic hyperplasia with LHRH-analogues in aged patients.

The effect of administration of an LHRH-analogue (LHRH-a) was evaluated in 11 patients with benign prostatic hyperplasia (BPH) in whom there were contraindications for surgery. These patients, who already had impaired potency due to age or serious illness, were given 1500 micrograms LHRH-a in the first week and 1200 micrograms from the eighth day onwards. They all improved significantly (P less than 0.001) with regard to their urological symptoms on day 60 of treatment. Our results demonstrate the influence of androgen in maintaining established BPH, the effectiveness of LHRH-a therapy in selected patients with BPH and the usefulness of a salivary testosterone assay for the follow-up of treatments expected to lower the bioavailability of androgen to target tissues.

Aged↗