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Biomedical subjects

A Conte

Publications and source records attributed to A Conte.

At least 73 records · Page 4Linked to original sources

Effects of chondroitin sulfates with different structures on leukemia cells: U-937 cell proliferation and differentiation.

Chondroitin sulfates extracted and purified by different manufacturers were tested to evaluate their effects on proliferation and differentiation processes of U-937 cells. The different chondroitin sulfates were evaluated for purity, structure and physicochemical properties. The three chondroitin sulfates utilized did not present other contaminant glycosaminoglycans and proteins and had about the same relative molecular mass but different disaccharide patterns and charge density. Chondroitin sulfates with small amounts of disulfated disaccharides and low charge density, at 5 micrograms/ml concentration, doubled (about + 133%) cell proliferation in comparison to controls. In contrast, chondroitin sulfates with large amounts of disulfated disaccharides and high sulfate to carboxyl ratio were less effective (about + 15%) in stimulating cell proliferation at low concentration. A decrease of U-937 cell proliferation was observed in proportion to the increased amounts of chondroitin sulfate with low sulfate to carboxyl ratio. On the contrary, chondroitin sulfate with large amounts of disulfated disaccharides produced increased cell proliferation depending on concentration. Small amounts (5-10 micrograms/ml) of chondroitin sulfates with low charge density reduced the differentiative process of U-937 cells. Chondroitin sulfate with large amounts of disulfated disaccharides and high charge density seemed to be able to produce a significant decrease of differentiative processes only at very high concentrations (1000 micrograms/ml). These contrasting effects of chondroitin sulfates with different disaccharide patterns (and structure) and charge density on a leukemia cell line could help to explain the regulation of proliferative and/or differentiative processes of hemopoietic cells. This is underlined by the changes of types, physicochemical properties and structure of glycosaminoglycans induced by different extracellular factors and agents.

Antigens, CD↗

Reversing of chlorambucil resistance by ethacrynic acid in a B-CLL patient.

We evaluated the reversing activity of ethacrynic acid in a B-CLL patient resistant to chlorambucil. The glutathione S-transferase (GST) activity, measured in peripheral blood lymphocytes, resulted extremely elevated. Ethacrynic acid, at pharmacological concentrations, partially reversed chlorambucil resistance and this result appeared related to the increased GST levels.

Aged↗

A new case of partial trisomy 19q (q13.2-->qter) owing to an unusual maternal translocation.

A new case of trisomy 19q13.2-->qter is described in a male child which was caused by a maternal balanced translocation (13;19)(p13;q13.2). The major clinical features detected in the patient included the following: facial dysmorphism, bilateral coloboma, narrow and hypoplastic nails, cardiac malformations (Fallot's tetralogy), genitourinary and gastrointestinal anomalies, and agenesis of the corpus callosum. A comparison with other reported cases of partial trisomy 19q is presented. A hypothesis is proposed to account for the involvement of p13 regions of different acrocentrics in some cases of familial translocations involving a chromosome 19.

Chromosomes, Human, Pair 19↗

Vitamin D3 administration and multidrug resistance in acute nonlymphoblastic leukemia.

This article reports preliminary results from a pilot study started in 1986 on patients with acute myeloblastic leukemia treated for several months with low-dose arabinosylcytosine and 1(OH)D3. During treatment or at the time of relapse, a monoblastic component was frequently found. A high percentage of patients were P-170-positive. In 2 patients it was possible to show that blasts, previously P-170-negative, became positive after treatment. In these 2 patients, failure of clinical response to antileukemic therapy was associated with this phenotype. The addition of the revertant drug nicardipine to the previously inactive treatment induced a partial response. Thus, previously reported in vitro observations on the differentiating activity of vitamin D3 metabolites, possible induction of multidrug chemoresistance by differentiating agents and the revertant activity of the Ca++ antagonist nicardipine appear to be confirmed in vivo in the reported patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Zinc, copper and oxalocalcic urolithiasis.

The possible effects of Zn and Cu in oxalocalcic urolithiasis were investigated. The formation of calcium oxalate crystals in the presence of Zn and Cu demonstrated that their morphology is clearly affected by these ions. Thus, when such ions were present in a number of higher concentrations, a notable increase in the primary aggregation was clearly detected. On the other hand, Zn and Cu urinary levels were determined in groups of stone-formers and healthy people. Zinc urinary concentration was significantly lower for lithiasic than for healthy people and the copper urinary concentration was lower for lithiasic than healthy males, but both female groups had a similar copper urinary concentration. The mentioned differences disappeared when serum levels were considered. These obtained results have been comparatively evaluated with those obtained by other authors. When considering all the commented aspects, it is concluded that no important direct action of zinc and copper on oxalocalcic calculi genesis takes place.

Calcium Oxalate↗

New aspects on the composition, structure and origin of calcium oxalate monohydrate calculi.

In this paper a thorough study on the composition and structure of calcium oxalate monohydrate (COM) papillary calculi is presented. In 86.4% of these calculi, small amounts of phosphates were detected and generally located at the calculi core. This demonstrates the importance of phosphates as the heterogeneous nucleus of 'pure' COM calculi. Study of the main biochemical parameters of these patients showed that the most frequent biochemical alteration was associated with hypocitraturia (25%), whereas hypercalciuria and/or hyperoxaluria were detected in very few cases. With respect to the urinary pH values, 70% of the patients presented values lower than 6 and 30% higher than 6. These facts indicate that in a number of cases the formation of phosphates is not the result of persistent high urinary pH values, and the presence of occasional papillary microinfections must be suspected. It is clear that, by avoiding the formation of heterogeneous phosphate nuclei, 'pure' COM calculi would not develop, and consequently therapies for these individuals under these conditions must take this into account.

Calcium↗

Activity of different revertant agents on multidrug resistance: in vitro evaluation of their combination.

The revertant activity of different compounds has been assayed on a multidrug-resistant human breast-cancer cell line (MCF 7/Dx). The calcium-channel blocker nicardipine showed the higher revertant ability when compared to cefoperazone or cyclosporin A at concentrations close to the pharmacological range. Interestingly, nicardipine was able to increase the revertant activities of both cefoperazone and cyclosporin A, but these latter were not able to enhance each other over a plateau. However, a limit of about 70% of growth inhibition of the line cultured in the presence of 60 microM doxorubicin seems to be insuperable at the concentrations employed. The combination of the three drugs brings the concentrations of drugs to the point at which the maximum possible inhibition is reached in the pharmacological range, but the complete reversion of chemoresistance is not reached when the doxorubicin is added at the concentration capable of reducing the cell proliferation by 50%.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Metabolic fate of partially depolymerized shark chondroitin sulfate in man.

Chondroitin sulfates and other glycosaminoglycans are administered as drugs to man by intravenous, intramuscular or oral routes. There are some studies on the pharmacokinetics of heparin, heparan sulfate and dermatan sulfate, whereas few data are available on the metabolic fate of chondroitin sulfate in man. Partially depolymerized chondroitin sulfate (mean mol. wt: 7.5 kd, range 5-10 kd) with a ratio of 1:3 between chondroitin-4-sulfate and chondroitin-6-sulfate has been administered as single administrations of 0.2 and 1.2 g by intramuscular and oral routes respectively to 10 healthy volunteers (5 males and 5 females), aging 25-53 years. After intramuscular administration the plasma level increased to a concentration peak at 90 min. The peak concentration, the elimination half-life and the apparent distribution volume were respectively 3.8 mcg/ml, 275 min and 0.40 ml/g. About 37% of the administered chondroitin sulfate is excreted in the urine during the first 24 h as high- and low-molecular-weight derivatives. After oral administration the concentration peak was observed at 240 min. The concentration at the peak, the elimination half-life and the apparent distribution volume were respectively 4.6 mcg/ml, 310 min and 0.44 ml/g. A peak of mono-, oligo- and polysaccharides with a molecular weight lower than 5 kd derived from partial digestion of exogenous chondroitin sulfate is also present in plasma. This study shows that about 10% and 20% of the orally administered drug is absorbed as high- and low-molecular-weight derivatives respectively. Comparison with the results obtained in experimental animals indicate that the metabolic fate of partially depolymerized chondroitin sulfate is similar in man and in experimental animals.

Administration, Oral↗

Studies on structure of calcium oxalate monohydrate renal papillary calculi. Mechanism of formation.

A scanning electron microscopy study of the ultrastructure of 18 calcium oxalate monohydrate papillary calculi was performed with the purpose of establishing the main steps in calculus formation. It is concluded that these calculi originate in a "core" located near the central part of the calculus. Significant quantities of organic matter as well as calcium phosphates can be found in the "core" and at the surface of adhesion to the papilla and, in some cases, fibers and calcified tubules can also be found in the contact zone. In no case did this material affect the crystalline structure of the calculi, indicating that its formation follows the calculus genesis. The study of the compact columnar zone revealed that its formation starts in a practically continuous surface formed by organic matter and crystals that surround the core. This layer favors the growth of oriented calcium oxalate monohydrate crystals upon it. Based on these observations, a feasible mechanism of papillary calcium oxalate monohydrate calculus formation is proposed.

Adolescent↗

Urolithiasis, inhibitors and promoters.

The aim of this work is to evaluate the role and importance of inhibitors and promoters in urolithiasis. Carrying in mind theoretical considerations, we conclude that in urolithogenic processes, inhibitors and promoters could only play a decisive role in the "idiopathic" oxalocalcic urolithiasis. We classify the "idiopathic" oxalocalcic stone-formers into three main groups, considering inhibitory and promoting factors. It is shown that such classification is in good agreement with the clinical results observed in a group of 88 "idiopathic" oxalocalcic stone-formers.

Adult↗

Inhibitors of calcium oxalate crystallization and urolithiasis.

In urolithogenic processes both, promoters and deficit of inhibitors, play an important role. The inhibitory action of added inhibitors (magnesium, citrate, pyrophosphate and chondroitin sulphate) was investigated using the urine of 72 patients with calcium urolithiasis. It was concluded that the deficit of inhibitors seems to be an important cause of stone formation in idiopathic oxalocalcic urolithiasis. Nevertheless, when that specific heterogeneous nucleation takes place it becomes an important factor and the inhibitor plays a complementary role in calcium oxalate urolithiasis.

Calcium Oxalate↗

Effect of coenzyme A on triglyceride and very-low-density lipoproteins secretion in cultured rat hepatocytes.

Exogenous coenzyme A (CoA) decreases plasma triglycerides, cholesterol, and Apo B in man. CoA regulates lipid metabolism favouring beta-oxidation in hepatic peroxisomes of very-long-chain fatty acids. Furthermore recent studies show that CoA participates in the transport processes which occur in the Golgi apparatus. The aim of this study was to establish whether exogenous CoA is able to modify the lipid composition of very-low-density lipoproteins (VLDL) and the VLDL secretion in rat hepatocyte culture. The presence of 5mM CoA produces a significant decrease of VLDL triacylglycerol, of VLDL total cholesterol and of VLDL esterified cholesterol by 32%, 39% and 41% respectively. This decrease is observed in all the three days of hepatocyte culture. On the third day a significant decrease of cytosolic triacylglycerols is also observed. The decrease in VLDL secretion depends on the concentration of CoA added to the culture medium. Our study shows that exogenous CoA decreases the plasma VLDL concentration because it reduces VLDL secretion by the hepatocytes.

Animals↗

Coenzyme A protects very-low-density lipoproteins against peroxidation and increases plasma triacylglycerol metabolism.

CoA (coenzyme A) has an antiperoxidative action and protects erythrocytes against oxygen free radicals. The peroxidation favours the uptake of the modified LDL (low-density lipoprotein) by macrophages and has a role in the development of foam cells. A possible relation between the antiperoxidative action of CoA and its normalizing activity on plasma lipids in type IIb and type IV hyperlipoproteinaemias, was investigated in order to see whether CoA protects VLDL (very -low-density lipoproteins) against peroxidation and produces a quicker removal of VLDL from circulation when administered intravenously to rats. The addition of 5 mM CoA to rat hepatocytes in culture was found to produce a significant decrease in VLDL secretion. The plasma clearance was significantly more rapid and the removal of triacylglycerols was significantly enhanced in CoA-treated rats as compared to untreated ones. Furthermore CoA reduced the formation of material reacting with thiobarbituric acid (TBA) in human VLDL peroxidized by exposure to Cu2+. Our study shows that CoA protects VLDL from peroxidation in a significant and concentration-dependent manner and increases plasma triacylglycerol metabolism.

Animals↗

Recent findings on the regulatory functions of CoA and the normalizing activity on plasma lipids of exogenous CoA.

In recent years many studies have shown that coenzyme A (CoA) is not only an acyl carrier coenzyme but it also has an important role in the regulation of metabolic functions and cell activities such as transport from the Golgi cisternae. This regulatory role is carried out by CoA, its precursor, catabolites and acylated derivatives. The acylation (myristylation and palmitylation) process of peptides and proteins dependent on CoA seems to be an important regulatory mechanism of cell activities. Furthermore exogenous CoA has been shown to decrease the triacylglycerols, cholesterol and Apo B of plasma lipoproteins in man. This regulatory mechanism acts either on VLDL synthesis and secretion or on their plasma clearance. CoA also protects cell-membrane and plasma lipoproteins against the peroxidative action of oxygen free-radicals.

Animals↗

[Urologic neoplasms in AIDS].

Report on 2 cases of urological neoplasia in HIV positive patients. The first one is a renal adenocarcinoma in a heroin-abuser patient, of a type we have only found mentioned in the literature in 4 other cases. The second case was a disseminated Kaposi's sarcoma, the first symptom being a scrotum impairment and the biopsy suggested the diagnosis. This is believed to be an interesting communication considering the increasing number of anti-HIV antibodies carriers seen in our Units.

Acquired Immunodeficiency Syndrome↗

Intensive alternating combination chemotherapy and high dose chest radiotherapy in small cell lung cancer.

Sixty-nine patients, 32 with limited and 37 with extensive small cell lung cancer (SCLC), were admitted to the present study. Patients with limited disease underwent alternating combination chemotherapy consisting of CAV (cyclophosphamide, adriamycin, vincristine) and PE (cisplatin and etoposide) regimens and concurrent high dose thoracic radiotherapy (6,000 cGy); prophylactic brain irradiation (3,000 cGy) was administered to complete responders. Patients with extensive disease received the same alternating chemotherapy but not radiotherapy. In the 25 evaluable patients with limited disease we obtained an objective response (OR) in 80% with a complete response (CR) in 54% and partial response (PR) in 24%, stable disease (SD) in 4% and progressive disease (PD) in 16%. Median duration of response was 9.5 months for CR and 8.5 months for PR. Median survival was 14 months for all patients with 12% long-term survivors. Toxicity was acceptable. In the 32 evaluable patients with extensive disease we observed 65.6% OR with 18.7% CR and 46.8% PR, 9.3% minimal response and 25% PD. Median duration of response was 7 months for CR and 8 months for PR. Median survival was 10 months for all patients. The treatment was well tolerated. Our study did not show a therapeutic advantage for alternating combination chemotherapy in SCLC and failed to show the use of high dose chest radiotherapy in combined modality for limited disease.

Adult↗