Search PubMed⌕ Search

Biomedical subjects

M Esposito

Publications and source records attributed to M Esposito.

At least 127 records · Page 7Linked to original sources

Para-aminobenzoic acid suppression of cis-diamminedichloroplatinum(II) nephrotoxicity.

Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues in rats killed 5 days after drug administration. The formation of cisplatin-DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound for reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity.

4-Aminobenzoic Acid↗

[Separation and identifying features of the cardiac aglycones and glycosides of Nerium oleander L. flowers by thin-layer chromatography].

The present work was aimed at extracting some cardiotonic glycosides from Nerium oleander L. (N.o.L.) flowers, free from phytosterols and their esters and at resolving themselves by thick- and thin-layer chromatography. This work may contribute to the scientific recognition of N.o.L. drugs in the field of forensic medicine. MATERIALS AND METHODS. Apparatus. Kieselgel F254 thin-layer (250 mu) and Kieselgel thick-layer (2 mm) glass plates were used. MATERIALS. Chromatographic solvents were used; detectors were p-toluene sulphonic acid (PTSA) and antimony trichloride (SbCl3). STANDARDS. The following standards were used: gitoxigenin, oleandrin, digitoxin, and stigmasterol. Standard solutions were prepared at a M-3 concentration. The solvent system is described in Table I. EXTRACT. The extract was prepared using a mixture of solvents (hexane-diethylether-acetic acis, 50:50:1 v/v). With this mixture we noted that, in thin-layer chromatography, the used standards remained at the origin, while phytosterols and their esters migrated. White flowers of N.o.L. were air dried in the shade at room temperature, powered, and macerated in hexane-diethylether acetic acid for 24 hours. After removal of the phytosterols the remacerating powder was further percolated using a chloroform-methanol mixture (1:1.7 v/v) in order to extract the aglycone and the cardiac glycosides. As the medium's thin-layer chromatogram showed the absence of corresponding spots to test samples, the chloroform-methanol media were combined and evaporated under vacuum. The residue was redissolved in the chloroform-methanol mixture. The obtained extract concentration consisted of 5 grammes of dried flowers in 1 milliliter of solution, called extract E (Fig. 1). RESULTS. The results are reported in Figures 2 and 4 and in Table II (see text for explanation of symbols). Extract E (Fig. 2) and the F1, F2, and F3 concentrated fractions were examined by thin-layer chromatography (Fig. 1 and 3). Only the F3 fraction revealed compounds with the same chromatographic path and colours (detected by PTSA and SbCL3) as the reference standards gitoxigenin, oleandrin, and digitoxin. This finding was confirmed by using five different solvent-systems (Fig. 4). DISCUSSION AND CONCLUSION. The present study shows that the cardiac steroids and other constituents of Nerium oleander's flowers are separated in three fractions by thick-layer chromatography free from phytosterols and their esters. This result may have useful implications in the fields of analytical toxicology and forensic medicine and potential application in clinical practice given that cytotoxic and antileukemic activities of the extracts from plants containing cardiac glucosides have been reported.

Cardiac Glycosides↗

Protective effect on cisplatin hematotoxicity by procaine hydrochloride.

The ability of procaine hydrochloride (P.HCl) to modulate the effects of cisplatin (DDP) on pluripotent (CFU-S) and committed (CFU-GM) murine hemopoietic stem cells was investigated. DBA/2NCrlBRF1 mice received DDP alone (10 and 16 mg/kg body wt. single i.p. injection) or in combination with P.HCl (40 mg/kg body wt. single i.p. injection). Hemopoietic progenitor cell (HPC) time survival curves were determined up to 14 days following treatment. The simultaneous administration of the lower DDP dose together with P.HCl greatly reduced the hemotoxicity of the antitumoral drug, while this protection was not significant with the higher DDP dose. These results support a role for P.HCl in protecting against DDP hematological toxicity.

Animals↗

Compartment syndrome of the scapula. Definition on clinical, neurophysiological and magnetic resonance data.

Compartment syndromes of the scapula and pelvic girdle have received scant attention in the literature. In 1938, Comolli first described a clinical sign which he considered specific to fracture of the scapula. We report data on two patients, one presenting with prolonged pressure on the posterior surface of the scapula and the other with symptoms associated with scapular fracture. In one of these patients we were able to measure pressures around the scapula, perform neurophysiological assessment of nerve function and produce magnetic resonance images of the area. In the other case, surgical exploration revealed an established ischaemic contracture of the infraspinatus muscle within its compartment. These findings suggest that the muscles around the scapula are vulnerable to the development of compartment syndrome.

Action Potentials↗

A teaching model to illustrate the variation in size and shape of the maxillary sinus.

A technique to produce teaching models of the maxillary sinus is described. Dental impression material is injected into the maxillary sinus of a cadaver and subsequently dissected out. Using an impression and mould technique in a series of steps, a stone model of the maxillary sinus is produced. The shape, size and configuration of the model can be seen and the dimensions measured. A radiopaque impression material can be used so that the radiographic outline of the maxillary sinus on standard radiographic projections can be shown. Models of both dentate and edentulous patients can be used to show anatomical variation and the relationship to teeth and are useful in teaching both gross and radiographic anatomy. Since 10 out of 11 specimens had 3 walls leading to the apex from a 4-sided base, it would appear that the classical description of a 4-sided pyramidal shape to the maxillary sinus is relatively uncommon.

Humans↗

[Medical treatment of chylous effusions in newborn infants. Apropos of 3 cases].

BACKGROUND: Chylous effusions are the most frequent cause of non immunologic hydrops fetalis. They can be recognized antenatally by ultrasonography. Their evacuation is sometimes necessary and medical treatment often effective. CASE REPORTS: Case n. 1: fetal ascites was detected by ultrasonography at the 30th week of gestation. Paracentesis was performed at 36 weeks, followed 3 days later by spontaneous delivery. The newborn was fed milk formula. A second paracentesis showed a milky fluid, rich in cholesterol, triglycerides and chylomicrons. The child was fed formula rich in medium-chain triglycerides and the chylous ascites disappeared completely within 2 weeks. Case n. 2: a diagnosis of bilateral hydrothorax and hydramnios was made at the 27th week of gestation. An in utero evacuation of the hydrothorax performed at the 30th week was ineffective and a pleuro-amniotic drainage was performed 2 weeks later. The baby was born at the 35th week, and presented a moderate respiratory distress due to the hydrothorax and ascites. Aspiration of the thoracic fluid confirmed its chylous origin. The chylous effusions completely disappeared when the child was fed a high medium chain triglycerides diet. A lymphedema of legs appeared at the age of 1 month. Case n. 3: ascites, hydramnios, hydrothorax and peripheral edema were found at the 21st week of a third pregnancy (the 2 first pregnancies were complicated by lethal hydrops fetalis). Bilateral hydrothorax and peripheral edema were found again after birth at the 37th week. Diuresis and albumin-infusion led to recovery, but chylothorax and chylous ascites reaccumulated after introduction of milk formula, despite repeated evacuations and feeding medium-chain triglycerides formula. The thoracic fluid remains chylous at the age of 9 months. CONCLUSIONS: In utero, and sometimes post-natal, evacuation of fluid present in the thoracic and peritoneal cavities can be necessary, depending of the functional tolerance. Medical management including feeding a low fat and/or high medium-chain triglycerides diet, and sometimes temporary total parental nutrition, is necessary, together with salt restriction, diuresis and albumin infusion as required. Most cases recover spontaneously or as a result of therapy within a few weeks.

Chylothorax↗

Liver and tumor uptake and plasma pharmacokinetic of arterial cisplatin administered with and without starch microspheres in patients with liver metastases.

Arterial chemoembolization of liver tumors should improve regional treatment by reducing native blood flow of the whole organ and redistributing residual flow toward hypovascular masses. Plasma cisplatin pharmacokinetics and its tissue uptake and relative tumor and liver vascularity were studied during surgical placement of arterial catheters in four patients and in four patients with colorectal metastases given intraoperative arterial cisplatin (DDP, 25 mg/m2), with an without coadministration of 600 mg degradable starch microspheres (DSM). Mean (+/- standard deviation) filterable plasma platinum levels peaked later (2 minutes) and were significantly lower after DDP with DSM (1.23 +/- 0.69 micrograms/ml) than after DDP alone (2.13 +/- 0.43 micrograms/ml, P less than 0.05), with the area under the curve (AUC0-30 min) values of 15.8 +/- 5.5 and 25.1 +/- 3.8 micrograms x min/ml (P less than 0.05), respectively. No differences in urine excretion, total body clearance, or plasma protein binding of platinum were observed. Tissue biopsies were started 15 minutes after DDP administration and completed in all cases within 5 minutes. Tumor platinum concentrations were significantly higher after DDP with DSM (3.03 +/- 1.60 micrograms/g) than after DDP alone (0.67 +/- 0.49 micrograms/ml, P less than 0.05). Liver concentrations and tumor-liver ratios of platinum also were higher, although not significantly, after DDP with DSM. Preoperative vascularization, studied with arterial perfusion scan, influenced individual tissue drug uptake in cases given DDP alone, with the lowest tumor levels in cold masses. Very high and almost superimposable liver and tumor concentrations were measured in those receiving DDP and DSM. The latter phenomenon was irrespective of native vascularization, indicating that DSM administration induced both an increased whole-liver extraction of the drug and a redistribution of blood flow and flow-dependent tissue uptake of platinum.

Chemoembolization, Therapeutic↗

Regional pharmacokinetic selectivity of intrapleural cisplatin.

The pharmacokinetics and toxicity of cisplatin were investigated in 3 patients affected by malignant mesothelioma who received 90 mg/m2 of the drug intrapleurally. The mean area under the pleural Pt concentration versus time curve (AUC) [12.83 (S.D. 4.06) mg.min/ml] was about 50 times greater than that detected in plasma [0.27 (0.03) mg.min/ml], indicating a clear pharmacological advantage for this route of administration. The mean plasma total Pt concentration was 1.1 micrograms/ml and the apparent total body clearance was 268 (101) ml/min. Platinum plasma pharmacokinetic data measured following intrapleural cisplatin administration (4 patients) were compared with those observed in 7 patients treated intravenously with the same dose of cisplatin (90 mg/m2) under the same modalities of hydration. Intrapleural administration of cisplatin resulted in significantly lower plasma total partial AUC (P less than 0.05) and prolonged plasma levels of filterable Pt compared with intravenous administration. No difference between the two routes of cisplatin administration in the renal clearance (S.D.) of filterable Pt [132 (64) ml/min and 122 (39) ml/min for intravenous and intrapleural cisplatin, respectively] were observed. None of the mesothelioma patients developed clinical symptoms or signs of pleural inflammation. The intrapleural treatment did not produce haemotoxicity and the emetic toxicity was lower compared with that observed in patients receiving cisplatin intravenously.

Aged↗

A balanced complex chromosomal rearrangement (BCCR) with phenotypic effect.

The authors report on a case of balanced complex chromosomal rearrangement (BCCR) with phenotypic effect, describe the dysmorphisms and malformations observed, and discuss the various pathogenetic mechanisms. On the basis of these considerations, they underline the need for careful reporting of examined cases, distinguishing the characteristic signs from dysmorphisms that are described in several other chromosomal aberrations as well. Finally, they stress the importance of a more precise description of BCCRs for the purpose, among others, of a correct formulation of reproductive risk.

Abnormalities, Multiple↗

Selenium therapy in patients with precancerous and malignant oral cavity lesions: preliminary results.

Baseline selenium (Se) levels in serum samples were collected from 22 patients with precancerous and 19 with malignant oral cavity lesions as well as from 13 healthy controls of the same geographic areas. Mean serum Se levels were 105, 101, and 77.03 ng/ml in the precancerous, controls, and malignancy groups, respectively. A statistically significant difference (p less than 0.005) was found between the neoplastic and both the precancerous and control groups. After careful clinical evaluation, precancerous patients received three 4-week cycles of Se, in either inorganic or organic form. Of the 22 precancerous patients entering the study, 18 were available for evaluation of clinical response. The analysis of serum Se variations revealed that serum Se levels tended to increase after the first and second cycles and then gradually returned to baseline values. At the end of the therapy, there were two complete responses (CR), five partial responses (PR), six minor responses (MR), and five stable diseases (SD) with an objective response (CR + PR) of 38.8%. Progression after suspension of therapy occurred in 7 of 18 patients; this may indicate the need of a longer treatment period with this essential trace element.

Adult↗

Improved therapeutic index of cisplatin by procaine hydrochloride.

The local anesthetic procaine hydrochloride (P.HCl) had little effect on the sensitivity of P388 leukemic cells to cisplatin (DDP) in vitro, but the simultaneous administration of DDP and P.HCl (40 mg/kg) to BDF1 mice produced 50% lethal dose (LD50) and 90% lethal dose (LD90) values approximately two times higher than those observed with DDP alone. DDP-P.HCl diluted in water and administered intraperitoneally (IP) on day 1 and on days 1 and 5 to BDF1 mice bearing P388 leukemic cells produced 33% and 50% cure rates, respectively, at the maximum tolerated dose (16 mg/kg for the single administration and 10 mg/kg given on days 1 and 5). In contrast, under the same conditions, the cure rates obtained with DDP alone (10 mg/kg for the single administration and 8 mg/kg given on days 1 and 5) were 17% and 9%, respectively. Protection from DDP nephrotoxicity seems to be the explanation for the higher doses of DDP that mice can tolerate when DDP is given simultaneously with P.HCl. In fact, the increased blood urea nitrogen (BUN) levels observed 4-7 days following a single IP administration of DDP (8 or 16 mg/kg), as well as the tubular degenerative changes detected by light microscopy, were not observed when the same doses of DDP were given simultaneously with P.HCl. Since DDP nephrotoxicity is known to be reduced when the drug is diluted in 0.9% NaCl solution, we compared the combinations DDP-P.HCl in water, and DDP and DDP-P.HCl in 0.9% NaCl solution. The antitumor activity of DDP diluted in water and administered with P.HCl was similar to that observed in mice treated with DDP alone diluted in 0.9% NaCl solution. However, further improvement of the therapeutic index was achieved after the administration of DDP-P.HCl diluted in 0.9% NaCl solution; this regimen produced a cure rate of 67% (12 of 18 animals). The clinical relevance of these findings is strengthened by the observation that similar results were obtained when P.HCl was given by the intravenous route.

4-Aminobenzoic Acid↗

Blood levels of reduced and oxidized glutathione in malignant and non-malignant human colorectal lesions.

Glutathione blood levels were determined in colorectal cancer patients (n = 10), patients with adenomatous colorectal polyps (n = 8), and healthy subjects (control group; n = 10). Mean GSH level (micrograms/ml) was significantly higher in cancer patients [515.4 +/- 76.1 (S.D.)] than in those with polyps [407.7 +/- 90.5 (S.D.), P less than 0.05] and the control group [360.9 +/- 67.9 (S.D.), P less than 0.001]. Statistically significant lower GSSG blood level were observed in cancer patients when compared to the other groups. The highest mean blood GSH/GSSG ratio (log transformed) was observed in cancer patients [2.17 +/- 0.108 (S.D.)] and the lowest in healthy subjects [1.88 +/- 0.032 (S.D.)]. All between-group differences in the GSH/GSSG ratio were statistically significant. These findings suggest that glutathione blood levels as well as GSH/GSSG ratio may have applicability as a guide for following the activity of colorectal diseases.

Adult↗

[HCV and HBV infection in 3 communities in the Neapolitan area].

Using the antibody to HCV and HBc (anti-HCV, anti-HBc), we studied the prevalence of Hepatitis C and B virus in three groups: intravenous drug abusers, subjects lodging in huts and elderly clergymen. Statistical analysis was carried out by chi-square and Fisher's exact tests. Our results show statistical significance for anti-HCV seroprevalence among the three groups, while anti-HBc doesn't differ. These preliminary data seem to show that the two viruses have different ways of transmission.

Adolescent↗