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Biomedical subjects

M Tedeschi

Publications and source records attributed to M Tedeschi.

At least 19 recordsLinked to original sources
PubMed2006

Lipid microencapsulation allows slow release of organic acids and natural identical flavors along the swine intestine.

The purpose of the present work was to investigate the in vivo concentrations of sorbic acid and vanillin as markers of the fate of organic acids (OA) and natural identical flavors (NIF) from a microencapsulated mixture and from the same mixture non-microencapsulated, and the possible consequences on the intestinal microbial fermentation. Fifteen weaned pigs were selected from 3 dietary groups and were slaughtered at 29.5 +/- 0.27 kg of BW. Diets were (1) control; (2) control supplemented with a blend of OA and NIF microencapsulated with hydrogenated vegetable lipids (protected blend, PB); and (3) control supplemented with the same blend of OA and NIF mixed with the same protective matrix in powdered form but without the active ingredient coating (non-protected blend, NPB). Stomach, cranial jejunum, caudal jejunum, ileum, cecum, and colon were sampled to determine the concentrations of sorbic acid and vanillin contained in the blend and used as tracers. Sorbic acid and vanillin were not detectable in pigs fed the control, and their concentrations were not different in the stomach of PB and NPB treatments. Pigs fed PB showed a gradual decrease of the tracer concentrations along the intestinal tract, whereas pigs fed NPB showed a decline of tracer concentration in the cranial jejunum and onwards, compared with the stomach concentrations. Sorbic acid and vanillin concentrations along the intestinal tract were greater (P = 0.02) in pigs fed PB compared with pigs fed NPB. Pigs fed PB had lower (P = 0.03) coliforms in the caudal jejunum and the cecum than pigs fed the control or NPB. Pigs fed the control or PB had a greater (P = 0.03) lactic acid bacteria plate count in the cecum than pigs fed NPB, which showed a reduction (P = 0.02) of lactic acid concentrations and greater (P = 0.02) pH values in the caudal jejunum. The protective lipid matrix used for microencapsulation of the OA and NIF blend allowed slow-release of both active ingredients and prevented the immediate disappearance of such compounds upon exiting the stomach.

Ammonia↗
PubMed2001

Naltrexone and acamprosate. Using new drugs for alcohol dependence.

BACKGROUND: Two new drugs for the treatment of alcohol dependence have recently become available in Australia. Both naltrexone and acamprosate have an 'anticraving' action, but act on different pathways and have different properties. OBJECTIVE: This article aims to give an outline of the major pharmacological features of the two new drugs and some guidelines on their use for general practitioners. DISCUSSION: The past 50 years have seen major advances in almost all medical disciplines. A notable exception has been the alcohol and drug field. The arrival of methadone to Australia in the 1960s was, until lately, the most recent advance in the field. Over the past 18 months, several new drugs have become available for use in alcohol and drug (A&D) clinics. These drugs have also become available to the GP, but their use by this group remains relatively small.

Acamprosate↗
PubMed1998

[Phantom rectum after Miles' operation].

The authors observed symptoms relating to the existence of a phantom rectum, a phenomenon about which little is still known, in 233 cases (32.1%) in a series of 724 patients undergoing amputation of the abdomino perineal rectum due to malignant neoplasm. The genesis of this phenomenon is attributed to an abnormal reactivity of the cortical and thalamic projection areas with greater response to stimuli from the stump or aspecific visceral stimuli, or even stimuli from the adjacent cortical regions. The psychodynamic aspects linked to the patient's need to develop a different body awareness should not be underestimated; this has to integrate a new anatomic reality, such as colostomy in the place of the anorectum, entailing the relinquishment of the previous body scheme. Prevention and treatment of phantom rectum, which is painful in 27% of cases, is essential for a correct operating technique, adequate psychotherapeutic support, the patient's active participation in a reeducation programme for colostomy management. It should not be forgotten that painful phantom rectum, especially with late onset, may be diagnostically significant as an indicator of the recurrence of neoplastic pathology, sometimes allowing diagnosis to be anticipated by several months. This underlines the importance of carrying out a careful postoperative clinical, biohumoral and radiological control in these patients, including pelvic CT. In the authors' experience of 233 patients suffering from phantom rectum, it was possible to document the presence of neoplastic recidivation in 30 cases (12.8%) using pelvic CT. In these cases, symptoms appeared after a disease-free interval of 26.3 months (range 3-75 months), whereas the presence of phantom rectum without recidivation is usually described in the first 2 months after surgery.

Abdomen↗
PubMed1997

Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial.

BACKGROUND: Early clinical trials have suggested that glutathione (GSH) offers protection from the toxic effects of cisplatin. PATIENTS AND METHODS: One hundred fifty-one patients with ovarian cancer (stage I-IV) were evaluated in a clinical trial of cisplatin (CDDP) +/- glutathione (GSH). The objective was to determine whether GSH would enhance the feasibility of giving six cycles of CDDP at 100 mg/m2 without dose reduction due to toxicity. RESULTS: When considering the proportion of patients receiving six courses of CDDP at any dose, GSH produced a significant advantage over control--58% versus 39%, (P = 0.04). For these patients there was a significant difference between the reduction in creatinine clearance for GSH treated patients compared with control--74% versus 62% (P = 0.006). Quality of life scores demonstrated that for patients receiving GSH there was a statistically significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As an indication of overall activity, these patients were statistically significantly more able to undertake housekeeping and shopping. Clinically assessed response to treatment demonstrated a trend towards a better outcome in the GSH group (73% versus 62%) but this was not statistically significant (P = 0.25). CONCLUSIONS: The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient's quality of life is improved.

Adult↗
PubMed1995

Pharmacokinetic evaluation of two different formulations of megestrol acetate in patients with advanced malignancies.

The bioequivalence of two megestrol acetate formulations, 160-mg "tablets" and 160-mg "sachets," was investigated in a single-dose, open-label, balanced-for-sequence cross-over study involving 12 advanced-cancer patients. The observed plasma megestrol-acetate time course obtained with both formulations was consistent with the literature data. The main source of variability in the pharmacokinetic parameters was intersubject variability; drug formulation played only a minor (and nonsignificant) role. The width of the 90% confidence interval of the area-under-the-curve (AUC) ratio (sachets: tablets) computed according to Schuirmann (0.9-1.4) was mainly due to the presence of a single outlier, showing an AUC ratio of 2.7. The trend to higher bioavailability of the new formulation was not significant, especially as compared with the dose-response data reported in the literature.

Administration, Oral↗
PubMed1994

Low-dose glutathione administration in the prevention of cisplatin-induced peripheral neuropathy in rats.

So far various drugs have been used in an attempt to prevent or reduce cisplatin (CDDP)-induced peripheral neuropathy. Of those tried reduced glutathione (GSH) is one of the most promising. Its effectiveness has already been demonstrated by means of morphological methods in CDDP-treated rats in which high doses of GSH (up to 1200 mg/kg) were given. In the current study neurophysiological and morphological methods were used to evaluate the effect of low doses (150-300 mg/kg) of GSH i.p. on the peripheral nervous system of the rat. Four groups of 8 female Wistar rats were treated as follows: (A) CDDP 2 mg/kg i.p. weekly for 9 courses; (B) same as (A) plus GSH 150 mg/kg i.p. weekly; (C) same as (A) plus GSH 300 mg/kg i.p. weekly; (D) same as (A) plus GSH 150 mg/kg i.p. on the day of DDP injection followed by 150 mg/kg/day over the next 2 days. Eleven age-matched untreated rats were used as controls. Sensory conduction velocity was recorded in the tail nerve and morphologic and morphometric examinations were performed on the dorsal root ganglia neurons (L4-L6) in each animal. The results demonstrated that the neurophysiological and pathological changes induced by CDDP administration were less severe in rats co-treated with GSH. No significant differences could be related to the 3 different regimens of GSH co-treatments. This experiment confirms that GSH is able to reduce the neurotoxicity of CDDP and that it is effective even at doses as low as those used in the present study.

Animals↗
PubMed1993

A phase II study of combination chemotherapy in advanced ovarian carcinoma with cisplatin and cyclophosphamide plus reduced glutathione as potential protective agent against cisplatin toxicity.

AIMS AND BACKGROUND: The clinical use of cisplatin (CDDP), one of the most active agents in advanced ovarian cancer, is limited by nephrotoxicity and cumulative neurotoxicity. In preclinical studies, reduced glutathione (GSH) demonstrated a protective action against CDDP nephrotoxicity. We treated 20 patients with advanced ovarian carcinoma, with polychemotherapy containing CDDP + GSH, to assess the protective action of GSH against CDDP nephrotoxicity. METHODS: Between January 1988 and December 1989, 20 patients, with advanced ovarian carcinoma (St. III-IV-FIGO), not pretreated received CDDP: 45 mg/m2 i.v., on day 1-2, + cyclophosphamide (CPA): 900 mg/m2 i.v. on day 2 + GSH 2500 mg i.v. in normal saline 100 ml (in 15 min), before CDDP, every 21-28 days. RESULTS: A pathologic complete response rate (PCR) of 55% (11/20) was observed (7/14 patients with bulky disease). Median survival was 26.5 months and 5 patients were still alive and disease free at 35 months. Toxicity was limited, without any case of nephrotoxicity. CONCLUSIONS: On the basis of our previous experience with the same regimen without GSH, this study suggests that also in the clinical setting, GSH has no negative interference on CDDP activity and that GSH might improve the therapeutic index of CDDP. However, our data need to be confirmed by large randomized clinical studies.

Adult↗
PubMed1993

Reduced glutathione protects against cisplatin-induced neurotoxicity in rats.

Reduced glutathione (GSH) is reported to diminish cisplatin-induced neurotoxicity, and it was for this reason that we studied GSH in an animal model of cisplatin neuropathy. The neuropathy was evaluated by measuring the sensory nerve conduction velocity (SNCV) in young adult Wistar rats. GSH injections (i.v.) were given twice weekly, within five minutes before cisplatin was injected (i.p.). In a first experiment GSH (500 mg/kg) in combination with a low-dose cisplatin treatment (1 mg/kg, 10 weeks) was investigated. Animals treated with cisplatin and placebo developed a neuropathy (SNCV at week 10: age controls, 61.9 m/s; cisplatin alone, 44.2 m/s), whereas rats treated with cisplatin and GSH did not (SNCV, 61.9 m/s). The same dose of GSH was used in combination with a high-dose cisplatin schedule (2 mg/kg, 5 weeks' treatment plus 5 weeks' recovery). Again, GSH protected animals against the development of neuropathy (SNCV at week 10: age controls, 61.9 m/s; cisplatin alone, 50.6 m/s; cisplatin plus GSH, 61.1 m/s). In another experiment four lower doses of GSH (25, 50, 100, and 200 mg/kg) were tested in combination with the low-dose cisplatin protocol (1 mg/kg, 11 weeks). The cisplatin group developed a neuropathy (SNCV at week 11: cisplatin alone, 50.2 m/s; age controls, 60.6 m/s). Only the dose of 200 mg GSH/kg was found to protect against the development of a neuropathy (SNCV, 61.0 m/s). In an antitumor study GSH administered at 300 mg/kg in combination with cisplatin at 1.5 mg/kg did not diminish the curative effect of cisplatin. We conclude that GSH prevents cisplatin-induced neuropathy and that it should be investigated further in the clinic.

Animals↗
PubMed1993

High-dose cisplatin and cyclophosphamide with glutathione in the treatment of advanced ovarian cancer.

BACKGROUND: On the basis of preliminary results achieved with a high-dose cisplatin regimen including glutathione as chemoprotector, the efficacy and toxicity of the new regimen was further evaluated in a larger series of patients with advanced ovarian cancer (stage III and IV). PATIENTS AND METHODS: The study included patients with bulky or extensive residual disease after primary laparotomy or with bulky inoperable tumor masses. A total of 79 patients were treated with up to five courses of high-dose cisplatin (40 mg/m2 daily in normal saline, for four days) plus glutathione (2500 mg as a short-term infusion before cisplatin), together with cyclophosphamide (600 mg/m2 as an i.v. bolus on day 4). A standard i.v. hydration consisting of a total of 2000 ml of fluids without diuretics was employed. RESULTS: All eligible patients, who received a total of 345 courses, were assessed for response and toxicity and 52 received the planned five courses of the protocol. Forty-five patients (57%) achieved complete clinical responses and 20 (25%) had partial remissions for an overall response rate of 82%. The response rate was critically dependent on tumor size before chemotherapy. Thirty-eight of 45 patients who had complete clinical responses underwent second-look laparotomy, and 29 had pathological complete responses (37%). Seventeen of these 29 patients subsequently relapsed (median disease-free interval, 12 months; range, 6-45). With a median follow-up time of 44 months, the median survival for the 79 analyzed cases was 40 months. The toxicity of the regimen was moderate. Nausea/vomiting was the most severe acute toxicity. Myelotoxicity was acceptable, with severe leukopenia and thrombocytopenia (grade 4) occurring in 8% and 3% of patients, respectively. Nephrotoxicity was minimal with a transient increase (to < 2 mg/dL) in serum creatinine in only 6 patients (8%). Peripheral neurotoxicity and ototoxicity were the most significant long-term toxicities. The severity of these side effects (grade 3 WHO neurotoxicity occurred in only 4% of patients) was apparently less than has been reported with other high-dose cisplatin regimens. Neurotoxicity required discontinuation of therapy in three patients after four courses. Most affected patients had complete or partial recovery of symptoms with time. DISCUSSION: The efficacy and tolerability of the regimen confirm the feasibility of this new approach including glutathione in order to increase cisplatin dose intensity. The superiority of this regimen over standard induction therapy should be confirmed in randomized trials.

Adult↗
PubMed1992

Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin.

The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

A preliminary clinical study of cyclophosphamide with reduced glutathione as uroprotector.

Reduced glutathione (GSH) has been reported to be an effective protector against cyclophosphamide-induced urotoxicity in experimental models, providing protection comparable to that of mesna. This paper describes our preliminary results of the clinical use of GSH in combination with cyclophosphamide. GSH was administered i.v. in two divided doses of 2.5 g, 15 min before and 30 min after escalating doses of cyclophosphamide ranging from 1.2 up to 1.6 g/m2 (1-h infusion). GSH was well tolerated and did not produce unexpected toxicity. The lack of bladder damage, including microscopic hematuria, supports the protective role of this thiol compound.

Adult↗
PubMed1985

[Anti-tetanus protection in a homogeneous group of vaccinated subjects from the city of Reggio Emilia].

The AA. have determined the antibodies against tetanus toxin of 739 young people that in 1968 underwent the first vaccination (passive haemagglutination test). 570 subjects (77.13%) entirely immunized and other 129 partially immunized turned out. Whereas the antibodies level of many examined subjects after fifteen years from vaccination was protective, the AA. suggest as correct a vaccination schedule with a dose every ten years to preserve the immunity.

Adolescent↗