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Biomedical subjects

M Marchetti

Publications and source records attributed to M Marchetti.

At least 55 records · Page 3Linked to original sources
PubMed1998

Vitamin B6 deficiency affects antioxidant defences in rat liver and heart.

We have evaluated the effects of a diet containing normal amounts of lipids and a marginal content of vitamin B6 on lipid peroxidation. Pyridoxal phosphate concentrations of plasma and liver indicated that an initial deficiency state was reached. Vitamin B6 deficiency led to peroxidative stress: TBARS production was higher in the liver (+18.6%) and even more in the heart (+61%) of deficient rats as compared with controls. Furthermore, significant stimulation of glutathione-dependent enzymes occurred in both heart and liver of deficient rats: glutathione peroxidase activity increased in heart (+144%) and liver (+505%); glutathione reductase increased in heart (+54.9%) and liver (+15.5%). No difference in the total glutathione content of the organs of the two groups was observed. The reduced glutathione/oxidized glutathione ratio was significantly lower in deficient rats. Although the activity of glutathione-dependent enzymes was significantly greater in deficient rats than in controls, this stimulation was only partially able to counteract the peroxidative damage due to vitamin B6 deficiency.

Animals↗
PubMed1998

The value of the prognostic factors in ovarian granulosa cell tumors.

The malignant potential of granulosa cell tumors (GCT) of the ovary is much debated. This study includes 18 patients with a diagnosis of GCT of the ovary. Clinical and pathologic data from patients were compared with flow cytometry ploidy, Ki-67 reactivity and p53 overexpression in order to determine their prognostic usefulness. There was no correlation between ploidy and stages or between ploidy and biological behavior. On the other hand, mitotic count, Ki-67 reactivity and p53 overexpression were associated with stages of disease, recurrent onset and survival. We believe that ploidy, Ki-67 and p53 should be considered important prognostic factors for GCT in association with the other more studied prognostic factors, even if no conclusions can be reached.

Adult↗
PubMed1998

Malignant ovarian tumors: conservative surgery and quality of life in young patients.

Better knowledge and adequate treatment of malignant ovarian tumors have improved the quality of life of young women--especially of child-bearing age. Nowadays preservation of ovarian function in women with tumors in early stage (I) or, in selected cases even in advanced stage (II-III), must be evaluated for conservative surgery (sometimes expressly requested by the patient herself). In our Institute we have followed this philosophy for many years and our experience confirms its value: 42 patients under age 40 (36 in stage I and 6 in advanced stage) underwent conservative surgery: 12 subsequently became pregnant and another 12 are able to conceive. Five- and ten-year survival rates are very good with 89.2% and 83.3% for all stages and 96.9% and 95% for early stages.

Adult↗
PubMed1998

Intrauterine ectopic pregnancy. A case report.

A case of vaginal bleeding occurring in a patient with a cervico-isthmic pregnancy located in a previous caesarean section scar was treated with curettage and systemic methotrexate. Metrorrhagia and uterine rupture are severe complications of this kind of ectopic pregnancy and sometimes require demolitive surgery, still today. Early ultrasonographic diagnosis is necessary to allow conservative treatment.

Adult↗
PubMed1997

Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non-synaptic mitochondria of aged rats.

We investigated NADH oxidation in non-synaptic and synaptic mitochondria from brain cortex of 4- and 24-month-old rats. The NADH oxidase activity was significantly lower in non-synaptic mitochondria from aged rats; we also found a significant decrease of sensitivity of NADH oxidation to the specific Complex I inhibitor, rotenone. Since the rotenone-binding site encompasses Complex I subunits encoded by mtDNA, these results are in accordance with the mitochondrial theory of aging, whereby somatic mtDNA mutations are at the basis of cellular senescence. Accordingly, a 5 kb deletion was detected only in the cortex of the aged animals.

Aging↗
PubMed1997

Coenzyme Q changes in liver and plasma in the rat after partial hepatectomy.

The levels of coenzyme Q were determined in blood plasma and regenerating liver mitochondria of hepatectomized rats, using as controls either sham-operated or non-operated animals. Mitochondrial CoQ9 content increased in sham-operated rats, whereas it was significantly lower in hepatectomized with respect to non-operated animals. Plasma CoQ9 levels decreased dramatically in hepatectomized animals, but increased strongly in sham-operated in comparison with non-operated rats. The data suggest the possibility of a rate-limiting step in CoQ biosynthesis in hepatectomized animals.

Animals↗
PubMed1997

Coenzyme Q deficiency in mitochondria: kinetic saturation versus physical saturation.

The coenzyme Q (CoQ) concentration in the inner membrane of beef heart mitochondria is not kinetically saturating for NADH oxidation inasmuch as the K(m) of NADH oxidation for endogenous CoQ10 is in the mM range in membrane lipids. Using CoQ1 as an electron acceptor from complex I, we have found additional evidence that the high Km of NADH oxidase for CoQ is not an artifact due to the use of organic solvents in reconstitution studies. We have also obtained experimental evidence that CoQ concentration may be rendered more rate-limiting for NADH oxidation either by a decrease of CoQ content (as in liver regeneration or under an acute oxidative stress), or by a possible increase of the Km for CoQ, as in some mitochondrial diseases and ageing. The possibility of enhancing the rate of NADH oxidation by CoQ therapy is hindered by the fact that the CoQ concentration in mitochondria appears to be regulated by its mixability with the membrane phospholipids. Nevertheless CoQ10 incorporated into heart submitochondrial particles by sonication enhances NADH oxidation (but not succinate oxidation) up to twofold. Nontoxic CoQ homologs and analogs having shorter side-chains with respect to CoQ10 can be incorporated in the mitochondrial membrane without sonication, supporting an enhancement of NADH oxidation rate above 'physiological' values. It is worth investigating whether this approach can have a therapeutical value in vivo in mitochondrial bioenergetic disorders.

Aging↗
PubMed1997

Development and pharmacological characterization of a modified procedure for the measurement of carbonic anhydrase activity.

Carbonic anhydrases (CAs) are a family of zinc metalloenzymes of molecular mass 30-60 kDa; seven different isoenzymes belong to this family (Okuyama et al., 1992, Proc Natl Acad Sci USA 89:1315-1319). They may be broadly recognized according to the efficiency with which they catalyze the reversible interconversion of CO2 and HCO3-, and they differ in physicochemical properties, in sensitivity to various inhibitors and in their subcellular localization; cytoplasmic (CA I, CA II, CA III, and CA VII), cell-surface membrane (CA IV), and mitochondrial (CA V) and secretory (CA VI) isoenzymes have been described. Several methods are reported in the literature for the measure of CA enzymatic activity; they may be broadly divided into two categories: those based on the measure of pH variation (pH-stat and colorimetric assays) (Wu et al., 1993, J Ocular Pharm 9:97-108; Maren, 1991, Molec Pharmacol 41:419-426) and the ones in which CO2 production is measured through pCO2 sensors (Botrè and Botrè, 1990, Anal Biochem 185:254-264).

Acetazolamide↗
PubMed1997

Detoxification of the Helicobacter pylori cytotoxin.

Treatment of the Helicobacter pylori vacuolating cytotoxin with very low concentrations of formaldehyde resulted in abrogation of toxic activity in both a HeLa cell vacuolation assay and an in vivo assay of gastric epithelial damage. Detoxification had only a minimal effect on the integrity of the oligomeric or monomeric structure. The toxoid retained the ability to bind to target cells and to induce high-titer neutralizing antibodies after immunization of rabbits. Furthermore, oral immunization of mice with the toxoid resulted in protection against infective challenge with mouse-adapted strains of H. pylori. The sensitivity of the toxin to formaldehyde treatment suggests that a few lysine residues in the protein may be essential for toxic activity and that VacA detoxified in this manner may be a potential candidate for inclusion in a vaccine against H. pylori infection and disease.

Animals↗
PubMed1997

Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection.

Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade gastric B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile enterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.

Animals↗
PubMed1997

Benign cystic mesothelioma of peritoneum: a case report.

A case of multicystic peritoneal mesothelioma involving the pelvic serosal surface is reported. Morphological and immunohistochemical findings agree with the suggested mesothelial origin of this lesion. Lymphangioma was excluded by the unreactivity to Factor VIII related antigen, ULEX-E1 and CD31. Recurrence after a few months from the first surgical resection disagrees with the reactive hyperplastic nature proposed; a tendency to recur was independent from the absence of an aggressive growth pattern and cytologic atypia.

Adult↗
PubMed1997

Mitochondrial complex I defects in aging.

According to the 'mitochondrial theory of aging' it is expected that the activity of NADH Coenzyme Q reductase (Complex I) would be most severely affected among mitochondrial enzymes, since mitochondrial DNA encodes for 7 subunits of this enzyme. Being these subunits the site of binding of the acceptor substrate (Coenzyme Q) and of most inhibitors of the enzyme, it is also expected that subtle kinetic changes of quinone affinity and enzyme inhibition could develop in aging before an overall loss of activity would be observed. The overall activity of Complex I was decreased in several tissues from aged rats, nevertheless it was found that direct assay of Complex I using artificial quinone acceptors may underevaluate the enzyme activity. The most acceptable results could be obtained by applying the 'pool equation' to calculate Complex I activity from aerobic NADH oxidation; using this method it was found that the decrease in Complex I activity in mitochondria from old animals was greater than the activity calculated by direct assay of NADH Coenzyme Q reductase. A decrease of NADH oxidation and its rotenone sensitivity was observed in nonsynaptic mitochondria, but not in synaptic 'light' and 'heavy' mitochondria of brain cortex from aged rats. In a study of Complex I activity in human platelet membranes we found that the enzyme activity was unchanged but the titre for half-inhibition by rotenone was significantly increased in aged individuals and proposed this change as a suitable biomarker of aging and age-related diseases.

Adult↗
PubMed1997

Testing for occult cancer in patients with idiopathic deep vein thrombosis--a decision analysis.

OBJECTIVE: To determine the effectiveness and cost-effectiveness of testing for occult cancer in idiopathic deep vein thrombosis (IDVT). DESIGN: Threshold analysis was performed on the risk-adjusted cancer prevalence in a cost-effectiveness model of ideal testing for selecting cancers with potentially desirable utility (candidate cancers). Decision analysis was employed to compare different testing programs for candidate cancers with that of no testing. Life expectancy (LE) of early- and late-detected cancers and costs of testing were the dimensions of utility. Cost-effectiveness was expressed as marginal cost per year of life saved. The perspective of the third payer was adopted, and a discount rate of 3% was applied to both costs and benefits. DATA SOURCES: Risk of cancer in IDVT, testing policies, test characteristics, and LE were gathered from literature. Costs were provided from our hospital rate book and accounting service. RESULTS: Ideal testing would support a gain of LE of 40 days or more for prostate, colon and bladder cancer in males and for colon, breast and endometrium cancer in females aged from 60 to 69 years. Testing females with colonoscopy and mammography in any sequence provides 70 days of life gained. Testing males with colonoscopy provides 27 days of life gained. Lower and older ages reduce testing effectiveness. The qualitative results are stable over plausible ranges of test characteristics, while variations in the value of benefit for early cancer diagnosis may modify the strategy. Incremental cost-effectiveness ranges from $1,789 to $ 6,979 per year of life gained. CONCLUSIONS: According to the effectiveness criterion adopted, the only worthwhile investigation strategy includes colon and breast cancer in females. Testing for colon cancer in males is desirable at a lower criterion of effectiveness. All the strategies are cost effective.

Aged↗
PubMed1997

[Dipyridamole-echocardiography test in the diagnosis of vasomotor angina].

Dipyridamole-atropine echocardiography testing is used extensively for the diagnosis of coronary artery disease and it is highly effective in diagnosing "organic" coronary artery disease by inducing myocardial ischemia via three different mechanisms: maximal coronary artery vasodilatation with phoenomena of flow-maldistribution caused by dipyridamole, increase in myocardial oxygen consumption and reduction of the oxygen supply to the myocardium caused by atropine. Moreover, the abrupt withdrawal of the coronary artery vasodilatation caused by aminophylline, which is routinely infused at the end of the test, may trigger coronary artery spasms in patients with variant angina, thus enhancing the diagnostic power of the test. We report two clinical cases of patients with rest angina and angiographically normal coronary arteries, in whom coronary artery spasm was induced by administering aminophylline during the stress test.

Coronary Vasospasm↗
PubMed1996

Inhibitor sensitivity of respiratory complex I in human platelets: a possible biomarker of ageing.

NADH-Coenzyme Q reductase was assayed in platelet mitochondrial membranes obtained from 19 pools of two venous blood samples from female young (19-30 years) individuals and 18 pools from aged ones (66-107 years). The enzyme activities were not significantly changed in the two groups, but a decrease of sensitivity to the specific inhibitor, rotenone, occurred in a substantial number of aged individuals. The results are in agreement with the predictions of the mitochondrial theory of ageing and may be used to develop a sensitive biomarker of the ageing process.

Adult↗
PubMed1996

All-trans-retinoic acid counteracts endothelial cell procoagulant activity induced by a human promyelocytic leukemia-derived cell line (NB4).

Therapy with all-trans-retinoic acid (ATRA) can rapidly improve the coagulopathy of acute promyelocytic leukemia (APL). This study was designed to evaluate whether the APL cell line NB4 induces the procoagulant activity (PCA) of human endothelial cells (ECs) in vitro, and whether this property is modified after ATRA-induced NB4 maturation. EC monolayers were incubated for 4 hours at 37 degrees C with the conditioned media (CM) of NB4 treated with 1 mumol/L ATRA (ATRA-NB4-CM) or the vehicle (control-NB4-CM). EC lysates were tested for PCA. ATRA-NB4-CM induced significantly more PCA:tissue factor (TF) than control-NB4-CM (P < .01). To identify the cause of TF induction, interleukin (IL)-1 beta antigen levels were measured in CM samples. ATRA-NB4-CM contained significantly more IL-1 beta than control-NB4-CM. EC PCA was significantly inhibited by an anti-IL-1 beta antibody. The addition to the media of 10 mumol/L ATRA counteracted the EC TF expression induced by NB4-CM. These data indicate that ATRA increases the promyelocyte-induced EC TF, partly through increased IL-1 beta production. However, ATRA can protect the endothelium from the procoagulant stimulus of leukemic cells.

Blood Coagulation Factors↗