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Biomedical subjects

G Beretta

Publications and source records attributed to G Beretta.

At least 19 recordsLinked to original sources

Antioxidant activity of polyphenols from solid olive residues of c.v. Coratina.

The antioxidant profile of extracts from solid olive residue (SOR) of c.v. Coratina, a cultivar widely diffused in the south of Italy, using both cell-free and cell-based experimental models, was investigated. A total hydroalcoholic extract (polyphenols content 19.7%) and a purified extract (Oleaselecttrade mark) (polyphenols content 35.1%) were tested for their ability to quench the stable free radical DPPH, the peroxyl radicals (ORAC assay), by monitoring the loss in fluorescence of R-phycoerythrin induced by the peroxyl radical generator AAPH and their ability to inhibit the cumene hydroperoxide-induced lysis of rat red blood cells (RBC). The total hydroalcoholic extract showed IC(50) 26.96+/-1.53 microg/ml in the DPPH assay, that 10 microg/ml were equivalent to 2.11+/-0.12 microg/ml Trolox (ORAC assay) and IC(50) 1.7+/-0.20 microg/ml in the RBC hemolysis. The Oleaselect extract was 4 to 5 folds more active than the hydroalcoholic extract in all the experimental models, with IC(50) values of 7.36+/-0.38 microg/ml in the DPPH test and of 0.38+/-0.03 microg/ml in RBC; the antioxidant activity in the ORAC assay was slightly greater than that of Trolox (10 microg/ml equivalent to 11.45+/-0.40 microg/ml). The scavenging effect of the extract in the ORAC assay was compared to that of verbascoside (the main polyphenol component) and of caffeic acid (the basic constituent of verbascoside): the results indicate that caffeic acid (10 microg/ml equivalent to 35.70+/-2.95 microg/ml Trolox) is more potent than verbascoside (10 microg/ml equivalent to 15.42+/-1.21 microg/ml Trolox) in entrapping peroxyl radicals. Finally the antioxidant activity of the Oleaselect extract was confirmed in human umbilical endothelial cells (EC) exposed to the site-specific peroxyl radical inducer AAPH, where a massive lipid peroxidation process (marker the fluorescence probe BODIPY) takes place, paralleled by a marked loss of cell viability (calcein assay). The purified extract (1-20 microg/ml) pre-incubated with EC for 1 h dose-dependently inhibited both the lipid-peroxidation damage and cell death. Taking into account the total polyphenol content, these results clearly indicate a greater antioxidant activity for the purified extract, due to a cooperative antioxidant interaction among its polyphenol constituents.

Amidines↗

Long-term effects of MDMA (Ecstasy) on the human central nervous system revealed by visual evoked potentials.

Several studies indicate long-term cognitive impairment of MDMA (ecstasy) users. In the present study we attempted to establish whether electrophysiological correlates of low-level cognitive processes present a long-term alteration, dependent on the level of use of ecstasy. We addressed this issue by investigating amplitude and latency of VEPs related to a very simple discrimination task involving sustained attention (arousal). Eight heavy-MDMA users, eight moderate-MDMA users and 18 drug-free control subjects were asked to discriminate whether the digit at the centre of the screen was 1 or 2. None of the subjects (except one) had used MDMA in the 6 months previous testing. We measured psychophysical performance and EEG, recorded in Oz and Fz during task execution. The heavy-MDMA users made significantly more errors than the other two groups (p < .05). Moreover, they presented reduced amplitude but not latency of VEPs in both Oz and Fz. The effect in Oz is present in P200 (for heavy users only, p < .05) and in P300 components (for both MDMA groups; heavy users: p < .001, moderate users: p < .0.5). In Fz, the amplitude effect is present in N250 (for heavy users only, p < .05) and in P300 components (for both MDMA groups; heavy users: p < .05, moderate users: p < .05). The three groups do not differ in early components, reflecting low-level processing. These results provide evidence of long-term electrophysiological abnormality displayed by ecstasy users and agree with the suggestion that even typical recreational doses of ecstasy are sufficient to cause long-term altered cortical activity in humans.

Adult↗

Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity.

In an attempt to synthesize potential anticancer agents acting by inhibition of topoisomerase I (Topo I) a new series of oxyiminomethyl derivatives in position 7 of camptothecin (CPT) was prepared. The synthesis relied on the condensation of 20S-CPT-7-aldehyde or 20S-CPT-7-ketones with alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl O-substituted hydroxylamines. The compounds were tested for their cytotoxic activity in vitro against H460 non-small lung carcinoma cell line, the activity being for 24 out of 37 compounds in the 0.01-0.3 microM range. A QSAR analysis indicated that lipophilicity is the main parameter correlated with cytotoxicity. Investigation of the DNA-Topo I-drug cleavable complex showed a rough parallelism between cytotoxicity and inhibition of Topo I. Persistence of the DNA cleavage after NaCl-mediated disruption of the ternary complex suggests that for the most potent compounds, e.g., 15, the cytotoxicity was at least in part related to stabilization of the complex, as also supported by the persistence of the DNA-enzyme complex in drug-treated cells. The in vivo antitumor efficacy of the most potent analogue (15) was evaluated in direct comparison with topotecan using human lung tumor xenograft models. In the range of optimal doses (2-3 mg/kg), the improved efficacy of 15 was documented in terms of inhibition of tumor growth and rate of complete response.

Animals↗

Survival and quality of life in gastrointestinal tumors: two different end points?

BACKGROUND: In gastrointestinal tumors, the traditional end point of medical treatment was represented mainly by survival. In the last few years, however, there has been an increasing awareness about the role of quality of life. DESIGN: This paper seeks to discuss these two important end points and their relationship in colorectal, gastric, pancreatic and liver cancers. RESULTS: Chemotherapy has doubled survival in comparison with best supportive care in gastrointestinal tumors. A subjective response, represented by a decrease in cancer-related symptoms is expected in about half of the symptomatic patients in colorectal and gastric cancer. In pancreatic cancer, the positive results in terms of clinical benefit helped define the role of chemotherapy. Although clinical benefit does not represent a validated tool to measure quality of life, it can be a first step in the definition of new, simpler tools to assess this end point. The frequent presence of a serious concomitant disease, liver cirrhosis, in patients with hepatocellular carcinoma (HCC) usually prevents the use of chemotherapy in these tumors, which are often treated with locoregional treatments. Unfortunately, their impact on the survival and quality of life of these patients has never been adequately assessed. CONCLUSIONS: In many gastrointestinal cancers, chemotherapy can produce a survival gain and an improvement in the quality of life. Further studies assessing new drugs and/or combinations should focus on these aspects and their relationships. In particular, the impact of treatments of HCC on both survival and quality of life must be investigated by well-designed prospective trials. When assessing the value of a particular anticancer treatment, it is important to consider the impact it may have not only on survival but also on quality of life. This is particularly so for cancer patients, whose life expectancy may be short.

Carcinoma, Hepatocellular↗

Short-term glucocorticoid administration decreases both hypothalamic and pituitary galanin synthesis in the adult male rat.

Galanin (GAL) is a peptide that has been implicated in the regulation of the growth axis. It is generally accepted that GAL can increase serum growth hormone (GH) levels, although the underlying mechanism for this increase is unknown. It is well known that long-term glucocorticoid treatment alters in vivo GH secretion, since there is a decrease in serum GH in response to stimuli. It has previously been shown in our laboratory that administration of GAL can overcome the effects of glucocorticoid administration on GH secretion. The aim of the present study was to determine the effects of long-term glucocorticoid administration on the regulation of hypothalamic and pituitary GAL mRNA levels. Adult male rats were treated for 72 hours with the synthetic glucocorticoid dexamethasone ([DEX] 40 microg/kg/d intraperitoneal injections). RNase protection assays were performed on both the hypothalamus and pituitary for the presence of GAL mRNA. As expected, DEX significantly decreased somatic growth, as evidenced by a decrease (50%) in the weight gain of glucocorticoid-treated versus control animals. It was also demonstrated that in both the hypothalamus and pituitary, glucocorticoid treatment reduced the level of GAL mRNA (to 11% and 6.5%, respectively) compared with the control condition. We conclude that the decrease in GAL mRNA may lead to a decrease in GAL secretion, which in turn may be involved in the glucocorticoid-induced inhibition of GH secretion.

Animals↗

Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies.

Lupus anticoagulant (LA) antibodies are acquired inhibitors of coagulation belonging-together with anticardiolipid (aCL) antibodies-to the family of antiphospholipid antibodies. Since LA antibodies affect coagulation reactions via recognition of the complex of lipid-bound prothrombin, they may be better named anti-prothrombin antibodies. We studied their immunological properties in the plasma of 59 patients with antiphospholipid antibodies by means of specific ELISA systems that allowed the characterization of the interaction of these antibodies with human prothrombin and anionic phospholipids. The mode of presentation of prothrombin was found to greatly influence the reactivity of anti-prothrombin antibodies. In fact, when plain polystyrene plates were used to immobilize prothrombin, virtually no binding was observed. Conversely, when prothrombin was coated on high-activated PVC ELISA plates, 34 samples (58%) contained antibodies that recognize human prothrombin in solid phase. In particular, IgG antibodies were found in 21 plasmas and IgM in 22; both IgG and IgM isotypes were present in 9 of these cases. A higher prevalence was observed in the ELISA for the detection of the antibodies directed at the calcium-mediated complex of phosphatidylserine (PS)-bound prothrombin: 53 samples (90%), preadsorbed with cardiolipin liposomes to remove aCL antibodies, showed the presence of IgG and/or IgM anti-prothrombin antibodies. When the results were analyzed according to the immunoglobulin isotypes, 44 (75%) and 39 (66%) samples were found to contain IgG and IgM anti-prothrombin antibodies, respectively. Both IgG and IgM were present in the plasma of 30 patients. Only half of these samples reacted also with PVC-bound prothrombin. Apparently, the higher rate of positivity of the ELISA for the detection of antibodies to the complex of PS-bound prothrombin was not due to differences in the amount of antigen available in the 2 systems, as judged by binding experiments performed with a rabbit polyclonal anti-human prothrombin antiserum. Finally, the anticoagulant properties of 14 total IgG preparations (12 of them contained anti-prothrombin antibodies positive in both ELISA systems, whereas the other 2 cases reacted either with PVC-bound prothrombin only or with PS-bound prothrombin only) were evaluated by diluted Russell's Viper Venom Time and by diluted activated Partial Thromboplastin Time. To rule out the beta 2-glycoprotein I (beta 2-GPI)-dependent anticoagulant effect of the aCL antibodies contained in the preparations, the coagulation tests were performed in beta 2-GPI deficient plasma. Six preparations failed to show anticoagulant activity in both assay systems, suggesting that 2 types of IgG anti-prothrombin antibodies exist, that differ with respect to their anticoagulant properties. These findings suggest that anti-prothrombin antibodies resemble aCL antibodies with respect to the behaviour in "in vitro" coagulation reactions and underline the wide heterogeneity of antiphospholipid antibodies.

Adult↗

[Management of sexual dysfunction in spinal cord injury].

In this paper we tried to report the sexual life aspect of spinal cord injury (SCI) patients and to explain how it should be treated in diagnostic and therapeutic pathways. We explain the sexual life alterations of male and female SCI patient and we report some dates about our experience.

Female↗

[Post-traumatic penoscrotal avulsion: cosmetic and uro-andrologic evaluation after surgical reconstruction].

A case of surgical reconstruction after penoscrotal skin avulsion is described. Penile coverage was gained by two full thickness grafts helicoidally placed to avoid retractions. Scrotal reconstruction was carried out in two steps, after testis subcutaneous implantation, with axial flaps expanded in abdominal region. The procedure has the advantage of flaps sure vitality, avoids patient discomfort produced by a perineal expansion with satisfactory cosmetic appearance and restore of a normal sexual function.

Humans↗

[Sexuality and neoplastic disease].

Authors review principles and occurrence of sex-impairment correlated with neoplasia and related treatments. Main altering effects appear due to chemotherapy and hormone manipulation, but even surgery and radiotherapy, as well as supportive care are able to induce sex dysfunctions, either physically or psychologically. A specific grading scale (with increasing intensity from 0 to 4) is proposed, following general WHO suggestions in medical oncology, with the aim of recording and prospectively evaluating clinical data in a reproducible fashion.

Adult↗

[Anti-sperm antibodies in dysspermia in spinal cord injury patients].

A relatively uninvestigated area of reproductive physiology is the changes of sperm quality in the anejaculatory man. The retention of sperm cells may result in increased pressure in the genital tract, initiating an autoimmune response to sperm as seen in cases of congenital absence of the vas deferens and vasectomy. Reports on this matter are very contradictory. We evaluated antisperm antibodies in two groups of anejaculatory men with SCI. In the first group of 16 patients there was no clinical and laboratory urogenital infection. In the second group of 13 patients there was clinical and laboratory evidence for urogenital infection. Sperm antibodies were found in 12% of the patients of the first group and in 38% of the patients of the second group.

Autoantibodies↗

Nerve conduction velocity of dorsal nerve of penis: a modified technique.

The dorsal nerve of the penis is involved in sexual function. Until now, the nerve conduction velocity (NCV) of the dorsal nerve of the penis has been measured by dividing the distance between the stimulating and the recording electrodes by the latency to the negative peak of the action potential. With the penis stretched with a 1 lb weight, the NCV in normal men was 33 m/sec +/- 3.8. Measuring the NCV in this way, we became aware that when we decreased the distance between the stimulating and the recording electrodes, the velocity decreased. Furthermore these different measurements were linearly related. Taking this into account, we calculated the NCV with mathematical formula. In normal people, it turned out to be faster than reported previously.

Action Potentials↗

Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. I. Isolation and characterization.

A novel antibiotic, GE2270 A, was isolated from the fermentation broth of a strain of Planobispora rosea. The product was found to inhibit bacterial protein synthesis. Structural characteristics showed similarities between GE2270 A and thiazolyl peptides such as micrococcin which is known to inhibit protein synthesis by acting directly on the ribosome. Despite this similarity GE2270 A showed functional analogy to kirromycin-like antibiotics and pulvomycin, as its molecular target was found to be elongation factor Tu (EF-Tu). GE2270 A is active against Gram-positive microorganism and anaerobes and differs from the other EF-Tu inhibitors in its spectrum of antimicrobial activity.

Actinomycetales↗

[Intracavernous injections of prostaglandin E1 in the treatment of erection disorders].

Vasoactive drugs have been widely used for the treatment of impotence in the last years. Recently Prostaglandin E1 has been employed with success as a therapy in erection problems. The Authors have treated with Prostaglandin E1 209 patients complaining erection failure. Positive results were obtained in 155 patients (74,16%). No complications or side effects occurred. 129 patients of the 155 in which the test resulted positive were proposed a self-injection program and 115 accepted. Until now no side effects or complications occurred.

Adult↗

[Anamnestic criteria for sexual evaluation in the andrological field].

What is the cause for impotence? In the recent years psychological studies have accredited some insights and modern neurological and vascular technologies have identified some previously idiopathic or misdiagnosed causes. The postulated ratio of psychogenic to organic dysfunction varies from 20:1 to 1:7 and this ratio may vary form one cultural area to the next. The authors underline that the main characteristic of the groups of males complaining of erectile dysfunction is heterogeneity and that the diagnostic procedure for finding the correct etiology may be rather cumbersome. Of primary importance is the patient's history to obtain a precise description of the dysfunction. Graber has suggested a more systematic approach to create a scientific nosology in the area of erectile failure. The phenomenon of morning erections must be inquired as well as the evaluation of the genital reflexes. A series of new diagnostic procedures has been developed but the Authors underline that it is preferable to use noninvasive techniques.

Circadian Rhythm↗