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Biomedical subjects

G Genovese

Publications and source records attributed to G Genovese.

At least 19 recordsLinked to original sources

Possible role of carbonic anhydrase, V-H(+)-ATPase, and Cl(-)/HCO3- exchanger in electrogenic ion transport across the gills of the euryhaline crab Chasmagnathus granulatus.

We studied the participation of carbonic anhydrase (CA), V-H(+)-ATPase, and Cl(-)/HCO3- exchanger in electrogenic ion absorption through the gills of Chasmagnathus granulatus. CA activity was measured in anterior gills and posterior gills after acclimation to 2 per thousand, 10 per thousand, 30 per thousand (about seawater), and 45 per thousand salinity. The highest CA specific activity was detected in the microsomal fraction in anterior gills, and in the cytosolic fraction, in posterior ones. Both fractions were strongly induced by decreasing salinity only in posterior gills. Perfusion of posterior gills from crabs acclimated to either 2 per thousand or 10 per thousand with acetazolamide inhibited CA activity almost completely. In posterior gills from crabs acclimated to 2 per thousand and perfused with 20 per thousand saline (iso-osmotic for these crabs), acetazolamide reduced transepithelial potential difference (V(te)) by 47%, further addition of ouabain enhanced the effect to 88%. Acetazolamide had no effect in the same gills perfused with 30 per thousand saline (iso-osmotic for seawater acclimated crabs). Bafilomycin A1 and SITS (inhibitors of V-H(+)-ATPase and Cl(-)/HCO3-) reduced V(te) by 15-16% in gills perfused with normal 20 per thousand saline, and by 77% and 45%, respectively when they were applied in Na-free 20 per thousand saline, suggesting the participation of those transporters and cytosolic CA in electrogenic ion absorption.

Acetazolamide↗

Mono- and diiodocyclophosphamide as possible internal standards for cyclophosphamide quantification: characterization by ion trap multi-stage mass spectrometry and effects of iodine-chlorine substitution on the fragmentation pattern.

Hospital personnel involved in antineoplastic drug preparation and administration to patients are exposed to large amounts of these drugs. Labour legislation indicates the necessity of planning monitoring strategies aimed at prevention and/or reduction of drug exposure. Monitoring strategies consist of quantitative determinations of indicators, present in environmental and biological matrices. Among the antineoplastic drugs widely used, cyclophosphamide (CP) has been identified as a suitable indicator of potential exposure to mixtures of antineoplastic drugs. Many literature methods for quantitative analysis of CP involve either liquid (LC) or gas chromatography (GC) with mass spectrometry (MS), both of which require use of a suitable internal standard. The present work focuses on the synthesis of mono- and diiodocyclophosphamide (CPI and CPI(2)) to be used as internal standard. These compounds were analyzed by GC/EI-MS/MS and LC/ESI-MS(n) using ion trap mass spectrometry. The product ion mass spectra are interpreted in terms of proposed structures of fragment ions. Iodine-chlorine substitution resulted in a weakening of the carbon-halogen bond with a noteworthy influence on the ion fragmentation processes. The proposed suitability of CPI and CPI(2) as internal standards was based on similarities to CP as regards ionization and fragmentation processes. The results obtained suggest that CPI could be used as internal standard for CP quantification by LC/ESI-MS/MS, and CPI(2) for GC/EI-MS/MS analyses.

Alkylating Agents↗

Modulation of ion uptake across posterior gills of the crab Chasmagnathus granulatus by dopamine and cAMP.

Cyclic AMP (cAMP) and dopamine modulate ion uptake across isolated and perfused posterior gills of Chasmagnathus granulatus acclimated to 10 per thousand salinity. Addition of cAMP agonists, such as cp-cAMP, forskolin, and IBMX, produced a significant increase in the transepithelial potential difference (Vte), which reflects ion transport activity. Dopamine (DA) also had a stimulatory effect on ion uptake, increasing Vte and Na(+) influx, although this effect was transient, since both variables remained elevated for less than 30 min. In addition, the dose-response curve for DA concentration-Vte was biphasic, and the maximum stimulation was obtained with 10 micromol l(-1). When the effects of forskolin and DA on the Na(+)/K(+)-ATPase activity were tested, they correlated well with the Vte and Na(+) influx experiments; the enzyme activity increased significantly after preincubation of gill fragments for 10 min with forskolin or DA (51 and 64%, respectively), but there was no effect after pre-incubation with DA for 20 min. Finally, KT5720, a specific inhibitor of cAMP-dependent protein kinase (PKA), completely abolished the stimulatory effect of DA on Vte, suggesting the involvement of PKA in this mechanism.

Animals↗

Determination of urinary S-phenylmercapturic acid by liquid chromatography-tandem mass spectrometry.

Urinary S-phenylmercapturic acid (S-PMA) is considered a useful biomarker for the measurement of low levels of benzene exposure, related to occupational exposure, smoking habits or environmental pollution. S-PMA quantitative analysis requires highly sensitive and specific techniques and purification procedures, mainly based on liquid-liquid or solid-phase extraction, which result in time expensive analyses. A method was developed for the quantitative determination of S-PMA in urine by using a simple, reproducible and easily automatizable HPLC purification followed by LC/ESI-NI/MS2 analysis. In order to reduce the cost of the analysis, related to the use of expensive labeled standards, p-bromo-S-phenylmercapturic acid (p-Br-S-PMA) was synthesized, characterized and used as internal standard. The feasibility and efficacy of the proposed method were examined by constructing calibration curves in the range from 6.2 to 200 microg/l and data were analyzed in terms of linearity and statistical parameters. The detection limit, related to the purification of 1 ml urine sample is 5 microg/l. The method was applied to the analysis of 12 urine samples from smoker subjects non-occupationally exposed to benzene. S-PMA urinary levels ranged from 13.6 to >200 microg/l, suggesting a high influence of life style in the S-PMA excretion. The proposed analytical method is suitable for the biological monitoring of both smoker and non-smoker workers, occupationally exposed to benzene. By processing at least 2 ml of urine samples, the method appears to be also useful for the evaluation of benzene uptake due to the environmental pollution.

Acetylcysteine↗

The morphometric changes in the gills of the estuarine crab Chasmagnathus granulatus under hyper- and hyporegulation conditions are not caused by proliferation of specialised cells.

Chasmagnathus granulatus is a hyper-hyporegulating crab that inhabits changing habitats of salinity in Brazil, Uruguay and Argentina. Since the gills are the main sites for active ion transport in crabs, the adaptive changes in the gill epithelium occurring under different conditions of salinity were studied by means of morphological and morphometric analysis, and immunohistochemical identification of cell proliferation (BrdU technique). In anterior (1-3) gills the epithelium thickness from crabs acclimatised to 12, 34 and 44 g/l ranged from 1.27 to 2.46 microm, with no significant change during acclimatisation, thus denoting a respiratory function. Medial (4-5) gill epithelium was slightly thicker in extreme salinities, but these differences were not statistically significant. In contrast, epithelial thickness of the posterior (6-8) gills increased significantly up to 8.10 microm (dorsal zone of gill 8) both in hyper- and hyposaline media compared with seawater. The dark areas measured in gill 8 treated with AgNO3 revealed putative ion transporting tissue, especially at 12 and 44 g/l, corresponding to the zones of higher epithelial thickness. Hence these areas seem to participate both in hyper- and hyporegulation. Proliferating cells labelled with BrdU almost never occurred in the gills/salinity combinations studied during the initial 48 h of transfer from seawater to hyperconcentrated or diluted media, thus suggesting an increase in cell size rather than cell proliferation.

Adaptation, Physiological↗

Ineffectiveness of dextromethorphan in cancer pain.

Experimental studies have indicated that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective analgesics in a wide variety of chronic pain states. The mechanism is presumed to be related to decreased firing of dorsal horn neurons after constant repeated C-fiber stimulation. Dextromethorphan (DM), a potent NMDA antagonist with a good safety profile, may be a promising agent for the treatment of persistent pain. An open-label randomized trial was designed to examine the effects of combining DM with NSAIDs, dextropropoxyphene, or morphine in cancer patients with pain. Patients who required a change in the step of the World Health Organization's (WHO) analgesic ladder because of a pain level of 4 or more on a numerical pain scale were randomly allocated to receive DM 30 mg three times a day (30 patients) or conventional treatment (30 patients). There were 20 patients randomized for each step of the analgesic ladder. Pain mechanisms, pain intensity (numerical 0-10 scale), symptoms more frequently present in advanced cancer patients or associated with opioid therapy (graded on a 0-3 scale--not at all, slight, a lot, awful), opioid escalation index, days on opioid treatment, and adverse effects were recorded. After 2 days 75%, 80%, and 100% of patients treated with DM in steps 1, 2, and 3, respectively, required conventional treatment, because adequate pain relief had not been achieved (pain scale > 4). Failure of this treatment was equally observed in neuropathic pain or nociceptive pain syndromes. Four patients treated with DM who did not require the conventional treatment immediately did require this change after some days, due to poor pain control. A highly significant reduction in pain was observed in patients directly treated with the conventional treatment in all the three steps of the analgesic ladder. No significant analgesic effects could be found when DM at this dose was combined with NSAIDs, dextropropoxyphene, or morphine.

Analgesics, Opioid↗

Home palliative care: results in 1991 versus 1988.

Home care is greatly expanding because of the savings it offers by avoiding unnecessary hospitalization and also because patients benefit from being in their own home environments. Since 1988, Societa Assistenza Malato Oncologico Terminale (SAMOT) has organized a pain relief and home palliative care unit for terminal cancer patients. Objectives, difficulties, protocols, and achievements of 4 years of experience were examined, and the findings of the various years were compared. Our results suggest that considerable progress has been made in home palliative care. There are still social and cultural difficulties to overcome, however.

Female↗

[Prospective study of HBV circulation and long-term evaluation of anti-hepatitis-B vaccination in patients undergoing hemodialysis].

Hemodialysis patients were screened and monitored for HBV markers and at renal unit (identification EDTA 13ND) Palermo. Eighty-five patients received the hepatitis B vaccine (Haevac B Pasteur); fifty-three were followed up for more than three years; they received one of the three following schedules: 5 micrograms at 0, 1, 2 and 14 months; 5 micrograms at 0, 1, 2, 3, and 14 or 10 micrograms at 0, 1, 2, and 14 months. The best result was obtained by third schedule with a sero-conversion to anti-HBs of 83% at one month after the booster doses; and with the same percentage of anti-HBs positivity two years after the booster dose. During the study time (January 1984, March 1989) no new HBV events in patients and in the hemodialysis staff, who was also on monitoring, were observed.

Adolescent↗

[Vascular changes in postmastectomy "thick arm"].

The authors, after shortly outlining some pathogenetic theories about postmastectomy "big arm", especially dwell upon the theory of the hindered venous discharge. They, subsequently, through a clear and interesting phlebographic iconography, illustrate ten of the 41 cases suffering from such syndrome, they recently had the opportunity to observe. On the basis of their own experience, and according to part of the literature thereabout, the authors think very probably the postmastectomy "big arm" is to be ascribed to the hindered venous reflux of upper limb (for thrombosis or compression), due to the operation of mastectomy. As a conclusion, they suggest the improvement or recovery of this syndrome by stepping over the stenosed venous tract through a by-pass.

Arm↗

[Permanent endocardiac electrostimulation. Considerations on 511 implantations and reimplantations in 7 years of practice].

Permanent pacemakers were implanted and reimplanted in a total of 511 patients (mostly men) during a period of about 7 yr. Mean age was 67.9 yr. The cephalic route was used in nearly every case, with subclavicular implantation of the generator. Mean hospital stay was 7.6 days. Ventricular inhibition pacemakers were used in over 84% and fixed-frequency models in 7%. Mean pacemaker life was 24.1 months, with longer periods in the last months of the period of observation. The evaluation of battery run-down and recent and long-term complications is discussed, together with a particular type of decubitus of electrolytic origin. Hospital mortality was 2%. Survival was 91% at 1 yr and 54% at 6 yr. Emphasis is placed on the fact that subjects continue to be heart patients. Their well-being depends on psychological and general medical care, together with help from their, families and society, quite apart from cardiological attention.

Adult↗