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Biomedical subjects

M Farina

Publications and source records attributed to M Farina.

At least 109 records · Page 6Linked to original sources

Adsorption of 5'-AMP and catalytic synthesis of 5'-ADP onto phosphate surfaces: correlation to solid matrix structures.

A non-enzymatic formation of 5'-ADP starting from phosphorylation of 5'-AMP in the presence of either calcium phosphate or calcium pyrophosphate precipitates is reported. This reaction is taken as a model for the study of heterogeneous catalysis of transphosphorylation in prebiotic conditions. Experiments were performed in completely aqueous media and in media containing dimethyl sulfoxide (Me2SO), to simulate periods of dehydration in primitive aquatic environments. It has been observed that the nucleotide is adsorbed onto both calcium phosphate and calcium pyrophosphate in accordance with Langmuir isotherms. Adsorptive capacity and affinity of the precipitates for nucleotide are changed by the presence of Me2SO, suggesting that the interaction between biomonomers and surfaces can be modulated by the degree of hydration of the anionic components of these compounds. In completely aqueous environments, formation of 5'-ADP from 5'-AMP adsorbed on precipitates of calcium phosphate and calcium pyrophosphate is very small. However, in the presence of 60% Me2SO this synthesis increases by factors of 3 and 6 for surfaces of calcium phosphate and calcium pyrophosphate, respectively, and follows first-order kinetics. Determinations of free energy changes show that phosphorylation of 5'-AMP adsorbed to these precipitates is thermodynamically favorable. Depending on the precipitation time of the samples and the composition of the medium, structural analysis of these precipitates by electron and X-ray diffraction shows changes in their cristallinity grade. It is proposed that these changes are responsible for the modulation of the quantity of adsorbed nucleotides to the surface of solid matrices as well as the catalytic activity of the precipitates.

Adenosine Diphosphate↗

Bioelectrical impedance and hemodialysis.

Bioimpedance is a simple and non-invasive method of assessing body fluid composition. The aim of our study was to evaluate the reilability of impedance: a) to measure urea distribution volume considered to be coextensive with total body water (TBW); b) to assess the changes in body fluid compartments before and after dialysis; c) to predict hypotensive episodes. In twelve hemodialysis patients, TBW measured by bioelectrical impedance analysis (BIA) before a dialysis session was significantly correlated with the urea distribution volume estimated by dialysis direct quantification (r = 0.64, p < 0.05) and with TBW calculated by the Watson equation (r = 0.65, p < 0.05). Anthropometric values were, on average, 4.8% higher. TBW measured by BIA at the end of treatment overestimated fluid losses induced by ultrafiltration by 14% to 70%, while TBW 6 h after dialysis reflected the weight losses. On line BIA during hemodialysis has a very low positive predictive value (41.6%) and poor sensitivity (66%) for the prediction of hypotension. In conclusion, BIA is helpful in assessing the urea distribution volume but is not reliable for assessing acute fluid changes nor for predicting hypotensive episodes related to hemodialysis.

Adult↗

Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif.

Interference with T cell activation signals by Human immunodeficiency virus (HIV) gene products is suggested to contribute to the impairment of immune functions observed in AIDS. Interleukin-2 (IL-2) and HIV share common stimulatory signals triggered during T cell activation. The role of HIV tat, which is the main enhancing factor for viral LTR, in the regulation of IL-2 gene transcription has been studied following transient expression of the tat gene in phorbol ester and calcium ionophore-activated Jurkat cells transfected with IL-2 promoter-chloramphenicol acetyltransferase reporter constructs. We observed that tat increased the IL-2 promoter transcriptional activity in response to phorbol ester and ionomycin. This tat-dependent synergism mapped to the (-279 to -263 bp) NFAT motif of the IL-2 enhancer, which was sufficient to be transactivated by tat. Our data suggest that tat links T cell activating signals to the shared IL-2 and HIV regulation. This may play a role in the early phase of HIV infection.

Calcium↗

Positive and negative regulation of the composite octamer motif of the interleukin 2 enhancer by AP-1, Oct-2, and retinoic acid receptor.

The differentiating agent retinoic acid (RA) has been previously reported to interfere with 12-O-tetradecanoyl-phorbol-13-acetate (TPA)/Ca2+-induced signals for the regulation of the -96 to -66-bp octamer motif found in the enhancer for the interleukin (IL)-2 gene, which encodes a major T lymphocyte growth factor. The IL-2 octamer motif is a composite cis-element which binds Oct-1 and Oct-2 as well as a TPA/Ca2+-inducible nuclear factor, previously termed octamer-associated protein (OAP40). We show here that Oct-2, despite the presence of an active transcriptional activation domain, requires TPA/Ca2+-induced signals to strongly transactivate the IL-2 octamer motif in Jurkat T cells. This Oct-2-dependent transactivation is inhibited by RA. The presence of an intact COOH-terminal domain of Oct-2 contributes to both TPA/Ca2+-induced transactivation and the RA-mediated repression. We also show that both Fos and Jun components of the AP-1 factors participate in the OAP40 complex. Furthermore, transfected c-jun, jun-B, jun-D, c-fos, or Fos-B expression vectors partially substitute for TPA and Ca2+ and cooperate with Oct-2 for the transactivation of the combined OAP/octamer cis-element. Mutations of the genuine octamer-binding site abrogate both the binding of Oct-1 and Oct-2 and the TPA/Ca2+-induced transactivation of the OAP/octamer motif. OAP confers to Oct-2 responsivity to both TPA/Ca2+ and RA, since specific mutations of the AP-1/OAP-binding site significantly reduce the transactivation by Oct-2 in response to TPA and Ca2+ and abolish the inhibition by RA. Furthermore, retinoic acid receptor (RAR) alpha is able to inhibit in vitro the formation of the complex between the nuclear AP-1/OAP and its specific binding site, resulting in the interference with Oct-2-dependent cis-regulatory function of this AP-1 element. Therefore, we propose that the TPA/calcium-activated AP-1/OAP element is the main target of positive or negative regulatory signals influencing the IL-2 octamer motif, through synergism with Oct-2 and antagonism by RAR.

Base Sequence↗

Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy.

OBJECTIVE: Our purpose was to clarify the mechanisms by which postmenopausal estrogen replacement therapy exerts its protective effect on cardiovascular risk. STUDY DESIGN: By means of a bidirectional Doppler ultrasonographic system we measured pulsatility index variations the internal carotid artery and middle cerebral artery in 25 early postmenopausal women during a 6-month period of hormone replacement therapy. Transdermal estradiol (50 micrograms/day) was continuously administered. A 12-day course of medroxyprogesterone acetate (10 mg/day) was added every second month. RESULTS: The pulsatility index showed a significant (p = 0.0001) reduction in both arteries after 6 weeks. At 22 weeks a 25% reduction was measured. No variation of the estrogen-induced pulsatility index reduction was observed at the end of every cyclic progestogen supplementation. CONCLUSIONS: In early postmenopausal women hormone replacement therapy causes a rapid reduction of pulsatility index in brain arteries. Cyclical progestational supplementation does not modify this positive effect on reactivity of the blood vessels.

Administration, Cutaneous↗

Stability studies with a high-performance liquid chromatographic method for the determination of a new anthracycline analogue, 3'-deamino-3'-[2-(S)-methoxy-4-morpholino)doxorubicin (FCE 23762), in the final drug formulation.

A high-performance liquid chromatographic method was studied to optimize the separation of FCE 23762, a new antitumour agent, from both synthetic impurities and degradation products having very similar molecular structures. The main problems faced in the analytical method development using the most common reversed-phase columns available arose from the presence of analytical peaks with poor symmetry, a long analysis time and the separation between FCE 23762 and its R-isomer, which was often unsuitable for the correct determination of the drug substance. The use of a new stationary phase, Zorbax Rx-C8, together with a suitable mobile phase resulted in a good separation between the diastereomers, with satisfactory peak symmetry and run time. The method permitted the study of the stability of the drug substance in formulations for clinical trials.

Antineoplastic Agents↗

Recombinant human basic-fibroblastic growth factor: different medical dressings for clinical application in wound healing.

Recombinant human basic-Fibroblastic Growth Factor (rhb-FGF) is a basic single-chain protein showing high activity as mitogenetic and angiogenetic agent. The application of rhb-FGF in wound healing as stimulator of the tissue repair process is strictly connected with the covering of the wound by means of a proper dressing. A wide number of synthetic occlusive or non-occlusive wound dressings has been developed. Owing to the delicate proteic structure of rhb-FGF, and generally of all the Growth Factors, compatibility with the dressings has to be every time tested, to avoid its inactivation and consequent loss of tissue repair properties.

Bandages↗

The use of a new laser particle sizer and shape analyser to detect and evaluate gelatinous microparticles suspended in reconstituted anthracycline infusion solutions.

The anthracyclines are an important group of antitumour drugs: the best known anthracyclines are doxorubicin (Adriamycin) and epirubicin (Pharmorubicin), both of which are very active against a wide range of solid tumours and haematological malignancies. They are marketed as lyophilized formulations that need to be reconstituted for administration with water for injections or sodium chloride injection. With the aim of reducing the risks of contamination during reconstitution (spillage, spray formation, etc.) and of enhancing the rate of dissolution (that is otherwise slow because of the formation of conglomerates and gelatinous masses), a new formulation (rapid dissolution formula, RDF) containing parabens (hydroxybenzoate esters) as anti-aggregants has been developed; the formulation is a freeze-dried product and is characterized by a practically instantaneous and complete reconstitution. A valid estimate of the completeness of dissolution has been objectively achieved by means of an instrument (Galai CIS-1) that acts both as a particle sizer and a shape analyser; the instrument is equipped with a rotating laser system that defines a toroidal-cylindrical space inside the solution in which every moving particle is measured and, at the same time, visualized on a monitor by an electronically driven video microscope. The instrument has been applied with very satisfactory results to the visualization of the reconstitutional behaviour of commercial lots of Adriamycin and Pharmorubicin lyophilized products, reconstituted at a concentration of 2 mg ml-1 with sodium chloride injection.

Doxorubicin↗

Effect of hemodialysis and hemodiafiltration on uremic neuropathy.

This study was undertaken to compare the effect of 1 year hemodialysis (HD) or hemodiafiltration (HDF) treatment on peripheral neuropathy. Thus 21 of 42 patients on chronic HD (1-1.3 m2 cuprophane dialyzer, Qb 300 ml/min) were switched to HDF (1.3 m2 polysulfone dialyzer, Qb 400 ml/min, substitution volume 9-13 liters, ultrafiltration rate 60-70 ml/min), while the remaining patients were considered as a control group. Treatment time was scheduled both in HD and HDF to maintain adequate BUN levels in relation to protein catabolic rate. However, HDF provided a significantly greater weekly inulin (MW 5,000) clearance than HD (5.8 +/- 1.2 vs. 1.6 +/- 0.2 ml/min; p less than 0.001). HD and HDF groups were comparable for age, time on dialysis and starting electroneurographic parameters, which were on average within the normal range. After 1 year follow-up, creatinine, hematocrit, calcium, phosphate, PTH, BUN, protein catabolic rate and residual GFR were comparable in the two groups, whereas beta 2-microglobulin was significantly reduced in HDF patients (29 +/- 6.7 vs. 38.8 +/- 13.9 mg/l in HD patients, p less than 0.01). During the 1-year treatment, electroneurographic parameters did not change in HDF patients, whereas a significant decrease of ulnar motor nerve conduction velocity, ulnar muscle action potential amplitudes, median sensory nerve conduction velocity and peroneal muscle action potential amplitudes was detected in HD patients. We conclude that HDF might prevent the worsening of the electroneurographic indices occurring during chronic HD treatment, as it provides a more effective removal of middle and larger molecules than HD. The use of a more biocompatible membrane in HDF might further contribute to this favorable effect on uremic neuropathy.

Adult↗

The management of cervical carcinoma in the Gynaecologic and Obstetric Institute of Sassari in ten-year period 1980-89.

We have considered 91 cases of uterine cervical carcinoma observed in the period 1980-89, of which 31 (34%) at stage 0, and 23 (25.2%) at stage IB. The operative index was of 85.7%. Of 78 cases operated, 22 (28.2%) were treated with post-surgical adjuvant radiotherapy because of the presence of risk factors. The relapse incidence (follow-up 8-118 months) was in total 14.6% (12 relapses) with an NED-survival of 79.1% (at the first stage B 4.3% of relapses with an NED-survival of 95.6%). We have emphasized the importance of adjuvant radiotherapy which has allowed the progressive improvement in the therapeutic results of the last years.

Adult↗

High-performance liquid chromatographic method for direct resolution of the indobufen enantiomeric components.

A high-performance liquid chromatographic method for the determination of (S)-(+)- and (R)-(-)-indobufen as diastereoisomeric derivatives has been applied and validated for stability control in tablet formulations. In order to obtain a less troublesome and more rapid method the direct resolution of the enantiomeric components by chiral stationary phases was investigated. The direct separation of the enantiomers was achieved using the cellulose tris(3,5-dimethylphenylcarbamate) derivative Chiralcel OD as a chiral stationary phase. The method was validated for the determination of the optical purity of (S)-(+)-indobufen as a quality control method for finished dosage forms.

Chromatography, High Pressure Liquid↗

Fist line chemotherapy in advanced ovarian cancer: a comparison of three therapeutic regimes.

The first line polichemotherapeutic regimens are compared (intracavitary Cyclophosphamide + CMF, ACy and PEC) in 47 patients with advanced ovarian carcinoma. The response was 56.4% for Ex-CMF (CR 39.1%), 76.8% for ACy (CR 61.5%) and 81.8% for PEC (CR 63.6%). The three-year survival was 39.1% with Ex-CMF, 53.8% with ACy and 72.7% (follow-up not yet completed) for PEC. Toxicity was modest in all the three therapeutic regimens.

Adult↗

The treatment of endometrial carcinoma: our experience in the period 1983-89.

The Authors evaluated 87 cases of endometrial carcinoma, of whom 65 (74.7%) at pathological stage I. The surgical ratio was (96.5% 84/87 cases), and 31 cases were subjected to adjuvant postsurgical Radiotherapy because of the presence of risk factors. The incidence of relapses resulted complessively in 14.2%, with a NED-survival of 86.1% and an overall survival of 91.9% at the pathological stage I. The Authors emphasise particularly the importance of post-surgical Radiotherapy in the cases at risk, which allowed an important decrease of the incidence of relapses at stage I with regard to previous studies.

Aged↗

Wertheim-Meigs operation in the Gynaecologic and Obstetric Institute of Sassari in the ten-year period 1980-89.

In a retrospective study we examined 42 radical hysterectomies according to Wertheim-Meigs in the ten year period 1980-89, of whom 39 for carcinoma of the cervix, two for endometrial carcinoma at stage II one for microinvasive vaginal carcinoma. The incidence of relapses was 11.9% (5 cases) globally, with 3.7% at pathologic stage I, while the actuarial survival was 95.4% at stage I. The intraoperative, perioperative and postactinic complications related to integrated treatment are described, underlining the importance of post-surgical Radiotherapy in cases at risk.

Female↗

Magnetotaxis.

The ability of magnetotactic bacteria to orientate and navigate along geomagnetic lines is due to intracellular magnetic particles. These are enclosed within a membrane to form a magnetosome, a specialized organelle of magnetotactic organisms. The magnetic crystallite of many of the magnetotactic bacteria and algae is the iron oxide magnetite (Fe3O4) but recently a multicellular bacterial aggregate has been found to contain magnetic iron sulphide. Magnetotactic bacteria are found in regions of low oxygen pressure. Those of the Northern hemisphere are north-seeking while those of the Southern hemisphere are south-seeking. The opposite polarity of their internal magnets enables both types to travel to the deeper, less oxygenated, regions of their aqueous environments.

Bacterial Physiological Phenomena↗