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Biomedical subjects

V Perez

Publications and source records attributed to V Perez.

At least 37 records · Page 2Linked to original sources

Paratuberculosis in wild rabbits (Oryctolagus cuniculus)

A survey of wild rabbits in Tayside, Scotland revealed that 67 per cent were infected with Mycobacterium avium subspecies paratuberculosis. In general, the infected rabbits had histopathological changes within the lymph nodes and intestines which were consistent with the changes due to paratuberculosis in ruminants. The survey raises the possibility that rabbits and other wildlife may be involved in the epidemiology of paratuberculosis, a possibility which has important implications for the control of the disease.

Animals↗

SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients.

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day).

1-Naphthylamine↗

Mapping the elicitor and necrotic sites of Phytophthora elicitins with synthetic peptides and reporter genes controlled by tobacco defense gene promoters.

Elicitins are 10-kDa proteins secreted by Phytophthora and Pythium fungi that elicit a hypersensitive-like necrotic reaction, leading to resistance against fungal and bacterial plant pathogens. Induction of necrosis and resistance were previously shown to be borne by different sites of the molecule. Furthermore, sequence comparison indicated several potential residues necessary for necrosis. The role of one of these residues was previously evidenced with site-directed mutagenesis. In order to locate other necrosis-determining sites and reveal the defense-eliciting sites, we synthesized a series of synthetic peptides. Tests were performed on two types of transgenic tobacco plants, both transformed with a construction containing the beta-glucuronidase reporter gene, in one case controlled by the promoter of the multiple stimulus response gene str 246C and in the other by the promoter of the pathogenesis-related gene PR1a. We report that only certain peptides were found to be active. Whereas PR1a induction was consistently correlated with induction of necrosis, four peptides were observed to induce only str 246C expression without necrosis, which led to differentiate the defense-eliciting sites from the necrotic sites. From the structure-function relationship thus obtained, two different defense pathways were inferred to be independently induced by elicitins.

Algal Proteins↗

In vitro cytotoxicity of S16020-2, a new olivacine derivative.

S16020-2 is a new olivacine derivative which has recently shown a marked antitumor activity in various experimental models. This study was undertaken in order to measure the inhibition of the proliferation of various sensitive and resistant tumor cell lines, by S16020-2, and to obtain information concerning its mechanism of action. For a continuous exposure, S16020-2 was as cytotoxic as adriamycin (ADR) (mean IC50 of about 28 nM) and on average, 46 fold more potent than elliptinium acetate (ELP), against a panel of 20 non-multidrug resistant cell lines. With a short exposure (1 hour) followed by a post-incubation of 95 hours in drug-free medium, S16020-2 was 5 and 6 fold more cytotoxic than ADR for human lung A549 and murine melanoma B16 cells, respectively. Furthermore, S16020-2 inhibited more actively the formation of colonies issued from proliferating cells, compared to colonies issued from quiescent A549 cells. Because quiescent cells demonstrated a 3 fold lower level of topoisomerase II alpha (topo II) than proliferating cells, these results suggest that this enzyme could be a potential target for S16020-2. In addition, as demonstrated by flow cytometric studies, S16020-2 intercalated into DNA and induced a cell cycle arrest in G2. Cell lines displaying the multidrug resistance (MDR) phenotype, P388/ADR-1, P388/ADR, P388/VCR-20, KB-A1, DC-3F/AD, S1/tMDR, and Colo320DM, were more sensitive to S16020-2 than to ADR or ELP, as shown by the mean resistance factors, 8, 201, and 23 respectively. In addition, the two cell lines displaying the pure classical MDR phenotype, linked exclusively to the P-glycoprotein (P-gp) overexpression (P388/VCR-20 and S1/tMDR), were as sensitive to S16020-2 as their sensitive parental counterparts, although they were resistant to ADR. S16020-2 is thus one of the most potent olivacine and ellipticine derivative yet characterized. The good cytotoxicity of S16020-2 against cells displaying a P-gp-mediated multidrug resistance, and its antitumor activity in vivo delineate an important chemotherapeutic potential for this drug.

Animals↗

Kinetic studies of N-allenic analogues of tryptamine as monoamine oxidase inhibitors.

A series of N-allenic analogues of tryptamine in which the side chain is located at the 2 position of the indole ring, but which differed in the ring and side-chain nitrogen substituents, were assayed kinetically as MAO A and MAO B inhibitors. All the compounds studied were mechanism-based inhibitors. The kinetic constants of each inhibition step Ki and ki, were determined for both MAO A and B. The data obtained indicated that these allenic derivatives show a greater selectivity and potency towards MAO A as inhibitors than the corresponding acetylenic derivatives.

Animals↗

Sex-related effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine treatment may be related to differences in monoamine oxidase B.

Effects of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine metabolism and the influence of sex on the recovery were investigated in adult (2-month-old) male and female C57/BL mice. We present here evidence that MPTP treatment (2 doses of 30 mg/kg i.p., each at 24 h interval) produced a similar reduction (-65% to -70%) of striatal dopamine in both sexes 24 h after the last injection of MPTP, and a greater loss of the metabolites in the female group. In contrast to the partial recovery observed in the male group, an increased dopamine loss occurred in the female group within 10 days following the last injection of MPTP. This impairment in recovery appears to be different to the one already observed in aged (24-month-old) male mice treated in similar conditions. As the neurotoxic effects of MPTP depend on its conversion to the 1-methyl-4-phenylpyridinium ion (MPP+) by monoamine oxidase B (MAO B), the presence of a different peripheral or central MAO B type in female mice could be in part responsible for these sex related effects. To investigate this possibility, MAO A and B activities were characterized in liver and brain of adult female control mice during the different steps of the oestrous cycle and compared to those of adult control male mice. Significant differences in MAO A and MAO B activities could be detected during the oestrous cycle and between the adult male and female groups. It is concluded that MAO B may be involved in the sex related effects of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Interactions between substituted tryptamine analogues, MAO inhibitors and cytochrome P-450.

The effects of some MAO inhibitors, N-acetylenic analogues of tryptamine, on rat liver microsomal cytochrome P-450 (cyt P-450) have been investigated. All the compounds tested interacted with cyt P-450 with Ks values ranging between 14 and 358 microM (clorgyline Ks = 10.5 microM). Compounds with a tertiary amine and those possessing a secondary amine group in the acetylenic side chain exhibited type I and type II difference spectra, respectively. Aniline hydroxylase activity was inhibited irreversibly and in a time-dependent fashion by all compounds tested with IC50 ranging between 7 x 10(-5) and 7 x 10(-3) M (clorgyline 10(-4) M).

Animals↗

Comparative study of three doses of interferon-alpha 2a in chronic active hepatitis B. The International Hepatitis Trial Group.

To determine the efficacy of interferon-alpha 2a in chronic active hepatitis B, 238 patients were randomly divided, into four groups: three groups received either 2.5 MIU m-2, 5.0 MIU m-2 or 10.0 MIU m-2, three times weekly by intramuscular injection for 12-24 weeks; and a control group received no treatment. Patients were followed for up to 12 months after treatment was discontinued. There was a statistically significant difference in response [clearance of hepatitis B e antigen (HBeAg) and hepatitis B viral DNA (HBV-DNA)] between treated and untreated patients (37 vs 13%) but no statistically significant difference was seen between treatment groups (33%, 34% and 43% for the 2.5, 5.0 and 10.0 MIU m-2 groups, respectively). A transient rise in transaminases (seroconversion hepatitis) was seen in responders, but levels returned to within the normal range after response to treatment. In patients responding to interferon therapy there was a significant reduction in the severity of the hepatitis. Interferon-alpha 2a was generally well tolerated with respect to vital signs and laboratory parameters.

Adolescent↗

Interactions of monoamine oxidase inhibitors, N-acetylenic analogues of tryptamine, with rat liver microsomal cytochrome P450.

Interactions between some novel and potent monoamine oxidase inhibitors (MAOIs), acetylenic analogues of tryptamine, and rat liver microsomal cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughout induced type II difference spectra and exhibited the highest affinity for P450, whereas tertiary amines induced type I spectral changes and showed diminished affinity. P450 dependent aniline hydroxylase activity was inhibited by all compounds in an irreversible time-dependent manner. Only tertiary aliphatic amines constituted the substrate for P450-dependent N-demethylase activity, with comparable kinetic parameters. The N-demethylated metabolites were identified by thin-layer chromatography and mass-spectrometric analyses. These findings describe the role of P450-dependent microsomal mono-oxygenase systems in the metabolism of some MAOI acetylenic tryptamine derivatives and the possible hepatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds.

Acetylene↗

A controlled trial of high dose interferon, alone and after prednisone withdrawal, in the treatment of chronic hepatitis B: long term follow up.

This study was designed to evaluate the safety and effectiveness of high dose interferon, with or without prednisone pretreatment, in patients with chronic hepatitis B. Patients were randomised to two treatment groups: group I (n = 26) received six weeks of prednisone followed by a two week, drug free period, and then 10 million units (MU) of interferon alfa-2b three times weekly subcutaneously for 16 weeks; group II (n = 24) were used as controls for 24 weeks and then treated with interferon. Loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV)-DNA, with a return to normal alanine aminotransferase (ALT) activity, was seen in 16 of 26 group I patients (61.5%), in one group II patient (4.2%) during the control phase, and in 13 of 23 group II patients (56.5%) after interferon. Three of 26 (11.5%) in group I and one of 23 (4.3%) in group II eliminated the surface antigen (HBsAg). There were no statistically significant differences in response between groups I and II. Liver biopsies carried out in 20 patients showed that responders had a noticeable reduction in inflammation and disappearance of core antigen in liver tissue, changes not seen in non-responders. On long term follow up (four years), nine out of 28 responders (32.1%) eliminated HBsAg, and four initial non-responders had a late seroconversion.

Alanine Transaminase↗

Recombinant interferon alfa-2b following prednisone withdrawal in the treatment of chronic type B hepatitis.

The aim of the study was to evaluate the safety and effectiveness of interferon alfa-2b, alone and following prednisone withdrawal, in patients with chronic type B hepatitis. Thirty-five patients (27 men and eight women) were randomly allocated to two treatment groups. Group I (n = 17) received 6 weeks of prednisone followed by interferon alfa-2b (INTRON A, Schering-Plough Corporation) 10 million units subcutaneously, three times a week for 16 weeks. Group II (n = 18) was used as an untreated control group for 24 weeks, after which they received 16 weeks of treatment with the same dose of interferon as Group I. Both groups were followed up for 24 weeks after treatment. In Group I, 10/17 patients (58.8%) eliminated hepatitis B e antigen; 8/17 (47.1%) developed antibodies to hepatitis B e antigen; 9/17 (52.9%) became hepatitis B virus DNA negative and 1/17 (5.9%) was hepatitis B surface antigen negative at the end of follow up. In Group II, during the control phase, 1/18 (5.5%) became hepatitis B e antigen negative. When treated with interferon, 7/15 (46.7%) eliminated the e antigen, and 6/15 (40%) developed antibodies to hepatitis B e antigen and were hepatitis B virus DNA negative at the end of follow up. Serum alanine aminotransferase reached normal levels in all seroconverted patients. Liver biopsies showed a marked reduction of inflammation and disappearance of hepatitis B core antigen in liver cell nuclei in almost all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sensitive method for the measurement of amiodarone and desethylamiodarone in serum and tissue and its application to disposition studies.

A high-performance liquid chromatographic (HPLC) method for the measurement of amiodarone (AM) and its metabolite(s) in serum and tissues was developed. The method uses a 5-micron silica column, methanol containing 0.02% perchloric acid at pH 4 as the mobile phase, and ultraviolet detection at 240 nm. The standard curves for AM and desethylamiodarone (DAM) were linear for serum (range 0.025-6.0 microgram/ml) and tissues (range 0.1-0.5 micrograms for 10-25 mg wet weight). There was a significant decrease as a function of time in AM and DAM concentrations in patients' sera left at ambient temperature in the presence of light. This HPLC method was applied to studies on serum AM elimination kinetics in patients and on tissue uptake during chronic AM administration to rabbits. The elimination half-life (5.8 h) of AM after a 5 mg/kg intravenous dose to a patient was similar to that after acute oral doses. AM, being lipophilic, accumulated maximally in the fat tissue (56 micrograms/g wet weight), followed by lung and liver in rabbits injected with AM for six weeks. The latter two tissues also contained nearly equal quantities of DAM. The high concentrations of AM and DAM in the liver and lungs may be related to the hepatic toxicity and pulmonary fibrosis associated with chronic AM therapy. Two new metabolites were found in the lung and bile of AM-treated rabbits, but these have not yet been identified.

Amiodarone↗

Microcomputer-controlled plotting of environmental health data.

A general microcomputer program has been developed which facilitates the preparation of finished plots of geographical and temporal variations in such data as: the concentrations of suspended airborne particulate matter and of metallic and organic components detected in the particulate; the incidences of several kinds of respiratory illnesses and symptoms; epidemiological information obtained from physicians, hospitals, pharmacies, and schools. Examples of plots produced by the program, detailed explanations of how it works and a complete program listing are included.

Air Pollutants↗

Razoxane in the treatment of psoriatic patients resistant to or intolerant of PUVA, methotrexate and etretinate.

Thirty-six psoriatic patients resistant to or intolerant to PUVA, methotrexate and/or etretinate were treated with razoxane (ICRF 159) and EDTA derivative with antimitotic effects. The drug is highly effective in cutaneous and arthropathic psoriasis. Razoxane is well tolerated and appears to be free of hepatotoxicity. Besides some nausea and lethargy, 60% of the patients showed neutropenia, which can be easily controlled.

Adult↗

Pseudomonas peritonitis and continuous ambulatory peritoneal dialysis.

In a population of 44 patients receiving continuous ambulatory peritoneal dialysis (CAPD) for a total of 591 patient months, there were 104 episodes of peritonitis. The organisms were gram-positive in 65.4%, gram-negative in 23.1%, and cultures of the dialysate were sterile in 11.5%. Pseudomonas aeruginosa was the most frequently encountered gram-negative organism, accounting for 38.5% of the gram-negative infections or 9.6% of all infections. In all cases of P aeruginosa peritonitis, aminoglycoside antibiotic therapy for up to four weeks failed to eradicate the infection, and all patients required removal of the Tenckhoff catheter because of the presence of a sinus tract infection. We conclude that P aeruginosa is the most frequent cause of gram-negative peritonitis in patients receiving CAPD. The presence of a sinus tract infection should be suspected in all patients in whom peritonitis secondary to this organism develops. Removal of the Tenckhoff catheter will be required to cure the peritoneal infection.

Adult↗