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Biomedical subjects

P Gutierrez

Publications and source records attributed to P Gutierrez.

42 records · Page 3Linked to original sources
PubMedDate not supplied

Cellular biochemical determinants modulating the metabolism of estrone 3,4-quinone.

The metabolism of the o-quinone derivative of estrone, 3,4-estrone quinone (3,4-EQ), has been investigated in human breast cancer cells. Unlike the p-quinone, diethylstilbestrol 4',4"-quinone, 3,4-EQ was not a substrate for the two-electron reduction catalyzed by the putative detoxifying enzyme, NAD(P)H:quinone reductase (DT diaphorase; DT D). Accordingly, the DNA damage induced by 3,4-EQ in human MCF-7 cells was not affected by an inhibitor of DT D. Although 3,4-EQ was not an apparent substrate for the two-electron reduction catalyzed by DT D, this o-quinone was a substrate for the one-electron reduction catalyzed by cytochrome P450 reductase. The one-electron reduction of 3,4-EQ catalyzed by cytochrome P450 reductase occurred in the face of a significant and potentially physiologically relevant spontaneous reduction of 3,4-EQ by NADPH. The impact of purified superoxide dismutase (SOD) upon the production of hydrogen peroxide produced as a consequence of 3,4-EQ metabolism was evaluated; surprisingly, SOD inhibited the hydrogen peroxide produced by this o-quinone. Possible reasons for the SOD-mediated inhibition of redox cycling of 3,4-EQ are discussed. In summary, important differences in the metabolism of 3,4-EQ vis-a-vis o- and p- quinones have been observed, and the implications of these differences are discussed.

Animals↗
PubMedDate not supplied

Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders.

In a prospective, placebo-controlled, one group crossover design study, we tested whether adding programmed intracavernous PGE1 injections (IC-PGE1) can improve the effectiveness of sildenafil in erectile dysfunction (ED) patients unresponsive to monotherapy with this drug. In all, 40 ED patients who had experienced unsatisfactory erections with both the 50 and 100 mg sildenafil doses were treated with four bi-weekly 20 microg IC-PGE1 injections given in the clinic and provided with either placebo or 50 mg sildenafil capsules for the next 4 weeks. Thereafter, they were crossed over to the other oral treatment for an additional 4-week period. The IIEF-Erectile Function domain score (IIEF-EFS), the main outcome measure, was found considerably higher (P<0.001) with the combined IC-PGE1-50 mg sildenafil treatment than with IC-PGE1-placebo or sildenafil alone (50 or 100 mg) in a subset of 26 subjects (65%). They thus shifted from the 'severe' or 'moderate' to the 'mild' grading of ED classification.

Aged↗
PubMedDate not supplied

Essential role of nitric oxide and interferon-gamma for tumor immunotherapy with interleukin-10.

Several laboratories have reported anti-tumor activity for high levels of interleukin-10 (IL-10) expressed as a transgene or administered as recombinant protein. The authors have reported a positive correlation for nitric oxide production and anti-tumor activity of IL-10 in a murine model of breast cancer. In the current study, they sought evidence of a mechanistic role for nitric oxide in IL-10-mediated tumor growth inhibition. They wanted to determine whether pharmacologic inhibition of nitric oxide synthase (NOS) activity reverses the therapeutic effect of IL-10. Administration of either of two NOS inhibitors, aminoguanidine (AG) or L-lysine,N6-1-iminoethyl-dihydrochloride, appears to abrogate in part the tumor growth inhibition observed when IL-10 is overexpressed as a transgene in two murine mammary tumor cell lines. Nitric oxide levels were assessed at the tumor site by measuring nitrosylated heme levels by electron spin resonance spectroscopy. Nitric oxide hemoglobin levels were lower in tumors from aminoguanidine-treated mice, indicating that effective inhibition of nitric oxide production occurred at the tumor site. Previous investigations showed that the inducible form of NOS protein (iNOS), but not constitutive NOS, was expressed at higher levels in IL-10-expressing tumors. Because iNOS is regulated at the transcriptional level, the authors compared iNOS mRNA levels in IL-10 and control tumors. Northern analysis revealed strong iNOS message expression in all six IL-10-expressing tumors examined, whereas message was faintly detected in parental or 66-neo tumors. The inducible form of NOS is responsive to induction by interferon-gamma (IFN-gamma). The role of IFN-gamma in IL-10-mediated tumor inhibition and iNOS mRNA induction was determined. When tumors were transplanted to IFN-gamma mutant mice, the tumor-inhibitory activity of IL-10 was lost. Furthermore, iNOS mRNA was no longer induced in the absence of host expression of IFN-gamma. These data indicate that nitric oxide contributes to the anti-tumor activity of IL-10 and that expression of iNOS in this context depends on IFN-gamma.

Animals↗
PubMedDate not supplied

Prevalence of anti-hepatitis C virus antibodies in positive FTA-ABS non-drug abusing female prostitutes in Spain.

The prevalence of antibodies against Hepatitis C Virus (anti-HCV antibodies) and its association with the presence of treponemal antibodies (FTA-ABS) was studied in 227 non-drug abusing female prostitutes. The overall anti-HCV antibody prevalence was 8.8%, and a significantly higher prevalence of anti-HCV antibodies was found in prostitutes testing positive for FTA-ABS (19.4%) than in prostitutes testing negative for FTA-ABS (3.9%) (PR = 5.023, P less than 0.001). No statistical association was found between patient age or the duration of prostitution and the presence of anti-HCV antibodies.

Adult↗