PubMed Health⌕ Search

Biomedical subjects

N García

Publications and source records attributed to N García.

At least 55 records · Page 3Linked to original sources
PubMed2000

Possible involvement of the adenine nucleotide translocase in the activation of the permeability transition pore induced by cadmium.

Low levels of cadmium induce a rapid calcium efflux in energized rat kidney mitochondria. This is accompanied by the collapse of the transmembrane gradient in a partial CSA-sensitive fashion. The binding of 109Cd2+ to mitochondria is a saturable function; in the presence of NEM, the binding of 2.5 nmol 109Cd2+/mg of protein suffices to induce the opening of the permeability transition pore. It was found that cadmium bound mainly to proteins of molecular weight between 30 and 50 kDa. In the presence of the monothiol reagent NEM, the label is concentrated in the 30 kDa protein. Following the addition of the reducing agent dithiothreitol, calcium is reaccumulated and the membrane potential restored. This correlates with a significant loss of label in the 30 kDa protein region. The 30 kDa protein was identified as the adenine nucleotide translocase by labelling experiments with eosin 5-maleimide and experiments of reconstitution.

Animals↗
PubMed2000

Inactivation of mitochondrial permeability transition pore by octylguanidine and octylamine.

Mitochondrial permeability transition occurs through a Ca2+-dependent opening of a transmembrane pore, whose identity has been attributed to that of the adenine nucleotide translocase (ANT). In this work, we induced permeability transition by adding 0.5 microM carboxyatractyloside. The process was evaluated analyzing Ca2+ efflux, a drop in transmembrane electric gradient, and swelling. We found that the amphiphyllic cations octylguanidine and octylamine, at the concentration of 100 microM, inhibited, almost completely, nonspecific membrane permeability. Hexylguanidine, hexylamine, as well as guanidine chloride and hydroxylamine failed to do so. The inhibition was reversed after the addition of 40 mM Li+, Na+ K+, Rb+, or Cs+; K+ was the most effective. We propose that the positive charge of the amines interact with negative charges of membrane proteins, more likely the ADP/ATP carrier, while the alkyl chain penetrates into the hydrophobic milieu of the inner membrane, fixing the reagent.

Adenosine Diphosphate↗
PubMed2000

Copper sensitizes the mitochondrial permeability transition to carboxytractyloside and oleate.

Addition of 5 microM copper to rat kidney mitochondria enhances the effect of carboxyatractyloside and oleate on pore opening, in a cyclosporin A-sensitive fashion. The effects of the pair copper-carboxyatractyloside were observed on matrix Ca2+ efflux, mitochondrial swelling and on the transmembrane electric gradient. The effect of Cu2+ emphasizes the importance of membrane thiol groups located, probably, in the ADP/ATP translocase (ANT), on permeability transition. It was also found that Cu2+ does not block the fluorescent label of ANT by eosin 5-maleimide, but abolishes the inhibition by CAT on the labeling. This suggests that the binding of Cu2+ to cysteine residues of ANT promotes a conformational change in the carrier, strengthening the effect of CAT and oleate on membrane leakage.

Animals↗
PubMed2000

A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection.

BACKGROUND: Although triple therapies with a proton pump inhibitor, clarithromycin and either amoxycillin or metronidazole are the most widely accepted treatment for Helicobacter pylori infection, there is no consensus on how long treatment should be maintained for. AIM: To evaluate whether increasing the length of triple therapies beyond 7 days improves treatment efficacy. METHODS: An extensive search of the literature was performed. Reports of randomized trials comparing different lengths of therapy were selected. Short (7-day) vs. long (10/14-day) therapies were compared, and three-way comparison of 7-day vs. 10-day, 10-day vs. 14-day and 7-day vs. 14-day therapies was performed. Meta-analysis was conducted using conventional shareware (Review Manager 4.0). The Peto Odds Ratio using a fixed model analysis was calculated for each comparison. RESULTS: Thirteen studies were identified. Pooled 10- to 14-day therapies achieved better results than 7-day schedules. In head-to-head comparisons, only 14-day therapies were significantly better than 7-day treatments. Improvement in cure rates ranged from 7 to 9%. Comparisons of 7-day vs. 10-day and 10-day vs. 14-day also showed a non-significant trend towards better cure rates with longer therapies. CONCLUSIONS: Fourteen-day, proton pump inhibitor-based triple therapy achieves better results than 7-day schedules. Additional data are necessary to evaluate 10-day therapies.

Amoxicillin↗
PubMed2000

Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta-analysis of eradication of Helicobacter pylori.

AIM: To perform a meta-analysis of studies comparing twice daily, one-week triple therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A) (PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole (N) (PCN) for H. pylori eradication. REVIEW METHODS SELECTION CRITERIA: Comparative randomized trials of PCA vs. PCN were included. DATA SOURCES: PubMed database and abstracts from congresses until September 1999. STATISTICS: Meta-analysis was performed combining the Odds Ratios (OR) of the individual studies in a global OR (Peto method) both on an intention-to-treat (ITT) and on a per protocol (PP) basis. RESULTS: Twenty-two studies fulfilled the inclusion criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori eradication rates were 81% (95% CI: 79-83%) ITT, and 84% (82-86%) PP with PCA, and 81% (78-83%) ITT and 84% (82-86%) PP with PCN; the odds ratio for the effect of PCA vs. PCN was 1 (0.83-1.22) on an ITT, and 0.98 (0.8-1.2) on a PP basis. Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A was 81% (78-85%) ITT, vs. 86% (83-89%) with PC(250 b.d.)N. The odds ratio for this comparison was 0.68 (0.48-0.98). Finally, when comparing PC(500 b.d. )A against PC(250 b.d.)N ITT cure rates were 77% (74-80%), and 75% (72-78%) with an odds ratio of 1.18 (0.93-1.5). CONCLUSION: Overall, one-week combination regimens of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the PCN regimen obtains significantly better results when using low doses of C (250 mg b.d.).

Amoxicillin↗
PubMed2000

Four-day, twice daily, quadruple therapy with amoxicillin, clarithromycin, tinidazole and omeprazole to cure Helicobacter pylori infection: a pilot study.

BACKGROUND: The best regimen for the treatment of Helicobacter pylori infection has yet to be defined. Four-day quadruple therapy with tetracycline, metronidazole, bismuth, and a proton pump inhibitor has been shown to obtain a very high cure rate. However, the fact that it must be taken four times daily may interfere with compliance. The objective of the study was to test the efficacy and tolerability of a new 4-day therapy with 4 drugs taken every 12 hours to cure H. pylori infection. Patients and Methods. Fifty-six consecutive patients with peptic ulcer disease and H. pylori infection were treated with an oral 4-day course with omeprazole (20 mg/12 hours), clarithromycin (500 mg/12 hours), amoxicillin (1 g/12 hours) and tinidazole (500 mg/12 hours). Efficacy of the treatment was determined at least 2 months after therapy either by biopsy (in the case of gastric ulcer) or by 13C-urea breath test. A second breath test was performed at least 6 months after therapy. RESULTS: Two patients were lost to follow-up. Forty-nine of the remaining 54 patients were cured at the first control [intention-to-treat cure rate: 87.5% (CI 95% 75-94%); per protocol cure rate: 90.7% (CI 95% 81-98%)]. Forty-three of these 49 cured patients returned for a second 13C urea breath-test at 6-12 months. Two of them were not cured, giving a long-term cure rate of 85.5% per protocol and 73.2% by intention-to-treat. Compliance was good, although 25 patients had mild side effects. CONCLUSION: This particular four-day therapy is well tolerated, easy to follow, and achieves an acceptably high cure rate.

Adult↗
PubMed1999

A complete human pelvis from the Middle Pleistocene of Spain.

The Middle Pleistocene site of Sima de los Huesos in Sierra de Atapuerca, Spain, has yielded around 2,500 fossils from at least 33 different hominid individuals. These have been dated at more than 200,000 years ago and have been classified as ancestors of Neanderthals. An almost complete human male pelvis (labelled Pelvis 1) has been found, which we associate with two fragmentary femora. Pelvis 1 is robust and very broad with a very long superior pubic ramus, marked iliac flare, and a long femoral neck. This pattern is probably the primitive condition from which modern humans departed. A modern human newborn would pass through the birth canal of Pelvis 1 and this would be even larger in a female individual. We estimate the body mass of this individual at 95 kg or more. Using the cranial capacities of three specimens from Sima de los Huesos, the encephalization quotients are substantially smaller than in Neanderthals and modern humans.

Adult↗
PubMed1999

Characterization of the semen quality of postpuberal boars with spontaneous unilateral abdominal cryptorchidism on the right side.

In recent studies, we found that the ectopic testis from postpuberal boars with unilateral abdominal cryptorchidism does not produce sperm. Therefore, in these males, the seminal characteristics can be used as indicators of the activity of the scrotal testis and its epididymis and also the accessory glands. The semen quality (ejaculate volume, cell-rich fraction volume, sperm concentration, sperm vitality, sperm motility, sperm morphology and cephalic stability of spermatozoa) was evaluated in healthy postpuberal boars and in postpuberal boars with unilateral abdominal cryptorchidism on the right side. In comparison with the healthy boars, the unilateral abdominal cryptorchid boars showed a significant decrease of the ejaculate volume, sperm concentration and sperm motility. The low sperm concentration indicated that unilateral abdominal cryptorchidism severely impairs the sperm production of the scrotal testis. The decrease of ejaculate volume was attributed to an abnormal activity of the accessory glands. The alterations in sperm motility develop as a result of dysfunctions in the epididymal epithelium and/or the accessory glands. The sperm vitality, sperm morphology and cephalic stability of spermatozoa maintained normal values; therefore, at testicular level, despite the low sperm production, the germ cell differentiation is not disturbed. At epididymal level, the morphological maturation of spermatozoa is not altered.

Animals↗
PubMed1999

Carboxyatractyloside increases the effect of oleate on mitochondrial permeability transition.

Addition of a low concentration of carboxyatractyloside (0.075 microM) renders mitochondria susceptible to the opening of the non-specific pore by 5 microM oleate, in a cyclosporin A-sensitive fashion. Matrix Ca2+ efflux as well as collapse of the transmembrane potential reveal permeability transition. The effect of oleate is reached after the titration, by carboxyatractyloside, of 38 pmol of adenine nucleotide translocase per mg mitochondrial protein. We propose that permeability transition may result from an additive action of carboxyatractyloside plus oleate on the ADP/ATP carrier.

Animals↗
PubMed1999

The hairless gene of the mouse: relationship of phenotypic effects with expression profile and genotype.

Various mutations of the hairless (hr) gene of mice result in hair loss and other integument defects. To examine the role of the hr gene in mouse development, the expression profile of hr has been determined by in situ hybridisation and correlated to the nature of genetic changes and morphological abnormalities in different mutant animals. Four variant alleles have been characterised at the molecular level. hr/hr mice produce reduced, but significant, levels of hr mRNA whereas other alleles contain mutations which would be expected to preclude the synthesis of functional product, demonstrating a correlation between allelic variation at the hr locus and phenotypic severity. hr expression was shown to be widespread and temporally regulated. It was identified in novel tissues such as cartilage, developing tooth, inner ear, retina, and colon as well as in skin and brain. Analysis of mice homozygous for the rhino allele of hairless revealed that, although no morphological defects were detectable in many tissues normally expressing hr, previously undescribed abnormalities were present in several tissues including inner ear, retina, and colon. These findings indicate that the hairless gene product plays a wider role in development than previously suspected. Dev Dyn 1999;216:113-126.

Animals↗
PubMed1999

Assessment of biliary bicarbonate secretion in humans by positron emission tomography.

BACKGROUND & AIMS: Positron emission tomography (PET) allows imaging and quantitative analysis of organ functions in basal and stimulated conditions. We have applied this method to the study of biliary bicarbonate secretion in humans. METHODS: PET was performed in 5 healthy subjects and 13 patients with hepatobiliary disorders after intravenous injection of NaH11CO3. In each case the study was performed in basal conditions and after secretin stimulation. Positron emission from the hepatic area was scanned, and normalized uptake values for parenchymal and hilar regions were estimated. RESULTS: In healthy individuals, the injection of NaH11CO3 resulted in a peak uptake of the label in parenchymal and hilar regions 2-3 minutes after the injection. In both normal and cirrhotic subjects, secretin administration increased bicarbonate uptake in the parenchymal region, followed by accumulation of the label in the perihilar area. Normal basal uptake with absent response to secretin was registered in extrahepatic biliary obstruction and in untreated primary biliary cirrhosis (PBC). The secretin response was present in patients with PBC undergoing treatment with ursodeoxycholic acid. CONCLUSIONS: PET allows investigation of biliary bicarbonate secretion in humans. An impaired response to secretin was observed in cholestatic conditions. Preliminary data suggest that ursodeoxycholic acid might improve the response to secretin in PBC.

Adult↗
PubMed1998

Transcriptional repression of gdhA in Escherichia coli is mediated by the Nac protein.

In this work we show that the nac gene from Escherichia coli is transcriptionally active, and that its expression is dependent on NRI (NtrC) and sigma-54. Northern blot experiments show a monocistronic nac-specific mRNA that is detected when wild-type cells are grown in nitrogen-limiting conditions. Our data also show that in nitrogen-limiting conditions Nac is involved in the transcriptional repression of the gdhA gene (encoding glutamate dehydrogenase) except when L-glutamine is used as the only nitrogen source. Moreover, the high level of GDH activity observed in a nac mutant strain is reduced when a wild-type nac gene is introduced under control of the lac promoter in N-limiting conditions, but not in L-glutamine or N-excess. These results suggest the existence of an additional mechanism responsible for overcoming repression by Nac.

Bacterial Proteins↗
PubMed1998

Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis C.

To investigate the involvement of T-cell response against hepatitis C virus (HCV) antigens in viral clearance after interferon therapy, we measured interleukin-2 (IL-2) production by peripheral mononuclear cells in response to HCV core in patients with chronic hepatitis C. In a cohort of 43 patients, we investigated the frequency of circulating core-specific T-helper (Th) cell precursors by the limiting-dilution assay, and in a second cohort of 60 patients, we analyzed the response to specific core epitopes using 52 synthetic 15-mer overlapping peptides. We observed that the frequency of core-specific Th cell precursors was significantly higher in patients with sustained biochemical and virological response (SR) after interferon (IFN) therapy (median, 1/55,736) than in untreated patients (1/274,023) or that in patients who remained viremic after completion of the treatment-nonresponders (NR) plus transient responders (TR) (1/1,909,972). Patients who failed to respond to IFN (NR) and those who relapsed after IFN discontinuation (TR) had a similarly low number of precursors. The number of core peptides recognized by SR, TR, NR, UT, and healthy controls was 8.2 +/- 1.5, 6.5 +/- 1.2, 2.0 +/- 0.5, 2.7 +/- 0.9, and 0.3 +/- 0.2, respectively. In SR, the intensity of the proliferative response to core peptides as estimated by the summation of stimulation indexes (sigmaSI) was significantly higher than in NR and than in UT, but not different from that of TR. Our results indicate that both expansion of HCV-specific Th cell precursors and Th cell recognition of multiple core epitopes seem to be important in the elimination of HCV after IFN therapy.

Adult↗
PubMed1998

Risk factors for recurrence of hepatitis C after liver transplantation.

Recurrent hepatitis C is a frequent complication after liver transplantation for hepatitis C virus-related cirrhosis, but risk factors related to its development remain ill defined. Twenty-three patients receiving a primary liver graft for hepatitis C virus-related cirrhosis and with an assessable biopsy performed at least 6 months after liver transplantation were studied retrospectively. The end point of this study was to look for risk factors associated with the development of histologic hepatitis C in the graft. Thirty-six major variables were studied, and those reaching significance by univariate analysis were included in a multivariate analysis. Eighteen patients (78%) developed posttransplant hepatitis C. On univariate analysis, six variables showed significant predictive value: increased immunosuppression for treatment of acute rejection; pretransplant hepatocellular carcinoma; cumulative doses of prednisone at 3, 6, and 12 months after transplantation; and mean blood trough levels of cyclosporine in the first 6 months posttransplantation. On multivariate analysis, two variables retained independent statistical significance as predictors of hepatitis C recurrence, namely receipt of antirejection therapy (P = .0087) and lower mean cyclosporine levels in the first 6 months after transplantation (P = .0134). Therefore, recurrence of hepatitis C after liver transplantation seems to be at least partially related to posttransplantation immunosuppressive therapy.

Adult↗
PubMed1998

Evaluation of Meridian ImmunoCard Mycoplasma test for the detection of Mycoplasma pneumoniae-specific IgM in paediatric patients.

The Meridian ImmunoCard Mycoplasma kit, a 10-min card-based enzyme-linked immunosorbent assay (ELISA) designed to detect immunoglobulin M (IgM) antibodies to Mycoplasma pneumoniae was evaluated. We compared the ImmunoCard with the Fujirebio Serodia Myco II particle agglutination test, as well as with the complement fixation (CF) test to detect M. pneumoniae antibodies in paediatric patients. The ImmunoCard test and Serodia Myco II test agreed in 93.95%, and ImmunoCard test and CF test agreed in 83.51% of the 182 specimens tested. Nine specimens gave negative particle agglutination titres in the acute phase sample, and 28 specimens gave negative CF titres in the acute phase sample, although in the ImmunoCard test they were positive. These results may indicate that the ImmunoCard assay detects lower IgM levels of antibodies than the Serodia Myco II and CF test. The ImmunoCard appears to be a good screening assay test for M. pneumoniae IgM in children in whom M. pneumoniae IgM is found frequently.

Acute-Phase Reaction↗