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C Cabrera

Publications and source records attributed to C Cabrera.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prescribed daily doses and 'risk factors' associated with the use of benzodiazepines in primary care.

OBJECTIVE: To assess the extent, characteristics and determinants of benzodiazepine prescription in outpatient Primary Health Care. METHODS: A clinical audit of a stratified random sample of Primary Health Care Centres in the seven islands and 1.6 million inhabitants region of 'Canarias' in Spain was carried out. From those centres, a random sample of 1045 clinical records was reviewed and information on diagnosis, prescription and prescribed dosages was collected in a structured questionnaire. A multivariate logistic regression analysis was performed in order to determine the 'risk factors' for the use of benzodiazepines. RESULTS: Benzodiazepine prescription was recorded in 23.4% of all clinical records; 87.7% of these were for benzodiazepines classified as anxiolytics (N05B) and 12.3% for hypnotics (N05C2). Benzodiazepine prescription was more common for women, elderly, widowed, divorced, low educational background, housewives and retired people. Using multivariate logistic regression, the probability of benzodiazepine prescription was found to be closely related to age, gender and employment status, but not with educational level. Prescribed Daily Doses were lower than Defined Daily Doses (DDD) in 77.1% of all anxiolytic prescriptions, but were in agreement with DDD in 90% of hypnotic prescriptions. The duration of treatment recorded in the clinical records was 25+/-21 months, with a range of 1 and 144 months. General Practitioners were responsible for 67% of all benzodiazepine prescription. Anxiolytics were prescribed as a single daily dose in 57% of the cases, and only 'at supper' in 48.6%. CONCLUSION: In the general population attending Primary Health Care Centres of the Canary Islands Health System the prescription of benzodiazepines is higher for women and the elderly, and the most common use is chronic, with a duration of over 2 years in most cases. Anxiolytics are prescribed in doses which are much lower than those used as DDD and were used only 'at night' in almost half of the cases. This could represent an overlapping of the indications with hypnotics, and explain part of the huge difference in the use of anxiolytics in Spain compared with other figures in Europe. This fact must also be taken into account when making inferences of benzodiazepine use from sales statistics, which are very imprecise measures of drug use.

Journal Article↗
PubMed1999

Trace element determination in different milk slurries.

We have studied the contents of trace elements of nutritional or toxicological interest in 90 samples of whole, low-fat, skim, condensed, evaporated and powdered milks. Slurries of the samples were prepared with Triton X-100 and analysed using electrothermal atomic absorption spectrometry. The temperature-time programme of the graphite oven was optimized for each element, and the accuracy, precision, selectivity and sensitivity of the method were verified. Concentrations of the trace elements we investigated were: Pb 0-0.211 microgram/g, Cd 0-28.985 ng/g, Al 0.528-4.025 micrograms/g, Cu 0.041-0.370 microgram/g, Cr 0-0.177 microgram/g, Mn 0.024-0.145 microgram/g, Se 0-23.333 ng/g, Zn 0.297-0.827 microgram/g and Ni 0.058-1.750 micrograms/g. (A value of zero indicates that the element was undetectable by our methods.) Concentrations of the pairs of elements Cu-Cd, Mn-Cd, Mn-Cu, Zn-Mn, Ni-Cu, Ni-Mn and Ni-Zn were significantly correlated (P < 0.001). Linear discriminant analysis confirmed the separation between the six types of milk analyzed.

Aluminum↗
PubMed1999

Activity of different bicyclam derivatives against human immunodeficiency virus depends on their interaction with the CXCR4 chemokine receptor.

Bicyclams represent a novel class of selective anti-HIV inhibitors with potent activity against T-cell tropic strains of HIV. The prototype compound, the bicyclam AMD3100, has an EC50 of 1 to 10 ng/ml against different strains of HIV-1, including clinical isolates. AMD3100 was shown to interact with the CXC-chemokine receptor CXCR4, the main coreceptor used by T-cell tropic strains of HIV. Here we describe the interaction of different bicyclam derivatives with CXCR4. A close correlation (r2 = 0.7) was found between the anti-HIV potency of the bicyclams and their ability to inhibit the binding of an anti-CXCR4 monoclonal antibody or the intracellular Ca++ signal induced by the stromal cell-derived factor-1alpha, the natural ligand of CXCR4. These results indicate that the mechanism of action of bicyclams is primarily mediated by their interaction with CXCR4. The most potent interaction with CXCR4 and thus anti-HIV activity was shown by bicyclam analogs with cyclam rings composed of fourteen members that are linked by an aromatic (phenyl) bridge. Elucidating the structural requirements for receptor interaction and the site(s) of interaction of bicyclams with CXCR4 will aid in the understanding of HIV-cell fusion.

Animals↗
PubMed1999

Shift of clinical human immunodeficiency virus type 1 isolates from X4 to R5 and prevention of emergence of the syncytium-inducing phenotype by blockade of CXCR4.

The emergence of X4 human immunodeficiency virus type 1 (HIV-1) strains in HIV-1-infected individuals has been associated with CD4(+) T-cell depletion, HIV-mediated CD8(+) cell apoptosis, and an impaired humoral response. The bicyclam AMD3100, a selective antagonist of CXCR4, selected for the outgrowth of R5 virus after cultivation of mixtures of the laboratory-adapted R5 (BaL) and X4 (NL4-3) HIV strains in the presence of the compound. The addition of AMD3100 to peripheral blood mononuclear cells infected with X4 or R5X4 clinical HIV isolates displaying the syncytium-inducing phenotype resulted in a complete suppression of X4 variants and a concomitant genotypic change in the V2 and V3 loops of the envelope gp120 glycoprotein. The recovered viruses corresponded genotypically and phenotypically to R5 variants in that they could no longer use CXCR4 as coreceptor or induce syncytium formation in MT-2 cells. Furthermore, the phenotype and genotype of a cloned R5 HIV-1 virus converted to those of the R5X4 virus after prolonged culture in lymphoid cells. However, these changes did not occur when the infected cells were cultured in the presence of AMD3100, despite low levels of virus replication. Our findings indicate that selective blockade of the CXCR4 receptor prevents the switch from the less pathogenic R5 HIV to the more pathogenic X4 HIV strains, a process that heralds the onset of AIDS. In this article, we show that it could be possible to redirect the evolution of HIV so as to impede the emergence of X4 strains or to change the phenotype of already-existing X4 isolates to R5.

Adaptation, Biological↗
PubMed1998

Aluminium levels in wine, beer and other alcoholic beverages consumed in Spain.

A reliable and rapid method is presented for the determination of Al by graphite furnace atomic absorption spectrometry (GFAAS) in wine, beer and other alcoholic beverages. The temperature-time program for the graphite furnace was optimized. Samples were digested with nitric acid and vanadium pentoxide. The results obtained were validated against microwave acid sample digestion. The analytical detection limit was 4.0 pg. The mean recovery of 98.2% and the relative standard deviation of 5.2% were obtained. The method was applied to determine Al in 70 different samples of alcoholic beverages widely consumed in Spain. The mean values ranged from 94.8 to 1682.6 micrograms/l in wine, from 36.5 to 795.2 micrograms/l in beer, and from 15.7 to 739.6 micrograms/l in other alcoholic beverages (cider, brandy, rum, whisky, gin, anisette and liquor). The influence of packaging and containers on Al contamination of alcoholic beverages and their contribution to Al dietary intake were estimated.

Alcoholic Beverages↗
PubMed1998

A catalytic antibody against cocaine prevents cocaine's reinforcing and toxic effects in rats.

Cocaine addiction and overdose have long defied specific treatment. To provide a new approach, the high-activity catalytic antibody mAb 15A10 was elicited using a transition-state analog for the hydrolysis of cocaine to nontoxic, nonaddictive products. In a model of cocaine overdose, mAb 15A10 protected rats from cocaine-induced seizures and sudden death in a dose-dependent fashion; a noncatalytic anticocaine antibody did not reduce toxicity. Consistent with accelerated catalysis, the hydrolysis product ecgonine methyl ester was increased >10-fold in plasma of rats receiving mAb 15A10 and lethal amounts of cocaine. In a model of cocaine addiction, mAb 15A10 blocked completely the reinforcing effect of cocaine in rats. mAb 15A10 blocked cocaine specifically and did not affect behavior maintained by milk or by the dopamine reuptake inhibitor bupropion. This artificial cocaine esterase is a rationally designed cocaine antagonist and a catalytic antibody with potential for medicinal use.

Animals↗
PubMed1998

Cadmium contamination of vegetable crops, farmlands, and irrigation waters.

Cadmium, a highly toxic element that can accumulate in living tissues, is a potential threat to the environment and to human health. The main sources of Cd contamination of vegetable crops via farm soils and irrigation waters are reviewed, as are the influence of residual sludges used as fertilizers and the indiscriminate use of pesticides. The principal sources of exposure and toxicological characteristics of Cd are described, together with its effects on human health. Current European technical and health regulations aimed at controlling Cd levels are noted, and the most common analytical techniques for measuring Cd content are summarized.

Biological Availability↗
PubMed1998

Human immunodeficiency virus glycoprotein gp120 as the primary target for the antiviral action of AR177 (Zintevir).

The human immunodeficiency virus (HIV) inhibitor AR177 (T30177, Zintevir) has been identified as a potent inhibitor of HIV integrase in vitro. The compound is currently the subject of clinical phase I/II trials. However, the primary target for the mechanism of action in vivo has not been identified unequivocally. We have found that AR177 inhibits syncytium formation between MOLT-4 cells and HUT-78 cells persistently infected with the HIV-1IIIB or NL4-3 strain, at a 50% effective concentration of 3 microg/ml, roughly 3-fold higher than the concentration required to inhibit HIV replication. Furthermore, flow cytometric analysis has shown that AR177 at 25 microg/ml interferes with the binding of the monoclonal antibody 9284 (directed to the V3 loop of gp120) on HIVIIIB-infected HUT-78 cells, pointing to inhibition of virus binding or virus fusion as the mechanism of action of AR177. To precisely characterize the site/target of intervention by AR177, we have selected HIV-1 (NL4-3) strains resistant to AR177. The binding of the AR177-resistant strain, unlike the parental HIV-1 NL4-3 strain, could not be inhibited by AR177. The resistant phenotype was associated with the emergence of mutations in the gp120 molecule. DNA sequence analysis revealed the presence of the K148E, Q278H, K290Q, and F391I mutations and a deletion of 5 amino acids (FNSTW) at positions 364-368 in the V4 region of the resistant strain but not of the wild-type HIV strain. Selection of resistant strains, although it takes a relatively long time to develop, may also select for strains with lower replicative capacity. No mutations were found in the integrase enzyme gene. Our data argue against HIV integrase being the primary target for the mechanism of anti-HIV action of AR177.

Amino Acid Sequence↗
PubMed1998

T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1alpha contains mutations in the envelope gp120 but does not show a switch in coreceptor use.

The NL4.3 T-cell-line-tropic human immunodeficiency virus type 1 strain is sensitive to the CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha), the natural ligand for CXC chemokine receptor 4 (CXCR4); the 50% inhibitory concentration (IC50) in MT-4 cells is 130 ng/ml. We generated resistant virus through passaging of the virus in the presence of increasing concentrations of SDF-1alpha. After 24 passages, the virus was no longer sensitive to SDF-1alpha (SDF-1alpha(res) virus) (IC50, >2 microg/ml) and became resistant to SDF-1beta (IC50, >2 microg/ml) and to a specific CXCR4 monoclonal antibody (IC50, >20 microg/ml). The SDF-1alpha(res) virus was about 10-fold less sensitive than the wild-type virus to the bicyclam AMD3100, a specific CXCR4 antagonist. The SDF-1alpha(res) virus contained the following mutations in the gp120 molecule: N106K in the V1 loop; S134N and F145L in the V2 loop; F245I in the C2 loop; K269E, Q278H, I288V, and N293D in the V3 loop; a deletion of 5 amino acids (FNSTW) at positions 364 to 368 in the V4 loop; and R378T in the CD4 binding domain. Replication of the NL4.3 wild-type virus and the SDF-1alpha(res) virus was demonstrated in U87 cells that coexpressed CD4 and CXCR4 (U87.CD4.CXCR4) but not in U87.CD4.CCR5 cells. Thus, the resistant virus was not able to switch to the CC chemokine receptor 5 (CCR5) coreceptor (the main coreceptor for macrophage-tropic viruses). The SDF-1alpha(res) virus replicated in HOS.CD4 cells expressing CCR1, CCR2b, CCR3, CCR4, CCR5, and CXCR4 but also in HOS.CD4.pBABE cells. However, all HOS transfectant cells expressed a low level of CXCR4. Neither of the two virus strains was able to infect HOS.CXCR4 or HOS.CCR5 transfectants, demonstrating the necessity of the CD4 receptor. The T-cell-line-tropic SDF-1alpha(res) virus was thus able to overcome the inhibitory effect of SDF-1alpha through mutations in gp120 but still needed CXCR4 to enter the cells.

CD4-Positive T-Lymphocytes↗
PubMed1996

Cadmium levels in wine, beer and other alcoholic beverages: possible sources of contamination.

An accurate and precise method is described for the direct determination of Cd in wine, beer and other alcoholic beverages by electrothermal atomization-atomic absorption spectrometry (ETA-AAS). The graphite furnace program was optimized and samples were pretreated with nitric acid and pentoxide vanadium in a digestion block at 120 degrees C for 90 min. The results obtained were validated against microwave acid sample digestion. The analytical detection limit was 0.5 pg. The proposed method was applied to determine Cd in 134 samples of 10 different alcoholic beverages. The mean values ranged from 0.10 to 15.38 microg/l in wine, from not detectable to 0.80 microg/l in beer, and from not detectable to 11.52 microg/l in other alcoholic beverages such as cider, brandy, rum, whisky, gin, anisette, liquor and spirits. The wide variability of the results obtained emphasizes the multiplicity of factors that can influence the presence of Cd in these products. Because alcoholic beverages are widely consumed, they contribute a large fraction of cadmium intake, and therefore, strict control of this element is advisable.

Alcoholic Beverages↗
PubMed1996

Quantitative HIV-1 RNA as a marker of clinical stability and survival in a cohort of 302 patients with a mean CD4 cell count of 300 x 10(6)/l.

OBJECTIVE: To analyse plasma HIV-1 RNA levels as a marker of clinical stability and survival in a cohort of HIV-infected patients whose time of seroconversion is unknown. DESIGN: Retrospective cohort study. SETTING: Retrovirology laboratory and AIDS Unit in a teaching hospital. PATIENTS: A total of 916 samples from 302 patients, most on antiretroviral therapy, were analysed. Mean initial CD4 cell counts and HIV-1 RNA were 299 x 10(6)/l (range: 0-1600) and 134,261 copies/ml (range: < 200-4,300,000), respectively. Sixty-six cases had been diagnosed previously with AIDS. METHODS: Analysis of progression to AIDS and survival, according to initial and longitudinal viral load (VL) and CD4 cell count measurements was performed by Kaplan-Meier test. Relative risks were calculated by Cox's proportional hazards model. RESULTS: During a mean follow-up of 444 +/- 309 days, 29 patients developed AIDS and 21 died. Relative risk (RR) of progression related to the group with VL < 35,000 was: 10.4 when CD4 > or = 250 x 10(6)/l and VL > or = 35,000 (P = 0.001); and 45.3 when CD4 < 250 x 10(6)/l and VL > or = 35,000 (P < 0.0001). Cumulative probability of progression was: 0%, 0% and 12.3%, at the first, second and third year respectively, for patients with all their sequential VL determinations < 60,000; and 13.3%, 34.7% and 79.3% for patients who did not maintain VL values always < 60,000 (RR = 23; P < 0.0001). The minimum value of VL that reached statistical significance for the survival analysis was 100,000 copies/ml (P < 0.0001). CONCLUSIONS: VL > or = or < 35,000 is a better discriminant for progression than a CD4 cell count > or = or < 250 x 10(6)/l. Sequential VL determinations < 60,000 are associated with a better prognosis.

CD4 Lymphocyte Count↗
PubMed1996

Efficacy of triple combination therapy with zidovudine (ZDV) plus zalcitabine (ddC) plus lamivudine (3TC) versus double (ZDV+3TC) combination therapy in patients previously treated with ZDV+ddC.

OBJECTIVE: To evaluate the immunological and virological efficacy of triple combination therapy with zidovudine (ZDV) plus zalcitabine (ddC) plus lamivudine (3TC) and a double (ZDV+3TC) combination therapy in patients previously treated with ZDV plus ddC. DESIGN: A 6-month follow-up open-label randomized study was undertaken in 46 HIV-1-infected patients previously treated for at least 6 months with ZDV plus ddC, who were allocated to receive either ZDV/ddC/3TC (n = 15) or ZDV/3TC (n = 15) or to continue with the ZDV/ddC regimen (control group; n = 16). METHODS: Changes in CD4+ cell counts and plasma viral load (VL) were analysed with analysis of variance. Sequencing of the reverse transcriptase gene was performed in a subset of 3TC-treated patients. RESULTS: Mean CD4+ cell counts increased significantly above baseline in both 3TC regimens whereas counts decreased in the control group. Significant plasma VL reduction was achieved in both 3TC combination therapy groups at weeks 4 and 24 compared with the control group. Coexistence of mutations conferring resistance to ZDV and 3TC were found in patients from both 3TC treatment groups. CONCLUSIONS: Both therapy strategies, switching ddC to 3TC or adding 3TC, significantly improved the virological and immunological efficacy compared with continuing ZDV/ddC. Our results support the use of 3TC in patients previously treated with the ZDV/ddC combination.

Adult↗
PubMed1996

Chromium, copper, iron, manganese, selenium and zinc levels in dairy products: in vitro study of absorbable fractions.

Because milk and dairy products are some of the most widespread foods in the human diet, they contribute a large fraction of mineral intake. We determined levels of chromium, copper, iron, manganese, selenium and zinc in 60 samples of 10 widely consumed dairy products. Graphite furnace atomic absorption spectrometry was used to analyze samples processed with a slurry procedure to minimize sample pretreatment. The accuracy and precision of our method were verified. In analyzed samples, mean values ranged from not detectable to 0.950 microgram/g for Cr, from 0.020 to 2.800 micrograms/g for Cu, from 0.750 to 20.0 micrograms/g for Fe, from 0.010 to 0.900 microgram/g for Mn, from not detectable to 0.140 microgram/g for Se, and from 0.250 to 4.500 micrograms/g for Zn. The highest levels of Cr, Cu, Fe, Mn and Zn were detected in children's milk. Increased concentrations of Cr, Cu, Fe and Mn were detected in products packaged in glazed ceramic containers. We also studied the absorbable fractions of these elements using in vitro techniques which simulate human gastric and intestinal digestion.

Absorption↗
PubMed1996

Short-term anti-HIV activity of the combination of didanosine and hydroxyurea.

The synergistic action of hydroxyurea with some other antiretroviral drugs led us to evaluate the effect of therapy with the combination of didanosine and hydroxyurea in HIV-1-infected patients. We aimed to assess the anti-HIV activity of therapy with this combination by measuring variations in viral load and in CD4 cell counts. We also evaluated the potential side effects of this drug combination in HIV-1-positive patients with advanced disease. A total of 15 HIV-1-seropositive homosexual men with a mean baseline CD4 cell count of 149 cells/mm3 (range: 1-430 cells/mm3) were recruited to the study, and received didanosine (200 mg) plus hydroxyurea (500 mg) twice daily for 12 weeks. Ten patients were didanosine naive and five had previously received didanosine (for > 3 months). The combination therapy was well tolerated, although grade 2-3 alopecia appeared in four patients who had very low CD4 cell counts (< 50 cells/mm3). No significant variation in renal, hepatic and pancreatic functions occurred. A significant reduction in the plasma HIV-1 RNA (> 0.5 logs) was observed in seven of ten patients naive to didanosine after weeks 4 and 12 of the study; five of these patients had a decrease in plasma HIV-1 RNA of > 1.5 logs, with two having a decrease of > 2.0 logs. The viral load became undetectable (below 200 copies/ml) in three patients. The patients whose plasma HIV-1 RNA levels were not significantly reduced by the combination therapy had a higher baseline viral load. CD4 cell counts did not increase significantly in most patients. We observed a better response in those patients who had virus of the non-syncytium-inducing phenotype. In conclusion, hydroxyurea in combination with didanosine was well tolerated and led to a reduction in viral load mainly in patients who were initially naive to didanosine.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Plasma HIV-1 RNA as a predictor of the efficacy of adding zalcitabine to a previous regimen with zidovudine.

The objective of this study was to determine whether or not plasma HIV-1 RNA levels, the syncytium-inducing phenotype assay or mutations at codon 215 of the gene encoding HIV-1 reverse transcriptase could have prognostic value in patients already undergoing therapy with zidovudine who were started on combination therapy with zidovudine and zalcitabine. A prospective study was performed in 37 HIV-1-infected individuals who had received at least 6 months (mean: 9 months; range: 6-24 months) of zidovudine to which zalcitabine was added. The mean initial CD4 cell count was 330 cells/mm3 (range: 20-520 cells/mm3). At baseline and at the end of the study (12 months), we analysed CD4 and CD8 cell counts, plasma HIV-1 RNA levels, the syncytium-inducing phenotype of virus isolated from peripheral blood mononuclear cells and mutations at codon 215 of the gene encoding reverse transcriptase. These variables were studied by Fisher's exact and U Mann-Whitney tests. There were statistically significant differences between progressor and non-progressor groups at baseline and after a 12-month period in the following parameters: CD4 and CD8 cell counts and HIV-1 RNA level (P < 0.05). Clinical progression occurred significantly more often in patients with CD4 cell counts < or = 300 cells/mm3 and HIV-1 RNA > 30000 copies/ml at baseline (P = 0.003). Moreover, we found that progression to AIDS only occurred in those patients whose viral load increased during the follow-up period and who had a CD4 cell count < 300 cells/mm3. Our results show the usefulness of HIV-1 RNA level as a surrogate marker for clinical outcome.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Speciation of methylmercury and Hg(II) using baker's yeast biomass (Saccharomyces cerevisiae). Determination by continuous flow mercury cold vapor generation atomic absorption spectrometry.

Baker's yeast cells (Saccharomyces cerevisiae) were successfully used to selectively separate methylmercury and Hg(II). Several parameters affecting the degree of biosorption and the binding kinetics of methylmercury and Hg(II) were evaluated: solution pH, temperature, incubation time, amount of biomass and analyte, and presence of foreign ions. Methylmercury is immediately bound to the yeast cells over a wide pH and temperature range. The fraction of methylmercury bound was in all cases 100% and was unaffected by the parameters mentioned above. Hg(II) has less affinity for yeast cells and remains in solution, although the percentage of Hg(II) bound to the cell does increase at high incubation time (3 h) and biomass. Of the foreign ions tested, chloride at high concentrations strongly increases the Hg(II) binding efficiency. Methylmercury and Hg(II) are quantitatively separated under optimum conditions, i.e., 30 min incubation time at pH 7.0 and 37 degrees C. The results were compared with those obtained using a purified S. cerevisiae isolate, and no significant differences were observed. Our work suggests that the cell rapidly reduces CH3Hg+ to more volatile species, such as Hg(I) or Hg0, whereas Hg2+ is slowly bound and reduced, perhaps because of the different toxicities of the two species. The method was applied to the selective determination of CH3Hg+ and Hg(II) in spiked water samples. In all cases good recoveries were obtained.

Cations↗
PubMed1995

The role of nitric oxide in the central control of blood pressure.

In these studies blood pressure responses to intracerebroventricular (i.c.v.) infusions were recorded in anesthetized rats. NO donors caused a fall in blood pressure, whereas L-NAME, which blocks the enzyme (NOS) that produces NO, caused a rise in blood pressure. Calcium, i.c.v., stimulates NOS to lower blood pressure. The depressor action of NO is reduced by blocking the action of cGMP. This central NO/cGMP system is tonically active to maintain blood pressure at a normal level.

Amino Acid Oxidoreductases↗