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Biomedical subjects

C Rojas

Publications and source records attributed to C Rojas.

At least 19 recordsLinked to original sources
PubMed2004

Managing metabolic complications of peritoneal dialysis.

AIMS: The purposes of this paper are: to report our experience employing a comprehensive, multifaceted treatment program to improve the metabolic disturbances of dyslipidemia, hyperglycemia and weight gain observed in our peritoneal dialysis patients, and by post-hoc analysis to demonstrate how the routine clinical lipid profile can be manipulated arithmetically to estimate levels of atherogenic low-density lipids and thereby achieve a more sophisticated clinical analysis of dyslipidemia and its response to therapy. METHODS: Data are reported for 56 patients who were stable on peritoneal dialysis for at least 6 months and who had metabolic data available prior to beginning peritoneal dialysis. Metabolic complications of peritoneal dialysis were treated by a comprehensive strategy involving diet, glycemic control and lipid-lowering medications with an emphasis on weight control and exercise. From the measured lipid profile (total cholesterol (TC), high-density lipoprotein (HDL) and triglyceride (TG)), levels of atherogenic low-density lipids (low-density lipoprotein (LDL), non-HDL, very-low-density lipoprotein (VLDL) and intermediate-low-density lipoprotein (IDL) were calculated. RESULTS: Before initiation of peritoneal dialysis therapy, the most common lipid abnormalities were low levels of HDL (59%) and elevated levels of triglyceride (41%) with infrequent elevations of total cholesterol (9%) and low-density lipoprotein (23%). After initiation of peritoneal dialysis therapy, all lipid levels, except HDL, increased significantly, and hyperlipidemia, hyperglycemia and obesity, singly or in combination, occurred in 84% of patients. With treatment, elevated lipid levels decreased significantly with reversal of the adverse cardiovascular risk profile of lipids that developed during peritoneal dialysis therapy, and HDL levels increased significantly. On peritoneal dialysis therapy, all diabetic patients required insulin, and glycemic control was achieved in most patients (79%). Excessive weight gain (10-24% body weight) occurred in 20% of peritoneal dialysis patients. Diabetic patients had a higher incidence of being overweight and obese. Post-hoc analysis revealed that levels of VLDL and IDL frequently were elevated both before (57-61%) and during (68-84%) peritoneal dialysis and that target levels of these atherogenic low-density lipoproteins infrequently (22-26%) were achieved. CONCLUSIONS: The metabolic complications of peritoneal dialysis are responsive to a comprehensive treatment strategy. Controlling weight gain on peritoneal dialysis therapy maybe a difficult challenge for some patients, particularly those who are diabetic. Patients with renal failure and on dialysis, especially peritoneal dialysis, frequently have elevated levels of the atherogenic lipoproteins fragments VLDL and IDL. Future clinical trials should focus on the efficacy and safety of aggressive therapy to achieve target levels of these atherogenic lipids.

Adult↗
PubMed2003

Recent advances in the development of phytoestrogens and derivatives: an update of the promising perspectives in the prevention of postmenopausal diseases.

Phytoestrogens constitute a promising alternative in the treatment of diseases associated with menopause. Nevertheless, the lack of data concerning their pharmacology and their toxicology requires use precautions. After reminding the pharmacology of estrogen receptors, this review outlines the estrogenicity and the therapeutic potentialities of phytoestrogens according to their structure.

Humans↗
PubMed2001

Binding of the glutamate carboxypeptidase II (NAALADase) inhibitor 2-PMPA to rat brain membranes.

2-Phosphonomethyl pentanedioic acid (2-PMPA) is a potent and selective inhibitor of glutamate carboxypeptidase II (NAALADase), and has shown robust neuroprotective activity in both in vitro and in vivo models of ischemia. In the brain, glutamate carboxypeptidase II (GCPII) (EC3.4.17.21) hydrolyzes the neuropeptide N-acetylaspartylglutamate (NAAG) to glutamate and N-acetylaspartate. We report the development and characterization of a [(3)H]2-PMPA binding assay. [(3)H]2-PMPA binding was dependent on protein concentration, saturable, and displaceable. The association (k(on)) and dissociation (k(off)) rate constants were 3x10(6) M(-1) s(-1) and 0.01 s(-1), respectively. The dissociation equilibrium constant (K(d)) determined from the ratio of the rate constants (K(d)=k(off)/k(on)) was 1 nM. Scatchard analysis revealed one binding site with K(d)=2 nM and B(max)=0.7 pmol/mg. Binding exhibited similar pharmacological properties to GCPII enzyme activity, including chloride dependency, cobalt stimulation and inhibition by phosphate and quisqualate. The binding of [(3)H]2-PMPA also showed tissue specificity in that tissues previously reported to be devoid of GCPII enzymatic activity were devoid of [(3)H]2-PMPA binding. [(3)H]2-PMPA binding represents an additional probe for the study of GCPII activity, and may be useful as a high throughput screening assay.

Animals↗
PubMed2001

EGb761 blocks MPP+-induced lipid peroxidation in mouse corpus striatum.

EGb761 has been suggested to be an antioxidant and free radical scavenger. Excess generation of free radicals, leading to lipid peroxidation (LP), has been proposed to play a role in the damage to striatal neurons induced by 1-methyl-4-phenylpyridinium (MPP+). We investigated the effects of EGb761 pretreatment on MPP+ neurotoxicity. C-57 black mice were pretreated with EGb761 for 17 days at different doses (0.63, 1.25, 2.5, 5 or 10 mg/kg) followed by administration of MPP+, (0.18, 0.36 or 0.72 mg/kg). LP was analyzed in corpus striatum at 30 min, 1 h, 2 h and 24 h after MPP+ administration. Striatal dopamine content was analyzed by HPLC at the highest EGb761 dose at 2 h and 24 h after MPP+ administration. MPP+-induced LP was blocked (100%) by EGb761 (10 mg/kg). Pretreatment with EGb761 partially prevented (32%) the dopamine-depleting effect of MPP+ at 24 h. These results suggest that supplements of EGb761 may be effective at preventing MPP+-induced oxidative stress.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Incidence and hospitalization rates of varicella and herpes zoster before varicella vaccine introduction: a baseline assessment of the shifting epidemiology of varicella disease.

BACKGROUND: A 15-year postmarketing evaluation of the impact of varicella vaccine on the age distribution of varicella disease is being conducted at Kaiser Permanente Medical Care Program, Northern California (KPMCP). We report on a baseline assessment of the age-specific incidence and hospitalization rates of varicella and herpes zoster that was conducted before vaccine introduction. METHODS: To assess the annual incidence of varicella, a telephone survey was conducted in a random sample of approximately 8,000 youths 5 to 19 years of age. The annual incidence of hospitalizations for varicella and herpes zoster in 1994 was assessed with the use of the computerized database at KPMCP. RESULTS: Varicella annual incidence was 10.3% in 5- to 9-year-olds, 1.9% in 10- to 14-year-olds and 1.2% in the 15- to 19-year age groups, respectively. Hospitalization rates among the entire KPMCP membership were 2.6 and 2.1 per 100,000 person years for varicella and zoster, respectively. Varicella incidence in the 15- to 19-year age group was higher among African-Americans than among Caucasians. CONCLUSIONS: Varicella rates were similar in the 5- to 9- and 10- to 14-year age groups to rates from other published studies conducted in 1972 to 1978, 1980 to 1988 and 1990 to 1992; however, the rate in 15- to 19-year-olds was 2 to 4 times higher than published rates in the same age category.

Adolescent↗
PubMed2001

Hepatitis C patients in Puerto Rico have an altered iron balance.

Iron overload is a major concern in hepatitis C virus (HCV) infection because excess iron can promote hepatocyte damage by activating iron-mediated lipid peroxidation. This may also facilitate viral replication. The objective of this pilot study was to test the hypothesis that Puerto Rican HCV patients have an altered serum iron (SIR) profile. Twenty-three HCV patients and 38 non-HCV controls were compared in terms of their serum iron, iron-binding capacity, percent saturation of transferrin, available binding capacity, and ferritin. Statistically significant differences (p < 0.01, Student's t-test) were found between the HCV patients and the non-HCV controls for SIR, transferrin saturation, and ferritin. The mean SIR concentration and transferrin saturation were 25% higher in HCV patients relative to controls. HCV patients had a mean ferritin value 48% higher than controls. These pilot study data indicate that Puerto Rican HCV patients have an altered iron balance and may be more susceptible to iron-induced oxidative stress.

Case-Control Studies↗
PubMed2001

[Molecular diagnosis of Prader-Willi and Angelman syndromes: methylation, cytogenetics and FISH analysis].

BACKGROUND: The diagnosis of Prader-Willi and Angelman syndromes is difficult, since their phenotypic manifestations are variable and unspecific. The study of the methylation state of DNA in 15(q11-q13) using polymerase chain reaction, called methylation test, allows the diagnosis of most patients with Prader-Willi and Angelman syndromes, irrespective if the underlying molecular alteration is a deletion, uniparental disomy or a punctual imprinting mutation. AIM: To assess the effectiveness of methylation test in the diagnosis of Prader-Willi and Angelman syndromes. PATIENTS AND METHODS: Thirty seven cases with a presumptive diagnosis of Prader-Willi syndrome and 25 with the presumptive diagnosis of Angelman syndrome were studied. Methylation test was done in genomic DNA obtained from peripheral lymphocytes. RESULTS: Methylation test confirmed the clinical diagnosis in 11 of 37 patients with Prader Willi (30%) and 6 of 25 patients with Angelman syndrome (24%). CONCLUSIONS: Clinical criteria overestimate the diagnosis of Prader-Willi and Angelman syndromes. The initial diagnosis should be confirmed with the methylation test and, if necessary, with FISH that will detect most deletions in the region.

Adolescent↗
PubMed2001

[Familial gout and nephropathy in a young woman. Report of one case].

We report a 29 years old woman with a chronic tophaceous gout, whose disease started at the age of 18. On clinical examination, the blood pressure was elevated. The laboratory assessment showed a serum uric acid of 15 mg/dl, a urinary uric acid of 155 mg/24 h, a creatinine clearance of 59 ml/min/1.73 m2 and a uric acid excretion fraction off 1.3% (normal 7 to 12%). The clinical and laboratory features of this patient suggest the diagnosis of a familial juvenile gouty nephropathy.

Adult↗
PubMed2000

Preconditioning of human smooth muscle cells via cyclopentenone prostaglandins protects against toxic effects of oxidized low-density lipoprotein.

Human vascular smooth muscle cells (SMC) exhibit upregulation of inducible heat shock protein 70 (Hsp70), upon exposure to oxidized low-density lipoproteins (LDL(ox)). The presence of Hsp70 is thought to protect the cell against the toxic effects of the modified lipoprotein. In order to test this hypothesis, Hsp70 in SMC was upregulated by exposure to Delta(12) prostaglandin J(2) (Delta(12)PGJ(2)) before cells were exposed to LDL(ox). Hsp70 levels were measured after exposure to Delta(12)PGJ(2) and before exposure to LDL(ox). Cell protection was monitored after LDL(ox) exposure by determination of cell toxicity measured by cell lactate dehydrogenase (LDH) release into the medium. Cells treated with Delta(12)PGJ(2) exhibited a 23-fold increase in Hsp70 levels and 56% lower LDH activity release after exposure to LDL(ox) when compared to cells that were not pretreated with Delta(12)PGJ(2). In addition, cells pretreated with prostaglandins that did not induce Hsp70 did not exhibit increased tolerance against the toxic effects of LDL(ox). The results support a protective role for Hsp70 against the toxic effects of LDL(ox) and hint at the potential for the use of small molecules for the prevention of deleterious effects of LDL(ox) through heat shock protein upregulation.

Cyclopentanes↗
PubMed2000

Essential fatty acid metabolism in the micropremie.

Lipids are structural components of all tissues and are indispensable for cell membrane synthesis. The brain, retina, and other neural tissues are particularly rich in LCPUFAs, affecting neural structural development and function. LCPUFAs serve also as specific precursors for eicosanoid production (prostaglandins, prostacyclins, thromboxanes, and leukotrienes). These autocrine and paracrine mediators are powerful regulators of numerous cell and tissue functions (e.g., thrombocyte aggregation, inflammatory reactions, and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, uterine contraction). Dietary lipid intake affects cholesterol metabolism at an early age and is associated with cardiovascular morbidity and mortality in later life. Over recent years, the role of fatty acids in modulating signal transduction and regulating gene expression have been described, emphasizing the complex of fatty acid effects. Dietary fatty acids, especially LCPUFA, can have significant effects in the modulation of developmental processes affecting the clinical outcomes of extremely premature infants.

Fatty Acids, Essential↗
PubMed2000

Terminal cancer. duration and prediction of survival time.

The duration of the terminal period of cancer allows us to determine its prevalence, which is necessary to plan palliative care services. Clinical prediction of survival influences access to palliative care and the healthcare approach to be adopted. The objective of this study was to determine the duration of the terminal period, the prognostic ability of healthcare professionals to predict this terminal period and the factors that can improve the prognostic accuracy. In the island of Mallorca, Spain, we followed 200 cancer patients at the inception of the terminal period. Twenty-one symptoms, quality of life, prognosis and duration of survival were measured. Using a Cox regression model, a predictive survival model was built. Median duration was 59 days; 95% confidence interval (CI)=49-69 days, mean=99 days. The oncologists were accurate in their predictions (+/-1/3 duration) in 25.7% of cases, the nurses in 21.5% of cases and the family physicians in 21.7% of cases. Errors of overestimation occurred 2.86-4.14 times more frequently than underestimation. In the final model, in addition to clinical prognosis (P=0.0094), asthenia (P=0.0257) and the Hebrew Rehabilitation Centre for Aged Quality of Life (HRCA-QL) Index (P=0.0002) were shown to be independent predictors of survival. In this study, the estimated duration of the terminal period was greater than that reported in a series of palliative care programmes, and survival was overestimated. Oncologists could estimate prognosis more accurately if they also take into account asthenia and HRCA-QL Index.

Adult↗
PubMed2000

Essential fatty acids in early life: structural and functional role.

Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4alpha. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

Animals↗
PubMed2000

MPTP decreases MT-I mRNA in mouse striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces parkinsonism in humans and non-human primates. Free radicals are thought to be involved in its mechanism of action. Recently, metallothionein has been proposed to play a role as a scavenger of free radicals. In the present work, we studied the effect of MPTP neurotoxicity on brain metallothionein-I (MT-I) mRNA expression. Male C-57 black mice were treated with MPTP (30 mg/kg, i.p., daily) for 3 or 5 days. All animals were killed by cervical dislocation 7 days after the last MPTP dose. The brains were removed quickly and immediately frozen, and quantitative in situ hybridization was performed using MT-I cDNA probe. MT-I mRNA content in striatum, a region which is known to be highly predisposed and sensitive to MPTP-induced oxidative stress, decreased by 30% (3 days) and 39% (5 days) respectively, after the last MPTP administration. These results suggest that MT-I gene expression is decreased in MPTP neurotoxicity. It is suggested that the reduction of MT, an anti-oxidant and a free radical scavenger, in the striatum by MPTP enables the neurotoxin to exert maximal oxidative damage to the striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Induction of heat shock protein 70 by herbimycin A and cyclopentenone prostaglandins in smooth muscle cells.

This study characterizes Hsp70 induction in human smooth muscle cells (SMC) by herbimycin A and cyclopentenone prostaglandins. The magnitude of Hsp70 induction by cyclopentenone prostaglandins was 8- to 10-fold higher than induction by herbimycin A. Hsp70 induction by delta12PGJ2 was first observed at 10 microM, rose to 4000-5000 ng/mL within one log unit and a maximum response was not observed; concentrations of delta12PGJ2 higher than 30 microM were toxic to the cells. A maximum response with herbimycin A (500 ng/mL) was reached at 0.05 microM and maintained to 1 microM without toxicity. Both, delta12PGJ2 and herbimycin A, were inhibited by dithiothreitol (DTT, 100 microM) at lower concentrations and became less sensitive to inhibition at higher concentrations. Hsp70 induction after incubation of SMC with delta12PGJ2 followed by addition of herbimycin A was significantly higher than Hsp70 induction after incubation with herbimycin A followed by addition of delta12PGJ2. When cells were incubated with [3H]-PGJ2, followed by protein denaturation, substantial radioactivity remained protein-bound suggesting that the prostaglandin must be covalently bound. Covalent binding was largely insensitive to DTT. Maximal Hsp70 induction was observed after 5 minutes of exposure of the cells to herbimycin A followed by a 20 hour recovery period in agent-free medium. Cells required 3-4 hours of exposure to delta12PGJ2 followed by a 20 hour recovery period in order to see high Hsp70 induction. Binding of the heat shock factor (HSF) to the heat shock element (HSE) in the presence of herbimycin A or delta12PGJ2, and the effects of DTT, mirrored the results of Hsp70 induction. The results suggest that probable differences between the 2 agents are at the level of the signal transduction prior to HSF activation.

Anti-Bacterial Agents↗
PubMed2000

In vitro recovery of triamcinolone acetonide in microdialysis.

The purpose of this study was to assess the factors affecting the calibration of the microdialysis probe for the in vitro recovery of triamcinolone acetonide (TA). Recoveries of TA were determined in microdialysis, retrodialysis, and no-net flux methods. Experiments were performed at room temperature or 37 degrees C while the reservoir medium was either stirred or unstirred. The effect of the viscosity of the medium on the recovery was studied using methylcellulose gel spiked with TA. Recovery was also calculated by the no-net-flux method in Ringer's solution and in plasma. Stirring the medium increased the recovery of TA by 30%. The recovery was higher at 37 degrees C under stirred or unstirred conditions and was same in either direction of dialysis. Increasing viscosity of the reservoir medium decreased the recovery (55% in Ringer's solution to 14% in 20% methylcellulose gel). Recovery from spiked plasma under stirred conditions was only 15% and this shift which was also seen in no-net-flux method was accounted for by the protein binding. Binding of TA, determined by ultrafiltration, was 20% in 5% gel and 81% in plasma. The recovery determined by the no-net-flux method was similar to the retrodialysis result. Stirring, temperature, viscosity and protein binding in the reservoir medium affected the in vitro recovery of TA.

Administration, Topical↗