Search PubMed⌕ Search

Biomedical subjects

L Contreras

Publications and source records attributed to L Contreras.

At least 19 recordsLinked to original sources
PubMed2005

Development of an HPLC method for determination of diphenidol in plasma and its application in an oral multi-dose bioequivalence study in a healthy female Mexican population.

Diphenidol was determined by an HPLC method developed in our laboratory. It was validated and proved to be linear in the 40-400 ng/ml range. Accuracy for quality-control samples for intra and inter day assays ranged from 96.1-98.9% and 98.8-101.4%, respectively. This method was applied to a multi-dose bioequivalence study. No serious side effects were observed in the multi-dose design. Pharmacokinetic parameters (mean+/-standard error [S.E.]) of Cavg (ng/ml) and AUCtau (ngh/ml) for reference and test products were 139.54+/-12.66 versus 148.60+/-16.51 and 551.07+/-53.53 versus 588.78+/-69.02, respectively. Log-transformed values were compared by analysis of variance (ANOVA) followed by the classical 90% confidence interval (CI 90%) test and Schuirmann's test. Confidence limits ranged from 91.48-116.18% for Cmax and from 91.24-117.65% for AUCtau. These results suggest that the analytical method was linear, precise, and accurate for our purpose, and that both assayed formulations were bioequivalent.

Adult↗
PubMed2005

Bioequivalence evaluation of two brands of meloxicam tablets (Promotion and Mobicox): pharmacokinetics in a healthy female Mexican population.

We conducted a randomized, crossover study in 23 healthy young female volunteers to compare the bioavailability of two brands of meloxicam (7.5 mg) tablets and to obtain pharmacokinetic parameters of this molecule in Mexican population not reported previously. Two tablets (15 mg) were administered as a single dose on 2 treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 72 h. Plasma harvested was analyzed for meloxicam by a modified and validated high-performance liquid chromatography (HPLC) method previously reported. Pharmacokinetic parameters AUC(0-t), AUC(0-alpha), C(max), T(max), k(e), MRT and t(1/2) were determined from plasma concentrations of both formulations, resulting in a C(max) 120% larger than and a T(max) 65% faster than those reported in other populations. AUC(0-t), AUC(0-alpha), and C(max) were statistically tested for bioequivalence after log transformation data in a non-balanced design, and no significant differences were found either in 90% classical confidence interval (90% CI) or in Schuirmann test (p < 0.05); thus, we concluded that bioequivalence existed between both formulations.

Administration, Oral↗
PubMed2004

Bioequivalence evaluation of two brands of ketoconazole tablets (Onofin-K and Nizoral) in a healthy female Mexican population.

A randomized, crossover study was conducted in 24 healthy female volunteers to compare the bioavailability of two brands of ketoconazole (200 mg) tablets; Onofin-K (Farmacéuticos Rayere S.A., Mexico) as the test and Nizoral (Janssen-Cilag, Mexico) as the reference products. The study was performed at the Clinical Pharmacology Research Center of the Hospital General de Mexico in Mexico City. Two tablets (400 mg) were administered as a single dose with 250 ml of water after a 12 h overnight fast on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 12 h. Plasma harvested was analysed for ketoconazole by a modified and validated HPLC method with UV detection in the range 400-14000 ng/ml, using 200 microl of plasma in a full-run time of 2.5 min. The pharmacokinetic parameters AUC(0-t), AUC(0-alpha), Cmax, Tmax and t(1/2) were determined from plasma concentrations of both formulations and the results discussed. AUC(0-t), AUC(0-alpha) and Cmax were tested for bioequivalence after log transformation of data, and no significant differences were found either in 90% classic confidence interval or in the Anderson and Hauck test (p < 0.05). Based on statistical analysis, it is concluded that Onofin-K is bioequivalent to Nizoral.

Adolescent↗
PubMed1998

Coating PTFE vascular prostheses with a fibroblastic matrix improves cell retention when subjected to blood flow.

An investigation was made into the effect of blood flow on endothelial cells (EC) and mesothelial cells (MC) seeded on a vascular expanded polytetrafluoroethylene (ePTFE) prosthesis coated with a fibroblastic matrix. Endothelial cells were obtained from the external jugular vein and MC from the omentum. To test the performance of prostheses, a custom designed, femoral "ex vivo" circuit was developed in mongrel dogs. Four study groups were established: a control group, A1, where prostheses were uncoated and seeded with EC; a second control group, A2, where prostheses were uncoated and seeded with MC; group B1 where prostheses were coated with a fibroblastic matrix and seeded with EC; and group B2 where coated prostheses were seeded with MC. All cells were labeled with 111Indium oxine (10 microCi/mL) before seeding. After the seeded cells had formed a monolayer on the ePTFE prostheses (which took approximately 24 h) the prostheses were placed in the "ex vivo" circuit. The rates of blood flow to which prostheses were exposed were measured at the point of inflow (117.5 +/- 12.50 mL/min, mean +/- SD) and outflow (72.6 +/- 14.3 mL/min). MC showed a greater baseline radionuclide uptake than did EC. The cells of groups B1 and B2 adhered sufficiently to the fibroblastic matrix and covered enough of the prosthetic surface to be positioned in the "ex vivo" circuit (76.90 +/- 8.24% surface covered in EC-seeded prostheses and 71.65 +/- 6.23% in MC-seeded prostheses). After exposure to blood flow the quantity of radionuclide-labeled cells and the prosthetic surface covered by them were greatly reduced though the fibroblast-coated prostheses showed greater cell retention.

Animals↗
PubMed1998

[Comparison of the efficacy of intraarticular and intraarterial injections of two betamethasone preparations in patients with osteoarthritis or epicondilytis].

BACKGROUND: Local infiltration with corticoids is a simple therapy for rheumatic disorders devoid of systemic adverse reactions. AIM: To compare the efficacy of two betametasone preparations from two different pharmaceutical laboratories in the treatment of patients with osteoarthritis or epicondylitis. PATIENTS AND METHODS: Fourty patients with knee osteoarthritis and 12 patients with epicondylitis were studied. Using a double blind protocol, one of the two betametasone preparations was used for local infiltration of the lesions. The change in a global score of clinical variables including pain and disability was assessed after 30 days of the infiltration. RESULTS: In patients with osteoarthritis, the global score decreased significantly with both preparations, but no differences were observed between preparations (7.3 +/- 1.8 to 3.9 +/- 2.3 with preparation A and 7.8 +/- 1.9 to 3.6 +/- 2.3 with preparation B). In patients with epicondylitis, pain was also significantly reduced but no differences between preparations was observed (7 +/- 2.1 to 1.4 +/- 2.5 for preparation A and 4.6 +/- 2.8 to 1.2 +/- 1.6 for preparation B). CONCLUSIONS: Local infiltration with both betametasone preparations was equally effective in the treatment of patients with knee osteoarthritis or epicondilytis.

Adolescent↗
PubMed1997

Mesothelial versus endothelial cell seeding: evaluation of cell adherence to a fibroblastic matrix using 111In oxine.

OBJECTIVES: The aim of this study was to compare the behaviour of mesothelial cells (MC) to that of endothelial cells (EC) when seeded onto a PTFE, prosthesis coated with a fibroblastic matrix. DESIGN, MATERIAL AND METHODS: Three study groups were examined: a control group (Control) of PTFE prostheses with a fibroblast matrix (n = 8); Group EC, PTFE prostheses seeded with EC on a fibroblastic matrix (n = 8); and Group MC, PTFE, prostheses seeded with MC on a fibroblastic matrix (n = 8). All cell types were labelled with 111In (100 microCi/ml) 24 h after seeding, when the cells had formed a monolayer on the prosthetic surface. Radioactive levels were measured at 2, 4, 6, and 24 h. RESULTS: Both EC and MC showed optimal adherence. The MC had a better radioactive uptake and retention than the EC. The number of EC and MC cells that remained adherent to the matrix was large enough to ensure complete covering of the prosthetic surface. CONCLUSION: The use of MC is therefore feasible as an optimal alternative for achieving a natural covering on vascular prostheses prepared with a fibroblastic matrix.

Blood Vessel Prosthesis↗
PubMed1997

[Twelve-year trends of hip fracture rates in Chile. Is there a relationship between their increase and population aging?].

BACKGROUND: Epidemiology of osteoporosis is assessed measuring bone density or measuring the rates of bone frailty-related fracture rates. Of these, the most important are hip fractures, that markedly increase after 65 years of age. AIM: To measure the incidence of hip fractures in Chile from 1982 to 1993. MATERIAL AND METHODS: All hospital discharges that occurred in Chile from 1982 to 1993 were analyzed, looking for the diagnosis of hip fracture. National censuses in the same period were also analyzed searching for possible changes in the age structure of the population. Fracture rates were analyzed for three age groups, and changes along the years were calculated correlating the rates with the number of the year. RESULTS: In the twelve year period, women aged 55-64 years old had a correlation of 0.32 (NS), women aged 65-74 years old had a correlation of 0.58 (NS) and women aged over 75 years old had a correlation of 0.95 (p < 0.001). This age group corresponded to 2.01% of the whole population in 1982 and to 2.52% in 1993. The mean age of the group increased from 80.7 to 80.9 years in the same lapse. CONCLUSIONS: Fracture rates increased in the 12 years period studied, specially among women older than 75 years old. During the same period the proportion of people over 75 years old also increased, but there was only a slight increase in its mean age. Thus, the increase in fracture rates is disproportionate to population aging and could be related to changes in lifestyles.

Age Factors↗
PubMed1996

[Patients with rheumatoid arthritis: study of the correlation between density of glucocorticoid receptors in synovial cells and clinical response to steroidal treatment].

BACKGROUND: The target cellular response to glucocorticoids is proportional to the concentrations or affinity of specific receptors to these substances. AIM: To look for a correlation between glucocorticoid receptor concentrations in synovial wall cells and the clinical response to steroidal treatment in patients with rheumatoid arthritis. PATIENTS AND METHODS: Twenty eight patients with rheumatoid arthritis were studied. Each subject was subjected to a synovial biopsy, in which a dry radioautographic technique for diffusible compounds was used. Patients were treated afterwards with three 500 mg intravenous pulses of methilprednisolone. RESULTS: A mean of 44.8% of synovial cells (range 30.1-62.8%) had binding sites for 3H dexamethasone. All patients had a significant clinical improvement after methylprednisolone. Multiple regression analysis did not show a correlation between clinical response and glucocorticoid receptor concentration. CONCLUSIONS: The lack of association between glucocorticoid receptor concentrations and clinical response could be due to the large steroid dose used, that saturated all available receptors.

Adolescent↗
PubMed1995

Atherogenic effects of cyclosporine in an experimental model of arterial autograft.

One of the effects attributed to CsA is a possible acceleration of atherogenic processes, which contributes to the failure of transplanted organs. This study was undertaken to evaluate the effect of CsA and two vehicles, cremophor and ethanol, in an experimental model of arterial autograft in the rat. Female Sprague-Dawley rats were distributed into 3 study groups: Group 1 (control) had an arterial autograft in the common iliac artery without pretreatment; group 2 (CsA-cremophor) animals were pretreated with a daily dose of CsA (5 mg/kg, Sandimmun) for 4 days before the autograft was made; and group 3 (CsA-ethanol + Tween) animals were pretreated for 4 days before implantation of the autograft with CsA in a vehicle of ethanol + Tween at the same dose as used in group 2 (5 mg/kg). The study periods were 7, 14, 21, 30, and 50 postoperative days. Studies were made by optical microscopy, transmission electron microscopy, scanning electron microscopy, and autoradiography. Evaluation of the results showed that in the control group the postoperative repair process lead to formation of an intimal neolayer throughout the entire surgical zone, with scant participation of white cells. Group 2 (CsA-cremophor) had a marked increase in luminal thrombogenicity, important adhesion and infiltration of white cells, loss of smooth muscle cells in the medial layer, and atherogenic degeneration of the medial layer. The generation of the neointimal layer is delayed by 2 weeks with respect to the control group. However, once the neointimal begins to form, its thickness increases rapidly, reaching values similar to those seen in the control group at 50 days. The myointima also shows atherogenic characteristics, such as monocyte-macrophage infiltration and dystrophic calcification. In group 3 (CsA-ethanol+Tween, that is, CsA in a nonoleaginous vehicle), the effects were similar to those seen in group 2 (CsA-cremophor), with a reduction in the presence of lipid-laden cells in the medial layer. Based on these observations, we conclude that CsA per se induced atherogenic changes in the repair process of the arterial lesion that were independent of the vehicle of administration. CsA delayed, but did not inhibit, formation of a myointima and the myointima formed exhibited atherogenic characteristics. The most important effects were noted in the medial layer, which experienced intense degeneration.

Animals↗
PubMed1995

Slowing proliferation in head and neck tumors: in vitro growth inhibitory effects of the polyamine analog BE-4-4-4-4 in human squamous cell carcinomas.

PURPOSE: These preclinical studies were carried out to examine the potential of the antiproliferative polyamine analog 1,19-bis-(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) to serve as a therapy adjuvant to radiation for patients with rapidly dividing tumors of the head and neck (H&N). METHODS AND MATERIALS: Cytostatic and cytotoxic effects of this polyamine analog were investigated in three squamous cell carcinoma (SCC) cell lines derived from human H&N tumors. RESULTS: Growth inhibition was achieved in all cell lines within 3-4 days of continuous 10 microM drug exposure, and inhibition of cell cycle proliferation kinetics was confirmed via flow cytometry. Cytotoxicity was pronounced (3-4 log cell kill) in the SCC-38 and SCC-4Y cell lines with continuous 10 microM analog exposure over 5 days, and was minimal in the SCC-13Y cell line. No demonstrable effect of BE-4-4-4-4 on single dose radiation survival was identified in any SCC cell line. Ornithine decarboxylase (ODC) activity was rapidly inhibited (1-2 h) following 10 microM BE-4-4-4-4 exposure in all SCC cell lines (approximately 90%), whereas identical exposure to 10 microM difluoromethylornithine (DFMO) induced animal ODC inhibition (approximately 10%). Dose-dependent depletion of endogenous polyamines (putrescine, spermidine, spermine) was achieved in all SCC cell lines following 1 microM and 10 microM BE-4-4-4-4 exposures. Difluoromethylornithine was significantly less potent than BE-4-4-4-4 in its capacity to deplete endogenous polyamines, with no measureable depletion of spermine pools even with 5 mM x 48 h DFMO exposures. CONCLUSIONS: These data evaluate cytostatic and cytotoxic properties of the polyamine analog BE-4-4-4-4 in human SCCs, and suggest a role for investigation of such agents as an adjuvant to radiation in the therapeutic approach to rapidly dividing human tumors such as those that occur in the H&N.

Carcinoma, Squamous Cell↗
PubMed1995

Integration of biomaterials implanted into abdominal wall: process of scar formation and macrophage response.

The behaviour of two biomaterials polytetrafluoroethylene (PTFE) and polypropylene (PL) has been studied, focussing especially on the macrophage response to the implant, as well as on certain aspects of the process of scar formation. A total of 24 animals (white New Zealand rabbits) received prostheses implanted into the anterior abdominal wall in such a way as to involve every layer over an area of 7 cm x 5 cm. The interfaces formed with the visceral peritoneum, subcutaneous tissue layer and the recipient muscle-aponeurotic tissue were assessed. The techniques employed were light microscopy, scanning electron microscopy and immunohistochemical methods, the latter using a monoclonal antibody specific for rabbit macrophages (RAM-11). From the results obtained, it can be seen that: (a) the structure of PL allows its total integration with the reparative tissue, while PTFE becomes encapsulated, on both the subcutaneous and the peritoneal aspects, by orderly connective tissue; (b) the macrophage response, determined on the basis of the presence of labelled macrophages, shows a similar pattern in both biomaterials; and (c) angiogenesis is very intense in the PL mesh, whereas the PTFE prosthesis undergoes almost no vascular colonization.

Abdominal Muscles↗
PubMed1995

[Comparison of 2 treatment schemes to eradicate Helicobacter pylori].

INTRODUCTION: Anti secretory drugs, antimicrobials and bismuth salts are used with variable success to eradicate Helicobacter pylori. AIM: To assess the effectiveness and rates of reinfection of two therapeutic modalities H pylori infection in adult patients with duodenal ulcer or non ulcer dyspepsia. METHODS: During upper gastrointestinal endoscopy, 5 antral and 2 fundic biopsies were obtained and sent for microbiological and anatomopathological study. Patients infected with Helicobacter pylori were randomly assigned to receive during two weeks omeprazole 20 mg od plus amoxicillin 500 mg tid (group A) or bismuth subsalicylate 260 mg bid, metronidazole 250 mg tid and amoxicillin 500 mg tid (group B). A new endoscopy with antral and fundic biopsies was performed to all patients four weeks after discontinuing treatment and six months later to those in whom H pylori was eradicated. RESULTS: Eighty patients (40 in each treatment group) completed the treatment and follow up. H pylori was eradicated in 22 patients of group A (55%) and 28 of group B (70%). Minor adverse effects were reported by 5 patients in group A (12%) and 11 in group B (27.5%). Six months later, reinfection was documented in 12 patients of group A and 8 of group B (54% and 30% of those with successful treatment respectively). Ten of twenty five patients with duodenal ulcer had reinfections, but there was only one ulcer relapse. CONCLUSIONS: These two treatment modalities have similar results.

Adolescent↗
PubMed1995

Assessment of cyclosporine A-induced ultrastructural changes in vascular wall using an experimental arterial autograft model.

The objective of this ultrastructural study was to assess the effects of cyclosporine A (CsA) in an experimental model of arterial autograft. Fifty female Sprague-Dawley rats weighing 250-300 g were employed. Using a microsurgical technique, an arterial autograft measuring approximately 5 mm in length was placed in the right common iliac artery. Two groups were established: group I (control), consisting of 25 animals subjected only to arterial autograft; and group II (pre- and postoperative CsA), also consisting of 25 animals which received a daily subcutaneous dose of 5 mg/kg CsA (Sandimmun, Sandoz) on the four days preceding the surgery and thereafter, until sacrifice. The animals were sacrificed on postoperative day 7, 14, 21, 30 and 50. The specimens (autografts) obtained were studied under transmission and scanning electron microscopes. In the control group, the process of endothelialization of the graft was completed by day 14. In the CsA-treated group, restoration of the endothelium took 50 days. The development of intimal hyperplasia was delayed in the treated group. There were no morphological changes in its structure when compared to the control group. The tunica media had thinned in the treated grafts, with loss of smooth muscle cells, fragmentation and lysis of the elastic lamina, presence of lipid-filled macrophages, and muscle cells with cytoplasmic lipid vacuoles. In our opinion, these results suggest that the action of CsA mainly targets on the endothelium and smooth muscle cells, exerting a toxic effect in an in vivo arterial graft model.

Animals↗
PubMed1995

[Fine needle aspiration biopsy of thyroid nodules. Analysis of results obtained using a new method with histological examination of the sample].

Fine needle aspiration biopsy (FNAB) is the most useful preoperative work up method for patients with nodular goiter. We analyze 173 patients that underwent FNAB and were subsequently operated. The sample with FNAB was processed both for cytological and histological study, using methods developed at the hospital. The preoperative diagnosis reached was compared with that obtained with the surgical piece. Results showed that the histological analysis of the FNAB sample improved the sensitivity of the method, when compared with the cytological study, from 68.5% to 87.8% (p < 0.035) without modifying specificity (100% for both methods). It is concluded that FNAB with histological study of the sample has a high diagnostic yield and is exempt of complications.

Adolescent↗
PubMed1994

Combining polyamine depletion with radiation therapy for rapidly dividing head and neck tumors: strategies for improved locoregional control.

PURPOSE: Locoregional control is adversely affected as clonogens from rapidly proliferating tumors repopulate during a course of radiation therapy. The cytostatic agent alpha-difluoromethylornithine (DFMO) was investigated for its capacity to slow proliferation kinetics in human squamous cell carcinomas (SCC) of the head and neck (H&N), with the ultimate objective of improving locoregional control in rapidly dividing tumors treated with radiation therapy. METHODS AND MATERIALS: Three human SCC cell lines established from primary H&N tumors were evaluated in vitro (cell culture) and in vivo (SCC tumor xenografts in athymic mice) for the capacity of DFMO to induce growth inhibition. Flow cytometry analysis of SCC tumor growth kinetics and quantitative assessment of polyamine biosynthesis inhibition was performed to verify DFMO activity. DFMO effects on in vitro SCC radiosensitivity using clonogenic survival were also studied. RESULTS: A noncytotoxic exposure to DFMO (5mM x 72 hours) induced pronounced growth inhibition in all three SCC cell lines (70-90% at 7 days), and induced a 2-3 fold delay in volume doubling time for SCC tumor xenografts when administered orally in the drinking water (1.5%) to athymic mice. Kinetic analysis via flow cytometry confirmed that DFMO produced a lengthening of SCC cell cycle times, but did not alter in vitro radiosensitivity. Inhibition of ornithine decarboxylase (ODC) activity and depletion of endogenous polyamines (putrescine and spermidine), were confirmed in normal tissue (mouse skin) and in human SCC tumor xenografts of athymic mice receiving continuous oral DFMO. CONCLUSION: These data indicate that antiproliferative agents, such as DFMO, are capable of altering human SCC growth kinetics without altering intrinsic radiosensitivity. Such kinetic modulation may therefore provide a strategy to reduce the adverse impact of tumor cell proliferation during a radiotherapy treatment course for rapidly dividing tumors such as those in the H&N.

Animals↗