Search PubMed⌕ Search

Biomedical subjects

L Alvarez

Publications and source records attributed to L Alvarez.

At least 91 records · Page 5Linked to original sources
PubMed1999

Glucose tolerance and serum insulin levels in an animal model of obesity induced by sub-acute or chronic administration of antipsychotic drugs.

1. To assess the role of insulin in the development of the obesity induced by antipsychotic drugs, a glucose tolerance test was conducted in female rats after 0 or 30 days of sulpiride administration. 2. At day 10, the area under the glucose curve did not differ between sulpiride and vehicle-treated rats, however, the area under the insulin curve was significantly decreased by sulpiride. At day, 30 the insulin response was similar in both groups, but the area under the glucose curve was significantly lower in the sulpiride-treated rats. 3. The results suggest that insulin resistance and hyperinsulinemia are not involved in the development and maintenance of the obesity induced by sulpiride. Contrarily, these findings may be related to an increased insulin sensitivity. 4. The absence of hyperinsulinemia and insulin resistance indicates important differences between primary obesity in humans and rodents and this model of drug-induced excessive weight gain.

Animals↗
PubMed1999

Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy.

The objective of this study was to evaluate the effect of surgical menopause and hormone replacement therapy (HRT) on the new biochemical markers of bone turnover. Fourteen women who had undergone surgical menopause and began HRT 3 months after surgery were recruited for a 1-year study. Results were compared with a control group of 31 healthy premenopausal women of similar age. Serum samples were obtained to determine total alkaline phosphatase, bone alkaline phosphatase, propeptides carboxy- and amino-terminal of type I procollagen (PICP, PINP), osteocalcin, tartrate-resistant acid phosphatase, and carboxy-terminal telopeptides of type I collagen (ICTP and serum CTX). Urine samples were analyzed for hydroxyproline, pyridinoline, deoxypyridinoline, alpha- and beta-carboxy-terminal telopeptides of type I collagen (alpha-CTX and beta-CTX), and amino-terminal telopeptide of type I collagen (NTX). Determinations were performed after 3 months of surgical menopause and after 3 and 9 months of HRT. All biochemical markers increased after menopause, and most of them normalized after 9 months of HRT. Serum PINP showed the highest proportion of increased values after surgery among bone formation markers (62%), as well as the highest mean percent increase (101%). Among bone resorption markers in postmenopausal women, urinary beta-CTX, alpha-CTX, NTX, and serum CTX showed the highest proportion of increased values (100%, 67%, 58%, 58%, respectively) as well as the greatest mean percent increase. They were also the markers with the most marked response to HRT. In conclusion, serum PINP is the most sensitive marker of bone formation, whereas beta-CTX is the most sensitive marker of bone resorption after surgical menopause. In addition, both markers showed the highest response after HRT.

Acid Phosphatase↗
PubMed1999

Titanium levels in rats implanted with Ti6Al4V treated samples in the absence of wear.

The effect of implantation time and implant nitriding on titanium ion concentration in several tissues of rats carrying Ti6Al4V implants was studied by means of inductively coupled plasma-mass spectroscopy (ICP-MS). Histological studies were also performed in order to check for tissue degeneration due to the Ti6Al4V implantation. The animals were divided into four groups: one received Ti6Al4V implants, the second received nitrided Ti6Al4V implants, the third group received nitrided and descaled Ti6Al4V implants and the last one was the control group. Half the animals of the implanted groups received the Ti6Al4V implant for 30 days, while the other half received the implant for 120 days. Spleen, muscle, kidney, lung, brain and bone samples were retrieved from these rats as well as the control group. Ion concentration measures did not show significant differences between control and implanted rats for the studied period of time, although histological studies showed minor differences, especially on liver tissue samples.

Journal Article↗
PubMed1999

Bioequivalence of ivermectin formulations in pigs and cattle.

The vehicle in which endectocide compounds are formulated plays a relevant role in their absorption kinetics and resultant systemic availability. The pharmaceutical bioequivalence and comparative plasma disposition kinetics of ivermectin (IVM), following the subcutaneous administration of two injectable formulations to pigs and cattle were investigated using parallel experimental designs. Sixteen parasite-free male Duroc Jersey-Yorkshire crossbred pigs (90-110 kg) (Expt 1) and 16 parasite-free male Holstein calves (100-120 kg) (Expt 2) were divided into two groups and treated subcutaneously at either 300 (pigs) or 200 (calves) microg/kg with two different propylene glycol/glycerol formal (60: 40) based IVM formulations; in both experiments pigs or calves in Group A received the test (IVM-TEST) formulation and those in Group B were treated with the reference formulation (IVM-CONTROL). Heparinized blood samples were taken from 0 h up to either 20 (pigs) or 30 (calves) days post-treatment and plasma was extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. Early detection of IVM (12 h) with a peak plasma concentration (C(max)) between 33 and 39 ng/mL was observed in pigs. The drug was detected in plasma up to 20 days post-administration of either formulation, resulting in elimination half-lives between 3.47 and 3.80 days. There were no differences between the IVM-TEST and IVM-CONTROL formulations in the kinetic parameters (except t(max)) obtained in pigs. IVM was detected in plasma between 12 h and 30 days post-administration of both formulations under investigation in cattle. The plasma disposition kinetics of IVM in calves was similar following treatment with both formulations. C(max) values (between 40.5 and 46.4 ng/mL) were achieved at 2 days post-administration of both formulations. None of the estimated kinetic parameters were statistically different between drug formulations. The injectable IVM formulations investigated were bioequivalent after their subcutaneous administration to both pigs and calves at recommended dose rates.

Animals↗
PubMed1999

Differences in plasma and abomasal kinetics of albendazole and its metabolites in calves grazed on pasture or fed a grain-based diet.

We evaluated the comparative plasma and abomasal fluid disposition kinetics of albendazole (ABZ) and its metabolites in calves either grazing on pasture or fed a grain-based concentrate diet. Six male Holstein calves (weight 180 to 200 kg) were allowed to graze on lush pasture for three weeks before intraruminal administration of ABZ at 10 mg kg-1(pasture group). After a three-week wash-out period, the same animals were housed and fed on a grain-based concentrate diet for three weeks prior to receiving the same ABZ treatment (concentrate group). Jugular blood and abomasal fluid samples were collected over 120 hours post-treatment. Plasma and abomasal fluid samples were analysed by high performance liquid chromatography (HPLC). The digesta transit time was measured using cobalt (Co) as a fluid marker; abomasal fluid and faecal samples were collected and Co concentrations measured by atomic absorption spectrophotometry. Complementary studies of the in vitro dissolution of ABZ particles at different pH values were also conducted. The pH of abomasal fluid collected from animals kept under both feeding conditions was registered. Increased concentrations of ABZ sulphoxide (ABZSO) and sulphone (ABZSO2) in plasma, resulting in significantly higher Cmax and area under the curve (AUC) values for both metabolites, were obtained in calves fed on the concentrate diet compared to those grazing on pasture. Enhanced abomasal fluid levels of ABZ and ABZSO were observed in concentrate-fed calves. The mean retention time of the digestive fluid marker in the gastrointestinal (GI) tract was significantly longer in the animals fed the grain-based diet. The in vitro dissolution of ABZ at a pH value equivalent to that obtained in the abomasum of the concentrate-fed calves (1.75) was significantly greater than that obtained at the pH registered in pasture-fed animals (2.00). The characterisation of the kinetic/metabolic behaviours and the resultant efficacy of antiparasitic drugs in animals reared under different management conditions may be relevant in increasing parasite control in livestock.

Abomasum↗
PubMed1999

Quantitative evaluation of bone scintigraphy in the assessment of Paget's disease activity.

Interest in the assessment of activity of Paget's disease has increased since the advent of effective therapies. The aim of this study was to develop a quantitative method for the scintigraphic assessment of Paget's disease activity in bone. Twenty patients with Paget's disease were studied prospectively. A scintigraphic visual activity index, together with a quantitative activity index that reflects both the extent and activity of the disease, was obtained for each patient. The quantitative activity index is calculated as the sum of the activity (geometric mean measured from the anterior and posterior views) for all affected bones divided by a reference obtained in non-affected bone. To evaluate the validity of the scintigraphic methods, several biochemical markers of bone turnover were assessed: serum total alkaline phosphatase and serum propeptide aminoterminal of type I procollagen (PINP) as markers of bone formation; urinary hydroxyproline and urinary N-terminal cross-linked telopeptide of type I collagen (NTx) as markers of bone resorption. The visual and quantitative scintigraphic indices were highly correlated (r = 0.78, P < 0.0001). The highest correlations between the biochemical markers and the quantitative activity index were found for PINP (r = 0.69, P < 0.001), which was the most sensitive marker of bone formation, and for urinary NTx (r = 0.63, P < 0.005), which was the most sensitive marker of bone resorption. In conclusion, quantitative evaluation of bone scintigraphy allows easy and objective assessment of Paget's disease activity and it may be useful in evaluating the effectiveness of therapies.

Adult↗
PubMed1999

Urinary porphyrin excretion measurements in healthy neonates.

The objective of this study was to establish normal reference ranges for porphyrins in healthy neonates. There is little information about urinary porphyrin excretion in this age group. This knowledge may provide an early diagnostic tool for detecting subtle alterations or latent forms in disorders of heme biosynthesis. Fifty healthy neonates were selected from the Department of Obstetrics. Total urinary porphyrins in random specimens were analysed by a spectrofluorometry method. The measurement of porphyrin fractions was made by fluorometric high-performance liquid chromatography (HPLC). The results were adjusted to urinary creatinine excretion to correct any imprecision and interindividual variation in body mass. The urinary total porphyrin had a median value of 331.50 (nmol/L). A statistically significant relationship between total porphyrin (nmol/L) and creatinine (mmol/L) was found (p < 0.01). The porphyrin/creatinine ratio showed a median value of 56.30 nmol/mmol creatinine. The study of individual porphyrins revealed that coproporphyrin and uroporphyrin were the major porphyrins excreted in neonates (coproporphyrin represents 81.98% and uroporphyrin 16.64% of total porphyrin); in both cases, isomer I was predominant with median values of 22.36 and 6.25 nmol/mmol creatinine, respectively. No significant relationships were found between porphyrin excretion and sex, gestational age, weight, or height. Our data provide the reference limits for porphyrins in neonates as a diagnostic guideline for evaluation of subtle alterations in heme biosynthesis.

Age Factors↗
PubMed1999

Multidrug resistance phenotype in the RMS-GR human rhabdomyosarcoma cell line obtained after polychemotherapy.

Classical cytotoxic treatment of rhabdomyosarcoma (RMS), the most common soft tissue malignacy in children, is often accompanied by significant morbidity and poor response. Chemotherapy may induce multidrug resistance (MDR) associated with the expression of P-glycoprotein, a drug efflux pump which modifies the sensitivity of tumoral cells to drugs. To analyze MDR in RMS we used the RMS-GR cell line, obtained from an embryonal rhabdomyosarcoma treated in vivo with polychemotherapy. The RMS-GR cells showed cross-resistance to vincristine, doxorubicin and actinomycin D, the drugs of choice in the conventional treatment of RMS. Polymerase chain reaction (PCR) analysis showed that these RMS cells overexpressed mdr1/P-glycoprotein. The pattern of resistance and the level of P-glycoprotein expression were similar to those found in the resistant RMS TE.32.7.DAC cell line obtained in vitro. Southern blot analysis showed that mdr1 overexpression was not due to amplification of the gene. Our results showed that the in vivo treatment of embryonal RMS may induce an MDR phenotype mediated by mdr1/P-glycoprotein in RMS cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Modulation of alpha-actin and alpha-actinin proteins in cardiomyocytes by retinoic acid during development.

Early heart development is known to be sensitive to retinoid concentrations. Although the influence of retinoids on cardiac morphogenesis has been described previously, the effect of retinoids on cardiomyocyte differentiation during development has not been characterized. We quantified the effects of the retinoic acids all-trans RA and 13-cis RA on alpha-actin and alpha-actinin at the subcellular level in cultures of chick embryo cardiomyocytes obtained from Hamburger and Hamilton's (HH) stage 22, 32 and 40 embryos. The retinoids increased the concentration of alpha-actin and alpha-actinin in the cytoplasmic and cytoskeletal fractions of cells at all three stages of development. The effect was greatest in cardiomyocytes treated for 24 h with all-trans RA and in cells from HH22 embryos. The greatest increases in alpha-actin concentration occurred in the cytoskeletal fraction of HH22 cells cultured for 24 h with all-trans or 13-cis RA, whereas the greatest increases in alpha-actinin were found in the cytoplasmic fraction of HH22 cells exposed to retinoids for 24 h. We conclude that retinoic acid plays a role in the reorganization of the pattern of sarcomeric protein expression during cardiomyocyte differentiation.

Actinin↗
PubMed1999

Pattern of expression of the jun family of transcription factors during the early development of the inner ear: implications in apoptosis.

Jun transcription factors have been implicated in the regulation of cell proliferation, differentiation and apoptosis. We have investigated the relationship between Jun expression and cell death in the developing chicken inner ear. c-jun and junD transcripts were expressed in the epithelium of the otic placode and otic vesicle. c-jun expression was restricted to the dorsal area of the otic pit (stages 14-17), dorsal otic vesicle and cochleo-vestibular ganglion (stages 18-20). junD expression was transient and occurred in the dorsal and upper medial aspects of the otic pit and otic cup, but it was down-regulated in the otic vesicle. A parallel TUNEL analysis revealed that expression of c-jun co-located within areas of intense apoptosis. Furthermore, phosphorylation of c-Jun at serine-63 by Jun amino-terminal-kinases was detected in the dorsal otic pit, otic vesicle and cochleo-vestibular ganglion. c-Jun protein exhibited DNA binding activity, as assessed by gel mobility shift assays. The association between c-Jun and apoptosis was further demonstrated by studying nerve growth factor-induced apoptosis in cultured otic vesicles. Nerve growth factor-induced cell death and c-Jun phosphorylation that were suppressed by insulin-like growth factor-I and by viral-mediated overexpression of Raf, which had survival effects. In conclusion, the precise regulation of the expression and activity of Jun proteins in the otic primordium suggests that it may operate as a fundamental mechanism during organogenesis.

Animals↗
PubMed1999

The placement of lumbar pedicle screws using computerised stereotactic guidance.

Computer-assisted frameless stereotactic image guidance allows precise preoperative planning and intraoperative localisation of the image. It has been developed and tested in the laboratory. We evaluated the efficacy, clinical results and complications of placement of a pedicle screw in the lumbar spine using this technique. A total of 62 patients (28 men, 34 women) had lumbar decompression and spinal fusion with segmental pedicle screws. Postoperative CT scans were taken of 35 patients to investigate the placement of 330 screws. None showed penetration of the medial or inferior wall of a pedicle. Registration was carried out 66 times. The number of fiducial points used on each registration averaged 5.8 (4 to 7) The mean registration error was 0.75 mm (0.32 to 1.72). This technique provides a safe and reliable guide for placement of transpedicular screws in the lumbar spine.

Adult↗
PubMed1999

Mechanisms involved in relaxation induced by exogenous nitric oxide in pig coronary arteries.

The aim of the present study was to analyze the mechanisms involved in the vasodilator responses elicited by nitric oxide (NO) in segments of porcine posterior descending coronary artery. Exogenous NO (0.1-30 microM) induced concentration-dependent relaxations in segments precontracted with a concentration of the thromboxane A2 mimetic, U-46619 (30-300 nM) that produced a contraction 70% (submaximal contraction) of that elicited by 75 mM K+ (maximal contraction). The relaxations were almost abolished by 6-anilinoquinoline-5,8-quinone (LY-83583, 10 microM), an inhibitor of guanylate cyclase, and with precontraction with 40 or 60 mM K+. Relaxations were reduced by 5 mM tetraethylammonium (TEA), a blocker of Ca(2+)-activated K+ channels (Kca channels) and unaltered by ouabain (500 microM), 4-aminopyridine (1 mM), glibenclamide (10 microM), apamin (1 microM) and charybdotoxin (0.3 microM), inhibitors of sodium pump, voltage-sensitive, ATP-sensitive, small-conductance Kca and large-conductance KcaK+ channels, respectively. These results suggest that the relaxation caused by exogenous NO is mediated by guanylate cyclase activation, with only a slight participation of a hyperpolarizing mechanism mediated by activation of Kca channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

The localizing value of ictal SPECT in children with tuberous sclerosis complex and refractory partial epilepsy.

Although multiple cortical tubers are a hallmark of tuberous sclerosis complex (TSC), seizures often originate from a single tuber, making excisional surgery a therapeutic option for intractable patients. To assess the role of ictal single photon emission computed tomography (SPECT) in defining the epileptogenic tuber, we reviewed videoelectroencephalography (V/EEG) data, magnetic resonance imaging (MRI) and SPECT scans of 15 patients (aged 3 months to 15 years, mean 5.1) with medically resistant partial seizures and TSC. SPECT scans were performed using Tc-99m-hexamethylpropyleneamine oxime (HMPAO) injected within 30 seconds of electrographic seizure onset and were graded on a scale from 1 to 5 (1 weakly perfused, 5 strongly perfused). The scalp EEG revealed localized seizure origin in ten patients; five had concordant hyperperfused SPECT regions consisting of comma-shaped areas surrounding hypoperfused areas in the candidate tuber. Strongly hyperperfused regions (grade 3-5) were noted in two patients whose ictal EEG patterns were characterized by sustained, rhythmic fast activity or spiking. The other five patients had nonlocalizing or poorly sustained ictal EEG patterns; one patient in this group had focal hyperperfusion. Invasive EEG recordings in two patients revealed propagated EEG patterns that correlated with the ictal SPECT findings. These findings indicate a strong correlation between ictal SPECT and ictal scalp EEG, especially when there are sustained rhythmic fast ictal EEG patterns.

Adolescent↗
PubMed1998

[Usefulness of anti-neutrophil cytoplasmic antibodies, anti-proteinase 3 and anti-myeloperoxidase in management of small vessel vasculitis].

BACKGROUND: Analysis of usefulness of antineutrophil cytoplasmic antibodies (AN-CA) as a marker of clinical activity in small vessel vasculitis. PATIENTS AND METHODS: 33 patients, 10 patients with Wegener's granulomatosis (WG) and 23 with microscopic polyangiitis (MPA) and rapidly progressive glomerulonephritis type III (RPGN III). The clinic and serologic follow-up was accomplished every 3 months during an average of 19 (SD, 24) months (range 3-52 months. The serologic follow-up included the determination of ANCA by indirect immunofluorescence (IFI) and ELISA, as well as the serum level of C reactive protein (RCP). RESULTS: At the time of diagnosis all patients were ANCA positive by IFI and ELISA. The seroconversion of ANCA from positive to negative was produced in 30/33 patients (90%). Twenty-six out of these 30 patients (87%) achieved the seroconversion within the first 6 months. During the follow-up 4 patients had a major relapse, all with positive ANCA. In 2 patients, one of each group, seroconversion from negative to positive was not associated with clinical relapse of vasculitis. CONCLUSION: ANCA should be used in conjunction with other indices of disease activity in patients with small vessel vasculitis.

Adult↗
PubMed1998

Cytotoxic isoflavans from Eysenhardtia polystachya.

Two new cytotoxic isoflavans, (3S)-7-hydroxy-2',3',4',5', 8-pentamethoxyisoflavan (1) and (3S)-3',7-dihydroxy-2',4',5', 8-tetramethoxyisoflavan (2), were isolated from the bark and trunks of Eysenhardtia polystachya (Leguminosae), together with the known constituents stigmasterol, isoduartin, cuneatin, 7-hydroxy-2',4', 5'-trimethoxyisoflavone, and 3,4-dimethoxy-8, 9-(methylenedioxy)pterocarpan. The structures of 1 and 2 were elucidated on the basis of spectroscopic methods. The antimicrobial, cytotoxic, and insecticidal potential of some of these compounds were evaluated. The isoflavans 1, 2, and isoduartin (2', 7-dihydroxy-3',4',8-trimethoxyisoflavan) displayed moderate cytotoxic activity against KB cell lines.

Animals↗
PubMed1998

Therapeutic differentiation in a human rhabdomyosarcoma cell line selected for resistance to actinomycin D.

Classical cytotoxic treatment of rhabdomyosarcoma (RMS) is accompanied often by significant morbidity and poor response. The use of cytotoxic agents may induce a multidrug resistance phenotype, which plays an important role in the sensitivity of tumoral cells to drugs. Using actinomycin D, a drug of choice in the treatment of RMS, we induced resistance in the TE.32.7 human RMS cell line. The TE.32.7-DAC-resistant cell line exhibited cross-resistance to vincristine and doxorubicin and showed mdr1/P-glycoprotein over-expression, suggesting that this mechanism was involved in the reduction in intracellular drug concentration and may be responsible for the failure of treatment of RMS with classical cycles of cytotoxics. Furthermore, this resistant cell line showed increased expression of the muscle differentiation markers desmin and alpha-actinin and ultrastructural changes which clearly indicated myogenic differentiation. Our findings suggest that, although this tumor is probably arrested along the normal myogenic pathway to maturation, induction of cell differentiation with anti-neoplastic drugs may be an alternative therapeutic approach. However, the failure of TE.32.7-DAC cells to completely re-enter the program of myogenic differentiation supports the hypothesis that multidrug resistance is a major obstacle in differentiation therapy for RMS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗