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Biomedical subjects

R Pérez

Publications and source records attributed to R Pérez.

At least 19 recordsLinked to original sources
PubMed2002

Disturbances of colonic ion secretion in inflammation: role of the enteric nervous system and cAMP.

We used the trinitrobenzenesulphonic acid (TNBS) rat model of experimental colitis to study the alterations in electrogenic ion transport in the inflamed distal colon. The distal colon exhibited decreased basal transport and reduced short-circuit current responses to carbachol and isobutylmethylxanthine (IBMX). The concentration/response curve for IBMX was also shifted to the right. Ion substitution experiments indicated that electrogenic transport was attributable chiefly to Cl(-) secretion. The mucosal layer of the inflamed distal colon (devoid of the submucosa) exhibited normal maximal responses to carbachol and IBMX, although the concentration/response curve for the latter was again shifted to the right. Tetrodotoxin markedly increased the response of the normal distal colon to both secretagogues and nullified the inhibition of the response to carbachol, but not that to IBMX, in the inflamed colon. The response of the mucosal preparation to 8-bromoadenosine 3',5'-cyclic monophosphate was similar in the normal and inflamed intestine, while the G protein activator NaF had a greater effect in the latter. The expression of the cystic fibrosis transmembrane conductance regulator (CFTR), as assessed by Northern blotting, was unchanged. cAMP levels in isolated colonocytes were markedly reduced by inflammation. We conclude that colonic inflammation produces disturbances of the enteric nervous system resulting in defective mucosal cAMP production and inhibition of ionic secretion.

1-Methyl-3-isobutylxanthine↗
PubMed2002

Subclinical pain and thermal sensory dysfunction in children and adolescents with Type 1 diabetes mellitus.

AIMS: To assess cutaneous thermal and pain thresholds in upper and lower limbs in neurologically asymptomatic children and adolescents, and to study the relationships of clinical parameters and these sensory thresholds in subclinical diabetic neuropathy. METHODS: Thirty-five neurologically asymptomatic patients, aged 8-16 years, diagnosed with Type 1 diabetes mellitus (DM), and a control group of 35 healthy age-matched subjects participated in the study. Warmth, cold, and heat-induced pain thresholds were measured in the dorsum of the right arm and foot, using quantitative sensory testing (QST). Relevant clinical parameters, retrieved from medical records or measured at the QST session, were obtained for each patient. RESULTS: Compared with controls, diabetic patients had increased thresholds for warmth in the hand (P = 0.002), and cold and warmth in the foot (P = 0.015 and P = 0.004, respectively). Of the diabetic patients, 43% showed abnormality of at least one sensory threshold. A significant correlation was observed for duration of diabetes and heat-induced pain threshold in the hand (P = 0.045), but no correlation was found for age, height, weight, pre-test blood glucose, age of onset, current insulin dose, and mean of glycosylated haemoglobin determinations of the previous 18 months. No significant correlation was found for other sensory thresholds. CONCLUSIONS: Using QST, abnormal cutaneous thermal perception is a common finding, in both upper and lower limbs, in neurologically asymptomatic young diabetic patients. Heat-induced pain threshold in the hand was correlated with the duration of the diabetes.

Adolescent↗
PubMed2002

Pharmacokinetics of doramectin and ivermectin after oral administration in horses.

A study was undertaken in order to compare plasma disposition kinetic parameters of doramectin (DRM) and ivermectin (IVM) in horses after oral administration. Ten crossbreed adult horses, clinically healthy, weighing 380-470 kg body weight (bw) were selected for study. Faecal examinations were performed to determine faecal parasite egg counts. Horses were allocated to two groups of five animals to provide an even distribution considering the variables sex, body weight and faecal egg count. Group I, were treated with an oral paste formulation of IVM at 0.2 mg/kg b/w and Group II, were treated with an oral dose of 0.2 mg/kg bw of DRM prepared as paste from the injectable formulation for oral administration. Blood samples were collected by jugular puncture between 0 h and 75 days post-treatment. Plasma was separated and later solid phase extraction and derivatization samples were analysed by high performance liquid chromatography (HPLC); a computerised kinetic analysis was carried out. Data were compared using the Mann-Whitney U-test. The mean plasma concentrations of DRM and IVM after oral administration in horses were detected until 30 and 20 days, respectively. Both drugs showed similar patterns of absorption and no significant differences were found for peak concentration, the time to peak concentration, or for absorptive half-life. The terminal elimination half-life was significantly (P<0.05) longer in the DRM treated group than for the IVM treated group. The differences observed in the elimination half-life explain the longer mean residence time and high values of area under the concentration time curve for the group treated with DRM, which are 30% higher than those of the IVM group. Considering its pharmacokinetics, tolerance and anthelmintic efficacy, the oral administration of DRM, could be an alternative to IVM for the control of parasitic diseases of horses.

Administration, Oral↗
PubMed2002

Placental transfer of albendazole sulphoxide enantiomers in sheep.

Albendazole sulphoxide (ABZSO) is an anthelmintic drug used in veterinary practice. Its molecule has a chiral centre in the sulphur atom and racemic formulations are always used. The kinetics of the ABZSO enantiomers in the last third of pregnancy in ewes, and the placental transfer to the fetus, were studied after a single-dose oral administration (7.5 mg/kg) of a racemic formulation. In mothers, the area under the plasma concentration-time curve (AUC) and C(max) values of (+)-ABZSO (42.4+/-10.5 microg/mL and 1.9+/-0.4 microg/mL, respectively) were higher than those of (-)-ABZSO (15.3+/-5.1 microg/mL and 1.0+/-0.3 microg/mL). The MRT values were 17.0+/-1.6 h for (+)-ABZSO and 13.1+/-1.8 h for (-)-ABZSO. Similar kinetic parameters were obtained in the fetus for both enantiomers, but the fetal concentrations were lower compared with values for the dam. The AUC ratio between (-)-ABZSO/(+)-ABZSO in the dam was 0.36 and in the fetuses 0.64, indicating a higher impairment for the (+)-enantiomer in its placental transfer to the fetus.

Administration, Oral↗
PubMed2002

Antiribosomal P protein antibodies in Chilean SLE patients: no association with renal disease.

The objective of this work was to determine the frequency and clinical associations of anti-ribosomal P protein antibodies (Anti-P) in a cohort of Chilean patients with systemic lupus erythematosus (SLE). Between 1996 and 1998, 141 consecutive patients with SLE were examined prospectively according with a standard protocol. Disease activity was measured by MEX-SLEDAI in 138 patients. Anti-P positivity was determined by double immune diffusion or Western blot and ELISA. Anti-P was found in 21 (15%) patients. In the Anti-P positive patients recent onset SLE (disease duration of 1 year or less) was more frequent (P = 0.018). Anti-P was found in 23% of 83 patients with active SLE vs 4% of the 55 patients with inactive SLE (Yates corrected P = 0.00479). An association with anti-dsDNA antibodies by Farr assay was observed. Anti-P positive patients had a median Farr of 65 IU/ml (1.4-1240) and Anti-P negative of 12 IU/ml (1.4-992; P-value = 0.0084). During the study only two patients had lupus psychosis and they were Anti-P positive. No association was found with liver disease (six patients, two with Anti-P antibodies) or active glomerulonephritis (22 patients four with Anti-P). Our data shows that the presence of Anti-P antibodies supports the clinical diagnosis of lupus psychosis.

Adolescent↗
PubMed2002

[Effect of sildenafil citrate on the cortical visual responses].

OBJECTIVE: To study the possible effect of oral sildenafil citrate on the response of cortical visual cells to visual stimulation. METHOD: Multiunit activity was recorded from cortical area V2 of one behaving monkey. Spatio-temporal receptive field maps were obtained by using a reverse cross correlation technique and white noise visual stimulation before and after oral administration of sildenafil citrate. RESULTS: The receptive field maps showed a reduction in response latency after administration of sildenafil citrate. CONCLUSIONS: Since sildenafil citrate is an inhibitor of retinal phosphodiesterase-6, an enhancement on light sensitivity in the photoreceptors is proposed as the cause of the observed reduction in response latency (Arch Soc Esp Oftalmol 2002; 77: 241-246).

Animals↗
PubMed2001

Surface soft phonon and the sqrt[3] x sqrt[3] <--> 3x3 phase transition in Sn/Ge(111) and Sn/Si(111).

Density functional theory calculations show that the reversible Sn/Ge(111) sqrt[3]xsqrt[3]<-->3x3 phase transition can be described in terms of a surface soft phonon. The isovalent Sn/Si(111) case does not display this transition since the sqrt[3]xsqrt[3] phase is the stable structure at low temperature, although it presents a partial softening of the 3x3 surface phonon. The rather flat energy surfaces for the atomic motion associated with this phonon mode in both cases explain the experimental similarities found at room temperature between these systems. The driving force underlying the sqrt[3]xsqrt[3]<-->3x3 phase transition is shown to be associated with the electronic energy gain due to the Sn dangling bond rehybridization.

Journal Article↗
PubMed2001

Effects of salinity, temperature and food level on the demographic characteristics of the seawater rotifer Synchaeta littoralis Rousselet.

A strain of the seawater species Synchaeta littoralis, isolated from a Spanish Mediterranean coastal salt marsh, was cultured in the laboratory and fed with the alga Tetraselmis sp. The effect of three salinities (25 per thousand, 30 per thousand and 35 per thousand), two temperatures (20 degrees C and 25 degrees C) and two food levels (75,000 and 150,000 cells ml(-1)) on demographic parameters was studied using a life table approach. Average lifespan (LS) ranged between 4.0 and 7.3 days, net reproductive rate (R(0)) between 4.2 and 9.1 offspring per female, and intrinsic growth rate (r) between 0.50 and 0.95 day(-1). Salinity and temperature had a significant negative effect (***p<0.001) on both average lifespan (LS) and net reproductive rate (R(0)). Nevertheless, S. littoralis grew adequately at 35 per thousand (average value of r=0.67 day(-1)). Intrinsic growth rate also increased with temperature due to the lower value of the generation time (ranged between 2.3 and 3.8 days in all assays). Food level only had a significant negative effect (***p<0.001) on R(0). The experiments designed allowed us to know the basic demographic parameters of S. littoralis.

Journal Article↗
PubMed2001

Can atomic force microscopy achieve atomic resolution in contact mode?

Atomic force microscopy operating in the contact mode is studied using total-energy pseudopotential calculations. It is shown that, in the case of a diamond tip and a diamond surface, it is possible for a tip terminated by a single atom to sustain forces in excess of 30 nN. It is also shown that imaging at atomic resolution may be limited by blunting of the tip during lateral scanning.

Journal Article↗
PubMed2001

A study of the electrospray ionisation and ion-trap fragmentation of [M - H](-) ions of new 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazin-2-thiones.

The electrospray ionisation (ESI) in negative mode of the pharmacologically significant 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazin-2-thiones, and their subsequent fragmentations using an ion-trap mass spectrometer, have been investigated. Experiments on sequential product ion fragmentations (MS(n)) were performed in order to elucidate the degradation pathways for these compounds. The data presented show that the fragmentation of the even-electron [M - H](-) ions could proceed through an internal nucleophilic substitution displacement. Decarboxylation and extrusion of carbon disulfide are other fragmentations observed.

Decarboxylation↗
PubMed2001

Faecal excretion profile of moxidectin and ivermectin after oral administration in horses.

A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days post-treatment. After faecal drug extraction and derivatization, samples were analysed by High Performance Liquid Chromatography using fluorescence detection and computerized kinetic analysis. For both drugs the maximum concentration level was reached at 2.5 days post administration. The ivermectin treatment groups' faecal concentrations remained above the detectable level for 40 days (0.6 +/- 0.3 ng/g), whereas the moxidectin treatment group remained above the detectable level for 75 days (4.3 +/- 2.8 ng/g). Ivermectin presented a faster elimination rate than moxidectin, reaching 90% of the total drug excreted in faeces at four days post-treatment, whereas moxidectin reached similar levels at eight days post-treatment. No significant differences were observed for the values of maximum faecal concentration (C(max)) and time of C(max)(T(max)) between both groups of horses, demonstrating similar patterns of drug transference from plasma to the gastrointestinal tract. The values of the area under the faecal concentration time curve were slightly higher in the moxidectin treatment group (7104 +/- 2277 ng.day/g) but were not significantly different from those obtained in the ivermectin treatment group (5642 +/- 1122 ng.day/g). The results demonstrate that although a 100% higher dose level of moxidectin was used, attaining higher plasma concentration levels and more prolonged excretion and gut secretion than ivermectin, the concentration in faeces only represented 44.3+/- 18.0% of the total parental drug administered compared to 74.3 +/- 20.2% for ivermectin. This suggests a higher level of metabolization for moxidectin in the horse.

Administration, Oral↗
PubMed2001

Synthesis of a new 5'-O-triphosphate analog of 5-methyl 2'-O-deoxycytidine. Preliminary in vitro labelling for non-radioactive detection of DNA.

We report the synthesis of the triphosphate of 5-methyl 4-N-[6-(p-bromobenzamido)hex-1-yl]-2'-O-deoxycytidine 3A. We also analyzed the formation of intramolecular H-bonds of 5-methyl 4-N-[n-[6-(p-bromobenzamido) caproyl amino]alk-1-yl]-2'-deoxycytidine compounds, and confirmed their presence by 1H-NMR studies. In vitro DNA labeling with modified nucleotides is preliminarily evaluated.

DNA↗
PubMed2001

Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in advanced brain tumor patients: preliminary study.

High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.

Adult↗
PubMed2001

Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor.

Ior egf/r3, a neutralizing monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR) was generated at the Cuban Institute of Oncology. Immunoscintigraphic studies in 148 patients with this 99-m Technetium (99Tc) labeled mAb, showed a high sensitivity and specificity for in vivo detection of epithelial tumors. To study safety, pharmacokinetic and immunogenicity of ior egf/r3 at high doses, a phase I clinical trial was conducted. Nineteen patients with advanced epithelial tumors received 4 mAb intravenous infusions at 6 dose levels: from 50 to 500 mg. Previously, immunoscintigraphic images using the same mAb labeled with 99Tc were acquired. Blood samples were collected for pharmacokinetic analysis and HAMA response. After mAb therapy, objective response was classified according to WHO criteria. Ior egf/r3 was well tolerated in spite of the high-administered doses. Only a severe adverse reaction consisting of hypotension and lethargy was observed. In 13 patients, selective accumulation of 99Tc-labeled mAb was observed at the site of the primary tumor or the metastasis. Pharmacokinetic analysis revealed that elimination half-life and the area under the time-concentration curve increased linearly with dose. HAMA response was detected in 17 patients. After 6 months of mAb therapy, 4 patients had stable disease. One patient had a tumor partial remission after 3 cycles of ior egf/r3.

Adult↗
PubMed2001

Microvascularized fibular graft for mandibular reconstruction: detection of viability by bone scintigraphy and SPECT.

Bone allografts are often used in reconstructive mandibular surgery, generally after extensive oncologic resection, post-traumatic pseudoarthrosis, or osteomyelitis. Vascularized fibular bone grafts have advantages compared with other bone grafts in the restoration of the contour and function of defective mandibles. Bone scintigraphy is often used to assess bone revascularization, because positive uptake of Tc-99m hydroxy methylene diphosphonate (HDP) reflects patent anastomoses and viability of the grafted bone. Mandibular reconstruction with a free fibular flap was performed in 11 patients. Bone scintigraphy and SPECT were applied in the follow-up of eight patients. The grafts were assessed semi-quantitatively using a six-grade scoring system based on a comparison of tracer uptake in the graft and in the calvarium. Complications were observed in one graft. Planar scintigrams showed a tracer uptake greater than grade 5 in grafts with an uncomplicated course. SPECT was performed in addition to planar imaging in two patients who had greater graft uptake. A lack of tracer uptake was observed in the failed graft. Bone scintigraphy performed within the first week after the mandibular reconstruction is a useful tool to monitor the viability and early complications of microvascularized fibular grafts and plays an important role in the decision-making process during repeated surgical exploration. SPECT is more sensitive than planar imaging for assessing graft viability.

Adult↗