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Biomedical subjects

R Vega

Publications and source records attributed to R Vega.

At least 19 recordsLinked to original sources
PubMed2006

Survival and dependence on home parenteral nutrition: experience over a 25-year period in a UK referral centre.

BACKGROUND: Home parenteral nutrition (HPN) is the standard treatment for severe intestinal failure in the United Kingdom. AIM: To review long-term survival and ongoing HPN dependence of patients receiving HPN treated at a specialist UK referral centre. METHODS: Medical records of patients commenced on HPN between 1979 and 2003 were reviewed retrospectively. Regression analysis was employed to identify factors associated with poor prognosis. RESULTS: Case notes of 188 patients were reviewed. Overall probability of survival was 86%, 77%, 73% and 71% at 1, 3, 5 and 10 years after starting treatment. In multivariate analysis, association was seen between mechanism of intestinal failure and survival: short bowel syndrome associated with a favourable prognosis, and intestinal dysfunction, dysmotility and obstruction with poorer prognoses. There was an association between increasing age and poor prognosis, but increased mortality was also seen in the youngest age groups. Only 9% of deaths were due to complications of HPN. Continued HPN dependence was 89%, 87%, 84% and 84% at 1, 3, 5 and 10 years in survivors. CONCLUSIONS: Long-term survival of patients receiving HPN remains better than that reported after intestinal transplantation. Mortality predominantly relates to underlying disease rather than complications of HPN.

Adolescent↗
PubMed2005

In vitro quantitative determination of ophthalmic irritancy by the chorioallantoic membrane test with trypan blue staining as alternative to eye irritation test.

The damage provoked by some substances on the chicken egg's chorioallantoic membrane (CAM) is used as an alternative assay to determine ocular irritation. There is good prediction of the eye irritation when compared to the in vivo Draize method. Nevertheless, this assay has some limitations, such as subjectivity. Hagino et al. developed an objective evaluation technique using the amount of trypan blue absorbed at the site of treatment as an indicator of injury to the CAM. The present work was aimed at the determination of ocular irritation of 21 substances (chemicals and cosmetics). We used the spectrophotometric quantification by trypan blue staining of the damage produced on CAM, of fertile chicken eggs. Results were compared with the values obtained by the traditional Draize assay. We observed a good correlation (r=0.835; p<0.0001) between the amount of dye absorbed by the CAM and the Draize eye irritation test score. The r values were 0.688; p<0.05 for cosmetics and 0.925; p<0.0001 for chemicals. Three chemicals turned as false positive and one cosmetic substance as false negative. The CAM-TBS assay is inexpensive, simple and provides an in vitro alternative method to predict the damage that chemical substances or cosmetics can cause to the ocular structures.

Animals↗
PubMed2005

Comparative study of red blood cell method in rat and calves blood as alternatives of Draize eye irritation test.

INTRODUCTION: Red blood cell assay (RBC) is used to estimate potential irritation of tensioactive agents and detergents. Cell membrane lysis and cell protein denaturation are measured photometrically. This study was aimed to determine if rat blood cells can be used to predict eye potential irritation in the same way of calves blood cells in RBC assay. METHODS: We evaluated 20 cosmetic formulations using rat and calves blood according to INVITOX protocol No 37. Data of media hemolysis concentration, denaturation index and the ratio of both parameters were compared with in vivo data of eye irritancy. RESULTS: There was a significant difference (p<0.01) between H50 value when evaluated the standard SDS with red blood cell method in rat and calves blood. According to the exact probability of Fisher taking as approach the acceptance or rejection of the substance there are no significant differences between in vitro assay with calves blood and in vivo results. Not happening the same way for the RBC assay with rat blood where significant differences were obtained (p<0.01) among the classification of in vitro and in vivo test. DISCUSSION: The RBC assay using calves blood showed better results. Several test substances were false negatives with rat blood. This high false negative rate would be correctly identified by the animal test but it may also lead to increased animal consumption. For that RBC assay with calf blood cells is preferable to the employment of rat blood as screening method with a reduction and refinement strategy.

Animal Testing Alternatives↗
PubMed2004

Efficacy of oral rofecoxib versus intravenous ketoprofen as an adjuvant to PCA morphine after urologic surgery.

BACKGROUND: Adjunctive use of nonsteroidal anti-inflammatory drugs has become increasingly popular in the perioperative period because of their opioid-sparing effects. This randomized, controlled, double-dummy study was designed to evaluate the cost-effectiveness of using oral rofecoxib as an alternative to intravenous ketoprofen for pain management in patients undergoing urologic surgery. METHODS: Seventy patients were randomly assigned to receive either a placebo (Control) or rofecoxib 50 mg po (Rofecoxib) 1 h prior to surgery. After a standardized spinal anesthetic, patients in the Control group received ketoprofen 100 mg IV q 8 h for 24 h, while the Rofecoxib group received an equivolume of saline at 8-h intervals for 24 h. Both groups were allowed to self-administer morphine (1 mg IV boluses) using a PCA delivery system. The need for 'rescue' analgesic medication, as well as pain scores [using an 11-point verbal rating scale (VRS) (0 = none to 10-severe)], were recorded at 1, 2, 6, 12, and 24-h intervals after surgery. In addition, the incidences of side-effects were recorded at the end of the study period. RESULTS: Total amount of morphine required in the initial 24-h postoperative period was nonsignificantly reduced in the Rofecoxib group (29 +/- 2 vs. 37 +/- 4 mg). More importantly, the percentage of patients reporting moderate-to-severe pain (VRS score > or =4) during the study period was lower in the Rofecoxib group (12 vs. 22%, P < 0.05). The daily cost of rofecoxib (USD 1.14 for 50-mg dose) was also significantly less than ketoprofen (USD 3.06 for three 100-mg doses). CONCLUSION: Premedication with oral rofecoxib (50 mg) is a cost-effective alternative to the parenteral nonselective NSAID, ketoprofen (100 mg q 8 h), when used as an adjuvant to PCA morphine for pain management after urologic surgery.

Administration, Oral↗
PubMed2004

A mathematical model of the response of semicircular canal and otolith to head rotation under gravity.

The mathematical model of the system composed of two sensors: semicircular canal and sacculus, is presented. The system is described by three series of blocks: biomechanical block, mechanoelectrical transduction mechanism and hair cell ionic currents and membrane potential dynamics. The response of the aforecited system to various stimuli (head rotation under gravity and falling) was investigated. The identification of the model parameters was fulfilled for the experimental data, obtained for the axolotle (Ambystoma tigrinum) in Institute of Physiology, Autonomous University of Puebla, Mexico. The comparative analysis of canal and sacculus membrane potential was realized.

Acceleration↗
PubMed2003

Opioid receptors mediate a postsynaptic facilitation and a presynaptic inhibition at the afferent synapse of axolotl vestibular hair cells.

This study was designed to determine the effects of opiate drugs on the electrical activity of afferent neurons and on the ionic currents of hair cells from semicircular canals. Experiments were done on larval axolotls (Ambystoma tigrinum). The multiunit spike activity of afferent neurons was recorded in the isolated inner ear under both resting conditions and mechanical stimulation. Ionic currents were recorded using voltage clamp of hair cells isolated from the semicircular canal. In the isolated inner-ear preparation, microperfusion of either non-specific opioid receptor antagonist naloxone (10 nM to 1 mM), mu receptor agonist [D-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin (1 pM to 10 microM), or kappa receptor antagonist nor-binaltorphimine (10 nM to 100 microM) elicited a dose-dependent long-lasting (>5 min) increase of the electrical discharge of afferent neurons. The mu receptor agonist funaltrexamine (1 nM to 100 microM) and the kappa receptor agonist U-50488 (1 nM to 10 microM) diminished the basal spike discharge of vestibular afferents. The delta receptor agonist D-Pen(2)-D-Pen(5)-enkephalin (1 nM to 10 mM) and the antagonist naltrindole (1 nM to 10 mM) were without a significant effect. The only drug that displayed a significant action on hair-cell ionic currents was trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl) benzeneacetamide methanesulfonate (U-50488) that reduced the Ca(2+) current in a dose-dependent fashion. On its own, mu receptor agonist [D-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin (0.01 and 10 microM) significantly potentiated the response of afferent neurons to the excitatory amino acid agonist (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (0.1 microM), while synaptic transmission was blocked by the use of high-Mg(2+), low-Ca(2+) solutions. Our data indicate that the activity of vestibular afferent neurons may be regulated in a complex fashion by opioid receptors: mu opioid receptors mediating an excitatory, postsynaptic modulatory input to afferent neurons, and kappa receptors mediating an inhibitory, presynaptic input to hair cells.

Afferent Pathways↗
PubMed2001

Immunohistochemical localization and electrophysiological action of nociceptin/orphanin-FQ in the snail (Helix aspersa) neurons.

We report the existence and anatomical distribution to nociceptin/orphanin-FQ (N/O FQ)-like immunoreactivity in neurons and fibers in the perioesophageal ganglia of the snail (Helix aspersa). Intracellular recordings from perioesophageal ganglion neurons showed that the application of 10 microM N/O FQ produced an excitatory action in 22% of the neurons studied and an inhibitory action in 33% of the neurons regardless of their origin (cerebral or parietal ganglion). Our result provides evidence that N/O FQ-like peptide is located in whole perioesophageal ganglia (mainly in the cerebral one), and that it may serve as a neuromodulator of the neuronal spike discharge. These data support the idea that the N/O FQ opioid system has an early phylogenetic origin and a functional continuity during the course of evolution.

Action Potentials↗
PubMed2001

Nitric oxide in the afferent synaptic transmission of the axolotl vestibular system.

This study was performed using intracellular and multiunit extracellular recording techniques in order to characterize the role of nitric oxide in the afferent synaptic transmission of the vestibular system of the axolotl (Ambystoma tigrinum). Bath application of nitric oxide synthase inhibitors N(G)-nitro-L-arginine (0.01microM to 10microM) and N-nitro-L-arginine methyl ester hydrochloride (0.1microM to 1000microM) elicited a dose-dependent decrease in the basal discharge of the semicircular canal afferent fibers. N(G)-Nitro-L-arginine also diminished the response to mechanical stimuli. Moreover, N(G)-nitro-L-arginine (1microM) produced a hyperpolarization associated with a decrease in the spike discharge and diminished the frequency of the excitatory postsynaptic potentials on afferent fibers recorded intracellularly. Nitric oxide donors were also tested: (i) S-nitroso-N-acetyl-DL-penicillamine (0.1microM to 100microM) increased the basal discharge and the response to mechanical stimuli. At the maximum effective concentration (100microM) this drug affected neither the amplitude nor the frequency of the excitatory postsynaptic potentials. However, it slightly depolarized the afferent neurons and decreased their input resistance. (ii) 3-Morpholino-sydnonimine hydrochloride did not significantly affect the basal discharge or the mechanically evoked peak response of afferent neurons at any of the concentrations used (1microM to 1000microM). However, after 10min of perfusion in the bath, 1microM and 10microM 3-morpholino-sydnonimine hydrochloride significantly modified the baseline of the mechanically evoked response, producing an increase in the mean spike discharge of the afferent fibers. These results indicate that nitric oxide may have a facilitatory role on the basal discharge and on the response to mechanical stimuli of the vestibular afferent fibers. Thus, nitric oxide probably participates in the sensory coding and adaptative changes of vestibular input in normal and pathological conditions.

Action Potentials↗
PubMed2001

Betahistine produces post-synaptic inhibition of the excitability of the primary afferent neurons in the vestibular endorgans.

Betahistine has been used to treat several vestibular disorders of both central and peripheral origin. The objective of this work was to study the action of betahistine in the vestibular endorgans. Experiments were done in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 microM to 10 mM; n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC50 of 600 microM. To define the site of action of betahistine, its interactions with the nitric oxide synthase inhibitor NG-nitro-L-arginine (3 microM) and with the cholinergic antagonists atropine (10 microM; n = 3) and d-tubocurarine (10 microM; n = 3) were studied. The action of betahistine when co-administered with these drugs was the same as that in control experiments, indicating that its effects did not include nitric oxide production or the activation of cholinergic receptors. In contrast, 0.01-1 mM betahistine reduced the excitatory action of kainic acid (10 microM; n = 6) and quiscualic acid (1 microM; n = 13). These results indicate that the action of betahistine on the spike discharge of afferent neurons seems to be due to a post-synaptic inhibitory action on the primary afferent neuron response to the hair cell neurotransmitter.

Ambystoma↗
PubMed2001

Action mechanism of betahistine in the vestibular end organs.

Betahistine has been used to treat several vestibular disorders of both central and peripheral origin. The objective of this work was to study the betahistine action mechanism at the vestibular end organs. Experiments were carried out in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 microM to 10 mM, n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC50 of 600 microM. To define the site of action of betahistine, its interactions with antagonists of nitric oxide sintethizing enzyme, cholinergic drugs, and excitatory amino acids were studied. Betahistine 1 mM (n = 5) was coadministered with NG-nitro-L-arginine 3 microM. The action of betahistine remained as in control experiments. Betahistine 1 mM reduced the excitatory action of carbachol (200 microM, n = 5) in a 30 +/- 3.4%. Cholinergic antagonists atropine (10 microM, n = 3) and d-tubocurarine (10 microM, n = 3) did not modify betahistine actions. Betahistine 1 mM also reduced kainic acid (10 microM, n = 4) excitatory action in 45.5 +/- 9.8%. These results corroborate that betahistine has a peripheral inhibitory action in the spike discharge of the afferent neurons in the vestibule. This action seems to involve neither NO production nor modifications in the release of acetylcholine from the efferent fibers. The inhibitory action of betahistine seems to be due to a postsynaptic binding site on the afferent neurons.

Ambystoma↗
PubMed2000

BgK anemone toxin inhibits outward K(+) currents in snail neurons.

We studied the effects of BgK toxin on outward K(+) currents in isolated neurons of the snail Helix aspersa, using the whole cell patch clamp technique. BgK partially and reversibly blocked K(+) currents in the 1 pM to 100 nM concentration range (n=53). The dose-response curve for BgK current inhibition had a maximum blocking effect at 100 nM. Our results indicate that BgK is a potent, apparently non-selective, K(+) channel blocker in molluscan neurons.

Animals↗
PubMed2000

Calcium channels functional roles in the frog semicircular canal.

Different types of voltage-operated calcium channels have been described in hair cells; however, no clear functional role has been assigned to them. As a first functional characterization of vestibular calcium channels, we studied the effect of several calcium channel agonists and antagonists on whole nerve firing rate in an isolated frog semicircular canal preparation. Resting activity was affected by all dihydropyridines tested and by omegaconotoxin GVIA, whereas only nimodipine was able to reduce the mechanically evoked activity. These results indicate that nimodipine-sensitive channels play a major role in afferent transmitter release, and omega-conotoxin GVIA sensitive channels regulate the afferent firing (possibly on the postsynaptic side) but with a less important role.

Animals↗
PubMed2000

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics.

A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.

Age of Onset↗
PubMed2000

Microcomputer program for automated action potential waveform analysis.

A program for action potential waveform analysis based on a PC compatible computer is described. Single or averaged action potentials are analyzed by obtaining its first derivative and using criteria which allow automatic measurement of several action potential components, including: depolarization rate, repolarization rate, amplitude, duration, resting membrane potential and afterhyperpolarization amplitude and slope. Data can be imported from pClamp (Axon Instruments) and exported to other software such as Excel, Sigmaplot and MatLab for example.

Action Potentials↗
PubMed2000

Molecular modeling of the complexes between Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase and the ATP analogs pyridoxal 5'-diphosphoadenosine and pyridoxal 5'-triphosphoadenosine. Specific labeling of lysine 290.

Molecular mechanics calculations have been employed to obtain models of the complexes between Saccharomyces cerevisiae phosphoenolpyruvate (PEP) kinase and the ATP analogs pyridoxal 5'-diphosphoadenosine (PLP-AMP) and pyridoxal 5'-triphosphoadenosine (PLP-ADP), using the crystalline coordinates of the ATP-pyruvate-Mn(2+)-Mg(2+) complex of Escherichia coli PEP carboxykinase [Tari et al. (1997), Nature Struct. Biol. 4, 990-994]. In these models, the preferred conformation of the pyridoxyl moiety of PLP-ADP and PLP-AMP was established through rotational barrier and simulated annealing procedures. Distances from the carbonyl-C of each analog to epsilon-N of active-site lysyl residues were calculated for the most stable enzyme-analog complex conformation, and it was found that the closest epsilon-N is that from Lys(290), thus predicting Schiff base formation between the corresponding carbonyl and amino groups. This prediction was experimentally verified through chemical modification of S. cerevisiae PEP carboxykinase with PLP-ADP and PLP-AMP. The results here described demonstrate the use of molecular modeling procedures when planning chemical modification of enzyme-active sites.

Adenosine Diphosphate↗
PubMed2000

Identity in adolescent survivors of childhood cancer.

OBJECTIVE: To investigate identify formation among adolescent survivors of childhood cancer. Family functioning, perceived emotional support from family and peers, life stress, and anxiety produced by the cancer experience also were examined as they influenced identity development. METHOD: Participants were 52 adolescent survivors and their mothers recruited from a medical center and 42 healthy adolescent counterparts and their mothers recruited from the community. RESULTS: A greater frequency of survivors than their healthy peers was found within the foreclosed identity status. Factors associated with the foreclosed identity status included the cancer diagnosis, symptoms of posttraumatic stress disorder (PTSD), and family functioning characterized by greater levels of conflict. CONCLUSIONS: Data were interpreted to suggest that the foreclosed identity status may serve a protective function in assisting survivors to cope with the stressors of the cancer experience.

Adolescent↗
PubMed1999

Cytomegalovirus infection in patients with inflammatory bowel disease.

OBJECTIVE: It has been suggested that, in inflammatory bowel disease, cytomegalovirus behaves in the intestine as a nonpathogenic bystander, and even its finding in intestinal mucosa has unclear clinical relevance. We report our experience with a small series of patients with refractory inflammatory bowel disease and cytomegalovirus infection and their clinical outcome. METHODS AND RESULTS: Nine patients with moderate-severe attacks of inflammatory bowel disease did not respond to i.v. prednisone (1 mg/kg/day) for a mean of 24 days. Four of these patients were further treated with i.v. cyclosporine A (4 mg/kg/day). Cytomegalovirus infection was diagnosed in two patients after resection for treatment failure. In the remaining patients, cytomegalovirus infection was diagnosed in endoscopic mucosal biopsies and i.v. ganciclovir was then administered at a dose of 10 mg/kg/day for 2-3 wk. Five of these patients went into clinical remission, allowing corticosteroid and cyclosporine A discontinuation. Follow-up biopsies were performed and in all cases cytomegalovirus could not be detected in the colonic tissue. Two patients needed to be treated with intravenous cyclosporine A after antiviral therapy because of persistence of clinical symptoms despite the elimination of cytomegalovirus infection. CONCLUSIONS: Cytomegalovirus infection may play a role in the natural history of refractory inflammatory bowel disease and in some of its complications. The clearance of cytomegalovirus in colonic mucosa may lead some of these patients to remission.

Adult↗