Biomedical subjects

I Medina

Publications and source records attributed to I Medina.

At least 19 recordsLinked to original sources

PubMed2005

Posthemipelvectomy hernia.

We report the case of a white male who underwent a classic hemipelvectomy due to a femur fibrosarcoma with inguinal metastases, which 33 years later, developed into a posthemipelvectomy hernia in the amputation stump that impaired the use of his Canadian prosthesis. The hernia was repaired with a polypropylene mesh in a subaponeurotic position. A seroma was drained in the postoperative and it was only 2 months after the operation that he could use his prosthesis with any difficulty. A year after the operation, the hernia had not recurred. Only seven similar cases have been published, and there are only four cases with details of their correction, two with a mesh as was our case, and the rest with a primary suture of the aponeurotic borders. A brief review of the bibliography is given on this subject.

Femoral Neoplasms↗

PubMed2004

Persistent subthreshold voltage-dependent cation single channels in suprachiasmatic nucleus neurons.

The hypothalamic suprachiasmatic nucleus (SCN) contains the primary circadian pacemaker in mammals, and transmits circadian signals by diurnal modulation of neuronal firing frequency. The ionic mechanisms underlying the circadian regulation of firing frequency are unknown, but may involve changes in membrane potential and voltage-gated ion channels. Here we describe novel tetrodotoxin- and nifedipine-resistant subthreshold, voltage-dependent cation (SVC) channels that are active at resting potential of SCN neurons and increase their open probability (P(o)) with membrane depolarization. The increased P(o) reflects changes in the kinetics of the slow component of the channel closed-time, but not the channel open-time or fast closed-time. This study provides a background for investigation of the possible role of SVC channels in regulation of circadian oscillations of membrane excitability in SCN neurons.

Animals↗

PubMed2003

Allergenicity of varieties of soybean.

BACKGROUND: Soybean hulls (SHs) cause respiratory allergies. This study investigates the allergenicity of soybean varieties (SVs) by in vivo and in vitro tests. METHODS: Ten SVs were studied: (a) five with a proved clinical relevance (SVs 1, 2, 3, 4, 5), the last four with a 'dull' phenotype; (b) five of undetermined relevance, three of them (SVs 6, 7, 8) with a 'shiny' phenotype, and two (SVs 9 and 10) with a 'dull' phenotype. Extracts from all 10 SVs were used to skin prick test (SPT) 21 subjects sensitized to SHs. Positive and negative sera pools prepared from sera of subjects sensitized or not to SHs, respectively, were utilized to perform in vitro experiments (specific IgE and IgG4 determinations, SDS-PAGE/IgE-Western blot, and IgE-inhibition). RESULTS: In this study, it was found that 52.4, 52.4, 57.1, 71.4, 80.9, 42.9, 57.1, 71.4, 52.4, and 38.1% subjects had a positive SPT with SVs 1-10, respectively (P NS). Specific IgE values to SVs 1-10 obtained with the positive pool are 28.3, 26.4, 29.9, 28.3, 26.8, 4.8, 13.4, 6.7, 24.7, and 17.5% total counts bound, respectively; and specific IgG4 values 0.851, 0.818, 0.721, 1.609, 0.789, 0.617, 0.662, 0.0, 1.127, and 0.934 OD units, respectively; the microgram of protein required to produce 50% inhibition are 2.5, 3.7, 4.5, 2.4, 5, 39.8, 25.2, 25.1, 4.5, and 8.9, respectively. A 7-kDa band is present in all SVs except in those with a 'shiny' phenotype. CONCLUSIONS: The SVs with a 'shiny' phenotype contain less allergens than the other SVs studied, as determined by in vitro tests. However, SPT results with the SVs do not differ. Genetic screens should be devised to select plants with reduced, preferably absent, allergenicity, but with a high nutritional value, and this allergenicity should be studied utilizing in vivo and in vitro tests.

Food Hypersensitivity↗

PubMed2003

Psoriasis, vasculitis and methotrexate.

Report on the association of the psoriasis and vasculitis are a very infrequent in the literature. Such an association as been described in extensive psoriasis and arthropathy psoriasis. In this paper we described two cases in which psoriasis, vasculitis and nephropathy are present together. In both cases the association might be produced by methotrexate. In both cases methotrexate is possible uleashing.

Adult↗

PubMed2001

Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection.

Entecavir (ETV) is a guanosine nucleoside analogue with potent antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus. To explore the consequences of prolonged virus suppression, woodchucks received ETV orally for 8 weeks and then weekly for 12 months. Of the 6 animals withdrawn from therapy and monitored for an additional 28 months, 3 had a sustained antiviral response and had no evidence of hepatocellular carcinoma (HCC). Of the 6 animals that continued on a weekly ETV regimen for an additional 22 months, 4 exhibited serum viral DNA levels near the lower limit of detection for >2 years and had no evidence of HCC. Viral antigens and covalently closed circular DNA levels in liver samples were significantly reduced in all animals. ETV was well tolerated, and there was no evidence of resistant variants. On the basis of historical data, long-term ETV treatment appeared to significantly prolong the life of treated animals and delay the emergence of HCC.

Animals↗

PubMed2001

Process formation results from the imbalance between motor-mediated forces.

Several reports have suggested that neurite outgrowth is mediated by opposing forces generated on microtubules and microfilaments but the molecular basis underlying these forces have not been determined. Here, we show that in non-neuronal cell lines, the inhibition of actomyosin activity by acidic calponin promotes the formation of processes. This effect is blocked by inhibition of the motor activity of cytoplasmic dynein. Therefore, neurite formation is due to an imbalance between tensile and compressive forces mediated by myosins and dyneins, respectively. We propose a mechanism that involves the motor-mediated forces in a tight regulation of the process formation.

Actin Cytoskeleton↗

PubMed2001

[Association between soybean dust exposure, allergic sensitivity and profile of respiratory symptoms].

The purpose of this study was to correlate soybean dust (SD) exposure, skin reactivity to soybean hull (SH) allergens, and symptoms of asthma and/or allergic rhinitis. A group of 365 subjects with asthma and/or allergic rhinitis and a control group of 50 individuals without respiratory symptoms were studied. The level of exposure to SD is defined as follows: 1) direct (DE); 2) indirect (ID), and 3) urban (UE). All subjects completed standard questionnaires. Skin tests with a SH extract and with common allergens were performed by the prick technique (SPT). Fifty-six (15.3%) patients and no subjects from control group had positive SPT (histamine index > or = 0.5) with a SH allergen extract. The percentages of positive SPT to SH extract were 38.7%, 20.3% and 8.4% in subjects with DE, IE and UE, respectively (p < 0.001). Monosensitization to SH was absent in all subjects. The percent of subjects with positive SPTs to mites (p < 0.01), pollen (p < 0.01) and molds (p < 0.05) were higher in subjects with a positive SPT to SH versus those with a negative SPT to SH. Sixty-six percent of subjects with DE and 13.6% of subjects with IE or UE reported respiratory symptoms after SD inhalation (Odds Ratio: 12.67 [2.4-74.9], p < 0.001). Compared to subjects exclusively sensitized to mites, patients sensitized to SH presented significantly different clinical characteristics. Soybean production has been increasing in Argentina during the last 20 years, determining an increase in the population exposed to chronic SD inhalation. This fact determines a high risk of sensitization and triggering of respiratory symptoms in atopic subjects. This study demonstrates that there is: 1) a high prevalence of skin reactivity to SH in subjects with asthma and/or allergic rhinitis from Argentina and that this prevalence is associated with the level of exposure to SD, and 2) an association between sensitivity to SH and severity of asthma. Measures to avoid release and inhalation of SD in rural areas from Argentina are needed.

Adolescent↗

PubMed2000

A switch mechanism for G beta gamma activation of I(KACh).

G protein-gated inwardly rectifying potassium (GIRK) channels are a family of K(+)-selective ion channels that slow the firing rate of neurons and cardiac myocytes. GIRK channels are directly bound and activated by the G protein G beta gamma subunit. As heterotetramers, they comprise the GIRK1 and the GIRK2, -3, or -4 subunits. Here we show that GIRK1 but not the GIRK4 subunit is phosphorylated when heterologously expressed. We found also that phosphatase PP2A dephosphorylation of a protein in the excised patch abrogates channel activation by G beta gamma. Experiments with the truncated molecule demonstrated that the GIRK1 C-terminal is critical for both channel phosphorylation and channel regulation by protein phosphorylation, but the critical phosphorylation sites were not located on the C terminus. These data provide evidence for a novel switch mechanism in which protein phosphorylation enables G beta gamma gating of the channel complex.

Amino Acid Sequence↗

PubMed2000

Interim results of a randomized trial of mitomycin C as an adjunct to radical radiotherapy in the treatment of locally advanced squamous-cell carcinoma of the cervix.

The purpose of this study was to determine the efficacy of mitomycin C as an adjunct to radiotherapy for the treatment of locally advanced cervix cancer. Patients with squamous-cell carcinoma of the cervix, stages IB2-IVA, were randomized to receive radiotherapy alone or radiotherapy with concomitant mitomycin C. An initial cohort of 160 patients, having a mean follow-up of 46 months, is analyzed. Intravenous mitomycin C, 15 mg/M(2), was given on the first and sixth week of radiotherapy. The 78 patients in the radiotherapy with mitomycin C group and 82 patients in the radiotherapy alone group have a comparable distribution by age and stage (mean age 47 years; stage IB 3%, IIA 11%, IIB 48%, IIIA 1%, IIIB 36%, IVA 3%). The four-year actuarial survival rates for radiotherapy with mitomycin C and radiotherapy alone were 72% and 56%, respectively (P = 0.13). The four-year actuarial disease-free survival rates for radiotherapy with mitomycin C and radiotherapy alone were 71% and 44%, respectively, a statistically significant difference (P = 0.01). The four-year actuarial local recurrence-free survival rates for patients receiving radiotherapy with mitomycin C and radiotherapy alone were 78% and 63%, respectively (P = 0.11). Differences in four-year distant recurrence-free survival between radiotherapy plus mitomycin C and radiotherapy alone were significantly different at 85% vs. 61% (P = 0.01); this analysis is not adjusted for local failure. On subgroup analysis, stage III-IVA patients had a four-year actuarial disease-free survival of 75% for radiotherapy plus mitomycin C compared with 35% for radiotherapy alone (P = 0.03). There were no treatment- related deaths. Mild hematologic toxicity was seen only in the group treated with mitomycin C. No excess in non-hematologic toxicity has been observed thus far with combined mitomycin C and radiotherapy. In this open phase III trial of mitomycin C as an adjunct to radical radiotherapy for squamous-cell carcinoma of the cervix, there were minimal hematologic effects and no increase in acute radiation reactions. A statistically significant difference in favor of patients receiving mitomycin C is shown for disease-free survival. Thus far, there are trends in favor of those patients receiving mitomycin C for survival and local control. Patients with more advanced stage disease, predominantly stage IIIB, appear to have the most benefit. These preliminary results support the hypothesis that targeting hypoxic cells may lead to a therapeutic enhancement in the radiotherapy of cervix cancer. This trial continues to accrue patients and follow-up data. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 206-223 (2000).

Actuarial Analysis↗

PubMed2000

Antiviral efficacy of lobucavir (BMS-180194), a cyclobutyl-guanosine nucleoside analogue, in the woodchuck (Marmota monax) model of chronic hepatitis B virus (HBV) infection.

Lobucavir (BMS-180194), a cyclobutyl-guanosine nucleoside analogue, effectively reduced WHV-viremia in chronically infected carrier woodchucks (Marmota monax) by daily per os treatment. WHV-viremia in the animals was measured by the serum content of hybridizable WHV-genomic DNA. Lobucavir, given at daily doses of 10 and 20 mg/kg body weight, reduced WHV-viremia by a 10- to 200-fold range during therapy. Lobucavir, given at 5 mg/kg, suppressed WHV-viremia by a 10- to 30-fold range, whereas a 0.5 mg/kg dose had no significant effect. WHV-viremia was also measured by hepadnaviral endogenous polymerase activity (EPA) in sera of animals treated for 6 weeks at 5 and 0.5 mg/kg. Changes in EPA in sera of lobucavir treated animals were comparable to changes in WHV DNA levels. Viremia in treated carriers recrudesced to pretreatment levels by 2 weeks of therapy cessation. These results indicated that the minimally effective antiviral daily per os dose of lobucavir in WHV-carrier woodchucks was approximately 5 mg/kg.

Animals↗

PubMed2000

Characterization in cultured cerebellar granule cells and in the developing rat brain of mRNA variants for the NMDA receptor 2C subunit.

N-Methyl-D-aspartate (NMDA) receptors are heteromeric structures resulting from the association of at least two distantly related subunit types, NR1 and one of the four NR2 subunits (NR2A-NR2D). When associated with NR1, the NR2 subunits impose specific properties to the reconstituted NMDA receptors. Although the NR1 mRNAs are expressed in the majority of central neurons, the NR2 subunits display distinct patterns of expression in the developing and adult rat brain. The NR2C subunit is barely expressed in the rat forebrain, whereas its expression increases substantially in the granule cells in the course of cerebellar development. We have identified novel NR2C splice variants in cultured cerebellar granule cells as well as in the developing cerebellum. When compared with the prototypic NR2C mRNA, these variants carry one (NR2Cb) or two (NR2Cd) insertions or a deletion (NR2Cc) and encode putative NR2C polypeptides that terminate between the third and fourth membrane segments or between the first and second membrane segments. RT-PCR analysis and in situ hybridization show that expression of the splice variants is developmentally regulated, both in the cerebellum and in the hippocampus. Electrophysiological recordings and microfluorimetry emissions in transfected human embryonic kidney 293 cells indicate that the NR2Cb variant, when expressed in combination with NR1, does not contribute to the formation of functional receptor channels. The significance of theses findings is discussed.

Aging↗

PubMed1999

Structure, G protein activation, and functional relevance of the cardiac G protein-gated K+ channel, IKACh.

The muscarinic-gated atrial potassium channel IKACh has been well characterized functionally, and has been an excellent model system for studying G protein/effector interactions. Complementary DNAs encoding the composite subunits of IKACh have been identified, allowing direct probing of structural and functional features of the channel. Here, we highlight recent approaches taken in our laboratory to determine the oligomeric structure of native cardiac IKACh, the mechanism of activation of IKACh by G proteins, and the relevance of IKACh to cardiac physiology.

Amino Acid Sequence↗

PubMed1999

Production of leukotriene B4 and prostaglandin E2 by turbot (Scophthalmus maximus) leukocytes.

Production of two eicosanoids derived from lipoxygenase and cyclooxygenase activities: leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), respectively, have been simultaneously determined in turbot (Scophthalmus maximus) blood leucocyte and kidney macrophage supernatants by a reverse phase high performance liquid chromatography (HPLC) system coupled with a Diode-Array detector. Levels of LTB4 after calcium ionophore challenge were 4.08 ng ml-1 in blood leukocyte supernatants and 0.25 ng ml-1 in kidney macrophage supernatants. The levels found for PGE2 were 428.23 and 606.67 ng ml-1 in blood leukocytes and kidney macrophage supernatants, respectively. When blood leukocytes were treated with the respective inhibitors for the enzymes implicated on the synthesis of both compounds an inhibition of 90.35% was observed for PGE2 and 76.44% for LTB4. The detection limit of the method was 0.15 ng ml-1 for LTB4 and 50 ng ml-1 for PGE2.

Animals↗

PubMed1999

Comparison of natural polyphenol antioxidants from extra virgin olive oil with synthetic antioxidants in tuna lipids during thermal oxidation.

Polyphenols extracted from extra virgin olive oil (EVOO) were tested for their ability to inhibit lipid oxidation of canned tuna. Hydroperoxide formation during oxidation was monitored by measurement of peroxide value and decomposition of hydroperoxides by static headspace gas chromatographic analysis of volatiles. In tuna oxidized at 40 and 100 degrees C, 400 ppm of the EVOO polyphenols was an effective antioxidant as compared with 100 ppm of a 1:1 mixture of the synthetic antioxidants butylated hydroxytoluene and butylated hydroxyanisole. However, at concentrations <100 ppm, the EVOO phenolic compounds promoted hydroperoxide formation and decomposition. The EVOO polyphenols were effective antioxidants when added to heated tuna muscle in the presence of either brine or refined olive oil. The oxidation rate in tuna muscle packed in brine was higher than that of tuna packed in refined olive oil. The EVOO polyphenols had higher antioxidant activity in the brine samples than in the refined olive oil. The higher antioxidant activity of EVOO polyphenols in tuna packed in brine may be explained by their greater affinity toward the more polar interface between water and the fish oil system.

Animals↗

PubMed1999

Mobilization of intracellular calcium stores participates in the rise of [Ca2+]i and the toxic actions of the HIV coat protein GP120.

The HIV envelope glycoprotein, GP120, increases intracellular Ca2+ concentration and induces degeneration of human and animal neurons in culture. Using patch-clamp recordings and Ca2+ imaging techniques, we have now examined the contribution of intracellular stores of calcium in the effects of GP120. We report that in rat hippocampal neuronal cultures, GP120 induces a dramatic and persistent increase in [Ca2+]i which is prevented by drugs that either deplete (caffeine, carbachol, thapsigargin) or block (dantrolene) Ca2+ release from intracellular stores. In contrast, N-methyl-d-aspartate (NMDA) receptors or voltage-dependent calcium channels do not participate in these effects, as: (i) the increase in [Ca2+]i was not affected by NMDA receptor antagonists or calcium channel blockers; and (ii) and GP120 did not generate any current in whole-cell recording. Dantrolene, a ryanodine stores inhibitor, also prevented neuronal death induced by GP120. Our results show that the GP120-induced rise in [Ca2+]i originates from intracellular calcium stores, and suggest that intracellular stores of calcium may play a determinant role in the pathological actions of GP120.

Animals↗

PubMed1999

Calcium-dependent inactivation of the monosynaptic NMDA EPSCs in rat hippocampal neurons in culture.

The effects of increased dendritic calcium concentration ([Ca2+]i) induced by single action potentials on monosynaptic glutamatergic excitatory postsynaptic currents (EPSCs) were studied in cultured rat hippocampal neurons. To investigate the respective roles of pre- and postsynaptic elements in the depolarization-induced NMDAR inactivation, we have performed simultaneous paired whole-cell recordings from monosynaptically connected pre- and postsynaptic hippocampal neurons. We report that the single firing of the postsynaptic neuron did not result in inactivation of the NMDAR-EPSC, whereas a burst of depolarizing steps transiently depressed the NMDAR-EPSCs in both pyramidal cells and interneurons. This effect was mediated by postsynaptic voltage-gated Ca2+ influx, as it was prevented by: (i) buffering postsynaptic [Ca2+]i with 30 mM BAPTA; (ii) removing extracellular Ca2+; or (iii) applying Cd2+o (100 microM), a voltage-gated calcium channel blocker. It does not involve presynaptic mechanisms as it selectively affected NMDA but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-mediated EPSCs. These results suggest that inactivation of NMDAR-channels by voltage-gated Ca influx is a general property of hippocampal neurons, which may play an important role in reducing postsynaptic NMDAR Ca2+ influx that leads to plasticity or excitotoxicity during sustained neuronal activity.

Animals↗

PubMed1999

Maturation of kainate-induced epileptiform activities in interconnected intact neonatal limbic structures in vitro.

In vivo studies suggest that ontogenesis of limbic seizures is determined by the development of the limbic circuit. We have now used the newly-developed in vitro intact interconnected neonatal rat limbic structures preparation to determine the developmental profile of kainate-induced epileptiform activity in the hippocampus and its propagation to other limbic structures. We report gradual alterations in the effects of kainate during the first postnatal week on an almost daily basis; from no epileptiform activity at birth, through interictal seizures around postnatal day (P) 2 and ictal seizures by the end of the first week. The developmental profile of kainate-induced hippocampal seizures is paralleled by the expression of postsynaptic kainate receptor-mediated currents in CA3 pyramidal cells. Intralimbic propagation of the hippocampal seizures is also age-dependent: whereas seizures readily propagate to the septum and to the contralateral hippocampus via the commissures on P2, propagation to the entorhinal cortex only takes place from P4 onwards. Finally, repeated brief applications of kainate to the hippocampus induce recurrent spontaneous glutamatergic ictal and interictal discharges which persist for several hours after the kainate is washed away and which replace the physiological pattern of network activity. Paroxysmal activities are thus generated by kainate in the hippocampus at an early developmental stage and are initially restricted to this structure. Before the end of the first week of postnatal life, kainate generates the epileptiform activities that may perturb activity-dependent mechanisms that modulate neuronal development. Although at this stage neurons are relatively resistant to the pathological effects of kainate, the epileptiform activities that it generates will perturb activity-dependent mechanisms that modulate neuronal development.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Intraneuronal [Ca2+] changes induced by 2-deoxy-D-glucose in rat hippocampal slices.

Temporary replacement of glucose by 2-deoxyglucose (2-DG; but not sucrose) is followed by long-term potentiation of CA1 synaptic transmission (2-DG LTP), which is Ca2+-dependent and is prevented by dantrolene or N-methyl--aspartate (NMDA) antagonists. To clarify the mechanism of action of 2-DG, we monitored [Ca2+]i while replacing glucose with 2-DG or sucrose. In slices (from Wistar rats) kept submerged at 30 degreesC, pyramidal neurons were loaded with [Ca2+]-sensitive fluo-3 or Fura Red. The fluorescence was measured with a confocal microscope. Bath applications of 10 mM 2-DG (replacing glucose for 15 +/- 0.38 min, means +/- SE) led to a rapid but reversible rise in fluo-3 fluorescence (or drop of Fura Red fluorescence); the peak increase of fluo-3 fluorescence (DeltaF/F0), measured near the end of 2-DG applications, was by 245 +/- 50% (n = 32). Isosmolar sucrose (for 15-40 min) had a smaller but significant effect (DeltaF/F0 = 94 +/- 14%, n = 10). The 2-DG-induced DeltaF/F0 was greatly reduced (to 35 +/- 15%, n = 16) by,-aminophosphono-valerate (50-100 microM) and abolished by 10 microM dantrolene (-4.0 +/- 2.9%, n = 11). A substantial, although smaller effect, of 2-DG persisted in Ca2+-free 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N', N'-tetraacetic acid (EGTA) medium. Two adenosine antagonists, which do not prevent 2-DG LTP, were also tested; 2-DG-induced DeltaF/F0 (fluo-3) was not affected by the A1 antagonist 8-cyclopentyl-3, 7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX 50 nM; 287 +/- 38%; n = 20), but it was abolished by the A1/A2 antagonist 8-SPT; 25 +/- 29%, n = 19). These observations suggest that 2-DG releases glutamate and adenosine and that the rise in [Ca2+] may be triggered by a synergistic action of glutamate (acting via NMDA receptors) and adenosine (acting via A2b receptors) resulting in Ca2+ release from a dantrolene-sensitive store. The discrepant effects of sucrose and 8-SPT on DeltaF/F0, on the one hand, and 2-DG LTP, on the other, support other evidence that increases in postsynaptic [Ca2+]i are not essential for 2-DG LTP.

Animals↗