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Biomedical subjects

M A Gonzalez

Publications and source records attributed to M A Gonzalez.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dissociation between anti-infarct effect and anti-edema effect of ischemic preconditioning.

This study tested the hypothesis that preconditioning, by reducing catabolite accumulation during ischemia, reduces osmotic swelling and myocardial necrosis during subsequent reperfusion. Farm pigs were randomly allocated to one of three groups of treatment: a control group undergoing a 48-min coronary occlusion (CO) of the middle left anterior descending artery, a preconditioned group (2 cycles of 5-min CO and 5-min reperfusion before the 48-min CO), or an intracoronary perfusion group receiving a substrate-free anoxic buffer perfusion into the area at risk between minutes 5 and 10 of the prolonged CO. Animals were killed after 30 min (n = 23) or 6 h (n = 31) of reperfusion. Compared with the control group, both ischemic preconditioning and washout of ischemic by-products by transient anoxic perfusion reduced myocardial edema after 30 min of reperfusion (P < 0.002) by 35 and 32%, respectively, but only ischemic preconditioning reduced final infarct size (by 55%, P < 0.006). Myocardial lactate content before reperfusion, measured in an additional series of 12 experiments, was reduced by 35% in animals receiving preconditioning or intracoronary perfusion. Thus ischemic preconditioning has a marked protective effect against reperfusion edema, and this effect can be explained by reduced catabolite accumulation during ischemia. However, there is no evidence from this study indicating that reduced catabolite accumulation and limited reperfusion edema explain the important anti-infarct effect of ischemic preconditioning.

Animals↗
PubMed1994

Intracranial pressure dynamics in clinical practice: online PC-based ICP monitoring system.

Correct patient management involves determining the exact point on the intracranial pressure/volume (P/V) curve that corresponds to the patient; this requires calculating intracranial elastance (IE). Intracranial pressure (ICP) monitoring systems should provide the necessary information for this purpose. An ICP monitoring unit is presented that acquires ICP, systemic arterial pressure (SAP) and airway pressure (AWP). The cerebral perfusion pressure (CPP) and the mean values and the peak-to-peak values of the two of them (ICPmean, SAPmean, ICPp-p, SAPp-p,) are calculated. Graphs display the temporal evolution (TE) of the ICP and SAP, as well as histograms of the ICP (%) and intracranial pulse amplitude (ICPAmP) with respect to the ICP or CPP during the preceding 3, 6, 12 or 24 h of monitoring. By digital filtering the ICP respiratory and cardiac components (RCICP, CCICP) are calculated. Finally, the pulse amplitudes (AmP) of the ICP, CCICP and RCICP are computed, as well as the average pulses per minute of SAP, CCICP, AWP and RCICP. Two off-line pulse-amplitude and pulse-morphology oriented toolkits display the afore-mentioned curves, histograms and average pulses per minute, and other additional ones, in order to achieve a deeper patient monitoring study.

Blood Pressure Determination↗
PubMed1993

An ODA-based coder/decoder for multimedia medical documents.

This paper describes the prototype of a coder/decoder based on the Open Document Architecture (ODA) standard for management of medical documents, as well as the working environment in which it has been developed. The prototype has been assessed in an X-Windows-equipped workstation with a relational database containing patient folders (text and still images) from the departmental information system of the liver transplantation unit.

Humans↗
PubMed1993

Oral pharmacokinetics of carbamazepine in dogs from commercial tablets and a cyclodextrin complex.

The extent of absorption of carbamazepine from a 2-hydroxypropyl-beta-cyclodextrin/carbamazepine complex was significantly greater and the rate of absorption was faster when compared with an immediate-release carbamazepine tablet in the dog. Six dogs were dosed orally in a two-way crossover study in which the tablet was compared with an equivalent dose of the complex in solution. The area under the curve of concentration versus time for the complex was 5.6 times greater than the tablet, whereas the mean time to reach maximum concentration for the tablet was 1.4 hours versus 0.5 hours for the complex. The complex, therefore, had a greater rate and extent of absorption. A rapidly acting and better absorbed carbamazepine product has the potential to decrease the daily dose of carbamazepine, increase its utility as emergency treatment of epileptic seizures, and provide an acceptable alternative dosage form in patients who are unable to swallow tablets.

Administration, Oral↗
PubMed1992

Dose proportionality of transdermal nitroglycerin.

The FDA Cooperative Efficacy Study of transdermal nitroglycerin utilized a combination of marketed products over a wide dose range. Unfortunately, plasma nitroglycerin concentrations were not determined. The current study was conducted to assess plasma nitrate concentrations after transdermal doses of 15, 30, 60, and 105 mg/24 hr employing the FDA Cooperative Study design. Plasma concentrations of nitroglycerin, 1,3-glyceryl dinitrate, and 1,2-glyceryl dinitrate were determined during the 24 hr of application and for 1 hr after transdermal system removal. Dose proportionality was assessed after normalizing the data by theoretical dose. For nitroglycerin, dose-normalized AUC(0-infinity) and Cmax were higher for the 105 mg/24 hr dose than for the other doses. For the metabolites, 1,3-glyceryl dinitrate and 1,2-glyceryl dinitrate, there were no differences in dose-normalized AUC(0-infinity) and dose-normalized Cmax between the dose levels. No differences were seen in Tmax between the dose levels for all three species. Based on the dinitrate metabolites, dose proportionality was seen over the 15 to 105 mg/24 hr dose range. Nitroglycerin, however, was found to be linear only between 15 and 60 mg/24 hr.

Administration, Cutaneous↗
PubMed1992

A 40-kilodalton protein binds specifically to an upstream sequence element essential for muscle-specific transcription of the human myoglobin promoter.

To define transcriptional control elements responsible for muscle-specific expression of the human myoglobin gene, we performed mutational analysis of upstream sequences (nucleotide positions -373 to +7 relative to the transcriptional start site) linked to a firefly luciferase gene. Transient expression assays in avian and mammalian cells indicated that a CCCACCCCC (CCAC box) sequence (-223 to -204) is necessary for muscle-specific transcription directed either by the native myoglobin promoter or by a heterologous minimal promoter linked to the myoglobin upstream enhancer region. A putative MEF2-like site (-160 to -169) was likewise necessary for full transcriptional activity in myotubes. Mutations within either of two CANNTG (E-box) motifs (-176 to -148) had only minimal effects on promoter function. We identified and partially purified from nuclear extracts a 40-kDa protein (CBF40) that binds specifically to oligonucleotides containing the CCAC box sequence. A mutation of the CCAC box that disrupted promoter function in vivo also impaired binding of CBF40 in vitro. These data suggest that cooperative interactions between CBF40 and other factors including MEF-2 are required for expression of the human myoglobin gene in skeletal muscle.

Animals↗
PubMed1991

Stability of diltiazem in different biological fluids.

The hydrolysis of diltiazem in biological fluids: whole blood, plasma, and gastric fluid was investigated under conditions considered close to the physiological situation. The most significant rate of hydrolytic degradation was found in whole blood (half-life of 27 h), followed by plasma (half-life of 88 h), while the least significant degradation rate was observed in gastric fluid (half-life 153 h). The kinetic profiles of diltiazem hydrolysis indicate that hydrolytic degradation in the biological fluids makes a minimal contribution to the clearance and disposition of the drug.

Biotransformation↗
PubMed1991

Beta- and alpha-adrenergic receptors are involved in regulating type II thyroxine 5'-deiodinase activity in the rat Harderian gland.

The role of alpha- and beta-adrenergic receptors in regulation of rat Harderian gland type II thyroxine 5'-deiodinase (5'-D) activity was investigated. Our results show that isoproterenol, a beta-adrenergic agonist, and phenylephrine, an alpha-adrenergic agonist, elicited increases in Harderian gland 5'-D activity. The activation was dependent on the time and the dose of the drug. Other adrenergic agonists, i.e., norepinephrine, methoxamine or terbutaline, also clearly increased the enzyme activity. Moreover, administration of propranolol, a beta-adrenergic blocker, or prazosin, an alpha-adrenergic blocker, completely prevented the activation of the enzyme induced by norepinephrine. Results show a clear regulation by adrenergic mechanisms of 5'-D activity in the rat Harderian gland, where alpha- and beta-adrenergic receptors appear to be involved.

Animals↗
PubMed1991

Reduction of cardiac hypertrophy in renal hypertensive rabbits with pindolol.

Arterial pressure, cardiac mass and coronary flow reserves were measured in untreated and chronically pindolol-treated rabbits, prepared as either one-kidney one clip (1K1C) hypertensive or uninephrectomized (sham) controls. Pindolol (200 micrograms/kg/day) was administered for either 23 or 30 days, beginning 1 week after, or the day of initial surgery, respectively. Coronary flow was measured, at day 30, using radioactive microspheres, during base-line and adenosine infusion (0.4 mg/kg/min) in anesthetized open-chest preparations. Heart weight of untreated 1K1C animals (9.13 +/- 0.73 g) was significantly greater than the controls (7.19 +/- 0.77 g). Myocardial mass of 1K1C (9.93 +/- 0.86 g) and sham controls (7.40 +/- 0.31 g) were unaffected by chronic pindolol for 23 days. Cardiac hypertrophy was prevented in 1K1C animals treated with pindolol for 30 days (7.53 +/- 1.28 g). Untreated 1K1C animals were hypertensive compared to sham controls (116 +/- 12 and 78 +/- 7 mm Hg) and neither pindolol regime affected blood pressure. Bradycardia was evident in all pindolol-treated animals. Base-line coronary flow was higher in the untreated 1K1C animals compared to untreated controls (228 +/- 43 vs. 182 +/- 31 ml/min/100 g). After chronic pindolol treatments, 1K1C base-line blood flows were reduced (158 +/- 48 and 175 +/- 59 ml/min/100 g, for 23- and 30-day protocols). Adenosine vasodilated flows were not different between the untreated 1K1C and sham animals and were not affected by pindolol treatment. Therefore, hypertension and cardiac hypertrophy were dissociable in this model when pindolol was administered from the onset of hypertension. This suggests immediate involvement of beta adrenergic activation in the development of hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Characterization of the biochemical properties of recombinant ribonuclease III.

An Escherichia coli double strand specific endoribonuclease, RNase III, was cloned, expressed in large amounts, and purified to homogeneity. Enzyme activity was monitored by assaying fractions for the ability to correctly process exogenous RNA containing specific RNase III cleavage sites. DEAE-Sepharose ion exchange chromatography in the presence of a linear KCl gradient (from 0.02 M to 0.75 M) demonstrated that RNase III exists as two distinct forms. One form elutes at a KCl concentration of 0.13 M and the other elutes at 0.33 M. The presence of stoichiometric amounts of the GTP-binding protein Era during purification results in the conversion of the low salt form into the high salt form. Size exclusion chromatography demonstrated that both forms exist as a dimer in solution. In order to investigate the nature of the dimer, protein cross-linking was performed and cross-linked products were detected by silver staining. The protein-protein dimer can be visualized at protein:cross-linker molar ratios as low as 1:15 within 1 minute of exposure to cross-linker in 0.1 M KCl. Upon addition of substrate RNA to the cross-linking reaction a second form of the protein-protein dimer (with a slightly smaller apparent molecular weight) becomes prominent. Induction of the new form is absolutely dependent upon the addition of substrate mRNA to the reaction mixture. We postulate that the RNase III dimer undergoes a dramatic conformational change upon recognition of RNA which we are able to trap by cross-linking.

Chromatography, Ion Exchange↗
PubMed1990

Application of a variance-stabilizing transformation approach to linear regression of calibration lines.

A variance-stabilizing transformation (VST) was applied to the linear regression of calibration standards of different drugs in plasma. This transformation involved the normalization of the dependent variable peak height or peak area ratio (Y), and the independent variable, plasma drug concentration (C). This transformation led to a constant variance in the regression error term across the measured concentration range and allowed the evaluation of the unbiased slope and y intercept with minimum variance. The utility of the VST procedure in comparison with the ordinary least squares (OLS) approach, routinely used in pharmaceutical studies for constructing calibration lines, is described. The principal advantage of the VST approach is allowing a lower minimum level of drug quantification while using a single calibration line over a wide range of drug concentrations. The VST method is especially useful to quantify drug plasma levels in pharmacokinetic evaluation of sustained-release dosage forms, where the precise quantification of low levels of drug is critical. The application of the VST method was explored and evaluated in comparison with the OLS method for pharmacokinetic assays of diltiazem, gallopamil, nitroglycerin, and nicotine.

Calibration↗
PubMed1989

Gas chromatographic determination of gallopamil and norgallopamil in human plasma.

A highly sensitive gas chromatographic assay is described for the simultaneous determination of gallopamil, a calcium channel blocking agent, and its major metabolite, norgallopamil. A multi-step extraction procedure is employed followed by on-column capillary gas chromatographic analysis using nitrogen-selective detection. Acetylation of norgallopamil is performed to enable accurate quantification of the metabolite. Linearity was achieved over the range 1-50 ng/ml for both analytes. Assay specificity, precision and accuracy were investigated.

Chemical Phenomena↗