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Biomedical subjects

R Carlos

Publications and source records attributed to R Carlos.

At least 37 records · Page 2Linked to original sources

Differential effects of valproic acid on the serum protein binding of lorazepam and diazepam.

Valproic acid and free fatty acids have been shown to displace diazepam from its plasma binding sites both in vitro and in vivo. Since lorazepam exhibits a substantial degree of binding, but differs from other benzodiazepines in that no increase in its free fraction in serum is observed when free fatty acids are raised, the effect of valproate on the serum protein binding of diazepam and lorazepam was assessed. Sodium valproate produced a marked increase in the free fraction of diazepam, but practically no effect on the percentage of free lorazepam.

Blood Proteins↗

Structural analysis of ribosomal RNA genes from the Hawaiian sea urchin species, Tripneustes gratilla.

Ribosomal gene sequences (rDNA) were isolated from the genomic DNA of the Hawaiian sea urchin Tripneustes gratilla by cloning in plasmid and phage vectors. The rRNA coding regions in four clones were localized by hybridizing Southern transfers of endonuclease-digested DNA with 32P-labeled 26S rRNA and 32P-labeled 18S rRNA. Three of the rDNA clones were isolated from a library of DNA from a single sea urchin and represent the two major types of rDNA repeats present in that individual's genome. Both repeat types appear identical within their rRNA coding regions but are dissimilar in an area of the nontranscribed spacer (NTS) adjacent to the 3' end of the 26S coding region. The cloned rDNA repeats were shorter than their genomic counterparts due to deletions occurring within internally repetitious NTS domains, probably as a result of unequal recombination during phage propagation.

Animals↗

Moya moya disease: use of digital subtraction angiography in its diagnosis.

Fourteen patients suspected of having Moya Moya disease underwent intravenous digital subtraction angiography (DSA), and the findings from nine of these patients were reviewed and analyzed. Obstruction or stenosis of the supraclinoid portion of the internal carotid artery and the proximal portions of the anterior and middle cerebral arteries was observed in all cases. Arteriography, however, was better than intravenous DSA in demonstrating Moya Moya vessels, differentiating complete occlusion from severe stenosis, and demonstrating important transdural collaterals. The disadvantages of intravenous DSA included inferior spatial resolution, the need for large amounts of contrast media, and relatively high radiation doses. Since the summation of vessels cannot be avoided using DSA, arteriography is necessary for the precise evaluation of cerebral hemodynamics before bypass surgery. Intravenous DSA is a safe, reliable method for diagnosing Moya Moya disease and is suitable for the screening and follow-up examinations of patients with the disease.

Adolescent↗

Underestimation of albumin content by bromocresol green, induced by drug displacers and uremia.

Phenylbutazone and clofibric acid, two drugs strongly bound to human albumin, produce low readings of albumin content in serum when the bromocresol green immediate reaction is used. This abnormality is observed at drug concentrations within the range obtained during therapeutic use, and tends to be more marked in diluted samples of serum. Abnormally low values of albumin content are also obtained when the bromocresol green method is used in uremic sera, and the disparity seems related to the degree of carbamylation of these samples. The reported interferences are great enough in some cases as to suggest that the use of the immediate reaction between bromocresol green and serum should not be considered a valid measure of albumin content when these factors cannot be totally excluded.

Adult↗

Procaine hydrolysis defect in uraemia does not appear to be due to carbamylation of plasma esterases.

Procaine esterase activity in plasma from patients with renal failure is decreased by 40%. Since cyanate is formed from urea and readily carbamylates certain blood proteins, a possible role for cyanate in the depression of plasma esterase activity in uraemic patients was considered. However, in vitro carbamylation of normal plasma in a range similar to that detected in uraemic patients did not influence procaine esterase activity. Kinetic analysis of the reaction showed that the maximal hydrolyzing capacity but not the Km in uraemic plasma was diminished (5.0 +/- 0.3 X 10(-5) moles hydrolyzed per litre of plasma per minute and a Km of 3.9 +/- 0.2 X 10(-5) mol/l in plasma from normal volunteers as compared to 3.1 +/- 0.1 X 10(-5) mol/l/min and 3.5 +/- 0.2 X 10(-5) ml/l in plasma from patients with renal failure). Therefore, not carbamylation but rather a decrease in enzyme synthesis is the likely explanation for the lower rate of procaine hydrolysis in uraemic plasma.

Adult↗

Effects of carbamylation of plasma proteins and competitive displacers on drug binding in uremia.

The effects of in vitro carbamylation of plasma with potassium cyanate on the binding of sulfisoxazole and diazepam have been investigated. Incubation of plasma with potassium cyanate produced varying degrees of carbamylation of plasma proteins which were associated with a decrease in the binding of sulfisoxazole (100 mg/l), a drug bound to site I on the human albumin. Scatchard plots showed that this decreased binding resulted from a decrease in affinity without changes in the number of binding sites. Similar changes were detected in uremia. Carbamylation of plasma proteins did not affect the binding of diazepam (3 mg/l), a drug bound to site II. The plasma protein binding of sulfisoxazole and diazepam was decreased in samples from uremic patients. Charcoal treatment did not modify the binding of sulfisoxazole to normal or carbamylated plasma while it reduced, but did not normalize, the binding defect in uremic plasma. On the other hand, charcoal treatment brought the binding of diazepam in uremic plasma to normal values. It seems that only drug binding site I is carbamylated in uremia, while competitive displacers bind to sites I and II.

Adult↗

Plasma protein binding of etomidate in different age groups and in patients with chronic respiratory insufficiency.

Plasma protein binding of etomidate, an intravenous anesthetic agent of basic nature, has been studied in healthy subjects of different age groups and in patients with chronic respiratory insufficiency. No differences were detected in the plasma protein binding of etomidate between young children and young adults, but elderly subjects exhibited decreased binding. Low levels of serum albumin may account in part for this decreased binding, but differences in the amount of etomidate bound per mol of albumin and in affinity constants for the binding were also apparent between young adults and elderly individuals. Although plasma protein binding of etomidate may also be decreased in patients with chronic respiratory insufficiency, further studies are needed to clarify this point.

Adult↗

Effects of disease and acetazolamide on procaine hydrolysis by red blood cell enzymes.

Procaine hydrolysis in vitro has been studied in whole blood, plasma, and washed erythrocytes. Esterase activity was higher in whole blood than in either diluted plasma or resuspended erythrocytes. Eserine and echothiophate specifically inhibited plasma procaine esterase activity, while acetazolamide blocked hydrolysis of procaine by washed erythrocytes. Kinetic studies in whole blood also identified 2 different enzymes. Procaine esterase activity associated with red blood cells was not impaired in patients with renal failure or hepatic cirrhosis, but procaine half-life (t 1/2) in whole blood of normal subjects was longer after 250 mg acetazolamide.

Acetazolamide↗

Plasma protein carbamylation and decreased acidic drug protein binding in uremia.

The effects of in vitro carbamylation of plasma with potassium cyanate on drug-protein binding have been investigated. Potassium cyanate added to samples of normal plasma and incubated for 30 to 150 min induced time-related plasma protein carbamylation. Carbamylation of plasma did not influence quinidine protein binding, but resulted in decreased salicylate binding. The increased free fraction of salicylate in plasma correlated with the degree of carbamylation of plasma proteins (r = 0.99; p less than 0.001). Plasma from patients with chronic renal disease showed varying degrees of plasma protein carbamylation, correlating with the values of free plasma salicylate (r = 0.80; p less than 0.05). Scatchard plots for sulfadiazine binding in plasma from patients with uremia and in normal plasma carbamylated in vitro with potassium cyanate showed changes in the 2 groups when compared with those in normal individuals. If cyanate is produced in vivo from urea in patients with uremia, plasma protein carbamylation may play a role in the decreased plasma protein binding of some acidic drugs.

Adult↗

Effect of premedication on etomidate anaesthesia.

The effect of premedication upon the induction of anaesthesia with etomidate was studied in 74 adult patients undergoing elective orthopaedic surgery. Premedication with fentanyl plus atropine or with diazepam plus atropine decreased the frequency of involuntary muscle movements without modifying the pattern of the circulatory effects of etomidate, although fentanyl increased the frequency of apnoea. Pain at the site of injection was not modified by premedication.

Adolescent↗

Etomidate and plasma esterase activity in man and experimental animals.

No hydrolysis of etomidate in plasma in vitro was detected in samples from man, horse, cow, sheep, guinea pig or white rabbit. Brown rabbits showed a moderate degree of hydrolysis and it was marked in plasma from Wistar rats. In this species, a single enzyme, an alliesterase, participated in the hydrolysis in plasma. Etomidate did not interfere with the hydrolysis of procaine by plasma pseudocholinesterase in man.

Animals↗

Sulfamethazine absorption and disposition: effect of surgical procedures for gastroduodenal ulcers.

This study was designed to determine whether the surgical procedures for gastroduodenal ulcers influence sulfamethazine (SMZ) absorption and disposition. Prior to and on the average 79 days after surgery, eight patients received 10 mg kg-1 of sulfamethazine orally. Blood samples were obtained at regular intervals over 24 h and urine was collected for 48 h. Vagotomy with pyloroplasty or with gastrojejunostomy had no effect on SMZ kinetics. Vagotomy with partial gastrectomy decreased the SMZ plasma peak concentrations from 43.9 +/- 7.1 (mean +/- SEM) to 17.2 +/- 5.2 micrograms ml-1 (p less than 0.05) and increased the time required to reach this peak from 2.6 +/- 0.8 to 9.8 +/- 2.8 h (p less than 0.05). SMZ rate constant of absorption decreased only slightly (1.22 +/- 0.45 to 0.24 +/- 0.07 h-1) and SMZ bioavailability was not affected at all. In two (out of four) patients, SMZ volume of distribution and total body clearance increased, as reflected in the 41 per cent decrease in the mean area under the SMZ plasma concentration-time curve. No changes were detected in SMZ protein binding. Computer simulations indicated that in some subjects SMZ plasma concentrations at steady state could be 76 per cent lower following vagotomy with partial gastrectomy than before surgery. It was concluded that vagotomy and antrectomy with a gastroduodenostomy or Billroth I reconstruction decreased the rate of SMZ absorption and only in some subjects increased the SMZ volume of distribution and rate of elimination. The possible mechanisms involved in these reported kinetic changes are discussed.

Adult↗

Recognition of food in weanling rats exposed to alcohol prenatally.

Offspring of rats fed a liquid diet containing ethanol during their pregnancies were compared to controls on a caloric discrimination test beginning at 22 days of age. All pups received simultaneous choice between a palatable, noncaloric diet and a similar diet containing starch. Each diet contained a distinctive flavor. To test for flavor preference learning, pups then received an extinction test: a simultaneous choice between two noncaloric diets, identical except for flavor. Prenatal alcohol exposure had no substantial effect on the caloric discrimination, and all groups preferentially ingested the starch diet on all test days. However, during the extinction test, alcohol-exposed pups showed a significantly weaker flavor preference than control pups. These data extend the effects of prenatal alcohol exposure on learning and ingestive behavior to include solid food discriminations at the time of weaning.

Analysis of Variance↗

The behavioral teratogenicity of alcohol is not affected by pretreatment with aspirin.

Prenatal alcohol exposure is associated with a variety of developmental abnormalities, including neuroanatomical, physical, and behavioral features. Several mechanisms for alcohol's teratogenic effects have been proposed. This study addresses the role of prostaglandins in the abnormal development that often occurs after maternal alcohol consumption. On gestation days 8 to 18, pregnant Sprague-Dawley rats were prenatally treated with 6 g/kg alcohol following pretreatment with 150 mg/kg aspirin. Behavioral testing of offspring included measures of open-field activity, exploratory behavior, passive avoidance, active avoidance, and acoustic startle response. In most cases, pretreatment with aspirin did not affect performance in alcohol-exposed or control rats.

Animals↗

Effects of prenatal alcohol exposure on serial pattern performance in the rat.

The effect of prenatal alcohol exposure on serial-pattern learning was investigated in adult rats. Pregnant dams were administered a liquid diet which contained 35% ethanol-derived calories (35% EDC) on days 6-20 of gestation. Two control groups were included: a liquid diet control which was pair-fed and had sucrose substituted for ethanol (0% EDC); and a group fed standard lab chow throughout pregnancy. Offspring from each of these prenatal groups were trained to run a straight alley for food pellets. Pellet amount on successive trials was 14, 7, 3, 1, 7. Subjects were exposed to this pattern four times a day for 8 consecutive days. The mean latency to enter the goal-box for the four trials that comprised a monotonically decreasing series of pellet amounts (14, 7, 3, 1) was indirectly related to pellet amount. The mean latency on each trial and the degree of change in running speed across trials was found to be directly related to in utero alcohol exposure. Alcohol exposed offspring demonstrated less change in latencies over trials than controls. Also, the mean latency on the last trial for 7 pellets was shorter than that seen on the previous trial (1 pellet) and similar to that seen after the first trial in which 7 pellets were available. This indicated that satiation was not a factor in the increasing latencies. These data indicate a deficit in serial pattern performance as a function of prenatal alcohol exposure similar to what is observed in children with FAS.

Animals↗

Plasma protein binding of etomidate in patients with renal failure or hepatic cirrhosis.

The influence of renal failure and of hepatic cirrhosis on the plasma protein binding of etomidate, an intravenous anaesthetic agent of basic nature, has been investigated. The percentage of free etomidate in plasma containing 1 microgram/ml was markedly increased in patients with renal failure and in patients with hepatic cirrhosis, when compared with a group of healthy volunteers (43.4 +/- 2.9% and 44.2 +/- 2.1 versus 24.9 +/- 1.4%). This decrease in binding correlated inversely with serum albumin levels in both conditions (r = -0.88 and r = 0.72, respectively) but a slight decrease in the amount bound per mole of albumin was also apparent in both types of disease.

Adult↗