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Biomedical subjects

A Pujol

Publications and source records attributed to A Pujol.

At least 37 records · Page 2Linked to original sources

Intentional overdose and death with 3,4-methylenedioxyethamphetamine (MDEA; "Eve"): case report.

We report a case of suicide following ingestion of a large dose of 3,4-methylenedioxyethamphetamine (MDEA, "Eve") in a 27-year-old woman with a history of depression. Several days before her death, she had attempted suicide with benzodiazepines resulting in a 24-hour hospital admission; at that time, no physiologic abnormalities were detected. Findings on autopsy were nonspecific. Toxicologic analysis showed a high concentration of MDEA and the appearance of benzodiazepines in body fluids. Ethanol and other drugs of abuse were not found. We discuss the clinical manifestations, toxicologic syndromes, and mechanisms of death with amphetamine intoxication. MDEA intoxication in young people may result in sudden death.

3,4-Methylenedioxyamphetamine↗

Transgenic mice in the analysis of metabolic regulation.

In normal animals, the extracellular concentration of glucose is maintained within a very narrow range by the matching of glucose flux into and out of the extracellular space through the tightly coordinated secretion of insulin and glucagon. Functional alterations in beta-cells, liver, or skeletal muscle and adipose tissue may disrupt glucose homeostasis and lead to the development of non-insulin-dependent diabetes mellitus (type 2 diabetes). This review outlines the contribution of these organs and tissues to the control of glucose homeostasis. We discuss new insights obtained through studies of transgenic mice that overexpress or show decreased expression of putative key genes in the regulation of pancreatic beta-cell function, in the control of hepatic glucose uptake and output, and in the regulation of glucose uptake and utilization by skeletal muscle and adipose tissue.

Adipose Tissue↗

[Air in the bone? Diagnosis and treatment of a pneumatocyst of the ilium. Apropos of a case].

We present a case of symptomatic pneumatocyst of the ilium observed in a professional scuba diver exposed to pressure variations. Pneumatocysts are rare and except for one case reported in a clavicular localization, are always found in subchondral bone of the iliac or sacral side of the sacroiliac joint. Undoubtedly, air fills an intraosseous node. We report here the first case of efficient treatment achieved by filling the cyst via percutaneous access under scopic control.

Adult↗

Sequence and analysis of a 36.2 kb fragment from the right arm of yeast chromosome XV reveals 19 open reading frames including SNF2 (5' end), CPA1, SLY41, a putative transport ATPase, a putative ribosomal protein and an SNF2 homologue.

The complete sequence of a 36 196 bp DNA segment located on the right arm of chromosome XV of Saccharomyces cerevisiae has been determined and analysed. The sequence includes the 5' coding region of the SNF2 gene, the CPA1 leader peptide sequence and 17 open reading frames (ORFs) of at least 100 amino acids. Two of these correspond to previously known genes (CPA1, SLY41), whereas 15 correspond to new genes. The putative translation products of three ORFs show significant similarity with known proteins: one is a putative transport ATPase, another appears to be a ribosomal protein, and the third is an Snf2p homologue.

Adenosine Triphosphatases↗

Inhibition of parvovirus minute virus of mice replication by a peptide involved in the oligomerization of nonstructural protein NS1.

The large nonstructural protein NS1 of the minute virus of mice and other parvoviruses is involved in essential steps of the viral life cycle, such as DNA replication and transcriptional regulation, and is a major contributor to the toxic effect on host cells. Various biochemical functions, such as ATP binding, ATPase, site-specific DNA binding and nicking, and helicase activities, have been assigned to NS1. Homo-oligomerization is a prerequisite for a number of proteins to be fully functional. In particular, helicases generally act as homo-oligomers. Indirect evidence of NS1 self-association has been recently obtained by a nuclear cotransport assay (J. P. Nüesch and P. Tattersall, Virology 196:637-651, 1993). In order to demonstrate the oligomerizing property of NS1 in a direct way and localize the protein region(s) involved, the yeast two-hybrid system was used in combination with deletion mutagenesis across the whole NS1 molecule, followed by high-resolution mapping of the homo-oligomerization domain by a peptide enzyme-linked immunosorbent assay method. This study led to the identification of a distinct NS1 peptide that contains a bipartite domain involved in NS1 oligomerization. Furthermore, this isolated peptide was found to act as a specific competitive inhibitor and suppress NS1 helicase activity in vitro and parvovirus DNA replication in vivo, arguing for the involvement of NS1 oligomerization in these processes. Our results point to drug targeting of oligomerization motifs of viral regulatory proteins as a potentially useful antiviral strategy.

Amino Acid Sequence↗

[Normalization of cognitive and functional assessment instruments for dementia (NORMACODEM) (I): objectives, content and population].

UNLABELLED: To adequately evaluate patients with 4 neuropsychological deficits a project for norming cognitive and functional instruments that assess dementia (NORMACODEM) was designed. Four hundred fifty-one subjects in three groups: 254 controls, 86 patients with minor memory/cognitive deficits without dementia (DWD) and 111 patients with probable Alzheimer-type dementia (ATD) according to the NINCDS/ADRDA criteria. Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale (ADAS), Abbreviated Barcelona Test (ABT), Global Dementia Staging (GDS), Functional Assessment Staging (FAST), Clinical Dementia Rating (CDR), Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale (BDRS), Interview for Deterioration in Daily life in Dementia (IDDD), Geriatric Evaluation by Relatives Rating Instrument (GERRI), Geriatric Depression Scale (GDS), Zung Self-Rating Anxiety Scale (ZSRAS). Descriptive statistics and analysis of variance. The characteristics of the sample were as follows. CONTROLS: 99 men, 155 women. Mean (SD) age: 64.6 (10.9) years. Mean (SD) educational level: 9.1 (4.9) years. DWD: 42 men, 44 women. Mean (SD) age: 65.8 (8.7) years. Men (SD) educational level: 8.4 (4.4) years. ATD: 48 mean, 63 women. Mean (SD) age: 68.3 (8.0) years. Mean (SD) educational level: 6.2 (4.3) years. The ATD patients were significantly older than the controls. Mean educational level was significantly lower in the ATD group than in the other two.

Adult↗

[Adaptation and normalization of the Alzheimer's disease Assessment Scale for Spain (NORMACODEM) (II)].

UNLABELLED: This report is part of a project for norming cognitive and functional instruments that assess dementia (NORMACODEM). To adapt and norm the Alzheimer's Disease Assessment Scale (ADAS) for use in Spain. Two hundred fifty-four controls, 86 patients with minor memory/cognitive disorders without dementia (deterioration without dementia, DWD), 111 patients with Alzheimer-type dementia (ATD). Statistical description. Multivariate linear regression. Crossed validation. Internal consistency and test-retest (n = 48). The mean scores (SD) obtained were as follows. CONTROLS: ADAS-Cog = 8.0 (3.4), ADAS-Noncog = 2.9 (2.9), ADAS-Tot = 10.9 (4.6). DWD: ADAS-Cog = 11.37 (5.1), ADAS-Noncog = 4.9 (4.3), ADAS-Tot = 16.2 (7.0). ATD: ADAS-Cog = 31.8 (5.1), ADAS-Noncog = 10.3 (4.3), ADAS-Tot = 42.2 (20.7). Multiple regression analysis revealed that educational level and age were significantly associated with the ADAS-Cog score. The internal consistency of the ADAS-Cog was 0.963. The test-retest procedure yielded linear correlation, coefficients of 0.93 for the ADAS-Cog, 0.86 for the ADAS-Noncog and 0.95 for the ADAS-Tot. Age and educational level/schooling are associated to the earned on the ADAS-Cog instrument. The present Spanish version of the ADAS has high internal consistency and reproducibility. The instruments can be use for assessment in Spanish populations.

Adult↗

Correction of diabetic alterations by glucokinase.

Hyperglycemia is a common feature of diabetes mellitus. It results from a decrease in glucose utilization by the liver and peripheral tissues and an increase in hepatic glucose production. Glucose phosphorylation by glucokinase is an initial event in glucose metabolism by the liver. However, glucokinase gene expression is very low in diabetic animals. Transgenic mice expressing the P-enolpyruvate carboxykinase/glucokinase chimeric gene were generated to study whether the return of the expression of glucokinase in the liver of diabetic mice might prevent metabolic alterations. In contrast to nontransgenic mice treated with streptozotocin, mice with the transgene previously treated with streptozotocin showed high levels of both glucokinase mRNA and its enzyme activity in the liver, which were associated with an increase in intracellular levels of glucose 6-phosphate and glycogen. The liver of these mice also showed an increase in pyruvate kinase activity and lactate production. Furthermore, normalization of both the expression of genes involved in gluconeogenesis and ketogenesis in the liver and the production of glucose and ketone body by hepatocytes in primary culture were observed in streptozotocin-treated transgenic mice. Thus, glycolysis was induced while gluconeogenesis and ketogenesis were blocked in the liver of diabetic mice expressing glucokinase. This was associated with normalization of blood glucose, ketone bodies, triglycerides, and free fatty acids even in the absence of insulin. These results suggest that the expression of glucokinase during diabetes might be a new approach to the normalization of hyperglycemia.

Animals↗

Sequencing analysis of a 40.2 kb fragment of yeast chromosome X reveals 19 open reading frames including URA2 (5' end), TRK1, PBS2, SPT10, GCD14, RPE1, PHO86, NCA3, ASF1, CCT7, GZF3, two tRNA genes, three remnant delta elements and a Ty4 transposon.

The complete sequence of a 40247 bp DNA segment located on the left arm of chromosome X of Saccharomyces cerevisiae has been determined and analysed. The sequence encodes the 5' coding region of the URA2 gene and 18 open reading frames of at least 100 amino acids. Ten of these correspond to known genes, whereas eight correspond to new genes. In addition, the sequence contains a tRNA-Ala gene, a tRNA-Asp gene, a Ty4 transposable element and three delta elements.

Chromosomes, Fungal↗

Afterdrop after hypothermic cardiopulmonary bypass: the value of tympanic membrane temperature monitoring.

OBJECTIVES: After weaning from cardiopulmonary bypass (CPB), a decrease in nasopharyngeal temperature (NPT) occurs (afterdrop). The pathophysiology of the afterdrop remains unclear: It might be caused by either inadequate total body rewarming on CPB or to heterogenous distribution of heat during CPB, with subsequent redistribution of heat from the warmer core to the cooler shell tissues. The study objectives were (1) to determine whether post-CPB afterdrop is the result of a negative CPB thermal balance, and (2) to investigate which sites (if any) could best predict the afterdrop. DESIGN: Prospective evaluation using within-patient comparisons during CPB cooling, CPB rewarming, and 45 minutes post-CPB. SETTING: Adult patients gave informed consent before a cardiac surgical procedure in a university hospital. PARTICIPANTS: Eight patients undergoing CABG or valvular replacement with hypothermic CPB (NPT near 29 degrees C) and standardized general anesthesia. INTERVENTIONS: Each patient was studied with temperature monitors (Mon-a-therm 7000; Mallinckrodt-Medexel, Gemenos, France) attached to disposable thermocouple probes placed as follows: urinary bladder, rectum, deltoid, esophagus, nasopharynx, tympanic membrane, and four skin sites. In addition, the temperatures from the thermistors of the pulmonary artery catheter, and the arterial and venous lines of the CPB circuit were considered. Thirteen sites for monitoring temperature were studied. MEASUREMENTS AND MAIN RESULTS: Temperatures were recorded every 5 minutes, from the beginning of CPB to the 45th minute after CPB, and thermal exchanges were calculated: change in body heat (QBH), thermal exchanges between the patient and the pump (QCPB), metabolic heat production (Qm) (equal to calculated VO2 at the pump level), and heat loss to the environment (QS) (equal to QBH-QCPB-Qm). Thermal exchanges were obtained in six patients during the plateaus of cooling and rewarming, during the whole CPB phase, and after CPB. It was found that despite a change in QBH during rewarming (1,017 +/- 88 kJ) that was slightly greater than during cooling (-1,008 +/- 104 kJ) (mean +/- SEM), a significant decrease in post-CPB "core" temperature occurred (afterdrop: -1.4 degrees C). Magnitude of the afterdrop was directly related to the magnitude of tympanic membrane cooling and was negatively correlated to the temperature difference between the warmest site (tympanic membrane) and the coolest site (cutaneous thigh temperature) observed at the end of rewarming (r = -0.667; p < 0.05). CONCLUSIONS: It is suggested that besides post-CPB heat loss, redistribution of heat may be involved in the mechanism of the afterdrop and that measurements of tympanic membrane and cutaneous thigh temperatures are the best monitors of adequacy of rewarming during CPB.

Adult↗

Prediction of carboplatin clearance from standard morphological and biological patient characteristics.

BACKGROUND: Hematologic toxicity of an antineoplastic drug, carboplatin, is largely dependent on its pharmacokinetics. Its therapeutic efficacy may be related to plasma drug exposure. Dosage adjustment based on isotopic determination of glomerular filtration rate has been proposed, but its ambulatory use is not yet conceivable. The dosage adjustment based on a patient's creatinine clearance relies on accurate measurement of urine volume per unit time and can be done with ease. PURPOSE: A population pharmacokinetics study was undertaken to determine a relationship between carboplatin clearance and patient characteristics. A predictive formula was derived that was then prospectively evaluated, and its outcome was compared with that obtained by other methods available to predict carboplatin clearance. METHODS: Plasma carboplatin pharmacokinetics determined as ultrafilterable platinum in 70 patients (age range, 23-84 years) treated with different combination regimens that included carboplatin at doses ranging from 184 mg to 950 mg (1-hour intravenous infusion) for various tumor types. Data were analyzed using the nonlinear mixed effects model (NONMEM). The data from 34 patients (46 cycles) were utilized to derive the most predictive formula. The reliability of the formula was subsequently evaluated by analyzing the data obtained from 36 other patients (49 cycles). RESULTS: Carboplatin clearance (mL/min) was found to be best predicted by the following formula: 0.134.weight + [218.weight.(1-0.00457.age).(1-0.314.sex)]creatinine expressed in micromolar concentration (with weight in kg, age in years, and sex = 0 if male and sex = 1 if female). Prospectively, this formula predicted the carboplatin clearance with good precision (median absolute percent error of 10% [range, 0% to 30%]) and minimal bias (median percent error of 2% [range, -25% to 30%]). This method of prediction was as accurate as the one derived from the measurement of glomerular filtration rate following the injection of 51 chromium-EDTA. CONCLUSION: This formula for the determination of carboplatin clearance can permit individualized determination of carboplatin dosage in adults by simply multiplying the calculated carboplatin clearance by the area under the curve for the desired dosage administration.

Adult↗

Neonatally administered naltrexone affects several behavioral responses in adult rats of both genders.

The effects of a daily injection of the opioid antagonist naltrexone (NALTX, 1 mg/kg SC), from birth to weaning day, on several behavioral parameters were investigated in adult rats of both genders. This work uses three behavioral tests. The use of the open-field test in addition to the holeboard and plus-maze tests allows the measurement of complementary parameters, and provided further information on diverse components of behavior. The effect of repeated testing (habituation) over 3 consecutive days of open-field testing was also assessed. In accordance with previous reports, female rats showed higher locomotor activity and exploration and a lower level of emotionality than their male counterparts. The response of the animals to repeated testing seemed to be both sex and treatment dependent. In both males and females, NALTX treatment during the preweanling period did not affect locomotor activity, but increased the animals' levels of anxiety and emotionality and decreased exploratory behavior. Our results indicate that neonatal opioids may play an important role in the development of behavioral responses in the adult.

Animals↗

Evidence from transgenic mice that myc regulates hepatic glycolysis.

The product of the c-myc proto-oncogene (c-Myc) is involved in the control of cell proliferation, differentiation, and apoptosis. It acts as a transcription factor that recognizes the CACGTG motif. This sequence has also been found in the glucose-responsive elements of genes involved in the control of liver glycolysis and lipogenesis. To determine whether c-Myc can regulate hepatic carbohydrate metabolism in vivo, transgenic mice that overexpress c-myc under control of the P-enolpyruvate carboxykinase (PEPCK) gene promoter have been generated. These mice showed a threefold increase in c-Myc protein in liver nuclei. Hepatocytes from transgenic mice were normal and did not acquire the fetal phenotype. However, transgenic mice showed higher levels (threefold) of L-type pyruvate kinase mRNA and enzyme activity than control mice. The increase in pyruvate kinase activity led to a three- to fivefold increase in liver lactate content and a fivefold induction of lactate production by hepatocytes in primary culture. The expression of the 6-phosphofructo-2-kinase gene was also increased in the liver of these transgenic mice. The induction of hepatic glycolysis was related with an increase in the expression (about fourfold) and activity (about threefold) of liver glucokinase, whereas no change was noted in hexokinase-I. This change in glucokinase activity led to an increase in both glucose 6-phosphate and glycogen contents in the liver of transgenic mice. The expression of the liver-specific glucose transporter GLUT2 was also increased in transgenic mice, whereas no change was noted in the mRNA concentration of GLUT1. Furthermore, the changes of liver glucose metabolism led to a marked reduction of blood glucose (25%) and insulin (40%) concentrations in starvation, whereas the fall in both was only 10% in fed mice. Thus, liver glucose metabolism could determine the blood glucose and insulin set points in the transgenic mice. All these results indicated that the increase in c-Myc protein was able to induce liver glucose utilization and accumulation, and suggested that c-Myc transcription factor is involved in the control in vivo of liver carbohydrate metabolism.

Animals↗