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Biomedical subjects

A Lorenzo

Publications and source records attributed to A Lorenzo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genetic polymorphism of alcohol dehydrogenase in europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1.

Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n = 251), France (n = 160), Germany (n = 184), Sweden (n = 88), and Poland (n = 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47. 6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholics (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P =.0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population.

Adult↗
PubMed2000

Membrane mechanisms for electrogenic Na(+)-independent L-alanine transport in the lizard duodenal mucosa.

The active Na(+)-independent transport of L-alanine across the duodenal mucosa of the lizard Gallotia galloti was studied in Ussing-type chambers using a computer-controlled voltage clamp. Addition of L-alanine to the Na(+)-free bathing solutions resulted in a significant L-alanine absorption (J(net)) that was paralleled by an increase in transepithelial short-circuit current (I(sc)) and potential difference (PD) without apparent changes in the tissue conductance. The concentration dependence of J(net), PD, and I(sc) displayed Michaelis-Menten kinetics. L-alanine-induced electrical changes were completely inhibited by external alkaline pH or by the H(+)-ionophore carbonyl cyanide m-chlorophenyl-hydrazone in the bathing solution. The alanine-induced electrogenicity was dependent on the presence of extracellular K(+) and could be blocked by serosal Ba(2+) or mucosal orthovanadate. These results suggest the existence of an H(+)-coupled L-alanine cotransport at the apical membrane of enterocytes. The favorable H(+) driving force is likely to be maintained by an apical vanadate-sensitive H(+)-K(+)-ATPase, allowing the extrusion of H(+) in an exchange with K(+). Potassium exit through a basolateral barium-sensitive conductance provides the key step for the electrogenicity of L-alanine absorption.

Alanine↗
PubMed2000

[Intraoperative control of mean arterial pressure and heart rate with alfentanyl with fuzzy logic].

OBJECTIVES: To describe a fuzzy logic controller that adjust alfentanil infusion during surgery based on changes in mean arterial pressure (MAP) and heart rate (HR). MATERIAL AND METHODS: We designed a fuzzy logic controller using if ... then ... conditions written in C language, to be executed by a 486 PC with a 66 Mhz CPU. The controller was used with eight ASA I-II patients undergoing gynecological surgery under anesthesia with propofol, alfentanil and ventilated with oxygen/air. MAP and HR were input every three minutes, after which the controller generated an infusion based on those figures. We performed a statistical study of alfentanil consumption time until extubation and time of hemodynamic stability. Relative error of MAP was calculated. RESULTS: The controller was used for a total of 373 min with the eight patients. MAP was 15% below the desired level for 2.14% (18 min) of that time and was 15% over the desired level for 5.6% (21 min) of the time. MAP held steady within the range of stability for the remaining 92.26% (334 min) of the time the controller was used. The relative error of MAP was 7.8 +/- 1.5%. Mean time until extubation was 7 min and 2 s. CONCLUSIONS: We believe the controller can be used to automate taks executed by experts. The controller was useful for stabilizing HR and MAP.

Adult↗
PubMed1998

Influence of chronic alcohol abuse and liver disease on hepatic aldehyde dehydrogenase activity.

Alcohol metabolism results in the production of acetaldehyde, a compound that is much more toxic than ethanol itself. Hepatic aldehyde dehydrogenase (ALDH) is the main enzymatic system responsible for acetaldehyde clearance from the hepatocyte. The objective of this study was to determine the modifications in ALDH activity due to chronic alcohol abuse and liver disease. ALDH activity was determined in samples of liver tissue from 69 alcoholic and 82 nonalcoholic subjects, with and without liver disease. According to the results of liver pathology examination, alcoholic patients were classified into the following groups: controls, with no liver disease (group 1), noncirrhotic liver disease patients (group 2), and cirrhotics (group 3). Nonalcoholic subjects were categorized, using the same criteria, into groups 4, 5, and 6, respectively. ALDH activity was determined spectrophotometrically at two substrate concentrations: 18 mM for total activity and 180 microM for low Km activity. High Km activity was calculated by subtracting the low Km activity value from that of total ALDH activity. Results obtained in each group were expressed as the mean +/- SD of mU of g of wet weight. There were no significant differences when the total ALDH activity from the alcoholic and the nonalcoholic patients with a similar degree of liver pathology were compared: group 1, 1257 +/- 587 vs. group 4, 1328.1 +/- 546.2 (p: NS); group 2, 919.1 +/- 452.4 vs. group 5, 753.5 +/- 412 (p: NS); and group 3, 430.2 +/- 162.4 vs. group 6, 473.2 +/- 225.3 (p: NS). On the other hand, total ALDH activity was significantly lower in cirrhotics than in controls, both among alcoholics (p < 0.01) and among nondrinkers (p < 0.05). The low Km activity was severely reduced in cirrhotics, both alcoholics and nonalcoholics (p < 0.01). High Km activities in cirrhotic patients were low, compared to controls, both in alcoholics and nonalcoholics, although the difference was nonsignificant. The results of the present study suggests that chronic alcohol abuse does not depress ALDH activity. A reduction in the ALDH activity detected in patients with severe liver disease (cirrhotics) was clearly a consequence of liver damage. This reduction was due mainly to a decrease of the low Km ALDH activity, but a trend to a decrease in the high Km ALDH activity was also detected.

Adult↗
PubMed1998

Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity.

The formation of fibrillar deposits of amyloid beta protein (Abeta) in the brain is a pathological hallmark of Alzheimer's disease (AD). A central question is whether Abeta plays a direct role in the neurodegenerative process in AD. The involvement of Abeta in the neurodegenerative process is suggested by the neurotoxicity of the fibrillar form of Abeta in vitro. However, mice transgenic for the Abeta precursor protein that develop amyloid deposits in the brain do not show the degree of neuronal loss or tau phosphorylation found in AD. Here we show that microinjection of plaque-equivalent concentrations of fibrillar, but not soluble, Abeta in the aged rhesus monkey cerebral cortex results in profound neuronal loss, tau phosphorylation and microglial proliferation. Fibrillar Abeta at plaque-equivalent concentrations is not toxic in the young adult rhesus brain. Abeta toxicity in vivo is also highly species-specific; toxicity is greater in aged rhesus monkeys than in aged marmoset monkeys, and is not significant in aged rats. These results suggest that Abeta neurotoxicity in vivo is a pathological response of the aging brain, which is most pronounced in higher order primates. Thus, longevity may contribute to the unique susceptibility of humans to Alzheimer's disease by rendering the brain vulnerable to Abeta neurotoxicity.

Aging↗
PubMed1998

Recovery of minimal change nephrotic syndrome and acute renal failure in a patient withRenal cell carcinoma.

We describe a 78-year-old patient with nephrotic syndrome due to minimal-change glomerulopathy, associated with a renal adenocarcinoma. Oliguric acute renal failure requiring hemodialysis was also observed. Surgical removal of the tumor and corticosteroid therapy resulted in resolution of the nephrotic state and improvement of the renal function. Nephrotic syndrome is an unusual complication of renal cell carcinomas, and the association of minimal-change glomerulopathy (MCG) and solid tumors is particularly uncommon. In spite of this, MCG should be considered in the nephropathies causing nephrotic syndrome and acute renal failure in patients with renal malignancies.

Acute Kidney Injury↗
PubMed1998

Neuronal apoptosis induced by HIV-1 Tat protein and TNF-alpha: potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia.

Apoptosis of neurons and non-neuronal cells has been demonstrated in the brain of AIDS patients with dementia. Previous studies suggest that the apoptotic stimuli are likely to be soluble factors. Several candidates for the soluble factors that lead to neuronal apoptosis in HIV-1 infection have been proposed, including the HIV-1 Tat protein and TNF-alpha. The mechanisms that lead to neuronal apoptosis in the brain of AIDS patients in vivo, may involve the combined effects of more than one pro-apoptotic factor. In this study, we examine whether exposure of primary human neurons to the combination of HIV-1 Tat and TNF-alpha can potentiate the induction of neuronal apoptosis compared with exposure to either factor alone. TNF-alpha was shown to potentiate the induction of neuronal apoptosis by HIV-1 Tat via a mechanism that involves increased oxidative stress. Antioxidants inhibited, but did not completely abolish the induction of neuronal apoptosis by Tat, suggesting that other mechanisms are also likely to be involved. These findings suggest that soluble HIV-1 Tat and TNF-alpha may play a role in neuronal apoptosis induced by HIV-1 infection of the CNS, particularly when present in combination. Our findings further suggest that one mechanism whereby combinations of pro-apoptotic factors may potentiate the induction of neuronal apoptosis in the brain of AIDS patients is by increasing oxidative stress. Understanding the role of oxidative stress and other mechanisms that lead to apoptosis in HIV-1 infection of the CNS may advance the development of new therapeutic strategies to prevent neuronal cell death and improve neurologic function in AIDS patients.

AIDS Dementia Complex↗
PubMed1997

Neuronal localization of presenilin-1 and association with amyloid plaques and neurofibrillary tangles in Alzheimer's disease.

Mutations in the presenilin-1 (PS1) gene is a cause of early- onset familial Alzheimer's disease (AD). Endogenous PS1 is associated with the endoplasmic reticulum in the cell body of undifferentiated SH-SY5Y neuroblastoma cells. At early stages of neuronal differentiation in rat hippocampal culture, PS1 appears in all neuritic processes and in growth cones. In mature differentiated neurons, PS1 is concentrated in the somatodendritic compartment but is also present at lower levels in axons. A similar localization of PS1 is observed in vivo in neurons of the adult human cerebral cortex. In sporadic AD, PS1 appears in the dystrophic neurites of mature amyloid plaques and co-localizes with a subset of intraneuronal neurofibrillary tangles (NFTs). About 30% of hippocampal NFTs are labeled with a highly specific antibody to the PS1 C-terminal loop domain but not with an antibody to the PS1 N terminus. This observation is consistent with a potential association of the PS1 C-terminal fragment with NFTs, because PS1 is constitutively cleaved to N- and C-terminal fragments in neurons. These results suggest that PS1 is highly expressed and broadly distributed during early stages of neuronal differentiation, consistent with a role for PS1 in neuronal differentiation. Furthermore, the co-localization of PS1 with NFTs and plaque dystrophic neurites implicates a role for PS1 in the diverse pathological manifestations of AD.

Alzheimer Disease↗
PubMed1996

Apoptosis induced by HIV-1 infection of the central nervous system.

Apoptosis plays a role in AIDS pathogenesis in the immune system, but its role in HIV-1-induced neurological disease is unknown. In this study, we examine apoptosis induced by HIV-1 infection of the central nervous system (CNS) in an in vitro model and in brain tissue from AIDS patients. HIV-1 infection of primary brain cultures induced apoptosis in neurons and astrocytes in vitro as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and propidium iodide staining and by electron microscopy. Apoptosis was not significantly induced until 1-2 wk after the time of peak virus production, suggesting induction by soluble factors rather than by direct viral infection. Apoptosis of neurons and astrocytes was also detected in brain tissue from 10/11 AIDS patients, including 5/5 patients with HIV-1 dementia and 4/5 nondemented patients. In addition, endothelial cell apoptosis was frequently detected in the brain of AIDS patients and was confirmed by electron microscopy. Most of the apoptotic cells were not localized adjacent to HIV-1-infected cells, providing further evidence for induction by soluble factors. In six non-AIDS control patients with normal brain, apoptotic cells were absent or limited to rare astrocytes. However, TUNEL-positive neurons and astrocytes were frequently detected in seven patients with Alzheimer's disease or abundant senile plaques. These studies suggest that apoptosis is a mechanism of CNS injury in AIDS which is likely to be induced by soluble factors. The apoptosis of endothelial cells in the CNS raises the possibility that some of these factors may be blood-derived.

AIDS Dementia Complex↗
PubMed1996

Amyloid fibril toxicity in Alzheimer's disease and diabetes.

Several lines of evidence suggest that amyloid deposition in the brain contributes to neuronal degeneration in Alzheimer's disease (AD). In the AD brain, diffuse plaques composed mostly of amorphous beta amyloid (Am-beta A) are inert, whereas compact plaques composed of beta amyloid fibrils (Fib-beta A) are associated with neurodegenerative changes. The effects of these two types of amyloid were tested on primary rat hippocampal neurons. Fib-beta A induced the formation of dystrophic neurites and caused neuronal cell death, whereas Am-beta A was not toxic. In addition, Fib-beta A caused synapse loss in the remaining viable neurons, whereas Am-beta A did not significantly affect synapse number. We also examined the effects of amylin, the primary constituent of the amyloid fibrils that form in the pancreas in adult-onset diabetes. Amylin was toxic to rat and human insulin-producing islet cells in the concentration range of fibril formation. The relative toxic potencies of amylin peptides of different species correlated with their fibril-forming capacity. Soluble amylin was not toxic. The amyloid fibril-binding dye Congo red inhibited the toxicity of both beta A and amylin. Congo red afforded protection against toxicity by a dual mechanism. When present during the phase of fibril polymerization, Congo red could inhibit fibril formation from some peptides. When added to preformed fibrils, Congo red bound to fibrils rendering them nontoxic. These results suggest that fibril formation is necessary for both beta A and amylin toxicity. Congo red appears to be a general inhibitor of amyloid fibril toxicity and may therefore be a useful prototype for drugs targeted to the amyloid pathology of AD and adult-onset diabetes.

Alzheimer Disease↗
PubMed1995

beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding.

A central issue in the pathogenesis of Alzheimer's disease (AD) is the relationship between amyloid deposition and neurofibrillary tangle formation. To determine whether amyloid fibril formation affects the phosphorylation state of tau, primary cultures of fetal rat hippocampal and human cortical neurons were treated with beta-amyloid (beta A) in a soluble, amorphous-aggregated, or fibrillar form. Fibrillar beta A, but not soluble or amorphous-aggregated beta A, markedly induces the phosphorylation of tau at Ser-202 and Ser-396/Ser-404, resulting in a shift in the tau M(r) in human cortical neurons. Hyperphosphorylated tau accumulates in the somatodendritic compartment of fibrillar beta A-treated neurons in a soluble form that is not associated with microtubules and is incapable of binding to microtubules in vitro. Dephosphorylation of beta A-induced tau restores its capacity to bind to microtubules. Thus, amyloid fibril formation alters the phosphorylation state of tau, resulting in the loss of microtubule binding capacity and somatodendritic accumulation, properties also exhibited by tau in the AD brain. Amyloid fibril formation may therefore be a cause of abnormal tau phosphorylation in AD.

Amyloid beta-Peptides↗
PubMed1995

[Esophageal intramural pseudodiverticulosis].

Esophageal intramural pseudodiverticulosis is an uncommon and benign primary disease of the esophagus. Less than 150 cases have been reported. We report a new case diagnosed by endoscopy during the investigation of an upper gastrointestinal bleeding, in a 48-year-old man who was assymptomatic from the esophageal point of view. We discuss the clinical, pathogenic, diagnostic and therapeutic aspects of this disease.

Diagnosis, Differential↗
PubMed1995

[Jejuno-ileal volvulus, a rare cause of intestinal obstruction].

Volvulus of the small bowel without predisposing anatomical defects is a rare cause of acute intestinal obstruction in the Western world, and its incidence is decreasing in Europe and America, although it is common in others parts of the world. The causes of primary volvulus of the small bowel and the mechanism of rotation of the entire root of the mesentery remain unexplained. Several anatomical and dietary factors have been implicated. This theory requires strong peristalsis, tense, firm abdominal muscles and feeding pattern of very bulky meals taken at long intervals. In the present case, a large quantity of bulky poorly digested food consumed previously, and strong abdominal muscles are in keeping with the above theory.

Abdominal Muscles↗