Fructose promotes more than glucose the adipocytic differentiation of pig mesenchymal stem cells.

The goal of this study was to evaluate how glucose and fructose affected the adipose differentiation of pig newborn mesenchymal stem cells (MSCs). Cells were grown with or without inosine in 7.5 mM glucose (substituted with 1.5 or 6 mM fructose). MSCs displayed adipose morphology after 70 days of differentiation. Fructose stimulated the highest levels of PPARγ and C/EBPß. Fructose at 6 mM, but not glucose at 7.5 mM or fructose at 1.5 mM, promotes differentiation of MSCs into adipocytes and increases 11-hydroxysteroid dehydrogenase (11ß-HSD1) and NADPH oxidase 4 (NOX4) mRNA in the absence of hepatic effects (as simulated by the inosine). Fructose and glucose increased xanthine oxide-reductase (XOR) catalytic activity almost 10-fold and elevated their products: intracellular reactive oxygen species (ROS) pool, extracellular H2 O2 pool by 4 orders of magnitude, and uric acid by a factor of 10. Therefore, in our experimental model, differentiation of MSCs into adipocytes occurs exclusively at the blood concentration of fructose detected after ingestion by people on a high fructose diet. PRACTICAL APPLICATIONS: The results of this study provide new evidence for fructose's adipogenic potential in mesenchymal stem cells, a model in which its effects on XOR activity had not been studied. The increased expression of genes such as C/EBPß, PPARγ, and NOX4, as well as the increased XOR activity and high production of ROS during the differentiation process in the presence of fructose, coincides in pointing to this hexose as an important factor in the development of adipogenesis in young animals, which could have a great impact on the development of future obesity.

Glucocorticoid gene regulation of aquaporin-7.

AQP7 is the primary glycerol transporter in white (WAT) and brown (BAT) adipose tissues. There are immediate and quantitatively important actions of cortisone over the expression of AQP7 in murine and human adipocytes. Short-term response (minutes) of cortisone treatment result in an mRNA overexpression in white and brown differentiated adipocytes (between 1.5 and 6 folds). Conversely, long-term response (hours or days) result in decreased mRNA expression. The effects observed on AQP7 mRNA expression upon cortisone treatment in brown and white differentiated adipocytes are concordant with those observed for GK and HSD1B11.

Newly synthesized cAMP is integrated at a membrane protein complex signalosome to ensure receptor response specificity.

Spatiotemporal regulation of cAMP within the cell is required to achieve receptor-specific responses. The mechanism through which the cell selects a specific response to newly synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and independent cAMP-responsive signaling protein macrocomplexes that produce, use, degrade, and regulate their own nondiffusible (sequestered) cAMP pool to achieve their specific responses. Each complex responds to the stimulation of an adenosine G protein-coupled receptor (Ado-GPCR), bound to either A2A or A2B , but not simultaneously to both. Each isoprotein involved in each signaling cascade was identified by measuring changes in cAMP levels after receptor activation, and its participation was confirmed by antibody-mediated inactivation. A2A -Ado-GPCR selective stimulation activates adenylyl cyclase 6 (AC6), which is bound to AKAP79/150, to synthesize cAMP which is used by two other AKAP79/150-tethered proteins: protein kinase A (PKA) and phosphodiesterase 3A (PDE3A). In contrast, A2B -Ado-GPCR stimulation activates D-AKAP2-attached AC5 to generate cAMP, which is channeled to two other D-AKAP2-tethered proteins: guanine-nucleotide exchange factor 2 (Epac2) and PDE3B. In both cases, prior activation of PKA or Epac2 with selective cAMP analogs prevents de novo cAMP synthesis. In addition, we show that cAMP does not diffuse between these protein macrocomplexes or 'signalosomes'. Evidence of coimmunoprecipitation and colocalization of some proteins belonging to each signalosome is presented. Each signalosome constitutes a minimal functional signaling unit with its own machinery to synthesize and regulate a sequestered cAMP pool. Thus, each signalosome is devoted to ensure the transmission of a unique and unequivocal message through the cell.

HSD1 and AQP7 short-term gene regulation by cortisone in 3T3-L1 adipocytes.

Adipose Tissue (AT) is a complex organ with a crucial regulatory role in energy metabolism and in the development of obesity and the Metabolic Syndrome (MS). Modified responses and the metabolism of hormones have been observed in visceral adiposity during obesity, specifically as related with cortisone. The objective of this study was to assess, in the 3T3-L1 adipocyte cell line, the short-term effect of cortisone on the expression of 11ß-Hydroxysteroid dehydrogenase 1 (Hsd1), which is responsible for activation of cortisone into cortisol, and for Aquaporin 7 (Aqp7), involved in glycerol transport through the cell membrane. Total RNA (tRNA) and complementary DNA (cDNA) were obtained from cell samples treated with cortisone (0.1, 1, and 10 µM) during different times (0, 5, 10, 15, and 20 min, and 48 h) to quantify the expression of the aforementioned genes by real time PCR employing MnSOD and Ppia as housekeeping genes. There was a time-dependent response of Aqp7, a dose-dependent response of Hsd1, and an increase observed in the expression of both genes during min 1 of treatment (5- and 6-fold, respectively), followed by a decrease during the following 5-10 min (P < 0.05). With the 1-µM cortisone treatment, both genes showed cubic tendencies in their expression; the Hsd1 tendency is described by the equation y = 0.18×(3)-1.65×(2)+3.59x+1.31, while the Aqp7 tendency is described by y = 0.33×(3)-2.67×(2)+4.93x+1.84. There are immediate and quantitatively important actions of cortisone on the expression of Aqp7 and Hsd1 in 3T3-L1 adipocytes.

Bovine (Bos taurus) Bone Marrow Mesenchymal Cell Differentiation to Adipogenic and Myogenic Lineages.

PURPOSE: We evaluated the effect of peroxisome proliferator-activated receptor (PPAR) agonists on the differentiation and metabolic features of bovine bone marrow-derived mesenchymal cells induced to adipogenic or myogenic lineages. METHODS: Cells isolated from 7-day-old calves were cultured in basal medium (BM). For adipogenic differentiation, cells were cultured for one passage in BM and then transferred to a medium supplemented with either rosiglitazone, telmisartan, sirtinol or conjugated c-9, t-11 linoleic acid; for myogenic differentiation, third-passage cells were added with either bezafibrate, telmisartan or sirtinol. The expression of PPARx03B3; (an adipogenic differentiation marker), myosin heavy chain (MyHC; a myogenic differentiation marker) and genes related to energy metabolism were measured by quantitative real-time PCR in a completely randomized design. RESULTS: For adipogenic differentiation, 20 µM telmisartan showed the highest PPARx03B3; expression (15.58 ± 0.62-fold, p < 0.0001), and differences in the expression of energy metabolism-related genes were found for hexokinase II, phosphofructokinase, adipose triglyceride lipase, acetyl-CoA carboxylase α(ACACα) and fatty acid synthase (p < 0.001), but not for ACACß (p = 0.4275). For myogenic differentiation, 200 µM bezafibrate showed the highest MyHC expression (73.98 ± 11.79-fold), and differences in the expression of all energy metabolism-related genes were found (p < 0.05). CONCLUSIONS: Adipocyte and myocyte differentiation are enhanced with telmisartan and bezafibrate, respectively, and energy uptake, storage and mobilization are improved with both.

Taurine in adipocytes prevents insulin-mediated H2O2 generation and activates Pka and lipolysis.

Among many actions assigned to taurine (Tau), the most abundant amino acid in numerous mammalian tissues, it prevents high-fat diet-induced obesity with increasing resting energy expenditure. To sustain this Tau action, the goal of the present study was to explore the acute effects of Tau on baseline and on adrenaline, insulin and their second messengers to modulate lipolysis in white adipose tissue (WAT) cells from rat epididymis. The Tau effects in this topic were compared with those recorded with Gly, Cys and Met. Tau on its own did not modify baseline lipolysis. Tau raised isoproterenol- and dibutyryl-cAMP (Bt2cAMP)-activated glycerol release. Gly diminished Bt2cAMP-activated glycerol release, and Cys and Met had no effect. Cyclic AMP-dependent activation of protein kinase A (PKA) in cell-free extracts decreased slightly by Gly and was unaltered by Cys, Met, and Tau. PKA catalytic activity in cell-free extracts was stimulated by Tau and unchanged by Cys, Gly and Met. Gly and Tau effects on PKA disappeared when these amino acids were withdrawn by gel filtration. Insulin-mediated NADPH-oxidase (NOX) raises H2O2 pool, which promotes PKA subunit oxidation, and precludes its cAMP activation; thus, lipolysis is diminished. Tau, but not Cys, Gly and Met, inhibited, by as much as 70%, insulin-mediated H2O2 pool increase. These data suggested that Tau raised lipolysis in adipocytes by two mechanisms: stimulating cAMP-dependent PKA catalytic activity and favoring PKA activation by cAMP as a consequence of lowering the H2O2 pool.

NOX2 activated by α1-adrenoceptors modulates hepatic metabolic routes stimulated by ß-adrenoceptors.

The NADPH oxidase (NOX) family of enzymes oxidase catalyzes the transport of electrons from NADPH to molecular oxygen and generates O(2)(•-), which is rapidly converted into H(2)O(2). We aimed to identify in hepatocytes the protein NOX complex responsible for H(2)O(2) synthesis after α(1)-adrenoceptor (α(1)-AR) stimulation, its activation mechanism, and to explore H(2)O(2) as a potential modulator of hepatic metabolic routes, gluconeogenesis, and ureagenesis, stimulated by the ARs. The dormant NOX2 complex present in hepatocyte plasma membrane (HPM) contains gp91(phox), p22(phox), p40(phox), p47(phox), p67(phox) and Rac 1 proteins. In HPM incubated with NADPH and guanosine triphosphate (GTP), α(1)-AR-mediated H(2)O(2) synthesis required all of these proteins except for p40(phox). A functional link between α(1)-AR and NOX was identified as the Gα(13) protein. Alpha(1)-AR stimulation in hepatocytes promotes Rac1-GTP generation, a necessary step for H(2)O(2) synthesis. Negative cross talk between α(1)-/ß-ARs for H(2)O(2) synthesis was observed in HPM. In addition, negative cross talk of α(1)-AR via H(2)O(2) to ß-AR-mediated stimulation was recorded in hepatocyte gluconeogenesis and ureagenesis, probably involving aquaporine activity. Based on previous work we suggest that H(2)O(2), generated after NOX2 activation by α(1)-AR lightening in hepatocytes, reacts with cAMP-dependent protein kinase A (PKA) subunits to form an oxidized PKA, insensitive to cAMP activation that prevented any rise in the rate of gluconeogenesis and ureagenesis.

Natural alcohol exposure: is ethanol the main substrate for alcohol dehydrogenases in animals?

Alcohol dehydrogenase (ADH) activity is widely distributed in all phyla. In animals, three non-homologous NAD(P)(+)-dependent ADH protein families are reported. These arose independently throughout evolution and possess different structures and mechanisms of reaction: type I (medium-chain) ADHs are zinc-containing enzymes and comprise the most studied group in vertebrates; type II (short-chain) ADHs lack metal cofactor and have been extensively studied in Drosophila; and type III ADHs are iron-dependent/-activated enzymes that were initially identified only in microorganisms. The presence of these different ADHs in animals has been assumed to be a consequence of chronic exposure to ethanol. By far the most common natural source of ethanol is fermentation of fruit sugars by yeast, and available data support that this fruit trait evolved in concert with the characteristics of their frugivorous seed dispersers. Therefore, if the presence of ADHs in animals evolved as an adaptive response to dietary ethanol exposure, then it can be expected that the enzymogenesis of these enzymes began after the appearance of angiosperms with fleshy fruits, because substrate availability must precede enzyme selection. In this work, available evidence supporting this possibility is discussed. Phylogenetic analyses reveal that type II ADHs suffered several duplications, all of these restricted to flies (order Diptera). Induction of type II Adh by ethanol exposure, a positive correlation between ADH activity and ethanol resistance, and the fact that flies and type II Adh diversification occurred in concert with angiosperm diversification, strongly suggest that type II ADHs were recruited to allow larval flies to exploit new restricted niches with high ethanol content. In contrast, phyletic distribution of types I and III ADHs in animals showed that these appeared before angiosperms and land plants, independently of ethanol availability. Because these enzymes are not induced by ethanol exposure and possess a high affinity and/or catalytic efficiency for non-ethanol endogenous substrates, it can be concluded that the participation of types I and III ADHs in ethanol metabolism can be considered as incidental, and not adaptive.

Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia-reperfusion injury.

The present study was aimed to assess the effect of protein carbonylation (PC) in hepatic cells and effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on indicators of tissue damage induced by liver ischemia-reperfusion injury (LIRI). Warm ischemia was performed by partial vascular occlusion during 90 min in Wistar rats. In serum, we determined the catalytic activity of Alanine Aminotransferase, Aspartate Aminotransferase, Lacticate Dehydrogenase, and Ornithine Carbamoyltransferase. In liver samples, we studied cellular alterations by means of histologic studies, lipid peroxidation, PC by immunohistochemistry, apoptosis and reactive oxygen species in bile by electron paramagnetic resonance. Based on PC data, sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were the first to exhibit LIRI-associated oxidative damage and prior to parenchymal cells. Administration of piroxicam or meloxicam during the pre-ischemic period produced a highly significant decrease in all studied injury indicators. No significant differences were revealed between the protective action of the two drugs. The data shown here suggest the potential use of NSAIDs such as piroxicam or meloxicam in minimizing ischemic event-caused damage in liver. We also propose that PC may be employed as an adequate tool to assess tissue damage after oxidative stress.

Role of ischemic preconditioning in liver surgery and hepatic transplantation.

INTRODUCTION: The purpose of this review is to summarize intraoperative surgical strategies available to decrease ischemia-reperfusion injury associated with liver resection and liver transplantation. MATERIAL AND METHOD: We conducted a critical review of the literature evaluating the potential applications of hepatic ischemic preconditioning (IPC) for hepatic resection surgery and liver transplantation. In addition, we provide a basic bench-to-bedside summary of the liver physiology and cell signaling mechanisms that account for the protective effects seen with hepatic IPC.

Factors in the pathophysiology of the liver ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury is commonplace in liver surgery, particularly in hepatic transplantation, hepatic resection, and trauma. The signaling events contributing to local hepatocellular damage are diverse and complex and involve the interaction between hepatocytes, sinusoidal endothelial cells, Kupffer cells, as well as infiltrating neutrophils, macrophages, and platelets. Signaling mediators include cytokines, reactive oxygen and nitrogen species, calcium, complement, and several transcription factors. The purpose of this review article was to summarize the factors that contribute to the pathophysiology of hepatic ischemia-reperfusion injury.

Adrenaline stimulates H2O2 generation in liver via NADPH oxidase.

It is known that adrenaline promotes hydroxyl radical generation in isolated rat hepatocytes. The aim of this work was to investigate a potential role of NADPH oxidase (Nox) isoforms for an oxidative stress signal in response to adrenaline in hepatocytes. Enriched plasma membranes from isolated rat liver cells were prepared for this purpose. These membranes showed catalytic activity of Nox isoforms, probably Nox 2 based on its complete inhibition with specific antibodies. NADPH was oxidized to convert O(2) into superoxide radical, later transformed into H(2)O(2). This enzymatic activity requires previous activation with either 3 mM Mn(2+) or guanosine 5'-0-(3-thiotriphosphate) (GTPgammaS) plus adrenaline. Experimental conditions for activation and catalytic steps were set up: ATP was not required; S(0.5) for NADPH was 44 microM; S(0.5) for FAD was 8 microM; NADH up to 1 mM was not substrate, and diphenyleneiodonium was inhibitory. Activation with GTPgammaS plus adrenaline was dose- and Ca(2+)-dependent and proceeded through alpha(1)-adrenergic receptors (AR), whereas beta-AR stimulation resulted in inhibition of Nox activity. These results lead us to propose H(2)O(2) as additional transduction signal for adrenaline response in hepatic cells.

Ethanol-mediated oxidative changes in blood lipids and proteins are reversed by aspirin-like drugs.

BACKGROUND: Previous work from our laboratory revealed that administration of selected nonsteroidal anti-inflammatory drugs (NSAIDs)-aspirin, naproxen, nimesulide, and piroxicam-prevented some signs of oxidative stress produced in rat livers acutely intoxicated with ethanol. Our final aim was to pursue these advantageous effects of NSAIDs in humans in relation to opposing the oxidative action of ethanol. In preparation for these studies, we conducted a search for tissues that were more accessible than liver, such as plasma and blood cells. METHODS: Either ethanol (5 g/kg body weight) or an isocaloric amount of glucose from a 30% solution alone or combined with one of the NSAIDs was administered orogastrically to rats; animals were sacrificed 5 h later. RESULTS: Ethanol increased both protein carbonylation (PCO) and thiobarbituric acid reactive substances (TBARS) in isolated lymphocytes, increased proteolysis in isolated red blood cells (RBC), and decreased the pool of plasma amino acids. The NSAIDs employed reversed the ethanol-mediated rise in PCO in plasma, but with the exception of aspirin failed to prevent the ethanol-produced decrease in the amino-acid serum pool. Additionally, the increase in TBARS and PCO promoted by ethanol in lymphocytes was reverted with aspirin. In contrast, ethanol-activated proteolysis was not modified by aspirin. CONCLUSIONS: The pro-oxidant effects of ethanol and certain beneficial actions of NSAIDs, especially those of aspirin, preventing these pro-oxidant effects can be followed in blood constituents of rats. Hence, these oxidative markers could be regarded as potential clinical monitors for ethanol-mediated oxidative stress.

In rat hepatocytes, different adenosine receptor subtypes use different secondary messengers to increase the rate of ureagenesis.

In rat hepatocytes, the role of cAMP and Ca(2+) as secondary messengers in the ureagenic response to stimulation of specific adenosine receptor subtypes was explored. Analyzed receptor subtypes were: A(1), A(2A), A(2B) and A(3). Each receptor subtype was stimulated with a specific agonist while blocking all other receptor subtypes with a battery of specific antagonists. For the A(1) and A(3) adenosine receptor subtypes, the secondary messenger was the cytoplasmic Ca(2+) concentration ([Ca(2+)](cyt)). Accordingly, the A(1) or A(3)-mediated increase in [Ca(2+)](cyt) and in ureagenic activity were both inhibited by chelating Ca(2+) with either EGTA or BAPTA-AM. Also, Gd(3+) blocked both the increase in [Ca(2+)](cyt) and ureagenesis, suggesting that a Ca(2+) channel may be involved in the response to both A(1) and A(3). A partial effect was observed with the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. The concentration of cyclic AMP ([cAMP]) increased in response to stimulation of either the A(2A) or the A(2B) adenosine receptor subtypes, while it decreased slightly in response to stimulation of either A(1) or A(3). The stimulation of either the A(2A) or A(2B) adenosine receptor subtypes resulted in an increase in [cAMP] and an ureagenic response which were not sensitive to EGTA, BAPTA-AM, Gd(3+) or to thapsigargin. In addition, the adenylyl cyclase inhibitor MDL12,330A blocked the ureagenic response to A(2A) and A(2B), but not the response to either A(1) or A(3). Our results indicate that in the ureagenic liver response to adenosine, the secondary messenger for both, the A(1) and A(3) adenosine receptor subtypes is [Ca(2+)](cyt), while the message from the A(2A) and A(2B) adenosine receptor subtypes is relayed by [cAMP].

Inosine released after hypoxia activates hepatic glucose liberation through A3 adenosine receptors.

Inosine, an endogenous nucleoside, has recently been shown to exert potent effects on the immune, neural, and cardiovascular systems. This work addresses modulation of intermediary metabolism by inosine through adenosine receptors (ARs) in isolated rat hepatocytes. We conducted an in silico search in the GenBank and complete genomic sequence databases for additional adenosine/inosine receptors and for a feasible physiological role of inosine in homeostasis. Inosine stimulated glycogenolysis (approximately 40%, EC50 4.2 x 10(-9) M), gluconeogenesis (approximately 40%, EC50 7.8 x 10(-9) M), and ureagenesis (approximately 130%, EC50 7.0 x 10(-8) M) compared with basal values; these effects were blunted by the selective A3 AR antagonist 9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino][1,2,4]-triazolo[1,5-c]quinazoline (MRS 1220) but not by selective A1, A2A, and A2B AR antagonists. In addition, MRS 1220 antagonized inosine-induced transient increase (40%) in cytosolic Ca2+ and enhanced (90%) glycogen phosphorylase activity. Inosine-induced Ca2+ mobilization was desensitized by adenosine; in a reciprocal manner, inosine desensitized adenosine action. Inosine decreased the cAMP pool in hepatocytes when A1, A2A, and A2B AR were blocked by a mixture of selective antagonists. Inosine-promoted metabolic changes were unrelated to cAMP decrease but were Ca2+ dependent because they were absent in hepatocytes incubated in EGTA- or BAPTA-AM-supplemented Ca2+-free medium. After in silico analysis, no additional cognate adenosine/inosine receptors were found in human, mouse, and rat. In both perfused rat liver and isolated hepatocytes, hypoxia/reoxygenation produced an increase in inosine, adenosine, and glucose release; these actions were quantitatively greater in perfused rat liver than in isolated cells. Moreover, all of these effects were impaired by the antagonist MRS 1220. On the basis of results obtained, known higher extracellular inosine levels under ischemic conditions, and inosine's higher sensitivity for stimulating hepatic gluconeogenesis, it is suggested that, after tissular ischemia, inosine contributes to the maintenance of homeostasis by releasing glucose from the liver through stimulation of A3 ARs.

Los estándares científicos de productividad en la Facultad de Medicina de la UNAM / Scientific Productivity Standards and the National Autonomous University of Mexico School of Medicine

En este trabajo se hizo un análisis de la producción científica que se reportó en los Informes Oficiales de la Facultad de Medicina de la Universidad Nacional Autónoma de México del año 1999 a 2002. 1) Se recuperó 94.83% del total de publicaciones internacionales ahí reportadas. 2) El factor de impacto de las revistas en donde publican los profesores e investigadores está dentro del promedio nacional de 2.5 reportado por el CONACYT para el periodo 1998-2002. 3) De las publicaciones 58.98% tiene como autor de correspondencia al personal académico de la Facultad de Medicina, mientras 27.80% fue de colaboraciones nacionales, 9.83% colaboraciones internacionales y 3.37% corresponde a publicaciones personales. 4) Con el criterio de autor de correspondencia y colaboraciones se identificaron a líderes académicos. 5) Existe desigualdad en laproducción en los diferentes departamentos académicos. 6) El área básica de la Facultad de Medicina contribuye con 14% de las publicaciones nacionales y atiende en promedio a 2450 alumnos anualmente. Se propone que análisis como el presente podría ser el idóneo para instrumentar políticas de investigación.

The scientific production at the National Autonomous University of Mexico (Universidad Nacional Autónoma de México, UNAM) School of Medicine was analyzed during the period from 1999 to 2002. We found the following: 1) 94.83% of total international scientific papers was recovered; 2) mean impact factor had a value of 2.5, ca. the value reported by CONACYT, México, for the period 1998-2002; 3) percentage of corresponding authors was 58.83%, 27.80% of papers were national collaborations, 9.83% were international collaborations, and 3.37% corresponded to personal publications; 4) by using corresponding author and collaborations, academic leaders were identified; 5) there are differences among academic departments, and 6) basic research from the UNAM School of Medicine contributes 14% of national research and teaches ca. 2,450 students per year. It is proposed that this type of analysis shouldbe used to establish the politics of science.

Release of mitochondrial rather than cytosolic enzymes during liver regeneration in ethanol-intoxicated rats.

BACKGROUND: Partial hepatectomy (PH) promoted rapid increase in serum of hepatic enzyme activities localized in mitochondria preferentially to increase enzyme activities from cytosol; low doses of ethanol (EtOH) administered to PH rats expedited return to normality of these elevated serum enzyme activities. The fate of released mitochondrial enzymes from liver was investigated in this study to advance knowledge of the role of mitochondria during priming phase of liver regeneration. METHODS: Catalytic activity of mitochondrial and cytosolic proteins was measured in remnant liver after PH and in elutes of perfused remnant livers from control and ethanol-intoxicated rats. RESULTS: During the first 24 h of liver regeneration (LR), mitochondrial enzymes--glutamate dehydrogenase, aspartate amino transferase, and malate dehydrogenase--diminished 33-58% in mitochondria, increased 17% in cytosol, and for two enzymes rose 68-86% in perfusates. Cytosolic lactate dehydrogenase decreased transiently in cytosol (24%) and increased only 13% in perfusates. Activity of cytochrome oxidase [corrected] (mitochondrial membrane-attached enzymes) was not modified. Ethanol intoxication after PH produced earlier and slightly higher extrusion of matrix mitochondrial enzyme activities. CONCLUSIONS: Selective increase of mitochondrial membrane permeability appeared as an important event during priming phase of LR after PH, thus sustaining preferential release of mitochondrial proteins outside the organelle in comparison with limited redistribution of cytosolic and mitochondrial membrane proteins. High doses of EtOH delayed LR and re-enforced mobilization of proteins produced by PH probably by enhancing greater mitochondrial membrane permeability.

[Scientific productivity standards and the National Automous University of Mexico School of Medicine]. / Los estándares científicos de productividad en la Facultad de Medicina de la UNAM.

The scientific production at theNational Autonomous University of Mexico (Universidad Nacional Autónoma de México, UNAM) School of Medicine was analyzed during the period from 1999 to 2002. We found the following: 1) 94.83% of total international scientific papers was recovered; 2) mean impact factor had a value of 2.5, ca. the value reported by CONACYT, México, for the period 1998-2002; 3) percentage of corresponding authors was 58.83%, 27.80% of papers were national collaborations, 9.83% were international collaborations, and 3.37% corresponded to personal publications; 4) by using corresponding author and collaborations, academic leaders were identified; 5) there are differences among academic departments, and 6) basic research from the UNAM School of Medicine contributes 14% of national research and teaches ca. 2,450 students per year. It is proposed that this type of analysis should be used to establish the politics of science.

Adrenaline (via alpha(1B)-adrenoceptors) and ethanol stimulate OH* radical production in isolated rat hepatocytes.

Adrenaline is able to increase the oxidative damage caused by some xenobiotic agents in the liver. Ethanol produces oxidative changes in hepatic tissue, while an acute intoxication with alcohol increases adrenaline blood levels. The aim of this study was to determine whether adrenaline increases ethanol-induced hydroxyl free radical production in isolated hepatocytes. Adrenaline augmented hydroxyl radicals in a concentration-dependent manner and was blocked by chloroethylclonidine, an alpha(1B)-adrenoceptor antagonist, while adrenaline plus ethanol added their individual effects. It is suggested that adrenaline increases hydroxyl radicals by an alpha(1B)-adrenoceptor-mediated mechanism, while ethanol does so by a receptor-independent mechanism.