Biomedical subjects

Manuel Rodriguez

Publications and source records attributed to Manuel Rodriguez.

8 recordsLinked to original sources

PubMed2007

Substantia nigra osmoregulation: taurine and ATP involvement.

An extracellular nonsynaptic taurine pool of glial origin was recently reported in the substantia nigra (SN). There is previous evidence showing taurine as an inhibitory neurotransmitter in the SN, but the physiological role of this nonsynaptic pool of taurine has not been explored. By using microdialysis methods, we studied the action of local osmolarity on the nonsynaptic taurine pool in the SN of the rat. Hypoosmolar pulses (285-80 mosM) administered in the SN by the microdialysis probe increased extrasynaptic taurine in a dose-dependent way, a response that was counteracted by compensating osmolarity with choline. The opposite effect (taurine decrease) was observed when osmolarity was increased. Under basal conditions, the blockade of either the AMPA-kainate glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dionine disodium or the purinergic receptors with pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid modified the taurine concentration, suggesting that both receptors modulate the extrasynaptic pool of taurine. In addition, these drugs decreased the taurine response to hypoosmolar pulses, suggesting roles for glutamatergic and purinergic receptors in the taurine response to osmolarity. The participation of purinergic receptors was also supported by the fact that ATP (which, under basal conditions, increased the extrasynaptic taurine in a dose-dependent way) administered in doses saturating purinergic receptors also decreased the taurine response to hypoosmolarity. Taken together, present data suggest osmoregulation as a role of the nonsynaptic taurine pool of the SN, a function that also involves glutamate and ATP and that could influence the nigral cell vulnerability in Parkinson's disease.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2006

Heterogeneous dopamine neurochemistry in the striatum: the fountain-drain matrix.

In contrast to the relatively high attention paid to the structural heterogeneity of striatal dopamine (DA) innervation, little attention has been focused on the possible striatal heterogeneity for release and uptake of DA. By using amperometric methods, we found striatal regions showing a DA decrease during the medial forebrain bundle stimulation (drain areas) near to other zones that showed an increase in DA concentration (fountain areas). Both areas were intermixed to form a tridimensional matrix to regulate DA concentration throughout the striatum (fountain-drain matrix). The response to electrical stimuli of different amplitudes and durations and to different drugs (alpha-methyl-l-tyrosine, cocaine, gamma-butyrolactone, and haloperidol) suggests that regional differences for both DA release/DA uptake and DA cell firing autoregulation are behind the striatal fountain-drain matrix. The high diversity of DA activity observed in the striatum is a new framework for analyzing experimental and clinical phenomena.

Animals↗

PubMed2005

Postoperative evolution of inflammatory response in a model of suprarenal aortic cross-clamping with and without hemorrhagic shock. Systemic and local reactions.

Surgery of the abdominal aorta generates a systemic inflammatory response (SIR), a source of operative morbidity-mortality. In the present work we attempted to evaluate the evolution of SIR in an experimental model that simulates elective and urgent surgery on the abdominal aorta. Fifteen mini-pigs divided into three groups were used. The animals were subjected to suprarenal aortic/iliac clamping and bypass with a Dacron-collagen prosthetic graft. Groups were as follows: (1) sham (only aortic dissection); (2) clamping and bypass; (3) hemorrhage of 40%, pre-clamping, and bypass. Determinations included (1) tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1beta, IL-6, IL-10, interferon-gamma; (2) myeloperoxidase (MPO), superoxide anion (SOA), superoxide dismutase (SOD), and malondialdehyde (MDA); (3) nitrites; (4) iNOS, (5) cell adhesion molecules (ICAM-1, VCAM-1) at 24 hours, 48 hours, and on day 7; and (6) NFkappaB at 48 hours. Our results point to an increase in all inflammatory variables, corroborated by their molecular regulators such as the expression of CAMs, iNOS, and NFkappaB. The alterations tended to normalize by day 7, after reperfusion. The results point to the great importance of SIR at all levels (molecular, nuclear, cellular, and systemic) in situations such as elective and urgent abdominal aorta surgery and the role that control of this response could represent for the future of vascular surgery.

Animals↗

PubMed2005

Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation.

The inducible transcriptional complex AP-1, composed of c-Fos and c-Jun proteins, is crucial for cell adaptation to many environmental changes. While its mechanisms of activation have been extensively studied, how its activity is restrained is poorly understood. We report here that lysine 265 of c-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of c-Fos preferentially occurs in the context of c-Jun/c-Fos heterodimers. Using nonsumoylatable mutants of c-Fos and c-Jun as well as a chimeric protein mimicking sumoylated c-Fos, we show that sumoylation entails lower AP-1 transactivation activity. Interestingly, single sumoylation at any of the three acceptor sites of the c-Fos/c-Jun dimer is sufficient to substantially reduce transcription activation. The lower activity of sumoylated c-Fos is not due to inhibition of protein entry into the nucleus, accelerated turnover, and intrinsic inability to dimerize or to bind to DNA. Instead, cell fractionation experiments suggest that decreased transcriptional activity of sumoylated c-Fos is associated with specific intranuclear distribution. Interestingly, the phosphorylation of threonine 232 observed upon expression of oncogenically activated Ha-Ras is known to superactivate c-Fos transcriptional activity. We show here that it also inhibits c-Fos sumoylation, revealing a functional antagonism between two posttranslational modifications, each occurring within a different moiety of a bipartite transactivation domain of c-Fos. Finally we report that the sumoylation of c-Fos is a dynamic process that can be reversed via multiple mechanisms. This supports the idea that this modification does not constitute a final inactivation step that necessarily precedes protein degradation.

Binding Sites↗

PubMed2005

Preintervention analysis and improvement of customer greeting in a restaurant.

We examined customer greeting by employees at one location of a sandwich restaurant chain. First, a preintervention analysis was conducted to determine the conditions under which greeting a customer within 3 s of his or her entry into the restaurant did and did not occur. Results suggested that an appropriate customer greeting was most likely to occur when a door chime was used to indicate that a customer had entered the store and when the store manager was present behind the service counter. Next, a performance improvement intervention, which consisted of the combination of the use of a door chime and manager presence, was evaluated. Results showed that during baseline, a mean of 6% of customers were greeted; during intervention a mean of 63% of customers were greeted. The addition of manager-delivered verbal and graphic group feedback resulted in 100% of customers being greeted across two consecutive sessions.

Adolescent↗

PubMed2004

Apoptosis: measurement and technical issues.

In this short review article we discuss the many uncertainties with the estimation of the relevance of data on the rate of apoptotic cell death in the myocardium. 1. The time course and duration of the apoptotic cascade is still almost completely unknown, in cardiac tissue as well as in myocytes in culture. 2. The mode of removal of dead cells from their connections to neigbouring myocytes at the intercalated disc is still unidentified. 3. At what step in the apoptotic cascade is this process still reversible? 4. Numerous methods exist for the identification of apoptotic cells. However, their sensitivity and specificity vary and issues such as different dwell times of cells with DNA fragmentation further complicate the reliability of apoptotic rates obtained. 5. Statistical principles should be applied for the quantification of apoptotic cells. Only after clarification of these technical issues an unequivocal answer to the problem of apoptotic myocyte loss in different cardiac pathologies can be expected.

Animals↗

PubMed2003

Hand-assisted laparoscopic surgery.

HYPOTHESIS: Hand-assisted laparoscopic surgery (HALS) has been proposed as a useful alternative to conventional open or laparoscopic surgery. However, most information is fragmented and comes from specific or selective indications. To assess the current situation of HALS, a general overview of the fields of application, results, and quality of the evidence of these results is necessary. DATA SOURCES: Current English-language literature review. STUDY SELECTION: Case reports, series, and opinion articles on HALS. DATA EXTRACTION AND SYNTHESIS: Evaluation of the type of study and results. Most of the articles are short case series. Only a few comparative or randomized comparative trials on HALS for splenectomy and colectomy have been published. CONCLUSIONS: Hand-assisted laparoscopic surgery seems to be a promising technique that has been applied with success in a wide range of digestive tract-related surgical procedures. The main role is to help in difficult cases before conversion is necessary or for training unskilled surgeons, and not as an alternative to pure laparoscopic surgery. However, not enough evidence-based data are available to know exactly the final outcome of this technique in general surgery. Prospective randomized trials with established open or laparoscopic procedures are lacking, and these trials are needed to support the final role of HALS.

Colectomy↗

PubMed2003

Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT.

Nonselective beta-blockers are very effective in preventing first variceal bleeding in patients with cirrhosis. Treatment with isosorbide-5-mononitrate (IS-MN) plus propranolol achieves a greater reduction in portal pressure than propranolol alone. The present multicenter, prospective, double-blind, randomized, controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding. A total of 349 consecutive cirrhotic patients with gastroesophageal varices were randomized to receive propranolol + placebo (n = 174) or propranolol + IS-MN (n = 175). There were no significant differences in the 1- and 2-year actuarial probability of variceal bleeding between the 2 groups (propranolol + placebo, 8.3% and 10.6%; propranolol + IS-MN, 5% and 12.5%). The only independent predictor of variceal bleeding was a variceal size greater than 5 mm. However, among patients with varices greater than 5 mm (n = 196), there were no significant differences in the incidence of variceal bleeding between the 2 groups. Survival was also similar. Adverse effects were significantly more frequent in the propranolol + IS-MN group due to a greater incidence of headache. There were no significant differences in the incidence of new-onset or worsening ascites or in impairment of renal function. In conclusion, propranolol effectively prevents variceal bleeding. Adding IS-MN does not further decrease the low residual risk of bleeding in patients receiving propranolol. However, the long-term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding.

Adrenergic beta-Antagonists↗