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1.
Open Biol ; 13(5): 220370, 2023 05.
Article in English | MEDLINE | ID: mdl-37192671

ABSTRACT

Nitric oxide (NO) plays a pivotal role in integrating dopamine transmission in the basal ganglia and has been implicated in the pathogenesis of Parkinson disease (PD). The objective of this study was to ascertain whether the NO synthase inhibitor, 7-nitroindazole (7-NI), is able to reduce L-DOPA-induced dyskinesias (LIDs) in a non-human primate model of PD chronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Six Parkinsonian macaques were treated daily with L-DOPA for 3-4 months until they developed LIDs. Three animals were then co-treated with a single dose of 7-NI administered 45 min before each L-DOPA treatment. Dyskinetic MPTP-treated monkeys showed a significant decrease in LIDs compared with their scores without 7-NI treatment (p < 0.05). The anti-Parkinsonian effect of L-DOPA was similar in all three monkeys with and without 7-NI co-treatment. This improvement was significant with respect to the intensity and duration of LIDs while the beneficial effect of L-DOPA treatment was maintained and could represent a promising therapy to improve the quality of life of PD patients.


Subject(s)
Dyskinesia, Drug-Induced , Parkinson Disease , Parkinsonian Disorders , Animals , Levodopa/adverse effects , Antiparkinson Agents/adverse effects , Quality of Life , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/drug therapy , Dyskinesia, Drug-Induced/drug therapy , Dyskinesia, Drug-Induced/etiology , Parkinson Disease/drug therapy , Primates
2.
Farm. comunitarios (Internet) ; 14(Supl 1): 1, junio 2022. graf, ilus
Article in Spanish | IBECS | ID: ibc-209390

ABSTRACT

JUSTIFICACIÓN: la atención farmacéutica ha sufrido un gran auge estas últimas décadas, debido al aumento de pacientes que padecen enfermedades crónicas, y al hecho de que las farmacias comunitarias son el punto de información sanitario más accesible y cercano para la población.OBJETIVOS: los objetivos del estudio consisten en la evaluación de la prevalencia de patologías crónicas en pacientes mayores de 50 años, así como el análisis de la adherencia al tratamiento mediante el uso de sistemas de dispensación personalizada (SDP) en una farmacia de Beniel, Región de Murcia.MATERIALES Y METODOS: en este trabajo se ha realizado un estudio a cuarenta participantes del municipio de Beniel a los cuales se les ha ofrecido el servicio de dispensación personalizada y el servicio de seguimiento farmacoterapéutico desde la farmacia. Además, se ha evaluado cuáles son las enfermadas crónicas más prevalentes en el municipio.RESULTADOS Y DISCUSIÓN: la enfermedad crónica con mayor prevalencia en Beniel es la hipertensión arterial (100 % de los encuestados), lo que coincide con los datos publicados por el Ministerio de Sanidad en los Informes Anuales de Salud. Por el contrario, la tercera enfermedad crónica más frecuente en el municipio de Beniel es la diabetes, de forma diferente a los datos nacionales que la establecen como la novena enfermedad más frecuente. Se han comparado los valores sociodemográficos en las patologías de depresión y ansiedad crónica, donde se ha visto reflejado una diferencia notable en hombres y mujeres, siendo estas últimas las más afectadas. Destaca el gran número de pacientes en tratamiento con Inhibidores de la bomba de protones (IBP) y antiagregantes plaquetarios.CONCLUSIONES: la población de Beniel no presenta grandes diferencias respecto a las patologías crónicas más frecuentes a nivel nacional. (AU)


Subject(s)
Humans , Pharmaceutical Services , Patients , Chronic Disease , Hypertension , Therapeutics
3.
J Crohns Colitis ; 13(8): 996-1002, 2019 Aug 14.
Article in English | MEDLINE | ID: mdl-30721954

ABSTRACT

BACKGROUND AND AIMS: The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS: This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS: A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS: The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.


Subject(s)
Fatigue , Glucocorticoids , Inflammatory Bowel Diseases , Quality of Life , Adult , Anxiety/diagnosis , Anxiety/epidemiology , Anxiety/physiopathology , Depression/diagnosis , Depression/epidemiology , Depression/physiopathology , Fatigue/diagnosis , Fatigue/epidemiology , Fatigue/etiology , Fatigue/psychology , Female , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/psychology , Inflammatory Bowel Diseases/therapy , Male , Prevalence , Prospective Studies , Risk Factors , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/physiopathology , Spain/epidemiology , Surveys and Questionnaires
4.
Prog Neuropsychopharmacol Biol Psychiatry ; 84(Pt A): 102-114, 2018 06 08.
Article in English | MEDLINE | ID: mdl-29407532

ABSTRACT

Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of CRF1R on opiate withdrawal memory acquisition, along with plasticity-related processes that occur after CPA within the basolateral amygdala (BLA) and dentate gyrus (DG). Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The CPA scores as well as the number of TH-positive neurons (in the NTS-A2 noradrenergic cell group), and the expression of the transcription factors Arc and pCREB (in the BLA and DG) were measured with and without CRF1R blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal robustly expressed CPA. Pre-treatment with the selective CRF1R antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition. CP-154,526 also antagonized the enhanced number of TH-positive neurons in the NTS-A2 that was seen after CPA. Increased Arc expression and Arc-pCREB co-localization were seen in the BLA after CPA, which was not modified by CP-154,526. In the DG, CPA was accompanied by a decrease of Arc expression and no changes in Arc-pCREB co-localization, whereas pre-treatment with CP-154,526 induced an increase in both parameters. These results indicate that CRF-CRF1R pathway could be a critical factor governing opiate withdrawal memory storage and retrieval and might suggest a role for TH-NA pathway in the effects of withdrawal on memory. Our results might indicate that the blockade of CRF1R could represent a promising pharmacological treatment strategy approach for the attenuation of the relapse to drug-seeking/taking behavior triggered by opiate withdrawal-associated aversive memories.


Subject(s)
Avoidance Learning/drug effects , Basolateral Nuclear Complex/drug effects , Conditioning, Psychological/drug effects , Dentate Gyrus/metabolism , Morphine Dependence/metabolism , Receptors, Corticotropin-Releasing Hormone/metabolism , Animals , Avoidance Learning/physiology , Basolateral Nuclear Complex/metabolism , Conditioning, Psychological/physiology , Corticotropin-Releasing Hormone/metabolism , Male , Memory/drug effects , Memory/physiology , Mice , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Neurons/drug effects , Neurons/metabolism , Random Allocation , Spatial Behavior/drug effects , Spatial Behavior/physiology
5.
Emergencias (St. Vicenç dels Horts) ; 25(6): 472-481, dic. 2013. ilus, tab
Article in Spanish | IBECS | ID: ibc-118112

ABSTRACT

La hemorragia digestiva alta no varicosa (HDANV) es una emergencia médica frecuente que se asocia a una considerable morbilidad y mortalidad. En los últimos años se han producido importantes avances en el manejo de la HDANV, que han permitido disminuirla recidiva hemorrágica y la mortalidad en estos pacientes. El objetivo del presente documento es ofrecer una guía de manejo de la HDANV eminentemente práctica basada en la evidencia científica y en las recomendaciones de los recientes consensos. Lostres puntos clave del manejo de la HDANV son: a) la reanimación hemodinámica precozy la prevención de las complicaciones de la patología cardiovascular de base, quees frecuente en pacientes con HDANV; b) el tratamiento endoscópico de las lesiones con alto riesgo de recidiva; y c) el uso de inhibidores de la bomba de protones a dosis altas pre y postendoscopia. La combinación de estas medidas permite reducir la recidiva y la mortalidad de la HDANV (AU)


Nonvariceal upper gastrointestinal (GI) bleeding is a common medical emergency associated with appreciable morbidity and mortality. The significant advances made in managing this condition in recent years have reduced the rates of rebleeding and mortality. These clinical guidelines for managing this emergency are intended to be highly practical, evidence-based, and take recent consensus statements into account. The 3 keys to managing nonvariceal upper GIbleeding are a) early restoration of fluids and blood pressure and the prevention of underlying cardiovascular disease, which is common in these patients; b) endoscopy to treat lesions at high risk of rebleeding; and c) medical therapy with high doses of proton pump inhibitors before and after endoscopy. These 3 measures, used in combination, reduce upperGI rebleeding and mortality rates (AU)


Subject(s)
Humans , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/therapy , Gastroscopy , Practice Patterns, Physicians' , Proton Pump Inhibitors/therapeutic use , Helicobacter pylori/pathogenicity , Helicobacter Infections/complications , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Stomach Ulcer/complications
6.
J Pharmacol Exp Ther ; 342(3): 665-75, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22647273

ABSTRACT

The negative affective states of withdrawal involve the recruitment of brain and peripheral stress circuitry [e.g., noradrenergic activity, induction of the hypothalamo-pituitary-adrenocortical (HPA) axis, and the expression and activation of heat shock proteins (Hsps)]. The present study investigated the role of extracellular signal-regulated protein kinase (ERK) and ß-adrenoceptor on the response of stress systems to morphine withdrawal by the administration of [amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile (SL327), a selective inhibitor of ERK activation, or propranolol (a ß-adrenoceptor antagonist). Dependence on morphine was induced by a 7-day subcutaneous implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by the injection of naloxone (2 mg/kg s.c.). Plasma concentrations of adrenocorticotropin and corticosterone were determined by radioimmunoassay; noradrenaline (NA) turnover in left ventricle was determined by high-performance liquid chromatography; and catechol-O-methyl transferase (COMT) and Hsp27 expression and phosphorylation at Ser82 were determined by quantitative blot immunolabeling. Morphine-withdrawn rats showed an increase of NA turnover and COMT expression in parallel with an enhancement of adrenocorticotropin and plasma corticosterone concentrations. In addition, we observed an enhancement of Hsp27 expression and phosphorylation. Pretreatment with SL327 or propranolol significantly reduced morphine withdrawal-induced increases of plasma adrenocorticotropin and Hsp27 phosphorylation at Ser82 without any changes in plasma corticosterone levels. The present findings demonstrate that morphine withdrawal is capable of inducing the activation of HPA axis in parallel with an enhancement of Hsp27 expression and Hsp27 phosphorylation at Ser82 and suggest a role for ß-adrenoceptors and ERK pathways in mediating morphine-withdrawal activation of the HPA axis and cellular stress response.


Subject(s)
Extracellular Signal-Regulated MAP Kinases/metabolism , HSP27 Heat-Shock Proteins/metabolism , Heart/drug effects , Hypothalamo-Hypophyseal System/physiopathology , Morphine/adverse effects , Pituitary-Adrenal System/physiopathology , Substance Withdrawal Syndrome/physiopathology , Adrenergic beta-Antagonists/pharmacology , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/metabolism , Aminoacetonitrile/analogs & derivatives , Aminoacetonitrile/pharmacology , Animals , Catechol O-Methyltransferase/metabolism , Corticosterone/blood , Corticosterone/metabolism , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Heart/physiopathology , Heart Ventricles/drug effects , Heart Ventricles/metabolism , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/metabolism , Male , Morphine Dependence/metabolism , Morphine Dependence/physiopathology , Naloxone/pharmacology , Norepinephrine/metabolism , Phosphorylation/drug effects , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/metabolism , Propranolol/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, beta/metabolism , Substance Withdrawal Syndrome/metabolism
7.
Am J Gastroenterol ; 107(8): 1197-204, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22613904

ABSTRACT

OBJECTIVES: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. RESULTS: Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. CONCLUSION: Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.


Subject(s)
Helicobacter Infections/drug therapy , Helicobacter pylori , Peptic Ulcer Hemorrhage/microbiology , Breath Tests , Female , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Peptic Ulcer/drug therapy , Peptic Ulcer/microbiology , Recurrence , Urea/analysis
8.
J Mol Cell Cardiol ; 51(1): 129-39, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21530534

ABSTRACT

Heat shock protein 27 (Hsp27) is a well-known stress response protein that becomes phosphorylated through extracellular signal-regulated kinase (ERK). Different drugs of abuse, such as morphine and/or its withdrawal, induce severe stress situations. In this study, we investigated Hsp27 and phospho-Hsp27 expression during morphine dependence and withdrawal and evaluated the involvement of ERK in the phosphorylation of Hsp27 in the rat right ventricle. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by injection of naloxone (2 mg/kg, s.c.). ERK1/2, Hsp27 and phospho-Hsp27 at Ser15 were determined by quantitative blot immunolabeling using specific antibodies. Hsp27 expression was increased 30, 60, 90 and 120 min (144.5±14.2%, P<0.0001; 128.9±4.6%, P=0.04; 177.4±12.7, P<0.0001; and 136.2±11.0%, P=0.042, respectively) after saline injection to rats dependent on morphine. Naloxone-precipitated morphine withdrawal also increased the phosphorylation of Hsp27 at Ser15 at those time points (146.8±19.8%, P=0.034; 143.9±17.9%, P=0.032; 161.2±33.3%, P=0.029; and 152.2±25.5%, P=0.008, respectively). However, there were no changes in Hsp27 phosphorylation in the morphine dependent group injected with saline. In addition, there was an increase in the phosphorylation of ERK 60 min after naloxone injection in morphine dependent rats (pERK1: 116.3±4.2%, P=0.015 and pERK2: 117.2±1.5%, P=0.05). Pretreatment with SL327, an inhibitor of ERK phosphorylation, decreased activation (phosphorylation) of both ERK and Hsp27 (pERK1: 4.5±3.6%, P<0.0001; pERK2: 42.3±3.3%, P<0.0001; and pHsp27: 97.6±1.5%, P=0.008), suggesting that ERK activation triggers Hsp27 phosphorylation. The present findings demonstrate that morphine withdrawal is capable of inducing the activation of Hsp27 in the heart and suggest that phosphorylation of Hsp27 is closely linked to and also dependent on the ERK pathway.


Subject(s)
Extracellular Signal-Regulated MAP Kinases/metabolism , HSP27 Heat-Shock Proteins/metabolism , Morphine Dependence/metabolism , Morphine/adverse effects , Myocardium/metabolism , Naloxone/pharmacology , Substance Withdrawal Syndrome/metabolism , Aminoacetonitrile/analogs & derivatives , Aminoacetonitrile/pharmacology , Animals , HSP27 Heat-Shock Proteins/genetics , Heart , Heart Ventricles/drug effects , Heart Ventricles/metabolism , Immunoblotting , Myocardium/enzymology , Phosphorylation , Protease Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley
9.
J Pharmacol Exp Ther ; 330(3): 771-82, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19567779

ABSTRACT

Our previous studies have shown that morphine withdrawal induced an increase in the expression of protein kinase (PK) A and mitogen-activated extracellular kinase (MAPK) pathways in the heart during morphine withdrawal. The purpose of the present study was to evaluate the interaction between PKA and extracellular signal-regulated kinase (ERK) signaling pathways mediating the cardiac adaptive changes observed after naloxone administration to morphine-dependent rats. Dependence on morphine was induced by a 7-day subcutaneous implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (2 mg/kg). ERK1/2 and tyrosine hydroxylase (TH) phosphorylation was determined by quantitative blot immunolabeling using phosphorylation state-specific antibodies. Naloxone-induced morphine withdrawal activates ERK1/2 and phosphorylates TH at Ser31 in the right and left ventricle, with an increase in the mean arterial blood pressure and heart rate. When N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), a PKA inhibitor, was infused, concomitantly with morphine, it diminished the expression of ERK1/2. In contrast, the infusion of calphostin C (a PKC inhibitor) did not modify the morphine withdrawal-induced activation of ERK1/2. The ability of morphine withdrawal to activate ERK that phosphorylates TH at Ser31 was reduced by HA-1004. The present findings demonstrate that the enhancement of ERK1/2 expression and the phosphorylation state of TH at Ser31 during morphine withdrawal are dependent on PKA and suggest cross-talk between PKA and ERK1/2 transduction pathway mediating morphine withdrawal-induced activation (phosphorylation) of TH.


Subject(s)
Analgesics, Opioid/adverse effects , Cyclic AMP-Dependent Protein Kinases/physiology , Heart/physiopathology , Mitogen-Activated Protein Kinases/physiology , Morphine/adverse effects , Signal Transduction/physiology , Substance Withdrawal Syndrome/physiopathology , Adaptation, Physiological/physiology , Aminoacetonitrile/analogs & derivatives , Aminoacetonitrile/pharmacology , Animals , Blotting, Western , Enzyme Inhibitors/pharmacology , Hemodynamics/drug effects , Hemodynamics/physiology , Isoquinolines/pharmacology , Male , Naloxone/pharmacology , Naphthalenes/pharmacology , Narcotic Antagonists/pharmacology , Phosphorylation , Protein Kinase C/biosynthesis , Protein Kinase C/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Sulfonamides/pharmacology , Tyrosine 3-Monooxygenase/physiology , Weight Gain/drug effects
11.
Br J Pharmacol ; 155(1): 73-83, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18536752

ABSTRACT

BACKGROUND AND PURPOSE: Our previous studies have shown that morphine withdrawal induced hyperactivity of cardiac noradrenergic pathways. The purpose of the present study was to evaluate the effects of morphine withdrawal on site-specific phosphorylation of TH in the heart. EXPERIMENTAL APPROACH: Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets in rats. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (2 mg kg(-1)). TH phosphorylation was determined by quantitative blot immunolabelling using phosphorylation state-specific antibodies. KEY RESULTS: Naloxone-induced morphine withdrawal induced phosphorylation of TH at serine (Ser)40 and Ser31 in the right ventricle, associated with both an increase in total TH levels and an enhancement of TH activity. When HA-1004 (PK A inhibitor) was infused, concomitantly with morphine, it diminished the increase in noradrenaline turnover, total TH levels and TH phosphorylation at Ser40 in morphine-withdrawn rats. In contrast, the infusion of calphostin C (PKC inhibitor), did not modify the morphine withdrawal-induced increase in noradrenaline turnover and total TH levels. In addition, we show that the ability of morphine withdrawal to stimulate phosphorylation at Ser31 was reduced by SL327, an inhibitor of ERK 1/2 activation. CONCLUSIONS AND IMPLICATIONS: The present findings demonstrate that the enhancement of total TH levels and the increased phosphorylation state of TH during morphine withdrawal were dependent on PKA and ERK activities and suggest that these transduction pathways might contribute to the activation of the cardiac catecholaminergic neurons in response to morphine withdrawal.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Morphine Dependence/enzymology , Morphine/administration & dosage , Myocardium/enzymology , Substance Withdrawal Syndrome/enzymology , Tyrosine 3-Monooxygenase/metabolism , Aminoacetonitrile/analogs & derivatives , Aminoacetonitrile/pharmacology , Animals , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Disease Models, Animal , Drug Implants , Isoquinolines/pharmacology , Male , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Naloxone , Naphthalenes/metabolism , Narcotic Antagonists , Norepinephrine/metabolism , Phosphorylation , Protein Kinase C-delta/metabolism , Protein Kinase Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Serine , Substance Withdrawal Syndrome/etiology , Sulfonamides/pharmacology
12.
Br J Pharmacol ; 151(6): 787-97, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17549049

ABSTRACT

BACKGROUND AND PURPOSE: We have previously demonstrated that morphine withdrawal induced hyperactivity of the heart by activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline turnover and c-Fos expression. The extracellular signal-regulated kinase (ERK) has been implicated in drug addiction, but its role in activation of the heart during morphine dependence remains poorly understood. Here, we have looked for activation of ERK during morphine withdrawal and if this activation induced gene expression. EXPERIMENTAL APPROACH: Dependence on morphine was induced by s.c. implantation of morphine pellets for 7 days. Morphine withdrawal was precipitated on day 8 by injection of naloxone (2 mg kg(-1), s.c.). ERK1/2, their phosphorylated forms and c-Fos were measured by western blotting and immunohistochemistry of cardiac tissue. KEY RESULTS: Naloxone-induced morphine withdrawal activated ERK1/2 and increased c-Fos expression in cardiac tissues. c-Fos expression was blocked by SL327, a drug that prevents ERK activation. CONCLUSIONS AND IMPLICATIONS: These results indicate that signalling through the ERKs is necessary for morphine withdrawal-induced hyperactivity of the heart and suggest that this pathway may also be involved in activation of immediate-early genes in both cytosolic and nuclear effector mechanisms that have the potential to bring about long-term changes in the heart.


Subject(s)
Extracellular Signal-Regulated MAP Kinases/metabolism , Morphine/adverse effects , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Narcotics/adverse effects , Substance Withdrawal Syndrome/metabolism , Aminoacetonitrile/analogs & derivatives , Animals , Blotting, Western , Gene Expression/drug effects , Genes, fos/drug effects , Heart Ventricles/drug effects , Immunohistochemistry , MAP Kinase Signaling System/drug effects , Male , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Substance Withdrawal Syndrome/physiopathology
14.
Am J Gastroenterol ; 96(8): 2341-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11513172

ABSTRACT

OBJECTIVES: To evaluate the safety of outpatient management of upper GI hemorrhage (UGIH) not associated with portal hypertension. METHODS: A prospective cohort of 983 subjects who went to the Accident & Emergency Department (A&ED) of a University hospital in Valencia (Spain), for UGIH not associated with portal hypertension during 1994 to 1997 were evaluated. After evaluation in the A&ED, 216 patients (22%) were discharged and referred for outpatient follow-up, but 15 patients could not be located thus, reducing the follow-up to 201 subjects. The main outcome measures were rebleeding within 10 days, emergency surgery within 15 days, and mortality for any cause during the 30 days after the initial hemorrhaging episode. RESULTS: UGIH in subjects under outpatient care were less severe than those subjects in the hospitalized group. Hemorrhaging recurred in 7.3% of inpatients versus 0.5% of outpatients (p < 0.01); emergency surgery was required in 5.6% of the hospitalized patients and 0.5% of the outpatients (p < 0.01); a total of 20 deaths occurred in the hospitalized group (2.6%), while three (1.5%) occurred in outpatients (p = 0.26). After adjusting for several significant risk factors, outpatient management was not associated with outcomes that were worse. CONCLUSIONS: Treatment under an outpatient regime is a safe alternative for a large percentage of selected patients with UGIH not associated with portal hypertension.


Subject(s)
Ambulatory Care , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Aged , Female , Gastroscopy , Hemodynamics , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Treatment Outcome
15.
Med Clin (Barc) ; 114 Suppl 2: 68-73, 2000.
Article in Spanish | MEDLINE | ID: mdl-10916810

ABSTRACT

BACKGROUND: The handling of upper gastrointestinal hemorrhage (UGH) usually includes the hospitalization of all patients, regardless of severity and prognosis. The aim of this paper is to assess the security of the outpatient control of some UGH, after their assessment in the hospital emergency room. PATIENTS AND METHODS: Prospective cohort of 533 patients who attended over 1994 and 1995 hospital emergency room for an episode of UGH not linked to portal hypertension. After clinical and endoscopical assessment in the emergency department, 422 cases (79%) were admitted and 111 (21%) discharged for outpatient care. An analysis is presented of the characteristics of both groups, their clinical outcomes and a multivariate analysis to assess the factors associated with the decision to admit the patient. RESULTS: Outpatients were young, with less comorbidity and better haemodynamic status than hospitalized patients. Most of outpatient cases UGH was due to gastroduodenitis, oesophagitis and Mallory-Weiss syndrome, as opposed to the greater importance of peptic ulcer in those admitted. All outpatients presented clean lesions or haematic remains. 25 (5.9%) hospitalized patients presented rebleeding, vs. only 1 (0.9%) outpatient (p < 0.05). When more severity cases were excluded from hospital group, the differences were not significant. All cases with active bleeding, severe haemodynamic repercussion or without endoscopy were admitted. For the remainder, the decision to admit was associated with the presence of bleeding stigmata, haemodynamic repercussion, some causes of hemorrhage, older age, and urea levels. CONCLUSIONS: Although the scarce sample do not permit definitive conclusions, results guide towards that a substantial part of UGH not linked to portal hypertension may be monitored without hospitalizing the patient, thereby minimizing care costs and increasing the productive capacity of the hospital, without increasing risks for the patient.


Subject(s)
Ambulatory Care/standards , Gastrointestinal Hemorrhage/rehabilitation , Hypertension, Portal/diagnosis , Cohort Studies , Female , Humans , Male , Middle Aged , Patient Admission , Prospective Studies , Risk Factors , Spain
16.
Int J Pancreatol ; 25(2): 107-11, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10360223

ABSTRACT

CONCLUSION: Serum increases of aminotransferases, especially alanine aminotransferase (ALT), were suggestive of microlithiasis in idiopathic acute pancreatitis, particularly when assessed early after the onset of abdominal pain. BACKGROUND: It has been shown that biochemical laboratory values only are useful parameters in distinguishing gallstone from nongallstone acute pancreatitis. We assessed the diagnostic usefulness of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for identification of occult microlithiasis in idiopathic acute pancreatitis. METHODS: Ninety-one patients with idiopathic acute pancreatitis who underwent microscopic examination of stimulated duodenal bile sediments were retrospectively studied. According to earliness of ALT and AST assay after the onset of abdominal pain, patients were divided into two groups: group A, within the first 24 h (n = 56) and group B, between 24 and 72 h (n = 35). RESULTS: ALT and AST values expressed as number of elevations of the upper limits of normal were higher in group A patients with positive biliary drainage than in group B. Median (range) ALT and AST values were 2.5 (0.1-18.1) vs 0.4 (0.1-8.6) and 3 (0.3-17.4) vs 0.5 (0.3-11.9), respectively. In the univariate analysis and receiver operating characteristic (ROC) curves, ALT within the first 24 h showed a sensitivity of 73%, specificity of 86%, and positive predictive value of 92% for a cutoff of 1.2 elevations of the upper limit of normal. These values were slightly higher, although without statistically significant differences, than those of AST (73, 80, and 89%, respectively).


Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Cholelithiasis/diagnosis , Cholelithiasis/enzymology , Pancreatitis/enzymology , Acute Disease , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Cholelithiasis/complications , Female , Humans , Male , Middle Aged , Pancreatitis/etiology , Retrospective Studies
18.
Rev Esp Enferm Dig ; 89(10): 741-6, 747-52, 1997 Oct.
Article in English, Spanish | MEDLINE | ID: mdl-9401431

ABSTRACT

The aim of our study was to analyze the influence of alcohol consumption on the early clinical manifestations of alcoholic chronic pancreatitis of the 517 patients in whom chronic pancreatitis was initially suspected, 158 were diagnosed with this disease; of these, alcohol was considered the cause in 136 (86.1%). Alcohol was considered a major etiologic factor when mean consumption was > or = 60 grams per day for at least 4 years. Alcohol consumption, initial clinical manifestations and time of onset were considered up until the moment of diagnosis in all patients. The sex distribution was 133 men (97.8%) and 3 women (2.2%). The average age was 22 +/- 6.5 years at onset of alcoholism, 38 +/- 9.4 years at onset of clinical features, and 44 +/- 9.4 years at diagnosis. The interval between the onset of alcoholism and the initial clinical manifestations was 15.8 +/- 8.8 years, and the interval between the latter and diagnosis was 6.1 +/- 4.9 years. Average alcohol consumption was 162 +/- 8 grams/day and total consumption was 1312 +/- 1017 kg. A statistically significant relationship was found only for mean alcohol consumption and abdominal pain. We found a higher frequency of acute pancreatitis outbreaks, calcifications, steatorrhea and diabetes until the moment of diagnosis in the higher alcohol consumption groups, although the relationship was not statistically significant.


Subject(s)
Alcohol Drinking/adverse effects , Pancreatitis, Alcoholic/etiology , Adult , Alcoholism/complications , Chronic Disease , Female , Humans , Male , Pancreatitis, Alcoholic/diagnosis , Statistics, Nonparametric
19.
Rev Esp Enferm Dig ; 89(9): 665-76, 1997 Sep.
Article in English, Spanish | MEDLINE | ID: mdl-9421553

ABSTRACT

The diagnosis of chronic pancreatitis continues to present difficulties. The nonspecific nature of the symptomatology, its low prevalence and the limited value of morphological and functional tests in the early stages are the most common causes of delay in diagnosis. Our aim was to analyze the most significant clinical manifestations and the diagnostic features of chronic pancreatitis, distinguishing between alcoholic and nonalcoholic etiologies. We studied 158 patients, 136 (86.1%) with alcoholic and 22 (13.9%) with nonalcoholic chronic pancreatitis. The initial symptomatology, the age at diagnosis, the delay in diagnosis from the onset of the clinical signs and the type of diagnosis (incidental or suspected) were considered for each patient. Men predominated in both the alcoholic and the nonalcoholic pancreatitis groups (97.8% and 68.2%, respectively). The mean ages at onset and diagnosis were 38 and 50.6 years, respectively, in alcoholic chronic pancreatitis and 44 and 55 years in the nonalcoholic group; the differences between the two parameters were statistically significant. The most common clinical signs in alcoholic chronic pancreatitis were abdominal pain (81.6%) and episodes of acute pancreatitis (64%), while patients with nonalcoholic pancreatitis presented abdominal pain (59%), diarrhea (40.9%) and weight loss (36.4%). The delay in diagnosis from the onset of the clinical manifestations was 5.8 years (6.1 years in alcoholic and 4.3 years in nonalcoholic pancreatitis. The diagnosis was incidental in 34% of cases of alcoholic chronic pancreatitis and in 50% of cases in the nonalcoholic group.


Subject(s)
Pancreatitis/diagnosis , Adult , Chi-Square Distribution , Chronic Disease , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatitis, Alcoholic/diagnosis , Retrospective Studies , Statistics, Nonparametric , Time Factors
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