Therapeutic treatment with fluoxetine using the chronic unpredictable stress model induces changes in neurotransmitters and circulating miRNAs in extracellular vesicles.

The most widely prescribed antidepressant, fluoxetine (FLX), is known for its antioxidant and anti-inflammatory effects when administered post-stress. Few studies have evaluated the effects of FLX treatment when chronic stress has induced deleterious effects in patients. Our objective was to evaluate FLX treatment (20 mg/kg/day, i.v.) once these effects are manifested, and the drug's relation to extracellular circulating microRNAs associated with inflammation, a hedonic response (sucrose intake), the forced swim test (FST), and corticosterone levels (CORT) and monoamine concentrations in limbic areas. A group of Wistar rats was divided into groups: Control; FLX; CUMS (for six weeks of exposure to chronic, unpredictable mild stress); and CUMS + FLX, a mixed group. After CUMS, the rats performed the FST, and serum levels of CORT and six microRNAs (miR-16, -21, -144, -155, -146a, -223) were analyzed, as were levels of dopamine, noradrenaline, and serotonin in the prefrontal cortex, hippocampus, and hypothalamus. CUMS reduced body weight, sucrose intake, and hippocampal noradrenaline levels, but increased CORT, immobility behavior on the FST, dopamine concentrations in the prefrontal cortex, and all miRNAs except miR-146a expression. Administering FLX during CUMS reduced CORT levels and immobility behavior on the FST and increased the expression of miR-16, -21, -146a, -223, and dopamine. FLX protects against the deleterious effects of stress by reducing CORT and has an antidepressant effect on the FST, with minimally-modified neurotransmitter levels. FLX increased the expression of miRNAs as part of the antidepressant effect. It also regulates both neuroinflammation and serotoninergic neurotransmission through miRNAs, such as the miR-16.

Nociceptive related microRNAs and their role in rheumatoid arthritis.

Rheumatoid Arthritis (RA) is an autoimmune disease with unknown etiology and a global incidence around 1%, a positive family history increases the risk of RA roughly three to five times. Pain is one of the first symptoms to appear in this disease. MicroRNAs (miRNAs) belong to the class of small non-coding RNAs; they regulate multiple cellular processes including embryonic development, cellular proliferation, differentiation and apoptosis among others. A great deal of evidence points to the employment of miRNAs as therapeutic targets and biomarkers for several pathologies. The main objective of this Review is to assess how miRNAs participate in the pathogenesis of RA. Two advanced searches were conducted in databases, one using "micro-RNA" and "rheumatoid arthritis" as key words, and another one with "micro-RNA", "pain" and "nociception". In this Review, we describe how six miRNAs: miR-16-5p, miR-23b-3b, miR-124-3p, miR-146a-5p, miR-155-5p and miR-223-3p, involved in the modulation and transmission of the nociceptive input are unregulated in RA patients. Key molecular pathways involved in nociception, inflammation and autoimmune responses, are regulated by these miRNAs; the NF-κB, TNF-α, interleukins and TLR4. By means of gene repression, the miRNAs here described modulate the nociceptive process as well as the autoimmune response that characterize this disease.

Manejo perioperatorio de feocromocitoma y paraganglioma / Perioperative management of paragangliomas and pheochromocytomas

Los feocromocitomas y paragangliomas son tumores neuroendocrinos raros, caracterizados por una alta tasa de morbilidad debida a un exceso de niveles de catecolaminas. Este exceso de catecolaminas es independiente de los estresores fisiológicos. Para el diagnóstico de un feocromocitoma-paraganglioma son fundamentales las pruebas bioquímicas. Las más utilizadas son las metanefrinas fraccionadas urinarias o metanefrinas libres plasmáticas. Seguido del diagnóstico bioquímico, debe realizarse un estudio imagenológico. La evaluación del paciente con diagnóstico de feocromocitoma-paraganglioma debe realizarse teniendo presente sus principales causas de morbimortalidad perioperatoria. Las dos grandes intervenciones que han disminuido la mortalidad perioperatoria son la introducción del α bloqueo y la restauración de la volemia. El otro gran avance ha sido la introducción de la cirugía laparoscópica como el estándar de oro para el abordaje quirúrgico. En relación con el manejo intraoperatorio, no se ha identificado que alguna técnica anestésica sea superior a otra. Sí se ha logrado establecer criterios de inestabilidad hemodinámica que se correlacionan con mayor morbilidad, por lo que los principales objetivos intraoperatorios son mantener estabilidad hemodinámica. El avance en el manejo preoperatorio e intraoperatorio con la consecuente disminución en la mortalidad relacionada a esta patología ha llevado el foco al manejo postoperatorio tanto agudo como a largo plazo. También se debe considerar el riesgo de recurrencia tumoral, por lo que estos pacientes deben tener un control anual de por vida.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, characterized by a high morbidity rate due to catecholamine excess. These high levels are independent of physiologic stressors. For the diagnosis, a biochemical workup is paramount. The most widely used are plasma-free metanephrines and urinary fractionated metanephrines. Imaging studies should be initiated once the biochemical diagnosis is established. Evaluation of the patient with pheochromocytomas and paragangliomas must be done taking into account the leading causes of perioperative morbidity and mortality. The two primary interventions that have reduced perioperative mortality are alpha-adrenergic blockade and intravascular volume normalization. Another significant advance has been the establishment of laparoscopic surgery as the gold standard for the surgical approach. No anesthetic technique has been found to be superior to another. Intraoperative hemodynamic instability has been correlated with poorer outcomes; thus one of the main intraoperative goals is maintaining hemodynamic stability. Lower morbidity and almost zero mortality rates due to preoperative and intraoperative management improvements have led to a focus on the immediate and long-term postoperative care. Anual lifelong follow-up is recommended to detect recurrent disease.

Levetiracetam as an antiepileptic, neuroprotective, and hyperalgesic drug.

The main purpose of this review was to expound upon the mechanism of action of Levetiracetam (LEV) as an antiepileptic, neuroprotective, and hyperalgesic drug. LEV is a second-generation anti-epileptic drug (AED) that is approved for clinical use as monotherapy and may also be used for adjunctive treatment of patients with seizures. Several researchers have recommended LEV as a treatment option in different diseases causing neuronal damage, and recently, LEV has been used as an antihyperalgesic drug. LEV exhibits favorable characteristics, including a low potential for interaction, a short elimination half-life, and has neither active metabolites nor major negative effects on cognition. This has generated many new research avenues for the utilization of this drug. However, the precise mechanism of action of LEV has not been fully elucidated. In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation index for studies evaluating the effects of LEV as an antiepileptic, neuroprotective, and hyperalgesic drug. A total of 32 studies related to the use of LEV suggested different mechanisms of action, such as binding to the synaptic vesicle glycoprotein 2A (SV2A) protein, inhibition of Ca2+ N-type channels, and its presence as a neuromodulator. These studies concluded that the pharmacodynamics of LEV should be viewed as a single pathway, and should not be based on specific molecular targets that depend on the physiological or pathological conditions prevalent at that time.

Liquid chromatography time-of-flight mass spectrometry following sorptive microextraction for the determination of fungicide residues in wine.

This work evaluates the suitability of sorptive microextraction, using disposable silicone sorbents, and liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) for the determination of 15 fungicides in wine. Under optimized conditions, wine samples (10 mL) were diluted with the same volume of ultrapure water and poured in a glass vessel containing a magnetic stirrer and 4 g of sodium chloride. Extractions were performed at room temperature for 4 h, using an inexpensive silicone disk (12 µL volume) exposed directly to the sample. Thereafter, analytes were recovered with 0.2 mL of acetonitrile. The electrospray ionization (ESI) source was operated in the fast polarity switching mode obtaining, in the same injection, selective LC-MS records (extracted with a mass window of 10 ppm) of compounds rendering [M + H](+) and [M-H](-) ions. The method provided limits of quantification (LOQs) between 0.1 and 2.2 ng mL(-1), linear response ranges up to 500 ng mL(-1), relative recoveries from 75% to 117% and an inter-day variability below 15% for all analytes in red and white wine samples. The feasibility of in situ sample enrichment followed by delayed desorption and analysis is also assessed.

Infinite penetration of a projectile into a granular medium.

An object falling in a fluid reaches a terminal velocity when the drag force and its weight are balanced. Contrastingly, an object impacting into a granular medium rapidly dissipates all its energy and comes to rest always at a shallow depth. Here we study, experimentally and theoretically, the penetration dynamics of a projectile in a very long silo filled with expanded polystyrene particles. We discovered that, above a critical mass, the projectile reaches a terminal velocity and, therefore, an endless penetration.

Success of medical therapy in a rare case of cecal ameboma.

INTRODUCTION: Colitis caused by Entamoeba histolytica (EH) is prevalent in developing countries. Clinical presentation ranges from mild diarrhoea episodes to dysentery and liver abscess. Ameboma, a complication caused by EH invasion of the intestinal wall, is a rare presentation of amebiasis, occurring approximately in 1.5% of cases. Because of its insidious and variable clinical presentation only few cases are diagnosed previous to surgical intervention. We report a 52 years old Mexican-mestizo female, presenting with a pain-less right lower quadrant abdominal mass and diagnosed of cecal ameboma prior to surgery by colonoscopy and histopathologic examination. The present case highlights the importance of early diagnosis and medical therapy with antiparasitic drugs in order to avoid complications that could lead these patients to unnecessary surgical management.

Solid-phase extraction followed by liquid chromatography quadrupole time-of-flight tandem mass spectrometry for the selective determination of fungicides in wine samples.

In this work, a reliable and selective procedure for the determination of thirteen fungicides in red and white wine samples is proposed. Solid-phase extraction (SPE) and liquid chromatography (LC) tandem mass spectrometry (MS/MS), based on a hybrid quadrupole time-of-flight (QTOF) system, were used as sample preparation and determination techniques, respectively. Extraction and purification of target analytes was carried out simultaneously by using a reversed-phase Oasis HLB (200mg) SPE cartridge combined with acetonitrile as elution solvent. Fungicides were determined operating the electrospray source in the positive ionization mode, with MS/MS conditions adjusted to obtain at least two intense product ions per compound, or registering two transitions per species when a single product was noticed. High selective MS/MS chromatograms were extracted using a mass window of 20 ppms for each product ion. Considering external calibration as quantification technique, the overall recoveries (accuracy) of the procedure ranged between 81% and 114% for red and white wine samples (10-20 mL), spiked at different concentrations between 5 and 100 ng mL(-1). Relative standard deviations of the above data stayed below 12% and the limits of quantification (LOQs) of the method, calculated for 10 mL of wine, varied between 0.1 ng mL(-1) for cyprodinil (CYP) and 0.7 ng mL(-1) for myclobutanil (MYC). The optimized method was applied to seventeen commercial wines produced in Spain and obtained from local supermarkets. Nine fungicides were determined, at levels above the LOQs of the method, in the above samples. The maximum concentrations and the highest occurrence frequencies corresponded to metalaxyl (MET) and iprovalicarb (IPR).

[Predicting very early rebleeding after acute variceal bleeding based in classification and regression tree analysis (CRTA).]. / Predicción de resangrado precoz en cirróticos con hemorragia variceal aguda. Función del análisis con árboles de clasificación y regresión (CART).

BACKGROUND: Variceal bleeding (VB) is the main cause of death among cirrhotic patients. About 30-50% of early rebleeding is encountered few days after the acute episode of VB. It is necessary to stratify patients with high risk of very early rebleeding (VER) for more aggressive therapies. However, there are few and incompletely understood prognostic models for this purpose. AIMS: To determine the risk factors associated with VER after an acute VB. Assessment and comparison of a novel prognostic model generated by Classification and Regression Tree Analysis (CART) with classic-used models (MELD and Child-Pugh [CP]). PATIENTS AND METHODS: Sixty consecutive cirrhotic patients with acute variceal bleeding. CART analysis, MELD and Child-Pugh scores were performed at admission. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the models. RESULTS: Very early rebleeding rate was 13%. Variables associated with VER were: serum albumin (p = 0.027), creatinine (p = 0.021) and transfused blood units in the first 24 hrs (p = 0.05). The area under the ROC for MELD, CHILD-Pugh and CART were 0.46, 0.50 and 0.82, respectively. The value of cut analyzed by CART for the significant variables were: 1) Albumin 2.85 mg/dL, 2) Packed red cells 2 units and 3) Creatinine 1.65 mg/dL the ABC-ROC. CONCLUSION: Serum albumin, creatinine and number of transfused blood units were associated with VER. A simple CART algorithm combining these variables allows an accurate predictive assessment of VER after acute variceal bleeding. Key words: cirrhosis, variceal bleeding, esophageal varices, prognosis, portal hypertension.

Diagnostic approach in suspected recurrent primary brain tumors using (18)FDG-PET/MRI, perfusion MRI, visual and quantitative analysis, and three dimensional stereotactic surface projections. First experience in Mexico.

UNLABELLED: Thirty patients with primary cerebral tumors WHO III and IV previously treated, undergoing evaluation for tumoral recurrence, they underwent (18)FDG-PET study, MRI and PMRI. PET uptake was determined by visual inspection and was quantified by use of standard uptake values, the ratio of tumor uptake to normal tissue and were z scored using automated voxel-based comparison. PMRI was quantified by use of ratios of cerebral blood volume (rCBV). The accuracies were determined by comparing imaging data with histologic findings and clinical follow up of up to 21 mo. RESULTS: Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy were 100 %, 82 %, 90 %, 100 % and 93 % respectively for the PET/MRI fusion and 68 %, 82 %, 87 %, 60 % and 73 % respectively for PMRI. There were two false positive cases for PET/MRI fusion that were confirmed by biopsy: chronic inflammation; and foreign body granulomas. The receiver operating characteristic (ROC) curve analysis showed statistically significant difference (p = 0.0225). CONCLUSIONS: (18)FDG SUVs, glucose uptake ratios and 3D stereotactic surface projections in brain tumors were not a reliable measure for evaluating recurrent tumors. PET/MRI fusion was more sensitive and accurate than PMRI for imaging recurrent primary brain tumors. The region of interest can be visually analyzed on the PET/MRI fusion images and described as recurrent tumor when any activity (lower, equal or greater than the contralateral cortex) is presented in the zone of hyperintensity seen on the post-gadolinium T1-weighted MRI.

Estudio comparativo de alteraciones electrocardiográficas, frecuencia cardiaca y presión arterial entre seropositivos y seronegativos para Trypanosoma cruzi en el valle de Vítor, Arequipa-Perú / Comparative study of electrocardiographic alterations, heart rate and arterial blood pressure between seropositives and seronegatives for Trypanosoma cruzi in valley of Vítor, Arequipa-Perú

Introducción: La forma clínica cardiaca es la principal causa de morbimortalidad de la enfermedad de Chagas, y su patogenia estaría relacionada con alteraciones del sistema nervioso autónomo que afectarían la fisiología cardiovascular. Objetivos: Comparar los valores de frecuencia cardiaca, presión arterial y las alteraciones electrocardiográficas de pobladores infectados con T. cruzi y sujetos control. Material y métodos: estudio analítico, observacional, transversal; realizado en el valle de Vítor de Arequipa en el período 2004-2005. Se estudiaron 75 voluntarios mayores de 15 años de edad, distribuidos en 25 seropositivos y 50 seronegativos para T. cruzi, pareados por edad y sexo. Se midió frecuencia cardiaca, presión arterial y se realizó electrocardiografía estándar, comparándose los resultados en ambos grupos. Resultados: Los valores de frecuencia cardiaca y presión arterial fueron similares entre los sujetos infectados con T. cruzi y los controles, al igual que la presencia de bradicardia sinusal, hipotensión e hipertensión arterial. En 40% de los sujetos seropositivos hubo alteraciones electrocardiográficas, y en sujetos control en 26% diferencia estadísticamente no significativa. Las alteraciones más frecuentes en ambos grupos fueron los cambios inespecíficos de repolarización, bradicardia sinusal, hemibloqueo anerior izquierdo, extrasistolias supraventriculares. Se presentó bloqueo completo de rama derecha y hemibloqueo anterior izquierdo en personas infectadas con T. cruzi menores de 40 años. Conclusiones: La prevalencia de alteraciones cardiovasculares fue similar en población infectada con T. cruzi y sujetos control. Las alteraciones al EKG más frecuentes no son las típicamente descritas en enfermedad de Chagas.

Introduction: the cardiac syndrome is the main cause of morbidty and mortality in Chagas disease, and its pathogenesis appears to be related to abnormalities of the autonomous nervous system which affect cardiovascular physiology. Objectives: to compare the values of heart rate ,blood pressure and electrocardiographic (EKG) abnormalities of the infected population with those of the control population. Materials and Methods: this is an analytic, observational, cross sectional study made in the valley of Vítor, Arequipa, from 2004 to 2005. Volunteers over 15 yearse of age ere studied: 25 T. cruzi seropositive an 50 T. cruzi seronegative persons. Examinations including heart rate, blood pressure and standard 12-lead EDGs were performed, comparing the results between the groups. Results: heart rate and blood pressure values were similar between seropositive subjects and their controls; the same was true of sinus bradycardia, hypotension and hypertension. EKG abnormalities were found in 40% of seropositives and 26% of the controls; the difference didn’t reach statistical significance. The EKG abnormalities detected most often in the 2 groups were nonspecific repolarization changes, sinus bradycardia, left anterior bundle block, and supraventricular estrasystoles. Complete right bundle block and partial left anterior bundle block were seen in seropositive persons under 40. Conclusions: the prevalence of cardiovascular abnormalities was similar between subjects infected with T. cruzi and their controls. The EKG abnormalities seen most frequently are different from those typically described in Chagas disease patients.

Human T cell lymphotropic virus type 1 infection and early neurologic development: a pilot study of 48 children.

To determine whether human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with delayed neurological development, we examined 48 Peruvian children with exposure to HTLV-1 who were identified at the Instituto Materno-Perinatal. Compared with 38 HTLV-1-seronegative children, the 10 seropositive children did not have higher rates of neurodevelopmental delay. Long-term follow-up is planned.

Myocardial perfusion scintigraphy (SPECT) in the evaluation of patients in the emergency room with precordial pain and normal or doubtful ischemic ECG. Study 60 cases.

OBJECTIVES: To evaluate the diagnostic utility of myocardial perfusion by SPECT and Gated-SPECT in the diagnosis of acute coronary syndrome in patients with precordial pain associated with normal or doubtful ischemic ECG within the first 6 hrs of the last episode of pain. METHODS: Sixty such patients who sought attention in the Emergency room were included. Myocardial perfusion SPECT and Gated-SPECT (GSPECT) was performed in all patients using two distinct protocols. All patients underwent resting and pharmacological stress test. In 30 cases coronary angiogram were performed. RESULTS: Resting myocardial perfusion was abnormal or positive in 25 patients (42%) and normal or negative in 35 patients (58%). In the latter group perfusion became abnormal in 15 patients (43%) under stress with dipyridamole, while it remained normal in 19 (54%). The last subgroup presented no coronary events during the 12 months following their hospital discharge. In the group of 25 patients with resting perfusion abnormalities acute myocardial infarction was diagnosed in 7 patients, ischemia in 12 and reverse-reversibility in 6. Myocardial perfusion scintigraphy showed in the resting phase a low sensitivity of 61% (95% CI 39-74%), and negative predictive value of 71% (95% CI, 58-82%). During the stress phase, the utility of the test increased significantly, with a sensitivity of 97% (95% CI, 83-99%), specificity of 79% (95% CI, 57-92%), positive predictive value of 87% (95% CI, 72-95%) and, most outstanding, a negative predictive value of 95% CI, 73-99%). CONCLUSIONS: Myocardial perfusion studies have a sensitivity of 97% for identifying patients with acute coronary syndrome, with precordial pain and normal or doubtful ischemic ECG. For the intermediate or low risk patients with acute coronary syndrome the non-invasive diagnostic techniques of SPECT and GSPECT systems of evaluating myocardial perfusion achieve a high degree diagnostic accuracy, safety and reduces unnecessary admissions and costs.

[Myocardial ischemia detection with adenosine administration and SPECT. Initial experience in Mexico]. / Detección de isquemia miocárdica mediante la administración de adenosina y técnica SPECT. Experiencia inicial en México.

UNLABELLED: Myocardial perfusion SPECT has a high sensitivity for the diagnosis of myocardial ischemia. Adenosine has been recently used to induce myocardial ischemia in the United States and Europe. At the present time there is not published experience using adenosine in Mexico. METHOD: We studied 22 patients with suspected myocardial ischemia. Coronary angiography was performed in 17 patients. We used a 8 mCi rest Tc-99m sestamibi followed by a 6 minute infusion of adenosine at a dose of 140 ug/kg/min; 24 mCi of Tc-99m were injected after the third minute of adenosine infusion. Patients returned 2 or 3 days later for a new stress study using physical stress or dipiridamole and the images were read using a 20 segments analysis and each segment was scored using a 5 points scale (0 = normal to 4 = absent uptake). The results were then compared with the adenosine images. RESULTS: The segmental score agreement between adenosine and physical or dipyridamole stress were good with 90% exact correlation. The side effects experienced by patients who received dipyridamole and adenosine were similar. CONCLUSION: Adenosine is a good alternative to induce myocardial ischemia. It showed a good correlation with physical or dipyridamole stress test.

Albendazole therapy for neurocysticercosis: a prospective double-blind trial comparing 7 versus 14 days of treatment. Cysticercosis Working Group in Peru.

OBJECTIVE: To compare the effectiveness of two regimens of albendazole therapy for neurocysticercosis. DESIGN: Randomized, double-blind clinical trial. SETTINGS: Patients admitted to neurologic wards in Lima, Peru. PATIENTS: Adult patients with active neurocysticercosis demonstrated by CT and Western blot (immunoblot). INTERVENTION: One week (n = 25) versus 2 weeks (n = 25) of albendazole therapy. MEASUREMENTS: Decrease in the number of cysts on CT. RESULTS: Effectiveness of albendazole was 78%, with no difference between the groups when compared 3 months after therapy. Complete cure was obtained in only 38% of patients. Patients with more than 20 cysts had poorer responses to therapy. The clinical course and EEG evolution improved in most patients. Side effects were present in 38% of patients, mainly mild, transient gastrointestinal symptoms. Therapy was also associated with exacerbation of neurologic symptoms. Two patients died in the first year after therapy, both because of aggregated infections of ventricle-peritoneal shunts. One-year follow-up CT showed lesions in three of 10 patients presumed to be cured 3 months after therapy. CONCLUSIONS: Extension of albendazole therapy for more than 7 days adds no benefits for the patients.

Patología neurológica del anciano: las alteraciones cognitivas. / Aged neurological patology: The cognitive alterations

Este trabajo revisa los aspectos cognitivos de dos cuadros fundamentales en la neuropatología del anciano: la `confusión mental' o delirio y las demencias. De ambas se examina la psicopatología, la clínica y el diagnóstico diferencial y los factores causales. En el caso de la `confusión mental' se examina las fases de la terapéutica; y en las demencias la fisiopatología y la biología molecular, con especial énfasis en los desarrollos recientes

[Acute appendicitis in children. Experience at a general hospital]. / Apendicitis aguda en el niño. Experiencia en un hospital general.

In order to establish a guide for the diagnosis of acute appendicitis, we reviewed the charts of patients with appendectomy. In a 7-year period, 385 patients were studied. The age range was 3 to 15 years. In 53% there was an administration of medications prior to surgery. Perforated appendicitis was found in the majority (53%) of the cases. We could not find any association between age and perforation. Only localized, persistent abdominal pain, peritoneal irritation, anorexia, and vomiting were useful for differential diagnosis. In patients with acute appendicitis (p greater than 0.05), leukocytosis (greater than 10,000/mm3), neutrophilia (greater than 70%) and bands (greater than 3%) were observed in 80% of the cases. The frequency of complications was elevated (39.5%), and the mortality was five times higher than referred in other studies. We propose an algorithm for both opportune diagnosis and treatment of the disease.