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Whether fever and antipyretic treatment are related to progression of organ dysfunction (POD) in sepsis is currently not known.To evaluate the association of fever and antipyretic treatment with POD in sepsis.Prospective cohort study of patients with sepsis. Maximum axillary temperature (T° Max), antipyretic drugs total dose and daily SOFA score were recorded. POD was defined as an increase ≥ 1 point on the SOFA score. A multivariate logistic regression model was used to evaluate the studied association.305 patients were included: 163 were women (53.4%), with a SOFA score of 8 points (6-11); 130 participants (42.62%) had T° Max ≥ 38°C, and 76 (24.9%), POD. Mortality in patients with fever was 26.2% vs. 20% (p = 0.21), and with POD, 73.7% vs. 5.7% (p = 0.01). T° Max ≥ 39°C had an OR of 4.96 (95% CI = 1.97-12.47, p = 0.01); and the use of antipyretics, an OR of 1.04 (95% CI: 0.58-1.86, p = 0.88).An axillary T° Max ≥ 39°C is a risk factor for POD in sepsis. The use of antipyretics was not associated with POD.No se conoce si la fiebre y el tratamiento antipirético se relacionan con progresión de la disfunción orgánica (PDO) en sepsis.Evaluar la asociación de la fiebre y el tratamiento antipirético con la PDO en sepsis.Estudio de cohorte prospectiva de pacientes con sepsis. Se registró temperatura axilar máxima (T° máx.), dosis total de fármacos antipiréticos y puntuación diaria de la escala SOFA. La PDO se definió como el incremento de SOFA ≥ 1 punto. Se utilizó un modelo de regresión logística multivariado para evaluar la asociación estudiada.Se incluyeron 305 pacientes: 163 mujeres (53.4 %) con puntuación SOFA de ocho puntos (6-11); 130 participantes (42.62 %) presentaron T° máx. ≥ 38 °C y 76 (24.9 %), PDO. La mortalidad en los pacientes con fiebre fue de 26.2 % versus 20 % sin fiebre (p = 0.21) y con PDO, de 73.7 % versus 5.7 % (p = 0.01). La T° máx. ≥ 39°C tuvo RM = 4.96 (IC 95 % = 1.97-12.47, p = 0.01) y el uso de antipiréticos, RM = 1.04 (IC 95 % = 0.58-1.86, p = 0.88).La T° máx. axilar ≥ 39°C es un factor de riesgo para PDO en sepsis. El uso de antipiréticos no se asoció a PDO.

Spinal cord injury (SCI) is a condition that puts the patient's life at risk in the acute phase and, during the chronic stage, results in permanent deficits in motor, sensory and autonomic functions. Isolated therapeutic strategies have not shown an effect on this condition. Therefore, this study aimed to evaluate the effects of electroacupuncture (EA) and curcumin, alone or combined, on the oxidative balance, motor function recovery and amount of preserved tissue following a traumatic SCI. Long-Evans rats were divided into five groups: SHAM, SCI, SCI + EA, SCI + Curcumin, and SCI + EA + Curcumin. Nitric oxide was significantly decreased in the Curcumin group; the EA, Curcumin and SCI + EA + Curcumin groups had significantly decreased hydroxyl radical and lipid peroxidation levels. Motor function recovery and the amount of preserved spinal cord tissue were significantly greater in the EA, Curcumin and EA + Curcumin groups. The results show that EA and Curcumin treatment alone or in combination decreased oxidative stress, improved functional motor recovery and increased the amount of preserved spinal cord tissue following a traumatic injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug–drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56–320 mg/kg), antiallodynic (100–562 mg/kg), and antihyperalgesic and anti-inflammatory (10–178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.

Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence pathophysiology and clinical response in UC. The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with UC as well as in healthy participants. Fecal samples were obtained from 18 patients with UC and clinical‐endoscopic evidenced pancolitis (active phase n = 9 and remission phase n = 9), as well as 15 healthy participants. After fecal DNA extraction, the 16S rRNA gene was amplified and sequenced (Illumina MiSeq), operational taxonomic units were analyzed with the QIIME software. Gut microbiota composition revealed a higher abundance of the phyla Proteobacteria and Fusobacteria in active pancolitis, as compared with remission and healthy participants. Likewise, a marked abundance of the genus Bilophila and Fusobacteria were present in active pancolitis, whereas a higher abundance of Faecalibacterium characterized both remission and healthy participants. LEfSe analysis showed that the genus Roseburia and Faecalibacterium were enriched in remission pancolitis, and genera Bilophila and Fusobacterium were enriched in active pancolitis. The relative abundance of Fecalibacterium and Roseburia showed a higher correlation with fecal calprotectin, while Bilophila and Fusobacterium showed AUCs (area under the curve) of 0.917 and 0.988 for active vs. remission pancolitis. The results of our study highlight the relation of gut dysbiosis with clinically relevant phases of pancolitis in patients with UC. Particularly, Fecalibacterium, Roseburia, Bilophila, and Fusobacterium were identified as genera highly related to the different clinical phases of pancolitis., The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with ulcerative colitis, as well as in healthy participants.

Despite increase in survival of human immunodeficiency virus (HIV) patients due to highly active antiretroviral therapy, non-infectious complications are still prevalent such as presentation of lung vasculopathy, even in asymptomatic patients. Endothelial nitric oxide synthase (eNOS) is necessary to produce nitric oxide that causes pulmonary endothelial vasodilation. Participation of this protein in the pulmonary circulation in HIV patients has not been elucidated. This work studied the presence and expression of eNOS in pulmonary complex vascular lesions associated with HIV (PCVL/HIV).In lung tissues from patients who died from complications of HIV, we used immunohistochemistry and immune chemiluminescence (imageJ) to determine the different degrees of expression of eNOS in PCVL-HIV in comparison with non-PCVL/HIV. Reagents used were anti-eNOS and an automated system. All data are presented as mean and standard deviation. Differences were analyzed with Wilcoxon; p0.05 was accepted as statistically significant.In 57 tissues, the histological evidence of pulmonary vasculopathy was showed as different types (proliferative, obliterative, and plexiform) and severe presentation of vasculopathy than non-PCVL/HIV. A statistically significant decrease of eNOS was observed in all PCVL/HIV tissue samples.eNOS has a relevant role in the pathogenesis of pulmonary vasculopathy in acquired immunodeficiency syndrome patients. It is necessary to determine in the future the participation of eNOS and other mechanisms involved in PCVL/HIV.A pesar del incremento en la sobrevivencia del paciente con virus de inmunodeficiencia humana (VIH) debido al uso del tratamiento antiretroviral altamente efectivo, las complicaciones no infecciosas siguen ocasionando vasculopatía pulmonar, aun en pacientes asintomáticos. La óxido nítrico sintetasa (ONSe) es necesaria para la producción de óxido nítrico la cual provoca vasodilatación pulmonar. La participación de esta proteína en la circulación pulmonar en los pacientes con VIH aún no se ha dilucidado. Este trabajo estudia la presencia y la expresión de ONSe en las lesiones vasculares pulmonares complejas asociadas al VIH (LVPC/VIH).En tejidos pulmonares de pacientes que fallecieron por complicaciones del VIH, se utilizó inmunohistoquímica e inmunoquimioluminescencia (imageJ) para determinar los diferentes grados de expresión de la ONSe en LVPC/VIH. Los reactivos utilizados son anti-ONSe en sistema automatizado. Todos los datos son presentados en media y desviación estándar. Las diferencias son analizadas con la prueba de Wilcoxon; se aceptó como estadísticamente significativa una p0.05.En 57 pacientes, la histología de la vasculopatía pulmonar mostró diferentes tipos (proliferativo, obliterativo y plexiforme) además de varias presentaciones de vasculopatía en tejidos no-LVPC/VIH. Se observó diferencia estadística en la disminución de ONSe en todos los tejidos LVPC/VIH.La ONSe tiene un papel relevante en la patogénesis de la vasculopatía pulmonar en el VIH. Es necesario determinar en el futuro la participación de ONSe y otros mecanismos involucrados en LVPC/VIH.

The aim of this study was to investigate the antinociceptive potential of (-)-epicatechin and the possible mechanisms of action involved in its antinociceptive effect. The carrageenan and formalin tests were used as inflammatory pain models. A plethysmometer was used to measure inflammation and L5/L6 spinal nerve ligation as a neuropathic pain model. Oral (-)-epicatechin reduced carrageenan-induced inflammation and nociception by about 59 and 73%, respectively, and reduced formalin- induced and nerve injury-induced nociception by about 86 and 43%, respectively. (-)-Epicatechin-induced antinociception in the formalin test was prevented by the intraperitoneal administration of antagonists: methiothepin (5-HT1/5 receptor), WAY-100635 (5-HT1A receptor), SB-224289 (5-HT1B receptor), BRL-15572 (5-HT1D receptor), SB-699551 (5-HT5A receptor), naloxone (opioid receptor), CTAP (μ opioid receptor), nor-binaltorphimine (κ opioid receptor), and 7-benzylidenenaltrexone (δ1 opioid receptor). The effect of (-)-epicatechin was also prevented by the intraperitoneal administration of L-NAME [nitric oxide (NO) synthase inhibitor], 7-nitroindazole (neuronal NO synthase inhibitor), ODQ (guanylyl cyclase inhibitor), glibenclamide (ATP-sensitive K channel blocker), 4-aminopyridine (voltage-dependent K channel blocker), and iberiotoxin (large-conductance Ca-activated K channel blocker), but not by amiloride (acid sensing ion channel blocker). The data suggest that (-)-epicatechin exerts its antinociceptive effects by activation of the NO-cyclic GMP-K channels pathway, 5-HT1A/1B/1D/5A serotonergic receptors, and μ/κ/δ opioid receptors.

Objectives In patients with heart failure, fluid alteration and low muscle strength frequently coexist because of their reduced physical activity and sedentary behavior; however, few studies have evaluated the effects of this coexistence on the prognosis of these patients. The aim of this study was to examine the independent association between fluid alteration and the low handgrip strength (HGS) index with mortality in patients with chronic heart failure. Methods This observational study included 546 (53.3% male) stable outpatients with heart failure. The presence of an abnormal fluid distribution was determined with a bioelectrical impedance ratio (200/5 kHz) ≥0.85. Handgrip strength (HGS) was measured with a hand dynamometer, and the HGS index was calculated by dividing the HGS (kg) by the squared height (meters). A low HGS index was defined if men had Results The mean age of the study population was 60.75 ± 17 y, and 30% were classified with a low HGS index, 9.5% with an abnormal fluid distribution, and 29% with both. During the 36 mo of follow-up, 16.5% of the participants reached the endpoint. In men but not in women, coexistence of a low HGS index and abnormal fluid distribution were independently associated with all-cause mortality with a hazard ratio of 2.8 (95% confidence interval, 1.25–6.4; P = 0.01). Conclusions In men with heart failure, co-existence of a low HGS index and abnormal fluid distribution was independently associated with all-cause mortality.

espanolIntroduccion: El exito en nefrolitotomia percutanea (NLP) se define como estatus libre de litos, sin embargo, las complicaciones mayores se presentan con alta frecuencia y han sido reportadas como resultado secundario. Objetivo: Presentar una nueva definicion de exito en NLP que comprenda la tasa libre de litos sin complicaciones mayores y una escala de riesgo para predecir este desenlace. Metodo: Cohorte historica de pacientes sometidos a NLP. Las variables incluidas fueron edad, sexo, urocultivo, indice de comorbilidad de Charlson (ICC) y lito complejo. Se definio exito: sin litos, sin o con complicacion Clavien ≤ 2; exito intermedio: con litos sin o con complicacion Clavien ≤ 2; fracaso: con o sin litos con complicacion Clavien > 2. Se realizo analisis bivariado para identificar los factores asociados con el desenlace. Por regresion logistica multiple se calculo el peso independiente de cada factor. Resultados: Se incluyeron 568 procedimientos, 59 % en el sexo femenino. La mediana de edad fue de 49 anos; 65, 22 y 13 % de los casos tuvieron exito, exito intermedio y fracaso. El sexo femenino, urocultivo positivo, lito complejo e ICC severo se asociaron con fracaso. Conclusion: La probabilidad de exito fue directamente proporcional al numero de factores de riesgo. EnglishIntroduction: Success in percutaneous nephrolithotomy (PCNL) is defined as a stone-free status; however, major complications are highly common and have been reported as a secondary outcome. Objective: To propose a new definition of PCNL success that comprises a stone free rate without major complications and a risk scale to predict this outcome. Methods: Historical cohort of patients undergoing PCNL. The included variables were age, gender, urine culture, Charlson’s comorbidity index (CCI) and complex stones. Success was defined as a stone free status with or without Clavien grade ≤ 2 complication; intermediate success: with stones, with or without Clavien grade ≤ 2 complication; and failure: with or without stones with Clavien grade ≤ 2 complication. Bivariate analysis was performed to identify which factors are associated with the outcome. The independent weight of each factor was calculated by multiple logistic regression analysis. Results: 568 procedures were included, 59% of which were in females. Median age was 49 years; 65%, 22% and 13% of cases were classified as success, intermediate success and failure, respectively. Female sex, positive urine culture, complex stones and severe CCI were associated with failure. Conclusions: The likelihood of success was directly proportional to the number of risk factors.

espanolIntroduccion: La ureteroscopia flexible con litotricia laser (URSLL) es una modalidad minimamente invasiva de tratamiento quirurgico de calculos renales. La seleccion inadecuada de pacientes para este procedimiento genera un desbalance de costo-efectividad. Objetivo: Conocer los factores predictores de estado libre de litos en un solo tiempo quirurgico en pacientes sometidos a URSLL. Metodo: Cohorte retrospectiva de pacientes sometidos a URSLL. Se realizo un analisis univariado y multivariado (regresion logistica) de los predictores de estado libre de calculos en la primera URSLL, global y categorizado por sexo. Resultados: El estado libre de calculos en la primera URSLL fue de 73.62 %. Los predictores de estado libre de calculos en hombres fueron edad y tamano, densidad y multiplicidad del calculo; en las mujeres, el indice de masa corporal y la multiplicidad del calculo. Conclusiones: Los factores pronosticos de estado libre de calculos en la primera URSLL son distintos en hombres y mujeres. Las mujeres con obesidad y sobrepeso probablemente tengan calculos de facil fragmentacion y extraccion asociados con acido urico. EnglishIntroduction: Flexible ureteroscopy and laser fragmentation (FURSL) is a minimally invasive modality for surgical treatment of renal stones. Inadequate selection of patients for this treatment generates a cost-effectiveness unbalance. Objective: To know the stone-free rate predictors in a single surgical time in patients undergoing FURSL. Method: Retrospective cohort of patients undergoing FURSL. Global and gender-categorized univariate and multivariate (logistic regression) analyses were performed to identify stone-free predictors at first FURSL. Results: Stone-free rate at first FURSL was 73.62%. Predictors in males were patient age and stone size, density and multiplicity; in females, body mass index and multiplicity of stones. Conclusions: Stone-free rate predictors at first FURSL are different in males and females. Women with overweight and obesity probably have easy-to-fragment and easy-to-extract stones associated with uric acid.

Objective A fixed-dose combination (FDC) of D-norpseudoephedrine, tri-iodothyronine, atropine, aloin, and diazepam is used in Mexico for the short-term treatment of obesity; however, its efficacy and safety have been scarcely studied. The aim of this study was to analyze the efficacy and safety of this FDC in Mexican adult overweight and obese patients by a prospective, uncontrolled, multicenter, phase IV open-label study. Materials and methods 3,290 patients with a body mass index (BMI) ˃ 27 kg/m2 were included in the current study. Primary outcome was the absolute body weight loss, whilst secondary outcomes were the improvement of anthropometric and cardiometabolic parameters as well as the description of adverse events. Results The FDC decreased the body weight and BMI by -9.0 ± 5.6 kg and -3.4 ± 2.2 kg/m2, respectively, at 6 months. In addition, 43.3% and 14.3% of subjects achieved at least 5% or 10% weight loss at 6 months, respectively. The FDC also significantly improved waist circumference, hip circumference, body fat, visceral fat, systolic blood pressure, diastolic blood pressure, diabetes risk, and mortality risk, at 3 and 6 months. Moreover, the FDC seems to have better results in the following order: obese grade 3 ≈ obese grade 2 ˃ obese grade 1 ˃ overweight patients. Mild mouth dryness, anxiety, and headache were the main reported adverse events. Conclusion Data suggest that the FDC is effective and well tolerated for the short-term therapy of overweight and obesity in Mexican patients. .

Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y1, P2Y6 and P2Y11 receptors have been described in the sensory nervous system, but their participation, at peripheral level, in behavioral pain models is scarcely understood. This study assessed the role of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain. Ipsilateral, but not contralateral peripheral pre-treatment with the endogenous P2Y1 (ADP, 100-1000nmol/paw), P2Y6 (UDP, 180-300nmol/paw) and P2Y11 (ATP, 100-1000nmol/paw), or selective P2Y1 (MRS2365, 0.1-10nmol/paw), P2Y6 (PSB0474, 0.1-0.10pmol/paw) and P2Y11 (NF546, 0.3-3nmol/paw) receptor agonists increased 0.5% formalin-induced flinching behavior. Concordantly, peripheral pre-treatment with the selective P2Y1 (MRS2500, 0.01-10pmol/paw), P2Y6 (MRS2578, 3-30nmol/paw) and P2Y11 (NF340, 1-10nmol/paw) receptor antagonists significantly decreased 1% formalin-induced flinching behavior. Furthermore, the pronociceptive effect of ADP (100nmol/paw) or MRS2365 (10nmol/paw), UDP (300nmol/paw) or PSB0474 (10pmol/paw) and ATP (1000nmol/paw) or NF546 (3nmol/paw) was blocked by the selective P2Y1 (MRS2500, 0.01nmol/paw), P2Y6 (MRS2578, 3nmol/paw), and P2Y11 (NF340, 1nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y1 (66kDa), P2Y6 (36kDa) and P2Y11 (75kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y1, P2Y6 and P2Y11 receptors plays a pronociceptive role in formalin-induced pain.

According to the high consumption of the mixture of B vitamins and diclofenac in several countries, this combination has constituted a frequently used option in pain therapy from inflammatory origin. Although the evidence obtained from inflammatory pain animal models has shown the existence of analgesic synergy between diclofenac and the B vitamins mixture, the corresponding clinical evidence is scarce. A double-blind, randomized clinical trial study was designed to characterize the analgesic effect and safety of diclofenac and B vitamins against diclofenac alone in patients with severe osteoarthritis. Forty eight patients programmed to total knee arthroplasty with a pain level ≥7 in a 1-10 cm visual analogue scale were allocated to receive a single intramuscular injection of sodium diclofenac (75 mg) alone or combined with thiamine (100 mg), pyridoxine (100 mg) and cyanocobalamin (5 mg), and the pain level was evaluated during 12 h post-injection. Diclofenac+B vitamins mixture showed a superior analgesic effect during the assessed period and also a better assessment of the pain relief perception by patients than diclofenac alone. This study constitutes a clinical support on the improvement of the analgesic effect of diclofenac by B vitamins in patients with osteoarthritis programmed to total knee arthroplasty, as a clinical model of inflammatory pain.

Vitamin B2 (riboflavin) has been proposed as a prophylactic therapy of migraine. However, so far there are no preclinical studies about the analgesic properties of this vitamin. The current study was designed to investigate the possible antinociceptive, antihyperalgesic and antiallodynic effect of riboflavin in formalin, carrageenan-induced thermal hyperalgesia, and spinal nerve ligation models, respectively. Oral riboflavin produced a dose-related antinociceptive (6.25-50 mg/kg), antihyperalgesic (25-150 mg/kg) and anti-inflammatory (50-150 mg/kg) effect. Gabapentin (100 mg/kg, positive control), but not riboflavin (150-600 mg/kg), reduced tactile allodynia in neuropathic rats. Riboflavin-induced antinociception in the formalin test was reversed by pretreatment with NG-L-nitro-arginine methyl ester and glibenclamide, but not by NG-D-nitro-arginine methyl ester or naloxone. Our results indicate that riboflavin is able to produce antinociception and anti-inflammatory, but not antiallodynic, effect in the rat. The effect of riboflavin could be due to the activation of K+ channels or nitric oxide release, but not activation of opioid mechanisms.

Background and Aims Despite increase in survival of HIV patients due to highly active antiretroviral therapy (HAART), non-infectious complications are still prevalent such as presentation of lung vasculopathy, even in asymptomatic patients. Endothelin-1 (ET-1) is a potent vasoconstrictor that causes pulmonary vasculopathy. Participation of this protein in the pulmonary circulation in HIV patients has not been elucidated. In this work we studied the presence and expression of ET-1 in pulmonary complex vascular lesions associated with human immunodeficiency virus (PCVL/HIV). Methods We used immunohistochemistry and immunochemiluminescence (imagej) to determine the different degrees of expression of ET-1 in PCVL/HIV in comparison with non-PCVL/HIV. Reagents used were anti-endothelin-1 and an automated system. All data are presented as mean and standard deviation (SD). Differences were analyzed with one-way ANOVA; p Results Lung tissues from 56 patients who died from complications of HIV pulmonary infection and with PCVL were studied. Histological evidence of pulmonary vasculopathy was shown as different types (proliferative, obliterative and plexiform). A statistically significant increase in ET-1 expression was observed in all PCVL/HIV tissue samples and is associated directly with different grades of severity of endothelial dysfunction. Conclusions ET-1 has a relevant role in the pathogenesis of pulmonary vasculopathy in acquired immunodeficiency syndrome (AIDS) patients. It is necessary to determine in the future the participation of ET-1 and other mechanisms involved in PCVL/HIV.

The relationship between blood levels of ketoprofen and its anti-hyperalgesic effects was examined in rat using the carrageenan-evoked thermal hyperalgesia model. Female adult Wistar rats were injected with carrageenan into the plantar surface of the right hind paw. Immediately after, rats were administered with ketoprofen po and hindpaw withdrawal latency measured and micro-whole blood samples were obtained over six hours via a cannula inserted in the caudal artery. Ketoprofen levels were measured by HPLC. Ketoprofen concentration increased in a dose-dependent manner and was reflected in dose-dependent anti-hyperalgesic effect. The pharmacokinetic and pharmacodynamic parameters expressed as mean ± s.e.m. following administration of 1, 3.2, and 10 mg/kg ketoprofen were: Cmax 1.27 ± 0.08, 3.44 ± 0.20 and 11.76 ± 0.81 μg/mL; AUClast 4.16 ± 0.17, 11.63 ± 0.65 and 28.15 ± 1.32 μg h/mL; and Emax observed (AUCE ): 65.41 ± 7.79, 92.06 ± 6.46 and 98.42 ± 7.53%. A direct relationship between blood concentrations and the anti-hyperalgesic effect of ketoprofen followed a maximum effect model equation. The results indicate that the anti-hyperalgesic effect of ketoprofen in the carrageenan pain model can be predicted by the pharmacokinetic properties of ketoprofen.