Rational use of short-term anorectic drugs for one-year effective treatment of obesity: An analysis of four studies.

BACKGROUND: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity. OBJECTIVE: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed. MATERIALS AND METHODS: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation. RESULTS: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%. CONCLUSION: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

Corrigendum to Article CP203292.

Cecilia Fernández Del Valle-Laisequilla, Cristian Trejo-Jasso, Juan Carlos Huerta-Cruz, Lina Marcela Barranco-Garduño, Juan Rodríguez-Silverio, Héctor Isaac Rocha-González, Juan Gerardo Reyes-García. Efficacy and safety of a fixed-dose combination of D-norpseudoephedrine, triiodothyronine, atropine, aloin, and diazepam in obese patients. Int J Clin Pharmacol Ther. 2018; 56: 531-538. doi: 10.5414/CP203292. Note from the authors: We realized only now that the affiliation of Cecilia Fernández Del Valle-Laisequilla was indicated in the title page, but due to an unintentional mistake in the final version, the affiliation was not declared in the conflict of interest section, which should read: "Cecilia Fernández Del Valle-Laisequilla is Medical Director of Productos Medix S.A. de C.V."

Three- and six-month efficacy and safety of phentermine in a Mexican obese population.

OBJECTIVE: Mexico has the second largest prevalence of obesity among adults worldwide, a condition especially affecting the low-income population. There is a pressing need to improve therapeutic options for weight loss. Phentermine is an old and low-cost agent given as an adjuvant therapy for obesity for a 12-week period, at an initial dose of 15 mg or 30 mg. However, there are no precise guidelines on the suitability of both the starting dose and the continuation of treatment for 6 months. The aim of this study was to evaluate the 3- and 6-month efficacy and safety of phentermine in obese Mexican patients to elucidate the aforementioned. MATERIALS AND METHODS: In this prospective, multi-center, open-label study, 932 obese adults received 15 mg or 30 mg phentermine once daily for 6 months. RESULTS: 30 mg phentermine was more effective than 15 mg phentermine in improving anthropometric variables in the 3-month follow-up, but not after completing the 6-month treatment period. Nearly 40% of 3-month non-responders reached a body weight reduction of at least 5% at 6 months. Conversely, ~ 65% and 25% of 3-month responders maintained or improved, respectively, their body weight reduction with long-term phentermine. Potential tolerance as weight regain was ~ 10% from 3 to 6 months. None of the doses increased cardiovascular risk, although mild-to-moderate adverse events were more frequent with 30 mg phentermine. CONCLUSION: 30 mg phentermine was more effective than 15 mg phentermine after 3 months, but not at 6 months of treatment. An important number of subjects could benefit following the therapy from 3 to 6 months.

Evaluation of the Antinociceptive, Antiallodynic, Antihyperalgesic and Anti-Inflammatory Effect of Polyalthic Acid.

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.

Association of fever and antipyretic treatment with progressive organ dysfunction in sepsis: Prospective cohort.

INTRODUCTION: Whether fever and antipyretic treatment are related to progression of organ dysfunction (POD) in sepsis is currently not known. OBJECTIVE: To evaluate the association of fever and antipyretic treatment with POD in sepsis. METHODS: 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. RESULTS: 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). CONCLUSIONS: An axillary T° Max ≥ 39°C is a risk factor for POD in sepsis. The use of antipyretics was not associated with POD.

INTRODUCCIÓN: No se conoce si la fiebre y el tratamiento antipirético se relacionan con progresión de la disfunción orgánica (PDO) en sepsis. OBJETIVO: Evaluar la asociación de la fiebre y el tratamiento antipirético con la PDO en sepsis. MÉTODOS: 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. RESULTADOS: 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). CONCLUSIONES: La T° máx. axilar ≥ 39°C es un factor de riesgo para PDO en sepsis. El uso de antipiréticos no se asoció a PDO.

Electroacupuncture and Curcumin Promote Oxidative Balance and Motor Function Recovery in Rats Following Traumatic Spinal Cord Injury.

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.

[Tasa libre de litos sin complicación mayor como definición de éxito en nefrolitotomía percutánea].

Introduction: 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.

Introducción: El éxito en nefrolitotomía percutánea (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 definición de éxito en NLP que comprenda la tasa libre de litos sin complicaciones mayores y una escala de riesgo para predecir este desenlace. Método: Cohorte histórica de pacientes sometidos a NLP. Las variables incluidas fueron edad, sexo, urocultivo, índice de comorbilidad de Charlson (ICC) y lito complejo. Se definió éxito: sin litos, sin o con complicación Clavien ≤ 2; éxito intermedio: con litos sin o con complicación Clavien ≤ 2; fracaso: con o sin litos con complicación Clavien > 2. Se realizó análisis bivariado para identificar los factores asociados con el desenlace. Por regresión logística múltiple se calculó el peso independiente de cada factor. Resultados: Se incluyeron 568 procedimientos, 59 % en el sexo femenino. La mediana de edad fue de 49 años; 65, 22 y 13 % de los casos tuvieron éxito, éxito intermedio y fracaso. El sexo femenino, urocultivo positivo, lito complejo e ICC severo se asociaron con fracaso. Conclusión: La probabilidad de éxito fue directamente proporcional al número de factores de riesgo.

Factores predictores del estado libre de cálculos en la primera ureteroscopia flexible con litotricia láser.

INTRODUCTION: 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.

INTRODUCCIÓN: La ureteroscopia flexible con litotricia láser (URSLL) es una modalidad mínimamente invasiva de tratamiento quirúrgico de cálculos renales. La selección 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 quirúrgico en pacientes sometidos a URSLL. MÉTODO: Cohorte retrospectiva de pacientes sometidos a URSLL. Se realizó un análisis univariado y multivariado (regresión logística) de los predictores de estado libre de cálculos en la primera URSLL, global y categorizado por sexo. RESULTADOS: EL estado libre de cálculos en la primera URSLL fue de 73.62 %. Los predictores de estado libre de cálculos en hombres fueron edad y tamaño, densidad y multiplicidad del cálculo; en las mujeres, el índice de masa corporal y la multiplicidad del cálculo. CONCLUSIONES: Los factores pronósticos de estado libre de cálculos en la primera URSLL son distintos en hombres y mujeres. Las mujeres con obesidad y sobrepeso probablemente tengan cálculos de fácil fragmentación y extracción asociados con ácido úrico.

Antinociceptive effect of (-)-epicatechin in inflammatory and neuropathic pain in rats.

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.

Efficacy and safety of a fixed-dose combination of D-norpseudoephedrine, triiodothyronine, atropine, aloin, and diazepam in obese patients
.

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.
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Relationship between blood levels and the anti-hyperalgesic effect of ketoprofen in the rat.

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.

[Characteristics of patients with systemic sclerosis who develop interstitial lung disease]. / Características de los pacientes con esclerosis sistémica que desarrollan enfermedad pulmonar intersticial.

Background: Systemic sclerosis associated-interstitial lung disease (SSc-ILD) show a high mortality. The factors associated SSc-ILD have shown variability in different populations. There are few studies in Mexican mestizos. Objective: To analyze the epidemiological, clinical and paraclinical factors associated with SSc-ILD. Material and methods: Cross-sectional study, where patients > 18 years of age with a diagnosis of SSc according to EULAR/ACR 2013 criteria and diagnosis of ILD by forced vital capacity (FVC) < 70% and > 5% of affected lung area on tomography were included. The strength of association of the factors for ILD was measured by odds ratio (OR) with 95% confidence intervals (95% CI). The significant variables were analyzed by multiple logistic regression with adjustment. Results: Of the 80 patients with SSc, 38 (47.5%) had ILD. Risk factors such as smoking, higher activity index, lower FVC, anti-topoisomerase I antibodies, and protective factors such as a limited SSc, early capillaroscopic pattern, and anti-centromere antibodies (ACA) were associated with ILD. In the multivariate analysis, a higher activity index with OR 4.17, (95% CI 2.01-8.65) persisted as a risk factor, while ACA with OR 0.17, (95% CI 0.03-0.85) persisted as a protective factor associated with SSc-ILD. Conclusions: A higher index of activity and ACA persisted as factors associated with SSc-ILD.

Introducción: la enfermedad pulmonar intersticial (EPI) está relacionada a una mayor mortalidad en esclerosis sistémica (ES). Los factores asociados a su presentación han mostrado variabilidad en diferentes poblaciones. Pocos estudios se han realizado en mestizos mexicanos. Objetivo: analizar los factores clínicos y paraclínicos asociados a EPI en pacientes con ES. Material y métodos: estudio retrospectivo de casos y controles en el que se incluyeron pacientes > 18 años con diagnóstico de ES, según criterios EULAR/ACR 2013 y EPI por capacidad vital forzada (CVF) < 70% y > 5% de área pulmonar efectada en tomografía. La fuerza de asociación de los factores para EPI se midió por razón de momios (RM) con intervalos de confianza del 95% (IC95%). Las variables significativas se analizaron por regresión logística múltiple con ajuste. Resultados: de los 80 pacientes con ES, 38 (47.5%) tenían EPI. Factores de riesgo como tabaquismo, mayor índice de actividad, menor CVF, anticuerpos antitopoisomerasa I y factores protectores como variedad limitada de ES, patrón capilaroscópico temprano y anticuerpos anticentrómero estuvieron asociados a EPI. En el análisis multivariado un mayor índice de actividad con RM 4.17, (IC95%: 2.01-8.65) persistió como un factor de riesgo; en cambio, los anticuerpos anticentrómero con RM 0.17, (IC95%: 0.03-0.85) persistieron como un factor protector asociado a EPI. Conclusiones: un mayor índice de actividad y la presencia anticuerpos anticentrómero persistieron como factores asociados a la presencia de EPI en ES.

Osteoprotegerin Gene Polymorphisms Are Associated with Subclinical Atherosclerosis in the Mexican Mestizo Population.

Subclinical atherosclerosis (SA) is the presence of coronary calcification in the absence of cardiovascular symptoms, and it usually progresses to atherosclerotic disease. Studies have shown an association of osteoprotegerin gene (OPG) variants with calcification process in cardiovascular diseases; however, to this day there are no studies that evaluate individuals in the asymptomatic stage of atherosclerotic disease. Therefore, the purpose of this study was to analyze the association of four genetic variants and haplotypes of the OPG gene with the development of SA, through TaqMan genotyping assays. We also aimed to identify potential response elements for transcription factors in these genetic variants. The study included 1413 asymptomatic participants (1041 were controls and 372 were individuals with SA). The rs3102735 polymorphism appeared as a protective marker (OR = 0.693; 95% CI = 0.493−0.974; pheterozygote = 0.035; OR = 0.699; 95% CI = 0.496−0.985; pcodominant 1 = 0.040) and two haplotypes were associated with SA, one as a decreased risk: GACC (OR = 0.641, 95% CI = 0.414−0.990, p = 0.045) and another as an increased risk: GACT (OR = 1.208, 95% CI = 1.020−1.431, p = 0.029). Our data suggest a lower risk of SA in rs3102735 C carriers in a representative sample of Mexican mestizo population.

GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats.

Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.

Anti-inflammatory and cytotoxic activities of chichipegenin, peniocerol, and macdougallin isolated from Myrtillocactus geometrizans (Mart. ex Pfeiff.) Con.

The oleanane-type triterpene chichipegenin and the sterols peniocerol and macdougallin, isolated from Myrtillocactus geometrizans, showed anti-inflammatory activities in both the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model and the carrageenan-induced rat paw edema model. All tested compounds inhibited the TPA-induced edema in a dose-dependent manner, with ED50 values less than or equal to that shown by indomethacin. Among them, peniocerol was the most active compound. However, only peniocerol and macdougallin reduced carrageenan-induced rat paw edema. On the other hand, peniocerol and macdougallin showed cytotoxicity against several human cancer cell lines. These results indicate that compounds isolated from M. geometrizans possess antiinflammatory and cytotoxic properties, and the presence of chichipegenin in the aerial parts could justify the medicinal uses attributed to the plant.

Bioassay-guided isolation of an anti-ulcer compound, tagitinin C, from Tithonia diversifolia: role of nitric oxide, prostaglandins and sulfhydryls.

Tithonia diversifolia is a medicinal plant from the Municipality of Suchiapa, Chiapas, Mexico, that according to local folk medicine is considered useful in the treatment of gastric ulcers. The aim of the present study was to investigate the gastroprotective activity of T. diversifolia by using an ethanol-induced gastric ulcer experimental model in male Wistar rats. The results showed that T. diversifolia had gastroprotective activity, and that the dichloromethane extract had the highest protective activity (close to 90% when using doses between 10 to 100 mg/kg), and that further the compound tagitinin C isolated from this extract was the main active gastroprotective agent. Rats treated with tagitinin C suspended in Tween 80 at 1, 3, 10 and 30 mg/kg showed 37.7, 70.1, 100, and 100% gastroprotection, respectively. The effect elicited by tagitinin C (30 mg/kg) was not attenuated by pretreatment with either N(G)-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups, or indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, which suggests that the gastroprotective mechanism of action of this sesquiterpene lactone does not involve NO, sulfhydryl groups or prostaglandins.

Gut dysbiosis and clinical phases of pancolitis in patients with ulcerative colitis.

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.

Underexpression of endothelial nitric oxide synthase leads to more severe pulmonary complex vascular lesions associated with HIV patients.

Background: 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). Methods: 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; p < 0.05 was accepted as statistically significant. Results: 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. Conclusion: 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.

Antecedentes: 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). Métodos: 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 p < 0.05. Resultados: 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. Conclusiones: 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.

Abnormal fluid distribution and low handgrip strength index as predictors of mortality in Mexican patients with chronic heart failure.

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 <10.1 and women <7.95 kg/m2. The primary outcome was all-cause mortality. 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.

Patient knowledge of fecal calprotectin in inflammatory bowel disease (IBD): An observational study in Mexico.

Background: Fecal calprotectin (FC) can be a valuable tool to optimize health care for patients with inflammatory bowel disease (IBD). The objective of this observational study was to determine the level of knowledge of the FC test in Mexican patients with IBD. Methods: A self-report questionnaire was distributed via Facebook to patients with IBD. The survey consisted of 15 questions in two categories: the first category assessed knowledge of IBD diagnosis, and the second category assessed knowledge of the FC test. Results: In total, 460 patients with IBD participated, of which 83.9% (386) had ulcerative colitis (UC) and 16.0% (74) had Crohn's disease (CD). Regarding IBD diagnosis, 41.9% of participants stated that they did not know of a non-invasive test for fecal matter to identify inflammation of the colon. Regarding the FC test, 57.5% (UC) and 58.1% (CD) stated that they did not know about the test. Additionally, 65.8% (UC) and 51.3% (CD) of participants stated that they had never received the FC test and 82.6% (UC) and 77.0% (CD) recognized that the FC test was difficult to access in their medical practice. Furthermore, 66% (UC) and 52.7% (CD) of participants noted that their specialist doctor had never suggested the FC test to them, yet 89.1% (UC) and 87.8% (CD) stated that they would prefer FC analysis for their IBD follow-up assessments. Conclusions: There is little knowledge of the FC biomarker among Mexican patients with IBD. This suggests the need for greater dissemination of its use and scope as a biomarker in IBD.