Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.

Diagnóstico de la apendicitis y su variación en el tiempo / Diagnosis of acute appendicitis: variation in time

OBJETIVOS: El uso de la tecnología ha transformado gradualmente el diagnóstico de la apendicitis, el cual continúa siendo un reto diagnóstico. Los objetivos de nuestro estudio fueron a) Describir la variación del diagnóstico de apendicitis en el tiempo y b) Evaluar las tasas de apendicectomías en blanco con el uso de diferentes medios diagnósticos. MATERIALES Y MÉTODOS: Revisión retrospectiva de base de datos. Descripción de la variación del diagnóstico de la apendicitis en el tiempo de 1.645 pacientes llevados a apendicectomía en una clínica de Bogotá de enero de 2011 a diciembre de 2016. Adicionalmente, se evaluó la tasa de apendicectomías en blanco con los diferentes métodos diagnósticos. RESULTADOS: El diagnóstico por hallazgos clínicos y ecográficos disminuyó, a la vez que el diagnóstico por tomografía se incrementó. La tasa de apendicectomías en blanco con el diagnóstico clínico fue 14,5%, mientras que con el uso de ecografía y tomografía fue 7,5% y 5,3% respectivamente. El número de apendicectomías disminuyó de 362 a 215 en seis años. Discusión: La disponibilidad de tecnología, su fácil realización y uso deliberado en urgencias, han transformado el diagnóstico de apendicitis, disminuyendo el número de pacientes operados y las apendicectomías en blanco. CONCLUSIÓN: Los resultados de este estudio sugieren que, el uso de tomografía abdominal ha incrementado con el tiempo, disminuyendo el diagnóstico por hallazgos clínicos y ecográficos; el número de apendicectomías en blanco es menor con el uso de la ecografía y la tomografía.

BACKGROUND: Technology changed progresively diagnosis of appendicitis, who is a challenge. The aims of our study were to a) Describe the variation of the diagnosis of appendicitis over time and b) Evaluate the rate of negative appendectomies with the use of different diagnostic tools. METHODS: Retrospective database review. Description of the variation of the diagnosis of appendicitis in time of 1645 patients in whom an appendectomy was performed in a health institution in Bogota from January 2011 to December 2016. In adition, The rate of negative appendectomy was also evaluated with the use of different diagnostic tools. RESULTS: The number of patients diagnosed by the clinical and ultrasound findings decreased in time, while the diagnosis by tomography increased. The rate of negative appendectomies with clinical evaluation was 14.5%, abdominal ultrasound 75% and tomography 5.3%. The number of appendectomies decreased from 362 to 215 in six years. DISCUSSION: The availability of technology, its easy realization and deliberate use in the emergency room, have gradually transformed the diagnosis of appendicitis, decreasing the number of patients operated and the rate of negative appendectomies. CONCLUSIONS: The results of this study suggest that a) the use of tomography has increased in time, decreasing the diagnosis of clinical and ultrasound findings, and b) the number of negative appendectomies was lower with the use of ultrasound and tomography.

Effect of surgeon's experience on complications from laparoscopic hysterectomy.

OBJECTIVE: To analyze the effect of learning in two surgeons on complications and conversion to laparotomy during total and subtotal laparoscopic hysterectomy. MATERIAL AND METHODS: We analyzed retrospectively 236 total and subtotal laparoscopic hysterectomies done by two surgeons from the time they first performed the procedure. The interventions were classified in three groups based on the surgeon's experience: the first 75 hysterectomies ("novice period"), the subsequent 75 hysterectomies ("intermediate"), and the subsequent 86 hysterectomies ("routine period"). RESULTS: Patient's characteristics changed as surgeons gained experience, with more complex operations (greater obesity, previous surgery and malignant disease) becoming more frequent. During the second group of operations when surgeons had an intermediate level of experience, the risk of major complications decreased (adjusted odds ratio: 0.28, 95% confidence interval: 0.10-0.85), as did the risk of type III complications of Clavien-Dindo classification (adjusted odds ratio 0.15, 95% confidence interval: 0.03-0.93). However, the percent rate of conversion to laparotomy remained stable in the second (intermediate experience) group. In the third group, after the surgeons had performed 150 procedures and when the risk of any type of complication was lowest, the risk of conversion to laparotomy decreased compared to the routine group. CONCLUSIONS: The surgeon's experience in performing laparoscopic hysterectomy plays an essential role in the decrease in the risk of complications, and this finding supports the importance of providing appropriate training for residents and gynecologists to enable them to perform this procedure with an optimal degree of competence and safety.

The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and regulates their hematopoietic fate.

Notch signaling is essential for definitive hematopoiesis, but its role in human embryonic hematopoiesis is largely unknown. We show that in hESCs the expression of the Notch ligand DLL4 is induced during hematopoietic differentiation. We found that DLL4 is only expressed in a sub-population of bipotent hematoendothelial progenitors (HEPs) and segregates their hematopoietic versus endothelial potential. We demonstrate at the clonal level and through transcriptome analyses that DLL4(high) HEPs are enriched in endothelial potential, whereas DLL4(low/-) HEPs are committed to the hematopoietic lineage, albeit both populations still contain bipotent cells. Moreover, DLL4 stimulation enhances hematopoietic differentiation of HEPs and increases the amount of clonogenic hematopoietic progenitors. Confocal microscopy analysis of whole differentiating embryoid bodies revealed that DLL4(high) HEPs are located close to DLL4(low/-) HEPs, and at the base of clusters of CD45+ cells, resembling intra-aortic hematopoietic clusters found in mouse embryos. We propose a model for human embryonic hematopoiesis in which DLL4(low/-) cells within hemogenic endothelium receive Notch-activating signals from DLL4(high) cells, resulting in an endothelial-to-hematopoietic transition and their differentiation into CD45+ hematopoietic cells.

Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E2 (PGE2, 2 μg/paw) in the rat’s hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE2, which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 μg/paw) and AM-630 (100 μg/paw) were used as CB1 and CB2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 μg dipyrone (mean = 5.825 ± 2.842 g), 20 μg diclofenac (mean = 4.825 ± 3.850 g) and 40 μg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac and indomethacin.

Impact of education, income and chronic disease risk factors on mortality of adults: does 'a pauper-rich paradox' exist in Latin American societies?

OBJECTIVES: To test the hypothesis that an inverse association exists between socio-economic position and all-cause mortality in a developing country in Latin America. STUDY DESIGN: Prospective cohort study carried out in Chile using data from a simple random sample of 920 apparently healthy subjects (weighted population 11,600 aged 30-89 years) followed for 8 years. METHODS: Education level (0-8 years, 9-12 years and > or = 13 years) and income quartiles were established at the outset of the study, along with behavioural and biological risk factors for chronic diseases: smoking, alcohol use, obesity, diabetes, hypertension, lipids and family history of death by cardiovascular disease. Relative risks of all-cause mortality were estimated using age-adjusted Cox regression models. RESULTS: During the follow-up period, 46 deaths were observed. Adjusting for age, gender, and behavioural and biological risk factors, the mortality risk for increasing categories of education after controlling for income was 1.0, 0.76 and 0.33 (P for trend<0.01). In contrast, the relative risk for increasing levels of income after controlling for education was 1.0, 0.98, 1.33 and 1.17 (P for trend=0.07). CONCLUSION: While education level had a protective effect on mortality risk of Chilean adults, income had a slightly unfavourable effect on survival. This finding is described as suggestive of a 'pauper-rich paradox', since the higher income quantiles in this study correspond with the lower income levels in most developed countries. Nevertheless, due to the small number of deaths, additional research is required to assess the validity of these findings.

Impact of parity on anthropometric measures of obesity controlling by multiple confounders: a cross-sectional study in Chilean women.

AIM: To find out whether there is an association between parity and obesity, evaluated through body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) in Chilean women after controlling for sociodemographic characteristics, health risk and gynaeco-obstetric factors. DESIGN: Cross-sectional study, using baseline data of the San Francisco Project. SETTING: San Francisco de Mostazal, located in the central region of Chile, 6512 Chilean-Hispanic women (Spanish heritage with a variable indigenous component). METHODS: A weighted random sample of 508 women who had their first pregnancy inside the primary child-bearing ages. Data were collected between 1997 and 1999. Statistical associations between parity and different anthropometric measurements of adiposity in multiple linear (MLnR) and logistic regression models (MLtR) were evaluated. RESULTS: In MLnR a modest parity-related increment in BMI and practically null increment in WC, WHR and WHtR was observed. Covariates that showed a statistically significant association with anthropometric measures of adiposity were age, low education, marital status, employment, smoking, smoking cessation, hypertension, diabetes, dyslipidaemia, parent's obesity, menarche and fetal macrosomia. Crude odds ratio (OR) showed a strong association between parity and anthropometric markers of obesity. Nevertheless, after adjustments in MLtR models, the association remained only for BMI. All the measures of abdominal obesity related to parous women showed OR smaller than 1 (95% confidence intervals 0.57 to 0.96). CONCLUSIONS: Parity modestly influences BMI, but does not seem to be related to WC, WHR and WHtR after controlling by confounders. Parity can increase adiposity but not necessarily following an abdominal pattern.

[Mixedematous ileus; acute abdomen exacerbate.]. / Ileo mixedematoso;exacerbante de abdomen agudo.

The surgical literature contains few reports about effects of hypothyroidism in patients with acute abdomen; has been reported that a glycoprotein infiltrate the lining of the bowel leading to denervation. We report the case of a woman with acute abdomen secondary to pyosalpynx with uncontrolled hypothyroidism postoperative complications.Hypothyroidism is called "big mimicker"because its clinic spectrum ranges from anasymptomatic subclinical condition to the rare,life-threatening myxedema coma, and thus can bea challenging diagnosis to make. Unrecognized hypothyroidism may lead to unnecessary surgery or even a potentially fatal outcome. A heightened awareness of this not so uncommon entity is mandatory

Evaluación del gradiente intraventricular durante ejercicio en pacientes con miocardiopatía hipertrófica no obstructiva / Evaluation of the intraventricular gradient during exercise in patients with nonobstructive hypertrophic cardiomyopathy

Introducción: Habitualmente el gradiente intraventricular en pacientes con miocardiopatía hipertrófica se estima en condiciones de reposo. En este estudio se evaluó el comportamiento de este gradiente durante ejercicio físico. Secundariamente se observó la respuesta de la presión arterial y la tolerancia al ejercicio. Material y Métodos: Se eligieron pacientes con diagnóstico ecocardiográfico de miocardiopatía hipertrófica en quienes no se encontró gradiente intraventricular significativo (>25mmHg) en reposo. A todos se les practicó una prueba máxima de inmediato se volvió a estimular el gradiente intraventricular por ultrasonido doppler. Resultados: Se reclutaron 12 pacientes (6 hombres) con edad promedio de 45.4 años (31-60) todos sin gradiente y presión arterial basal promedio 117.91/72.5 mmHg. El tiempo promedio de ejercicio en el grupo fue 8.3 minutos, el gradiente intraventricular promedio al máximo esfuerzo fue 14.41 mmHg y la presión arterial promedio al esfuerzo máximo fue 140.911/76.66 mmHg. Tres pacientes presentaron falta de incremento normal de la presión arterial con ejercicio. Conclusión: En los pacientes con miocardiopatía hipertrófica sin gradiente intraventricular significativo estimado en reposo, no se observó mayor incremento de éste con ejercicio, sin embargo, algunos de ellos presentaron falta de incremento sistólico normal de la presión arterial lo que los incluyó en el grupo de alto riesgo. En general, la tolerancia al ejercicio fué baja. Palabras claves: Gradiente intraventricular, ejercicio, miocardiopatía hipertrófica.

Inheritable variable sizes of DNA stretches in the human MHC: conserved extended haplotypes and their fragments or blocks.

The difference in sizes of conserved stretches of DNA sequence within the major histocompatibility complex (MHC) in human individuals constitutes an underappreciated genetic diversity that has many practical implications. We developed a model to describe the variable sizes of stretches of conserved DNA in the MHC using the known frequencies of four different kinds of small (< 0.2 Mb) blocks of relatively conserved DNA sequence: HLA-Cw/B; TNF; complotype; and HLA-DR/DQ. Each of these small blocks is composed of two or more alleles of closely linked loci inherited as one genetic unit. We updated the concept of the conserved extended haplotype (CEH) using HLA allele identification and TNF microsatellites to show that specific combinations of the four blocks form single genetic units (>/= 1.5 Mb) with a total haplotype frequency in the Caucasian population of 0.30. Some CEHs extend to the HLA-A and -DPB1 loci forming fixed genetic units of up to at least 3.2 Mb of DNA. Finally, intermediate fragments of CEHs also exist, which are, nevertheless, larger than any of the four small blocks. This complexity of genetic fixity at various levels should be taken into account in studies of genetic disease association, immune response control, and human diversity. This knowledge could also be used for matching CEHs and their fragments for patients undergoing allotransplantation.

Amniotic membrane inlay and overlay grafting for corneal epithelial defects and stromal ulcers.

OBJECTIVES: To determine the effect of amniotic membrane transplantation (AMT) on persistent corneal epithelial defects (PEDs) and to compare the efficacy between inlay and overlay techniques. METHODS: Thirty patients (30 eyes) underwent AMT for PED. The use of AMT was restricted to patients in whom all previous measures, including bandage contact lens and tarsorrhaphy, had failed. The amniotic membrane was placed on the surface of the cornea in overlay (group A) or inlay (group B) fashion. RESULTS: The PED healed after the first AMT in 21 eyes (70%) within an average of 25.5 days after surgery and recurred in 6 eyes (29%). Among the 22 eyes treated with an overlay AMT (group A), the PED healed after the first AMT in 14 eyes (64%) within an average of 24.5 days and recurred in 4 eyes (29%). Among the 8 eyes treated with an inlay AMT (group B), the PED healed within an average of 27.4 days after AMT, which did not statistically significantly differ from group A (P = .72). The PED healed after the first AMT in 7 eyes (88%) and recurred in 2 (29%) of 7 eyes. CONCLUSIONS: The AMT can be helpful in the treatment of PED in which all other conventional management has failed. However, the success rate in our study was not as high as that previously reported, and our results showed a high incidence of recurrences of epithelial defects. We did not find any difference between overlay and inlay techniques in terms of healing time and recurrence rate.

A multimodality approach to the diagnosis of breast hamartomas with atypical mammographic appearance.

The ultrasonographic appearance of breast hamartomas (BHs) is described and its diagnostic utility is discussed in this study of 27 women with mammographic findings both typical and atypical of BH. The role of computed tomography (CT) in the diagnosis of BH of atypical mammographic appearance is also analyzed. These 27 cases of BH were detected in women submitted to mammographic screening. Ages ranged from 45 to 65 years (mean age 52.6 years). In all cases physical and ultrasonographic examinations were carried out. CT studies were carried out in seven cases. Core biopsy was performed in 18 cases of lesions with a mammographic appearance atypical of BH. Lesions were palpable in 9 cases and nonpalpable in 18. Mammographic appearance was characteristic in nine cases. In 19 cases a hypoechoic solid mass with hyperechoic lines and/or bands was seen. This ultrasonographic image is suspicious of BH. Finally, both CT and core biopsy findings were of great help in the diagnosis of BH in the cases where mammographic and ultrasonographic studies were inconclusive. We consider that a combination of mammography, ultrasonography, CT, and core biopsy is fundamental for the successful diagnosis of breast hamartomas not seen in typical form in mammograms.

[Reversible posterior leukoencephalopathy in a patient with non-Hodgkin's lymphoma after treatment with CHOP]. / Leucoencefalopatía posterior reversible en un paciente con linfoma no-Hodgkin tras tratamiento con CHOP.

Reversible posterior leukoencephalopathy syndrome is a newly characterised and increasingly recognized clinico-radiologic syndrome. Underlying conditions that reportedly trigger this syndrome include hypertensive encephalopathy, eclampsia, renal failure, and immunosuppressive drug therapy with cyclosporine, tacrolimus and interferon alpha. We describe a 51-year-old woman with non-Hodgkin's lymphoma treated with conventional CHOP chemotherapy. Eight days after this treatment she developed severe headache, bilateral visual loss and focal seizures with secondary generalization. Neurologic examination showed confusion, cortical blindness, and left hemiparesis with hyperreflexia and sensory loss. A cranial T2-weighted magnetic resonance imaging revealed increased signal intensity in the occipital and frontal lobes in both hemispheres and right parietal lobe. A diagnosis of reversible posterior leukoencephalopathy was made. She presented a favourable outcome with conservative treatment with mannitol and phenytoin. A new cranial scanning showed nearly complete resolution of the abnormalities. To the best of our knowledge, this is the first case of reversible posterior leukoencephalopathy in a patient treated with standard-dose CHOP. In this patient, we confirm the theoretical pathophysiologic mechanisms suggested explaining how these drugs can cause the syndrome.

[Cardiac rehabilitation as a first step in the secondary prevention of coronary heart disease]. / La rehabilitación cardíaca como punto de partida en la prevención secundaria de la enfermedad coronaria.

Despite that coronary heart disease is still the major cause of death in the industrialized countries and in some with emerging economies, a steady decline in the mortality for coronary heart disease has been observed in the last 30 years. This has been attributed predominantly to a reduction in smoking and in the cholesterol blood levels, two of the major risks factors for coronary heart disease. Cardiac rehabilitation programs represent today one of the most cost effective interventions to reduce the morbidity and mortality after a coronary event. They offer a unique opportunity to guide a patient immediately after an acute coronary episode through the inpatient care to the outpatient environment. In these programs a strong emphasis is made in the educational aspects of secondary prevention of coronary heart disease as well as in motivating patients to achieve life long lasting behavioral changes impacting on the major risk factors (smoking cessation, regular exercise, weight control, etc). The current subutilization of the Cardiac Rehabilitation Programs appears to be related to a variety of factors that include, among others, financial restraints and cultural values and perceptions with reference to health care.

Métodos de aglutinación con partículas de látex y rantz-randall para el diagnóstico de las infecciones estreptocócicas / Agglutination and rantz-randall methods for the diagnosis of streptococcal infections

En el presente trabajo se compararon los métodos de aglutinación con partículas de látex (AL) y Rantz-Randall (RR) para investigar anticuerpos antiestreptolisina "O" en 72 muestras de sueros sanguíneos. Este estudio reveló un mayor porcentaje de positividad, por el método RR (55,5 por ciento) que por AL (16,6 por ciento). Cuando evaluamos la discordancia en nuestros datos, se observa que un suero positivo por AL (título 400 UI/ml) fue negativo para RR, lo cual pudo ser un falso positivo por la presencia de anticuerpos inespecíficos. En el caso de las 19 muestras de suero que resultaron positivas por RR a diluciones superiores a 1:240 y negativas por AL, podría explicarse por la mayor sensibilidad de la primera técnica y/o la presencia de falsos negativos por la técnica de AL, debido al fenómeno de prozona. El análisis estadístico mediante el Chi cuadrado, determinó que entre los métodos de RR y AL, hubo diferencia significante, lo cual reveló la importancia de este estudio ya que demuestra que el método de RR constituye una alternativa superior al de AL, como complemento del diagnóstico clínico y bacteriológico de las infecciones estreptocócicas

[Cardiac tamponade as first clinical manifestation of small cell carcinoma]. / Taponamiento cardiaco como primera manifestación clínica de un carcinoma de células pequeñas.

A 69 year old man was diagnosed of cardiac tamponade. At surgery a large hemopericardias was evacuated, cardiac and pericardial metastasis of an oat cell carcinoma was demonstrated. The patient died 4 weeks later. A review of the literature is done about patients with cardiac tamponade as the first manifestation of a neoplastic process.