Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes.

We recently reported that lowering the high, habitual palmitic acid (PA) intake in ovulating women improved insulin sensitivity and both inflammatory and oxidative stress. In vitro studies indicate that PA can activate both cell membrane toll-like receptor-4 and the intracellular nucleotide oligomerization domain-like receptor protein (NLRP3). To gain further insight into the relevance to human metabolic disease of dietary PA, we studied healthy, lean and obese adults enrolled in a randomized, crossover trial comparing 3-week, high-PA (HPA) and low-PA/high-oleic-acid (HOA) diets. After each diet, both hepatic and peripheral insulin sensitivities were measured, and we assessed cytokine concentrations in plasma and in supernatants derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as proinflammatory gene expression in skeletal muscle. Insulin sensitivity was unaffected by diet. Plasma concentration of tumor necrosis factor-α was higher during the HPA diet. Lowering the habitually high PA intake by feeding the HOA diet resulted in lower secretion of interleukin (IL)-1ß, IL-18, IL-10, and tumor necrosis factor-α by PBMCs, as well as lower relative mRNA expression of cJun and NLRP3 in muscle. Principal components analysis of 156 total variables coupled to analysis of covariance indicated that the mechanistic pathway for the differential dietary effects on PBMCs involved changes in the PA/OA ratio of tissue lipids. Our results indicate that lowering the dietary and tissue lipid PA/OA ratio resulted in lower leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes, but the relevance to diabetes risk is uncertain.

Extended-release opioids in the management of cancer pain: a systematic review of efficacy and safety.

Despite the increased availability of strong analgesics and evidence-based recommendations for pain management, under-treatment of cancer-related pain is still common. Extended-release (ER) opioids, in contrast to immediate-release opioids, provide prolonged analgesia. In this review, we aimed to compare the efficacy and safety of ER opioid analgesics in managing moderate-to-severe pain in patients with cancer. We identified randomized controlled trials (RCTs) and controlled observational studies that compared ER opioids in cancer pain by searching several databases, including MEDLINE, EMBASE and the Cochrane Library. Two independent reviewers screened and evaluated retrieved records to select relevant studies. We dually assessed the risk of bias for included studies and evaluated the overall strength of evidence for six critical outcomes using Grading of Recommendations Assessment, Development and Evaluation level of evidence. A total of three double-blind RCTs (comparative efficacy and adverse events), two non-blinded RCTs and four observational studies (comparative adverse events) were included in this review. All randomized trials and one observational study were of high risk of bias, and three observational studies of unclear risk of bias. The level of evidence for the selected efficacy and safety outcomes was low and very low. We synthesized the findings qualitatively because of the paucity of relevant studies as well as variable study design and quality. This systematic review indicates no substantial differences in efficacy and frequent adverse events among ER opioids for cancer pain. The body of evidence, however, is limited to few comparisons and fraught with methodological shortcomings.

Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood.

BACKGROUND: The Western diet increases risk of metabolic disease. OBJECTIVE: We determined whether lowering the ratio of saturated fatty acids to monounsaturated fatty acids in the Western diet would affect physical activity and energy expenditure. DESIGN: With the use of a balanced design, 2 cohorts of 18 and 14 young adults were enrolled in separate randomized, double-masked, crossover trials that compared a 3-wk high-palmitic acid diet (HPA; similar to the Western diet fat composition) to a low-palmitic acid and high-oleic acid diet (HOA; similar to the Mediterranean diet fat composition). All foods were provided by the investigators, and the palmitic acid (PA):oleic acid (OA) ratio was manipulated by adding different oil blends to the same foods. In both cohorts, we assessed physical activity (monitored continuously by using accelerometry) and resting energy expenditure (REE). To gain insight into a possible mood disturbance that might explain changes in physical activity, the Profile of Mood States (POMS) was administered in cohort 2. RESULTS: Physical activity was higher during the HOA than during the HPA in 15 of 17 subjects in cohort 1 (P = 0.008) (mean: 12% higher; P = 0.003) and in 12 of 12 subjects in the second, confirmatory cohort (P = 0.005) (mean: 15% higher; P = 0.003). When the HOA was compared with the HPA, REE measured during the fed state was 3% higher for cohort 1 (P < 0.01), and REE was 4.5% higher in the fasted state for cohort 2 (P = 0.04). POMS testing showed that the anger-hostility score was significantly higher during the HPA (P = 0.007). CONCLUSIONS: The replacement of dietary PA with OA was associated with increased physical activity and REE and less anger. Besides presumed effects on mitochondrial function (increased REE), the dietary PA:OA ratio appears to affect behavior. The second cohort was derived from a study that was registered at clinicaltrials.gov as R01DK082803.

Short-term effects of dietary fatty acids on muscle lipid composition and serum acylcarnitine profile in human subjects.

In cultured cells, palmitic acid (PA) and oleic acid (OA) confer distinct metabolic effects, yet, unclear, is whether changes in dietary fat intake impact cellular fatty acid (FA) composition. We hypothesized that short-term increases in dietary PA or OA would result in corresponding changes in the FA composition of skeletal muscle diacylglycerol (DAG) and triacylglycerol (TAG) and/or the specific FA selected for ß-oxidation. Healthy males (N = 12) and females (N = 12) ingested a low-PA diet for 7 days. After fasting measurements of the serum acylcarnitine (AC) profile, subjects were randomized to either high-PA (HI PA) or low-PA/high-OA (HI OA) diets. After 7 days, the fasting AC measurement was repeated and a muscle/fat biopsy obtained. FA composition of intramyocellular DAG and TAG and serum AC was measured. HI PA increased, whereas HI OA decreased, serum concentration of 16:0 AC (P < 0.001). HI OA increased 18:1 AC (P = 0.005). HI PA was associated with a higher PA/OA ratio in muscle DAG and TAG (DAG: 1.03 ± 0.24 vs. 0.46 ± 0.08, P = 0.04; TAG: 0.63 ± 0.07 vs. 0.41 ± 0.03, P = 0.01). The PA concentration in the adipose tissue DAG (µg/mg adipose tissue) was 0.17 ± 0.02 in those receiving the HI PA diet (n = 6), compared to 0.11 ± 0.02 in the HI OA group (n = 4) (P = 0.067). The relative PA concentration in muscle DAG and TAG and the serum palmitoylcarnitine concentration was higher in those fed the high-PA diet.

Effects of the in vivo supply of butyrate on histone acetylation of cecum in piglets.

BACKGROUND: In vitro, butyrate inhibits histone deacetylase and down-regulates expression of cyclin D1. We hypothesized that an increased entry rate of butyrate into the cecal lumen would have similar effects in vivo. METHODS: We used frozen cecal tissue and data from previous studies, one showing that lactulose supplementation caused an increased rate of cecal synthesis of butyrate and decreased cecal cell proliferation and density of clostridia and the other showing that cecal cell proliferation was increased by an exogenous cecal butyrate infusion at a comparable rate. The ratio of acetylated to total histones (AH ratio) and cyclin D1 mRNA expression were measured in cecal tissue. RESULTS: Lactulose supplementation caused a 189% increase in the AH ratio (p = .004), which inversely correlated with cecal cell proliferation (r = -0.782; p = .008). With cecal butyrate infusion, we observed a significant decrease in histone acetylation (p = .02), which also inversely correlated with cecal cell proliferation (r = -0.797; p = .002). Cyclin D1 expression was increased 6.5-fold by lactulose feeding (p = .02) but decreased 50% with cecal butyrate infusion (p = .004). CONCLUSIONS: The effects on histone acetylation of increased "endogenous" butyrate production produced by lactulose feeding, but not exogenous cecal infusion of butyrate, mirror those in vitro. Thus, bacterial production and exogenous infusion of butyrate have opposite effects on histone acetylation and cyclin D1 expression, suggesting that the composition of bacterial flora may play a role in butyrate's in vivo effects on the cell cycle.

Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates implies evolutionary changes and functional redundancy of calbindins at implantation.

The endometrium is hostile to embryo implantation except during the 'window of receptivity'. A change in endometrial gene expression is required for the development of receptivity. Calbindin-d9k (CaBP-d9k) and calbindin-d28k (CaBP-d28k) are proteins possessing EF-hand motifs which have high affinity for Ca2+ ions. Previously, it has been demonstrated that, in mouse endometrium, the expression of both calbindins is highly regulated during implantation and that both proteins play critical but functionally redundant roles at implantation. This study was the first to determine the expression of these two calbindins in the human and rhesus monkey endometrium. Initial RT-PCR analysis demonstrated that CaBP-d28k but not CaBP-d9k mRNA expression is detectable in the endometrium of both species. Western blot analysis confirmed the presence of immuno-reactive CaBP-d28k protein in the primate endometrium. Furthermore, the endometrial expression pattern of CaBP-d28k mRNA and protein was examined by Northern blot analysis and immunohistochemistry respectively in both species across the menstrual cycle and during early pregnancy. Semi-quantitative statistical analysis of the immunohistochemistry results revealed that, in the human, CaBP-d28k protein expression was maximal in luminal and glandular epithelium during the mid-secretory phase, coinciding with the time when the endometrium is receptive to embryo implantation. Expression in rhesus monkey showed a similar trend. These results suggest that, in the primate endometrium, only CaBP-d28k is expressed and that the specific regulation of this calbindin is potentially important for the establishment of uterine receptivity.

Endometrial calbindins are critical for embryo implantation: evidence from in vivo use of morpholino antisense oligonucleotides.

The endometrium is receptive to embryo implantation only for a short period in each reproductive cycle: development of receptivity requires alterations in endometrial gene expression. Calbindin (CaBP)-d9k and CaBP-d28k are related proteins containing EF hand motifs that have a high affinity for Ca2+. We previously demonstrated that endometrial expression of CaBP-d9k mRNA is highly regulated during implantation in the mouse. This project aimed to determine the temporal and spatial expression of both CaBP proteins during early pregnancy and to establish whether they are necessary for blastocyst implantation. CaBP-d28k protein, like CaBP-d9k, was up-regulated in the endometrial epithelium just before implantation but disappeared at implantation sites after attachment. By the judicious intrauterine injection of morpholino oligonucleotides (MO) against CaBP-d9k into WT and CaBP-d28k null mice just before implantation, we selectively eliminated one or both CaBPs from the uterine epithelium. Implantation was blocked only when both CaBP-d9k and CaBP-d28k were absent: treated WT mice and untreated CaBP-d28k null mice were fertile. Furthermore, the effect on implantation was highly dependent on the timing of injection of MO. This report examining the function of implantation-related genes in the uterus using MO demonstrates that this technique is a highly effective means to specifically target uterine proteins in vivo. This study provides evidence for an absolute requirement for CaBPs during the early phase of embryo implantation, and thus that regulation of Ca2+ availability in the uterine environment of the implanting embryo is critical for successful implantation.

Effects of prefeeding a prebiotic on diarrhea and colonic cell proliferation in piglets fed lactulose.

OBJECTIVES: Severe lactulose malabsorption causes osmotic diarrhea and decreased cecal cell proliferation. We tested the hypothesis that prefeeding with inulin, a prebiotic, would attenuate these effects. METHODS: Piglets aged 10 days were randomized to 3 feeding groups (n = 6 each group): Control (CON), fed sow-milk replacement formula (SMR; lactose, 60 g/L) for 14 days; a lactulose-challenged group (LAC) that was fed SMR for 7 days and then a formula containing lactose (30 g/L) and lactulose (60 g/L) for 7 days; and a group prefed SMR containing inulin (3 g/L) for 7 days and then fed the lactulose-supplemented formula (INULIN). Groups CON and INULIN were pair-fed to LAC. Then, cecal tissue was collected for histology, determination of crypt cell proliferation index, apoptosis, and Western blot determination of expression of Bax, a pro-apoptotic protein. RESULTS: The fraction of days when diarrhea was present (mean +/- SD) was greater for LAC (0.87 +/- 0.14; p = .004) than CON (0.28 +/- 0.22; INULIN: 0.52 +/- 0.44; p = .058 vs LAC). Cell proliferation index for the total crypt was less for LAC (0.12 +/- 0.04; p = .016) compared with CON (0.20 +/- 0.04; INULIN: 0.15 +/- 0.04; p = .06 vs LAC). BAX protein expression and apoptosis were similar in the 3 groups. CONCLUSIONS: We observed trends consistent with the hypothesis that prefeeding inulin attenuates diarrhea and the reduction in cell proliferation caused by lactulose.

Complicaciones de los implantes faciales con fines estéticos / Complications for the application implants for aesthetic purposes

Las sustancias para implantes faciales se han utilizado desde los años 60. La introducción de nuevos materiales y las crecientes complicaciones por tratamientos estéticos determinan que estos pacientes consulten al dermatólogo. Presentamos cuatro pacientes de sexo femenino, con edades que van de los 51 a 88 años, que consultaron por presentar infiltraciones granulomatosas persistentes en distintas áreas de la cara, correspondientes a zonas de implantes efectuados para el relleno de arrugas. Estas manifestaciones se presentaron uno a diez años después de la aplicación de los implantes. Los hallazgos histopatológicos distintivos de cada material nos orientaron hacia el diagnóstico correcto de la sustancia inyectada

Evaluation of methods to assess physical activity in free-living conditions.

PURPOSE: The purpose of this study was to compare different methods of measuring physical activity (PA) in women by the doubly labeled water method (DLW). METHODS: Thirteen subjects participated in a 7-d protocol during which total daily energy expenditure (TDEE) was measured with DLW. Body composition, basal metabolic rate (BMR), and peak oxygen consumption were also measured. Physical activity-related energy expenditure (PAEE) was then calculated by subtracting measured BMR and the estimated thermic effect of food from TDEE. Simultaneously, over the 7 d, PA was assessed via a 7-d Physical Activity Recall questionnaire (PAR), and subjects wore secured at the waist, a Tritrac-R3D (Madison, WI), a Computer Science Application Inc. activity monitor (CSA; Shalimar, FL), and a Yamax Digi Walker-500 (Tokyo, Japan). Pearson-product moment correlations were calculated to determine the relationships among the different methods for estimating PAEE. Paired t-tests with appropriate adjustments were used to compare the different methods with DLW-PAEE. RESULTS: There was no significant difference between PAEE determined from PAR and DLW. The differences between the two methods ranged from -633 to 280 kcal.d(-1). Compared with DLW, PAEE determined from CSA, Tritrac, and Yamax was significantly underestimated by 59% (-495 kcal.d(-1)), 35% (-320 kcal.d(-1)) and 59% (-497 kcal.d(-1)), respectively. VO2peak explained 43% of the variation in DLW-PAEE. CONCLUSION: Although the group average for PAR-PAEE agreed with DLW-PAEE, there were differences in the methods among the subjects. PAEE determined by Tritrac, CSA, and Yamax significantly underestimate free-living PAEE in women.

Splanchnic uptake of leucine in healthy children and in children with cystic fibrosis.

Interpretation of tracer studies of amino acid kinetics in the fed state is dependent on knowledge of splanchnic uptake of diet-derived amino acids. We studied five healthy control children and five children with cystic fibrosis (CF). After an overnight fast, the children ingested, hourly, a formula diet for 11 h. 5,5,5-[2H3]Leucine was added to the feedings during the last 6 h, and an i.v. infusion of 1-[13C]leucine was administered during the last 2 h of the formula feeding. The mean rate of splanchnic uptake of leucine was similar in the CF and control group, 23.8 +/- 24.0 and 21.5 +/- 21.2 mumol.kg-1.h-1, respectively. Fractional splanchnic uptake of leucine was not significantly different in the patients with CF (0.16 +/- 0.112 mean +/- SD) compared with the control children (0.244 +/- 0.256(-1)). The rate of whole body protein breakdown was not significantly different between the groups (CF versus control) with (159 +/- 18 versus 135 +/- 28 mumol.kg-1.h-1) or without (135 +/- 14 versus 114 +/- 20 mumol.kg-1.h-1) correction for splanchnic leucine uptake. However, for the 10 cases combined, protein breakdown corrected for splanchnic leucine uptake (147 +/- 26 mumol.kg-1.h-1) was 18% greater than uncorrected protein breakdown (124 +/- 20 mumol.kg-1.h-1) (p = 0.009). The data suggest that companion studies of splanchnic uptake might enhance the interpretation of leucine kinetics in the fed state.

Enfermedad de Kyrle secundaria: a propósito de dos casos / Secondary Kyrle's disease: two cases

La enfermedad de Kyrle es una dermatosis excepcional, de etiología desconocida y difícil diagnóstico clínico, precisando estudios histopatológicos para llegar a él. Presentamos dos pacientes con enfermedad de Kyrle secundaria a enfermedades sistémicas

Eritema pernio en dos gemelas de ocho meses de vida / Chillblains in two tween sisters eigth months old

Se comunican 2 pacientes gemelas, de ocho meses de vida, que presentan lesiones maculares eritematovioláceas localizadas en el dorso y regiones laterales de los pies, con edema de los dedos. Se realizan los estudios histopatológicos que son compatibles con eritema pernio, entidad que se diagnostica con poca frecuencia en lactantes

Tuberculosis cutánea e inmunodepresión / Cutaneous tuberculosis and immunodeficiency

Se presentan dos casos de tuberculosis cutánea en pacientes inmunodeprimidos. El primero es un paciente HIV+ y el segundo es una mujer inmunodeprimida por corticoterapia. Es muy importante realizar un diagnóstico temprano para implementar un tratamiento exitoso

Neurofibromatosis segmentaria / Segmental neurofibromatosis

La neurofibromatosis segmentaria (tipo V en la clasificación de Riccardi), se manifiesta con neurofibromas y/o máculas café con leche con distrubución segmentaria. La etiología no está totalmente aclarada, pero se ha postulado una mutación somática postcigótica. Presentamos una paciente de 62 años de edad con esta forma particular de neurofibromatosis y realizamos una revisión de la literatura

Foliculitis pustulosa eosinofílica: presentación de cuatro casos y revisión de la literatura / Eosinophilic pustular folliculitis: presentation four cases and review of literature

La foliculitis pustulosa eosinofílica es una condición rara que está siendo declarada en pacientes HIV positivos de manera cada vez más frecuente. Generalmente, afecta a adultos y clínicamente se caracteriza por brotes recurrentes de papulopústulas estériles y pruriginosas agrupadas en forma anular y policíclica, afectando preferentemente áreas seborreicas. El examen histopatológico revela abscesos eosinofílicos. Presentamos 4 pacientes, 3 HIV positivos, con foliculitis pustulosa eosinofílica y revisamos la literatura

Stable isotope model for assessing production of short chain fatty acids from colon-derived sugar: application in pigs.

Sugar reaching the colon because of intestinal maldigestion or malabsorption may be fermented to acetate and other short-chain fatty acids, resulting in stimulation of colonic water absorption and cell proliferation. To explore this phenomenon in more detail, we have developed a stable isotope model for estimating the fraction of colon-derived glucose or lactose that is fermented to acetate, propionate and butyrate. In an initial application of the model, [d3]-acetate and either [1-(13)C]-glucose or [D-1-(13)C]-lactose were infused into the cecum or colon of piglets, and plateau plasma acetate enrichment was monitored in the carotid artery. In acutely anesthetized piglets, the fractions of glucose and lactose fermented to acetate were 17.0 and 20.0%, respectively. In a chronically catheterized piglet, fermentation was higher (34.2%). When conducted in chronically catheterized animals or via a colostomy or ileostomy in infants, this model may be used to determine how age, previous surgery or antibiotic therapy affects the efficiency of colonic assimilation of carbohydrate.