Effect of milking frequency and α-tocopherol plus selenium supplementation on sheep milk lipid composition and oxidative stability.

The aim of this research was to study the effect of milking frequency [once-daily milking (ODM) vs. twice-daily milking (TDM)] and antioxidant (AOX) supplementation on fatty acid (FA) profile and oxidative stability in sheep milk. Sixteen Assaf ewes were used; 8 did not receive any vitamin-mineral supplement (control), and the other 8 received an oral dose of 1,000 IU of α-tocopherol and 0.4 mg of Se daily. The experiment consisted of 2 consecutive periods; the first was 3 wk with TDM of both mammary glands. The second period was 8 wk and consisted of ODM of one mammary gland and TDM of the other gland. All ewes were fed ad libitum the same total mixed ration from lambing and throughout the experiment. There were no differences in plasma or milk Se concentrations between control and AOX ewes. However, plasma and milk α-tocopherol concentrations and AOX capacity were increased in ewes receiving the AOX supplement. Milk FA profile was practically unaffected after 21 d of AOX supplementation. However, after 77 d, AOX supplementation increased the relative percentage of C16:0 and cis-9 C18:1 and reduced the proportions of some saturated FA with less than 16 carbons and cis-9 C12:1. Antioxidant supplementation had no effect on the proportions of conjugated linoleic acid or total polyunsaturated FA (PUFA) but decreased the proportion of trans-7,cis-9 C18:2 and increased that of n-6 C20:3. Once-daily milking did not affect α-tocopherol, Se, or fat resistance to oxidation in milk. Total monounsaturated FA, cis-9 C16:1, and several cis and trans isomers of C18:1 were increased and total saturated FA were decreased in milk from ODM glands. Compared with TDM, ODM increased the proportions of cis-9,cis-12 C18:2 and several isomers of C18:2 and reduced those of cis-9,cis-12,cis-15 C18:3 and some PUFA of 20 and 22 carbons, but total proportion of PUFA was unaffected. Once-daily milking and AOX supplementation modified milk FA profile, but the effects of ODM could be considered of little biological relevance for consumer health. Supplementing ewes with α-tocopherol plus Se could be considered an effective strategy to improve plasma AOX status and reduce milk fat oxidation without substantial changes in the milk FA profile.

Validity of criteria for hospital admission in exacerbations of COPD.

AIMS: To validate a previously developed set of explicit criteria for the appropriateness of hospital admission among these patients using the RAND/UCLA Appropriateness Methodology (RAM). METHODS: We conducted a prospective cohort study of patients experiencing symptoms of COPD exacerbation seen in the emergency departments (ED) of 16 hospitals belonging to the Spanish National Health Service. Sociodemographic and clinical variables needed to assess appropriateness were recorded. Main outcomes were mortality, severe COPD evolution, complications at follow up, and three patient-reported measures: dyspnoea level, capacity for physical activity and perceived health status. RESULTS: Appropriately admitted patients were more likely to die (6.70% vs. 2.68%, p = 0.0102) than inappropriately admitted patients, and were more likely to develop severe evolution (27.09% vs. 6.08%, p < 0.0001) and complications (18.72% vs. 11.92%, p = 0.0244). Among discharged patients, no significant differences were observed in clinical outcomes. All patients exhibited worse dyspnoea and capacity for physical activity after exacerbation, but changes among appropriately admitted patients were less than among appropriately discharged patients. CONCLUSION: Our appropriateness criteria identified patients in worse condition at ED arrival who were more likely to benefit from admission in terms of mortality and COPD evolution.

Effect of reduction of milking frequency and supplementation of vitamin E and selenium above requirements on milk yield and composition in Assaf ewes.

The aim of this research was to study the effect of milking frequency and supplementation with a vitamin-mineral complex above requirements on intake, body weight (BW), and milk yield and composition in high-yielding Assaf ewes. Sixteen lactating Assaf ewes were used in this study, separated into 4 groups of 4 ewes each. Animals in 2 of the groups (control groups) did not receive any extra vitamin-mineral supplement, whereas animals in the other 2 groups (supplement groups) received daily an oral dose of 1g of vitamin E (1,000 IU, DL-α-tocopherol acetate) and 0.4 mg of selenium (sodium selenite anhydrous). The experiment consisted of 2 consecutive periods of 3 wk (twice-daily milking in both mammary glands) and 8 wk (once-daily milking in one mammary gland and twice-daily milking in the other gland). Intake, BW, and milk composition were controlled weekly, and milk production was recorded 3 times a week. Administration of the vitamin-mineral supplement had no effect on dry matter intake, BW, or milk production and composition. The reduction of milking from twice to once a day caused a decrease in milk production and lactose concentration and a significant increase in protein concentration, total solids, and somatic cell count, without affecting the fat content. Administration of a vitamin E and Se supplement at the doses used in the present study does not seem to exert, in the short term, a noticeable effect on the mammary gland when milking frequency is reduced.

Relation between personality dimensions and symptomatology of depression in skin cancer patients.

BACKGROUND: Environmental psychological factors such as mood states can modify and trigger an organic response; depressive disorder is considered a risk factor for oncological development, leading to alterations both in the genesis and in the progression of the disease. Some authors have identified that personality relates to mood since a high score in neuroticism is associated with intense and long-lasting emotions of stress and therefore with the development of depressive behaviors. The objective of this study was to analyze the relationship between personality and depression in skin cancer patients. METHODS: A total of forty-seven clinically and histopathologically diagnosed patients were scheduled for an hour-long interview, during which they provided informed consent and sociodemographic information. The psychological questionnaires applied were the revised Eysenck Personality Questionnaire and the clinical questionnaire for the diagnosis of the depressive syndrome. RESULTS: The patient's mean age was 66.5 years (SD ± 12.4) and the majority were diagnosed with basal cell carcinoma (70.2%). The frequency of anxious/depressive symptoms was 42.5%, with an increase in depression scores in the female gender (p < 0.001). Furthermore, a difference was found in the neuroticism dimension related to gender, with higher values in women (p = 0.002). Depressive symptomatologic portraits were correlated with the dimensions of neuroticism (p < 0.001, r = 0.705), psychoticism (p = 0.003, r = 0.422) and lying (p = 0.028, r = - 0.321). CONCLUSIONS: Our results support the hypothesis that personality dimensions are related to the presence of anxiety/depressive symptomatology in patients with skin cancer, especially in the female gender. Highlighting the need for future research that delves into the implications at the psychological level, the quality of life, and the biological mechanisms that link personality and depressive symptoms in the development and evolution of skin cancer.

Identification of TNF-alpha and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array.

BACKGROUND: Several drugs are available to treat metastatic renal-cell carcinoma (MRCC), and predictive markers to identify the most adequate treatment for each patient are needed. Our objective was to identify potential predictive markers of sunitinib activity in MRCC. METHODS: We collected sequential serum samples from 31 patients treated with sunitinib. Sera of six patients with extreme phenotypes of either marked responses or clear progressions were analysed with a Human Cytokine Array which evaluates 174 cytokines before and after treatment. Variations in cytokine signal intensity were compared between both groups and the most relevant cytokines were assessed by ELISA in all the patients. RESULTS: Twenty-seven of the 174 cytokines varied significantly between both groups. Five of them (TNF-alpha, MMP-9, ICAM-1, BDNF and SDF-1) were assessed by ELISA in 21 evaluable patients. TNF-alpha and MMP-9 baseline levels were significantly increased in non-responders and significantly associated with reduced overall survival and time-to-progression, respectively. The area under the ROC curves for TNF-alpha and MMP-9 as predictive markers of sunitinib activity were 0.83 and 0.77. CONCLUSION: Baseline levels of TNF-alpha and MMP-9 warrant further study as predictive markers of sunitinib activity in MRCC. Selection of patients with extreme phenotypes seems a valid method to identify potential predictive factors of response.

Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes.

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators.

Biology of BMP signalling and cancer.

In recent years, it has been proposed that tumours are not homogeneous but composed of several cellular types like normal tissues. A cellular subtype, which is though to be the origin of tumours as well as their malignant properties (i.e., capacity for regrowth and metastasis), are the cancer stem cells (CSCs). CSCs, like normal stem cells, have a nearly unlimited capacity to self-renew and to proliferate so that are responsible, besides their same auto-perpetuation giving rise to the features previously depicted, also for the generation of the bulk of more differentiated cells in tumour. The altered behaviour of CSCs may be caused by the malfunction of a number of signalling pathways involved in normal embryonic development and in tissue homeostasis in adulthood. Among these signalling pathways are Wnt, Hedgehog, Notch and BMP pathways. In this review, we will focus on the study of molecular aspects of BMP signalling as well as its involvement in cancer.

[Neonatal morbidity and mortality associated with low adherence to prenatal corticosteroids]. / Morbimortalidad neonatal en un entorno de baja adherencia a corticosteroides prenatales.

INTRODUCTION: Prenatal corticosteroids reduce neonatal mortality and morbidity; however, there are few studies in developing countries, and with inconsistent results. The purpose of this study was to quantify the frequency of the use of prenatal corticosteroids and to estimate its effect on the morbidity and mortality of premature newborns. METHODS: A retrospective cohort study was performed on premature newborns selected from a census conducted between January 2016 and August 2017. The use of corticosteroids was taken from the maternal records, and the dependent variables from the neonatal records. An analysis was made of the relationship using logistic regression, adjusted to gestational age and weight. RESULTS: The study included 1083 premature infants of which 53.3% were male. The mean gestational age was 33.4 weeks. Corticosteroids were received by 42%, with latency ≥24hours in 23.6% and ≥48hours in 13.8%. Respiratory distress syndrome was observed in 35% (379/1083), early neonatal sepsis in 4.4% (48/1083), late neonatal sepsis in 10.7% (116/1083), intraventricular haemorrhage in 15.1% (137/908), chronic lung disease in 51.4% (165/321), and death in 22.3% (242/1083). Prenatal corticosteroids decreased the risk of death in children under 34 weeks (OR 0.63, 95% CI 0.40-0.98). The decrease was greater if they presented with latency ≥48hours (OR 0.40, 95% CI 0.20-0.80). The rest of the dependent variables were not modified by the intervention. CONCLUSIONS: In preterm infants, 42% received antenatal corticosteroids. In those with less than 34 weeks, there was a decrease in the risk of death without changes in morbidity.

[Molecular biology of the clear cell renal cell carcinoma: principles for a selective treatment]. / Biología molecular del carcinoma de células claras renales: principios para un tratamiento selectivo.

Renal cell carcinoma (RCC) and its most frequent subtype, the clear cell hystology type, has shown resistance to chemotherapy and radiotherapy treatment when disease was already spread in patients. Recently, a huge advance in the molecular biology of this tumor has been performed. This fact allowed a deeper and better knowledge of the disease and the development of new drugs that work against the growth factors involved in tumor origin. In this review article it is summarized the molecular milestones that are involved in the development of clear cell renal cell carcinomas.

Relation of serum IL-32 levels and gene polymorphism rs45499297 with obesity in Mexican patients: a laboratory and in silico analysis / Relación de los niveles séricos de IL-32 y del polimorfismo rs45499297 con la obesidad en pacientes mexicanos: un análisis de laboratorio e in silico

Background: many genes have been involved in the development of obesity. Interleukin 32 (IL-32) is a proinflammatory cytokine; rs45499297 is a T/C promoter, single-nucleotide polymorphism of the IL-32 gene. Objectives: this study aimed to evaluate the rs45499297 polymorphism and its association with obesity. Another objective of this study was to carry out an in silico analysis. Methods: this study was cross-sectional, and included 333 subjects classified by body mass index and fat percentage. The plasma glucose and lipid profile were measured. We measured serum IL-32 protein by ELISA and the rs45499297 polymorphism by PCR-RFLP. We used several databases to build the IL-32 gene network and infer transcription factors that bind to this polymorphic site. Results: subjects underweight and with low fat percentages had lower levels of IL-32. CT genotype and allele C were less frequent in the overweight/obesity group than in the normal-weight group. Interestingly, this result remained only in the male gender. We found that the transcription factors Hepatocyte Nuclear Factor and Specificity Protein 1 bind to this polymorphic site. In addition, we infer that IL-32 is involved in metabolic pathways related to viral infections. Conclusion: the TC genotype is associated with overweight/obesity. The decrease in levels of IL-32 observed in underweight and low fat percentage groups could be due to an impaired inflammatory profile. The in silico analysis showed that several transcriptional factors bind at this polymorphic site, and that the enrichment of the metabolic pathways is diverse (AU)

Introducción: la interleucina 32 es una citocina proinflamatoria. El rs45499297 es un polimorfismo de nucleótido simple del gen de IL-32, situado en la región promotora y caracterizado por un cambio de T/C. Objetivo: evaluar el polimorfismo rs45499297 y su asociación con la obesidad, y realizar un análisis in silico. Métodos: el estudio fue transversal e incluyó 333 sujetos clasificados por índice de masa corporal y porcentaje de grasa. Se midieron la glucosa y el perfil lipídico, así como los niveles séricos de IL-32 mediante ELISA y el genotipo del polimorfismo rs45499297 mediante PCR-RFLP. Para el análisis in silico se utilizaron varias bases de datos para hacer la red de genes de IL-32 e inferir factores de transcripción unidos al sitio polimórfico. Resultados: los sujetos con bajo peso y bajo porcentaje de grasa tienen niveles más bajos de IL-32. El genotipo TC y el alelo C se encontraron con menos frecuencia en los sujetos con sobrepeso/obesidad que en los normopeso, resultado que permaneció solo en el género masculino. Se encontró que el factor nuclear de los hepatocitos y la proteína de especificidad 1 se unen a este sitio polimórfico. Se infiere que IL-32 está involucrado en vías metabólicas relacionadas con las infecciones virales. Conclusión: el genotipo TC está asociado al sobrepeso/la obesidad. La disminución de los niveles de IL-32 observada en los sujetos con bajo peso y bajo porcentaje de grasa podría ser por un perfil inflamatorio alterado. El análisis in silico mostró que varios factores de transcripción se unen al sitio polimórfico y que el enriquecimiento de las vías metabólicas es diverso (AU)

Efficacy of L-arginine for preventing preeclampsia in high-risk pregnancies: A double-blind, randomized, clinical trial.

OBJECTIVE: This study aimed to estimate the effectiveness of L-arginine for preventing preeclampsia in high-risk pregnancy. METHODS: We performed a randomized, double-blind, placebo-controlled, clinical trial in patients with high-risk factors for preeclampsia. Fifty subjects received L-arginine, beginning from the 20th week of gestation. An additional 50 patients received homologated placebo. RESULTS: The placebo group had a higher number of cases of preeclampsia (11/47) compared with the L-arginine group (3/49, P = 0.01). Birth weight was higher in the L-arginine group and there was a smaller number of preterm births (P = 0.03). CONCLUSION: L-arginine is effective for preventing preeclampsia.

Therapeutic implications of interleukin-10 in surgical disease.

Pharmacological therapy of surgical disease often involves manipulating the physiologic balance between pro- and anti-inflammatory responses. Many agents target only one aspect of the inflammatory cascade. Originally identified as a protein elaborated by T-lymphocytes, IL-10 appears to globally inhibit cytokine production. The purpose of this manuscript is to examine the immunomodulatory and anti-inflammatory effects of interleukin-10 (IL-10) in an attempt to define the clinical utility of IL-10, both as a marker of and as a therapeutic strategy for intervention in inflammatory and immune-mediated diseases. IL-10 is elaborated from multiple sources and has diverse cellular effects to regulate immune and inflammatory responses. Accumulating evidence suggests that the anti-inflammatory influence of IL-10 observed at the cellular level may be manipulated to impact the immune and inflammatory-mediated responses associated with injury and sepsis, gastrointestinal and cardiovascular disease, and transplantation. In conclusion, IL-10 is an important mediator of immune and anti-inflammatory responses in surgical disease and, as such, has therapeutic promise as an immunomodulator and as an anti-inflammatory agent.

Interleukin-10 stabilizes inhibitory kappaB-alpha in human monocytes.

Interleukin-10 (IL-10) protects animals from lethal endotoxemia. This beneficial effect is mediated, in part, by inhibition of inflammatory cytokine production, including tumor necrosis factor-alpha (TNF-alpha). Evidence suggests that IL-10 may inhibit activation of the transcription factor nuclear factor-kappaB (NF-kappaB) through an unknown mechanism. NF-kappaB activation in response to inflammatory signals is dependent upon degradation of its associated inhibitory peptide, inhibitory kappaB-alpha (IkappaB-alpha). We hypothesized that IL-10 prevents human monocyte NF-kappaB activation and resultant TNF-alpha production by stabilization of IkappaB-alpha. The purpose of this study was to determine the effect of IL-10 on lipopolysaccharide (LPS)-induced human monocyte TNF-alpha production, NF-kappaB activation, and IkappaB-alpha degradation. Monocytes were isolated from human donors. Cells were stimulated with endotoxin (LPS, 100 ng/mL) with and without human IL-10 (10 ng/mL). Following stimulation, TNF-alpha was measured in cell supernatants by ELISA, NF-kappaB activity by electrophoretic mobility shift assay, and IkappaB-alpha levels by Western blot. We observed that after LPS stimulation of human monocytes, TNF-alpha increased to 798+/-67 pg/mL (p < .001 versus control). IL-10 attenuated LPS-stimulated TNF-alpha production (297+/-54; p < .001 versus LPS alone). After LPS stimulation in human monocytes, IkappaB-alpha protein levels decreased, and NF-kappaB DNA binding increased. IL-10 pretreatment prevented LPS-induced decreases in IkappaB-alpha protein levels and attenuated NF-kappaB DNA binding. IL-10 appears to prevent activation of NF-kappaB by preserving IkappaB-alpha protein levels, leading to a reduction in TNF-alpha release.

Chemokines as mediators of diseases related to surgical conditions.

Chemokines are important mediators of inflammation. Animal studies suggest that inhibition of chemokine action results in a decrease in inflammation. Novel anti-inflammatory agents directed against chemokines are now available. Surgeons are uniquely positioned to treat multiple chemokine-mediated diseases. In this article, we review the biology and nomenclature of chemokines as well as their role in neutrophil migration. Further, the potential role of chemokines in various diseases related to surgical conditions, including adult respiratory distress syndrome, atherosclerosis, inflammatory bowel disease, and solid organ rejection, is reviewed. Finally, the idea that chemokines could be targets for novel therapeutic agents is discussed.

The biology of estrogen-mediated repair of cardiovascular injury.

Women appear to be protected from cardiovascular disease until the onset of menopause. Considerable evidence supports the atheroprotective effects of endogenous and supplemental estrogens. The beneficial effects of estrogens on lipid metabolism cannot wholly explain this phenomenon. Accumulating data suggest that estrogen may act at the cellular and molecular level to influence atherogenesis. The purpose of this review is to examine lipid-independent mechanisms of estrogen-mediated atheroprotection after cardiovascular injury.