Evaluating the effects of hypoxic storage on platelet function and health using a novel storage system.

BACKGROUND: Thousands of units of whole blood (WB) and blood components are transfused daily to treat trauma patients. Improved methods for blood storage are critical to support trauma-related care. The Hemanext ONE® system offers a unique method for hypoxic storage of WB, with successfully demonstrated storage of clinically viable RBCs. This work evaluated the system for the storage of WB, focusing on platelet health and function. STUDY DESIGN AND METHODS: WB was collected from healthy donors and processed through the Hemanext ONE® system. Hemoglobin oxygen saturation (HbSO2) levels of WB were depleted to 10%, 20%, or 30% of total HbSO2 and then stored in PVC bags sealed in oxygen-impermeable bags (except for normoxic control) with samples collected on days 1, 7, and 14 post-processing. Flow cytometry assessed the activation and apoptosis of platelets. Clot dynamics were assessed based on aggregometry and thromboelastography assays, as well as thrombin generation using a calibrated-automated thrombogram method. RESULTS: Hypoxic storage conditions were maintained throughout the storage period. Hypoxia triggered increased lactate production, but pH changes were negligible compared to normoxic control. Storage at 10% HbSO2 had a significant impact on platelet function, resulting in increased activation and reduced clot formation and aggregation. These effects were less significant at 20% and 30% HbSO2. DISCUSSION: This study indicates that platelets are sensitive to hypoxic storage and suffer significant metabolic and functional deterioration when stored at or below 10% HbSO2.

Still-face effect in domestic dogs: comparing untrained with trained and animal assisted interventions dogs.

The still-face effect has been extensively studied in human infants and comprises the reduction in affiliative behaviors and increased stress that occurs after a sudden interruption of social interaction with a caregiver. Domestic dogs (Canis familiaris) are model candidates for showing this effect, as they form deep bonds with their owners and interspecific social interaction is reinforcing to them. The aim of these studies was to assess if companion dogs exhibit the still-face effect and whether prior experiences during ontogeny modulate this effect. To this end, Study 1 compared dogs with different levels of training (untrained, intermediate, and advanced), while Study 2 assessed dogs that participated in Animal Assisted Interventions (AAIs) and companion dogs (CDs). The procedure was carried out virtually and comprised three phases lasting 1 min: interaction, still-face (the owner turned suddenly indifferent), and reunion (the interaction was resumed). Dogs exhibited a decrease in proximity to and contact with the owner, as well as an increase in begging and stress behaviors during the still-face phase. Moreover, this was not observed in a control condition in which the interaction continued in the same way during all three phases, discarding alternative explanations for these changes. These results show that dogs experience a still-face effect in a similar way to infants, highlighting the value interspecific social interaction has for dogs. Nevertheless, the absence of differences according to their training level or participation in AAIs suggests this is a robust phenomenon, which appears to be less susceptible to the influences of ontogenetic experiences.

SARS-CoV-2 en atención odontológica: vías de transmisión y sus consideraciones en la práctica clínica

We analyze the transmission routes, possible viral reservoirs in the oral cavity and considerations about dental care of SARS-CoV-2 virus infection. We also analyze the protocols required before and after a dental procedure, aiming to increase the awareness of dentists about the importance of virus spread prevention among health care workers and patients. The evaluation of symptoms associated with SARS- CoV-2 such as fever, fatigue, dry cough, myalgia, dyspnea, and the inquiry about possible contacts with infected people is of utmost importance. The tongue and oral mucosa are important viral reservoirs and the transmission of the virus occurs primarily by saliva droplets. Therefore, elective dental care should be postponed, attending only dental emergencies during this period, incorporating the use of protective personal equipment (PPE) and using manual instruments to prevent the production of aerosols.

Oxytocin effects on gazing at the human face in retriever dogs.

Oxytocin is a neurohormone involved in domestic dogs' socio-cognitive abilities which appears to be key in the display of gazing behavior as a communicative signal. However, differential effects of oxytocin have been reported in various tasks according to the dogs' breed. In the present study, we evaluated the effect of the intranasal administration of oxytocin on gazing towards the human face in Golden and Labrador Retrievers. This was assessed during a learning task in which dogs had to gaze at the human face in order to receive food that was visible but inaccessible. Results indicate that only intact dogs who received oxytocin exhibited an increase in gazing behavior, while no differences were observed for neutered dogs. This effect could be related to an interaction between oxytocin and steroid hormones in intact dogs. These findings highlight the importance of including modulating factors, such as breed and neutered status, when studying the mechanisms of oxytocin.

[Dental care during SARS-CoV-2 pandemic]. / SARS-CoV-2 en atención odontológica: vías de transmisión y sus consideraciones en la práctica clínica.

We analyze the transmission routes, possible viral reservoirs in the oral cavity and considerations about dental care of SARS-CoV-2 virus infection. We also analyze the protocols required before and after a dental procedure, aiming to increase the awareness of dentists about the importance of virus spread prevention among health care workers and patients. The evaluation of symptoms associated with SARS- CoV-2 such as fever, fatigue, dry cough, myalgia, dyspnea, and the inquiry about possible contacts with infected people is of utmost importance. The tongue and oral mucosa are important viral reservoirs and the transmission of the virus occurs primarily by saliva droplets. Therefore, elective dental care should be postponed, attending only dental emergencies during this period, incorporating the use of protective personal equipment (PPE) and using manual instruments to prevent the production of aerosols.

The Mexican consensus on non-cardiac chest pain. / Consenso mexicano sobre dolor torácico no cardiaco.

INTRODUCTION: Non-cardiac chest pain is defined as a clinical syndrome characterized by retrosternal pain similar to that of angina pectoris, but of non-cardiac origin and produced by esophageal, musculoskeletal, pulmonary, or psychiatric diseases. AIM: To present a consensus review based on evidence regarding the definition, epidemiology, pathophysiology, and diagnosis of non-cardiac chest pain, as well as the therapeutic options for those patients. METHODS: Three general coordinators carried out a literature review of all articles published in English and Spanish on the theme and formulated 38 initial statements, dividing them into 3 main categories: (i)definitions, epidemiology, and pathophysiology; (ii)diagnosis, and (iii)treatment. The statements underwent 3rounds of voting, utilizing the Delphi system. The final statements were those that reached >75% agreement, and they were rated utilizing the GRADE system. RESULTS AND CONCLUSIONS: The final consensus included 29 statements. All patients presenting with chest pain should initially be evaluated by a cardiologist. The most common cause of non-cardiac chest pain is gastroesophageal reflux disease. If there are no alarm symptoms, the initial approach should be a therapeutic trial with a proton pump inhibitor for 2-4weeks. If dysphagia or alarm symptoms are present, endoscopy is recommended. High-resolution manometry is the best method for ruling out spastic motor disorders and achalasia and pH monitoring aids in demonstrating abnormal esophageal acid exposure. Treatment should be directed at the pathophysiologic mechanism. It can include proton pump inhibitors, neuromodulators and/or smooth muscle relaxants, psychologic intervention and/or cognitive therapy, and occasionally surgery or endoscopic therapy.

Low-dose curcuminoid-loaded in dextran nanobubbles can prevent metastatic spreading in prostate cancer cells.

Preventing recurrences and metastasis of prostate cancer after prostatectomy by administering adjuvant therapies is quite a controversial issue. In addition to effectiveness, absence of side effects and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 d, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way. Significant biological effects were detected in PC-3 and DU-145 cell lines where Curc-NBs were able to inhibit adhesion and migration, to promote cell apoptosis and to affect cell viability and colony-forming capacity in a dose-dependent manner. Since the favourable effects are already detectable at very low doses, which can be reached at a clinical level, the actual drug concentration can be visualized and monitored by US or MRI, Curc-NBs can be proposed as an effective adjuvant theranostic tool.

Imitadores y camaleones de ictus, para tenerlos siempre en mente / Stroke mimics and chameleons, have them always on mind

INTRODUCCIÓN: Se denominan imitadores de ictus (falsos positivos, sobrediagnosticados) así como camaleones de ictus (falsos negativos, infradiagnosticados) a los casos que inducen a cometer errores en el diagnóstico y tratamiento del ictus. Los mismos deben ser considerados para aproximarse de una manera certera al diagnóstico y tratamiento más adecuados. El objetivo es relatar el caso de una paciente que se presenta con un imitador de ictus, afortunadamente con evolución favorable posterior. CASO CLÍNICO: Paciente de 17 años, procedente y residente de la ciudad de El Alto, segundigesta, sin antecedentes personales patológicos, cuadro clínico de 8 horas de evolución, caracterizado por alteración de la conciencia de manera progresiva así como crisis convulsivas tónico clónicas generalizadas; se realiza neuroprotección, tratamiento neurointensivo y se considera tratamiento trombolítico, el cual debido a una adecuada disquisición diagnóstica se decide evitar, orientándose el diagnóstico hacia epilepsia, realizándose el tratamiento respectivo con evolución favorable. DISCUSIÓN: El caso presenta varios datos importantes, tales como la edad de la paciente y la ausencia de crisis convulsivas con anterioridad, sin embargo debido a la urgencia del caso se consideró trombolisis, sin administrase la misma y decidiéndose por el tratamiento de epilepsia, evitando tanto el riesgo asociado a hemorragia intracerebral por la administración de trombolítico en un caso que no correspondía su utilización ya que como se pudo evidenciar la literatura cita como un importante imitador de ictus a las crisis convulsivas.

INTRODUCTION: Stroke mimics (false positives, over diagnosed) and stroke chameleons (false negative, underdiagnosed) are special cases that induce to commit mistakes on stroke diagnoses and treatment. They have to be considered to approximate an adequate treatment. The objective is report the case of a patient with stroke mimic, fortunately identified and treated with favorable evolution. CASE REPORT: Female 17 year-old patient, from El Alto city, without pathologic antecedents with 8 hours clinical manifestations with consciousness impairment and tonic-clonic seizures, neuroprotection is performed such as neurocritical care, thrombolysis is considered, but after an adequate diagnostic disquisition is avoided, the diagnoses of epilepsy is achieved and treatment is performed. DISCUSSION: Several important data are reviewed, such as the early age, lack of seizures antecedent, nevertheless thrombolysis is considered, throughout a careful literature review, epilepsy treatment is performed, avoiding intracraneal bleeding complications.

Magnetization switching in high-density magnetic nanodots by a fine-tune sputtering process on a large-area diblock copolymer mask.

Ordered magnetic nanodot arrays with extremely high density provide unique properties to the growing field of nanotechnology. To overcome the size limitations of conventional lithography, a fine-tuned sputtering deposition process on mesoporous polymeric template fabricated by diblock copolymer self-assembly is herein proposed to fabricate uniform and densely spaced nanometer-scale magnetic dot arrays. This process was successfully exploited to pattern, over a large area, sputtered Ni80Fe20 and Co thin films with thicknesses of 10 and 13 nm, respectively. Carefully tuned sputter-etching at a suitable glancing angle was performed to selectively remove the magnetic material deposited on top of the polymeric template, producing nanodot arrays (dot diameter about 17 nm). A detailed study of magnetization reversal at room temperature as a function of sputter-etching time, together with morphology investigations, was performed to confirm the synthesis of long-range ordered arrays displaying functional magnetic properties. Magnetic hysteresis loops of the obtained nanodot arrays were measured at different temperatures and interpreted via micromagnetic simulations to explore the role of dipole-dipole magnetostatic interactions between dots and the effect of magnetocrystalline anisotropy. The agreement between measurements and numerical modelling results indicates the use of the proposed synthesis technique as an innovative process in the design of large-area nanoscale arrays of functional magnetic elements.

Is previous experience important for inhibitory control? A comparison between shelter and pet dogs in A-not-B and cylinder tasks.

This study compares the performance of two groups of dogs with different levels of social interaction with humans, shelter and pet dogs, in two inhibitory control tasks. (1) In the A-not-B task, dogs were required to resist searching for food in a previously rewarded location, and (2) in the cylinder task, dogs were required to resist approaching visible food directly in favor of a detour reaching response. Our first aim was to evaluate the importance of learning and ontogeny in performing inhibitory tasks. Also, we assessed whether there is a correlation between the two tasks by comparing performance in the same subjects. Results showed significant differences between shelter and pet dogs in the A-not-B task, with poorer performance in shelter dogs. However, no differences were found in the cylinder task. The poorer performance of shelter dogs might be related to their infrequent interaction with humans, which reduces the chances to learn to inhibit certain behaviors. This result would highlight the importance of ontogeny in developing that ability. On the other hand, no correlations were found between the two tasks, which contributes information to the debate about the context specificity of inhibitory control in dogs.

Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins.

Trefoil factors are effector molecules in gastrointestinal tract physiology. Each one improves healing of the gastrointestinal tract. Trefoil factors may be grouped into three classes: the gastric peptides (TFF1), spasmolytic peptide (TFF2) and intestinal trefoil factor (TFF3). Significant amounts of TFF3 are present in human breast milk. Previously, we have reported that trefoil factor 3 isolated from human breast milk produces down regulation of cytokines and promotes human beta defensins expression in intestinal epithelial cells. This study aimed to determine the molecular mechanism involved. Here we showed that the presence of TFF3 strongly correlated with protease activated receptors 2 (PAR-2) activation in human intestinal cells. Intracellular calcium ((Ca2+)i)mobilization was induced by the treatment with: 1) TFF3, 2) synthetic PAR-2 agonist peptide. The co-treatment with a synthetic PAR-2 antagonist peptide and TFF3 eliminates the latter's effect. Additionally, we demonstrated the existence of interactions among TFF3 and PAR-2 receptors through far Western blot and co-precipitation. Finally, down regulation of PAR-2 by siRNA resulted in a decrease of TFF3 induced intracellular (Ca2+)i mobilization, cytokine regulation and defensins expression. These findings suggest that TFF3 activates intestinal cells through PAR-2 (Fig. 4, Ref. 19).

Premature loss of muscle mass and function in type 2 diabetes.

INTRODUCTION: Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. AIM: To study whether adult DM2 patients up to 60years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. METHODOLOGY: Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. RESULTS: ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but did not correlate with ApFFM. CONCLUSIONS: We found a clear deterioration of lean mass and muscle functions among adult DM2 patients of up to 60years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.

Tolerance to delayed reward tasks in social and non-social contexts.

Domestic dogs have demonstrated striking social skills towards humans, however, there are few studies investigating impulsivity with delay-choice tasks in communicative contexts. In Study 1 we introduced a novel social delay-choice task in which subjects had to choose between one human cueing an immediate, low quality reward and another human signaling a delayed, high quality reward. In Study 2 we evaluated the tolerance to increasing delays using social and non-social cues. We also explored if more self-controlled dogs show any distinct behaviours during delays. Finally, we correlated all results with the Dog Impulsivity Assessment Scale (Wright et al., 2011). In Study 1 dogs reached an average maximum delay of 11.55s. In Study 2 that average was 52.14s with social cues and 40.2s with non-social, but differences were not significant. Tolerance to delays showed high interindividual variation. Dogs remained mostly standing and near the delayed experimenter in the social tasks although we could not to find any distinct coping strategies. No significant correlations were found between the delay reached and behaviours, neither with the scale. These results show the relevance of the parameters and methods used to investigate tolerance to delay of reinforcements. More investigations are required, especially an assessment of the same subjects performing the same tasks using different contexts.

YAP activation protects urothelial cell carcinoma from treatment-induced DNA damage.

Current standard of care for muscle-invasive urothelial cell carcinoma (UCC) is surgery along with perioperative platinum-based chemotherapy. UCC is sensitive to cisplatin-based regimens, but acquired resistance eventually occurs, and a subset of tumors is intrinsically resistant. Thus, there is an unmet need for new therapeutic approaches to target chemotherapy-resistant UCC. Yes-associated protein (YAP) is a transcriptional co-activator that has been associated with bladder cancer progression and cisplatin resistance in ovarian cancer. In contrast, YAP has been shown to induce DNA damage associated apoptosis in non-small cell lung carcinoma. However, no data have been reported on the YAP role in UCC chemo-resistance. Thus, we have investigated the potential dichotomous role of YAP in UCC response to chemotherapy utilizing two patient-derived xenograft models recently established. Constitutive expression and activation of YAP inversely correlated with in vitro and in vivo cisplatin sensitivity. YAP overexpression protected while YAP knockdown sensitized UCC cells to chemotherapy and radiation effects via increased accumulation of DNA damage and apoptosis. Furthermore, pharmacological YAP inhibition with verteporfin inhibited tumor cell proliferation and restored sensitivity to cisplatin. In addition, nuclear YAP expression was associated with poor outcome in UCC patients who received perioperative chemotherapy. In conclusion, these results suggest that YAP activation exerts a protective role and represents a pharmacological target to enhance the anti-tumor effects of DNA damaging modalities in the treatment of UCC.

Skeletal muscle ceramide species in men with abdominal obesity.

BACKGROUND: Obesity is a risk factor for diabetes and its consequences, including accelerated ageing and mortality. The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function. AIM: First, to study the relationship between body composition and age (independent variables) with skeletal muscle accumulation of lipid species, oxidative injury and strength. Second, to analyze the relationship between muscle tissue metabolites and insulin resistance, inflammation and lymphocyte telomere length, the latter as an indicator of ageing. METHODOLOGY: The sample included 56 healthy sedentary males, scheduled for inguinal hernia surgery, aged 27 to 80 y. Each individual was subject to anthropometric measurements, body composition assessment through radiologic densitometry (DEXA), measurement of handgrip and quadriceps strength, serum biochemical parameters (lipoproteins, creatinine, high sensitivity C reactive protein [hsCRP], fasting and post glucose insulin and glucose concentrations for calculation of IR through the Matsuda and HOMA-IR indexes), and extraction of peripheral leukocytes for measurement of telomere length. During the surgical procedure, a sample of muscle tissue was obtained (anterior abdominal oblique) in order to measure CER and DAG (and sub species according to chain length and saturation) by mass spectrometry, 4 hydroxy-2-nonenal adducts (4-HNE) using electron microscopy immunohistochemistry, and carboxymethyl-lisine (CML) by immunohistochemistry, the latter as indicators of oxidative stress (OS). RESULTS: Body mass index (BMI) of twenty six individuals was > 25 k/m2, while BMI of 7 was > 30 k/m2. Overweight/obese individuals, did not exhibit differences in skeletal muscle lipid metabolites, however total CER and specific long chain CER sub-species (20 and 22 carbon) increased significantly among individuals with a central fat distribution (n = 14) as well as in glucose intolerant subjects (n =23). A negative association was found between mononuclear leukocyte telomere length and 20 and 22 carbon CER (rho = - 0.4 and -0.5 0 p < 0.05). Muscle strength was not associated with any of the measured muscle metabolites or markers of OS. A multiple regression analysis accepted central abdominal fat and telomere length as significant predictors of CER (R2 = 0.28). CONCLUSIONS: An association was found between accumulation of specific ceramide species in muscle tissue and abdominal obesity, glucose intolerance and shortening of leukocyte telomeres, although not with muscle oxidative injury or dysfunction.

Effect of weight maintenance or gain in a 10 years period over telomere length, sirtuin 1 and 6 expression and carotid intima media thickness.

BACKGROUND: Lack of weight gain throughout adult life could mimic the beneficial effects of energy restriction in humans. The present study aimed to assess the effects of weight stability or gain, over a period of 10 years, on telomere length, sirtuin 1 and 6 expression, and carotid intima media thickness. METHODS: We studied 148 healthy adults (age range 20-59 years; 101 females) who had an objective record of their weight 10 years before. They were classified as weight losers, weight maintainers, weight gainers and extreme weight gainers. A fasting blood sample was obtained for routine laboratory and isolation of peripheral blood mononuclear cells, to extract DNA and RNA, and to measure telomere length and sirtuin 1 and 6 expression, respectively. Carotid intima media thickness was measured by ultrasound. Body composition was measured by Dual-energy X-ray absorptiometry. RESULTS: In the 10-year period, 24 participants lost weight (17 females), 65 maintained weight (41 females), 25 gained weight (15 females) and 34 were extreme weight gainers (28 females). Female weight gainers had a higher body mass index, waist circumference, total body fat and homeostatic model assessment insulin resistance. Male weight gainers had a higher hip circumference and total body fat. No differences in telomere length, sirtuin 1 expression and carotid intima media thickness were observed between weight gainers and maintainers. CONCLUSIONS: No effect of weight maintenance or gain was observed on metabolic and vascular markers of ageing.

Solid lipid nanoparticles of cholesteryl butyrate inhibit the proliferation of cancer cells in vitro and in vivo models.

BACKGROUND AND PURPOSE: Solid lipid nanoparticles containing cholesteryl butyrate (cholbut SLN) can be a delivery system for the anti-cancer drug butyrate. These nanoparticles inhibit adhesion of polymorphonuclear and tumour cells to endothelial cells and migration of tumour cells, suggesting that they may act as anti-inflammatory and anti-tumour agents. Here we have evaluated the effects of cholbut SLN on tumour cell growth using in vitro and in vivo models. EXPERIMENTAL APPROACH: Cholbut SLNs were incubated with cultures of four tumour cell lines, and cell growth was analysed by assessing viability, clonogenic capacity and cell cycle. Effects on intracellular signalling was assessed by Western blot analysis of Akt expression. The in vivo anti-tumour activity was measured in two models of PC-3 cell xenografts in SCID/Beige mice. KEY RESULTS: Cholbut SLN inhibited tumour cell line viability, clonogenic activity, Akt phosphorylation and cell cycle progression. In mice injected i.v. with PC3-Luc cells and treated with cholbut SLN, . in vivo optical imaging and histological analysis showed no metastases in the lungs of the treated mice. In another set of mice injected s.c. with PC-3 cells and treated with cholbut SLN when the tumour diameter reached 2 mm, analysis of the tumour dimensions showed that treatment with cholbut SLN substantially delayed tumour growth. CONCLUSION AND IMPLICATIONS: Cholbut SLN were effective in inhibiting tumour growth in vitro and in vivo. These effects may involve, in part, inhibition of Akt phosphorylation, which adds another mechanism to the activity of this multipotent drug.

Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic patients.

INTRODUCTION: Advanced glycation end products are produced endogenously, in association with hyperglycemia and oxidative stress. They can also be generated during cooking or food processing and, once absorbed, alter protein function and promote inflammation. METHODS: We selected 40 healthy male subjects, 17 patients with type 2 diabetes of both sexes and 15 patients with type 1 diabetes of both sexes. Each participant underwent both a food frequency questionnaire (FFQ) and 24-hour dietary recall specially adapted for measuring CML intake, anthropometry, measurement of blood pressure and biochemical parameters in blood and urine. RESULTS: Serum CML levels were significantly higher in patients with diabetes compared to healthy subjects (p 0.04), showing a direct relationship between dietary intake and serum levels of CML in T2D patients (r 0.53 p 0.03). sCML levels correlated positively with length of diabetes mellitus, and inversely with body mass index (BMI). The most important dietary factor contributing to raise CML levels in these patients with diabetes was the consumption of milk powder. CONCLUSION: Serum levels of CML were found to be higher among diabetic subjects, associated to length of diabetes as expected, but also with the ingestion of foods containing higher amounts of ML. The consumption of milk powder in this group is a major determinant of increased serum levels.

Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic patients / La ingesta dietaria de carboximetil-lisina (CML) aumenta los niveles plasmáticos de este compuesto en pacientes diabéticos

Introduction: Advanced glycation end products are produced endogenously, in association with hyperglycemia and oxidative stress. They can also be generated during cooking or food processing and, once absorbed, alter protein function and promote inflammation. Methods: We selected 40 healthy male subjects, 17 patients with type 2 diabetes of both sexes and 15 patients with type 1 diabetes of both sexes. Each participant underwent both a food frequency questionnaire (FFQ) and 24-hour dietary recall specially adapted for measuring CML intake, anthropometry, measurement of blood pressure and biochemical parameters in blood and urine. Results: Serum CML levels were significantly higher in patients with diabetes compared to healthy subjects (p 0.04), showing a direct relationship between dietary intake and serum levels of CML in T2D patients (r 0.53 p 0.03). sCML levels correlated positively with length of diabetes mellitus, and inversely with body mass index (BMI). The most important dietary factor contributing to raise CML levels in these patients with diabetes was the consumption of milk powder. Conclusion: Serum levels of CML were found to be higher among diabetic subjects, associated to length of diabetes as expected, but also with the ingestion of foods containing higher amounts of ML. The consumption of milk powder in this group is a major determinant of increased serum levels (AU)

Introducción: Los productos avanzados de la glicación se producen de forma endógena en relación con la hiperglucemia y el estrés oxidativo. También pueden generarse durante el cocinado o el procesamiento de los alimentos; una vez absorbidos, alteran la función proteica y favorecen la inflamación. Métodos: Seleccionamos a 40 hombres sanos, 17 pacientes con diabetes tipo 2 de ambos sexos y 15 pacientes con diabetes tipo 1 de ambos sexos. A cada participante se le realizó un cuestionario de frecuencia de consumo de alimentos (CFA) y un recordatorio de 24 horas especialmente adaptado para medir el consumo de CML, antropometría, medición de la presión sanguínea y parámetros bioquímicos en la sangre y la orina. Resultados: Las concentraciones séricas de CML fueron significativamente mayores en pacientes con diabetes en comparación con los individuos sanos (p = 0,04). Se encontró una relación directa entre el consumo dietético y las concentraciones séricas de CML en los pacientes con diabetes tipo 2 (r = 0,53; p = 0,03). Las concentraciones séricas de CML se correlacionan positivamente con la duración de la diabetes mellitus e inversamente con el índice de masa corporal (IMC). El alimento que más contribuye al aumento de las concentraciones plasmáticas de CML en estos pacientes fue el consumo de leche en polvo. Conclusión: Se encontró que las concentraciones séricas de CML eran mayores en los sujetos diabéticos, asociado con la duración de la diabetes, como era de esperar, pero también con la ingestión de alimentos que contienen mayores cantidades de CML. El consumo de leche en polvo en este grupo es un factor determinante en el aumento de las concentraciones séricas de CML (AU)

Cholesteryl butyrate solid lipid nanoparticles inhibit the adhesion and migration of colon cancer cells.

BACKGROUND AND PURPOSE Cholesteryl butyrate solid lipid nanoparticles (cholbut SLN) provide a delivery system for the anti-cancer drug butyrate. These SLN inhibit the adhesion of polymorphonuclear cells to the endothelium and may act as anti-inflammatory agents. As cancer cell adhesion to endothelium is crucial for metastasis dissemination, here we have evaluated the effect of cholbut SLN on adhesion and migration of cancer cells. EXPERIMENTAL APPROACH Cholbut SLN was incubated with a number of cancer cell lines or human umbilical vein endothelial cells (HUVEC) and adhesion was quantified by a computerized micro-imaging system. Migration was detected by the scratch 'wound-healing' assay and the Boyden chamber invasion assay. Expression of ERK and p38 MAPK was analysed by Western blot. Expression of the mRNA for E-cadherin and claudin-1 was measured by RT-PCR. KEY RESULTS Cholbut SLN inhibited HUVEC adhesiveness to cancer cell lines derived from human colon-rectum, breast, prostate cancers and melanoma. The effect was concentration and time-dependent and exerted on both cancer cells and HUVEC. Moreover, these SLN inhibited migration of cancer cells and substantially down-modulated ERK and p38 phosphorylation. The anti-adhesive effect was additive to that induced by the triggering of B7h, which is another stimulus inhibiting both ERK and p38 phosphorylation, and cell adhesiveness. Furthermore, cholbut SLN induced E-cadherin and inhibited claudin-1 expression in HUVEC. CONCLUSION AND IMPLICATIONS These results suggest that cholbut SLN could act as an anti-metastastic agent and they add a new mechanism to the anti-tumour activity of this multifaceted preparation of butyrate.