Fermented food: Should patients with cardiometabolic diseases go back to an early neolithic diet?

Fermentation has been used since the Early Neolithic period to preserve foods. It has inherent organoleptic and nutritive properties that bestow health benefits, including reducing inflammation and oxidative stress, supporting the growth of salutogenic microbiota, enhancing intestinal mucosal protection and promoting beneficial immunometabolic health effects. The fermentation of food with specific microbiota increases the production salutogenic bioactive compounds that can activate Nrf2 mediated cytoprotective responses and mitigate the effects of the 'diseasome of aging' and its associated inflammageing, which presents as a prominent feature of obesity, type-2 diabetes, cardiovascular and chronic kidney disease. This review discusses the importance of fermented food in improving health span, with special reference to cardiometabolic diseases.

Characterization and comparison of commercial oils used for human embryo culture.

STUDY QUESTION: Are there significant differences between the available commercial oil brands used for human IVF? SUMMARY ANSWER: Important differences have been detected among the tested oil brands in their potential to stabilize culture conditions and, more importantly, in their direct effect on embryo development and viability. WHAT IS KNOWN ALREADY: Mineral oil is a critical component of the human culture system due to its protective and stabilizing roles during in vitro embryo development. Many different oils are available on the market, with differences in their viscosity, density and overall quality. STUDY DESIGN, SIZE, DURATION: Thirteen different commercial oil brands were compared. PARTICIPANTS/MATERIALS, SETTING, METHODS: Each oil was firstly analyzed to assess its viscosity, density, peroxide value and potential oxidation. Secondly, the capacity of each oil to reduce pH, osmolality and temperature fluctuations during embryo culture and manipulation was compared. Lastly, a sensitive mouse embryo assay (MEA) protocol, previously optimized to detect toxicity in oils samples, was used to compare the overall quality of the different brands in terms of embryo developmental rates up to the blastocyst stage. At the end of the MEAs, a triple labeling protocol was applied to analyze Oct4+ cells, apoptotic cells and total cell counts in the blastocysts obtained by fluorescence microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: Significant divergences were detected in the rise of osmolality and the equilibration and stability of pH between different oils, which could be correlated to their physico-chemical characteristics. In particular, oil samples with a higher viscosity tended to offer an additional protection against fluctuations in the culture conditions, however, the differences in temperature stability between oils were minor. Two out of the 13 oil samples, which were commercially available, were identified as embryo-toxic by applying the MEA protocol with increased sensitivity for toxicity detection. Additionally, substantial differences in the total number of cells and the number of cells in the inner cell mass of the obtained blastocysts were also detected between oil groups. LIMITATIONS, REASONS FOR CAUTION: A single lot of oil was used for each brand and, thus, lot-to-lot variations in oil quality could not be determined. However, several bottles from the same oil were included to account for potential intra-lot variability. WIDER IMPLICATIONS OF THE FINDINGS: Commercial oils differ in both their physical characteristics and their performance in maintaining the stability of the culture conditions during in vitro embryo culture. Oil selection is important for embryo culture success. Additionally, the detection of embryo-toxic oils which had already been released to the human IVF market showcases the importance of applying sensitive MEA protocols for a better detection of toxicity in this type of samples. STUDY FUNDING/COMPETING INTEREST(S): This study was privately funded. TRIAL REGISTRATION NUMBER: N/A.

Factors of the human embryo culture system that may affect media evaporation and osmolality.

STUDY QUESTION: Which lab-related factors impact the culture system's capacity to maintain a stable osmolality during human embryo culture? SUMMARY ANSWER: Incubator humidity, the volume of mineral oil, the type of culture media and the design of time-lapse dishes have been identified as important parameters that can cause an impact on media evaporation and consequently osmolality during culture. WHAT IS KNOWN ALREADY: Culture medium is a critical component in human embryo culture. Minimizing its evaporation during culture is an adequate strategy to stabilize osmolality and, as a result, improving culture conditions and clinical outcomes. STUDY DESIGN, SIZE, DURATION: The studied variables included media composition and supplementation; volume of mineral oil; incubator humidification; and the type of dish and incubator used. Additionally, six time-lapse dish models were compared in their ability to prevent evaporation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Dishes were incubated in parallel to analyze osmolality during culture between groups: synthetic oviductal medium enriched with potassium versus human tubal fluid medium; protein versus no protein supplementation; dry versus humid atmosphere; high versus low volume of mineral oil. Additionally, media evaporation was compared between six models of time-lapse dishes with distinct designs, cultured in a joint incubator. Two of them were retested in their corresponding incubator to analyze the dish-incubator fit. Daily osmolality measurements were compared between groups. Linear regression was performed to analyze evaporation rates. MAIN RESULTS AND THE ROLE OF CHANCE: Protein supplementation did not significantly affect evaporation. Contrarily, humidity levels inside the incubators, the volume of mineral oil and the type of culture media, played an important role in osmolality stabilization. The design of time-lapse dishes and their recommended preparation protocol heavily influenced their evaporation rates, which were further altered by each incubator's characteristics. Media with initially high osmolalities had a bigger risk of reaching hypertonic levels during culture. LIMITATIONS, REASONS FOR CAUTION: While numerous, the studied variables are limited and therefore other factors could play a role in osmolality dynamics, as well. Incontrollable atmospheric factors could also result in some variation in the observed results between different centers and laboratories. WIDER IMPLICATIONS OF THE FINDINGS: Published literature has extensively described how hypertonic media may impair embryo development and negatively affect clinical outcomes; therefore, maintaining a stable osmolality during culture should be considered essential. This work is of interest both for embryologists when analyzing their culture system and methodologies, as well as manufacturers in charge of designing IVF consumables. STUDY FUNDING/COMPETING INTEREST(S): This study was privately funded. TRIAL REGISTRATION NUMBER: N/A.

Evidence that human and equine erythrocytes could have significant roles in the transport and delivery of amino acids to organs and tissues.

Erythrocytes have a well-defined role in the gaseous exchange of oxygen and carbon dioxide in the mammalian body. The erythrocytes can contain more than half of the free amino acids present in whole blood. Based on measures showing that venous erythrocyte levels of amino acids are much less than arterial erythrocyte levels, it has previously been proposed that erythrocytes also play a role in the delivery of amino acids to tissues in the body. This role has been dismissed because it has been assumed that to act as an amino acid transport vehicle, the erythrocytes should release their entire amino acid content in the capillary beds at the target tissues with kinetic studies showing that this would take too long to achieve. This investigation set out to investigate whether the equine erythrocytes could rapidly take up and release smaller packages of amino acids when exposed to high or low external concentrations of amino acids, because it seemed very unlikely that cells would be able to release all of their amino acids without serious impacts on osmotic balance. Freshly prepared erythrocytes were placed in alternating solutions of high and low amino acid concentrations in PBS to assess the capacities of these cells to rapidly take up and release amino acids depending on the nature of the external environment. It was found that amino acids were rapidly taken up and released in small quantities in each cycle representing 15% of their total load in equine erythrocytes and 16% in human erythrocytes. The capacity for rapid uptake/release of amino acids by equine and human erythrocytes provided evidence to support the theory that mammalian erythrocytes have a significant role in transport of amino acids from the liver to tissues, muscles and organs.

Are hypohydrated older adults at increased risk of exhaustion?

BACKGROUND: Dehydration appears to affect muscle strength and weakness, although its influence on exhaustion remains unclear. The present study aimed to quantify the association between hydration status and exhaustion among older adults. METHODS: A cluster sampling approach was used, representing Portuguese older adults (≥65 years) according to age, sex, education level and region within the Nutrition UP65 cross-sectional study. A 24-h urine sample was collected to estimate free water reserve (FWR), which was categorised into tertiles according to sex. Subjects with incomplete 24-h urine and renal disease were excluded. From a sample size of 1500 subjects, 1143 were eligible. Exhaustion was self-reported according to the Center for Epidemiologic Studies Depression Scale. A logistic regression model was conducted to evaluate the association between FWR and exhaustion. Odds ratios and the respective 95% confidence intervals were calculated by sex and age. RESULTS: Free water reserve median (interquartile range) was 0.52 (0.68) L in women and 0.36 (0.77) L in men. Hypohydration affected 11.6% of women and 25.1% of men, whereas exhaustion was reported by 39.3% of women and 25.1% of men. After adjusting for confounders, women ≥80 years classified in the highest tertile of FWR showed a decreased risk of exhaustion (third tertile: odds ratio = 0.38; 95% confidence interval = 0.15-0.96) compared to women in the lowest FWR tertile. No such significant association was observed in women with <80 years and in men. CONCLUSIONS: These results show an association between worse hydration status and exhaustion in older women, highlighting the need to implement further studies clarifying this association.

PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features.

Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrPC (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrPSc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrPC modulate prion strain features. IMPORTANCE: The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrPC sequence may affect the selection of the substrain replicating in the animal model.

Plant growth-promoting Burkholderia species isolated from annual ryegrass in Portuguese soils.

AIMS: To search for culturable Burkholderia species associated with annual ryegrass in soils from natural pastures in Portugal, with plant growth-promoting effects. METHODS AND RESULTS: Annual ryegrass seedlings were used to trap Burkholderia from two different soils in laboratory conditions. A combined approach using genomic fingerprinting and sequencing of 16S rRNA and recA genes resulted in the identification of Burkholderia strains belonging to the species Burkholderia graminis, Burkholderia fungorum and the Burkholderia cepacia complex. Most strains were able to solubilize mineral phosphate and to synthesize indole acetic acid; some of them could produce siderophores and antagonize the phytopathogenic oomycete, Phytophthora cinnamomi. A strain (G2Bd5) of B. graminis was selected for gnotobiotic plant inoculation experiments. The main effects were the stimulation of root growth and enhancement of leaf lipid synthesis and turnover. Fluorescence in situ hybridization and confocal laser microscopy evidenced that strain G2Bd5 is a rhizospheric and endophytic colonizer of annual ryegrass. CONCLUSIONS: This work revealed that annual ryegrass can naturally associate with members of the genus Burkholderia. A novel plant growth promoting strain of B. graminis was obtained. SIGNIFICANCE AND IMPACT OF THE STUDY: The novel strain belongs to the plant-associated Burkholderia cluster and is a promising candidate for exploitation as plant inoculant in field conditions.

Ultrasonographic imaging of the temporomandibular joint in healthy cattle and pathological findings in one clinical case.

AIMS: To describe the normal ultrasonographic appearance of the temporomandibular joint (TMJ) in cattle, and to describe the ultrasonographic pathology of the TMJ as assessed in one cow with TMJ disease. METHODS: The TMJ of 12 healthy Holstein-Friesian cows were examined using a portable ultrasonographic unit with a 7.5 MHz linear probe and a 6.0 MHz convex probe. Each TMJ was scanned in a rostrolateral, lateral and caudolateral plane. In addition, the TMJ of one 2-year-old cow with clinical signs of food retention in the mouth, head tilt, swelling and pain in the right TMJ region and an infected horn fracture was examined ultrasonographically. RESULTS: The bone surfaces of the temporal process, the zygomatic process and the temporal bone, the larger muscles of the TMJ region, the superficial temporal vein, and the parotid salivary gland could be imaged in all normal healthy cattle. Using the linear probe, the joint capsule was visible in 17/24 (71%) cases in the caudolateral plane, but the articular disc could not be visualised. With the convex probe, the joint capsule could be imaged in all cases in the caudolateral plane, and the articular disc in 13/24 (54%) cases in the caudolateral plane. It was never possible to see the synovial pouch in healthy cattle using either probe. By contrast, in the cow diagnosed with septic arthritis of the right TMJ, a marked anechoic and heterogeneous hypoechoic effusion of the TMJ with distension of the joint capsule was visualised. CONCLUSIONS: The results of this descriptive study serve to provide a reference for ultrasonography of pathological conditions of the TMJ region in cattle. CLINICAL RELEVANCE: As many veterinarians are equipped with ultrasound machines with 5-8 MHz linear rectal probes, the authors recommend using these probes for further investigation of clinical cases with swelling of the TMJ region and/or masticatory problems of unclear origin to exclude or diagnose TMJ disorders.

Analysis of the BRAF V600E mutation in primary cutaneous melanoma.

BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors.

Localized in vivo prodrug activation using radionuclides.

Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof-of-principle, we tested whether this strategy of " RA dionuclide i nduced D rug E ngagement for R elease" ( RAiDER ) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing exposure to activated chemotherapy in off-target sites. Methods: We screened the ability of radionuclides to chemically activate a model radiation-activated prodrug consisting of the microtubule destabilizing monomethyl auristatin E caged by a radiation-responsive phenyl azide ("caged-MMAE") and interpreted experimental results using the radiobiology computational simulation suite TOPAS-nBio. RAiDER was evaluated in syngeneic mouse models of cancer using fibroblast activation protein inhibitor (FAPI) agents 99m Tc-FAPI-34 and 177 Lu-FAPI-04, the prostate-specific membrane antigen (PSMA) agent 177 Lu-PSMA-617, combined with caged-MMAE or caged-exatecan. Biodistribution in mice, combined with clinical dosimetry, estimated the relationship between radiopharmaceutical uptake in patients and anticipated concentrations of activated prodrug using RAiDER. Results: RAiDER efficiency varied by 250-fold across radionuclides ( 99m Tc> 177 Lu> 64 Cu> 68 Ga> 223 Ra> 18 F), yielding up to 1.22µM prodrug activation per Gy of exposure from 99m Tc. Computational simulations implicated low-energy electron-mediated free radical formation as driving prodrug activation. Clinically relevant radionuclide concentrations chemically activated caged-MMAE restored its ability to destabilize microtubules and increased its cytotoxicity by up to 600-fold compared to non-irradiated prodrug. Mice treated with 99m Tc-FAPI-34 and caged-MMAE accumulated up to 3000× greater concentrations of activated MMAE in tumors compared to other tissues. RAiDER with 99m Tc-FAPI-34 or 177 Lu-FAPI-04 delayed tumor growth, while monotherapies did not ( P <0.03). Clinically-guided dosimetry suggests sufficient radiation doses can be delivered to activate therapeutically meaningful levels of prodrug. Conclusion: This proof-of-concept study shows that RAiDER is compatible with multiple radionuclides commonly used in nuclear medicine and has the potential to improve the efficacy of radiopharmaceutical therapies to treat cancer safely. RAiDER thus shows promise as an effective strategy to treat disseminated malignancies and broadens the capability of radiopharmaceuticals to trigger diverse biological and therapeutic responses.

May polydextrose potentially improve gut health in patients with chronic kidney disease?

Polydextrose (PDX) is a non-digestible oligosaccharide with a complex structure widely used in the food industry. Studies have shown many health benefits of polydextrose, including modulating the gut microbiota, improving the immune system, altering the lipid profile, and stimulating bowel function. Patients with chronic kidney disease (CKD) report gut dysbiosis, inflammation, dyslipidemia and constipation. These are major concerns that affect the quality of life. In this context, PDX can promote beneficial effects. However, little is known about PDX in CKD. This review discusses the possible beneficial effects of PDX on gut health for patients with CKD, particularly its impact on constipation.

Hypomagnesemia in critically ill medical patients.

BACKGROUND: Hypomagnesemia is an important but underdiagnosed electrolyte abnormality in critically ill patients. There are many studies to find the prevalence of hypomagnesemia and its effects on mortality and morbidity in these patients. Most of these studies have been carried out in intensive care units caring for patients with medical and surgical conditions and postoperative patients or those in respiratory intensive care unit, or critically ill cancer patients. This study was carried out on patients admitted to the medical acute care unit in a major tertiary care hospital. AIMS AND OBJECTIVES: To study serum magnesium levels in critically ill patients and to correlate serum magnesium levels with patient outcome considering the following parameters: length of stay in MICU, need for ventilatory support, duration of ventilatory support, APACHE score and mortality. To identify the primary medical conditions associated with abnormalities of serum magnesium. To identify the factors predisposing or contributing to hypomagnesemia in critically ill patients admitted in a medical intensive care unit. To detect other electrolyte abnormalities associated with hypomagnesemia, if any. RESULTS: On admission to MICU 52% patients had hypomagnesemia, 7% patients had hypermagnesemia and 41% patients had normomagnesemia. The patients with hypomagnesemia had higher mortality rate (57.7% vs 31.7%), more frequent need for ventilatory support (73% vs 53%), longer duration of mechanical ventilation (4.27 vs 2.15 days), more frequently had sepsis (38% vs 19%), hypocalcemia (69% vs 50%) and hypoalbuminemia (80.76% vs 70.8%). Patients with diabetes mellitus had hypomagnesemia more frequently (27% vs 14%). The duration of stay in the MICU or APACHE score on admission did not vary in patients with low or normal magnesium. CONCLUSIONS: There was a high prevalence of hypomagnesemia in the critically ill patients. Hypomagnesemia was associated with a higher mortality rate in critically ill patients. The need for ventilatory support was significantly higher in hypomagnesemic patients. Hypomagnesemic patients required ventilator support for longer duration. Hypomagnesemia was commonly associated with sepsis and diabetes mellitus. The duration of MICU stay and APACHE score on admission did not vary in patients with low magnesium and normal magnesium. Hypomagnesemia is more commonly seen in patients with hypocalcemia and hypoalbuminemia.

Bioavailability of two oral suspension and two oral tablet formulations of nimesulide 100 mg in healthy Brazilian adult subjects.

A specific, fast and sensitive high performance liquid chromatography coupled to an electro spray tandem triple quadrupole mass spectrometer (LC-MS/MS) assay was developed for the determination of nimesulide in human plasma using carbamazepine as the internal standard. The lower limit of quantification (LLOQ) was 50 ng/ml and the calibration curves were linear in the concentration range of 50 - 6,000 ng/ml. Method inter-batch precision and accuracy ranged from 2.78 to 10.80%, and 94.92 to 102.46%, respectively. Intra-batch precision ranged from 2.44 to 7.74%, while intra-batch accuracy ranged from 91.70 to 104.73%. The analytical method was applied to evaluate the pharmacokinetic and relative bioavailability of two different pharmaceutical formulations containing nimesulide, one tablet and one oral suspension, manufactured by the same pharmaceutical factory, comparing with two reference Nisulid formulations in 52 volunteers of both sexes previously divided in two groups of 26 subjects (13 men and 13 females each group). The test tablet formulation was not bioequivalent to the Nisulid 100 mg tablet with respect to the rate of absorption, but was bioequivalent according to the extent of drug absorption. On the other hand, since the 90% CI for Cmax, AUC0-t and AUCinf were within the 80 - 125% interval in the oral suspension study, it was concluded that test oral suspension were bioequivalent to Nisulid 50 mg/ml with respect to both the rate and extent of absorption.

Predictors of nutritional and inflammation risk in hemodialysis patients.

BACKGROUND: Malnutrition and chronic inflammation are prevalent complications in hemodialysis (HD) patients. Different nutritional assessment tools are used to identify patients at risk. A composite and comprehensive malnutrition inflammation score (MIS) has been correlated with morbidity and mortality, and appears to be a robust and quantitative tool. OBJECTIVES: Determine malnutrition risk profile in a sample of portuguese HD patients; determine the association of clinical and laboratory factors with MIS, and the impact of each parameter on MIS. METHODS AND RESULTS: We performed, between September 15th of 2015 and January 31st of 2016, a cross sectional analysis of 2975 patients, representing 25% of portuguese HD patients. 59% were men (66.7 ± 14.8 years); 31% diabetic; 79% and 21% performed, respectively, high-flux HD and HDF. A MIS >5 was considered to indicate higher risk and was present in 1489 patients (50%). Amongst all parameters, comorbilities/dialysis vintage, transferrin, functional capacity, changes in body weight and decreased fat stores showed the higher impact, while albumin had one of the lowest impact on the nutritional risk. MULTIVARIABLE ANALYSIS: Higher age (>75 years, OR 1.71, p < 0.001), diabetes (OR 1.25, p = 0.026), lower P levels (OR 1.57,p = 0.001), higher Ca levels (OR 1.51, p < 0.001), higher ERI (OR 1.05, p < 0.001), higher Kt/V (OR 2.14, p < 0.001) and higher CRP (OR 1.01, p < 0.001) were independently associated with a higher risk of MIS>5; higher nPNA (OR 0.29, p < 0.001) and higher Pcreat (OR 0.88, p < 0.001) were associated with a risk reduction of MIS>5 (95% CI). CONCLUSIONS: Routine clinical and analytic parameters were found to be associated with MIS range that might indicate higher risk, and may represent a simple alert sign for the need of further assessments.

Adherence to a Mediterranean Dietary Pattern and Functional Parameters: A Cross-Sectional Study in an Older Population.

OBJECTIVES: In older adults, diet and physical activity are among the most important behaviours that influence health. The Mediterranean Dietary Pattern has been related to longevity and can benefit physical function in older adults. The present study aims to quantify the association of adherence to a Mediterranean Dietary Pattern with physical functioning through by handgrip strength, as well as, with sedentary behaviour based on sitting time, in a sample of older adults. METHODS: A cross-sectional study was conducted in 1,491 older adults ≥ 65 years old. The adherence or non-adherence to a Mediterranean Dietary Pattern was assessed using the previously validated and translated 14 item questionnaire, the PREDIMED (Prevención com Dieta Mediterránea). Handgrip strength was measured with a Jamar Dynamometer. Sitting time per day was used as an indicator of sedentary behaviour. Multinomial logistic regressions were performed to quantify the association of adherence to a Mediterranean Dietary Pattern with handgrip strength and sitting time. RESULTS: Compared to participants who adhered to a Mediterranean Dietary Pattern, those who did not adhere to this diet have a significantly higher adjusted odds ratio for low handgrip strength [adjusted odds ratio: 1.50; 95% confidence interval: 1.09-2.05], as well as for longer sitting time [adjusted odds ratio: 1.43; 95% confidence interval: 1.04-1.96]. CONCLUSION: In older adults, the non-adherence to a Mediterranean Dietary Pattern was associated with both lower values of handgrip strength and longer sitting time.

A simple high-performance liquid chromatographic method for the determination of diclofenac in human plasma: application to a comparative bioavailability study.

A rapid, sensitive and specific method to quantify diclofenac in human plasma using indomethacin as the internal standard (IS) is described. Samples were extracted using protein precipitation protocol and analyzed by high performance liquid chromatography coupled to ultraviolet detection at 276 nm. Chromatography was performed isocratically with a run time of 8.0 min and the retention time observed for diclofenac and IS was 6.0 and 7.0 min, respectively. The calibration curve was linear over the range 50 - 4,000 ng/ml (r2 > 0.9995). The mean recovery of diclofenac ranged from 88.76 to 99.14% and the limit of quantification was 50 ng/ml. Intrabatch precision and accuracy (%CV) of the method ranged from 0.86 to 7.60%, and 99.34 to 103.8%, respectively. Interbatch precision (%CV) and accuracy ranged from 0.26 to 11.4%, and 92.00 to 105.34%, respectively. This HPLC method was used to determine the relative pharmacokinetics of two diclofenac-cholestyramine 140 mg capsule formulations. The study was conducted using an open, randomized and crossover design with a 1-week washout interval. A single 140 mg dose (equivalent to 70 mg of diclofenac) of each formulation was administered to 26 healthy volunteers (13 males and 13 females) and blood samples were obtained over 12-h interval. The geometric mean of diclofenac-cholestyramine/Flotac ratio was 90.53% for AUC0-12 and 100.22% for Cmax. Since the 90% CI for Cmax and AUCs ratios were all inside the 80 - 125% interval, it was concluded that the diclofenac-cholestyramine test formulation is bioequivalent to Flotac regarding both the rate and the extent of absorption.

Comparison of the nutritional diagnosis, obtained through different methods and indicators, in patients with cancer.

OBJECTIVE: The aim of this article is to compare the diagnosis, obtained through different methods and indicators, of nutritional risk in patients with cancer. METHODS: It was assessed nutritional risk in of 144 oncology patients was assessed, making use of Subjective Global Assessment (SGA, Detsky 1987), Malnutrition Universal Screening Tool (MUST, 2003), Body Mass Index (BMI) and Serum Albumin. STATISTICAL ANALYSIS: Kappa, chi-square and McNemar tests. RESULTS: It was found a high prevalence of malnutrition (MUST, 78.32%; SGA, 77.08%; serum albumin level< 3.5 g/dL, 45.60%; BMI < 20.0 kg/m(2), 36.11%) in patients with cancer. In general, there was a higher prevalence in patients with Gastrointestinal Tract Cancer (72.22%), with the stomach cancer being the most common one (29.17%). Tumors of the digestive tract presented with higher nutritional risk according to SGA (p < 0.0001), MUST (p < 0.01), BMI (p < 0,05) and serum albumin level < 3,0 g/dL (p < 0.05); these patients have twenty three times more chances of nutritional risk than patients with cancer in other organs. The patients that have also metastasis presented greater nutritional impairment, according to MUST (p < 0.05) and serum albumin level< 3,0 g/dl (p < 0,01). According to this study, we demonstrate that there is no difference between the Diagnosis of Nutritional Risk, according to MUST and SGA. However, these values are different when confronted with the ones of serum albumin level and BMI. CONCLUSION: The MUST and the Serum Albumin proved to be sensitive methods for the identification of nutritional risk in patients with metastatic cancer. The SGA and MUST tests are good diagnostic tests which presented convergence of results.

Vitamin D status and functional parameters: A cross-sectional study in an older population.

The present study aims to clarify the association of vitamin D status with functionality, measured through gait speed and hand grip strength, in a sample of older adults, considering sex-specific characteristics and the potential confounding effect of lifestyle factors, disease, skin phenotype, season of blood collection and vitamin D supplementation. The Nutrition UP 65 cross-sectional study was conducted in a population-based sample of 1,425 older adults ≥ 65 years old. Serum levels of 25-hydroxyvitamin D were quantified through electrochemiluminescence immunoassay. Multinomial logistic regressions were carried out using quartiles of gait speed and of hand grip strength as dependent variables. Participants at risk of vitamin D inadequacy (30.0-49.9 nmol/L) and deficiency (< 30.0 nmol/L) presented higher adjusted odds ratio of the lowest values of gait speed and hand grip strength than those with adequate vitamin D levels (≥ 50.0 nmol/L). These associations were strongest among men at risk of vitamin D deficiency [adjusted odds ratio for the lowest quartile of gait speed = 3.24; 95% CI: 1.56-6.73 and for the lowest quartile of hand grip strength = 3.28; 95% CI: 1.47-7.31] than in women at risk of vitamin D deficiency [adjusted odds ratio for the lowest quartile of gait speed = 2.72; 95% CI: 1.37-5.41 and for the lowest quartile of hand grip strength = 1.56; 95% CI: 0.81-3.00]. In conclusion, in older adults, particularly in men, the risk of vitamin D deficiency was directly associated with the lowest values of gait speed and of hand grip strength. However, randomized controlled trials are needed to overcome the possibility of reverse causation and residual confounding. Present results emphasise the need for strategies to promote the reduction of the high prevalence of low vitamin D status among the Portuguese older adult population.

Weakness: The most frequent criterion among pre-frail and frail older Portuguese.

AIM: In Portugal, the burden of pre-frailty and frailty in community-dwelling older adults is still unknown. The purpose of this study is to estimate the frequency of frailty in a Portuguese sample with ≥ 65years and to evaluate its associated factors. We also intend to identify which criterion has more impact on the diagnosis of frailty. METHODS: 1457 older adults with ≥ 65years from the Nutrition UP 65 study were evaluated in a cross-sectional analysis. Frailty was identified according to Fried et al. by the presence of three or more of the following factors: unintentional weight loss, self-reported exhaustion, slowness, weakness and low physical activity. Pre-frailty was defined as the presence of one or two of these criteria. The association between individuals' characteristics and frailty status was analysed through logistic regression analysis. RESULTS: The frequency of pre-frailty and frailty is 54.3% and 21.5%, respectively. In older adults classified as pre-frail or frail, 76.7% presented weakness and 48.6% exhaustion. In multivariate analyses, frailty was associated with age >75, lower education level, being single, divorced or widower, being professionally inactive, poor self-perception of health status, not drinking alcohol, being obese and undernourished or at undernutrition risk. CONCLUSION: This condition is very prevalent in Portuguese older adults, one fifth are frail whereas half are pre-frail. Weakness identified by low handgrip strength is the most prevalent criterion in pre-frail and frail Portuguese older adults.

Comparative bioavailability study of two phenoxymethylpenicillin potassium tablet formulations in healthy volunteers.

OBJECTIVE: The aim of this study was to evaluate the performance of 2 phenoxymethylpenicillin 500,000 UI tablet formulations in healthy human volunteers. MATERIAL AND METHODS: The study was conducted using an open, randomized crossover design with a 7-day washout interval. A single dose of each formulation was administered to 26 healthy volunteers as assessed by clinical and laboratory test evaluations. The plasma samples were obtained over an 8-h interval and phenoxymethylpenicillin concentrations were quantified by a suitable and validated HPLC-UV method with detection at 220 nm. Systolic and diastolic blood pressure and pulse rate measurement were taken pre dose and at intervals up to 8 h. RESULTS: Tolerance of both products was adequate. The mean of Meracilina/Pen-Ve-Oral 500,000 UI% geometric mean was 99.89% for AUC0-t, 100.86% for AUC0-infinity and 101.11% for Cmax. The 90% confidence intervals were 94.62 - 105.46%, 95.22 - 106.83% and 98.61 - 103.87%, respectively. The mean recovery of phenoxymethylpenicillin was 94.8%, while the retention time observed for phenoxymethylpenicillin and phenytoin (internal standard) was 4 and 10 min, respectively. The limit of quantification was 0.10 mg/l. CONCLUSION: Since the 90% CI for AUC0-t, AUC0-infinity and Cmax ratios were all within the 80 - 125% interval proposed by the US FDA and accepted by ANVISA, it was concluded that the Meracilina formulation (manufactured by AchA(c) S.A.) is bioequivalent to Pen-Ve-Oral (manufactured by Eurofarma) for both the rate and the extent of bioavailability.