Blood Chemistry Variables Research Articles

Il supporto nutrizionale nell’anoressia nervosa

Paediatric departments are increasingly faced with adolescents with anorexia nervosa in severe nutritional and metabolic decompensation. Artificial nutritional support, often indispensable in the most critical phases of the course, requires careful evaluation of the clinical conditions at the time of hospitalization and equally punctual monitoring of blood chemistry variables during re-feeding. Prolonged reduced caloric intake and malnutrition, especially in its most extreme forms, can cause damage to various organs and systems and the refeeding syndrome must be kept in mind as a further comorbidity and aggravating factor of the patient's conditions. Through the description of a clinical case of particular complexity, some aspects related to the hospital treatment of anorexia nervosa are discussed.

85 Evaluation of an Oral Supplemental Cannabidiol Product for Acceptability in Mature Horses

Abstract Thirty stock type geldings (15 ± 3 y; 556 ± 63 kg BW) were used in a randomized complete design for a 28-d trial to evaluate the influence of cannabidiol (CBD) oil supplementation on health of mature horses by conducting a blood chemistry panel and evaluating the presence of banned substances. Horses were stratified by BW and age, and randomly assigned to 1 of 3 dietary treatments formulated with canola oil to provide.50 mg CBD/kg BW (TRT1; n = 10), 0.75 mg CBD/kg BW (TRT2; n = 10), or 0.00 mg CBD/kg BW (canola oil; CON; n = 10) only as determined by manufacturer (Arrowhead Labs). Treatments were individually fed and top-dressed onto a commercially available concentrate twice daily at 12 h intervals using attachable feed bags. Diets were formulated to meet or slightly exceed nutritional requirements for mature horses at maintenance. Between meals, horses were maintained in adjacent dry lots and received coastal bermudagrass hay ad libitum. Body weight was obtained, and body condition scores (BCS) were assigned every4 d. On d 0 and 28, blood was collected via jugular venipuncture and serum was harvested to perform a blood chemistry panel and drugs of abuse screening at the Texas Veterinary Medical Diagnostic Laboratory (TVMDL; College Station, TX). Data were analyzed using PROC MIXED of SAS (v9.4), and the model included treatment, time, and the treatment × time interaction for BW and BCS. Blood chemistry variables on d 0 were used as a covariate and the main effect tested was treatment. Linear and quadratic orthogonal polynomial contrasts were used to partition sum of squares. Analysis of supplement samples revealed supplemented products contained lower CBD concentrations then indicated from initial testing. Therefore, horses in TRT1 and TRT2 received an average of 0.13 mg CBD/kg and 0.12 mg CBD/kg BW, respectively. Dietary treatments did not affect concentrate intake, BW, or BCS. Supplementation of CBD did not result in the presence of any banned substances in serum, including CBD, 7-carboxycannabidiol, 7-Nor-7-carboxycannabidiol, and tetrahydrocannabinol (THC). Following 28 d of supplementation, gamma-glutamyl transferase (GGT) responded quadratically (P = 0.06) to treatment, with a peak in GGT in horses receiving TRT2. Serum creatinine concentration tended (P = 0.06) to decrease with increasing inclusion of CBD in the diet. In contrast, the main effect of treatment on Ca concentrations was linear (P = 0.01) and characterized by decreased Ca values for TRT1 compared with TRT2 and CON. Canola based CBD oil was well-accepted by mature horses, banned substances were not detectible in blood, and blood chemistry parameters were not adversely affected as a result of supplementation; however, more information is needed to improve stability of CBD used in dietary products.

Effect of Haemodialysis on Serum Magnesium Level in Patients with Chronic Renal Failure: A Cross-sectional Study

Introduction: The dialysate Magnesium (Mg) concentration is the primary determinant of serum Mg levels in individuals on maintenance haemodialysis. A stable dialysate Mg content of 0.5 mmol/L is currently recommended. An alteration in this concentration can lead to altered serum magnesium levels. Few studies indicate that dialysate Mg concentration needs to be altered for maintenance of stable serum magnesium level. Aim: To compare pre and postdialysis serum magnesium levels in patients with chronic renal failure and the effect of drug intake and duration of dialysis on serum magnesium levels. Materials and Methods: This prospective observational cross- sectional study was conducted in a tertiary care hospital of Coimbatore, Tamil Nadu, India, for a period of three months, from June 2021 to August 2021. The predialysis and postdialysis serum magnesium levels of 100 chronic renal failure patients undergoing maintenance haemodialysis were measured. Parameters such as dialysis period, predialysis weight, predialysis routine blood chemistry variables (estimated glomerular filtration rate, serum urea, serum creatinine, serum sodium, serum potassium and serum calcium, serum phosphate measurements) history of diabetes, history of hypertension and history of medications, were assessed for all the patients. Statistical analysis of the data were done using Analysis Of Variance (ANOVA), Students’ t-test and Pearson’s correlation coefficient. Results: Total 71% of the study population were males and 29% were females. The mean age of the study population was found to be 51.34 years. The mean predialysis serum magnesium levels was 2.28±0.48 mg/dL. The mean postdialysis serum magnesium level was 1.69±0.52 mg/dL. Total 2% of the chronic renal failure patients had hypomagnesemia before dialysis, while 27% of the patients developed hypomagnesemia after dialysis. There was significant difference between pre and postdialysis Mg levels, p<0.001. There was no significant correlation between pre and postdialysis magnesium levels and drug intake. Patients undergoing dialysis for more than 300 days had a significantly decreased serum magnesium levels than those undergoing dialysis for less than 90 days. Conclusion: The risk of hypomagnesemia is definite in patients undergoing dialysis. Uniformity of dialysis fluids for all patients may not be advisable. Dialysate should be titrated in individual patients according to the predialysis serum magnesium levels.

Body weight and blood chemistry of wild coatis that feed on discarded human food

ABSTRACT: The coati (Nasua nasua, Linnaeus 1766) is a generalist species, feeding on often-discarded human food in dumpsters around ecological tourism sites. We investigated the body weight and some blood chemistry variables related to the diet of wild coatis from three parks: Parque Municipal das Mangabeiras (PM), Parque Nacional do Caparaó (PNC) e Estação Ecológica Água Limpa (EEAL). We tested the plasma of 53 coatis for high-density lipoprotein (HDL), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), cholesterol (Chol), triglycerides (Trig), and alkaline phosphatase (ALP). Male and female adults did not significantly differ on the weight (P > 0.05) and blood chemistry indexes (P > 0.05). The adult coatis of the PM were heavier than the adult coatis of the other two parks. There were significant differences in HDL (P < 0.04), AST (P < 0.001), ALT (P < 0.001), and GGT (P < 0.001) between adults of the three parks. Only ALT and ALP were significantly different (P < 0.05) among the young coatis. The results suggested the coatis of the three parks have different health status. The consumption of discarded human food seems to affect body weight of the PM coatis. The coatis from PNC and EEAL had blood chemistry profiles suggestive of liver disorder. We recommend carrying on environmental education programs to visitors and additional clinical investigations on coatis from these parks.

Carp Edema Virus Infection Is Associated With Severe Metabolic Disturbance in Fish.

Significant mortalities associated with emerging viral diseases are challenging the economy of common carp aquaculture. As such, there is an increased need to disentangle how infected fish cope with progressive disease pathology and lose the ability for homeostatic maintenance of key physiological parameters. A natural carp edema virus (CEV) infection outbreak at a carp fish farm provided an opportunity to examine diseased and healthy carp in the same storage pond, thereby contributing to our better understanding of CEV disease pathophysiology. The disease status of fish was determined using PCR-based virus identification combined with analysis of gill pathology. Compared with healthy control carp, the blood chemistry profile of CEV-infected fish revealed major disruptions in electrolyte and acid-base balance (i.e., hyponatraemia, hypochloraemia, hyperphosphatemia, elevated pH, base excess, and anion gap and decreased partial dissolved carbon dioxide). In addition, we recorded hyperproteinaemia, hyperalbuminaemia, hypotonic dehydration, endogenous hyperammonaemia, and decreased lactate along with increased creatinine, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Red blood cell associated hematology variables were also elevated. The multivariate pattern of responses for blood chemistry variables (driven by sodium, pH, partial dissolved carbon dioxide, ammonia, and albumin in the principal component analysis) clearly discriminated between CEV-infected and control carp. To conclude, we show that CEV infection in carp exerts complex adverse effects and results in severe metabolic disturbance due to the impaired gill respiratory and excretory functioning.

Exploratory Factor Analysis of Rainbow Trout Serum Chemistry Variables.

Clinical chemistry offers a valuable, affordable, moderately invasive, and nondisruptive way to assess animal physiological status and wellness within defined ranges and is widely used as a diagnostic clinical tool. Because of physiological differences between mammals, clinical correlates of blood chemistry variables are not known in detail in fish, in which tissue/organ function tests are inferred from mammal-derived clinical chemistry data. The aim of the present study was to apply exploratory factor analysis on a serum chemistry dataset from clinically healthy, reared rainbow trout Oncorhynchus mykiss (Walbaum, 1792) to select the most correlated variables and to test for possible underlying factors explaining the observed correlations as possible physiological status estimates in trout. The obtained factors were tested for correlation with hepatosomatic and splenosomatic indexes. Thirteen highly correlated variables were selected out of 18 original serum chemistry variables, and three underlying factors (Factors 1, 2, and 3) were identified that explained the observed correlations among variables. Moreover, Factor 1 correlated negatively with the hepatosomatic index and Factors 2 and 3 negatively with the splenosomatic index. The obtained factors were tentatively associated with: protein (liver) metabolism (Factor 1), cell turnover (Factor 2), and lipid (muscle) metabolism (Factor 3).

Effects of a Supervised Nordic Walking Program on Obese Adults with and without Type 2 Diabetes: The C.U.R.I.A.Mo. Centre Experience.

Exercise is a convenient non-medical intervention, commonly recommended in metabolic syndrome and type 2 diabetes (DM2) managements. Aerobic exercise and aerobic circuit training have been shown to be able to reduce the risk of developing DM2-related complications. Growing literature proves the usefulness of Nordic walking as exercise therapy in different disease populations, therefore it has a conceivable use in DM2 management. Aims of this study were to analyze and report the effects of two different supervised exercises (gym-based exercise and Nordic walking) on anthropometric profile, blood pressure values, blood chemistry and fitness variables in obese individuals with and without DM2. In this study, 108 obese adults (aged 45–65 years), with or without DM2, were recruited and allocated into one of four subgroups: (1) Gym-based exercise program (n = 49) or (2) Nordic walking program (n = 37) for obese adults; (3) Gym-based exercise program (n = 10) or (4) Nordic walking program (n = 12) for obese adults with DM2. In all exercise subgroups, statistically significant improvements in body weight, body mass index, fat mass index, muscular flexibility and maximal oxygen uptake (VO2 max) were observed. Moreover, a higher percentage of adherence to the gym-based program compared to Nordic walking was recorded. Our findings showed that, notwithstanding the lower adherence, a supervised Nordic walk is effective as a conventional gym-based program to improve body weight control, body composition parameters, muscular flexibility and VO2 max levels in obese adults with and without type 2 diabetes.

Growth Restriction and Systemic Immune Development in Preterm Piglets.

Background: Many preterm infants are born with growth restriction (GR) following maternal or fetal complications before birth. Such infants may continue to grow slowly after birth, regardless of birth weight (BW), due to morbidities related to their immature organs. Severe GR increases the susceptibility to infections, but it is not clear if this is a consequence of impaired systemic immunity or other factors, such as prolonged hospital stay or poor mucosal barrier function. Using preterm pigs as models for preterm infants, we hypothesized that moderate GR, exerting limited clinical effects, does not influence systemic immune development.Methods: Preterm pigs were delivered by cesarean section and fed bovine milk diets until 19 d. Piglets with fetal growth restriction (F-GR, the lowest 25% of BW, n = 27, excluding those with BW <350 g) and postnatal growth restriction (P-GR, the lowest 25% of postnatal growth rate, n = 24) were compared with their corresponding controls (F-CON, n = 92, and P-CON, n = 85, respectively). Organ weights were determined and blood collected for assessment of clinical status (blood chemistry and hematology). For a subgroup (n = 58), in depth analyses of neutrophil function, T cell counts, plasma cytokine levels, and leucocyte gene expression were performed.Results: For F-GR pigs, adrenal gland weight was increased and bone mineral content decreased at 19 d. Total leucocyte levels were lower at birth and interleukin-10 levels increased at d 8–10. In P-GR pigs, total leucocyte, neutrophil, monocyte, and eosinophil counts along with helper T cell fractions were elevated at 8–19 d of age, while the fraction of neutrophils with phagocytic capacity was reduced. Diarrhea and all remaining organ weights, blood chemistry, and immune variables were not affected by F-GR or P-GR.Conclusion: Moderate GR before and after preterm birth has limited effect on systemic immune development in preterm pigs, despite marginal effects on immune cell populations, adrenocortical function, and body composition. Similar responses may be observed for preterm infants with moderate fetal and postnatal growth restriction.

Blood chemistry reference intervals of captive Asiatic black bears (Ursus thibetanus)

Data on blood chemistry values can make fundamental contributions to our understanding of physiological changes. However, there is a lack of information regarding blood chemistry in Asiatic black bears (Ursus thibetanus). Thus, the objects of this study were to determine reference ranges for 29 blood chemistry variables, and to evaluate differences between age groups and between seasons. Blood samples (n = 138) were collected from 44 (20 males, 24 females; age range, 1–15 years) clinically healthy, captive Asiatic black bears (Ursus thibetanus) in the Republic of Korea. Young and adult bears showed significantly higher levels of creatinine and total cholesterol, and lower levels of blood urea nitrogen, blood urea nitrogen/creatinine ratio, lactate dehydrogenase and creatine kinase MB during hibernation compared to during non-hibernation. Adults also showed significantly higher levels of triglyceride, but lower levels of inorganic phosphorus, aspartate transaminase, alkaline phosphatase, high density lipoprotein cholesterol and creatine phosphokinase during hibernation than during non-hibernation. During hibernation, the urea nitrogen/creatinine ratio and levels of alkaline phosphatase, lactate dehydrogenase, and creatine phosphokinase in young bears were significantly higher than in adults, whereas creatinine levels were lower than in adults. During non-hibernation, the urea nitrogen/creatinine ratio and levels of calcium, alkaline phosphatase, lactate dehydrogenase, creatine phosphokinase and creatine kinase MB in young bears were significantly higher, whereas creatinine, total protein, albumin, gamma-glutamyl transferase and haemoglobin levels were lower than in adults. The results of this study provide reference values that will aid in understanding the physiology of Asiatic black bears and in assessing the health of these animals in captive environments.

Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects

Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.

Relationship between Blood Haemoglobin and Glucose Concentrations in Adult Great Tits (Parus Major) and Blue Tits (Cyanistes Caeruleus)

Haematological and blood chemistry variables are widely used in ecophysiological research as physiological indices of body condition in various vertebrate taxa. In this study, we analysed relationships between blood glucose and blood haemoglobin concentrations of adult birds in wild populations of Blue Tits ( Cyanistes caeruleus) and Great Tits ( Parus major) during the breeding season in central Poland. We found that blood glucose and blood haemoglobin concentrations are negatively correlated. We also show that individual Blue Tits have higher mean haemoglobin levels adjusted for the common value of glucose concentration than individual Great Tits and that females of both species have higher mean haemoglobin concentrations than males. Our results suggest that haematological as well as biochemical variables may be used in tune as complementary indices of body condition in wild bird populations.

The Impact of Systemic Factors on Clinical Response to Ranibizumab for Diabetic Macular Edema

To evaluate the effect of systemic factors on best-corrected visual acuity (BCVA) achieved with ranibizumab (Lucentis; Genentech, Inc, South San Francisco, CA) for treatment of diabetic macular edema (DME) in the RIDE and RISE phase 3 studies. Exploratory, post hoc analysis of 2 randomized, double-masked, sham-injection controlled studies. Adults with DME, BCVA of 20/40 to 20/320 Snellen equivalent, and central foveal thickness of 275 μm or more. Analysis of RIDE (clinicaltrials.gov identifier, NCT00473382) and RISE (clinicaltrials.gov identifier, NCT00473330) pooled ranibizumab data through month 24. Change in BCVA was assessed for association with the following covariates: age, body mass index (BMI), blood pressure, serum glucose, glycosylated hemoglobin (HbA1c), blood urea nitrogen, serum creatinine, estimated glomerular filtration rate, and blood chemistry variables. Change in BCVA at month 24 was assessed according to the following categories of diabetes medication use history: insulin only (n= 193), insulin plus other medications (n= 221), or other noninsulin medications (n= 331). Change in BCVA from baseline assessed by randomized treatment group in pooled 0.3- and 0.5-mg monthly ranibizumab groups. In patients with DME, vision improvement with ranibizumab was not influenced by systemic factors such as diabetes medication history, serum glucose, HbA1c, renal function, BMI, and blood pressure. Patients taking insulin with or without other medications at baseline had longer diabetes disease duration (mean, 17.4 and 20.9 years, respectively) compared with those taking other noninsulin medications (mean, 11.9 years). At month 24, among ranibizumab-treated patients, the mean BCVA change from baseline (Early Treatment Diabetic Retinopathy Study letters ± standard deviation) was not different between patients taking only insulin (12.6±11.2 letters), insulin plus other medications (12.2±12.4 letters), or other noninsulin medications (14.0±13.7 letters). Mean BCVA change also was comparable among patients taking thiazolidinediones (12.9±9.7 letters) and those not taking thiazolidinediones (13.2±13.3 letters). There were no associations between systemic factors (baseline values or change from baseline) and mean change of BCVA at month 24. These results suggest that visual response to ranibizumab therapy in DME was not influenced by nonocular factors related to systemic management of diabetes in the RIDE and RISE studies.

Differences between two japanese health-promotion programs on measures of health and wellness

We implemented and compared two 10-month health education programs in Minowa town and Matsumoto city, Nagano prefecture, Japan. The Matsumoto city cohort underwent a program of monthly classroom activities (CA group), whereas the Minowa town cohort were not only subjected to classroom activities but also performed 90-min strength and weight training once a week and were termed the classroom/training (CT) group. We measured anthropometric, blood pressure, physical fitness, blood chemistry, and brain function variables. All participants were provided pedometers and were encouraged to walk. Monthly seminars included education regarding yoga, exercise, blood pressure, nutrition, and other health-related topics. In total, 92 healthy participants were included in the CA group [age, 66.5 ± 5.4 years (mean ± standard error of mean); 30 males and 62 females] and 46 healthy participants were included in the CT group (mean age 62.7 ± 4.7 years; 22 males and 24 females). We observed significant differences between the average number of steps walked in the CA (7241.7 ± 113.6) and CT (8686.7 ± 167.2) groups. Both the groups both showed significant improvements in anthropometric, blood pressure, physical fitness, blood chemistry, and brain function tests; however, the CT group showed markedly greater improvement after the health education program than before participation. In conclusion, the CT program had added benefits over the CA program because of the higher average amount of walking (approximately 1,400 steps) and the inclusion of a weekly weight-training activity.

Production of a wheat-based fermented rice enriched with γ-amino butyric acid using Lactobacillus plantarum MNZ and its antihypertensive effects in spontaneously hypertensive rats

This study aimed to develop and characterize a wheat-based fermented rice (dosa) with potential anti-hypertensive effects using γ-aminobutyric acid (GABA)-producing Lactobacillus plantarum. Results showed that lactic acid bacterial fermentation enhanced the angiotensin converting enzyme inhibitory, radical scavenging activities and the GABA content (143 mg/kg at 120 h fermentation) of the dosa. The rats in the in-vivo trial were fed experimental diets containing dosa (T1), fermented dosa (T2) or dosa + pure GABA (T3). The systolic blood pressure, aortic endoteline-1 protein, plasma norepinephrine, serum level of thiobarbituric acid reactive substances and superoxide dismutase activity indicated improvement upon feeding of the diets containing GABA. While, the blood chemistry variables were not significantly affected in this experiment. GABA-enriched fermented dosa could therefore be considered as a functional food with the promising blood-pressure lowering effect.

The blood biochemistry of overwintering diamondback terrapins (Malaclemys terrapin)

Estuarine ectothermic vertebrates, such as diamondback terrapins (Malaclemys terrapin, Schwartz 1955), inhabit a dynamic environment, and many aspects of their biology reflect their ability to withstand and respond to these environmental challenges. The physiological adjustments necessary to maintain water and salt balance and the metabolic adjustments that accompany seasonal changes in activity and behavior have not been well-characterized for overwintering terrapins under field conditions. To investigate terrapin osmotic and metabolic physiology during winter when activity levels are depressed, we obtained repeat blood samples from 10 radio-tagged female terrapins maintained in a semi-natural, open-air salt marsh enclosure in southeastern North Carolina, USA. From November 2011 to April 2012, we measured monthly plasma osmolality, plasma concentrations of inorganic osmolytes (Na+, K+, Cl−), and protein catabolic indices (urea and uric acid), as well as monthly plasma concentrations of total Ca2+, lactate, and glucose as metabolic indices. We used linear mixed models to determine the best predictors of blood chemistry, where time (i.e., day) and environmental variables were fixed factors and individual terrapins were random factors. Day was a poor predictor of blood chemistry concentrations, indicating that the progression of winter did not elicit corresponding changes in biochemical indices as documented in other semi-aquatic turtles exposed to more severe winter and/or laboratory conditions. Carapace temperature was the most common predictor of blood chemistry concentrations in all models, underscoring its relative influence on physiology. In contrast to previous laboratory-based studies on the overwinter physiology of terrapins, our study demonstrates that terrapins in their natural environment are able to maintain biochemical homeostasis throughout winter. The use of evasive behavioral strategies may be an important factor for terrapins to reduce the passive exchange of water and salts with the estuarine environment.

Serum levels of pigment epithelium-derived factor (PEDF) are inversely associated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans

BackgroundWe have previously found that advanced glycation end products (AGEs) stimulate the proteolytic cleavage of dipeptidyl peptidase-4 (DPP-4) from plasma membranes, and circulating AGE levels are independently correlated with serum DPP-4 values. Since pigment epithelium-derived factor (PEDF), one of the adipocytokines, inhibits the AGEs-induced insulin resistance and vascular damage, it is conceivable that besides AGEs, PEDF might also regulate soluble DPP-4 levels. In this study, we addressed the issue. Study design and methodsThe study involved 188 subjects (123 males and 65 females; mean age of 61.1±9.2) who visited our hospital for a risk-screening test or treatment for cardiovascular disease. They underwent complete history and physical examinations, and determination of blood chemistry and anthropometric variables, including visceral and subcutaneous fat areas. Serum levels of DPP-4 and PEDF levels were examined by enzyme-linked immunosorbent assay. ResultsMedian (interquartile range) serum levels of DPP-4 and PEDF were 466.6 (400.2–545.1) ng/mL and 14.0 (10.6–17.0) μg/mL, respectively. Multiple stepwise regression analysis revealed that female (p<0.001), aspartate aminotransferase (p<0.001), glycated hemoglobin (p<0.001) and PEDF (inversely, p=0.020) were independently associated with DPP-4 levels (R2=0.267). ConclusionWe found here for the first time that serum PEDF levels were one of the independent correlates of circulating DPP-4 levels in humans. Since DPP-4 could impair insulin action and evoke vascular damage, our present study suggests that insulin-sensitizing and atheroprotective properties of PEDF might be ascribed partly to its inhibitory actions on DPP-4.

Tolerance of poultry against an overdose of canthaxanthin as measured by performance, different blood variables and post-mortem evaluation

Canthaxanthin (CXN) is a red pigment, which is broadly used in broiler chickens for skin pigmentation, in laying hens for the coloration of egg yolks and in poultry breeders for improving the antioxidant status of eggs. In order to investigate the safety of this feed additive under conditions of an accidental oversupply, studies in all target poultry categories were performed, comparing a non-supplemented control to treatments with the respective recommended dietary supplementation of CXN and a ten times overdose of the recommended CXN level. Performance, mortality and a number of hematological and blood biochemical variables as well as post-mortem evaluations were taken as parameters to assess the effects of CXN overdosing. In broilers performance was not influenced by treatment with CXN at 25 or 250mg/kg feed. The hematological traits of the CXN groups were either not different from the control or remained within the normal physiological range. Concentration of CXN in blood plasma increased (P<0.001) in a proportional manner to the CXN supplementation in the feed. Some blood chemistry variables responded to the CXN treatments, but remained close to normal values. No mortality occurred in the overdose treatment and neither regular health examination nor post-mortem evaluation revealed any detrimental effects of CXN on broiler health. Laying performance of hens was not influenced by CXN supplementation with 8 or 80mg/kg feed. The CXN content in eggs responded linearly to supplementation (P<0.001). None of the measured blood variables were affected by treatment. The dissection of experimental birds showed indications of friable livers in the CXN supplemented hens, but no other effects on gross-morphology were observed. In breeders body weight and productive performance were not different among treatments. Egg weight with 6mg CXN/kg feed was higher (P=0.045) than in the control group. The CXN content in eggs increased proportionally to CXN supplementation (P<0.001). No differences in fertility were observed among the treatments, but hatchability of fertile eggs was depressed by overdosing CXN (P<0.001). Certain hematology and blood chemistry traits differed between the treatments, but the values remained within the normal range. The final post-mortem examination did not reveal any health problems in these breeders, which were related to the dietary treatments or attributable to the high CXN contents. In summary CXN at dietary supplementation doses of up to ten times the recommended levels is safe for broilers, laying hens and poultry breeders.

A Pharmacokinetic/Pharmacodynamic Model of Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia Patients Treated with Flavopiridol

Flavopiridol, the first clinically evaluated cyclin-dependent kinase inhibitor, shows activity in patients with refractory chronic lymphocytic leukemia, but prevalent and unpredictable tumor lysis syndrome (TLS) presents a major barrier to its broad clinical use. The purpose of this study was to investigate the relationships between pretreatment risk factors, drug pharmacokinetics, and TLS. A population pharmacokinetic/pharmacodynamic model linking drug exposure and TLS was developed. Plasma data of flavopiridol and its glucuronide metabolite (flavo-G) were obtained from 111 patients treated in early-phase trials with frequent sampling following initial and/or escalated doses. TLS grading was modeled with logistic regression as a pharmacodynamic endpoint. Demographics, baseline disease status, and blood chemistry variables were evaluated as covariates. Gender was the most significant pharmacokinetic covariate, with females displaying higher flavo-G exposure than males. Glucuronide metabolite exposure was predictive of TLS occurrence, and bulky lymphadenopathy was identified as a significant covariate on TLS probability. The estimated probability of TLS occurrence in patients with baseline bulky lymphadenopathy less than 10 cm or 10 cm or more during the first 2 treatments was 0.111 (SE% 13.0%) and 0.265 (SE% 17.9%), respectively, when flavo-G area under the plasma concentration versus time curve was at its median value in whole-patient group. This is the first population pharmacokinetic/pharmacodynamic model of TLS. Further work is needed to explore potential mechanisms and to determine whether the associations between TLS, gender, and glucuronide metabolites are relevant in patients with chronic lymphocytic leukemia treated with other cyclin-dependent kinase inhibitors.

Hematologic and blood chemistry values of healthyCebus flaviuskept in northeast of Brazil

Cebus flavius is a New World Monkey found in the northeast of Brazil, listed as critically endangered. So far, no hematologic or blood chemistry reference intervals have been determined for this species. Hematologic and biochemistry reference values were determined for 20 clinically healthy C.flavius, kept in captivity in the Wild Animals Screening Center, João Pessoa, Paraíba, Brazil. The influence of gender and age on these variables was evaluated. Considering sex, significant differences are found for the total count of erythrocytes, hematocrit, hemoglobin, mean corpuscular hemoglobin, and creatine kinase. Regarding the age, levels of creatinine and alanine aminotransferase are significantly higher in adults and levels of creatine kinase and calcium are significantly higher in juveniles. Considering age, no hematologic differences were found. The factors age and gender had influence on some hematologic and blood chemistry variables and should not be neglected for a correct blood interpretation.

Serum levels of advanced glycation end products (AGEs) are independently correlated with circulating levels of dipeptidyl peptidase-4 (DPP-4) in humans

ObjectivesInhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a potential therapeutic target for type 2 diabetes. Although soluble DPP-4 has been identified in human serum and could be associated with DPP-4 activity, the kinetics and regulation of circulating DPP-4 levels remain unknown. In this study, we examined which anthropometric and metabolic variables, including serum levels of advanced glycation end products (AGEs), were independently associated with serum DPP-4 levels. Further, we investigated the effects of AGEs on DPP-4 expression in, and soluble DPP-4 release from human cultured proximal tubular epithelial cells. Design and methodsThe study involved 432 consecutive outpatients (301 males and 131 females; mean ages 61.8±8.8) who underwent complete history and physical examinations, and determinations of blood chemistry and anthropometric variables. Serum DPP-4 and AGE levels were examined by enzyme-linked immunosorbent assay. Protein expression levels of DPP-4 and its release from the cells were analyzed with western blot analysis. ResultsMean serum levels of DPP-4 and AGEs were 520.2±39.9ng/mL and 8.96±2.57U/mL, respectively. In multiple regression analysis, female (p<0.001), HDL-cholesterol (p<0.001), glycated hemoglobin (p<0.001), AGEs (p<0.03), and the absence of hypertension medication (p<0.05) are independently associated with DPP-4 levels (R2=0.167). Western blot analysis revealed that AGEs significantly increased DPP-4 expression in, and soluble DPP-4 release from tubular cells. ConclusionsThe present study reveals that serum levels of DPP-4 are independently associated with various metabolic parameters in a general population. AGEs may up-regulate cellular DPP-4 expression and subsequently increase circulating levels of DPP-4 in humans.