Blood Chemistry Analysis Research Articles

Proof-of-concept study of electrospun PLGA membrane in the treatment of limbal stem cell deficiency

ObjectiveThe aim of this study was to assess the safety of poly-lactic co-glycolic acid (PLGA) electrospun membranes as carriers for limbal tissue explants for treatment of limbal stem cell deficiency...

Reference intervals for Cu, Mg, and Zn in captive gyrfalcons and other falcon species in the United Arab Emirates.

Falconry is a long-standing tradition in the United Arab Emirates (UAE), and in 2016, falconry was included by UNESCO in the list of intangible cultural heritage of humanity. The health and wellness of falconry raptors is a priority for the local culture; plasma chemistry analysis plays an important role in monitoring, assessing, and managing diseases in avian patients. Imbalances of Cu, Mg, and Zn have been linked to several diseases in avian species; therefore, determining the reference intervals (RIs) of these minerals has important implications in the clinical management of falcons. We determined the RIs in plasma for Cu, Mg, and Zn in captive (falconry-managed) falcons according to the Quality Assurance and Laboratory Standards Committee of the American Society for Veterinary Clinical Pathology, and the Clinical Laboratory Standards Institute guidelines. Blood chemistry analyses were carried out on 252 clinically healthy falcons examined at the Dubai Falcon Hospital in the UAE: 124 gyrfalcons (Falco rusticolus) and 128 falcons of other species. We observed no significant variation in RIs of Cu (1.5-7.0 µmol/L), Mg (0.49-0.78 mmol/L), or Zn (11.8-34.1 µmol/L) based on different species or sex.

Short Term Safety, Immunogenicity, and Reproductive Effects of Combined Vaccination With Anti-GnRH (Gonacon) and Rabies Vaccines in Female Feral Cats.

Overpopulation of free-roaming cats is a major problem leading to negative impacts on animal health and welfare, public nuisance, transmission of zoonotic diseases, and well-documented harm to wildlife. Surgical sterilization had failed to provide a practical solution to free-roaming cats' overpopulation under field conditions; therefore, efficient and safe non-surgical immunocontraception methods are aspired. Rabies is a deadly virus that may infect people and animals. However, the safety and efficacy of combined vaccination with anti-GnRH and rabies vaccines in feral cats, which often suffer from disrupted health conditions and experienced high stress level, has never been studied. Therefore, our objective was to examine the short-term safety and efficacy of anti-GnRH vaccine (Gonacon), in combination with rabies vaccine in female feral cats. Mature feral female cats were captured and divided into the following groups: (I) GonaconX1-Rabies: queens vaccinated with both Gonacon and rabies (n = 5); (II) GonaconX2-Rabies: queens vaccinated twice with Gonacon (3 weeks apart) and with Rabies (n = 4); (III) OVx-Rabies: queens ovariohysterectomized and vaccinated with rabies (n = 4); (IV) Intact-Rabies: queens vaccinated against rabies and remained intact (n = 3). Comprehensive veterinary examinations and blood tests were performed every 2 weeks for 14 weeks. Data were analyzed by Repeated-Measures-ANOVA or Fisher-Exact-Test. There were neither systemic nor local adverse reactions at the vaccination sites. Blood count (PCV, TS, RBC, HGB, HCT, WBC) and chemistry (Total protein, Total globulin, Albumin, Urea, Creatinine, Creatine kinase, Bilirubin, GGT, ALT, AST) analyses revealed no differences among groups. There were no differences in serum rabies antibodies titers among groups, and queens kept a protective titer (>0.5 IU/mL) starting at 2–4 weeks after vaccination. Anti-GnRH antibodies were detected in all Gonacon-vaccinated queens, excluding one queen (GonaconX2-Rabies group). Anti-müllerian hormone serum concentrations reduced significantly after ovariohysterectomy, as well as gradually following vaccination with Gonacon, but it remained high in intact queens. Evaluation of vaginal cytology and ovarian histology suggested that reproductive cyclicity was suppressed in Gonacon-vaccinated queens. Our results support the conclusion that in the short term, the combined vaccination with Gonacon and rabies is safe and effective in female feral cats. However, further long-term studies are warranted to test this immunologic regimen in feral cats.

Knockout of the Endothelin B receptor in adipocytes improves insulin sensitivity and the metabolic profile of male mice fed a High fat Diet

Endothelin-1 (ET-1) is elevated in patients who are overweight and suffer from obesity; however, its contribution to the pathophysiology related to obesity is not fully understood. Obesity is associated with dyslipidemia and insulin resistance, which may in part be mediated adipocyte hypertrophy and dysfunction leading to a reduction in circulating insulin sensitizing adipokines. Pharmacological blockade of ETB receptors improves insulin sensitivity in mice fed a high fat diet for 8 weeks, which is associated with increased Peroxisome proliferator-activated receptor gamma (pparg) levels in visceral adipose and increased circulating adiponectin, suggesting a role for ETB receptor activation on adipocytes in pathophysiology related to obesity. We hypothesized that elevated ET-1 in obesity promotes insulin resistance by reducing adipose pparg leading to a reduction in the secretion of adipokines, such as adiponectin. To test this hypothesis, adipocyte-specific ETB receptor knockout mice (adETBKO) were generated by crossing adiponectin Cre mice with ETB floxed mice. AdETBKO or wild type (WT) littermates were fed either normal diet (NMD) or high fat diet (HFD) for 8 weeks. WT HFD fed mice had significantly higher body weight and fat mass compared to WT NMD, although there was no difference between WT HFD and adETBKO HFD mice. KEGG pathway analysis of differentially expressed genes determined by RNA-Sequencing of gonadal adipose indicated that compared to WT HFD fed mice, adETBKO HFD mice have an attenuation of over 500 genes enriched within insulin signaling and fatty acid metabolism pathways including adiponectin, insulin receptor substrate 1, Glucose transporter 4, fatty acid synthase, and adipolin. In addition, adETBKO HFD mice had significantly improved glucose tolerance (4510±395 vs 6610±582 AUC, p<0.05)and insulin tolerance (-6867±517 vs -2927±584 AUC, p<0.05)compared to insulin resistant HFD fed mice. Plasma adiponectin was reduced by 2-fold in WT HFD compared to WT NMD mice (6.82±0.253 vs 10.8±0.624 ug/ml, p<0.05), and this was attenuated in adETBKO HFD fed mice (6.82±0.253 vs 9.90±0.352 ug/ml, p<0.05). Plasma insulin and leptin levels were significantly increased in WT HFD mice, an effect that was attenuated in adETBKO HFD mice (1.59±0.276 vs 0.809±0.064 ng/ml insulin, p<0.05, 22.6±1.08 vs 16.4±1.52 ng/ml leptin, p<0.05). Blood chemistry analysis showed that adETBKO HFD mice had significantly improved ALT (15.5±1.26 vs 46.5±6.16 U/L, p<0.05), HDL (98.3±3.68 vs 84.6±1.76 mg/dl, p<0.05), LDL (19.6±0.945 vs 29.2±2.63 mg/dl, p<0.05) and NEFA (0.377±0.035 vs 0.751±0.076 mEq/L, p<0.05) levels compared to WT HFD mice. These data indicate that loss of the ETB receptor in adipocytes improves peripheral glucose homeostasis, dyslipidemia and the metabolic/cholesterol profile in mice fed a HFD. Coupled with the transcriptomic profile of visceral adipose tissue in adETBKO HFD mice, which reflects a more insulin sensitive phenotype, these data suggest a role for the adipocyte ETB receptor in the development of insulin resistance exhibited by overweight and obese individuals.

Prednisolone-induced diabetes mellitus without pancreatic islet pathology in a dog

A one-year-old, intact male Maltese was referred with dehydration, anorexia, and marked hyperglycemia. The dog had been managed due to meningoencephalitis of unknown etiology (MUE) for three months. The dog had been treated with long-term prednisolone administration. Diabetic ketoacidosis (DKA) was identified based on the blood chemistry and venous gas analyses, and intensive treatments including insulin administration were initiated. On further examinations, there was no any other disease that contributed to the occurrence of DKA. Insulin resistance resulted from the administration of prednisolone was highly suspected, but the agent could not be tapered due to managing MUE. Following resolution of DKA, the dog was discharged with life-long insulin and prednisolone therapy. Over the next two years, the dog continued to be routinely re-evaluated and was managed with permanent insulin therapy (0.8–1.4 units/kg SC 12 hourly) and medications including prednisolone (0.4–1.1 mg/kg PO 12 hourly). Because MUE severely progressed, the dog was euthanized by owner’s request. Histopathologic examination of pancreas obtained by post-mortem revealed that both endo- and exocrine pancreas was within normal limit. The case described herein showed the risk of ketoacidosis as well as hyperglycemia after long-term prednisolone administration in a dog without pancreatic islet pathology.

Glucose Variability is Independently Correlated with Serum Level of Pigment Epithelium-Derived Factor in Type 2 Diabetes.

IntroductionPigment epithelium-derived factor (PEDF) may play a role in cardiometabolic disorders. The aim of this study was to investigate which biochemical and clinical parameters are independently associated with serum PEDF levels in patients with type 2 diabetes mellitus (T2DM).MethodsWe performed a cross-sectional analysis of 124 patients with T2DM who underwent continuous glucose monitoring (CGM) and blood chemistry analysis, including the diacron-reactive oxygen metabolites (d-ROMs) test and serum PEDF measurement (study 1). Then we investigated whether the changes in the studied biochemical and clinical parameters after 24 weeks of treatment (Δparameters) with anti-hyperglycemic agents, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and/or insulin and anti-hypertensive drugs and statins, were independently correlated with change in PEDF (ΔPEDF) in 52 of the patients with T2DM for whom there was sufficient serum samples to perform the post-treatment analysis (study 2). Serum levels of PEDF were measured with an enzyme-linked immunosorbent assay. CGM metrics were calculated on days 2 and 3. Oxidative stress was evaluated using the d-ROMs test.ResultsBody mass index (BMI), triglycerides, fasting C-peptide, mean amplitude of glycemic excursions (MAGE), urinary albumin-to-creatinine ratio (UACR), and d-ROMs were positively associated with serum PEDF level, and high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) were inversely associated with serum PEDF level. Because these parameters were correlated with each other, multivariate stepwise analysis was performed: eGFR, HDL-C, BMI, MAGE, and UACR remained significant (R2 = 0.452). Furthermore, ΔMAGE and Δd-ROMs were positively correlated with ΔPEDF in study 2.ConclusionsThe results of this study suggest that MAGE may be independently correlated with elevations in serum PEDF level in patients with T2DM.

Resveratrol ameliorates type 2 diabetes mellitus-induced alterations to the knee joint articular cartilage ultrastructure in rats

ABSTRACT Diabetes-induced osteoarthritis (OA) is a chronic inflammatory disease that damages the cartilage in the joints and could lead to disability. The protective effect of the antioxidant and anti-inflammatory agent, resveratrol, against alterations to the knee articular cartilage ultrastructure induced by type 2 diabetes mellitus (T2DM) associated with the inhibition of dyslipidemia, oxidative stress, and inflammation has not been investigated before. Therefore, we modeled OA in rats 10 weeks post diabetic induction using a high carbohydrate and fat diet and a single injection of streptozotocin (50 mg/kg body weight), and the protective group of rats started resveratrol (30 mg/kg; orally) treatment 2 weeks before diabetic induction and continued on resveratrol until the end of the experiment at week 12. Blood chemistry analysis confirmed hyperglycemia (elevated glucose and glycated hemoglobin, HbA1c), dyslipidemia (elevated triglyceride, cholesterol, and low-density lipoprotein-cholesterol), and upregulation of oxidative stress (malondialdehyde) and inflammatory (C-reactive protein and tumor necrosis factor-α) biomarkers in the model group. In addition, using light and electron microscopy examinations, we also observed in the model group substantial damage to the articular cartilage and profound chondrocyte and territorial matrix ultrastructural alterations such as chondrocytes with degenerated nucleus and mitochondria, scarce cytoplasmic processes, and absence of the fine fibrillar appearance of territorial matrix. Resveratrol pretreatment significantly (p ≤ 0.0029) but not completely protected from T2DM-induced OA. We conclude that resveratrol protects against alterations to the articular cartilage ultrastructure induced secondary to T2DM in rats, which is associated with the inhibition of glycemia, hyperlipidemia, and biomarkers of oxidative stress and inflammation.

Some important blood parameters of dairy-beef crossbred calves

<p class="MsoNormal" style="text-align:justify"><span style="font-size:10.0pt;line-height:106%;font-family:&quot;Times New Roman&quot;,serif;color:black;mso-themecolor:text1">In this report, we describe the differences in hematology and bloodchemistry between Holsten × Angus (HA) and Holsten × Angus × Simmental (AHS)calves. This report also includes the correlations (R, R = Pearson correlationcoefficients) of those blood parameters with average daily gain (ADG).&nbsp; Blood (jugular) was drawn from 18 AH and 12 AHScalves at 6, 45, and 90 d of age. Body weight was recorded on the same days andADG during 6 to 45 d (P1) and 45 to 90 d (P2) were calculated. The correlationswere analyzed aligning ADG of P1 with blood parameters of d 45, and ADG of P2with blood parameters of d 90. The results highlighted that several parametersin blood chemistry and hematology analysis were significantly different betweenAH and AHS. Regardless of them being different or similar between breeds,several blood parameters had strong relationships with ADG.&nbsp; For example, serum albumin was significantly affectedby breed (<i>P</i> = 0.008) and had a strongrelationship with ADG (R = 0.73), even though there was not significant differencein ADG between HA and HAS. Among, hematological parameters, hemoglobinconcentration was different between HA and HAS (<i>P </i>= 0.050) but again had a significant relationship with ADG (R =0.52). On the other hand, blood creatinine concentrations were similar betweenbreeds but had strong relationship with ADG (R = -0.78). Overall, this reportprovides valuable information that would be useful in developing tools to describeand evaluate within or between breed heterogeneity in the performance of dairy-</span><span style="font-size:10.0pt;line-height:106%;font-family:&quot;Times New Roman&quot;,serif">beefcrossbred cattle.<o:p></o:p></span>

Influence of a Polyherbal Mixture in Dairy Calves: Growth Performance and Gene Expression.

A polyherbal feed mixture containing (Achyrantes aspera, Trachyspermum ammi, Citrullus colocynthis, Andrographis paniculata, and Azadirachta indica) was evaluated in growing calves through blood chemistry, blood biometry, and gene expression during the pre-ruminant to weaning period. Forty Holstein calves (initial BW 45.6 ± 3.2 kg; 22.8 ± 0.9 days post birth) from a dairy farm were randomly assigned to the following treatments: 0, 3, 4, and 5 g/d of a polyherbal mixture, dosed in colloid gels with gelatin. Calves were housed in individual outdoor boxes with ad libitum access to a 21.5% CP calf starter and water and fed individually with a mixture of milk and a non-medicated milk replacer (22% CP). Blood samples were collected on day 59 for blood chemistry, blood biometry, and gene expression analysis in leukocyte through microarray assays. Immunoglobulins were quantified by enzyme-linked immunosorbent assay. The animals treated with the polyherbal mixture showed a quadratic effect on final body weight, daily weight gain, final hip height, and final thoracic girth. The best performance results were obtained with a treatment dose of 4 g/d. The serum IgG increased linearly with the treatment doses. Gene set enrichment analysis of upregulated genes revealed that the three biological processes with higher fold change were tight junction, mucin type O-Glycan biosynthesis, and intestinal immune network for IgA production. Also, these upregulated genes influenced arachidonic acid metabolism, and pantothenate and CoA biosynthesis. Gene ontology enrichment analysis indicated that the pathways enriched were PELP1 estrogen receptor interacting protein pathways, nuclear receptors in lipid metabolism and toxicity, tight junction, ECM-receptor interaction, thyroid hormone signaling pathways, vascular smooth muscle contraction, ribosome function, glutamatergic synapse pathway, focal adhesion, Hippo, calcium, and MAPK signaling pathways.

Variability study of immune status modified by polymorphic genetic profile in women with pregnancy loss under hydroxybenzene exposure

The study was performed in Perm, an industrially developed Russian city where hydroxybenzene concentrations are excessive due to dust and gaseous emissions from non-ferrous metallurgic plants. Their concentrations exceed average daily and single maximally permissible amounts. Hydroxybenzene and its derivatives are hormone-like substances, thus being hazardous to female reproductive system. The goal of our study was to analyze variability of immune state influenced by polymorphic genetic profile of women with pregnancy loss under hydroxybenzene exposure. Chemical analysis of ambient air quality was performed according to MG 4.1.617-96 regulations. Biological samples were taken from 129 women with reproductive disorders at their fertile age during the five-year observation period. Hydroxybenzene contents in blood were detected with gas chromatography with inductively coupled plasma. The test group 1 included women with reproductive disorders and phenol contents in blood exceeding the reference level ( 0.016 mg/cm3 ). Test group 2 consisted of women with reproductive disorders and phenol contents in blood within standard ranges. The control group 1 consisted of conditionally healthy women with phenol contents in their blood being higher than 0.016 mg/cm3 . Control group 2 included conditionally healthy women with phenol contents in their blood corresponding to the standard values. Serotonin content in blood serum considered catecholamine regulation marker was estimated with ELISA technique; phenol-specific IgG contents were measured by means of modified competitive ELISA method. PCR technique was used for detection of ACTN3 rs1815739 gene polymorphism associated with catecholamine metabolism. We found that a half of the total study group were exposed to phenol and cresols at concentrations 1.0 MPC average daily and single maximal dose. Incidence of endometriosis among them tended to increase over the examined 5-year periodL this disorder is known to contribute to pregnancy loss. Chemical analysis of blood allowed us to reveal phenol contamination in all the women to varying degrees. Regression analysis allowed to reveal a significant dependence between phenol contents in blood and phenol-specific IgG, as well as significant correlation between blood serotonin contents and cresols concentrations (p 0.05). Kruskal–Wallis test revealed significant intergroup differences by serotonin levels. There were significant differences between the test groups 1 and 2 by serotonin contents (at p 0.0083 with Bonferroni correction). Frequencies of ACTN3 rs1815739 genotypes, using a multiplicative model, allowed us to assign T allele to the factors contributing to risk of reproductive losses induced by biological media contaminated with phenol in excess. Cross-classification analysis revealed a causal relationship between serotonin contents and ACTN3 rs1815739 genotype.

Subcutaneous toxicity of a dual ionically cross-linked atelocollagen and sodium hyaluronate gel: Rat in vivo study for biological safety evaluation of the injectable hydrogel.

Hydrogels are commonly used in wound dressing, as they retain moisture, accelerate healing, and break down necrotic tissue. This process enhances patient comfort levels while simultaneously reducing pain caused by dead tissue. The purpose of this study was to investigate the in vivo toxicity of a dual hydrogel consisting of type I atelocollagen cross-linked with sodium hyaluronate hydrogel used for wound dressing. Porcine type I atelocollagen was cross-linked with sodium hyaluronate to form the hydrogel. For subcutaneous implantation, 0.5 ml of dual hydrogel was injected into two different sites of twenty rats per group. High density polyethylene rods were implanted subcutaneously to serve as a control material. Hematological assessment, blood biochemistry, histopathological, and histological evaluations were scored and graded after 4 weeks. A bioreactivity rating was used for evaluation of subacute toxicity. Differences observed in blood chemical analysis and hematological analysis between control and test groups were within normal variations and considered unrelated to the test article implantation. No significant implantation-related lesions were observed in any of the major organs of all test animals. The overall histopathological index of the test article implantation sites was evaluated as 0. The bioreactivity rating was evaluated as non-irritant after 4-week subcutaneous implantation. Overall, these results indicate that the dual hydrogel of type I atelocollagen and sodium hyaluronate is biologically and chemically safe for clinical application as a wound dressing.

Growth Performance, Cellular Immunity and Blood Chemical Analysis of Two Broilers Strains after Phytogenic Supplementation

Abstract: Genetically, the basis of all commercial breeds is the same. Therefore, the selection pressure for traits such as performance and carcass yield results in particular products. Genetic variation of two different broiler strains (Avian48 and Cobb500) in response to black pepper and red hot pepper supplementation was studied. Two hundred chicks from each broiler strain were randomly distributed on the following treatments, 1. Control treatment; 2. Red hot pepper treatment (0.5 %); 3. Black pepper treatment (0.5%); 4. Mixture treatment (0.25 % black pepper plus 0.25 % red pepper), these additives were added to drinking water from the first week until the fifth week of age, every group containing 50 birds distributed on five replicates (10 birds/replicate). The growth performance, carcass traits, abdominal fat, edible giblets, blood pictures, cellular immunity, and chemical blood lipid profile were estimated. Cobb500 broilers strain respond better to water supplement of red hot pepper, black pepper, and their mixture than Avian48 strain. Moreover, adding red hot pepper (0.5), black pepper (0.5), and their mixture (0.25+0.25) to drinking water significantly improved growth performance compared to control treatments with the best results obtained from mixture supplementation. However, it's better to supplying these additives until the third week of age, especially black pepper. Using black pepper, red hot pepper, and their mixture as feed additives by 0.5% had a significant role in further improving carcass quality by lowering fat percent and blood cholesterol. LDL so decrease their percent in meat and increasing the dressing and carcass cuts as a general, with the best results reported for mixture supplement. Additionally, these herbs had the desired effect on improving broilers' cellular immunity by increasing phagocytic index and differential leukocyte count. Finally, further examinations are required to studying the response of other broiler strains and breeds to these supplements and evaluating its effect on carcass characteristics, abdominal fat, cellular immunity, blood picture, and lipid profile if used within the first three weeks of age only.

Perpanjangan Usia Tikus Tua Setelah Xenotransplantasi Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs)

Currently, mesenchymal stem cells (MSCs) for implementing regenerative medicine in aging become interest in medical research science, especially in degerative disease and other aging problems. This research was aimed to determine the effectiveness of hUC-MSCs on inhibiting the aging process through the lifetime of the rat and the effect of intravenous administration of hUC-MSCs in phisiologycally aging female rat on the blood analysis. This study was used 40 aged female rats with 29-30 months of age divided into four groups with 10 rats each. The control rat group was given physiological NaCl (0.9%) 0.5 mL, and the treated rat group was given hUC-MSCs 1x107 cells/kg body weight in 0.5 mL NaCl 0.9%, was injected intravenously in caudo lateralis tail vein with stratified frequency; one time injection (SC1), three times injections (SC3) and five times injections (SC5). Perifer blood was collected from retro-ortbital sinus vein 30 days before and after injection of hUC-MSCs for hematology and blood chemistry analysis. Based on the results were obtained, it indicated that hUC-MSCs increased the survival of aging rat were in treatment group, life span of rats was extended up to 40 months compared to the average life of control rat aged up to 34±2 months. The injection of hUC-MSCs 1x107 cells/kg of body weight with one, three and five times injection were affected to blood profiles and blood chemistry with correlation were low. The conclusions are hUC-MSCs extend the lifespan of aging rat and were affect the blood in general but in normal range of aging rat, affect in ALT and creatinin as tissue repair and tolerated by aging rat.

Severe offtarget effects following intravenous delivery of AAV9-MECP2 in a female mouse model of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent genetic cause of intellectual disability in girls, and there is currently no cure for the disease. We have previously shown that gene therapy using a self-complementary AAV9 viral vector expressing a codon-optimized Mecp2 version (AAV9-MCO) significantly improved symptoms and increased survival in male Mecp2-deficient mice. Here, we pursued our studies and investigated the safety and efficacy of long-term gene therapy in the genetically relevant RTT mouse model: the heterozygous (HET) Mecp2 deficient female mouse. These mice were injected with the AAV9-MCO vector through the tail vein and an array of behavioral tests was performed. At 16- and 30-weeks post-injection, this treatment was able to rescue apneas and improved the spontaneous locomotor deficits and circadian locomotor activity in Mecp2 HET mice treated with AAV9-MCO at a dose of 5 × 1011 vg/mouse.To examine whether a higher dose of vector could result in increased improvements, we injected Mecp2 HET mice with a higher MCO vector dose (1012 vg/mouse), which resulted in some severe, sometimes lethal, side effects. In order to confirm these effects, a new cohort of Mecp2 HET mice were administered increasing doses of MCO vector (1011, 5 × 1011 and 1012 vg/mouse). Again, two weeks after vector administration, some Mecp2 HET mice were found dead while others displayed severe side effects and had to be euthanized. These deleterious effects were not observed in Mecp2 HET mice injected with a high dose of AAV9-GFP and were directly proportionate to vector dosage (0, 23 or 54% mortality at an AAV9-MCO dose of 1011, 5 × 1011, 1012 vg/mouse, respectively), and no such lethality was observed in wild-type (WT) mice.In the Mecp2 HET mice treated with the high and medium AAV9-MCO doses, blood chemistry analysis and post-mortem histology showed liver damage with drastically elevated levels of liver transaminases and disorganized liver architecture. Apoptosis was confirmed by the presence of TUNEL- and cleaved-caspase 3-positive cells in the Mecp2 HET mice treated with the higher doses of AAV9-MCO. We then studied the involvement of the unfolded protein response (UPR) in triggering apoptosis since it can be activated by AAV vectors. Increased expression of the C/EBP homologous protein (CHOP), one of UPR downstream effectors, was confirmed in Mecp2 HET mice after vector administration.The toxic reaction seen in some treated mice indicates that, although gene therapy for RTT improved breathing deficits observed in Mecp2 HET mice, further studies are needed to better understand the underlying mechanisms and caution must be exercised before similar attempts are undertaken in female Rett patients.

Detection of Lumpy Skin Disease during an Outbreak in Summer 2019 in Menoufia Governorate, Egypt using Clinical, Biochemical and Molecular Diagnosis

Lumpy skin disease is an infectious disease affecting the bovines and caused by Lumpy skin disease virus (LSD virus; LSDV). It is considered an endemic disease in African continent and was recorded in Egypt since 1988. This study aimed to monitor the cattle health condition along the course of the disease through the estimation of biochemical parameters. Besides, investigations on the incriminated strains of LSD virus circulating during outbreak in summer 2019 were performed. One hundred and eighteen cattle of different ages and sex were examined for LSD in some villages of Menoufia Governorate, Egypt. The clinical signs were recorded, and blood chemical analyses were applied on the infected animals. Conventional PCR was used to identify the LSDV using two conservative genes, fusion and P32 coding genes. The infected animals showed typical symptoms of the LSDV infection. Morbidity rates in cattle were high in males (43%) and in 6–12 months of age (44.4%). The hemogram showed significant (P < 0.05) decrease in the count of red blood cells (RBCs) (6.13 ± 0.51× 106/µl), hemoglobin (Hb) (9.07 ± 0.15 g%), hematocrit (HCT) (17.47 ± 0.48%), mean corpuscular volume (MCV) (41.77 ± 0.79fL), mean corpuscular hemoglobin (MCH) (13.53 ± 0.29Pg), and mean corpuscular hemoglobin concentration (MCHC) (30.43 ± 0.53g/dL) in infected animals compared with control. The leukocytes showed significant (P < 0.05) increase in the count of white blood cells (WBCs) (15.13 ± 0.03 x103/μl), lymphocyte (LYM) (7.17 ± 0.12 x103/ μl), monocytes and some eosinophil (MID) (2.93 ± 0.08 x103/ μl), and granulocytes (GRAN) (5.03 ± 0.09 x103/ μl) in infected animals. Serum biochemistry of the infected animals showed significant (P < 0.05) increase in all biochemical parameters except serum albumin (2.61 ± 0.35g/dL). Lumpy skin disease virus was detected by Polymerase chain reaction (PCR) for both genes and the sequences of the fusion and P32 proteins were deposited in the GenBank by the accession numbers MN699855 and MN699856, respectively. Thus, attention should be directed to the circulating LSDV strain in the field and comparing it with the previously isolated strains. Field practitioners should depend on the blood parameters of the infected animals to select the appropriate remedies.

Glutamine Antagonist JHU-083 Normalizes Aberrant Hippocampal Glutaminase Activity and Improves Cognition in APOE4 Mice

Given the emergent aging population, the identification of effective treatments for Alzheimer's disease (AD) is critical. We investigated the therapeutic efficacy of JHU-083, a brain-penetrable glutamine antagonist, in treating AD using the humanized APOE4 knock-in mouse model. Cell culture studies were performed using BV2 cells and primary microglia isolated from hippocampi of adult APOE4 knock-in mice to evaluate the effect of JHU-083 treatment on LPS-induced glutaminase (GLS) activity and inflammatory markers. Six-month-old APOE4 knock-in mice were administered JHU-083 or vehicle via oral gavage 3x/week for 4-5 months and cognitive performance was assessed using the Barnes maze. Target engagement in the brain was confirmed using a radiolabeled GLS enzymatic activity assay, and electrophysiology, gastrointestinal histology, blood chemistry, and CBC analyses were conducted to evaluate the tolerability of JHU-083. JHU-083 inhibited the LPS-mediated increases in GLS activity, nitic oxide release, and pro-inflammatory cytokine production in cultured BV2 cells and primary microglia isolated from APOE4 knock-in AD mice. Chronic treatment with JHU-083 in APOE4 mice improved hippocampal-dependent Barnes maze performance. Consistent with the cell culture findings,postmortem analyses of APOE4 mice showed increased GLS activity in hippocampal CD11b+ enriched cells versus age-matched controls, which was completely normalized by JHU-083 treatment. JHU-083 was well-tolerated, showing no weight loss effect or overt behavioral changes. Peripheral nerve function, gastrointestinal histopathology, and CBC/clinical chemistry parameters were all unaffected by chronic JHU-083 treatment. These results suggest that the attenuation of upregulated hippocampal glutaminase by JHU-083 represents a new therapeutic strategy for AD.

Economic and Technical Analysis of Utilization Pistia Stratiotes as Magelang Duck Alternative Feed: An Agribusiness Paradigm

This study was conducted to determine the economic analysis, performance analysis and chemical quality of the meat of the utilization of pistia stratiotes (PS) in Magelang duck feed. Most duck feed is still very dependent on imports from other countries so there is a need to find alternative feedstuff that are not competing with humans. The experimental research was conducted at the Faculty of Animal Husbandry and Agriculture Undip using 4 treatments, namely T0 duck feed without the addition of PS in feed, T1 added 6% PS in feed, T2 added 12% PS in feed and T3 added 18% PS in duck feed. Parameters observed were final body weight, feed consumption, Feed Conversion Ratio (FCR), mortality, cholesterol, triglycerides, LDL, HDL, antioxidants, feed costs, income over feed costs, return on investment (ROI) and RC ratio. Feed consumption on T3 was the highest. Final body weight on T3 was not significantly different (P&gt; 0.05) compared to T1 and T2 but higher than T0 (P&lt;0.05). The FCR between T3, T2 and T1 was not significantly different (P&gt;0.05), but was lower than T0, duck mortality in this study 0. Blood chemistry analysis (cholesterol, triglycerides, LDL, HDL) showed that T2 and T3 were significantly better than T0 and T1. The results of the economic analysis showed that ducks given PS at T2 and T3 had significant lower feed costs compared to T0 and T1, while ROI from T1, T2 and T3 were significantly higher than T0. The highest IOFC was achieved when duck were fed (T2), while the lowest IOFC was at T0. R/C ratio of T1, T2 and T3 was not significantly different, but higher when compared to T0. Based on the results of technical and economic analysis, the use of PS in 12% duck feed gave the best result of technical and economic performance

An Investigation Into the Effects of Long-Term 50-Hz Power-Frequency Electromagnetic Field Exposure on Hematogram, Blood Chemistry, Fibrosis, and Oxidant Stress Status in the Liver and the Kidney From Sprague-Dawley Rats.

Power-frequency electromagnetic fields (PF-EMFs) at 50 Hz are potential health risk factors. This study aimed to explore the effects of long-term exposure to 50-Hz PF-EMFs on general physiological conditions in Sprague-Dawley (SD) rats. During a 24-week exposure period, the body mass and water and food intake of the animals were recorded regularly. The hematologic parameters were detected every 12 weeks, and blood chemistry analyses were performed every 4 weeks. After sacrifice, morphology was identified by hematoxylin-eosin, Masson, and immunohistochemical staining. Fibrosis-related gene expression and oxidative stress status were also detected. Compared with the control group, exposure to 30, 100, or 500 μT PF-EMF did not exert any effect on body mass, food intake, or water intake. Similarly, no significant differences were found in hematologic parameters or blood chemistry analyses among these groups. Furthermore, morphological assays showed that exposure to PF-EMFs had no influence on the structure of the liver or kidney. Finally, fibrosis-related gene expression and oxidative stress status were unaltered by PF-EMF exposure. The present study indicates that 24 weeks of exposure to PF-EMFs at intensities of 30, 100, or 500 μT might not affect hemograms, blood chemistry, fibrosis, or oxidative stress in the liver or kidney in SD rats. © 2020 Bioelectromagnetics Society.

A Measuring Instrument for In-Line and Real-Time Measurement of Blood-pCO2in Extracorporeal-Circulation

Since the late 1950s, blood $p$ CO2 can be measured by using electrodes and, more recently, also by using point-of-care instruments such as blood gas and chemistry analyzers. Nevertheless, nowadays no measurement method has succeeded in providing an economic, reliable, and accurate estimate of the blood- $p$ CO2 to be routinely used for the monitoring of extracorporeal (blood) circulation (ECC) treatments. Indeed, blood is a very complex biological matrix composed of several different constituents, thus apart from a limited maximum-admitted measurement error (about some mmHg) and a quite wide measuring interval (about [20, 100] mmHg), the measuring systems have to provide significant selectivity taking hemocompatibility and safety for the patient as a primary concern. In this article, we propose and demonstrate a measuring instrument consisting of a low-cost and disposable fluorescent pco-sensor that can be inserted in series with the bloodline, and a nondisposable optical head that contactless reads the sensor. The proposed measuring system is intrinsically safe for the patient, has adequate metrological performance, avoids blood sampling and the related issues, and may allow to comply with cost requirements. Preliminary tests, conducted simulating a 6-h ECC treatment by using bovine blood, revealed deviations from the reference measuring instrument of less than ±4 mmHg, while the blood- $p$ CO2 was varied in the range [20, 100] mmHg.

Comparison of different energy response for lipolysis using a 1,060-nm laser: An animal study of three pigs.

Non-invasive body-sculpting procedures are becoming increasingly popular. The application of 1,060nm of laser energy transcutaneously to hyperthermically induce the disruption of fat cells in the abdomen is a type of non-invasive procedure. The purpose of this study was to compare the treatment results from two parameters of the same system, each with different energy output levels, in an in vivo porcine model to determine the most effective application. Female pigs (n=3) were used in this study. We examined the effects of the treatment using photography, ultrasonography, gross and microscopic pathology, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. Blood chemistry analysis was performed before each session to check lipid levels and to monitor for any adverse changes in markers that may indicate liver damage. Biopsies were taken and routinely processed with hematoxylin and eosin and Oil Red O stains to examine for tissue damage at baseline and after each treatment. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assays were performed to check for apoptotic-related DNA damage. Ultrasonic imaging of the same area before and after the application of 1,060nm of laser energy at outputs of 0.9 and 1.4W/cm2 showed that the density of the fat layer changed immediately after irradiation due to the transient heat transfer in the fat layer. Preclinical evaluation was performed to obtain comparison data on the safety and efficacy of subcutaneous fat reduction after applying the different energy outputs of 0.9 and 1.4W/cm2 . Based on our findings, we suggest that long-term histologic changes through the use of these devices suggest a comparative effectiveness of the treatment energy.