Glutamine Oxaloacetate Transaminase Research Articles

SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1.

The silent information regulator T1 (SIRT1) is linked to longevity and is a crucial mediator of osteoblast function. We investigated the direct role of Sirt1 during bone modeling and remodeling stages in vivo using Tamoxifen-inducible osteoblast-specific Sirt1 conditional knockout (cKO) mice. cKO mice exhibited lower trabecular and cortical bone mass in the distal femur. These phenotypes were coupled with lower bone formation and bone resorption. Metabolomics analysis revealed that the metabolites involved in glycolysis were significantly decreased in cKO mice. Further analysis of the quantitative acetylome revealed 11 proteins with upregulated acetylation levels in both the femur and calvaria of cKO mice. Cross-analysis identified four proteins with the same upregulated lysine acetylation site in both the femur and calvaria of cKO mice. A combined analysis of the metabolome and acetylome, as well as immunoprecipitation, gene knockout, and site-mutation experiments, revealed that Sirt1 deletion inhibited glycolysis by directly binding to and increasing the acetylation level of Glutamine oxaloacetic transaminase 1 (GOT1). In conclusion, our study suggested that Sirt1 played a crucial role in regulating osteoblast metabolism to maintain bone homeostasis through its deacetylase activity on GOT1. These findings provided a novel insight into the potential targeting of osteoblast metabolism for the treatment of bone-related diseases.

Abstract 4012: SOT302: Dual expression of exogenous glutamine oxaloacetate transaminase (GOT2) and TP53-induced glycolysis and apoptosis regulator (TIGAR) enhance CAR T cell activity in preclinical solid tumor models

Abstract Background: Despite success in hematological malignancies, CAR T therapy has had limited efficacy against solid tumors. The suppressive tumor microenvironment limits CAR T activity through various mechanisms including competition for available nutrients and chronic stimulation resulting in reduced effector functions or T cell exhaustion. CAR T cells with enhanced metabolic fitness or more durable memory phenotype could potentially improve the clinical outcome in solid tumors. GOT2 plays an important role in mitochondrial function and maintenance of redox homeostasis. We have previously demonstrated enhancement of CAR T cells overexpressing GOT2. TIGAR is an enzyme known to promote antioxidative activites and reduce reactive oxygen species and has a role in protecting against apoptosis. Here we tested SOT302 CAR T cells expressing both GOT2 and TIGAR in preclinical solid tumor models. Results: Expression of GOT2 and TIGAR transgenes were confirmed by qRT-PCR and western blot. Activity of GOT2 and TIGAR were confirmed by measuring aminotransferase activity (AST) and glutathione production, respectively. Compared to control CAR T cells, SOT302 is enriched for CD8+ Tscm cells and has a higher percentage functional, non-senescent (CD28+CD57-) cells. SOT302 has similar cytokine expression and cytotoxicity in standard co-culture assays compared to controls. SOT302 cells were chronically stimulated with plate-bound antigen every 3-4 days for 4 rounds. SOT302 had greater expansion of cells and were less exhausted and had better cytolytic capacity compared to controls. SOT302 cells were then evaluated in tumor xenograft mouse models. Consistent with our previous findings, CAR T cells expressing the single GOT2 transgene were more efficacious compared to CAR T cells alone. Expression of the single TIGAR transgene had no apparent benefit over CAR alone, however SOT302 cells expressing both GOT2 and TIGAR had superior anti-tumor activity compared to CAR alone and CAR+GOT2. No overt toxicity or significant body weight loss was observed. Ex vivo analyses to measure peripheral expansion, tumor infiltration and exhaustion were also performed. Preliminary findings indicate that SOT302 has better peripheral expansion compared to CAR alone and similar expansion compared to CAR+GOT2 controls. SOT302 cells had better tumor infiltration compared to both the CAR alone and CAR+GOT2 cells. Tumor infiltrating SOT302 cells also exhibited lower levels of exhaustion compared to CAR alone or CAR+GOT2 controls. Summary: SOT302 cells express exogenous GOT2 and TIGAR transgenes and have superior anti-tumor activity in preclinical solid tumor models. These data suggest that SOT302 may be a promising candidate for patients with solid tumor cancers. Citation Format: Emily Kuiper, Samyabrata Bhaduri, Daniel Garafola, Kshitij Sharma, Jennifer Coccia, Kathleen Whiteman, Amy Jensen-Smith. SOT302: Dual expression of exogenous glutamine oxaloacetate transaminase (GOT2) and TP53-induced glycolysis and apoptosis regulator (TIGAR) enhance CAR T cell activity in preclinical solid tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4012.

Assessment of the Phytochemical Profile, Antioxidant Capacity, and Hepatoprotective Effect of Andrographis paniculata against CCl4-Induced Liver Dysfunction in Wistar Albino Rats.

Recent studies have highlighted the necessity to thoroughly evaluate medicinal plants due to their therapeutic potential. The current study delves into the phytochemical profile, antioxidant capacity, and hepatoprotective effect of Andrographis paniculata. The investigation specifically targets its effectiveness in mitigating liver dysfunction induced by carbon tetrachloride (CCl4) in Wistar albino rats, aiming to uncover its promising role as a natural remedy for liver-related ailments. A. paniculata leaf extract was screened for phytoconstituents and antioxidant and hepatoprotective effects in Wistar albino rats against CCl4-induced liver dysfunction. Phytochemical analysis revealed the presence of flavonoids, alkaloids, and phenolic compounds in all extracts. The phenolic concentration ranged from 10.23 to 19.52 mg gallic acid per gram of the sample, while the highest flavonoid concentration was found in the ethanol fraction (8.27 mg rutin equivalents per gram). The antioxidant activity varied from 10.23 to 62.23. GC-MS analysis identified several phytochemicals including octadecanoic acid, stigmasterol, phenanthrenecarboxylic acid, and others. Effects of the ethanol extract of A. paniculata were evaluated in four groups of animals. Biochemical estimations of serum glutamine oxaloacetate transaminase, serum glutamine pyruvate transaminase, and serum bilirubin were significantly higher (p < 0.05) in the CCl4-treated group. Treatment with 300 mg/kg b.w. of the ethanol extract of A. paniculata significantly (p < 0.05) decreased these serum enzymes. Lipid peroxidation levels in carbon tetrachloride-treated animals showed a substantial (p < 0.05) rise when compared to untreated animals, while the lipid peroxidation levels were considerably (p < 0.05) reduced after treatment with ethanol extract at 300 mg/kg b.w. Liver biochemical catalase activities were significantly reduced in the carbon tetrachloride-treated animals. The results of this study conclusively demonstrate that A. paniculata extracts are a rich source of phytochemicals and possess significant antioxidant, free radical scavenging, and hepatoprotective properties.

Preliminary evaluation of hepatoprotective potential of the polyherbal formulation.

Aim:The aim of this study was to investigate the antioxidant and hepatoprotective effects of the polyherbal formulation (PHF)containing Cajanus cajan (L.)Millsp., Lawsonia inermis L. Linn, Mimosa pudica L., Uraria picta (Jacq.)DC. and Operculina turpethum (L.)Silva Manso on carbon tetrachloride (CCl4)induced acute liver damage in albino rats.Materials and Methods:The groups of animals were administered with PHF at the doses 100, 200 and 400 mg/kg b.w. (per oral [p.o.])once in a day for 7 days and at day 6th and 7th the animals were administrated with Carbon tetrachloride (1.0 mL/kg b.w. 50% v/v with olive oil,; p.o.). The effect of PHF on serum glutamine pyruvate transaminase (SGPT), serum glutamine oxaloacetate transaminase, alkaline phosphatase (ALP)and total bilirubin were determined in CCl4 - induced hepatotoxicity in rats. Further, the effects of PHF on glutathione (GSH), superoxide dismutase (SOD)level and lipid peroxidation (LPO)activity were also investigated.Results:The results demonstrated that PHF (400 mg/kg b.w.)significantly reduces the CCl4 induced increase in level of serum SGPT, serum ALP and total bilirubin. PHF (400 mg/kg b.w.)prevents the depletion level of GSH and decrease in the activity of SOD in CCl4 -induced liver injury in rats. In addition, PHF also showed a significant decrease in the LPO levels signifying the potent antioxidant activity.Conclusion:All our findings suggest that PHF could protect the liver cells from CCl4 - induced liver damages and the mechanism may be through the anti-oxidative effect of PHF.

Hepatoprotective bioactivity of the glycoprotein, antrodan, isolated from Antrodia cinnamomea mycelia.

Antrodan, a protein-bound polysaccharide isolated from Antrodia cinnamomea mycelia, was demonstrated to exhibit significant anti-inflammatory bioactivity in vitro. However, its role in hepatic injury in vivo still remains unclear. We hypothesized that antrodan may have beneficial hepatoprotective effects. To verify this, a lipopolysaccharide (LPS)-Sprague-Dawley rat model was used. Antrodan protected against liver damage by suppressing LPS-stimulated serum glutamine-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), interleukin (IL)-6, hepatic thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), inducible NO synthase (iNOS) and nuclear factor (NF)-κB, and by effectively alleviating the downregulated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px). Hematoxylin-eosin staining revealed that antrodan at a dosage of 40 mg/kg was able to alleviate LPS-induced liver damage to a normal status. In addition, we identified the partial main architectural backbone of antrodan to have a 1→3 linear β-glycosidic backbone of mannan linked by β-1→3 glucosidic branches. Conclusively, antrodan can potentially ameliorate liver damage in vivo by suppressing oxidative stress induced by LPS.

The mechanisms of protective effects of erythropoietin (EPO) on sepsis induced myocardial injury in rat

Objective To investigate the protective effects of erythropoietin (EPO) on myocardium injury after sepsis in rats in order to clarify the mechanisms.Methods The rat models of sepsis were produced by cecal ligation and perforation method (CLP).Ninty-six healthy SD rats were randomly (random number) divided into 3 groups:the sham operation group (Sham group,n =32),the sepsis group (CLP group,n =32),and the EPO treatment group (EPO group,n =32) treated with EPO 1000 IU/kg intraperitoneal injection after the CLP.The observation intervals were set at 3 h,6 h,12 h and 24 h after the surgery.The cardiac hemodynamics of the CLP group were measured.Plasma levels of inflammatory factors and myocardial enzyme indicators were determined by enzyme-linked immunosorbent assay (ELISA) ; Membrane potential levels of chondriosome of myocardial cells,cell apoptosis rates and expressions of nuclear factor-κB p65 of myocardium tissue were detected by flow cytometer; Then the pathological change of myocardium with HE staining was observed under light microscopy.Results (1) Compared with the CLP group,left ventricle systolic pressure (LVSP),left ventricle diastolic end pressure (LVEDP),the maximum rate of left ventricle rise and fall (+ dp/dtmax and-dp/dtmax) in the EPO group improved (P ＜0.05,P＜0.01); (2) Compared with the Sham operation group,plasma levels of tumor necrosis factoralpha (TNF-α),interleukin-6 (IL-6),C-reactive protein (CRP),cardiac troponin-I (cTNI),creatine kinase (CK),lactate dehydrogenase (LDH) and glutamine-oxaloacetic transaminase (GOT) in the CLP group increased at each interval (P ＜ 0.05),and those biomarkers in the EPO group were lower than those in the CLP group (P ＜ 0.05) ; On the contrary,plasma level of anti-inflammatory factor IL-10 in EPO group was higher than that in the CLP group (P ＜ 0.01) ; (3) Compared with the Sham operation group,the cell apoptosis rates in the CLP group increased significantly (P ＜ 0.01),and it decreased obviously in the EPO group (P ＜ 0.01); (4) Compared with the Sham group,membrane potential levels of chondriosome of myocardial cell in the CLP group decreased (P ＜0.01),while it increased in the EPO group in comparison with the CLP group (P ＜ 0.01) ; (5) Pathological changes of myocardium after the CLP could be lessened by the EPO treatment.Conclusions EPO may increase membrane potential levels of chondriosome and decrease the apoptosis rates of myocardial cell in rats after sepsis,and it may reduced the production of inflammatory factors to protect the myocardial cell by down-regulating NF-κB p65.Both increased membrane potential level of chonriosome and decreased inflammatory factor may implicate in myocardium protection thereby improving cardiac function after sepsis. Key words: Sepsis; Myocardial injury ; Apoptosis ; Chondriosome membrane potential; Nuclear factor κB p65 ; Erythropoietin; Inflammatory cytokines; Rat

Fungal Biotransformation of Fenofibrate

Abstract: In the present study, the petroleum ether extract of Dregea volubilis (PEDV) was evaluated for its protective effect on paracetamol-induced liver damage in Wistar rats. Serum biochemical parameters viz. serum glutamine oxaloacetate transaminase (SGOT), serum glutamine pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), total protein, bilirubin, cholesterol, triglyceroides; and liver biochemical parameters such as lipid peroxidation, reduced glutathione (GSH) content and catalase (CAT) activity were estimated. Overall biochemical observations indicated that PEDV exerted remarkable hepatoprotective efficacy against paracetamol-induced hepatic damage in rats that is may be due to its augmenting endogenous antioxidant mechanisms. Keywords: Dregea volubilis, Hepatoprotective, lipid peroxidation, glutathione, silymarin

Potentiality of Immobilized Pig Hepatocyte Spheroids in Bioartificial Liver System

Various extracorporeal bioartificial liver (BAL) systems have been developed. To treat fulminant hepatic failure (FHF) patients. Direct cell-cell interaction is one of the major factors influencing the functions of cultured hepatocytes, which increase with progressing of cell aggregation in this study, we investigated the effects of plasma viability and function single and spheroid pig hepatocytes in vitro. Hepatocytes were cultured as spheroids by suspension culture in spinner flasks. We obtained pig plasma from animals in hepatic failure. Immobilized single pig hepatocytes exposed to the toxic pig plasma lost viability and liver function. However, immobilized pig hepatocyte spheroids showed stable ammonia removal functions and urea synthesis and lower lactate dehydrogenase, glutamine oxaloacetate transaminase, and glutamine pyruvate transminase levels during BAL operation. At 5 hours, the ammonia concentration in plasma decreased to 370 and 150 μg/dL by immobilized single and spheroid hepatocytes, respectively, the concentrations at which they were maintained thereafter. The urea concentrations in plasma were 44 versus 72 μg/dL in immobilized single versus spheroid hepatocytes respectively, at 5 hours of operation. Spheroid hepatocytes not only showed in vivo structure, but also maintained high levels of liver-specific functions. The spheroid-based BAL system may be a good candidate to treat FHF patients.

Serum biochemical analysis to indicate pathogenic risk on mouse Mus musculus exposure to source of drinking water

The 18 biochemical parameters of serum were measured to analyze the pathogenic risks of the Yangtze River Source of Drinking Water in Nanjing area (YZR-SDW-NJ) on mouse Mus musculus for protection of human health in this research. The male mice Mus musculus were sampled and fed with YZR-SDW-NJ for 90 days then the eighteen serum biochemical levels were measured with Automatic Biochemical Analysis/RerLi 600. And the parameter data were treated by One-Way ANOVA statistic approach. The results showed that five parameter levels for the sample group mice were different from those for the control group significantly (0.01 < P or 0.05 < P). Four 4 of the 5 altered parameter levels were decreased including glutamate pyruvate transaminase 38% lower, glutamine-oxaloacetic transaminase 24% lower, triglyceride 76% lower and cystatin C 73% lower, only creatinine level was 26% higher than that in the control group. The data suggest that YZR-SDW-NJ had toxicity on the mouse and the organic pollutants in YZR-SDW-NJ might lead to liver, kidney, cardiovascular and metabolic pathogenic risks on the human beings. The results might be cited as evidence to control pollutants in the source water for the protection of NJ people's health.

Hepatoprotective Activity of Cyperus tegetum Rhizome Against Paracetamol-Induced Liver Damage in Rats

In present study the methanol extract of Cyperus tegetum rhizome (MECT) was evaluated for its effect on paracetamol-induced liver damage in Wistar rats. Serum biochemical parameters viz. serum glutamine oxaloacetate transaminase (SGOT), serum glutamine pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), total serum protein, total bilirubin content and liver biochemical parameters such as thiobarbituric acid reactive substances (TBARS) and reduced glutathione content were estimated. Biochemical and histopathological observations indicated that MECT had remarkable hepatoprotective effect against paracetamol-induced liver damage in rats.

Universal Definition of Myocardial Infarction

Myocardial infarction is a major cause of death and disability worldwide. Coronary atherosclerosis is a chronic disease with stable and unstable periods. During unstable periods with activated inflammation in the vascular wall, patients may develop a myocardial infarction. Myocardial infarction may be a minor event in a lifelong chronic disease, it may even go undetected, but it may also be a major catastrophic event leading to sudden death or severe hemodynamic deterioration. A myocardial infarction may be the first manifestation of coronary artery disease, or it may occur, repeatedly, in patients with established disease. Information on myocardial infarction attack rates can provide useful data regarding the burden of coronary artery disease within and across populations, especially if standardized data are collected in a manner that demonstrates the distinction between incident and recurrent events. From the epidemiological point of view, the incidence of myocardial infarction in a population can be used as a proxy for the prevalence of coronary artery disease in that population. Furthermore, the term myocardial infarction has major psychological and legal implications for the individual and society. It is an indicator of one of the leading health problems in the world, and it is an outcome measure in clinical trials and observational studies. With these perspectives, myocardial infarction may be defined from a number of different clinical, electrocardiographic, biochemical, imaging, and pathological characteristics. In the past, a general consensus existed for the clinical syndrome designated as myocardial infarction. In studies of disease prevalence, the World Health Organization (WHO) defined myocardial infarction from symptoms, ECG abnormalities, and enzymes. However, the development of more sensitive and specific serological biomarkers and precise imaging techniques allows detection of ever smaller amounts of myocardial necrosis. Accordingly, current clinical practice, health care delivery systems, as well as epidemiology and clinical trials all require a …

Antioxidant and Hepatoprotective Effects of Rosa damascena

The fresh juice of Rosa damascena Mill. flower exhibited promising in vitro antioxidant potential. The partially purified acetone fraction (AF) from silica gel column chromatography was found to be the active fraction with antioxidant properties. The AF required for 50% inhibition of superoxide radical production, hydroxyl radical generation and lipid peroxide formation were 13.75, 135 and 410µg/ml, respectively. Oral administration of AF at 50mg/kg body weight significantly reduced the serum alkaline phosphatase (ALP), glutamine pyruvate transaminase (GPT) and glutamine oxaloacetate transaminase (GOT) activity and lipid peroxide level in rats receiving an acute dose of CCl 4. This indicated that R. damascena could protect against CCl 4 induced hepatotoxicity, possibly by its free radical scavenging activity.

Nasopharyngeal endoscopy adds to reliability of clinical diagnosis of infectious mononucleosis.

Frequently, the clinical picture in the oropharynx alone does not lend itself to a reliable differentiation between acute pharyngotonsillitis in infectious mononucleosis and a streptococcal inflammation. Such a differentiation, however, is essential for the indication of antibiotic therapy. Therefore, it was the aim of the present study to investigate whether or not endoscopic verification of larger-than-normal lymphatic tissue with fibrinous membranes in the nasopharynx would enhance the reliability of diagnosis. Fifty hospitalized patients exhibiting the clinical picture of acute pharyngotonsillitis were examined for the following parameters: nasopharyngeal endoscopy, determination of glutamine-oxaloacetic transaminase (GOT), glutamine-pyruvic transaminase (GPT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), leucocytes and haemogram, antibodies to viral capsid antigen (VCA)-IgM, Epstein-Barr virus nuclear antigen (EBNA), and cytomegalovirus (CMV). In 24 patients with acute tonsillitis/peritonsillar abscess, and in 26 patients with infectious mononucleosis, the total leucocyte count in the blood and the blood/erythrocyte sedimentation rate were comparable. Atypical lymphocytes or absolute lymphocytosis were not seen in acute tonsillitis, but were found in 88.5 per cent of patients with infectious mononucleosis. Elevated transaminase levels were noted in 77 (GOT) and 88.5 per cent (GPT) of patients with infectious mononucleosis, and in acute tonsillitis in 4.2 (GOT) and 12.5 per cent (GPT) of patients. The CRP was higher than normal in 91.7 per cent of patients with acute tonsillitis, and in 57.7 of patients with infectious mononucleosis. In none of the patients with acute tonsillitis was lymphatic tissue with fibrinous membranes seen in the nasopharyngeal cavity. In contrast, nasopharyngeal endoscopy in infectious mononucleosis was positive in 24 out of 26 patients. Hence, the sensitivity was 92.3 per cent, the specificity 100 per cent, and the prediction value for a positive test turned out to be 1. Endoscopy of the nasopharngeal cavity employed as a simple and supplementary procedure adds to the reliability of diagnosis of infectious mononucleosis.

EFFECTS OF LIVER FUNCTION DISORDER ON SUCCESSFUL VISUALIZATION FOR THE EXTRAHEPATIC BILIARY DUCT IN DRIP INFUSION CHOLANGIOGRAPHY

For biliary tract dieases, drip infusion cholangiography (DIC) offers available visualization and information relating to levels of impaired liver function. In this paper, serum total bilirubin, glutamine oxaloacetic transaminase (GOT), glutamine pyruvic transaminase (GPT) and alkaline phosphatase (ALP) were examined as the indexes of liver function in 268 cases of cholelithiasis mainly. On those cases, Meglumine iotroxate was drip-injected as a contrast medium of DIC, and the relation between the respective level and optimum time for the best visualization of the common hepatic duct and common bile duct was analysed. Furthermoer Meglumine adipiodon was also examined, and both succesful visualizations were comparied. As a result, it was proposed that the successful visualization of Meglumine iotroxate was shown earlier and clearer than that of Meglumine the successful visualization of Meglumine iotroxate was shown earlier and clearer than that of Meglumine iotroxate was more useful and more sensitive to get successful visualization of the extrahepatic duct as contrast media of DIC in liver function disorder cases in some extent.

Genetics of allozyme variation in Cuphea lanceolata Ait.

Genetic markers are needed for mating systems and breeding experiments in Cuphea lanceolata Ait.; however, none have been described in this species. Allozyme variation was analyzed among 14 F2 populations assayed for aconitase (ACO), diaphorase (DIA), esterase (EST), fluorescent esterase transaminase (FEST), glutamine oxaloacetate transaminase (GOT), menadione reductase (MNR), phosphoglucomutase (PGM), phosphoglucose isomerase (PGI), and shikimate dehydrogenase (SKDH) enzyme activity. At least 23 loci were resolved in these enzyme systems: 6 monomorphic loci, 5 poorly resolved loci, and 12 clearly resolved polymorphic loci. Observed segregation ratios were generally not significantly different (P &gt; 0.05) from expected segregation ratios; however, segregation distortion was observed at Skdh-1 and Mnr-1 (Dia-1) in some F2 populations. Skdh-1 and Pgm-2 and Est-1, Est-2, Fest-1, and Mnr-1 comprise putative linkage groups. Allozyme variation was observed between and within accessions. The expected average heterozygosity was 16.3%. There were one to eight polymorphic loci among the F2 populations analyzed. There were an average of 2.05 alleles per locus. Several useful codominant markers were identified and a partial allozyme linkage map was constructed. Additional work is needed to revise and complete the map.Key words: Cuphea, isozymes, goodness of fit test statistics, lauric acid, capric acid.

Changes in the intestinal enzyme activity of lambs during chronic infection with Trichostrongylus vitrinus

The pathology and enzymology of the intestinal mucosae of lambs dosed daily with 2500 Trichostrongylus vitrinus larvae and killed at five, nine or 14 weeks were compared with worm-free animals. The proximal small intestines of the infected lambs exhibited extensive mucosal damage at five and nine weeks, but only isolated lesions were found at 14 weeks. Activities of the brush border enzymes alkaline phosphatase, leucine amino-peptidase, maltase and glycyl-L-leucine dipeptidase were all significantly depleted during infection, although the magnitude, time of onset and duration of the individual enzyme responses varied. Mucosal activities of the pancreatic enzymes, trypsin and to a lesser extent chymotrypsin were also markedly decreased particularly during the first nine weeks of infection. Specific acetylcholinesterase activity was significantly increased throughout the study, maximal levels being observed at five weeks. In contrast 'pseudo'-cholinesterase levels were consistently within the control range. During the early stages of infection (five weeks) glutamine-oxaloacetate transaminase activity was significantly decreased, while aldolase and creatine phosphokinase levels were significantly elevated. At nine weeks low glutamine-oxaloacetate transaminase activities were again detected and lactate dehydrogenase activity was also markedly reduced. At 14 weeks the mean activities of all four enzymes were within the normal range as were superoxide dismutase levels throughout. Significant correlations were found between alkaline phosphatase, trypsin, chymotrypsin, aldolase and glutamine-oxaloacetate transaminase activities and the degree of mucosal damage within the individual lambs.

Some normal clinical chemistry values for cerebrospinal fluid of the rhesus monkey (Macaca mulatta).

The concentrations of many components of the cerebrospinal fluid are much lower than in serum. Values for sodium, potassium, calcium and magnesium are similar to those in other primates. Activities of alkaline phosphatase (18.7 U/1), creatine phosphokinase (9.9 U/1), glutamine oxaloacetate transaminase (13.7 U/1), glutamine pyruvate transaminase (9.2 U/1), gamma-glutamyl transpeptidase (3.1 U/1), alpha-hydroxybutyrate dehydrogenase (33.0 U/1, lactate dehydrogenase (47.2 U/1) and sorbitol dehydrogenase (3.9 U/1), and levels of zinc (1.0 mu g/dl), copper (2.6 mu g/dl), iron (35.9 mu g/dl) and triglycerides (33.2 mu g/dl) have not previously been reported for this species. Values for free amino acids, total protein, creatinine and urea nitrogen are compared with those of other primates. The use of gradient pore polyacrylamide gel electrophoresis for analysing proteins of CSF is described.

Toxicity studies of liposome-encapsulated immunomodulators administered intravenously to dogs and mice

Multilamellar liposomes containing lymphokines from mitogen-stimulated rat lymphocytes were injected IV into BALB/c or (C57BL/6×C3H)F1 mice and Beagle dogs to evaluate their potential toxicity. Animals received either single or multiple (×3, ×4, or ×6) injections. All animals receiving liposomes remained clinically healthy. No hematologic changes were detected in liposome-treated mice, but lymphocytosis was detected in the treated dogs. Slight elevation of serum alkaline phosphatase and glutamine oxalo-acetic transaminase levels was also found in treated dogs, and occasional animals showed elevated serum bilirubin levels. No histologic evidence of liver damage was found in these animals. No gross or histologic changes were detected in any major organ systems in treated animals. Mononuclear cells isolated from the peripheral blood of dogs that received liposome-encapsulated lymphokines IV were tested for in vitro cytotoxicity against allogeneic tumor cell lines. Lymphocyte-, monocyte-, and natural killer cell-mediated cytotoxicity in vitro was unaltered. Murine alveolar and peritoneal macrophages harvested 24 h after injection of liposome-encapsulated lymphokines exhibited significant tumoricidal activity in vitro, but activation depended on the route of liposome administration. These data indicate that liposome-encapsulated lymphokines do not cause significant toxicity in vivo and are able to activate macrophages in specific anatomic compartments.

Degeneration of the intersegmental muscles: Alterations in hemolymph during muscle degeneration

Alterations in hemolymph constituents during the degeneration of the intersegmental muscles of Manduca sexta and Antheraea polyphemus have been followed by several techniques. An antigen to muscle protein appears in the blood within 5–10 hr after the adult has emerged. When tritiated leucine is injected into developing pupae, labeled protein and amino acids are released into the blood during the period over which the muscles degenerate. Blood levels of lactic dehydrogenase, glutamine-oxaloacetate transaminase, arginine phosphokinase, and aldolase increase approximately 8–9 hr after the insects emerge. The latter two enzymes increase sixfold over preemergence levels, and are highest during the period over which muscle integrity is compromised. The levels of circulating muscle proteins decrease after 30–50 hr. These several data suggest that a fraction of the muscle protein is not digested within the muscle fiber, but is solubilized or otherwise released into the hemolymph, to be digested elsewhere.