Interferon γ and α Have Differential Effects on SAMHD1, a Potent Antiviral Protein, in Feline Lymphocytes.

Sterile alpha motif and histidine/aspartic domain-containing protein 1 (SAMHD1) is a protein with anti-viral, anti-neoplastic, and anti-inflammatory properties. By degrading cellular dNTPs to constituent deoxynucleoside and free triphosphate, SAMHD1 limits viral DNA synthesis and prevents replication of HIV-1 and some DNA viruses such as HBV, vaccinia, and HSV-1. Recent findings suggest SAMHD1 is broadly active against retroviruses in addition to HIV-1, such as HIV-2, FIV, BIV, and EIAV. Interferons are cytokines produced by lymphocytes and other cells that induce a wide array of antiviral proteins, including some with activity again lentiviruses. Here we evaluated the role of IFNs on SAMHD1 gene expression, transcription, and post-translational modification in a feline CD4+ T cell line (FeTJ) and in primary feline CD4+ T lymphocytes. SAMHD1 mRNA in FetJ cells increased in a dose-related manner in response to IFNγ treatment concurrent with increased nuclear localization and phosphorylation. IFNα treatment induced SAMHD1 mRNA but did not significantly alter SAMHD1 protein detection, phosphorylation, or nuclear translocation. In purified primary feline CD4+ lymphocytes, IL2 supplementation increased SAMHD1 expression, but the addition of IFNγ did not further alter SAMHD1 protein expression or nuclear localization. Thus, the effect of IFNγ on SAMHD1 expression is cell-type dependent, with increased translocation to the nucleus and phosphorylation in FeTJ but not primary CD4+ lymphocytes. These findings imply that while SAMH1 is inducible by IFNγ, overall activity is cell type and compartment specific, which is likely relevant to the establishment of lentiviral reservoirs in quiescent lymphocyte populations.

The expression profile of sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) in feline tissues.

SAMHD1 restricts lentiviruses by limiting availability of deoxynucleoside triphosphates for reverse transcription. HIV-2 and SIV have virion-associated proteins to counteract SAMHD1. Cats have an ortholog to human SAMHD1 and the FIV is restricted by human SAMHD1, but expression of feline SAMHD1 is unknown. Using a whole-body tissue microarray consisting of 24 tissues for immunohistochemistry, SAMHD1 expression was identified in a wide range of cat tissues. SAMHD1 was most strongly expressed in skin and mucosal epithelium, and in hemolymphatic and spermatogenic tissues. Both nuclear and cytoplasmic expression was detected. Feline cell lines susceptible to FIV infection also highly expressed SAMHD1. Preferential expression of SAMHD1 at sites of viral entry and replication supports a role for feline SAMHD1 in restricting FIV.

Effects of Ghrelin on Testicular Ischemia/Reperfusion-Induced Injury.

Ischemia-reperfusion injury is a possible cause of testicular damage and infertility after testicular torsion and detorsion. The purpose of this study was to evaluate the effect of ghrelin on testicular ischemia-reperfusion damage. A total of 30 adult male rats were selected for the study and divided randomly into 3 groups, each containing 10 rats. Animals in the testicular torsion and ghrelin treated groups were subjected to unilateral 720° counterclockwise testicular torsion for 1 hour, and then reperfusion was allowed after detorsion for 7 and 30 days. The ghrelin-treated group and the other two groups received intraperitoneally 40 nmol of ghrelin and physiological saline 15 min before detorsion, respectively. The animals were sacrificed at the end of reperfusion times, and their testes were taken for later histopathological examination. The seminiferous tubules diameter, germinal epithelium height, as well as volume densities in testicular torsion / detorsion plus saline group, were significantly lesser versus control group, which clearly indicates an ischemia-reperfusion injury. Ghrelin treatment resulted in a partial increment in examined histological parameters on day 30 after reperfusion. Current results showed that ghrelin ameliorates the testicular ischemia-reperfusion damage.

Liver fibrosis impairs hepatic pharmacokinetics of liver transplant drugs in the rat model.

This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl(4)-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver. The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models. The results showed a marked increase in the liver fibrosis index for CCl(4)-treated rats compared to controls (p<0.05). The extraction ratios (E) for all drugs were significantly lower (p<0.05) in fibrotic than in normal livers and the decrease in E was consistent with the decrease in intrinsic clearance and permeability-surface area product. In addition, other than for furosemide, the mean transit times for all drugs were significantly longer (p<0.01) in the fibrotic livers than in normal livers. Pharmacokinetic model and stepwise regression analyses suggest that these differences arise from a reduction in both the transport of drugs across the basolateral membrane and their metabolic clearance and were in a manner similar to those previously found for another group of drugs.

Serum electrolyte and nonelectrolyte status in freshwater juvenile Persian sturgeon Acipenser persicus.

Status of serum electrolyte and nonelectrolyte variables can be used for managing sturgeon species cultured in freshwater or living in seawater. The aim of the present study was to evaluate serum biochemical variables in clinically healthy juvenile Persian sturgeon Acipenser persicus cultured in freshwater. Serum samples from 11 females and 10 males were analyzed, and levels (mean +/- SD) of the following variables were compared between sexes: glucose (Glc; 5.58 +/- 1.25 mmol/L for females and 8.56 +/- 1.80 mmol/L for males), total cholesterol (TC; 2.50 +/- 0.45 and 2.40 +/- 0.65 mmol/L), triglyceride (TG; 7.13 +/- 2.68 and 5.14 +/- 1.27 mmol/L), blood urea nitrogen (BUN; 1.28 +/- 0.2 and 1.01 +/- 0.2 mmol/L), total protein (TOP; 55.84 +/- 8.77 and 41.44 +/- 8.62 g/L), inorganic phosphate (P(i); 6.19 +/- 1.02 and 5.23 +/- 0.49 mmol/L), calcium (Ca; 2.80 +/- 0.43 and 2.63 +/- 0.32 mmol/L), magnesium (Mg; 0.9 +/- 0.23 and 0.99 +/- 0.22 mmol/L), sodium (Na; 152.80 +/- 13.81 and 156.38 +/- 12.67 mmol/L), potassium (K; 2.64 +/- 0.58 and 2.27 +/- 0.39 mmol/L), and chloride (Cl; 143 +/- 13.85 and 151.67 +/- 21.08 mmol/L). There were no differences in TC, Ca, Mg, Na, K, or Cl between sexes. The Glc value was lower in female Persian sturgeon than in males, whereas the values of TG, BUN, TOP, and P(i) were higher in females than in males. Freshwater adaptation may affect serum ion concentrations in juvenile Persian sturgeon.

Composition and electrophoretic mobility of plasma lipoproteins of dromedary camels (Camelus dromedarius).

OBJECTIVE: To determine the lipid composition and electrophoretic pattern of plasma lipoproteins in samples obtained from healthy 1-humped camels (Camelus dromedarius). ANIMALS: 34 healthy camels raised under similar farming and dietary conditions. PROCEDURES: Plasma samples were subjected to density-gradient ultracentrifugation for separation of plasma lipoproteins, including very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Purity of the separation was assessed by use of polyacrylamide gel disk electrophoresis. Concentrations of triglycerides, cholesterol, and phospholipids were measured in each lipoprotein fraction, and lipoprotein electrophoretic patterns were determined in plasma samples. RESULTS: Phospholipid was the major constituent of VLDL (mean +/- SD concentration, 10.62 +/- 1.2 mg/dL), LDL (24.66 +/- 3.12 mg/dL), and HDL (38.08 +/- 0.76 mg/dL). Low-density lipoprotein, VLDL, and HDL were important plasma lipoprotein carriers for cholesterol (67.94 +/- 9.51%), triglyceride (55.83 +/- 7.81%), and phospholipid (51.91 +/- 1.55%), respectively. On the basis of electrophoresis results, relative percentages of alpha- and beta-lipoproteins were 31.72 +/- 4.88% and 68.3 +/- 4.68%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The lipoprotein profile in 1-humped camels differed substantially from that of other ruminants. Results may be useful in the evaluation of metabolic disorders in camels.

Serum biochemistry and hematology values and hemoglobin electrophoresis in Persian squirrels (Sciurus anomalus).

BACKGROUND: Serum biochemical and hematologic parameters are important in the management of game species in Iran, such as Persian squirrels. OBJECTIVE: The purpose of this study was to establish baseline serum chemistry and hematology values in Persian squirrels (Sciurus anomalus) and describe blood cell morphology and the electrophoretic pattern of hemoglobin. METHODS: Blood samples were collected from 30 Persian squirrels (Sciurus anomalus) maintained in captivity in the Tehran Zoo. Blood was placed into EDTA and serum clot tubes and analyzed using standard manual hematology and biochemical techniques. Hemoglobin electrophoresis was done on cellulose acetate paper strips. RESULTS: Minimum, maximum, and median values were obtained for 11 hematologic and 12 serum chemistry parameters. Hypersegmented neutrophils were observed frequently. We did not find basophils or band neutrophils. Hemoglobin electophoresis resulted in a band slightly anodal to that of human hemoglobin A. CONCLUSION: Biochemical and hematologic values in Persian squirrels were comparable to those of related species, and may be used as a standard profile for healthy Persian squirrels kept in captivity.