Evaluation of potential antiviral activities of antimicrobial peptides in fish mucus.

BACKGROUND: Fish skin mucus contains innate immune factors and acts as the first line of physical or chemical defense against pathogens. OBJECTIVE: The primary aim of this study was to determine the antiviral activity of sea bream (SBr), rainbow trout (RT), and sea bass (SBa) fish skin mucus against herpes simplex virus (HSV)-1. In addition, it was aimed to associate possible antiviral activity with antimicrobial peptides (AMPs) such as cathelicidin, hepcidin, galectin 2, and C10ORF99, whose levels were determined in the mucus. METHODS: The antiviral activity and oxidative/antioxidant status of mucus against HSV-1 virus was evaluated. In addition, AMPs, SOD, and CAT activities, and immunoglobulin M levels were also analyzed in mucus of fish. RESULTS: Antiviral activity mucus of SBr, RT, and SBa against HSV-1 were determined as 2-4, 2-5, and 2-2, respectively. The higher antiviral activity of SBr and RT mucus compared to the mucus of SBa can be associated with higher AMP levels in them. CONCLUSION: The skin mucus of SBr and RT may be nutritional supplement, adjuvant, and a new agent that can potentiate the effects of antimicrobial/antiviral agents.

Protective Effect of Nerium oleander Distillate and Tarantula cubensis Alcoholic Extract on Cancer Biomarkers in Colon and Liver Tissues of Rats with Experimental Colon Cancer.

BACKGROUND: Colon cancers are among the top three causes of cancer-related deaths. This study is a continuation of previous research aiming to identify effective treatments. OBJECTIVE: This study investigated the effects of Tarantula cubensis alcoholic extract (TCAE) and Nerium oleander (NO) distillate on the levels of midkine, transforming growth factor (TGF)-ß, vascular endothelial growth factor (VEGF), alpha-fetoprotein (AFP), cyclooxygenase (COX)-2, insulin-like growth factor (IGF) and caspase-3 in the liver and colon tissues of rats with experimentally induced colon cancer. METHODS: The liver and colon tissues of rats were homogeneously divided into control, colon cancer (azoxymethane, AZM), AZM + TCAE, and AZM + NO distillate groups. The levels of midkine, TGF-ß, VEGF, AFP, COX-2, IGF, and caspase-3 in the colon and liver tissues were measured by ELISA. RESULTS: The levels of all parameters in colon and liver tissues in the AZM group were higher (p<0.05) than those in the control group. TCAE and NO distillate prevented (p < 0.05) increases in midkine, TGF-ß, VEGF, AFP, COX-2, IGF, and caspase-3 levels in the colon. NO distillate prevented the increase in all parameters except IGF, whereas TCAE prevented the increase in all values apart from COX-2 and IGF levels in the liver (p<0.05). CONCLUSION: NO distillate and TCAE may prevent the studied markers from reaching specified levels observed in the colon in AZM-induced colon cancer. The increases in the levels of the parameters in the liver were not as severe as those in the colon; however, an 18-week study period may not be sufficient for liver metastasis formation. Future molecular studies should investigate the mechanisms and pathways of these treatments in greater detail.

Different Chemical Structures and Physiological/Pathological Roles of Cyclooxygenases.

This review describes cyclooxygenase (COX), which synthesizes prostanoids that play an important role in living things. The authors conducted a national and international literature review on the subject. The COX enzyme uses arachidonic acid to form prostanoids, which play a role in several physiological and pathological conditions. This enzyme has different isoforms, mainly COX-1 and COX-2. The constitutive isoform is COX-1, while COX-2 is the inducible isoform. Both are expressed in different tissues and at different levels, but they may also coexist within the same tissue. Both isoforms show essentially the same mode of action, but their substrates and inhibitors may differ. The COX-1 isoform, which plays a role in the continuation of physiological events, has an increased expression level in various carcinomas, and the COX-2 isoform, which is increased in inflammatory conditions, is typically expressed at low physiological levels in some tissues such as the brain, kidney, and uterus. In addition to investigating the efficacies of the COX-1 and COX-2 isoforms, the discovery of potential new COX enzymes and their effect continues. This review also looks at the roles of the COX enzyme in certain physiological and pathological conditions.

Effect of doxycycline and meloxicam on cytokines, brain-derived neurotrophic factor, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and cyclooxygenase-2 in brain.

OBJECTIVES: Prevention of inflammation in early stages will be useful in maintaining vitality of the organism. The objective of this study was to evaluate the effects of doxycycline (DOX) or meloxicam (MLX) monotherapy and combination therapy on the levels of inflammatory mediators in the brain tissues of rats with Escherichia coli lipopolysaccharide (LPS)-induced brain inflammation. MATERIALS AND METHODS: Seventy-eight rats were divided into the following groups: control (n=6), LPS (0.5 µg/10 µl intracranial) (n=18), LPS (0.5 µg/10 µl intracranial)+DOX (40 mg/kg intraperitoneal) (n=18), LPS (0.5 µg/10 µl intracranial)+MLX (2 mg/kg intraperitoneal) (n=18) and LPS (0.5 µg/10 µl intracranial)+DOX (40 mg/kg intraperitoneal)+MLX (2 mg/kg intraperitoneal) (n=18) groups. Brain tissues were harvested from all rats in the control group and from six rats each in the four experimental groups at 1, 3 and 6 hr under anaesthesia. The levels of tumor necrosis factor α (TNFα), interleukin 4 (IL-4), IL-6, IL-10, IL-17, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 3 (TIMP-3) and cyclooxygenase 2 (COX-2) in the brain tissues were measured using ELISA kits with ELISA device. RESULTS: LPS administration increased proinflammatory cytokines (TNF, IL-6, IL-17), and MMP-3 levels and decreased anti-inflammatory cytokines (IL-10, IL-4), and BDNF levels. The lowest TNFα levels were detected in the LPS+MLX group (P<0.05). All the drug treatment groups showed decreased IL-17 and COX-2 levels compared to the LPS groups. CONCLUSION: DOX or MLX monotherapy exerts neuroprotective effects against brain inflammation by decreasing proinflammatory cytokine levels and by increasing anti-inflammatory cytokines levels.

Alterations in levels of 8-Oxo-2'-deoxyguanosine and 8-Oxoguanine DNA glycosylase 1 during a current episode and after remission in unipolar and bipolar depression.

INTRODUCTION: Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders. METHODS: Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction. RESULTS: At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index. CONCLUSION: Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.

Pharmacokinetics of tolfenamic acid in red-eared slider turtles (Trachemys scripta elegans).

OBJECTIVE: To determine the pharmacokinetics of tolfenamic acid (TA) after different routes of administration [intravenous (IV) and intramuscular (IM), 2 mg kg-1] and doses (IV, 2 and 4 mg kg-1) in red-eared slider turtles (Trachemys scripta elegans). STUDY DESIGN: Randomized experimental trial. ANIMALS: Sixteen healthy red-eared slider turtles. METHODS: Turtles were randomly assigned to two groups (n = 8 each). Group 1 received TA at a dose of 2 mg kg-1 IV and then IM, after a washout period of 30 days. Group 2 received 4 mg kg-1 TA IV. A noncompartmental analysis was used to calculate pharmacokinetic variables. RESULTS: No local and/or systemic adverse drug effects were observed in any turtle. Elimination half-life and mean residence time following IM administration at 2 mg kg-1 were significantly longer than those following IV administration. The bioavailability following IM administration was complete. The area under the plasma concentration-time curve, elimination half-life, mean residence time and total clearance were significantly different between the dose groups. CONCLUSIONS AND CLINICAL RELEVANCE: The absence of adverse reactions in the turtles of the study of TA along with the favourable pharmacokinetic properties (the long half-life and the complete bioavailability) of TA administered at the single doses of 2 and 4 mg kg-1 suggest the possibility of its effective use in turtles. However, further studies are required to establish a multiple dosage regimen of TA and to evaluate the clinical efficacy of administering TA.

Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after intravenous administration of increasing doses to sheep.

OBJECTIVE: To determine the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after IV administration of increasing doses of PTX to sheep. ANIMALS: 6 healthy adult Merino sheep. PROCEDURES: Each sheep received 10-, 20-, and 40-mg/kg doses of PTX, IV, with a 15-day washout period between doses. Blood samples were collected before and at predetermined times after administration of each dose to determine plasma PTX and M-I concentrations by high-performance liquid chromatography. Pharmacokinetic parameters for PTX and M-I were estimated by noncompartmental analysis. RESULTS: No adverse effects were observed after administration of the 10- and 20-mg/kg doses. Following administration of the 40-mg/kg dose, all sheep developed tachycardia and hypersalivation and appeared agitated for approximately 4 hours. Plasma PTX concentrations considered therapeutic in other species were achieved in all sheep after administration of all 3 doses. Pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner. For PTX, the mean area under the concentration-time curve (AUC), elimination half-life, and volume of distribution increased with dose and ranged from 15.67 to 94.66 h·µg/mL, 0.68 to 0.91 hours, and 0.55 to 0.66 L/kg, respectively, whereas clearance decreased with dose and ranged from 0.42 to 0.64 L/h/kg. The mean ratio of the AUC for M-I to AUC for PTX ranged from 0.38 to 0.46. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner in healthy sheep. Further studies are warranted to determine the therapeutic threshold and optimal dosage for PTX in sheep.

Pharmacokinetics of levamisole in the red-eared slider turtles (Trachemys scripta elegans).

The pharmacokinetics and bioavailability of levamisole were determined in red-eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three-way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high-performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half-life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr-1  kg-1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 µg/ml, respectively, with 0.5 hr of Tmax . The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t1/2ʎz , can be recommended as an effective way for treating nematodes in turtles.

Pharmacokinetics of intravenous and intramuscular danofloxacin in red-eared slider turtles (Trachemys scripta elegans).

This study aimed to investigate the pharmacokinetics of danofloxacin in red-eared slider turtle (Trachemys scripta elegans) following a single intravenous (IV) and intramuscular (IM) administrations of 6 mg/kg, using a two-way crossover study with 30-day washout period. Eight clinically healthy red-eared slider turtle weighing 410-600 g (mean 490 g) were used for the study. Danofloxacin concentrations were measured using the reversed-phase high-performance liquid chromatography. The plasma concentration-time data were evaluated by a non-compartmental method. After IV administration, the elimination half-life (t1/2ʎz), mean residence time (MRT0-∞), area under the concentration-time curve (AUC0-∞), volume of distribution at steady state and total body clearance in plasma were 24.17 hr, 30.64 hr, 143.31 hr·µg/ml, 1.29 l/kg and 0.04 l/hr/kg, respectively. Following IM administration, t1/2ʎz, MRT0-∞, AUC0-∞, peak concentration (Cmax), time to reach Cmax, and bioavailability in plasma were 32.00 hr, 41.15 hr, 198.23 hr·µg/ml, 8.75 µg/ml, 1.5 hr and 139.89%, respectively. Danofloxacin has clinically superior pharmacokinetic properties, including the complete IM absorption, slow elimination and wide volume of distribution in red-eared slider turtles. However, further pharmacokinetics/pharmacodynamics studies are necessary for the treatment of diseases caused by susceptible bacteria with known minimum inhibitory concentration values in red-eared slider turtles.

Doxycycline and meloxicam can treat neuroinflammation by increasing activity of antioxidant enzymes in rat brain.

The aim of this study is to determine the effects of alone or combined usage of doxycycline and meloxicam on brain superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and matrix metalloproteinase (MMP)-9 levels of lipopolysaccharide (LPS)-induced brain inflammation. Totally 78 rats were divided into 5 groups; Healthy control (n=6), LPS (n=18, 0.05µg/µL/rat, intracranially), LPS+D (n=18, LPS 0.05µg/µL/rat, intracranially and doxycycline 40 mg/kg, intraperitoneally), LPS+M (n=18, LPS 0.05 µg/µL/rat, intracranially and meloxicam 2 mg/kg, intraperitoneally), LPS+Combination (n=18, LPS 0.05 µg/µL/rat, intracranially and simultaneously both drug combination) groups. Animals were euthanized at 1, 3 and 6 hours following injections and the brains were removed. Brain SOD, CAT, MDA and MMP-9 levels were determined by ELISA reader. Parameters of LPS groups generally different from Healthy control group. When compared to LPS group, increased SOD level of LPS+D at 3 hours and CAT levels of LPS+M and LPS+D groups were determined (P<0.05) at 3 and 6 hours, respectively. In addition, all treatments statistically significantly (P<0.05) decreased MMP-9 levels at 6 hours. In conclusion, doxycycline and meloxicam may show antioxidant effect via increasing antioxidant enzyme production in the brain; however combined usage of drugs may show more beneficial effect for neuroinflammation. .

Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep.

The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 ± 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC-UV method. Pharmacokinetic parameters were calculated using non-compartmental methods. The elimination half-life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 ± 11.54%. The area under the curve (AUC0-∞ ) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is ≤1.0 µg/ml in sheep.

Cortical thickness and surface area as an endophenotype in bipolar disorder type I patients and their first-degree relatives.

OBJECTIVES: So far, few studies have investigated cortical thickness (CT) and surface area (SA) measures in bipolar disorder type I (BDI) in comparison to a high genetic risk group such as first-degree relatives (FR). This study aimed to examine CT and SA differences between BDI, FR and healthy controls (HC). METHODS: 3D T1 magnetic resonance images were acquired from 27 euthymic BDI patients, 24 unaffected FR and 29 HC. CT and SA measures were obtained with FreeSurfer version 5.3.0. Generalized estimating equations were used to compare CT and SA between groups. Group comparisons were repeated with restricting the FR group to 17 siblings (FR-SB) only. RESULTS: \Mean age in years was 36.3 ±â€¯9.5 for BDI, 32.1 ±â€¯10.9 for FR, 34.7 ±â€¯9.8 for FR-SB and 33.1 ±â€¯9.0 for HC group respectively. BDI patients revealed larger SA of left pars triangularis (LPT) compared to HC (p = .001). In addition, increased SA in superior temporal cortex (STC) in FR-SB group compared to HC was identified (p = .0001). CONCLUSIONS: Our result of increased SA in LPT of BDI could be a disease marker and increased SA in STC of FR-SB could be a marker related with resilience to illness.

Plasma and tissue disposition of danofloxacin in brown trout (Salmo trutta fario) after intravenous and intramuscular administrations.

Plasma and muscle pharmacokinetics of danofloxacin were investigated after 10 mg/kg intravenous (IV, caudal vein) and intramuscular (IM, right epaxial muscles) administrations in 168 healthy brown trout (Salmo trutta fario) at 10°C-13°C. High-performance liquid chromatography was used to determine its plasma and muscle concentrations. Pharmacokinetic parameters were analysed with a non-compartmental model. After IV administration, elimination half-life (t1/2ʎz), area under the concentration-time curve (AUC0-∞), mean residence time (MRT0-∞), volume of distribution at steady state, total body clearance in plasma and AUCMuscle/AUCPlasma ratio were 22.22 h, 140.66 h*µg/mL, 23.15 h, 2.28 L/kg, 0.07 L/h/kg and 3.79, respectively. After IM administration, t1/2ʎz, AUC0-∞, MRT0-∞, peak concentration (Cmax), time to reach Cmax, bioavailability in plasma and AUCMuscle/AUCPlasma ratio were 28.28 h, 84.39 h*µg/mL, 37.31 h, 4.79 µg/mL, 1 h, 59.99% and 8.46, respectively. Danofloxacin exhibited long t1/2ʎz and good bioavailability after IM administration. Therefore, 10 mg/kg IM administration of danofloxacin in brown trout can provide AUC0-24/MIC of > 125 and Cmax/MIC of > 10 to treat diseases caused by susceptible bacteria with ≤ 0.336 µg/mL MIC.

Pharmacokinetics and bioavailability of tolfenamic acid in sheep.

The pharmacokinetics, bioavailability, and tolerability of tolfenamic acid (TA) were determined after treating sheep with TA via different routes and doses. This crossover study was carried out with a washout period of 15 days. In the study, 16 clinically healthy sheep were randomly assigned to two equal groups. In the first group (n = 8), animals received TA by intravenous (IV), intramuscular (IM), subcutaneous (SC), or oral (OR) routes at 2 mg/kg. In the second group (n = 8), TA was administered intravenously to each sheep at 2, 4, 8, and 16 mg/kg. Plasma samples were analyzed with a high-performance liquid chromatography assay. Noncompartmental pharmacokinetic analyses were used to evaluate the data. The area under the concentration-time curves (AUC0-∞ ), elimination half-life (t1/2ʎz ), and the mean residence time (MRT) significantly differed among the administration routes at 2 mg/kg of TA. Following IM, SC, and OR administrations, TA demonstrated different peak concentrations (Cmax ) and time to reach Cmax (Tmax ), with a bioavailability of 163%, 127%, and 107%, respectively. The dose-normalized AUC0-∞ revealed a significant difference among the dose groups; however, the relationship between dose and AUC0-∞ was linear. Both t1/2ʎz and MRT increased depending on the dose. Although the total clearance (ClT ) decreased depending on dose, the volume of distribution at steady-state (Vss ) increased. Tolfenamic acid indicated a long half-life and high bioavailability following IM, SC, and OR administrations at 2 mg/kg. TA exhibited linear kinetics and was well tolerated by the animals, except at 16 mg/kg. Thus, TA may be used in different routes and doses (≤8 mg/kg) in sheep; however, further studies are needed to determine the clinical efficacy of TA during the inflammatory and painful conditions and the pharmacokinetics and safety of repeated administration in sheep.

Pharmacokinetics of ceftiofur in healthy and lipopolysaccharide-induced endotoxemic newborn calves treated with single and combined therapy.

The aim of this research was to compare plasma pharmacokinetics of ceftiofur sodium (CS) in healthy calves, and in calves with experimentally induced endotoxemia. Six calves received CS (2.2 mg/kg, IM) 2 hr after intravenous administration of 0.9% NaCl (Ceft group). After a washout period, the same 6 calves received CS 2 hr after intravenous injection of lipopolysaccharide (LPS+Ceft group). Another group of 6 calves received a combination of drug therapies that included CS 2 hr after administration of 0.9% NaCl (Comb group). A third group of 6 calves received the same combination therapy regimen 2 hr after intravenous injection of lipopolysaccharide (LPS+Comb group). Plasma concentrations of CS and all desfuroylceftiofur-related metabolites were determined using HPLC, and its pharmacokinetic properties were determined based on a two-compartment model. The peak concentration of CS in the LPS+Comb group occurred the earliest, and the clearance rate of CS was the highest in the Comb and LPS+Comb groups (P<0.05). The elimination half-life of CS in the LPS+Ceft group was longer than that in the Ceft and Comb groups (P<0.05). The results of this study indicate that combined therapies and endotoxemic status may alter the plasma pharmacokinetics of CS in calves.

Response inhibition and interference control in patients with bipolar I disorder and first-degree relatives.

OBJECTIVES: The current study aimed to assess both response inhibition (RI) and interference control (IC) in euthymic patients with bipolar disorder (BD-Ps) as well as asymptomatic first-degree relatives (BD-Rs) and healthy controls (HCs) in order to evaluate trait-as opposed to illness-associated features of these components. METHODS: BD-Ps (n = 35) who had been in the euthymic state for at least six months, BD-Rs (n = 30), and HCs (n = 33) completed a Stop-Signal Task (SST) and Stroop Task to assess RI and IC, respectively. Groups were compared on the stop-signal reaction time (SSRT), stop-signal delay (SSD), mean reaction time on go trials (go-RT), Stroop interference score (S-interference), and number of errors on the color-word-naming trial (S-error). Associations between the patient's clinical features and RI and IC, between the patient's treatment and RI and IC, and between RI and IC in each group were investigated. RESULTS: BD-Ps and BD-Rs had significantly shorter go-RT and SSD, and longer SSRT compared to HCs, with these scores being similar between the BD-Ps and BD-Rs. Also, both BD-Ps and BD-Rs made significantly more S-errors than HCs, whereas, the S-interference score was not significantly different between groups. There were no significant correlations between Stroop Task and SST scores within each group, nor between clinical features or treatment variables and RI and IC in BD-Ps. CONCLUSIONS: Overall, impairment in RI and IC (only on S-error score) was present in both patients and relatives. The persistence of these deficits in the absence of mood symptoms suggests that these features may represent candidate endophenotypes for bipolar disorder.

The effects of florfenicol on the values of serum tumor necrosis factor-α and other biochemical markers in lipopolysaccharide-induced endotoxemia in brown trout.

The aim of the present study was to determine the effects of florfenicol on the expected changes in sTNF-α, damage markers of the liver and kidney, and the lipid metabolism parameters in endotoxemic brown trout. Ninety-six brown trout were included in this study. After six of the fish were reserved as the control group, the remaining 90 fish were divided equally into 3 groups as follows: LPS (2 mg/kg, IP), LPS (2 mg/kg, IP) + florfenicol (40 mg/kg, IM), and florfenicol (40 mg/kg, IM). Blood samples were obtained from the tail of the fish at 1.5, 3, 6, 10, and 24 hours. The levels of sTNF-α were determined by ELISA and biochemical markers were evaluated with an autoanalyzer. A significant increase was observed in the values of sTNF-α in the LPS and LPS + florfenicol groups (P < 0.05). Significant increases were found in the kidney and liver damage determinants in the LPS and LPS + florfenicol groups (P < 0.05). Irregular changes in the lipid metabolism parameters were observed in all the subgroups. In conclusion, florfenicol does not affect the increases of sTNF-α caused by LPS and does not prevent liver or kidney damage; at least, it can be said that florfenicol does not have any evident positive effects on the acute endotoxemia of fish.

Azithromycin prevents pregnancy loss: reducing the level of tumor necrosis factor-alpha and raising the level of interleukin-10 in rats.

The aim of this study was to determine the effect of azithromycin on LPS-induced pregnancy loss. Thirty-six pregnant female Wistar rats were divided into 4 equal groups as follows: control group, where 0.3 mL of normal saline solution was administered intravenously on day 10 of pregnancy; azithromycin group, where azithromycin was administered orally at 350 mg kg(-1) day on days 9, 10, and 11 of pregnancy; lipopolysaccharide group, where LPS was administered intravenously via the tail vein at 160 µg kg(-1) on day 10 of pregnancy; and the azithromycin + LPS group, where azithromycin was administered orally at 350 mg kg(-1) day on days 9, 10, and 11 of pregnancy and LPS was administered intravenously at 160 µg kg(-1) on day 10 of pregnancy. Blood samples were obtained from the tail vein on day 10 of the experiment. Pregnancy rates were determined. Tumor necrosis factor-alpha (TNF- α ) and interleukin (IL-10) levels were measured by ELISA. Azithromycin prevented (P < 0.05) LPS-induced pregnancy loss. Higher TNF- α and IL-10 levels were measured (P < 0.05) in the LPS and azithromycin + LPS groups, respectively. In conclusion, azithromycin may be useful in infection- or endotoxemia-dependent pregnancy loss.

Cardiac safety of diclofenac at a single dose in ram.

Nonsteroidal anti-inflammatory drugs are frequently prescribed drug group in human and veterinary medicine. However, diclofenac, a traditional nonsteroidal anti-inflammatory drug, related to cardiotoxicity is reported, and blood cardiac damage markers may increase within the first hours after damage. The aim of the current research was to determine the effect of diclofenac on the blood cardiac damage markers. Single dose of diclofenac (2.5 mg/kg, IM) was injected to 6 rams. Blood samples were collected in before (0 hour, control) and 6 hours after injection. Specific (troponin I, and creatine kinase-MB) and nonspecific (lactate dehydrogenase, aspartate aminotransferase) blood cardiac damage marker concentrations, routine biochemical (hepatic damage, renal damage, lipid metabolism, glucose, and phosphorus) parameters, and hemogram values were measured. Diclofenac increased (P < 0.05) specific (troponin I) and nonspecific cardiac (lactate dehydrogenase, aspartate aminotransferase), hepatic (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase), and muscular (creatine kinase) damage markers and high density lipoprotein level, while it decreased (P < 0.05) low density lipoprotein level. Moreover, diclofenac decreased (P < 0.05) white blood cell counts and increased (P < 0.05) red blood cell counts. In conclusion, it may be stated that diclofenac shows slight cardiotoxicity, whereas it may show potent hepatic and muscular damage effects at an intramuscularly single dose in sheep. Thereby, repeated injections of diclofenac may be more harmful in sheep.

Effects of tylosin, tilmicosin and tulathromycin on inflammatory mediators in bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury.

The aim of this study was to determine the anti-inflammatory effects of macrolides through kinetic parameters in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide-induced lung injury. Rats were divided into four groups: lipopolysaccharide (LPS), LPS + tylosin, LPS + tilmicosin and LPS + tulathromycin. BALF samples were collected at sampling times. TNF, IL-1ß, IL-6, IL-10 and 13,14-dihydro-15-keto-prostaglandin F2α (PGM) and C-reactive protein (CRP) were analysed. Area under the curve (AUC) and maximum plasma concentration (Cmax) values of inflammatory mediators were determined by a pharmacokinetic computer programme. When inflammatory mediator concentrations were compared between the LPS group and other groups for each sampling time, the three macrolides had no pronounced depressor effect on cytokine levels, but they depressed PGM and CRP levels. In addition, tylosin and tilmicosin decreased the AUC0-24 level of TNF, while tilmicosin decreased the AUC0-24 level of IL-10. Tylosin and tulathromycin decreased the AUC0-24 of PGM, and all three macrolides decreased the AUC0-24 of CRP. Especially tylosin and tulathromycin may have more expressed anti-inflammatory effects than tilmicosin, via depressing the production of inflammatory mediators in the lung. The AUC may be used for determining the effects of drugs on inflammation. In this study, the antiinflammatory effects of these antibiotics were evaluated with kinetic parameters as a new and different approach.