The onset of puberty in colony-housed male and female titi monkeys (Plecturocebus cupreus): Possible effects of oxytocin treatment during peri-adolescent development.

Oxytocin has been used to treat neurodevelopmental conditions in adolescent patients but possible effects on reproductive development have not been well investigated. The effects of daily intra-nasal oxytocin treatment (12-18 months of age) on puberty and fertility were studied in colony-housed, male and female titi monkeys (Plecturocebus cupreus). Body weight, urinary conjugated pregnanes and estrogens (defining cyclicity) in females, and androgens and sperm in urine of in males, were measured from 1 to 3 years of age to detect puberty. Serum testosterone was also measured in males at 13, 23 and 33 months of age and hemi-castration at 3 years of age enabled assessment of testicular morphometry and oxytocin receptor expression. An oxytocin treatment*time interaction suggested a minor, transient suppression in weight gain after treatment ended. Note that females weighed 10% less across all ages. Oxytocin-treated females exhibited early, spurious ovulations but neither regular cyclicity (≈30 months) nor pregnancies were affected by treatment. Oxytocin did not affect the pubertal increase in urinary androgen or the first appearance of sperm, which occurred as early as 15 months of age. Treatment did delay the puberty-associated rise in serum testosterone in males. All males were pubertal by 22 months and all females by 32 months of age. Although no major male or female fertility outcome was observed, oxytocin demonstrated some physiological effects through a delay of testosterone secretion in males, induction of precocious ovulation in females, and a suppression of general weight gain for the months following treatment.

Oligodendrocyte gene expression is reduced by and influences effects of chronic social stress in mice.

Oligodendrocyte gene expression is downregulated in stress-related neuropsychiatric disorders, including depression. In mice, chronic social stress (CSS) leads to depression-relevant changes in brain and emotional behavior, and the present study shows the involvement of oligodendrocytes in this model. In C57BL/6 (BL/6) mice, RNA-sequencing (RNA-Seq) was conducted with prefrontal cortex, amygdala and hippocampus from CSS and controls; a gene enrichment database for neurons, astrocytes and oligodendrocytes was used to identify cell origin of deregulated genes, and cell deconvolution was applied. To assess the potential causal contribution of reduced oligodendrocyte gene expression to CSS effects, mice heterozygous for the oligodendrocyte gene cyclic nucleotide phosphodiesterase (Cnp1) on a BL/6 background were studied; a 2 genotype (wildtype, Cnp1+/- ) × 2 environment (control, CSS) design was used to investigate effects on emotional behavior and amygdala microglia. In BL/6 mice, in prefrontal cortex and amygdala tissue comprising gray and white matter, CSS downregulated expression of multiple oligodendroycte genes encoding myelin and myelin-axon-integrity proteins, and cell deconvolution identified a lower proportion of oligodendrocytes in amygdala. Quantification of oligodendrocyte proteins in amygdala gray matter did not yield evidence for reduced translation, suggesting that CSS impacts primarily on white matter oligodendrocytes or the myelin transcriptome. In Cnp1 mice, social interaction was reduced by CSS in Cnp1+/- mice specifically; using ionized calcium-binding adaptor molecule 1 (IBA1) expression, microglia activity was increased additively by Cnp1+/- and CSS in amygdala gray and white matter. This study provides back-translational evidence that oligodendrocyte changes are relevant to the pathophysiology and potentially the treatment of stress-related neuropsychiatric disorders.

Host-response patterns of intramammary infections in dairy cows.

Many different bacterial species have the ability to cause an infection of the bovine mammary gland and the host response to these infections is what we recognize as mastitis. In this review we evaluate the pathogen specific response to the three main bacterial species causing bovine mastitis: Escherichia coli, Streptococcus uberis and Staphylococcus aureus. In this paper we will review the bacterial growth patterns, host immune response and clinical response that results from the intramammary infections. Clear differences in bacterial growth pattern are shown between bacterial species. The dominant pattern in E. coli infections is a short duration high bacteria count infection, in S. aureus this is more commonly a persistent infection with relative low bacteria counts and in S. uberis a long duration high bacteria count infection is often observed. The host immune response differs significantly depending on the invading bacterial species. The underlying reasons for the differences and the resulting host response are described. Finally we discuss the clinical response pattern for each of the three bacterial species. The largest contrast is between E. coli and S. aureus where a larger proportion of E. coli infections cause potentially severe clinical symptoms, whereas the majority of S. aureus infections go clinically unnoticed. The relevance of fully understanding the bovine host response to intramammary infection is discussed, some major gaps in our knowledge are highlighted and directions for future research are indicated.

Efficacy of carprofen on conception rates in lactating dairy cows after subcutaneous or intrauterine administration at the time of breeding.

Manipulation of the reproductive tract can cause inflammatory processes in the endometrium and release of cytokines and prostaglandins. It has been shown that PGF2α has direct negative effects on embryonic survival and development. Treatment with nonsteroidal antiinflammatory drugs (e.g., ibuprofen lysinate, flunixin meglumine) might improve pregnancy rates after embryo transfer in recipient heifers. The primary objective of this study was to evaluate the effect of a nonsteroidal antiinflammatory drug on reproductive performance in lactating dairy cows when administered at the time of first-service artificial insemination (AI) based on the hypothesis that uterine manipulation during AI might be similarly intense compared with embryo transfer in its effect on prostaglandin release. A total of 970 cows (333 primiparous and 637 multiparous) from 17 Holstein dairy farms were enrolled. On the day of first AI, cows were randomly allocated to 1 of 3 treatment groups. Cows of group 1 received 1.4 mg/kg of body weight (BW) of carprofen subcutaneously immediately after AI (SC group). In group 2, 1.4 mg/kg of BW of carprofen was administered into the uterus using a sterile disposable catheter 12 to 24 h after AI (IU group). Animals of group 3 remained as untreated controls. First AI conception rate was similar for the SC group (42.2%) compared with the untreated control group (45.1%). A binary logistic regression model for the odds of conception at first AI revealed a negative effect of an intrauterine administration of carprofen on conception rate (38.3%). Cows allocated to the IU group had a lower likelihood of being pregnant within 200 d in milk than cows in the control group. In summary, subcutaneous treatment with the nonsteroidal antiinflammatory drug carprofen at the time of AI did not influence conception rate, whereas an intrauterine administration of carprofen 12 to 24 h after first AI had a negative effect on first-service conception rate in lactating dairy cows.

Intrarenal effects of ecadotril during acute volume expansion in dogs with congestive heart failure.

Neutral endopeptidase 24.11 (NEP) inhibitors are known to have vascular, diuretic, and natriuretic effects that may be helpful in the treatment of congestive heart failure (CHF). Most NEP inhibitors may act principally through intrarenal mechanisms, which are not completely understood. The purpose of this study was to determine the principal renal effects of the NEP inhibitor ecadotril in dogs with progressive CHF induced by rapid ventricular pacing. Renal function was measured before, during, and after acute i.v. infusion of normal saline in a total of six dogs during normal cardiac function, early left ventricular dysfunction, and overt CHF. During overt CHF, each dog was treated with either ecadotril or placebo orally for 1 week. Parameters measured included glomerular filtration rate, renal blood flow, urine output, sodium clearance, sodium fractional excretion, and proximal and distal sodium reabsorption. Ecadotril treatment resulted in increased urine output, sodium clearance, and renal sodium excretion relative to placebo-treated controls. The principal intrarenal effect of ecadotril was decreased distal renal tubular sodium reabsorption. Both glomerular filtration rate and renal blood flow declined during overt CHF and were unaffected by ecadotril treatment. The results of this study are consistent with the principal action of ecadotril occurring by way of intrarenal events as opposed to changes in renal hemodynamics. The principal effect of ecadotril on distal tubular sodium reabsorption suggests that inhibition of NEP activity in the proximal renal tubules may allow increased binding of filtered atrial natriuretic peptide to natriuretic peptide receptor sites in the distal renal tubules and collecting ducts.

Acute, subchronic, and chronic toxicity of ecadotril in dogs.

OBJECTIVE: To determine the toxicity of ecadotril in dogs. ANIMALS: 74 healthy 4- to 11-month-old Beagles. PROCEDURE: To determine acute toxicity, ecadotril (2,000 mg/kg of body weight, PO) in a gelatin capsule was administered once to 2 dogs, and dogs were observed for 2 weeks. To determine subchronic and chronic toxicity, ecadotril was administered every day for 3 months (50 mg/kg [n = 8], 100 mg/kg [8], 300 mg/kg [12]) and 12 months (25 mg/kg [n = 8], 50 mg/kg [8], 100 mg/kg [8]), respectively. Dogs in control groups (n = 12 or 8) received an empty gelatin capsule. Physical examinations, CBC, plasma biochemical analyses, and urinalyses were performed before and at various times during each experiment. Dogs were euthanatized at the end of each experiment, and necropsies were performed. RESULTS: Dogs that received 1 dose of 2,000 mg of ecadotril/kg developed nonspecific clinical signs of toxicosis. Dogs that received 300 mg of ecadotril/kg/d for 3 months developed pronounced anemia, bone marrow suppression, and some evidence of liver impairment. There was no evidence of an effect accumulated over time, and reversibility of toxic effects was evident. Dogs that received < or =100 mg of ecadotril/kg/d for 3 or 12 months tolerated treatment without apparent effect. CONCLUSIONS AND CLINICAL RELEVANCE: Degree of acute toxicity of a single high dose of ecadotril in dogs was low. The no-observable adverse effect level of ecadotril following daily oral administration was 100 mg/kg/d; repeated administration of 300 mg/kg/d revealed the hematopoietic system as the primary toxicologic target.

Nimodipine for treatment of idiopathic epilepsy in dogs.

OBJECTIVE: To evaluate efficacy and safety of the calcium channel antagonist nimodipine in dogs with idiopathic epilepsy. DESIGN: Prospective clinical trial. ANIMALS: 10 dogs with idiopathic epilepsy. Dogs were included if seizures were inadequately controlled despite treatment with barbiturates and serum phenobarbital concentrations were > 25 micrograms/ml, if dogs had intolerable adverse effects when treated with barbiturates, or if dogs had mild, inadequately treated seizures. PROCEDURES: Dogs were treated with nimodipine (2.5 mg/kg [1.1 mg/lb] of body weight, PO, q 12 h), and other medications were slowly withdrawn. Dogs were monitored for seizure frequency and severity as well as any adverse effects to the medication. RESULTS: Few adverse effects were reported. Seizure control, however, was generally inadequate. All but 2 dogs were withdrawn from the study because of poor seizure control. Plasma nimodipine concentrations were low, with a mean peak concentration of 105.3 ng/ml. CLINICAL IMPLICATIONS: Nimodipine was not successful in controlling seizures in dogs used in this study.

Vertical ground reaction force distribution during experimentally induced acute synovitis in dogs.

The pattern of vertical ground reaction force redistribution among limbs during episodes of acute synovitis of the stifle in 12 mixed-breed dogs was investigated as an adjunct to a blinded nonsteroidal anti-inflammatory drug efficacy study. Without regard to drug efficacy groupings, the redistribution of vertical forces before and during the acute synovitis episode was evaluated by analysis of gait, using a force platform. Acute synovitis was induced by intrasynovial injection of sodium urate crystals. Simultaneously, each dog was given 1 of 4 treatment regimens, including IV injection of sterile saline solution (as a negative control), phenylbutazone (as a positive control), or 1 of 2 proprietary nonsteroidal anti-inflammatory drugs. Postinjection analyses took place at 2, 4, 8, 12, 24, and 36 hours. The peak vertical force redistribution in the 3 untreated limbs of the dogs was described. The greatest redistribution was observed 4 hours after substance injection when the synovitis was clinically at maximum. Thereafter, there was steady improvement and the dogs had a clinically normal gait 24 hours after substance injection. During synovitis, peak vertical force increased in the contralateral hind limb. During the more severe synovitis episodes, force was decreased in both forelimbs. There was good correlation between severity of lameness and peak vertical force response in the contralateral hind limb. Results of the study indicate that the untreated limbs of the same animal should not be used as a control during acute lameness studies.

[Drug residues in food fish]. / Arzneimittelrückstände im Lebensmittel Fisch.

The present paper reviews different possibilities of pharmacolegal residues in fish. Sometimes the treatment of fish with registered drugs in therapeutical dosage is provable in spite of keeping the withdrawal time. To that experiences of the persistence and values of Chloramphenicol, Chlortetracycline and Furazolidone proved after therapeutical treatment in fish correlated to the water temperature are compared with results of experiments documented in literature. Investigations on the residues of Enrofloxacin after application of different doses to rainbow trout were carried out. Sometimes the proof of drug residues in fish can be done without an advanced treatment. The recontamination of fish with drugs or their metabolites in environment is discussed as a possibility for drug residues. The carry-over-effect of drug during the animal food production can be also the reason for residues in fish. Experiments with Chloramphenicol contaminated feed in rainbow trout show residues in muscle of fish higher than 10 ppb during the feeding period. Finally the results of residues different drug used in fish--given in literature--are collected in two tables.

[The therapy of hypovolemic shock in cows with right-sided abomasal displacement]. / Untersuchungen zur Therapie des hypovolämischen Schocks bei Kühen mit rechtsseitiger Labmagenverlagerung.

In this trial, the effect of supplementary administration of the opioid antagonist Naloxone was tested, in comparison to infusion of Ringer's-solution only, in the treatment of hypovolemic shock in cows suffering from right-sided abomasal displacement. Twenty cows were selected by several criteria (pulse rate greater than 95/min; plasma chloride content less than 90 mmol/l; body temperature less than 39.5 degrees C) and alternatively assigned to the Naloxone group and the control group. All animals were treated surgically by the usual clinical method. After opening the abdominal cavity paralumbally from the right, intravenous administration of 13 l of Ringer's-solution was started and continued for about 5 hours. In addition, the cows of the experimental group received 0.75 g Naloxone as an intravenous bolus before, and 1 g Naloxone dissolved in 7 l fluid during the first hour of the permanent drip infusion. Further treatments (additional fluid therapy or administration of purgatives and ruminomotorics on the following days) were given according to the condition of the animal. The evaluation of efficacy was done in regard to the clinical (course of disease), and clinicochemical (e.g. hemogram, blood gas analysis, plasma chloride, plasma lactate) parameters as well as to blood pressure. No statistically significant differences were found between both groups. Only nine of the twenty cows were sent home cured, one patient of each group died one day after surgery, and the remaining 9 animals had to be sent to the slaughterhouse within 3 to 22 days after surgery after only transient improvement. These results suggest, that under the conditions described, conventional fluid therapy is equivalent to fluid therapy with addition of Naloxone. Hypoxic damage of the abomasum caused by its displacement and the subsequent hypovolemic shock are discussed as main causes for the poor postsurgical prognosis of right-sided abomasal displacement.