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PubMed2005

Endothelin receptor--a blockade decreases ventricular arrhythmias after myocardial infarction in rats.

OBJECTIVE: Endothelin-1 (ET-1) production increases during acute myocardial infarction (MI) and may contribute to the genesis of ventricular tachycardia (VT) and ventricular fibrillation (VF). However, the antiarrhythmic effects of ET-1 receptor blockade, examined shortly after MI, have been debated. In the present study, we examined the effects of such treatment on VT/VF during the first 24 h post-MI. METHODS: Thirty-five Wistar rats (223+/-22 g) were randomly allocated to either the ET-1 receptor-A (ETA) antagonist BQ-123 (0.4 mg/kg, BQ-123 group, n=17), or normal saline (control group, n=18) and were subjected to coronary artery ligation. A single-lead electrocardiogram was continuously recorded for 24 h post-MI, using an implanted telemetry system, and episodes of VT/VF were analyzed. Monophasic action potential (MAP) recordings were obtained from the left (LV) and right (RV) ventricular epicardium at baseline, 5 min after treatment and 24 h post-MI. RESULTS: There were 15.94+/-19.35 episodes/h/rat of VT/VF in the control group and 1.66+/-2.22 in the BQ-123 group (p=0.010), resulting in a lower (p=0.030) arrhythmic mortality in treated animals. The mean episode duration was 7.40+/-7.16 s for the control group and 2.30+/-1.37 s for the BQ-123 group (p=0.011). The maximum decrease in VT/VF was observed during the 1st, 5th and 6th hours post-MI. In the control group, LV MAP duration increased 24 h post-MI, displaying an increased beat-to-beat variation, but remained unchanged in the BQ-123 group. CONCLUSION: Acute ETA blockade reduces the incidence of VT/V F during the first 24-h post-MI in the rat, through a decrease in the dispersion of repolarization.

Action Potentials↗

PubMed2006

Systemic and regional hemodynamics in pigs with acute liver failure and the effect of albumin dialysis.

OBJECTIVE: Acute liver failure (ALF) is haemodynamically characterized by a hyperdynamic circulation. The aims of this study were to investigate the systemic and regional haemodynamics in ALF, to measure changes in nitric oxide metabolites (NOx) and to evaluate whether these haemodynamic disturbances could be attenuated with albumin dialysis. MATERIAL AND METHODS: Norwegian Landrace pigs (23-30 kg) were randomly allocated to groups as controls (sham-operation, n = 8), ALF (hepatic devascularization, n = 8) and ALF + albumin dialysis (n = 8). Albumin dialysis was started 2 h after ALF induction and continued for 4 h. Systemic and regional haemodynamics were monitored. Creatinine clearance, nitrite/nitrate and catecholamines were measured. A repeated measures ANOVA was used to analyse the data. RESULTS: In the ALF group, the cardiac index increased (PGT < 0.0001), while mean arterial pressure (PG = 0.02) and systemic vascular resistance decreased (PGT < 0.0001). Renal resistance (PG = 0.04) and hind-leg resistance (PGT = 0.003) decreased in ALF. There was no difference in jejunal blood flow between the groups. ALF pigs developed renal dysfunction with increased serum creatinine (PGT = 0.002) and decreased creatinine clearance (P = 0.02). Catecholamines were significantly higher in ALF, but NOx levels were not different. Albumin dialysis did not attenuate these haemodynamic or renal disturbances. CONCLUSIONS: The haemodynamic disturbances during the early phase of ALF are characterized by progressive systemic vasodilatation with no associated changes in metabolites of NO. Renal vascular resistance decreased and renal dysfunction developed independently of changes in renal blood flow. After 4 h of albumin dialysis there was no attenuation of the haemodynamic or renal disturbances.

Albumins↗

PubMed1994

Effect of different housing conditions on behaviour and foot lesions in Friesian heifers.

Spring-calving Friesian heifers were randomly allocated either to Dutch Comfort cubicles (2130 x 1160 mm) bedded with rubber mats or to modified Newton Rigg cubicles (2060 x 1090 mm) without bedding. Their behavioural activities, including lying down and standing, were monitored every 30 minutes for two days and two nights each week from November to March, and all four feet of each animal were examined at housing, at calving and monthly thereafter. During January, February and March the 22 heifers in the Dutch Comfort cubicles lay down significantly longer and spent significantly less time standing half-in the cubicles than the 21 heifers in the Newton Rigg cubicles (P < 0.01). Claw health deteriorated in all the animals after housing, but less in the heifers in the Dutch Comfort cubicles, at both one and two months after calving (P < 0.05). There were moderate correlations between the lying behaviour and the total foot lesions and the lesions in the sole ulcer area of the heifers in the Dutch Comfort cubicles but none for the heifers in the Newton Rigg cubicles, possibly because lameness is a multifactorial condition and other factors may have masked the effect of lying down on foot lesions in this group. The better conditions provided by the Dutch Comfort cubicles were associated with better claw health and this effect was partially mediated through the increased time spent lying down by the heifers in these cubicles.

Animal Husbandry↗

PubMedDate not supplied

[Breast histologic changes in female rats treated with sex steroids].

OBJECTIVE: To evaluate the association of histologic changes in the breasts of female rats undergoing therapy with sex steroids. METHODS: An experimental study was conducted of 40 castrated female non-pubertal rats, 20 had given birth (Group B) and 20 had no offspring (Group A). After four weeks, these rats were randomly allocated to subgroups: A1, A2, A3, A4, A5 and B1, B2, B3, B4, B5. Steroids were given to subgroups as follows: A1 and B1--estradiol benzoate; A2 and B2--medroxyprogesterone acetate; A3 and B3--estradiol benzoate and medroxyprogesterone acetate; A4 and B4--tibolone; A5 and B5--placebo. After 10 weeks of treatment, animals were sacrificed and their mammary glands were analyzed. Histologic parameters evaluated were: epithelial cell proliferation, epithelial cells with secretory activity; and cell atypia in terminal duct units and buds or terminal alveoli. The association between microscopic analysis and diverse therapeutic regimens were analyzed by calculating the odds ratio and its respective 95% confidence interval. RESULTS: Histologic changes were observed in 29 rats: moderate hyperplasia (52.5%), hyperplastic alveolar nodule (42.5%), epithelial atypia (35%), mild hyperplasia (32.5%), secretory activity (20%) and severe hyperplasia (5%). In rats with no offspring when compared to the control, 1.3 times more hyperplastic alveolar nodules were found in the group treated with estradiol, the same was true for moderate hyperplasia in the rats that received medroxyprogesterone acetate, hyperplastic alveolar nodules and epithelial atypia in the group treated with estradiol plus medroxyprogesterone acetate. In the rats with offspring 1.3 times more secretory activity was found with estradiol. CONCLUSION: Epithelial hyperplasia and epithelial atypia with no proliferation are strongly associated to combined therapy with estradiol plus medroxyprogesterone acetate, mainly in the rats without offspring.

Animals↗

PubMed1987

Physical training as treatment for type 2 (non-insulin-dependent) diabetes in elderly men. A feasibility study over 2 years.

At a health examination of men approximately 60 years old, 48 were found to have Type 2 (non-insulin-dependent) diabetes. All had been healthy 10 years earlier. The intention was to randomly allocate those with mild diabetes to a training or a control group and study the long-term influence of regular training on the progress of the disease. However, it was found that the majority--39 of 48--had other diseases or were on treatment which made regular training difficult and would have complicated the interpretation of the metabolic effects of training. Eight men took part in a physical training programme for up to 2 years. Aerobic capacity, glucose tolerance and serum lipoproteins were measured before and at the end of the training period. Another group of eight men with Type 2 diabetes, of similar weight, age and relative aerobic capacity, who did not undergo the physical training, served as control subjects. The oxygen uptake increased by 16% in the training group and decreased by 12% in the control group but no significant changes could be demonstrated in body weight, fasting blood glucose, serum lipoproteins, glucose tolerance or insulin values at a 75-g oral glucose tolerance test between the two groups. Two patients in the training group developed coronary heart disease, two deteriorated metabolically (drug treatment had to be added), and there were two drop-outs. The results cast doubts on the feasibility and efficacy of physical training as a long-term treatment for the majority of Type 2 diabetic patients, who are older than 60 years.

Diabetes Mellitus, Type 2↗

PubMed2002

Effects of morphine, butorphanol, buprenorphine, and U50488H on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 12 healthy, female, spayed cats. PROCEDURE: Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. RESULTS: All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2002

In vivo and in vitro comparisons of spray-drying and solvent- evaporation preparation of microencapsulated Mycoplasma hyopneumoniae for use as an orally administered vaccine for pigs.

OBJECTIVE: To evaluate the efficacy of an orally administered vaccine of Mycoplasma hyopneumoniae that was prepared by spray drying or solvent evaporation. ANIMALS: Thirty 6-week-old, crossbred, specific-pathogen-free (SPF) pigs. PROCEDURE: Pigs were randomly allocated into 5 groups and housed in an SPF facility. Pigs in 2 groups (groups AQ and CAP) were fed M hyopneumoniae enteric-coated vaccine on days 0, 10, and 20. A third group (group IM) received an IM injection of M hyopneumoniae vaccine with aluminium hydroxide as an adjuvant on days 0, 10, and 20. The last 2 groups (non-vaccinated-challenged [NV-C] and nonchallenged [NC]) were fed a sham treatment. All 24 pigs in groups AQ, CAFP IM, and NV-C were challenge exposed with 5 ml of a 10% pneumonic lung suspension administered on day 40 via intubation of the trachea. All pigs were slaughtered and the lungs removed and examined for lesions on day 68. RESULTS: In vitro studies indicated that these 2 microencapsulation techniques formed an effective shell and protected mycoplasmal antigen from gastric acid. Results of inoculation and challenge tests indicated that microencapsulated M hyopneumoniae were sufficiently potent to induce an immune response and provide good protection. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered microencapsulated M hyopneumoniae vaccines induced an immune response and reduced the severity of lung lesions in challenge-exposed pigs. Results suggest that this novel method can be applied to other antigens, because the spray-drying process yielded an orally administered M hyopneumoniae vaccine that induced a good immune response.

Administration, Oral↗

PubMed1998

Nifurtimox plus pyrimethamine for treatment of murine toxoplasmosis.

In the search for novel antitoxoplasmic agents, we evaluated the efficacy of nifurtimox (3-methyl-4[5'-nitrofurfurylidene-amino]-tetrahydroe-4H-1,4- thiazine-1,1-dioxide), an antiprotozoal drug effective against trypanosomiasis, in an experimental model of acute toxoplasmosis in mice. One hundred NIH mice were inoculated intraperitoneally, each with 2,614 RH tachyzoites of Toxoplasma gondii, and randomly allocated into 5 groups (n = 19-21). Animals from each group were orally treated for 10 days either with nifurtimox 25 mg/kg/day (NF1), nifurtimox 50 mg/kg/day (NF2), pyrimethamine 60 mg/kg/day (P), the combination nifurtimox 50 mg/kg/day plus pyrimethamine 60 mg/kg/day (NF2-P), or with corn oil (controls). Survival of mice was recorded daily for 1 mo after the experimental infection. Comparisons of cumulative mortality between groups were made applying the chi2 test. Mean survival time was longer in animals from P and NF2-P groups than those from NF1, NF2, and control groups. Cumulative mortality was less in mice from the NF2-P group (25%), than that in mice from the P (65%), the NF1 (100%), the NF2 (89%), or the control (95%) groups (P < 0.01). The doses of nifurtimox used in the present study were not significantly effective against murine toxoplasmosis. However, when combined with pyrimethamine, a strong anti-toxoplasma effect was obtained in comparison with survival rates associated with pyrimethamine or nifurtimox alone. It seems feasible that nifurtimox inhibits the replication of T. gondii tachyzoites similar to that of other protozoans, e.g., Trypanosoma and Leishmania. It will be important to determine if the reduction of mortality in mice treated with the nifurtimox-pyrimethamine combination results from summation or from synergism. Further studies on the toxic mechanisms exerted by nifurtimox on T. gondii seem warranted.

Administration, Oral↗

PubMed2000

Influence of hypovolemia on the pharmacokinetics and the electroencephalographic effect of propofol in the rat.

BACKGROUND: Hypovolemia decreases the dose requirement for anesthetics, but no data are available for propofol. As it is impossible to study this in patients, a rat model was used in which the influence of hypovolemia on the pharmacokinetics and pharmacodynamics of propofol was investigated. METHODS: Animals were randomly allocated to either a control (n = 9) or a hypovolemia (n = 9) group, and propofol was infused (150 mg x kg(-1) x h(-1)) until isoelectric periods of 5 s or longer were observed in the electroencephalogram. The changes observed in the electroencephalogram were quantified using aperiodic analysis and used as a surrogate measure of hypnosis. The righting reflex served as a clinical measure of hypnosis. RESULTS: The propofol dose needed to reach the electroencephalographic end point in the hypovolemic rats was reduced by 60% (P < 0.01). This could be attributed to a decrease in propofol clearance and in distribution volume. Protein binding was similar in both groups. To investigate changes in end organ sensitivity during hypovolemia, the electroencephalographic effect versus effect-site concentration relation was studied. The effect-blood concentration relation was biphasic, exhibiting profound hysteresis in both hypovolemic and control animals. Semiparametric minimization of this hysteresis revealed similar equilibration half-lives in both groups. The biphasic effect-concentration relation was characterized by descriptors showing an increased potency of propofol during hemorrhage. The effect-site concentration at the return of righting reflex was 23% (P < 0.01) lower in the hypovolemic animals, also suggesting an increased end organ sensitivity. CONCLUSIONS: An increased hypnotic effect of propofol occurs during hypovolemia in the rat and can be attributed to changes in both pharmacokinetics and end organ sensitivity.

Anesthesia, Intravenous↗

PubMed1984

Cyvadic in advanced soft tissue sarcoma: a randomized study comparing two schedules. A study of the EORTC Soft Tissue and Bone Sarcoma Group.

Two hundred forty-six adults with advanced progressive soft tissue sarcoma received combination chemotherapy with cyclophosphamide, vincristine, Adriamycin (doxorubicin), and DTIC. They were randomly allocated to receive the four drugs simultaneously every 4 weeks (S1: CYVADIC), or pairs of drugs (S2: ADIC-CYV) alternating at 4 weekly intervals. One hundred sixty-two patients completed 8 weeks of chemotherapy, and were considered to be evaluable for response. There were 18 complete remissions and 25 partial remissions, an overall response rate of 26%, with a highly significant difference between the two arms in favor of S1 (38% versus 14%, P = 0.001). There were no significant differences between S1 and S2 in terms of median duration of remissions (62 versus 39 weeks), and median survival of responders (85 versus 80 weeks) and of all evaluable patients (43 versus 45 weeks). Karnofsky index (KI) was the single most important prognostic factor. Patients with KI 90-100 showed a remission rate of 41% (56% on the S1 regimen) in contrast with 14% in those with KI 50-80. No patient with a KI of 50 responded to chemotherapy. The main toxicities were nausea, vomiting, anorexia, alopecia and myelosuppression, but did not differ significantly between the two regimens. Our findings suggest that stratification according to KI is essential for studies on chemotherapy for advanced soft tissue sarcomas in order to make a valuable comparison of treatment results.

Adolescent↗

PubMed2005

A new approach to enhance reproductive performance in sheep using royal jelly in comparison with equine chorionic gonadotropin.

The objective was to compare the effects of royal jelly (RJ) and eCG treatments on reproductive performance of ewes synchronized using intravaginal progesterone-releasing devices. Forty-two cycling Awassi ewes were treated intramuscularly (i.m.) with 15 mg PGF2alpha. On the following day, all ewes were administered with CIDR-G for 12 days and were randomly allocated to three (RJ, eCG and control) groups of 14 ewes each. Ewes in the RJ-treated group received daily i.m. treatments of 400mg RJ during the period of CIDR-treatment. Each ewe in the eCG-treated group received an i.m. treatment of 500 IU eCG at the time of CIDR-G removal (day 0) and no further treatment was given to ewes in the control group. Ewes were exposed to four fertile rams for 72 h, from the time of CIDR-G removal, and checked for breeding marks at 6-h intervals. Blood samples were collected from day -13 until day 0 and thereafter until day 19 for progesterone analysis. Royal jelly treatment resulted in a greater rate of decline and lower (P<0.02) progesterone concentrations between days -10 and 0 than eCG-treated and control ewes. Expression of estrus was similar among the three groups and intervals to onset of estrus were shorter (P<0.01) in RJ-treated (31.3h) and eCG-treated (29.8h) than control (41.3h) ewes. First-cycle pregnancy and lambing rates were greater (P<0.05) in RJ-treated (71.4 and 71.4%) and eCG-treated (85.7 and 78.6%) than in control (42.9 and 35.7%) ewes, respectively. Results demonstrate that the treatments of RJ and eCG in conjunction with CIDR-G were similarly effective in induction of estrus and improvement of pregnancy and lambing rates.

Animals↗

PubMed2025

Impact of L-citrulline on meat production and quality: A study on its effects on meat attributes and nutritional composition.

BACKGROUND: Amino acids are fundamental in sustaining physiological homeostasis during stress conditions. l-citrulline (l-Cit), a non-essential amino acid (NEAA) and metabolic precursor of arginine, has been reported to exert beneficial effects on the health and performance of broiler chickens. OBJECTIVE: This study aimed to investigate the effects of dietary supplementation with varying inclusion levels of l-Cit on growth performance, meat quality, plasma biochemical indices, and thermoregulatory responses in broiler chickens. METHODS: A total of 120 one-day-old chickens of the Lohman meat (Indian River) strain were randomly allocated to four dietary treatments, and each treatment included 30 birds in 3 replicates each. A 7-day feeding trial was conducted, beginning at 21 days of age. The control group (T0) was fed only a basal diet, while l-Cit was administered through the drinking water at concentrations of 0.5 % (T1), 0.75 % (T2), and 1.0 % (T3) to the respective treatment groups, in addition to the basal diet. RESULTS: Dietary inclusion of l-Cit significantly affected broiler performance and physiology. The T2 group demonstrated the highest body weight gain and lowest feed conversion ratio (FCR) compared with T0, T1, and T3 (p < 0.05). Organ development was increased in T2, with significant increases in bursa, heart, and liver indices, alongside reduced abdominal fat (p < 0.05). Meat quality improved through reduced drip loss and elevated muscle pH, particularly in T2. Plasma biochemical analysis showed lower cholesterol, triglycerides, and LDL in all l-Cit groups, with optimal in T2 (p < 0.05), while HDL and uric acid remained unaffected. Moreover, rectal temperature decreased significantly across l-Cit groups (p < 0.05). CONCLUSION: Overall, this study suggests that a diet supplemented with 0.75 % l-Cit (T2), which could be a promising amino acid without affecting meat quality or consumer preferences, may improve growth performance, meat quality, the lipid profile (blood plasma), and thermoregulation in broilers.

Animals↗

PubMed2004

Accuracy of pulse oximetry readings in an animal model of low perfusion caused by emerging pneumonia and sepsis.

OBJECTIVE: To test the effects of low perfusion caused by emerging sepsis on the performance of two new pulse oximetry techniques: Masimo SET in comparison with Nellcor Oxismart XL. DESIGN: Cohort study with random allocation of two pulse oximetry devices to two sensor sites. SETTING. University animal research facility. SUBJECTS: Twenty-five adult, anesthetized, ventilated rabbits. INTERVENTIONS: Pneumonia/sepsis was induced by tracheal instillation of E. coli. MEASUREMENTS AND RESULTS: Oxygen saturation was measured by pulse oximetry (SpO(2)) and recorded continuously until death. Arterial oxygen saturation (SaO(2)) was measured hourly by CO oximetry and whenever a difference of >5% between the devices occurred. SpO(2) sensors were positioned at both forelegs and switched hourly. There was no difference in total signal dropout time [median 3.8 min (range 0.4-66.6 min) vs 3.3 min (range 0-94.5 min), Masimo SET vs Oxismart XL]. There were fewer episodes with a false SpO(2) reading [1 (range 0-7) vs 2 (range 0-17)] using the Masimo SET vs the Oxismart XL as verified by CO oximetry; p<0.05. Average bias (SpO(2)-SaO(2)) was significantly different between the two devices, and variability of bias values increased across time with both devices. CONCLUSIONS: Both devices were capable to measure SpO(2) during most of the experimental time in this model of low perfusion and therefore appear to be highly sensitive to pick up a signal; however, low perfusion caused by emerging sepsis may result in inaccurate measurements with both devices. These episodes were less common with the Masimo SET vs the Oxismart XL.

Animals↗

PubMed2006

Antibody response to Mycoplasma hyopneumoniae infection in vaccinated pigs with or without maternal antibodies induced by sow vaccination.

Vaccination with bacterins is an important tool for the control of Mycoplasma hyopneumoniae infection of pigs. Because such vaccination often involves piglets that have suckled M. hyopneumoniae antibody-positive dams it is important to understand the effect of pre-existing (passively acquired) antibody on vaccine-induced immunity. To investigate this issue experimentally, 20 sows that were seronegative for M. hyopneumoniae were selected from a M. hyopneumoniae-infected herd and then randomly allocated to one of four treatment groups (five sows/group): Group A, vaccinated sows/vaccinated piglets; Group B, vaccinated sows/non-vaccinated piglets; Group C, non-vaccinated sows/vaccinated piglets; Group D, non-vaccinated sows/non-vaccinated piglets. Sows (Groups A and B) were vaccinated 14 days before farrowing and seroconverted within the next 14 days. Conversely, none of the non-vaccinated sows was seropositive at farrowing. Piglets (Groups A and C) were vaccinated when they were 7 days of age. Regardless of treatments none of the piglets had any evidence of an active immune response until many of those of Groups A and C and a few of those of Groups B and D seroconverted after it had been shown that at least some pigs of all groups had been naturally infected with a field strain of M. hyopneumoniae. This pattern of immune responsiveness (i.e. the collective results of Groups A, B, C and D) suggested that vaccination of pigs had primed their immune system for subsequent exposure to M. hyopneumoniae, and that passively acquired antibody had little or no effect on either a vaccine-induced priming or a subsequent anamnestic response. According to the statistical analysis sow serological status did not interfere with the antibody response in early vaccinated piglets. In conclusion, the results pointed out that early vaccination of piglets may assist M. hyopneumoniae control independently from the serological status of sows.

Animals↗

PubMed1992

[Myocardium-protective effects of phosphocreatine in experimental ischemia-reperfusion].

The protective effects of exogenous phosphocreatine were evaluated in vitro on isolated perfused rat hearts during reperfusion of ischemic myocardium. The hearts were randomly allocated in 2 groups. In the first (n 6) phosphocreatine was added at a concentration of 10 mM. The latter was utilized as control (n 7). In both groups the results showed a slight decrease in the post-ischemic myocardial performance. Aortic systolic pressure and flow respectively decreased on reperfusion by 17% and 12.5% in the phosphocreatine group and by 25.6% and 35% in the control group. Coronary flow was reduced by 10% in the phosphocreatine and by 18% in the control group. No statistically relevant differences were reported within or between the groups. No changes in heart rate occurred in the same period in the phosphocreatine and in the control group. Myocardial enzyme release during reperfusion showed significant lower levels of CK and LDH in the phosphocreatine group compared to controls (p less than 0.001 after 65 min and p less than 0.025 after 75 min between the 2 groups). The occurrence of serious ventricular arrhythmias was considerably higher in controls with respect to the phosphocreatine group. The overall incidence of major rhythm disturbances was 66% in the phosphocreatine group and 100% in the control group. Irreversible ventricular fibrillation (57%) occurred only in control hearts. The present findings indicate that phosphocreatine exerts a protective effect during myocardial ischemia and reperfusion, especially by preventing serious ventricular arrhythmias and by reducing myocardial enzyme release.

Animals↗

PubMed2004

Pharmacokinetic evaluation of four ivermectin generic formulations in calves.

The plasma concentration profiles of four randomly chosen ivermectin (IVM) generic formulations (IVM G1-G4) were compared after their subcutaneous (SC) administration to healthy calves. The disposition of other avermectin-type endectocide compounds, doramectin (DRM) and abamectin (ABM), was also assessed in the same pharmacokinetic trial. Forty-two parasite-free Aberdeen Angus male calves were randomly allocated into six treatment groups. Animals in each group (n = 7) received SC treatment (200 microg/kg) with one of the commercially available endectocide formulation used in the trial. Blood samples were taken into heparinised vacutainer tubes from the jugular vein prior to and up to 35 days post-treatment. The recovered plasma was analysed by HPLC with fluorescence detection. Large kinetic differences were observed among the DRM, ABM and IVM formulations under evaluation. The DRM plasma concentration profiles were higher than those measured for ABM and all the IVM generic formulations. The higher and sustained plasma concentrations of DRM accounted for greater area under concentration-time curve (AUC) and longer mean residence time (MRT) values compared to those obtained for both ABM and the IVM generic preparations. The pattern of IVM absorption from the site of subcutaneous administration showed differences among the generic formulations under evaluation. The IVM G2 preparation showed higher peak plasma concentration and AUC values (P < 0.05) compared to those obtained after the administration of the IVM G1 formulation. Longer (P < 0.05) MRT values were obtained after the administration of the IVM G3 compared to other IVM generic preparations. The kinetic behaviour of ABM did not show significant differences with that described for most of the IVM formulations. This study demonstrates that major differences on drug kinetic behaviour may be observed when using different endectocide injectable formulations in cattle.

Animals↗

PubMed2002

A histomorphometric study of adaptive responses of cancellous bone in different regions in the sheep mandibular condyle following experimental forward mandibular displacement.

Forward mandibular displacement in animal models is associated with faster and/or redirected condylar growth. Here the effect of forward displacement induced with an intraoral appliance on modelling/remodelling of the mandibular condyle was investigated in eight, 4-month-old, castrated male Merino sheep, randomly allocated to experimental and control groups (n=4 in each group). The study period was 15 weeks, during that time, (1). calcein, (2). tetracycline, and (3). alizarin red S fluorochromes were given to all animals from day 1. Midsagittal sections of the temporomandibular joints were selected for analysis. Dynamic variables of bone formation, static indices of bone-forming and -resorbing activity, and structural indices of trabecular bone were estimated histomorphometrically. The sampling site was divided into two regions for analysis: (a). a 'subchondral region' (2 and 3 labels only), believed to be the bone newly formed during the experimental period; (b). a 'central region' (labelled by all three fluorochromes), believed to be the bone that existed before the experiment. Regional differences in adaptive response were found. In the experimental group, the bone-volume fraction (BV/TV) of the subchondral regions had decreased, although the specific bone-surface and bone-formation rates had increased. This low BV/TV was associated with decreased trabecular thickness and increased trabecular separation. In the central condylar region of the experimental group, BV/TV was unchanged, but an increased osteoid surface was apparent when the eroded surface was taken into consideration. These adaptive condylar responses to forward mandibular displacement appeared to be the result of increased osteoblastic activity. Further studies are recommended to examine why the subchondral and central regions responded differently.

Adaptation, Physiological↗

PubMed2005

Exogenously administered substance P and neutral endopeptidase inhibitors stimulate fibroblast proliferation, angiogenesis and collagen organization during Achilles tendon healing.

BACKGROUND: In the last few years much research has been conducted in methods to promote tendon healing. The aim of this study was to determine if the healing process after operative repair of rat Achilles tendons could be stimulated by the paratendinous injection of a sensory peptide, substance P (SP). METHODS: Ninety-six male Sprague-Dawley rats were randomly allocated to four groups: (I) control buffer injections, (II) injections of SP 10(-6) mol/kg body weight combined with a carrier, (III) injections of SP 10(-8) mol/kg BW with the carrier, and (IV) injections with the carrier only (thiorphan 1 micromol/kg BW and captopril 30 micromol/kg BW, both neutral endopeptidase inhibitors). The influence on tissue repair was determined from the histologic measurement of fibroblast proliferation, angiogenesis, and collagen organization. On days 7, 14, 28 and 42, animals were sacrificed and histologic evaluations were performed on the injured Achilles tendon constructs. RESULTS: The two groups subjected to SP injections showed a significant initial fibroblast proliferation on day 7 (p < 0.05), which rapidly declined by day 14 to the level of cellular proliferation observed with the use of thiorphan and captopril. Capillary proliferation showed a similar evolution, except that in the second week angiogenesis in the treated groups was below the level of the control group. Strikingly, collagen orientation increased faster in the groups injected with SP. This was obvious from the second week already and the difference remained until the completion of the study. CONCLUSION: This is the first study to demonstrate that paratendinous injections of SP after operative repair of the Achilles tendon in rats appears to provide a boost to the initial stages of healing and significantly accelerate the reparative phase of the healing process.

Achilles Tendon↗