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A comparison of prophylactic efficacy of tilmicosin and a new formulation of oxytetracycline in feedlot calves.

Two replicated-pen field studies were performed under commercial feedlot conditions in western Canada to compare the administration of long-acting oxytetracycline at 30 mg/kg body weight (BW) versus tilmicosin at 10 mg/kg BW to feedlot calves upon arrival at the feedlot. Ten thousand nine hundred and eighty-nine, recently weaned, auction market derived, crossbred beef steer and bull calves were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: oxytetracycline, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at a rate of 30 mg/kg BW; or tilmicosin, which received subcutaneous tilmicosin (300 mg/mL formulation) at a rate of 10 mg/kg BW. There were 20 pens in each experimental group. In Study 1 and in the combined analysis, the initial undifferentiated fever (UF) treatment rate was significantly (P < 0.05) higher in the oxytetracycline group as compared with the tilmicosin group. There were no significant (P > or = 0.05) differences in first UF relapse, second UF relapse, third UF relapse, overall chronicity, overall rail, overall mortality, bovine respiratory disease (BRD) mortality, hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates between the experimental groups in either study or in the combined analysis. In addition, there were no significant (P > or = 0.05) differences in initial weight, final weight, weight gain, days on feed, daily dry matter intake, average daily gain, or the dry matter intake to gain ratio between the experimental groups in either study or in the combined analyses. In the economic analysis, there was a net economic advantage of $5.22 CDN per animal in the oxytetracycline group, due to a lower prophylactic cost, even though the UF therapeutic cost was higher.

Animals↗

Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog.

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day. This schedule was chosen in order to measure acebutolol plasma concentrations just before ligation from 60 to 540 min after the last dose of the drug. Long term oral treatment with acebutolol protected against postischaemic ventricular fibrillation and significantly reduced the incidence of both early phase (0-10 min postocclusion) ventricular arrhythmias and ventricular fibrillation. As a result the outcome was significantly improved after 60 min of ischaemia in acebutolol compared with placebo treated animals. The results in the control animals were similar to those in the placebo treated dogs. The protective effect of long term oral treatment with acebutolol lasted for nine hours and was apparently independent of the plasma concentrations of the drug. These data show that improved outcome in this canine model is due to the prevention of ischaemia induced ventricular fibrillation by long term beta adrenoceptor blockade, which is able to overcome the effect, if any, of partial agonist activity of acebutolol. A direct myocardial anti-ischaemic effect might explain the effectiveness of long term oral treatment, which is independent of plasma concentrations of the drug.

Acebutolol↗

Is routine episiotomy necessary?

One hundred and eighty one primigravid women delivering vaginally in July and August 1982 in the Rotunda Hospital, Dublin, were randomly allocated to one of two groups. Patients in one group were to undergo episiotomy. Those in the other group were not to undergo episiotomy unless it was considered to be essential. The outcome was compared with that of the clinical practice over the previous six months at the hospital. Of the 92 patients allocated not to undergo episiotomy, seven (8%) had one done for medical reasons compared with 507 (89%) in the previous six months. First degree tears occurred in 23 (25%) and second degree tears in 43 (47%). Nineteen (21%), however, retained an intact perineum compared with only 35 (6%) of the women who had delivered in the preceding six months. Assessments of perineal pain, bruising, swelling, and healing and records of ingestion of analgesics were made for the first four days after delivery, and again at a check up six weeks after delivery, in patients who had had spontaneous vertex deliveries. Forty patients who underwent episiotomy and 37 who sustained a second degree tear formed two comparable groups. There was no difference in outcome between them. Data were also evaluated for 19 women who retained an intact perineum, 22 who sustained a first degree tear, and 11 who underwent episiotomy and epidural anaesthesia; all 52 of these women had spontaneous vertex deliveries. Despite severe soft tissue injury in two patients those who fared best were those who retained an intact perineum. First degree tears were associated with symptoms similar to those associated with second degree tears. Those who fared worst were women who underwent episiotomy after epidural anaesthesia. The value of routine episiotomy in primigravid patients is questioned, but the final decision can be made only by the accoucheur at the time of imminent delivery.

Adolescent↗

Ventilation in chronic heart failure: effects of physical training.

OBJECTIVE: To assess the effects of exercise training on ventilatory function in chronic heart failure. DESIGN: Observer blinded random allocation crossover training and detraining trial. SETTING: Assessment in hospital based clinical laboratory; training home based. PATIENTS: 22 patients with chronic heart failure (New York Heart Association (NYHA) class II or III) recruited from a tertiary referral centre. All finished the study. INTERVENTION: Bicycle ergometer exercise for 20 minutes a day, five days a week for eight weeks at 70%-80% of maximum heart rate. MAIN OUTCOME MEASURES: Exercise capacity on graded incremental exercise test, minute ventilation, oxygen consumption and carbon dioxide output. RESULTS: Peak work load increased from 96 W to 112 W and peak oxygen consumption from 14.1 ml/kg/min to 15.4 ml/kg/min (p < 0.01). At submaximal workloads carbon dioxide excretion (VCO2) and minute ventilation (Vi) decreased significantly (p < 0.05) though oxygen consumption was unchanged. The relation between Vi and carbon dioxide excretion changed: the slope of the Vi to VCO2 plot decreased from 38.6 to 35.3, indicating an improvement in overall ventilary efficiency. The instantaneous carbon dioxide ventilatory equivalent (Vi/VCO2) decreased at submaximal workloads, and reached a lower minimum value after training, indicating that optimum ventilatory performance improved. The exercise capacity of patients was related to the optimum ventilatory performance. It is suggested that this may in part be mediated through changes in skeletal muscles. CONCLUSION: Exercise training reduces the ventilatory abnormalities in chronic heart failure; thus some of these changes may be due to physical deconditioning.

Aged↗

5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction: an autoradiographic study in the rat.

This study was conducted to test if tumour drug uptake could be increased in experimental colorectal cancer peritoneal metastases, by using pretreatment with peritoneal vasoconstriction or radioimmunotherapy. A total of 29 nude rats with peritoneal metastases were injected intraperitoneally (i.p.) with 14C-labelled 5-FU. The animals were randomly allocated to 5 groups. Six days prior to 5-FU, group I (control) received i.p. NaCl, group II was subjected to i.p. radioimmunotherapy (RIT) 131I-labelled anti-CEA monoclonal antibody (150 MBq) and group III received i.p. Norbormide 10 minutes before 5-FU. Two days prior to 5-FU group IV and V received i.p. NaCl (control) and RIT, respectively. 5-FU uptake was visualised with autoradiography and quantified by computer-based image analysis. Tumours in group III showed a higher uptake (mean+/-SD, 21.4+/-17) than in group I (11.8+/-10, p=0.04). This was also true when the analysis was restricted to larger tumours (> or = median 627 pixels) group III (23.2+/-19) vs. group I (11.8+/-7, p=0.002). Peritoneal tumours in group II were of smaller size (median area 308 pixels) than in group I (619 pixels), in group III (901 pixels), in group IV (769 pixels) and in group V (808 pixels). RIT decreased the tumour size whereas it did not affect 5-FU uptake. The uptake of 5-FU was potentiated by pretreating the animals with Norbormide. These results demonstrate that 5-FU uptake in experimental peritoneal metastases is increased when the peritoneal absorption of the drug is blocked using pretreatment with a vasoconstrictive agent. This principle may also be relevant when treating patients with colorectal cancer peritoneal metastases.

Adenocarcinoma↗

Systemic and colonic venous plasma eicosanoid and endotoxin concentrations, and colonic venous serum tumor necrosis factor and interleukin-6 activities in horses during low-flow ischemia and reperfusion of the large colon.

Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Blood samples were collected from the colonic vein and main pulmonary artery (systemic venous [SV]) for measurement of plasma endotoxin, 6-keto prostaglandin F1 alpha (6-kPG), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) concentrations. Tumor necrosis factor and interleukin-6 activities were measured in colonic venous (CV) serum samples. Data were analyzed, using two-way ANOVA, and post-hoc comparisons were made, using Dunnett's and Tukey's tests. Statistical significance was set at P < 0.05. Endotoxin was not detected in CV or SV plasma at any time. There was no detectable tumor necrosis factor or interleukin-6 activity in CV samples at any time. There were no differences at BL among groups for CV or SV 6-kPG, PGE2, or TXB2 concentrations, nor were there any changes across time in group-1 horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Impact of management interventions on helminth levels, and body and blood measurements in working donkeys in South Africa.

The aim of the study was to determine the effect of alternative management interventions on levels of nematodes and the condition of working donkeys in South Africa. Twenty-four adult donkeys (Equus asinus) within an area of 200km radius were randomly allocated to eight paddocks. Two replicates each of three management interventions together with a control group were tested in a 16-month study. The interventions included monthly removal of feces from paddocks where the donkeys grazed, a pre-winter moxidectin treatment, and a combination of a pre-winter moxidectin treatment and monthly fecal removal. The influence of the different interventions on the nematode fecal egg counts, animal live weights, body condition scores and general blood chemistry were compared. In addition, herbage samples were collected from the pastures in each paddock to determine the number of third-stage larvae (L(3)) per kg dry matter. At the end of the study worm recoveries and counts were performed on eight of the animals following euthanasia. The cyathostomes represented the largest portion of the helminth species composition in both the fecal egg counts and larval cultures. Monthly fecal removal alone did not significantly reduce the L(3) on pasture and consideration of more frequent removal is discussed. Pre-winter moxidectin treatment resulted in a 100% reduction in fecal egg counts, an average egg reappearance period of 42-55 days, a reduced average egg count for up to 8 months, and reduced total helminth burdens in all the treated donkeys. It also resulted in improved live weights, hemoglobin concentration, packed cell volumes and to some extent body condition score of the donkeys.

Animal Husbandry↗

Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal cord injury in rabbits.

STUDY DESIGN: Occlusion of the infrarenal abdominal aorta with administration of pentoxifylline was applied to adult rabbits, followed by removal of aortic clamp and reperfusion. Tissue levels of cytokines, lipid peroxides, and antioxidant enzymes were assayed and compared within groups. OBJECTIVES: To examine the effect of pentoxifylline (PTX) on cytokine levels, lipid peroxidation, and antioxidant enzymes in a rabbit model of spinal cord ischemia-reperfusion injury induced by aortic occlusion. SETTING: Isparta, Turkey. METHODS: Rabbits were randomly allocated into four groups of sham laparotomy (SHAM), sham laparotomy with PTX administration (SHAM+PTX), aortic occlusion and reperfusion (AOR), aortic occlusion and reperfusion with PTX administration (AOR+PTX). An intravenous bolus of 50 mg/kg PTX was given just before aortic cross clamping. An atraumatic microvascular clamp was then placed on the abdominal aorta immediately distal to the left renal artery for 30 min. PTX was infused at a rate of 0.5 mg/kg/min during the aortic occlusion. Animals were subjected to 120 min of reperfusion after removal of the aortic clamp. All animals were sacrificed at the end of reperfusion. The lumbosacral segments of spinal cords were quickly harvested and stored at -78 degrees C for biochemical assays of IL-6, TNF-alpha, MDA, SOD, and CAT levels. Differences among groups were analyzed by one-way analysis of variance followed by a post hoc Tukey's honestly significant difference test. RESULTS: No differences in mean levels of IL-6, TNF-alpha, MDA, SOD, and CAT were noted between SHAM and SHAM+PTX groups (P>0.05). There was a significant increase in all biochemical parameters in the AOR group (P<0.05). Administration of PTX significantly attenuated the levels of all biochemical parameters in the AOR+PTX group (P<0.05). CONCLUSION: PTX pretreatment attenuated ischemia-reperfusion induced spinal cord injury in a rabbit model, in terms of biochemical parameters of ischemia and reperfusion.

Animals↗

Evaluation of patient partners in the teaching of the musculoskeletal examination.

OBJECTIVE: To evaluate student preferences and examination outcomes of 2 different methods of teaching musculoskeletal (MSK) medicine examination techniques. METHODS: Year 2 students in a 4 year graduate medical school were randomized to 3 teaching groups: students in Group 1 were taught by rheumatology fellows, Group 2 by patient partners, while group 3 were randomly allocated to either patient partner (3A) or rheumatology trainee (3B) teaching. All students were debriefed at the end of each teaching block of 4 weeks for feedback on their teaching experience using a standardized questionnaire. In addition, at the end of the academic year, all students sat an objective structured clinical examination (OSCE) in clinical skills that contained a rheumatology station. The effect of method of teaching on students' performance in the rheumatology station was analyzed. RESULTS: Eighty medical students participated in the study. Overall, there was no difference in student ratings of either mode of teaching, although the students reported that patient partner teaching gave more opportunity to practice MSK examination skills and also provided greater feedback to the student. Students reported a preference for rheumatology trainee teaching because they believed the teaching would be more relevant to the content of the examination. There was no statistically significant difference in the performance of the students in the OSCE rheumatology station in regard to the mode of teaching they had received prior to the examination. CONCLUSION: Patient partner teaching is as effective a method of teaching clinical skills in MSK medicine as a traditional resident based form of teaching, with student benefits from patient feedback and greater "hands-on" opportunities. The assessment process should incorporate patient partners to assess the unique aspects of patient educator based teaching of MSK examination techniques.

Clinical Competence↗

Effect of human hepatocyte growth factor on promoting wound healing and preventing scar formation by adenovirus-mediated gene transfer.

OBJECTIVE: To evaluate the effects of hepatocyte growth factor (HGF) on the prevention of scar formation and the promotion of wound healing by gene transfer. METHODS: A total of 12 female New Zealand rabbits were used in this study. Rabbits were anesthetized with an intravenous injection of sodium pentobarbital, and identical wounds were made over the ventral surface of each ear. Five circular wounds, 7 mm in diameter, were created in each ear by excision through the skin to the underlying cartilage using sterile technique. After the surgical procedures, 10 of the rabbits were randomly allocated to five groups, with 2 rabbits in each group: Ad-HGF group 1, Ad-HGF group 2, Ad-HGF group 3, Ad-GFP (a reporter gene) group and the solvent group. Immediately after surgery, 6 x 10(7) pfu Ad-HGF, 6 x 10(8) pfu Ad-HGF, 6 x 10(9) pfu of Ad-HGF, 6 x 10(9) pfu of Ad-GFP, or same volume of solvent (PBS, pH 7.2) was applied once to each wound in groups 1 to 5, respectively. One additional rabbit was used to evaluate the transfer efficiency of the adenovirus vector by transferring Ad-GFP (6 x 10(9) pfu) into its wounds. Ice slides of wounds from this animal were observed under fluorescence microscopy. Another additional rabbit was used to evaluate the expression of HGF and TGFbeta1 after transferring Ad-HGF (6 x 10(9) pfu) into each of its wound. Immunohistochemistry was used for detection. RESULTS: The effect of HGF on reducing excessive dermal scarring was observed by adenovirus-mediated gene transfer. Transfection of the human HGF cDNA into skin wounds through an adenoviral vector suppressed the over-expression of TGFbeta1, which plays an essential role in the progression of dermal fibrogenesis. Application of HGF to the wounds significantly enhanced wound healing and inhibited over scarring. CONCLUSION: HGF gene therapy could be a new approach for preventing excessive dermal scarring in wound healing.

Animals↗

Digital resistance and tendon strength during the first week after flexor digitorum profundus tendon repair in a canine model in vivo.

BACKGROUND: After flexor tendon repair, the strength of the repair and the resistance to digital motion are important considerations in deciding when to initiate postoperative rehabilitation. Our objective was to assess these factors in a short-term in vivo canine model of flexor tendon repair. METHODS: Forty-eight dogs were randomly allocated to four groups based on the duration of postoperative follow-up (one, three, five, or seven days). In each group, two flexor digitorum profundus tendons of one forepaw were exposed. One tendon (the repair tendon) was sharply transected and repaired with a modified Kessler suture, and the other one (the sham tendon) was simply exposed without laceration. The involved paw was immobilized until the animal was killed on the designated day. Three tendons from each dog, including the repair tendon, the sham tendon, and a control tendon from a corresponding normal digit on the contralateral side, were tested. RESULTS: The mean peak total digital resistance force in the repair group was lowest at five days (p < 0.01 compared with seven days; p > 0.05 compared with one and three days). The mean peak force needed to overcome the internal gliding resistance between the repaired tendon and sheath was significantly higher than that in both the sham and control groups at all time-points (p < 0.001); however, this value was also smallest at five days. There was no significant difference in suture strength at any time-point (p > 0.05). CONCLUSIONS: When we evaluated tendon-gliding and suture strength after flexor tendon repair, the least favorable ratio of repair strength to force needed to overcome the resistance to digital motion was noted on Day 7, whereas the best combination of tendon strength and low peak resistance force was noted on Day 5.

Animals↗

Suppression of chemically-induced liver tumors by castration or estradiol-3-benzoate treatment in F344 rats.

Epidemiological data reveal that the incidence of liver cancer is markedly higher in men than women. To clarify the mechanism responsible for the induction of higher incidence of liver tumors in male animals, we investigated the modifying effect of sex hormones in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. F344 male rats (n=120) were divided into two experiments, experiment I (Exp I) and experiment II (Exp II). In each experiment, 60 rats were randomly allocated into four groups. The mini-osmotic pumps containing doses of 47.5 mg (Exp I) or 23.75 mg (Exp II) of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. Animals in group 2 were castrated one week prior to DEN treatment, and animals in groups 3 and 4 were treated with 1 or 10 microg of estradiol-3-benzoate (EB), respectively, one week prior to DEN treatment. Animals in group 1 were treated with DEN alone and sham-operated at the same time. All animals were sacrificed 26 weeks after DEN treatment. In Exp I, liver tumor incidence of group 3 decreased significantly compared with that of group 1 (p<0.05), and tumor multiplicities of groups 2, 3 and 4 were decreased significantly compared to that of group 1 (p<0.01). In Exp II, tumor incidence of group 3 was significantly different (p<0.05) when compared to that of group 1. Immunohistochemical expression of ERalpha was shown in normal appearing cells, but not in tumor cells. Western blot analysis confirmed that ERalpha expression was higher in normal liver tissue compared to tumor tissues. Taken together, we conclude that castration or EB treatment has an inhibitory effect in DEN-induced hepatocarcinogenesis in F344 rats. The reason for ERalpha loss in tumor cells should be further elucidated.

Animals↗

Special status consultation for frequent attenders. Who are the candidates?

BACKGROUND: The need to optimize frequent attender (FA) care and to economize on scarce resources in primary care has given rise to calls for intervention. However, precise knowledge of the specifics of this need is scarce, as is knowledge of how best to orchestrate intervention vis-à-vis particular FA groups. The aim of the study was to analyse the need for a special FA status consultation and to analyse if such need springs from physical, mental or social factors among FAs. METHOD: Half of the 270 general practices in the County of Aarhus, Denmark, were randomly allocated to the study group (in total 132 practices; 220 general practitioners (GPs)). From these practices age- and gender-stratified samples of FAs were drawn. FAs were defined as the top 10 per cent attenders in 12 months. Questionnaires were used to elicit FA and GP attitudes to the introduction of a status consultation and to obtain GPs' evaluation of their FAs' physical, mental and social status. The special FA consultation was introduced as a reimbursed half-hour consultation where the FA and the GP could discuss the patient's current and future care status. RESULTS: Over three-quarters of the FAs would accept the offer to have the status consultation, and the GPs would recommend it for one-fourth of their FAs. The expressed need was highly associated with an expected positive effect on health (prevalence ratio (PR) for GPs: 11.7 (8.9-15.5), PR for FAs: 1.6 (1.5-1.8)) and a decrease in attendance (PR for FAs: 1.4 (1.3-1.5)). The GPs quoted physical, mental and social indications for the consultation. The FAs who had high levels of functional symptoms were most likely to accept the consultation. CONCLUSIONS: There was an expressed need for an FA status consultation, which may lead to a positive effect on health and attendance. The GPs pointed to physical, mental and social indicators for a special FA consultation.

Adult↗

[Therapeutic effect of fuzheng yangying oral solution on immune-induced aplastic anemia mice].

OBJECTIVE: To observe the effect of fuzheng yangying oral solution on bone marrow proliferation and serum interleukin 2 in immune-induced aplastic anemia mice. METHODS: The immune-induced aplastic anemia mouse models were built up, and then were divided into 4 groups by randomized allocation. The models were fed with physical salts (Group A, n = 10 ), fuzheng yangying oral solution (Group B, n = 10), cyclosporin A (Group C, n = 10), and fuzheng yangying oral solution plus cyclosporin A (Group D, n =10), respectively. Another 10 healthy mice served as controls (Group E). The changes in blood cells, bone marrow karyocyte count, marrow hematopoietic tissue capacity, and serum interleukin 2 level were observed. RESULTS: The blood cells, bone marrow karyocyte count, and marrow hematopoietic tissue capacity in Group A were significantly lower than those of Group E (P < 0. 05) ; those in the 3 treated groups (Group B, C, and D) were significantly higher than those of Group A ( P < 0. 05 ); and Group D was the highest ( P < 0. 05 ). There were no significant difference between Group B and C ( P > 0. 05 ). The level of interleukin 2 in Group A was obviously higher than that of Group E (P < 0. 05 ); The levels of interleukin 2 in the 3 treated group ( Group B, C, and D) were significantly lower than those of Group A ( P < 0. 05 ); and Group D was the lowest ( P < 0. 05). There was no significant difference in the level of interleukin 2 between Group B and C ( P < 0. 05). CONCLUSION: Fuzeng yangying oral solution can impove the bone marrow proliferation and reduce the level of serum interleukin 2 in immune-induced aplastic anemia mice.

Anemia, Aplastic↗

Therapeutic efficacy of doxycycline against experimental Pasteurella multocida infection in broiler chickens.

The efficacy of doxycycline was investigated in two sets of experiments. In the first experiment 40, in the second experiment 60, hence altogether 100 five-week-old Ross broilers of both sexes were used. The birds were randomly allocated into groups (A and B in experiment 1; A, B and C in experiment 2) of 20 birds in each. All birds were infected intramuscularly with approx. 2 x 10(3) colony forming units of Pasteurella multocida strain X-73 (serotype A:1). Birds in groups A were non-medicated controls. Chickens in groups B were given doxycycline via the drinking water at a dose of 10 mg/kg body weight for 5 days, while group C was treated with chlortetracycline at a dose of 20 mg/kg body weight for 5 days. The trial lasted for 9 days, then the surviving chickens were sacrificed. Clinical symptoms, number of deaths, post mortem lesions and bacteriological findings were recorded using a special score system. Acute fowl cholera developed in broilers within a few hours after infection, as evidenced by the clinical symptoms, the high mortality rate (90% of the birds died within 4 days after infection), the pathological lesions and the recovery of P. multocida from the challenged birds. Doxycycline reduced the number of deaths (30% and 5% of birds died in experiments 1 and 2, respectively) and the severity of the clinical symptoms, and P. multocida could be re-isolated only from one of the survivors. In contrast, chlortetracycline slightly influenced the mortality; however, it delayed death and reduced the severity of clinical symptoms. These data indicate that doxycycline is highly effective for the treatment of experimental pasteurellosis in chickens.

Animals↗

SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT) inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs.

Male Hartley guinea pigs were randomly allocated to one of four treatments, 10 guinea pigs per group, for 12 weeks. The control diet contained no ASBT inhibitor (ASBTi) or simvastatin. Low ASBTi (LowASBTi) and high ASBTi (HighASBTi) were monotherapies containing 0.03 g/100 g and 0.1 g/100 g of the ASBTi SC-435. Combination therapy (COMBO) was a combination therapy consisting of 0.03 g/100 g ASBTi and 0.05 g/100 g simvastatin. Based on food consumption, guinea pigs received 17.2 and 47.8 mg/kg per day ASBTi in the ASBTi groups or 13.7 mg/kg per day ASBTi and 21.4 mg/kg per day simvastatin in the COMBO group. The amount of cholesterol in each diet was 0.25 g/100 g. LDL cholesterol was 40 and 70% lower with the HighASBTi and COMBO treatments compared to controls. Plasma triglycerides (TG) were 70% lower with COMBO therapy while HDL cholesterol was 43-47% higher with all treatments. Hepatic free cholesterol was reduced 60-80% with all treatments. Cholesterol content in the aortic arch was reduced by 25 and 42% in the HighASBTi and COMBO groups. Fecal bile acids were increased by 2.5- and 4-fold with HighASBTi and COMBO treatments. These data suggest that the interruption in the enterohepatic circulation of bile acids by ASBTi and statin co-administration therapy cause a significant reduction in plasma cholesterol concentrations and attenuate the progression of atherosclerosis in guinea pigs.

Animals↗

Diazepam does not prevent succinylcholine-induced fasciculations and myalgia. A comparative evaluation of the effect of diazepam and d-tubocurarine pretreatments.

To determine the effectiveness of diazepam pretreatment in preventing succinylcholine (SCh)-induced fasciculations and body pains, 587 patients were randomly allocated to six groups. Patients in Group I received no pretreatment and served as controls. Patients in Groups II and III were pretreated with 0.05 mg/kg of diazepam either 4-5 min (Group II) or 8-10 min (Group III) prior to SCh administration. Patients in Groups IV and V received 0.1 mg/kg of diazepam either 4-5 min (Group IV) or 8-10 min (Group V) prior to SCh administration, while patients in Group VI were pretreated with 0.05 mg/kg of d-tubocurarine (dTc) 4-5 min prior to SCh. The succinylcholine dosage was 1.0 mg/kg in Groups I through V and 1.5 mg/kg in Group VI. Fasciculations, intubation conditions and postoperative body pains were evaluated in all groups. Fasciculations were seen in 90% of patients in the control group and 15% in the dTc pretreatment group, while diazepam was ineffective in altering the frequency or intensity of fasciculations. Conditions for intubation were judged to be clinically adequate in all groups. Body pains were seen in 33% of patients in the control group and 28-36% in diazepam-pretreated groups and in only 8% of patients in the dTc pretreatment group. There was no statistically significant difference in the incidence of body pains by virtue of site of operation, age, sex, and inpatient/outpatient status. It is concluded that the problem of postoperative myalgia is significant and that dTc pretreatment is the effective method for prevention of fasciculations and postoperative myalgia. Diazepam pretreatment was ineffective for the prevention of fasciculations and myalgia.

Anesthesia, General↗

Altering dietary cation-anion difference in lactating dairy cows to reduce phosphorus excretion to the environment.

Four early-lactating dairy cows were randomly allocated to 4 diets with dietary cation-anion difference [DCAD; (Na + K) - (Cl- + S2-) mEq/100 g dry matter)] values of +14, +18, +24, and +45. Diets were formulated to be isoenergetic and isonitrogenous, and supplied similar levels of P (0.46%) and Ca (0.77%). The salts, MgCl2, MgSO4, K2CO3, and NaHCO3 were used to alter DCAD. The main objective of the study was to ascertain whether a decrease in DCAD would reduce fecal P excretion in lactating dairy cattle. The experiment was conducted as a 4 x 4 Latin square design with 21-d periods. During the last 5 d, diets were offered at a restricted level and samples of blood, milk, feces, and urine were collected. Measures of acid-base status of the cows were linearly related to DCAD, but the animals did not experience metabolic acid stress. Neither fecal P nor urinary P was affected by DCAD, and there was no change in overall P balance. Plasma P tended to increase and blood concentrations of ionized Ca were enhanced as DCAD decreased; P excretion in milk showed a quadratic response to DCAD. Milk yield and milk composition were unaffected by changes in DCAD. Although DCAD may have influenced P homeostasis in lactating cows, there was no evidence that, within the range of + 14 to + 45 mEq/ 100 g dry matter, DCAD could be used as a nutritional strategy to reduce manure P from dairy cattle.

Acid-Base Equilibrium↗