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Effects of amiodarone on cardiac electrophysiology in right ventricular rapid pacing-induced heart failure dogs.

AIM: To study the effects of amiodarone (Ami) on cardiac electrophysiologic properties and ventricular fibrillation threshold (VFT) in right ventricular rapid pacing-induced congestive heart failure (CHF) dogs. METHODS: Dogs (n = 25) were randomly allocated into 3 groups: A) control group; B) CHF group induced by right ventricular rapid pacing (4 pulses.s-1) for 4-5 wk; C) CHF models p Ami 300 mg.d-1 for 4-5 wk. The electrophysiologic parameters and VFT were evaluated by electric stimulation and monophasic action potential (MAP) recording. RESULTS: In CHF models, ventricular MAP duration (MAPD90), ventricular late repolarization duration (VLRD), and intra-ventricular conduction time (IVCT) were prolonged by 43%, 318%, and 19%, respectively; the ratio of ventricular effective refractory period (VERP) to MAPD90 (VERP/ MAPD90) and VFT were decreased by 13% and 48% respectively; the dispersion of ventricular recovery time (RT-D) was increased by 185%. In CHF models, Ami had no effects on ventricular MAPD90, but increased VERP/ MAPD90, IVCT, and VFT by 15%, 10%, and 67%, respectively, shortened VLRD by 87%; and decreased RT-D by 87%. Ami had no significant influences on the hemodynamic parameters of the CHF dogs. CONCLUSION: Ami normalizes the cardiac electrophysiologic properties in CHF dogs.

Action Potentials↗

[Effect of ischemic preconditioning on myocardial bcl-2, bax, p53 gene expression during ischemia/reperfusion period in rabbits].

OBJECTIVE: To investigate the effects of ischemic preconditioning on myocardial bcl-2, bax, p53 gene expression during ischemia/reperfusion period in rabbits. METHODS: Twenty four rabbits were randomly allocated to three groups (n = 8), pseudo-operation group(Group P), ischemia/reperfusion group (Group IR) and ischemic preconditioning group(Group IP). Group IR and Group IP were subjected to three hours of left anterior descending coronary artery occlusion followed for three hours of reperfusion. Ischemic preconditioning was achieved by three 5-minute cycles of ischemia, each followed by 5 minutes of reperfusion. Apoptosis index(AI) and protein expression of Bcl-2, Bax, and p53 in the border zone of myocardium of ischemic area at risk were obtained with a flow cytometry. RESULTS: Compared with Group IR, AI was significantly reduced in Group IP(P < 0.01). Bcl-2 expressions was higher in Group IP than in Group IR, while bax and p53 expressions were lower in Group IP than in Group IR. CONCLUSION: The rabbit myocardial apoptosis induced by ischemic preconditioning inhibited ischemia-reperfusion in vivo partly related to the modulating of bcl-2, bax and p53 expression.

Animals↗

Successful xenotransplantation of microencapsulated newborn pig parathyroid cells in the treatment of hypoparathyroidism in rats.

OBJECTIVE: To study the effect of xenotransplantation with pig parathyroid cells, which was prepared using cell microencapsulation technique, on the treatment of hypoparathyroidism in rats without immunosuppressor. METHODS: Parathyroid cells were isolated from 10 healthy newborn pigs and encapsulated in alginate-polylysine-alginate (APA) membranes. Thirty-two aparathyroid Wistar rats were randomly allocated to microcapsule, non-microcapsule, empty microcapsule, and control groups. Each rat was injected intraperitoneally with encapsulated porcine parathyroid cells, free porcine parathyroid cells, empty capsules or 0.9% NaCl, respectively. Total serum calcium and parathyroid hormone levels were monitored continuously for 40 weeks. And then, the transplant beds were retrieved and subjected to morphologic and electron microscopic examination. RESULTS: In those animals xenotransplanted with microencapsulated porcine parathyroid cells, the calcium and PTH levels were consistently within the normal range during the 40 weeks. In contrast, no therapeutic effects were observed in rats in the non-microcapsule group. Furthermore, neither empty capsules nor 0.9% NaCl were shown to have any effect on the recipient's serum calcium or PTH levels. After 40 weeks, electron microscopic examination demonstrated that the parathyroid cells within the microcapsules had survived well in vivo. CONCLUSIONS: Xenotransplantation of microencapsulated newborn pig parathyroid cells can successfully treat hypoparathyroidism in rats without using immunosuppressive drugs. The results of this study show the possible clinical use of microencapsulated porcine parathyroid cells.

Animals↗

Zimelidine-induced variations in alcohol intake by nondepressed heavy drinkers.

The effect of zimelidine, a specific serotonin-reuptake inhibitor, on alcohol intake was tested in 13 healthy male, nondepressed heavy drinkers who were randomly allocated to receive zimelidine or placebo in a double-blind, crossover experiment. There were five 2-wk experimental periods (baseline, placebo 1 and 2, and zimelidine 1 and 2). Treatment was discontinued in three subjects due to a suspected adverse reaction and three other subjects dropped out. Thus, 13 subjects participated in at least two experimental drug periods and only 10 participated in all the periods. In the 13 subjects zimelidine increased the days of abstinence and decreased the daily number of drinks consumed, whereas in the 10 subjects only the number of days of abstinence increased. Subjects did not report aversive alcohol-sensitizing reactions. Spielberger state-anxiety test scores and depression scores (Montgomery/Asberg and Hamilton) were low at the beginning and throughout the study. Our data suggest that zimelidine modifies alcohol intake by a different mechanism than previously tested drugs, possibly by modulating the central neural mechanism that controls drinking of alcohol.

Adult↗

[Pneumococcal vaccine effectiveness in the elderly. Systematic review and meta-analysis].

AIM: Estimate pneumococcal vaccine effectiveness in preventing Streptococcus pneumoniae illness in the elderly. DESIGN: Systematic review and meta-analysis. DATA SOURCE. MEDLINE, years 1964 to the 2000; EMBASE, from 1988 to the 2000; Cochrane Library, identified studies and previously published systematic reviews citations peruse, and contacts with field experts. STUDY SELECTION: Clinical trials, cohort and case-control studies, published in Spanish, English or French, that estimated pneumococcal disease rates in vaccinated or not vaccinated elderly. DATA EXTRACTION: The studies were valued independently by four investigators with predefined criteria of validity, such as results comparing rates of disease caused by serotypes included in the vaccine, random allocation, double blind design, included subjects pertaining to the same study base, and losses of less than 10% in clinical trials and 20% in observational studies. RESULTS: Eight clinical trials considered the relative risk (RR) of pneumococcal pneumonia, three did not make estimations on pneumonia originated by serotypes included in the vaccine and only one study fulfilled all the inclusion criteria. Vaccinated versus not vaccinated pneumococcal pneumonia RR was 0.86 (95%CI, 0.24 to 2.99). Vaccine effectiveness was 14% (95%CI, -199 to 76%). Ten studies performed estimations on the effectiveness of the vaccine on invasive disease by vaccine serotypes. Of these, two clinical trials and two observational studies fulfilled the required quality criteria. RR of invasive disease was of 0.68 (95%CI, 0.39-1.18); vaccine effectiveness was 32% (95%CI, 18-61%). CONCLUSIONS: No evidence was found supporting pneumococcal vaccine effectiveness to reduce or avoid S. pneumoniae disease in the elderly.

Adult↗

Field efficacy of doramectin pour-on against naturally-acquired, gastrointestinal nematodes of cattle in North America.

Seven studies were conducted under field conditions in North America to evaluate the therapeutic efficacy of doramectin in a pour-on formulation at a dosage of 500 microg/kg (1 ml/10 kg) for cattle harboring naturally-acquired infections of gastrointestinal nematodes, including species of Haemonchus, Ostertagia, Trichostrongylus, Bunostomum, Cooperia, and Oesophagostomum. In each study, 40 to 100 cattle were randomly allocated to a saline- or doramectin-treated group in a tiered manner based on Day -7 bodyweight. On Day 0, the cattle received either saline or doramectin topically, according to their treatment group. Weather and safety observations were made following treatment. No adverse reaction to treatment was observed at any time during these studies. Fecal egg count (FEC) determinations were carried out on each animal on Days -7, 0, 7, 14, and 21. Reductions in FEC for the doramectin-treated animals compared to saline-treated cattle were > or = 96.0% by Day -7 and > or = 99.0% on Days 14 and 21 for each study. Across all studies regardless of weather conditions, the reduction by Day 21 for the doramectin-treated animals compared to saline controls was 99.7% (p < or = 0.0001) and compared to pretreatment levels in doramectin-treated cattle was 99.9% (p < or = 0.0001). Doramectin pour-on should provide a useful new treatment for controlling nematode parasites of cattle.

Animals↗

An in vitro comparison of pH changes in root dentine following canal dressing with calcium hydroxide points and a conventional calcium hydroxide paste.

AIM: This study aimed to measure and compare pH changes at apical and cervical sites on the external root surface of extracted teeth dressed with calcium hydroxide in two different formulations. METHODOLOGY: Root canals of 45 single-rooted extracted human teeth were accessed and shaped using a step-down technique with rotary instrumentation. Standard cavities were prepared on the external root surface at specific apical and cervical sites. The teeth were randomly allocated to three groups. Teeth in group A were dressed with calcium hydroxide points, those in group B were dressed with an aqueous calcium hydroxide paste and teeth in group C were left unfilled. Following storage in humid conditions, the pH of the dentine at apical and cervical sites was measured at baseline and then at 24 h, 72 h, 1 week, 10 days, 2 weeks and 3 weeks. RESULTS: The pH of the root dentine at both apical and cervical sites was significantly greater (P < 0.001) in teeth dressed with aqueous calcium hydroxide paste compared with those dressed with calcium hydroxide points, when averaged out across all time periods. For all groups, there was a significant difference between the mean apical and cervical pH values for each tooth with lower values for the apical sites (P < 0.001). CONCLUSION: The results of this study indicate that an aqueous calcium hydroxide paste was more effective than calcium hydroxide points at raising the pH on the external root surface of extracted teeth.

Analysis of Variance↗

The effect of different fibre components on growth rate, nutrient digestibility, rate of digesta passage and hindgut fermentation in domesticated rabbits.

Trials were conducted to study the effect of dietary fibre on performance and nutrient digestibility in growing rabbits. The basal diet was supplemented with 12% cellulose, pectin, lignin, or alfalfa, in four different treatments. Twenty-four 4-week-old California male rabbits were randomly allocated into four groups and placed in individual cages. The lignin supplement severely affected both feed intake and performance, pectin second, with dietary cellulose having the least effect. Dietary lignin significantly decreased the digestibility of crude protein, gross energy and dry matter content (P < 0.05). Rabbits on the pectin supplemented diet digested dry matter, crude fibre and neutral detergent fibre (NDF) better (P < 0.05) than other treatment groups. On the other hand, rabbits in the lignin group digested crude fibre, acid detergent fibre (ADF) and NDF significantly less well than rabbits in other groups (P < 0.05). Dietary lignin also significantly decreased the caecal concentration of volatile fatty acids (VFA, P < 0.05) but did not significantly affect the molar ratios of the VFAs among treatment groups. The turnover rate of the marker, chromic oxide, in the gastrointestinal (GI) tract of rabbits was 64.94, 51.81, 44.05 and 29.59 h in the pectin, alfalfa, lignin and cellulose treatment groups, respectively. The rate of turnover in the digestive tract significantly influenced digestibility of fibre components but did not significantly influence caecal fermentation.

Animal Feed↗

The combination of insulin and sulphonylurea in the treatment of secondary drug failure in patients with type II diabetes.

Thirteen patients (6 females and 7 males) who were secondary failures on oral drug therapy were randomly allocated to either 2 months of treatment with insulin + glibenclamide or insulin + placebo. Thereafter the treatment schedules of the two groups were switched over for another two months. The combination of insulin and glibenclamide was more effective in lowering the fasting blood glucose (P = 0.026) and 24 h urine glucose (P = 0.042) than the combination of insulin and placebo. The combination therapy with insulin and glibenclamide revealed higher basal (P = 0.021) and glucagon-stimulated C-peptide concentrations (P = 0.037) than therapy with insulin and placebo. However, insulin binding to erythrocytes did not differ between the two study periods. The results indicate that the addition of glibenclamide to insulin in type II diabetics poorly controlled by oral antidiabetics alone may slightly improve diabetic control. The mechanism of this action is due at least partly to sulphonylurea-induced stimulation of endogenous insulin secretion. The effectiveness of the combination treatment during long-term therapy still remains to be proven, however.

Adult↗

Two-, three-, and four-breed rotational crossbreeding of beef cattle: carcass traits.

Carcass data from 1,494 straightbred and rotational crossbred steers were collected over four generations. Mating systems included straightbreds (Angus [A], Brahman [B], Charolais [C], and Hereford [H]); two-breed rotations (A-B, C-B, and H-B); three-breed rotations (A-B-C, A-B-H, and B-C-H); and a four-breed rotation (A-B-C-H). Steers were randomly allocated to one of four postweaning treatments that varied in length of grazing and feeding periods. Treatment and breed group (four straightbreds and seven rotational combinations) significantly influenced hot carcass weight (HCWT), retail yield (RY), longissimus muscle area (LM), fat thickness (FT), marbling score (MS), USDA quality grade (QG), and Warner-Bratzler shear force (WBS). Feeding for longer periods resulted in greater (P < .05) HCWT, RY, FT, and MS, higher QG, and lower (P < .05) WBS values. Among the straightbreds, C was heavier and larger for HCWT, RY, and LM (P < .01), whereas A and H had greater (P < .01) FT and MS. The B was similar to H for HCWT, RY, and LM and to C for FT but ranked last (P < .01) for MS and WBS. Three- and four-breed rotational mating systems were superior (P < .05) to the two-breed rotation for HCWT, RY, and LM but were similar for FT, MS, and WBS. Rotational combinations exceeded (P < .05) the straightbreds for all carcass traits except MS.

Adipose Tissue↗

Heparin, heparin plus ASA and dipyridamole, and arteriovenous fistula as adjuvant methods to prevent rethrombosis after venous thrombectomy. Experimental study in rabbits.

Venous rethrombosis following thrombectomy is a common event. The aim of the present study was to verify the action of heparin, heparin plus acetyl salicylic acid (ASA) and dipyridamole, and of an arteriovenous fistula (AVF) in the prevention of this complication. Thrombosis was induced in 48 male rabbits by the injection of thrombin in a segment of the left jugular vein, in which the blood flow was arrested for 10 minutes. After 48 hours, the animals were randomly allocated into one of 4 groups of treatment: (1) control, (2) subcutaneous heparin (600 S.I. Units/kg--8/8 hours), (3) heparin, in the same dose, plus ASA (10 mg/kg/once a day), and dipyridamole (0.5 mg/kg thrice a day), (4) an AVF was surgically constructed between the left carotid artery and the left maxillar vein. After 30 minutes, thrombectomy was performed. The venous blood flow, the hematocrit, activated partial thromboplastin time and thrombin time tests were performed before, right after the thrombectomy and 48 hours after thrombectomy. Venography was performed after thrombectomy and at the end of the experiment. The animals were killed 48 hours after thrombectomy and the veins were examined macroscopically. Venous rethrombosis was significantly prevented only in the AVF group (9/12), when compared to control group (0/12), heparin group (1/12) and heparin plus antiaggregating agents group (2/12). These results validate further clinical and experimental investigations with the use of AVF to prevent rethrombosis after venous thrombectomy, when a reduction of venous flow is present.

Animals↗

Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies.

Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin.

Animals↗

Increased insufflation pressure enhances the development of liver metastasis in a mouse laparoscopy model.

Despite the widespread use of laparoscopic techniques for colorectal cancer surgery, little is known about the potential risk of liver metastasis following CO2 pneumoperitoneum. We investigated the effect of different insufflation pressures and durations of CO2 pneumoperitoneum on the growth of liver metastasis in a mouse model. Six- to 7-week old male BALB/C mice were intraportally inoculated with 2 x 10(4) Colon 26 cells and randomly allocated to receive either CO2 pneumoperitoneum at different pressures (5 mmHg, 10 mmHg, or 15 mmHg), xiphoid-pubic laparotomy, or no treatment other than tumor cell inoculation. Mice undergoing pneumoperitoneum or laparotomy were then subdivided by the duration of treatment (30 minutes or 60 minutes). Cancer nodules on the liver surface from a total of 122 mice were evaluated on the 14th postoperative day. Similar to full laparotomy, CO2 pneumoperitoneum at 10 mmHg and 15 mmHg for 60 minutes, and pneumoperitoneum at 15 mmHg for 30 minutes significantly promoted the growth of cancer nodules on the liver surface. Enhancement of tumor growth was influenced by increased insufflation pressures (p < 0.05) rather than the prolonged length of pneumoperitoneum (p = 0.53) without significant interaction (p = 0.49). These results suggest that an increased insufflation pressure promotes the growth of liver metastases as well as laparotomy in this animal model. growth of liver metastases in a mouse laparoscopy model, following different pressures and durations of CO2 pneumoperitoneum, which is used most often in laparoscopic procedures.

Animals↗

Effects of exercise on Achilles tendon healing in a rat model.

The effects of motion, or lack of it, on Achilles tendon healing are not well defined. We have recently shown that immobilization has a detrimental effect on tendon healing in a rat model. The aim of this experiment was to determine whether enforced exercise had an additional beneficial effect on the mechanical and functional recovery of divided Achilles tendons in rats. Male Sprague-Dawley rats were randomly allocated into a nonexercise and an exercise group (N = 10 for each group). In both groups the right Achilles tendon was surgically transected. The left, uninjured lower limb served as an internal control. Both groups of animals were housed under identical conditions with the exception that the exercise group swam for 15 minutes per day. Functional performance was determined from the measurement of hindpaw prints of walking rats preoperatively and on alternate postoperative days. On day 15, the animals were killed and weighed, and biomechanical evaluations were performed on both the injured and uninjured Achilles tendon constructs. There were no differences in weight at time of death. All animals had an initial functional deficit that returned to near-normal by day 15. There were significant differences in the morphological and the mechanical properties of the healing Achilles tendon constructs at day 15 when comparing the injured with the uninjured Achilles tendon constructs. Supplemental exercise, however, had no effect on the functional or mechanical recovery of injured or uninjured Achilles tendons in the rat model.

Achilles Tendon↗

Protein metabolism in skeletal muscle tissue from hyperthyroid patients after preoperative treatment with antithyroid drug or selective beta-blocking agent. Results from a prospective, randomized study.

Protein metabolism in skeletal muscle tissue was studied in three groups of patients undergoing thyroid surgery: group I (n = 8), hyperthyroid patients preoperatively treated with an antithyroid drug and T4; group II (n = 8), hyperthyroid patients preoperatively treated with the beta 1-selective adrenoreceptor blocking agent metoprolol; group III (n = 5), euthyroid patients operated on for nodular goiter or adenoma. The study was prospective and hyperthyroid patients were randomly allocated to one of the two preoperative regimens. During operation a biopsy was taken from the sternohyoid muscle and rates of protein synthesis and degradation were measured in incubated muscle tissue. Clinical improvement was equal in the two groups of hyperthyroid patients during preoperative treatment but serum T3 concentrations remained elevated in patients treated with metoprolol. Thus, these patients were biochemically hyperthyroid at the time of operation. The rate of protein degradation was significantly higher in hyperthyroid patients treated with metoprolol than in patients of groups I and III. A significant positive correlation was found between serum T3 and rate of protein degradation in skeletal muscle. Protein synthesis rates were similar in the three groups of patients. This study demonstrated for the first time increased proteolysis in skeletal muscle tissue from patients with high serum T3 concentrations. The results indicate that changes of skeletal muscle protein metabolism in hyperthyroid patients are not normalized by beta 1-blockade despite the fact that this treatment effectively controlled symptoms and signs of hyperthyroidism.

Adrenergic beta-Antagonists↗

Influence of portal branch ligation on the outcome of repeat dearterializations of an experimental liver tumor in the rat.

It has been suggested that the portal vein should be occluded during intermittent hepatic dearterialization in order to induce a more complete ischemia of the tumor. In this experiment the influence of portal branch ligation in combination with repeat dearterializations on a liver tumor was investigated. Twenty-seven rats were randomly allocated to sham treatment (n = 6); portal branch ligation (PBL) (n = 7); 120 min of repeat dearterialization (n = 7); and portal branch ligation (PBL) in combination with 50 min of repeat dearterialization (n = 7) (once a day during 5 days). The results showed that portal branch ligation alone did not alter the tumor growth compared with sham treatment (P > 0.05), nor did portal branch ligation in combination with repeat dearterializations for 50 min (P > 0.05). However, tumor growth delay was achieved following 120 min of repeat dearterializations without occlusion of the portal branch (P < 0.01 versus all the other groups). There was a significant weight loss of the lobe undergoing PBL, whether dearterialization was added or not (P < 0.001). The liver nucleotide/DNA and RNA/DNA ratio significantly decreased as well. Histological examination showed that > 50% of tumor cells became necrotic after repeat dearterializations for 2 hr indicating a significant damage to tumor tissue. In contrast, PBL in combination with repeat dearterializations for 50 min induced extensive liver necrosis without having any influence on tumor growth.

Analysis of Variance↗

Comparative study of early-season prophylaxis using ivermectin with lungworm vaccination in the control of parasitic bronchitis and gastroenteritis in cattle.

Twenty-four first-season calves were randomly allocated to three similar groups (1-non-treated controls; 2 - vaccinated against lungworm; 3 - treated with ivermectin 21, 56 and 91 days after turnout) and set-stocked on separate pastures. Parasitic bronchitis became evident in the controls and signs of parasitic gastroenteritis were seen later in the vaccinates, but the ivermectin-treated calves remained healthy. After autumn housing, all were kept as a single group for the winter. The following summer, six of the ivermectin-treated animals and their matching vaccinates were grazed together, without further prophylaxis, along with six first-season calves. The latter displayed evidence of mild but debilitating pulmonary and gastrointestinal parasitic disease while both groups of yearlings remained healthy (with the exception of one diarrhoeic vaccinate). Thus, the immune status of the ivermectin-treated animals appeared to be comparable to that of the vaccinates. This conclusion was supported by parasitological observations and by artificial challenge at the end of the second grazing season.

Animals↗

Guided tissue regeneration and local delivery of insulinlike growth factor I by bioerodible polyorthoester membranes in rat calvarial defects.

Thirty 8-week-old male Wistar rats were randomly allocated into three groups of 10 rats each. A 5-mm defect in the left parietal bone was made in each rat. In the defects of the first group of rats, no implant was used (control group). In the second group, polyorthoester membranes were placed in the defects without active substance. In the third group, polyorthoester membranes were placed with insulinlike growth factor I. The rats were sacrificed 6 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on radiographs. Host-tissue response was evaluated by light microscopy. The area of residual bone defect was greatest in the control group, less for the defects with polyorthoester membrane without active substance, and least for the defects with polyorthoester membranes with the growth factor. During histologic evaluation, no inflammation was seen, and only traces of the polyorthoester were detected in the defects with polyorthoester membrane with or without the growth factor.

Animals↗