MRI evaluation of topical heat and static stretching as therapeutic modalities for the treatment of eccentric exercise-induced muscle damage.

The aim of this study was to monitor the effects of topical heat and/or static stretch treatments on the recovery of muscle damage by eccentric exercise. For this purpose, 32 untrained male subjects performed intense eccentric knee extension exercise, followed by 2 weeks of treatment (heat, stretch, heat plus stretch) or no treatment (control, n=8/group). Isometric strength testing, pain ratings, and multi-echo magnetic resonance imaging of the thigh were performed before and at 2, 3, 4, 8, and 15 days following the exercise. Increased T2 relaxation time, muscle swelling, pain ratings, and strength loss confirmed significant muscle damage during the post-exercise period. Pain ratings and muscle volume recovered to baseline by 15 days, although muscle strength remained lower [77 (4) vs. 95 (3) kg pre-exercise, mean (SE)] and T2 values higher [32.2 (0.8) vs. 28.6 (0.2) ms pre-exercise]. Our results indicate that heat and/or static stretching does not consistently reduce soreness, swelling or muscle damage. The practical implication of our findings is that clinicians should be aware that prescribing heat and/or static stretching following intense eccentric or unaccustomed exercise will not enhance the recovery of damaged muscles.

Continuous low-level topical heat in the treatment of dysmenorrhea.

OBJECTIVE: To compare the efficacy of topically applied heat for menstrual pain with oral ibuprofen and placebo treatment. METHODS: We conducted a randomized placebo and active controlled (double dummy), parallel study using an abdominal patch (heated or unheated) for approximately 12 consecutive hours per day and oral medication (placebo or ibuprofen 400 mg) three times daily, approximately 6 hours apart for 2 consecutive days. Pain relief and pain intensity were recorded at 17 time points. There was at least 85% power to detect a true one-unit difference in the 2-day pain relief treatment means for comparisons with the unheated patch plus oral placebo group using a one-tailed test at the.05 level of significance, based on an observed within-group standard deviation of 1.147. RESULTS: Eighty-four patients were enrolled and 81 completed the study protocol. Over the 2 days of treatment, the heated patch plus placebo tablet group (mean 3.27, P <.001), the unheated patch plus ibuprofen group (mean 3.07, P =.001), and the combination heated patch plus ibuprofen group (mean 3.55, P <.001) had significantly greater pain relief than the unheated patch plus placebo group (mean 1.95). Greater pain relief was not observed for the combination heated patch plus ibuprofen group compared with the unheated patch plus ibuprofen group (P =.096); however, the time to noticeable pain relief was statistically significantly shorter for the heated patch plus ibuprofen group (median 1.5 hours) compared with the unheated patch plus ibuprofen group (median 2.79 hours, P =.01). CONCLUSION: Continuous low-level topical heat therapy was as effective as ibuprofen for the treatment of dysmenorrhea.

Effect of topical heat on electromyographic power density spectrum in subjects with myofascial pain and normal controls: a pilot study.

OBJECTIVE: To investigate the influence of superficial heat on the fatigue cascade of the upper trapezius muscle in subjects with myofascial pain and matched normal controls. DESIGN: In a prospective randomized block crossover pilot study, eight female subjects, ages 20-35 yr, with upper trapezius muscle trigger points and eight matched female control subjects without pain were studied. Subjects performed six 100-sec shoulder shrug contractions to fatigue, with subjects randomly chosen to receive heat during the first three or last three trials. The initial median frequency and the slope of the median frequency decline were calculated from the data. RESULTS: In the subjects with pain, the slope of the median frequency was elevated in ambient room temperature as compared with controls. There was no difference in slope of the median frequency under heated conditions. Heat application in controls before fatiguing exercise caused an increase in initial median frequency, whereas exercise before heat treatment resulted in a significantly lower initial median frequency. Subjects with myofascial pain had no significant change in initial median frequency. CONCLUSIONS: Heat seems to have a positive effect on muscle function in normal individuals when applied before exercise. Subjects with myofascial pain respond differently to exercise and heat challenge, which suggests a difference in their muscle physiology.

Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia.

BACKGROUND: Hypercholesterolemia is a major risk factor for coronary heart disease and nutrition management is the initial therapeutic approach. OBJECTIVE: This multicenter study evaluated the long-term effectiveness of psyllium husk fiber as an adjunct to diet in the treatment of persons with primary hypercholesterolemia. DESIGN: Men and women with hypercholesterolemia were recruited. After following an American Heart Association Step I diet for 8 wk (dietary adaptation phase), eligible subjects with serum LDL-cholesterol concentrations between 3.36 and 4.91 mmol/L were randomly assigned to receive either 5.1 g psyllium or a cellulose placebo twice daily for 26 wk while continuing diet therapy. RESULTS: Serum total and LDL-cholesterol concentrations were 4.7% and 6.7% lower in the psyllium group than in the placebo group after 24-26 wk (P < 0.001). Other outcome measures did not differ significantly between groups. CONCLUSIONS: Treatment with 5.1 g psyllium twice daily produces significant net reductions in serum total and LDL-cholesterol concentrations in men and women with primary hypercholesterolemia. Psyllium therapy is an effective adjunct to diet therapy and may provide an alternative to drug therapy for some patients.

Association between interleukin-8 concentration in nasal secretions and severity of symptoms of experimental rhinovirus colds.

The purpose of this study was to examine the association between experimental rhinovirus infection and the elaboration of interleukin-8 (IL-8) into nasal secretions of volunteers and to determine the effect of pentoxifylline on IL-8 elaboration and rhinovirus-associated common cold symptoms. Fifty-four subjects with experimental rhinovirus infections and 20 sham-inoculated subjects were studied. Pentoxifylline had no effect on rhinovirus-induced symptoms or nasal-secretion IL-8 concentrations. IL-8 concentrations were significantly greater in nasal secretions from infected symptomatic subjects than in those from infected asymptomatic or sham-challenged subjects on days 2-4 after virus challenge. In infected subjects, there was significant rank correlation between nasal obstruction severity, rhinorrhea severity, and nasal-wash albumin concentrations and the change in IL-8 concentration from baseline on days 2-4 after virus challenge.

Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing.

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies using dose levels not substantially lower than those used in the long-duration studies. For repeated-dose studies in nonrodent species, clinical pathology testing is recommended at study termination and at least once at an earlier interval. For studies of 2 to 6 weeks in duration in nonrodent species, testing is also recommended within 7 days of initiation of dosing, unless it compromises the health of the animals. If a study contains recovery groups, clinical pathology testing at study termination is recommended. The core hematology tests recommended are total leukocyte (white blood cell) count, absolute differential leukocyte count, erythrocyte (red blood cell) count, evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the absence of automated reticulocyte counting capabilities, blood smears from each animal should be prepared for reticulocyte counts. Bone marrow cytology slides should be prepared from each animal at termination. Prothrombin time and activated partial thromboplastin time (or appropriate alternatives) and platelet count are the minimum recommended laboratory tests of hemostasis. The core clinical chemistry tests recommended are glucose, urea nitrogen, creatinine, total protein, albumin, calculated globulin, calcium, sodium, potassium, total cholesterol, and appropriate hepatocellular and hepatobiliary tests. For hepatocellular evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile acids. For hepatobiliary evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or total bile acids. Urinalysis should be conducted at least once during a study. For routine urinalysis, an overnight collection (approximately 16 hr) is recommended. It is recommended that the core tests should include an assessment of urine appearance (color and turbidity), volume, specific gravity or osmolality, pH, and either the quantitative or semiquantitative determination of total protein and glucose. For carcinogenicity studies, only blood smears should be made from unscheduled sacrifices (decedents) and at study termination to aid in the identification and differentiation of hematopoietic neoplasia.

Effect of bleeding site on clinical laboratory testing of rats: orbital venous plexus versus posterior vena cava.

We sought to determine if there were any differences in the results of clinical laboratory tests between blood samples collected from the orbital venous plexus and the posterior vena cava of adult male rats. Thirty healthy adult male Sprague Dawley rats were anesthetized by ether inhalation, and blood samples were collected successively from the orbital venous plexus (OVP) and the posterior vena cava (PVC) for hematologic (n = 10), serum chemistry (n = 10), and coagulation (n = 10) analyses. The prothrombin and partial thromboplastin times of samples from the OVP were prolonged (17% and 288%, respectively) when compared with samples from the PVC. Respective hematologic biases were as follows: red blood cell count (7%), hemoglobin (6%), hematocrit (5%), mean corpuscular volume (-3%), mean corpuscular hemoglobin (-1%), mean corpuscular hemoglobin content (1%), white blood cell count (13%), and platelet count (-7%). Respective serum chemistry biases were as follows: sorbitol dehydrogenase (-7%), glucose (-7%), blood urea nitrogen (-10%), creatinine (-2%), total protein (4%), albumin (2%), globulin (9%), alkaline phosphatase (5%), lactate dehydrogenase (-6%), aspartate aminotransferase (-5%), alanine aminotransferase (-2%), total bilirubin (0%), direct bilirubin (0%), magnesium (-17%), sodium (4%), potassium (0), chloride (4%), calcium (-2%), phosphorous (-17%), cholesterol (3%), triglycerides (24%), creatinine kinase (-8%), 5'nucleotidase (0%), and total bile acids (4%). For hematologic testing, there were no biologically significant differences between samples collected from the OVP and PVC. The coagulation times and serum Mg and P showed biologically significant differences between samples collected from the OVP and PVC.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical pathology testing recommendations for nonclinical toxicity and safety studies. AACC-DACC/ASVCP Joint Task Force.

Clinical pathology testing in nonclinical toxicity and safety studies is an important part of safety assessment. In recent years, clinical laboratory testing has rapidly expanded and improved. Some government regulatory agencies provide guidelines for clinical pathology testing in nonclinical toxicity and safety studies. To improve these testing guidelines and the resultant safety assessments, the American Association for Clinical Chemistry's Division of Animal Clinical Chemistry and the American Society for Veterinary Clinical Pathology formed a joint committee to provide expert recommendations for clinical pathology testing of laboratory species involved in subchronic and chronic nonclinical toxicity and safety studies. These recommendations include technical recommendations on blood collection techniques and hematology, serum chemistry, and urinalysis tests.

Effects of dietary cholesterol and fasting on hamster plasma lipoprotein lipids.

Hamsters are commonly utilized for comparative study of cholesterol metabolism. The present study was conducted to assess the effects of fasting on the plasma lipoprotein cholesterol concentrations of hamsters. Over a period of 3 weeks, adult male Golden Syrian hamsters (n = 32) were fed chow with or without the addition of 2 g/kg cholesterol. Half of the animals consuming each diet were fasted for 18 hours prior to blood sampling. Comparison of diets showed the following increases in those animals receiving cholesterol: total plasma cholesterol (180%) and triacylglycerols (75%), high density (75%), low density (250%), and very low density (560%) lipoprotein cholesterol. Compared with fasted animals, total plasma triacylglycerols were higher in both non-fasted diet groups. Compared with fasted hamsters that had received cholesterol, total plasma cholesterol (mean +/- SE mmol/l) was greater (6.36 +/- 0.18 vs 5.43 +/- 0.21; p less than or equal to 0.05) in the non-fasted group, due primarily to higher VLDL cholesterol (2.07 +/- 0.18 vs 1.58 +/- 0.18; p less than or equal to 0.05). There were no differences in HDL cholesterol (2.07 +/- 0.05 vs 2.17 +/- 0.08) or LDL cholesterol (1.29 +/- 0.08 vs 1.37 +/- 0.05) between fasted and non-fasted hamsters fed cholesterol. Fasting is not necessary for the study of the plasma HDL cholesterol and LDL cholesterol of hamsters fed cholesterol.

A model of postprandial hyperinsulinemia in miniature swine.

This report describes a new animal model of postprandial hyperinsulinemia (PPH) in adult miniature swine that consume a diet simulating that of affluent Western societies. Two progressive levels of PPH were induced experimentally by injecting subcutaneously low and high doses of purified porcine insulin without causing acute detrimental clinical effects or significant biological effects on total serum cholesterol, sodium and potassium concentrations, mean arterial blood pressure, or heart rate. Physiologic postprandial increments in total serum triglyceride concentrations were inhibited by experimentally-induced PPH. With this model, the in vivo effects of homologous PPH can be studied in a dose-responsive manner. Areas of potential research use of this model include study of the chronic effects of PPH on lipoprotein metabolism, the development of atherosclerosis and diabetes mellitus, and the association with regional body fat distribution and metabolism.

Atherosclerosis research in cynomolgus monkeys (Macaca fascicularis).

This is a review of the utilization of cynomolgus monkeys (Macaca fascicularis) in atherosclerosis research. Naturally occurring and experimentally induced atherosclerosis progression and regression studies are described. This species has been utilized as an animal model to study the effects of immunologic injury, aging, exercise, and drug intervention on atherosclerotic lesions. Cynomolgus macaque atherosclerosis induced by feeding cholesterol is a good model of human atherosclerosis because of similar gender-related differences in susceptibility to coronary artery atherosclerosis, a relatively high incidence of myocardial infarction, and characterized psychosocial factors that influence the development of atherosclerosis.

A minipig model of body adipose tissue distribution.

A relatively increased central (truncal) distribution of body adipose tissue has been associated with increased risk for the development of coronary heart disease in human beings. Animal models available to study this phenomenon have been limited. Validity and reliability studies of B-mode ultrasound for the measurement of subcutaneous adipose tissue thickness in miniature swine were conducted. The results showed that ultrasound measurements of subcutaneous adipose tissue thickness were accurate (+/- 0.1 cm) 95 percent of the time when compared to direct in situ ruler measurements. There was no significant systematic measurement error. Ultrasound measurements were repeatable (+/- 0.2 cm) 95 percent of the time. A computerized tomographic (CT) method to quantitate intra-abdominal adipose tissue was also developed. Serial CT measurement of total cross-sectional, density-contoured adipose tissue area correlated significantly (r = 0.91, P less than 0.01) with total intra-abdominal adipose tissue weight. This model should be useful for comparative study of the association of regional body adipose tissue distribution with the development of atherosclerotic lesions and other coronary heart disease risk factors.

Correction for sample free glycerol is needed for accurate measurement of plasma triglyceride concentrations in miniature Swine.

Methods for the measurement of plasma or serum triglyceride concentrations usually quantify the glycerol released by enzymatic hydrolysis of the triglyceride molecule. Any free glycerol in the sample is measured erroneously as triglyceride in these methods. As miniature swine have been used commonly for comparative studies of plasma lipoprotein lipids, this study was conducted to assess the need for free glycerol correction of plasma triglyceride measurements by comparing glycerol-blank corrected and non-corrected total plasma triglyceride concentrations from fasted minipigs. Fasting plasma free glycerol concentrations range from 9 to 14 mg/dl. The mean +/- SD (n = 16) glycerol-blank corrected total plasma triglyceride value (77 +/- 8 mg/dl) was significantly (p < 0.001) less than the uncorrected measurement value (189 +/- 12 mg/dl). Poor correlation (r = 0.24) between corrected and uncorrected total plasma triglyceride measurements suggests that mathematic correction by a constant correction factor would yield inaccurate results for miniature swine. Free glycerol blanking is essential for determination of the true total plasma triglyceride concentration.

Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet.

We studied the effect of propranolol on the diet-induced coronary artery atherosclerosis (CAA) in 30 adult male cynomolgus monkeys living in social groupings of five animals each. Animals in the "treated" segment (n = 15) consumed propranolol, which was mixed into an atherogenic diet. Animals in the "untreated" group (n = 15) consumed only the atherogenic diet. Finally, the social groupings were subjected to disruption through monthly redistribution of monkeys among the groups within each treatment segment. The experiment lasted 26 months, following which all animals underwent autopsy during which the coronary arteries were evaluated for atherosclerosis. Regarding atherosclerosis, we observed a significant interaction between social status and experimental condition (p less than .03). Socially dominant animals had (as in previous studies) significantly exacerbated CAA, but only in the untreated segment; the effect of social dominance on CAA was abolished by long-term administration of propranolol. The antiatherogenic effect of propranolol on dominant animals was independent of the influences of serum lipid concentrations, blood pressure, and resting heart rate. We conclude that treatment with beta-adrenergic-blocking agents may confer a degree of protection against CAA among individuals behaviorally predisposed to coronary heart disease.

Effect of atherogenic diet on lipoprotein lipase activity in cynomolgus monkeys.

Cynomolgus monkeys (Macaca fascicularis) fed monkey chow (n = 10) had a mean +/- SD post-heparin plasma lipoprotein lipase (LPL) activity level (14.7 +/- 5.5 units/ml) similar to that found in human beings (15.7 +/- 3.9 units/ml). However, the hepatic triglyceride lipase (H-TGL) in these monkeys was extremely low (0.5 +/- 0.3 units/ml) when compared with that in human beings (10.9 +/- 4.3 units/ml). The consumption of isocaloric atherogenic diets (0.2 mg cholesterol/Cal) with either saturated (P/S = 0.34) or polyunsaturated (P/S = 2.2) fat led to increased LPL activity levels (27.6 +/- 6.5 and 28.8 +/- 16.1 units/ml, respectively) and the accumulation of plasma low density lipoprotein cholesterol (LDL-C). The results indicate that cholesterol-containing atherogenic diets with either primarily saturated or polyunsaturated fat have similar potential for the increase of LPL activity. However, it is not clear whether the high dietary cholesterol content represents an obligatory component for the increase of LPL. We speculate that the high level of LPL in cynomolgus monkeys when fed a cholesterol-rich, high fat diet could be a contributing factor to the accumulation of excessive plasma LDL-C.