PubMed Health⌕ Search

Biomedical subjects

M A Bush

Publications and source records attributed to M A Bush.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacokinetics and pharmacodynamics of 7-nitroindazole, a selective nitric oxide synthase inhibitor, in the rat hippocampus.

PURPOSE: This study was conducted to assess the pharmacokinetics and pharmacodynamics of 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (NOS). METHODS: Male Sprague-Dawley rats were equipped with peritoneal/ venous cannulae and a microdialysis probe in the hippocampal cortex. Rats received 7-NI in peanut oil (25 mg/kg) ip every 2 h for 14 h or peanut oil alone. Blood samples were obtained at timed intervals for serum 7-NI; brain tissue microdialysate for determination of extracellular 7-NI and NO was obtained every 20 min. A pharmacokinetic-pharmacodynamic model was constructed to evaluate the effects of 7-NI on NOS activity. RESULTS: Consistent with previous reports. NOS activity in controls evidenced circadian variation. These cyclic changes in NO production were incorporated into the model of 7-NI effects on NOS. 7-NI produced a rapid (within 2 h) decrease in hippocampal NO. Under the conditions of this experiment, 7-NI produced an approximately 50% decrease in hippocampal NO, which was sustained during 7-NI administration. The decrease in NOS activity by 7-NI was concentration-dependent with an apparent IC50 of approximately 17 microg/ml. CONCLUSIONS: Multiple ip injections of 7-NI result in a predictable, sustained decrease in NO production in the hippocampus. The pharmacokinetic-pharmacodynamic model developed allows design of dosing regimens that can produce designated changes in brain NO content, facilitating use of 7-NI to probe the pharmacological implications of NO in the central nervous system.

Algorithms↗
PubMed2001

Pharmacokinetics and pharmacodynamics of recombinant FGF-2 in a phase I trial in coronary artery disease.

Fibroblast growth factor-2 (FGF-2) is a heparin-binding protein capable of inducing angiogenesis in multiple animal models of chronic ischemia. The pharmacokinetics and pharmacodynamics of a single dose of recombinant FGF-2 (rFGF-2) administered by intracoronary or intravenous infusion were evaluated in a Phase I trial in 66 patients with severe coronary artery disease. rFGF-2 displayed biphasic elimination with a mean studywide distribution t1/2 of 21 minutes and a mean apparent terminal elimination t1/2 of 7.6 hours. Systemic exposure to rFGF-2 was comparable following intracoronary or intravenous administration. Peak plasma concentration and area under the concentration-time curve increased proportionally with dose, indicating linear pharmacokinetics over the dose range examined (0.33 to 48.0 micrograms/kg). Greater systemic exposure was observed when heparin was administered closer to rFGF-2 infusion, consistent with slower clearance of heparin/rFGF-2 complexes. Infusion of rFGF-2 was associated with changes in acute hemodynamics. While a clear PK/PD dose-response relationship was not established, a trend toward hypotension and tachycardia with higher rFGF-2 doses was observed.

Adult↗
PubMed2000

Pharmacokinetics and protein binding of the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole.

Utilization of nitric oxide (NO) synthase (NOS) inhibitors to probe the role of NO in various central nervous system processes requires use of an inhibitor selective for neuronal NOS, and is facilitated by knowledge of the pharmacokinetics of the inhibitor. The present project was undertaken to elucidate the disposition of the selective neuronal NOS inhibitor 7-nitroindazole (7-NI). A simple, specific HPLC assay was developed with requisite sensitivity to quantitate 7-NI in serum after administration of pharmacologically relevant doses. Further experiments were performed to assess the effects of administered dose on 7-NI disposition. 7-NI displayed marked nonlinearity, consistent with saturable elimination, when administered by ip injection in peanut oil. The nonlinearity was related to total dose, but not to the concentration of 7-NI in the vehicle. Binding of 7-NI in rat serum was concentration-independent and does not contribute to the nonlinearity. Various formulations for iv administration of this water-insoluble compound were evaluated; the optimal vehicle, from the standpoint of 7-NI solubility, appeared to inhibit the clearance of 7-NI from the systemic circulation. Considering the nonlinear disposition of 7-NI, knowledge of the pharmacokinetics of this inhibitor is requisite to designing administration protocols to achieve the desired magnitude and duration of NOS inhibition.

Animals↗
PubMed1997

What can be done about home health fieldwork?

The literature indicates that health care is moving away from institutional care and specialization to the community and home where providers need generalist competencies. As educators strive to prepare students for this environment, fieldwork experiences in the community and home are opportunities for students to develop generalist competencies. Because of the current scarcity of fieldwork sites, in general, scheduling placements is difficult. As educators seek new sites, home health settings and therapists who provide home health care as a component of their service need to be considered. Home health occupational therapy requires a practitioner to adopt a holistic perspective in order to assist clients to function optimally in their home environment. Because a large number of students work in addition to taking classes, they can be encouraged to find jobs as home health aides or chore providers as part-time employment before and during their didactic education. This work experience can help them to acculturate to the home setting. By encouraging students' participation in home health experiences, educators are helping to facilitate generalist competencies.

Home Care Services↗
PubMed1995

Spherical grip strength in children 3 to 6 years of age.

OBJECTIVE: The purpose of this study was to establish normative data on spherical grip strength of children 3 to 6 years of age with the Martin Vigorimeter. METHOD: Two hundred twenty-five preschoolers in the Kalamazoo, Michigan, area were tested with standardized positioning and instructions. The mean of three trials for each hand was used as the grip-strength score. A repeated measure design was used and the right and left hands were alternated during testing to allow a 20-sec rest period between trials. Hand width also was measured in inches from the head of the second metacarpal to the head of the fifth metacarpal. RESULTS: Hand width and grip strength were significantly correlated for both the right (p < .0001) and the left hands (p < .001). Grip strength increased linearly across all of the age groups (p < .001). The results of paired t tests did not show a significant difference in grip strength between the right and left hands or between boys and girls. A table of mean grip-strength scores and hand width measurements along with their standard deviations is presented for clinical use. CONCLUSION: The vigorimeter could be used to assess the grip strength of children with rheumatic disorders without putting excessive pressure on the joints or skin of the hand.

Anthropometry↗
PubMed1992

Comparison of performance in materials-based occupation, imagery-based occupation, and rote exercise in nursing home residents.

Materials-based occupation, imagery-based occupation, and rote exercise have been examined individually by several researchers. The present study compares all three approaches with one another (i.e., kicking a balloon, imagining kicking a balloon, and a control rote exercise) in nursing home residents. The dependent variable was the number of exercise repetitions. The subjects were 12 women and 3 men between 56 and 93 years of age residing in two nursing homes. All subjects experienced the three approaches but in different orders. One-way analysis of variance for related measures indicated a significant difference among conditions (p = .004). The Tukey procedure (Stevens, 1986) determined that the materials-based occupation condition elicited significantly more repetitions than the other two conditions. The difference between the imagery-based occupation and rote exercise was not statistically significant. These findings support our profession's historical emphasis on the use of physical materials to enhance performance.

Activities of Daily Living↗
PubMed1992

A method to redefine stays on the 1985 National Nursing Home Survey.

This report describes a method for standardizing definitions of episodes of nursing home care in the 1985 National Nursing Home Survey. The method shows how the information on nursing home admissions and discharges collected on the Current and Discharged Resident Questionnaires can be used to redefine the endpoints of nursing home stays. The report also explains how errors caused by missing and inconsistent nursing home admission and discharge data were resolved.

Bias↗
PubMed1990

Adding purpose to the repetitive exercise of elderly women through imagery.

Many studies have documented the effectiveness of verbally elicited imagery in the enhancement of motor skills in young, nondisabled populations. The present study examined the effects of verbally elicited imagery in the encouragement of two exercises (i.e., reaching up to pick apples and reaching down to pick up coins) in elderly women. The subjects were 27 women between 62 and 96 years of age who were selected from a nursing home, a residential retirement home, and a foster care home. All of the subjects received imagery as well as control conditions, but in a counterbalanced fashion. The Wilcoxon matched-pairs signed rank tests indicated that the imagery condition elicited significantly more repetitions of the reaching-up exercise than did the control condition (z = 2.25, p [one-tailed] = .012). The results in the reaching-down exercise were generally in the same direction but difficult to interpret statistically. The results are discussed in terms of other recent research investigating ways to add purpose to therapeutic exercise through occupation. Clinicians are urged to explore the advantages and disadvantages of imagery-based occupations in treatment.

Aged↗
PubMed1988

Exogenous insulin therapy slows weight loss in type 2 diabetic patients.

The impact of exogenous insulin therapy on the ability of obese, noninsulin dependent diabetic patients to lose weight was studied. Weight loss data from seven insulin-requiring type 2 diabetic patients, 11 sulfonylurea-treated type 2 diabetic patients and 12 non-diabetic controls on very-low-calorie diets were analyzed. Upon starting the diet, insulin doses were reduced by 50 percent and given once daily as intermediate-acting insulin. Doses were adjusted to maintain capillary blood glucoses between 6.7 and 10 mM. Sulfonylureas were stopped upon initiation of the diet. Patients were seen weekly for determination of their dietary compliance, medical status, glucose control, activity level and amount of weight loss. The insulin-treated subjects lost significantly less weight per week, whether expressed as kilograms, change in body mass index or percent of initial body weight lost. Treatment of obese type 2 diabetic patients with insulin retards their ability to lose weight independent of caloric intake.

Adult↗
PubMed1986

Effects of caloric restriction and exercise on insulin receptors in obesity: association with changes in membrane lipids.

We have studied the effects of supervised caloric restriction and exercise on mononuclear leukocyte lipid composition, membrane fluidity, and insulin receptors in ten nondiabetic obese adults, (175 +/- 9.3% of ideal body weight) and ten normal adult subjects. In a second study, we examined the effects of caloric restriction alone using a very low calorie liquid diet in the treatment of another ten obese adults. In both groups of obese adults, fasting insulin levels were elevated and fell to normal levels following treatment. Insulin binding to monocytes, which was reduced in obese subjects, increased toward normal after short-term treatment; this was due to the restoration of total insulin binding capacity to levels one half of that seen in the normal adult group. Obese subjects undergoing either treatment had elevated membrane cholesterol/phospholipid ratios prior to treatment (0.499 +/- 0.050 and 0.446 +/- 0.011 v 0.400 +/- 0.025 mol/mol in normal adults P less than 0.005 by ANOVA). Prior to treatment, for all subjects there was a significant inverse correlation between insulin tracer binding and membrane cholesterol/phospholipid ratios (r = .484, n = 34, P less than 0.005). This relationship did not change significantly in obese subjects in either treatment group. Cell membrane microviscosity was determined by fluorescence polarization (FP) using DPH (2 X 10(-6) mol/L). Prior to weight loss, obese subjects had significantly higher FP values than controls (0.304 +/- 0.006 and 0.319 v 0.259 +/- 0.009, P less than 0.005, by ANOVA) indicating greater microviscosity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Protein phosphorylation in a myogenic cell line: effects of insulin, epinephrine and glucose.

Protein phosphorylation was studied in L6 cultured muscle cells by incubating cells with Na 32Pi and subsequently exposing them to external agents. L6 cells readily incorporated 32Pi into a number of peptides approaching steady-state incorporation by 2 h. Insulin stimulated the phosphorylation of one peptide of molecular mass 29,000 daltons by 37% with an ED50 of 3 mU/ml. This peptide was located in the high-speed pellet (105,000 g 60 min) which is consistent with an S6 ribosomal protein. Epinephrine (10(-5) M) led to only a modestly stimulated (less than 14%) phosphorylation of three peptides of molecular masses 39,000, 29,000 and 21,000 daltons. Glucose (5-50 mM) stimulated the phosphorylation of one peptide of molecular mass 19,000 daltons by 24%.

Autoradiography↗
PubMed1979

Insulin and the phosphorylation of intracellular proteins.

Protein phosphorylation is a ubiquitous form of posttranslational protein modification in mammalian cells which often serves to regulate protein function. Insulin alters the activity of a number of enzymes known to be regulated via phosphorylation. With the premise that altered protein phosphorylation might be an obligatory intermediate step in insulin action, we have examined the effects of insulin on the phosphorylation of the major phosphopeptides in adipocytes and hepatocytes. Insulin affects overall protein phosphorylation in two ways: 1) Insulin selectively stimulates the phosphorylation of a major peptide in adipose tissue (MW 123,000) and liver (MW 46,000) through a mechanism independent of cAMP and the cAMP-dependent protein kinase. Net dephosphorylation is not observed with insulin as the sole hormone. 2) Insulin antagonizes cAMP-directed protein phosphorylation. The mechanism of insulin-stimulated phosphorylation and the possible role of this phenomenon in overall insulin action is discussed.

Adipose Tissue↗