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Biomedical subjects

S Farley

Publications and source records attributed to S Farley.

13 recordsLinked to original sources
PubMed2007

Calcineurin (protein phosphatase 2B) is involved in the mechanisms of action of antidepressants.

Calcineurin (PP2B) is a Ca(2+)-dependent protein phosphatase enriched in the brain that takes part in intracellular signaling pathways regulating synaptic plasticity and neuronal functions. Calcineurin-dependent pathways are important for complex brain functions such as learning and memory. More recently, they have been suggested to play a role in the processing of emotional information. The aim of this study was to investigate whether calcineurin may be involved in the effect of antidepressants. We first found that chronic antidepressant treatment in mice leads to an increase of calcineurin levels in the hippocampus. We then studied the behavioral and molecular responses to fluoxetine of mice with a genetic overactivation of calcineurin in the hippocampus (constitutively-activated calcineurin transgenic mouse line #98, CN98 mice). We observed that CN98 mice are more sensitive to the behavioral effect of fluoxetine and desipramine tested in the tail suspension test. Moreover, the basal expression of growth factor brain-derived neurotrophic factor and subunit 1 of AMPA glutamate receptor, GluR1, both of which are modified after chronic antidepressant administration, are altered in the hippocampus of CN98 mice. These results suggest that calcineurin-dependent dephosphorylation plays an important role in the mechanisms of action of antidepressants, providing a new starting point for developing improved therapeutic treatments for depression.

Animals↗
PubMed2001

Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease.

Convenient techniques for measuring rates of bone turnover have been developed in recent years with the advent of biochemical markers of bone metabolism. One recent of these techniques is a collection method and quantitative enzyme immunoassay for free pyridinoline crosslinks in human sweat. The concentrations of pyridinoline crosslinks in 5-day sweat collections and first morning void and 24-hour urine collections from healthy subjects and subjects with established metabolic bone disorders were determined. T-scores were higher in the sweat system than in the urine system by up to 10-fold in postmenopausal subjects, women with hyperparathyroidism, and subjects with postmenopausal osteoporosis. For subjects with postmenopausal osteoporosis, receiver-operating characteristic curve analysis yielded areas under the curve of 0.699, 0.629, and 0.520 for sweat pyridinoline, first morning void urine pyridinoline, and 24 hour urine pyridinoline respectively. The areas under the curve of the sweat and first morning void urine measurements were significantly greater (p<0.05) than the 24-hour pyridinoline measurements. Healthy postmenopausal subjects and subjects with postmenopausal osteoporosis were monitored before and during estrogen replacement therapy or alendronate therapy. Sweat pyridinoline values declined by 49.0 +/- 12.4% and 19.4 +/- 19.9% for estrogen and alendronate subjects respectively. We conclude that this non-invasive technique is a sensitive and specific measure of bone resorption and is appropriate as an adjunct to techniques such as bone density and may also be useful in monitoring of response to anti-resorptive therapies.

Adult↗
PubMed1998

A comparative bear model for immobility-induced osteopenia.

The National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) are seeking solutions to the human problem of osteopenia, or immobility-induced bone loss. Bears, during winter dormancy, appear uniquely exempted from the debilitating effects of immobility osteopenia. NIH and ESA, Inc. are creating a large database of metabolic information on human ambulatory and bedrest plasma samples for comparison with metabolic data obtained from bear plasma samples collected in different seasons. The database generated from NASA's HR113 human bedrest study showed a clear difference between plasma samples of ambulatory and immobile subjects through cluster analysis using compounds determined by high performance liquid chromatography with coulometric electrochemical array detection (HPLC-EC). We collected plasma samples from black bears (Ursus americanus) across 4 seasons and from 3 areas and subjected them to similar analysis, with particular attention to compounds that changed significantly in the NASA human study. We found seasonal differences in 28 known compounds and 33 unknown compounds. A final database contained 40 known and 120 unknown peaks that were reliably assayed in all bear and human samples; these were the primary data set for interspecies comparison. Six unidentified compounds changed significantly but differentially in wintering bears and immobile humans. The data are discussed in light of current theories regarding dormancy, starvation, and anabolic metabolism. Work is in progress by ESA Laboratories on a larger database to confirm these findings prior to a chemical isolation and identification effort. This research could lead to new pharmaceuticals or dietary interventions for the treatment of immobility osteopenia.

Animals↗
PubMed1997

Serum fluoride and serum osteocalcin levels in response to a novel sustained-release monofluorophosphate preparation: comparison with plain monofluorophosphate.

In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n = 9) or placebo (n = 8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5-10 microM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p < 0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p < 0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.

Aged↗
PubMed1997

Antidiabetic agents.

Explore the source record for details and available documents.

Diabetes Complications↗
PubMed1994

Pharmacokinetic profile of a new fluoride preparation: sustained-release monofluorophosphate.

The pharmacokinetic profiles of a sustained-release monofluorophosphate (MFP-SR) preparation (76 mg) and of plain MFP (76 mg) were compared in six osteoporotic females. These studies were performed in a randomized, crossover, double-blind design to select a preparation that would result in therapeutic serum levels while avoiding high serum peak values. Following a single dose of 76 mg MFP-SR, the serum fluoride levels remained within the accepted therapeutic range (5-10 microM/liter) for 24 hours. In contrast, following a single dose of 76 mg plain MFP, serum fluoride levels exhibited a wide circadian fluctuation and serum levels approximately threefold higher than those of the MFP-SR preparation (9.5 +/- 1.6 vs 3.5 +/- 0.8 microM/liter, P < 0.005). Compared with plain MFP, the sustained-release MFP had a significantly lower peak concentration (Cmax MFP-SR: 10.6 +/- 3 vs CmaxMFP: 18.9 +/- 5 microM/liter, P < 0.005) and a significantly longer absorption lag time (TmaxMFP-SR 7.3 +/- 1.6 vs TmaxMFP: 3.0 +/- 0.6 h, P < 0.05). Twenty-four-hour urinary fluoride excretion after ingestion of plain or SR fluoride was significantly increased from pretreatment values documenting absorption with either MFP formulation. Our results show that the use of sustained-release MFP preparation that we tested prevents the development of high peak levels associated with the use of plain MFP preparations. Furthermore, a single dose of MFP-SR resulted in serum fluoride levels within the accepted range of 5-10 microM/liter for 24 hours.

Aged↗
PubMed1994

Interpretation bias in responses to ambiguous cues in pain patients.

Pain patients and control subjects responses to ambiguous cues were compared in two separate investigations. In the first, pain patients, control subjects and physiotherapists were asked to produce a list of spontaneous associations to ambiguous cues (such as terminal and growth). To control for mood effects the experiment was repeated with three more groups: Pain patients, osteopaths and a control group. Measures of anxiety and depression were incorporated in the analysis. Results indicate that pain patients systematically produce more pain related associations than the other groups, and that this effect is independent of anxiety and depression levels. The discussion concentrates on the implications of these findings both for the theory of pain processing and for clinical interventions.

Adult↗
PubMed1994

The effect of fluoride therapy on blood chemistry parameters in osteoporotic females.

To determine the potential adverse effects, if any, of long-term fluoride ingestion in humans, samples were collected from 25 adult females taking daily doses of fluoride (mean, 23 mg elemental F) for the treatment of osteoporosis and from 38 osteoporotic female controls. Patients in the fluoride group had been receiving therapy for approximately 18 months with a mean duration of 4.2 years and had serum fluoride values of at least 10 mumol/l. Laboratory analyses for fluoride were conducted on plasma, urine and drinking water samples collected from each panelist. Blood was also collected for blood chemistry analyses and plasma lymphocytes were examined for the frequency of sister chromatid exchange (SCE). Plasma and urine fluoride levels were significantly different between the two groups, while water fluoride was not. The SCE frequency, a measurement of potential genotoxicity, did not differ between the two groups. Of the blood chemistry parameters measured, albumin, alkaline phosphatase, sodium, chloride, the albumin/globulin (A/G) ratio, indirect bilirubin, lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) were found to be significantly different between the two groups (P < or = 0.05). However, none of the mean group values were outside stated normal ranges for any of these parameters. We conclude that the risk of developing adverse systemic effects from the ingestion of fluoride, at dosages and for a duration comparable with that of our panel, is minimal.

Aged↗
PubMed1993

Evidence that fluoride therapy increases trabecular bone density in a peripheral skeletal site.

We measured the spinal bone density (SBD) and femoral condyle bone density (FCD) in normal and osteoporotic females (n = 219) both before and during fluoride therapy. SBD and FCD in untreated osteoporotics were significantly lower (P < 0.05) than those in the age-matched controls. SBD and FCD were correlated in the untreated (r = 0.62; P < 0.0001) as well as in the fluoride-treated osteoporotics (r = 0.42; P < 0.0001). SBD and FCD were significantly increased (P < 0.05) in response to fluoride therapy. The average rates of increase in FCD and SBD were similar (1.3 +/- 1.3 vs. 1.24 +/- 1.4 mg/cc.month). We conclude that the osteogenic action of fluoride is not limited to the axial skeleton. An increase in trabecular bone density also occurs at peripheral weight-bearing sites such as the femoral condyle.

Aged↗
PubMed1992

Factors associated with intestinal amyloidosis in pigtailed macaques (Macaca nemestrina).

Factors associated with intestinal amyloidosis in pigtailed macaques (Macaca nemestrina) were studied in 74 cases at the Washington Regional Primate Research Center. The medical records of monkeys during the 5-year period from 1983 to 1988 were analyzed to determine the age at death, age at first episode of diarrhea, number of episodes of diarrhea, episode and cumulative duration of diarrhea, and etiologies of diarrhea. Univariate analysis, using one control for each case, indicated that only episode duration was related to intestinal amyloidosis. Affected monkeys had significantly longer mean episode durations of diarrhea. None of the etiologies examined--bacteria, protozoa, fungi, and simian retrovirus--were significant risk factors for amyloid deposition in the intestinal tract.

Age Factors↗
PubMedDate not supplied

After the funding is gone: evaluating the sustainability of a community-based project.

The Rural Elderly Enhancement Project was a nurse-initiated grant funded by the W.K. Kellogg Foundation and administered by an urban school of nursing. The major purpose of the nine-year grant was the development of a model of community participation and empowerment. An informal evaluation was conducted to assess the communities' perception of the project and to determine the sustainability of the project's initiatives. A random sample of individuals from community agencies, schools, and churches were interviewed by six senior baccalaureate nursing students enrolled in a community nursing course. Results demonstrated that the communities had a very positive view of the project and that many project initiatives were sustained and have expanded.

Aged↗