Fracture toughness is dependent on bone location--a study of the femoral neck, femoral shaft, and the tibial shaft.

The fracture toughness of the right femoral neck, femoral shaft, and tibial shaft of matched cadaveric bones, ages 50 to 90 years, was compared. Results of this study indicate that tensile (G(Ic)) and shear (G(IIc)) fracture toughness vary depending on bone location. The femoral neck has the greatest resistance to crack initiation for both tension and shear loading while the femoral shaft has the least.

Melatonin sensitivity to dim white light in affective disorders.

Both dim and bright light has been shown to suppress the nocturnal secretion of the pineal hormone melatonin. Early reports suggests that an abnormal response to light occurs in patients with bipolar affective disorder, where as patients with major depressive disorder respond similarly to controls. It has been suggested that this abnormal sensitivity of the melatonin response to light could be a trait marker of bipolar affective disorder.

Determination of nefazodone and its pharmacologically active metabolites in human blood plasma and breast milk by high-performance liquid chromatography.

A method is described for the determination of nefazodone and its active metabolites hydroxynefazodone, the dione BMS-180492 and m-chlorophenylpiperazine in blood plasma and expressed human milk based on reversed-phase high-performance liquid chromatography. Measurements were performed on drug-free plasma and expressed human milk spiked with nefazodone and metabolites to prepare and validate standard curves and specimens collected from nursing mothers. Parent drug and metabolites were separated from the biological matrices by solid-phase extraction using CERTIFY columns.

The evaluation of depression in inpatients with HIV disease.

Objectives: The aim of this paper is: to compare the utility of four approaches to the diagnosis of depression in patients with human immunodeficiency virus (HIV) disease; to examine the utility of four rating scales to assess the presence and severity of depression; and to devise a set of substitutive criteria that would be appropriate in patients with HIV disease.

Method: A group of inpatients was assessed using standard clinical interview. Patients found to have major depression using DSM-III-R (aetiological) criteria were assessed using inclusive, substitutive and exclusive criteria for the diagnosis of depression.

The effect of age and pre-light melatonin concentration on the melatonin sensitivity to dim light.

The hormone melatonin is secreted at night from the pineal gland, with light being a potent inhibitor of its secretion. Age related decreases in plasma melatonin concentrations have indicated that this may be related to pineal calcification with aging. Recently, it was shown that the melatonin sensitivity to light may be a biological marker of bipolar disorder.

Genetic selection of peptide inhibitors of biological pathways.

Genetic selections were used to find peptides that inhibit biological pathways in budding yeast. The peptides were presented inside cells as peptamers, surface loops on a highly expressed and biologically inert carrier protein, a catalytically inactive derivative of staphylococcal nuclease. Peptamers that inhibited the pheromone signaling pathway, transcriptional silencing, and the spindle checkpoint were isolated.

Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors.

Background: Purines constitute a structural class of protein ligands involved in mediating an astonishing array of metabolic processes and signal pathways in all living organisms. Synthesis of purine derivatives targeting specific purine-binding proteins in vivo could lead to versatile lead compounds for use as biological probes or drug candidates.

Results: We synthesized several libraries of 2,6, 9-trisubstituted purines using both solution- and solid-phase chemistry, and screened the compounds for inhibition of cyclin-dependent kinase (CDK) activity and human leukemic cell growth.

Onset of the effects of the 5-HT1A antagonist, WAY-100635, alone, and in combination with paroxetine, on olfactory bulbectomy and 8-OH-DPAT-induced changes in the rat.

5-HT1A receptor antagonists have recently been shown to accelerate the effects of some antidepressant drugs in clinical trials. In this study we investigate the effects of combining a full antagonist at the 5-HT1A receptor, WAY 100635 (0.2 mg/kg, SC) with the selective serotonin reuptake inhibitor (SSRI) paroxetine (5 mg/kg.

Effect of the menstrual cycle stage on the melatonin suppression by dim white light.

Patients with bipolar disorder have been shown to have a supersensitive melatonin suppression to dim white light (200 and 500 lux) compared to normal healthy subjects. Previous studies suggest menstrual cycle dependent changes in the melatonin rhythm, but it is not known if the melatonin sensitivity to light changes during the menstrual cycle. The present study investigated the melatonin suppression to dim white light (200 lux) in different stages of the menstrual cycle.

(+)-S-20499 -- a potential antidepressant? A behavioural and neurochemical investigation in the olfactory bulbectomised rat.

The study was designed to assess the potential antidepressant properties of the 5-HT1A receptor agonist, (+)-S-20499 (10 mg kg(-1) i.p.) in the olfactory bulbectomised (OB) rat.

Treatment of anxiety during pregnancy: effects of psychotropic drug treatment on the developing fetus.

Pregnancy is a time of great emotional change for a woman, producing increased stress and anxiety. Medication may be required for the treatment of anxiety disorders at this time. Given the fact that psychotropic drugs readily cross the placenta and could have important implications for the developing fetus, it is necessary to balance the possible effects of medication against the potential effects to both the mother and fetus if the anxiety disorder is left untreated.

Antidepressant efficacy and tolerability of the selective norepinephrine reuptake inhibitor reboxetine: a review.

Reboxetine is a unique selective norepinephrine reuptake inhibitor (NRI) with proven antidepressant efficacy in pharmacologic and biochemical tests predictive of antidepressant properties. Comprehensive clinical trials, including 8 placebo-controlled and/or active treatment-controlled studies, plus 4 open studies, have assessed the short-term and long-term efficacy and tolerability of reboxetine in patients with major depressive disorders and dysthymia. Results from a total of 690 patients who entered 5 open or placebo-controlled studies are summarized in this paper.

Neurochemical effects of the enantiomers of mirtazapine in normal rats.

The present study was designed to examine the neurochemical effects of (+/-)-mirtazapine (10 mg kg(-1) i.p.) and its enantiomers in rats.

Influence of microdamage on fracture toughness of the human femur and tibia.

The relationship between microdamage accumulation and bone fragility is not well understood. Previous work has demonstrated a positive relationship between microdamage and age in human cortical bone. Prior investigations have also demonstrated that fracture toughness decreases with age in the same bone.

Combining pindolol and paroxetine in an animal model of chronic antidepressant action--can early onset of action be detected?

The realisation that pindolol may accelerate the effects of some antidepressant drugs in clinical trials has added extra impetus to the search for faster acting antidepressants. Currently, no animal model of depression can identify potential faster acting antidepressant drugs or drug combinations. In this study, we investigate the effects of combining pindolol (2 mg/kg, s.

Evidence for 5-HT1A receptor control of pineal melatonin concentrations in the rat.

The effect of some serotonin agonists on day and night-time melatonin in the pineal gland was investigated in male rats. Dose dependent increases in nocturnal melatonin concentrations were observed for all serotonin agonists investigated. Statistically significant increases were observed only for D-fenfluramine (20 mg/kg) and the full 5-HT1A agonists S(+)-20499 (10 mg/kg, 20 mg/kg) and flesinoxan (20 mg/kg).

Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.

Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). By iterating chemical library synthesis and biological screening, potent inhibitors of the human CDK2-cyclin A kinase complex and of Saccharomyces cerevisiae Cdc28p were identified. The structural basis for the binding affinity and selectivity was determined by analysis of a three-dimensional crystal structure of a CDK2-inhibitor complex.

Negative symptoms, depression, and parkinsonian symptoms in chronic, hospitalised schizophrenic patients.

Background: Negative symptoms of schizophrenia are often confounded by overlapping depressive and parkinsonian symptoms. The role of medication as an aetiological factor in the development of these symptoms is an important issue for prevention and treatment.

Methods: A total of 45 inpatients in chronic wards who met RDC criteria for schizophrenia were assessed with the Hamilton depression rating scale (HDRS) and negative symptom rating scale (NSRS) and the targeting abnormal kinetic effect scale (TAKE).

The effect of venlafaxine treatment on the behavioural and neurochemical changes in the olfactory bulbectomised rat.

In the present study, the effect of chronic treatment with venlafaxine on beta1 and 5-HT2 receptor populations was examined in the frontal cortex of olfactory bulbectomised (OB) and sham operated (SO) animals. The effect of these drugs on the behaviour of the animals on the elevated plus maze and the "open field" was also assessed. Removal of the bulbs resulted in a characteristic increase in locomotor activity in the OB animals in the "open field" which was reversed by chronic venlafaxine treatment.

Modulation of plasma melatonin concentrations by changes in posture.

Posture change from a lying position to a standing position results in a decrease in plasma volume, which leads to an increase in plasma constituents, especially that of proteins and blood constituents bound to them. The aim of the present study was to investigate the physiological effects of postural changes on plasma nocturnal melatonin concentrations in healthy human volunteers. The study was divided into four stages.

Influence of bone composition and apparent density on fracture toughness of the human femur and tibia.

The influence of wet and dry apparent density, apparent and real percentage of mineral, organic and water contents on the tension and shear fracture toughness, i.e., the mode I and mode II strain energy release rate (GIc and GIIc), respectively, was investigated for the human femur and the tibia.

Panic in australia.

Panic disorder is widespread in Australia, often in combination with other psychiatric conditions such as agoraphobia or major depression. Pharmacotherapy for panic disorder in Australia commenced with benzodiazepines, and later progressed to tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). More recently, treatment has moved towards use of the selective serotonin reuptake inhibitors (SSRIs), which are effective and better tolerated.

The effect of atenolol, a beta1-adrenergic antagonist, on nocturnal plasma melatonin secretion: evidence for a dose-response relationship in humans.

Pineal beta1-adrenergic receptors are involved in the regulation of melatonin secretion. The involvement of beta1-adrenergic receptors has been demonstrated by the ability of acute administration of beta-antagonists to suppress the nocturnal rise of circulating melatonin and its urinary metabolite 6-sulphatoxymelatonin (aMT6s). The present study was undertaken to examine the relationship between increasing doses of atenolol and nocturnal plasma melatonin concentrations.

CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation.

The activity of cyclin-dependent kinase 2 (CDK2) is essential for progression of cells from G1 to the S phase of the mammalian cell cycle. CVT-313 is a potent CDK2 inhibitor, which was identified from a purine analog library with an IC50 of 0.5 microM in vitro.