Cerebrovascular diseases and depression: epidemiology, mechanisms and treatment

Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evidence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcortical CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after several years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neuroticism, low social support as well as genetic factors are associated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging correlate of depression. Potential mechanisms mediating the association between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have demonstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive recovery, potentially through restorative mechanisms. Psychotherapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.     

Biomechanical characterization of osseointegration: An experimental in vivo investigation in the beagle dog

This study reports the results of torsion tests, pull-out tests, and lateral Ioading tests on osseointegrated commercially pure titanium fixtures. The tests were performed in vivo on six beagie dogs. Three fixtures, each with a diameter of 3.7mm, were installed bilaterally in the tibia of each animal. The mean maximal pull-out load was 1.55 kN (n = 4) the mean maximal lateral transverse load was 0.21 kN (n = 2), the mean maximal lateral axial load was (0.18 kN (n = 2)) the mean breakpoint torque was 0.31 Nm (n = 3), and the mean maximal torque was 0.43 Nm (n = 3). The torsion test revealed an almost immediate plastic deformation of the interface between the implant and bone: this indicates that although the contact between the bone and the implant is close, there is no strong bond, at least not in shear. The major transfer of load from the implant to the surrounding bone tissue must therefore depend on the design of the implant. A histological evaluation with measurements of the amount of bone in contact with the fixtures was performed. By the use of the histological and mechanical data, it is possible to estimate shear stresses in bone tissue (pull-out test) and in the interface (torque test), The mean maximal shear stress in bone tissue in the pull-out tests was 100 MPa (n = 4); the mean shear stress in the interface was 4.3 MPa (n = 3) in the torsion tests at the breakpoint torque and was 6.0 MPa (n = 3) at the maximal torque. It was also possible to estimate the shear modulus of elasticity in the pull-out and torque tests. The mean shear modulus in pull-out was 119 MPa (n = 4), and the mean apparent shear modulus in torsion was 9 kPa (n = 3) for an assumed interface thickness of 100 nm and was 86 kPa (n = 3) for an assumed interface thickness of 1.000 nm.     

Absolute determination of molar masses of standard polystyrenes by means of sedimentation-diffusion measurements in cyclohexane

Accurate measurements of the sedimentation coefficients at unit pressure and zero-concentration s, the diffusion coefficients at zero concentration D₀, and the intrinsic viscosities [η] were conducted at theta-conditions (cyclohexane, 34,5°C) on 11 polystryrene standard samples with narrow molar mass distribution. These samples with nominal mass-average molar masses (5 · 10⁴ < M_w < 2 · 10⁶ g · mol^?1), provided by three manufacturers for the use as calibration standards, were the same as in the previous paper of this series summarizing our measurements in toluene. Logarithmic correlations between s, D₀ and [η] are linear with deviations lower than ± 3% and indicate good consistency of all three independent sets of measured quantities. The molar masses M_sD as determined from s and D₀ by means of the Svedberg equation are in very good accordance with those previously determined in toluene, but for most samples the M_sD are lower than the nominal values M_w as given by the manufacturers. For some standards the deviations amount to 15?35% and cannot be explained by experimental errors or by the polydispersity of the samples. On the other hand, two pairs of standards exhibit the same values of s, D₀ and [η] in both solvents, although the nominal molar masses differ by 20%. These results lead to the conclusion that the experimentally determined M_sD values are more reliable characteristics of the standard samples than the nominal M_w values and that the sedimentation-diffusion technique is a powerful, though laborious, tool for an absolute determination of the molar mass.     

Hemodialysis in the Treatment of Chronic Schizophrenic Patients: A Double-Blind Crossover Study

In order to examine the reported beneficial effects of hemodialysis in chronic schizophrenic patients, a double-blind crossover study was carried out. Of the 47 patients considered for treatment, 10 diagnosed as chronic schizophrenics according to the Feighner and DSM-III criteria were accepted to the study. Seven of these patients completed the full program, four of whom belonged to a large family with a high incidence of schizophrenia. All patients were on antipsychotic medication throughout the study. Psychopathological evaluations were performed regularly in a blind fashion using the Comprehensive Psychopathological Rating Scale (CPRS) and the Nurse Observation Scale for Inpatient Evaluation (NOSIE-30). Samples of blood, urine, cerebrospinal fluid, and dialysate were obtained for examination. Three patients improved during active dialysis and two patients improved during sham treatment. Improvement in the five patients took place during the first treatment period. This study failed to demonstrate a therapeutic effect of hemodialysis superior to the sham procedures.     

Release of corticotropin after administration of corticotropin-releasing hormone in depressed patients in relation to the dexamethasone suppression test

The possible hypersecretion involvement of corticotropin-releasing hormone (CRH) in the pathophysiology of hypothalamic-pituitary-adrenocortical axis disturbances in patients with major depressive episode and with an abnormal dexamethasone suppression test (DST) was investigated. The corticotropin (ACTH) and cortisol response to the injection of 45 μg of synthetic human CRH at 1630 were analyzed in 24 inpatients with normal (suppressors) or abnormal (nonsuppressors) DST. The outcome of the DST was analyzed using 3 cut-off points for the cortisol levels. The clinical assessments included two rating scales. The results showed that nonsuppressors had a significantly lower ACTH response to CRH stimulation than suppressors at all cut-off points (calculated as net area under the curve and as the difference between the peak and the baseline level) despite no significant differences in the severity of depression.     

Studies of some characteristics of molecular dissolution kinetics from rotating discs

The maximum mass transfer from solid to liquid phase i.e. the intrinsic rate of dissolution has been shown to be experimentally accessible with good precision using a generalized rotating disc method in combination with extrapolation to infinite speed of revolution and/or infinite distance from the disc to the center of rotation. The method has with very good result been applied to the determination of dissolution rates from non-disintegrating discs of sulfamethizole and alaproclate hydrochloride in water. In the present paper assumptions for the theory of such experiments are reviewed and compared with numerical values for a number of characteristic kinetic parameters applying simple mathematical models. This comparison supports the assumptions made. The modified rotating disc method described in this paper could therefore be recommended as part of a preformulation program for new solid drug compounds.