Singlet oxygen induced cerebral vasospasm: an experimental study in rats

A new experimental model is described which can be used as an alternative to study the effects of subarachnoid hemorrhage (SAH) in rats. Vasospasm of the basilar artery is induced photochemically after transpalatal illumination of intracisternally injected rose bengal in two different rat strains. Singlet oxygen, generated in the subarachnoid space, elicits vasospasm which has been demonstrated angiographically at 90 min and 24 h after photosensitisation. Sprague Dawley rats responded better than Wistar rats. Dilution of rose bengal in water was more vasospastic than dilution of rose bengal in artificial CSF. Since the action of singlet oxygen is similar to that of free radicals, this experiment gives an argument for the hypothesis that free radicals play a leading role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage.     

Fibroepithelial polyps of the ureter. Etiology, diagnosis, treatment and pathology

In order to draw attention to this rather rare condition affecting all age groups, 4 cases of fibroepithelial polyps of the ureter are reported. Conservative surgery is mandatory after adequate preoperative work-up. The pathological findings, incidence and diagnostic and therapeutic modalities are discussed and some etiological factors proposed.     

Total-body protein turnover in parenterally fed neonates: effects of energy source studied by using [15N]glycine and [1-13C]leucine

The effects of nonprotein energy source (ie, glucose only vs glucose and lipid) on nitrogen retention and total-body protein turnover were studied in 20 parenterally fed newborn infants. All infants received approximately 3 g amino acids and 80-90 kcal.kg body wt.d. Total-body protein synthesis was estimated by using three constant-infusion, end-product methods: enrichment of urinary urea and ammonia in response to a [15N]glycine label and exhaled carbon dioxide enrichment in response to a [1-13C]leucine label. No differences were seen in nitrogen retention between the two energy sources. The estimate of total-body protein turnover obtained from the 13C label was similar to that obtained with the [15N]urea label. No differences in turnover rates were observed between the two diet groups. Use of the glucose-plus-lipid fuel system enhanced energy storage and the reutilization of amino acid for protein synthesis.     

Stemmed femoral knee prostheses: Effects of prosthetic design and fixation on bone loss

Although the revision rates for modern knee prostheses have decreased drastically, the total number of revisions a year is increasing because many more primary knee replacements are being done. At the time of revision, bone loss is common, which compromises prosthetic stability. To improve stability, intramedullary stems are often used. The aim of this study was to estimate the effects of a stem, its diameter and the interface bonding conditions on patterns of the bone remodeling in the distal femur.

We created finite element models of the distal half of a femur in which 4 types of knee prostheses were placed. The bone remodeling process was simulated using a strain-adaptive bone remodeling theory. The amount of such remodeling was determined by calculating the changes in bone mineral density in 9 regions of interest from simulated DEXA scans.

The computer simulation model showed that revision prostheses tend to cause more bone resorption than primary ones, especially in the most distal regions. Predicted long-term bone loss due to a revision prosthesis with a thin stem equalled that around a prosthesis with an intercondylar box. However, strong regional differences were found- the stemmed prostheses having more bone loss in the most distal areas and some bone gain in the more proximal ones. A prosthesis with a thick stem led to an increase in bone loss. When the prosthesis-cement interface was bonded, more bone loss was predicted than with an unbonded interface. These results suggest that a stem which increases stability initially may reduce stability in the long term. This is due to an increase in stress shielding and bone resorption.     

Activation of glucocorticoid receptors and the effect of naloxone during hemorrhagic hypotension.

Evidence indicates that endogenous opioid peptides and glucocorticoids participate in the control of cardiovascular regulation during hemorrhagic shock. In the present study, we investigated a possible interaction between brain opioid peptides and adrenal corticosteroids regarding the control of arterial pressure during hemorrhage. The bleeding volumes required to lower arterial pressure to 80, 60 and 40 mmHg were studied in anesthetized sham-operated (SHAM) and adrenalectomized (ADX) rats. I.c.v. administration of 10 micrograms of naloxone resulted in a significant increase in the bleeding volume required to lower arterial pressure from 60 to 40 mmHg in SHAM animals, whereas no effect of naloxone was observed in ADX animals. Replacement therapy with a 100% corticosterone pellet (100 mg, s.c.), but not with a 12.5% corticosterone pellet (12.5 mg corticosterone and 87.5 mg cholesterol, s.c.), resulted in an effect of naloxone on the bleeding volume in ADX animals. The effect of replacement therapy could be inhibited by i.c.v. pretreatment with the synthetic glucocorticoid receptor antagonist, RU38486 (100 ng). These data suggest that (1) opioid mechanisms are involved in the regulation of blood pressure during hemorrhage, and (2) occupancy of glucocorticoid receptors is required for naloxone to exert its hemodynamic effect during hemorrhagic hypotension in ADX rats.     

Simulated home treatment of depression with nortriptyline

1. Twenty-two patients hospitalized for treatment of depression were treated under conditions simulating those of home treatment. 2. Full doses of nortriptyline, from 100 to 150 mg/day, were started after baseline observations were made. 3. Two patients were dropped from the study, one for orthostatic hypotension, one for an aberrant response to nortriptyline. Two additional patients developed orthostasis which was easily managed. Otherwise no unusual side effects were noted. 4. After six days of treatment, 9 of 20 patients showed significant improvement with an overall reduction in scores on the Hamilton Depression Scale of 49% for the entire group. 5. Using the weight-adjusted dosage schedule, 18 of the 21 patients attained plasma concentrations of nortriptyline within the presumed therapeutic range; however, no clear relationship could be established between plasma concentrations and clinical response. 6. With proper selection of patients, it should be possible to treat at home some patients who currently are considered to require hospitalization.     

The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.     

Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)