In vitro and in vivo effects of selenium and selenium with vitamin E on platelet functions in diabetic rats relationship to platelet sorbitol and fatty acid distribution

In vitro 30 min of incubation with selenomethionine (Sm) + vitamin E multiplied by about five platelet selenium (Se) decreased significantly platelet thrombin and ADP-induced aggregation decrease. Four groups of streptozotocin-induced diabetic rats were fed with a supplemented purified diet with an Se-rich yeast (Selenion): DSel, Sm: DSm, Sm alpha-tocopherol: DSmE or unsupplemented diet: D. After 24 wk of supplementation, only a decrease in thrombin-induced aggregation in group DSel compared to DSm and DSmE and D was observed. However, after 24 wk of diet compared to 14 wk, in group D and DSm, a significant increase in thrombin-induced aggregation occurred (p < 0.0001), whereas a significant decrease in groups DSel and DSmE (p < 0.0001, p < 0.03) was noted. After 21 wk of diet, in DSmE, platelet adhesion to fibronectin was significantly decreased compared to group D (p < 0.05). These changes in DSmE were associated with a significant decrease in platelet sorbitol (p < 0.02) and a very significant increase in platelet Se (p < 0.0005). Sm associated with vitamin E would appear more efficient to prevent oxidative damage of diabetic platelet membrane and thus to modulate its hyperactivity.     

In vivo vascular freezing in clinical microvascular transfer

Free flap transfer to the lower limb in chronic post-traumatic conditions is known to have a higher complication rate, with flap loss in up to 10% of cases, due mainly to the recipient vessels (Godina: Plast Reconstruct Surg 78:285-291, 1986]). The dissection of these vessels often leads to refractory spasm, due to the so-called perivascular post-traumatic disease (PVPTD) (Khouri [Clin Plast Surg 19:773-785, 1992]). A case is presented of the use of a fairly new spasmolytic maneuver, i.e., in vivo vascular freezing, in a patient who developed intractable spasm of the recipient artery.     

In vitro and in vivo calcification of vascular bioprostheses

Efficacy of different chemical treatments on calcification of vascular graft in vitro and in vivo was studied. Culture medium-filled rat aortas were separately treated in 0.2% glutaraldehyde and epoxy compound, and photooxidized in 0.01% methylene blue for a shorter period (group 1). Another group of rat aortas were separately treated in the same chemicals for a longer period (group 2). All fresh and treated aortas of both groups were cultured for 21 days in an organ culture medium and implanted (except for group 1) in weanling rats for five months. Histology and immunohistochemistry revealed that differently treated aortas of group 1 grow and calcify, and the smooth muscle cells between elastin fibers are the primary site of calcium deposition. In contrast, differently treated aortas of group 2 neither grew, nor did calcify in the medium except the epoxy compound cross-linked aorta of group 2 which did not grow but did calcify. Untreated aorta did not calcify. All fresh and differently treated aortic homografts calcified severely in rats. Our whole arterial segment-calcification system would be useful for analyzing the molecular and cellular mechanisms of both bioprosthetic and atherosclerotic calcification of vascular graft. New anticalcification technique is the only hope for better outcome of future vascular bioprostheses.     

In vivo (31)P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice

The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using (31)P magnetic resonance spectroscopy (MRS), fluorescence microscopy and two-dimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (P(i)/NTP) ratio increased rapidly as mean intervascular distances increased from 100 microm to 300 microm. Two morphometric parameters - the percentage of intervascular distances larger than 200 microm (ivd200) and the non-perfused area fraction at a distance larger than 100 microm from a nearest perfused vessel (area100), - were deduced from these experiments and related to the P(i)/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the P(i)/NTP ratio increased linearly with the percentage of ivd200 and the area100.     

In vivo evidence of the critical role of cadherin-5 in murine vascular integrity

Vascular endothelial cell-cell adhesion is crucial for the regulation of vascular functions and is associated with many circulatory disorders. We isolated a rat monoclonal antibody (VECD1) recognizing the mouse vascular endothelial cell adhesion molecule and found that it inhibited vascular endothelial cell-cell association. We sequenced a full-length cDNA of the antigen that was identical to mouse cadherin-5. L-cells transfected with its cDNA acquired cell-cell adhesiveness, and these transfectants reacted with VECD1 at cell-cell contact areas. We studied the role of mouse cadherin-5 in vascular functions. The addition of VECD1 antibody to a cultured vascular endothelial cell line (F-2) caused the detachment of each cell. Although normal F-2 cells formed tubular structures on Matrigel, VECD1 disturbed the tubulogenesis. VECD1 also increased the permeability through the F-2 cell layer. To clarify the in vivo function of mouse cadherin-5, we intraperitoneally injected the hybridomas producing VECD1 into adult mice. Severe venous stasis and subcutaneous hemorrhage were induced within several days after the injection, resulting in the early death of the animals. These findings are evidence of an essential role of cadherin-5 in the regulation of vascular endothelial cell-cell adhesion in vivo.     

Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.     

In vitro and in vivo biodurability of a compliant microporous vascular graft

We examined the extent to which program integrity (i.e., the degree to which programs were implemented as planned) was verified and promoted in evaluations of primary and early secondary prevention programs published between 1980 and 1994. Only 39 of 162 outcome studies featured specified procedures for the documentation of fidelity. Of these, only 13 considered variations in integrity in analyzing the effects of the program. Lowered adherence to protocol was often associated with poorer outcome. There was mixed evidence of dosage effects. The omission of integrity data, particularly measures of adherence, may compromise the internal validity of outcome studies in the prevention literature. We do not view procedures for integrity verification as inconsistent with the adaptation of interventions to the needs of receiving communities.     

Cognitive profiles of mild cognitive impairment with and without vascular disease.

This study examined whether the cognitive profile of subjects with mild cognitive impairment (MCI) with vascular disease differs from that of MCI subjects with no vascular disease. Consecutive MCI subjects with vascular disease (n=60) and matched MCI subjects with no vascular disease (n=60) were included in the study and were compared with healthy control subjects (n=60). The neuropsychological assessment comprised tests of speed and attention, episodic memory, visuospatial function, language, and executive function. Control subjects performed significantly better than did both MCI groups on the neuropsychological battery. MCI subjects with no vascular disease performed better overall than did MCI subjects with vascular disease, most clearly on tests of speed and attention, visuospatial function, and executive function. MCI subjects with and without vascular disease exhibited differences, both in terms of overall performance and of cognitive profiles. These differences can be largely explained by deficits in speed and attention and in executive function of the MCI subjects with vascular disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation of thrombosis with increased platelet turnover in thrombocytosis

There are no readily applicable methods to routinely assess thrombosis risk and treatment response in thrombocytosis. Reticulated platelets (RP) define the most recently released platelets in the circulation, and the RP% has been shown to estimate platelet turnover in thrombocytopenic states. We examined whether increased RP values were associated with thrombotic complications in thrombocytosis. Platelet count, RP%, and absolute RP count were measured at presentation in 83 patients with chronic or transient thrombocytosis, 46 patients with deep vein (DVT) or arterial (ART) thrombosis and normal platelet counts, and 83 healthy controls with normal platelet counts. Chronic thrombocytosis patients presenting with thrombosis (n = 14) had significantly higher RP% (14.7% +/- 10. 1%, mean +/- SD) than asymptomatic chronic thrombocytosis patients (n = 23, RP% = 3.4% +/- 1.8%), healthy controls (3.4% +/- 1.3%), DVT patients (n = 21, 3.8% +/- 2.1%), or ART patients (n = 25, 4.5% +/- 4.1%, P < .05 for all comparisons). Chronic thrombocytosis patients with thrombosis also had significantly higher absolute RP counts than asymptomatic chronic thrombocytosis patients (98 +/- 64 x 10(9)/L [range, 54 to 249 x 10(9)/L] v 30 +/- 13 x 10(9)/L [range, 11 to 51 x 10(9)/L]; P = .0004), whereas healthy controls, DVT, and ART patients had similarly low absolute RP counts (6 +/- 6 x 10(9)/L, 9 +/- 7 x 10(9)/L, and 11 +/- 7 x 10(9)/L, respectively; P > .49). The RP% and absolute RP counts remained significantly higher in chronic thrombocytosis patients with thrombosis when patients were further subdivided into primary myeloproliferative disorders versus secondary thrombocytosis. Similarly elevated RP percentages and absolute counts were also noted in transient thrombocytosis patients with thrombosis (n = 6, 11.5% +/- 4.4% and 90 +/- 46 x 10(9)/L, respectively) when compared with asymptomatic transient thrombocytosis patients (n = 40, 4.5% +/- 2.7% and 35 +/- 16 x 10(9)/L, respectively) and to all control groups (P < .05 for all comparisons). In addition, 7 of 8 thrombocytosis patients who were studied before developing symptoms of thrombosis had elevated absolute RP counts compared with only 1 of 63 thrombocytosis patients who remained asymptomatic. Follow-up studies in seven chronic thrombocytosis patients showed that successful aspirin treatment of symptomatic recurrent thrombosis significantly reduced the RP% from 17.1% +/- 10.9% before therapy to 4.8% +/- 2.0% after therapy; absolute RP counts decreased from 102 +/- 67 x 10(9)/L to 26 +/- 10 x 10(9)/L (P < .01 for both). We conclude that thrombosis in the setting of an elevated platelet count is associated with increased platelet turnover, which is reversed by aspirin therapy. Measurement of reticulated platelets to assess platelet turnover may be useful in evaluating both treatment response and thrombotic risk in thrombocytosis.     

In vivo and in vitro studies of the inhibitory effect of propofol on human platelet aggregation

BACKGROUND: The inhibitory effects of propofol on platelet aggregation are controversial because the fat emulsion used as the solvent for propofol may affect platelet function. The effects of propofol on platelet intracellular calcium ion concentration and on aggregation were investigated. METHODS: Platelet aggregation was measured in 10 patients who received an intravenous infusion of propofol. Intralipos, the propofol solvent, was infused in 10 healthy volunteers and platelet aggregation were measured. The in vitro effects of propofol and Intralipos on platelets were also investigated. The inhibitory effects of various concentrations of propofol were studied. The effects of propofol on the changes in intracellular calcium level using a fluorescent dye, fura-2, were also observed. Template bleeding time was measured to determine the effect of propofol in clinical use. RESULTS: Platelet aggregation was significantly inhibited by infusion of propofol, although bleeding time was not prolonged. Intralipos did not inhibit platelets either in vivo or in vitro. Propofol significantly inhibited platelet aggregation in vitro and at 5.81 +/- 2.73 microg/ml but not at 2.08 +/- 1.14 microg/ml. The increase of intracellular calcium concentration was inhibited both in influx and discharge of calcium. CONCLUSIONS: Propofol inhibited platelet aggregation both in vivo and in vitro. Inhibition of platelet aggregation appeared to be caused by propofol itself and not by the fat emulsion. This inhibitory effect was also supported by the suppressed influx and discharge of calcium. No change in the bleeding time suggests that this inhibitory effect does not impair hemostasis clinically.     

In vivo study of halothane hepatotoxicity in the rat using magnetic resonance imaging and 31P spectroscopy

Using magnetic resonance imaging (MRI) and spectroscopy (MRS), in vivo halothane hepatotoxicity was assessed in male Wistar rats. With 1.5% halothane in 100 or 20% O2, an edematous region, characterized by increased intensity on T2 weighted images and an increase in regional tissue water content (rho water), was seen proximal to the hepatic portal vein in the liver. Both spin-lattice relaxation (T1) and spin-spin relaxation (T2) increased in this region, relative to distal regions of the liver. Similarly, a high signal intensity on proton density weighted images was observed in this area. As halothane anaesthesia progressed, a decrease in the adenosine triphosphate-inorganic phosphate ratio (ATP/Pi) and an increase in the phosphomonoester-phosphodiester (PME/PDE) ratio was detected in the liver. In addition, intracellular pH decreased and intracellular free magnesium concentration [Mg2+] increased with time of exposure. Excessive vacuolation, ribosomal disappearance from rough endoplasmic reticulum, mitochondrial swelling and fragmentation of smooth endoplasmic reticulum were observed by transmission electron microscopy (TEM) in samples from the edematous region of the liver.     

In vivo quantification of brain volumes in subcortical vascular dementia and Alzheimer''s disease. An MRI-based study

Ibuprofen is one of the most effective and widely used non-steroidal analgesic and anti-inflammatory agent. It is marketed as a racemic mixture though it is known that the pharmacological activity resides in the (S)-(+)-enantiomer only. Several direct/indirect liquid chromatographic methods involving a variety of chiral/achiral phases along with their possible role in resolution, chiral and achiral agents used for derivatisation have been discussed with special reference to ibuprofen, and mentioning their application to the resolution of other 2-aryl-propionic acids/profens.     

Time-based prospective memory impairment in patients with thalamic stroke.

The role of the thalamus in memory is potentially very complex. However, most studies on the memory impairments of thalamic lesions have focused on retrospective memory, rarely on prospective memory. To explore the effect of thalamic lesions on event-based prospective memory (EBPM) and time-based prospective memory (TBPM), respectively, and to verify the hypothesis that the thalamus is involved in the prospective memory, EBPM and TBPM tasks were administered to 18 thalamic stroke patients and 18 age- and education-matched healthy controls. In the EBPM task, subjects were asked to perform an action whenever particular words were presented. In the TBPM task, subjects were asked to perform an action at certain times. Compared with the performance of healthy controls on EBPM and TBPM tasks (EBPM, 4.3 ± 1.5; TBPM, 5.4 ± 1.0), there was a significant difference in the performance of thalamic stroke patients in the TBPM tasks (2.4 ± 1.6), but no difference was found in EBPM tasks (3.7 ± 1.1). These results may indicate that the thalamus is involved in PM and particularly in TBPM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Forgetting in traumatic brain-injured patients with persistent memory impairment.

The rate of forgetting words, pictures, and designs was assessed in a subsample of individuals with moderate to severe traumatic brain injury (TBI) who showed disproportionately severe persistent memory impairment. Relative to control Ss, the patients had an abnormally fast rate of forgetting pictures, but not words or designs. TBI patients with persistent memory impairment may process some forms of information inefficiently but do not appear to have a fundamental deficit in memory consolidation. This finding may be related to the tendency of TBI patients to less readily apply encoding strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vivo kinetics of lipoprotein(a) in homozygous Watanabe heritable hyperlipidaemic rabbits

In vivo kinetics of lipoprotein(a) [Lp(a)] were investigated in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits (an animal model of familial hypercholesterolemia (FH)), and in normolipidemic Japanese White rabbits (controls). 125I-labelled Lp(a) and 131I-labelled LDL were simultaneously injected intravenously. Blood samples were then taken periodically. Kinetic parameters were calculated from the plasma radioactivity decay curves. The fractional catabolic rates (FCRs) of both Lp(a) and LDL (1.355 +/- 0.189 pools per day and 1.278 +/- 0.397 pools per day, respectively) in the WHHL rabbits were significantly (P < 0.005) smaller than those in the control rabbits (2.008 +/- 0.083 pools per day and 2.855 +/- 0.759 pools per day, respectively). In WHHL rabbits, the FCRs of Lp(a) and LDL were similar. However, in control rabbits, the FCR of Lp(a) was significantly (P < 0.01) smaller than that of LDL. In WHHL rabbit organs, the mean ratio of 125I-Lp(a): 131I-LDL, 48 h after injection, normalized to the corresponding isotope ratio in plasma, were 1.525, 1.020, 1.819 and 1.967, in liver, kidney, spleen and bile, respectively. These values were significantly higher than the corresponding values in control rabbits (0.590, 0.677, 0.862 and 0.766, respectively). Our data strongly suggest that Lp(a) clearance is not entirely dependent upon LDL receptors and may be mediated by some other mechanisms.     

The autoregulation of the skin microcirculation in healthy subjects and diabetic patients with and without vascular complications

PURPOSE: To identify risk factors for mortality after postoperative myocardial infarction. METHOD: Retrospective study of 266 patients. RESULTS: The crude in-hospital mortality rate was 25%. This was more than twice as high as the mortality rate in patients admitted from home with an acute myocardial infarction. Women with postoperative infarction were the same age as men, but had a lower Acute Physiology and Chronic Health Evaluation (APACHE) II score prior to infarction (P = 0.03) and a higher crude mortality rate. Multivariate analysis showed that female gender (relative risk 2.2, 95% confidence limits 1.2 to 4.2), current cigarette smoking (relative risk 2.3 [1.2 to 4.7]), a history of congestive heart failure (relative risk 2.1 [1.04 to 4.1], resuscitation status (relative risk 8.1 [2.0 to 32.9]), and high preoperative APACHE II score were significant independent predictors of in-hospital mortality. CONCLUSION: Postoperative myocardial infarction is one of the most serious events a patient can experience. Women and current smokers are at especially high risk for mortality after postoperative myocardial infarction.     

In vivo aortic muscle cell growth kinetics. Differences between thoracic and abdominal segments after intimal injury in the rabbit

Focal proliferation of smooth muscle cell (SMC) is an integral part of atherosclerotic plaque formation: characterization of regional variation in SMC growth kinetics is therefore important to the understanding of atherogenesis. SMC growth kinetics of rabbit abdominal and thoracic segments were compared. Rabbit aortas were denuded of endothelium and the animals killed after 3H-thymidine and Evans blue injections at 0 to 48 days after denudation. Incorporation of 3H-thymidine into both aortic segments peaked at 48 hours; no detectable incorporation occurred in the first 24 hours. Abdominal segment DNA specific activity (SA, dpm/micrograms DNA) and total kinetic activity (TKA, dpm/0.1 mm internal elastic lamina) at 48 hours were significantly greater than values for the thoracic aorta. Abdominal SA and TKA curves decreased exponentially after the 48-hour peak and parallel thoracic levels after day 7. SA and TKA values for each segment reflected the subsequent SMC intimal growth rates as measured morphometrically. Therefore, both segments share similar growth kinetic characteristics; however, the abdominal response to initimal injury is greater than the thoracic and leads to greater myointimal proliferation. The difference in response to injury in the two segments suggests regional variation in SMC's which are phenotypically similar.