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Validation of a 40 MHz B-scan ultrasound biomicroscope for the evaluation of osteoarthritis lesions in an animal model.

OBJECTIVE: To evaluate high frequency (40 MHz) B-mode ultrasound for the detection of osteoarthritis (OA) lesions of varying severity in an animal model of OA. DESIGN: Ultrasound biomicroscopy (UBM) was performed on the femoral articular surface of adult rabbits with unilateral transection of the anterior cruciate ligament at 4, 8 and 12 weeks post-surgery and on control rabbits. The articular cartilage was examined and graded macroscopically and histologically for OA lesions. Histological examination was used as a reference to determine sensitivity and specificity of ultrasonographic and macroscopic examination regarding fibrillation and ulceration of articular cartilage. RESULTS: Identification of slight surface irregularities was made possible with UBM. The sensitivity and specificity of UBM were 92.3% and 96.4%, respectively, to detect histological fibrillation and 90.9% and 97.6%, respectively, to identify histological ulceration. Macroscopic examination using India Ink had a sensitivity and specificity of 80% and 96.4%, respectively, for fibrillation and 90.9% and 90.5%, respectively, for ulceration when compared to histology. A high correlation (rsp=0.90) was found between ultrasonographic and histological scores. CONCLUSIONS: UBM of articular cartilage reflects histological structure and can accurately detect early changes such as fibrillation. UBM has the potential to be a valuable tool for the in vivo identification of early lesions of OA and for monitoring the disease or efficacy of novel therapy if it can be packaged in a minimally invasive format suitable for intra-articular imaging.

Animals↗

Sealing ability of three materials in the orifice of root canal systems obturated with gutta-percha.

There were 130 single roots randomly assigned to one of 12 experimental or two control groups. Forty specimens each were sealed with 1, 2, 3, or 4 mm of Cavit, ProRoot MTA, or Tetric. After creation of a uniform orifice diameter, the smear layer was removed and the canal systems obturated using warm lateral compaction of gutta-percha (GP). GP was removed to the experimental depth, experimental materials placed in the orifice, and roots submerged in India ink in a vacuum flask. Specimens were demineralized and leakage measured using a 10x stereomicroscope and graded for depth of leakage by one calibrated, blinded rater. There was no significant interaction (p > 0.05) between test materials and orifice depths, nor main effect of orifice depth (p > 0.05). However, there was a statistically significant main effect of test materials with Tetric demonstrating a significantly better seal than Pro Root or Cavit (p < 0.0001) irrespective of orifice depth.

Aluminum Compounds↗

The effect of formalin storage on the apical microleakage of obturated canals.

Infection control guidelines recommend disinfection of extracted teeth in 10% formalin for 2 weeks before use. Although extracted teeth are routinely used for in vitro endodontic research, the potential influence of formalin has not been evaluated. The purpose of this study was to investigate the effect of formalin storage on the apical seal integrity of obturated canals. There were 100 single-rooted human teeth decoronated, accessed, and randomly divided into four groups. Group 1 was composed of specimens that were instrumented and obturated after extraction without storage in formalin. Groups 2, 3, and 4 were stored in formalin for 2, 4, and 8 weeks, respectively, before treatment. Canals were instrumented to a master apical file size #7 ProFile .04 Taper Series 29 and obturated with Obtura II thermoplasticized gutta-percha and Roth 801 sealer. The teeth were immersed in India ink, cleared, and the greatest extent of linear dye leakage was measured. Microleakage testing displayed significantly less microleakage after 2 and 4 weeks of formalin storage. Leakage measurements after 4 weeks of storage were 62.3% lower than nonfixed specimens. The 8-week storage group demonstrated lower dye penetration compared with the nonfixed group; however, the difference was not statistically significant. Within the scope of this study, storage of extracted teeth in formalin for 2 and 4 weeks resulted in a significant decrease in apical microleakage compared with nonfixed specimens.

Analysis of Variance↗

Distraction osteogenesis of the canine mandible: the impact of acute callus manipulation on vascularization and early bone formation.

PURPOSE: Manipulations of the newly created regenerate, using adjustable multiplanar devices during distraction osteogenesis or as a 1-step molding procedure at the end of the distraction process, may be necessary to correct the position of the mandible. Treatment of complex deformities may require preplanned major angulation provided by adjustable devices. We sought to assess the effects of molding the fresh regenerate on vascularization and early bone formation within clinically relevant dimensions. MATERIALS AND METHODS: Evaluation of the nature of the problem in mechanical terms was based on a geometrical model, its dimensions chosen with clinical relevance. Custom-made devices, allowing the simultaneous compression and stretching of a regenerate 10 mm long, were fixed bilaterally in the angular region of beagle mandibles (n = 14). Angulation of 20 degrees (n = 7) or 30 degrees (n = 7) was performed immediately after ending the lengthening period, and the animals were killed after a 7-day consolidation period. The vascular system was stained via intravital Procion red infusion and post mortem carbon ink (Deperussol P130; Degussa AG, Frankfurt, Germany) perfusion to assess possible damages. Qualitative and quantitative evaluations of the mineralized tissue were performed with contact radiography, quantified computed tomography, and histologic assessment. RESULTS: The only finding indicating mechanical forces acting on the regenerate was related to orientation of the collagenous fibers. Vascular damage was not observed. Mineralization patterns were identical in both the compressed and the stretched zone. The degree of angulation had no visible impact on early bone formation, even if compression and stretching of the regenerate at a range of 33% to 54% exceeds most clinical requirements. However, the amount of callus formation differed independent of the shaping angle, revealing parameters other than the degree of angulation to be important. CONCLUSIONS: Although the newly forming bone is highly sensitive to nonphysiologic strain during the lengthening process, a completed fresh regenerate, created by distraction osteogenesis, can be manipulated to a considerable extent without endangering early callus formation. Manipulation of the regenerates would provide a precise final result, minimizing the need for secondary corrections and diminishing treatment duration and costs.

Animals↗

A technique to detect and to quantify fasciocutaneous blood vessels in small laboratory animals ex vivo.

PURPOSE: A microangiographical technique is described, which allows visualization of small and capillary blood vessels and quantification of fasciocutaneous blood vessels by means of digital computer analysis in very small laboratory animals. MATERIALS AND METHODS: The left carotid artery of 20 nu/nu mice was cannulated (26 gauge) and a mixture of gelatin, bariumsulfate, and green ink was injected according to standardized protocol. Fasciocutaneous blood vessels were visualized by digital mammography and analyzed for vessel length and vessel surface area as standardized units [SU] by computer program. RESULTS: With the described microangiography method, fasciocutaneous blood vessels down to capillary size level can be clearly visualized. Regions of interest (ROIs) can be defined and the containing vascular network quantified. Comparable results may be obtained by calculating the microvascular area index (MAI) and the microvascular length index (MLI), related to the ROIs size. Identical ROIs showed a high reproducibility for measured [SU] < 0.01 +/- 0.0012%. CONCLUSION: Combining microsurgical techniques, pharmacological knowledge, and modern digital image technology, we were able to visualize small and capillary blood vessels even in small laboratory animals. By using our own computer analytical program, quantification of vessels was reliable, highly reproducible, and fast.

Angiography↗

Lung regeneration: implantation of fetal rat lung fragments into adult rat lung parenchyma.

OBJECTIVE: The capability of regeneration of lung tissues in adults is limited after chronic destruction. Bone marrow-derived stem cells, retinoic acid, growth factors, and other approaches have been attempted to promote or facilitate this process. We hypothesized that fetal lung tissues, with great potential for growth and differentiation, could be used for lung regeneration. METHODS: Day 17 fetal lung tissue fragments at the pseudoglandular stage of lung development from Lewis rats were implanted into adult Lewis rat lungs. For group 1, fetal lung fragments were injected into the adult left lung parenchyma; for group 2, fetal fragments were injected with the left lung partially resected; for group 3, adult fragments were injected; and for groups 4 and 5, fetal fragments were implanted into the omentum and subcutaneous tissue, respectively. RESULTS: The grafts implanted into pulmonary parenchyma were differentiated with opening of the alveolar space after 4 weeks and were advanced further with morphologic features similar to those of neonatal lungs after 8 and 12 weeks. The implants were connected with pulmonary circulation determined by means of perfusion with India ink. These changes appeared to be further enhanced in animals with partial lung resection that might have facilitated the maturation of implanted fetal lung tissues through mechanical factors, soluble factors, or both. Fetal lung tissues did not mature when implanted into the omentum or subcutaneous tissue. Adult lung fragments did not expand after being reimplanted back into the same animal. CONCLUSIONS: Fetal lung tissue might be an option for further investigation into lung regeneration.

Age Factors↗

Vascular endothelial growth factor naked DNA gene transfer enhances thrombus recanalization and resolution.

OBJECTIVES: Enhancing thrombus resolution may reduce the long-term complications of venous thrombosis. The aim of this study was to examine whether a sustained release of vascular endothelial growth factor (VEGF) would further improve thrombus recanalization. METHODS: Inferior caval vein thrombosis was induced in a cohort of 21 male Wistar rats. A plasmid encoding the human VEGF gene (phVEGF) was injected directly into thrombus (30 to 50 microg) and the muscle adjacent to the inferior vena cava (300 to 400 microg). A plasmid containing the gene encoding beta-galactosidase (pCMVbeta) was injected into the same sites of a separate cohort of rats to act as a control. Tissues were harvested after 1 and 2 weeks, and beta-galactosidase activity was measured to estimate transfection efficiency. Muscle and serum VEGF were measured by enzyme-inked immunosorbent assay. Thrombus size, recanalization, and organization were determined by computer-assisted image analysis. RESULTS: The efficiency of control plasmid transfection into muscle was about 1%. No serum hVEGF was detected in phVEGF- or pCMVbeta-treated animals. Significantly raised levels of hVEGF (P < .01) were detected in the muscle injected with phVEGF after 2 weeks compared with control muscle. There was a significant reduction in thrombus size of 23% (P < .05) and 48% (P < .001) in phVEGF-treated animals compared with pCMVbeta-treated controls after 1 and 2 weeks, respectively. Thrombus recanalization was a significantly greater in the phVEGF-treated group after 2 weeks (mean 19% +/- 2% [SEM]) compared with controls (mean 13% +/- 2%, P < .01). There were no differences in the thrombus organization score. CONCLUSION: VEGF gene therapy of venous thrombus resulted in smaller thrombi with greater recanalization. Angiogenic gene therapy may form the basis of a novel treatment that may improve the resolution of venous thrombi. CLINICAL RELEVANCE: Deep vein thrombosis may lead to residual venous obstruction or reflux and result in post-thrombotic complications that are debilitating and have a substantial socioeconomic impact. Enhancing the resolution of venous thrombi may reduce post thrombotic complications.

Animals↗

A Genomic Alteration in GATA3 Affects Treatment Responses With a CDK4/6 Inhibitor Collaborating With p18INK4C Expression in Advanced Breast Carcinoma.

Cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) with endocrine therapy benefits patients with hormone receptor-positive, human epidermal growth receptor 2-negative breast carcinomas. However, most tumors develop resistance to CDK4/6i during the course of therapy. Although preclinical studies have proposed molecular mechanisms for the resistance, predictive markers are yet to be discovered. We investigated the tumor molecular profiling in 42 patients with advanced-stage breast carcinoma who received CDK4/6i therapy. The tumors carrying a GATA-binding protein 3 (GATA3) gene mutation, mainly a frameshift variant, showed a better treatment response compared with other tumors. Furthermore, we explored the potential underlying mechanism of this association. To that end, nuclear expression of p18, one of the INK family proteins, was found to be positively associated with the GATA3 mutation, as well as a CDK4/6i treatment response. Therefore, our study suggests that a GATA3 gene mutation, collaborating with p18 protein expression in tumor nuclei, may have a predictive value for CDK4/6i therapy in breast carcinoma.

Humans↗

In vitro mutagenicity and metabolism of the cycloaliphatic epoxy Cyracure UVR 6105.

Cyracure UVR 6105 is a cycloaliphatic epoxy monomer and has both carboxylate and epoxy groups, with the potential for rapid polymerization. It is widely used in industry for the preparation of inks, resins, coatings, and was proposed for incorporation into dental composites. The objective of this study was to determine the mutagenic potential of this chemical related to its metabolite products. Several doses of Cyracure UVR 6105 were dissolved in DMSO and subjected to the Ames Salmonella mutagenicity assay. A metabolic activation system (S9-mix) was used consisting of Arochlor-induced liver S9 homogenate enriched with NADP and glucose-6-phosphate cofactors. In contrast to studies without S9-mix, Cyracure UVR 6105 exhibited enhanced genotoxic activities with strains TA100 and TA1535 in the presence of liver S9-mix. From in vitro metabolism of Cyracure UVR 6105 with S9-mix, as used in the Ames assay, several metabolites were identified. The alcohol metabolite, 3,4-epoxycyclohexylmethanol, containing intact epoxy group was identified in the organic solvent extract. This metabolite was synthesized and proved to be mutagenic against TA100 when assayed in the presence and absence of S9-mix. Results showed that the increased mutagenicity of Cyracure UVR-6105 in the presence of liver enzymes is due to the formation of the mutagenic metabolite 3,4-epoxycyclohexylmethanol.

Animals↗

Intraventricular administration of hepatocyte growth factor treats mouse communicating hydrocephalus induced by transforming growth factor beta1.

Communicating hydrocephalus may occur spontaneously in elderly patients or occur as a complication of meningitis or intracranial hemorrhage, typically as a result of fibrosis along the route of cerebrospinal fluid (CSF) flow. Hepatocyte growth factor (HGF) has anti-fibrotic properties and is a promising candidate for the treatment of various fibrotic diseases. Thus, the goal of this study was to examine the effect of exogenous HGF (30 microg of human recombinant (hr) HGF intraventricularly for 7 or 14 days) in a model of hr transforming growth factor beta1-induced communicating hydrocephalus in C57BL/6 mice. HGF treatment resulted in a reduction of ventriculomegaly, as demonstrated by magnetic resonance imaging, and improved spatial memory. Further, ink passage test demonstrated improvement of normalized CSF in flow in mice receiving HGF treatment as opposed to delayed CSF flow in the hydrocephalic mice at baseline. Finally, histological examination in hydrocephalic mice undergoing HGF treatment revealed reduction of collagen fibers in the meninges and normalization of their structures. These results indicate that exogenous HGF may be of utility in the treatment of hydrocephalus in humans.

Animals↗

Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation.

The contribution of nitric oxide (NO) to capsaicin-evoked airway responses was investigated in rats. The measurement of plasma NO level, airway dynamics, airway smooth muscle electromyogram, and plasma extravasation by India ink and Evans blue leakage technique was adapted. Capsaicin-evoked hypotension, bronchoconstriction, trachea plasma extravasation as well as increases in plasma NO level in a dose-dependent manner. L-732138 (NK1 receptor antagonist) or SR-48968 (NK2 receptor antagonist) pretreatment reduced capsaicin-enhanced hypotension, bronchoconstriction, plasma extravasation, and plasma NO level. N(G)-nitro-L-Arginine methyl ester (L-NAME, 10 mg/kg, i.v.), a non-selective NO synthase (NOS) inhibitor, or aminoguanidine (10 mg/kg, i.v.), a selective inducible NOS (iNOS) inhibitor, reduced capsaicin-induced increases in plasma NO level and protected against capsaicin-induced plasma extravasation, whereas L-arginine (150 mg/kg, i.v.), a NO precursor, enhanced capsaicin-evoked plasma NO level and plasma extravasation. L-Arginine pretreatment ameliorated capsaicin-induced bronchoconstriction, whereas L-NAME and aminoguanidine exaggerated capsaicin-induced bronchoconstriction. In summary, NK1 and NK2 receptors and iNOS play a role in NO formation and on capsaicin-induced bronchoconstriction and plasma extravasation. NO generated by iNOS counteracts tachykinin-mediated bronchoconstriction, but exacerbates tachykinin-mediated plasma extravasation.

Animals↗

EEG/(f)MRI measurements at 7 Tesla using a new EEG cap ("InkCap").

We aimed at improving the signal-to-noise ratio (SNR) of electroencephalography (EEG) during magnetic resonance imaging (MRI) by introducing a new EEG cap ("InkCap") based on conductive ink technology. The InkCap was tested with temperature measurements on an electrically conductive phantom head and during structural and functional MRI (fMRI) recordings in 11 healthy human volunteers at 7 T. Combined EEG/fMRI measurements were conducted to study the interaction between the two modalities. The EEG recordings with the InkCap demonstrated up to a five-fold average decrease in signal variance during echo-planar imaging, with respect to a cap made of standard carbon fiber leads. During concurrent EEG/fMRI measurements in human volunteers, alpha oscillations were clearly detected at 7 T. Minimal artifacts were present in the T2* and high-resolution structural MR images of the brain parenchyma. Our results show that the InkCap technology considerably improves the quality of both EEG and (f)MRI during concurrent measurements even at 7 T.

Adult↗

Gerbilline cholesteatoma development Part I: Epithelial migration pattern and rate on the gerbil tympanic membrane: comparisons with human and guinea pig.

OBJECTIVE: To determine the migration rate and pattern for keratin on the tympanic membrane (TM) of the gerbil and guinea pig in comparison to human data and determine which species is an appropriate model for investigating the relationship of epithelial clearance to cholesteatoma formation. STUDY DESIGN AND SETTING: Ink drops were placed on the TM and their locations plotted daily. RESULTS: Gerbils demonstrated a radial migration pattern away from the umbo, identical to that reported for humans, although the rate was 0.32 mm/day-3 times the human rate of 0.1 mm/day. Guinea pigs were significantly different from gerbils and humans, with a rate of 0.79 mm/day and a pattern of superior/inferior migration without anterior-posterior movement. CONCLUSION: Gerbils more closely resemble humans in rate and pattern of epithelial migration. SIGNIFICANCE: Gerbils represent the most appropriate model for determining the relationship between keratin migration and cholesteatoma formation.

Animals↗

Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its [Lys-8]-substituted analog.

The predicted conformation of ranatuerin-1 (SMLSVLKNLG(10)KVGLGFVACK(20)INK QC), an antimicrobial peptide first isolated from the skin of the bullfrog Rana catesbeiana, comprises three structural domains: alpha-helix (residues 1-8), beta-sheet (residues 11-16) and beta-turn (residues 20-25). Circular dichroism studies confirm significant alpha-helical character in 50% trifluoroethanol. Replacement of Cys-19 and Cys-25 by serine resulted only in decreased antimicrobial potency but deletion of either the cyclic heptapeptide region [residues (19-25)] or the N-terminal domain [residues (1-8)] produced inactive analogs. Substitution of the glycine residues in the central domain of the [Ser-19, Ser-25] analog by lysine produced inactive peptides despite increased alpha-helical content and cationicity. The substitution Asn-8-->Lys gave a ranatuerin-1 analog with increased alpha-helicity and cationicity and increased potency against a range of Gram-positive and Gram-negative bacteria and against C. albicans but only a small increase (21%) in hemolytic activity. In contrast, increasing alpha-helicity and hydrophobicity by the substitution Asn-22-->Ala resulted in a 3.5-fold increase in hemolytic activity. Effects on antimicrobial potencies of substitutions of neutral amino acids at positions 4, 18, 22, and 24 by lysine were less marked. Strains of pathogenic E. coli from different groups showed varying degrees of sensitivity to ranatuerin-1 (MIC between 5 and 40 microM) but [Lys-8] ranatuerin-1 showed increased potency (between 2- and 8-fold; P < 0.01) against all strains. The data demonstrate that [Lys-8] ranatuerin-1 shows potential as a candidate for drug development.

Amino Acid Substitution↗

Morphological signs of cirrhosis regression. Experimental observations on carbon tetrachloride-induced liver cirrhosis of rats.

Regression of hepatic cirrhosis is a controversial issue. Recently, a list of histopathological features, observed in human material, was suggested as a hallmark of cirrhosis in the process of regression. An investigation for the presence of these morphologic features was performed at monthly intervals in rats with proved carbon tetrachloride (CCl4)-induced cirrhosis over a period of 9 months following discontinuation of treatment, using sequential liver biopsies. Within the first 4 months, features of the "hepatic repair complex" were identified, together with the enlargement of the hepatic nodules and thinning of the fibrous septa. Subsequent to the 4 months, the histological picture, composed of large and inconspicuous nodules and delimited by thin and frequently incomplete fibrous septa "incomplete septal cirrhosis", appeared to be stabilized. These fibrous septa, when injected with India ink from the portal trunk, presented blood vessels that were seen to drain directly into the sinusoids. These findings suggested that when the cause of cirrhosis is removed, the liver may adapt itself to a new and permanent structure, probably compatible with normal or near-normal function, which may render hepatic cirrhosis clinically, although not morphologically, reversible.

Animals↗

Pathogenesis of septal fibrosis of the liver. (An experimental study with a new model.).

Septal fibrosis is an important, frequent, and non-specific type of fibrosis associated with chronic liver diseases, but its pathogenesis is still poorly understood. An interesting model of septal fibrosis occurs in rats infected with the nematode Capillaria hepatica. This model was used to investigate the pathogenesis, site of origin, structure, and cell-types of septal fibrosis. Forty young adult Wistar rats were inoculated with 800 embryonated eggs of C. hepatica. Daily liver samples were obtained from the 20th to the 39th day after inoculation to cover the critical period when septal fibrosis usually starts. Routine histology, electron microscopy, immunohistochemistry, and indirect immunofluorescence were applied to the study of liver sections. Septal blood vessels were demonstrated by India ink perfusion of the portal vein system. Prominent angiogenesis was observed to precede collagen deposition. Besides angiogenesis and mesenchymal-cell mobilization, septal fibrosis was seen to originate from portal spaces and to course through acinar zone I in between sinusoids, inducing no alterations in them, with no evident participation of stellate hepatic cells. Septal fibrosis appeared as an adaptative type of response of the liver to chronic injury, which resulted in a new structure that is normal to other species and creates accessory vessels that drain portal blood into hepatic sinusoids.

Animals↗

Stroop performance in pathological gamblers.

Pathological gambling is a relatively prevalent psychiatric disorder that typically leads to severe family, social, legal, and occupational problems and is associated with a high rate of suicide attempts. Understanding the neurobiological basis of pathological gambling is a current focus of research, and emerging data have demonstrated that pathological gamblers may have impaired decision-making because of an inability to inhibit irrelevant information. In this study, we examined pathological gamblers by using the Stroop Color-Word Test, a neurocognitive task used to assess interference control. The "reverse" variant of the Stroop Color-Word Test was administered to a cohort of medication-free pathological gamblers (n=62) and a cohort of age-matched controls (n=83). In the reverse variant of the Stroop task, subjects are asked to read the meaning of the word rather than name the ink color. The reverse Stroop task was chosen because it highly discriminates ability to inhibit interference in a population of psychiatric patients. In our study, performance on the reverse Stroop task in the pathological gamblers was significantly slower and less accurate than in the healthy subjects. A new finding in our study was that for pathological gamblers, the average reaction time in the neutral condition (where the color names are displayed in black letters) was slower than the average reaction time in the incongruent condition (where the meaning of the color name and the color of the printed letters are different). This controlled study extends previous findings by showing that performance on the Stroop task is impaired in a sample of medication-free pathological gamblers.

Adult↗

Monoclonal antibody against E selectin attenuates subarachnoid hemorrhage-induced cerebral vasospasm.

BACKGROUND: Increasing evidence indicates that inflammatory responses are implicated in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). However, the role of adhesion molecules in SAH-induced vasospasm is less clear. This study was designed to examine the effect of a highly specific antibody, monoclonal anti-E-selectin antibody, on cerebral vasospasm in a new murine SAH model. METHODS: Experimental SAH was induced in C57Black/6J mice by injecting autogenous blood into the cisterna magna, and anti-E-selectin antibody was administered intravenously immediately after SAH. All animals were killed by perfusion-fixation 24 hours after SAH. The diameters of anterior cerebral arteries (ACAs) were measured after arteries were cast with gelatin and india ink. Peripheral white blood cell count was also investigated. RESULTS: The average diameters of ACA were reduced by 22% and 25% in the SAH only and SAH plus vehicle groups, respectively, when compared with the healthy control group. After treatment with 12.5, 4, and 1 microg of anti-E-selectin antibody in mice subject to SAH, the average diameter of ACA was decreased by 9%, 10%, and 22%, respectively, when compared with the healthy control group. The protective effects of anti-E-selectin antibody achieved statistical significance at doses of 12.5 and 4 microg. Animals in the SAH only and SAH plus vehicle groups exhibited leukopenia. Administration of 12.5, 4, and 1 microg of anti-E-selectin antibody reduced leukopenia, and the total white blood cell count obtained in animals treated with 12.5- and 4-microg doses were significantly higher as compared with SAH animals. CONCLUSIONS: These findings provide the first evidence that anti-E-selectin antibody was effective in prevention of SAH-induced vasospasm and imply a possible role of E selectin in the pathogenesis of vasospasm after SAH.

Animals↗