Biomedical subjects

M C Chang

Publications and source records attributed to M C Chang.

At least 73 records · Page 4Linked to original sources

PubMed1999

Thrombin activates the growth, cell-cycle kinetics, and clustering of human dental pulp cells.

Thrombin is activated during vascular injury and inflammation of the dental pulp. In the present study, we found that thrombin can stimulate the proliferation of pulp cells in a dose-dependent manner as analyzed by modified MTT assay. The cell number increased by 1.6, 1.77, and 2.14-fold over that of control after exposure to 5, 10, and 20 units/ml of thrombin for 5 days. Flow cytometry studies also found that thrombin (10 units/ml) can induce the cell cycle progression of pulp cells after 24 h of incubation, as revealed by increasing the proportion of cells in the S phase and the G2/M phase from 29 to 72%. Moreover, exposure to thrombin (> 5 units/ml) for 3 days led to marked clustering of pulp cells. We concluded that thrombin can regulate the growth, cell cycle progression, and functional reorganization of the pulp tissue during pulp healing and inflammatory processes.

Cell Aggregation↗

PubMed1999

Stress, social relations, and old age mortality in Taiwan.

The research analyzed the relationships among stress, social relations, and mortality in a probability sample of 4,049 Taiwanese adults, aged 60 and over. The baseline survey was conducted in 1989 and the survival status of the respondents was ascertained during the subsequent 4 years. Death of a spouse or a child was found to increase the risk of dying directly and indirectly, whereas major financial difficulty during the past 5 years and current financial strain influenced mortality indirectly through their effects on self-rated health disability. In addition to their direct effect on mortality, martial status and work status lowered the probability of dying through decreased disability and subjective ill health. Finally, no buffering effects of social support were substantiated.

Adaptation, Psychological↗

PubMed1999

Dynamics of docosahexaenoic acid metabolism in the central nervous system: lack of effect of chronic lithium treatment.

Using a method and model developed in our laboratory to quantitatively study brain phospholipid metabolism, in vivo rates of incorporation and turnover of docosahexaenoic acid in brain phospholipids were measured in awake rats. The results suggest that docosahexaenoate incorporation and turnover in brain phospholipids are more rapid than previously assumed and that this rapid turnover dilutes tracer specific activity in brain docoshexaenoyl-CoA pool due to release and recycling of unlabeled fatty acid from phospholipid metabolism. Fractional turnover rates for docosahexaenoate within phosphatidylinositol, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserine were 17.7, 3.1, 1.2, and 0.2 %.h(-1), respectively. Chronic lithium treatment, at a brain level considered to be therapeutic in humans (0.6 micromol.g(-1)), had no effect on turnover of docosahexaenoic acid in individual brain phospholipids. Consistent with previous studies from our laboratory that chronic lithium decreased the turnover of arachidonic acid within brain phospholipids by up to 80% and attenuated brain phospholipase A2 activity, the lack of effect of lithium on docosahexaenoate recycling and turnover suggests that a target for lithium's action is an arachidonic acid-selective phospholipase A2.

Acyl Coenzyme A↗

PubMed1999

Reduced palmitate turnover in brain phospholipids of pentobarbital-anesthetized rats.

Our laboratory has reported that pentobarbital-induced anesthesia reduced the incorporation of intravenously injected radiolabeled palmitic acid into brain phospholipids. To determine if this decrease reflected a pentobarbital-induced decrease in palmitate turnover in phospholipids, we applied our method and model to study net flux and turnover of palmitate in brain phospholipids (1). Awake, light and deep pentobarbital (25-70 mg/kg, iv) anesthetized rats were infused with [9,10-3H]palmitate over a 5 min period. Brain electrical activity was monitored by electroencephalography. An isoelectric electroencephalogram characterized deep pentobarbital anesthesia. Net incorporation rates (J(FA,i)) and turnover rates (Fi) of palmitate were calculated. J(FA,i) for palmitate incorporated into phospholipids was dramatically reduced by pentobarbital treatment in a dose-dependent manner, by 70% and 90% respectively for lightly and deeply anesthetized animals, compared with awake controls. Turnover rates for palmitate in total phospholipid and individual phospholipid classes were decreased by nearly 70% and 90% for lightly and deeply anesthetized animals, respectively. Thus, pentobarbital decreases, in a dose-dependent manner, the turnover of palmitate in brain phospholipids. This suggests that palmitate turnover is closely coupled to brain functional activity.

Adjuvants, Anesthesia↗

PubMed1999

Systemic inflammatory response syndrome in the trauma intensive care unit: who is infected?

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is common in trauma patients, and infection represents an important and treatable source of SIRS. C-Reactive protein (CRP), an acute phase protein, is elevated in infection and discriminates between infected and uninfected patients in other patient populations. Our goal was to examine the ability of CRP and other commonly used markers of infection (maximum temperature [Tmax], and white blood cell count [WBC]) to distinguish between infectious and noninfectious causes of SIRS. METHODS: This was a prospective study of a consecutive series of trauma patients who spent greater than 48 hours in the intensive care unit. Studied variables included CRP, Tmax, WBC, and culture-proven infection compared with standard definitions of infection and the presence of SIRS. The ability of these variables to correctly classify patients as infected (INF) or not infected was examined by using receiver operating characteristic curves. Values on the day of infection diagnosis in the INF group and on postadmission day 5 (the mean day of onset of infection in the INF group) in the not infected group were used. Multivariate discriminant analysis was used to examine the relative contributions of Tmax and CRP in predicting infection. Significance was defined as p < 0.05. RESULTS: Fifty-nine patients were admitted over a 4-month period. Of these, 35 patients (59%) had SIRS at the time of comparison (29 INF, 6 not infected). Thirty-three patients (56%) developed an infection. Both CRP and Tmax discriminated between patients with and without infection whereas WBC did not (areas under receiver operating characteristic curve: 0.86, 0.81, and 0.47, respectively). In patients with SIRS, cutoff values of 17 mg/dL for CRP (specificity 100%) and 102 degrees F for Tmax (specificity 83%) were identified. CRP added significant discriminatory power to Tmax in determining presence of infection in patients with SIRS (p = 0.003). CONCLUSION: Infection must be presumed to be the source of SIRS in patients with CRP more than 17 mg/dL and Tmax more than 102 degrees F after postinjury day 4. WBC is not useful in determining the presence of infection.

Adult↗

PubMed1999

Effects of areca nut, inflorescence piper betle extracts and arecoline on cytotoxicity, total and unscheduled DNA synthesis in cultured gingival keratinocytes.

Betel quid (BQ) chewing has a strong correlation with oral leukoplakia, submucous fibrosis and oral cancer. For elucidation of its pathogenesis, we investigated the effects of areca nut (AN) and inflorescence piper betle (IPB) extracts and arecoline on the growth, total DNA synthesis (TDS) and unscheduled DNA synthesis (UDS) of cultured human gingival keratinocytes (GK). Arecoline and AN extract suppressed the growth of GK over 5 days of incubation in a dose-dependent fashion. At concentrations of 100, 200 and 400 microg/ml, AN extract suppressed the growth of GK by 31%, 46% and 90%, respectively. The IPB extracts exerted less inhibitory effect on the growth of GK. IPB extract (200-400 microg/ml) decreased cell numbers by 20-40% over 5 days of incubation. Moreover, at a concentration of 0.1, 0.2 and 0.4 mM, arecoline suppressed cell growth by 44%, 77% and 96%, respectively. However, only AN extract induced TDS and UDS in cultured GK within 6 h of exposure. Induction of UDS by AN extract was concomitant with the presence of apparent intracellular vacuolization. Arecoline was also toxic to GK, but did not induce intracellular vacuolization. At a concentration range of 200-1600 microg/ml, AN extract induced TDS by 2.1- to 6.5-fold. Furthermore, at a concentration of 400-1600 microg/ml, AN extract elevated the UDS by 2.4- to 5.5-fold more than that of untreated control. On the contrary, IPB extract (200-1600 microg/ml) and arecoline (0.2-1.6 mM) inhibited the TDS and UDS of GK to a different extent. Simultaneous exposure of confluent GK to AN extract, IPB extract and arecoline for 1 to 5 days led to different degrees of cytotoxicity that was dose- and time-dependent. These results indicate that AN, IPB and arecoline take part in the pathogenesis of BQ chewing-related oral mucosal lesions, possibly through both genotoxic and non-genotoxic mechanisms.

Areca↗

PubMed1999

The effects of extracellular citric acid acidosis on the viability, cellular adhesion capacity and protein synthesis of cultured human gingival fibroblasts.

Root surface demineralization is widely used as an adjunct to periodontal treatment. To clarify the influence of citric acid root conditioning on periodontal wound healing, the effects of citric acid and associated extracellular acidosis on the viability (MTT assay), attachment and protein synthesis ([3H]-proline incorporation into trichloroacetic acid-precipitated proteins) of human gingival fibroblasts (GF) were investigated. A concentration of 47.6 mmol/L of citric acid (pH 2.3) in water led to total cell death within three minutes of incubation. Media containing 23.8 mmol/L and 47.6 mmol/L of citric acid exerted strong cytotoxicity (47 to 90 per cent of cell death) and inhibited protein synthesis (IC50 = 0.28 per cent) of GF within three hours of incubation. Incubation of cells in a medium containing 11.9 mmol/L of citric acid also suppressed the attachment and spreading of fibroblasts on culture plates and Type I collagen, with 58 per cent and 22 per cent of inhibition, respectively. Culture medium supplemented with 11.9, 23.8 and 47.6 mmol/L of citric acid also led to extracellular acidosis by decreasing the pH value from 7.5 to 6.3, 5.2 and 3.8, respectively. In addition, it was confirmed that the toxic effect of media containing citric acid was due to their acidity rather than the citrate content. Most of the citric acid-induced cell death could be prevented by adjusting the pH value of the culture medium to pH 7.5. Sodium citrate, at a concentration of 47.6 mmol/L, also exerted little cytotoxicity. The results suggested that toxicity of citric acid in specific stages of the healing process must be considered prior to its clinical application. Careful management of citric acid in order to avoid contact with tissue or the development of other demineralizing agents is important in enhancing periodontal wound healing.

Acidosis↗

PubMed1999

Effects of butyrate and propionate on the adhesion, growth, cell cycle kinetics, and protein synthesis of cultured human gingival fibroblasts.

BACKGROUND: Various periodontal and root canal pathogens, such as the Bacteroides species, can produce significant amounts of short chain fatty acids (SCFA). The roles of SCFA in the pathogenesis of periodontal disease are still not fully understood. METHODS: We therefore investigated 2 main SCFA, butyrate and propionate, on the functional behavior of cultured human gingival fibroblasts (GF) such as cell growth, protein synthesis, cell adhesion capacity, and cell cycle progression. RESULTS: Butyrate and propionate inhibited the growth of healthy (HGF) and inflamed gingival fibroblasts (IGF) in a dose dependent manner. At concentrations of 4, 8, and 16 mM, butyrate suppressed the cell growth by 11 to 58%, 16 to 60%, and 50 to 71%, respectively. The response of cultured gingival fibroblasts to SCFA showed individual differences. Morphologically, GF became larger and more flattened in appearance following exposure to butyrate (>8 mM) and propionate (>24 mM) for 5 days. Inhibitory effects of butyrate (>2 mM) and propionate (>8 mM) on the growth of GF were due possibly to their inhibition of cell-cycle progression. At concentrations of 2 and 8 mM, butyrate led to G0/G1 arrest. Elevation of the exposure concentration to 8 to 24 mM further result in G2/M phase arrest of GF. On the other hand, propionate, at concentrations ranging from 4 to 24 mM, led to G0/G1 arrest. Butyrate (>2 mM) inhibited the proline-rich protein synthesis of GF. At concentrations of 4, 8, 16, and 24 mM, butyrate inhibited the protein synthesis of HGF-1 by 42%, 43%, 51%, and 54%, respectively. In all strains of cultured GF, the suppressive effect of propionate is less than that of butyrate. At concentration range of 4 to 24 mM, propionate suppressed the protein synthesis of HGF-1 by 23 to 43%. However, both butyrate and propionate (4 to 48 mM) exerted little effects on the adhesion of GF to type I collagen within 3 hours of incubation. CONCLUSIONS: These results suggested that SCFA released by pathogenic microorganisms can contribute to the gingival tissue dysfunction and breakdown through their actions on specific biological functions of GF.

Butyrates↗

PubMed1999

Treatment of large skeletal defects in the lower extremities using double-strut, free vascularized fibular bone grafting.

This article reports on the use of double-strut, free vascularized fibular grafts to treat six patients with infected nonunion or traumatic bone loss in the femur or tibia after prolonged treatment and multiple operations. The defects were 6-13 cm long. Five patients achieved solid union within 6 months, and one patient required additional cancellous grafting to achieve union at the distal end of the fibula. One patient experienced a stress fracture due to strenuous exercise, and union was achieved 3 months after reapplying an external fixator. Although three patients had some restricted knee motion, all patients had a satisfactory outcome in regard to walking, and no limb-length discrepancies were noted in any patient.

Adult↗

PubMed1999

Percutaneous A1 pulley release for trigger digits.

BACKGROUND: Recently, percutaneous trigger digit release has been reported as a safe, effective office procedure. The purpose of this study was to further assess the safety and efficacy of this technique. METHODS: From November, 1996, to August, 1997, 69 consecutive patients with 71 primary trigger digits were treated with percutaneous A1 pulley release. The operations were performed using the tip of a 19-gauge needle, mounted on a 3-ml syringe. The mean age of the patients was 66 years. The mean duration of follow-up was 21 weeks. The patients were prospectively classified into two groups according to age, sex, digit involved, duration of symptoms and whether or not they had had previous local steroid injection. RESULTS: Sixty-three digits were completely free of triggering. Residual triggering or inadequate release was found in eight digits at final follow-up. The success rate was not associated with sex, age, digit involved, duration of symptoms or history of local steroid injection. No major complications were found in this study, but minor complications included persistent local tenderness in nine digits and subcutaneous hematoma in six digits. Risk factors related to persistent local tenderness were female gender and trigger thumb. CONCLUSIONS: Percutaneous A1 pulley release is an effective, safe and convenient procedure for the treatment of trigger digits.

Adult↗

PubMed1999

Discordance between uterine cervical cytology and biopsy: results and etiologies of a one-year audit.

To investigate the etiologies of discrepancies between cervicovaginal smear and corresponding cervical biopsy results, a total of 15,474 cervicovaginal smears were sampled in a one-year period. Among these, 427 patients were diagnosed with atypical squamous cells of undetermined significance (ASCUS), dysplasia, or malignancy. The screen positive rate was 2.8%. All of the positive cases had histologic follow-up. Forty-nine of the 427 patients had a discrepancy of at least two grades (the grades are divided to negative, ASCUS, mild dysplasia, moderate dysplasia, severe dysplasia and invasive carcinoma), between the cytologic and histologic diagnoses. The discrepancy rate was 11.5%. Ten of these discrepant cases had poorly-preserved slides or a not definitely final diagnosis. A total of 39 cases (79.6%) of discrepancy were reviewed in this study. In thirty (77%) of the 39 discrepant cases, the errors were cytologic and in 9 cases (23%) the errors were histologic. Cytologic error was the major cause of cytohistologic discrepancy. The etiologies of cytohistologic discrepancy included: cytologic interpretation error, 17 cases (44%); cytologic sampling error, 10 cases (25%); biopsy sampling error, 6 cases (15%); cytologic screen error, 3 cases (8%); and biopsy interpretation error, 3 cases (8%). The major etiology of cytohistologic discordances was cytologic interpretation error. In this retrospective study, we determined the etiologies of cytohistologic discrepancies. This information can be useful for improving diagnostic accuracy and the quality of patient care.

Biopsy↗

PubMed1999

Vascularized iliac bone graft for displaced femoral neck fractures in young adults.

From November 1989 to September 1994, a total of 26 patients (18 men and 8 women) with acute displaced femoral neck fractures were treated with closed reduction and Knowles pinning combined with vascularized iliac bone grafting. Mean patient age was 37.5 years (range: 24-48 years). The mean time interval from injury to surgery was 3.6 days (range: 1-10 days). One patient experienced loss of the reduction at 6 weeks postoperatively and subsequently went on to hip replacement. Mean follow-up for the remaining 25 patients was 56.2 months (range: 20-78 months). All fractures united within 4 months. The average union time was 3.3 months. Plain radiographs confirmed the presence of avascular necrosis in 2 patients during the final follow-up; 1 of these patients developed systemic lupus erythematous 1 year after the fracture and had been treated with high doses of corticosteroid. Functional and radiographic results were satisfactory in the remaining patients.

Adult↗

PubMed1999

"Blind" placement of long-term central venous access devices: report of 589 consecutive procedures.

Placement of long-term central venous access devices, such as Hickman catheters and implanted subcutaneous ports, has traditionally been performed in the operating room with fluoroscopy. This study reports our experience with percutaneous placement of these devices in the outpatient clinic setting without the use of real-time imaging. Results were generated from a prospective database of all adult patients undergoing placement of central venous access in the outpatient clinic of the Wake Forest University Baptist Medical Center. This database revealed that during the years 1996 and 1997, long-term central venous catheter placement was attempted in 589 adult patients in the outpatient clinic. Technical success was achieved in 558 patients (92%). This included 278 tunneled catheters and 280 totally implanted devices. Repositioning of the catheter tip was required in 16 patients (2.9%). The incidence of pneumothorax was 1.9 per cent. Late complications, including infection and thrombosis, occurred in 9 per cent. The average procedure-related charge for placement of a single-lumen central venous port in the outpatient clinic was $1691 versus $4559 in the operating room and $3890 in the radiology department. We conclude that routine placement of long-term central venous access devices in the outpatient clinic, without the use of real-time imaging, yields acceptable success rates and may have economic advantages over procedures performed in the operating room or radiology department.

Adolescent↗

PubMed1999

Ligament reconstruction and tendon interpositional arthroplasty for degenerative arthritis of the thumb trapeziometacarpal joint.

BACKGROUND: The trapeziometacarpal joint provides important functions for the hand. This joint is often involved in primary osteoarthritis. METHODS: From November 1982 to December 1995, we encountered 42 patients (47 hands) with osteoarthritis (OA). All the patients were Chinese. Thirty-six patients (36 hands) were treated surgically. Ligament reconstruction and tendon interposition arthroplasty were done with total removal of the trapezium or partial removal of trapeziometacarpal joint depending on the stage of the disease. These patients were monitored for an average of 106 months and evaluated both clinically and roentgenographically. RESULTS: Of three stage II cases, the results of two were excellent and one was good. Of the 18 stage III patients, 14 had excellent (77.8%) and four had good (22.2%) results. In the 15 stage IV patients, 10 had excellent (66.6%), four had good (26.7%) and one had fair (6.7%) results. No patient had poor results. CONCLUSIONS: Ligament reconstruction and tendon interpositional arthroplasty is a good alternative in treating degenerative arthritis of the trapeziometacarpal joint of the thumb. Partial removal of the diseased joint is indicated for stage II, and total removal of the trapezium is indicated for stage III and IV patients. Men seek treatment more often than women due to their need to work, even though women are more commonly afflicted with this disorder.

Adult↗

PubMed1998

Fatty acid incorporation depicts brain activity in a rat model of Parkinson's disease.

Following pulse labeling with [3H]arachidonic acid ([3H]AA), its incorporation pattern in brain reflects regional changes in neurotransmitter signal transduction using phospholipase A2, that is, functional activity. In a rat model of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia nigra, [3H]AA acid incorporation from blood was increased in cerebral cortex, caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata ipsilateral to the lesion. This increased [3H]AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input.

Animals↗

PubMed1998

Tumor promoting effect of N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (a nitrosated Maillard reaction product) in benzo(a)pyrene-initiated mouse skin carcinogenesis.

N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (NO-HNTA) is a product generated in a model browning system in the presence of sodium nitrite. The chemical structure of this compound has been confirmed by UV, mass, nuclear magnetic resonance and infrared spectroscopy in our study. Twenty weeks, twice weekly, topical application of NO-HNTA at the concentration of 10, 50 and 250 mumol to mice previously initiated with benzo(a)pyrene (B[a]P) increased their tumor formation by 3.2-, 4.6- and 5.8-fold respectively. Application of the same amount of NO-HNTA not only caused significant induction of hyperplasia but also the activity of epidermal ornithine decarboxylase (ODC). Treatment of mouse skin with various amounts of NO-HNTA (10, 50 and 250 mumol) caused production of hydrogen peroxide by 1.38-, 1.95- and 3.26-fold respectively, and induction myeloperoxidase (MPO) by 24-, 63- and 102-fold. These results indicate that the formation of NO-HNTA or its derivatives derived from the reaction of tyrosine and glucose in the presence of sodium nitrite has the potential as a tumor promoter.

Animals↗

PubMed1998

The hyaluronan receptor RHAMM regulates extracellular-regulated kinase.

We have identified two RHAMM (receptor for hyaluronan-mediated motility) isoforms that encode an alternatively spliced exon 4 (Hall, C. L., Yang, B., Yang, X., Zhang, S., Turley, M., Samuel, S., Lange, L. A., Wang, C., Curpen, G. D., Savani, R. C., Greenberg, A. H., and Turley, E. A. (1995) Cell 82, 19-26 and Wang, C., Entwistle, J., Hou, G., Li, Q., and Turley, E. A. (1996) Gene 174, 299-306). One of these, RHAMM variant 4 (RHAMMv4), is transforming when overexpressed and regulates Ras signaling (Hall et al.). Here we note using flow cytometry and confocal analysis that RHAMM isoforms encoding exon 4 occur both on the cell surface and in the cytoplasm. Epitope-tagging experiments indicate that RHAMMv4 occurs only in the cytoplasm. Several observations suggest that both cell surface RHAMM isoforms and RHAMMv4 are involved in regulating extracellular-regulated kinase (ERK) activity. Affinity-purified anti-RHAMM exon 4 antibodies block the ability of platelet-derived growth factor to activate ERK, and these reagents modify the protein tyrosine phosphorylation profile of proteins resulting from treatment with platelet-derived growth factor. A dominant negative form of RHAMMv4 inhibits mutant active Ras activation of ERK and coimmunoprecipitates with both mitogen-activated protein kinase kinase and ERK, suggesting that the intracellular RHAMMv4 acts downstream of Ras, possibly at the level of mitogen-activated protein kinase kinase-ERK interactions. Consistent with this, overexpression of RHAMMv4 constitutively activates ERK. These results identify a novel mechanism for the regulation of the Ras-ERK signaling pathway and suggest that RHAMM plays multiple roles in this regulation.

Animals↗

PubMed1998

Antithrombotic effect of crotalin, a platelet membrane glycoprotein Ib antagonist from venom of Crotalus atrox.

A potent platelet glycoprotein Ib (GPIb) antagonist, crotalin, with a molecular weight of 30 kD was purified from the snake venom of Crotalus atrox. Crotalin specifically and dose dependently inhibited aggregation of human washed platelets induced by ristocetin with IC50 of 2.4 microg/mL (83 nmol/L). It was also active in inhibiting ristocetin-induced platelet aggregation of platelet-rich plasma (IC50, 6.3 microg/mL). 125I-crotalin bound to human platelets in a saturable and dose-dependent manner with a kd value of 3.2 +/- 0.1 x 10(-7) mol/L, and its binding site was estimated to be 58,632 +/- 3, 152 per platelet. Its binding was specifically inhibited by a monoclonal antibody, AP1 raised against platelet GPIb. Crotalin significantly prolonged the latent period in triggering platelet aggregation caused by low concentration of thrombin (0.03 U/mL), and inhibited thromboxane B2 formation of platelets stimulated either by ristocetin plus von Willebrand factor (vWF), or by thrombin (0.03 U/mL). When crotalin was intravenously (IV) administered to mice at 100 to 300 microg/kg, a dose-dependent prolongation on tail bleeding time was observed. The duration of crotalin in prolonging tail bleeding time lasted for 4 hours as crotalin was given at 300 microg/kg. In addition, its in vivo antithrombotic activity was evidenced by prolonging the latent period in inducing platelet-rich thrombus formation by irradiating the mesenteric venules of the fluorescein sodium-treated mice. When administered IV at 100 to 300 microg/kg, crotalin dose dependently prolonged the time lapse in inducing platelet-rich thrombus formation. In conclusion, crotalin specifically inhibited vWF-induced platelet agglutination in the presence of ristocetin because crotalin selectively bound to platelet surface receptor-glycoprotein Ib, resulting in the blockade of the interaction of vWF with platelet membrane GPIb. In addition, crotalin is a potent antithrombotic agent because it pronouncedly blocked platelet plug formation in vivo.

Animals↗