PURPOSE: The purpose of this study was to evaluate the effect of two sustained release systems (Pluronic F-127 gel and Fibrin glue) on the diffusion of dexamethasone across the human sclera. METHODS: Scleral sections excised from moist-chamber-stored human globes were mounted in a perfusion chamber that can create transscleral pressure. In the sustained release study, sample (100 muL) of 3H-dexamethasone in Pluronic F-127 gel or Fibrin glue was added to the episcleral side of the tissue, while BSS plusR was perfused across the uveal side at an transscleral pressure of 15 mmHg. Perfusate fractions were collected and measured using scintillation spectrometry and scleral permeability was calculated. RESULTS: The apparent permeability constants of the human sclera to 3H-dexamethasone in BSS plus(R) (the control value), Pluronic F-127 gel, and Fibrin glue were 1.15+/-0.11x10(-5) cm/s (n=5), 1.49+/-0.33x10-6 cm/s (n=5), and 7.32+/-0.98x10(-6) cm/s (n=7), respectively. The permeability values of Pluronic F-127 gel and Fibrin glue were relatively lower than the control value. Pluronic F-127 gel and Fibrin glue showed a uniform sustained release characteristic during a 24-hour period. The cumulative release rates of dexamethasone through the human sclera from BSS plus(R) (the control value), Pluronic F-127 gel, and Fibrin glue were 84.0+/-1.5% (n=5), 29.3+/-5.8% (n=5), and 61.5+/-5.9% (n=4) at 20 hours, respectively. There were significant differences in the human scleral permeability constants and cumulative release rates among the three vehicles (p<0.0001). CONCLUSIONS: Pluronic F-127 gel and Fibrin glue provided a slow, uniform sustained release during a 24- hour period. This study established a strong possibility of the new transscleral drug delivery in vitro using the sustained release systems of Pluronic F-127 gel and Fibrin glue. This may be a good experimental tool in the future development of a practical drug delivery system across the sclera for the treatment of a variety of chorioretinal disorders.
Dexamethasone ; Diffusion ; Drug Delivery Systems ; Fibrin Tissue Adhesive* ; Fibrin* ; Humans ; Perfusion ; Permeability ; Poloxamer* ; Sclera ; Spectrum Analysis

OBJECTIVETo analyze clinical manifestation and genetic mutations in 8 Chinese pedigrees featuring hereditary dysfibrinogenemia.

METHODSProthrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), calibration of plasma protamine sulfate against TT, fibrinogen (Fg) activity, coagulation factors II, V, VII, VIII, IX, X, XI and XII of all probands and their family members were detected with an automatic blood coagulation analyzer; D-dimer(D-D) and fibrin(ogen) degradation products(FDPs) were also dtected by automatic blood coagulation analyzer, Fg antigen were detected with an immunoturbidimetry method. Exons of fibrinogen genes FGA, FGB and FGG and flanking sequences were amplified by polymerase chain reaction(PCR) and sequenced.

RESULTSAll of the probands showed normal levels of FDPs, D-dimer(D-D) and activity of coagulation factor II,V,VII, VIII, IX,X,XI, XII. Plasma PT and APTT were normal or slightly prolonged. Prolonged TT was found in all of the probands, whilst TT was not significantly shortened by protamine sulfate. Fg antigen was within the normal range, but Fg activity was significantly decreased. The Fg antigen/activity ratio was greater than 2. One proband has carried a heterozygous variant of the FGA gene g.1233G>A(p.A α Arg35His). Four have carried a heterozygous mutation of the FGB gene g.9692A>G(p.Bβ Asn190Ser). The remaining 3 had heterozygous substitution of FGG gene g.10819G>A(p.γ Arg301His). In addition, 2 polymorphisms (p.A α Thr331Ala) and p.B β Arg478Lys) were identified in FGA and FGB genes.

CONCLUSIONp.A α Arg35His, p.B β Asn190Ser and p. γ Arg301His are responsible for the inherited dysfibrinogenemia in the 8 Chinese pedigrees. p.B β Asn190Ser is firstly reported in China. p.B β Asn190Ser and p. γ Arg301His may be mutation hot spot in the Chinese population.

Afibrinogenemia ; blood ; genetics ; Fibrin Fibrinogen Degradation Products ; analysis ; Fibrinogen ; analysis ; genetics ; Humans ; Pedigree

Many screening tests have been developed for the detection of FDP for the last decade. Of these, Thrombo-Wellcotest was chosen in our laboratory as a screening procedure. For the last one year, there were 121 determinations performed on 82 patients. Of the patients suspected to have DIC, 27 patients with clinical, and laboratory evidence of DIC showed the Thrombo-Wellcotest to be positive with titers ranging from 1:5 to 1:1280. Those patients without clinical or laboratory evidence of DIC gave all negative results except for 7 positives with low titers. It is our opinion that the Thrombo-Wellcotest is a simple procedure to be performed by ordinary laboratory personnel and an inexpensive test which can be afforded by most of the patients. As a whole, the Thrombo-Wellcotest is considered to be a useful screening test for the detection of FDP in serum.
Disseminated Intravascular Coagulation/diagnosis* ; Fibrin Fibrinogen Degradation Products/analysis* ; Human ; Latex Fixation Tests

OBJECTIVETo detect the plasma activity of von Willebrand factor-cleaving protease (ADAMTS13) in the patients with prothrombotic status, and explore the effect and significance of ADAMTS13 in the prothrombotic status. The correlation of ADAMTS13 with von Willebrand factor (vWF), thrombospondin 1 (TSP1), C-reactive protein etc, and blood pressure was simultaneously analyzed．

METHODSThe activity of ADAMTS13 in patient groups (atherosclerosis, diabetes, acute promyelocytic leukemia, cancer and sepsis, a total of 260 cases) and in control group 50 cases were evaluated by residue collagen binding assay（R-CBA）, the protein levels of TSP1 and vWF were measured by ELISA kits； the correlation of ADAMTS13 activity with CRP, creatinine, and blood pressure was analyzed with statistical soft ware.

RESULTSThe activity of plasma ADAMTS13 in patient group was significantly lower than that in normal control group(P<0.05). And the protein levels of TSP1 and vWF in the patients with prothrombotic status were higher than those in the normal controls(P<0.05). Analysis of the correlation showed that the ADAMTS13 activity correlated negatively with the levels of TSP1 protein, blood sugar, blood pressure, D-dimer, creatinine,and CRP levels (P<0.05), however, the ADAMTS13 activity did not significantly correlate with the levels of serum lipids, blood type, platelet number and hemoglobin level(P>0.05).

CONCLUSIONThe plasma ADAMTS13 activity is decreased in the patients with prothrombotic status, suggesting that the decreased ADAMTS13 activity may participate in the occurrence of prothrombotic status, and the dectection of plasma ADAMTS13 activity may help the diagnosis of pro-thrombotic disease.

ADAMTS13 Protein ; Factor Analysis, Statistical ; Fibrin Fibrinogen Degradation Products ; Humans ; Sepsis ; Thrombosis ; von Willebrand Factor

No abstract available.
Female ; Fibrin Fibrinogen Degradation Products/*analysis ; Humans ; Male ; Venous Thromboembolism/*diagnosis

No abstract available.
Female ; Fibrin Fibrinogen Degradation Products/*analysis ; Humans ; Male ; Venous Thromboembolism/*diagnosis

Acute Disease ; Aged, 80 and over ; Fibrin Fibrinogen Degradation Products ; analysis ; Humans ; Male ; Pulmonary Embolism

OBJECTIVETo observe changes in plasma thrombomodulin (TM) and D-dimer (DD) levels in neonates with sepsis, and to investigate their significance in evaluating the patients' condition and prognosis.

METHODSFifty-six neonates with sepsis were classified into extremely critical (n=13), critical (n=22) and non-critical groups (n=21) based on neonatal critical illness score (NCIS). Fasting venous blood samples were collected on admission and in the recovery phase. Plasma TM and D-dimer levels were measured using enzyme-linked immunosorbent assay and immune turbidimetry, respectively. Twenty-six healthy neonates were selected as the control group. Plasma TM and D-dimer levels were compared between groups, and the changes after treatment were determined.

RESULTSPlasma TM levels in the extremely critical, critical and non-critical groups were 25.5±6.6, 17.3±4.7 and 13.3±2.8 µg/L respectively, significantly higher than in the control group (9.8±2.7 µg/L) (P<0.01). Plasma D-dimer levels in the extremely critical and critical groups were 744±262 and 436±147 µg/L respectively, also significantly higher than in the control group (205±61 µg/L) (P<0.01). The extremely critical group had significantly higher plasma TM and DD levels than the critical group (P<0.05), and the critical group had significantly higher plasma TM and DD levels than the non-critical group (P<0.05). All patients showed significant decreases in plasma TM and DD levels in the recovery phase after treatment (P<0.01). Plasma TM and DD levels were significantly negatively correlated with NCIS (r=-0.428, P<0.01; r=-0.363, P<0.01).

CONCLUSIONSDetermination of plasma TM and DD levels may be helpful in evaluating severity and prognosis in neonates with sepsis.

Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Humans ; Infant, Newborn ; Male ; Protein Multimerization ; Sepsis ; blood ; Thrombomodulin ; blood

Humans ; COVID-19 ; Fibrin Fibrinogen Degradation Products ; Blood Coagulation Factors ; Survival Analysis

OBJECTIVE: To evaluate the value of conventional and age-adjusted D-dimer cut-off value combined with 2-level Wells score for diagnosis of suspected pulmonary embolism. METHODS: In the study, 335 patients with suspected pulmonary embolism who visited Peking University People's Hospital were enrolled retrospectively, then 274 patients with age over fifty years were chosen. The 2-level Wells score was applied to evaluate the clinical probability of pulmonary embolism, the diagnostic value of traditional D-dimer cut-off value (500 μg/L) and age adjusted D-dimer cut-off value (age×10 μg/L above 50 years) combined with Wells score no greater than 4 were compared. Computed tomography pulmonary arteriography (CTPA) was considered as the gold standard for diagnosis of pulmonary embolism. RESULTS: (1) The area under a receiver operating characteristic (ROC) curve (AUC) in analysis of the combination of Wells score no greater than 4 and traditional D-dimer cut-off value was 0.764 (95%CI: 0.703-0.818). On the other hand, the AUC in a ROC analysis of the combination of Wells Score no greater than 4 and age-adjusted D-dimer cut-off value was 0.814 (95%CI:0.756-0.863). These two results did not differ statistically (Z=0.05, P=0.121). (2) The sensitivity, specificity, positive predictive value, negative predictive value and Youden index of the diagnosis of pulmonary embolism of the combination of traditional D-dimer cut-off value and 2-level Wells Score were 100%, 48.9%, 28.8%, 100%, and 0.49, respectively. Meanwhile, the sensitivity, specificity, positive predictive value, negative predictive value and Youden index of the diagnosis of pulmonary embolism of the combination of age-adjusted D-dimer cut-off value and 2-level Wells Score were 97.4%, 62.3%, 35.5%, 99.1%, and 0.60, respectively. Compared with using traditional D-dimer cut-off value, using age-adjusted D-dimer cut-off value could improve the diagnosis specificity (traditional D-dimer cut-off value group: 48.9%, age-adjusted D-dimer cut-off value group: 62.3%) of pulmonary embolism without reducing the sensitivity (traditional D-dimer cut-off value group: 100%, age-adjusted D-dimer cut-off value group: 99.1%). (3) Among the 222 patients with Wells Score no greater than 4, 90 patients were with D-dimer less than traditional cut-off value (500 μg/L), and 25 patients (account for 11.3% of all 222 patients) were with D-dimer between traditional cut-off value and age-adjusted cut-off value. CONCLUSION The application of age-adjusted D-dimer cut-off value can improve the diagnostic specificity of pulmonary embolism in patients over 50 years, without reducing the sensitivity. It can be used for ruling out suspected pulmonary embolism safely.
Fibrin Fibrinogen Degradation Products/analysis* ; Humans ; Predictive Value of Tests ; Pulmonary Embolism/diagnosis* ; Retrospective Studies ; Sensitivity and Specificity