Application of the pulmonary embolism rule-out criteria (PERC rule) and age-adjusted D-Dimer in patients undergoing computed tomography pulmonary angiography for diagnosis of pulmonary embolism / Aplicação dos critérios PERC e do D-Dímero ajustado para idade em pacientes submetidos a angiotomografia pulmonar para o diagnóstico de embolia pulmonar

Abstract Background Diagnosis of pulmonary embolism (PE) constitutes a challenge for practitioners. Current practice involves use of pre-test probability prediction rules. Several strategies to optimize this process have been explored. Objectives To explore whether application of the pulmonary embolism rule-out criteria (PERC rule) and age-adjusted D-dimer (DD) would have reduced the number of computed tomography pulmonary angiography (CTPA) examinations performed in patients with suspected PE. Methods A retrospective cross-sectional study of adult patients taken for CTPA under suspicion of PE in 2018 and 2020. The PERC rule and age-adjusted DD were applied. The number of cases without indications for imaging studies was estimated and the operational characteristics for diagnosis of PE were calculated. Results 302 patients were included. PE was diagnosed in 29.8%. Only 27.2% of 'not probable' cases according to the Wells criteria had D-dimer assays. Age adjustment would have reduced tomography use by 11.1%, with an AUC of 0.5. The PERC rule would have reduced use by 7%, with an AUC of 0.72. Conclusions Application of age-adjusted D-dimer and the PERC rule to patients taken for CTPA because of suspected PE seems to reduce the number of indications for the procedure.

Resumo Contexto O diagnóstico de embolia pulmonar (EP) representa um desafio para o profissional. A prática atual envolve o uso de modelos de previsão de probabilidade pré-teste e, para otimizar esse processo, várias estratégias têm sido exploradas. Objetivos Investigar se a aplicação dos critérios de exclusão de EP (pulmonary embolism rule-out criteria, PERC) e do D-dímero (DD) ajustado para idade diminui o número de angiografias computadorizadas (ATCs) pulmonares realizadas em pacientes com suspeita de EP. Métodos Estudo transversal retrospectivo com pacientes adultos submetidos a ATC pulmonar com suspeita de EP em 2018 e 2020. Foram aplicados os critérios PERC e o DD ajustado para idade. Foi estimado o número de casos não indicados para exames de imagem, e foram calculadas as características operacionais para o diagnóstico de EP. Resultados Foram incluídos 302 pacientes, dos quais 29,8% apresentaram diagnóstico de EP. Apenas 27,2% dos casos não prováveis ​​de acordo com os critérios de Wells apresentaram DD; o ajuste implicou em uma diminuição de ACTs de 11,1%, com área sob a curva de 0,5. Os critérios PERC diminuiriam em 7%, com área sob a curva de 0,72. Conclusões A aplicação do DD ajustado para idade e dos critérios PERC em pacientes submetidos a ATC pulmonar por suspeita de EP parece diminuir a indicação para tais exames.

Correspondência de teor de dissulfeto de captopril com odor de enxofre em comprimidos de captopril 25 mg, provenientes de farmácias públicas (postos de saúde) e drogarias comerciais / Correspondence of captopril disulfide content with sulfur odor in 25 mg captopril tablets from public pharmacies (health clinics) and commercial drugstores

Introdução: O captopril (CP) é o medicamento de escolha para o tratamento da hipertensão arterial. Sua degradação leva à formação do dímero dissulfeto de captopril (DSCP), este associado a um odor forte no medicamento, podendo causar abandono do tratamento pelo paciente. Objetivo: Determinar DCSP, associar a percepção olfativa de odor de enxofre desprendido do produto e realizar a avaliação de bula de comprimidos de captopril 25 mg distribuídos pelos setores público e privado. Método: Foi verificado o desempenho do método de determinação do CP e DSCP pela Farmacopeia Brasileira 6a ed. por HPLC (DAD). Foram analisados 13 produtos de comprimidos de captopril 25 mg, sendo dois provenientes do setor público de lotes diferentes e mesmo fabricante e 11 do setor privado de diferentes fabricantes e lotes. Foram avaliados aspectos do comprimido quanto à percepção de odor, determinação de peso, identificação e teor de CP e de DSCP e análise do conteúdo da bula. Resultados: Dentre os 13, o medicamento vencido apresentou 4,4% de DSCP, os demais estavam de acordo com a especificação. Verificouse  correspondência do odor de enxofre perceptível com teor de DSCP acima de 0,5%. Considerando os textos de bula sobre odor de enxofre, as constatações foram: nenhuma informação (três produtos), odor característico (dois), leve odor de enxofre (um), leve odor de enxofre sem diminuir a eficácia (sete). Conclusões: As amostras apresentaram resultados satisfatórios para os ensaios realizados. Verificou-se falta de homogeneidade nas informações das bulas sobre o odor dos comprimidos. A percepção do paciente quanto ao odor de enxofre, mesmo dentro do limite tolerado de DSCP, pode levar a não aceitação do medicamento e consequente não adesão ao tratamento da hipertensão, além de gerar prejuízos ao SUS.

Introduction: Captopril (CP) is the drug of choice for the treatment of hypertension. Its degradation leads to the formation of captopril disulfide dimer (DSCP), associated with a strong odor in the drug, which can cause the patient abandonment of treatment. Objective: To determine DCSP, associate the olfactory perception of the sulfur odor given off by the product and carry out the evaluation of the package insert for captopril 25 mg tablets distributed in the public and private sectors. Method: The performance of CP and DSCP determination method of the Brazilian Pharmacopoeia 6 ed was verified by HPLC (DAD). Thirteen products of 25 mg captopril tablets were analyzed, 2 of which came from the public sector from different batches and the same manufacturer: the other 11 came from the private sector from different batches and manufacturers. The samples were analyzed regarding appearance, odor perception, identification, weight determination, CP and DSCP content (by HPLC) and package insert content. Results: Among the 13, the expired drug had 4.4% DSCP; the others were in accordance with the specification. Correspondence of perceptible sulfur odor was established for drugs with DSCP content above 0.5%. Considering the texts on sulfur odor in the package inserts, the findings were: none information (3 products), characteristic odor (2), slight sulfur odor (1), slight sulfur odor without decreasing effectiveness (7). Conclusions: The samples showed satisfactory results for the tests performed. There was a lack of homogeneity in the information in the package inserts about odor of the tablets. The patient's perception of sulfur odor, even within the tolerated limit of DSCP, can lead to non-acceptance of the drug and consequent non- adherence to the treatment of hypertension, in addition to causing damage to the SUS.

Study on influencing factors of plasma FDP and D-dimer levels of newborns in NICU / 国际儿科学杂志

Objective:To investigate the influencing factors of physiological and pathological conditions at birth of newborn and gestational conditions of pregnant mothers on plasma fibrin/fibrinogen degradation products(FDP)and D-dimer levels.Methods:From May 1, 2018 to October 31, 2018, 222 newborns admitted to NICU of the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were enrolled in this study.Newborns were sent to NICU within 2 hours after birth and venous blood was collected immediately.The levels of FDP and D-dimer were detected by immunoturbidimetry.Groups were divided according to different gender, gestational age, birth weight, relationship between gestational age and birth weight, mode of delivery, asphyxia at birth, acidosis, antenatal hormone use, anticoagulant drugs, and perinatal risk factors(gestational hypertension, premature rupture of membranes, abnormal placenta, gestational diabetes). The levels of plasma FDP and D-dimer were compared among the groups.Mann Whitney U test, Kruskal Wallis H test, Spearman rank correlation and generalized linear model were used for statistical analysis. Results:The plasma FDP and D-dimer values of 222 NICU neonates were skewed at birth, with median values of 6.00 mg/L and 1.74 mg/L, and quartile distances of 10.40 mg/L and 2.55 mg/L, respectively.The concentrations of FDP in neonates born to natural labour and cesarean section were 11.70 mg/L and 5.30 mg/L, respectively, and D-dimer concentrations were 2.92 mg/L and 1.52 mg/L, respectively.The FDP and D-dimer levels were significantly higher in the former(Z values were -4.006 and -4.198, respectively, P<0.05). The levels of FDP and D-dimer in newborns with different gestational age, different birth weight and different blood pH values were compared respectively, and the differences were statistically significant( χ2 values were 15.322, 18.394, 9.677, 11.492, 7.023 and 8.345, respectively, P<0.05). Further analysis showed that the levels of FDP and D-dimer in neonates with gestational age < 34 weeks were significantly higher than those in~<37 weeks group and ≥37 weeks group( P<0.05). The FDP and D-dimer levels in the birth weight<1 500 g group were significantly higher than those in~<2 500 g group and ≥2 500 g group( P<0.05). Higher FDP and D-dimer levels were found in the pH<7.20 group than in the pH ≥7.35 group( P<0.05). A generalized linear model was established for multifactor analysis.The results showed that the concentration of FDP and D-dimer in plasma was related to gestational age, birth weight and arterial pH value. Conclusion:The levels of plasma FDP and D-dimer in NICU newborns at birth were influenced by gestational age, birth weight and acid-base balance.

Luliconazole: Stability-indicating LC method, structural elucidation of major degradation product by HRMS and in silico studies / Luliconazol: método por LC indicativo de estabilidad, elucidación estructural del producto de degradación mayoritario por HRMS y estudios in silico / Luliconazol: método LC indicativo de estabilidade, elucidação estrutural do principal produto de degradação por HRMS e estudos in sílico

SUMMARY Aim: A new stability-indicating liquid chromatography method was developed and validated for the quantitative determination of luliconazole. Materials and methods: Preliminary forced degradation study demonstrated an additional peak of the degradation product at the same retention time to the drug, due to this, the method was developed optimizing the chromatographic conditions to provide sufficient peak resolution (R ≥ 2). The experimental design was evaluated to assess the robustness and the best chromatographic conditions to be used for the validation. Methodology: Luliconazole solutions were exposed to various stress conditions to evaluate the method indication stability, in which the degradation product (DP-1) formed was isolated, identified, and evaluated in silico to predict degradation pathway and toxicity. The procedure was validated by robustness, selectivity, linearity, precision, and accuracy. Liquid chromatography was performed in a Phenomenex® RP-18 column with a mixture of acetonitrile and 0.3% (v/v) triethylamine solution as a mobile phase in isocratic elution. Results and conclusions: The method demonstrated robustness, good recovery, precision, linear response over a range from 5.0 to 40.0 μg.mL-1- and to be stability indicating. The alkaline stress condition resulted in the formation of DP-1. HRMS studies identified this product as an hydroxyacetamide derivative, and in silico studies did not show toxic potential.

RESUMEN Objetivo: Un nuevo método indicativo de estabilidad por cromatografía líquida fue desarrollado y validado para la determinación cuantitativa de luliconazol. Materiales y métodos: Estudios preliminares de degradación forzada demostraron un pico adicional en el mismo tiempo de retención del fármaco. El método desarrollado para optimizar las condiciones cromatográicas proporcionó una adecuada resolución (R ≥ 2). El diseño experimental fue evaluado para verificar su robustez y la mejor condición cromatográica para validación. Metodología: Las soluciones de luliconazol fueron expuestas a diferentes condiciones de estrés para evaluar la indicación de estabilidad del método, el aislamiento del producto de degradación formado (DP-1), su identificación y análisis in silico para predecir su ruta de degradación y toxicidad. El procedimiento se validó por robustez, selectividad, linealidad, precisión y exactitud. Las condiciones cromatográficas incluyeron una columna Phenomenex® RP-18, como fase móvil una mezcla de acetonitrilo y solución 0,3% (v/v) de trietilamina en elución isocrática. Resultados y conclusiones: El método mostró ser robusto, con buena recuperación, precisión, respuesta lineal en el rango de 5,0 a 40,0 μg.mL-1 e indicativo de la estabilidad. La condición de estrés alcalina resultó en la formación de DP-1. Estudios por HRMS identificaron este producto como un derivado hidroxiacetamida y los estudios in silico no mostraron potencial de toxicidad.

RESUMO Objetivo: Um novo método indicativo de estabilidade por cromatograia líquida foi desenvolvido e validado para a determinação quantitativa de luliconazol. Materiais e métodos: Estudos preliminares de degradação forçada demonstraram um pico adicional no mesmo tempo de retenção do medicamento. O método desenvolvido para otimizar as condições cromatográficas proporcionou resolução adequada (R ≥ 2). O delineamento experimental foi avaliado para verificar sua robustez e a melhor condição cromatográica para validação. Metodologia: Soluções de luliconazol foram expostas a diferentes condições de estresse para avaliar a indicação da estabilidade do método, o isolamento do produto de degradação formado (DP-1), sua identificação e análise in silico para predizer sua rota de degradação e toxicidade. O procedimento foi validado quanto à robustez, seletividade, linearidade, precisão e exatidão. As condições cromatográficas incluíram uma coluna Phenomenex® RP-18, como fase móvel uma mistura de acetonitrila e solução de trietilamina 0,3% (v/v) em eluição isocrática. Resultados e conclusões: O método mostrou-se robusto, com boa recuperação, precisão, resposta linear na faixa de 5,0 a 40,0 μg.mL-1 e indicativo de estabilidade. A condição de estresse alcalino resultou na formação de DP-1. Os estudos da HRMS identificaram este produto como um derivado da hidroxiacetamida e os estudos in silico não mostraram nenhum potencial de toxicidade.

Development of stability-indicating LC method assisted by Design of Experiment for fenticonazole cream analysis in presence of degradation product

Fenticonazole is an antifungal drug widely used in a cream formulation including as a generic medicine. Stability studies of fenticonazole in a cream formulation are very scarce. In this research, we intent to contribute to generic medicines quality control and provide reliable data seeking for insertion of fenticonazole monograph in official compendia. Therefore, in this work it was studied the behavior of fenticonazole under several conditions and developed a stability-indicating LC method to separate the degradation products and quantify the drug in presence of them, using the Design of Experiments (DoE) as tool to achieve robust and easy transferable method. Fenticonazole stability was evaluated under aqueous, alkaline (0.1 M NaOH), acidic (0.1 M HCL) and oxidative (3% v/v, H2O2) at ambient temperature and heating at 90°C, over 6 hours. The drug shows to be unstable under all stressed test conditions. It was completely degraded under acid medium with arising of degradation products. The robust and stability indicating LC method was validated. It is able to reveal the fenticonazole instability and to separate its degradation product with accuracy and precision (CV ˂ 2%) and without any placebo interferences.(AU)

Correlation study of serum homocysteine with renal function and coagulation indexes in hypertensive patients / 中华检验医学杂志

Objective The purpose of this study was to investigate the correlation of serum homocysteine with renal function and coagulation indexes in hypertensive patients .Methods Through retrospective design , 224 hypertensive patients and 212 healthy subjects who sought medical service in Henan Province Hospital of TCM during 2017 to 2018, were divided into four groups according to hypertension and homocysteine level, that was normotensive normal Hcy group (103 patients), normotensive high Hcy group (109 patients), hypertensive normal Hcy group (115 patients), and hypertensive high Hcy group ( 109 patients ) .Serum homocysteine , serum lipid and renal function indexes were detected by automatic biochemical analyzer .The level of coagulation indexes were detected by automatic coagulation analyzer and platelet was tested by automatic blood cell analyzer .Comparisons of variables between four groups were evaluated by one way ANOVA .The correlation was expressed by the Pearson′s correlation coefficient analysis.Multivariate linear regression analysis was performed to identify variables and influence factor associated with Hcy.Results The concentration of Urea in hypertensive high Hcy group (5.73 ± 1.67)mmol/L was significantly increased compared to normotensive normal Hcy group (4.79 ±1.05)mmol/L (t=3.508, P=0.001).The leve of Urea in hypertensive high Hcy group (5.73 ±1.67) mmol/L was significantly increased compared to normotensive high Hcy group (5.21 ±1.21) mmol/L ( t=1.983, P=0.049) and hypertensive normal Hcy group (4.81 ±1.21)mmol/L (t=3.600, P=0.000).The level of Crea in hypertensive high Hcy group ( 79.52 ±25.92 )μmol/L was significantly increased compared to normotensive normal Hcy group (58.39 ±12.83)μmol/L (t=6.121, P=0.000) and hypertensive normal Hcy group (60.93 ±13.74)μmol/L (t=5.526, P=0.000).The level of UA in hypertensive high Hcy group (389.96 ±96.03)μmol/L were significantly higher than normotensive normal Hcy group (293.65 ± 89.94)μmol/L (t=5.722, P=0.000),normotensive high Hcy group (327.02 ±66.55)μmol/L (t=3.837, P=0.000 ) and hypertensive normal Hcy group ( 291.50 ±73.42 )μmol/L ( t=6.128, P=0.000).The level of BMG,CysC in hypertensive high Hcy group and normotensive high Hcy group were higher than normotensive normal Hcy group and hypertensive normal Hcy group .The level of RBP ,D-Dimer, FDP in hypertensive high Hcy group were significantly higher than that of the other three groups .Serum homocysteine correlated positively with Urea (r=0.276,P=0.000),Crea(r=0.389,P=0.000),UA(r=0.339,P=0.000),BMG(r=0.221,P=0.002),RBP(r=0.396,P=0.000),CysC(r=0.200,P=0.006).Multivariate regression analysis showed that the Hcy level was the influencing factors of Urea , Crea and RBP, and hypertension was the influencing factor of Crea , UA, BMG RBP and CysC. Conclusions Hypertensive patients with hyperhomocysteinemia caused renal injury easily . Serum homocysteine may play an important role in renal injury and further affect the occurrence and development of hypertension by impairing the function of platelet , coagulation and fibrinolysis system .

Study on Degradation of Oxidized Regenerated Cellulose Absorbable Hemostatic Products / 中国医疗器械杂志

<p><b>OBJECTIVE</b>To study the degradation of oxidized regenerated cellulose absorbable hemostatic products.</p><p><b>METHODS</b>The morphology of the oxidized regenerated cellulose hemostatic products before and after degradation was observed by FTIR and SEM. The degradation products were determined by GPC and HILIC-ELSD.</p><p><b>RESULTS</b>In the initial stage of degradation, there was a great change in morphology. GPC determined its degradation end point was 10 d; it was determined that its degradation products contained glucose (0.13%) and cellobiose (0.17%) and other components.</p><p><b>CONCLUSIONS</b>A method was established for determining the end point of degradation of oxidized regenerated cellulose, which provided a new idea and reference for the study of the degradation end point.</p>

Fibrinogen degradation product levels on arrival for trauma patients requiring a transfusion even without head injury / 世界急诊医学杂志（英文）

@#BACKGROUND:There have been few reports on the clinical significance of the fibrinogen degradation product (FDP) level in trauma patients with and without head injury. We retrospectively analyzed trauma patients with or without head injury to investigate the clinical significance of the FDP level. METHODS:From April 2013 to June 2015, a medical chart review was retrospectively performed for all patients with trauma. The exclusion criteria included patients who did not receive a transfusion. The patients were divided into two groups:a FDP>100 group, which included patients who had an FDP level on arrival over 100 ng/mL, and a FDP≤100 group. RESULTS:The ratio of open fractures and the prothrombin ratio in the FDP>100 group were significantly smaller than those observed in the FDP≤100 group. The average age, ratio of blunt injury, Injury Severity Score (ISS), volume of transfusion and mortality ratio in the FDP>100 group were significantly greater than those in the FDP≤100 group. There was a weakly positive correlation between the FDP level and ISS (R=0.35, P=0.002), but it was not associated with the transfusion volume. The results of an analysis excluding patients with head injury showed a similar tendency. CONCLUSION:The FDP levels may be a useful biochemical parameter for the initial evaluation of the severity of trauma and mortality even in blunt traumatized patients without head injury or with stable vital signs.

Plasma Levels of D-dimer and Fibrin Degradation Product Could Be Predictors of Endoleaks after Endovascular Abdominal Aortic Aneurysm Repair / 日本心臓血管外科学会雑誌

<b>Objective</b> : Although an endoleak is the most common complication after endovascular abdominal aortic aneurysm repair (EVAR), the proper and noninvasive method for the detection of endoleaks is not established. The purpose of this study is to investigate whether plasma levels of D-dimer and fibrin degradation product (FDP) could be predictors of endoleaks after EVAR. <b>Methods</b> : Between June 2011 and January 2014, 65 consecutive patients underwent EVAR at our institution. We evaluated 55 patients excluding 10 patients pre-existing conditions such as aortic dissection, arterial or venous thrombosis, conversion to open surgery, and difficulties in making outpatient visits. Enhanced computed tomography (CT) examination was performed during 12 months after EVAR. Persistent endoleaks and maximum aneurysmal diameter were evaluated at each follow-up time. Patients were divided into groups according to CT findings at 12 months after EVAR. There were 26 patients with endoleaks vs. 29 non-endoleak patients, 34 with unchanged aneurysm findings vs. 21 with shrinkage. No patient showed aneurysmal enlargement. Plasma levels of D-dimer, FDP, counts of platelet, prothrombin time (PT), and activated partial thromboplastin time (APTT) were also measured at the time of CT examinations. <b>Results</b> : There was no operative death and no major complication. Endoleaks in all patients were identified as type II. None of them required re-intervention. In the endoleak group, plasma levels of D-dimer and FDP were significantly higher than in the non-endoleak group in each postoperative period. In addition, postoperative counts of platelet were significantly lower in the endoleak group. PT and APTT test results showed no significant difference in the two groups. In the unchanged aneurysm group, postoperative D-dimer and FDP tended to be higher compared with the shrinkage group. Postoperative counts of platelet also tended to be lower in the unchanged group. There were no differences in PT and APTT test results. <b>Conclusion</b> : Plasma levels of D-dimer and FDP are potentially useful predictors of endoleaks after EVAR.

Isolation and characterization of a degradation product in leflunomide and a validated selective stability-indicating HPLC-UV method for their quantification / 药物分析学报

Leflunomide (LLM) is subjected to forced degradation under conditions of hydrolysis, oxidation, dry heat, and photolysis as recommended by International Conference on Harmonization guideline Q1A(R2). In total, four degradation products (I–IV) were formed under different conditions. Products I, II and IV were formed in alkaline hydrolytic, acidic hydrolytic and alkaline photolytic conditions. LLM and all degradation products were optimally resolved by gradient elution over a C18 column. The major degradation product (IV) formed in hydrolytic alkaline conditions was isolated through column chromatography. Based on its 1H NMR, IR and mass spectral data, it was characterized as a British Pharmacopoeial impurity B. The HPLC method was found to be linear, accurate, precise, sensitive, specific, rugged and robust for quantification of LLM as well as product IV. Finally, the method was applied to stability testing of the commercially available LLM tablets.

Four new degradation products of doxorubicin:An application of forced degradation study and hyphenated chromatographic techniques / 药物分析学报

Forced degradation study on doxorubicin (DOX) was carried out under hydrolytic condition in acidic, alkaline and neutral media at varied temperatures, as well as under peroxide, thermal and photolytic conditions in accordance with International Conference on Harmonization (ICH) guidelines Q1(R2). It was found extremely unstable to alkaline hydrolysis even at room temperature, unstable to acid hy-drolysis at 80 °C, and to oxidation at room temperature. It degraded to four products (O-I-O-IV) in oxidative condition, and to single product (A-I) in acid hydrolytic condition. These products were re-solved on a C8 (150 mm × 4.6 mm, 5μm) column with isocratic elution using mobile phase consisting of HCOONH4 (10 mM, pH 2.5), acetonitrile and methanol (65:15:20, / / ). Liquid chromatography-pho-todiode array (LC-PDA) technique was used to ascertain the purity of the products noted in LC-UV chromatogram. For their characterization, a six stage mass fragmentation (MS6) pattern of DOX was outlined through mass spectral studies in positive mode of electrospray ionization (+ESI) as well as through accurate mass spectral data of DOX and the products generated through liquid chromato-graphy-time of flight mass spectrometry (LC-MS-TOF) on degraded drug solutions. Based on it, O-I-O-IV were characterized as 3-hydroxy-9-desacetyldoxorubicin-9-hydroperoxide, 1-hydroxy-9-desacetyldox-orubicin-9-hydroperoxide, 9-desacetyldoxorubicin-9-hydroperoxide and 9-desacetyldoxorubicin, re-spectively, whereas A-I was characterized as deglucosaminyl doxorubicin. While A-I was found to be a pharmacopoeial impurity, all oxidative products were found to be new degradation impurities. The mechanisms and pathways of degradation of doxorubicin were outlined and discussed.

Effects of different dose tranexamic acid in fibrinolysis during liver transplantation / 实用医学杂志

Objective To investigate the effects of different dose of tranexamic acid in fibrinolysis during liver transplantation. Methods Sixty ASA Ⅱ~ Ⅳ liver transplant recipients, were randomly, double-blind assigned to one of 3 groups (n = 20): group control (group C), group tranexamic acid 1 (group T1) and group tranexamic acid 2 (group T2). The patients in group C received a loading dose of normal saline 10 mL, then continued infuse normal saline at 20 mL/h until neohepatic phase 120 min, while in other two groups, patients received a loading dose of tranexamic acid 1 g, totally 10 mL, followed by continuous infusion at 10 mg/(kg·h) in group T1 or 20 mg/(kg·h) in group T2 until neohepatic phase 120 min. Prothrombin time, fibrinogen, fibrin degradation product and D-dimers were measured before operation (T0), 120 min after the skin incision (T1), nonhepatic phase 30 min (T2), neohepatic phase 120 min (T3). Blood loss, fresh frozen plasma dosage, fibrinogen dosage and thromboembolic events were recorded. Results The plasma concentration of fibrin degradation product and plasma concentration of D-dimers were different in the 3 groups, group T2 0.05). Conclusions Continuous infusion of tranexamic acid can inhibit fibrinolysis during liver transplantation. No adverse event of thrombosis was detected. Larger dose of tranexamic acid can reduce blood loss and fresh frozen plasma transfusion.

Clinical significance of plasma D-dimer, fibrinogen and fibrin/fibrinogen degradation product detection in patients with chronic obstructive pulmonary disease / 中国医师进修杂志

Objective To investigate clinical significance of plasma D-dimer (D-D),fibrinogen (FIB) and fibrin/fibrinogen degradation product (FDP) in patients with chronic obstructive pulmonary disease (COPD).Methods The level of plasma D-D,FIB and FDP in 150 patients with COPD and 80 healthy persons were detected,and compared.Results The level of plasma D-D,FIB and FDP in COPD patients were significantly higher than those in healthy persons[(2.16 ± 0.61) mg/L vs.(0.55 ± 0.04) mg/L,(5.88 ± 1.52) g/L vs.(3.12 ± 0.35) g/L,(7.18 ± 1.63) mg/L vs.(3.62 ± 1.55) mg/L],there were significant differences (P ＜ 0.01).Conclusion Monitoring the level of plasma D-D,FIB and FDP in COPD patients can provide reliable basis in hypercoagulable state and primary and secondary hyperfibrinolysis.

Development of forced degradation and stability indicating studies of drugs-A review / 药物分析学报

Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions. It is required to demonstrate specificity of stability indicating methods and also provides an insight into degradation pathways and degradation products of the drug substance and helps in elucidation of the structure of the degradation products. Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. In addition, the regulatory guidance is very general and does not explain about the performance of forced degradation studies. Thus, this review discusses the current trends in performance of forced degradation studies by providing a strategy for conducting studies on degradation mechanisms and also describes the analytical methods helpful for development of stability indicating method.

Studies on Stability of Hesperidin in Alkaline Solution / 世界科学技术-中医药现代化

This article was aimed to study the stability of hesperidin in alkaline solution, in order to provide experi-ment evidences for quality control of extraction and purification as well as formulation development. RP-HPLC was applied to determinate content changes of hesperidin in alkaline solution by changing the temperature, pH and heat-ing time. The results showed that hesperidin was degraded in alkaline solution by heating. The content of hesperidin decreased along with the increasing of heating temperature and heating time. The hesperidin appeared to be more stable in a weak base. It was concluded that for the purpose of ensuring of the stability of hesperidin in alkaline so-lution, it should be kept at low temperature (below 50℃), weak base conditions and shorten the heating time during the preparation process.

Validated stability-indicating HPLC method for simultaneous estimation of ofloxacin and satranidazole from pharmaceutical dosage form.

The present paper describes development of stability- indicating RP- HPLC method for the simultaneous determination of Ofloxacin and Satranidazole in presence of its degradation products, generated from forced degradation studies. Ofloxacin and Satranidazole and their combination drug product were exposed to acid, base, neutral hydrolysis; oxidation, dry heat, photolytic stress conditions and the stressed samples were analyzed by proposed method. The proposed HPLC method utilizes HiQ sil C18W column (250mm × 4.6mm i.d., 5μm) of KYA TECH, Corporation and a mobile phase comprising of acetonitrile: phosphate buffer (pH3) in ratio of 35:65v/v with flow rate of 1ml/min. The retention time of OFLX and STZ was found to be 2.85min and 6.25min respectively. Quantitation was achieved with UV detection at 296nm for OFLX and 320nm for STZ. The method has been validated for ofloxacin and satranidazole in terms of accuracy, precision, linearity, LOD, LOQ and robustness. The developed validated stability-indicating HPLC method was found to be simple, specific, accurate and reproducible for the determination of instability of these drugs in bulk and commercial products.

Fibrin(ogen), Its Degradation Products and their Motif Antagonist and Atherosclerosis / 国际脑血管病杂志

Atherosclerosis is the most important pathological basis of ischemic cerebrovascular diseases. As an independent risk factor of atherosclerosis, fibrin(ogen) and its degradation products involve in the processes of the formation and development of atherosclerosis. This article reviews the relationship between fibrin(ogen) and/or its degradation products and atherosclerosis, and also introduces the development and application prospects for some specific motif antagonists of fibrin(ogen) in the treatment of atherosclerosis and ischemic cerebrovascular diseases.

The latest development of two-compartment peritoneal dialysis fluids with low glucose degradation products / 医学研究生学报

The biological incompatibility of traditional peritoneal dialysis fluids(PDF) is the main reason for the poor outcomes of long-term peritoneal dialysis and the high rate of technical failure.Recently,two-compartment PDF has been applied in the treatment of peritoneal dialysis patients,and reportedly has lots of clinical advantages due to its better biocompatibility.This paper presents an overview of recent advances in the studies of two-compartment PDF.

Macrovascular dysfunction detected by comparison of serum FDP detected by simplified venous occlusion test in patients with NIDDM and CVA / 대한내과학회지

OBJECTIVES: In diabetic patients, the incidence of atherosclerotic disease are increased, which may be due to decreased fibrinolytic activity. The aim of study is to elucidate the relationship between angiopathies and vascular function evaluated by simplified venous occlusion test in patients with non-insulin dependent diabetes mellitus (NIDDM) and cerebrovascular accident (CVA). METHODS: The study was conducted on 63 patients who were hospitalized during the period from March 1, 1994 to May 30, 1997. The serum concentration of fibrinogen degradation products (FDP) was measured before and 5 min after venous occlusion in 31 NIDDM patients, 16 CVA patients and 16 age-matched control subjects. FDP was measured with the anti-fibrinogen- coated latex particle agglutinin assay system. RESULTS: 1) The basal serum FDP level was higher in diabetic patients with macroangiopathy (12.3+/-5.8 ug/ml) and patients with CVA (11.2+/-5.1 ug/ml) than in control subjects (5.7+/-1.8 ug/ml) (p<0.05). 2) The increment of serum FDP level after venous occlusion in diabetic patients with microangiopathy (6.6+/-2.2 to 10.3+/-4.1 ug/ml) and control subjects (5.7+/-1.8 to 11.4+/-4.3 ug/ml) was significantly higher than basal serum FDP level (p<0.05). But the increment of serum FDP level after venous occlusion in diabetic patients with macroangiopathy (12.3+/-5.8 to 15.2+/-5.1 ug/ml) and patients with CVA (11.2+/-5.1 to 13.7+/-4.8 ug/ml) wasn't significantly higher than basal serum FDP level. 3) The increment rate of serum FDP after venous occlusion in diabetic patients with macroangiopathy (24.4+/-29.3%) and patients with CVA (29.4+/-34.5%) was significantly lower than diabetic patients with microangiopathy (66.3+/-71.7%) and control subjects (84.1+/-69.3%) (p<0.05). CONCLUSION: The responsiveness of fibrinolytic activity to venous occlusion was significantly lower in diabetic patients with macroangiopathy, as in patients with CVA, compared with that in control subjects. We conclude that measurement of the increase in serum FDP concentration 5 min after venous occlusion may be useful to detect vascular dysfunction in patients with macrovascular disease caused by atherosclerosis.

The fibrinogen degradation products (FgDP) levels in liver disease

We measured plasma levels of fibrinogen degradation products (FgDP) with newly developed enzyme-linked immunosorbent assay based on monoclonal antibody to assess the fibrinogenolytic state in 52 patients with various liver diseases (27 patients with liver cirrhosis, 10 with chronic hepatitis, 7 with acute hepatitis, 6 with hepatocellular carcinoma, 2 with intrahepatic cholestasis). As compared with 20 healthy subjects (upper limit: 580 ng/ml), elevated plasma levels (660-32000 ng/ml) of FgDP were found in 19 (36.5%) patients. When analyzed according to the underlying disease categories, the magnitude of elevations of FgDP were most prominent in patients with chronic hepatitis. No correlation was found between plasma FgDP levels and serum AST or ALT activity. These findings indicate that increased primary fibrinogenolysis is not rare in liver disease, but poorly correlates with liver function.