Efficacy and safety of Nafamostat mesylate in patients with endstage renal failure

BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fiber activity.AIM To evaluate the efficacy and safety of Nafamostat mesylate in patients with end-stage renal failure.METHODS Seventy-five patients with end-stage renal failure who received hemodialysis at our hospital between January 2020 and August 2021 were selected and divided into the observation group(Nafamostat mesylate for injection,n=33)and control group(heparin sodium injection,n=32).General patient data,indicators of clinical efficacy,dialyzer hemocoagulation parameters,coagulation function indices,and hemoglobin concentration and platelet count before and after treatment,and the occurrence of adverse reactions after treatment were compared between the two groups.RESULTS The two groups showed no significant differences in general patient data(P>0.05).The post-treatment effectiveness rate in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the number of patients in grade I(P>0.05),while the number of patients in grade 0 was lower in the control group,and the number of patients in grades II and III was higher in the control group(P<0.05).The post-treatment prothrombin time,activated partial thromboplastin time,thrombin time,and international normalized ratio values in the control group were higher than those in the observation group,while the fibrinogen level in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the platelet count and hemoglobin level before and after treatment(P>0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(P<0.05).CONCLUSION Treatment of patients showing end-stage renal failure with Nafamostat mesylate can significantly improve therapeutic efficacy and has high safety and clinical value.

Imatinib mesylate in clinically suspected gastric stromal tumors

Gastrointestinal stromal tumors （GISTs） occur most frequently in the stomach.Diagnosis of gastric GIST is not always clear before surgery.Flexible endoscopy may suggest the nature of the lesion （a bulky tumor with preserved mucosa）; however,biopsy is rarely diagnostic.Therefore,diagnostic medication with safe drugs may provide a feasible way under such conditions after an informed consent is obtained.Based on the excellent efficacy of imatinib mesylate （IM） in the treatment of GIST,we successfully applied it in the diagnostic medication of two patients with clinically suspected gastric stromal tumors.In conclusion,the diagnostic medication with IM can be an alternative option for patients with suspected GIST that can not be confirmed pathologically.

Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor(GIST) . Computed tomography(CT) and magnetic resonance imaging(MRI) 107 mo after the operation,revealed a cystic mass(14 cm in diameter) and a solid mass(9 cm in diameter) in the right and left lobes of the liver,respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate(IM) treatment,400 mg/day orally. Following the IM treatment for a period of 35 mo,the patient underwent partial hepatectomy(S4 + S5) . The effect of IM on the metastatic lesions was interpreted as pathologic complete response(CR) . Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

Effect of ziprasidone on QTc interval in Chinese patients with schizophrenia

Objective： To investigate the effect of ziprasidone on QTc in Chinese patients with schizophrenia. Methods： The study involved 27 patients with schizophrenia. Ziprasidone was initiated with 40 mg/day. From day 3 to day 7, the dose was increased gradually to 120-160 mg/d according to the effectiveness and tolerahility. QTc values were measured at the beginning and month 6. Results： At the beginning of the 6 months treatment, the mean QTc interval of patients was （387.5±19.0） ms. At the end of the study, it was （402.9±23.6） ms. The difference has statistically significance （P〈0.05）. The mean QTc interval changed significantly throughout 6-months period but no one exceed the QTc dangerous limits. Significant correlation was found between QTc interval and the dose. Conclusion： In summary, our results suggest that ziprasidone has good tolerance in patient with schizophrenia despite its dose-related QTc prolongation. Ziprasidone have no pro-arrhythmic profile

Advanced gastrointestinal stromal tumor patients with complete response after treatment with imatinib mesylate

AIM： Most gastrointestinal stromal tumors （GISTs） express constitutively activated mutant isoforms of kit kinase or platelet-derived growth factor receptor alpha （PDGFRA）, which are potential therapeutic targets for imatinib mesylate （Glivec）. Partial response occurred in almost two thirds of GIST patients treated with Glivec. However, complete response （CR） after Glivec therapy was sporadically reported. Here we illustrated advanced GIST patients with CR after Glivec treatment. METHODS： Between January 2001 and June 2005, 42 advanced GIST patients were treated with Glivec. Patients were administered 400 mg of Glivec in 100-mg capsules, taken orally daily with food. The response of the tumor to Glivec was evaluated after one month, three months, and every three months thereafter or whenever medical need was indicated. Each tumor of patients was investigated for mutations of kit or PDGFRA. RESULTS： The median follow-up time of the 42 ad-vanced GIST patients treated with Glivec was 16.9 months （range, 1.0- 47.0 months）. Overall, 3 patients had complete response CR （7.1%）, 26 partial response （67.8%）, 5 stationary disease （11.9%）, and 3 progressive disease （11.9%）. The median duration of Glivec administration for the three patients was 36 months （range, 23-36 months）. The median time to CR after Glivec treatment was 20 months （range, 9-26 months）. Deletion and insertion mutations of c-kit exon 11 and insertion mutation of c-kit exon 9 were found in two cases and one case, respectively. CONCLUSION： Complete response （CR） can be achieved in selected advanced GIST patients treated with Glivec. The median time to CR after Glivec treatment was 20 months. Deletion and insertion mutations of kit exon 11 and insertion mutation of kit exon 9 contribute to the genetic features in these selected cases.

Evaluation of imatinib mesylate(Gleevec) on KAI1/CD82 gene expression in breast cancer MCF-7 cells using quantitative real-time PCR

Objective: To evaluate the effect of imatinib mesylate on cell viability, anti cancer effect through modulation of KAI1/CD82 gene expression in breast cancer MCF-7 cell line.Methods: The effects of imatinib mesylate on cell viability in MCF-7 cell line were assessed using MTT assay and IC_(50) value was determined. GAPDH and KAI1/CD82 were selected as reference and target genes, respectively. Quantitative real time PCR technique was applied for investigation of KAI1/CD82 gene expression in human breast cancer MCF-7 cells. Subsequently, the quantity of KAI1 compared to GAPDH gene expressions were analyzed using the formula; 2^(-DDCt).Results: Imatinib was showed to have a dose-dependent inhibitory effect on the viability of MCF-7 cells. CD82/GAPDH gene expression ratios were 1.322 ± 0.030(P > 0.05),2.052 ± 0.200(P < 0.05), 2.151 ± 0.270(P < 0.05) for 10, 20 and 40 mmol/L of imatinib concentrations.Conclusions: Based on the present data, imatinib mesylate might modulate metastasis by up-regulating KAI1/CD82 gene expression in human breast MCF-7 cancer cell line.

Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia

Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acute pancreatitis,and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East.The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia.Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases,neuroinflammatory signaling cascades,and the endoplasmic reticulum stress responses,downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents,modulating the activity of intracellular signal transduction pathways,and supporting neuronal survival brain-derived neurotrophic factor/TrkB/ERK1/2/CREB,nuclear factor kappa B.The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture.Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac,hepatic,renal,or intestinal transplant,preventing allograft rejection,and treating solid organ malignancies.Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.

Literature review and economic evaluation of oral and intramuscular ziprasidone treatment among patients with schizophrenia in China

Background Over 10 million Chinese are affected by schizophrenia. The annual cost of schizophrenia in China was estimated at US$2586 per patient.Aims The study has two aims:(1) to conduct a targeted literature review of the economic literature on oral ziprasidone in China, and(2) to develop an inpatient economic model that compared the cost of intramuscular ziprasidone with other regimens including electroconvulsive therapy(ECT) for the management of acute agitation in patients with schizophrenia from a hospital's perspective in China.Methods A targeted literature review was conducted using PubMed and the Chinese literature databases for studies published between January 2007 and December2017. Studies that assessed costs associated with oral ziprasidone treatment for schizophrenia in China were summarised. In the inpatient economic model,cost measures included hospital room and board,antipsychotics,ECT and medications for the management of extrapyramidal symptoms(EPS). Input for standard antipsychotic regimens and unit cost were obtained from the literature. Hospital length of stay(LOS), utilisation of ECT and incidence of EPS were derived from the literature and supplemented/validated with a survey of psychiatrists in China. Cost was presented in 2017 Chinese yuan.Results The average estimated LOS was 29 days with ziprasidone, 33 days with risperidone+benzodiazepine,32 days with olanzapine, 35 days with haloperidol and 29 days with ECT. The cost of antipsychotics was $1260 with ziprasidone, $137 with risperidone+benzodiazepine, $913 with olanzapine and $210 with haloperidol; ECT treatment costs $785. The base-case analysis suggested that higher antipsychotic cost with ziprasidone was offset by savings with shorter LOS. Using intramuscular ziprasidone for acute management was associated with a total cost of $11157, the lowest among all antipsychotic regimens($11 424 with risperidone+benzodiazepine, $11 711 with olanzapine and $11 912 with haloperidol) and slightly higher than ECT($10 606). The cost of antipsychotics and ECT accounted for 1 %-11 % of the total cost. Varying LOS between the lower and upper bounds of the 95% CI, the total cost was comparable between these regimens.Conclusions Overall, the cost for the management of acute agitation was similar between intramuscular ziprasidone and other antipsychotics. Compared with other antipsychotics, the higher medication cost of intramuscular ziprasidone can be offset by savings with shorter hospital stay. The results from this economic analysis were complementary to the findings in the published literature assessing the economic outcomes of oral ziprasidone.

Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate:a case report

Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, co- existance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST.

Assessment of gastrointestinal stromal tumors with computed tomography following treatment with imatinib mesylate

AIM: To evaluate and characterize the patterns of disease progression of metastatic or unresectable gastrointestinal stromal tumor (GIST) treated with imatinib mesylate, and to determine the prognostic significance associated with disease progression. METHODS: Clinical data and computed tomography (CT) images were retrospectively reviewed in 17 GIST patients who were treated with imatinib mesylate from October 2002 to October 2006. Apart from using size measurement for evaluation of tumor response [Response Evaluation Criteria in Solid Tumors (RECIST) criteria], patterns of CT changes during treatment were evaluated and correlated with clinical data. RESULTS: There were eight non-responders and nine responders. Five patterns of CT change during treatment were found: focal progression (FP), generalized progression (GP), generalized cystic change (GC), new cystic lesion (NC) and new solid lesion (NS). At the end of study, all non-responders showed GP, whereas responders showed cystic change (GC and NC) and response according to RECIST criteria. Overall survival was significantly better in patients with cystic change or response within the RECIST criteria compared with GP patients (P = 0.0271). CONCLUSION: Various patterns of CT change in patients with GIST who responded to imatinib mesylate were demonstrated, and might determine the prognosis of the disease. A combination of RECIST criteria and pattern of CT change are proposed for response evaluation in GIST.

Binding interactions of pefloxacin mesylate with bovine lactoferrin and human serum albumin

The binding of pefloxacin mesylate （PFLX） to bovine lactoferrin （BLf） and human serum albumin （HSA） in dilute aqueous solution was studied using fluorescence spectra and absorbance spectra. The binding constant K and the binding sites n were obtained by fluorescence quenching method. The binding distance r and energy-transfer efficiency E between pefloxacin mesylate and bovine lactoferrin as well as human serum albumin were also obtained according to the mechanism of Forster-type dipole-dipole nonradiative energy-transfer. The effects of pefloxacin mesylate on the conformations of bovine lactoferrin and human serum albumin were also analyzed using synchronous fluorescence spectroscopy.

Evaluation of the Pharmacokinetics of Nafamostat Mesylate during Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) is the preferred dialysis modality in critical care settings for patients with hemodynamic instability. Nafamostat mesylate (NM) is an anticoagulant commonly used (mainly in Japan) during CRRT in patients with high bleeding risk. In this study, we evaluated the pharmacokinetics of NM during CRRT. Patients undergoing CRRT therapy and using NM as the anticoagulant in the intensive care unit were enrolled in the study. Blood was collected from the CRRT circuit just after blood removal, just before and after the membrane for CRRT, and from the filtrates after the membrane. NM concentrations were measured using high-performance liquid chromatography. NM was detected in the intracorporeal circulation during CRRT in some cases, and liver enzymes were severely elevated in almost all of the cases. Coagulation time was prolonged even before the initiation of NM administration in these cases and may be associated with liver damage. This study suggests that NM dosage should take into account liver damage assessed by elevated liver enzymes.

Gastrointestinal stromal tumors and second primary malignancies before and after the introduction of imatinib mesylate

Gastrointestinal stromal tumor （GIST） is the most common mesenchymal malignancy of the gastrointestinal tract.GISTs may coexist with different types of cancer,either synchronous or metachronous （1）.Most GISTs develop in a sporadic fashion,but familial occurrence,such as neurofibromatosis and Carney-triad,has also been reported （2）.The overall frequency of second tumors in different series varied from 4.5% to 33%.The most frequent types of GIST-associated cancers were gastrointestinal carcinomas （47%）,lymphoma/leukemia （7%）,carcinomas of prostate （9%）,breast （7%）,kidney （6%）,lung （5%）,female genital tract （5%）,carcinoid tumors （3%）,soft tissue and bone sarcomas （3%）,malignant melanoma （2%） and seminoma （1%） （1,3-5）.

治疗转移性乳腺癌新药——甲磺酸阿贝西尼(abemaciclib mesylate)

治疗转移性乳腺癌新药甲磺酸阿贝西尼(abemaciclib mesylate)是周期蛋白依赖激酶(CDK)4/6抑制药,由美国礼来公司(Eli Lilly and company)研发,曾用名为Bemaciclib,用于治疗激素受体(HR)阳性(HR+)及人表皮生长因子受体2(HER2)阴性(HER2-),经内分泌治疗后乳腺癌已进展或转移的成人晚期患者。阿贝西尼于2015年10月9日获得美国食品药品管理局(FDA)突破性疗法的认定,给予在HR+/HER2-乳腺癌患者中优先评审资格,2017年9月28日批准上市,商品名为Verzenio。该文对甲磺酸阿贝西尼的非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。

CdS nanocrystals as fluorescent probe for detection of dolasetron mesylate in aqueous solution:Application to biomedical analysis

A simple and straightforward method for the determination of dolasetron mesylate(DM) in aqueous solution was developed based on the fluorescence quenching of 3-Mercaptopropionic acid(MPA) capped Cd S quantum dots(QDs).The structure,morphology,and optical properties of synthesized QDs were characterized by using UV-Vis absorption spectroscopy,fluorescence spectroscopy,transmission electron microscopy(TEM) and dynamic light scattering(DLS) measurements.Under the optimum conditions,the MPA-Cd S QDs fluorescence probe offered good sensitivity and selectivity for detecting DM.The probe provided a highly specific selectivity and a linear detection of DM in the range of 2–40 μg/m L with detection limit(LOD) 1.512 μg/m L.The common excipients did not interfere in the proposed method.The fluorescence quenching mechanism of Cd S QDs is also discussed.The developed sensor was applied to the quantification of DM in urine and human serum sample with satisfactory results.

Preparation and Characterization of Danofloxacin Mmesylate Liposomes

Five different methods were tested and compared to prepare danofloxacin mesylate liposomes, the ammonium sulfate gradient method with freeze-thawing steps was validated as the best one; the optimal preparation condition confirmed by orthogonal experiment was as follows： EPC-CH ratio was 3 ： 2 and 2.6% SA was added to gain the positive electricity; drug-lipoid was 2 ： 5, the concentration of ammonium sulfate was 250 mmol·L-1, water-oil ratio was 1：5, and they were incubated at 35℃ for 15 min. The prepared liposome products were ivory white semitransparent suspension, the electron microscope appearance was intact and globular or globular-like vesicles with uniformed distribution; the particle size was centralized from 3 to 7 gm, zeta-electric potential valued＋ （15.92＋1.49） mV, pH valued 6.02~0.09; HPLC method was established in quantitative analyses of danofloxacin and reverse dialysis with RP-HPLC method was validated for determination of entrapment efficiency. The entrapment efficiency results were all above 90%. They were stored at 4℃ with satisfied stability. Six months later, the appearance, characters and entrapment efficiency were almost with no change

Bilateral Masculine Mastoplasia Associated with Imatinib Mesylate:A Case Report and Literature Review

1 CASE REPORT In June 2009, a 29-year-old Chinese male was diagnosed as having Philadelphia chromosome-positive chronic myeloid leukemia （chronic phase）; other than a high white blood cell count in peripheral blood （WBC, 254.00×10^9/L） and splenomegaly, the patient exhibited no abnormal physical signs in mammary glands. He was given hydroxyurea for several days before he received treatment with 400 mg of imatinib mesylate daily.

Development and Validation of Stability Indicating HPTLC Assay for Determination of Gemifloxacin Mesylate in Dosage Forms

Simple and sensitive stability-indicating high performance thin layer chromatography (HPTLC) assay was developed and validated for quantitative determination of the antibacterial drug, gemifloxacin mesylate (GFX) in presence of its degradation products and ambroxol hydrochloride. The chromatographic separation was performed on HPTLC precoated silica gel plate 60F254 as stationary phase. The mobile phase consisted of a mixture of ethyl acetate: methanol: 25% ammonia, (8:4.5:3, v/v/v). The detection was performed using fluorescence mode and the emission intensity was measured using optical filter K400 after excitation at 342 nm. The Rf value for GFX was 0.47 ± 0.03. Good correlation coefficient was obtained over the concentration range of 1.5 - 180 ng/band. The LOD and LOQ of the proposed method were 0.28 and 0.86 ng/band, respectively. The proposed method was successfully applied for the analysis of GFX in its single and combined dosage forms. Moreover, it was utilized to investigate the kinetics of acidic, alkaline, neutral, oxidative and photolytic degradation of the drug. The apparent kinetic-order rate constants and half-life times of the degradation process were calculated. Furthermore, the proposed method was successfully applied for investigating the factors affecting the storage of GFX.