OBJECTIVETo develop a HPLC assay for the determination of metformin hydrochloride-related substances.

METHODSThe separation was performed on SHIMADZU VP-ODS (250 4.6 mm, 5 microm) column. The mobile phase of dicyandiamide was composed of methyl alcohol-1 mmol x L(-1) sodium dodecylsulfate in 10 mmol x L(-1) phosphate salt solution (60:40) (pH=5.5). The mobile phase of other related substances was composed of methyl alcohol-1 mmol x L(-1) sodium dodecysulfate in 10 mmol x L(-1) phosphate salt solution (55:45)(pH=5.5). The detection wavelength was 232 nm, and the running speed was 0.8 ml min(-1) at room temperature.

RESULTGood resolution of dicyandiamide and main peak was obtained. The test results were reproducible.

CONCLUSIONThe method is simple, rapid and suitable for the determination of dicyandiamide and other metformin hydrochloride-related substances.

Chromatography, High Pressure Liquid ; Guanidines ; analysis ; Hypoglycemic Agents ; chemistry ; Metformin ; chemistry ; Sensitivity and Specificity ; Tablets

PURPOSE: Systemic anticoagulation, usually with heparin, is required to prevent thrombosis in the blood circuit of hemodialysis. In patients at high bleeding risk, strategies to minimize the bleeding risk include heparin-free or regional anticoagulation methods. Nafamostat mesilate with conventional dose (35 mg/hr) has been used for this purpose. But it is an expensive anticoagulant to use conveniently for the dialysis therapy. Application of low-dose nafamostat mesilate has almost never been tried yet on hemodiaysis management. In this study, we examined the effect of low-dose nafamostat mesilate compared to heparin-free in hemodialysis patients with high risk of bleeding. METHODS: The current study was conducted on 35 hemodialysis patients with high bleeding risk (on-going bleeding, hemorrhage, surgery or severe thrombocytopenia). In the low-dose nafamostat group (n=17, mean age: 59+/-15 years), 238 sessions were performed with continuous infusion of nafamostat mesilate (12.5 mg/hr). In the control group with saline-flushing no heparin methods (n=18, mean age: 57+/-17 years), 247 sessions were analyzed. RESULTS: No significant differences were found in baseline characteristics between the low-dose nafamostat group and the saline group. In the progress of bleeding complications, there were no significant differences between the two groups (11.8% vs. 11.1%). In saline group, however, massive clotting occurred in 44.5 per 1000 sessions, while it occurred in 4.2 per 1000 sessions in the low-dose nafamostat group (p=0.006). CONCLUSION: In patients at high bleeding risk, low-dose nafamostat mesilat can be used as an inexpensive, effective, and safe anticoagulant for hemodialysis.
Dialysis ; Guanidines ; Hemorrhage ; Heparin ; Humans ; Mesylates ; Renal Dialysis ; Thrombosis

No abstract available.
Metformin

Introduction: Diabetes in the Philippines is a major and growing health issue. From its prevalence of 2.8 million in 2000, it was projected by the World Health Organization to reach 7.8 million by 2030. Glimepiride has been found to be effective and well-tolerated, as monotherapy and in combination with metformin, in managing glycemic levels among type II diabetes mellitus (T2DM) patients. This study aimed to assess the safety and efficacy of a sustained release (SR) fixed-dose combination (FDC) preparation of glimepiride and metformin in the treatment of Filipino patients with T2DM. Methods: This open-label, observational, multicenter, post-marketing study, conducted from April 2012 to December 2013, included 20 to 75-year-old patients with T2DM, presenting with 7% to 11% HbA1c or 110-250 mg/dL fasting blood sugar, insulin-naive, and in consideration for management with a glimepiride-metformin FDC. Baseline data were collected. Patients were prescribed with glimepiride-metformin FDC SR 2/500 mg/tab for a six-month treatment period. Follow-up data were collected on the third and the sixth month of treatment. Patients who missed one follow-up were included in population for safety analysis. Patients who completed both follow-up schedules make up the per-protocol population for efficacy analysis. Adverse events (AEs) were reported in frequencies and percentages. Repeated measures analysis of variance (ANOVA) was used for efficacy analysis on HbA1c and FBG data. Results: From 1,052 enrollees, 795 patients had sufficiently filled data forms and attended at least one follow-up schedule; this is the population whose data was analyzed for this study. Fifty-nine AEs were reported; only 21 incidents of hypoglycemia were assessed to be definitely, probably, or possibly related to the study drug. Repeated measure ANOVA showed that the mean ± SD HbA1c at month three (7.15 ± 1.22%) and month six (6.80 ± 1.17%) were significantly lower than baseline (8.67 ± 1.10%). The mean ± SD FBG at month three (133.20 ± 35.46 mg/dL) and month six (122.47 ± 29.34 mg/dL) were also significantly lower than baseline (176.85 ± 41.24 mg/dL). The differences in HbA1c and FBG changes between those with concomitant OAD and those without were non-significant. Conclusion Fixed-dose combination of glimepiridemetformin is a drug with a tolerable profile and favorable benefits in treating patients with T2DM.
Metformin

BACKGROUND: The patch test is widely used for diagnosis of allergic contact dermatitis. However, nearly half of positive reactions can be observed only on day 2 or day 4 and it is difficult to interpret these reactions. OBJECTIVE: The purpose of this study is to assess the frequency of transient and delayed reactions in TRUE-test and detect common antigens that provoke these reactions. METHODS: A total of 311 patients with allergic contact dermatitis were evaluated by TRUE-test between Jan 2007 and December 2011. Records of patch test results of day 2 and day 4 were reviewed and analyzed. RESULTS: A total 311 cases of T.R.U.E. TEST(R) records (male 79, female 232) were analyzed. Persistent reactions were observed in 80.1% patients tested, transient reactions were observed in 18.3%, and delayed reaction in 5%. Frequent allergens which showed transient reactions were cobalt dichloride (2.9%), nickel sulfate (2.2%), thiomersal (1.9%), and carba mix (1.6%), in order of frequency. Allergens which showed delayed reactions were nickel sulfate (0.3%), fragrance mix (0.3%), p-tert-butylphenol formaldehyde resin (0.43). CONCLUSION: Our results showed a relatively high frequency of transient reaction in T.R.U.E. TEST(R). This suggests that additional reading at day 4 in the patch test would be of value.
Allergens ; Cobalt ; Dermatitis, Allergic Contact ; Ditiocarb ; Female ; Formaldehyde ; Guanidines ; Humans ; Nickel ; Patch Tests ; Resins, Synthetic ; Thimerosal

PURPOSE:In patients with a higherrisk of bleeding, performing CVVH with heparin or saline anticoagulation is associated with increased bleeding or thrombotic risk. Nafamostat mesilate (NM), a serine proteinase inhibitor, while inhibiting various clotting factors in filter circuit, is characterized by short half life resulting in little systemic anticoagulation effect. Accordingly, we prospectively evaluated the anticoagulant effect and safety of NM in patients with a higher risk of bleeding who underwent CVVH. METHODS:Among 43 patients with high risk of bleeding [defined by (1) INR>2, aPTT>20 sec, platelet< 50,000/mm3 or (2) ongoing bleeding, major hemorrhage/surgery in the last 48 hrs], 20 patients were treated with continuous nafamostat mesilate infusion (10-20 mg/hr) and remaining 23 patients were treated with saline bolus infusion (100 mLq 1 hr) for CVVH anticoagulation. RESULTS:As compared with saline bolus group, mean circuit life was significantly longer in NM infusion group (28.73+/-12.67 versus 16.34+/-7.86, p=0.001). There was no significant bleeding complication in either saline bolus or NMinfusion group. In subgroup analysis according to the presence of abnormal coagulation status (defined by INR>2, aPTT>20 sec, platelet<50,000/mm3), the positive effect of NM on circuit lifespan persisted irrespective of the coagulation status. CONCLUSION:As compared with saline bolus, nafamostat mesilate infusion was associated with higher CVVH filter life. In patients with high risk of bleeding, nafamostat mesilate can be used as a safe and effective anticoagulant for CVVH with acceptable filter life
Guanidines ; Half-Life ; Hemofiltration ; Hemorrhage ; Heparin ; Humans ; Mesylates ; Prospective Studies ; Serine Proteases

BACKGROUND/AIMS: The protease inhibitors, nafamostat and gabexate, have been used to prevent pancreatitis related to endoscopic retrograde cholangiopancreatography (ERCP). In vitro, nafamostat inhibits the pancreatic protease activities 10-100 times more potently than gabexate. We evaluated the efficacy of nafamostat for prophylaxis against post-ERCP pancreatitis in comparison with gabexate. METHODS: Five hundred patients (208 patients in the nafamostat-treated group and 292 in the gabexate-treated group) were analyzed retrospectively after selective exclusion. The incidences of pancreatitis and hyperamylasemia after the ERCP were compared between the nafamostat and gabexate groups. RESULTS: The incidences of acute pancreatitis and hyperamylasemia were 9.1% and 40.9%, respectively, in the nafamostat-treated group, and 8.6% and 39.4% in the gabexate-treated group. The frequencies of post-ERCP pancreatitis and hyperamylasemia did not differ significantly between the two groups, Post-ERCP pancreatitis in two group did not vary according to the different ERCP procedures. The mean serum amylase level at 6 h after ERCP was significantly lower in the nafamostat-treated group than in the gabexate-treated group (p=0.020). However, the difference in serum amylase level did not persist at 18 h and 36 h post-ERCP. CONCLUSIONS: Administration of nafamostat before ERCP was not inferior to gabexate in protecting against the development of pancreatitis.
Amylases ; Cholangiopancreatography, Endoscopic Retrograde ; Gabexate ; Guanidines ; Humans ; Hyperamylasemia ; Incidence ; Pancreatitis ; Protease Inhibitors ; Retrospective Studies

OBJECTIVES: This study investigated occupational contact dermatitis in a tire factory, prompted by a long history of complaints of skin ailments by the factory workers. METHODS: Participants (n=160) completed a questionnaire concerning job characteristics and skin symptoms, and received a medical examination. Fifty-four workers with suspected work-related contact dermatitis were chosen for a patch test of contact-related dermatitis. RESULTS: The most frequent positive reactions of patch test were produced by diphenylguanidine, formaldehyde and cobalt. Twenty-one of the 54 individuals (38.9%) were judged to have work-related skin disease. CONCLUSIONS: Exposure to natural and synthetic rubbers and additive materials pose a risk of contact dermatitis in a tire manufacturing environment. Improved sanitary work practices and public health awareness measures are suggested.
Cobalt ; Dermatitis, Contact ; Dermatitis, Occupational ; Elastomers ; Formaldehyde ; Guanidines ; Patch Tests ; Public Health ; Questionnaires ; Skin

Air Pollutants, Occupational ; analysis ; Guanidines ; analysis ; Humans ; Occupational Exposure ; analysis ; Threshold Limit Values ; Workplace

OBJECTIVETo study the chemical constituents of the whote plant Biebersteinia heterostemon (Geraniaceae).

METHODThe ethanol extract of the whole plants was separated by various chromatographic methods and the compounds from the extract were identified by spectroscopic evidence including MS, IR, NMR and X-ray crystallographic analysis.

RESULTThree isoprenyl guanidine derivatives were isolated from the whole plant of Biebersteinia heterostemon and identified as galegine (1) , cis-4-hydroxygalegine (2) and trans-4-hydroxygalegine (3).

CONCLUSIONThe three compounds were isolated from this plant for the first time.

Geraniaceae ; chemistry ; Guanidines ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry