Combined ns5a & ns5b nucleotide inhibitor therapy for patients with chronic hepatitis c with stage 5 chronic kidney disease on hemodialysis / Terapia inibidora de nucleotídeo NS5A& NS5B combinada para pacientes com hepatite C crônica com doença renal crônica em estágio 5, em hemodiálise

ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é a infecção viral hepática mais comum que afeta pacientes em hemodiálise de manutenção. O tratamento da infecção crônica por HCV no estágio 4 e 5 da doença renal crônica inclui uma combinação de elbasvir/grazoprevir e glecaprevir/pibrentasvir, que não estão disponíveis em muitos países. OBJETIVO: Portanto, realizamos este estudo para procurar a segurança e eficácia da terapia combinada de sofosbuvir nesta população de difícil tratamento. MÉTODOS: Realizamos um estudo de centro único, prospectivo e aberto, no qual pacientes com doença renal crônica em estágio 5 em hemodiálise de manutenção com infecção por HCV. Um total de 18 pacientes foi incluído. Sofosbuvir com daclatasvir ou ledipasvir foi usado de acordo com o genótipo por 12 semanas. O HCV RNA, genótipo, elastografia transitória foi considerado para cada paciente. O HCV RNA foi quantificado na 4ª semana, 12ª semana e 12 semanas após o tratamento para procurar uma resposta virológica sustentada. RESULTADOS: A infecção por genótipo 1 foi observada em 12 (66,7%) pacientes, seguido pelo genótipo 3 em 4 (22,3%), em um paciente do genótipo 2 e em outro, 5. O valor mediano do HCV RNA foi de 2.35.000 IU/mL. Na elastografia transitória, todos tinham rigidez hepática de <9.4 KPa. Todos os pacientes tinham RNA HCV <15 IU/mL na 4ª e 12ª semana de tratamento e 12 semanas após o tratamento. Não foi observada nenhuma alteração significativa na hemoglobina, eGFR e rigidez hepática. CONCLUSÃO: A dose completa sofosbuvir ou seja, 400 mg, em combinação com inibidores NS5A daclatasvir ou ledipasvir foi considerada segura e eficaz em pacientes com doença renal em estágio final, que estão em manutenção hemodiálise.

Clinical observation of acupuncture at Zhiyang (GV 9) points combined with pantoprazole for gastroesophageal reflux cough with damp-heat type / 中国针灸

<p><b>OBJECTIVE</b>On the basic treatment, to observed the effect difference between acupuncture at Zhiyang (GV 9) points combined with pantoprazole and simple pantoprazole for gastroesophageal reflux cough with damp-heat type.</p><p><b>METHODS</b>A total of 102 patients were randomly assigned into an observation group and a control group, 51 cases in each group. The patients in the two groups were given domperidone tablets (10 mg each time, 3 times a day). The patients in the control group were treated with pantoprazole capsule (40 mg each time, once a day). On the basis of the control group, the patients in the observation group were treated with Zhiyang (GV 9) points, once a day, 5 times a week. All the treatment was given for 8 weeks. The indexes were observed before and after treatment, including cough symptom at daytime and nighttime scores, TCM symptom (heartburn, acid regurgitation, chest pain, epigastric pain, throat discomfort) scores and quality of life scores of cough questionnaire in Leicester (physiological, psychological and social aspects). The clinical effects were compared.</p><p><b>RESULTS</b>After treatment, the daytime and nighttime cough scores, TCM symptom (heartburn, acid regurgitation, chest pain, epigastric pain, throat discomfort) scores were lower, and the quality of life scores of cough questionnaire in Leicester (physiological, psychological and social aspects) were higher than those before treatment in the two groups (all <0.05), with better results in the observation group (all <0.05). The total effective rate of the observation group was 94.1% (48/51), which was better than 80.4% (41/51) of the control group (<0.05).</p><p><b>CONCLUSION</b>On the basic treatment, acupuncture at Zhiyang (GV 9) points combined with pantoprazole can improve TCM symptoms, such as cough, of the patients with gastroesophageal reflux cough with damp-heat type, and improve their quality of life.</p>

Impact of drug combination of clopidogrel and pantoprazole In the prognosis of patients with transient ischemic attack

The study aimed to investigate the impact of clopidogrel combined with proton pump inhibitors [PPI] pantoprazole treatment on the prognosis of patients with transient ischemic attack [TIA]. A total of 478 cases of TIA patients treated with clopidogrel were randomly assigned half to clopidogrel combined with pantoprazole treatment and the control groups [clopidogrel treatment alone] from January 2012 to January 2014. The platelet aggregation before and after treatment and cerebrovascular events incidence within 90 days were compared and analyzed. Multivariate analysis was used to estimate the incidence of cerebrovascular events within 90 days. The platelet aggregation rate before treatment was 73.2 +/- 6.1% in the treatment group, 74.1 +/- 8.8% in the control group. The platelet aggregation rate after treatment was 38.1 +/- 10.7% in the treatment group, 36.8 +/- 9.7% in the control group. The platelet aggregation before and after treatments between the two groups had not significant difference [P>0.05]. The incidence of cerebrovascular events within 90 days [11.7% in the treatment group, 9.6% in the control group] between the two groups had not significant difference [P>0.05]. Multivariate analysis showed that the incidence of cerebrovascular events within 90 day was associated with hypertension [P=0.008], diabetes [P=0.000], hyperlipidemia [P=0.002] and ABCD2 score >3 points [P=0.000]. Clopidogrel combined with pantoprazole treatment had no significant effect on the prognosis of TIA patients

Role of rebamipide and or pantoprazole in preventing dexamethasone induced gastritis in senile male albino rats

Aim of the work: gastritis is the inflammation of the lining of the stomach .It is caused by many factors like infection by Helicobacter pylori, drug induced such as aspirin, Non-Steroidal Anti-Inflammatory Drugs [NSAIDs], corticosteroids and alcohol consumption. Pantoprazole prevents HCL formation by blocking proton pumps in parietal cells of the stomach leading to stoppage of pepsinogen enzyme activation

Rebamipide stimulates prostaglandins synthesis so the mucous barrier can be build up to protect the gastric mucosa, so this study aimed to evaluate the efficacy of Pantoprazole and Rebamipide on stomach mucosa protection from the gastritis that was induced by Dexamethasone in rats

Material and methods: twenty-five male senile albino rats were included in this study and divided into five groups: Gl [Control group], G2 [Dexamethasone administrated group], G3 [Pantoprazole administrated group], G4 [Rebamipide administrated group] and G5 [Pantoprazole and Rebamipide administrated group]

The collected stomach specimens were subjected to hematoxylin and eosin, PAS and alcian blue stains

Results: the most weight loss was detected in Dexamethasone administrated group, while the least weight loss was realized in dexamethasone and Rebamipide administrated group. Gastric samples showed improvement in gastric mucosa in G3 and G4, but the best improvement was demonstrated in G3

Conclusion: Rebamipide has a better protective effect than the Pantoprazole in prevention of gastric mucosal injuries

Meta-analysis of the efficacy of proton pump inhibitors for the symptoms of laryngopharyngeal reflux

The objective of this study was to perform a systematic review and meta-analysis to assess the effectiveness of proton pump inhibitors (PPI) for reflux disease in adult patients with laryngopharyngeal symptoms. A comprehensive search of Cochrane Library, EMBASE, Ovid EBM Reviews, and PubMed was performed for English-language literature about laryngopharyngeal reflux (LPR), in September 2014. The papers were filtered using pre-defined inclusion and exclusion criteria. Eight papers were identified and included in this meta-analysis. The sample comprised a pooled total of 370 patients, of which 210 and 160 patients took PPIs and placebo, respectively. The difference between PPIs and placebo groups in overall improvement of symptoms in adult patients with LPR was not statistically significant (RR=1.22; 95%CI=0.93-1.58; P=0.149). The difference in cough improvement was also not significant between PPIs and placebo groups (RR=0.65; 95%CI=0.30-1.41; P=0.279).

Comparison on Oral versus Intravenous Proton Pump Inhibitors for Prevention of Bleeding after Endoscopic Submucosal Dissection of Gastric Lesions / 대한소화기학회지

BACKGROUND/AIMS: Although intravenous proton pump inhibitor (PPI) has been used for the prevention of post endoscopic submucosal dissection (ESD) bleeding, the route of administration has not been confirmed. The aim of the present study was to compare the efficacy of intravenous and oral PPI administration for the prevention of delayed post ESD bleeding. METHODS: Total 166 consecutive patients were randomly assigned to 30 mg lansoprazol twice a day (PO group) and 120 mg pantoprazole intravenous injection (IV group) for 48 hours. Finally, 65 patients in PO group and 87 patients in IV group were analyzed. After ESD, all patients underwent follow up endoscopy after 24 hours and were observed the symptoms of bleeding up to 60 days after ESD. RESULTS: Age, sex and use of anticoagulants were not different between groups. At follow up endoscopy after 24 hours, oozing and exposed vessel was noted in 4.6% of PO group and 8.0% of IV group and there was no significant difference. Delayed bleeding occurred in 4 of 65 patients (6.2%) in the PO group and 8 of 87 patients (9.2%) in the IV group (p>0.999). By multivariate analysis, oozing or exposed vessels at follow up endoscopy were risk factors for delayed bleeding (OR=17.5, p=0.022). CONCLUSIONS: There was no significant difference in the delayed bleeding, length of hospital stay according to the administration route. Bleeding stigmata at follow up endoscopy was risk factor of delayed bleeding. Oral PPI administration can cost-effectively replace IV PPI for prevention of post ESD bleeding.

Diagnosis and treatment of vocal process granuloma induced by gastroesophageal reflux: four cases report / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the mechanism, clinical characterization, diagnosis and therapeutic approach of vocal process granuloma(VPG) induced by gastroesophageal reflux.@*METHOD@#We performed a retrospective review of 4 cases.@*RESULT@#In 4 male cases, 3 cases had no obvious symptoms of stomach and esophagus and 1 case had symptoms of bloating and acid reflux. Additionally, 4 cases in which lesions were all located to the left side were diagnosed by trial therapy with proton pump inhibitors (PPIs) with good responding. 2 of 4 cases were relapsed after operations. Meanwhile 4 patients were treated by Rabeprazole for acid suppression therapy and 3 cases were cured and 1 invalid case was cured by Pantoprazole. All patients were followed up for 4-48 months with no recurrence.@*CONCLUSION@#Gastroesophageal reflux is an important pathogenic factor to the VPG. The majority of patients with VPG do not have gastroesophageal reflux symptoms. Besides, most lesions located in the left are associated with sleeping position. The diagnosis is mainly based on the laryngoscope examination and trial of acid suppression therapy. Moreover, recurrence risk is high-with simple operation in VPG therefore the main treatment is a antireflux and it is also valid by replacing byother PPI treatment. The treatment must be long enough. Meanwhile, the comprehensive treatment should be noticed.

Comparison of intravenous ranitidine with pantoprazole in decreasing gastric fluid acidity in emergency cesarean section

Peri-operative aspiration of gastric contents is a problem that causes certain respiratory problems including ARDS. Prophylaxis against aspiration of gastric contents is performed routinely in elective surgeries, but there is rare evidence on the efficacy of this method in emergency cesarean section. This is a randomized, controlled, double-blinded clinical trial. 60 parturients undergoing emergency cesarean section were randomly assigned into three groups of 20 each. They were allocated into two study and one placebo groups. The study group one and two received intravenous ranitidine [IV] 50 mg or IV pantoprazole 40 mg, half an hour before induction of GA, respectively. The placebo group was administered just 5 ml of isotonic saline half an hour before GA induction. After intubation and confirmation of endotracheal tube insertion, the gastric contents were aspirated through a nasogastric tube for evaluation of acidity and volume. A statistical difference between group one and two with the control group was observed in the acidity of gastric contents, but there was no difference in volume. Also, the PH level of gastric contents in patients receiving pantoprazole was significantly higher than the isotonic saline [p<0.001] and ranitidine groups. The difference in average level of acidity of gastric contents in patients receiving pantoprazole and ranitidine showed a marginal significance [p

Inhibitory effects of a beta-dunnione compound MB12662 on gastric secretion and ulcers / 한국실험동물학회지

The effects of a beta-dunnione compound MB12662 on the gastric secretion and ulcers were investigated in rats. In order to assess the effects of MB12662 on the gastric secretion and acidity, rats were subjected to pylorus ligation operation, and 6 hours later, gastric fluid was collected. Treatment with MB12662 reduced the gastric fluid volume to 47.3% of control level and increased pH. In an alcohol-induced ulcer model, rats were orally administered 3 mL/kg of ethanol, and 1 hour later, the ulcer lesions ware measured under a stereomicroscope. MB12662 reduced ulcer index in a dose-dependent manner which was much stronger than a proton-pump inhibitor pantoprazole. In a stress-induced ulcer model, rats were subjected to water-immersion restraint stress, and 5 hours later, the ulcer lesions ware examined. MB12662 also attenuated the stress-induced gastric lesions, although the efficacy of MB12662 was lower than that of pantoprazole. Therefore, it is suggested that MB12662 could be a candidate compound for the prevention or treatment of gastric ulcers induced by gastric over-secretion and alcoholic hangover.

Levofloxacin, Metronidazole, and Lansoprazole Triple Therapy Compared to Quadruple Therapy as a Second-Line Treatment of Helicobacter pylori Infection in Korea

BACKGROUND/AIMS: Several rescue therapies have been recommended to eradicate Helicobacter pylori infection in patients with a failure of first-line eradication therapy, but they still fail in more than 20% of cases. The aim of this study was to evaluate the efficacy and safety of levofloxacin, metronidazole, and lansoprazole (LML) triple therapy relative to quadruple therapy as a second-line treatment. METHODS: In total, 113 patients who failed first-line triple therapy for H. pylori infection were randomly assigned to two groups: LML for 7 days and tetracycline, bismuth subcitrate, metronidazole and lansoprazole (quadruple) for 7 days. RESULTS: According to intention-to-treat analysis, the infection was eradicated in 38 of 56 patients (67.9%) in the LML group and 48 of 57 (84.2%) in the quadruple group (p=0.042). Per-protocol analysis showed successful eradication in 38 of 52 patients (73.1%) from the LML group and 48 of 52 (92.3%) from the quadruple group (p=0.010). There were no significant differences in the adverse effects in either treatment group. CONCLUSIONS: LML therapy is less effective than quadruple therapy as a second-line treatment for H. pylori infection. Therefore, quadruple therapy should be considered as the primary second-line strategy for patients experiencing a failure of first-line H. pylori therapy in Korea.

DICS Behavior Pattern and Medication Errors by Nurses / 간호행정학회지

PURPOSE: Human factor is one of the major causes of medication errors. The purpose of this study was to identify nurses' perception and experience of medication errors, examine the relationship of Dominance, Influence, Steadiness, Conscientiousness (DISC) behavior patterns and medication errors by nurses. METHODS: A descriptive survey design with a convenience sampling was used. Data collection was done using self-report questionnaires answered by 308 nurses from one university hospital and two general hospitals. RESULTS: The most frequent DISC behavioral style of nurses was influence style (41.9%), followed by steadiness style (23.7%), conscientiousness style (20.4%), and dominance style (14.0%). Differences in the perception and experience level of medication errors by nurses' behavioral pattern were not statistically significant. However, nurses with conscientiousness style had the lowest scores for in experience of medication errors and the highest scores for perception of medication errors. CONCLUSION: The results of this study show that identification of the behavior pattern of nurses and application of this education program can prevent medication errors by nurses in hospitals.

A Randomized, Double Blinded, Clinical Trial to Assess the Efficacy and Cost Effectiveness of Omeprazole Compared to Rabeprazole in the Maintenance Therapy of Patients With Gastroesophageal Reflux Disease

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and cost efficiency of omeprazole 10 mg and rabeprazole 10 mg once daily for 24 weeks in the maintenance therapy. METHODS: This was a randomized, open-label study enrolling 279 patients with erosive esophagitis A or B (Los Angeles classification) and typical gastroesophageal reflux disease symptoms. Patients who showed complete endoscopic and symptomatic healing after 8 weeks of proton pump inhibitor treatment were randomly allocated to maintenance treatment with omeprazole 10 mg once daily or rabeprazole 10 mg once daily for 42 weeks. The primary efficacy endpoint was the proportion of patients with symptomatic remission at 42 weeks. RESULTS: At the end of 42 weeks of maintenance therapy, 96.4% of omeprazole and 95.1% of rabeprazole treated patients remained symptom free (P > 0.05). Two drugs were also comparable with regard to the severity and frequency of reflux symptoms during the maintenance phase (P > 0.05). By the cost-minimization analysis, the mean total costs per patient for remaining symptom-free for 6 months were 241,775 won for omeprazole and 287,115 won for rabeprazole, respectively. CONCLUSIONS: Omeprazole 10 mg appeared to have similar efficacy in maintaining symptomatic remission as rabeprazole 10 mg, but was superior to rabeprazole 10 mg in terms of cost efficiency in the maintenance therapy of gastroesophageal reflux disease symptoms.

Pharmacokinetics and Pharmacodynamics of the Proton Pump Inhibitors

Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H+, K+-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.

Clinical Predictors for Response to Proton Pump Inhibitor Treatment in Patients With Globus

BACKGROUND/AIMS: Globus is a persistent or intermittent non-painful sensation of a lump or foreign body in the throat. Given the benign nature of the condition and the association of gastroesophageal reflux disease, empirical therapy with proton pump inhibitor seems reasonable for patients with typical globus. The aim of this study was to investigate the clinical predictors for symptom response to short-term proton pump inhibitor treatment in patients with globus symptom. METHODS: Fifty-four patients with globus symptom were enrolled prospectively. All patients were treated with pantoprazole 40 mg daily for 4 weeks. Treatment response was defined as a > 50% reduction in symptom scores between symptom assessments. Univariate and multivariate logistic regression analysis between responders and non-responders was performed to identify variables predicting response to pantoprazole treatment. RESULTS: Of the 54 consecutive patients considered, 13 were excluded on the basis of exclusion criteria and/or refusal to participate in the study. Finally, 41 patients were included in this study. After 4-week pantoprazole treatment, 22 patients (53.7%) were classified as responders. On multivariate analysis, the presence of reflux symptom was associated with a higher response rate to 4-week pantoprazole treatment (OR, 68.56; P = 0.043), and long symptom duration (> or = 3 months) were associated with a lower response rate to pantoprazole treatment (OR, 0.03; P = 0.034). CONCLUSIONS: Presence of reflux symptom and short symptom duration were independent predictors of responsiveness to 4-week pantoprazole treatment in patients with globus.

Effects of the Addition of Mosapride to Gastroesophageal Reflux Disease Patients on Proton Pump Inhibitor: A Prospective Randomized, Double-blind Study

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) which are the most effective agents for the treatment of gastroesophageal reflux disease (GERD), have been known to delay gastric emptying. Mosapride has been used as prokinetics by accelerating gastric emptying. We evaluated the efficacy of mosapride to prevent PPI-induced delayed gastric emptying in a prospective randomized, double-blind and placebo-controlled trial. METHODS: Thirty patients who were diagnosed as GERD and had normal gastric emptying were included in this study. PPI monotherapy group was treated with placebo drug in addition to pantoprazole and PPI plus mosapride group was treated with mosapride in addition to pantoprazole for 8 weeks. Gastric emptying scan and questionnaires about GERD and dyspeptic symptoms were assessed by scoring before and after treatment. To evaluate the changes of gastrointestinal endocrine hormones by PPI which are associated gastric acid secretion and gastric motility, fasting plasma gastrin and cholecystokinin were taken at weeks 0 and 8. RESULTS: Half gastric emptying time was increased (P = 0.023) in PPI monotherapy group, and there were no significant changes in PPI plus mosapride group. Plasma gastrin level increased in PPI monotherpay group (P = 0.028) and there were no significant changes in PPI plus mosapride group. Plasma cholecystokinin level was not changed after treatment in both groups. GERD symptoms were improved after treatment in both groups, and postprandial bloating and nausea were improved in PPI plus mosapride group. CONCLUSIONS: Mosapride showed to be effective in preventing delayed gastric emptying and the increase in plasma gastrin level induced by PPI treatment, but did not show prominent clinical symptom improvements.

The Effect of Cochinchina momordica Seed Extract on Gastric Acid Secretion and Morphologic Change in Aged Rat Stomach

BACKGROUND/AIMS: Cochinchina momordica seed extract (SK-MS10) has a gastric protective effect. We aimed to assess the effect of SK-MS10 on gastric acid secretion with morphologic changes in the aged rat. METHODS: Acid secretions were evaluated in the male F344 rats of four different ages (6-, 31-, 74-week, and 2-year). The 31-week-old rats were divided to three groups and continuously administered chow containing vehicle, SK-MS10 and lansoprazole, respectively. At the age of 74 weeks and 2 years, basal and stimulated acid was measured and the expression of mRNA and protein of H(+)-K(+)-ATPase were determined. The area of connective tissue of lamina propria was measured. RESULTS: Basal and stimulated gastric acid significantly decreased and connective tissue of lamina propria increased with age. The expression of mRNA and protein of H(+)-K(+)-ATPase significantly decreased with age. However, 74-week-old rats in the SK-MS10 group had higher stimulated gastric acid secretion than those in the vehicle and lansoprazole groups. In 2-year-old rats of SK-MS10 group, there was no increase of connective tissue. CONCLUSIONS: As SK-MS10 kept the capacity of acid secretion as well as connective tissue area to comparable to young rats, it might valuable to perform further research regarding mechanism of SK-MS10 as an antiaging agent in the stomach.

Comparison of the effect of non-antifungal and antifungal agents on Candida isolates from the gastrointestinal tract

Non-antifungal drugs appear promising in treatment of opportunistic infections of Candida spp. that are often resistant to current antifungals. The broth macrodilution method [NCCLS M27-P document] was used to compare the antifungal activity of trifluoperazine, pro-pranolol, and lansoprazole with that of ketoconazole and amphotericin B, using 50 yeast isolates from the Gl tract. The minimum fungicidal concentrations [MFCs], resistance rates and the time required for fungicidal activity of the drugs [2 - 48 hours] were determined. The most effective antifungal activity was exhibited by trifluoperazine. Its MFC was 32 microg/mL for Candida albicans [3.3% resistance] and Candida spp. [0% resistance] yeasts, and 64 ug/mL for Candida tropicalis with 10% resistance. The MFC for C. albicans and Candida spp. was comparable to that of ketoconazole. However, the time required for the inhibitory effect [6 hr] was shorter than that of ketoconazole [48 hr] or amphotericin B [24 hr]. The time required for the inhibitory activity on C. tropicalis was 24 hr, which was shorter than that of ketoconazole and amphotericin B [48 hr]. A considerable number [40%] of Candida spp. showed resistance to ketoconazole, and 20% of C. tropicalis showed resistance to amphotericin B. Trifluoperazine, an antipsychotic drug, exhibited effective antifungal activity with the MFC, comparable to ketoconazole [32 microg/mL]. Among the three yeast groups, C. tropicalis showed resistance to trifluoperazine and amphotericin B, and Candida spp. was considerably resistant to ketoconazole. Trifluoperazine could be considered as an alternative antifungal when encountering Candida spp. resistant to current antifungals

Effects of rhubarb on the intestinal barrier function of patients with acute myocardial infarction-heart / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To clarify the intestinal barrier function (IBF) state of patients with acute myocardial infarction-heart failure (AMI-HF), and to compare the therapeutic effects of rhubarb and Pantoprazole (proton pump inhibitor).</p><p><b>METHODS</b>Enrolled were 107 AMI patients from ICU, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2008 to April 2010. Of them, 47 AMI patients without HF were recruited as the control group, while 60 AMI-HF patients were randomly assigned to the rhubarb group (30 cases, treated by rhubarb + Pantoprazole) or the Pantoprazole group (30 cases, treated by Pantoprazole + routine treatment). All patients were treated till the 14th day of the onset. The fecal occult blood (FOB) test was performed daily. The occurrence of the digestive tract hemorrhage on the 14th day after onset was compared. The N-terminal pro-brain natriuretic peptide (NT-proBNP), serum D-lactic acid, plasma glutamine (Gln), endotoxin and cytokines [high sensitive C reaction protein (hsCRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10)], and heart function were compared among the three groups before and after treatment.</p><p><b>RESULTS</b>There was no statistical difference in the case number of using aspirin, clopidogel, low molecular weight heparin, ACEI/ARB, statins, insulin, and antibiotics among the 3 groups. The case number of using beta-blocker was obviously lower in the two medication groups than in the control group (P < 0.05). The case number of using diuretics was obviously higher in the two medication groups than in the control group (P < 0.05). There was no statistical difference in the incidence of digestive tract hemorrhage (P = 0.413). Compared with the control group before treatment, Gln and ejection fraction (EF) were both lowered, NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10 increased in the two medication groups (P < 0.01). There was no statistical difference in each index between the two medication groups (P > 0.05). Compared with before treatment, NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10 decreased in the Pantoprazole group (P < 0.01), and no obvious change in Gin or EF was found (P > 0.05). Gin and EF increased in the rhubarb group after treatment, and they were higher than those of the control group. Blood NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10 decreased in the rhubarb group after treatment, showing statistical difference when compared with the control group (P < 0.01, P < 0.05).</p><p><b>CONCLUSIONS</b>Impaired IBF and endotoxemia existed in AMI-HF patients. Rhubarb not only could prevent the digestive tract hemorrhage, but also could reduce endotoxemia, inhibit inflammatory reactions, and improve the heart function through ameliorating the IBF.</p>

Effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19 / 药学学报

This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ, respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/- 0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH, AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and 0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH, AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and 4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78 +/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were not significantly different with those of P, but the activity of CYP2C19 in AHH was significantly higher than that of P. This study found significant changes in the activity of CYP2C19 under the special environment of acute high altitude hypoxia.

Anti-Helicobacter pylori effects of IgY from egg york of immunized hens / 한국실험동물학회지

Effects of egg york containing IgY specific for Helicobacter pylori on the bacterial growth and intragastric infection were investigated in comparison with a proton-pump inhibitor pantoprazole. For in vitro anti-bacterial activity test, H. pylori (1x108 CFU/mL) was incubated with a serially diluted IgY for 3 days. As a result, IgY fully inhibited the bacterial growth at 16 mg/mL, which was determined to a minimal inhibitory concentration. In vivo elimination study, male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1x108 CFU/mouse) 3 times at 2-day intervals, and 2 weeks later, orally treated twice a day with 50, 100, 200 or 500 mg/kg IgY for 18 days. After the final administration, biopsy sample of the gastric mucosa was assayed for the bacterial identification via urease, oxidase, catalase, nitrate reduction and H2S tests in addition to microscopic examination for mucosal inflammation. In CLO kit test, 75, 50, 12.5 and 12.5% of the animals revealed positive reaction following treatment with 50, 100, 200 and 500 mg/kg IgY, respectively, resulting in a superior efficacy at 200 mg/kg than 30 mg/kg pantoprazole that displayed 75% elimination. The CLO test results were confirmed by bacterial identification. Microscopic examination revealed that H. pylori infection caused severe gastric mucosal inflammation, which were not observed in the CLO-negative mice following treatment with IgY or pantoprazole. Taken together, IgY inhibited the growth of H. pylori, and improved gastritis and villi injuries by eliminating the bacteria from the stomach. The results indicate that IgY could be a good candidate overcoming tolerance of antibiotics for the treatment of H. pylori-mediated gastric ulcers.