[The effects of pronase on drugs concentrations for treatment of Helicobacter pylori infection in gastric tissue].

OBJECTIVE: To evaluate the effect of pronase on amoxicillin and metronidazole concentrations in gastric tissue. METHODS: C57BL/6 mice were randomly divided into experimental group (n = 70) and control group (n = 70). Amoxicillin (28.6 mg/kg), metronidazole (22.5 mg/kg) and omeprazole (138.2 mg/kg) were administered orally to C57BL/6 mice, combined with pronase (110 mg/kg) or same amount of sterile PBS. Gastric tissue and blood plasma samples were taken at 10 point-in-time (7 mice/time) from 15 min up to 360 min after administration. Concentrations of amoxicillin and metronidazole were detected by high performance liquid chromatography. Gastritis index of gastric mucosa (hematoxylin-eosin staining) and the gastric tissue expressions of mucin 5AC (Western blot) were detected at 120 min and 360 min after administration. RESULTS: The time to peak concentration of amoxicillin and metronidazole in gastric tissue appeared earlier than that in blood plasma (15 min vs 60 min). Tissue concentrations of amoxicillin and metronidazole of experimental group were significantly higher than those of control, and they were mainly at 15 min to 90 min (P < 0.05). Plasma concentrations of amoxicillin and metronidazole of experimental group at 15 min and 30 min were higher than those of control (P < 0.05). There was no difference in gastritis index between experimental group and control at 120 min and 360 min after administration (0.28 ± 0.18 vs 0.14 ± 0.14, P > 0.05; 0.43 ± 0.20 vs 0.28 ± 0.18, P > 0.05). The expressions of mucin 5AC in experimental group were lower than those of control (0.036 ± 0.006 vs 0.197 ± 0.058; P < 0.05; 0.039 ± 0.008 vs 0.208 ± 0.072, P < 0.05). CONCLUSIONS: Pronase can significantly enhance the drugs penetration from mucus into gastric tissue. Concentrations of amoxicillin and metronidazole of experimental group in local gastric tissue and plasma are higher than those of control, especially in improving concentrations of gastric tissue and prolongation of exposed time.

Low levels of vitamin C in dialysis patients is associated with decreased prealbumin and increased C-reactive protein.

BACKGROUND: Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers. METHODS: In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height(2)), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis. Patients were classified into three subgroups by vitamin C level according to previous recommendation 12 in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above). RESULTS: Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups. Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log(10)hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects. CONCLUSIONS: The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.

Three aromatic amino acids in gastric juice as potential biomarkers for gastric malignancies.

For screening early-stage gastric malignancies, the existing serum biomarkers have limited sensitivity and specificity. Gastric juice biomarkers are scarce and require further investigation. We divided this study on searching potential biomarkers into four parts: (1) detection of differential fluorescence spectrum and peaks in the gastric juice from patients using fluorescence spectroscopy and HPLC, (2) identification and validation of differential peaks using LC/MS and NMR, (3) quantification of potential biomarkers, and (4) establishment of diagnostic detection. The fluorescence intensity (FI), tyrosine, phenylalanine, tryptophan and total protein content were significantly higher in the gastric juice of patients with gastric malignancies (all P<0.01). With all P<0.001, the areas under the receiver operating characteristic curves of the biomarkers were tyrosine, 0.838; phenylalanine, 0.856; and tryptophan, 0.816. At a specificity of 79.4%, the sensitivity for gastric malignancy detection with phenylalanine was 87.9% only. Aromatic amino acids in gastric juices could be used as potential diagnostic biomarkers to screen gastric malignancies. It is a less-invasive and economical method compared to gastric biopsy.

Differential efficacy of clarithromycin in lung versus thigh infection models.

BACKGROUND: Differences in clarithromycin disposition and the resulting changes in bacterial density were studied using mouse lung and thigh infection models. METHODS: Clarithromycin activity was evaluated against seven Streptococcus pneumoniae isolates with efflux-mediated resistance in both murine lung and thigh infection models. Intrapulmonary disposition of clarithromycin was also studied. RESULTS: Consistent bacterial kill was observed in the lung model, whereas no drug effect was observed in the thigh model. CONCLUSION: These differences in bacterial density were supported by high concentrations observed in epithelial lining fluid as compared to serum.

Determination of the in vivo pharmacodynamic profile of cefepime against extended-spectrum-beta-lactamase-producing Escherichia coli at various inocula.

Cefepime was evaluated in vivo against two inoculum sizes of four strains of Escherichia coli that produced extended-spectrum beta-lactamases (ESBLs) in a murine neutropenic thigh infection model to characterize the pharmacodynamic activity of cefepime in the presence of ESBL-producing bacteria and to evaluate if differences in lengths of cefepime exposure are required with various inocula. Three strains possessed a single enzyme each: TEM-10, TEM-12, and TEM-26. The fourth strain possessed two TEM-derived ESBLs and a third uncharacterized enzyme. Two non-ESBL-producing E. coli strains were included for comparison. Mice received various doses of cefepime to achieve a spectrum of percentages of time the drug was above the MIC (%T>MICs) for each isolate at both inocula. No significant difference in cefepime exposure was required to achieve similar bactericidal effects for ESBL- and non-ESBL-producing isolates when the starting inoculum was 10(5) CFU of E. coli per thigh. The increased MICs observed in vitro for the ESBL-producing strains at 10(7) CFU/ml did not predict the amount of exposure required to achieve a comparable level of bactericidal activity in vivo at the corresponding starting inoculum of 10(7) CFU/thigh. Compared to the cefepime exposure in tests with the lower inoculum (10(5) CFU/thigh), less exposure was required when the starting inoculum was 10(7) CFU/thigh (%T>MIC, 6% versus 26%), such that similar doses (in milligrams per kilogram of body weight) produced similar bactericidal effects with both inocula of ESBL-producing isolates. Equivalent exposures of cefepime produced similar effects against the microorganisms regardless of the presence of ESBL production. Pharmacodynamic profiling undertaken with conventional cefepime MIC determinations predicted in vivo microbial outcomes at both inoculum sizes for the ESBL-producing isolates evaluated in this study. These data support the use of conventional MIC determinations in the pharmacodynamic assessment of cefepime.

[Significance of changes in plasma lipid peroxide levels in critically ill patients after liver transplantation].

OBJECTIVE: To investigate the relationship between plasma lipid peroxide (LPO) levels and prognosis in critically ill patients after liver transplantation. METHODS: Plasma LPO levels were measured in 18 patients within 21 days after liver transplantation, and their relations to the prognosis were analyzed. RESULTS: Plasma LPO levels were markedly elevated in patients before state of illness got severe, especially in those with fatal outcome. The peak LPO levels were much higher in non-survivors than in survivors, and mortality rate in patients whose plasma LPO exceeding 10 micromol/L (5/6 cases) was significantly higher than those under 10 micromol/L (1/12 cases, P<0.01). The mortality rate in patients with daily fluctuation range of plasma LPO levels over 1.2 micromol.L(-1).d(-1) was higher than those under 1.2 micromol.L(-1).d(-1), and the difference was significant between two groups (P<0.01). CONCLUSION: Measurement of plasma LPO level might be of clinical significance to properly judge the critically ill conditions, and it can be used as routine examination for patients after liver transplantation.

[Study of autofluorescence spectrum of dilute gastric juice in the diagnosis of gastric carcinoma].

OBJECTIVE: To investigate the value of the autofluorescence spectrum of dilute gastric juice in the diagnosis of gastric carcinoma. METHODS: The autofluorescence spectrum of dilute gastric juice was scanned with RF-5000 spectrophotofluorometer when the excitation wavelength was set to 288 nm and the emission wavelength ranged from 300 nm to 800 nm. RESULTS: We enrolled 251 patients with different gastric diseases including 40 cases with gastric carcinoma in our study. There were three characteristic peaks in the autofluorescence spectrum of gastric juice, which appeared in the spectra of both dilute and indilute specimens, but relative fluorescence intensity index (FI) of the peaks changed with concentration. The spectra of dilute gastric juice (1:20) of both benign and malignant gastric diseases had those three peaks. However, the fluorescence intensity index of the first peak (P1FI) at 320-360 nm of patients with gastric carcinoma was higher than that of patients with benign gastric diseases. The diagnosis model for gastric carcinoma was made by CART V2.0 software. The diagnosis standard for gastric carcinoma was P1FI > 38.995. The model's sensitivity and specificity of prior probability were 85.0% and 91.9% respectively. The sensitivity and specificity of posterior probability were 82.5% and 91.9% respectively. When the diagnosis standard was set to P1FI > 24.34, the sensitivity and specificity were 95.0% and 75.8%, respectively. CONCLUSION: The autofluorescence spectrum of dilute gastric juice may become an effective means in the diagnosis and screening of gastric carcinoma.

[Evaluation oxygen free radicals related index before liver transplantation to forejudge prognosis].

OBJECTIVE: To research the relationship of oxygen free radicals related index before liver transplantation with prognosis. METHODS: Lipid peroxide (LPO), total antioxidant capacity (TAC), nitric oxide (NO) and total bilirubin (T-BIL) in blood from 18 patients were measured before liver transplantation, and the relationship with prognosis was analyzed. RESULTS: The blood LPO of death group was (17.13+/-4.16) micromol/L, it was obviously higher than that of survival group (7.97+/-3.52) micromol/L (P<0.05). The blood TAC of survival group was (38.05+/-19.13) kU/L, it was higher than that of death group (32.54+/-3.07) kU/L, but there was no obvious difference(P>0.05). There was no obvious difference between the blood NO of death group was (50.80+/-14.80) micromol/L, and survive group was (150.46+/-19.54) micromol/L (P>0.05). The blood T-BIL of death group was (425.98+/-214.18) micromol/L, it was obviously higher than that of survival group (172.10+/-144.32) micromol/L (P<0.05). So the blood LPO and TAC were chosen as the index to forejudge prognosis, and an equation was established to forecast if the patient would be death or survive: Y(1)=0.329 0 X(1)+0.099 8 X(2)-3.9040, Y(2)=1.352 0 X(1)-0.0500 X(2)-11.4640, X(1) represented serum LPO, X(2) represented serum TAC. 100.0 percent accuracy was forecasted in the survival group by the equation, 83.3 percent accuracy was in the death group. The overall patients were forejudged 94.4 percent accurately. CONCLUSION: Measuring LPO and TAC in blood maybe forejudging prognosis properly and can be used as routine examination before liver transplantation. The equation is preferable to forejudging prognosis, it can be used to choose from high risk patients to improve survival rate of the patients after operation. Therefore, it is valuable in clinical practise.

Simultaneous determination of ticarcillin and clavulanate in rabbit serum and tissue cage fluid by liquid chromatography.

A gradient elution HPLC method with a wavelength switch technique was developed to simultaneously analyze the beta-lactam ticarcillin and the beta-lactamase inhibitor clavulanate in rabbit serum and tissue cage fluid (TCF). A C18 reversed-phase column with a programmable UV detector changing the wavelength from 218 to 254 nm at 9 min was used for chromatographic separation. The mobile phase consisted of acetonitrile, phosphate buffer and tetrabutylammonium hydrogen sulfate by following a gradient elution program at a flow-rate of 1 ml/min. Sample processing was carried out with liquid-liquid extraction. Good linearity, recoveries, precision and accuracy were obtained. The ranges of the standard curves were 1-100 microg/ml for ticarcillin, and 0.2-20 microg/ml for clavulanate. This assay has been successfully applied to analyze ticarcillin and clavulanate in rabbit serum and tissue cage fluid samples from a pharmacokinetic study.

[The value of autofluorescence spectrum analysis of gastric juice in diagnosing gastric carcinoma: a preliminary result].

OBJECTIVE: To reveal the difference of autofluorescence spectrums of gastric juice derived from malignancy and benignancy for screening and diagnosis of gastric carcinoma. METHOD: Gastric juice from 202 patients with different gastric diseases were collected, then detected their autofluorescence spectrums (the excitation wavelength is 288 nm, whereas the range of emission wavelength is 300 - 800 nm) after diluted by 1:10. The diagnostic model for gastric cancer was made by Classification and Regression Trees V2.0 software. RESULTS: There were three peaks (the emission wavelength were 320 - 360 nm, 576 nm and 670 - 690 nm respectively) in the autofluorescence spectrums of all patients, though the intensity of the first peak (with the emission wavelength of 320 - 360 nm) were enhanced distinctively in malignance than those in benignancy. The diagnostic model's sensitivity and specificity of prior probability were 91.4% and 83.2% respectively, whereas the sensitivity and specificity of posterior probability were 85.7% and 82.6%. CONCLUSION: Detection of autofluorescence spectrum of gastric juice has great prospect in the diagnosis and screening gastric carcinoma.