Comparison of drug concentrations in blood and gastric lavage fluid before and after gastric lavage: A case report.

BACKGROUND: Gastric lavage (GL) is one of the most important early therapies to remove unabsorbed toxins from the gastrointestinal tract. However, the details of performing gastric lavage remain to be established. There is controversy in clinical practice regarding individual choice of the timing of GL and its efficiency. CASE SUMMARY: We report the case of a young woman who presented to the Emergency Department with drug intoxication for four hours. We used the latest toxicological screening techniques to compare drug concentrations in the patient's blood and gastric lavage fluid before and after gastric lavage. The results confirmed that gastric lavage was effective in reducing drug concentrations in the stomach; a small amount of drug remained in the stomach at the end of gastric lavage. CONCLUSION: Gastric lavage is effective in reducing drug concentrations in the stomach, with a small amount of drug remaining in the stomach at the end of gastric lavage.

Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant (MDR) bacteria-induced VAP often has high lethality. We present this systematic review and meta-analysis to assess the risk factors for MDR bacterial infection in patients with VAP. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies regarding MDR bacterial infection in VAP patients, from Jan 1996 to Aug 2022. Study selection, data extraction, and quality assessment of included studies were conducted by two reviewers independently, and potential risk factors for MDR bacterial infection were identified. RESULTS: Meta-analysis showed that the score of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) [OR = 1.009, 95% (CI 0.732, 1.287)], Simplified Acute Physiology Score II (SAPS-II) [OR = 2.805, 95%CI (0.854, 4.755)], length of hospital-stay before VAP onset (days) [OR = 2.639, 95%CI (0.387, 4.892)], in-ICU duration [OR = 3.958, 95%CI (0.894, 7.021)], Charlson index [OR = 1.000, 95%CI (0.889, 1.111)], overall hospital-stay [OR = 20.742, 95%CI (18.894, 22.591)], Medication of Quinolones [OR = 2.017, 95%CI (1.339, 3.038)], medication of carbapenems [OR = 3.527, 95%CI (2.476, 5.024)], combination of more than 2 prior antibiotics [OR = 3.181, 95%CI (2.102, 4.812)], and prior use of antibiotics [OR 2.971, 95%CI (2.001, 4.412)] were independent risk factors of MDR bacterial infection in VAP patients. Diabetes and mechanical ventilation duration before VAP onset showed no association with risk for MDR bacterial infection. CONCLUSIONS: This study has identified 10 risk factors associated with MDR bacterial infection in VAP patients. Identification of these factors would be able to facilitate the treatment and prevention of MDR bacterial infection in clinical practice.

Tuberculosis combined with Burkitt lymphoma in a kidney transplant recipient: A case report and literature review.

RATIONALE: Tuberculosis (TB) and post-transplant lymphoproliferative disorder are serious complications affecting the long-term survival of kidney transplant recipients (KTRs). Both of complications have overlapping clinical symptoms, signs, and high similar imaging presentation, which make early clinical diagnosis challenging. In this paper, we reported a rare case of post-transplant pulmonary TB combined with Burkitt lymphoma (BL) in KTR. PATIENT CONCERNS: A 20-year-old female KTR presented to our hospital with abdominal pain and multiple nodules throughout the body. DIAGNOSES: TB is diagnosed based on the lung histopathology showed fibrous connective tissue hyperplasia with number of chronic inflammatory changes, localized necrosis, granuloma formation and multinucleated giant cells were seen in the lung tissue. Moreover, lung histopathology specimen tested positive for TB gene. TB The culture for tuberculosis was positive. BL was diagnosed as metastatic after completion of liver and bone marrow biopsy. INTERVENTIONS: After an early diagnosis of TB, the patient received intensification of anti-tubercular therapy. Because the patient was diagnosed with BL, rituximab, cardioprotection, hepatoprotection and alkalinization of urine were added. OUTCOMES: After an early diagnosis of TB, the patient received anti-tubercular therapy and her clinical symptoms and imaging manifestations improved. After the diagnosis of BL was made, the patient's condition progressed rapidly, followed by multi-organ damage and died 3 months later. LESSONS: Therefore, in organ transplant patients, who present with multiple nodules and normal tumor markers, they should be alerted to the possibility of concurrent TB and post-transplant lymphoproliferative disorder, and perfect tests such as Epstein-Barr virus, ß2-microglobulin, lactate dehydrogenase, γ-interferon release test and Xpert Mycobacterium TB/rifampicin test and perform early lesion site biopsy to clarify the diagnosis with a view to improving the prognosis.

The Clinical Impact of Metagenomic Next-Generation Sequencing (mNGS) Test in Hospitalized Patients with Suspected Sepsis: A Multicenter Prospective Study.

Background: Metagenomic Next Generation Sequencing (mNGS) has the potential to detect pathogens rapidly. We aimed to assess the diagnostic performance of mNGS in hospitalized patients with suspected sepsis and evaluate its role in guiding antimicrobial therapy. Methods: A multicenter, prospective cohort study was performed. We enrolled patients with suspected sepsis, collected clinical characteristics and blood samples, and recorded the 30-day survival. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on antibiotic regimen modification was analyzed. Results: A total of 277 patients were enrolled, and 162 were diagnosed with sepsis. The mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time (27.0 (26.0, 29.0) vs. 96.0 (72.0, 140.3) hours, p < 0.001) and higher sensitivity (90.5% vs. 36.0%, p < 0.001) compared with blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotic use, and early stage of infection than blood culture, and was capable of guiding antibiotic regimen modification and improving prognosis. Higher reads of pathogens detected by mNGS were related to 30-day mortality (p = 0.002). Conclusions: Blood mNGS testing might be helpful for early etiological diagnosis of patients with suspected sepsis, guiding the antibiotic regimen modification and improving prognosis.

Perioperative Risk Factors for Post-operative Pneumonia after Type A Acute Aortic Dissection Surgery.

OBJECTIVE: Type A acute aortic dissection (TAAAD) is a dangerous and complicated condition with a high death rate before hospital treatment. Patients who are fortunate to receive prompt surgical treatment still face high in-hospital mortality. A series of post-operative complications further affects the prognosis. Post-operative pneumonia (POP) also leads to great morbidity and mortality. This study aimed to identify the prevalence as well as the risk factors for POP in TAAAD patients and offer references for clinical decisions to further improve the prognosis of patients who survived the surgical procedure. METHODS: The study enrolled 89 TAAAD patients who underwent surgical treatment in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China from December 2020 to July 2021 and analyzed the perioperative data and outcomes of these patients. Logistic regression analyses were used to identify the risk factors for POP. RESULTS: In the study, 31.5% of patients developed POP. Patients with POP had higher proportions of severe oxygenation damage, pneumothorax, reintubation, tracheotomy, renal replacement therapy, arrhythmia, gastrointestinal bleeding, and longer duration of mechanical ventilation, fever, ICU stay, and length of stay (all with P<0.05). The in-hospital mortality was 2.3%. Smoking, preoperative white blood cells, and intraoperative transfusion were the independent risk factors for POP in TAAAD. CONCLUSION: Patients who underwent TAAAD surgery suffered poorer outcomes when they developed POP. Furthermore, patients with risk factors should be treated with caution.

Effectiveness and safety of Liuhedan for treating cellulitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Liuhedan is a famous traditional Chinese Medicine formula used to treat cellulitis in China. However, there are no systematic reviews for the evidence and the therapeutic effectiveness and safety of Liuhedan for treating cellulitis. The aim of this study is to summarize previous evidence, assessing the efficacy and safety of Liuhedan treating cellulitis. METHODS: We will search the EMBASE, WANFANG DATA, Web of Knowledge, CNKI, PubMed, ClinicalTrials.gov, and Cochrane Library from inception to June 30, 2021 to retrieve relevant studies using the search strategy: ("Liuhedan" OR "Liuhe Pill" OR "Liu-He-Dan") AND ("cellulitis" OR "phlegmon" OR "skin and soft tissue infection" OR "skin tissue infection" OR "soft tissue infection"). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic. RESULTS: This study assessed the efficiency and safety of Liuhedan for treating cellulitis. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of Liuhedan for treating cellulitis. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.

Nasopharyngeal Swabs Are More Sensitive Than Oropharyngeal Swabs for COVID-19 Diagnosis and Monitoring the SARS-CoV-2 Load.

Objective: Detection of SARS-CoV-2 by oropharyngeal swabs (OPS) and nasopharyngeal swabs (NPS) is an essential method for coronavirus disease 2019 (COVID-19) management. It is not clear how detection rate, sensitivity, and the risk of exposure for medical providers differ in two sampling methods. Methods: In this prospective study, 120 paired NPS and OPS specimens were collected from 120 inpatients with confirmed COVID-19. SARS-CoV-2 nucleic acid in swabs were detected by real-time RT-PCR. The SARS-CoV-2 detection rate, sensitivity, and viral load were analyzed with regards NPS and OPS. Sampling discomfort reported by patients was evaluated. Results: The SARS-CoV-2 detection rate was significantly higher for NPS [46.7% (56/120)] than OPS [10.0% (12/120)] (P < 0.001). The sensitivity of NPS was also significantly higher than that of OPS (P < 0.001). At the time of sampling, the time of detectable SARS-CoV-2 had a longer median duration (25.0 vs. 20.5 days, respectively) and a longer maximum duration (41 vs. 39 days, respectively) in NPS than OPS. The mean cycle threshold (Ct) value of NPS (37.8, 95% CI: 37.0-38.6) was significantly lower than that of OPS (39.4, 95% CI: 38.9-39.8) by 1.6 (95% CI 1.0-2.2, P < 0.001), indicating that the SARS-CoV-2 load was significantly higher in NPS specimens than OPS. Patient discomfort was low in both sampling methods. During NPS sampling, patients were significantly less likely to have nausea and vomit. Conclusions: NPS had significantly higher SARS-CoV-2 detection rate, sensitivity, and viral load than OPS. NPS could reduce droplets production during swabs. NPS should be recommended for diagnosing COVID-19 and monitoring SARS-CoV-2 load. Chinese Clinical Trial Registry, number: ChiCTR2000029883.

CXCL12 G801A polymorphism and cancer risk: An updated meta-analysis.

Many studies have reported the relationship between CXCL12 G801A polymorphism and cancer risk, with conflicting results. In this study, we tried to clarify the possibility that this polymorphism may increase cancer risk by conducting an updated meta-analysis. PubMed and EMbase were searched for case-control studies regarding the association of the gene polymorphism and cancer risk. Data were extracted and odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Heterogeneity among articles and publication bias was also assessed. Significantly increased risk for cancer was found (A vs. G: OR=1.26, 95% CI=1.13-1.40, P<0.01; AA+AG vs. GG: OR=1.33, 95% CI=1.16-1.52, P<0.01). In subgroup analysis, statistically elevated cancer risk was found in both Asian and Caucasian populations (for Asian, AA+AG vs. GG: OR=1.74, 95% CI=1.22-2.47, P<0.01; for Caucasian, AA+AG vs. GG: OR=1.24, 95% CI=1.09-1.42, P<0.01). Our result indicated that CXCL12 G801A polymorphism is a risk factor for cancer. To validate the finding, further large-size case-control studies are warranted.

[Prognostic significance of serum lactic acid in evaluation of acute paraquat poisoning patients].

OBJECTIVE: To discuss the role of serum lactic acid (Lac) level in evaluation of prognosis of acute paraquat poisoning (APP) patients. METHODS: Clinical data from 168 APP patients were retrospectively analyzed. The serum Lac level and the plasma paraquat concentrations at admission were collected, and the severity index of paraquat poisoning (SIPP) were calculated. The patients were divided into <10, 10-50, ≥50 h×mg×L(-1) groups on the basis of SIPP. The correlation between Lac and SIPP was analyzed, as well as the role in evaluating prognosis. RESULTS: The higher the SIPP level, the higher the Lac level [2.00 (1.50, 2.83) mmol/L, 3.10 (1.73, 5.15) mmol/L, 8.95 (5.90, 13.10) mmol/L, all P<0.05]; Lac was correlated positively with SIPP (r=0.569, P<0.05). The higher the SIPP, the higher the mortality of patients [17.4% (15/86), 61.5% (24/39), 97.7% (42/43), all P<0.05]. The survival days of SIPP≥50 h×mg×L(-1) group was shorter than that in SIPP<10 h×mg×L(-1) group and 10-50 h×mg×L(-1) group [2.0 (1.0, 3.0) days vs. 9.0 (4.0, 11.0) days and 5.0 (3.0, 10.0) days, both P<0.05]. A negative correlation was found between Lac, SIPP and survival days in non-survivors (r1=-0.778, r2=-0.621, both P<0.05). Logistic regression analyses showed either Lac or SIPP was of prognostic significance [odds ratio (OR) of Lac: 1.758, 95% confidence interval (95%CI) 1.278-2.417;OR of SIPP: 1.063,95%CI 1.025-1.103, both P=0.001]. The area under the receiver operating characteristic curve (ROC curve) of Lac, SIPP and prognosis were 0.885 and 0.897 respectively (both P<0.05), Lac≥3.35 mmol/L was the best cut-off value, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy for predicting the death were 74.07%, 90.80%, 88.24%, 79.00%, 8.056, 0.286 and 82.74% respectively; the evaluation value was closed to SIPP≥13.83 h×mg×L(-1) (77.78%, 91.95%, 90.00%, 81.63%, 9.677, 0.242 and 85.12%, respectively). CONCLUSIONS: The change in serum Lac level has evaluation value of the severity and prognosis for APP patients, and Lac≥3.35 mmol/L can be made as a simple and easy indicator for prognosis of APP patients.

[Pharmacokinetic characteristics of ferulic acid in patients with different syndromes of deficiency of spleen qi, stagnation of liver qi and spleen deficiency, and excess of stomach heat].

OBJECTIVE: To investigate the nature of syndrome of traditional Chinese medicine by means of pharmacokinetic (PK) method. METHODS: Twenty-one healthy volunteers, 20 patients with syndrome of stagnation of liver qi and spleen deficiency, 22 patients with syndrome of deficiency of spleen qi and 19 patients with syndrome of excess of stomach heat were included and administered to take Jiawei Xiaoyaosan Recipe (JWXYSR). The serum PK parameters of ferulic acid (FA) were examined by high performance liquid chromatography (HPLC) method. RESULTS: The absorption rate constant (alpha) and the elimination rate constant (beta) were both decreased while the apparent first-order absorption constant (K(a)) was enhanced significantly in the patients with syndrome of deficiency of spleen qi; the alpha, beta and Ka were all reduced in the patients with syndrome of stagnation of liver qi and spleen deficiency; the beta and K(a) were increased in the patients with syndrome of excess of stomach heat, as compared with the corresponding PK parameters in the healthy volunteers (P<0.01). CONCLUSION: The PK analysis of FA in the patients with syndrome of deficiency of spleen qi shows that the absorption rate is accelerated, and both the distribution and elimination rates are slowed down. The absorption, distribution and elimination rates of AF are all slowed down in the patients with syndrome of stagnation of liver-qi and spleen deficiency, while the absorption and elimination rates of AF are both accelerated in the patients with syndrome of excess of stomach heat. There are obvious differences in the PK characteristics among these three syndromes.

Effect and mechanism of total saponin of Dioscorea on animal experimental hyperuricemia.

In this study, we investigated the effects and mechanisms of Total Saponin of Dioscorea (TSD) on animal experimental hyperuricemia. Mouse and rat hyperuricemic models were made by orally administering yeast extract paste once a day (30 and 20 g/kg, respectively), for 7 days. Yeast would disturb normal purine metabolism by increasing xanthine oxidase (XOD) activity and generating large quantities of uric acid. This model is similar to human hyperuricemia, which is induced by high-protein diets, due to a purine and nucleic acid metabolic disturbance. Another mouse hyperuricemia model was generated by intraperitoneal injection once with uric acid 250 mg/kg or potassium oxonate 300 mg/kg. Potassium oxonate, a urate oxidase inhibitor, can raise the serum uric acid level by inhibiting the decomposition of uric acid. Likewise, injecting uric acid can also increase serum uric acid concentration. The concentration of uric acid in serum or urine was detected by the phosphotungstic acid method, and the activity of XOD was assayed by a test kit. The results showed that TSD (240, 120 and 60 mg/kg, ig) could significantly lower the level of serum uric acid in hyperuricemic mice. TSD (120 and 60 mg/kg, ig) could also lower the level of serum uric acid in hyperuricemic rats, reduce the activity of XOD in the serum and liver of hyperuricemic rats, and increase the level of urine uric acid concentration as well as 24-hour total uric acid excretion. In conclusion, TSD possesses a potent anti-hyperuricemic effect on hyperuricemic animals, and the mechanism may be relevant in accelerating the excretion and decreasing the production of uric acid.

Melatonin-selenium nanoparticles inhibit oxidative stress and protect against hepatic injury induced by Bacillus Calmette-Guérin/lipopolysaccharide in mice.

Melatonin-selenium nanoparticles (MT-Se), a novel complex, were synthesized by preparing selenium nanoparticles in melatonin medium. The present investigation was designed to determine the protective effects of MT-Se against Bacillus Calmette-Guérin (BCG)/lipopolysaccharide (LPS)-induced hepatic injury in mice. In BCG/LPS-induced hepatic injury model, MT-Se administered (i.g.) at doses of 5, 10, or 20 mg/kg to BCG/LPS-treated mice for 10 days, significantly reduced the increase in plasma aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. The MT-Se particles also attenuated the increase in the content of thiobarbituric acid-reactive substances and enhanced the decrease in reduced activities of superoxide dismutase and glutathione peroxidase (GPx). However, treatment with MT-Se suppressed the increase in nitric oxide levels both in plasma and liver tissue. Furthermore, supplementation with MT-Se at the dose of 10 mg/kg (composed of 9.9 mg/kg melatonin and 0.1 mg/kg selenium) had great capability to protect against hepatocellular damage than a similar dose of melatonin (10 mg/kg) or selenium (0.1 mg/kg) alone. This effect may relate to its higher antioxidant efficacy in decreasing lipid peroxidation and increasing GPx activity. These results suggest that the mode of MT-Se hepatic protective action is, at least in part, related to its antioxidant properties.

Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress.

Melatonin is reported to exhibit a wide variety of biological effects, including antioxidant and anti-inflammatory. Evidence shows the important role of oxidative stress in the etiopathogenesis of hepatic fibrosis. The aim of this study was to investigate the protective effects of administration of melatonin in rats with carbon tetrachloride-induced fibrosis for 6 weeks. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examinations. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) levels were evaluated in tissue homogenates by spectrophotometry. The nuclear factor-kappaB (NF-kappaB) in liver tissue was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations in Kupffer cells (KCs) culture supernatants were measured with ELISA. The rats injected subcutaneously with CCl4 for 6 weeks resulted in hepatic fibrotic changes increased hydroxyproline and MDA levels, and decreased GSH-px and SOD levels, whereas melatonin reversed these effects. Furthermore, melatonin inhibited the expression of NF-kappaB in liver tissue and decreasing production of proinflammatory cytokines such as TNF-alpha and IL-1beta from KCs in fibrotic rats. These present results suggest that melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress and proinflammatory cytokines production.

Melatonin-selenium nanoparticles protects liver against immunological injury induced by bacillus Calmette-Guerin and lipopolysaccharide.

AIM: Melatonin-selenium nanoparticle (MT-Se), a novel complex, was synthesized by preparing selenium nanoparticles in a melatonin medium. The present investigation was designed to determine the protective effects of MT-Se against immunological liver injury in mice induced by bacillus Calmette-Guerin (BCG)/lipopolysaccharide (LPS). METHODS: The model of immunological liver injury in mice was prepared. The levels of alanine aminotransferase, aspartate amino-transferase, nitric oxide (NO) in serum, malondialdehyde content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities in a liver homogenate were assayed by spectrophotometry. The content of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) were determined by ELISA. The splenocyte proliferation was assayed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) dye reduction. Meanwhile, a hepatic pathological examination was observed. RESULTS: In the BCG/LPS-induced hepatic injury model, MT-Se administered at doses of 5, 10, or 20 mg/kg to the BCG/LPS-treated mice for 10 d significantly reduced the increase in serum aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. It also attenuated the increase in the content of thiobarbituric acid-reactive substances and enhanced the decrease in activities of SOD and GSH-px. In contrast, the treatment with MT-Se suppressed the increase in NO level in both the serum and liver tissue. Furthermore, MT-Se significantly lowered an increase in TNF-alpha and IL-1beta levels in the liver and inhibited the production of TNF- alpha and IL-1beta by peritoneal macrophages. A downregulation effect of MT-Se on splenocyte proliferation was also observed. CONCLUSION: MT-Se showed a hepatic protective action on immunological liver injury in mice.

Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide liposomes in vivo and in vitro.

AIM: To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro. METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry. RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100 micromol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore, IC50 of 5-Fu-GCL (34.5 micromol/L) was lower than that of free 5-Fu (51.2 micromol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased. CONCLUSION: 5-Fu-GCL appears to have anti-hepato-carcinoma effects and its drug action is better than free 5-Fu. Its mechanism is partly related to increased drug concentrations in intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate and arrest of cell cycle in S phase.

Effects of total glucosides of peony on immunological hepatic fibrosis in rats.

AIM: To study the effects of total glucosides of peony (TGP) on immunological hepatic fibrosis induced by human albumin in rats. METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into: Normal group, model group, TGP (60 and 120 mg/kg) treatment groups and colchicines (0.1 mg/kg) treatment group. On the day before the rats were killed, those in TGP or colchicine groups received TGP or colchicine as above from the first day of tail vein injection of human albumin. The rats in normal and model groups were only administered with the same volume of vehicle. At the end of the 16th wk, rats in each group were killed. Blood and tissue specimens were taken. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO), content of malondialdehyde (MDA), activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), were measured by biochemical methods. Serum procollagen type III (PC III) and laminin (LN) were determined by radioimmunoassay. Liver collagen level was determined by measuring hydroxyproline content in fresh liver samples. Hepatic tissue sections were stained with hematoxylin-eosin and examined under a light microscope. RESULTS: Histological results showed that TGP improved the human albumin-induced alterations in the liver structure, alleviated lobular necrosis and significantly lowered collagen content. The antifibrotic effect of TGP was also confirmed by decreased serum content of LN and PCIII in TGP-treated group. Moreover, the treatment with TGP effectively reduced the hydroxyproline content in liver homogenates. However, the level of ALT and AST increased in fibrotic rat but had no significance compared with normal control, whereas the ratio of A/G decreased without significance. TGP had no effect on level of ALT, AST and the ratio of A/G. Furthermore, TGP treatment significantly blocked the increase in MDA and NO, associated with a partial elevation in liver total antioxidant capacity including SOD and GSH-px. CONCLUSION: TGP has beneficial effects on hepatic fibrosis in rats by inhibition of collagen synthesis and decreasing oxidative stress.

Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotype in healthy Chinese subjects.

AIM: To investigate whether the pharmacodynamics and pharmacokinetics of rabeprazole are dependent on CYP2C19 genotype status in healthy Chinese Han subjects. METHODS: The CYP2C19 genotype status of healthy Chinese Han volunteers was determined using the polymerase chain reaction-restriction fragment length polymorphism method. Twenty healthy subjects volunteered to participate in the study. There were seven homozygous extensive metabolizers (homEM), six heterozygous extensive metabolizers (hetEM), and seven poor metabolizers (PM). All subjects were Helicobactor pylori-negative, which was determined by sero-logy and 13C-urea breath tests. Rabeprazole (20 mg) was taken orally once daily in the morning for 8 days, and intragastric pH values were monitored for 24 h by Digitrapper pH after day 1 (single dose) and day 8 (repeated dose). Meanwhile, blood samples were collected at various time-points for 24 h after administration. The serum concentrations of rabeprazole were measured using high-performance liquid chromatography. RESULTS: The mean area under the curve (AUC) values for rabeprazole differed among the three different genotype groups, with a relative ratio of 1.0, 1.3, and 1.8 after a single dose and 1.0, 1.1, and 1.7 after repeated doses in the homEM, hetEM, and PM groups, respectively. Mean AUC values for rabeprazole after a single dose and after repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM or hetEM and PM groups. No significant differences in intragastric pH median, pH>4 total time, and pH>4 time percentage of 24 h, were observed among the three different genotype groups after a single dose or after repeated doses of rabeprazole. CONCLUSION: In healthy Chinese Han subjects, the pharmacokinetics of rabeprazole are dependent on a certain degree on CYP2C19 genotype status; however, the acid-inhibitory efficacy of rabeprazole is not influenced significantly by CYP2C19 genetic polymorphism.

Pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated by galactosylceramide liposomes in mice.

AIM: To study the pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated by galactosylceramide liposomes (5-Fu-GCL) in mice. METHODS: The concentration of 5-fluorouracil (5-Fu) in serum was detected by high performance liquid chromatography after 5-Fu-GCL (80, 40, 20 mg/kg) and free 5-Fu (40 mg/kg) were injected intravenously into mice. The tissue distribution of 5-Fu-GCL (40 mg/kg) and free 5-Fu (40 mg/kg) was investigated, and concentration-time profile of the two preparations in the liver were studied. Data were analyzed by 3p97 program. RESULTS: Serum concentration-time curves of 5-Fu-GCL and free 5-Fu conformed to one compartment model of first order absorption. 5-Fu-GCL at 80, 40, and 20 mg/kg had T(1/2Ke) of 25.8+/-4.2, 27.3+/-4.4, and 28.2+/-5.6 min; C0 of 24.9+/-4.9, 17.7+/-3.6, and 11.5+/-2.7 mg/L; and AUC of 990.0+/-45.2,622.5+/-38.3, and 340.4+/-25.6 mg x min x L(-1), respectively. In contrast free 5-Fu at 40 kg/mg had T(1/2Ke) of 15.8+/-2.2 min, C0 of 35.8+/-6.2 mg/L, AUC of 639.0+/-35.9 mg x min x L(-1). The tissue distribution of 5-Fu-GCL in the liver and immune organs was significantly increased, while in heart and kidney it was remarkably decreased. The AUC of 5-Fu-GCL in the liver was 3 times higher than that of free 5-Fu. CONCLUSION: The pharmacokinetics and tissue distribution of 5-Fu-GCL appears to be linear-related and dose-dependent, and exhibits sustained-release and hepatic target characteristics.

[The active metabolite of leflunomide A771726 inhibits proliferation and collagen synthesis of hepatic stellate cell].

OBJECTIVE: To investigate the effect of the metabolite of leflunomide, A771726,on proliferation and collagen synthesis of hepatic stellate cell (HSC). METHODS: HSC and Kupffer cells were isolated from the rat liver by collagenase IV and pronase perfusion, and purified by density gradient separation. The effects of A771726 on cell proliferation and collagen synthesis were examined by 3H-thymidine and 3H-proline incorporation assays, respectively. The TGF-beta, TNF-alpha and IL-1 levels in Kupffer cell conditioned medium (KCCM) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: HSC and Kupffer cells in rat liver were well separated. The KCCM of CCl4-injured rats had significant stimulation effect on proliferation and collagen synthesis of HSC in primary culture. Addition of A771726 (0.001-10 micromol/Lein HSC culture stimulated by KCCM significantly inhibited proliferation and collagen synthesis of HSC. Furthermore, the elevated TGF-beta, TNF-alpha and IL-1 levels in KCCM of CCl4-injured rats were significantly reduced in A771726 treatment groups. CONCLUSION: A771726 has markedly inhibitory effect on proliferation and collagen synthesis of HSC and secretion of TGF-beta,TNF-alpha and IL-1 from Kupffer cells.