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Arsenic trioxide induces gallbladder carcinoma cell apoptosis via downregulation of Bcl-2.

Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of apoptotic stimuli. Here, we report for the first time the pro-apoptosis role of arsenic trioxide (As2O3) in gallbladder carcinoma and identify the contribution of Bcl-2 in the As2O3-induced apoptosis. The treatment of As2O3 in gallbladder carcinoma cells could induce apoptosis in a dose-dependent manner and downregulate the expression of anti-apoptotic protein Bcl-2 at mRNA level. Moreover, Bcl-2 overexpression could protect gallbladder carcinoma cells from As2O3-induced apoptosis, indicating the contribution of Bcl-2 in As2O3-induced apoptosis. Taken together, these results suggest that arsenic trioxide induces gallbladder carcinoma cell apoptosis via downregulation of Bcl-2, which may have important therapeutic implications in gallbladder carcinoma patients.

Antineoplastic Agents↗

Effects of antibacterials use in aquaculture on biogeochemical processes in marine sediment.

The effects of chloramphenicol on microorganism in marine sediment were studied by spiked experiments in this paper. The results showed that high concentrations of chloramphenicol could inhibit the activities of microorganism in sediment, and that the growth of strains Pseudomons and Acinetobacter in sediment that can degrade organic matters were inhibited apparently. Furthermore, the resistance of heterotrophic bacteria in sediment had developed due to the use of antibacterials. Based on the above results potential environmental effects of antibacterials on microorganism in marine sediment were analyzed.

Acinetobacter↗

Decreasing effluent loads through bleaching modification.

Almost all of the kraft pulp bleach plants worldwide are now practicing elemental chlorine-free (ECF) process to comply with environmental regulations in different countries. Usually, these conventional ECF bleaching sequences contain one or two alkaline extraction stages of which the first one is often the principal source of color and chemical oxygen demand (COD) in the resulting effluent. However, the results of this study showed that the ECF sequences which did not include any alkaline extraction stage and contained solely chlorine dioxide decreased both the color and COD loads of the effluent. On the other hand, the ECF sequences containing both chlorine dioxide and hydrogen peroxide but excluding the alkaline extraction stage could lower only the color but not the COD load. It is suggested that the total kappa factor (the ratio of the total active chlorine to the kappa number) affected the COD load and that the content of hexeneuronic acid groups influenced the color of the bleach effluent. Compared to the reference pulp, the viscosity of the pulp from the exclusively chlorine-dioxide-based ECF sequence without the alkaline extraction stage was lower but the tear index and sheet density at a given tensile index were similar.

Chlorine Compounds↗

Effects of antihyperlipidemic drugs and diet plus exercise therapy in the treatment of patients with moderate hypercholesterolemia.

We compared the efficacy of two antihyperlipidemic drugs and the efficacy of diet plus exercise therapy in the treatment of patients with moderate hypercholesterolemia. The study included 48 patients with moderate hypercholesterolemia (serum total cholesterol [TC], 250 to 320 mg/dL). Patients were divided into three groups: group A--patients administered 10 mg/d of pravastatin; group B--patients administered 500 mg/d of probucol and 600 mg/d of pantethine; and group C--patients administered diet plus exercise therapy. The serum TC and serum high-density lipoprotein cholesterol (HDL-C) values were determined via enzymatic methods before initiation of each therapy and after 4 and 8 weeks of therapy. An atherogenic index (AI) was also calculated. The results indicated that TC showed a statistically significant decrease in all three groups at 4 and 8 weeks (P < 0.001 and P < 0.05, respectively); the HDL-C value did not change significantly in groups A and C, but it had a statistically significant decrease in group B at 4 and 8 weeks. The AI showed a statistically significant decrease in group A at 4 and 8 weeks of treatment and group C at 8 weeks; there were no significant changes in AI in group B. It may be concluded that as an antihyperlipidemic agent, pravastatin is more useful than probucol and that appropriate exercise and strict dietary management for 8 weeks achieve an efficacy close to that achieved by drug therapy.

Cholesterol, HDL↗

Two cases of cutaneous cryptococcosis.

We report two cases of cutaneous cryptococcosis in male patients without underlying disease. Case 1 had a granulomatous mass on his right neck, gradually enlarging for 3 months. After the mass was debrided surgically in a hospital, the incision wound gradually developed into a severe ulceration. Mycological examination revealed Cryptococcus neoformans infection. It was significant that histopathology of both pre-surgery granuloma and post-surgery ulceration revealed thick-walled spores with thick capsule. Chest X-ray revealed a shadow in the left lower lung. After treatment with amphotec for 21 days, the lesion healed. Case 2 had an approximately 2 x 2 cm solitary dull nodule on his right thigh, which had been present for 8 months. Mycological examination confirmed that the lesion was caused by C. neoformans. The patient's ratio of peripheral blood CD4(+) cell was slightly reduced. After 14 days of treatment with oral fluconazole, followed by oral itraconazole for 2 months, mycological and clinical cure were achieved. The two isolates were identified as C. neoformans var. gattii serotype C and C. neoformans var. grubii serotype A.

Adult↗

Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar).

Lonafarnib (Sarasar), a farnesyl transferase inhibitor, is currently under development for the treatment of solid tumors. Incubation of lonafarnib with human liver microsomes resulted in the formation of four oxidative metabolites (M1, M2, M3, and M4). Minor to trace levels of these metabolites were detected in humans after multiple-dose administration of lonafarnib. Liquid chromatography-mass spectrometry analyses exhibited a mass to charge ratio (m/z) for the (M+H)(+) ion of M1, M2, M3, and M4 at 653, 635, 669, and 653 Th, respectively. These metabolites, respectively, resulted from changes of +O, -2H, +2O, and +O relative to lonafarnib. Recombinant human CYP3A4 and CYP3A5 exhibited catalytic activity with respect to the formation of M1, M2, and M3, whereas CYP2C8 exhibited catalytic activity with respect to the formation of M4. There was a high correlation between the formation of M1, determined in 10 human liver microsomal samples, and 6beta-hydroxylation of testosterone catalyzed by CYP3A4/5 (r = 0.93). The IC(50) values of ketoconazole for inhibition of M1 and M2 were 0.61 and 0.92 microM, respectively. The formation of M4 by human liver microsomes was inhibited 72% by 50 microM quercetin, suggesting that the formation of M4 was mediated via CYP2C8. A CYP3A4/5-specific inhibitory monoclonal antibody inhibited the formation of M1, M2, and M3 by 85, 75, and 100%, respectively. In conclusion, the formation of metabolites M1, M2, and M3 from lonafarnib was mediated via CYP3A4 and CYP3A5.

Antineoplastic Agents↗

Apolipoprotein synthesis and secretion in Hep G2 cells: effects of monensin and cycloheximide.

Hep G2 cells were used to study the relationship between apolipoprotein synthesis and secretion, as revealed by their interaction with agents modulating these processes. Cycloheximide inhibited the secretion of both apolipoproteins (apo) AI and B, but the reduction in apo AI secretion was evident at earlier times. Monensin also inhibited secretion of apo AI and apo B, but only apo AI accumulated intracellularly. Pulse-chase studies showed that, at concentrations of monensin that had no effect on total protein synthesis, apo B synthesis was specifically inhibited. Triacylglycerol synthesis was inhibited to the same extent as apo B synthesis, but this preceded the latter inhibition and unlike apo B there was an accumulation of intracellular triglyceride. These results suggest that distinctive mechanisms modulate the synthesis and secretion of apo AI and apo B, and that apo B synthesis can be specifically inhibited by mechanisms that initially block triglyceride production.

Apolipoprotein A-I↗

Ramosetron versus ondansetron in the prevention of chemotherapy-induced gastrointestinal side effects: A prospective randomized controlled study.

BACKGROUND: This study observed and compared the preventive effects of ramosetron and ondansetron on gastrointestinal side effects caused by cisplatin-containing chemotherapy. METHODS: Fifty patients with malignant tumors undergoing their first chemotherapy were randomly divided into two groups, and each group received 0.3 mg of ramosetron and 16 mg of ondansetron in a prospective crossover comparison study. RESULTS: Data were collected for analysis of the therapeutic effect in 47 cases and for adverse events in 50 cases. Both drugs showed similar results in regard to chemotherapy-induced gastrointestinal side effects, emesis and appetite loss on day 1, but by day 5, ramosetron was significantly better than ondansetron in terms of controlling appetite loss. From days 3-5, ramosetron tended to be more effective than ondansetron in its antiemetic action. The incidence of headache, fatigue and constipation was the same for both drugs. CONCLUSIONS: Ramosetron is a long-lasting and safe antiemetic agent.

Adolescent↗

Reactive cutaneous cytophagocytosis in nocardiosis.

Cutaneous nocardiosis, which usually manifests in the form of pustules, abscesses, or subcutaneous nodules, is occasionally found in immunocompromised patients. A 59-yr-old Korean man with myasthenia gravis and thymoma developed nodular skin lesions on his trunk. Histopathologically, abscess formation with a dense infiltrate of neutrophils and many cytophagic histiocytes were observed. Numerous filamentous organisms, which turned out to be Nocardia asteroides by culture, were also found. After sulfamethoxazole-trimethoprim therapy, all of the skin lesions rapidly decreased in size, with a marked diminution of the number of cytophagic histiocytes, and cleared up within four months. On reporting a case of cutaneous nocardiosis showing unusual histopathologic findings, we considered that reactive conditions should be included in the differential diagnosis of the cutaneous cytophagocytosis, and that nocardiosis could be one of the diseases showing reactive cytophagocytosis.

Anti-Bacterial Agents↗

Inhibitory effect of oxymatrine on serum hepatitis B virus DNA in HBV transgenic mice.

AIM: To study the inhibitory effect of oxymatrine on serum hepatitis B virus (HBV) DNA in HBV transgenic mice. METHODS: HBV transgenic mice model was established by microinjection, and identified by HBV DNA integration and replication. Transgenic mice with replicating HBV were divided into 3 groups, and injected with normal saline (group A, n=9), 50 mg/kg (group B, n=8) and 100 mg/kg (group C, n=9) oxymatrine intraperitoneally once a day for 30 d, respectively. Quantitation of serum HBV DNA in HBV transgenic mice was performed by competitive polymerase chain reaction (PCR) in combination with DNA hybridization quantitative detection technique before and after treatment. RESULTS: Compared with pre-treatment, the serum HBV DNA in group A (F=1.04, P=0.9612) and group B (F=1.13, P=0.8739) had no changes after treatment. However, in group C serum HBV DNA was significantly decreased (F=13.97, P=0.0012). The serum HBV DNA after treatment was lower in group C than in groups B and A (F=8.65, P=0.0068; F=12.35, P=0.0018; respectively). The serum HBV DNA after treatment was lower in group B than in group A, but there was no statistical significance (F=1.43, P=0.652). CONCLUSION: Oxymatrine has inhibitory effects on serum HBV DNA in HBV transgenic mice.

Alkaloids↗

[Effect of peritoneal lavage with povine-iodine on prevention of postoperative sepsis after exposure of peritoneal cavity to sea water in rat].

OBJECTIVE: To observe the effects of peritoneal lavage with povine-iodine on prevention of sepsis after exposure of peritoneal cavity to sea water in rat. METHODS: Eighty-four SD rats were randomly divided into two groups, and the peritoneal cavity was exposed to sea water. Rats in group A were not treated (group A, n=42), and the peritoneal cavity was lavage with povine-iodine in group B (n=42). Plasma levels of endotoxin and tumor necrosis factor (TNF) were measured preimmersion, and 0, 12, 24 hours after seawater immersion (n=6), and positive incidence of blood bacterial culture was performed (n=18 in each group) in groups A and B. RESULTS: 1. Plasma levels of endotoxin and TNF in group A and B were increased significantly after exposure of peritoneal cavity to sea water (compared with baseline values, all P<0.05). Plasma levels of endotoxin and TNF in group B became lower than those in group A from 12 hours after seawater immersion (P<0.05 or P<0.01). 2. Positive incidence of bacterial culture in group B was 16.7 % (3/18) and it was lower than that in group A (77.8 % (14/18), P<0.01). CONCLUSION: Povine-iodine lavage in the peritoneal cavity can reduce levels of plasma endotoxin and TNF, and lower positive incidence of bacterial culture in rats after exposure of peritoneal cavity to sea water, thereby preventing the development of postoperative sepremia.

Animals↗

[A multicenter randomized controlled study of the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population].

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population. METHODS: A randomized, open, control trial was conducted from Nov. 2002 to Feb. 2003. Patients with chronic respiratory disease, such as chronic bronchitis, obstructive emphysema, bronchial asthma, bronchiectasis or chronic cardiac disease, and with symptoms of influenza were enrolled. They should satisfy the following criteria: Fever > or = 37.8 degrees C plus at least two of the following influenza symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscle aches and pain, fatigue, headache and chills/sweats. Within 48 h after the onset of the symptoms, the patients were randomly assigned to oseltamivir group (oseltamivir 75 mg, twice daily for 5 days) or control group (symptom relief medicine only). RESULTS: Fifty-six of the 108 recruited patients were identified as influenza-infected through laboratory test. They were defined as intent-to-treat infected population (ITTI) (27 oseltamivir, 29 control). The duration of influenza symptom was 64 h shorter (36.7%) and AUC score of the influenza symptom was decreased by 618 (43.1%) in the oseltamivir group as compared with those in the control group. The fever duration was 46.8 h (45.0%) less in the oseltamivir group than that in the control group. It took 6 d for the oseltamivir group and 11 days for the control group to recover to the basic health status. Secondary complications such as bronchitis, sinusitis and pneumonia occurred 11% (3/27) in the oseltamivir group and 45% (13/29) in the control group. The treatment expense for influenza and its complication was 587.4 RMB in the oseltamivir group and 786.5 RMB in the control group, which showed no significant difference (P = 0.246). CONCLUSIONS: It is suggested that oseltamivir is effective and well tolerated in patients with chronic respiratory or cardiac diseases. It can reduce the fever duration and severity of influenza symptom, and decrease the incidence of secondary complications and antibiotic use, while does not increase the total medical cost.

Acetamides↗

[Integration and expression of sdh gene in Escherichia coli].

The chloramphenicol-resistant cassette with short shared sequences of ptsG gene on both ends was PCR-generated from plasmid pKF3 and ligated to pMD18-T to construct pMD18-PC. The sdh gene for sorbose dehydrogenase was generated from plasmid pQE60-SDH and inserted into pMD18-PC, then pMD18-PC-SDH was constructed. It was digested with Pvu II and the target fragment ptsG1-cat-sdh-ptsG2 was recovered and electroporated into Escherichia coli JM109/pKD46. Homologous-recombination between linear DNA cassettes and Escherichia coli chromosomes took place by Red recombination. The detection result showed that the integron JM109s was of sorbose dehydrogenase activity. The PCR products assay using the upstream and downstream sequences of ptsG gene as primers and JM109s genomic DNA as template, indicated that sdh gene had been integrated at the ptsG gene site in Escherichia coli.

Anti-Bacterial Agents↗

[Intraocular penetration of cefotiam hydrochloride, a kind of cephalosporin after filtration surgery in rabbit eyes].

PURPOSE: In this study, we measured the cefotiam dihydrochloride (CTM) concentration in ocular tissue after filtration surgery in rabbit eyes. METHODS: CTM (20 mg/kg body weight) was administered intravenously 30 min before filtration surgery which was performed by double flap procedure on the right eyes of white rabbits. The aqueous humor and serum were extracted at 10 min after surgery and at 30 min, 60 min, and 120 min. Drug concentration in all of the specimens was measured by high performance liquid chromatography (HP-LC). RESULT: The CTM concentrations of aqueous humor in the nonoperated eyes were 0.44 +/- 0.16(mean +/- standard deviation) microg/ml (n = 4) (40 min after intravenous dosage), 0.36 +/- 0.17microg/ml (n = 4) (60 min after intravenous dosage), 0.38 +/- 0.34, microg/ml(n = 3) (90min after intravenous dosage) and 0.27 +/- 0.10 microg/ml (n = 5) (150 min after intravenous dosage). In contrast, CTM concentration in the aqueous humor of the operated eyes was 2.4 +/- 0.95 microg/ml (n = 4) at 10 min after surgery (40 min after intravenous dosage), 2.11 +/- 1.10 microg/ml (n = 4) at 30 min after surgery (60 min after intravenous dosage), 1.18 +/- 0.78 microg/ml (n = 4) at 60 min after surgery (90 min after intravenous dosage) and 0.47 +/- 0.1 microg/ml (n = 5) at 120 min after surgery (150 min after intravenous dosage). The intraocular penetration of CTM at 10 min and at 120 min after filtration surgery was significantly higher in comparison with the drug concentration in the nonoperated eyes (p < 0.05). CONCLUSION: The intraocular penetration of CTM after filtration surgery was much higher in comparison with the drug concentration in the nonoperated eyes. These results may be useful to predict the intraocular penetration of CTM in human eyes after filtration surgery.

Animals↗

[Study on the sequences of amino-acids and their gene codes of the related proteins of rifampin-dependent Mycobacterium tuberculosis].

OBJECTIVE: To study the sequences of amino-acids and their related genes of rifampin-dependent Mycobacterium tuberculosis. METHODS: The strains of rifampin-dependent, rifampin-resistant and rifampin-sensitive Mycobacterium tuberculosis were evaluated by L-J method. The proteins of 134 strains were analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (SDS-PAGE). The sequences of amino-acids of the proteins with differential expressions were determined by Q-TOF2 liquid chromatography-electra mist spray-quadrupole -time of flight cascade mass spectrograph (LC-ESI-MS-MS, Q-TOF2). The corresponding gene codes for the proteins were analyzed. RESULTS: The protein SDS-PAGE profile of 41 of 49 (41/49) rifampin-dependent strains showed a high expression of a protein band (molecular weight 43,000), representative of 30%-50% of the total proteins differed from rifampin resistance and the control strains. The protein profile of H(37)Rv standard strains, 28 (28/30) rifampin-sensitive strains and 44 (44/54) rifampin-resistant strains showed no relevant high expression. The protein of high expression was identified as the hypothetical protein Rv0341 of Mycobacterium tuberculosis H(37)Rv with a molecular weight (M) of 43,894, a iso-potential point of 5.25 and a score of 183. No mutation was found in the 1,440 bp encoding sequence in various strains. CONCLUSIONS: The hypothetical protein Rv0341 is related to the rifampin-dependent strains, so it can be regarded as an indicator for rifampin-dependent Mycobacterium tuberculosis. Rifampin upregulated the expression of Rv0341 in rifampin-dependent Mycobacterium tuberculosis. Whether the hypothetical protein Rv0341 is related to virulence and synthesis of the cell wall of Mycobacterium tuberculosis needs further study.

Amino Acid Sequence↗