The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.

Carbon-nitrogen lyases (E.C.4.3) are a group of enzymes that release ammonia, amidine or amino group etc, and also show ability to form double bond or ring structure. Specifically, enzymes forming amino group are called amine-lyases (E.C.4.3.3), which are critical in the industrial production of many medicine intermediates. In this review is a summary of four major amine-lyases in terms of their source, enzymatic characteristics and their applications in preparation of pharmaceutical intermediates.

The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.
Administration, Oral ; Adult ; Aged ; Antimetabolites, Antineoplastic ; pharmacokinetics ; Capsules ; Drug Combinations ; Female ; Fluorouracil ; blood ; urine ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Oxonic Acid ; blood ; pharmacokinetics ; urine ; Pyridines ; blood ; urine ; Stomach Neoplasms ; blood ; metabolism ; pathology ; urine ; Tegafur ; blood ; pharmacokinetics ; urine ; Uracil ; blood ; urine

Objective To investigated the effects of combined arsenic trioxide(ATO) and resveratrol(Res)on the viability of NB4 human leukemia cells. Methods NB4 human leukemia cell was used in this experiment.Cells were cultured in ATO (0,0.1875,0.3750,0.7500, 1.1250, 1.5000,2.2500,3.0000,5.0000 μmol/L) and Res (0, 1.5625,3.1250,6.2500, 12.5000, 18.7500,25.0000,37.5000,50.0000 μmol/L). Cell viabilities were measured by MTT in different treatment groups. Half inhibitory concentration(IC50) was calculated. The ratio of concentration of ATO and Res 1.5∶ 18,1.5∶ 25,1.5∶ 35 was added to cells, and the combination index(CI) was calculated. The level of ROS in control, ATO( 1.5000 μmol/L), Res(25.0000 μmol/L) and ATO(0.9000 μmol/L) + Res( 12.5000μmol/L) groups was measured by chemiluminescence assay. Results ①ATO( ≥0.7500 μmol/L) reduced the viability of NB4 cells in a concentration-dependent manner(P ＜ 0.05 ), and IC50 was (1.78 ± 0.11 )μmol/L. ②)Res (≥18.7500 μ mol/L) dose-dependently decreased the viability of NB4 cells (P ＜ 0.05 ), and IC50 was ( 18.71 ±0.18)μ mol/L. ③Combination of ATO and Res showed an antagonistic effect on NB4 cells viability. ④The ROS in Res group( 1670.55 ± 13.97) was significantly lower than that in control group(2345.88 ± 14.48,P ＜ 0.05). The ROS in ATO group (3092.42 ± 94.84) was significantly higher than that in control group(P ＜ 0.05). The ROS in ATO + Res group (1860.27 ± 15.99) was significantly lower than that in ATO group(P ＜ 0.05). Conclusions NB4 cell survival rate can be decreased by ATO and Res. The combination of arsenic trioxide and Res presents an antagonistic effect on NB4 cell viability, in part by reducing intracellular ROS formation.

Objective: : The present study aimed to investigate the clinical characteristics of electrolyte imbalance in patients with moderate to severe traumatic brain injury (TBI) who underwent craniotomy and its influence on prognosis. Methods: : A total of 156 patients with moderate to severe TBI were prospectively collected from June 2019 to June 2021. All patients underwent craniotomy and intracranial pressure (ICP) monitoring. We aimed to explore the clinical characteristics of electrolyte disturbance and to analyze the influence of electrolyte disturbance on prognosis. Results: : A total of 156 patients with moderate and severe TBI were included. There were 57 cases of hypernatremia, accounting for 36.538%, with the average level of 155.788±7.686 mmol/L, which occurred 2.2±0.3 days after injury. There were 25 cases of hyponatremia, accounting for 16.026%, with the average level of 131.204±3.708 mmol/L, which occurred 10.2±3.3 days after injury. There were three cases of hyperkalemia, accounting for 1.923%, with the average level of 7.140±1.297 mmol/L, which occurred 5.3±0.2 days after injury. There were 75 cases of hypokalemia, accounting for 48.077%, with the average level of 3.071±0.302 mmol/L, which occurred 1.8±0.6 days after injury. There were 105 cases of hypocalcemia, accounting for 67.308%, with the average level of 1.846±0.104 mmol/L, which occurred 1.6±0.2 days after injury. There were 17 cases of hypermagnesemia, accounting for 10.897%, with the average level of 1.213±0.426 mmol/L, which occurred 1.8±0.5 days after injury. There were 99 cases of hypomagnesemia, accounting for 63.462%, with the average level of 0.652±0.061 mmol/L, which occurred 1.3±0.4 days after injury. Univariate regression analysis revealed that age, Glasgow coma scale (GCS) score at admission, pupil changes, ICP, hypernatremia, hypocalcemia, hypernatremia combined with hypocalcemia, epilepsy, cerebral infarction, severe hypoproteinemia were statistically abnormal (p<0.05), while gender, hyponatremia, potassium, magnesium, intracranial infection, pneumonia, allogeneic blood transfusion, hypertension, diabetes, abnormal liver function, and abnormal renal function were not statistically significant (p>0.05). After adjusting gender, age, GCS, pupil changes, ICP, epilepsy, cerebral infarction, severe hypoproteinemia, multivariate logistic regression analysis revealed that hypernatremia or hypocalcemia was not statistically significant, while hypernatremia combined with hypocalcemia was statistically significant (p<0.05). Conclusion : The incidence of hypocalcemia was the highest, followed by hypomagnesemia, hypokalemia, hypernatremia, hyponatremia and hypermagnesemia. Hypocalcemia, hypomagnesemia, and hypokalemia generally occurred in the early post-TBI period, hypernatremia occurred in the peak period of ICP, and hyponatremia mostly occurred in the late period after decreased ICP. Hypernatremia combined with hypocalcemia was associated with prognosis.

BACKGROUNDIntermediate filament (IF) proteins have been thought to play a role in nuclear centration, organelle movement and maintenance of cell shape. dl-praeruptorin A (Pd-Ia), a novel Ca2+-influx blocker and K+-channel opener isolated from Chinese traditional herbal medicine Qian-Hu, has been demonstrated to inhibit expression of apoptosis related proteins and reduce the level of proinflammatory factors in ischemia/reperfusion myocardiocytes. Morphologically, whether Pd-Ia effects myocardiocyte IFs remains unclear. The purpose of this study was, for the first time, to evaluate the in vivo effects of Pd-Ia on IF desmin and vimentin content in order to further explore its cardioprotection against ischemia and elucidate its mechanism of action.

METHODSRats underwent a 30 minutes coronary occlusion followed by 120 minutes reperfusion. Assessment of desmin and vimentin content of myocardiocytes was performed by immunohistochemistry, Western blot, Hematoxylin-Eosin staining and densitometry.

RESULTSPretreatment with i.v. infusion of Pd-Ia prior to ischemia significantly increased desmin and vimentin content and alleviated defects caused by the ischemia/reperfusion insult, e.g. with Pd-Ia at a dose of 0.5 or 1.0 mg/kg, integrated density values of desmin were increased from 61 478 +/- 10 074 to 177 408 +/- 10 395 and 195 784 +/- 20 057, and vimentin from 59 189 +/- 19 853 to 164 781 +/- 19 543 and 185 696 +/- 20 957 (P < 0.01, vs placebo), respectively. The recovery of desmin seemed to be stronger and appeared earlier than that of vimentin.

CONCLUSIONPd-Ia protectively increased IF desmin and vimentin content in ischemia/reperfusion myocardiocytes, which might be partially responsible for its cardioprotection against ischemia.

Animals ; Blotting, Western ; Calcium ; metabolism ; Coumarins ; pharmacology ; Desmin ; analysis ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; chemistry ; drug effects ; pathology ; Rats ; Rats, Wistar ; Vimentin ; analysis

OBJECTIVETo assess the value of fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) in carcinoma of the esophagogastric junction.

METHODSFrom December 1998 to April 2002, 27 patients were imaged with FDG-PET and FDG avid masses in the esophagogastric junction were found in every patient. FDG-PET data was analyzed by visual method and standardized uptake value (SUV). FDG-PET results were compared with pathological results and follow-up survey.

RESULTS16 carcinomas of the esophagogastric junction and 11 non-specific FDG-avid masses of normal stomach were all considered malignant by visual method. Maximum and mean Standard uptake value (SUV) of cancer were 6.71 +/- 2.75 and 5.46 +/- 2.31, respectively; SUVmax and SUVmean of non-specific FDG avid mass were 2.99 +/- 0.67 and 2.38 +/- 0.51 respectively; SUV of cancer was higher than that of non-specific FDG avid mass (Z = -4.171, Z = -4.195, P < 0.01).

CONCLUSIONSFDG-PET has limited value in differentiating carcinoma of the esophagogastric junction from non-specific FDG avid mass of normal stomach.

Adult ; Aged ; Diagnosis, Differential ; Esophagogastric Junction ; diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Radiopharmaceuticals ; Retrospective Studies ; Stomach Neoplasms ; diagnostic imaging

Objective To investigate antimicrobial resistance among gram-positive cocci in China in 2009. Methods From June to December 2009, 1169 consecutive and non-repetitive gram-positive cocci were collected from 12 teaching hospitals at 9 cities. The minimal inhibitory concentration (MIC) of antibacterial agents was determined by agar dilution method. Results The prevalences of methicillinresistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCoNS) were 45.3% (211/466) and 89. 5% (214/239), respectively. The isolation rate of MRSA was 33. 3%-68. 1% from different samples. All Staphylococci isolates were susceptible to vacomycin, teicoplanin and linezolid. Five point five percent (7/128) E. faecium strains were resistant to vacomycin. All E.faecalis strains were susceptible to vacomycin. About 99. 1% (108/109) of E. faecalis and E. faecium were susceptible to linezoild. The prevalence of penicillin-intermediate Streptococcus pneumoniae (PISP) was 21.6% (48/222). Only 1 (0. 5%, 1/222) Streptococcus pneumoniae strain was resistant to penicillin.Teicoplanin, vancomycin, linezolid and tigecycline were the most active agents against Streptococcus pneumoniae (susceptible rate 100% ). Conclusions The high prevalence of methicillin-resistance is among Staphylococcus strains. Different samples show a different MRSA prevalence. Teicoplanin, vancomycin and linezolid show very high activity to Staphylococci,E. faecalis, E. faecium and Streptococcus pneumoniae.

Objective To investigate antimicrobial resistance among gram-positive cocci in China in 2008.Methods From June 2008 to December 2008,1171 consecutive and non-repetitive gram-positive cocci were collected from 12 teaching hospitals.The MICs of antibacterial agents was determined by agar dilution method.Results The prevalence of MRSA and methicillin-resistant coagulase-negative Staphylococci(MRSCoN) was 49.9%(232/465) and 74.0%(179/242),respectively.The MRSA prevalence ranged from 33.3% to 65% in different regions.About 71.1%(108/152) of Staphylococcus aureus from respiratory tract specimens,48.3%(28/58) of Staphylococcus aureus from blood samples,and 36%(68/189) of Staphylococcus aureus from the pus,wound and sterile body fluid samples were resistant to methicillin.The susceptible rates of MRSA to trimethoprim/sulfamethoxazole(SXT) and chloramphenicol were 81.5%(183/232) and 89.7%(208/232).Susceptibility to gentamicin, erythromycin, clindamycin, tetracyclines,rifampicin,and quinolones were from 3.9% to 35.0%.All Staphylococci isolates were susceptible to vancomycin,teicoplanin,and linezolid.Three vacomycin-resistant Enterococcus faecium strains were found in this study.About 96.2%(101/105) of Enterococcus faecalis and 97%(130/134) of Enterococcus faecium were susceptible to linezoild.Fifty-one out of 105 of Enterococcus faecalis(48.6%)and 101 out of 134 Enterococcus faecium(75.4%)were resistant to high concentration gentaroicin.The susceptibility of Enterococcus faecalis to all the antibiotics except for chloramphenicol and tetracycline was higher than that of Enterococcus faecium.Enterococcus faecium isolates showed a high resistant prevalence to most of antibiotics except glycopeptides and linezolid.The prevalence of PISP among 225 isolates was was 36.6%(15/41),and the prevalence of PNSSP from the other patients ranged from 15.4% to 26.6%.The susceptible rates of PSSP to cefprozil,cefuroxime and cefaclor were 67.5%(114/169),66.3%(112/169) and 61.5%(104/169),respectively.All the PISP isolates were resistant to the above three antibiotics.Teicoplanin,vancomycin and linezolid were the most active agents against Staphylococcus pneumoniae(susceptible rate,100%).About 96.9%,97.8% and 98.2% Staphylococcus pneumoniae isolates were susceptible to gatifloxacin,levofloxacin,and moxifloxacin,respectively.The susceptible rates of Staphylococcus pneumoniae to ceftriaxone,chloramphenicol and amoxicillin/clavulanic acid were 81.3%,77.3%,and 68.0%,respectively.The susceptibility of Staphylococci pneumoniae to macrolides,SXT and tetracycline ranged from 11.6% to 23.6%.Conclusions The prevalence of VRE is low in China.However,methicillin-resistance among Staphylococci isolates was high.The prevalence of PNNSP isolated from (≤)3 years children is higher than in the other age population.Teicoplanin,vancomycin,and linezolid remain high activity against Staphylococci,Enterococcus faecalis,Enterococcus faecium,and Staphylococcus pneumoniae.

OBJECTIVETo evaluate the clinical value of (89)SrCl(2) (Ke xing Inc, Shanghai) as a palliative therapy modality for cancer patients with bone metastasis.

METHODSIn 504 cancer patients with painful limitation of movement due to bony metastasis, a dose of 1.48-2.22 MBq/kg (40-60 uCi/kg) iv infusion of (89)SrCl(2) was given.

RESULTSIn 97 patients (19.2%) there was no improvement in pain and life quality, 298 patients (59.1%) showed mild to moderate improvement (moderately effective), 109 patients (21.6%) became free of pain and were subsequently fully ambulatory (markedly effective). The pain relief appeared from D1-D46 after (89)SrCl(2) administration, most frequently from D5-D14. The palliative effect could last for about 56 days to 13 months. Repeated bone scans of some patients showed that the metastatic foci in the bone became smaller or even disappeared gradually after the administration of (89)SrCl(2). Approximately 55% of patients experienced grade I approximately III bone marrow depression attributable to (89)SrCl(2), which would return to the pre-treatment level within 3 approximately 9 months.

CONCLUSION(89)SrCl(2) is effective and safe for the relief of bone pain and improvement of quality of life in cancer patients with painful bony metastasis.

Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms ; complications ; radiotherapy ; secondary ; Breast Neoplasms ; pathology ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Pain Measurement ; Pain, Intractable ; etiology ; radiotherapy ; Quality of Life ; Strontium Radioisotopes ; therapeutic use