To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.
Administration, Oral ; Asian Continental Ancestry Group ; Calibration ; Chromatography, Liquid ; Delayed-Action Preparations ; metabolism ; Healthy Volunteers ; Humans ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
Administration, Oral ; Adolescent ; Adult ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Antihypertensive Agents ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Cross-Over Studies ; Drug Liberation ; Humans ; Hydrochlorothiazide ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Male ; Tablets ; Tandem Mass Spectrometry ; Therapeutic Equivalency ; Valsartan ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Young Adult

Female ; Gastroscopy ; Humans ; Infant ; Intestinal Obstruction ; diagnosis ; therapy ; Treatment Outcome

OBJECTIVETo explore the effects of hyperbaric oxygen (HBO) treatment on the neuronal apoptosis at an earlier stage and the expressions of Cytochrome C (Cyt C), Bcl-2 (B-cell lymphoma-2 family) and Bax (Bcl-2 associated X protein) in rat brain tissues after traumatic brain injury (TBI).

METHODSForty adult rats were divided into two groups, i.e., Group A (the rats with untreated TBI) and Group B (rats with HBO treatment after TBI). Sections of brain tissues of these two groups were then detected at 3, 6, 12, 24, 72 hours after TBI by immunohistochemistry and electronmicroscope, respectively.

RESULTSHBO treatment could up-regulate the expression of Bcl-2 within 72 hours, reduce the release of Cyt C from mitochondria, attenuate the formation of dimeric Bax and alleviate the mitochondrial edema within 24 hours after TBI.

CONCLUSIONSHBO treatment can alleviate neuronal apoptosis after TBI by reducing the release of Cyt C and the dimers of Bax and up-regulating the expression of Bcl-2.

Analysis of Variance ; Animals ; Apoptosis ; physiology ; Brain Injuries ; pathology ; therapy ; Cytochromes c ; biosynthesis ; Disease Models, Animal ; Hyperbaric Oxygenation ; Immunohistochemistry ; Male ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; biosynthesis

OBJECTIVETo study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved.

METHODSTwelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer's (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly.

RESULTSInfusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P<0.01 and P<0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise increase was present. At T(4), blood SOD level was significantly higher in Group II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T(4)) was higher in Group II than in Group I (P<0.05).

CONCLUSIONSMP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.

Analysis of Variance ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Lipid Peroxidation ; Male ; Methylprednisolone ; pharmacology ; Probability ; Random Allocation ; Reference Values ; Reperfusion Injury ; drug therapy ; physiopathology ; Sensitivity and Specificity ; Shock, Hemorrhagic ; drug therapy ; physiopathology ; Survival Rate

OBJECTIVETo improve the accuracy of preoperative evaluation of cervical lymph node metastasis in thoracic esophageal squamous carcinoma.

METHODSForty-two patients with thoracic esophageal squamous carcinoma underwent neck ultrasonography. Enlarged lymph nodes with their long axis greater than 10 mm and a short-to-long axis ratio greater than 0.5 were considered as metastatic.

RESULTSPreoperative neck ultrasonography revealed the enlarged lymph nodes in 16 patients, but only in 5 (31%) cases the nodes were palpable. Among them 9 were classified as metastatic (cM(1-LN)), including 4 patients with palpable nodes. In 5 cM(1-LN) patients surgical intervention was canceled and the remaining 37 patients underwent trans-thoracic esophagectomy. Cervical node metastasis (pM(1-LN)) was confirmed pathologically in 6 surgical patients, 4 with tumors invading the adventitia (pT3) and the other 2 into the surrounding structure (pT(4)) (pT(1), pT(2) vs. pT(3), pT(4), P = 0.020). All 6 pM(1-LN) patients had concomitant mediastinal node metastasis and 4 of them had upper abdominal node metastasis. Statistically significant relationship was detected between cervical and abdominal nodal status (r = 0.536, P = 0.007). In comparison with the results of pathological examination and treatment response, the accuracy and sensitivity were 81% and 95% (P = 0.043), 36% and 82% (P = 0.081), respectively, for palpation and ultrasonography. Five out of 39 (13%) patients had their therapy changed due to ultrasonographic findings.

CONCLUSIONSNeck ultrasonography for cervical lymphadenopathy is of high sensitivity and accuracy, which plays an important role in the preoperative evaluation and therapeutic decision-making.

Adult ; Aged ; Carcinoma, Squamous Cell ; diagnostic imaging ; secondary ; surgery ; Esophageal Neoplasms ; pathology ; surgery ; Female ; Head and Neck Neoplasms ; diagnostic imaging ; secondary ; surgery ; Humans ; Lymph Node Excision ; methods ; Lymph Nodes ; diagnostic imaging ; Lymphatic Metastasis ; diagnosis ; Male ; Middle Aged ; Neck ; diagnostic imaging ; Sensitivity and Specificity ; Ultrasonography

OBJECTIVETo investigate the effect of radix paeoniae rubra (RPR) on expression of p38 mitogen activated protein kinase (MAPK)/iNOS/HO-1 in rats with lipopolysaccharide-induced acute lung injury and explore the molecular mechanism.

METHODSForty healthy male Wistar rats, weighing 200-250 g, aged 6-8 weeks (mean equal to 7 weeks), provided by the Experimental Center, Medical College, Wuhan University, Wuhan, China, were employed in this study. Under anesthesia with 7% chloraldurat (5 ml/kg body weight) through intraperitoneal injection, the trachea of the rat was exposed and an arterial puncture needle pricked into the trachea via cricothyroid membrane. Then they were randomly divided into five groups: 8 rats receiving 1 ml normal saline through the puncture needle (Group A), 8 receiving 1 ml lipopolysaccharide (LPS, 2.5 mg/kg, Group B), 8 receiving LPS and RPR (30 mg/kg, pumped through the femoral vein for 2 hours, Group C), 8 receiving RPR 2 hours before dripping LPS (Group D), and 8 receiving hemin (75 micromol/L through intraperitoneal injection) 18 hours before dripping LPS (Group E). After 6 hours of LPS dripping, blood samples were obtained through the carotid artery to perform blood gas analysis, then all the rats were exsanguinated to death and specimens of lung tissues were obtained. The pathomorphological changes of the lung tissues were observed. The expression of p38 MAPK/iNOS/HO-1, the neutrophil ratio, protein content in alveolar irrigating solution and malonaldehyde (MDA) content in the lung tissues were also detected.

RESULTSCompared with Group A, the expression of p38 MAPK, iNOS and HO-1 markedly increased in Groups B, C, D, and E (P < 0.01). But in Groups C, D and E the expression of p38 MAPK and iNOS were significantly lower than that of Group B, while expression of HO-1 was obviously higher than that of Group B (P < 0.05). The protein content, the ratio of neutrophils in bronchoalveolar lavage fluid (BALF), the content of MDA and the activities of serum NO in Group B were significantly higher than those of Group A (P < 0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in Group B (P < 0.01). Compared with Group B, these indexes of lung injury were significantly lower while the levels of arterial bicarbonate and partial pressure of oxygen increased significantly in Groups C, D and E (P < 0.05 or P < 0.01). Under light microscope, the pathological changes induced by LPS were significantly attenuated by RPR and hemin.

CONCLUSIONSThe high expression of MAPK plays an important role in lipopolysaccharide-induced acute lung injury. Protective effect of RPR on lipopolysaccharide-induced acute lung injury may be related to the inhibition of the abnormal high expression of p38 MAPK/iNOS/HO-1.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Heme Oxygenase-1 ; analysis ; Immunohistochemistry ; Lipid Peroxidation ; drug effects ; Lipopolysaccharides ; toxicity ; Lung ; pathology ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type II ; analysis ; Paeonia ; Phytotherapy ; Rats ; Rats, Wistar ; Respiratory Distress Syndrome, Adult ; drug therapy ; metabolism ; pathology ; p38 Mitogen-Activated Protein Kinases ; analysis

OBJECTIVETo detect the influencing factors for posttraumatic hydrocephalus in patients with severe traumatic brain injuries and provide theoretical reference for clinical treatment.

METHODSRetrospective study was made on 139 patients with severe traumatic brain injuries in our hospital. The patients were divided into two groups: hydrocephalus group and non-hydrocephalus group. Single factor analysis and multiple factor analysis were used to determine the related factors and hydrocephalus. Multiple factor analysis was conducted with logistic regression.

RESULTSPosttraumatic hydrocephalus was found in 19.42% of patients. Age(OR equal to 1.050, 95%CI: 1.012-1.090), decompressive craniectomy (OR equal to 4.312, 95%CI: 1.127-16.503), subarachnoid hemorrhage(OR equal to 43.421, 95%CI: 7.835-240.652) and continuous lumbar drainage of cerebrospinal fluid (OR equal to 0.045, 95%CI: 0.011-0.175) were screened out from nine factors as the influencing factors for posttraumatic hydrocephalus.

CONCLUSIONSRisk factors for PTH are as follows: age, decompressive craniectomy and subarachnoid hemorrhage (SAH). Continuous lumbar drainage of cerebrospinal fluid can greatly reduce posttraumatic hydrocephalus.

Adult ; Age Factors ; Brain Injuries ; complications ; Cerebrospinal Fluid ; Craniotomy ; Drainage ; Factor Analysis, Statistical ; Female ; Humans ; Hydrocephalus ; etiology ; Male ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Subarachnoid Hemorrhage ; complications

OBJECTIVETo further investigate and discuss the cause of species endangerment, the status and present problem of conservation of traditional Tibetan medicine in China.

METHODPrevious relevant investigations and literatures were summed up in the field. The present situation of conservation of traditional Tibetan medicine was analyzed.

RESULTThe status of endangered resources, cause of species endangerment, the conserving status and conserving measures etc were elaborated. The classification was made and suggestion of species conservation of traditional Tibetan medicine were put forward.

CONCLUSIONThe endangered species conservation of traditional Tibetan medicine was carried out by building protective area of endangered species resources and plant garden, setting up germplasm bank, developing the domestication and cultivation of Tibetan medicinal herbs most in use, strengthening the investigation and study of endangered species, launching exchange and cooperation of conservation techniques on endangered species, enhancing the protective awareness of endangered species traditional Tibetan medicine etc. By so doing we can facilitate the sustainable development of traditional Tibetan medicine in China.

Conservation of Natural Resources ; Ecosystem ; Materia Medica ; Pharmacognosy ; Plants, Medicinal ; Tibet

OBJECTIVETo investigate the effects of hypertonic sodium chloride hydroxyethyl starch 40 (HSH) on brain edema and morphological changes during whole body hyperthermia (WBH) in rats.

METHODSSixty adult male SD rats were randomized into control group, WBH group without fluid infusion (group HT), WBH group with Ringer's infusion (group RL), WBH group with HAES + Ringer's infusion (group HRL) and WBH group with HSH infusion (group HSH). WBH was induced by exposure to 36 degrees celsius; for 3 h to achieve a rectal temperature of 41-42 degrees celsius;, and the corresponding fluids were administered intravenously within 30 min at the beginning of WBH. The control rats were housed at a controlled room temperature (22∓1) degrees celsius; for 4 h. After cooling at room temperature for 1 h, the rats were sacrificed and brain water content and morphological changes were evaluated.

RESULTSCompared with the control group, all the WBH groups had significantly increased brain water content (P<0.05 or 0.01), but group HSH showed a significantly lower brain water content than group HT (P<0.05). The rats in groups HT, RL and HRL showed serious to moderate structural changes of the brain tissue and nerve cells, but HSH group had only mild pathologies.

CONCLUSIONHSH can reduce brain edema and ameliorate the damages to brain cells in rats exposed to WBH.

Animals ; Brain ; pathology ; Brain Edema ; pathology ; prevention & control ; Hydroxyethyl Starch Derivatives ; therapeutic use ; Hyperthermia, Induced ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Saline Solution, Hypertonic ; therapeutic use