To research the pharmacokinetic of Danshensu in brain via microdialysis method and automated blood technique. A microdialysis probe was inserted into the left lateral ventricle, and then dialysate samples and blood samples were continuously collected after iv Danshensu. LC-MS/MS was used to determinate for Danshensu in the dialysate samples. The in vivo recovery was used for the calibration of probe. WinNonlin was used for analyzing all pharmacokinetic data. Pharmacokinetic parameters of DSS in blood and in brain showed that Ke, t1/2,, AUC0-t, MRT were 0.04, 0.018 min(-1), 16.64, 58.76 min, 812.59, 51.19 min x mg x L(-1), 15.28, 79.97 min, respectively. The results were indicated that the study was successfully established LC-MS/MS detection method for Danshensu. Microdialysis combined with automated blood technique could better reflect the dynamic characteristics of Danshensu in the rat brain, and it provides a new perspective for pharmacokinetic study.
Animals ; Brain ; metabolism ; Brain Chemistry ; Lactates ; blood ; pharmacokinetics ; Male ; Microdialysis ; Rats ; Rats, Sprague-Dawley

To identify the metabolites of Danshensu in plasma and urine in rats by using UHPLC-LTQ-Orbitrap method. After oral gavage of Danshensu CMC-Na suspension in SD rats, urine and plasma samples were collected and processed by solid phase extraction. ACQUITY UPLC BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) was utilized, with 0.1% formic acid (A)-acetonitrile (B) solution as the mobile phase for gradient elution. Negative electrospray ion mode based data-acquisition method was established to collect the mass spectrometry data of biological samples. As a result, Danshensu and 21 Danshensu Ⅰ phase and Ⅱ phase metabolites were finally identified according to the accurate mass measurements, mass fragmentation behaviors and comparing with the reference standards. The main metabolic pathways included dehydration, methylation, glucuronide conjugation, sulfate conjugation and their composite reactions. Consequently, our study expounded metabolites of Danshensu in rats based on UHPLC-LTQ-Orbitrap method and provided a reference for further researches on therapeutic material basis and mechanism of Danshensu.
Animals ; Chromatography, High Pressure Liquid ; Lactates ; blood ; metabolism ; urine ; Mass Spectrometry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the hormonal and metabolic responses of fetal lamb during cardiopulmonary bypass.

METHODSSix pregnant ewes underwent fetal cardiopulmonary bypasses with artificial oxygenators and roller pumps for 30 minutes, which maintained the blood gas value at the fetal physiological level. The fetal blood pressure, heart rate, pH value and blood lactate levels were monitored. The levels of catecholamine, cortisol and insulin were measured pre-bypass and then again 30 minutes later. The blood glucose and free fatty acid levels were monitored continuously during the bypass. Fetal hepatic PAS staining was also carried out.

RESULTSThere were no changes before and during the bypass in fetal blood pressure, heart rate and blood gas. However, pH values decreased and blood lactate levels increased (P < 0.05). The fetal catecholamine and cortisol levels increased significantly (P < 0.01), while the levels of insulin did not change. The blood glucose and free fatty acid levels increased at the beginning of the bypass (P < 0.01), and then gradually slowed down during the bypass. The fetal hepatic PAS staining showed that hepatic glycogen was consumed in large amounts. After 30 minutes of bypass, the fetal lamb would not survive more than 1 hour.

CONCLUSIONThe fetal lamb has a strong negative reaction to cardiopulmonary bypass.

Animals ; Blood Gas Analysis ; Blood Glucose ; analysis ; Cardiopulmonary Bypass ; adverse effects ; Catecholamines ; blood ; Fatty Acids, Nonesterified ; blood ; Fetus ; physiology ; Hemodynamics ; physiology ; Hydrocortisone ; blood ; Lactates ; blood ; Sheep

Objective: To investigate the clinical characteristics and risk factors of postoperative atrial fibrillation (POAF) in patients with critical burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, two hundred and twenty-seven critically burned aldult patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University, including 173 males and 54 females, aged 19-83 (43±14) years. The admission years of patients were collected, and the percentage of patients complicated with POAF in each year was calculated. According to whether the patients were complicated with POAF or not, they were divided into POAF group (n=17) and non-POAF group (n=210). Following data were collected in patients in POAF group, including operation methods, duration of operation, intraoperative blood loss before occurrence of POAF each time, occurrence time and times of POAF, postoperative body temperature, blood pressure, hemoglobin, blood glucose, blood lactate, sepsis, and electrolyte, and type, duration, and treatment of POAF. General data of patients in the two groups including age, gender, burn reason, total burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sepsis-related organ failure evaluation (SOFA) scores on admission, combined with underlying diseases (hypertension, diabetes, and other types of arrhythmias), and sepsis were collected and analyzed. The mortality and factors influencing the prognosis of patients in the two groups such as mechanical ventilation time, operations times, and burn intensive care unit (BICU) length of stay were also collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test or Kruskal-Wallis H test. The multivariate logistic regression analysis was performed on the general data with statistically significant differences between the two groups, and the independent risk factors influencing the onset of POAF in 227 patients with critical burns were screened. Results: From 2017 to 2021, the percentage of critically burned patients complicated with POAF increased year by year. In POAF group, eschar debridement in limbs was the main surgical procedure prior to POAF complication, with the operation time of (3.5±1.2) h and the intraoperative blood loss volume of (365±148) mL.The POAF occurred 25 times in total in patients of POAF group, mostly within one week after the injury and within 6 hours after the operation with most of these patients having POAF only once. When POAF happened, the patients were often complicated with hypothermia, anemia, hyperglycemia, high blood lactate, sepsis, and electrolyte disturbance, and few patients had complications of hypotension. The POAF lasted (5±3) h, with all being paroxysmal atrial fibrillation, and most of POAF patients were reverted to sinus rhythm after amiodarone intervention. Most patients in the two groups suffered from flame burn, and the gender, age, and SOFA score on admission of patients in the two groups were similar (P>0.05); the APACHEⅡ score on admission, total burn area, full-thickness burn area, incidence proportion of sepsis, combined with diabetes and hypertension and other types of arrhythmias of patients in POAF group were significantly higher or larger than those in non-POAF group (t=3.47, with χ² values of 7.44, 10.86, 12.63, 14.65, 6.49, and 7.52, respectively, P<0.05 or P<0.01). The full-thickness burn area, combined with other types of arrhythmias, and sepsis were the independent risk factors for POAF in 227 critically burned patients (with odds ratios of 4.45, 0.04, and 3.06, respectively, with 95% confidence intervals of 2.23-8.87, 0.01-0.22, and 1.77-5.30, respectively, P<0.01). Compared with those in non-POAF group, the mechanical ventilation time, BICU length of stay, number of operations, and mortality rate of patients in POAF group were significantly increased (Z=3.89, Z=2.57, t=3.41, χ²=3.72, P<0.05 or P<0.01). Conclusions: POAF is a common postoperative complication in critically burned patients, and the incidence is increasing year by year, which seriously affects the prognosis of patients. The full-thickness burn area together with other types of arrhythmias and sepsis are the high-risk factors for POAF complication in patients with critical burns.
Atrial Fibrillation/etiology* ; Blood Loss, Surgical ; Female ; Humans ; Hypertension ; Lactates ; Male ; Prognosis ; Retrospective Studies ; Risk Factors ; Sepsis

OBJECTIVETo investigate the absorption of the water soluble components of Salvia miltiorrhiza and establish methods to determine Danshensu in rat serum after ig compound Salvia recipe.

METHODUsed liquid-liquid extraction to deal with the serum, then determined the sample by high-performance liquid chromatography. The conditions for HPLC were as the following: the mobile phase, CH3OH-CH3CN-0.5% CH3COOH (2.5:3.5:94) with a flow rate of 1.0 mL.min-1; detection wavelength, 281 nm; internal standard, 4-hydroxy-benzoic acid.

RESULTDanshensu and an unknown compound whose reserved time was little shorter than protocatechuic aldehyde were found in the rat serum after ig compound Salvia recipe, while protocatechuic aldehyde weren't found in the serum.

CONCLUSIONDanshensu can be absorbed into blood after ig compound Salvia recipe.

Animals ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Female ; Lactates ; blood ; Male ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

The correlation between muscle glycogen content and physical performance in mice was evaluated by investigating whether an increase in glycogen content in skeletal muscle with insulin administration can improve the physical performance without other effects of exercise. Albino rats(group I) were divided into two groups, i.e., insulin and saline administered group. The former experimental group was treated with protamine zinc insulin(15U/kg/day) subcutaneously for two weeks to increase the content of the muscle glycogen and the latter control group with saline. Mice (group II) were also divided into insulin treated and control groups and both groups were subjected to running exercise on an animal treadmill up to point of exhaustion once every day. After two weeks of insulin treatment, the muscle glycogen content, the maximal running time and the maximal swimming time were measured in non-exercised group I. In group II, after 12 days of insulin and saline administration, the muscle glycogen content, the maximal running time, concentrations of lactate and pyruvate in the blood were measured before and after the maximal exhaustive running. The results were summarized as follows. In group I, the muscle glycogen content, the maximal running time and the maximal swimming time of the insulin administered group were significantly greater of the control groups. In group II, the maximal running time was significantly greater(P < 0.01) in the experimental group than of the control group, while the muscle glycogen content revealed no significant difference between the two groups. On the other hand, lactate concentration and lactate/pyruvate ratios in the blood were significantly lower in the experimental group than those of the control groups. From the above results, it may be concluded that the elevation of muscle glycogen content alone by insulin treatment without any previous physical training can improve physical performance of rats. And insulin was also found to improve physical performance even in experimental animals which had been subjected to a longterm of exercise.
Anaerobiosis/drug effects* ; Animal ; Blood Glucose/analysis ; Body Weight ; Exertion/drug effects* ; Glycogen/analysis* ; Injections, Subcutaneous* ; Insulin/administration & dosage ; Insulin/pharmacology* ; Lactates/blood ; Male ; Metabolism/drug effects* ; Mice ; Muscles/analysis* ; Pyruvates/blood ; Rats

OBJECTIVETo study the changes in gut microbiota and serum D-lactate level and their significance in children with recurrent pneumonia.

METHODSThe stool and blood samples were collected from 30 children with recurrent pneumonia (recurrent group), 30 children with acute pneumonia (acute group), and 15 children receiving surgical operation (surgery group). The 16S rRNA fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to determine the numbers of Bifidobacterium and Escherichia coli in stool samples, and the ratio between the logarithmic values of the numbers of Bifidobacterium and Escherichia coli (B/E value) was calculated. The serum D-lactate level was measured, and correlation analysis was performed.

RESULTSThe recurrent group had a significantly lower number of Bifidobacterium and a significantly lower B/E value than the acute group and the surgery group (P<0.05), as well as a significantly higher number of Escherichia coli than the surgery group (P<0.05). There was no significant difference in the number of Escherichia coli between the recurrent group and the acute group. The recurrent group had a significantly higher serum D-lactate level than the acute group and the surgery group (P<0.05). In the recurrent group, B/E value was negatively correlated with serum D-lactate level (r=-0.539, P<0.05).

CONCLUSIONSChildren with recurrent pneumonia may have biological and mechanical barrier damage in the intestinal mucosa.

Bacteria ; classification ; genetics ; isolation & purification ; Bifidobacterium ; genetics ; isolation & purification ; Child ; Child, Preschool ; Escherichia coli ; genetics ; isolation & purification ; Feces ; microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Lactates ; blood ; Pneumonia ; blood ; microbiology ; pathology ; Recurrence

PURPOSE: To investigate the hypothesis that resuscitation with hypertonic saline (HTS) in hemorrhagic shock (HS) will improve the pulmonary function and inflammatory changes in post-hemorrhage induced acute lung injury. METHODS: HS was induced in anesthetized Swiss-Webster mice by removing 0.025cc blood/g. body weight via the carotid artery while under blood pressure monitoring. Mice were divided into 5 groups: Group I (n=12) were cannulated but not bled (sham); Group II (n=12) were bled and received 4mL/kg 7.5% HTS; Group III (n=10) were bled and received 3 times their shed blood (SB) volume of normal saline (NS); Group IV (n=11) were bled and received SB and 4mL/kg 7.5% HTS; Group V (n=9) were bled and received SB and two times their SB volume of NS after 30 minutes shock. Serum lactates (LA) were evaluated at the end of the shock period and after resuscitation. Pulmonary function was measured by whole-body plethysmography prior to any instrumentation and again 24hr, 48hr and 72hr after resuscitation. Pulmonary inflammation was assessed by quantifying bronchoalveolar lavage neutrophil infiltration (BALN) and myeloperoxidase (MPO) activity after 72hr of observation. RESULTS: There were no differences in baseline BP, shock BP, shock LA and LA after resuscitation in each shock group. The survival rates were as follows: Group I, 75.0%; Group II, 33.3%; Group III, 60%; Group IV, 81.8%; and Group V, 88.8% (p=0.046). There were no significant differences in the changes of airway resistance after resuscitation in each group. BALN and MPO activity in Group III were increased. CONCILUSION: HTS resuscitation alone was associated with higher mortality. HTS was decreased pulmonary inflammation but it did not alter respiratory function.
Acute Lung Injury* ; Airway Resistance ; Animals ; Blood Pressure Monitors ; Body Weight ; Bronchoalveolar Lavage ; Carotid Arteries ; Lactates ; Mice ; Mortality ; Neutrophil Infiltration ; Peroxidase ; Plethysmography ; Pneumonia ; Resuscitation* ; Shock ; Shock, Hemorrhagic* ; Survival Rate

OBJECTIVETo investigate the effect and mechanism of Tanshensu on experimental fibrotic rats.

METHODSPigs serum was used to induce liver fibrosis in Wistar rats. The rats in Tanshensu-treated group were injected peritoneally with Tanshensu solution at the dose of 300 mg x kg(-1) x d(-1), and the rats in model-control group and normal-control group received the same volume of double distill water. At the end of the twelfth week, the hepatic stellate cells (HSCs) were isolated from the liver of one rat in model-control group using in-situ perfusion with pronase and collagenase, then density gradient centrifugation, and the other rats were killed to take the serum and liver samples. MTT colorimetric assay was used for detecting the proliferation of HSCs and flow cytometry was used for observing the cell cycles of HSCs under different concentrations of Tanshensu. The hyaluronic acid (HA) level in serum was detected and the morphological changes of liver tissue were observed.

RESULTSThere was a decline of serum HA level in Tanshensu-treated group compared to that of the model-control group (231.4 ng/ml +/- 41.1 ng/ml vs. 398.7 ng/ml +/- 54.5 ng/ml, F =154.796, P < 0.05). Both HE and VG stain showed a decline of liver fibrosis degree in Tanshensu-treated group. And Tanshensu had an inhibition effect on the proliferation of HSCs at the concentrations of 50 mg/L, 100 mg/L, and 200 mg/L (1.60x10(-2) +/- 8.17x10(-4), 1.10x10(-2) +/- 1.41x10(-3), and 6.75x10(-3) +/- 3.30x10(-3) vs. 7.18x10(-2) +/- 1.71x10(-3), F =1154.221, P <0.01).

CONCLUSIONSTanshensu shows a therapeutic effect on liver fibrosis in rats induced by pig's serum through inhibiting the proliferation of hepatic stellate cells.

Animals ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hepatocytes ; pathology ; Hyaluronic Acid ; blood ; Lactates ; pharmacology ; therapeutic use ; Liver Cirrhosis, Experimental ; drug therapy ; pathology ; Male ; Phytotherapy ; Rats ; Rats, Wistar

To develop a LC-MS/MS method for the determination of protocatechuic acid, protocatechuic aldehyde, salvianolic acid A, salvianolic acid B, cryptotanshinone and tanshinone II(A) in rat plasma and brain. The plasma and brain samples were precipitated with ethyl acetate, then were separated on an Agilent eclipse plus-C18 column (2.1 mm x 50 mm, 3.5 microm) using acetonitrile (consisting of 0.1% formic acid) and water (consisting of 0.1% formic acid) as mobile phase in gradient elution mode. The mass spectrometer was operated under both positive and negative ion mode with the ESI source, and the detection was performed by MRM. The transition of 154.3/153.1 m/z for protocatechuic acid, 137.3/108 m/z for protocatechuic aldehyde, 493.0/295.2 m/z for Salvianolic acid A, 718.0/520.0 m/z for salvianolic acid B, 321.4/152.3 m/z for chloramphenicol, 297.4/254.3 m/z for cryptotanshinone, 295.5/249.3 m/z for tanshinone II(A) and 285.2/154.0 m/z for Diazepam. The calibration curves in the range of 0.625-1 000 microg x L(-1) for protocatechuic acid and protocatechuic aldehyde, 1.25-1 000 microg x L(-1) for salvianolic acid A, 2.5-1 000 microg x L(-1) for salvianolic acid B, 0.15-1 000 microg x L(-1) for cryptotanshinone, 0.625-1 000 microg x L(-1) for tanshinone II(A) are with good linearityin rat plasma and brain. The analysis method is sensitive, simple, and suitable enough to be applied in the pharmacokinetic study of the 6 main components. Animal testing gives the lgBB of the drugs and further studies of the 6 components cross the blood-brain barrier can be carried out.
Animals ; Benzaldehydes ; administration & dosage ; blood ; pharmacokinetics ; Benzofurans ; administration & dosage ; blood ; pharmacokinetics ; Blood-Brain Barrier ; metabolism ; Brain ; metabolism ; Caffeic Acids ; administration & dosage ; blood ; pharmacokinetics ; Catechols ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, Liquid ; methods ; Diterpenes, Abietane ; administration & dosage ; blood ; pharmacokinetics ; Hydroxybenzoates ; administration & dosage ; blood ; pharmacokinetics ; Injections, Intravenous ; Lactates ; administration & dosage ; blood ; pharmacokinetics ; Phenanthrenes ; administration & dosage ; blood ; pharmacokinetics ; Plant Preparations ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry ; Tandem Mass Spectrometry ; methods