The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

OBJECTIVETo prepare matrine double-sensitive colon-specific pellets and study the factors affecting its quality and evaluateing the colon-specific effects of preparation.

METHODMatrine enzyme-sensitive pellets core were prepared by carboxymethyl konjac glucomannan as the main carrier material, and coated the core by acrylic resin II and III to prepare matrine double-sensitive colon-specific pellets. The prescription and technology of the matrine colon-specific pellets were studied by the single factor investigation, through the in vitro release test and coating rate determination.

RESULTThe optimized process conditions: FeCl3 concentration is 4.0 g x L(-1), chitosan concentration is 3.0 g x L(-1), carboxymethyl konjac glucomannan concentration is 20 g x L(-1), mixed gel solution pH value is 3. The release of matrine is less than 30% in the simulation of the upper gastrointestinal medium. The release of matrine is close to 100% in simulated full gastrointestinal medium, the coating weight is 7%.

CONCLUSIONThe prepared pellets have good colon positioning effect in vitro.

Acrylic Resins ; chemistry ; Administration, Oral ; Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Chitosan ; chemistry ; Chlorides ; chemistry ; Colon ; metabolism ; Delayed-Action Preparations ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Ferric Compounds ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Mannans ; chemistry ; Quinolizines ; administration & dosage ; chemistry ; pharmacokinetics ; Reproducibility of Results ; Tablets, Enteric-Coated ; Time Factors

OBJECTIVETo explore the effect of MnCl(2) on the mitochondrial function of human lung cells, and to study the changes of protein expression level of nuclear respiratory factor-1 (NRF-1) in mitochondrial dysfunction induced by MnCl(2).

METHODSThe effects of MnCl(2) on cell survival rate were assessed by the reductions of tetrazolium dye (MTT) in cultured cell lines 16HBE and A549 cells. All tested16HBE and A549 cells were incubated with different concentrations of MnCl(2). The permeability transition pore (PTP) of mitochondria, mitochondrial membrane potential and the inhibition rate of mitochondrial enzymes as indicators of mitochondrial damage were measured by fluorescent spectrometry and MTT assay, respectively. Apoptosis was determined by flow cytometry. Protein levels of NRF-1 and mtTFA were measured by Western blot assay.

RESULTSMnCl(2) decreased the survival rate of the two cell lines. The IC(50) of 16HBE and A549 cells were 1.91 mmol/L and 1.98 mmol/L, respectively. MnCl(2) caused a concentration-dependent decrease of mitochondrial enzymes and the inhibition rate of mitochondrial enzymes of the two cell lines induced by 1.00 mmol/L MnCl(2) were (52.8 ± 5.4)% and (50.6 ± 2.2)%, respectively. The PTP opening increased in MnCl(2)-treated cells in a dose- and time-dependent manner. Compared with the control group, mitochondrial membrane potential in the two cell lines was decreased by MnCl(2), by (7.9 ± 3.0)%, (26.2 ± 2.2)% and (27.8 ± 4.1)% in the 16HBE cells, and (4.7 ± 1.0)%, (14.9 ± 2.4)% and (27.5 ± 1.2)% in the A549 cells. Increased apoptosis rates of the two cell lines were induced by 1.00 mmol/L MnCl(2), (12.3 ± 1.9)% and (6.0 ± 0.4)%, respectively. The results of Western blot assay revealed that the protein levels of NRF-1 and mtTFA were decreased in manganese-treated cells in a dose-dependent manner, with a significant difference compared with that of the control cells (P < 0.05).

CONCLUSIONMnCl(2) induces mitochondrial dysfunction in 16HBE and A549 cells, and decreases the expression level of nuclear respiratory factor-1 (NRF-1), indicating that NRF-1 may play an important role in mitochondrial dysfunction.

Apoptosis ; drug effects ; Bronchi ; cytology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cells, Cultured ; Chlorides ; administration & dosage ; toxicity ; DNA-Binding Proteins ; metabolism ; Dose-Response Relationship, Drug ; Epithelial Cells ; cytology ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Manganese Compounds ; administration & dosage ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondria ; drug effects ; physiology ; Mitochondrial Membrane Transport Proteins ; drug effects ; Mitochondrial Proteins ; metabolism ; Nuclear Respiratory Factor 1 ; metabolism ; Transcription Factors ; metabolism

The effect of NaCl plus 3% chitosan on the systolic blood pressure of spontaneously hypertensive rats (SHR) were evaluated and compared with NaCl plus KCl (NaCl, 49.36% + KCl 49.36%) and chitosan or NaCl treatment alone. In SHR, administration of NaCl plus chitosan (44 mM Na/day) for two months significantly decreased the systolic blood pressure greater than of NaCl plus KCl and NaCl alone. NaCl plus chitosan resulted, though not statistically significant, in decreased urinary Na+ excretion and decreased blood urea nitrogen levels. Urinary creatinine of NaCl plus chitosan was slightly decreased compared to 3 treated groups. Serum electrolytes levels, however, remained unchanged. The combination of NaCl and chitosan may be superior to the conventional use of NaCl plus KCl or NaCl alone in the prevention of hypertension. Even though these supplementary diets have demonstrated potential anti-hypertensive effects in the experimental animal model, further research is needed before any recommendations can be made.
Angiotensin I/blood ; Angiotensin II/biosynthesis ; Animals ; Blood Pressure/*drug effects/physiology ; Blood Urea Nitrogen ; Body Weight/drug effects ; Chitosan/*administration & dosage ; Chlorides/blood/urine ; Creatinine/urine ; Heart/physiology ; Histocytochemistry ; Hypertension/*prevention & control ; Kidney/physiology ; Male ; Potassium/blood/urine ; Potassium Chloride/administration & dosage ; Random Allocation ; Rats ; Rats, Inbred SHR ; Sodium/blood/urine ; Sodium Chloride, Dietary/*administration & dosage ; Systole/drug effects/physiology

OBJECTIVETo evaluate the effects of sequential colon dialysis (SCD), hemodialysis (HD) and peritoneal dialysis (PD) on the serum level of uric acid (UA) in patients with hyperuricemia.

METHODSA total of 293 patients with mild, moderate and severe degree of hyperuricemia were randomly assigned to three groups according to digital randomized method, and treated with SCD, HD and PD respectively. The serum level of UA was determined with unicase-peroxidase conjugate method, the blood levels of K+, Na+, Cl-, Ca2+ were determined by automatic biochemical analysor, and changes of body weight were measured before and after dialysis.

RESULTSIn the 293 cases, the three modes of dialysis showed no difference in lowering uric acid in patients of mild degree (P > 0.05). But the HD did show a better efficacy than that of the other two in severe degree patients (P<0.01), while in patients of moderate degree, significant difference (P<0.01) showed between HD and SCD, PD and SCD, but not between HD and PD (P > 0.05). No obvious effect of the various modes of dialysis on the level of K+, Na+, Cl-, Ca2+, body weight.

CONCLUSIONSCD can decrease the serum level of UA effectively and reduce the incidence of complication of hyperuricemia to some extent, as hemodialysis and peritoneal dialysis can.

Administration, Rectal ; Adolescent ; Adult ; Aged ; Calcium ; blood ; Chlorides ; blood ; Colon ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Hyperuricemia ; blood ; therapy ; Male ; Middle Aged ; Peritoneal Dialysis ; methods ; Potassium ; blood ; Renal Dialysis ; methods ; Sodium ; blood ; Uric Acid ; blood ; Young Adult

OBJECTIVETo assess the efficacy and safety of reduced osmolarity oral rehydration salts (ROORS) in treatment of mild to moderate dehydration caused by acute diarrhea in children.

METHODSA multicenter, randomized, double-blind, positive drug controlled clinical trial was conducted in 125 cases aged 1 to 17 years. These children with acute diarrhea and signs of dehydration were randomly assigned to receive either ROORS (trial group, n = 62) or oral rehydration salts II (ORS II) (control group, n = 63). The volume of intravenous infusion were recorded. The improvements of systemic symtoms and signs, diarrhea, dehydration and total scores were compared between the two groups. The adverse events and changes of electrolyte and other laboratory tests during treatment were also observed and analyzed.

RESULTSThe overall effective rates in trial group and control group were 96.8% and 96.8%, respectively. The recovery of systemic symptoms, dehydration signs and diarrhea occurred in 96%, 97% and 78% patients in trial groups, and 96%, 98% and 85% patients in control group. The scores of symptoms and signs in both groups decreased significantly after treatment. All the above parameters and the number of cases who needed intravenous infusion (41 vs. 39) were not statistically different between two groups. However, the average volume of intravenously infused fluids in trial group was (450.98 +/- 183.07) ml, 24.5% less than that in the control group (597.30 +/- 343.37) ml (P < 0.05). The mean serum Na(+) concentration elevated from (137.48 +/- 4.55) mmol/L to (139.52 +/- 3.25) mmol/L (P < 0.01) in control group after treatment, but the change was not statistically significant in trail group. Serum K(+), Cl(-), HCO(3)(-) and other laboratory result did not change significantly after treatment. The total scores in both groups decreased obviously after treatment, but no significant difference was demonstrated between two groups (P > 0.05). A case in trial group had mild abdominal distention and recovered spontaneously.

CONCLUSIONROORS was shown to be effective and safe in the treatment of mild and moderate dehydration induced by acute diarrhea. Compared to ORS II, ROORS could decrease the intravenous supplement of fluid and lower the risk of hypernatremia.

Adolescent ; Child ; Child, Preschool ; Chlorides ; blood ; Dehydration ; etiology ; therapy ; Diarrhea ; complications ; therapy ; Double-Blind Method ; Female ; Fluid Therapy ; methods ; Humans ; Infant ; Infusions, Intravenous ; Male ; Osmolar Concentration ; Potassium ; blood ; Rehydration Solutions ; administration & dosage ; Sodium ; blood ; Treatment Outcome ; Water-Electrolyte Balance

OBJECTIVETo study the effects of resvaratrol derivatives on spontaneous HR and CF of isolated guinea pig atrium.

METHODThe dose-effect curve of resvaratrol was observed. The possible mechanism of potassium channels responsible for changes of CF and HR after administering with resvaratrol was measured.

RESULTResvaratrol reduced the spontaneous HR and weakened the CF in a dose-dependent manner ranging from 10(-6) to 3 x 10(-4) mol x L(-1) (P < 0.05). As compared with Res group, the effects were partly blocked by Gli (P < 0.05) and TEA (P < 0.01), but not blocked by 4-AP, BaCl2, Atropine.

CONCLUSIONResvaratrol can induce negative chronotropic action and negative (inotropic action. The mechanism(s) may relate to the opening of K(ATP) and Kc(Ca).

Animals ; Barium Compounds ; pharmacology ; Cardiotonic Agents ; administration & dosage ; isolation & purification ; pharmacology ; Chlorides ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Glyburide ; pharmacology ; Guinea Pigs ; Heart Rate ; drug effects ; In Vitro Techniques ; KATP Channels ; antagonists & inhibitors ; Male ; Myocardial Contraction ; drug effects ; Plants, Medicinal ; chemistry ; Potassium Channel Blockers ; pharmacology ; Potassium Channels, Calcium-Activated ; antagonists & inhibitors ; Potassium Channels, Inwardly Rectifying ; antagonists & inhibitors ; Stilbenes ; administration & dosage ; isolation & purification ; pharmacology ; Tetraethylammonium ; pharmacology

AIMTo study the effect of ZD7288 on synaptic transmission in the pathway from perforant pathway (PP) fibers to CA3 region in rat hippocampus.

METHODSThe extracellular recording technique in vivo was used to record the CA3 region field potentials. High-performance liquid chromatography (HPLC) with fluorescence detection was applied to measure the content of amino acids in hippocampal tissues. The effect of ZD7288 and CsCl on the amplitudes of population spike (PS) in CA3 region evoked by stimulation (0.5 Hz) of the perforant pathway (PP) fibers, and the content of amino acids in hippocampal tissue were observed.

RESULTSMicroinjection of ZD7288 (20, 100 and 200 nmol) and CsCl (1, 5 and 10 micromol) into CA3 region decreased the population spike (PS) amplitudes in a dose-dependent manner. The inhibitory effects appeared at 5 min after microinjection and lasted at least 90 min. In those rats treated with ZD7288 (100 nmol), the contents of glutamate, aspartate, glycine and GABA decreased significantly as compared to those of saline control (all P < 0.01, except P < 0.05 for that of glycine). A similar decrease in the contents of amino acids was observed when the rats were microinjected with CsCl (5 micromol). CONCLUSION; ZD7288 could obviously inhibit synaptic transmission in the pathway from PP fibers to CA3 region in rat hippocampus, and this action of ZD7288 may be associated with altered contents of amino acids.

Amino Acids ; metabolism ; Animals ; Cesium ; pharmacology ; Chlorides ; pharmacology ; Dose-Response Relationship, Drug ; Evoked Potentials ; Hippocampus ; metabolism ; physiology ; Male ; Microinjections ; Perforant Pathway ; physiology ; Pyrimidines ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission ; drug effects

The hemodynamic effects of rapid intravenous (IV) administration of 10% dextran 40 in saline solution (D40) and 7.2% hypertonic saline solution (HSS) in calves were compared. Calves received isotonic saline solution (ISS), HSS or D40 (3 calves/group) and were monitored of blood pressure, and cardiac output (CO) for 180 min. HSS and D40 infusions induced a significant increase in relative plasma volume reaching 134.9 +/- 2.8 and 125.0 +/- 1.9%, respectively at the end of fluid infusion. In the HSS group, CO, cardiac index (CI) and stroke volume (SV) remained constant at low levels after 90 minutes despite the maximal values of CO, CI and SV at the end of infusion, reaching 21.0 +/- 6.3 l/min (p<0.05), 177.8 +/- 14.2 ml/min/kg (p < 0.001) and 0.20 +/- 0.03 l/beat (at t = 10 min, p < 0.001), respectively. In contrast, CI and SV in the D40 group showed significant increases to 14.7 +/- 2.9 l/min and 153.5 +/- 17.2 ml/min/kg, respectively, at the end of fluid infusion. And those values remained constant at higher levels than those of the before infusions values throughout the experimental periods. Positive effects for hemodynamic alternations of D40 in calf practice were milder and longer than those of HSS. Therefore, the D40 infusion should be explored as a possible treatment for dehydrated calves, since rapid infusion of D40 may be safe and more beneficial for rehydrating more than HSS treatment.
Animals ; Blood Pressure/drug effects ; Cardiac Output/drug effects ; Cattle ; Cattle Diseases/blood/pathology/physiopathology/*therapy ; Chlorides/blood ; Dextrans/*administration&dosage ; Heart Rate/drug effects ; Hypovolemia/blood/pathology/physiopathology/*therapy/*veterinary ; Infusions, Intravenous/veterinary ; Plasma Substitutes/*administration&dosage ; Plasma Volume/veterinary ; Potassium/blood ; Saline Solution, Hypertonic/*administration&dosage ; Sodium/blood

OBJECTIVETo study the effects of alum, aluminum chloride and aluminum hydroxide on aluminum contents in serum and brain of mice with high performance capillary.

METHOD60 days after the mice were given daily alum, aluminum chloride and aluminum hydroxide with the same aluminum content of 14.25, 57 mg x kg(-1) x d(-1), respectively, the aluminum content in serum and brain of mice were determined with high performance capillary chromatography.

RESULTThe average recoveries of serum aluminum determination was 96.5%-103%. The average recoveries of brain aluminum assay was 92.2%-105.3%. Except control group, serum aluminum increased obviously. Brain aluminum increased in all the large doses groups. 2 weeks after the mice were stopped being given these drugs, serum and brain aluminum recovered to normal level, except aluminum chloride large doses group.

CONCLUSIONThe metabolism and excretion mechanism of aluminum in mice depends on the chemical states of the aluminum compound.

Administration, Oral ; Alum Compounds ; administration & dosage ; pharmacokinetics ; Aluminum ; blood ; metabolism ; Aluminum Compounds ; administration & dosage ; pharmacokinetics ; Aluminum Hydroxide ; administration & dosage ; pharmacokinetics ; Animals ; Brain ; metabolism ; Chlorides ; administration & dosage ; pharmacokinetics ; Electrophoresis, Capillary ; methods ; Male ; Mice