Objective To increase the understanding in protein-losing enteropathy (PLE).Methods Sixty-one PLE patients were enrolled in the study and the clinical characteristics, complicated disease, diagnosis and treatment were analyzed. Results The age of the patients was 16-77 (40±15)years, and the gender ratio was 35:26 (female: male). The main clinical manifestations were bilateral lower limb edema in 51 cases, ascites in 41 cases, bilateral pleural effusion in 23 cases, pericardial effusion in 13cases, abdominal pain in 16 cases and diarrhea in 33 cases. The prominent abnormality in laboratory examinations was hypoalbuminemia. The underlying diseases include systemic lupus erythematosus (SLE) in 28 cases, intestinal lymphangiectasia in 12 cases, hepatic cirrhosis in 5 cases, heart diseases in 5 cases,Crohn's disease in 3 cases, membranous nephropathy in 2 cases, Budd-Chiari syndrome in 1 case. Four cases happened after abdominal operation and 1 case after radiation therapy of gastric cardia cancer. Thirtyseven cases were diagnosed by 99Tcm-labelled human serum albumin scintigraphy and 24 cases were diagnosed clinically. Treatment was focused on underlying diseases. The clinical manifestations in 21 cases of SLE improved after SLE was controlled. In 2 cases of intestinal lymphangiectasia and one with Crohn's disease, the clinical manifestations improved after surgery. The other patients had no improvement.Conclusions PLE was not uncommon in clinical practice. Its predominant characteristics were severe hypoalbuminemia, edema and dropsy of serous cavity. PLE can complicate other diseases such as SLE,intestinal lymphangiectasia. Treatment should be focused on primary disease.

To improve the quality of personnel training,carry out the complementary ascendancy and resource sharing,grasp the law and optimize the program of practice teaching,we designed the undergraduate practice teaching of 9 disciplines including clinical medicine,biotechnology,pharmacy,etc.,formulated the practice teaching pattern named "two-stage & two-model",and carried out the practice teaching step by step. The results show that the profession level and overall quality of students have been improved.

A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
Biological Transport ; Blood-Brain Barrier ; Bornanes ; chemistry ; Cell Line, Tumor ; Dendrimers ; Doxorubicin ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Folic Acid ; chemistry ; Glioma ; Humans

Five new megastigmanes (1-5) were isolated from a decoction of Uncaria rhynchophylla by separation techniques of column chromatography using a combination of multiple stationary phases, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40F, and reversed phase HPLC. Their structures were characterized by spectroscopic data analysis of HR-ESI-MS, NMR, and CD, in combination with Mosher's mothed as well as ECD and NMR calculations. The new compounds were named uncarphyllonone A (1), uncarphyllonols A (2) and B (3), and uncarphabscisic acids A (4) and B (5). Although the structures of 3 and 4 were previously reported, the reported NMR spectroscopic data were incorrect or do not support the assigned structures in literatures. This is also the first report of discovery of new megastigmane natural products from the Uncaria genus.

OBJECTIVETo investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms and its association with the development of Kawasaki disease and coronary artery lesion (CAL).

METHODSA total of 81 children with Kawasaki disease (among whom 11 had CAL) and 100 normal children who underwent physical examination (control group) were enrolled in a case-control study. Sequencing was performed to investigate the distribution of adiponectin +45T/G and +276G/T polymorphisms.

RESULTSThere were no significant differences between the Kawasaki disease and control groups in the frequencies of TT, TG, and GG genotypes and T/G alleles of +45T/G polymorphism in the adiponectin gene (P>0.05). In the Kawasaki disease group, there were also no significant differences in the genotype and allele frequencies of the +45T/G polymorphism between the children with CAL and those without (P>0.05). There were significant differences between the Kawasaki disease and control groups in the frequencies of GG, GT, and TT genotypes and G/T alleles of +276G/T polymorphism in the adiponectin gene (P<0.05). GG genotype was a risk factor for the development of Kawasaki disease (OR=2.313, P=0.006). In the Kawasaki disease group, there was no significant difference in the genotype distribution of the +276G/T polymorphism between the children with CAL and those without (P>0.05).

CONCLUSIONSThe adiponectin +276G/T polymorphism may be associated with the development of Kawasaki disease, but not associated with CAL. The adiponectin +45T/G polymorphism may not be associated with Kawasaki disease or CAL.

Adiponectin ; genetics ; Case-Control Studies ; Child ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Mucocutaneous Lymph Node Syndrome ; genetics ; Polymorphism, Single Nucleotide

The purpose of this study was to develop a quantitative and objective method for evaluating neurological deficits in mice with focal cerebral ischemia. After middle cerebral artery occlusion (MCAO), the neurological deficits were evaluated 24 h later. We measured the mean angles, dominant angles and turns in a hanged test in which the mice were sticked on the wall, and the holding angles in an inclined plane test as well, Then we determined the cerebral infarct volumes, neuron density in hippocampus, cortex and subcortical areas 24 h after MCAO. The correlations among infarct volume, neuron density and neurological deficits were analyzed. We also compared the quantitative method with two typical complex methods of behavioral assessment. The effect of [pranlukast, 4-oxo-8-[p-(4-phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate] (ONO-1078), a neuroprotective agent, on ischemic injury was observed using this method. We found that the variables measured by both quantitative and typical behavioral methods significantly changed in the ischemic mice, and correlated with the infarct volumes and neuron densities. The quantitative variables well correlated with those of typical behavioral assessment, too. ONO-1078 inhibited ischemic injury and reduced the total scores of quantitative assessment. Thus, the quantitative method we developed is useful in evaluating neurological deficits of focal cerebral ischemia with the advantages of objectivity, quantification, simplicity and non-invasion, and can be used in the evaluation of neuroprotective effects of drugs.
Animals ; Behavior, Animal ; Brain ; pathology ; physiopathology ; Brain Ischemia ; etiology ; pathology ; physiopathology ; Chromones ; pharmacology ; therapeutic use ; Female ; Hippocampus ; pathology ; Infarction, Middle Cerebral Artery ; complications ; pathology ; physiopathology ; Leukotriene Antagonists ; pharmacology ; therapeutic use ; Male ; Mice ; Mice, Inbred ICR ; Neurologic Examination ; Neuroprotective Agents ; pharmacology ; therapeutic use

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

BACKGROUNDAstrocyte swelling is an important consequence of hepatic encephalopathy, and aquaporin-4 has been reported to play a vital role in this swelling. Ammonia causes astrocyte swelling and is also known to modulate aquaporin-4 expression in the astrocyte foot processes. The purpose of this study was to explore the mechanism of ammonia-induced aquaporin-4 expression, which has been suggested to involve the p38 mitogen-activated protein kinase pathway.

METHODSWe exposed cultured astrocytes to ammonium chloride, an in vitro model of hepatic encephalopathy. The purity of cultured astrocytes was evaluated by fluorescent glial fibrillary acidic protein labeling; cell morphology was assessed by light microscopy; the expression of aquaporin-4, phospho-p38, and p38 were detected by Western blotting analysis. Statistical analysis was performed by one-way factorial analysis of variance, and the relationship between variables was calculated by linear regression using SPSS version 13.0 program for Windows (SPSS, Chicago, IL, USA).

RESULTSThe purity of cultured astrocytes was (96.6 +/- 1.4)%. Astrocytes swelled significantly when exposed to 5 mmol/L ammonium chloride for 24 hours as compared to non-exposed astrocytes. Co-treatment with 10 micromol/L SB203580 (an inhibitor of p38) attenuated the degree of ammonium chloride induced astrocyte swelling. Western blotting analysis revealed that the expression levels of phospho-p38 and aquaporin-4 in ammonium chloride treated cells were significantly increased relative to the control group (P < 0.001); SB203580 co-treatment inhibited the increased expression of phospho-p38 and aquaporin-4 relative to the ammonium chloride treated group (P = 0.002 and P = 0.015 respectively). The phosphorylation of p38 and upregulation of aquaporin-4 were highly correlated (r = 0.909). There were no significant differences in total p38 expression among the groups (P = 0.341).

CONCLUSIONSAmmonium chloride induced upregulation of aquaporin-4 in astrocytes is regulated by the p38 mitogen-activated protein kinase pathway. Inhibiting p38 activation prevented ammonium chloride induced aquaporin-4 protein upregulation.

Ammonium Chloride ; pharmacology ; Animals ; Aquaporin 4 ; genetics ; metabolism ; Astrocytes ; drug effects ; metabolism ; Blotting, Western ; Cells, Cultured ; Enzyme Inhibitors ; pharmacology ; Imidazoles ; pharmacology ; Phosphorylation ; drug effects ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

To decrease the hemolysis side effect of puerarin, the basic formula and preparation of puerarin submicron emulsion were optimized and the physicochemical properties were evaluated. Puerarin submicron emulsions were prepared by phase inversion-ultrasound combining with phospholipids complexes technology. The effects of preparative parameters, such as emulsification time, stirring velocity and ultrasound time, on mean diameter, span of dispersity, entrapment efficiency and overall desirability were investigated. The three dimensional response surface graphs were produced by second-order polynomial and liner equation, which predict the optimal experiment conditions. All response variables were found to be greatly dependent on three independent variables. Second-order polynomial equations were fitter than liner equations for this study. The optimal emulsification time, stirring velocity and ultrasound time was 15 min, 2 000 r x min(-1), 30 min, respectively. The mean diameter, span of dispersity, entrapment efficiency, drug content and zeta potential of emulsions prepared by the method were 228.23 nm, 0.628 4, 84. 32%, 9.98 mg x mL(-1), - 29.03 mV, respectively. Puerarin submicron emulsion was prepared by the optimized preparation method. The narrow particle diameter distribution, high envelopment efficacy and good stability were obtained. The physicochemical properties were suitable for the requirement of the intravenous emulsion.
Emulsions ; Isoflavones ; administration & dosage ; chemistry ; Particle Size