Child ; Humans ; Male ; Paralyses, Familial Periodic ; diagnosis ; therapy

Chemotherapy-induced neuropathy is a serious clinical problem for patients receiving cancer treatment. The aim of this study was to investigate the potential efficacy of pregabalin in chemotherapy-induced neuropathy in rats. A total of 35 male Sprague-Dawley rats were randomly divided into 5 groups: group 1, naive control; group 2, treated with pregabalin (30 mg/kg p.o., for 8 days); group 3, docetaxel was given by single intravenous infusion at 10 mg/kg; groups 4 and 5, pregabalin at 10 mg/kg and 30 mg/kg respectively was orally administered for 8 days after the docetaxel treatment. On day 8, behavioral test was performed, and substance P and CGRP release in dorsal root ganglion (DRG) and sciatic nerve were analyzed by electron microscope. Our results showed that docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, cold allodynia, and sciatic nerve impairment and substance P and CGRP release in DRG. However, oral administration of pregabalin (10 mg/kg and 30 mg/kg) for 8 consecutive days significantly attenuated docetaxel-induced neuropathy by ameliorating heat hypoalgesia, cold allodynia, impairment of sciatic nerve and reducing the release of substance P and CGRP. The findings in the present study reveal that pregabalin may be a potential treatment agent against chemotherapy-induced neuropathy.

OBJECTIVETo investigate the effect of different permeation enhancer on transdermal permeation of anemonin through human skin.

METHODThe permeation experiments were performed using human skin on modified Franz diffusion cells in vitro. The concentrations of anemonin in receptor compartment at specified time points were determined by HPLC. The steady flux and the cumulative quantity of anemonin through skin were calculated.

RESULTThe flux of anemonin permeating through human skin from 30% ethanol, 50% ethanol solution and a combination of 3% laurocapm -5% polysorbate 20 and 30% ethanol -3 % laurocapm -5% polysorbate 20 of anemonin was (9.30 +/- 0.32), (18.56+/-0.58), (7.29+/-0.35), (13.77+/-0. 16) microg x cm(-2) x h(-1) and 7.9, 15.9, 6.2, 11.8 times higher than from saturated water solution respectively.

CONCLUSIONEthanol and laurocapm can remarkably improve the transdermal permeation of anemonin and the anemonin have the potential to be developed to new transdermal preparation.

Administration, Cutaneous ; Azepines ; pharmacology ; Clematis ; chemistry ; Ethanol ; pharmacology ; Furans ; administration & dosage ; isolation & purification ; pharmacokinetics ; Humans ; In Vitro Techniques ; Permeability ; drug effects ; Plants, Medicinal ; chemistry ; Skin ; drug effects ; metabolism ; Skin Absorption ; drug effects

To establish a LC-MS/MS method to determine the concentrations of liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma, and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction, the blood was collected from retinal vein plexus of different time points. Specifically, tetrahydropalmatine was taken as internal standard for determining ephedrine, while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above, the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0.1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring (MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using Win-Nonlin 4.1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients, i.e., liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine within the ranges of 1.04-1040, 1.04-1040, 0.89-445, 1.05-4200, 1.25-2490, 0.3-480, 0.3-480, 0.3-480 microg x L(-1), with a good linearity and satisfactory precision, recovery and stability in the above ingredients. After modeling, except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing, all of the rest components showed significant higher Cmax, AUC(0-1) and lower clearance rate (CL) than that of the normal group, indicating the increase in absorption in rats in the pathological state by reducing the clearance rate. The method is accurate and sensitive and so can be used to determine the plasma concentrations of the eight active ingredients in Maxing Shigan decoction. RSV pneumonia-infected rats absorbed more ingredients in Maxing Shigan decoction.
Animals ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacokinetics ; Male ; Pneumonia, Viral ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Respiratory Syncytial Virus Infections ; drug therapy ; metabolism ; Tandem Mass Spectrometry

Prostate cancer is a common neoplasm of the genitou-rinary system for male, and tumor metastasis of prostate cancer is a common complication and a lethal factor. Researching on prostate cancer metastasis is very important for clinical research and treatment. Proper models of prostate cancer metastasis are important tools for the study of occurrence, progression, metas-tasis, and drug research for prostate cancer. This article intro-duces the common model of human prostate cancer metastasis, including the points of operation, evaluation, application of me-tastatic models and comparing the characteristics of various mod-els, to the benefit of researching and selecting models of prostate cancer.

Chemotherapy-induced neuropathy is a serious clinical problem for patients receiving cancer treatment. The aim of this study was to investigate the potential efficacy of pregabalin in chemotherapy-induced neuropathy in rats. A total of 35 male Sprague-Dawley rats were randomly divided into 5 groups: group 1, naive control; group 2, treated with pregabalin (30 mg/kg p.o., for 8 days); group 3, docetaxel was given by single intravenous infusion at 10 mg/kg; groups 4 and 5, pregabalin at 10 mg/kg and 30 mg/kg respectively was orally administered for 8 days after the docetaxel treatment. On day 8, behavioral test was performed, and substance P and CGRP release in dorsal root ganglion (DRG) and sciatic nerve were analyzed by electron microscope. Our results showed that docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, cold allodynia, and sciatic nerve impairment and substance P and CGRP release in DRG. However, oral administration of pregabalin (10 mg/kg and 30 mg/kg) for 8 consecutive days significantly attenuated docetaxel-induced neuropathy by ameliorating heat hypoalgesia, cold allodynia, impairment of sciatic nerve and reducing the release of substance P and CGRP. The findings in the present study reveal that pregabalin may be a potential treatment agent against chemotherapy-induced neuropathy.
Animals ; Ganglia, Spinal ; drug effects ; Male ; Nervous System Diseases ; chemically induced ; drug therapy ; Pregabalin ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; drug effects ; Taxoids ; adverse effects ; gamma-Aminobutyric Acid ; analogs & derivatives ; pharmacology

OBJECTIVETo study the effect of hypoxia-inducible factor-1α (HIF-1α) on human gastric cancer cells apoptosis in simulated CO2 pneumoperitoneum environment.

METHODSApplied closed box to simulated CO2 pneumoperitoneum environment under the pressure of 0, 5, 10 and 15 mm Hg (1 mm Hg = 0.133 kPa). Compared HIF-1α mRNA and protein expression of MKN-45 cells before and after silencing HIF-1α by RT-PCR and Western blot. Study the changes of bcl-2/bax expression in MKN-45 cells before and after silencing HIF-1α by immunohistochemistry. The apoptosis ratio of MKN-45 was measured by using Annexin V-FITC/PI double labelled staining.

RESULTSIn 15 mm Hg group, HIF-1α mRNA and protein expression of MKN-45 cells (1.48 ± 0.22, 1.34 ± 0.09) and HIF-1α protein expression in 10 mm Hg group (1.25 ± 0.10) were significantly higher than those in control group (0.55 ± 0.17, 0.83 ± 0.04) (P < 0.05). But there was no significant differences among 0, 5, 10 mm Hg group and control group in HIF-1α mRNA (P > 0.05); and no obvious difference was found among 0, 5 mm Hg group and the control group in HIF-1α protein expression (P > 0.05). In 15 mm Hg CO2 pressure, bcl-2/bax expression (0.78 ± 0.05) was obviously lower than that in the control group (1.43 ± 0.15) (P < 0.05) and the apoptosis ratio (11.70 ± 0.12) was significantly higher than the control group (0.22 ± 0.07) (P < 0.01) before silencing HIF-1α. But once HIF-1α was silenced, HIF-1α mRNA (0.52 ± 0.11), HIF-1α protein expression (0.92 ± 0.02), bcl-2/bax ratio (1.57 ± 0.04) and apoptosis ratio (0.45 ± 0.11) in MKN-45 were not significantly different between 15 mm Hg group and the control group (P > 0.05).

CONCLUSIONSThe apoptosis ratios of MKN-45 under 0, 5, 10 mm Hg CO2 pneumoperitoneum are comparable with that in the control group before the silencing of HIF-1α. The apoptosis ratio of MKN-45 is increased under 15 mm Hg CO2 pneumoperitoneum environment and HIF-1α may be one of the important factor to improve the apoptosis of human gastric cancer cell.

Apoptosis ; Carbon Dioxide ; physiology ; Cell Line, Tumor ; Genetic Vectors ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Pneumoperitoneum, Artificial ; RNA Interference ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo study the BRCA1 mutations in patients with early-onset breast cancer and their affected relatives in Guangdong province and explore the relationship between BRCA1 mutation and the expressions of estrogen receptor(ER), progesterone receptor(PR), HER2 and ALN.

METHODSFrom 58 patients with early-onset breast cancer and their affected relatives, the genomic DNA was extracted from the peripheral blood mononuclear cells and the coding regions of the BRCA1 gene was amplified using polymerase chain reaction. BRCA1 gene mutations were screened by denaturing high performance liquid chromatography (DHPLC) and subsequent direct DNA sequencing. The expression of ER, PR, HER2 and ALN were detected with immunohistochemistry and their relations with the gene mutation were analyzed.

RESULTSDisease-related BRCA1 mutations were detected in 2 of the 58 patients, who were younger than 35 years old, including 1 with a novel splice-site mutation (IVS5-1 G-->A). No association was found between this novel mutation and the expressions of ER, PR, HER2 and ALN.

CONCLUSIONThe incidence of BRCA1 mutation is significantly lower in patients with early-onset breast cancer and their affected relatives in Guangdong province than in the Western populations. The novel mutation identified in BRCA1 gene may represent a mutation characteristic of the patients in Guangdong province. BRCA1 gene mutations may not have any relation with the expression of ER, PR, HER2 and ALN.

Adult ; Age of Onset ; Base Sequence ; Breast Neoplasms ; genetics ; China ; DNA Mutational Analysis ; Female ; Genes, BRCA1 ; Genotype ; Humans ; Molecular Sequence Data ; Mutation ; Receptor, ErbB-2 ; genetics ; Receptors, Estrogen ; genetics ; Receptors, Progesterone ; genetics

OBJECTIVETo study the clinicopathologic features of follicular dendritic cell sarcoma (FDCS) and its differential diagnosis.

METHODSTen cases of FDCS were studied by light microscopy, immunohistochemistry and in-situ hybridization. The clinical features and follow-up information were analyzed.

RESULTSAmongst the 10 cases of FDCS studied, the male-to-female ratio was 1:1. The mean age of the patients was 42 years. Six of them were located in cervical and peritoneal lymph nodes and four in extranodal sites (including tonsil, pelvic cavity, tail of pancreas and spleen). Histologically, the tumor cells had whorled, storiform or diffuse growth patterns. They were spindle in shape and contained syncytial eosinophilic cytoplasm, with round or oval nuclei, vesicular chromatin, distinct nucleoli and a variable number of mitotic figures. Multinucleated tumor giant cells and intranuclear pseudoinclusions were occasionally seen. There was a sprinkling of small lymphocytes and neutrophils within the tumor as well as in the perivascular region. Immunohistochemical study showed that the tumor cells were diffusely or focally positive for CD21, CD23, CD35 and D2-40, but negative for LCA, CD20, CD3, CD1a, HMB45 and CK. Some of them showed EMA, CD68 and S-100 reactivity. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed positive signals in only one case (which was diagnosed as inflammatory pseudotumor-like FDCS). Of the 7 patients with follow-up information available (duration: 2 months to 39 months; mean: 14 months), 2 cases with paraneoplastic pemphigus died of pulmonary infection at 5 and 7 months respectively. The remaining 5 patients were alive and disease-free after surgical excision (+/- chemotherapy and radiotherapy).

CONCLUSIONSFDCS is a rare low to intermediate-grade malignant tumor. Appropriate application of FDC markers, such as CD21, CD35 and D2-40, would be helpful for arriving at a correct diagnosis. Most cases are associated with good prognosis after surgical treatment, with or without chemotherapy and radiotherapy. Patients with paraneoplastic pemphigus carry a less favorable prognosis.

Adult ; Antibodies, Monoclonal, Murine-Derived ; metabolism ; Dendritic Cell Sarcoma, Follicular ; complications ; metabolism ; pathology ; surgery ; Dendritic Cell Sarcoma, Interdigitating ; pathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Male ; Meningioma ; pathology ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; Paraneoplastic Syndromes ; complications ; Pemphigus ; complications ; Receptors, Complement 3b ; metabolism ; Receptors, Complement 3d ; metabolism ; Receptors, IgE ; metabolism ; Tonsillar Neoplasms ; metabolism ; pathology ; surgery ; Young Adult

OBJECTIVETo study the changes in the plasticity of the neurons and astrocytes in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus of rats exposed to a humid and hot environment.

METHODSThe rats were subjected to stimulation with a humid and hot environment for 120 min in a climate chamber (dry bulb temperature of 40.0-/+0.5 degrees C with relative humidity of 60-/+5%). During the exposure, the behavioral responses of the rats were observed, and the changes in the expressions of Fos and GFAP in the PVN and SON in response to the exposure evaluated using immunohistochemical ABC methods.

RESULTSExposure to a humid and hot environment caused restlessness and agitation in the rats, which showed increased respiratory frequency and scratching of the face with the forelimbs. Two rats died after the 120-min exposure. Significantly increased expressions of Fos and GFAP were detected in the PVN and SON following the exposure as compared with the control group.

CONCLUSIONThe neurons and astrocytes in the PVN and SON both participate in the regulation of responses to exposure to a humid and hot environment.

Animals ; Astrocytes ; cytology ; physiology ; Glial Fibrillary Acidic Protein ; analysis ; Hot Temperature ; Humidity ; Hypothalamus ; cytology ; metabolism ; Immunohistochemistry ; Male ; Neuronal Plasticity ; physiology ; Neurons ; cytology ; physiology ; Oncogene Proteins v-fos ; analysis ; Paraventricular Hypothalamic Nucleus ; cytology ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Supraoptic Nucleus ; cytology ; metabolism