Khat leaves chewing/use, which imparts amphetamine like effects on the user, is widely practiced in parts of Africa, the Arabian Peninsula, and among the diaspora communities from these regions. Basic clinical and epidemiological studies from different settings have reported associations of acute coronary syndrome, heart failure, and cardiomyopathy, with khat chewing /use. This review aims to analyse the current evidence of the impact that khat, or its active constituent, cathinone, has on the cardiovascular system (CVS), particularly in two parameters, heart rate (HR) and blood pressure (BP). Subsequently, the possible mechanism of actions of how khat impacts these cardiovascular parameters is discussed, and different studies’ findings are summarised appropriately. The analysis of literature suggests that khat could influence HR and BP by most likely causing tachycardia and hypertension and the impacts might be dose-dependent and time-dependent. However, most of the studies involved different species and study designs, and had different limitations. Additionally, the underlying mechanisms of khat effects on these CVS parameters remain unclear. Therefore, more studies are needed to further support the current evidence of the impacts that khat has on the CVS parameters of HR and BP.
Khat, cardiovascular system (CVS) ; heart rate ; blood pressure ; cathinone ; Review

To increase the in vivo half-life of human CNTF mutein AX15 (R13K), HSA-AX15 (R13K) fusion protein was constructed by the fusion of the C-terminus of HSA to the N-terminus of AX15 (R13K) via an 11 amino acids linker. HSA-AX15 (R13K) fusion protein was purified to homogeneity by cation exchange chromatography, reverse phase chromatography and gel filtration after expressed in pichia pastoris. TF-1 cell survival bioassay showed the biological activity of AX15 (R13K) was not affected by the fusion to HSA. It was demonstrated that tertian injection of 4.8 mg/kg HSA-AX15 (R13K) fusion protein could produce more potent anti-obesity effects on KM mice than daily injection of 1.6 mg/kg AX15 (R13K). The long-acting form of hCNTF variant has the potential to reduce discomfort by requiring fewer injections and to minimize the side-effects by decreasing the dosage and fluctuation of plasma concentration, and thus has superior clinical application.
Animals ; Ciliary Neurotrophic Factor ; genetics ; Humans ; Mice ; Mutant Proteins ; biosynthesis ; genetics ; Pichia ; genetics ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; isolation & purification ; Serum Albumin ; genetics

AX15 is a mutein of naturally occurring human ciliary neurophic factor (hCNTF), with improved biological activity, stability and solubility. AX15 is susceptible to protease degradation when expressed in Pichia pastoris. Amino acid sequencing revealed the degradation was occurred behind position 12 and 13 amino acid residues, which constitute a dibasic site, RR. Based on the substrate specificity of KEX2, a KEX2 resistant mutein of AX15-AX15 (R13K) was constructed, in which RR was replaced by RK. It was demonstrated that the stability of AX15 (R13K) improved significantly, as no degradation was detected even after 120 hours of induction. AX15 (R13K) was purified to homogeneity by ultrafiltration and gel filtration. TF-1 cell survival bioassay showed AX15 (R13K) had equivalent specific activity to AX15. The protease resistant mutein of AX15 may have greater in vivo stability and thus have superior therapeutic potential.
Ciliary Neurotrophic Factor ; biosynthesis ; genetics ; Genetic Vectors ; Humans ; Mutant Proteins ; biosynthesis ; genetics ; Mutation ; Peptide Hydrolases ; chemistry ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification

OBJECTIVETo evaluate the efficacy of hepatitis B vaccination on hepatitis B prevention and on hepatocellular carcinoma.

METHODSBirth cohort study, cross-sectional seroepidemiological survey, and surveillance of hepatitis B (HBV) and hepatocellular carcinoma were used to evaluate the efficacy of hepatitis B vaccination.

RESULTSDuring the 14 years after hepatitis B vaccination, the HBsAg positive rates were found to be 0.7% - 2.9%, with an average of 1.5%, and the protective rates were 83.5% - 96.6%. Hepatitis B virus infection rates of children immunized with hepatitis B vaccine were 1.1% - 5.1%, with an average of 2.2% and the protective rates of 93.5% - 98.4%. 15 years after hepatitis B vaccination, the incidence of hepatitis B dropped from 3.27/10 000 to 0.17/10 000, a 94.8% decrease, in the group of 0 - 19 year-olds.

CONCLUSIONThe universal infant hepatitis B vaccination has proved to be effective in reducing the incidence rate of acute hepatitis B as well as the mortality of hepatocellular carcinoma.

Adolescent ; Adult ; Carcinoma, Hepatocellular ; epidemiology ; prevention & control ; virology ; Child ; Child, Preschool ; China ; epidemiology ; Cohort Studies ; Cross-Sectional Studies ; Hepatitis B ; epidemiology ; prevention & control ; Hepatitis B Vaccines ; immunology ; Humans ; Immunization Schedule ; Infant ; Liver Neoplasms ; epidemiology ; prevention & control ; virology ; Middle Aged ; Prevalence ; Vaccination ; Vaccines, Synthetic ; immunology

OBJECTIVETo investigate the role of platelet-derived growth factor-BB (PDGF-BB) in the degeneration of the hypertrophied ligamentum flavum (LF) in the lumbar spine.

METHODSSurgical specimens of degenerative hypertrophied LF were obtained from 11 patients with lumbar spinal stenosis (LSS, mean age 57.8 years), with those from 10 age-matched patients with lumbar disc herniation (LDH, mean age 53.5 years) as the normal controls. The thickness of the LF was measured preoperatively by axial T1-weighted magnetic resonance imaging (MRI) at the facet joint level. Immunohistochemistry was employed to determine the expression of PDGF β and PDGF-BB in the LF. The mRNA and protein expressions of PDGF-BB in the LF were detected using real-time PCR and Western blotting, respectively.

RESULTSThe thickness of the LF was 5.30±1.12 mm in the degenerative group and 2.80±1.53 mm in the control group, showing a significant difference between the two groups (P<0.001). PDGF-β and PDGF-BB were positive in the fibroblasts in hypertrophied LF. The mRNA and protein expressions of PDGF-BB were significantly higher in the degenerative group than in the control group (P=0.013 and 0.023, respectively).

CONCLUSIONThe high expression of PDGF-BB in the hypertrophied LF suggests its important role in the development of hypertrophy of LF in lumbar spinal canal stenosis.

Adult ; Aged ; Female ; Humans ; Hypertrophy ; metabolism ; Intervertebral Disc Degeneration ; metabolism ; pathology ; Ligamentum Flavum ; metabolism ; pathology ; Lumbar Vertebrae ; Male ; Middle Aged ; Proto-Oncogene Proteins c-sis ; metabolism ; Spinal Stenosis ; metabolism ; pathology

BACKGROUNDMelilotus suaveolens Ledeb (M. suaveolens Ledeb) has long been used as a folk medicine in inflammation-related therapy. This study was undertaken to determine the anti-inflammatory effect of the plant.

METHODSPetroleum ether fraction, ethyl acetate fraction, n-butanol fraction, aqueous fraction were obtained from ethanol extract of M. suaveolens Ledeb and evaluated by high performance liquid chromatography (HPLC). While dexamethasone (DM) was used as a positive control, the effects of different solution fractions of ethanol extract on tumor necrosis factor alpha (TNF-alpha) mRNA, cyclooxygenase 2 (COX-2) mRNA, COX-2 and nuclear factor kappaB (NF-kappaB) of LPS-stimulated RAW 264.7 cells were studied by real-time PCR, Western blot analysis and immunocytochemical assay, respectively.

RESULTSCoumarin was one of the main ingredients in different solution fractions of ethanol extract except the aqueous fraction with no inflammatory effect. The petroleum ether fraction, ethyl acetate fraction and n-butanol fraction of ethanol extract could inhibit the production of TNF-alpha mRNA, COX-2 mRNA and NF-kappaB to some extent.

CONCLUSIONSDifferent solution fractions of ethanol extract from M. suaveolens Ledeb had similar anti-inflammatory effect as did dexamethasone except the aqueous fraction. Coumarin was likely to be essential to the anti-inflammatory effect, and other ingredients might attribute to their different anti-inflammatory effects from the HPLC fingerprint.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Cell Line ; Cyclooxygenase 2 ; genetics ; Lipopolysaccharides ; pharmacology ; Melilotus ; chemistry ; Mice ; NF-kappa B ; antagonists & inhibitors ; Plant Extracts ; analysis ; pharmacology ; RNA, Messenger ; analysis ; Tumor Necrosis Factor-alpha ; genetics

BACKGROUNDOur previous in vivo study in the rat demonstrates that Shenfu injection, a clinically used extract preparation from Chinese herbs, attenuates neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a local anesthetic. This study was designed to investigate whether bupivacaine could induce a toxic effect in primary cultured mouse spinal cord neuron and if so, whether the Shenfu injection had a similar neuroprotective effect in the cell model.

METHODSThe spinal cords from 11- to 14-day-old fetal mice were minced and incubated. Cytarabine was added into the medium to inhibit the proliferation of non-neuronal cells. The immunocytochemical staining of beta-tubulin was used to determine the identity of cultured cells. The cultured neurons were randomly assigned into three sets treated with various doses of bupivacaine, Shenfu and bupivacaine + Shenfu, for 48 hours respectively. Cell viability in each group was analyzed by methyl thiazoleterazolium (MTT) assay.

RESULTSThe viability of the cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%, 0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant influence on the viability of cultured neurons (P < 0.05 vs control), the injection significantly increased the cellular viability of cultured neurons pretreated with 0.03% bupivacaine (P < 0.05).

CONCLUSIONAlthough Shenfu injection itself has no effect on spinal neurons, it was able to reduce the bupivacaine-induced neurotoxicity in vitro.

Anesthetics, Local ; toxicity ; Animals ; Bupivacaine ; toxicity ; Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Injections ; Mice ; Neurons ; drug effects ; Spinal Cord ; cytology ; drug effects

OBJECTIVETo investigate the changes of the T lymphocytes and their subsets before and after receiving highly active anti-retroviral therapy (HAART) in children who were infected with HIV or AIDS patients.

METHODSNinety-nine children met the criteria were recruited. All of them had received HAART in Guangxi Center for Disease Control and Prevention from May 2006 to April 2009. Peripheral blood of 2 milliliter was collected before treatment (D0) and after 3, 6, 12, 18, 24, 30, and 36 months (M3, M6, M12, M18, M24, M30 and M36), respectively. Four-color fluorescence flow cytometry was used for the detection of the absolute numbers of CD3(+), CD4(+), CD8(+) T lymphocytes in peripheral blood. And then, the percentages of CD3(+), CD4(+), CD8(+) T lymphocytes in the CD45(+) cells and the ratio of CD4/CD8 were calculated.

RESULTSSixteen-five (65.66%) cases were treated with lamivudine (3TC)/zidovudine (AZT)/nevirapine (NVP), and 16 (16.16%), 8 (8.08%) and 10 (10.10%) cases were treated with 3TC/stavudine (D4T)/NVP, 3TC/AZT/efavirenz (EFV) and 3TC/AZT/lpv-rtv (LPV/r), respectively. The median of the ratio of CD4/CD8 were 0.39, 0.51, 0.61, 0.65, 0.70, 0.73 and 0.76 in M3, M6, M12, M18, M24, M30 and M36, respectively which were significantly higher than that in D0 (0.19) (Z values were -5.158, -7.375, -9.078, -8.853, -8.373, -5.845 and -5.844 respectively, P < 0.000). The median of CD4% were 16.92%, 22.70%, 25.54%, 26.66%, 27.99%, 30.36% and 29.30% respectively in M3, M6, M12, M18, M24, M30 and M36 respectively, which were also higher significantly than that in D0 (9.92%) (Z values were -5.268, -7.568, -9.496, -9.171, -8.760, -6.190 and -5.964 respectively, P < 0.000). In addition, the median of the absolute numbers of CD4(+)T lymphocytes in peripheral blood were 631, 813, 1050, 946, 1057, 1166 and 894 cells/mm(3) respectively in M3, M6, M12, M18, M24, M30 and M36, which were higher significantly than that of D0 (382 cells/mm(3)) (Z values were -3.318, -5.288, -6.661, -5.886, -5.801, -4.110 and -3.600 respectively, P < 0.000). However, the median of CD8% were 47.25%, 43.01%, 43.04%, 42.60%, 41.37%, 40.83% and 38.31% respectively in M3, M6, M12, M18, M24, M30 and M36, which were lower significantly than that of D0 (53.17%) (Z values were -3.082, -4.697, -5.282, -5.846, -5.757, -3.883 and -4.380 respectively, P < 0.001).

CONCLUSIONThere is certain rules for the changes of T lymphocytes and their subsets, which may play important roles in the evaluation of the therapeutic effect and the clinical application guidance of HAART.

Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Child ; Child, Preschool ; Female ; HIV Infections ; drug therapy ; immunology ; Humans ; Infant ; Lymphocyte Count ; Male ; T-Lymphocyte Subsets

Fifteen batches of Glycyrrhizeae Radix standard decoction were prepared for determination of the content of the glycyrrhizic acid and liquiritin, then the transfer rate and the extract rate were calculated and a method was established to analyze the fingerprint by HPLC. According to the measurement of 15 batches of samples,the transfer rate of the glycyrrhizic acid and liquiritin were 59.4%-87.4% and 49.8%-78.9% with extract rate of 29.9%-38.9%. Moreover,10 common chromatographic peaks were determined based on their fingerprint by using similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (TCM)(2012A) .The similarity results of 15 batches of samples were analyzed and compared,and the results showed that the similarity was all higher than 0.9. Fifteen batches of samples,prepared by a standard method,have stable quality and the high similarity.The method displayed good precision,stability and repeatability in fingerprint analysis. Therefore,this study can provide a reference for the quality control of Glycyrrhizae Radix dispensing granules.

INTRODUCTION: Treatment of pain is an important component of prehospital care. Inhalational analgesia agents have attractive strengths, but there is a paucity of studies comparing these with more conventional agents. We aimed to compare inhalational methoxyflurane and intramuscular (IM) tramadol as first-contact analgesia in the Singapore national ambulance service. METHODS: Ambulances were randomised to carry either methoxyflurane or IM tramadol for the first six months and crossed over to the other arm after six months. Patients aged ≥ 16 years, with acute pain arising from musculoskeletal trauma with Numerical Rating Scale (NRS) score ≥ 3 were enrolled. Variables included NRS reduction, time variables, adverse effects, Ramsay Sedation Scores, and patient and paramedic satisfaction scores on a Likert scale. RESULTS: A total of 369 patients were enrolled into this study, but 26 patients were excluded due to missing data. The methoxyflurane arm had a shorter median time taken from arrival at the scene to drug administration (9.0 [interquartile range 6.0-14.0] minutes vs. 11.0 [interquartile range 8.0-15.0] minutes). For patients who achieved reduction in NRS ≥ 3 within 20 minutes, those in the methoxyflurane arm took a shorter time. However, the methoxyflurane (46.7%) arm experienced lower proportion of patients not achieving NRS reduction ≥ 3 when compared to the tramadol (71.6%) arm after over 20 minutes. The methoxyflurane arm had significantly higher paramedic and patient satisfaction scores. CONCLUSION For the doses of medication used in this implementation study, methoxyflurane was superior in efficacy, speed of onset and administration, but had more minor adverse effects when compared to IM tramadol.