Cardiovascular protection and antioxidant activity of the extracts from the mycelia of Cordyceps sinensis act partially via adenosine receptors.

Mycelia of cultured Cordyceps sinensis (CS) is one of the most common substitutes for natural CS and was approved for arrhythmia in China. However, the role of CS in ameliorating injury during ischemia-reperfusion (I/R) is still unclear. We examined effects of extracts from CS on I/R and investigated the possible mechanisms. Post-ischemic coronary perfusion pressure, ventricular function, and coronary flow were measured using the Langendorff mouse heart model. Oxidative stress of cardiac homogenates was performed using an ELISA. Our results indicate that CS affords cardioprotection possibly through enhanced adenosine receptor activation. Cardioprotection was demonstrated by reduced post-ischemic diastolic dysfunction and improved recovery of pressure development and coronary flow. Treatment with CS largely abrogates oxidative stress and damage in glucose- or pyruvate-perfused hearts. Importantly, observed reductions in oxidative stress [glutathione disulfide (GSSG)]/[GSSG + glutathione] and [malondialdehyde (MDA)]/[superoxide dismutase + MDA] ratios as well as the resultant damage upon CS treatment correlate with functional markers of post-ischemic myocardial outcome. These effects of CS were partially blocked by 8-ρ-sulfophenyltheophylline, an adenosine receptor antagonist. Our results demonstrate a suppressive role of CS in ischemic contracture. Meanwhile, the results also suggest pre-ischemic adenosine receptor activation may be involved in reducing contracture in hearts pretreated with CS.

[Intranasal administration of low dosage recombinant human erythropoietin inhibits seizure in rats].

OBJECTIVE: To investigate the effect of intranasal administration of low dosage recombinant human erythropoietin (r-HuEPO) on seizure in rats. METHODS: After intranasal or intraperitoneal administration of r-HuEPO, the behavioral and electroencephalographic changes were observed in pentylenetetrazol (PTZ) and maximal electroshock (MES) induced seizure or electrical amygdaloid-kindled seizure of rats. RESULT: Intranasal administration of low dosage r-HuEPO increased the seizure latency, and decreased the seizure grade and duration, and the number of convulsive episodes in PTZ induced seizure, with the most potential dosage of 2.4 IU. Intraperitoneal administration of r-HuEPO (3 000, 4 000 IU/kg) only decreased the seizure duration and number of convulsive episodes. The seizure grade, forelimb or hindlimb extension duration were decreased in MES-induced seizure by intranasal administration of 2.4 IU r-HuEPO. In addition, intranasal administration of 2.4 IU r-HuEPO decreased the seizure grade, generalized seizure duration and afterdischarge in electrical amygdaloid-kindled rats stimulated with generalized seizure threshold. CONCLUSION: Intranasal administration of low dosage r-HuEPO can inhibit the seizure in rats.

Quantitative determination of domperidone in human plasma by ultraperformance liquid chromatography with electrospray ionization tandem mass spectrometry.

A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for determining domperidone in human plasma. The analyte and internal standard (IS; mosapride) were isolated from plasma samples by protein precipitation with methanol (containing 0.1% formic acid). The chromatographic separation was performed on an Xterra MS C(18) Column (2.1 x 150 mm, 5.0 microm) with a gradient programme mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.30 mL/min. The total run time was 4.0 min. The analyses were carried out by multiple reaction monitoring using the parent-to-daughter combinations m/z 426 --> 175 and m/z 422 --> 198 (IS). The areas of peaks from the analyte and IS were used for quantification of domperidone. The method was validated according to the FDA guidelines on bioanalytical method validation. Validation results indicated that the lower limit of quantification was 0.2 ng/mL, and the assay exhibited a linear range of 0.2-60.0 ng/mL and gave a correlation coefficient (r(2)) of 0.999 or better. Quality control samples (0.4, 0.8, 15 and 50 ng/mL) in six replicates from three different analytical runs demonstrated an intra-assay precision (RSD) 4.43-6.26%, an inter-assay precision 5.25-7.45% and an overall accuracy (relative error) of <6.92%. The method can be applied to pharmacokinetic and bioequivalence studies of domperidone.

Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: drug metabolism and its related interactions.

AIM: To review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of medicines in clinical practice. METHODS: Relevant literature was identified by performing MEDLINE/Pubmed searches covering the period from 1988 to 2006. RESULTS: Seven classes of drugs were chosen, including gastric proton pump inhibitors, histamine H(2)-receptor antagonists, benzamide-type gastroprokinetic agents, selective 5-HT(3) receptor antagonists, fluoroquinolones, macrolide antibiotics and azole antifungals. They showed significant differences in metabolic profile (i.e., the fraction of drug metabolized by cytochrome P450 (CYP), CYP reaction phenotype, impact of CYP genotype on interindividual pharmacokinetics variability and CYP-mediated drug-drug interaction potential). Many events of severe adverse drug reactions and treatment failures were closely related to the ignorance of the above issues. CONCLUSION: Clinicians should acquaint themselves with what kind of drug has less interpatient variability in clearance and whether to perform CYP genotyping prior to initiation of therapy. The relevant CYP knowledge helps clinicians to enhance the management of patients with gastrointestinal disease who may require treatment with polytherapeutic regimens.

[Effect of l-tetrahydropalmatine on expression of adhesion molecules induced by lipopolysaccharides in human umbilical vein endothelium cell].

OBJECTIVE: To investigate the effect of l-tetrahydropalmatine (l-THP) on adhesion molecule expression induced by LPS in human umbilical vein endothelium cell (HUVEC). METHOD: HUVEC were obtained from the human umbilical cord vein and treated by LPS or LPS plus different concentration of l-THP. Expression of ICAM-1 and E-selectin was assayed by flow cytometer. RESULT: l-THP(250 mg x L(-1)) markedly attenuated ICAM-1 and E-selectin expression induced by LPS(P <0.05). l-THP(50 mg x L(-1) inhibited E-selectin expression (P < 0.05) but had no effect on ICAM-1 (P > 0.05). l-THP (10 mg x L(-1)) had no effect on expression of both adhesion molecules. DXM (50 mg x L(-1)) completely inhibited both responses induced by LPS (P < 0.05). CONCLUSION: l-THP depresses expression of ICAM-1 and E-selectin induced by LPS, which suggests that I-THP represent a promising candidate to be developed into therapies for the treatment of inflammation.

[Reversing effect of histamine on neuron death induced by N-methyl-D-aspartate].

OBJECTIVE: To determine the effect of histamine on N-methyl-D-aspartate (NMDA) induced neuron death and to elucidate its mechanism. METHODS: The primary cortical cell culture was adopted. Neuron morphology and MTT assay were used to evaluate the drugs effects. RESULT: Histamine at doses of 10(-4) 10(-6) 10(-7) 10(-8) mol/L reversed the neuron death induced by NMDA (50 micromol/L) for 3 h. The protection of histamine peaked at doses of 10(-4) mol/L and 10(-7)mol/L. The effect of histamine of 10(-7) mol/L was reversed only by cimetidine an H(2)receptor antagonist. However, the effect of histamine of 10(-4) mol/L was reversed only by pyrilamine but not cimetidine. CONCLUSION: Histamine could reduce neuron death induced by NMDA; its protection at a low dose might be mediated by H(2)receptor, and at a high dose by H(1)receptor.

[Effects of L-tetrahydropalmatine on concentrations of neurotransmitter amino acids in mice with cerebral ischemia].

OBJECTIVE: To observe the effects of L-tetrahydropalmatine (L-THP) on concentrations of neurotransmitter amino acids in mice with cerebral ischemia and to discuss the mechanisms of L-THP in tyreating cerebral ischemia. METHOD: Mice were randomly divided into six groups: control group, cerebral ischemia group, L-THP treated group (doses were 14, 28, 56 mg x kg(-1) respectively) and Ginkgo biloba extract treated group. Concentrations of Glu and GABA were determined by HPLC. RESULT: Compared with control group, Glu and GABA in mice with cerebral ischemia were much higher. The ratio of Glu/GABA increased significantly. L-THP markedly reduced the concentrations of Glu and the ratio of Glu/GABA in mice with cerebral ischemia. CONCLUSION: Decrease in Glu concertration and ratio of Glu/GABA may be one of the mechanisms of L-THP in treating cerebral ischemia.

[Role of phospholipase D in priming of rat peripheral leukocytes by lipopolysaccharide and antigen].

OBJECTIVE: To investigate whether or not lipopolysaccharide (LPS) and ovalbumin (OA) prime rat peripheral leukocytes, the effect of sensitization on priming and the role of phospholipase D in priming. METHODS: The peripheral leukocytes were separated and purified from sensitized or unsensitized rats. LPS or OA was used as a priming agent and formylmethionylphenylalanine (fMLP) as an activating agent. Degradation of leukocyte was determined by measurement of elastase release and myeloperoxidase (MPO) activity. Phospholipase D (PLD) activity was assayed by the generation of choline,which was measured by choline-oxidase-catalyzed formation of H(2)O(2) and Trinder reaction. RESULT: Compared with cells treated by fMLP alone,leukocytes from unsensitized rat challenged with fMLP after incubated with LPS released more elastase and MPO (P<0.05). But there was no significant difference between leukocytes challenged with fMLP after incubated with OA and fMLP treated alone. In sensitized rat,there was no difference between leukocytes challenged with fMLP after incubated with LPS and fMLP treated alone. But leukocytes challenged with fMLP after incubated with OA released significantly more elastase and MPO than fMLP treated alone (P<0.05). A significant correlation was obtained between the release of elastase and PLD activity (r(s)=0.51,P<0.01), and also between the release of MPO and PLD activity (r(s)=0.73,P<0.01) in unsensitized rat. In sensitized rat, it was 0.48 (P<0.01) and 0.37 (P<0.05) respectively. CONCLUSION: (1) LPS primes peripheral leukocytes from unsensitized rats; (2) OA primes peripheral leukocytes from actively sensitized rats; (3) PLD plays a role in priming of rat peripheral leukocytes.