Animals ; Berberine/pharmacology* ; Blood Glucose ; Diabetes Mellitus, Experimental/drug therapy* ; Diabetes Mellitus, Type 2 ; Insulin ; Insulin Resistance ; Rats

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate (HR) and cardiac functions were observed in anesthetized normal rats by an eight-channel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), the left ventricular systolic pressure (LVSP), and the left ventricular end-diastolic pressure (LVEDP) (P > 0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR (P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP (P < 0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR (P > 0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them (P < 0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP, LVEDP and HR (P > 0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.
Amlodipine ; pharmacology ; Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Drug Synergism ; Heart Rate ; Hydrochlorothiazide ; pharmacology ; Hypertension ; Propranolol ; pharmacology ; Propylamines ; pharmacology ; Rats

To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application.
Aconitine ; analogs & derivatives ; isolation & purification ; Aconitum ; chemistry ; Alkaloids ; isolation & purification ; Chromatography, High Pressure Liquid ; Drug Stability ; Drugs, Chinese Herbal ; isolation & purification ; Hot Temperature ; Plant Extracts ; isolation & purification ; Steam ; Tandem Mass Spectrometry ; Time Factors

OBJECTIVETo compare the event-related potentials (ERPs) waves of verbs and prepositions in the brain.

METHODSWe recorded ERPs in the brain while participants judged the legality of the collocation for verbs and prepositions.

RESULTSBoth verbs and prepositions elicited a negativity at the frontal site in 230-330 ms and 350-500 ms window. No difference was seen in 230-330 ms and 350-500 ms window; In difference waves, a negativity was elicited in the left and right hemisphere at about 270-400 ms and 470-600 ms window for both open and closed-class words.

CONCLUSIONThese may demonstrate that prepositions in modern Chinese are probably not a separate class from verbs and that N280 may be not a specific component for only prepositions (or closed-class words).

Adult ; Asian Continental Ancestry Group ; Brain ; physiology ; Electroencephalography ; Evoked Potentials ; physiology ; Female ; Humans ; Language ; Male ; Photic Stimulation ; Reading

OBJECTIVETo study the chemical constituents from the herb of Gentianopsis paludosa.

METHODColumn chromatogrophy and spectral analysis were used to isolate and identify the constituents.

RESULTSix compounds were isolated and identified as 1,7-dihydroxy-3,8-dimethoxyxanthone (I), 1-hydroxy-3, 7, 8-trimethoxyxanthone (II), 1, 8-dihydroxy-3, 7-dimethoxyxanthone (III), 1-hydroxy-3, 7-dimethoxyxanthone (IV), beta-sitosterol (V), daucosterol (VI).

CONCLUSIONCompounds III-VI were isolated from the plant for the first time.

Gentianaceae ; chemistry ; Plants, Medicinal ; chemistry ; Sitosterols ; chemistry ; isolation & purification ; Xanthones ; chemistry ; isolation & purification

AIMTo study the effect of aspirin on chronic hypoxia and hypercapnic pulmonary hypertension.

METHODSSD rats were randomly divided into normal control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + aspirin group (C). The concentration of TXB2 and 6-keto-PGF1alpha in plasma and in lung were detected by the technique of radioimmunology.

RESULTS(1) mPAP was significantly higher in B group than those of A and C group. Differences of mCAP were not significant in three groups. (2) Light microscopy showed that WA/TA (vessel wall area/total area) and PAMT (the thickness of medial smooth cell layer) were significantly higher in B group than those of A and C group. (3) The concentration of TXB2 and 6-keto-PGF1alpha in plasma and lung as well as the ratio of TXB2/6-keto-PGF1alpha were significantly higher in rats of B group than those of A and C group.

CONCLUSIONAspirin may inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Aspirin ; pharmacology ; Carotid Arteries ; pathology ; physiopathology ; Epoprostenol ; metabolism ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; metabolism ; pathology ; physiopathology ; Hypoxia ; physiopathology ; Male ; Pulmonary Artery ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; metabolism

AIMTo study the effect of chronic hypoxic hypercapnia on expression of COX-2 mRNA in pulmonary arterioles.

METHODSSD rats were randomly divided into two groups: control group and hypoxic hypercapnic group. COX-2 mRNA was observed in pulmonary arterioles by the technique of in situ hybridization.

RESULTSmPAP, weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) and COX-2 mRNA in pulmonary arterioles were much higher in rats of hypoxic hypercapnic group than those of control group. Light microscopy showed that vessel smooth muscle cell hypertrophy and vessel cavity straightness were found in hypoxic hypercapnic group.

CONCLUSIONChanges of expressions of COX-2 mRNA may regulate hypoxic hypercapnic pulmonary hypertension.

Animals ; Cyclooxygenase 2 ; genetics ; metabolism ; Hypercapnia ; metabolism ; physiopathology ; Hypoxia ; metabolism ; physiopathology ; Male ; Pulmonary Artery ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley

Objective To explore the value of intra-voxel incoherent motion diffusion weighted imaging(IVIM-DWI)in brain perfusion of early hypertensive patients. Methods Totally 36 hypertensive patients and 14 volunteers were recruited and scanned using routine MRI sequences including axial T2WI, T1WI, T2FLAIR, TOF-MRA and IVIM-DWI sequence. Perfusion-related diffusion coefficient (D*) values and perfusion fraction (f) values in various regions were measured separately.The independent sample t test was used to analyze the data.Results Compared with the volunteers,both D*values and f values in lenticular nucleus,thalamus,superior frontal gyrus,occipital lobe,genu of corpus callosum(CC)and posterior horns of periventricular WM, were found to be lower (P<0.05) in hypertensive patients. For other regions, there were no significant difference(P>0.05).Conclusion IVIM-DWI has the ability to detect subtle brain perfusion abnormalities at early stages of hypertension.It has an important value to the prevention and treatment of hypertensive encephalopathy.

To research the structure-activity relationship (SAR) of glycinamide-bearing compounds that used as inhibitors of dipeptidyl peptidase IV (DPP-IV), P32/98 and compound A were chosen as the leading compounds, heterocycles containing nitrogen atom were introduced to form amide, and different residues on a-position of carbonyl were designed. The nineteen designed compounds were synthesized by a simple route and were evaluated as inhibitors of DPP-IV. All of the structures were characterized by 1H NMR and HRMS. The preliminary SAR result was obtained.
Dipeptidyl Peptidase 4 ; metabolism ; Dipeptidyl-Peptidase IV Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Glycine ; analogs & derivatives ; chemistry ; Magnetic Resonance Spectroscopy ; methods ; Molecular Structure ; Piperazines ; chemistry ; pharmacology ; Structure-Activity Relationship

OBJECTIVESequence and analysis the complete nucleotide of the Japanese encephalitis virus (JEV) newly strain SD08-10, isolated in 2008 in Shandong, China in order to understand the characterization of the virus.

METHODSOverlapping primers were designed according to the full-length genomes in GenBank. RT-PCR was used to amplify the fragments and the full-length genome was obtained by sequencing and splicing. Using the computer software to analysis the nucleic acid data, deduced amino acid sequence and phylogenetic tree, including Clustal X (1.8), DNASTAR, GENEDOC (3.2).

RESULTSThe result of sequence analysis shows that the genome of SD08-10 strain was 10 965 nucleotides long. An open reading frame from 96 to 10 392 including 10 296 nucleotides is capable of coding for a 3432 amino acid polyprotein. Compared with the live attenuated vaccine strain SA-14-14-2 in China, there was 1253 nucleotide difference and 82 amino acid divergence. Comparison of the complete genome sequences with 59 different JEV isolates showed a 0.7%-18.9% nucleotide sequence divergence among them, which resulted in 0.1%-5.2% amino acid sequence divergence. Phylogenetic analysis of full-length genome showed that the SD08-10 strain was belonging to genotype I.

CONCLUSIONAnalysis based on the complete genome sequences of different JEV isolates showed that the SD08-10 strain isolated in 2008 in Shandong was belonging to genotype I and close to SH17M-07 isolated in 2007 in China.

China ; Encephalitis Virus, Japanese ; classification ; genetics ; isolation & purification ; Encephalitis, Japanese ; virology ; Genome, Viral ; Molecular Sequence Data ; Phylogeny