The intestinal mucosal barrier (IMB), which consists of mechanical barrier, chemical barrier, biological barrier and immune barrier, plays an important role in the maintenance of intestinal epithelium integrity and defense against invasion of bacteria, endotoxins and foreign antigens. Impaired IMB, characterized by increased intestinal mucosal permeability (IMP) and decreased transmembrane resistance (TR), has been implicated in the pathogenesis of various digestive, urinary, circulatory, neurological and metabolic dysfunctions. Electrophysiological recording of TR in the ex vivo intestinal tissues or cultured epithelial cell monolayers, or biochemical quantification of transepithelial movement of orally-administered molecular probes or specific endogenous protein molecules has frequently been used in the evaluation of IMB. In this paper, the composition and function of IMB will be summarized, with emphasis on the evaluation methods of IMP.
Cells, Cultured ; Inosine Monophosphate/metabolism* ; Intestinal Mucosa ; Permeability

Adenosine deaminase (ADA), an enzyme essential for the differentiation of lymphoid cells, has been used for monitoring diseases with altered immunity. The purpose of this study was to investigate the changes in serum ADA activity throughout normal pregnancy. We measured the catalytic values of serum ADA from 202 normal pregnant women using a commercial kit. Subjects were divided into four groups according to the gestational age in weeks (Gwks) (Group I: 5-9 Gwks [n=58]; Group II: 15-20 Gwks [n= 63]; Group III: 24-30 Gwks [n=34]; Group IV: 30-39 Gwks [n=47]). The serum ADA levels for the Groups I, II, III, and IV were as follows: 20.1+/-6.9 IU/L, 20.0+/-7.6 IU/L, 37.9+/-19.9 IU/L, and 24.5+/-8.6 IU/L, respectively. The serum ADA activity of group III was significantly higher than the other groups (p<0.05). However, there was no significant correlation between the Gwks and the serum ADA activity. Furthermore, other parameters, such as maternal age (p=0.29), gestational age at delivery (p=0.07), delivery mode (p=0.39), and birth weight (p=0.59) had no correlation with ADA activity. Reference values of serum ADA in normal pregnancy may provide important database for making clinical decisions in pregnancies complicated by conditions where cellular immunity has been altered.
Adenosine/metabolism ; Adenosine Deaminase/*blood/*metabolism ; Adult ; Analysis of Variance ; Birth Weight ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Inosine/metabolism ; Logistic Models ; Maternal Age ; Pregnancy ; Substrate Specificity

OBJECTIVETo explore the germination effects of Bacillus anthracoides spores germinant to nutrient germinant.

METHODSHeat factors and nutrient germinant were used to stimulate the Bacillus anthracoides spores and to germinate. Ultraviolet spectrophotometer was used to measured the A value of spore solution in the wavelength of 600 nm. Accrding to the A value, the germination rates in different condition. Transmission electron microscope was used to observe the ultrastructure changes of spores.

RESULTSThe rate of germination effects were 68.0% under 6 mmol/L inosine at 37 degrees C, pH 7.9; 74.5% under 70 mmol/L L-alanine at 30 degrees C, pH 8.9; and 85.6% under 6 mmol/L inosine and 70 mmol/L L-alanine at 37 degrees C, pH 8.2. Under transmission electron microscope, the germinated spores' coat and cortex were brokendown and degraded with its core completely exposed.

CONCLUSIONUnder suitable environment, the nutrient germinant with inosine and L-alanine might be helpful for germinating the bacillus anthracoides spores.

Alanine ; pharmacology ; Bacillus anthracis ; drug effects ; metabolism ; physiology ; Bacterial Proteins ; metabolism ; Culture Media ; Inosine ; pharmacology ; Spores, Bacterial ; drug effects ; metabolism ; physiology

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo GMP biosynthesis. The expression and activity of IMPDH can be affected by diseases and physiological process. It is the drug target for anticancer, antiviral, antimicrobial and immunosuppressive therapeutics. Not only catalytic action but the other biological functions of IMPDH also play an important role in diseases. The basic functions, mechanism of catalysis, classification of inhibitors, biological functions and the latest advances to IMPDH will be illustrated in this review. It is expected to be helpful to the discovery of new inhibitors and biological functions of IMPDH.
Animals ; Binding Sites ; Catalysis ; Drug Design ; Drug Discovery ; Enzyme Inhibitors ; classification ; pharmacology ; Humans ; IMP Dehydrogenase ; antagonists & inhibitors ; genetics ; metabolism ; Inosine Monophosphate ; metabolism ; Molecular Structure ; NAD ; metabolism ; Polymorphism, Genetic

AIMTo investigate the vasodilating effect and its mechanism of ethanol on isolated rat thoracic aorta at different resting tension.

METHODSThe tension of the isolated Sprague-Dawley rat thoracic aorta rings perfused with different concentrations of ethanol was measured using organ bath technique.

RESULTSAt different resting tension (1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 g), ethanol (0.1-7.0 per thousand) caused a concentration-dependent relaxation on endothelium-denuded aortic rings precontracted with KCl (6 x 10(-2)mol/L) or phenylephrine (PE, 10(-6) mol/L), and the vasodilating effect was the most potent when the aortic rings were at the resting tension of 3 g. Ethanol had much less vasodilating effect on endothelium-intact aortic rings. Ethanol at 3 per thousand (the maximum-effect concentration) inhibited the CaCl2 induced contraction and downward shifted concentration-response curve of endothelium-denuded aortic rings pre-contracted with KCI or PE at the resting tension of 3 g. Incubation of aorta with ruthenium red (10(-5) mol/L) or heparin (50 mg/L) decreased the vasodilating effect of ethanol (3.0 per thousand) on endothelium-denuded aorta precontracted with PE at the resting tension of 3 g.

CONCLUSIONEthanol induces endothelium-independent relaxation on rat thoracic aorta, which is concerned with the resting tension. This effect of ethanol may be mediated by the inhibition of voltage-dependent and receptor-operated Ca2+ channels in the vascular smooth muscle cells. The inhibition of the ryanodine receptor and trisphosphate inositol (IP3) pathway may also contribute to this effect.

Animals ; Aorta, Thoracic ; drug effects ; Calcium Channel Blockers ; pharmacology ; Ethanol ; pharmacology ; In Vitro Techniques ; Inosine Triphosphate ; metabolism ; Male ; Muscle, Smooth, Vascular ; drug effects ; Rats ; Rats, Sprague-Dawley ; Ryanodine Receptor Calcium Release Channel ; drug effects ; Vasodilation ; drug effects

OBJECTIVEIt has been reported that neuronal apoptosis plays a critical role in pathology of hypoxic-ischemic encephalopathy (HIE). Cytochrome C (CytC) is an important apoptotic protease activating factor. Inosine might have a neuroprotective effect against cerebral ischemia reperfusion injury by inhibiting the neuronal apoptosis and the expression of CytC mRNA in adult rats. This study examined the effects of inosine on neuronal apoptosis and CytC mRNA expression following hypoxic-ischemic brain damage (HIBD) in order to investigate the neuroprotectivity of inosine against cerebral ischemia injury in neonatal rats and the possible mechanism.

METHODSA total of 140 healthy 7-day-old Sprague-Dawley rat pups were randomly assigned into Control (n=40), HIBD (n=50) and Inosine treatment groups (n=50). HIBD rat models were established by ligating the left common carotid artery, followed by 8% O2 hypoxia exposure for 2 hrs in the HIBD and Inosine treatment groups. The Control group was not subjected to hypoxia-ischemia (HI). The Inosine treatment and the HIBD groups were randomly divided into 5 sub-groups sacrificed at 6 and 12 hrs, and 1, 3 and 7 days post- HI (n=10 each). The Control group rats were sacrificed at the corresponding time points (n=8 each). Inosine was administered to the Inosine treatment group by intraperitoneal injection immediately after HIBD at the dosage of 100 mg/kg twice daily for 7 days. TUNEL staining and in situ hybridization method was used to detect neuronal apoptosis and CytC mRNA expression respectively.

RESULTSFew apoptotic cells and CytC mRNA positive cells were found in brain tissues of the Control group. In the HIBD group, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas increased 6 hrs after HI, peaking at 1 day after HI and then decreased gradually. Until the 7th day, the number of apoptotic cells and the CytC mRNA expression in the cortical and hippocampal gyrum CA1 areas in the HIBD group remained significantly higher than in the Control group. Inosine treatment decreased the apoptotic cells and the CytC mRNA expression in both areas from 6 hrs to 7 days after HI compared with the HIBD group. The linear correlation analysis demonstrated that the number of apoptotic cells was positively correlated to the CytC mRNA expression in neonatal rats with HIBD (r=0.88, P < 0.01) .

CONCLUSIONSInosine can reduce the number of apoptotic cells and down-regulate the expression of CytC mRNA following HIBD in neonatal rats. The decreased number of apoptotic cells was positively correlated to the decreased CytC mRNA expression after inosine treatment, suggesting that inosine offered neuroprotectivity against HIBD possibly through inhibiting the CytC mRNA expression and resulting in a decrease of cell apoptosis.

Animals ; Apoptosis ; drug effects ; Cytochromes c ; genetics ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; pathology ; In Situ Nick-End Labeling ; Inosine ; pharmacology ; therapeutic use ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Adenosine deaminase (ADA), an enzyme involved in purine metabolism, catalyzes the hydrolytic deamination of adenosine or 2-deoxyadenosine to inosine or 2-deoxyinosine. Human ADA consists of three molecular forms: ADA1, ADA1+CP, and ADA2. The two ADA isoenzymes represent two different gene products and have different tissue distributions, and their concentrations in serum appear to reflect different pathological conditions or physiological responses. Elevation of serum ADA activity has been described especially in leukemia and lymphoma. The purpose of this study was to evaluate the clinical utility of ADA isoenzyme determination in the diagnosis of leukemia. METHODS: We studied the activity of serum ADA and its isoenzyme in 44 leukemic patients. The study population consisted of 17 patients with acute lymphoblastic leukemia (ALL), 23 with acute myeloid leukemia (AML), and 4 with chronic myelogenous leukemia (CML). ADA isoenzyme was measured by erythro-9- (2-hydroxy-3-nonyl) adenine [EHNA] inhibitory assay using the Hitachi 7170 autoanalyzer. RESULTS: The rates of abnormally high total ADA activity were 100% for ALL, 60.8% for AML, and 50% for CML. In isoenzyme pattern, there was a clear difference between ALL and AML. High level of ADA1 activity was found in patients with ALL (P <0.01). The ADA1/ADA2 ratio was significantly higher (P <0.001) in ALL than AML. There was a correlation between ADA1 and absolute number of peripheral blasts in AML (r=0.840). CONCLUSIONS: It is concluded that the measurement of ADA isoenzyme may be a useful biochemical marker for leukemic diagnosis.
Adenine ; Adenosine Deaminase* ; Adenosine* ; Biomarkers ; Deamination ; Diagnosis ; Humans ; Inosine ; Isoenzymes ; Leukemia* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Lymphoma ; Metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Tissue Distribution