Analgesia produced by intrathecal administration of the kappa opioid agonist, U-50,488H, on formalin-evoked cutaneous pain in the rat

The antinociceptive activity of the selective k opioid agonist U-50,488H, given intrathecally (i.t.) against chemically induced cutaneous pain in rats, was assessed from cumulative dose-response experiments and the formalin test. Three successive i.t. doses of 5, 10 and 35 nmol of U-50,488H produced a gradual reduction of pain scores which was statistically significant at all observation periods. This effect was antagonized significantly by 3 mg/kg i.p. of the opiate antagonists, naloxone and WIN 44,441-3. The analgesia profile showed a clear dose-response relationship. A dose producing 50% ‘maximum posible analgesia’ of 6.20 nmol (95% confidence interval: 3.05–12.59 nmol) was calculated. The results indicated that cutaneous pain of a chemical/inflammatory nature is highly sensitive to activation of k receptors of the spinal cord dorsal horn.     

Expression of differential nitric oxide synthase isoforms in human gastric mucosa infected with Helicobacter pylori

Objective: To study the relationship between nitric oxide synthase ( NOS) expression in human gastric mu-cosa and Helicobacter pylori (H. pylori) infection. Methods: Gastric mucosa samples were obtained from antrum of 33 patients received gastroendoscopy. H. pylori infection was confirmed by Giems staining and bacteria culture under mi-croaerophilic conditions. Expression of iNOS, eNOS and nitrotyrosine were detected by immunohistochemistry. Results: (1) The positive rate of H. pylori infection was 66. 7% (22/33) . (2) iNOS positive staining in inflammatory cells was detected in 77. 3% (17/22) of samples with H. pylori and 27. 3% (3/11) without H. pylori infection (P < 0.01). (3) eNOS expression in inflammatory cells was found in 77. 3% (17/22) of samples with H. pylori and 18.2% (2/11) without H. pylori infection ( P < 0. 01) . (4) Nitrotyrosine expression in inflammatory cells was observed in 59. 1% ( 13/22) of samples with H. pylori and 54.5%(6/11) without H. pylori infection (P>0.05). (5) Moderate a     

Accelerated 3D echo-planar spectroscopic imaging at 4 Tesla using modified blipped phase-encoding.

Whole-brain echo-planar spectroscopic imaging (EPSI) often substantially lengthens MRI/MRSI (magnetic resonance spectroscopic imaging) protocols. To halve acquisition time, application of a blipped phase-encoding (PE) gradient during the EPSI readout (RO) was previously suggested by PE of the even RO echoes in k-space at an interstitial location along k(PE), separated from the odd RO echoes, effectively reducing the number of PEs by a factor of 2. However, the approach is very susceptible to phase inconsistencies between even and odd RO echoes in the presence of B(0) inhomogeneities and gradient imbalance, leading to ghosting in the PE direction. In this work, the blipped PE gradient is placed in between pairs of even/odd RO gradient lobes to avoid these problems. This approach is demonstrated in a phantom and in normal human brain in vivo at 4T. While the proposed method allows substantial reduction in metabolite ghosting, it may be limited by the presence of a relatively large spurious signal at the Nyquist frequency.     

氯沙坦通过下调单核细胞趋化蛋白1受体表达抑制单核细胞活化

目的探讨血管紧张素Ⅱ对单核细胞趋化蛋白1受体CCR2表达的影响及氯沙坦的干预作用。方法人单核细胞株与血管紧张素Ⅱ(10-7mol/L)孵育,加或不加氯沙坦(10-7、10-6和10-5mol/L),检测上清液中单核细胞趋化蛋白1水平、单核和内皮细胞粘附情况以及CCR2mRNA的表达。结果与对照组比较,血管紧张素Ⅱ明显增加单核细胞培养上清液中单核细胞趋化蛋白1水平(26.46±3.58ng/L比10.56±2.34ng/L,P<0.01),增加单核内皮细胞间粘附(596±27比268±16,P<0.01)。血管紧张素Ⅱ刺激细胞后明显上调CCR2mRNA表达,氯沙坦能显著抑制血管紧张素Ⅱ的作用,降低单核细胞趋化蛋白1的水平,减少单核内皮细胞间粘附,下调CCR2 mRNA表达。结论氯沙坦通过下调单核细胞趋化蛋白1受体CCR2基因表达抑制单核细胞活化。     

CHARACTERISTICS OF MEMBRANE TRANSPORT PROCESSES OF MACULA DENSA CELLS

1. Macula densa (MD) cells are located within the thick ascending limb (TAL) and have their apical surface in contact with tubular fluid and their basilar region in contact with the glomerulus. These cells sense changes in luminal fluid sodium chloride concentration ([NaCl]) and transmit signals resulting in changes in vascular resistance (tubuloglomerular feedback) and renin release. 2. Current efforts have focused on understanding the cellular transport mechanisms of MD cells. Progress in this area has benefited from the use of the isolated perfused TAL-glomerular preparation, which permits direct access to MD cells. 3. Using microelectrodes to measure basolateral membrane potential (V_BL) of MD cells, it was found that VBL was very sensitive to changes in luminal fluid [NaCl]. As [NaCl] was elevated from 20 to 150mmol/L, V_BL was found to depolarize by over 30 mV. 4. Basolateral membrane potential measurements were also used to identify an apical Na⁺: 2CI^?: K⁺ cotransport pathway in MD cells that is the major pathway for NaCl entry into these cells. 5. Other work identified a basolateral chloride channel that is presumed to be responsible for changes in V_BL during alterations in luminal [NaCl]. This channel, which is the predominant conductance across the basolateral membrane, may be regulated by intracellular Ca²⁺ and cAMP. 6. An apical Na⁺: H⁺ exchanger in MD cells was detected by measuring changes in intracellular pH using the fluorescent probe 2′,7′-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein. 7. Using patch-clamp techniques, a high density of pH- and Ca²⁺-sensitive K⁺ channels was observed at the apical membrane of MD cells. 8. Other studies found that, at the normal physiological conditions prevailing at the end of the TAL (luminal [NaCl] of 20–60 mmol/L), reabsorption mediated by MD cells is very sensitive to changes in luminal [NaCl].     

HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic hemochromatosis

Abstract: Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA-H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty-seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and Bcll/Mbo 1 for H63D. Ferritin, transferrin serum levels and total iron-binding capacity were determined prior to therapeutic intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P >0.0001). Fifty-one (90%) patients were Tyr-282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P =NS) with none of the patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr-282-negative patients, whereas no difference was observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients.     

EFFECT OF SOME TRICYCLIC AND NONTRICYCLIC ANTIDEPRESSANTS ON [3H]IMIPRAMINE BINDING AND SEROTONIN UPTAKE IN RAT CEREBRAL CORTEX AFTER PROLONGED TREATMENT

Chronic administration of different antidepressant drugs reduced the number of [3H]imipramine [( 3H]IMI) binding sites in rat cerebral cortex. In the same experimental conditions, fluvoxamine and dothiepin, as well as desmethylimipramine, induced an increase in the maximal velocity of high affinity serotonin (5HT) uptake in cortical slices, whereas citalopram and viloxazine were ineffective in this regard. Our results indicate that even if 5HT uptake and [3H]IMI binding sites are located on the same nerve terminals, they are differently modulated. Increased Vmax of the 5HT uptake process could be due to a rebound phenomenon after withdrawal from drugs that acutely inhibit 5HT uptake. The effect on [3H]IMI sites might be explained through either the agonist properties of the drugs towards these sites or the involvement of mechanisms still unknown.     

Cytoprotective effect of epidermal growth factor on acid- and pepsininduced damage to rat gastric epithelial cells: Roles of Na+/H+ exchangers

We have previously established a cell damage model, with damage induced by either acid or pepsin treatment for 30 min, involving a rat gastric epithelial cell line (RGM1). In the present study, pretreatment of cells with epidermal growth factor (EGF; 0.1–10ng/mL) or sucralfate (0.1–3 mg/mL) for 4 h prevented such cell damage in a concentration-dependent manner. Protection of cells by these drugs was not affected by pretreatment with indomethacin (10⁻⁵ mol/L) for 4 h. Removal of Na⁻, but not Ca²⁺, from the acidified medium totally abolished the inhibitory effect of EGF, but not that of sucralfate. Genistein (a tyrosine kinase inhibitor) apparently reduced the inhibitory effect of EGF. DNA synthesis by RGM1 cells did not increase when cells were incubated with EGF for 4 h. We conclude that both EGF and sucralfate protect RGM1 cells from acid- and pepsin-induced damage and that the mechanism of protection by EGF against acid-induced damage seems to be via activation of Na⁺/H⁺ exchangers.     

Influence of peripheral afferents on cortical and spinal motoneuron excitability.

The objective of this study was to establish to what extent muscle, cutaneous, and joint afferents alter the excitability of spinal and cortical motor neurons. This question was examined by studying the impact of electrical stimulation of the second and third digits, the median nerve at the wrist, and the recurrent thenar motor branch on the F/H and magneto-electrical cortical motor responses (MEPs) of the thenar muscles. The firing frequencies of single F/H motor unit action potentials were unaltered by the foregoing conditioning peripheral stimuli. MEPs conditioned by motor threshold stimulation of the median nerve at the wrist or the recurrent motor branch were significantly increased in size at conditioning to test intervals of 50 to 80 milliseconds. No significant change in MEP size resulted from conditioning stimulation of the digital nerves. We conclude that muscle afferents were primarily responsible for the increase in MEP size. Conditioning stimuli may allow examiners to assess central motor conduction where it would otherwise be impossible.     

磺胺噻二嗪硫酮衍生物的合成及其抑菌活性

利用药物化学骈合原理设计并合成了一系列新的３，５－二取代１，３，５－噻二嗪－２－硫酮类化合物，其结构经红外光谱，紫外光谱及元素分析证实，抑菌活性试验显示了良好的抑菌活性。