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81.
Abstract: Infection with Herpes simplex virus type 1 (HSV-1) typically causes lesions of the mouth, face, skin, esophagus, or brain. Herpes simplex virus type 2 (HSV-2) usually causes infections of the genitals, rectum, skin, hands, or meninges. The herpes viruses are a major cause of blindness from keratitis. The usual drugs used for herpes are Vidarabine, Acyclovir, Penciclovir and Ganciclovir; they are associated with several complications. The aim of this study was to investigate if a formulation containing 2.5 mg melatonin and 100 mg SB-73 would help patients with herpes, and to compare the preparation with 200 mg Acyclovir. SB-73 is a mixture of magnesium, phosphate, fatty acids extracted from Aspergillus sp. which has anti-herpes virus properties. A single blind randomized study was performed in which 70 patients underwent treatment using the supplement cited above (group A) and 75 received treatment of 200 mg Acyclovir (group B). Sixty-seven patients of the group A (95.7%) reported a complete regression of symptoms after 7 days of treatment. By comparison, 64 subjects (85.3%) of the Acyclovir reported regression of symptoms in the same period. There was statiscally significant difference between the groups ( P < 0.05). 相似文献
82.
Behm DJ McAtee JJ Dodson JW Neeb MJ Fries HE Evans CA Hernandez RR Hoffman KD Harrison SM Lai JM Wu C Aiyar NV Ohlstein EH Douglas SA 《British journal of pharmacology》2008,155(3):374-386
Background and purpose:
The recent development of the UT ligand palosuran (1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulphate salt) has led to the proposition that urotensin-II (U-II) plays a significant pathological role in acute and chronic renal injury in the rat.Experimental approach:
In the present study, the pharmacological properties of palosuran were investigated further using a series of radioligand binding and functional bioassays.Key results:
Palosuran functioned as a ‘primate-selective'' UT ligand in recombinant cell membranes (monkey and human UT Ki values of 4±1 and 5±1 nM), lacking appreciable affinity at other mammalian UT isoforms (rodent and feline Ki values >1 μM). Paradoxically, however, palosuran lost significant (10- to 54-fold) affinity for native and recombinant human UT when radioligand binding was performed in intact cells (Ki values of 50±3 and 276±67 nM). In accordance, palosuran also exhibited diminished activity in hUT (human urotensin-II receptor)-CHO (Chinese hamster ovary) cells (IC50 323±67 nM) and isolated arteries (Kb>10 μM in rat aorta; Kb>8.5 μM in cat arteries; Kb>1.6 μM in monkey arteries; Kb 2.2±0.6 μM in hUT transgenic mouse aorta). Relative to recombinant binding Ki values, palosuran was subjected to a 392- to 690-fold reduction in functional activity in monkey isolated arteries. Such phenomena were peculiar to palosuran and were not apparent with an alternative chemotype, SB-657510 (2-bromo-N-[4-chloro-3-((R)-1-methyl-pyrrolidin-3-yloxy)-phenyl]-4,5-dimethoxybenzenesulphonamide HCl).Conclusions and implications:
Collectively, such findings suggest that caution should be taken when interpreting data generated using palosuran. The loss of UT affinity/activity observed in intact cells and tissues cf. membranes offers a potential explanation for the disappointing clinical efficacy reported with palosuran in diabetic nephropathy patients. As such, the (patho)physiological significance of U-II in diabetic renal dysfunction remains uncertain. 相似文献83.
目的 探讨转化生长因子-β1(transforminggrowthfactor-β1,TGF-β1)和SB431542(TGF-β1受体酶抑制剂)对甲状腺相关性眼病(thyroid-associatedophthalmopathy,TAO)患者眼眶成纤维细胞α平滑肌激动蛋白(α-smoothmuscleactin,α-SMA)及结缔组织生长因子(connectivetissuegrowthfactor,CTGF)基因表达的影响,为TAO眼外肌纤维化的治疗寻找潜在的药物治疗靶点。方法 实验分为3组。第1组:采用实时荧光定量逆转录聚合酶链反应(real-timePCR,RT-PCR)检测不同浓度TGF-β1(0μg?L-1、1μg?L-1、5μg?L-1、10μg?L-1、20μg?L-1)刺激TAO患者眼眶成纤维细胞后α-SMA及CT-GFmRNA的表达情况;第2组:采用RT-PCR检测10μg?L-1TGF-β1在不同的时间点(0h、3h、6h、12h、24h、48h)刺激TAO患者眼眶成纤维细胞后α-SMA及CTGFmRNA的表达情况;第3组(分为4小组处理):眼眶成纤维细胞不加任何干预、使用30μmol?L-1 SB431542刺激眼眶成纤维细胞、10μg?L-1 TGF-β1 单独刺激眼眶成纤维细胞、30μmol?L-1 SB431542联合10μg?L-1 TGF-β1刺激眼眶成纤维细胞(SB431542预先刺激眼眶成纤维细胞1h,然后再加入TGF-β1),采用RT-PCR检测α-SMA及CTGFmRNA的表达。结果 TGF-β1在一定的浓度范围内(1~10μg?L-1)以剂量依赖的方式诱导眼眶成纤维细胞表达α-SMAmRNA及CTGFmRNA,随着浓度增加mRNA表达增加,各浓度组(1μg?L-1、5μg?L-1、10μg?L-1、20μg?L-1)与空白对照组(0μg?L-1)相比,差异均有统计学意义(均为P<0.05)。TGF-β1在一定的时间范围内(0~24h)以时间依赖的方式诱导眼眶成纤维细胞表达α-SMAmRNA及CTGFmRNA,随着时间延长mRNA表达增加,各时间组(3h、6h、12h、24h、48h)与0h相比,差异均有统计学意义(均为P<0.05)。10μg?L-1的TGF-β1诱导眼眶成纤维细胞表达α-SMAmRNA在24h达到峰值,而CTGFmRNA在12h即可达到峰值。SB431542对眼眶成纤维细胞α-SMAmRNA及CTGFmRNA的表达均有抑制作用。结论 一定范围内,TGF-β1以剂量和时间依赖的方式诱导眼眶成纤维细胞α-SMA及CTGFmRNA的表达,SB431542可抑制其表达。 相似文献
84.
RATIONALE: 5-HT(6) receptors are predominantly located in the brain and may be involved in cognitive processes. The aim of this study was to assess the effects of two potent and selective 5-HT(6) receptor antagonists, SB-271046-A and SB-357134-A, on learning and memory in the rat. METHODS: Spatial learning and memory was assessed by testing the effects of SB-271046-A and SB-357134-A on acquisition and retention of a water maze task. RESULTS: In the water maze, administration of SB-271046-A or SB-357134-A (3 or 10 mg/kg) had no effect on learning per se. At 10 mg/kg, however, both compounds produced a significant improvement in retention of a previously learned platform position when tested 7 days after training. By contrast, the acetylcholinesterase inhibitor, Aricept (donepezil, 0.1, 0.3 mg/kg PO) had no effect in this task. CONCLUSIONS: This study demonstrates that systemic administration of SB-271046-A and SB-357134-A produces improvements in retention of a water maze task in the rat. These data indicate that 5-HT(6) receptor antagonism may be involved in cognitive function. 相似文献
85.
目的观察p38激酶抑制剂SB203580和牛磺酸对烧伤后心肌细胞心肌肌钙蛋白T(cTnT)、肿瘤坏死因子α(TNFα)的影响。方法将原代培养的心肌细胞在缺氧、10%烧伤血清条件下培养,建立心肌细胞损伤模型。随机分为A、B、C、D组。A组为对照组,B组加入终浓度为20 mmol/L牛磺酸,C组加入终浓度为10μmol/L的SB203580,D组加入终浓度为20 mmol/L牛磺酸及10μmol/L的SB203580。用酶联免疫法及放射免疫法分别检测各组培养1、3、6、12 h培养液中的cTnT和TNFα。结果从培养3 h开始,B、C、D组培养液cTnT、TNFα水平均比A组低(P均〈0.05);D组比B、C组低(P均〈0.05),B、C组相比P均〉0.05。结论 牛磺酸和SB203580均可降低烧伤后心肌细胞cTnT、TNFα,二者联用具有协同作用。 相似文献
86.
Effects of matrix metalloproteinase 9 inhibition on the blood brain barrier and inflammation in rats following cardiopulmonary resuscitation 总被引:3,自引:0,他引:3
Background Neuroprotective strategies following cardiopulmonary resuscitation (CPR) are an important focus in emergency and critical care medicine. Matrix metalloproteinases (MMPs), especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemiareperfusion injury after CPR. Methods One hundred and twenty rats were randomly assigned to sham-operated (n=40), resuscitation treatment (n=40), and resuscitation control (n= 40) groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation, In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation (ROSC), defined as restoration of supraventricular rhythm and mean arterial pressure (MAP) 〉 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours (n=-8). Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy. Results In the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group (P 〈0.05). 1issue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group (P 〈0.05), they were lower than in the resuscitation control group (P 〈0.05). Conclusions Expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury. 相似文献
87.
Jakub P. Piwowarski Sebastian Granica Marta Zwierzyńska Joanna Stefańska Patrick Schopohl Matthias F. Melzig Anna K. Kiss 《Journal of ethnopharmacology》2014
Ethnopharmacological relevance
Ellagitannin-rich plant materials are widely used in traditional medicine as effective, internally used anti-inflammatory agents. Due to the not well-established bioavailability of ellagitannins, the mechanisms of observed therapeutic effects following oral administration still remain unclear. The aim of the study was to evaluate if selected ellagitannin-rich plant materials could be the source of bioavailable gut microbiota metabolites, i.e. urolithins, together with determination of the anti-inflammatory activity of the metabolites produced on the THP-1 cell line derived macrophages model.Materials and Methods
The formation of urolithins was determined by ex vivo incubation of human fecal samples with aqueous extracts from selected plant materials. The anti-inflammatory activity study of metabolites was determined on PMA differentiated, IFN-γ and LPS stimulated, human THP-1 cell line-derived macrophages.Results
The formation of urolithin A, B and C by human gut microbiota was established for aqueous extracts from Filipendula ulmaria (L.) Maxim. herb (Ph. Eur.), Geranium pratense L. herb, Geranium robertianum L. herb, Geum urbanum L. root and rhizome, Lythrum salicaria L. herb (Ph. Eur.), Potentilla anserina L. herb, Potentilla erecta (L.) Raeusch rhizome (Ph. Eur.), Quercus robur L. bark (Ph. Eur.), Rubus idaeus L. leaf, Rubus fruticosus L. and pure ellagitannin vescalagin. Significant inhibition of TNF-α production was determined for all urolithins, while for the most potent urolithin A inhibition was observed at nanomolar concentrations (at 0.625 μM 29.2±6.4% of inhibition). Urolithin C was the only compound inhibiting IL-6 production (at 0.625 μM 13.9±2.2% of inhibition).Conclusions
The data obtained clearly indicate that in the case of peroral use of the examined ellagitannin-rich plant materials the bioactivity of gut microbiota metabolites, i.e. urolithins, has to be taken under consideration. 相似文献88.
In the CA3 region of rat hippocampal slices gamma-amino-butyric acid (GABA)(A/B) receptor antagonists induce low frequency bursting activity that was either inhibited (in 21% of slices) or increased by the selective 5-HT receptor agonists 5-carboxy-tryptamine (0.1-1 microM) and 8-hydroxydipropylaminotetralin (8-OH-DPAT). The selective 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide (WAY 100635) reversed the depression of bursting activity whereas the 5-HT7 receptor antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970; 1-10 microM), but not the 5-HT1A, 4 or 6 receptor antagonists WAY100635 (10 microM), SB-204070 (10 microM) and SB-271046 (10 microM), reversed the increase in bursting activity. The apparent -log10 K(D) value (8.4) for the effect of SB-269970 was consistent with a selective action at 5-HT7 receptors. Accompanying the 5-CT-induced increase in bursting frequency there was a shortening of the burst event waveform and a reduction in the after-hyperpolarization following each bursting event both of which were inhibited by SB-269970. These effects appeared to result predominantly from a direct 5-HT(7) receptor-mediated inhibition of a Ca2+ activated K+ channel. 相似文献
89.
Tony W. Hsiao Vimal P. Swarup Balagurunathan Kuberan Patrick A. Tresco Vladimir Hlady 《Acta biomaterialia》2013,9(7):7200-7208
Surface-adsorbed fibrinogen (FBG) was recognized by adhering astrocytes, and was removed from the substrates in vitro by a two-phase removal process. The cells removed adsorbed FBG from binary proteins’ surface patterns (FBG + laminin, or FBG + albumin) while leaving the other protein behind. Astrocytes preferentially expressed chondroitin sulfate proteoglycan (CSPG) at the loci of fibrinogen stimuli; however, no differences in overall CSPG production as a function of FBG surface coverage were identified. Removal of FBG by astrocytes was also found to be independent of transforming growth factor type β (TGF-β) receptor based signaling as cells maintained CSPG production in the presence of TGF-β receptor kinase inhibitor, SB 431542. The inhibitor decreased CSPG expression, but did not abolish it entirely. Because blood contact and subsequent FBG adsorption are unavoidable in neural implantations, the results indicate that implant-adsorbed FBG may contribute to reactive astrogliosis around the implant as astrocytes specifically recognize adsorbed FBG. 相似文献
90.
《Expert opinion on therapeutic patents》2013,23(6):939-960
This review addresses the recent highlights and progress made in the neurokinin-3 (NK-3) receptor area since the last update, provided in this journal in 1997. Whereas in the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) biological areas literature information based on clinical data account for a high therapeutic potential (in emesis and depression for NK-1 and asthma for NK-2 receptor antagonists), there is a total deficiency of information from NK-3 receptor antagonists in clinical development. No other chemical classes in addition to dichlorophenylalkylpiperidines, represented by SR 142,801 and quinolines, represented by SB-222200 and SB-223412, have been identified by pharmaceutical companies and scientists involved in the specific field. Biological evidence indicates pain/inflammation as a suitable CNS-related therapeutic target, this conclusion is based on localisation studies and efficacy of selected NK-3 receptor antagonists in rat disease models of inflammatory pain. In the periphery, the most likely therapeutic indications might be pulmonary and gastrointestinal tract diseases. It is clearly still premature to anticipate any therapeutic potential in man. 相似文献