Modifying the Bitterness of Selected Oral Pharmaceuticals with Cation and Anion Series of Salts

Purpose. NaCl has proven to be an effective bitterness inhibitor, but the reason remains unclear. The purpose of this study was to examine the influence of a variety of cations and anions on the bitterness of selected oral pharmaceuticals and bitter taste stimuli: pseudoephedrine, ranitidine, acetaminophen, quinine, and urea. Method. Human psychophysical taste evaluation using a whole mouth exposure procedure was used. Results. The cations (all associated with the acetate anion) inhibited bitterness when mixed with pharmaceutical solutions to varying degrees. The sodium cation significantly (P < 0.003) inhibited bitterness of the pharmaceuticals more than the other cations. The anions (all associated with the sodium cation) also inhibited bitterness to varying degrees. With the exception of salicylate, the glutamate and adenosine monophosphate anions significantly (P < 0.001) inhibited bitterness of the pharmaceuticals more than the other anions. Also, there were several specific inhibitory interactions between ammonium, sodium and salicylate and certain pharmaceuticals. Conclusions We conclude that sodium was the most successful cation and glutamate and AMP were the most successful anions at inhibiting bitterness. Structure forming and breaking properties of ions, as predicted by the Hofmeister series, and other physical-chemical ion properties failed to significantly predict bitterness inhibition.     

Mice Chronically Infected with Chimeric HIV Resist Peripheral and Brain Superinfection: A Model of Protective Immunity to HIV

Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.     

反复呼吸道感染患儿IgG亚类与血锌相关性的临床研究

目的：探讨反复呼吸道感染（RRTI）患儿血清IgG亚类与血锌之间的关系,为临床治疗小儿反复呼吸道感染提供一定的理论依据。方法：采用免疫散射比浊法测定IgG、IgG亚类含量,利用原子吸收法测定血锌含量。结果：64例RRTI患儿IgG2、IgG4及血锌水平明显低于对照组;IgG亚类缺陷28例,检出率为43．75％（28／64）,在检出的患儿中IgG。缺陷发生率最高,为35．71％（10／28）,联合缺陷以IgG2＋IgG4最多,发生率为21．42％（6／28）。结论：RRTI患儿虽然IgG正常但存在IgG亚类异常;RRTI患儿血锌水平低于正常儿童,IgG2、IgG4异常与低血锌有关。     

椎弓根钉联合伤椎自体骨移植与联合注射性硫酸钙治疗胸腰椎骨折的对比研究

目的 比较椎弓根钉联合伤椎自体骨移植与椎弓根钉联合注射性硫酸钙治疗胸腰椎骨折的效果及预后.方法 选择四川省彭州市人民医院骨科2013年8月-2015年9月收治的胸腰椎骨折60例,根据入院顺序分为A、B组,每组30例.2组均给予脊柱后路椎弓根钉系统复位内固定+脊柱融合术,A组在此基础上给予自体骨移植,B组给予注射性硫酸钙,观察2组手术效果及预后情况.结果 2组手术成功率均为100.00％.2组手术时间、术中出血量、住院时间比较差异无统计学意义(P＞0.05),但B组住院费用高于A组(P＜0.05).B组术后骨缺损发生率低于A组,骨缺损程度较A组轻(P＜0.05).2组术后即刻、出院时、术后各时段Cobb角、椎体前缘高度压缩率、视觉模拟量表(V AS)评分均较术前降低,出院时和术后各时段Cobb角和椎体前缘高度压缩率较术后即刻增高,VAS评分低于术后即刻(P＜0.05);B组术后即刻、出院时、术后3个月VAS评分高于A组,术后即刻和出院时Cobb角小于A组,推体前缘高度压缩率高于A组(P＜0.05).2组出院时、术后各时段ODI评分较术前明显降低,且术后各时段低于出院时(P＜0.05).结论 椎弓根钉联合自体骨移植和椎弓根钉联合注射性硫酸钙治疗胸腰椎骨折手术效果相当,虽然注射性硫酸钙术后骨缺损发生率低且程度轻微,但其费用高昂,临床应合理选择手术方案.     

Further Aspects of Ochratoxin A-Cation Interactions: Complex Formation with Zinc Ions and a Novel Analytical Application of Ochratoxin A-Magnesium Interaction in the HPLC-FLD System

Ochratoxin A (OTA) is a mycotoxin produced by different Aspergillus and Penicillium species. Since its mechanism of action is not fully understood yet, it is important to gain further insight into different interactions of OTA at the molecular level. OTA is found worldwide in many foods and drinks. Moreover, it can also be detected in human and animal tissues and body fluids, as well. Therefore, the development of highly sensitive quantitative methods for the determination of OTA is of utmost importance. OTA most likely forms complexes with divalent cations, both in cells and body fluids. In the present study, the OTA-zinc interaction was investigated and compared to OTA-magnesium complex formation using fluorescence spectroscopy and molecular modeling. Our results show that zinc(II) ion forms a two-fold higher stable complex with OTA than magnesium(II) ion. In addition, based on the enhanced fluorescence emission of OTA in its magnesium-bound form, a novel RP-HPLC-fluorescence detector (FLD) method was also established. Our results highlight that the application of magnesium chloride in alkaline eluents results in an approximately two-fold increase in sensitivity using the HPLC-FLD technique.     

Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO₂ and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO₂ particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation.     

Modification of cardiovascular responses to adenosine A1 receptor stimulation in the posterior hypothalamus of anaesthetized rats by cAMP and by GABAB receptor blockade

1 Injection of N⁶‐cyclohexyladenosine (CHA; 1, 5 and 10 nmol), an adenosine A₁ receptor agonist, into the posterior hypothalamus of rats produced a dose‐dependent decrease in blood pressure (BP) and heart rate (HR). 2 Pretreatment with 8‐cyclopentyl‐1,3‐dimethylxanthine (CPDX; 50 nmol), an adenosine A₁ receptor antagonist, blocked the depressor and bradycardic effects of CHA (10 nmol). 3 Pretreatment with 8‐bromo‐cyclic adenosine monophosphate (AMP) (10 nmol), a cAMP analogue, attenuated the depressor and bradycardic effect of CHA (10 nmol); 8‐bromo‐cyclic guanosine monophosphate (GMP) (10 nmol), a cGMP analogue, did not modify those effects of CHA. 4 In addition, pretreatment with 5‐aminovaleric acid (25 nmol), a γ‐aminobutyric acid (GABA)_B receptor antagonist, attenuated the depressor and bradycardic effects of CHA (10 nmol). 5 These results suggest that adenosine A₁ receptors in the posterior hypothalamus have an inhibitory role in the central cardiovascular regulation and that these vasodepressive and bradycardic actions are modified by raised cAMP and by GABA_B receptor inhibition.     

A Combined Specific Target Site Binding and Pharmacokinetic Model to Explore the Non-linear Disposition of Draflazine

The capacity-limited high-affinity target site binding ofdraflazine to the nucleoside transporters located on the erythrocytes isa source of nonlinearity in the pharmacokinetics of the drug. Anattractive feature of draflazine is that the specific target sitebinding characteristics can be determined easily by simultaneouslymeasuring plasma and whole blood concentrations of the drug. Measureddrug concentrations following various infusion rates and infusiondurations were used to develop a model in which the interrelatedblood–plasma distribution, elimination, and specific target sitebinding of draflazine were incorporated simultaneously. The estimatedbinding (dissociation) constant K_d was0.57 ng/ml plasma and the maximal specific erythrocyte bindingcapacity was 163 ng/ml RBC. The maximal specific binding capacity to the tissues was estimated to be about 1 mg. The estimated volume of the central compartment(V_{plasma + tissue fluids}) was12.9 L and the total intrinsic CL was 645 ml/min. Aftervalidation, the model was used to further investigate the impact of thespecific high-affinity target site binding of draflazine on itsdisposition in plasma. The time required to reach steady-state plasmaconcentrations of draflazine decreased with an increasing infusion rate.Time profiles of the plasma concentrations were not alwaysrepresentative for the time profiles of the specific target site(RBC) occupancy of draflazine, but the t _1/2,z in plasma paralleled that of the drug at target sites. Theapparent V_d and the t _1/2,z decreased with increasing single doses whereas the total CLremained constant. The recovery of draflazine was also dosedependent and increased with increasing doses. Finally, the totalCL and apparent V_d of the first dose weregreater than those of the second dose of draflazine.     

替加环素联合舒巴坦制剂治疗鲍曼不动杆菌感染的meta分析

目的 系统评价替加环素联合舒巴坦制剂治疗多重耐药/泛耐药鲍曼不动杆菌感染的疗效。方法 系统检索CNKI、Wangfang Data、CBM、PubMed、The Cochrane Library、Web of science、Embase,检索时间为建库至2018年7月1日,检索方式为主题词结合自由词检索,语种不限,由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行meta分析。结果 检索到相关文献共1 062篇,按纳入及排除标准从中选择符合标准的46篇文献。Meta分析结果显示,替加环素联合舒巴坦制剂对比单用替加环素或单用舒巴坦制剂在总的有效率和细菌清除率方面有一定优势[OR=3.90,95%CI（3.25,4.68）,P<0.000 01],[OR=3.29,95%CI（2.76,3.92）,P<0.000 01];在不良反应方面,联合用药不会增加其发生率[OR=0.87,95%CI（0.67,1.14）,P=0.31]。亚组分析显示,联用舒巴坦制剂可降低替加环素的不良反应发生率[OR=0.51,95%CI（0.28,0.93）,P=0.03]。结论 替加环素联合舒巴坦制剂治疗多重耐药/泛耐药鲍曼不动杆菌感染优于单用替加环素或单用舒巴坦制剂。     

喜炎平联合银黄滴丸、甘草锌颗粒治疗手足口病的疗效观察

目的探讨喜炎平联合银黄滴丸、甘草锌颗粒治疗手足口病的疗效。方法将临床确诊为手足口病的117例患儿随机分成两组。观察组60例采用喜炎平静滴联合银黄滴丸+甘草锌颗粒口服方案,对照组57例采用炎琥宁静滴联合蓝芩颗粒治疗方案,疗程3～10d。结果疗程结束,观察组皮疹的消退、口腔溃疡的的愈合及体温和生化指标的恢复明显优于对照组,观察组和对照组的优良率分别为96.67%和78.95%,两组比较差异有统计学意义(P<0.05)。结论喜炎平联合银黄滴丸、甘草锌颗粒治疗手足口病效果显著、安全性好、疗效确切。     

Peripheral vascular effects of bufuralol in hypertensive and normal subjects: A comparison with propranolol and pindolol

Summary In a double-blind, single oral dose, crossover study, the effects of bufuralol (60 mg) on heart rate, blood pressure, and peripheral vascular responses were compared with those of propranolol (160 mg), pindolol (10 mg), and placebo in a group of 12 healthy volunteers.All three beta-adrenoceptor antagonists reduced exercise tachycardia, but at the doses chosen the effects of bufuralol were less than those of propranolol.Forearm blood flow was reduced by propranolol and pindolol, but not by bufuralol.The antihypertensive and peripheral vascular effects of bufuralol (30–60 mg bd) were also compared with those of propranolol (40–80 mg bd) in a double-blind crossover study in 10 patients with mild hypertension.Propranolol and bufuralol produced comparable reductions in systemic blood pressure over a two-week period, but the decreases in forearm and finger blood flow were greater with propranolol.These studies suggest that bufuralol is a beta-adrenoceptor antagonist with antihypertensive properties, and that it produces less peripheral vasoconstriction than propranolol or pindolol.     

Antifungal efficiency of miconazole and econazole and the interaction with transport protein: A comparative study

Abstract

Context: Miconazole (MIZ) and econazole (ECZ) are clinically used as antifungal drugs.

Objective: The drug effect and binding property with transport protein human serum albumin of MIZ and ECZ were studied.

Materials and methods: The antifungal efficiency was investigated by microdiluting drug solutions from 0 to 48?μmol?L^?1 through microcalorimetry and voltammetry studies. Transmission electron microscopy was used for morphological observations of C. albicans. The interaction with HSA was studied by electrochemical methods, fluorescence spectrometry, electron microscopy, and molecular simulation.

Results: IC₅₀ of MIZ and ECZ for C. albicans were obtained as 19.72 and 29.90?μmol?L^?1. Binding constants of MIZ and ECZ with HSA of 2.36?×?10⁴ L?mol^?1 and 3.73?×?10⁴ L?mol^?1 were obtained. After adding MIZ solution of 12 and 40?μmol?L^?1, the peak currents increased to 4.887 and 6.024?μA. The peak currents of C. albicans in the presence of 20 and 48?μmol?L^?1 ECZ were 4.701 and 5.544?μA. The docking scores for MIZ and ECZ of the best binding conformation in site I and site II were 5.60, 4.79, 5.63, and 5.85.

Discussion and conclusion: Strong inhibition to the metabolism of C. albicans and destructive effect was proved for both drugs. The lower IC₅₀, growth rate constant of C. albicans, and higher peak current, reveal stronger antifungal activity of MIZ. Both drugs show an efficient quenching effect to intrinsic fluorescence residues of protein. MIZ mainly binds on site I while ECZ on site II. Molecular modeling experiments give further insight of the binding mechanism.     

紫杉醇联合奈达铂治疗卵巢癌的Meta分析

摘 要 目的：系统评价紫杉醇联合奈达铂对卵巢癌患者进行治疗的安全性和有效性。方法：计算机检索PubMed、Cochrane Library、Embase、CNKI、WanFang Data、SinoMed数据库,搜集有关紫杉醇联合奈达铂治疗卵巢癌的随机对照试验（RCTs）。检索时限均为建库至2018年4月,由两名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用 RevMan 5.3软件进行分析。 结果：共纳入12 项研究,包括1 219 例患者。Meta分析结果显示,紫杉醇联合奈达铂治疗卵巢癌的总有效率与其他化疗方案相比,差异无统计学意义[OR=1.14,95%CI （0.88,1.48）,P=0.16],但紫杉醇联合奈达铂可提高患者1年生存率[OR=3.37,95%CI（1.47,7.71）,P=0.004]和2年生存率[OR=2.24,95%CI（1.27,3.97）,P=0.006],并且该方案显著减少了不良反应的发生率：血小板降低[OR=0.49,95%CI（0.36,0.66）,P=0.000 01]、恶心呕吐[OR=0.65,95%CI（0.47,0.89）,P=0.007]、外周神经毒性[OR=0.43,95%CI（0.28,0.67）,P=0.000 2]及肝功能损伤[OR=0.39,95%CI（0.20,0.77）,P=0.006]等不良反应的发生率。 结论：紫杉醇联合奈达铂治疗卵巢癌可延长患者1年及2年生存率且不良反应较轻,受研究数量和质量的限制,结论还需更多高质量的RCTs进行验证。     

玻璃体腔注射雷珠单抗联合曲安奈德治疗视网膜静脉阻塞继发黄斑水肿的meta分析

目的 评价玻璃体腔注射雷珠单抗联合曲安奈德（IVR+IVT）与单用雷珠单抗（IVR）治疗视网膜静脉阻塞继发黄斑水肿的疗效和安全性差异。方法 检索数据库资源,包括PubMed、Embase、Cochrane图书馆、中国知网（CNKI）、维普中文科技期刊数据库（VIP）和万方数据,收集建库至2019年1月治疗方案为IVR+IVT与IVR治疗视网膜静脉阻塞继发黄斑水肿的随机对照临床研究文献,纳入符合标准的文献,评价其质量,提取相关数据,采用RevMan 5.3统计软件进行Meta分析。结果 本研究共纳入4项RCTs文献,病例数215例,217眼。Meta分析结果提示,IVR+IVT组患者随访3个月时黄斑中心凹视网膜厚度（CMT）优于IVR组,差异有统计学意义,随访1,2,4,5,6个月2组间CMT差异无统计学意义;4项研究最佳矫正视力（BCVA）治疗后较治疗前提高,其中2项研究随访1个月时差异有统计学意义,随访2,3,4,5,6个月差异无统计学意义;在不良反应发生率方面,IVR+IVT组眼压升高并发症风险明显高于IVR组;2组在发生皮质性白内障方面,差异无统计学意义;在注射次数上,IVR+IVT组较IVR组明显减少,差异有统计学意义。结论 IVR+IVT与IVR治疗视网膜静脉阻塞继发黄斑水肿均有效,在随访3个月降低CMT和随访1个月改善BCVA方面存在统计学差异。IVR+IVT治疗虽增加眼压升高风险,但注射次数较IVR减少,同时也减轻患者经济负担。临床医师可根据实际情况,酌情选取合适治疗手段。     

氟桂利嗪联合血塞通治疗偏头痛有效性和安全性Meta分析

目的评价氟桂利嗪联合血塞通治疗偏头痛的有效性和安全性。方法计算机检索中国期刊全文数据库(CNKI)、PubMed和维普数据库,检索时限为各数据库自建库起至2021年2月24日,收集氟桂利嗪联合血塞通治疗偏头痛的随机对照试验(RCT),提取资料,采用Cochrane偏倚风险评估工具评估文献质量,采用Rev Man 5.3统计学软件进行Meta分析。结果最终纳入29篇文献,共2 867例患者;与对照组比较,观察组的总有效率[RR=1.24,95%CI(1.20,1.28),P <0.000 01]显著升高,发作次数[MD=-6.17,95%CI(-8.19,-4.15),P <0.000 01]显著减少,发作持续时间[MD=-2.86,95%CI(-3.82,-1.89),P <0.000 01]显著缩短,疼痛程度[MD=-1.42,95%CI(-1.47,-1.37),P <0.000 01]显著减轻,两组患者的不良反应发生率相当[RR=0.85,95%CI(0.57,1.26),P=0.42]。结论氟桂利嗪联合血塞通治疗偏头痛的疗效优于前者单用,且安全性较高,但...     

中西药结合治疗婴幼儿哮喘34例

目的观察参附注射液静脉滴注联合异丙托溴铵雾化吸入治疗婴幼儿哮喘的疗效.方法采用随机对照方法,对照组30例用氨茶碱等综合治疗,治疗组34例用参附注射液1～2mL*kg-1*d-1稀释后静脉滴注替代氨茶碱,联合异丙托溴铵雾化吸入治疗.结果治疗组疗效优于对照组,而副作用小于对照组.结论参附注射液联合异丙托溴铵治疗婴幼儿哮喘具有高效性和安全性.     

Algal Toxic Compounds and Their Aeroterrestrial,Airborne and other Extremophilic Producers with Attention to Soil and Plant Contamination: A Review

The review summarizes the available knowledge on toxins and their producers from rather disparate algal assemblages of aeroterrestrial, airborne and other versatile extreme environments (hot springs, deserts, ice, snow, caves, etc.) and on phycotoxins as contaminants of emergent concern in soil and plants. There is a growing body of evidence that algal toxins and their producers occur in all general types of extreme habitats, and cyanobacteria/cyanoprokaryotes dominate in most of them. Altogether, 55 toxigenic algal genera (47 cyanoprokaryotes) were enlisted, and our analysis showed that besides the “standard” toxins, routinely known from different waterbodies (microcystins, nodularins, anatoxins, saxitoxins, cylindrospermopsins, BMAA, etc.), they can produce some specific toxic compounds. Whether the toxic biomolecules are related with the harsh conditions on which algae have to thrive and what is their functional role may be answered by future studies. Therefore, we outline the gaps in knowledge and provide ideas for further research, considering, from one side, the health risk from phycotoxins on the background of the global warming and eutrophication and, from the other side, the current surge of interest which phycotoxins provoke due to their potential as novel compounds in medicine, pharmacy, cosmetics, bioremediation, agriculture and all aspects of biotechnological implications in human life.     

Predicting the Reactivity of Nitrile-Carrying Compounds with Cysteine: A Combined Computational and Experimental Study

相似文献   

脾多肽注射液辅助化疗治疗肿瘤的疗效与安全性meta分析

目的 系统评价脾多肽注射液辅助化疗治疗肿瘤的疗效与安全性,为临床治疗提供循证参考。方法 计算机检索中国知网（CNKI）、万方期刊论文数据库、维普期刊数据库、中国生物医学文献数据库（CBM）、Medline、Embase和CochraneCentral Register of Controlled Trials （CENTRAL）,收集脾多肽注射液辅助化疗治疗肿瘤的随机对照试验（randomizedcontrolled trials,RCT）,对符合纳入标准的临床研究进行资料提取,采用Cochrane系统评价员手册5.0版进行质量评价,采用Rev Man 5.3统计软件进行meta分析。结果 共纳入25项RCT,合计2 055例患者。Meta分析结果显示,脾多肽注射液辅助化疗治疗肿瘤能显著提高有效率[OR=1.85,95%CI（1.50,2.28）,P<0.000 01]和生存质量改善率[OR=4.55,95%CI（3.19,6.51）,P<0.000 01],同时还能降低白细胞、血小板、血红蛋白减少率和恶心呕吐、骨髓抑制、神经毒性等不良反应发生率,差异均有统计学意义。结论 当前证据表明,脾多肽注射液辅助化疗治疗肿瘤疗效与安全性均较好。