Stem cell therapy and diabetic erectile dysfunction: A critical review

Erectile dysfunction (ED) has been identified as one of the most frequent chronic complications of diabetes mellitus (DM). The prevalence of ED is estimated to be about 67.4% in all DM cases worldwide. The pathophysiological process leading to ED involves endothelial, neurological, hormonal, and psychological factors. In DM, endothelial and neurological factors play a crucial role. Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM. The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery. However, these treatments are limited in terms of just relieving the symptoms, but not resolving the cause of the problem. The use of stem cells for treating ED is currently being studied mostly in experimental animals. The stem cells used are derived from adipose tissue, bone, or human urine. Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue. However, research on stem cell therapy for ED in humans remains to be limited. Nevertheless, significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.     

噬菌体治疗——旧概念, 新阶段

噬菌体治疗技术由来已久.噬菌体治疗的研究始于上世纪初,之后由于抗生素的出现及其他原因在美国和西欧等国家中断.近年来,全球范围的细菌耐药性使得科学家们重新审视和评估噬菌体治疗技术,显示出巨大潜力.论述噬菌体发现历程及早期研究、人类及动物细菌感染的应用、噬菌体治疗与抗生素的不同之处、存在的问题等,并探讨噬菌体技术可能的发展...     

糖尿病性下肢缺血性血管病的外科治疗

目的：探讨糖尿病性下肢缺血性血管病的治疗方法.方法：对24例Ⅰ型糖尿病患者合并下肢动脉缺血性疾病的39条肢体体进行了手术,其中动脉旁路手术31例,占79%.对3例患者进行了下肢截肢处理.结果：接受动脉旁路手术的患者出院时动脉血流均保持通畅.一例51岁男性患者四肢肿胀、变黑,经治疗无效死亡.结论：糖尿病性缺血性血管病可以通过外科手术治疗.如下肢远端动脉旁路移植、腔内血管成型术等.外科治疗的方法正在探讨阶段,研究方法不断进展.外科治疗不仅可以挽救肢体或降低截肢平面,而且可为足部创面的愈合提供较好的营养环境,有利于创面的愈合和提高生活质量.     

糖尿病性下肢缺血性血管病的外科治疗

目的:探讨糖尿病性下肢缺血性血管病的治疗方法。方法:对24例Ⅰ型糖尿病患者合并下肢动脉缺血性疾病的39条肢体体进行了手术,其中动脉旁路手术31例,占79%。对3例患者进行了下肢截肢处理。结果:接受动脉旁路手术的患者出院时动脉血流均保持通畅。一例51岁男性患者四肢肿胀、变黑,经治疗无效死亡。结论:糖尿病性缺血性血管病可以通过外科手术治疗。如下肢远端动脉旁路移植、腔内血管成型术等。外科治疗的方法正在探讨阶段,研究方法不断进展。外科治疗不仅可以挽救肢体或降低截肢平面,而且可为足部创面的愈合提供较好的营养环境,有利于创面的愈合和提高生活质量。     

Exploring the role of the immune response in preventing antibiotic resistance

For many bacterial infections, drug resistant mutants are likely present by the time antibiotic treatment starts. Nevertheless, such infections are often successfully cleared. It is commonly assumed that this is due to the combined action of drug and immune response, the latter facilitating clearance of the resistant population. However, most studies of drug resistance emergence during antibiotic treatment focus almost exclusively on the dynamics of bacteria and the drug and neglect the contribution of immune defenses. Here, we develop and analyze several mathematical models that explicitly include an immune response. We consider different types of immune responses and investigate how each impacts the emergence of resistance. We show that an immune response that retains its strength despite a strong drug-induced decline of bacteria numbers considerably reduces the emergence of resistance, narrows the mutant selection window, and mitigates the effects of non-adherence to treatment. Additionally, we show that compared to an immune response that kills bacteria at a constant rate, one that trades reduced killing at high bacterial load for increased killing at low bacterial load is sometimes preferable. We discuss the predictions and hypotheses derived from this study and how they can be tested experimentally.     

Static recipient cells as reservoirs of antibiotic resistance during antibiotic therapy

How does taking the full course of antibiotics prevent antibiotic resistant bacteria establishing in patients? We address this question by testing the possibility that horizontal/lateral gene transfer (HGT) is critical for the accumulation of the antibiotic-resistance phenotype while bacteria are under antibiotic stress. Most antibiotics prevent bacterial reproduction, some by preventing de novo gene expression. Nevertheless, in some cases and at some concentrations, the effects of most antibiotics on gene expression may not be irreversible. If the stress is removed before the bacteria are cleared from the patients by normal turnover, gene expression restarts, converting the residual population to phenotypic resistance. Using mathematical models we investigate how static recipients of resistance genes carried by plasmids accumulate resistance genes, and how specifically an environment cycling between presence and absence of the antibiotic uniquely favors the evolution of horizontally mobile resistance genes. We found that the presence of static recipients can substantially increase the persistence of the plasmid and that this effect is most pronounced when the cost of carriage of the plasmid decreases the cell's growth rate by as much as a half or more. In addition, plasmid persistence can be enhanced even when conjugation rates are as low as half the rate required for the plasmid to persist as a parasite on its own.     

糖尿病足感染的细菌学调查及耐药性分析

目的 了解临床糖尿病足患者感染的细菌分布及耐药性分析.方法 2009年至2010年,共调查135例糖尿病足患者.结果 检出细菌株数为107株,其中革兰阳性菌44株,占41.1％;革兰阴性菌57株,占53.3％;真菌6株,占5.6％.需氧菌感染80例,检出率59.3％.以金葡菌、链球菌、变形杆菌和大肠埃希菌为主要感染菌.金黄色葡萄球菌的耐药率明显低于其他葡萄球菌.大肠埃希菌治疗以亚胺培南首选,也可选用β-内酰胺类加酶抑制剂.结论 检出革兰阴性菌57株,革兰阳性菌44株,应根据药敏情况合理应用抗菌素.     

糖尿病患者无乳链球菌尿路感染临床表现及药物敏感性分析

目的了解糖尿病患者无乳链球菌尿路感染的临床表现及耐药状况,为临床用药提供依据。方法回顾性分析温州医学院附属第一医院2003年至2005年糖尿病患者继发尿路感染的临床特点及耐药情况。结果280例送检尿培养的住院糖尿病患者致病菌阳性有169例,共检出无乳链球菌25株,其中女性23例,男性2例。药敏结果显示无乳链球菌对氨曲南、林可霉素、复方新诺明、红霉素、阿米卡星的耐药率高达50%以上,而对头孢唑啉、万古霉素的耐药率为0%,对替考拉宁、青霉素、氨苄西林的耐药率为5.88%、7.69%、10%。结论糖尿病患者无乳链球菌引起尿路感染应引起注意,临床医生需根据药敏结果合理选用抗生素。     

糖尿病并发尿路感染患者病原菌分布与危险因素分析

目的 研究糖尿病并发尿路感染患者病原菌分布情况及其影响因素,为此类患者的治疗提供参考.方法 选取我院2016年1月至2019年6月收治的60例糖尿病合并尿路感染患者为观察组,选取同期我院治疗的60例单纯性糖尿病患者为对照组,分析糖尿病合并尿路感染患者病原菌分布情况,并分析糖尿病患者合并尿路感染的危险因素.结果 患者尿路...     

医院感染不动杆菌和肠球菌的分离及耐药性调查分析

目的了解医院感染不动杆菌和肠球菌的分离及耐药情况,为临床合理用药提供依据。方法采用回顾性资料,对医院2008年9月至2010年12月,从临床送检标本中分离到的不动杆菌和肠球菌及其药敏结果进行统计分析。结果从临床标本中分离到191株不动杆菌和319株肠球菌,不动杆菌主要来源是痰液,达77.50%,肠球菌主要来源是尿液、痰液,分别为31.70%和28.8%。不动杆菌对亚胺培南耐药率最低,为10.3%,对头孢噻肟耐药率最高,为7 2.0%,而其余各种抗生素耐药率均处于47%～60%,肠球菌对万古霉素耐药率最低,为2.0%,耐药率最高是四环素为63.9%,对高浓度的庆大霉素和链霉素耐药率分别是52.8%和39.4%。结论医院感染不动杆菌和肠球菌的分离及耐药性高,且呈多重耐药,临床要关注。     

糖尿病足患者病原菌分布及其耐药性

目的研究糖尿病足患者病原菌分布情况及其耐药性,为后续研究提供参考。方法选择2016年1月至2018年12月间在我院接受治疗的116例糖尿病足感染(DFI)患者为研究对象,患者入院后使用抗生素之前,在感染部位提取样本进行细菌检测,确定DFI感染病原菌特点及主要病原菌耐药情况。结果 2016年收治的35例DFI患者病原菌检出率为71.43%。2017年收治的38例DFI患者病原菌检出率为71.05%。2018年收治的43例DFI患者病原菌检出率为72.09%。3年内DFI患者革兰阴性菌总阳性率呈下降趋势,革兰阳性菌总阳性率呈上升趋势。铜绿假单胞菌对庆大霉素及氨曲南耐药性最高,对丁胺卡霉素及亚胺培南耐药性最低,耐药性为0.00%。奇异变形菌对氨曲南耐药性最高,为46.15%,而对他唑巴坦、美罗培南、替卡西林、丁胺卡霉素及亚胺培南耐药性最低,均为0.00%。葡萄球菌对红霉素及青霉素G呈高耐药性,对亚胺培南及莫西沙星耐药性最低,均为0.00%。肠球菌对红霉素、丁胺卡霉素、头孢曲松耐药性均达100.00%,而对青霉素G、阿莫西林/棒酸的耐药性为0.00%。结论 DFI患者病原菌分布会随时间变迁而改变,及时、反复的细菌培养和药敏试验是合理应用抗生素,减少细菌耐药性的前提,其在控制患者糖尿病足感染程度,改善患者预后中具有重要意义。     

A novel antibiotic free plasmid selection system: advances in safe and efficient DNA therapy

The presence of antibiotic resistance genes in the delivered plasmids is one of the drawbacks of modern gene therapy and DNA vaccine applications. Here, we describe a strategy that allows for plasmid selection in bacterial hosts, without the requirement of any selection marker. Several bacterial strains were modified, so that the plasmid's replicational inhibitor RNA I could suppress the translation of a growth essential gene by RNA-RNA antisense reaction. An essential gene (murA) was modified such that a repressor protein (tetR) would hamper its expression. Only in the presence of plasmid and, hence, RNA I, was tetR turned down and murA expressed. Different commercially available plasmids could be selected by various modified Escherichia coli strains. We further designed a minimalistic plasmid devoid of any selection marker. All of the clones (n=6) examined, when the modified strain JM109-murselect was used for selection, contained plasmids. Thus, we have designed bacterial host strains that for the first time serve to select and maintain plasmids without the use of any selection marker or other additional sequence on the plasmid. Consequently, such plasmids may not only be safer, but due to their decreased size, advantages for the manufacturer and higher transfection efficiencies are anticipated.     

Shinrin-yoku (forest-air bathing and walking) effectively decreases blood glucose levels in diabetic patients

 The influence of ”shinrin-yoku” (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg · 100 ml^–1 to 108 (SEM 2) mg · 100 ml^–1 (P<0.0001). The level of glycated haemoglobin A_1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P<0.05). Blood glucose values declined by 74 (SEM 9) mg · 100 ml^–1 and 70 (SEM 4) mg · 100 ml^–1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels. Received: 9 July 1997/Accepted: 20 October 1997     

Zinc and copper in the serum of diabetic patients

The Zn/Cu ratio was examined in the serum of three groups of persons: healthy volunteers, diabetic patients on diabetic diet (NIDDM), and diabetic patients on diabetic diet and insulin (IDDM). Zinc, copper, the Zn/Cu serum ratio, and the blood glucose level were determined during fasting and 2 h after breakfast. Zn and Cu serum levels in NIDDM and IDDM patients were decreased. The Zn/Cu ratio was higher in both groups of diabetic patients. These changes in the Zn and Cu levels as well as in the Zn/Cu ratio were not related to chronic diabetic complications.     

Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats

Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (P<0.05). Additionally, peripheral blood mononuclear cells isolated from glycine-treated diabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (P<0.05). Glycine-treated rats had a less intense corporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.     

糖尿病足复发感染病原菌的分布及耐药性分析

目的对糖尿病足复发感染病原菌的分布及耐药性进行分析。方法选取杭州师范大学附属医院2014年6月至2015年6月收治的且符合纳入标准的糖尿病足复发感染患者120例。对所有患者糖尿病足复发感染病原菌的分布及耐药性进行分析。结果 120例糖尿病足复发感染患者共检出病原菌145株,其中18例为混合细菌感染。145株细菌中革兰阳性菌91株(62.8%),前三位的分别为金黄色葡萄球菌、粪肠球菌、链球菌,分别占28.3%、24.8%、6.2%;革兰阴性菌41株(28.3%),以大肠埃希菌、绿脓假单胞菌属、奇异变形杆菌为主,分别占6.9%、6.2%、5.5%。不同病原菌对常用抗菌药物呈现不同程度的耐药;革兰阳性球菌对青霉素、红霉素耐药严重,而对头孢曲松、万古霉素较为敏感,对万古霉素未出现耐药情况。革兰阴性菌对亚胺培南、美罗培南均敏感,其次对阿米卡星较敏感,对氨苄西林耐药率最高。结论糖尿病足患者复发感染病原菌分布广泛,应根据药物敏感性试验结果及时调整抗菌药物,以利于促进创面早期愈合。     

Sodium molybdate improves the phagocytic function in alloxan-induced diabetic rats

Diabetes mellitus is a disease, which virtually affects all the systems in the body including the immune system. Bacterial infections are important causes of increased morbidity and mortality in diabetic patients. In the present study, we assessed the effect of molybdate on immune responses of diabetic rats. The phagocytic potency and nitroblue tetrazolium dye reduction capacity were found to be considerably lowered whereas soluble immune complex formation enhanced significantly in diabetic rats when compared with control rats. From our findings, it is suggested that dietary intake of molybdate may have a vital role in enhancing immune functions during diabetic mellitus.     

Direction of aminoacylated transfer RNAs into antibiotic synthesis and peptidoglycan-mediated antibiotic resistance

Prokaryotic aminoacylated-transfer RNAs often need to be efficiently segregated between translation and other cellular biosynthetic pathways. Many clinically relevant bacteria, including Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa direct some aminoacylated-tRNA species into peptidoglycan biosynthesis and/or membrane phospholipid modification. Subsequent indirect peptidoglycan cross-linkage or change in membrane permeability is often a prerequisite for high-level antibiotic resistance. In Streptomycetes, aminoacylated-tRNA species are used for antibiotic synthesis as well as antibiotic resistance. The direction of coding aminoacylated-tRNA molecules away from translation and into antibiotic resistance and synthesis pathways are discussed in this review.     

The relationship between short-term antibiotic treatments and fatigue in healthy individuals

Antibiotic treatment tends sometimes to result in sensations of fatigue and decreased physical performance. The effects of antibiotics were therefore studied in 50 healthy, male trainees, aged 18–25 years, assigned in a random, double-blind fashion to one of the following treatments: tetracycline, ampicillin, trimethoprim/sulphamethoxazole, placebo I and placebo II. Duration of treatment was five times the half-life of each agent and the placebo was matched accordingly. Muscle enzyme activity (serum glutamine oxaloacetate transaminase, lactate dehydrogenase, creatine phosphokinase), maximal aerobic capacity ( O_2max), muscle strength (MS), and rating of subjective sensation of fatigue were assessed prior to and upon conclusion of treatment. Compared to pretreatment values, plasma enzymes activity was elevated in all five groups (P<0.005). No differences in O_2max or in MS were found among the subjects treated with either one of the antibiotics or those given a placebo. A significant difference in O_2max was found between the groups treated for 1 day (antibiotic and placebo) and the groups treated for 3 days (antibiotic and placebo) (P<0.0001). The rating of subjective sensation was not affected by any of the agents. We concluded that in healthy individuals, a short-term antibiotic treatment had no deleterious effect on aerobic capacity or on muscle strength and was not associated with subjective side effects. The time interval between the two maximal tests could, however, have affected the aerobic capacity. Physiological disturbances associated with a sensation of fatigue following a longer period of antibiotics cannot be excluded.