瑞舒伐他汀联合氨氯地平对ox-LDL诱导的人单核巨噬细胞MMP-9mRNA和蛋白表达的影响

目的瑞舒伐他汀联合氨氯地平降低对氧化修饰的低密度脂蛋白(ox-LDL)诱导的健康人单核巨噬细胞基质金属蛋白酶-9(MMP-9)mRNA及蛋白的表达进而促进粥样斑块的稳定。方法体外密度梯度离心法分离并培养单核巨噬细胞并传至2代～4代用于实验,根据实验要求分为空白对照组(单核巨噬细胞培养24h)、ox-LDL对照组(ox-LDL 100μg/mL诱导后单独培养24h)、瑞舒伐他汀组(单独加入瑞舒伐他汀0.01μmol/L、0.1μmol/L、1.0μmol/L培养24h)、瑞舒伐他汀联合氨氯地平组(加入不同剂量瑞舒伐他汀联合氨氯地平0.01μmol/L、0.1μmol/L、1.0μmol/L共同作用24h);分别提取各组细胞RNA,用半定量逆转录聚合酶链式反应法(RT-PCR)测定MMP-9mRNA表达;用ELISA法测定MMP-9的蛋白含量。结果单核巨噬细胞经100μg/mLox-LDL诱导后,与空白对照组比较MMP-9mRNA和蛋白表达显著增加;ox-LDL诱导后不同剂量瑞舒伐他汀联合氨氯地平组,与ox-LDL对照组及瑞舒伐他汀组比较可加强抑制MMP-9mRNA和蛋白表达作用。并呈剂量-效应关系,差异有统计学意义(P<0.05)。结论外周血单核巨噬细胞在ox-LDL诱导后,MMP-9mRNA和蛋白含量明显增加,瑞舒伐他汀与氨氯地平联合后,可以加强抑制单核巨噬细胞MMP-9mRNA和蛋白表达的作用,进而增强急性冠脉综合征(ACS)患者粥样斑块的稳定性。     

阿托伐他汀对THP-1源性巨噬细胞CD40及MMP-9的抑制作用

目的观察他汀类药物对人单核/巨噬细胞(THP-1细胞)基质金属蛋白酶-9(MMP-9)的表达是否存在抑制作用及其作用是否与CD40-CD40L信号通路有关,探讨他汀类药物可能的非调脂抗动脉粥样硬化机制。方法先加入不同浓度的阿托伐他汀(1.25μmol/L、2.50μmol/L、5.00μmol/L)作用1h,再向培养的THP-1细胞中加入氧化型低密度脂蛋白(80mg/L)共同孵育24h,分别运用反转录聚合酶链反应(RT-PCR)法检测CD40及MMP-9mRNA,酶联免疫吸附测定法(ELISA)测定培养基的MMP-9浓度。结果阿托伐他汀抑制THP-1细胞CD40和MMP-9mRNA的表达,同时抑制MMP-9蛋白的表达(P<0.05),并呈浓度依赖性。结论阿托伐他汀能抑制THP-1细胞CD40的表达以及MMP-9的表达和分泌,这种作用可能是他汀类药物减轻动脉粥样斑块炎症,防止斑块破裂的机制之一。     

Ang-Ⅱ对血管内皮细胞线粒体膜电位的影响及阿托伐他汀的保护作用

目的:观察血管紧张素-Ⅱ(Ang-Ⅱ)对血管内皮细胞线粒体膜电位的影响及阿托伐他汀的保护作用.方法:将血管内皮细胞分为:空白对照组(仅给予细胞培养液)、Ang-Ⅱ组(细胞培养液中加入Ang-Ⅱ,使其终浓度为10-7mol/L)、Ang-Ⅱ加小剂量阿托伐他汀组(在单纯Ang-Ⅱ组的基础上加入阿托伐他汀,使阿托伐他汀的终浓度为0.1 μmol/L)、Ang-Ⅱ加大剂量阿托伐他汀组(在单纯Ang-Ⅱ组的基础上加入阿托伐他汀,使阿托伐他汀的终浓度为1 μmol/L).用激光共聚焦显微镜测量各组细胞的线粒体膜电位水平.结果:①Ang-Ⅱ组的线粒体膜电位显著低于空白对照组(P<0.01);②Ang-Ⅱ加阿托伐他汀组的线粒体膜电位显著高于Ang-Ⅱ组(P<0.01).③Ang-Ⅱ加大剂量阿托伐他汀组的线粒体膜电位水平高于Ang-Ⅱ加小剂量阿托伐他汀组(P<0.05).结论:Ang-Ⅱ可引起血管内皮细胞线粒体膜电位的显著降低,而阿托伐他汀可呈剂量依赖性的逆转Ang-Ⅱ的这一作用.     

瑞舒伐他汀对ox-LDL诱导的人单核巨噬细胞MMP-9 mRNA和蛋白表达的影响

目的 探讨瑞舒伐他汀对ox-LDL诱导的健康人单核巨噬细胞基质金属蛋白酶-9（MMP-9）mRNA及蛋白表达的影响.方法 体外密度梯度离心法分离并培养单核巨噬细胞并传至2～4代用于实验.单核巨噬细胞培养24 h作为空白对照组,ox-LDL 100 mg/ml培养24 h作为ox-LDL对照组,实验组分别用ox-LDL 100 mg/ml培养2 h后,各加入不同剂量瑞舒伐他汀（0.01、0.1、1.0、10.0 μmol/L）共同作用24 h.分别提取各组细胞RNA,用半定量逆转录聚合酶链式反应法（RT-PCR）测定MMP-9 mRNA表达,用ELISA法测定MMP-9的蛋白含量.结果 单核巨噬细胞经100 mg/ml ox-LDL诱导后,与空白对照组比较MMP-9mRNA和蛋白表达显著增加;ox-LDL诱导后,不同剂量瑞舒伐他汀组与ox-LDL对照组比较MMP-9 mRNA和蛋白表达显著降低,并呈剂量-效应关系,P＜0.05;与空白对照组比较,瑞舒伐他汀10.0μmol/L组MMP-9蛋白表达无明显变化,差异无统计学意义（P＞0.05）.结论 外周血单核巨噬细胞在ox-LDL诱导后,MMP-9mRNA和蛋白含量明显增加.瑞舒伐他汀呈剂量依赖性,可能通过ox-LDL途径来下调人单核巨噬细胞MMP-9 mRNA和蛋白含量的表达,起到抗炎和稳定斑块的作用.     

西立伐他汀抑制单核细胞基质金属蛋白酶及组织因子的表达及活性

目的观察西立伐他汀对单核/巨噬细胞系的THP-1细胞的基质金属蛋白酶-2(matrixmetalloproteinase-2,MMP-2)及组织因子(tissuefactor,TF)的表达及活性的作用.方法培养的THP-1细胞中加入不同浓度的西立伐他汀,用RT-PCR法检测MMP-2及TFmRNA,酶原电泳法测定培养基中MMP-2活性,ELISA法测定细胞内TF抗原.结果随着西立伐他汀浓度增加,THP-1细胞的MMP-2及TFmRNA水平逐渐降低.在1μmol/L时MMP-2mRNA从93.5±10.2降至58.9±8.2,P＜0.05.对培养基中MMP-2活性的抑制作用呈浓度依赖性.0.1、1.0μmo1/L时的光密度值分别从667.7±41.1降至498.8±7.4、469.0±21.4(P＜0.05).THP-1细胞的TFmRNA水平在浓度为0.1、1.0μmol/L时,分别降低36%及67%(80.0±15.7及41.3±16.4vs125.1±21.0,P＜0.05).细胞内TF抗原含量在1μmol/L时减少50%(0.22±0.04vs0.43±0.06,P＜0.05).结论西立伐他汀能抑制THP-1细胞表达MMP-2及TF,降低MMP-2及TF活性.     

阿托伐他汀对培养的兔脂肪细胞凝血和纤溶因子的影响及其机制

目的:观察阿托伐他汀对培养的兔脂肪细胞表达组织因子(TF,凝血因子Ⅲ)、I型纤溶酶原激活物抑制剂(PAI1)的影响,并探讨其可能的作用机制。方法:取正常兔(n=4)脂肪组织分离培养脂肪细胞,实验分3组:空白对照组、阿托伐他汀干预组和甲羟戊酸加阿托伐他汀干预组,后两组分别设有不同浓度,以阿托伐他汀或甲羟戊酸孵育兔脂肪细胞24小时后收集细胞。逆转录聚合酶链反应测定脂肪细胞TF和PAI1信使核糖核酸(mRNA)表达。用酶联免疫吸附法测定TF和PAI1蛋白浓度。结果:阿托伐他汀干预组随着阿托伐他汀浓度的增加,TF和PAI1蛋白水平逐渐下降,在阿托伐他汀浓度为10μmol/L时,其抑制作用最大,脂肪细胞TF、PAI1蛋白水平较空白对照组有极显著性差异(P<0.01)。甲羟戊酸加阿托伐他汀干预组加入1μmol/L甲羟戊酸后阿托伐他汀对脂肪细胞TF、PAI1mRNA表达的抑制作用可以被甲羟戊酸逆转,与空白对照组比较,有极显著性差异(P<0.01);加入100μmol/L的甲羟戊酸几乎完全逆转了阿托伐他汀对脂肪细胞TF、PAI1mRNA表达的抑制作用。结论:阿托伐他汀能抑制兔脂肪细胞TF、PAI1mRNA和蛋白表达,其机制可能是通过甲羟戊酸代谢途径实现的。     

阿托伐他汀对高葡萄糖诱导的血管平滑肌细胞增殖的抑制作用

目的研究阿托伐他汀对醛糖还原酶(AR)和核因子NF-κB的表达及血管平滑肌细胞增殖的影响,探讨阿托伐他汀抗细胞增殖的可能机制。方法用高浓度葡萄糖诱导大鼠血管平滑肌细胞(VSMC)AR基因表达,然后加入不同浓度的阿托伐他汀,培养3d后用台盼蓝染色行细胞计数。并采用RT-PCR、免疫组化、原位杂交等方法,观察阿托伐他汀对NF-κB和AR基因表达及VSMC增殖的影响。结果1)随着阿托伐他汀浓度的提高,VSMC计数逐渐减少。2)正常浓度葡萄糖(5·6mmol/L)时,NF-κB表达不明显,高浓度葡萄糖(22·5mmol/L)时,NF-κB表达强阳性,阿托伐他汀则可明显抑制这一表达,0·1μmol/L阿托伐他汀时,NF-κB表达即有降低,10μmol/L阿托伐他汀几乎完全抑制NF-κB的表达。3)高浓度葡萄糖可明显诱导AR基因的表达,阿托伐他汀对其表达有抑制作用,且呈剂量依赖性。与高浓度葡萄糖组相比,阿托伐他汀0·1、1、10μmol/L分别使VSMC的ARmRNA下调12%、45%和80%(P均<0·05)。结论1)阿托伐他汀可抑制VSMC增殖。2)阿托伐他汀可抑制AR及NF-κB的表达。3)阿托伐他汀可能是通过抑制AR及NF-κB的表达继而抑制VSMC的增殖。     

阿托伐他汀对氧化型低密度脂蛋白诱导的人脐静胁内皮细胞增殖及白细胞介素-18分泌的影响

目的:观察阿托伐他汀对氧化型低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVEC)增殖及白细胞介素-18(IL-18)分泌的影响.方法:体外培养的HUVEC株,第3～9代用于实验.实验分3组:①空白对照组;②ox-LDL组(100 mg/L);③阿托伐他汀组:先将阿托伐他汀0.01、0.05、0.1、0.5、1.0μmol/L分别,作用于内皮细胞4 h,然后加ox-LDL(100 mg/L)作用细胞24 h.采用细胞酶联免疫吸附分析检测细胞培养上清液IL-18含量;采用四唑盐比色法检测各孔的吸收度(OD),以评价增殖效果.结果:与空白对照组比较,100 mg/L ox-LDL抑制内皮细胞增殖(P＜0.01),阿托伐他汀呈剂量依赖性地促进ox-LDL诱导的内皮细胞增殖(P＜0.05,P＜0.01).正常内皮细胞不分泌IL-18,而100 mg/L ox-LDL促进IL-18分泌.0.01/μmol/L阿托伐他汀对ox-LDL诱导的HUVEC分泌IL-18无影响(P＞0.05),0.05,0.1,0.5,1.0 μmol/L阿托伐他汀能明显抑制oxLDL诱导的HUVEC分泌IL-18(P＜0.05,P＜0.01),抑制效应呈浓度依赖性.结论:阿托伐他汀呈剂量依赖性地抑制ox-LDL诱导的人HUVECs分泌IL-18,促进内皮细胞增殖,保护内皮功能,从而发挥他汀类药物调脂外抗动脉粥样硬化作用.     

阿托伐他汀对人肺腺癌细胞的凋亡作用及其调控机制研究

目的研究阿托伐他汀对人肺腺癌(A549)细胞的抑制作用,并探讨可能的作用机制。方法采用CCK-8法检测不同浓度(0、10、20、40μmol/L)阿托伐他汀对A549细胞增殖的影响; AnnexinV-FITC/PI双染后流式细胞术检测不同浓度阿托伐他汀(0、10、20、40μmol/L)对A549细胞凋亡的影响;分光光度法检测不同浓度阿托伐他汀(0、10、20、40μmol/L)对A549细胞caspase-3活性的影响。结果阿托伐他汀抑制A549细胞的增殖,随着浓度的增加,时间的延长,其抑制作用逐渐增强(P0.01)。阿托伐他汀能有效地诱导A549细胞的凋亡,随着浓度的增加,凋亡率增加。阿托伐他汀显著增加A549细胞的caspase-3酶的活性,且呈剂量相关性。结论阿托伐他汀抑制人肺癌A549细胞增殖,促进其凋亡,并且呈明显的时间和剂量依赖,阿托伐他汀通过增加细胞Caspase-3的活性诱导A549细胞凋亡。     

阿托伐他汀对高葡萄糖诱导的血管平滑肌细胞增殖的抑制作用

目的研究阿托伐他汀对醛糖还原酶(AR)和核因子NF-κB的表达及血管平滑肌细胞增殖的影响,探讨阿托伐他汀抗细胞增殖的可能机制.方法用高浓度葡萄糖诱导大鼠血管平滑肌细胞(VSMC)AR基因表达,然后加入不同浓度的阿托伐他汀,培养3 d后用台盼蓝染色行细胞计数.并采用RT-PCR、免疫组化、原位杂交等方法,观察阿托伐他汀对NF-κB和AR基因表达及VSMC增殖的影响.结果 1)随着阿托伐他汀浓度的提高,VSMC计数逐渐减少.2)正常浓度葡萄糖(5.6 mmol/L)时, NF-κB表达不明显,高浓度葡萄糖(22.5 mmol/L)时,NF-κB表达强阳性,阿托伐他汀则可明显抑制这一表达,0.1 μmol/L阿托伐他汀时, NF-κB表达即有降低,10 μmol/L阿托伐他汀几乎完全抑制NF-κB的表达.3)高浓度葡萄糖可明显诱导AR基因的表达,阿托伐他汀对其表达有抑制作用,且呈剂量依赖性.与高浓度葡萄糖组相比,阿托伐他汀0.1、1、10 μmol/L分别使VSMC的AR mRNA下调12%、45%和80%(P均＜0.05).结论 1)阿托伐他汀可抑制VSMC增殖.2)阿托伐他汀可抑制AR及NF-κB的表达.3)阿托伐他汀可能是通过抑制AR及NF-κB的表达继而抑制VSMC的增殖.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Language of CTO interventions – Focus on hardware

The knowledge of variety of chronic total occlusion (CTO) hardware and the ability to use them represents the key to success of any CTO interventions. However, the multiplicity of CTO hardware and their physical character and the terminology used by experts create confusion in the mind of an average interventional cardiologist, particularly a beginner in this field. This knowledge is available but is scattered. We aim to classify and compare the currently used devices based on their properties focusing on how physical character of each device can be utilized in a specific situation, thus clarifying and simplifying the technical discourse.     

High prevalence of distal sensory polyneuropathy in antiretroviral-treated and untreated people with HIV in Tanzania

Objectives To describe the prevalence of distal sensory polyneuropathy (DSP), a complication of both advanced HIV disease and of antiretroviral therapy (ART), amongst Tanzanians with HIV, on and off ART (including stavudine) with CD4 counts above and below 200 cells/μl. Methods We recruited participants attending ART clinic into four groups: >6 months ART exposure and (i) CD4 < 200 cells/μl or (ii) CD4 > 200 cells/μl (ART/CD4 < 200 and ART/CD4 > 200, respectively); ART‐naïve and (iii) CD4 < 200 cells/μl or iv)CD4 > 200 cells/μl (noART/CD4 < 200 and noART/CD4 > 200, respectively). Primary outcome was DSP, as defined by presence of at least one symptom and one sign. Results Of 326 evaluable participants, 81 (32 men, median age 38 years, median CD4 142 cells/μl) were enrolled in the ART/CD4 < 200 group, 78 (17 men, median age 37 years, median CD4 345 cells/μl) in ART/CD4 > 200, 81 (30 men, median age 37 years, median CD4 128 cells/μl) in noART/CD4 < 200 and 86 (22 men, median age 33 years, median CD4 446 cells/μl) in noART/CD4 > 200. Numbness was the most commonly reported symptom. DSP prevalence ranged from 43.2% in ART/CD4 < 200 to 20.9% in noART/CD4 > 200. DSP was more common among men (adjusted odds ratio [aOR] 1.9, 95% confidence interval [CI] 1.2–3.3) and older participants (aOR 2.7, 95% CI 1.1–6.2 for age 40 + vs. <30 years). Conclusion Distal sensory polyneuropathy is common amongst those attending this clinic, even those with no ART exposure and a CD4 count above 200 cells/μl. Stavudine and didanosine expose HIV‐infected patients to an additional avoidable risk of DSP. Access to non‐neurotoxic ART regimes as well as earlier HIV diagnosis and initiation of ART is needed.