Comparison of cisternal and lumbar cerebrospinal fluid pH in high altitude natives

Samples of cisternal or lumbar cerebrospinal fluid were obtained from 20 young male volunteers born and living at high altitude (3500 to 4800 m). The pH, carbon dioxide and oxygen tensions, and bicarbonate concentration were measured and compared with those in the arterial and jugular venous blood. A consistent difference between the two CSF compartments was noted, particularly a lower pH (0.05), a higher PCO2 (7 Torr), and a lower PO2 (7 Torr) at the lumbar site. Mean bicarbonate concentration was not significantly different at the two sites. The main factor is PCO2, which controls the pH variation. These differences were more marked in high-altitude natives than in man at sea level. The existence of a consistent inhomogeneity of CSF acid-base content emphasizes the inaccuracy of using lumbar CSF pH to estimate the ECF pH as regulator of pulmonary ventilation and determinant of cerebral blood flow.     

Different adaptation patterns of antioxidant system in natives and sojourners at high altitude

Comparative studies on the adaptation pattern of antioxidant status among high altitude natives and acclimatized sojourners are very scanty. The aim of the present study was to compare the differences in antioxidant profile between two groups of active male volunteers, i.e. native highlanders (HAN, n = 66) in their natural hypoxic environment with that of sojourners (SOJ, n = 81) from sea level (SL) after 4 weeks of stay at an altitude of 4560 m. Blood samples of SOJ were collected at SL and HA. Same was collected from HAN once at HA. HAN had significantly higher SOD activity and significantly lower catalase, GPX and GR activities than SOJ at HA. Ratio of GSH/GSSG was also significantly higher in HAN than SOJ at HA. In SOJ, antioxidant profile showed an upregulation after HA stay but it was not effective to reduce the levels of oxidative stress markers. Therefore, it can be stated that lifelong exposure to hypoxia has beneficial adaptive effects on antioxidant system in HAN. Similarly, acclimatization to HA also has beneficial preconditioning effects on antioxidant system in SOJ, but, may not be sufficient to ameliorate oxidative stress completely. Transient increase in metabolic rate due to hypoxia may be a causative factor for excess free radical generation among sojourners at HA.     

Population genetic aspects and phenotypic plasticity of ventilatory responses in high altitude natives

Highland natives show unique breathing patterns and ventilatory responses at altitude, both at rest and during exercise. For many ventilatory traits, there is also significant variation between highland native groups, including indigenous populations in the Andes and Himalaya, and more recent altitude arrivals in places like Colorado. This review summarizes the literature in this area with some focus on partitioning putative population genetic differences from differences acquired through lifelong exposure to hypoxia. Current studies suggest that Tibetans have high resting ventilation (V (E)), and a high hypoxic ventilatory response (HVR), similar to altitude acclimatized lowlanders. Andeans, in contrast, show low resting V (E) and a low or "blunted" HVR, with little evidence that these traits are acquired via lifelong exposure. Resting V (E) of non-indigenous altitude natives is not well documented, but lifelong hypoxic exposure almost certainly blunts HVR in these groups through decreased chemosensitivity to hypoxia in a process known as hypoxic desensitization (HD). Together, these studies suggest that the time course of ventilatory response, and in particular the origin or absence of HD, depends on population genetic background i.e., the allele or haplotype frequencies that characterize a particular population. During exercise, altitude natives have lower V (E) compared to acclimatized lowland controls. Altitude natives also have smaller alveolar-arterial partial pressure differences P(AO2) - P(aO2) during exercise suggesting differences in gas exchange efficiency. Small P(AO2) - P(aO2) in highland natives of Colorado underscores the likely importance of developmental adaptation to hypoxia affecting structural/functional aspects of gas exchange with resultant changes in breathing pattern. However, in Andeans, at least, there is also evidence that low exercise V (E) is determined by genetic background affecting ventilatory control independent of gas exchange. Additional studies are needed to elucidate the effects of gene, environment, and gene-environment interaction on these traits, and these effects are likely to differ widely between altitude native populations.     

模拟急进高原过程对清醒和麻醉状态大鼠血压和呼吸的影响

目的:为了全面地反映急进高原过程中机体的一些真实改变,本实验通过动态监测清醒和麻醉2种不同状态下大鼠血流动力学指标,旨在探讨清醒和麻醉状态大鼠在急性缺氧时血流动力学的差异,并以此进一步探讨其可能的机制。方法:实验将SD大鼠随机分为麻醉组、清醒组、5 000 m麻醉对照(A-5000-control)组、5 000m麻醉氨基胍(A-5000-AG)组、5 000 m清醒对照(C-5000-control)组和5 000 m清醒氨基胍(C-5000-AG)组。麻醉组和清醒组大鼠在低压氧舱从2 260 m开始,以2 m/s模拟急进高原5 000 m过程;其余4组均在模拟5 000 m海拔条件下进行。实验期间通过Power Lab生理记录仪实时、动态地监测整个过程中大鼠的系统动脉压(system arterial pressure,Psa)、中心静脉压(central venous pressure,CVP)、心率(heart rate,HR)和呼吸频率(breathing rate,BR)。结果:清醒组大鼠的HR和BR明显高于麻醉组,但MAP明显低于麻醉组。随着海拔的逐渐升高,清醒组和麻醉组大鼠均出现平均动脉压(mean arterial pressure,MAP)降低,且清醒组大鼠降低更为显著。另外,在5 000 m时,清醒组大鼠HR明显降低,而整个过程中2组大鼠的BR均无明显改变。静脉注射诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)抑制剂氨基胍后,C-5000-AG组和A-5000-AG组大鼠动脉血压均明显升高,而HR和BR未见明显变化。结论:在急进高原过程中,血压和心率会明显下降,而呼吸频率变化不大。该现象可能的机制为:急性缺氧早期机体启动自我保护机制,活化i NOS,大量产生并释放NO,使血管舒张,可调节肺通气、引起血压下降;达到海拔5 000 m左右甚至更早时,机体可能出现失代偿,使心率减慢,引起血压进一步降低。由于受麻醉药物戊巴比妥钠的影响,麻醉状态的大鼠血压下降出现得较为迟缓,而清醒大鼠对急进高原性低氧反应迅速,能够更真实全面地反映急进高原过程中低氧引起的血流动力学改变。     

Body composition of high altitude natives on descent to the plains: A densitometric,hydrometric, and anthropometric evaluation

Summary Body density was experimentally determined at a field location at 3,920 m on 32 medically fit and active high altitude native males using a water displacement technique. Stature, body weight and the bony widths at the elbow, wrist, knee, and ankles; and thickness of skin folds at eight sites were measured. Based on body density and bony widths, body fat, total body water (TBW), mineral mass and total cell solids (TCS) were calculated.Similar measurements were made on another group of 16 high altitude natives after one months stay in Dehli (200 m). TBW of 11 of these subjects was experimentally determined by the oral administration of 200 Ci of tritiated water. This group of subjects was physically less active in Delhi. At high altitude the natives consumed a balanced diet which provided 20.21 MJ, but in the plains the diet provided only 15.69 MJ though it was nutritionally balanced.In spite of the reduced calorie intake this group showed greater fat content in Delhi than the group located at high altitude. These men were also hyperhydrated. Hyperhydration of the lean body could be an adaptive response of the high altitude natives to the new environment. Due to the disturbed state of hydration of the lean body of these men in the plains, use of Siri's formula for the computation of total body fat is questioned.     

高原肺水肿患者血流动力学变化及对吸氧反应的测定

目的:探讨高原肺水肿的发病机理。方法:采用右心漂浮导管检测法, 对9例高原肺水肿患者及9例同海拔高原健康人的血流动力学指标进行了检测, 同时也观察了吸入纯氧对高原肺水肿患者血流动力学的影响。结果:高原肺水肿患者发病时, 肺动脉平均压、肺血管阻力、心脏指数均明显高于同海拔高度健康人, 而患者肺动脉楔压, 右心房压力同对照组相比, 未见显著差异;吸氧后, 高原肺水肿患者心率、肺动脉平均压力, 肺血管阻力及心脏指数均较吸氧前明显下降, 特别是肺动脉平均压及肺血管阻力下降尤为明显, 肺动脉平均压力在吸氧1min后即明显下降, 吸氧5min后, 下降至最低值, 但吸氧20min后仍未达对照组水平。结论:高原肺水肿是非心源性肺水肿, 肺动脉高压在其发病中起重要作用。     

急性高原病患者支气管肺泡灌洗前后肺功能及血气的改变

目的:探讨急性高原反应(HAAR)及高原肺水肿(HAPE)的发病机理。方法:对10例HAAR患者及6例HAPE患者灌洗前和灌洗后进行肺功能和动脉血气检测, 并与10例高原健康者进行对比。结果:HAAR患者及HAPE患者灌洗前动脉血氧分压明显低于对照组, HAAR同HAPE均存在弥散功能障碍;HAPE肺弥散功能(DLCO%)由灌洗前的(76.01±6.29)%, 上升到灌洗后的(103.31±9.23)%;气体转化因子(DLCO/VA%)由灌洗前的(150.30±15.20)%, 上升到灌洗后的(176.04±16.10)%;动脉血氧分压(PaO₂)由(31.73±3.01)mmHg上升到(45.31±3.56)mmHg。而HAAR及对照组灌洗后上述指标差异不显著。结论:HAPE患者肺泡内大量的液体渗出是HAPE病情恶化的主要原因之一。HAAR属HAPE发展的初级阶段, 存在着间质性肺水肿。     

Effects of long-term testosterone exposure on ovarian function and morphology in the rhesus monkey

This study was aimed at developing a model in the rhesus monkey for the human gynecologic disorder termed the polycystic ovary syndrome (PCOS). The effects of chronic constant androgen exposure upon quantitative ovarian morphology and ovulatory function were examined. Twenty-five normally cycling females, aged 4-12 yr and weighing 3.3-8.2 kg, were enrolled in the study in random fashion. Seventeen animals were implanted subcutaneously (s.c.) with 10 or 25 mg testosterone-filled silastic tubing so as to maintain steady serum levels of testosterone averaging 80 ng/dl (low-dose group, n = 8) and 115 ng/dl (high-dose group, n = 9) for 13-16 months. Eight animals served as controls (sham implants); in these, mean serum testosterone levels averaged 24 ng/dl. No effect of androgen treatment was observed on ovulatory function as gauged by periodic luteal phase progesterone determinations and the presence of a fresh corpus luteum at laparoscopy. Menstrual cycle frequency (number of cycles over number of months of observation) was, however, slightly but significantly (P less than 0.05) reduced in the high-dose (88.9%) vs. the control (96.7%) and low-dose (95.0%) groups. Quantitative morphology, performed by light microscopy on a single ovary obtained from 16 of the 25 animals and read in a blinded fashion, revealed no differences in ovarian weight, capsular width and numbers, size, or proportion of healthy and atretic follicles among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性低氧时牦牛和迁饲黄牛颈动脉体组织形态的比较

目的对牦牛、迁饲黄牛及低海拔黄牛颈动脉体(CB)形态及CB中低氧相关因子的表达进行比较,探讨高原土生或迁饲动物CB适应慢性低氧的模式。方法采集青海地区海拔3000~4000m的9头牦牛、2500m的9头高山迁饲黄牛及甘肃平原海拔1300米的12头低海拔黄牛的CB,固定、切片、染色后行光学显微镜和电子显微镜比较观察,并对CB中低氧诱导因子-1α(HIF-1α)、一氧化氮合酶(NOS)、瘦素受体(LEPR)、促红细胞生成素(EPO)等低氧相关因子的表达进行免疫组织化学观察。结果相比黄牛,牦牛CB体积较小,不同海拔牦牛的CB大小、形态及主细胞数量差异无显著性,而迁饲黄牛CB体积较低海拔黄牛大。牦牛CB主细胞中明细胞、暗细胞和固缩细胞的数量百分比比例为67.1%∶28.2%∶4.7%,迁饲黄牛为78.5%∶18.6%∶2.9%,低海拔黄牛为87.3%∶10.2%∶2.5%;与低海拔黄牛相似,牦牛CB少部分明细胞胞质透亮,暗细胞胞核染色质较致密并呈粗颗粒状,而迁饲黄牛CB大部分明细胞胞质透亮,暗细胞胞核染色质致密,颗粒稀少。3种牛支持细胞形态差异无显著性。与低海拔黄牛相比,迁饲黄牛CB主细胞的少数核异染色质增多,个别形态异常,胞质内多数细胞器肿胀溶解,残留少量细胞器和致密核心囊泡。3种牛CB中均有不同程度的HIF-1a、NOS、LEPR、EPO的蛋白表达,其中牦牛CB中EPO蛋白表达阳性率较低海拔黄牛明显降低(P0.05)。结论海拔高度不是影响牦牛颈动脉体大小和主细胞数量的主要因素。迁饲黄牛CB主细胞中细胞类型的比例与牦牛有趋同性改变,但缺氧时行使功能的I型细胞功能系统受损,尚处于低氧环境下的习服阶段。慢性低氧可能主要影响牦牛和迁饲黄牛CB中EPO蛋白表达。     

白内障超声乳化摘除术对睑板腺形态和功能的影响

目的评估白内障超声乳化摘除术后早期患者睑板腺形态和功能的改变。方法选取行白内障超声乳化摘除联合人工晶状体植入术的年龄相关性白内障患者53例(53眼)进行前瞻性自身对照研究,分别于术前、术后1周、术后1个月进行眼表疾病指数(OSDI)问卷评分、睑缘形态评估、睑板腺缺失率测量、泪膜脂质层厚度测量、泪膜破裂时间评估。结果白内障超声乳化摘除术后1周、术后1个月的OSDI问卷评分、睑缘形态评分较术前显著升高(P<0.05),术后1周、术后1个月泪膜脂质层厚度和泪膜破裂时间较术前显著减小/缩短(P<0.05),而术后1周和术后1个月睑板腺缺失率较术前无明显改变(P>0.05)。结论白内障超声乳化摘除术后早期患者会出现睑板腺形态改变及功能下降,而睑板腺功能下降与睑板腺数量无关。     

Morphometric and histologic changes in the pulmonary system of broilers raised at simulated high altitude

Broilers were reared in conditions of hypobaric hypoxia (3500 m altitude) to investigate the development of pulmonary nodules in birds reared in hypobaric hypoxia and judged by clinical observation to be developing broiler pulmonary hypertension syndrome (BPHS); in unaffected birds reared in hypobaric hypoxia; and in birds reared at ambient atmospheric pressure. Gross pulmonary morphometric measurements, packed cell volume, electrocardiogram QRS amplitude and body weight also were compared among the three experimental groups. Results indicate that hypobaric hypoxia alone exercised little influence on the development of pulmonary nodules. Nodule numbers per section and nodule area per section were numerically greater in birds reared in hypobaric hypoxia, but there were no consistent significant differences in nodule numbers in birds which developed BPHS. As expected, absolute lung length, inter-rib distance and lung volume increased significantly with increasing age and size; but when these parameters were expressed as a function of body weight, they decreased with increasing age. Again, intergroup differences were inconsistent. Packed cell volume and electrocardiogram QRS amplitude were significantly increased in birds reared in hypobaric hypoxia.     

Japanese and North American/European patients with Beckwith-Wiedemann syndrome have different frequencies of some epigenetic and genetic alterations

Beckwith-Wiedemann syndrome (BWS) is an imprinting-related human disease. The frequencies of causative alterations such as loss of methylation (LOM) of KvDMR1, hypermethylation of H19-DMR, paternal uniparental disomy, CDKN1C gene mutation, and chromosome abnormality have been described for North American and European patients, but the corresponding frequencies in Japanese patients have not been measured to date. Analysis of 47 Japanese cases of BWS revealed a significantly lower frequency of H19-DMR hypermethylation and a higher frequency of chromosome abnormality than in North American and European patients. These results suggest that susceptibility to epigenetic and genetic alterations differs between the two groups.     

Effect of gold nanoparticle morphology on adsorbed protein structure and function

Many biomedical applications of gold nanoparticles (NPs) rely on proteins that are covalently attached or adsorbed on the NP surface. The biological functionality of the protein-NP conjugate depends on the protein's ability to interact with target molecules, which is affected by NP characteristics such as size, curvature, aspect ratio, morphology, crystal structure, and surface chemistry. In the present study, the effect of gold nanoparticle morphology on the structure and function of adsorbed enzymes, lysozyme (Lyz) and α-chymotrypsin (ChT), has been investigated. Gold nanospheres (AuNS) were synthesized with diameters 10.6 ± 1 nm, and gold nanorods (AuNR) were synthesized with dimensions of (10.3 ± 2) × (36.4 ± 9) nm. Under saturating conditions, proteins adsorb with a higher surface density on AuNR when compared to AuNS. In the case of Lyz, adsorption on AuNS and AuNR resulted in a 10% and 15% loss of secondary structure, respectively, leading to conjugate aggregation and greatly reduced enzymatic activity. ChT retained most of its secondary structure and activity on AuNS and AuNR at low surface coverages; however, as protein loading approached monolayer conditions on AuNR, a 40% loss in secondary structure and 86% loss of activity was observed. Subsequent adsorption of ChT in multilayers on the AuNR surface allowed the conjugates to recover activity and remain stable. It is clear that AuNP morphology does affect adsorbed protein structure; a better understanding of these differences will be essential to engineer fully functional nanobioconjugates.     

Changes in structure and function of the human left ventricle after acclimatization to high altitude

Summary To analyse the role of changes in structure and function of the left ventricle in determining cardiac function at rest and during exercise, several two-dimensional and Doppler echocardiographic measurements were performed on 11 healthy subjects immediately before an Himalayan expedition (Nun, 7135 m), during acclimatization (3 weeks) and 14 days after the return. At rest decreases were found in cardiac index (CI) (3.23 l · min^–1 · m^–2, SD 0.4 vs 3.82 l · min^–1 · m^–2, SD 0.58,P < 0.01), left ventricular mass (55.3 g · m^–2, SD 9.4 vs 65.2 g · m^–2, SD 13.5,P < 0.005) and left ventricular end-diastolic volume (LVEDV) (53.9 ml · m^–2, SD 6.9 vs 64.8 ml · m^–2, SD 9.1,P < 0.001) after acclimatization; by contrast the coefficient of peak arterial pressure to left ventricular end-systolic volume (PAP/ESV) (7.8, SD 1.6 vs 6.0, SD 1.8,P < 0.005) and mean wall stress [286 kdyn · cm^–2, SD 31 vs 250 kdy · cm^–2, SD 21 (2.86 N · cm^–2, SD 0.31 vs 2.50 N · cm^–2, SD 0.21),P < 0.005] increased. After return to sea level, low values of CI and mass persisted despite a return to normal of LVEDV and preload. A reduction of PAP/ESV was also observed. At peak exercise, PAP/ESV (8.7, SD 2.4 vs 12.8, SD 2.0,P < 0.0025), CI (9.8 l · min^–1 m^–2, SD 2.5 vs 11.61 · min^–1 · m^–2, SD 1.6,P < 0.05) and the ejection fraction (69%, SD 6 vs 76%, SD 4,P < 0.05) were lower after return to sea level than before departure. The depressed left ventricular performance after prolonged exposure to hypoxia may be related to changes in structure and function including reduction in preload, loss of myocardial mass and depression of inotropic state.