微粒计数器计数法与药典法检测微粒的比较

用国产ＫＦ－４微粒计数器、药典微孔滤膜－显微镜法对２５批注射液中不溶性微粒进行了检测比较试验，结果表明，二法检测结果基本一致。     

INHALATION OF POORLY SOLUBLE PARTICLES. I. DIFFERENCES IN INFLAMMATORY RESPONSE AND CLEARANCE DURING EXPOSURE

Results from animal studies have indicated some uncertainties over the validity of a single general occupational control limit for all types of ''particulates (insoluble) not otherwise classified'' (PNOC) (ACGIH, 2000). Therefore, to examine the extent to which a given control limit may be valid for nontoxic dusts with different physical characteristics, this study compared the pulmonary effects in rats of inhalation exposure to two poorly soluble dusts of similar density and with relatively low toxicity: titanium dioxide and barium sulfate. The objectives were to compare the dusts in (a) their buildup and clearance in the lungs during inhalation; (b) their transfer to lymph nodes; (c) the changes, with time, in the lavageable cell population; and (d) the pathological change from histology. The exposure aerosol concentrations were selected to achieve similar mass and volume lung burdens for both dusts and to attain ''overload'' over the common exposure periods of about 4 mo and 7 mo. Despite obtaining similar lung burdens for both dusts, there was significantly more translocation of TiO2 to the hilar lymph nodes than with BaSO4. It was also found that clearance of TiO2 was retarded whereas clearance of BaSO4 was not. Trends in these data were clarified by the use of a simple model of particle clearance. Retardation of particle clearance and translocation to the lymph nodes are markers of the condition known as ''overload'' in which the alveolar macrophage-based clearance of particles from the deep lung is impaired. In addition, bronchoalveolar lavage showed that TiO2 caused significantly more recruitment of inflammatory neutrophils to lungs than BaSO4. These differences between the dusts were not due to differences in toxicity, solubility, or lung deposition. The explanation that the different responses are due to the different particle size distributions of the two dust types is examined in a companion paper (Tran et al., this issue).     

EXPLORATION OF THE MECHANISMS OF RETENTION AND CLEARANCE OF LOW-TOXICITY PARTICLES IN THE RAT LUNG USING A MATHEMATICAL MODEL

A mathematical model of the mechanisms of clearance or retention of inhaled particles in rat lungs is used to explore the extent to which a hypothesized sequence of events (including phagocytosis, macrophage-mediated clearance, transfer into the interstitium, transfer to lymph nodes, and overloading of the defense mechanisms) can account for data from a series of inhalation experiments with a low-toxicity, insoluble dust - titanium dioxide, TiO₂. These data include mean lung burdens and mean lymph-node burdens in groups of rats exposed to concentrations of 1, 10, 30, 50, and 90 mg m^-3, with exposure periods for as long as 2 yr (at 10 mg m^-3), up to 7 mo at 50 mg m^-3, and 3.5 mo at 1 and 30 mg m^-3. The estimation of the parameters in the model is based mainly on information from other experimental studies or prior modeling. Values within the biologically plausible range were evaluated for the main parameters by inspection of predictions in comparison with data from the lowest concentration experiments. The suitability of the selected values was then confirmed by comparison of model predictions with data from the higher concentration experiments (at 30, 50, and 90 mg m-3). During inhalation, clearance rates are affected by translocation of dust and by overloading. The characterization of overload appears to describe these experiments well. Comparison with the effect of lung burden reported for other types of particles supports the hypothesis that overload is more dependent on the volume rather than the mass of the particles.     

INHALATION OF POORLY SOLUBLE PARTICLES. II. INFLUENCE OF PARTICLE SURFACE AREA ON INFLAMMATION AND CLEARANCE

In this article the volumetric overload hypothesis, which predicts the impairment of clearance of particles deposited in the lung in terms of particle volume, is reevaluated. The degree to which simple expressions of retained lung burden explain pulmonary responses to overload was investigated using data from a series of chronic inhalation experiments on rats with two poorly soluble dusts, titanium dioxide and barium sulfate. The results indicated that the difference between the dusts in the level of inflammation and translocation to the lymph nodes could be explained most simply when the lung burden was expressed as total particle surface area. The shape of the statistical relationship for both lung responses indicated the presence of a threshold at approximately 200–300 cm2 of lung burden. On the basis of this and other similar results, a hypothesis regarding a generic mechanism for the impairment of clearance and associated lung responses is proposed for such ''low-toxicity'' dusts.     

TRANSLOCATION OF ULTRAFINE INSOLUBLE IRIDIUM PARTICLES FROM LUNG EPITHELIUM TO EXTRAPULMONARY ORGANS IS SIZE DEPENDENT BUT VERY LOW

Recently it was speculated that ultrafine particles may translocate from deposition sites in the lungs to systemic circulation. This could lead to accumulation and potentially adverse reactions in critical organs such as liver, heart, and even brain, consistent with the hypothesis that ultrafine insoluble particles may play a role in the onset of cardiovascular diseases, as growing evidence from epidemiological studies suggests. Ultrafine 192 Ir radio-labeled iridium particles (15 and 80 nm count median diameter) generated by spark discharging were inhaled by young adult, healthy, male WKY rats ventilated for 1 h via an endotracheal tube. After exposure, excreta were collected quantitatively. At time points ranging from 6 h to 7 d, rats were sacrificed, and a complete balance of 192 Ir activity retained in the body and cleared by excretion was determined gamma spectroscopically. Thoracic deposition fractions of inhaled 15- and 80-nm 192 Ir particles were 0.49 and 0.28, respectively. Both batches of ultrafine iridium particles proved to be insoluble (<1% in 7 d). During wk 1 after inhalation particles were predominantly cleared via airways into the gastrointestinal tract and feces. This cleared fraction includes particles deposited in the alveolar region. Additionally, minute particle translocation of <1% of the deposited particles into secondary organs such as liver, spleen, heart, and brain was measured after systemic uptake from the lungs. The translocated fraction of the 80-nm particles was about an order of magnitude less than that of 15-nm particles. In additional studies, the biokinetics of ultrafine particles and soluble 192 Ir was studied after administration by either gavage or intratracheal instillation or intravenous injection. They confirmed the low solubility of the particles and proved that (1) particles were neither dissolved nor absorbed from the gut, (2) systemically circulating particles were rapidly and quantitatively accumulated in the liver and spleen and retained there, and (3) soluble 192 Ir instilled in the lungs was rapidly excreted via urine with little retention in the lungs and other organs. This study indicates that only a rather small fraction of ultrafine iridium particles has access from peripheral lungs to systemic circulation and extrapulmonary organs. Therefore, the hypothesis that systemic access of ultrafine insoluble particles may generally induce adverse reactions in the cardiovascular system and liver leading to the onset of cardiovascular diseases needs additional detailed and differentiated consideration.     

AUTORADIOGRAPHIC LOCALIZATION OF RECEPTORS IN THE MAMMALIAN CARDIOVASCULAR SYSTEM

1. Autoradiographic techniques have been used to examine the location of beta-adrenoceptors in the heart and beta-adrenoceptors, substance P receptors and muscarinic cholinoceptors in blood vessels. 2. Both beta 1-adrenoceptors and beta 2-adrenoceptors were present in guinea-pig and human heart, on the myocardium and associated with the cardiac nerves and blood vessels. 3. Nerves on the vasculature and vascular smooth muscle contained beta-adrenoceptors and muscarinic cholinoceptors. 4. Receptors for substance P and beta-adrenoceptors, but not muscarinic cholinoceptors were present on endothelial cells.     

ROLE OF PULMONARY INNERVATION IN CANINE IN SITU LUNG-PERFUSION PREPARATION: A NEW MODEL OF NEUROGENIC PULMONARY OEDEMA

1. In situ canine lungs were perfused in the presence or absence of the nerves which coursed to the heart and lungs (the cardiopulmonary nerves, CPN). 2. A right heart-bypassed preparation was made first, so that the respiratory and circulatory conditions could be controlled beforehand. It was then switched to a lung-perfusion preparation, in which the lungs receive all influences of sudden cessation of the brain and systemic circulations solely via the CPN. Hydrostatic mechanisms causing pulmonary oedema were excluded by adjusting the pulmonary arterial pressure under 300 mmH2O (less than 24 mmHg). 3. Accumulation of extravascular lung water and the rate of reservoir blood loss were significantly lower in the CPN-severed group than in the CPN-intact group. 4. After perfusion of 90 min, total loss of reservoir blood was correlated significantly with extravascular water content in lungs. The former was larger than the latter. 5. Elevation of left atrial pressure caused an increase in the rate of reservoir blood loss. When the CPN was severed, the relation between these two parameters was shifted to the right. 6. These findings indicate a CPN-mediated genesis of permeability pulmonary oedema.     

A SIMPLE PULMONARY RETENTION MODEL ACCOUNTING FOR DISSOLUTION AND MACROPHAGE-MEDIATED REMOVAL OF DEPOSITED POLYDISPERSE PARTICLES

This article describes a mechanistic two-compartmental model to simulate the disposition by dissolution and particulate clearance of particles deposited in the pulmonary region of the lung. The model provides a general solution for the size distribution of particles in the surfactant layer of the alveolar surface and in the cell plasma of alveolar macrophages. Thus it allows for different dissolution rates in the two compartments and accounts for potentially different kinetics and/or biological effects of particles and their solute in surrounding fluids. The input parameters are, among others, the size distribution density function of the deposited particles and the time constants characterizing the dissolution process as well as phagocytosis rate and particle transport by macrophages to the tracheobronchial tract. Relevant dose parameters such as retained and dissolved mass can be calculated from the temporally retained size distributions. For the first time, this theoretical presentation considers the polydispersity of aerosol particles deposited in the lung and thus provides an indispensable mathematical basis for a multicompartmental retention model that may combine particulate removal from the pulmonary region and the lymph nodes by a competition of the rates of dissolution and particulate clearance in all relevant lung model compartments.     

EFFECTS OF PANAX GINSENG ON BLOOD ALCOHOL CLEARANCE IN MAN

1. Fourteen healthy male volunteers were studied to assess the effects of Panax ginseng on blood alcohol clearance, utilizing each subject as his own control. 2. At 40 min after the last drink, the blood alcohol level in the test group receiving ginseng extract (3 g/65 kg body weight) along with alcohol (72 g/65 kg body weight) was about 35% lower than their control values. 3. When the blood alcohol level was compared on individual bases, alcohol concentrations in 10 out of 14 test subjects ranged from 32 to 51% lower than their control values. 4. These results demonstrate that P. ginseng extract enhances blood alcohol clearance in man.     

DOSE-RESPONSE ASSESSMENT AND EFFECT OF PARTICLES IN GUINEA PIGS EXPOSED CHRONICALLY TO DIESEL EXHAUST: ANALYSIS OF VARIOUS BIOLOGICAL MARKERS IN PULMONARY ALVEOLAR LAVAGE FLUID AND CIRCULATING BLOOD

To elucidate dose-response and other effects of diesel particles in guinea pigs chronically exposed to diesel exhaust, various biomarkers for chronic obstructive lung diseases were studied using bronchoalveolar lavage (BAL) fluid and blood specimens. Guinea pigs were exposed 16 h/day, 6 days/wk, for 6, 12, 18, or 24 mo to filtered air (control group, n = 8-10), a low level of diesel exhaust (L group: NO 2 = 0.22 ± 0.03 ppm; SO 2 = 0.6 ± 0.19 ppm; particles = 0.21 ± 0.07 mg/m 3, n = 8-10), medium level of diesel exhaust (M group; NO 2 = 1.07 ± 0.09 ppm; SO 2 = 2.83 ± 0.73 ppm; particles = 1.14 ± 0.26 mg/m 3, n = 8-10), and high level of diesel exhaust (H group: NO 2 = 2.88 ± 0.29 ppm; SO 2 = 6.49 ± 1.75 ppm; particles = 2.94 ± 0.69 mg/m 3, n = 8-10), or at a medium concentration of diesel exhaust without particulate matters (MG group: NO 2 = 1.01 ± 0.09 ppm; SO 2 = 2.66 ± 0.64 ppm; particles = 0.01 ± 0.01 mg/m 3, n = 8-10). Anesthetized animals were sacrificed and BAL fluid from the lung and blood from right ventricle were collected. Various biomarkers of inflammation, components of mucus and surfactant, bronchoconstrictors were determined. Changes of leukotriene C4 in plasma, eosinophil counts, biomarkers of inflammation and cytotoxicity, and mucus and surfactant components in BAL fluid were statistically different among the C, L, M, and H groups after adjustment for the exposure period and group-by-exposure period with respect to their interactions in two-way analysis of variance (ANOVA). The levels of these biomarkers in the H group were higher than those of the M group, whereas those of the L group showed no significant changes compared with those of the C group during experimental period. Onset of significant changes of these biomarkers for the M group was at 18 mo of exposure, whereas that for the H group was at 12 mo of exposure, which resulted in changes in the levels of biomarkers in BAL fluid. Although numbers of eosinophils in BAL fluid increased significantly in the M and H groups at 12 mo, only leukotrine C4 increased at 18 and 24 mo in blood and at 24 mo in BAL fluid. Animals exposed to the medium level of diesel exhaust without particulate matter showed significantly less increase of these biomarkers as compared with animals exposed to the same level of diesel exhaust with particulate matters. These findings indicate that chronic exposure to diesel exhaust induced continuous inflammation, overproduction of mucus, and phospholipids in the lung. Animals exposed to the high dose of diesel exhaust showed a plateau of biological responses at 12 mo of exposure. Particulate matter in diesel exhaust appears to play an important role in development of lung injury by chronic emission exhaust exposure.     

高效液相色谱法测定护肝颗粒中芍药甙的含量

用ＨＰＬＣ法测定了护肝颗粒中芍药甙的含量，其分析柱为ＯＤＳ－Ｃ_(１８)，流动相为甲醇－异丙醇－醋酸（３６％）－水（２５：２：２：７１），检测波长为２３０ｎｍ，样品提取溶剂为水，提取方法和时间为超声振荡１０ｍｉｎ。芍药甙的平均回收率为９７．４４％，ＲＳＤ＝０．６１％（ｎ＝６）．线性范围０．２０８～０．８５２μｇ。方法简便、快速，精密度和稳定性良好，适于护肝颗粒生产的质量控制。     

ELECTRICAL BASIS OF PERISTALSIS IN THE MAMMALIAN UPPER URINARY TRACT

1. Peristalsis in the mammalian upper urinary tract (UUT) is mostly myogenic in origin, originating predominately in the proximal pelvicalyceal regions of the renal pelvis, an area that is enriched with specialized smooth muscle cells termed ‘atypical’ smooth muscle cells. Propagating peristaltic contractions are little affected by blockers of either autonomic nerve function or nerve impulse propagation; however, blockers of sensory nerve function or prostaglandin synthesis reduce both the frequency and the strength of the spontaneous contractions underlying peristalsis. 2. The electrical drive for these peristaltic contractions has long been considered to involve mechanisms analogous to the heart, such that ‘atypical’ smooth muscle cells generate spontaneous ‘pacemaker’ action potentials. These pacemaker potentials trigger the firing of action potentials and contraction in the muscular regions of the renal pelvis, which propagate distally to the ureter, propelling urine towards the bladder. 3. Recent intracellular microelectrode and single cell/channel patch-clamp studies have revealed that the ionic conductances underlying the action potentials recorded in the UUT are likely to involve the opening and slow closure of voltage-activated ‘L-type’ Ca2+ channels, offset by the time-dependent opening and closure of both voltage- and Ca2+-activated K+ channels. 4. In the present review we summarize the current knowledge of the ionic mechanisms underlying action potential discharge in the UUT, as well as present our view on how this electrical activity supports the initiation and conduction of UUT peristalsis.     

MEASUREMENT OF PULMONARY FLOW RESERVE IN HIGHER PRIMATES

• 1 There are currently limited diagnostic methods for assessing the integrity of the pulmonary microvasculature. We hypothesized that a novel, invasively determined physiological index of ‘pulmonary flow reserve’ (PFR = maximal hyperaemic pulmonary blood flow divided by basal pulmonary flow) may facilitate microvascular assessment in the lung. Therefore, we developed a baboon model in which to: (i) validate the use of Doppler flow velocity for PFR assessment; (ii) define the optimal drug and dose regimen for attainment of maximal pulmonary hyperaemia; and (iii) demonstrate the feasibility of measuring PFR in healthy higher primates.
• 2 Doppler sensor guidewires were placed in segmental pulmonary arteries of 11 ketamine‐anaesthetized baboons. Vessel diameter, flow velocity and haemodynamics were recorded before and after direct intrapulmonary artery administration of saline, adenosine (50–500 µg/kg per min) and papaverine (3–60 mg), enabling calculation of PFR.
• 3 Saline (either bolus injection or infusion) did not alter vessel diameter or flow velocity (P > 0.1), validating local drug administration. Both adenosine and papaverine induced dose‐dependent increases in flow velocity from baseline (from 22.5 ± 2.3 to 32.7 ± 4.8 cm/s for 400–500 µg/kg per min adenosine; and from 23.9 ± 1.1 to 34.6 ± 4.0 cm/s for 24 mg papaverine; both P < 0.0001), without affecting pulmonary artery pressure or vessel diameter (P > 0.3). Healthy primate PFR values were 1.35 ± 0.10 and 1.39 ± 0.10 using 200 µg/kg per min adenosine and 24 mg papaverine, respectively (P > 0.8).
• 4 In conclusion, pulmonary flow reserve in higher primates can be assessed using Doppler sensor guidewire and either adenosine or papaverine as microvascular hyperaemic agents. Measurements of PFR may facilitate pulmonary microvascular assessments.

     

CENTRIFUGAL CONTROL IN MAMMALIAN HEARING

• 1 Centrifugal control of many sensory systems is well established, notably in the γ motorneuron of skeletal muscle stretch receptors.
• 2 Efferent (olivocochlear) innervation of the mammalian cochlea was first established through anatomical studies. Histological studies confirmed synaptic terminals in contact with hair cells and afferent dendrites.
• 3 Electrophysiology has elucidated the cellular mechanisms of efferent modulation in the cochlea.
• 4 The system has potential roles in noise protection, homeostatic feedback control of cochlear function and signal processing. There is some evidence in support of each, but also contraindications.
• 5 It is concluded that the role of the olivocochlear innervation is still contentious but, on balance, the evidence appears to favour a role in enhancing signal detection in noise.

     

COMPARATIVE NEUROANATOMY OF ANGIOTENSIN II RECEPTOR LOCALIZATION IN THE MAMMALIAN HYPOTHALAMUS

1. The distribution of angiotensin II (AII) receptor binding sites in the hypothalamus of rat, rabbit, sheep and human was determined by in vitro autoradiography using 125I-[Sar1,Ile8]-AII as radioligand. 2. High receptor binding levels were observed in the continuum of tissue comprising the anterior wall of the third ventricle, including the subfornical organ, the median pre-optic nucleus and the organum vasculosum of the lamina terminalis. 3. High levels of binding sites were also found in the paraventricular and supra-optic nuclei, the median eminence and the arcuate nucleus. 4. These findings demonstrate sites in the hypothalamus of rat, rabbit, sheep and human where AII could exert its known actions on fluid and electrolyte balance, pituitary hormone release and cardiovascular function.     

胸部CT用于隐蔽性肺结核的诊断

为提高隐蔽性肺结核诊断率。对１２例胸片隐蔽性肺结核临床、Ｘ线、ＣＴ等特点进行分析。胸部Ｘ线难以发现或显示不清楚，常常延误诊断；而胸部ＣＴ薄层横断面能早期发现病灶，有利于及时诊治。认为对临床可疑隐蔽性肺结核应早期行ＣＴ扫描     

聚乙二醇双水相体系在分离纯化蛋白质中的应用

蛋白质等生物大分子在聚乙二醇双水相体系中分配系数不同,可依此而进行分离纯化。此法分离的选择性优于硫酸铵、丙酮分段等经典方法,且对蛋白质有保护作用。该法操作简便,处理量大,回收率高,正日益广泛的应用。     

尾孢属的几个新种

本文报导了作者1985～1987年间在广东省肇庆地区调查栽培药用植物病害过程中发现的尾孢属新种:Cercospora alpinicola sp.nov.寄生于益智(Alpinia oxyphylla Miq.),C.alpinii-Ka'sumadaicola sp.nov.C.alpini-katsumadae sp.nov.寄生于草豆蔻(Alpinia katsumadaiHayata),C.ardrographicola sp.nov.寄生于穿心莲(Andrographis paniculata(Burmf.)Nee.),C.sauropi sp.nov.寄生于龙利叶(Sauropus apatulifolius Beille)C.evodio-rutaeearpae.sp.nov.寄生于吴茱萸(Evod:a ruttaecarpa(Juss.)Benth.),C.pueraria-thomsona ap.nov.寄生于葛(Pueraria thomsoni Benth.)。文中对以上各菌进行了形态学描述。标本存华南农业大学植保系标本室。     

VASODILATORY EFFECTS OF MILRINONE ON PULMONARY VASCULATURE IN DOGS WITH PULMONARY HYPERTENSION DUE TO PULMONARY EMBOLISM: A COMPARISON WITH THOSE OF DOPAMINE AND DOBUTAMINE

1. The limited therapeutic role of pulmonary vasodilation reflects lack of their selectivity for the pulmonary vasculature, and many drugs have been evaluated for effectiveness; however, none has gained widespread clinical use. 2. Milrinone (MIL) is a newly synthetized phosphodiesterase inhibitor, which has potent positive inotropic and vasodilatory effects. 3. The present study shows the effects of MIL on the pulmonary circulation in dogs with pulmonary hypertension due to autologous muscle-induced pulmonary embolism, and also demonstrates a comparison with those of dopamine and dobutamine. 4. As MIL showed potent vasodilatory effects on the pulmonary vasculature, it had a potential clinical role in the treatment of pulmonary hypertension.