Effect of occupational mercury exposure on plasma lysosomal hydrolases

Summary The activities of three plasma lysosomal hydrolases, -galactosidase, -glucuronidase and -N-acetylglucosaminidase, were studied in 20 workers exposed to metallic mercury vapor in a chlorine alkali plant and in 10 nonexposed referents. The urinary excretion and blood levels of mercury were determined on the day of study, and the history of mercury exposure was reviewed from the records of mercury concentrations in urine and blood over periods of up to 133 months. The average levels of -N-acetylglucosaminidase and -glucuronidase were higher in the plasma of exposed workers, but the difference was not significant. No significant positive correlation was seen between lyosomal enzyme activities and cumulative long-term exposure to mercury. It is concluded that measurement of plasma lysosomal hydrolase-activities is not of great value in the biological monitoring of workers exposed to low concentrations of metallic mercury vapor.In line with published data, the concentration of mercury showed a clearcut diurnal variation in nonexposed persons, persons currently exposed and persons with a history of past exposure. The excretion rate of mercury remained constant throughout the day.     

Effect of deltamethrin on antipyrine pharmacokinetics and metabolism in rat

The effect of deltamethrin pretreatment on the pharmacokinetics and metabolism of antipyrine was studied in male rats. The total plasma clearance of antipyrine was significantly decreased by deltamethrin pretreatment (20 mg/kg and 40 mg/kg daily for 6 days prior to antipyrine administration), while the elimination half-life at phase, the area under the concentration-time curve and the mean residence time of antipyrine were significantly increased. The magnitude of the observed changes was dose dependent. The urinary excretion of norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was decreased by 39%, 32% and 26%, respectively (p<0.001) in the presence of deltamethrin. In addition, the rate constants for formation of each of these metabolites were significantly decreased by an average of approximately 71%. These results suggest that deltamethrin is capable of inhibiting oxidative metabolism, a finding which could be of clinical and toxicological significance.     

载重卡车和拖拉机振动参数的测量及对人体健康影响的研究

本研究对8种载重卡车、拖拉机驾驶员座位的振动进行测量,均超过ISO 2631—1985规定的暴露极限(E·L)界限值。特别是上海50型拖拉机、解放牌4吨翻斗车更为明显。对490名驾驶员进行了一般查体、心电图检查、视觉运动反应时测定和脊柱骨关节X线摄像,并与162名科室办公人员相对照。腰背痛主诉、血压偏高、心电图节律异常、视觉运动反应时减慢、胸腰椎增生性改变等均有较高的检出率,并随工龄的延长而增加。全身振动及其联合因素对人体健康的影响有必要进一步研究;我国全身振动的卫生标准及防治措施急待研制。     

Induction of vascular haemostasis by Nd:YAG laser light in melanin-rich and melanin-free tissue

Haemostasis was effected in vessels of melanin-rich (MR: choroid) and melanin-free (MF: mesentery) rabbit tissue irradiated with a cw-Nd: YAG laser. The following parameters were employed: - pulse duration: 200 ms (MR) and 100ms (MF); focal spot diameter: 200 m (MR) and 80 m (MF); pulse energies: 100–250 mJ (MR) and 0.5-1J (MF); irradiances: 1.6–4.0kWcm^–2 (MR) and 1–2 × 10²kWcm² (MF). In melanin-rich tissue, laser energy is absorbed principally by melanin granules contained within the stromal melanocytes. The heat generated in these structures radiates into the surrounding tissue where it is dissipated. The damage thus incurred by the endothelium of blood vessels encompassed within this field triggers the haemostatic mechanism whereby blood flow is arrested. This effect is realized by the formation of an occluding plug of platelets, which is stabilized by the deposition of fibrin, particularly in capillaries, and to a lesser degree in larger vessels of the vascular lamina. In melanin-free tissue, haemoglobin serves as the primary site of energy absorption, which is thus shifted from the stroma to the vessel lumen. Irradiation of vessels in such tissue leads to thermocoagulation of plasma proteins and consequent stasis of blood flow.     

Local Enhanced Topical Delivery (LETD) of Drugs: Does It Truly Exist?

There is considerable uncertainty over whether and to what extent topically applied drugs can be delivered directly to anatomical sites beneath the skin, without prior entry into the systemic blood circulation. The in vivo studies reported in this work were designed to assess whether local enhanced topical delivery (LETD) can be achieved with piroxicam, a nonsteroidal antiinflammatory drug. Equivalent doses of tritium-labeled drug were administered by the i.v. or topical routes to male rats. The topical plasma profile reveals a maximum concentration (Cp_max) at 12 hr, compared to a typical, multiexponential decline in plasma concentration after i.v. dosing. All four muscles from the topically dosed shoulder exhibit two distinct peaks, the first at 4 hr and a later one at 12 hr (which coincides with the topical Cp_max). The contralateral muscles from the non-dosed shoulder, in contrast, produce only a single peak at 12 hr after topical dosing. After the i.v. administration of piroxicam, the concentration-time profiles for each muscle closely parallel that seen for the i.v. plasma. Tissue-to-plasma ratios (T/P) show that the topical nondosed and the i.v. muscles are nearly constant over the entire time course of this study, indicating a pseudo-equilibrium between the plasma and those muscles. However, the early T/P ratios for the topically dosed muscles are markedly elevated and gradually decline to a constant value only after 12 hr, indicating that a similar pseudo-equilibrium is not established in this case. Thus, these results strongly imply that the topical administration of a drug can lead to LETD for tissues subjacent to the skin. Further, based on the elevated T/P ratios, these local enhanced drug levels cannot be solely attributed to entry from the systemic blood and suggest summarily that the cutaneous microvasculature is simply not an infinite sink for removal of all topically applied drugs.     

Quantified ultrastructural study of spermatozoa in unexplained failure of in vitro fertilization

Failure of in vitro fertilization or very low cleavage rates may occur even though oocyte and semen parameters seem satisfactory. Quantified ultrastructural study of spermatozoa was performed in such cases of failure (n =6) or low cleavage rate (<20%; n =4). Through 1 to 11 retrievals, the number of inseminated oocytes ranged from 14 to 145. The results were compared to those of six fertile men. Quantification was achieved by cataloguing cell defects of the spermatozoon heads and mid-/principal pieces of the flagella. Using the data from each specimen, the percentages of total cellular abnormalities in the head/mid-/principal pieces were established. At the level of the head overall percentages for six groups of defects were determined. The overall percentage of combined head abnormalities, defined as the presence of at least three of these six defects on the same spermatozoon head, was established. Statistical differences among control and patient groups were analyzed by nonparametric Mann—Whitney Utest. The percentages of anomalies of the midpiece and of the principal piece were not significantly different between patients and controls. Motility assessed by spermogram was considered functionally uncompromised. In eight patients the percentage of cell alterations of the head (93–100 vs 77.3 ± 6.4%) and the percentage of combined anomalies of the head (78.1–100 vs 60.8 ± 8.5%) were significantly different between patients and controls. In two cases, the percentages established for all head parameters considered were not globally different from those observed in controls. Thus in 8 cases of 10, electron microscopy with quantified analysis supplied valuable evidence about the poor quality of these sperm samples judged as normal under light microscopy and may provide an explanation for their impaired fertilizability. In the two other cases the fact that the sperm appeared to be ultrastructurally normal does not rule out functional sperm pathology. Alternatively, defects in the oocyte may also account for unexplained failures of in vitro fertilization.     

国产长效皮下埋植剂和Norplant的药物体外释放比较

本文研究了国产18-甲基炔诺酮硅橡胶长效皮下埋植剂的药物体外释放,并与进口Norplant进行了比较。释放试验采用水平振荡法,实验条件符合“漏槽”状态的要求。用紫外分光光度法在240 nm波长处测定18-甲基炔诺酮每天的体外释放量。二年多体外释放试验的实验结果表明:国产埋植剂的药物体外释放无爆破效应,释药速度稳定,为零级速度。平均每天释放量为85μg。体外释放的重现性好。进口Norplant则有明显的爆破效应,经10天释放,才趋于稳定,平均每天释药量为68μg。     

Bacterial β-lactamase is efficiently secreted in Saccharomyces cerevisiae under control of the invertase signal sequence

Summary The enzyme -lactamase, a secretory protein that is located in the Escherichia coli periplasmic space, can be highly expressed in Saccharomyces cerevisiae. Although the protein can cross eukaryotic membranes, it is only inefficiently secreted by yeast. To determine whether the lack of secretion in yeast is due to the nature of the bacterial signal sequence, it was replaced with the signal peptide of yeast invertase. The presence of the invertase signal peptide led to -lactamase secretion of up to 75%. The results indicate that the bacterial signal peptide is not functional in yeast, although cleavage can take place at the authentic processing site. The mature enzyme does not interfere with the yeast secretion pathway.     

Region-specific age effects on AMPA sensitivity: electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1.

The effects of aging on the responsiveness of hippocampal neurons to iontophoretic application of L-glutamate and AMPA were studied in vitro. There were no effects of age on neuronal responses to L-glutamate; however, CA1 pyramidal cells of old rats, but not granule cells in the fascia dentata, showed both a smaller reduction in extracellularly-recorded synaptic responses following application of AMPA (presumably mediated by depolarization), and smaller extracellular "DC" fields (measured by subtracting the DC potentials at the dendrite and soma following AMPA application in the dendrites). To examine the cellular bases of this age-related alteration in AMPA sensitivity, two additional electrophysiological approaches were used: (1) measurement of the amplitude ratios of extracellular EPSP and fiber potential components of the Schaffer collateral-CA1 response; (2) measurement of intracellularly recorded unitary EPSPs and quantal analysis of their fluctuations. The interpretations that would be placed on four hypothetical possible outcomes of such experiments are outlined and assessed in relation to the experimental data. The pattern of results obtained in the present experiments supports the following conclusions: In old rats, individual Schaffer collateral synapses do not appear to have altered AMPA receptor properties, as neither the mean size of the unitary synaptic response nor the apparent quantal size differs between age groups; however, the data do support the conclusion that there are fewer synapses per Schaffer collateral branch in old versus young CA1 pyramidal cells.