Naloxone and TRH affect regional blood flows in the anesthetized rabbit

The cardiovascular effects of IV naloxone and a subsequent administration of TRH IV were studied in the rabbit. Naloxone caused a vasodilation in the myocardium and adrenal glands. Naloxone elicited an increment in cerebral blood flow in several regions which attenuated the cerebrovasodilating effect of TRH in a few regions. The blockade of endogenous opioids with naloxone did not modify the peripheral vasoconstricting effect of TRH or affect the vascular effects of TRH mediated by the peripheral sympathetic nerves. The results indicate that naloxone has a vasodilating effect in the myocardium and CNS in anesthetized rabbits. The major part of the cardiovascular effect of TRH is not dependent on mechanisms sensitive to naloxone.     

Genetic variation in relation to demography of peripheral pool frog populations (Rana lessonae)

Summary Genetic variation in an isolated northern metapopulation of the pool frog (Rana lessonae) in Sweden was compared to that of Central European populations using enzyme electrophoresis and literature data. Of the 31 loci scored, two (EST-2 andIDH-2) were polymorphic while no variation occurred in seven of the eight loci which are polymorphic in Central European populations.The heterozygosity level of the Swedish pool frogs is very low compared to that of other anuran populations, but their mean proportion of fertilized eggs within egg masses (97.5%) was not lower than in more heterozygous species, and their body size-specific fecundity did not differ from that of Polish conspecifics. The low genetic variability of the Swedish pool frogs is discussed in relation to features of the local populations such as size (N), calculated effective size (N _e ) reproductive success and probable history. It is concluded that long-term strong fluctuations in population size caused by reporductive failure in cold years have contributed more to the low genetic variability than could a single founder event due to a recent introduction by man.     

Evaluation of nongenotoxic and genotoxic factors modulating the frequency of micronucleated erythrocytes in the peripheral blood of mice

The hematological micronucleus test is regarded as an indicator of the clastogenic effect of chemicals and acute cytogenetic damage. The test can be carried out in red blood cells of the bone marrow and of the spleen, as well as in peripheral erythrocytes. We have determined the precise background values of micronucleated red blood cells for the peripheral blood of BALB/c DBA/2, and NMRI mice. Bleeding, phenylhydrazine-induced hemolysis, and splenectomy generated an increase of micronucleated erythrocytes in the peripheral blood of mice. Our data thus demonstrate that such factors should be taken into consideration when the micronucleus test is used for screening the genotoxic potential of chemicals. Furthermore, the micronucleus-inducing effect of cyclophosphamide was studied in normal and splenectomized mice and, in addition, a comparison of the sensitivity of the micronucleus test was carried out in peripheral blood and bone marrow after cyclophosphamide treatment. Our data demonstrate that the kinetics of micronucleus formation were similar in normal and in splenectomized mice in which the micronucleus levels had returned to normal. The comparison of micronucleus formation in bone marrow and peripheral blood after cyclophosphamide treatment revealed the generation of similar quantities of micronucleated red blood cells in both tissues. The physiological mechanisms of micronucleus formation and removal and the potential role of chemically induced spleen damage during this process are discussed; the usefulness of the peripheral micronucleus test as a simple, rapid, and animal-saving modification of the standard bone marrow test is evaluated.Abbreviations CP cyclophosphamide - MN micronuclei - MNCE micronucleated normochromatic erythrocytes - MNPCE micronucleated polychromatic erythrocytes - MNRBC micronucleated red blood cells - NCE normochromatic erythrocytes - PCE polychromatic erythrocytes     

Acrylamide-Induced Increases in Deposition of Axonally Transported Glycoproteins in Rat Sciatic Nerve

The axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve was examined in adult rats exposed to acrylamide via intraperitoneal injection (40 mg/kg of body weight/day for nine consecutive days). The L5 dorsal root ganglion was injected with either [35S]methionine to label proteins or [3H]glucosamine to label, more specifically, glycoproteins and gangliosides. At times ranging from 2 to 6 h later, the sciatic nerve and injected ganglion were excised and radioactivity in consecutive 5-mm segments determined. In both control and acrylamide-treated animals, outflow profiles of [35S]methionine-labeled proteins showed a well defined crest which moved down the nerve at a rate of approximately 340 mm/day. Similar outflow profiles and transport rates were seen for [3H]glucosamine-labeled glycoproteins in control animals. However, in animals treated with acrylamide, the crest of transported labeled glycoprotein was severely attenuated as it moved down the nerve. This finding suggests that in acrylamide-treated animals, axonally transported glycoproteins were preferentially transferred (unloaded or exchanged against unlabeled molecules) from the transport vector to stationary axonal structures. We also examined the clearance of axonally transported glycoproteins distal to a ligature on the nerve. The observed impairment of clearance in acrylamide-treated animals relative to controls is supportive of the above hypothesis. Acrylamide may directly affect the mechanism by which axonally transported material is unloaded from the transport vector. Alternatively, the increased rate of unloading might reflect an acrylamide-induced increase in the demand for axonally transported material.     

P0 phosphorylation in nerves from normal and diabetic rats: Role of protein kinase C and turnover of phosphate groups

The effects of phorbol ester and forskolin on the net phosphorylation and turnover of P₀ phosphate groups was studied in normal and exprimentally diabetic rats. In sciatic nerve segments isolated from normal rats and incubated with [³²P]-inorganic phosphate, phosphorylation of the major peripheral myelin protein, P₀, was increased 2–5 fold in a time and dose-dependent manner by phorbol 12,13 dibutyrate (PDB). This increase was blocked by the protein kinase inhibitors, H-7 and staurosporine. Both the basal and PDB-stimulated phosphorylation of P₀ were significantly greater in segments of sciatic nerve from streptozotocin-induced diabetic rats. Prolonged exposure of nerve segments to PDB abolished the stimulated phosphorylation of P₀ and immunoblots of nerve proteins revealed a decrease in the content of the protein kinase C -isoform. The adenylate cyclase activator, forskolin, had no affect on the PDB-stimulated phosphorylation of P₀ in normal nerve but decreased phosphorylation in diabetic nerve. To measure turnover of P₀ phosphate groups, nerves were incubated with³²P and incorporated label was then chased in radioactivity-free medium for up to 4 hours. P₀ from normal nerve prelabeled under basal conditions lost 25% of its radioactivity during this time. In contrast, nearly all of the additional phosphate groups prelabeled in the presence of PDB disappeared after 2 hours of chase. P₀ phosphate groups from diabetic nerve displayed similar turnover kinetics. When forskolin was added to the chase medium, the turnover of P₀ phosphate moieties was accelerated in normal, but not in diabetic nerve. These findings clearly establish a prominent role for protein kinase C in P₀ phosphorylation, provide evidence for heterogeneous turnover of P₀ phosphate groups and suggest that cyclic AMP-mediated processes may modulate P₀ phosphorylation. Further, these results indicate that the metabolism of P₀ phosphate moieties is perturbed in nerve from diabetic animals.Special issue dedicated to Dr. Marjoris B. Lees.     

不同FIGO分期子宫内膜癌患者外周血红细胞分布宽度、血清对氧磷酶-1表达水平差异及其诊断价值分析

摘要 目的：探讨不同国际妇产科学联合会（FIGO）分期子宫内膜癌患者外周血红细胞分布宽度（RDW）、血清对氧磷酶-1（PON-1）表达水平差异及其诊断价值。方法：选取我院2018年1月到2020年1月收治的80例子宫内膜癌患者作为研究对象,根据FIGO分期对所有患者进行分组,分为Ⅰ期组23例,Ⅱ期组22例,Ⅲ期组18例,Ⅳ期组17例。另选取同期来我院体检的30名健康志愿者作为对照组,对比所有受检者RDW、PON-1表达水平,并应用ROC曲线分析外周血红细胞分布宽度、血清对氧磷酶-1表达水平对不同FIGO分期子宫内膜癌的诊断价值。对80例子宫内膜癌患者进行2年随访,将2年内死亡的25例患者分为死亡组,将其余55例患者分为存活组,对比死亡组与存活组临床一般情况与RDW、PON-1表达水平,并应用logistic回归分析分析RDW、PON-1对子宫内膜癌的预后预测价值。结果：五组受检者RDW、PON-1水平对比差异显著,Ⅳ期组RDW水平高于Ⅲ期组、Ⅱ期组、Ⅰ期组和对照组,Ⅳ期组PON-1水平低于Ⅲ期组、Ⅱ期组、Ⅰ期组和对照组（P＜0.05）;RDW结合PON-1联合诊断的准确度、敏感度、阳性预测值高于RDW单一诊断和PON-1单一诊断（P＜0.05）。RDW诊断子宫内膜癌不同分期价值曲线下面积为89.63,最佳诊断着色界限值为75.73 %,PON-1的曲线下面积为78.89,最佳诊断着色界限值为82.53 %,两者联合的曲线下面积为84.26,最佳诊断着色界限值为87.57 %;存活组与死亡组患者性别、年龄、病理类型对比无明显差异（P＞0.05）,两组患者FIGO分期、基层浸润、组织分化程度、血清RDW与PON-1表达水平对比差异显著（P＜0.05）;logistic回归分析结果表明：基层浸润、RDW与PON-1为子宫内膜癌患者预后的独立影响因素（P＜0.05）。结论：RDW、PON-1联合对子宫内膜癌FIGO分期的诊断价值较高,且基层浸润、RDW与PON-1为子宫内膜癌患者预后的独立影响因素。临床上需针对基层浸润、RDW升高与PON-1水平降低的患者采取相关措施,改善治疗方案,降低患者死亡率情况。     

食管癌患者放射治疗中照射体积和时间与外周血淋巴细胞绝对值的相关性研究

摘要 目的：探究照射体积和时间与食管癌患者外周血淋巴细胞绝对值的相关性。方法：本研究方案将纳入2019年1月~2019年12月蚌埠医学院第一附属医院放疗科收治的放疗或同步放化疗食管癌患者84例,其中单独放疗患者24例,同步放化疗患者60例,采用血液细胞分析仪测定患者放疗期间每周复查外周血白细胞（WBC）、中性粒细胞（N）、淋巴细胞（L）、血红蛋白（HB）及血小板（PLT）计数等指标。Pearson相关性分析照射时间、剂量及体积与外周血指标之间的相关性。结果：食管癌放疗患者,包括同步放化疗及单纯放疗亚组,在治疗1-6周,照射时间与外周血指标均无相关性（P>0.05）。但在放疗第5-6周,患者放疗剂量与WBC、N、L、HB呈负相关（P<0.05）,同步放化疗亚组患者照射剂量与WBC、N、L、HB呈负相关（P<0.05）。在治疗1-4周,不同照射剂量下各梯度照射剂量对应照射体积与外周血指标均无相关性（P>0.05）。但在第5-6周时,患者不同梯度照射剂量下各照射体积与WBC、N呈负相关（P<0.05）,同时在20Gy-60Gy照射剂量,尤其20Gy和30Gy照射剂量下照射体积与L呈负相关（P<0.05）。同步放化疗亚组患者不同照射剂量下各照射体积与WBC、N呈负相关（P<0.05）,同时在20Gy-60Gy照射剂量下照射体积与L呈负相关（P<0.05）,而且在60Gy照射剂量下照射体积与HB呈负相关（P<0.05）。结论：放疗患者特别是同步放化疗亚组患者照射体积、照射剂量与食管癌患者外周血淋巴细胞计数成负相关,基线淋巴细胞与食管癌患者外周血淋巴细胞计数成正相关,而照射时间与食管癌患者外周血淋巴细胞计数无相关性。     

Intracellular heteroplasmy for disease-associated point mutations in mtDNA: implications for disease expression and evidence for mitotic segregation of heteroplasmic units of mtDNA

Studies in vitro have shown that a respiratorydeficient phenotype is expressed by cells when the proportion of mtDNA with a disease-associated mutation exceeds a threshold level, but analysis of tissues from patients with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) have failed to show a consistent relationship between the degree of heteroplasmy and biochemical expression of the defect. One possible explanation for this phenomenon is that there is variation of heteroplasmy between individual cells that is not adequately reflected by the mean heteroplasmy for a tissue. We have confirmed this by study of fibroblast clones from subjects heteroplasmic for the MELAS 3243 (A G) mtDNA mutation. Similar observations were made with fibroblast clones derived from two subjects heteroplasmic for the 11778 (GA) mtDNA mutation of Leber's hereditary optic neuropathy. For the MELAS 3243 mutation, the distribution of mutant mtDNA between different cells was not randomly distributed about the mean, suggesting that selection against cells with high proportions of mutant mtDNA had occurred. To explore the way in which heteroplasmic mtDNA segregates in mitosis we followed the distribution of heteroplasmy between clones over approximately 15 generations. There was either no change or a decrease in the variance of intercellular heteroplasmy for the MELAS 3243 mutation, which is most consistent with segregation of heteroplasmic units of multiple mtDNA molecules in mitosis. After mitochondria from one of the MELAS 3243 fibroblast cultures were transferred to a mitochondrial DNA-free (⁰) cell line derived from osteosarcoma cells by cytoplast fusion, the mean level and intercellular distribution of heteroplasmy was unchanged. We interpret this as evidence that somatic segregation (rather than nuclear background or cell differentiation state) is the primary determinant of the level of heteroplasmy.     

Nippostrongylus brasiliensis: Peripheral leukocyte responses and correlation of basophils with blood histamine concentration during infection in rats

Rats infected on Day 0 with 3000 infective L₃ larvae of Nippostrongylus brasiliensis, and uninfected controls, were monitored daily through Day 23 postinfection for changes in peripheral leukocytes and blood histamine concentrations. A generalized leukocytosis was observed between Days 7 and 18, the period leading up to and immediately following the time of expulsion of adult worms from the small intestine. The total number of lymphocytes was elevated between Days 11 and 17 post-infection; however, there was no change in the percentage of lymphocytes relative to other white blood cell types. The total number and percentage of monocytes were no different from controls, with the exception of Day 5 postinfection. On that day, there was a significant elevation in the number (614/mm³ blood in infected rats, as compared to 160/mm³ blood in controls) and relative proportion (2.7% of total leukocytes in infected animals, compared to 0.8% in controls) of monocytes, coinciding with the termination of the pulmonary migration of larvae. A period of moderate neutrophilia occurred between Days 7 and 12, but this was not accompanied by any changes in the proportion of neutrophils. A biphasic eosinophil response was observed. An early elevation of eosinophils occurred between Days 3 and 5, corresponding to the period of larval migration through the lungs. A second period of eosinophilia began on Day 11, when worm expulsion was beginning, and continued through Day 19, i.e., beyond the period of worm expulsion. Basophilia was observed as early as Day 6 after infection, rising to a peak on Day 13 (6.8% of total leukocytes in the infected animals, as compared to 0.5% in controls), and declining thereafter, but remaining above control levels until termination of the experiment on Day 23. The histamine content of blood samples, as determined by an enzymic-isotopic assay, closely paralleled the development and decline of basophilia; histamine levels also peaked on Day 13 postinfection (422.5 pg histamine/mm³ blood in infected rats, compared to 66.0 pg histamine/mm³ blood in controls). As basophilia progressed during the course of infection, there was a decline in the amount of histamine per basophil. In uninfected rats and during the first week after infection, basophils contained about 1.5–2.0 pg histamine per cell. In the third week of infection, there was about 0.6 pg histamine per basophil. The time course of the basophilia suggests that these cells may be involved in the expression of immunity to N. brasiliensis.     

狗静脉注射高渗溶液后的血流动力学分析

在15只戊巴比妥钠麻醉的开胸狗身上观察高渗溶液对血流动力学的影响,主要结果如下:1.静脉内注射50%葡萄糖溶液(3m1/kg,15s 内注毕),规律地引起心动徐缓、动脉血压降低、左心室(-dp/dt)减小、左心室 dp/dt 和心输出量增加,以及肾和股薄肌的血流阻力降低。25%甘露醇溶液具有类似作用。2.切断两侧颈迷走神经后,注射高渗溶液不再能诱发动脉低血压以及肾和股薄肌血流阻力的反射性降低,提示此类效应的传入通路主要为迷走神经。3.在切断迷走神经后注射高渗溶液,还使左心室 dp/dt 进一步增加,表明高渗溶液增强心肌收缩性。根据以上结果似可认为,静脉注射高渗溶液所致动脉血压降低,实质上反映着心输出量的增加不足以抵销外周阻力的减小。