松果体切除及褪黑素对垂体─肾上腺轴的影响

松果体切除后ｄ１４，大鼠垂体促肾上腺皮质激素细胞呈现功能活跃状态：核仁明显，粗面内质网扩张，高尔基复合体池变宽，囊泡增大；肾上腺皮质束状带细胞出现功能受抑制表现：胞体变小，线粒体及滑面内质网减少，并伴有血清皮质酮水平下降。褪黑素（１０μｇ·ｋｇ－１·ｄ－１，×７ｄ）对肾上腺皮质束状带细胞有刺激作用：胞体变大，线粒体及脂滴增多，滑面内质网更丰富；并且能使血清皮质酮水平升高，对松果腺切除引起的皮质酮水平下降有拮抗作用。提示松果体对垂体─肾上腺轴有调节作用。     

黄磷中毒性肾上腺皮质损害的研究

实验结果表明,黄磷急性中毒血浆皮质酮波动在正常水平,亚急性中毒早期下降,以后恢复正常,肾上腺抗坏血酸含量无异常;组织学检查可见肾上腺皮质束状带细胞肿胀透亮,部分细胞边界不清,核消失,脂质减少;电镜下可见束状带细胞浆电子密度降低,出现大量髓鞘样体,线粒体后期消失,与此同时,肝脏已呈明显损害。认为黄磷在引起肝损害同时,可能直接影响皮质激素的生物合成;肝损害影响皮质激素在肝的代谢,故血浆皮质激素水平波动在正常水平或下降。     

高胆固醇饮食对孕鼠肾上腺束状带的影响

本文应用光镜和电镜形态计量,结合血浆皮质酮RIA等方法,探讨妊娠期间持续高胆固醇饮食15天和21天孕鼠肾上腺皮质速状带的形态和功能变化。结果表明,高胆固醇饮食虽然可引起不同时期孕鼠肾上腺相对重量、束状带体积比和束状带细胞的平均体积增加,但在本质上其效应不同。孕15天时,其线粒体和SER体密度增加,血浆皮质酮水平明显升高;而孕21天时,这些指标变化则相反。     

Inhibitory effects of cyproheptadine on pituitary-thyroid axis and pancreatic β cells in rats

目的：研究赛庚啶（Ｃｙｐ）对大鼠垂体甲状腺轴和胰岛β细胞内分泌功能的影响．方法：用放射免疫测定法及生化分析法观察赛庚啶对大鼠垂体甲状腺轴和胰岛β细胞内分泌功能的影响．结果：Ｃｙｐ２３ｍｇ·ｋｇ－１，ｉｇ１０ｄ，使大鼠血清ＴＳＨ、胰岛素含量均降低，而Ｔ３、Ｔ４及血糖水平无明显改变．Ｃｙｐ４６ｍｇ·ｋｇ－１引起血清ＴＳＨ、Ｔ３、Ｔ４和胰岛素含量显著降低，血糖水平明显升高；垂体ＴＳＨ细胞和胰岛β细胞的超微结构亦发生不同程度的退行性变化．结论：Ｃｙｐ对垂体甲状腺轴和胰岛β细胞的内分泌功能有抑制作用     

赛庚啶对大鼠垂体-肾上腺皮质轴作用及机制的研究

目的　研究赛庚啶 (cyproheptadineCyp)对大鼠垂体 肾上腺皮质轴内分泌功能及机制的影响。方法　用放射免疫分析法 (RIA)观察Cyp对大鼠血清ACTH、可的松水平的影响。用电镜及荧光定量PCR技术 ,观察Cyp对ACTH细胞、肾上腺皮质束状带细胞超微结构及钙调素 (calmodulinCaM)mRNA在垂体、肾上腺皮质基因表达的影响。结果　Cyp 2 3、4 6mg·kg- 1 ·d- 1 ,ig,连续用药 1 4d ,可使大鼠血清ACTH和可的松含量降低 (P <0 0 5 ,P <0 0 1 )。组织形态电镜观察 ,该药亦可引起大鼠垂体ACTH细胞、肾上腺皮质束状带细胞超微结构的退行性改变。同时发现CaMmRNA在垂体、肾上腺皮质的基因表达较对照组减少 (P <0 0 5 ,P<0 0 1 )。结论　Cyp对大鼠垂体 肾上腺皮质轴分泌功能有抑制作用 ,其机制可能与抑制CaMmRNA在垂体、肾上腺皮质的基因表达有关     

松果腺对血清皮质酮的影响及其作用部位分析

松果腺对血清皮质酮有抑制作用，对其昼夜节律的中值及峰值位相亦产生影响．松果腺抑制肾上腺增重，切除松果腺使血浆ＡＣＴＨ升高，注射地塞米松或戊巴比妥钠均阻断了松果腺激素褪黑素的降皮质酮作用。提示：松果腺对血清皮质酮的抑制作用是通过其激素——褪黑素实现的，而褪黑素则主要是通过下丘脑－垂体－肾上腺皮质轴起的作用．     

黄磷抑制肾上腺皮质激素分泌水平机理探讨

实验结果表明：黄磷对豚鼠经腹腔多次染毒后（五周），可致血、尿、肾上腺匀浆皮质醇水平全面下降（Ｐ＜０．０１），其中毒机理可能是：１．黄磷直接损害肾上腺皮质束状带细胞，致其变性和坏死，线粒体损害较明显。２．黄磷影响肾上腺皮质激素的生物合成过程，使激素合成原料血胆固醇含量降低，抑制线粒体酶Ｃ２０－２２碳链裂解酶和１１β羟化酶活性，致使皮质醇合成减少。（３）黄磷可致肾上腺皮质结合球蛋白（ＣＢＧ）含量明显减少（Ｐ＜０．０１），影响皮质醇的运送。     

松果体和褪黑激素通过下丘脑影响大鼠腹腔巨噬细胞化学发光

研究松果体和褪黑激素是否通过下丘脑影响腹腔巨噬细胞功能。松果体切除术；腹腔巨噬细胞化学发光测定；正后脑地诺前列酮放射免疫测定；下丘脑注射Ｍｅｌ。松果体切除后腹腔巨噬细胞化学发光值降低，下丘脑地诺前列酮含量升高，１６：００ｉｐＭｅｌ（１０μｇｋｇ＾－１ｄ＾－１×７ｄ）可使其恢复并升高正常大鼠腹腔巨噬细胞化学发光值，降低其下丘脑前列酮含量。腹腔巨噬细胞化学发光值与下丘脑地诺前列酮含量的变化存在负相关（     

海洛因依赖者内分泌和生殖系统超微病理变化研究

目的 :探讨海洛因依赖者内分泌系统、生殖系统超微病理损害。方法 :应用透射电镜对 4例海洛因依赖者内分泌系统、生殖系统进行观察 ,并与对照组进行比较。结果 :海洛因依赖者垂体腺细胞线粒体肿胀 ,嵴断裂 ,内质网扩张 ,神经内分泌细胞及神经内分泌颗粒减少 ;甲状腺滤泡上皮细胞胞浆内细胞器减少 ;肾上腺皮质线粒体肿胀 ,可见多量溶酶体、脂滴、滑面内质网和脂褐素 ,可见髓鞘样结构 ;胰岛细胞神经内分泌颗粒丰富 ,可见脂质体退化 ,部分细胞内分泌颗粒稀少 ;睾丸和卵巢可见生殖细胞和间质细胞数量减少 ,胞内细胞器减少。对照组除偶见线粒体肿胀外 ,组织结构未见其它异常。结论 :海洛因依赖者内分泌系统和生殖系统超微病理改变呈急、慢性缺氧性变性、坏死和退行性改变     

赛庚啶对大鼠垂体-甲状腺轴功能的影响

目的研究赛庚啶对大鼠垂体－甲状腺轴内分泌功能的影响。方法用放射免疫分析法和电镜观察赛庚啶对大鼠垂体－甲状腺轴内分泌功能及垂体ＴＳＨ细胞超微结构的影响。结果赛庚啶２．３ｍｇ·ｋｇ－１，ｉｇ，连续用药１０ｄ，可使大鼠血清促甲状腺激素（ＴＳＨ）含量明显降低（Ｐ＜０．０５），而甲状腺激素（Ｔ３，Ｔ４）则无显著变化。４．６ｍｇ·ｋｇ－１赛庚啶可引起大鼠血清ＴＳＨ，Ｔ３，Ｔ４水平均显著降低（Ｐ＜０．０１及０．０５），组织形态电镜观察，该药亦引起大鼠垂体ＴＳＨ细胞超微结构的退行性改变。结论赛庚啶对大鼠垂体－甲状腺轴的内分泌功能有抑制作用。     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.