Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with Toxocara canis

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection.     

Fish recolonization of a lowland river with non-buffered storm water discharges but with abated pollution from a large municipality

Water pollution from industrial Metro Łódź (ML), Poland, made the Ner River almost fishless in its middle-lower course for most of the 19th and 20th century. The new sewage treatment plant of ML and reduction of industry have caused pollution abatement there since the 1990s. As a result, the Ner became repopulated, which was shown by fish samples collected along its course in 2000–2012. Multivariate statistical methods helped distinguish unpolluted (I and II, in the upper course), and recovered (III, IV and V, in the middle-lower course) sections of the river. Historical and present data indicated that section III (downstream of ML) recovered least, both before and during the study. Section V (outflow one) recovered most and its fish fauna (almost exclusively native) now displays high and stable biomass, abundance and species richness, including those of obligatory riverine species. Non-native Prussian carp's dominance followed the river degradation gradient, i.e. was highest in section III, and in section V declined to almost absence. This study shows that the revival of native fish fauna seems to be a method of restricting the dominance of this highly tolerant species. Despite the abatement, storm events are very harmful to fish (mostly in section III), because the Ner discharge may then increase manifold and all storm water is drained by the ML combined sewer system to the Ner in several hours. Other stressors are numerous dams and desorption of pollutants from sediment in the middle Ner, and perhaps pollutant inflow from agriculture or local urban areas. Some moderation of storm impact on water entering the Ner from ML by constructing buffer reservoirs would probably cause further fish recovery in section III.     

2-(Trimethylammonium) Ethyl (R)-3-Methoxy-3-oxo-2-Stearamidopropyl Phosphate Suppresses Osteoclast Maturation and Bone Resorption by Targeting Macrophage-Colony Stimulating Factor Signaling

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.     

Osmotic relations during elongation growth in hypocotyls of Helianthus annum L.

The relationship between growth, change in cell osmotic pressure and accumulation of osmotic solutes was investigated in hypocotyls of sunflower (Helianthus annum L.) seedlings. During growth in darkness the osmotic pressure decreased by 50% between days 2 and 6 after sowing. After irradiation of dark-grown seedlings with continuous white light (WL) an inhibition of hypocotyl growth was measured, but the osmotic pressure of the growing cells was not lower than in the dark-grown control. Growth in darkness and after WL irradiation was accompanied by an increase in the amount of osmotic substances (soluble sugars) which was proportional to the increase in length of the organ. During growth in continuous WL the cell osmotic pressure decreased by 45 % between days 2 and 6 after sowing. The transfer of WL-grown seedlings to darkness (“re-etiolation”) resulted in a rapid acceleration of hypocotyl growth, but the cell osmotic pressure was the same as that of the WL grown control. Growth in continuous WL was accompanied by a corresponding accumulation of osmotic substances (soluble sugars). The transition from WL to darkness resulted in an enhanced accumulation of osmotica and an increase in cell-wall extensibility. The results indicate that the relative maintenance of cell osmotic pressure during rapid hypocotyl growth in darkness is caused by an enhanced accumulation of soluble sugars into the growing cells of the organ.     

Effects of prepubertal castration on the spinal motor nucleus of the ischiocavernosus muscle of the rat

Summary The location, number and size of the motoneurons innervating the ischiocavernosus muscle, identified by means of horseradish-peroxidase (HRP) retrograde transport, were studied (1) in adult untreated male rats, (2) in adult male rats castrated before puberty, and (3) in adult male rats castrated before puberty and injected with testosterone from the day of castration. After injection of HRP into the ischiocavernosus muscle, labeled motoneurons were found in the dorsolateral and dorsomedial columns of the lamina IX, at the level of L6 and S1 segments of the spinal cord. Morphometric analysis demonstrated that prepubertal castration induces a statistically significant reduction in the somatic and nuclear areas (40% and 35%, respectively, if compared to those of the control rats) of both the dorsolateral and dorsomedial motoneurons, but does not affect their number. The effects of castration are prevented by exogenous testosterone.Preliminary results were presented at the International Conference on Hormones, Brain and Behaviour, Liège, Belgium, August, 1989     

N-phenyl ureidobenzenesulfonates,a novel class of promising human dihydroorotate dehydrogenase inhibitors

N-phenyl ureidobenzenesulfonates (PUB-SOs) is a new class of promising anticancer agents inducing replication stresses and cell cycle arrest in S-phase. However, the pharmacological target of PUB-SOs was still unidentified. Consequently, the objective of the present study was to identify and confirm the pharmacological target of the prototypical PUB-SO named 2-ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) leading to the cell cycle arrest in S-phase. The antiproliferative and the cytotoxic activities of SFOM-0046 were characterized using the NCI-60 screening program and its fingerprint was analyzed by COMPARE algorithm. Then, human dihydroorotate dehydrogenase (hDHODH) colorimetric assay, uridine rescuing cell proliferation and molecular docking in the brequinar-binding site were performed. As a result, SFOM-0046 exhibited a mean antiproliferative activity of 3.5 μM in the NCI-60 screening program and evidenced that leukemia and colon cancer cell panels were more sensitive to SFOM-0046. COMPARE algorithm showed that the SFOM-0046 cytotoxic profile is equivalent to the ones of brequinar and dichloroallyl lawsone, two inhibitors of hDHODH. SFOM-0046 inhibited the hDHODH in the low nanomolar range (IC₅₀ = 72 nM) and uridine rescued the cell proliferation of HT-29, HT-1080, M21 and MCF-7 cancer cell lines in the presence of SFOM-0046. Finally, molecular docking showed a binding pose of SFOM-0046 interacting with Met43 and Phe62 present in the brequinar-binding site. In conclusion, PUB-SOs and notably SFOM-0046 are new small molecules hDHODH inhibitors triggering replication stresses and S-phase arrest.     

Ames test evaluation of two commercially available zero-valent nickel compounds

Zero-valent nickel compounds are organometallic chemicals that are used in synthetic applications and may also occur as intermediates in nickel-catalyzed hydrogenation reactions used in food processing. Few studies have been performed on their possible genotoxic actions. We have tested two commercially available examples of this class of compounds. Solubility and stability were examined. Mutagenicity testing did not confirm a previous report that bis(1,5-cyclooctadiene)nickel is positive in the Ames assay. No stimulation of lipid peroxidation was observed in studies of bovine erythrocytes exposed in vitro. Our results do not indicate that zero-valent nickel compounds have genotoxic effects.     

木瓜三萜对吲哚美辛致胃黏膜损伤小鼠胃酸分泌及胃黏膜屏障的影响

观察木瓜三萜对吲哚美辛致胃黏膜损伤小鼠胃酸分泌及胃黏膜屏障的影响,在此基础上探讨其可能的机制。实验时,将小鼠随机分为正常组、模型组、木瓜三萜(50、100mg/kg)和奥美拉唑(20mg/kg)组。将给药组灌胃给予相应的药物,正常组和模型组灌胃给予0.5%羧甲基纤维素钠溶液,给药6小时后,除正常组外,灌胃给予20mg/kg的吲哚美辛,每天一次,连续7天。末次给药次日,小鼠用水合氯醛麻醉后,固定,剪开腹腔,进行胃黏膜血流量的测定,然后取胃检测胃液量、胃液酸度和胃结合黏液量;检测胃黏膜中表皮生长因子基因(EGF)和三叶因子1基因(TFF1)的mRNA和蛋白表达。研究发现:吲哚美辛致胃黏膜损伤模型组小鼠胃液分泌量,胃液酸度、胃黏膜血流量、胃结合黏液量及胃黏膜组织中EGF和TFF1的mRNA和蛋白表达明显降低,与正常组比较均具有统计学差异(P<0.01);用木瓜三萜预处理后,上述异常的变化均得到了有效逆转,与模型组比较具有显著性差异(P<0.05,P<0.01)。实验结果表明木瓜三萜(50、100mg/kg)对吲哚美辛致小鼠胃黏膜损伤具有较好的保护作用,通过上调EGF和TFF1的表达水平,增加胃液分泌量、胃液酸度、胃黏膜血流量、胃结合黏液量,恢复胃黏膜防御屏障的功能可能是其治疗吲哚美辛致胃黏膜损伤的机制之一。