Toxocariasis: a silent threat with a progressive public health impact

Background: Toxocariasis is a neglected parasitic zoonosis that afflicts millions of the pediatric and adolescent populations worldwide, especially in impoverished communities. This disease is caused by infection with the larvae of Toxocara canis and T. cati, the most ubiquitous intestinal nematode parasite in dogs and cats, respectively. In this article, recent advances in the epidemiology, clinical presentation, diagnosis and pharmacotherapies that have been used in the treatment of toxocariasis are reviewed. Main text: Over the past two decades, we have come far in our understanding of the biology and epidemiology of toxocariasis. However, lack of laboratory infrastructure in some countries, lack of uniform case definitions and limited surveillance infrastructure are some of the challenges that hindered the estimation of global disease burden. Toxocariasis encompasses four clinical forms: visceral, ocular, covert and neural. Incorrect or misdiagnosis of any of these disabling conditions can result in severe health consequences and considerable medical care spending. Fortunately, multiple diagnostic modalities are available, which if effectively used together with the administration of appropriate pharmacologic therapies, can minimize any unnecessary patient morbidity. Conclusions: Although progress has been made in the management of toxocariasis patients, there remains much work to be done. Implementation of new technologies and better understanding of the pathogenesis of toxocariasis can identify new diagnostic biomarkers, which may help in increasing diagnostic accuracy. Also, further clinical research breakthroughs are needed to develop better ways to effectively control and prevent this serious disease

Primenenija o protivolentochnykh medikamentakh dlja domashnikh zhivotnykh

The author gives a review of parasiticides, beginning from the oldest ones used for domestic animals. Particular attention is given to new preparations against tapeworms, their dosage, effectiveness and toleration by the treated animal's organism being discussed. This is done on the example of a new drug against tapeworms - Resorantel (TerenolR). There are presented the results of investigations on the mechanism and effectiveness of its action on mature and immature forms of the parasite, on removal from the animal and toleration of the preparation by the host

Ubiquitin conjugation and deconjugation in NF-κB signaling.

Transcription factor NF‑κB regulates the physiological response to a variety of stimuli. The NF‑κB pathway has served as a paradigm for analyzing the impact of the covalent protein modifier ubiquitin on signal transduction. The discovery in the early 1990s that degradation of cytosolic NF‑κB inhibitors (IκBs) is mediated by the ubiquitin proteasome system (UPS) was the first example for a direct involvement of ubiquitination in cellular signaling. By now it has become clear that the role of the ubiquitin system in the NF‑κB pathway extends far beyond triggering IκB destruction. The IκB kinase (IKK) complex is the key regulator of NF‑κB. Attachment of ubiquitin chains to the IKK complex and to further upstream components drives NF‑κB signaling pathways by promoting the clustering of the signaling network. Whereas ubiquitin conjugation serves a positive function in the NF‑κB pathway, ubiquitin deconjugation acts as a negative regulatory feedback mechanism that is critically involved in balancing the strength and the duration of the NF‑κB response. Moreover, inactivation of deconjugating enzymes can cause sustained NF‑κB activity under pathological conditions like chronic inflammation or cancer. Here we review the impact of the ubiquitin system on the NF‑κB signaling network by putting a focus on the enzymes that help to shape the plasticity of the NF‑κB response

Radiosensitization of wildtype p53 cancer cells by the MDM2-inhibitor PXN727 is associated with altered Heat shock protein 70 (Hsp70) levels.

The oncoprotein MDM2 (murine double minute 2) is often overexpressed in human tumors and thereby attenuates the function of the tumor suppressor p53. In this study, we investigated the effects of the novel MDM2-inhibitor PXN727 on p53 activation, cell proliferation, cell cycle distribution and radiosensitivity. Since the localization of heat shock protein 70 (Hsp70) exerts different effects on radioresistance of tumor cells, we investigated the impact of PXN727 on intracellular, membrane, and secreted Hsp70 levels. We could show that PXN727 exerts its effects on wildtype p53 (HCT116 p53(+/+), A549) but not p53 depleted (HCT116 p53(-/-)) or mutated (FaDu) tumor cells. PXN727 activates p53, induces the expression of p21, reduces the proportion of cells in the radioresistant S-phase and induces senescence. Radiosensitivity was significantly increased by PXN727 in HCT116 p53(+/+) tumor cells. Furthermore, PXN727 causes a downregulation of Hsp70 membrane expression and an upregulated secretion of Hsp70 in wildtype p53 tumor cells. Our data suggest that re-activation of p53 by MDM2-inhibition modulates Hsp70 membrane expression and secretion which might contribute to the radiosensitizing effect of the MDM2-inhibitor PXN727