The Link between Iron Turnover and Pharmacotherapy in Transplant Patients.

Iron is a transition metal that plays a crucial role in several physiological processes. It can also exhibit toxic effects on cells, due to its role in the formation of free radicals. Iron deficiency and anemia, as well as iron overload, are the result of impaired iron metabolism, in which a number of proteins, such as hepcidin, hemojuvelin and transferrin, take part. Iron deficiency is common in individuals with renal and cardiac transplants, while iron overload is more common in patients with hepatic transplantation. The current knowledge about iron metabolism in lung graft recipients and donors is limited. The problem is even more complex when we consider the fact that iron metabolism may be also driven by certain drugs used by graft recipients and donors. In this work, we overview the available literature reports on iron turnover in the human body, with particular emphasis on transplant patients, and we also attempt to assess the drugs' impact on iron metabolism, which may be useful in perioperative treatment in transplantology.

Zika virus: mapping and reprogramming the entry.

BACKGROUND: The flaviviridae family comprises single-stranded RNA viruses that enter cells via clathrin-mediated pH-dependent endocytosis. Although the initial events of the virus entry have been already identified, data regarding intracellular virus trafficking and delivery to the replication site are limited. The purpose of this study was to map the transport route of Zika virus and to identify the fusion site within the endosomal compartment. METHODS: Tracking of viral particles in the cell was carried out with confocal microscopy. Immunostaining of two structural proteins of Zika virus enabled precise mapping of the route of the ribonucleocapsid and the envelope and, consequently, mapping the fusion site in the endosomal compartment. The results were verified using RNAi silencing and chemical inhibitors. RESULTS: After endocytic internalization, Zika virus is trafficked through the endosomal compartment to fuse in late endosomes. Inhibition of endosome acidification using bafilomycin A1 hampers the infection, as the fusion is inhibited; instead, the virus is transported to late compartments where it undergoes proteolytic degradation. The degradation products are ejected from the cell via slow recycling vesicles. Surprisingly, NH4Cl, which is also believed to block endosome acidification, shows a very different mode of action. In the presence of this basic compound, the endocytic hub is reprogrammed. Zika virus-containing vesicles never reach the late stage, but are rapidly trafficked to the plasma membrane via a fast recycling pathway after the clathrin-mediated endocytosis. Further, we also noted that, similarly as other members of the flaviviridae family, Zika virus undergoes furin- or furin-like-dependent activation during late steps of infection, while serine or cysteine proteases are not required for Zika virus maturation or entry. CONCLUSIONS: Zika virus fusion occurs in late endosomes and is pH-dependent. These results broaden our understanding of Zika virus intracellular trafficking and may in future allow for development of novel treatment strategies. Further, we identified a novel mode of action for agents commonly used in studies of virus entry. Schematic representation of differences in ZIKV trafficking in the presence of Baf A1 and NH4Cl.

Canine Respiratory Coronavirus, Bovine Coronavirus, and Human Coronavirus OC43: Receptors and Attachment Factors.

Despite high similarity of canine respiratory coronavirus (CRCoV), bovine coronavirus, (BCoV) and human coronavirus OC43 (HCoV-OC43), these viruses differ in species specificity. For years it was believed that they share receptor specificity, utilizing sialic acids for cell surface attachment, internalization, and entry. Interestingly, careful literature analysis shows that viruses indeed bind to the cell surface via sialic acids, but there is no solid data that these moieties mediate virus entry. In our study, using a number of techniques, we showed that all three viruses are indeed able to bind to sialic acids to a different extent, but these molecules render the cells permissive only for the clinical strain of HCoV-OC43, while for others they serve only as attachment receptors. CRCoV and BCoV appear to employ human leukocyte antigen class I (HLA-1) as the entry receptor. Furthermore, we identified heparan sulfate as an alternative attachment factor, but this may be related to the cell culture adaptation, as in ex vivo conditions, it does not seem to play a significant role. Summarizing, we delineated early events during CRCoV, BCoV, and HCoV-OC43 entry and systematically studied the attachment and entry receptor utilized by these viruses.

Prognostic Value of the Modified Atherogenic Index of Plasma during Body Mass Reduction in Polish Obese/Overweight People.

Although weight loss is recommended for obese patients, it remains questionable how much weight loss is optimal. A novel index that accurately determines the risk of cardiovascular diseases (CVDs) in terms of weight loss is needed. The modified Atherogenic Index of Plasma (AIP), presented here is unique in the literature. It is calculated based on data for anti-atherogenic, high-density lipoprotein cholesterol (HDL-C) fractions, instead of the total HDL-C. This study investigates whether weight loss correlates with CVD risk, and whether the modified AIP allows more accurate diagnostics in obese/overweight people. According to the increase or decrease of AIP during weight loss, 52 Polish patients were subdivided into two groups: group I (increased AIP; n = 16) and group II (decreased AIP; n = 36). The patients' body mass composition and fasting serum lipid parameters (total cholesterol, triglycerides, HDL-C, and LDL-C (low-density lipoprotein cholesterol)), and cholesterol in 21 lipoprotein sub-fractions were determined. Over six months, all patients reduced their body mass by about 10%. There were no significant differences in anthropometric measures between groups. Increases in large and intermediate HDL-C fractions 1 to 6 and decreases in smaller fractions 7 to 10 were observed in group II. In group I, HDL-C fractions 1 and 10 decreased, while cholesterol in other fractions increased. Increases were observed in the antiatherogenic HDL-C of 52% of group II and 4% of group I. As for atherogenic HDL-C, a decrease of 24% was observed in group II and an increase of 9% in group I. In group I, increases of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and large LDL fractions were noticed, and the reverse in group II. The results show that the modified AIP is a more accurate indicator of CVD risk than existing indices, and that uncontrolled weight reduction does not necessarily have a beneficial influence, and may adversely affect the cardiovascular system.

The effect of occupational chronic lead exposure on the complete blood count and the levels of selected hematopoietic cytokines.

Associations among lead exposure, blood morphology, and cytokines influencing hematopoiesis are still inconclusive. Therefore, the objective of the present study was to demonstrate whether workers chronically exposed to lead demonstrate changes in complete blood count (CBC) parameters associated with altered levels of selected cytokines influencing hematopoiesis. The study covered 80 male subjects employed in the zinc-lead works in Miasteczko Slaskie. The subjects were divided into two groups: control group (24 healthy administration workers without a history of occupational exposure to lead compounds) and lead exposed group (56 subjects exposed to lead compounds in their work environment). The values of HTC, MCV, MCH, RDW-CV, PDW, and LMR were significantly lower in the exposed group than in the controls by 3%, 5%, 3%, 4%, 15%, and 47%, respectively. However, the levels of MCHC and MPV were higher in the exposed group than in the controls by 3% and 11%, respectively. Analogically, the values of MXD and MXD% were also significantly higher by 118% and 70%, respectively. The concentration of IL-7 was significantly higher in the exposed group compared to the controls by 143%. In this study, chronic lead exposure in the occupational setting at levels <50 µg/dl does not affect RBC count and hemoglobin level but decreases MCV and hematocrit. Similarly, chronic lead toxicity does not affect WBC count but alters proportions of different types of leukocytes with significant increase of MXD count associated with elevated level of IL-7. Oppositely to a short-term lead exposure, chronic lead exposure elevates MPV and does not alter PLT count.

Effect of L-arginine on memory in rats.

Effect of intracerebroventricularly (icv) or subcutaneously (sc) injected L-arginine (L-Arg) on memory was determined using the procedure of passive avoidance test. Moreover, locomotor and exploratory activity was determined in rats in an open field test. We found that either the peripheral (sc) or icv administration of L-Arg significantly prolonged latency time in the passive avoidance test. This effect appeared at 20-100-fold higher doses in comparison to such effect of arginine vasopressin (AVP) observed in our previous study. This memory improving effect was not correlated with the inhibition of locomotor and exploratory activity. The effect of the lower icv dose (10 nmoles) of L-Arg was blocked by L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor. Moreover, the effect of both used doses (10 and 100 nmoles) of L-Arg was also blocked by S-methylisothiourea (Mtu), a selective inhibitor of inducible isoform of NOS. On the other hand, the effect of higher icv dose of L-Arg (100 nmoles) was prevented by 7-nitroindazole (7-NI), an inhibitor of neuronal NOS. We conclude that a uniform effect of L-Arg on memory is mediated by different isoforms of NOS, mainly by neuronal and inducible NOS.