Histopathological effects of cisplatin,doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats

Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs.     

The Ras guanine nucleotide exchange factor RasGRF1 promotes matrix metalloproteinase-3 production in rheumatoid arthritis synovial tissue

Introduction  

Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases (MMPs). Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to contribute to inflammation and joint destruction in RA, and abrogation of Ras family signaling is therapeutic in animal models of RA. Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to contribute to spontaneous MMP production in melanoma cancer cells. Here, we examine the potential relationship between RasGRF1 expression and MMP production in RA, reactive arthritis, and inflammatory osteoarthritis synovial tissue and FLS.     

Natural occurrence of deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol,nivalenol, 4,7-dideoxynivalenol,and zearalenone in polish wheat

Three wheat samples collected in 1987 in Central Poland and naturally infected withFusarium spp were analyzed for the presence ofFusarium spp andFusarium toxins. Heads were separated into three fractions: kernels with visibleFusarium damage, healthy looking kernels, and chaff + rachis. The samples contained deoxynivalenol (2.0 – 40.0μg/g), nivalenol (O.O1μg/g), 4,7-dideoxynivalenol (0.10 – 0.15μg/g). 15-acetyldeoxynivalenol (0.10–2.00 μg/g), 3-acetyldeoxynivalenol (O/1Oμg/g), and zearalenone (0.01–2.00μg/g). This is the first report about 15 - acetyldeoxynivalenol in European wheat and the co-occurrence of 3 - acetyldeoxynivalenol and 15-acetyldeoxynivalenol in the same sample of contaminated cereals.     

Transport of Oxygen by the Blood of the Land Crab, Gecarcinus lateralis

Parameters relating to transport of oxygen were measured inthe pericardial blood and venous outflow from the first walkingleg of Gecarcinus lateralis. O₂-equilibrium curves of the hemocyaninof G. lateralis were found to be sigmoid and, at 27°C andpH 7.45, to have a half-saturation pressure of about 17 mm Hgoxygen. Average partial pressures of oxygen as measured by O₂-electrodewere 32 mm Hg in pericardial blood and 9 mm Hg in the venoussamples. Analysis of the O₂-content in corresponding samplesby the Van Slyke technique revealed an average of 2.17 volumes% O₂-capacity for whole blood, 1.45 volumes % for pericardialblood, and 0.61 volumes % for venous blood. Estimates basedon the Van Slyke analyses indicated an average pO₂ of 29 and14 mm Hg in pericardial and venous samples, respectively. Thesefigures agree fairly well with those obtained by means of O₂-electrodes.Of the oxygen carried to the tissues, about 94% is carried asoxyhemocyanin and about 6% is carried in physical solution.As the blood passes through the gills, the hemocyanin, on anaverage, becomes 80–85% saturated with oxygen and returnedfrom the tissues 18–45% saturated with oxygen. These resultsindicate that the blood of G. lateralis has a higher O₂-capacitythan the blood of most other decapod crustaceans for which similarinformation is available. In addition, the blood of G. lateralistransports more oxygen to the tissues per unit volume than doother crustacean bloods.     

Expression and characterization of ovine major histocompatibility complex class II (OLA-DR) genes

Previous work made use of nucleic acid probes corresponding to different subtypes of the class II regions of the human and murine major histocompatibility complex (MHC) to isolate seven different alpha and 24 different beta genes of the ovine MHC from two cosmid libraries. In an attempt to identify pairs of alpha and beta genes capable of cell surface expression, all permutations of alpha and beta genes were in turn transfected into mouse L-cells. Two pairs of alpha and beta genes co-expressed and stable ovine MHC class II L-cell lines were developed. The expressed alpha genes had previously been defined as DR-alpha homologues (DRA) by differential Southern hybridization to human subtype specific class II probes. The expressed ovine beta genes were also assigned as ovine DR-beta homologues (DRB) on the basis of their sequence having a higher degree of similarity with human DRB than any other subtype. A total of eight out of 23 anti-sheep class II specific monoclonal antibodies were typed OLA-DR specific by FACScan analysis using the L-cell lines.     

Multimodal alarm behavior in urban and rural gray squirrels studied by means of observation and a mechanical robot

Urbanization of animal habitats has the potential to affect the natural communication systems of any species able to survive in the changed environment. Urban animals such as squirrels use multiple signal channels to communicate, but it is un-known how urbanization has affected these behaviors. Multimodal communication, involving more than one sensory modality, can be studied by use of biomimetic mechanical animal models that are designed to simulate the multimodal signals and be pre-sented to animal subjects in the field. In this way the responses to the various signal components can be compared and contrasted to determine whether the multimodal signal is made up of redundant or nonredundant components. In this study, we presented wild gray squirrels in relatively urban and relatively rural habitats in Western Massachusetts with a biomimetic squirrel model that produced tail flags and alarm barks in a variety of combinations. We found that the squirrels responded to each unimodal component on its own, the bark and tail flag, but they responded most to the complete multimodal signal, containing both the acoustic and the moving visual components, providing evidence that in this context the signal components are redundant and that their combination elicits multimodal enhancement. We expanded on the results of Parian et al. (2009) by providing data on sig-naling behavior in the presence and absence of conspecifics, suggesting that alarm signaling is more likely if conspecifies are present. We found that the squirrels were more active in the urban habitats and that they responded more to tail flagging in the urban habitats as compared to the rural ones, suggesting the interesting possibility of a multimodal shift from reliance on audio to visual signals in noisier more crowded urban habitats.