Endothelin-1-induced PMN infiltration and mucosal dysfunction in the rat small intestine

The objectives of this study were to characterize the effects of endothelin (ET)-1 on intestinal mucosal parameters and to assess the contribution of polymorphonuclear leukocytes (PMNs), intercellular adhesion molecule-1 (ICAM-1), and a platelet-activating factor (PAF) to the mucosal dysfunction induced by ET-1. Different concentrations of ET-1 (100, 200, and 400 pmol/kg) were infused into the superior mesenteric artery for 10 min, and tissue samples were obtained 30 min after terminating the infusion. ET-1 administration significantly elevated tissue myeloperoxidase activity, plasma carbonyl content, and tissue chemiluminescence intensity, indicating that ET-1 produces PMN infiltration and oxidant stress. Blood-to-lumen clearance of (51)Cr-EDTA significantly increased after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2 mg/kg), antineutrophil serum, and PAF antagonist (WEB-2086, 10 mg/kg) attenuated the mucosal barrier dysfunction induced by ET-1. Overall, our data indicate that ET-1 causes PMN accumulation, oxidant stress, and mucosal dysfunction in the rat small intestine and that ET-1-induced mucosal dysfunction involves a mechanism that includes a role for PMNs, ICAM-1, and PAF.     

Hepatocellular carcinoma in a squirrel monkey (Saimiri sciureus)

Abstract: A well-differentiated hepatocellular carcinoma of the liver was diagnosed in a female squirrel monkey. The lesion showed trabecular, solid and glandular features that are characteristics of malignant liver tumours.     

Fast and Forceful Refolding of Stretched α-Helical Solenoid Proteins

Anfinsen's thermodynamic hypothesis implies that proteins can encode for stretching through reversible loss of structure. However, large in vitro extensions of proteins that occur through a progressive unfolding of their domains typically dissipate a significant amount of energy, and therefore are not thermodynamically reversible. Some coiled-coil proteins have been found to stretch nearly reversibly, although their extension is typically limited to 2.5 times their folded length. Here, we report investigations on the mechanical properties of individual molecules of ankyrin-R, β-catenin, and clathrin, which are representative examples of over 800 predicted human proteins composed of tightly packed α-helical repeats (termed ANK, ARM, or HEAT repeats, respectively) that form spiral-shaped protein domains. Using atomic force spectroscopy, we find that these polypeptides possess unprecedented stretch ratios on the order of 10-15, exceeding that of other proteins studied so far, and their extension and relaxation occurs with minimal energy dissipation. Their sequence-encoded elasticity is governed by stepwise unfolding of small repeats, which upon relaxation of the stretching force rapidly and forcefully refold, minimizing the hysteresis between the stretching and relaxing parts of the cycle. Thus, we identify a new class of proteins that behave as highly reversible nanosprings that have the potential to function as mechanosensors in cells and as building blocks in springy nanostructures. Our physical view of the protein component of cells as being comprised of predominantly inextensible structural elements under tension may need revision to incorporate springs.     

Preserving effects of melatonin on the levels of glutathione and malondialdehyde in rats exposed to irradiation

In this study we investigated whether pretreatment with melatonin was protective against the injury of the central nervous system (CNS) in rats receiving LD(50) whole body irradiation. The wistar rats were randomized into four groups: i) the control group (CG), ii) melatonin-administered group (MG; 1 mg/kg body weight), iii) irradiated group (RG; 6.75 Gy, one dose), and iv) melatonin-administered and irradiated group (MRG). Blood samples were drawn from the rats 24 h after the treatment and plasma glutathione levels were assayed. Plasma glutathione level was significantly higher in RG than CG. The melatonin pretreatment prevented GSH increase induced by irradiation. Lipid peroxidation and glutathione levels of rat cerebral cortex were determined in all groups after 24 h. Cortical malondialdehyde (MDA) was significantly higher in the RG. The melatonin pretreatment prevented cortical MDA increase induced by irradiation. Cortical GSH was significantly lower in RG than the CG. The melatonin pretreatment prevented cortical GSH decrease induced by irradiation. Tissue samples were obtained from cerebral cortex and hypothalamus which also were affected by ionizing irradiation in the CNS and were evaluated with electron microscopy. Histopathological findings showed that LD(50) whole body irradiation resulted in damage of the neuronal cells of CNS. The results obtained from this study demonstrated that pretreatment with melatonin prevented the damage that develops in CNS following irradiation. The beneficial effect of melatonin can be related to protection of the CNS from oxidative injury and preventing the decrease in the level of cortical glutathione.     

Recent developments in effector biology of filamentous plant pathogens

Filamentous pathogens, such as plant pathogenic fungi and oomycetes, secrete an arsenal of effector molecules that modulate host innate immunity and enable parasitic infection. It is now well accepted that these effectors are key pathogenicity determinants that enable parasitic infection. In this review, we report on the most interesting features of a representative set of filamentous pathogen effectors and highlight recent findings. We also list and describe all the linear motifs reported to date in filamentous pathogen effector proteins. Some of these motifs appear to define domains that mediate translocation inside host cells.     

Glial precursor cell transplantation therapy for neurotrauma and multiple sclerosis

Traumatic injury to the brain or spinal cord and multiple sclerosis (MS) share a common pathophysiology with regard to axonal demyelination. Despite advances in central nervous system (CNS) repair in experimental animal models, adequate functional recovery has yet to be achieved in patients in response to any of the current strategies. Functional recovery is dependent, in large part, upon remyelination of spared or regenerating axons. The mammalian CNS maintains an endogenous reservoir of glial precursor cells (GPCs), capable of generating new oligodendrocytes and astrocytes. These GPCs are upregulated following traumatic or demyelinating lesions, followed by their differentiation into oligodendrocytes. However, this innate response does not adequately promote remyelination. As a result, researchers have been focusing their efforts on harvesting, culturing, characterizing, and transplanting GPCs into injured regions of the adult mammalian CNS in a variety of animal models of CNS trauma or demyelinating disease. The technical and logistic considerations for transplanting GPCs are extensive and crucial for optimizing and maintaining cell survival before and after transplantation, promoting myelination, and tracking the fate of transplanted cells. This is especially true in trials of GPC transplantation in combination with other strategies such as neutralization of inhibitors to axonal regeneration or remyelination. Overall, such studies improve our understanding and approach to developing clinically relevant therapies for axonal remyelination following traumatic brain injury (TBI) or spinal cord injury (SCI) and demyelinating diseases such as MS.     

Fine needle aspiration biopsy of the parotid gland. Diagnostic problems and 2 uncommon cases

OBJECTIVE: To describe the diagnostic problems and present our findings in 2 uncommon tumors, malignant myoepithelioma and small cell undifferentiated carcinoma, by examining fine needle aspiration (FNA) biopsies of parotid gland masses. STUDY DESIGN: The study group consisted of 34 females and 41 males 12-80 years old, with an average of 44. Excluding inflammatory results, all adequate aspirates were confirmed histologically to determine the correlation. RESULTS: Sensitivity of FNA cytology was 91%, with specificity of 98%. We encountered some difficulties, and therefore misdiagnoses, in evaluating specific neoplasms, such as adenoid cystic carcinoma and Warthin's tumor, which have well-established cytologic diagnostic criteria. Two cases of uncommon neoplasms of salivary glands, small cell undifferentiated carcinoma and malignant myoepithelioma, were cytologically found to be malignant but not further classified. In addition, tuberculous parotitis, with its well-defined features, should to be referred since unnecessary surgery can be avoided by using FNA cytology. CONCLUSION: FNA is a sensitive and specific diagnostic tool for parotid gland masses. However, specific classification of neoplasms may sometimes be difficult. Pathologists should be aware of specific entities, such as malignant myoepithelioma, when evaluating high grade neoplasms.     

The role of stratifin in fibroblast–keratinocyte interaction

Stratifin is a member of 14-3-3 protein family, a highly conserved group of proteins constituted by seven isoforms. They are involved in numerous crucial intracellular functions such as cell cycle and apoptosis, regulation of signal transduction pathways, cellular trafficking, cell proliferation and differentiation, cell survival, and protein folding and processing, among others. At epidermal level, stratifin (also called 14-3-3 sigma) has been described as molecule with relevant functions. For instance, this isoform is a marker associated with keratinocyte differentiation. In this maturation process, the presence of dominant negative molecules of p53 induces a “stemness condition” of keratinocyte precursor cells and suppression of stratifin expression. In addition, the recently described keratinocyte-releasable form of stratifin is involved in dermal fibroblast MMP-1 over-expression through c-Fos and c-Jun activity. This effect is mediated, at least in part, by p38 mitogen-activated protein kinase (MAPK). Other MMP family members such as stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), neutrophil collagenase (MMP-8), and membrane-type MMP-24 (MT5-MMP) are also up-regulated by stratifin. Within fibroproliferative disorder of skin, hypertrophic scar and keloids exhibit a high content of collagen, proteoglycans, and fibronectin. Thus, the MMP profile induced by stratifin is an interesting starting point to establish new therapeutic tools to control the process of wound healing. In this review, we will focus on site of synthesis and mode of action of stratifin in skin and wound healing.     

How Methylammonium Cations and Chlorine Dopants Heal Defects in Lead Iodide Perovskites

Lead tri‐iodide methylammonium (MAPbI₃) perovskite polycrystalline materials show complex optoelectronic behavior, largely because their 3D semiconducting inorganic framework is strongly perturbed by the organic cations and ubiquitous structural or chemical inhomogeneities. Here, a newly developed time‐dependent density functional theory‐based theoretical formalism is taken advantage of. It treats electron–hole and electron–nuclei interactions on the same footing to assess the many‐body excited states of MAPbI₃ perovskites in their pristine state and in the presence of point chemical defects. It is shown that lead and iodine vacancies yield deep trap states that can be healed by dynamic effects, namely rotation of the methylammonium cations in response to point charges, or through slight changes in chemical composition, namely by introducing a tiny amount of chlorine dopants in the defective MAPbI₃. The theoretical results are supported by photoluminescence experiments on MAPbI_3?mCl_m and pave the way toward the design of defect‐free perovskite materials with optoelectronic performance approaching the theoretical limits.     

Melatonin treatment for prevention of oxidative stress: involving histopathological changes

This study was undertaken to test the effect of irradiation on the histopathology of the hypothalamus and cerebral cortex. In addition, the probable effects of radiotherapy on the activities of antioxidant enzymes and levels of nitric oxide (NO) in the plasma were investigated as well. The effects of melatonin treatment on radiotherapy-based central nervous system (CNS) damage were also studied. For this purpose, the rats were randomized into four groups. The first group was the control group (sham-exposed group), the second group received only melatonin, the third group was irradiated and the fourth group received both melatonin and irradiation. Plasma samples of rats were collected for measuring the activities of superoxide dismutase (SOD), catalase (CAT) and the levels of NO. 24 h after the interventions, tissue samples were obtained from the hypothalamus and the cerebral cortex for the light microscopic investigations. These tissues were mostly affected by radiation. The results indicated that the application of radiation significantly enhanced the levels of plasma SOD and NO. On the other hand, melatonin pretreatment prevented the decrease in plasma CAT activity induced by irradiation. It was found that the application of melatonin could significantly prevent the irradiation-induced damages. Light microscopic results revealed that the damage of the CNS by radiation was prevented by the application of melatonin.