Sexual dimorphism and seasonal cariation in submandibular gland histology of Bolomys lasiurus (Rodentia, Muridae).

Wild rodents (Bolomys lasiurus) of both sexes were caught in a cerrado grassland area during the dry (July–September) and rainy (January–March) seasons of Brazil. Fasted animals were perfused with Karnovsky fixative through the left ventricle, under ether anesthesia, and the submandibular gland was processed for embedding in historesin. Histological and histometric data show sexual dimorphism at both seasons. In the volume percentage of the granular convoluted tubules (GCT) and their secretory granules, the males exhibited higher values. The absolute volume occupied by these structures, however, was dimorphic only in the rainy season. The diameter of the GCT, the height of its epithelium, and its total length were also greater in males during the rainy season. The absolute volumes of the acini and of the ductal tree were identical in both sexes in the dry and rainy seasons but the acinar diameter increased in the males and females during the rainy season. The sexual dimorphismand the seasonal variations now described in the B. lasiurus submandibular glands could be explained by the augmented reproductive activity of the males in the rainy period

Histopathology of Leishmania major infection: revisiting L. major histopathology in the ear dermis infection model

We describe the relationship between lesion outcome and histopathological hallmarks in susceptible (BALB/c) and resistant (C57BL/6 and IL-4-deficient BALB/c) mouse strains over the course of a 12-week-infection with Leishmania major in the ear. The infiltration of mononuclear cells and polymorphonuclear cells occurred within 6 h and mononuclear cells predominated one week post-infection. Permissive intracellular growth of the pathogen was associated with non-healing lesions. In contrast, tissue damage and clearance of the parasite was observed in healing lesions and was associated with inducible nitric oxide synthase expression. The identification of the structural components of tissue reaction to the parasite in this study furthers our understanding of subjacent immune effector mechanisms

The endogenous cytokine profile and nerve fibre density in mouse ear Leishmania major-induced lesions related to nociceptive thresholds.

Several reports have shown that cutaneous leishmaniasis lesions are painless, suggesting that Leishmania infection interferes with pain perception. Comparisons of inflammation-induced hyperalgesia between BALB/c and C57BL/6 mice have been little explored in the literature, and comparative data regarding nociception in leishmaniasis are non-existent. In susceptible BALB/c mice and resistant C57BL/6 mice that were intradermally inoculated with a low dose of Leishmania major in the ear, we investigated the variation in nociception over a 12-wk period post-infection and this variation’s association with the structure of nerve fibres and the presence of endogenous cytokines that are classically considered hyper- or hyponociceptive. Infected BALB/c mice presented susceptibility and severe lesions. Infected C57BL/6 mice exhibited resistance and healing lesions. The immune response involved pro- and anti-inflammatory cytokine secretion, respectively. The infection-induced hypoalgesia in BALB/c mice after wks 9 was accompanied by decreased levels of IL-6 and IL-10 in ear tissue with intact nerves. C57BL/6 mice showed short-lived hyperalgesia in wks 2, which was related to increased local levels of IL-6, KC/CXCL-1, TNF-a and IL-10 and a decrease in nerve density. The increase in pro-inflammatory cytokine IL-6, KC/CXCL-1 and TNF-a levels during hyperalgesia suggested a role for these mediators in afferent nerve sensitisation, which was secondary to the inflammatory damage of nerve fibres stained by PGP 9.5. In contrast, the mechanisms of hypoalgesia may include the downregulation of cytokines, the preservation of the structure of nerve endings, and as yet uninvestigated unidentified differences in neurotransmitter release or a direct role of the parasites in the context of the progressive and permissive inflammatory response of BALB/c mice

Neutrophil vacuolization in peripheral blood smear assessed with May Grünwald-Giemsa stain in direct correlation with the severity of hemorrhagic shock and serum lactate in trauma patients.

Tissue trauma induces migration and activation of neutrophils through specific mediators. Vacuolated neutrophils in peripheral blood smear of septic patients correlated with mortality. However, scarce data exist with respect to findings in hemorrhagic shock (HS) trauma patients. The aim of this work was to evaluate the number and size of cytoplasmic and nuclear vacuoles in polymorphonuclear neutrophil (PMN) obtained from a peripheral blood smear stained with the May-Grunwald-Giemsa method in trauma patients with hemorrhagic shock. Seven sequential blood samples were taken from 20 patients with severe hemorrhagic shock and 20 patients who sustained mild thoracic trauma (control group). The first sample was obtained shortly after admission to the hospital followed by new samples taken at 6, 12, 18, 24, 48 and 72 h. Blood smears from both groups were processed to assess vacuolization and vacuole morphology in one hundred PMNs at each time point. The number and the area of vacuoles in the nucleus and the cytoplasm were determined using the program Image-Pro Express version 4.0 for Windows (Media Cybernetics, Bethesda, MD, USA). The number and the area of vacuoles in the cytoplasm and nucleus were significantly different (p <0.05) between shock and control groups. Moreover, serum lactate and heart rate correlated directly with the number (r=0.634) and the area (r=0.624) of cytoplasmic vacuoles as shown by multivariate analysis (p<0.05). Severe hemorrhagic shock induces greater vacuolization of PMNs as compared to mild trauma. PMN vacuolization has direct correlation with serum lactate, a known marker of severe shock

Correction: Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term Murine Model of Tripanosoma cruzi Infection.

[This corrects the article DOI: 10.1371/journal.pone.0153038.]

Enteric neuronal damage, intramuscular denervation and smooth muscle phenotype changes as mechanisms of chagasic megacolon : evidence from a long - term murine model of Tripanosoma cruzi infection.

We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatoryinduced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, he architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long-term inflammatory process mediates neuronal damage and intramuscular and intramural denervation, leading to phenotypic changes in smooth muscle cells associated with fibrosis. These long-term structural changes may represent the basic mechanism for the formation of the Chagasic megacolon