PATHOLOGY OF EQUINE INFECTION WITH SALMONELLA TYPHIMPRIUM VAR COPENHAGEN

Twelve horses were divided into three equal groups. Group I animals were inoculated orally with (3.7 X1012)CFU of a highly virulent strain of Salmonella typhimurium 3,;a_r cop§_n__hagen. Group 11 animals were inoculated orally with 2 doses of Salmonella and then challenged with a high dose. Group III horses, served as non - infected control. ‘ The main lesions were primarily confined to the digestive tract and were characterized by catarrhal enteritis. Pseudornembrane covered the mucosa of the ileum at the ileo — cecal Valve region. Histopathological examination revealed marked rnononuclear cellular infiltration in the lamina propria and occasionally necrosis and edema in the mucosa and submucosa of the intestine.

Evaluating the Biocompatibility of an Injectable Wound Matrix in a Murine Model

(1) Background: Developing a high-quality, injectable biomaterial that is labor-saving, cost-efficient, and patient-ready is highly desirable. Our research group has previously developed a collagen-based injectable scaffold for the treatment of a variety of wounds including wounds with deep and irregular beds. Here, we investigated the biocompatibility of our liquid scaffold in mice and compared the results to a commercially available injectable granular collagen-based product. (2) Methods: Scaffolds were applied in sub-dermal pockets on the dorsum of mice. To examine the interaction between the scaffolds and the host tissue, samples were harvested after 1 and 2 weeks and stained for collagen content using Masson’s Trichrome staining. Immunofluorescence staining and quantification were performed to assess the type and number of cells infiltrating each scaffold. (3) Results: Histological evaluation after 1 and 2 weeks demonstrated early and efficient integration of our liquid scaffold with no evident adverse foreign body reaction. This rapid incorporation was accompanied by significant cellular infiltration of stromal and immune cells into the scaffold when compared to the commercial product (p < 0.01) and the control group (p < 0.05). Contrarily, the commercial scaffold induced a foreign body reaction as it was surrounded by a capsule-like, dense cellular layer during the 2-week period, resulting in delayed integration and hampered cellular infiltration. (4) Conclusion: Results obtained from this study demonstrate the potential use of our liquid scaffold as an advanced injectable wound matrix for the management of skin wounds with complex geometries.

Conjunctivitis

Conjunctivitis represents an inflammation of conjunctiva with cellular infiltration, exudation, and vascular dilation. According to the course of the disease, conjunctivitis can be acute, hyperacute, and chronic. Morphologically, conjunctivitis can appear with papillary reaction, follicular reaction, cicatrizing, granulomatous and membranous changes. This chapter discusses all types of conjunctivitis, their clinical signs and symptoms, and basic approaches of treatment. This chapter includes before and after treatment photos of atypical inferiorly localized shield ulcer, Tularemia-associated Parinaud oculoglandular syndrome, and Stevens-Johnson disease. Pictures are included In the ligneous conjunctivitis patient's case taken at diagnosis as well as 10 years later, demonstrating stable condition with appropriate treatment throughout the period.

VEGF Expression, Cellular Infiltration, and Intratumoral Collagen Levels after Electroporation-Based Treatment of Dogs with Cutaneous Squamous Cell Carcinoma

Canine cutaneous squamous cell carcinoma (SCC) is the most common type of skin cancer in tropical countries and is generally associated with exposure to solar ultraviolet light. It has a low metastatic rate, and local treatments, such as electrochemotherapy (ECT), promote long-term control or even complete remission. This study aimed to evaluate pre- and post-ECT treatment expression levels of vascular endothelial growth factor (VEGF) and CD31, cellular infiltration, and intratumoral collagen levels in dogs with cutaneous SCC. A prospective nonrandomized clinical study was performed using dogs with spontaneous SCC treated with ECT. Eighteen lesions from 11 dogs were included in the study. The expression levels of VEGF and CD31; cellular infiltration; and intratumoral collagen levels, as determined by Masson’s trichrome staining, were not significantly different from pre-treatment measurements on day 21 (p > 0.05). However, among cellular infiltration, the mixed subtype was correlated with better overall survival time when compared to lymphoplasmacytic and neutrophilic infiltration (p < 0.05). In conclusion, ECT had no effect on VEGF expression, cellular infiltration, or intratumoral collagen levels in dogs with cutaneous SCC at the time of evaluation, suggesting that early and late post-ECT-treatment phases should be considered.

Two Potential Syphilis Vaccine Candidates Inhibit Dissemination of Treponema pallidum

Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a major public health problem worldwide. Recent increases in the number of syphilis cases, in addition to the lack of an efficient vaccine against T. pallidum for humans, highlights an urgent need for the design and development of an efficacious syphilis vaccine. Here, we assess the vaccine potential of the adhesion protein Tp0136 and the outer membrane protein Tp0663. Rabbits were subcutaneously immunized with recombinant proteins Tp0136, Tp0663, or control PBS. Immunization with Tp0136 or Tp0663 generated a strong humoral immune response with high titers of IgG, as assessed by ELISA. Moreover, animals immunized with Tp0136 or Tp0663 exhibited attenuated lesion development, increased cellular infiltration at the lesion sites, and inhibition of treponemal dissemination to distant organs compared to the unimmunized animals. These findings indicate that Tp0136 and Tp0663 are promising syphilis vaccine candidates. Furthermore, these results provide novel and important information for not only understanding the pathogenic mechanisms of spirochetes, but also the development of spirochete-specific subunit vaccines.

Microstructural Periventricular White Matter Injury in Post-Hemorrhagic Ventricular Dilatation

Background and Objectives:The neurological deficits of neonatal post-hemorrhagic hydrocephalus (PHH) have been linked to periventricular white matter injury. To improve understanding of PHH-related injury, diffusion basis spectrum imaging (DBSI) was applied in neonates, modeling axonal and myelin integrity, fiber density, and extra-fiber pathologies. Objectives included characterizing DBSI measures in periventricular tracts, associating measures with ventricular size, and examining MRI findings in the context of post-mortem white matter histology from similar cases.Methods:A prospective cohort of infants born very preterm underwent term equivalent MRI, including infants with PHH, high-grade intraventricular hemorrhage without hydrocephalus (IVH), and controls (VPT). DBSI metrics extracted from the corpus callosum, corticospinal tracts, and optic radiations included fiber axial diffusivity, fiber radial diffusivity, fiber fractional anisotropy, fiber fraction (fiber density), restricted fractions (cellular infiltration), and non-restricted fractions (vasogenic edema). Measures were compared across groups and correlated with ventricular size. Corpus callosum postmortem immunohistochemistry in infants with and without PHH assessed intra- and extra-fiber pathologies.Results:Ninety-five infants born very preterm were assessed (68 VPT, 15 IVH, 12 PHH). Infants with PHH had the most severe white matter abnormalities and there were no consistent differences in measures between IVH and VPT groups. Key tract-specific white matter injury patterns in PHH included reduced fiber fraction in the setting of axonal and/or myelin injury, increased cellular infiltration, vasogenic edema, and inflammation. Specifically, measures of axonal injury were highest in the corpus callosum; both axonal and myelin injury were observed in the corticospinal tracts; and axonal and myelin integrity were preserved in the setting of increased extra-fiber cellular infiltration and edema in the optic radiations. Increasing ventricular size correlated with worse DBSI metrics across groups. On histology, infants with PHH had high cellularity, variable cytoplasmic vacuolation, and low synaptophysin marker intensity.Discussion:PHH was associated with diffuse white matter injury, including tract-specific patterns of axonal and myelin injury, fiber loss, cellular infiltration, and inflammation. Larger ventricular size was associated with greater disruption. Postmortem immunohistochemistry confirmed MRI findings. These results demonstrate DBSI provides an innovative approach extending beyond conventional diffusion MRI for investigating neuropathological effects of PHH on neonatal brain development.

Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin

Burn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.

From Cellular Infiltration Assessment to a Functional Gene Set-Based Prognostic Model for Breast Cancer

BackgroundCancer heterogeneity is a major challenge in clinical practice, and to some extent, the varying combinations of different cell types and their cross-talk with tumor cells that modulate the tumor microenvironment (TME) are thought to be responsible. Despite recent methodological advances in cancer, a reliable and robust model that could effectively investigate heterogeneity with direct prognostic/diagnostic clinical application remained elusive.ResultsTo investigate cancer heterogeneity, we took advantage of single-cell transcriptome data and constructed the first indication- and cell type-specific reference gene expression profile (RGEP) for breast cancer (BC) that can accurately predict the cellular infiltration. By utilizing the BC-specific RGEP combined with a proven deconvolution model (LinDeconSeq), we were able to determine the intrinsic gene expression of 15 cell types in BC tissues. Besides identifying significant differences in cellular proportions between molecular subtypes, we also evaluated the varying degree of immune cell infiltration (basal-like subtype: highest; Her2 subtype: lowest) across all available TCGA-BRCA cohorts. By converting the cellular proportions into functional gene sets, we further developed a 24 functional gene set-based prognostic model that can effectively discriminate the overall survival (P = 5.9 × 10−33, n = 1091, TCGA-BRCA cohort) and therapeutic response (chemotherapy and immunotherapy) (P = 6.5 × 10−3, n = 348, IMvigor210 cohort) in the tumor patients.ConclusionsHerein, we have developed a highly reliable BC-RGEP that adequately annotates different cell types and estimates the cellular infiltration. Of importance, the functional gene set-based prognostic model that we have introduced here showed a great ability to screen patients based on their therapeutic response. On a broader perspective, we provide a perspective to generate similar models in other cancer types to identify shared factors that drives cancer heterogeneity.

Histological Study on the effect of losartan in healing of an experimentally induced muscle laceration in adult male albino rat

Background Skeletal muscle injuries are frequently encountered in athletes and military personnel. Incomplete functional recovery of these injuries usually occurs due to fibrosis of the skeletal muscle. Recently, oral administration of losartan antihypertensive drug was claimed to have a role in improving skeletal muscle healing, but still to be furtherly investigated. Aim of the work This work aimed to assess the healing effect of losartan on the histological structure of induced lacerated skeletal muscle fibers of adult male albino rats. Material and Methods Forty male albino rats were used in this study. They were divided into three groups: Group I: served as a control group and included 15 adult rats. Group II (muscle laceration group): consisted of 15 rats that were subjected to muscle laceration injury. They were subdivided into subgroup IIa: consisted of five rats that were sacrificed one day after injury, subgroup IIb: it included 10 rats that were left for spontaneous recovery for two weeks after injury. Group III (losartan-treated group): it consisted of 10 rats that were subjected to muscle laceration injury then they received oral losartan from day three till end of experiment. All rats, except rats of subgroup IIa, were sacrificed two weeks after injury. Right gastrocnemius muscle specimens were taken and processed for light microscopic examination by H & E and Masson's trichome stains as well as morphometric and statistical analysis. Results In group II, there was almost complete affection of myofibers at site of injury after 1 day of induced laceration in the form of myofibers fragmentation, disorganization and distortion with apparent mononuclear cellular infiltration mainly neutrophils and macrophages. After 2 weeks some myofibers were seen distorted and ended abruptly into connective tissue, others were branched with unclear striations. Mononuclear cellular infiltration between myofibers and apparent dilated blood vessels at laceration site were also noticed. A significant increase in collagen fibers deposition between regenerating muscle fibers (p&lt;0.05) was also demonstrated. Treatment of the muscle laceration by losartan in group III showed apparent partial improvement in the form of significant decrease in collagen fibers deposition (p&lt;0.05) and apparent decrease in mononuclear cellular infiltration as compared to that of group II. Also, some of the regenerated myotubes were noticed with chains of central nuclei. Conclusion Excess collagen fibers deposition between myofibers hinders regular arrangement of generating myotubes. Losartan might enhance muscle regeneration through decreasing collagen fibers deposition. However, it needs longer duration to assure complete muscle healing.

Tamoxifen administration induces histopathologic changes within the lungs of Cre-recombinase-negative mice: A case report

Tamoxifen is commonly used as a cancer treatment in humans and for inducing genetic alterations using Cre-lox mouse models in the research setting. However, the extent of tamoxifen off-target effects in animal research is underappreciated. Here, we report significant changes in cellular infiltration in Cre-recombinase-negative mice treated with tamoxifen intraperitoneally. These changes were noted in the lungs, which were characterized by the presence of alveolitis, vasculitis, and pleuritis. Despite significant immunological changes in response to tamoxifen treatment, clinical symptoms were not observed. This study provides a cautionary note that tamoxifen treatment alone leads to histologic alterations that may obscure research interpretations and further highlights the need for the development of alternative mouse models for inducible Cre-mediated deletion.