Minimal Inflammatory Infiltration Research Articles

Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model

BackgroundIt is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics.ResultsThe bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively.In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1β), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL.Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues.ConclusionCombining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

Fosfomycin mitigated apoptosis while increased mucin secretion in swine intestinal explants challenged by Lawsonia intracellularis

Lesions induced by the obligate intracellular bacterium Lawsonia intracellularis, the etiological agent of porcine proliferative enteropathy, are characterized by crypt hyperplasia in the intestinal epithelium with minimal inflammatory infiltration. An increased population of immature enterocytes at the expense of reduced goblet cells suggests that dysregulated apoptosis may be crucial in the pathogenesis of L. intracellularis.Fosfomycin, a widely employed antibiotic in swine production, has also exhibited non-microbicidal effects, encompassing immunomodulation, augmentation of phagocytosis, and the promotion of cell survival. In this study, we assessed the immunomodulatory impact of fosfomycin on intestinal epithelial homeostasis using porcine intestinal explants challenged with L. intracellularis.Our findings reveal that L. intracellularis elicited significant nuclear alterations, increased apoptotic indices, and prompted extensive mucin secretion in the intestinal explants. When fosfomycin was added to L. intracellularis-challenged intestinal explants, it mitigated the degree of apoptosis but also induced an inflammatory response. Consequently, treatment with fosfomycin in the context of L. intracellularis challenge appears to initiate an early mucosal response, maintaining cell viability, preserving the mucin barrier, and fostering inflammatory recruitment.

Use of rainbow trout skin treated with glutaraldehyde as a mesh for abdominal hernioplasty in rats.

To test the use of rainbow trout skin as a surgical mesh in abdominal hernioplasties in rats. The experiment involved 20 Wistar rats receiving implants of trout skin processed for disinfection in 0.5% glutaraldehyde and preserved in 100% glycerin. The animals were divided into four groups, divided at 7, 15, 30, and 90 days postoperatively. Clinical and infrared thermography evaluations were performed, and after euthanasia, assessments of adhesion formations and sample collection for histological evaluation were conducted. The implant was observed to be intact, ensuring the integrity of the abdominal wall, support for the viscera, and normal mobility for the rats for up to 90 days. Low rates of clinical alterations were observed, with an intense inflammatory reaction up to day 7, chronic inflammation and the onset of angiogenesis at day 15, and a low inflammatory reaction with collagenous infiltrate and fibrosis at day 30. At day 90, the implants showed a collagenous and fibrotic infiltrate with a minimal inflammatory infiltrate. The surgical mesh of trout skin performed well, making it a potential alternative for surgical procedures in muscle aponeurotic corrections in the abdominal wall.

Clinical and histological comparison of healing by steel scalpel, diode laser, and radiofrequency in palatal wound: An animal study.

Wound healing following periodontal soft tissue procedures can differ owing to different techniques, the feasibility of which can be determined through detailed macroscopic and microscopic observations. This study aimed to clinically and histologically evaluate palatal wound healing in rats by secondary intention after excision using a steel scalpel, diode laser, and radiofrequency. An excision was made in the edentulous anterior maxilla of 42 4-month-old male Wistar rats weighing 289-428 g. Part of the connective tissue was left in the surgical area to observe the dynamics of secondary intention wound healing. Three experimental groups were established: the steel scalpel, an 810-nm diode laser at a power output of 1.5 W in continuous mode, and a monopolar radiofrequency in a fully rectified waveform at 15 W. Clinical and histological analyses were performed on days 2, 4, and 7. Hemostasis, changes in body weight, defect size, epithelial gap, and inflammatory infiltration were evaluated. The epithelial gap closed completely in all groups on day 7. Bleeding occurred significantly more in the scalpel group (P < 0.001). No significant changes were observed in body weight between the groups. Macroscopically, the mean wound area decreased over time in all groups. Wound healing was significantly slower in the laser group on day 2 and in the radiofrequency group on days 4 and 7 (P < 0.001). Microscopically, the laser created the cleanest wound area, with minimal inflammatory infiltration and no thermal injury. More damage occurred in the connective tissue of the radiofrequency group. Wound healing was observed on day 7 in all groups. Palatal wound healing with secondary intention yielded different outcomes in a rat model when different techniques were used. However, almost complete healing was observed in all wounds, which highlights the importance of the soft tissue left in the surgical area. Wound healing in periodontal soft tissue procedures is not compromised by different techniques, as long as the clinician has sufficient knowledge and experience.

Medialisation laryngoplasty with bone wax in a sheep model.

To evaluate the safety and biocompatibility of bone wax as an implant material for medialisation laryngoplasty in a large animal model. Three Dorper-cross ewes underwent type I thyroplasty of the right vocal fold with bone wax. The animals were monitored for four weeks for general wellbeing. The animals were euthanised and the larynges harvested. Histological evaluation was performed to assess for adverse tissue reaction and biocompatibility. The mean (± standard deviation) amount of bone wax implanted was 0.49 g (± 0.12 g). No adverse events were reported. Ex vivo vibration was present on high-speed imaging for all medialised vocal folds. Histology demonstrated implanted paraffin embedded within the thyroarytenoid muscle with no evidence of resorption, a minimal inflammatory infiltrate, and a thin fibrotic capsule. The results of this investigation suggest that bone wax may be a safe and efficacious implant material for medialisation laryngoplasty. Further studies are necessary to assess its long-term safety and efficacy.

Phenotypic PIA-Dependent Biofilm Production by Clinical Non-Typeable Staphylococcus aureus Is Not Associated with the Intensity of Inflammation in Mammary Gland: A Pilot Study Using Mouse Mastitis Model.

Simple SummaryStaphylococcus aureus-associated human clinical infections are predominantly caused by the encapsulated strains, with non-typeable strains representing less than 25%. In contrast, 80% of the S. aureus from bovine mastitis cases are non-typeable as they do not possess the Capsular Types 1, 2, 5, and 8. In our previous studies, it was demonstrated that the extent of mammary tissue damage was associated with the strength of biofilms formed by encapsulated S. aureus strains. This study assesses the impact of biofilm formation, as a virulence factor of non-typeable Staphylococcus aureus, causing mammary tissue damage in a mouse mastitis model. The study demonstrates no association between the strength of biofilm production by non-typeable S. aureus and the mammary tissue damage. However, the mice infected with strong biofilm producing non-typeable S. aureus died 6h earlier than those infected with weak biofilm producing non-typeable S. aureus suggesting the role of biofilm in the advancement of the time of mice mortality.Non-typeable (NT) Staphylococcus aureus strains are associated with chronic bovine mastitis. This study investigates the impact of biofilm formation by clinical NT S. aureus on cytokine production and mammary tissue damage by using a mouse mastitis model. Mice infected with two different NT S. aureus strains with strong and weak biofilm forming potential demonstrated identical clinical symptoms (moderate), minimal inflammatory infiltrates, and tissue damage (level 1 histopathological changes) in the mammary glands. However, the S. aureus load in the mammary glands of mice and the level of pro-inflammatory cytokines (IL-1β, IL-6, IL-12, IL-17 and IFN-γ) in serum were significantly higher (p ≤ 0.05) in those infected with the strong biofilm forming NT S. aureus strain. The level of IL-6 in sera samples of these mice was extremely high (15,479.9 ± 532 Pg/mL). Furthermore, these mice died in 24h of post infection compared to 30 h in the weak biofilm forming NT S. aureus infected group. The study demonstrates no association between the strength of PIA (polysaccharide intercellular adhesion)-dependent biofilm production by clinical NT S. aureus and mammary gland pathology in a mouse mastitis model. However, the role of biofilm in the virulence of S. aureus advancing the time of mortality in mice warrants further investigation.

CLINICAL AND MORPHOLOGICAL FEATURES OF LUMINAL A SUBTYPE OF INVASIVE DUCTAL BREAST CANCER

The aim of this article was to study clinical and morphological features of luminal A subtype of breast cancer to assess its relationship with disease progression. Methods: This study included 79 patients with luminal A subtype of breast cancer who treatment in 2017 at the Lviv State Oncological Regional Treatment and Diagnostic Center. The Luminal A subtype was identified by immunohistochemistry (IHC) as ER+, PR+/-, HER2- and Ki-67 less than 20 percent on surgically resected breast cancer tissue. Results: The mean age of patients was 60,41±12,25 (range, 32–85 years), 26 (32,9%) were under 55 years. Nottingham Histologic Grade distribution was as follows: G1 – 10 (12,66%), G2 – 56 (70,88%), and G3 – 13 (16,46%) cases. Clinical stage II – 35 (44,3%) and III – 31 (39,24%) was observed. Menopausal status was in 67,1% of cases. Morphological analysis of the tumor tissue showed that except alveolar structures, there were trabecular, solid, tubular structures and separately located groups of tumor cells. The stromal component of the tumor was weak or moderate, most tumors showed minimal or marked inflammatory infiltration and low proliferative activity. Conclusions: To predict the probability of lymphogenic metastasis should be considered: menstrual function, histologic grade, the presence of alveolar structures in the infiltrative component, the different types of structures in the infiltrative component, hyalinosis in the stroma of the tumor node and inflammatory infiltration of tumor.

MO1032HISTORY OF THE PARADIGMS OF INFLAMMATION IN KIDNEY DISEASES

Abstract Background and Aims The term "inflammation" is undoubtedly one of the oldest medical terms and yet in use. However, its meaning has changed over the centuries. This work gives a historical and critical view of the concept of inflammation, with particular reference to kidney diseases. Method The term "inflammation" was used in Galenic medicine to specify a collection of symptoms. Celsus (c. 25 BC – c. 50 AD) described "rubor et tumor cum calor et dolor", but the list became much longer in subsequent Galenic scholars. It is interesting to note that one of the inflammation symptoms, "tumor," was then used to indicate cancer (tumor=swelling due to a mass or due to edema). Virchow (1821 –1902) is often quoted for introducing a fifth symptom, "function Lasa", but his significant contribution relies on introducing the microscope to study diseases: thanks to this instrument, the paradigm of inflammation was undergoing a revolution. Thereby, the definition of inflammation shifted from a pure collection of symptoms to a histopathological classification, characterized by the tissue "inflammatory infiltrates" with subcategories according to the cell types involved. Numerous authors added their names to pathology textbooks when describing a new kind of cellular infiltration. Overall, the tremendous success of the histopathologic paradigm of inflammation or "inflammatory infiltrates" was the possibility to contain and revert this phenomenon with corticosteroids (with few exceptions). Subsequently, specific drugs were proposed for each inflammatory infiltrate. This type of paradigm is still used today to define, e.g., tubulointerstitial nephritis or intra- and peri-glomerular inflammations. The subsequent classification of inflammatory infiltrates using immunohistochemistry did not modify our classification system (the distinction of, e.g., CD20 lymphocytes from CD4 T-cells is not used, unfortunately, in today's classification system). Results Towards the 1940s, Avery et al. recognize that some plasma proteins (specifically the famous C-reactive protein) increase during acute infection, which is a typical inflammatory state. This observation led to a new "molecular definition of inflammation". The idea to identify the presence of inflammatory infiltrates in tissues just by looking at plasma constituents had great success: after all, the histological processing of tissues was no longer needed. Even though many authors were alerting that these plasma constituents are often increased even in the absence of any "inflammatory infiltrate", the plasma proteins were so easily accessible that the new direction was not modifiable. A modern generalization of this type of approach is called "liquid biopsy, " even though it is not limited to the inflammatory states, but to a larger number of identifiable diseases today only histologically. The effect of the new "molecular" definition of inflammation was that a large number of diseases without significant inflammatory infiltrates (such as obesity, atherosclerosis, aging, dialysis, and chronic kidney disease) are notwithstanding accompanied by the increase of plasma proteins labeled as "inflammatory". Therefore, the list of "inflammatory" diseases (in the new terms) is now much more extensive. The price for such enlargement of conditions is that most new entries do not respond to steroids or other anti-inflammatory drugs. Conclusion The new definition of" inflammatory disease" comprises classical steroid-dependent disorders characterized by inflammatory infiltrates and new conditions with minimal inflammatory infiltrates plus the presence of "inflammatory" plasma proteins plus little response to steroids. It might be beneficial to distinguish these types of inflammation.

Therapeutic management of immune-mediated necrotizing myositis.

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders characterized by skeletal muscle inflammation leading to chronic muscle weakness. Immune-mediated necrotizing myopathy (IMNM) is a distinct subgroup of inflammatory myopathy typically characterized by myofiber necrosis with minimal inflammatory infiltrates on muscle biopsy, highly elevated creatine kinase levels, and infrequent extra-muscular involvement. This review provides an overview of currently recommended treatment strategies for IMNM, including discussion of disease activity monitoring and recommended first-line immunomodulatory agents depending on clinical phenotype and autoantibody status. IMNM can be divided into three subtypes based on autoantibody positivity: anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) IMNM, anti-signal recognition particle (SRP) IMNM, and antibody negative IMNM. Autoantibody status in IMNM has considerable correlation with clinical phenotype, prognosis, and recommended choice of immunosuppressive agent. Patients with anti-HMGCR IMNM tend to respond well to intravenous immunoglobulin (IVIG), and IVIG monotherapy may be sufficient treatment for certain patients. In anti-SRP IMNM, early rituximab is commonly favored. More generally, prompt initiation of aggressive immunosuppression is often indicated, as both anti-SRP and anti-HMGCR IMNM can potentially cause debilitating weakness, and muscle atrophy and irreversible fatty replacement happen early in the disease course. Patients with IMNM frequently require combination therapy to achieve disease control, and have a high rate of relapse when tapering immunosuppression. Young age of onset is a poor prognostic factor. IMNM can be severely disabling and often requires aggressive immunosuppression. For any given patient, the treatment strategy should be informed by the severity of their presenting features and autoantibody status. While our ability to treat IMNM has certainly improved, there remains a need for more prospective trials to inform optimal treatment strategies.

Multiple depressed plaques over back in a young boy.

A 12-year-old boy presented with a 6-month history of asymptomatic but gradually progressive depressed lesions over the back. There was no history of any preceding local trauma, infection, ulceration, or any inflammatory dermatoses. He was not on any medications and his family members had no history of similar skin lesions. On examination, multiple discrete, sharply demarcated, hyperpigmented, smooth-surfaced, nonindurated, noninflammatory atrophic plaques of varying diameters (2 cm to 7 cm) were noticed dispersed over the back; an abrupt border transitioning into normal skin gave it the typical ‘cliff drop’ appearance (Figure 1). Other mucocutaneous and systemic examination was unremarkable. Routine laboratory investigation was noncontributory and serum antibody for Borrelia burgdorferi was negative. Histopathological examination revealed normal epidermis, hyalinization of collagen in dermis with minimal scattered inflammatory infiltrate, and decrease in the thickness of dermis compared to surrounding skin. What is the diagnosis? ... Based on distinctive clinical and corroborative histopathological features, a diagnosis of idiopathic atrophoderma of Pasini and Pierini (IAPP) was established. He was counselled about the benign nature of the condition; topical tacrolimus (0.1%) ointment was started twice daily with subsequent partial improvement of lesions in 3 months.

CLINICAL AND IMMUNOHISTOPATHOLOGICAL STUDY OF ORAL LESIONS OF LEPROSY

Objective. To compare clinical and immunohistopathological features of oral lesions with clinically normal oral mucosa from patients with leprosy. Study design. This is a cross-sectional study of patients with leprosy showing specific oral lesions selected from January 2000 to June 2018. Patients with leprosy who did not have oral lesions and agreed to oral biopsy were included in the comparisons of analysis, which consisted of clinical and immunohistopathological (anti-PGL1 and MLSA expression) study. Results. A total of 416 patients with leprosy were evaluated and patients with leprosy-specific oral lesions (n = 14) were included. All were men, and the majority had the lepromatous form. The oral mucosa showed acanthosis, lymphocyte exocytosis, foamy macrophages, and nonfragmented bacilli. Patients without oral lesions (n = 14) mostly had the multibacillary (MB) form, and the oral mucosa showed minimal inflammatory infiltrates and no foamy macrophages in most of the samples. PGL1 and MLSA were detected in all oral lesions and in 6 specimens from clinically normal mucosa. Conclusions. The oral cavity may be affected by leprosy in advanced stages of the MB form. Histopathological findings of oral lesions seem similar to cutaneous lesions, and anti-PGL1 and MLSA are effective markers to determine Mycobacterium leprae presence either in oral lesions or clinically normal mucosa of patients with the MB form of leprosy.

Palatal Wound Healing with Primary Intention in a Rat Model-Histology and Immunohistomorphometry.

Background and objectives: Subepithelial connective tissue graft (SCTG) from the palate has been considered as the “gold standard” for the treatment of deep gingival recessions. A single-incision technique was reported to allow primary wound healing. A palatal single incision was performed in a rat model. The present study assessed the histology and histomorphometry of palatal wound healing following surgical closure with primary intention. Materials and Methods: Twenty-six 6-month-old male Wistar rats weighing 427–650 g. An incision was made on the maxillary palate. A full thickness flap was raised palatally, and then repositioned and sutured. Two experimental groups: S—Study group, I—Intact control group. Half of the animals were sacrificed 7 days and the remaining 14 days postoperatively. Outcome parameters included—epithelial gap; inflammatory infiltration; vascular fraction, expression of myofibroblasts and stem cell markers within the oral epithelium and stromal cells and physical properties of stromal collagen fibers. Investigations were performed at two time-points (7 and 14 days) during the wound healing process. Results: The epithelial gap closed completely after 14 days. The inflammatory reaction and vascular fraction were relatively low. Surgical trauma downregulated the expression of cytokeratin (CK) 14 and CK 15, which returned to normal after 14 days. Epithelial differentiation was mediated through upregulation of connective tissue sex- determining-region-Y-box2 (SOX2). Epithelial SOX2, CD34, alpha smooth muscle actin (αSMA) and physical properties of stromal collagen fibers were not influenced by the surgical trauma. Conclusions: Surgical trauma followed by palatal wound healing with primary intention in a rat model heals within 14 days. It induces minimal inflammatory infiltration and vascular proliferation. Epithelization is exerted through promotion of epithelial differentiation from stem cells by connective tissue SOX2.

High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California

High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California

Human Clinical and Histologic Evaluations of Laser-Assisted Periodontal Therapy with a 9.3-μm CO² Laser System.

This investigation was designed to evaluate the healing response of 9.3-μm CO2 laser-assisted periodontal therapy. Five patients presenting with moderate to severe periodontitis, with an initial pocket depth (PD) ≥ 5 mm and with teeth predetermined to be surgically extracted, were enrolled and consented to treatment with full-mouth CO2 laser-assisted therapy. The laser treatment was carried out in the Ultraguide Mode at a setting of 0.25-mm spot size, with an average power of 0.65 to 1.15 watts and 20% mist. The laser tip was passed from the gingival margin and down apically to the base of the pocket with a sweeping L motion. The teeth were intensely scaled with piezoultrasonic instrumentation afterwards. A second pass of the laser tip was performed for the study teeth. At 9 months, all patients were clinically reevaluated. For sites with an initial pocket depth of ≥ 7 mm, a mean PD reduction of 3.97 ± 1.36 mm and a mean clinical attachment level gain of 3.54 ± 1.54 mm were achieved, resulting in a mean PD of 3.91 ± 0.77 mm. En bloc biopsy samples of four teeth were obtained and analyzed; two demonstrated histologic evidence of new bone formation while the other two healed with a long junctional epithelium with minimal inflammatory infiltrate. Further long-term clinical studies are needed to investigate the treatment stability obtained with a 9.3-μm CO2 laser compared to conventional surgical therapy. Nevertheless, the encouraging clinical results indicated that adjunctive use of the 9.3-μm CO2 laser-assisted periodontal therapy can be beneficial for treatment of periodontally compromised patients.

A novel group A rotavirus associated with acute illness and hepatic necrosis in pigeons (Columba livia), in Australia.

Cases of vomiting and diarrhoea were reported in racing pigeons in Western Australia in May, 2016. Morbidity and mortality rates were high. Similar clinical disease was seen in Victoria in December and by early 2017 had been reported in all states except the Northern Territory, in different classes of domestic pigeon–racing, fancy and meat bird–and in a flock of feral pigeons. Autopsy findings were frequently unremarkable; histological examination demonstrated significant hepatic necrosis as the major and consistent lesion, often with minimal inflammatory infiltration. Negative contrast tissue suspension and thin section transmission electron microscopy of liver demonstrated virus particles consistent with a member of the Reoviridae. Inoculation of trypsin-treated Vero, MDBK and MA-104 cell lines resulted in cytopathic changes at two days after infection. Next generation sequencing was undertaken using fresh liver samples and a previously undescribed group A rotavirus (genotype G18P[17]) of avian origin was identified and the virus was isolated in several cell lines. A q-RT-PCR assay was developed and used to screen a wider range of samples, including recovered birds. Episodes of disease have continued to occur and to reoccur in previously recovered lofts, with variable virulence reported. This is the first report of a rotavirus associated with hepatic necrosis in any avian species.

Can crocin play a preventive role in Wistar rats with carbon tetrachloride-induced nephrotoxicity?

Objective(s):To investigate protective role of crocin by attempting to create nephrotoxicity with carbon tetrachloride.Materials and Methods:Ethics committee approval was obtained and 50 male Wistar rats were randomly divided into 5 groups that included 10 rats each: Control, Corn oil, Crocin, Carbon tetrachloride (CCl4), and Crocin + Carbon tetrachloride. Following the experiments, the rats were decapitated under anesthesia and incised kidney tissues were subjected to biochemical and histological examinations.Results:In the CCl4 administered group, MDA, TOS, Bun, and creatinine levels increased, GSH, SOD, CAT, and TAS levels decreased (P≤0.05), glomerular collapse in kidney sections, narrowing and local occlusion in Bowman’s space in certain glomeruli, inflammatory cell infiltration and congestion were observed when compared to all other groups. There was a significant decrease in increased MDA, TOS, Bun, and creatinine levels, and a significant increase in decreased GSH, SOD, CAT, and TAS levels in CCl4 + crocin administered group compared to the CCl4 group (P≤0.05), local minimal glomerular damage, tubular damage, inflammatory infiltration, and vascular collagen symptoms were observed in kidney sections, however significant improvement was observed in damage findings when compared to the CCl4 group.Conclusion:At this dose and time interval, against a highly toxic chemical such as CCl4, crocin was able to suppress oxidative stress by playing a protective role in the kidney tissue.

Alterações histopatológicas da encefalite de Rasmussen

Os autores estudam oito casos de encefalite de Rasmussen sob o ponto de vista das alterações histopatológicas correlacionadas com os achados da neuroimagem. Cinco desses casos encontravam-se em uma fase tardia da doença (fase IV), com grande atrofia dos giros cerebrais, acentuada espongiose cortical, com perda de nenrônios e intensa gliose reacional, com a presença de raros nódulos microgliais e discreto infiltrado inflamatório perivascular. Nos demais três casos, havia discreta espongiose, com perda nítida de neurônios e gliose reacional. Havia maior número de nódulos microgliais e infiltração inflamatória linfomononuclear perivascular evidente. Esses casos encontravam-se em uma fase remota da doença {fase 111). Os casos estudados no presente trabalho se encontravam em fase mais avançada da doença, com intensa atrofia de giros cerebrais. Isto se explica pelo fato de o diagnóstico ser suspeitado clinicamente quando o paciente já apresenta hemiatrofia cerebral e a decorrente sintomatologia.

Gangrenous dermatitis in chickens and turkeys.

Gangrenous dermatitis (GD) is a disease of chickens and turkeys that causes severe economic losses in the poultry industry worldwide. Clostridium septicum, Clostridium perfringens type A, and occasionally Clostridium sordellii are considered the main causes of GD, although Staphylococcus aureus and other aerobic bacteria may also be involved in some cases of the disease. GD has become one of the most significant diseases of commercial turkeys in the United States. Several infectious and/or environmental immunosuppressive factors can predispose to GD. Skin lesions are considered to be the main portal of entry of the microorganism(s) involved. GD is characterized by acute onset of mortality associated with gross skin and subcutaneous tissue lesions consisting of variable amounts of serosanguineous exudate together with emphysema and hemorrhages. The underlying skeletal muscle can also be involved. Ulceration of the epidermis may be also noticed in cases complicated with S. aureus. Microscopically, necrosis of the epidermis and dermis, and subcutaneous edema and emphysema are commonly observed. Gram-positive rods can be identified within the subcutis and skeletal muscles, usually associated with minimal inflammatory infiltrate. A presumptive diagnosis of GD can be made based on history, clinical signs, and gross anatomic and microscopic lesions. However, confirmation should be based on demonstration of the causative agents by culture, PCR, immunohistochemistry, and/or fluorescent antibody tests.

Injectable Polymeric Cytokine-Binding Nanowires Are Effective Tissue-Specific Immunomodulators.

Injectable nanomaterials that interact with the host immune system without surgical intervention present spatially anchored complements to cell transplantation and could offer improved pharmacokinetics compared to systemic cytokine therapy. Here we demonstrate fabrication of high aspect ratio polycaprolactone nanowires coupled with cytokine-binding antibodies that assemble into porous matrices when injected into the subcutaneous space. These structures are fabricated using a nanotemplating technique that allows for tunability of particle dimensions and utilize a straightforward maleimide conjugation chemistry to allow site-specific coupling to proteins. Nanowires are well tolerated in vivo and incite minimal inflammatory infiltrate. Nanowires conjugated with antibodies were designed to capture and potentiate endogenous interleukin-2 (IL-2), an important leukocyte activating cytokine. Together these nanowire-antibody matrices were capable of localizing endogenous IL-2 in the skin and activated targeted specific natural killer and T cell subsets, demonstrating both tissue- and cell-specific immune activation. These self-assembling nanowire matrices show promise as scaffolds to present engineered, local receptor-ligand interactions for cytokine-mediated disease.

Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology.

Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients.