Perivascular Mononuclear Infiltrates Research Articles

Subcortical plaques and inflammation reflect cortical and meningeal pathologies in progressive multiple sclerosis.

It remains elusive whether lesions and inflammation in the sub/juxtacortical white matter reflect cortical and/or meningeal pathologies. Elucidating this could have implications for MRI monitoring as sub/juxtacortical lesions are detectable by routine MRI, while cortical lesions and meningeal inflammation are not. By large-area microscopy, we quantified total and mixed active plaque loads along with densities and sizes of perivascular mononuclear infiltrates (infiltrates) in the sub/juxtacortical white matter ≤2 mm from the cortex, intra-cortically and in the meninges. Data were related to ante-mortem clinical parameters in a false discovery rate-corrected analysis. We compared 12 patients with primary progressive multiple sclerosis (PPMS) and 15 with secondary progressive MS to 22 controls. Fifteen patients and 11 controls contributed with hemispheric sections. Sections were stained with haematoxylin-eosin, for myelin and for microglia/macrophages. B cells and T cells were confirmed in a subset. Immunoglobulin G depositions in selected cortical plaques resembled depositions described before in "slowly expanding" plaques in the white matter. We quantified plaque activity by measuring microglia-dominated and macrophage-dominated areas. Sub/juxtacortical plaques (load and activity) reflected plaque activity in the cerebral cortex. Plaque activity and infiltrates were more pronounced in the sub/juxtacortical white matter than in the cerebral cortex while conversely, the total plaque load was highest in the cortex. Infiltrates correlated trans-cortically and sub/juxtacortical plaque activity reflected cortical and meningeal infiltrates. Sub/juxtacortical infiltrate sizes correlated with shorter survival after progression onset. Two patients with PPMS and putatively fatal brain stem lesions argue against incidental findings. Trans-cortical inflammatory flares and plaque activity may be pathogenic in progressive MS. We suggest emphasis on sub/juxtacortical MRI lesions as plausible surrogates for cortical and meningeal pathologies and, when present, as indicators for cognitive testing.

CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in the murine model of the acute respiratory distress syndrome.

Introduction: The acute respiratory distress syndrome (ARDS), secondary to viral pneumonitis, is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019)-ongoing SARS-CoV-2 infection- reached more than 0.7 billion registered cases. Methods: Recently, we elaborated a non-surgical and reproducible method of the unilateral total diffuse alveolar damage (DAD) of the left lung in ICR mice-a publicly available imitation of the ARDS caused by SARS-CoV-2. Our data read that two C-C chemokine receptor 5 (CCR5) ligands, macrophage inflammatory proteins (MIPs) MIP-1α/CCL3 and MIP-1β/CCL4, are upregulated in this DAD model up to three orders of magnitude compared to the background level. Results: Here, we showed that a nonpeptide compound TAK-779, an antagonist of CCR5/CXCR3, readily prevents DAD in the lung with a single injection of 2.5mg/kg. Histological analysis revealed reduced peribronchial and perivascular mononuclear infiltration in the lung and mononuclear infiltration of the wall and lumen of the alveoli in the TAK-779-treated animals. Administration of TAK-779 decreased the 3-5-fold level of serum cytokines and chemokines in animals with DAD, including CCR5 ligands MIP-1α/β, MCP-1, and CCL5. Computed tomography revealed rapid recovery of the density and volume of the affected lung in TAK-779-treated animals. Discussion: Our pre-clinical data suggest that TAK-779 is more effective than the administration of dexamethasone or the anti-IL6R therapeutic antibody tocilizumab, which brings novel therapeutic modality to TAK-779 and other CCR5 inhibitors for the treatment of virus-induced hyperinflammation syndromes, including COVID-19.

Leucoderma in Buffaloes (Bubalus bubalis) in the Amazon Biome.

Leucoderma is a condition that affects the skin and hair of animals, causing depigmentation and acromotrichia. In buffaloes, this condition results in significant economic losses for the production chain due to its impact on the leather trade. This study aimed to investigate the epidemiological and clinicopathological aspects of leucoderma in buffaloes in the Amazon biome and describe the prophylactic treatment to control the disease. The study included 40 buffaloes, 16 males and 24 females, aged between 1 and 10 years, and were of the Murrah, Jafarabadi, Mediterranean, and Murrah × Mediterranean crossbreed breeds. The animals were raised without mineral supplementation. The clinical signs observed in the animals included acromotrichia and depigmentation, with varying degrees and distribution of skin lesions. Histological examination of the epidermis showed interrupted melanin production, mild dermal fibrosis, mild perivascular mononuclear inflammatory infiltrate, and pigmentary incontinence. None of the animals had the genotype for albinism. After 120 days of mineral supplementation based on the use of copper sulfate, the clinical signs of leucoderma regressed. There was no predisposition by breed, sex, or age for the occurrence of the disease. The regression of skin lesions after proper mineral supplementation suggests that copper deficiency may be considered an important factor for the occurrence of leucoderma in buffaloes in the Amazon biome.

Cutaneous Sporotrichosis of Face with Verrucous Lesions over Nose, Successfully Treated with a Combination of Itraconazole and Terbinafine: A Case Report.

Dear Editor, A 13-year-old boy presented with nasal erythematous, crusted, confluent papules, and nodules persisting for approximately 35 days [Figure 1]. The patient denied contact with sick cats but mentioned playing in the bushes. The clinical diagnosis was cutaneous sporotrichosis, and he started treatment with itraconazole 100 mg per day, which was administered orally for 10 days and then increased to 200 mg per day. The exudate from the skin lesions was directly examined by a potassium hydroxide test, which was negative for fungal presence. At 25°C, a mycosal media culture of the exudate revealed colonies resembling Sporothrix sp, which appeared membranous, beige, wrinkled, and with a blackened halo [Figure 2]. At 37°C, phenotypic reversal for creamy colonies with beige and colorless verse was observed, thus demonstrating dimorphism. The lactophenol cotton blue stain revealed hyaline septate hyphae [Figure 3]. On day 44 of itraconazole treatment alone, the lesions became severely crusted, demonstrating no improvements. Thus, 250 mg of oral terbinafine was added to the treatment regimen. On day 60 of itraconazole use, a skin biopsy was performed. Grocott silver stain revealed rare samples of fungal structures [Figure 4]. Histopathology showed acanthosis of the epidermis, areas with perivascular mononuclear inflammatory infiltrate and fibrosis [Figure 5]. On day 226 of itraconazole and day 182 of terbinafine use, clinical improvement was noted, indicating the end of oral antifungal drugs [Figure 6]. The patient underwent Laser Erbium YAG, an ablative laser, to achieve favorable aesthetic results for the scar and uniformization of the skin of the nasal region.Figure 1: Infiltrated erythematous nodules of sporotrichosis on the nose with verrucous appearanceFigure 2: Culture at 25°C, showing colonies of membranous, beige, wrinkled with a blackened halo, resembling Sporothrix speciesFigure 3: The hyaline septate hyphae of Sporothrix spp. with one pyriform microconidia in daisy arrangement (lactophenol cotton blue stain, ×40)Figure 4: Grocott silver stain presenting a fungal structures (40x)Figure 5: Acanthosis of the epidermis, areas with perivascular mononuclear inflammatory infiltrate, and intense remodeling of dermal collagen with fibrosis. (H and E, 10x)Figure 6: Clinical improvement after terbinafine and itraconazole use. Only residual erythema, papules and nodulesSporotrichosis is a subcutaneous mycosis caused by a thermodimorphic fungus, Sporothrix spp., most commonly S. brasiliensis, S. schenckii, and S. globosa.[1] The lesions manifest in different clinical forms: mainly lymphocutaneous, fixed, cutaneous, disseminated, and extracutaneous. Recently, the incidence of various diseases caused by Sporothrix has been increasing in Brazil, particularly a high disease rate in urban areas. Felines have been reported as a new source of infection that spreads diseases.[2] Itraconazole is a first-line treatment for Sporothrix, but some strains, mainly S. brasiliensis, are resistant.[3–5] Moreover, itraconazole content sometimes does not match the concentrations indicated by manufacturers.[3] Itraconazole has certain pharmacokinetic concerns because of several drug interactions. For example, a high gastric pH reduces its bioavailability. Terbinafine is an alternative drug that can effectively treat cutaneous sporotrichosis, and it is affordable and has fewer interactions with other drugs.[1,4,5] To improve therapeutic outcome, itraconazole has been combined with a second drug and demonstrated good results, for example, with supersaturated potassium iodide (SSKI) solution.[6] SSKI is an alternative for cutaneous forms, which is primarily used for infants. However, compared with terbinafine, SSKI has side effects and issues, such as a lack of standardized commercial formulation and unknown mechanisms of action.[1,4] Studies describing the use of itraconazole with terbinafine are limited. In vitro, terbinafine and itraconazole have synergistic effects because both disrupt ergosterol synthesis in the cell membrane of fungi at different stages. This mechanism is beneficial due to accelerated response against chromoblastomycosis, onychomycosis, and sporotrichosis, where facial lesions can cause aesthetic stigmas and affect the quality of life of patients. In conclusion, the combination of terbinafine and itraconazole can effectively inhibit disease progression faster and thus prevent excessive fibrosis and scars.[5,7–10] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

An Unusual Presentation of Lichen Striatus.

An Unusual Presentation of Lichen Striatus.

Nevus Lipomatosus Cutaneous Superficialis Masquerading as Giant LipomaA Rare Case Report

Nevus Lipomatosus Cutaneous Superficialis (NLCS) is an idiopathic, rare skin hamartoma. It occurs due to ectopic deposition of adipocytes in dermis. There are two main clinical forms of NLCS- classic and solitary. Both have different clinical presentations but histologically they show similar morphology characterised by bundles of mature adipocytes in the superficial and deep dermis separated by bundles of collagen. The hallmark of this lesion is absence of connection between subcutaneous fat and adipocyte clusters in dermis.Though NLCS is benign developmental disorder and remains static for a long time, it can be cosmetically unpleasant if grows to a large size. Herein, authors report a case of a 21-year-old male with a solitary painless pedunculated lump in right thigh for 10 years that clinically presented as giant lipoma due to its soft consistency, cut surface of the mass was yellow and fibrofatty. There was no connection of these adipocytes seen with the subcutaneous fat. Focal collections of adipocytes were also seen around the blood vessels. Sparse perivascular mononuclear inflammatory infiltrate also noted. Final diagnosis of NLCS was made.

Pathohistological changes in aborted foetuses of cows due to neosporosis: Evidence from Ukraine

Neosporosis is a parasitic disease characterized by abortions and the birth of weak offspring in cows. The causative agent of Neospora caninum is an obligate, protozoan parasite that belongs to the type Apicomplexa. The relevance of the study is conditioned upon the adverse impact of neosporosis on the economy of Ukraine (loss of productivity, veterinary and diagnostic costs). Furthermore, the issue of neosporosis is understudied. In this regard, the purpose of this study was to establish pathohistological changes in aborted foetuses and the foetal part of placentas and to confirm the involvement of the parasite (Neospora caninum) in cases of abortions recorded in different regions of the country. Two methods were used to investigate this problem: histological and real-time polymerase chain reaction. In aborted foetuses positive for N. caninum, the following pathohistological changes were most often detected: focal gliosis and perivascular mononuclear infiltrates in the brain; focal or diffuse mononuclear infiltration in the heart and skeletal muscles; periportal mononuclear infiltrates in the liver; focal necrosis of the mucous membrane and mononuclear infiltration in the foetal part of the placenta. Changes were less often detected in the lungs – mononuclear infiltration of the interstitium and diffuse lymphocytic alveolitis, and in the kidneys – diffuse interstitial mononuclear infiltration. No changes were found in the spleen. Neospore-like cysts were found in one out of twelve foetuses. Lesions established of foetal organs and placentas are inherent in neosporosis. The results of histological studies substantially complement the data of other authors, confirm the involvement of N. caninum in the occurrence of abortions in cows in certain regions of Ukraine, and also represent practical value for the diagnosis and control of neosporosis in cattle

Prurigo pigmentosa and diabetes: A case report

Sir, Prurigo pigmentosa is a rare inflammatory disease first reported in 1971 by Nagashima et al. as a “peculiar pruriginous dermatosis with gross reticular pigmentation” in Japan [1], where the largest number of such cases have been described, with only several cases having been described elsewhere. Herein, we report a new case of prurigo pigmentosa. A 32-year-old Moroccan female presented at our dermatology department with a several-week-old history of pruritic eruptions on the chest, abdomen, lumbosacral area, and neck. According to the patient, the onset was marked by itchy papules coalescing to plaques, secondarily becoming hyperpigmented reticulated macules. The patient was treated with antifungal drugs without improvement. Additionally, the patient had recently been diagnosed with type II diabetes and was treated by oral antidiabetics. A physical examination revealed hyperpigmented macules arranged in a reticulate pattern, mainly on the chest, abdomen, lumbosacral area, and neck (Figs. 1 and 2). She had no acanthosis nigricans or other associated symptoms. The main diagnoses considered were pityriasis versicolor, confluent and reticulated papillomatosis of Gougerot–Carteaud, and prurigo pigmentosa. A histological examination revealed a discreetly atrophic epidermis surmounted by compact orthokeratotic hyperkeratosis and slight basal pigmentation. The dermis was the site of perivascular mononuclear infiltrates associated with a small number of melanophages. Periodic acid–Schiff staining was negative. This was consistent with the diagnosis of prurigo pigmentosa.

Laryngotracheal Stenoses Post-Acute Respiratory Distress Syndrome due to COVID-19: Clinical Presentation, Histopathological Findings and Management. A Series of 12 Cases

Coronavirus disease 2019 (COVID-19) has increased the risk of developing severe acute respiratory distress syndrome and subsequent moderate to severe laryngotracheal stenoses (LSTs) with an early presentation that occurs between two and three months after SARS-CoV-2 infection. We present a series of 12 cases of LST following SARS-CoV-2 infection. Dense lymphocyte infiltration with multinuclear giant cell granulomas was found on biopsy with intranuclear inclusions, suggestive of viral cytopathic effects in one case and intravascular fibrin thrombi with perivascular mononuclear infiltrate of CD3 + T lymphocytes. We present the largest and only series that describes clinical and histopathological characteristics of LTS and the management and outcomes after early laryngotracheal reconstruction in the context of the SARS-CoV-2 outbreak.

New Insights Into Blue Light Phototherapy in Experimental Trypanosoma cruzi Infection.

The search for an effective etiologic treatment to eliminate Trypanosoma cruzi, the causative agent of Chagas disease, has continued for decades and yielded controversial results. In the 1970s, nifurtimox and benznidazole were introduced for clinical assessment, but factors such as parasite resistance, high cellular toxicity, and efficacy in acute and chronic phases of the infection have been debated even today. This study proposes an innovative strategy to support the controlling of the T. cruzi using blue light phototherapy or blue light-emitting diode (LED) intervention. In in vitro assays, axenic cultures of Y and CL strains of T. cruzi were exposed to 460 nm and 40 µW/cm2 of blue light for 5 days (6 h/day), and parasite replication was evaluated daily. For in vivo experiments, C57BL6 mice were infected with the Y strain of T. cruzi and exposed to 460 nm and 7 µW/cm2 of blue light for 9 days (12 h/day). Parasite count in the blood and cardiac tissue was determined, and plasma interleukin (IL-6), tumoral necrosis factor (TNF), chemokine ligand 2 (CCL2), and IL-10 levels and the morphometry of the cardiac tissue were evaluated. Blue light induced a 50% reduction in T. cruzi (epimastigote forms) replication in vitro after 5 days of exposure. This blue light-mediated parasite control was also observed by the T. cruzi reduction in the blood (trypomastigote forms) and in the cardiac tissue (parasite DNA and amastigote nests) of infected mice. Phototherapy reduced plasma IL-6, TNF and IL-10, but not CCL2, levels in infected animals. This non-chemical therapy reduced the volume density of the heart stroma in the cardiac connective tissue but did not ameliorate the mouse myocarditis, maintaining a predominance of pericellular and perivascular mononuclear inflammatory infiltration with an increase in polymorphonuclear cells. Together, these data highlight, for the first time, the use of blue light therapy to control circulating and tissue forms of T. cruzi. Further investigation would demonstrate the application of this promising and potential complementary strategy for the treatment of Chagas disease.

Renal Involvement in Mediterranean Spotted Fever: Clinical and Histopathological Data

Objective: Mediterranean spotted fever (MSF) is a tick-borne rickettsial infection endemic to the Mediterranean coastline countries. As a result of growing tourism, imported cases have been registered in many nonendemic countries and regions. We present clinical laboratory parameters and histopathological data on renal impairment in patients with MSF. The study meets our goal of identifying kidney involvement and detecting renal damage in people with MSF. Subjects and Methods: Three hundred fifty patients with MSF with a diagnosis confirmed by immunofluorescence analysis were tested for serum urea, creatinine, and albumin. Fifty-five patients with malignant form of MSF were divided into 2 groups: 19 fatalities and 36 survivors. The percentage of patients with acute renal failure (ARF) was compared in both groups. Results: Subjects with elevated urea and creatinine levels increased from 5.21 to 3.47% in mild to 48.78 and 29.26% in severe MSF, respectively. Loss of serum albumin also increased from mild to severe MSF. Renal impairment comprised 60% of the cohort of 55 patients with malignant MSF: 89.4% in the group of deaths and almost twice less in the survivors. ARF developed in 84.2% of fatal cases and was >2 times less in survivors. Postmortem light microscopy of renal samples of 9 fatal cases revealed perivascular mononuclear inflammatory infiltrates, vasculitis with fibrinoid necrosis, acute tubular necrosis, interstitial edema, hemorrhage, and thrombosis. Conclusion: Renal pathology associated with MSF rickettsial infection consists of systemic small vessel vasculitis and vascular injury, leading to ARF in the most severe cases.

Restrictive Cardiomyopathy Revealing Systemic Sclerodermia

Primary myocardial involvement is common in systemic sclerosis. There is growing evidence strongly suggesting that this involvement is linked to repeated focal ischemic lesions causing irreversible myocardial fibrosis. It can affect all heart structures. We report the case of a 65 years old male patient, without any personal medical history, admitted for inaugural right heart decompensation. The diagnosis of restrictive cardiomyopathy is based mainly on the following criteria: on echocardiography, hypertrohy of the right ventricle with alteration of the longitudinal systolic function, dilation of the right atrium, with good overall contractility. On right cardiac catheterization: elevation and equalization of the telesystolic pressures of the right atrium, right ventricle, and pulmonary artery with appearance of dip plateau on the right ventricle curve. Scleroderma was evoked considering following statements: the presence of Raynaud's phenomenon, unknown by the patient (presence of dermal sclerosis with pericapillary oedema and capillary dystrophy on capillaroscopy), cutaneous involvement (presence of perivascular and perineural mononuclear infiltrates, with collagen fibers increased in number and thickness), pulmonary involvement (diffuse bilateral interstitial lung disease) and renal involvement (moderately impaired function and positive proteinuria). The concept of cardiac dysfunction in scleroderma and other rheumatologic conditions has received new interest with the advent of newer non-invasive imaging techniques. Therfore, it would be necessary to search the cardiac involvement especially subclinical one in this type of system disease, as well as to confirm the systemic origin in front of certain forms of cardiopathies in particular restrictive cardiomyopathy.

Restrictive Cardiomyopathy Revealing Systemic Sclerodermia

Primary myocardial involvement is common in systemic sclerosis. There is growing evidence strongly suggesting that this involvement is linked to repeated focal ischemic lesions causing irreversible myocardial fibrosis. It can affect all heart structures. We report the case of a 65 years old male patient, without any personal medical history, admitted for inaugural right heart decompensation. The diagnosis of restrictive cardiomyopathy is based mainly on the following criteria: on echocardiography, hypertrohy of the right ventricle with alteration of the longitudinal systolic function, dilation of the right atrium, with good overall contractility. On right cardiac catheterization: elevation and equalization of the telesystolic pressures of the right atrium, right ventricle, and pulmonary artery with appearance of dip plateau on the right ventricle curve. Scleroderma was evoked considering following statements: the presence of Raynaud's phenomenon, unknown by the patient (presence of dermal sclerosis with pericapillary oedema and capillary dystrophy on capillaroscopy), cutaneous involvement (presence of perivascular and perineural mononuclear infiltrates, with collagen fibers increased in number and thickness), pulmonary involvement (diffuse bilateral interstitial lung disease) and renal involvement (moderately impaired function and positive proteinuria). The concept of cardiac dysfunction in scleroderma and other rheumatologic conditions has received new interest with the advent of newer non-invasive imaging techniques. Therfore, it would be necessary to search the cardiac involvement especially subclinical one in this type of system disease, as well as to confirm the systemic origin in front of certain forms of cardiopathies in particular restrictive cardiomyopathy.

Histopathological Study of Psoriasis and Its Grading According to Trozak Scoring System

Background: Psoriasis is a chronic papulosquamous disorder of undefined etiology, occuring in 0.09 to 11.4% population. Different clinical types occur with varying histopathology. Early and Late onset psoriasis have been defined based on age at presentation. Methods: Cases diagnosed as Psoriasis, both clinically and histologically, were examined for the individual features of Psoriasis. Histomorphological grading of the lesions was also done using the Trozak scoring system. Result: The mean age of the patients was 42.26 with a male predominance (M:F=3.5: 1). Early onset cases constituted 71% of the total cases, while late onset cases were 29%. The histopathological features were found to be variably present. Acanthosis was observed in 96% cases. Hyperkeratosis (94%), parakeratosis (66%), club shaped rete ridges (88%) with regular elongation of rete ridges (72%) with, suprapapillary plate thinning (74%), hypogranulosis (72%), elongation and edema of dermal papillae (88%) were other features seen in majority of cases. Perivascular mononuclear infiltrate in upper dermis of papillae (76%), dermal (76%) and epidermal (78%) neutrophils, spongiform pustules of Kogoj (24%), Munro’s microabscess (28%), were the inflammatory changes observed, present to a greater extent in the early onset cases than the late onset cases. The Trozak scoring system gave an average score of 9.44, with no significant difference in the early and late onset cases of Psoriasis. Conclusion: Entirely typical histological features are found only in a small percentage of biopsy specimens, even if only clinically typical lesions of psoriasis are examined.

LEVAMISOLE-INDUCED VASCULITIS COMPLICATED BY PRESEPTAL CELLULITIS

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Approximately 0.6% of the US adult population use cocaine each month. Cocaine use is accountable for over 33% of all drug-related ED visits. There have been several rare but serious complications described in literature. We present a case of cocaine-induced vasculitis complicated by preseptal cellulitis. CASE PRESENTATION: A 50 year-old woman with a history of cocaine use, presented with altered mental status. On examination, patient was drowsy but arousable and mildly hypotensive. Necrotic skin with eschar was noted on her face (Figure 1). Labs revealed leukocytosis, acute kidney injury (AKI), and metabolic acidosis. CK was 16,000; ESR 29, CRP 424, and procalcitonin 17. Urine was positive for cocaine and amphetamines. CT head revealed edema and tissue stranding extending into the left preseptal orbit. Based on history and examination, a diagnosis was made of levamisole-induced vasculitis. Patient was admitted to the ICU and treated with IV fluids, broad spectrum antibiotics for preseptal cellulitis, and bicarbonate infusion for cocaine-induced rhabdomyolysis. Her hypotension resolved and her AKI improved. Blood cultures grew Prevotella oralis. Further work up revealed positive c-ANCA. HIV, HBV, HCV were negative; c3, c4 levels normal; p-ANCA, cryoglobulin, ANA, and anti-cardiolipin antibodies were negative. Biopsy of the facial lesion revealed sparse perivascular and periadnexal dermatitis with neutrophils and lymphocytes, indicating dermal hypersensitivity and early vasculitic changes. PAS and DIF were negative for fungal elements and immunoreactant deposition, respectively. Her facial lesions were treated conservatively and improved. DISCUSSION: This patient’s presentation is consistent with vasculitis induced by the cocaine adulterant, levamisole. Levamisole is an anti-helminthic medication with veterinarian-restricted use. It is known to cause vasculitis. The possible mechanism is via mimicking thymopoietin, which may potentiate macrophage activity, enhance T-cell function, and stimulate antibody production. Levamisole has been described to increase the potency of recreational cocaine, and is frequently used as a cutting agent. As of 2011, over 80% of cocaine seized in the US contained levamisole. While most individuals do not experience negative effects attributed to levamisole, there have been reports of ANCA-positive vasculitis. While p-ANCA is the most commonly found high-titer autoantibody, levamisole can also cause elevated ANA, anti-human neutrophil elastase, and c-ANCA. Biopsy usually reveals small vessel thrombosis and perivascular mononuclear infiltration with few neutrophils. CONCLUSIONS: In conclusion, levamisole is a clinically relevant adulterant that must be considered in ANCA-positive vasculitis in cocaine users. Reference #1: National Institute on Drug Abuse. “Nationwide Trends.” NIDA, 2015. Reference #2: Abdul-Karim, R et al. Proceedings (BaylorMedical Center). 2013;26: 163. Reference #3: Pieterse E et al. Pathogenesis of cocaine-induced vasculitis. Rheumatology 2017; 56: 503. https://doi.org/10.1093/rheumatology/kew381. DISCLOSURES: No relevant relationships by Debapriya Datta, source=Web Response No relevant relationships by Jose Soriano, source=Web Response No relevant relationships by Katherine Stettmeier, source=Web Response

Inflammation induced by different plasmid types of russian <i>Yersinia pseudotuberculosis</i> strains

In the 2000s, a scientific interest to the Far Eastern scarlet-like fever (FESLF) mainly recorded In Russia and Japanwas remarkably increased. Such clinical and epidemic manifestation of human pseudotuberculosis is related to a certain bacterial clonal lineage characterized by a specific plasmid profile (pVM82, pYV48), sequence type (2ST) as well as the yadA gene allele (1st allele). In our study we examined features of inflammatory changes characterizing plasmidassociated pathogenicity of the FESLF pathogen. In addition, organ histopathology in experimental animals infected intraperitoneally with Y. pseudotuberculosis strains of the four plasmid types 48+:82+; 48+:82-; 48-:82+; 48-:82-; and 48-:82- was investigated. It was found that the mortality rate in animals infected with Y. pseudotuberculosis H-5015 strain (82+:48+) bearing two plasmids with a molecular weight of 82 and 48 MDa was 40%. A picture of diffuse pneumonia with moderate inflammatory infiltration in pulmonary tissue and changes in lymphoid organs characterizing immunodeficiency we observed as early as 3 days postinfection (p.i.). On the contrary, animals infected with Y. pseudotuberculosis H-5015 strain (82+:48) bearing a single plasmid 82 MDa pVM, mortality rate was 30%. A vascular reaction in the lungs and liver as well as deteriorated vascular destructive changes were revealed starting from day 3 and on day 57 days p.i., respectively, which was paralleled with perivascular infiltration mainly by mononuclear cells and focal pneumonia as well as a reaction of bronchialassociated lymphoid tissue and minimal organ destructive changes. On day 7 p.i., signs of granulomatous inflammation in the liver in a form of small mononuclear cell clusters and perivascular compact infiltrates were found. At all time points, lymphoid organ hyperplasia was noted. In case the infection caused by H-5013 strain (48+), the mortality rate was 80%. Inflammatory changes with dominant mononuclear cells were detected as early as 1 day p.i. associated with a picture of large focal bronchopneumonia, more pronounced in the non-survivor animals, also demonstrating signs of severe immunosuppression in the lymphoid organs. Starting from day 3 p.i., lymphoid hypoplasia in the spleen and lymph nodes was detected in all infected animals paralleled with pathogen-associated tissue damage in various organs. Animals infected with the plasmid-free H-5013 strain 48-) resulted in 25% mortality rate. Moreover, starting from day 3 p.i., a slight mononuclear inflammatory infiltration in the lungs and liver, a moderate giant cell reaction in the splenic pulp, and loose perinodal inflammatory infiltration in the lymph nodes were observed. Thus, while modeling infection caused by different plasmid types of Y. pseudotuberculosis, the data on differences in histopathology of changes in diverse organs regarding dynamics and generalization of the inflammatory response, as well as the severity of pathogen-associated damage in the lymphoid tissue were obtained. In case Y. pseudotuberculosis strains contained pVM82 plasmid with or without virulence plasmid pYV vs. single pYV-positive strains, an area of the inflammatory response as well as severity of immunosuppression manifested by splenic and lymph node delymphatization were decreased. It allowed to suggest that pVM82 plasmid found In Russia-originating Y. pseudotuberculosis strains might be implicated in limiting intensity of inflammatory response, bacterial dissemination and severity of lymphoid organ damage.

Toxico-Pathological Studies of <i>Foeniculum vulgare</i> Plant in Mice

Background and objective: Foeniculum vulgare-Mill (Umlliferae), is widely used in the Arabian Peninsula for treating various human and animal diseases. There is need to insure the safety of this plant as a remedy that could be used for a long time. This study aimed to determine the LD50 of the aerial parts of Foeniculum vulgare in mice, as well as to investigate its toxic pathological effects. Methodology: A total of eighty (80) albino mice of both sexes, weighing 25 - 30 g, were used in the present study. Ten (10) mice were used for the determination of LD50 of Foeniculum vulgare in mice. Fifty (50) mice were used in the acute toxicity, and twenty (20) mice were used to study the subacute toxicity of the aerial parts of Foeniculum vulgare juice. Results: the present results revealed that the LD50 of Foeniculum vulgare juice in mice was 9.772 mg/kg/body weight (BW). On the other hand, mice received 0.9 mg/kg/BW of Foeniculum vulgare juice intraperitoneally showed slightly closed eyes intermittent convulsions itching of the nose and increased respiratory rate and abdominal movements. Histopathological examination of the liver showed hepatocytic degeneration and necrosis, congestion with perivascular mononuclear cell infiltrations and peribiliary mononuclear cell aggregations. Whereas the spleen of mice showed depletion of lymphocytes and mononuclear as well as multinuclear cells. The duodenum showed sub-epithelial congested blood vessels, numerous areas of lymphocytic infiltrations and vascular and hydropic degeneration of epithelial cells lining the duodenal Brunner’s glands. Moreover, the kidney showed degenerated tubular epithelial cells, congestion with excess of mononuclear cells, necrotic and desquamated epithelial cells of the proximal convoluted tubules. The lung of mice showed congestion, emphysema with variable degrees of mononuclear cell infiltrations and peribronchial congested blood capillaries and mononuclear cell infiltration. Conclusion: It could be concluded that Foeniculum vulgare juice is toxic to mice when administered in a dose of 9.772 mg/kg/BW. However, the recommended dose for treatment could be less than 0.98 ml/kg BW. (1/10 of the LD50) of Foeniculum vulgare juice.

Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair

BackgroundWhile many groups use experimental autoimmune encephalomyelitis (EAE) as a model to uncover therapeutic targets and understand the pathology underlying multiple sclerosis (MS), EAE protocol variability introduces discrepancies in central nervous system (CNS) pathogenesis and clinical disease, limiting the comparability between studies and slowing much-needed translational research. Optimized methodHere we describe a detailed, reliable protocol for chronic EAE induction in C57BL/6 mice utilizing two injections of myelin oligodendrocyte glycoprotein (35–55) peptide mixed with complete Freund’s adjuvant and paired with pertussis toxin. ResultsThe active MOG35-55-EAE protocol presented here induces ascending paralysis in 80–100% of immunized mice. We observe: (1) consistent T cell immune activation, (2) robust CNS infiltration by peripheral immune cells, and (3) perivascular demyelinating lesions concurrent with axon damage in the spinal cord and various brain regions, including the optic nerve, cortex, hippocampus, internal capsule, and cerebellum. Comparison with existing method(s)Lack of detailed protocols, combined with variability between laboratories, make EAE results difficult to compare and hinder the use of this model for therapeutic development. We provide the most detailed active MOG35-55-EAE protocol to date. With this protocol, we observe high disease incidence and a consistent, reliable disease course. The resulting pathology is MS-like and includes optic neuritis, perivascular mononuclear infiltration, CNS axon demyelination, and axon damage in both infiltrating lesions and otherwise normal-appearing white matter. ConclusionsBy providing a detailed active MOG35-55-EAE protocol that yields consistent and robust pathology, we aim to foster comparability between pre-clinical studies and facilitate the discovery of MS therapeutics.

Eruptive Facial Postinflammatory Lentigo: Clinical and Dermatoscopic Features.

The face has not been considered a common site of fixed drug eruption, and the authors lack dermatoscopic studies of this condition on the subject. The authors sought to characterize clinical and dermatoscopic features of 8 cases of an eruptive facial postinflammatory lentigo. The authors conducted a retrospective review of 8 cases with similar clinical and dermatoscopic findings seen from 2 medical centers in 2 countries during 2010-2014. A total of 8 patients (2 males and 6 females) with ages that ranged from 34 to 62 years (mean: 48) presented an abrupt onset of a single facial brown-pink macule, generally asymmetrical, with an average size of 1.9 cm. after ingestion of a nonsteroidal antiinflammatory drugs that lasted for several months. Dermatoscopy mainly showed a pseudonetwork or uniform areas of brown pigmentation, brown or blue-gray dots, red dots and/or telangiectatic vessels. In the epidermis, histopathology showed a mild hydropic degeneration and focal melanin hyperpigmentation. Melanin can be found freely in the dermis or laden in macrophages along with a mild perivascular mononuclear infiltrate. The authors describe eruptive facial postinflammatory lentigo as a new variant of a fixed drug eruption on the face.

Lipedematous alopecia: clinical and histological analysis of the first male Chinese.

BackgroundLipedematous alopecia (LA) is a rare disorder clinically characterized by a thick boggy scalp and varying severity of hair loss, which primarily occurs in black female adults. In this study, we reported one male adult Chinese diagnosed with lipedematous alopecia for the first time.Case presentationA Chinese male, aged 20 years old, admitted to Shandong Provincial Hospital for Skin Diseases was diagnosed with LA. Clinical, histological and imaging data were collected and analyzed. Literature review was performed.ResultsSkin biopsy and pathological examination revealed the signs of increased subcutaneous adipose tissue, slight perivascular mononuclear infiltration into superficial dermis, adipocyte disruption and mucin deposition. CT scan demonstrated diffuse thickening of subcutaneous tissue in the occipital region. The symptoms were not significantly alleviated after 6-month combined therapy of prednisone and acupuncture.ConclusionsWe reported one male Chinese of LA, who was the first case reported in China. Clinical and pathological findings of this case deepened the understanding of LA.