Granulomatous Tissue Research Articles

Recurrent ulcerated nodules and erythematous plaques in a patient with Kartagener syndrome.

Cutaneous manifestations associated with Kartagener syndrome (KS) are exceptional and only two cases of patients with recurrent furunculosis and pyoderma gangrenosum have been described. We report a patient with KS presenting with recurrent sterile exudative nodules and erythematous plaques mimicking an infectious disorder and showing histologically an abscessified granulomatous tissue reaction.

Patologia da infecção por Spirorchiidae (Digenea: Schistosomatoidea) em tartarugas verdes (Chelonia mydas) na Bacia de Campos, Rio de Janeiro

ABSTRACT: Spirorchidiasis is one of the most common diseases in green turtles. Eggs and the adult form of trematodes are mainly found in the heart, liver, lung, spleen, and gastrointestinal tract. The present study aimed to describe the pathological aspects of Spirorchiidae trematode infection in green turtles (Chelonia mydas) in the Campos Basin, Rio de Janeiro. The current study was based on the necropsy of 99 green turtles (Chelonia mydas, Chelonidae) from April to December 2021. Epidemiological data were obtained from the Aquatic Biota Monitoring Information System (SIMBA). A histopathological examination was performed at the “Setor de Anatomia Patológica” (SAP) from “Universidade Federal Rural do Rio de Janeiro” (UFRuralRJ). Tissue fragments (buccal papilla, esophagus, trachea, lung, heart, kidney, bladder, stomach, liver, spleen, intestines, gonads, adrenal, thyroid, pancreas, salt glands, muscle, and skin) were sampled for histological examination. The green turtles had lesions compatible with parasitic infection in 89% (88/99) cases. Out of 88 turtles, 87 were juveniles (99%), 75% (66/88) were females, and 25% (22/88) were males. Adult parasites and their eggs were found to cause granulomatous tissue reactions in 14% (12/88) of turtles. Egg-associated granulomatous inflammation was found in 86% (76/88) of the turtles. The organs with the highest number of egg-associated granulomas in order of occurrence were: the spleen, small intestine, adrenal gland, pancreas, and lungs. The adult trematodes were observed in histological lesions in order of occurrence, mainly in the esophagus, stomach, and small intestine. Out of the total number of turtles parasitized, 33% (29/88) of deaths occurred due to multiple causes such as fractures, interaction with fishing, predation, and fibropapillomas. The other 67% (59/88) presented multisystemic granulomatous disease caused by Spirorchiidae infection as a cause of death. Evidence is presented that spirorchidiasis is highly prevalent in young green turtles, is responsible for extensive chronic lesions, and responsible for significant debilitation and mortality.

MANAGEMENT OF SUSPECT GRANULOMATOUS EPULIS OF ANTERIOR MANDIBULAR TEETH WITH GINGIVECTOMY

ABSTRACT Gingival enlargement is a manifestation of hypertrophy (increase in cell size) and hyperplasia (increase in cell number). Epulis is a gingival hyperplasia (tumor-like) that originates from periodontal connective tissue. One type of epulis that often occurs is granulomatous epulis. Granulomatous epulis is a type of epulis that occurs from a granulomatous tissue reaction due to chronic irritation due to calculus, root residues, or carious edges. This case report discusses the management of suspect epulis granulomatous in mandibular anterior teeth. A 45-year-old female patient complained of swollen lower front gums and frequent bleeding when brushing her teeth. Intraoral examination showed that there was gingival enlargement in the form of papules with a size of 6 mm x 8 mm, reddish in color, smooth surface, soft consistency, well demarcated, painless but bleeding on palpation in the tooth area 41. OHI score 4.9 (moderate), BOP ( Bleeding in probing) was positive, and the probing depth of the mesiolabial, midlabial, and distolabial surfaces i.e. for tooth 41 was 5-5-5. The diagnosis in this case led to suspect epulis granulomatous on tooth 41. The treatment plan was KIE (Communication, Information and Education), initial therapy in the form of scaling and root planing, gingivectomy and then control. The results of the treatment showed that the gingival contour was physiologically formed, there was no swelling, negative palpation, negative BOP, and decreased pocket depth from the mesiolabial, midlabial, and distolabial surfaces of tooth 41 to 2-2-3.Keywords: epulis, granulomatous epulis, gingivectomy, gingival enlargement

Protective effects of Brenania brieyi (De Wild) E.M.A.Petit root bark fractions against inflammatory-mediated hemolysis and dyslipidemia in rats

Background and Aims: The inflammatory response, though protective, is the major cause of debilitating diseases when provoked excessively or if left unresolved. Brenania brieyi (De Wild) E.M.A.Petit is widely used in folk medicine for the treatment of inflammatory-related diseases. This study investigated the protective effects of methanol and chloroform root bark fractions of Brenania brieyi on inflammation-induced hemolysis and dyslipidemia. Methods: Anti-inflammatory activity was investigated by inserting 20 mg of autoclaved cotton pellets into forty-five rats randomly distributed into nine groups (n=5), this excluded group 1 (baseline). The extent of hemolysis and dyslipidemia in the inflamed rats was ascertained from hematological parameters, lipid profile, and lipidemic index, while the possible underlying mechanisms of inflammation were determined using standard procedures. Results: Treatment with varying doses of the root bark fractions of B. brieyi elicited a significant (p< 0.05) decrease in granuloma tissue and an increase (p<0.05) in hemoglobin, red and white blood cell count, packed cell volume, and platelets compared with the untreated group 2. A significant (p<0.05) decrease in cholesterol, triacylglycerols, and low-density lipoprotein, and a non-significant (p>0.05) increase in high-density lipoprotein were observed in almost all the test groups compared with group 2. There was a significant restoration of atherogenic and dyslipidemia indices and inhibition of acetic acid-induced vascular permeability, membrane hemolysis, and platelet aggregation in the fraction-treated groups compared with the control. Conclusion: The findings from this study suggest that B. brieyi inhibits exudation and proliferation of granuloma-forming cells and also has the potential to restore the hematological parameters and lipid anomalies to their physiologic state under chronic inflammation. The possible mechanisms of its action could be inhibition of vascular permeability, stabilization of the membrane, or inhibition of platelet aggregation. This justifies the use of the plant in traditional medicine and also demonstrates its potential as a target for the discovery of new anti-inflammatory agents.

Improved Lentiviral In Vivo Gene Therapy for Chronic Granulomatous Disease

Background: Chronic granulomatous disease (CGD) is a congenital immunodeficiency characterized by severe life-threatening infections. CGD patients lack reactive oxygen species (ROS) in phagocytic leukocytes and often develop widespread tissue granulomas. The current treatment for CGD is lifelong antibiotic prophylaxis or hematopoietic stem cell transplantation (HSCT). However, most patients cannot find matched donors, and HSCT is known to have increased risk in CGD patients. Gene therapy has become a promising treatment for CGD. At present, "ex vivo" HSC gene therapy is the widely applied strategy. "In vivo" gene therapy is based on direct delivery of gene therapy vectors into patients, which could overcome the difficulties in HSCT. Methods: We have developed an in vivo CGD gene therapy strategy by intravenous (iv) injection of lentiviral vectors (LVs) carrying an universal EF1a promoter or a myeloid-specific miR223 promoter driving the expression of CYBB (cytochrome B-245 beta chain, or p91-phox) in X-CGD mice (X-CGD; B6.129S-Cybbtm1Din/J). Each mouse received 1x109 transduction units (TU) of LV-CYBB via iv injection after non-myeloablative conditioning. A second injection of 1x109 TU of LV-CYBB after re-conditioning was given 12 weeks later. Results: We developed a chemotherapy conditioning regimen to improve gene delivery efficiency by using busulfan, cyclophosphamide and dexamethasone. The X-CGD mice received two iv injections of LVs, and the expression and function of the LV-CYBB gene were analyzed by intracellular gp91-phox staining and DHR123 assay 4 weeks after each injection. Based on flow cytometry, we detected gp91-phox positive cells in the blood as the following, EF1a: 1.14-5.18% and 5.27-14.36%, and miR223: 1.65-5.17% and 4.59-17.89% after the first and the second injections, respectively, as compared with the WT mice: 79.9-87.6%. Functional analyses of ROS showed the following, EF1a: 1.93-5.2% and 2.39-18.51%, miR223: 2.65-6.67% and 3.75-19.8%, after the first and the second injections respectively, as compared with WT: 72.6-85.31% (Figure A). The LV vector copy number (VCN) in the peripheral blood mononuclear cells was detected by qPCR as the following, EF1a: 1.11-2.32% and 1.35-9.32%, and miR223: 1.01-2.39% and 2.71-8.51% after the first and the second injections, respectively. These results indicated that iv LV injection effectively delivered and expressed the LV-CYBB gene in vivo, and repeated injection of the LVs could increase the gene transfer efficiency in the CGD mice. Importantly, after the second injection, we found no antibody response to the LV particle-associated protein p24. However, after 3-12 months, markedly reduced VCN was found in the blood of the treated mice, suggesting exhaustion of the transgenes in the somatic cells. To improve the gene delivery into HSCs, we treated the mice with AMD3100 to mobilize HSCs into peripheral blood. The mice were treated with chemo-conditioning and AMD3100 prior to LV ivinjection. After four weeks, the gp91-phox positive HSCs of total Sca1+ HSCs in blood with or without (+/-) AMD3100 treatment were examined by flow cytometry, and the results showed the following, EF1a: (-) 9.52-15.43%, (+) 16.1-29.4%, and miR223: (-) 4.49-10.35% and (+) 7.06-16.84%. To confirm stem cell gene transfer, we transplanted the bone marrow cells from the LV-CYBB-treated CGD mice into untreated CGD mice. The VCN in blood was examined before (donor mice) and 4 weeks after (recipient mice) the HSCT, and the results showed the following, EF1a: before 4.49% (in the donor) and after 1.05-2.57% (in the recipients), and miR223: before 4.91% (in the donor) and after 1.04-2.69% (in the recipients) (Figure B). This transplantation study confirmed that the AMD3100 treatment effectively increased iv LV gene delivery into HSCs. Conclusion: We have developed an improved LV iv gene delivery strategy by applying chemo-conditioning and AMD3100 mobilization prior to the injection of the LVs into CGD mice. This in vivo LV gene therapy strategy could potentially be translated into future CGD gene therapy applications. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Biochemical and genomic identification of novel biomarkers in progressive sarcoidosis: HBEGF, eNAMPT, and ANG-2.

Progressive pulmonary fibrosis is a serious complication in subjects with sarcoidosis. The absence of reliable, non-invasive biomarkers that detect early progression exacerbates the difficulty in predicting sarcoidosis severity. To potentially address this unmet need, we evaluated a panel of markers for an association with sarcoidosis progression (HBEGF, NAMPT, IL1-RA, IL-6, IL-8, ANG-2). This panel encompasses proteins related to inflammation, vascular injury, cell proliferation, and fibroblast mitogenesis processes. Plasma biomarker levels and biomarker protein expression in lung and lymph nodes tissues (immunohistochemical studies) from sarcoidosis subjects with limited disease and progressive (complicated) sarcoidosis were performed. Gene expression of the protein-coding genes included in this panel was analyzed using RNAseq in sarcoidosis granulomatous tissues from lung and lymph nodes. Except for IL-8, plasma levels of each biomarker-eNAMPT, IL-1RA, IL-6, ANG-2, and HBEGF-were significantly elevated in sarcoidosis subjects compared to controls. In addition, plasma levels of HBEGF were elevated in complicated sarcoidosis, while eNAMPT and ANG-2 were observed to serve as markers of lung fibrosis in a subgroup of complicated sarcoidosis. Genomic studies corroborated HBEGF and NAMPT among the top dysregulated genes and identified cytokine-related and fibrotic pathways in lung granulomatous tissues from sarcoidosis. These findings suggest HBEGF, eNAMPT, and ANG-2 may serve as potential novel indicators of the clinical severity of sarcoidosis disease.

The gut microbial metabolic capacity of microbiome-humanized vs. wild type rodents reveals a likely dual role of intestinal bacteria in hepato-intestinal schistosomiasis.

Increasing evidence shows that the host gut microbiota might be involved in the immunological cascade that culminates with the formation of tissue granulomas underlying the pathophysiology of hepato-intestinal schistosomiasis. In this study, we investigated the impact of Schistosoma mansoni infection on the gut microbial composition and functional potential of both wild type and microbiome-humanized mice. In spite of substantial differences in microbiome composition at baseline, selected pathways were consistently affected by parasite infection. The gut microbiomes of infected mice of both lines displayed, amongst other features, enhanced capacity for tryptophan and butyrate production, which might be linked to the activation of mechanisms aimed to prevent excessive injuries caused by migrating parasite eggs. Complementing data from previous studies, our findings suggest that the host gut microbiome might play a dual role in the pathophysiology of schistosomiasis, where intestinal bacteria may contribute to egg-associated pathology while, in turn, protect the host from uncontrolled tissue damage.

Immunogenic cell death as driver of autoimmunity in granulomatosis with polyangiitis.

Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with polyangiitis (GPA), a neutrophil-driven autoimmune disorder, is characterized by necrotizing inflammation predominantly of the respiratory tract and an anti-neutrophil cytoplasmic autoantibody (ANCA)-associated systemic necrotizing vasculitis. Defective regulation of neutrophil homeostasis and cell death mechanisms have been demonstrated in GPA. Disturbed efferocytosis (i.e., phagocytosis of apoptotic neutrophils by macrophages) as well as cell death-related release of damage-associated molecular patterns (DAMP) such as high mobility group box 1 (HMGB1) contribute to chronic non-resolving inflammation in GPA. DAMP have been shown to induce innate as well as adaptive cellular responses thereby creating a prerequisite for the development of pathogenic autoimmunity. In this review, we discuss factors contributing to as well as the impact of regulated cell death (RCD) accompanied by DAMP-release as early drivers of the granulomatous tissue inflammation and autoimmune responses in GPA.

Pathogenetic aspects of aseptic peri-implant and paraprosthetic complications in traumatology (review)

The use of metal implants and joint prosthetics occupy an important place in modern traumatology and orthopedics. With the increasing proportion of surgical methods for treating bone fractures and joint diseases, complications develop more frequently. Along with early and late wound infections, there are various response changes in tissues in the area of the implant of an abacterial nature. The results of clinical and experimental studies in the development of fibro-proliferative, immuno-allergic and granulomatous tissue changes around implants determine the important role of macrophages, fibroblasts, cells of the immune system, the peculiarities of the pathophysiology of which this article is devoted to.

Assessment of anti-inflammatory activity of Tridax procumbens in wistar rats

Background: Tridax procumbens Linn. is a spreading herb found throughout India. Tridax procumbens is known for several potential therapeutic effects like antiviral, antioxidant, anti-infective, wound healing, insecticidal and anti-inflammatory, hepatoprotective, and antidiabetic. Novel therapies for inflammation are essential to overcome the adverse effects of existing anti-inflammatory drugs. Thus, this study was designed to evaluate anti-inflammatory activity in the experimental animal. Objective: To evaluate anti-inflammatory efficacy in experimental animal Materials and Methods: Tridax procumbens plant leaves were taken for the study. The Plant extraction was prepared by using the Soxhlet apparatus. The ethanolic extract was used as a test drug. Indomethacin and Dexamethasone were used as control drugs. Wistar rats weighing 150g to -200g were used in the study. Results: At dosages of 200 and 400 mg kg-1, the ethanolic leaf extracts of Tridax Procumbens demonstrated substantial anti-inflammatory activity against Irish Moss-triggered inflammation. After 3 hours, 400 mgkg-1 showed a significant reduction in inflammation (48 percent), with the impact increasing after 3 hours (52 percent). The anti-inflammatory efficacy of Tridax Procumbens ethanol (EtOH) extracts was substantial and comparable to that of indomethacin (10 mg/kg). Tridax procumbens ‘s Ethanol (EtOH) leaf extract at a dose of 200 and 400 mgkg-1, demonstrated considerable anti-inflammatory action. The average weight of granulomatous surrounding tissue in the threading was considerably smaller in the Tridax procumbens extraction group after 7 days than in the comparison group. The 400 mg kg-1 dose was shown to be the most effective of the two. the greatest reduction in the production of granuloma tissue. Tridax procumbens at doses of 200 mg/kg and 400 mg/kg resulted in substantial reductions in granuloma weights of 38.16 ± 0.04 (7.4 percent inhibition) and 34.58 ± 0.04 (16.1 percent inhibition), respectively. The lower dose of 400 mg/kg resulted in a little lesser reduction in granumola weight than the conventional medication dexamethasone (28.92 ± 0.04). (29.8 percent inhibition). Conclusion: The present study concludes that Tridax Procumbens possess anti-inflammatory effects in animal models.

Genital mycobacteriosis caused by Mycobacterium marinum detected in two captive sharks by peptide nucleic acid-fluorescence in situ hybridization.

Mycobacterium marinum is a prevalent nontuberculous mycobacterium (NTM)-infecting teleosts. Conversely, little is known about mycobacteriosis in elasmobranchs, and M.marinum infection has never been reported from the subclass. This study investigated the histopathological characteristics and localization of this mycobacterium through molecular analysis of two captive sharks, a scalloped hammerhead Sphyrna lewini and a Japanese bullhead shark Heterodontus japonicus, exhibited in the same aquarium tank. We detected genital mycobacteriosis caused by M.marinum infection using molecular analyses, including polymerase chain reaction (PCR) and DNA sequencing targeting the 60 kDa heat-shock protein gene (hsp65), and peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) targeting the 16S rRNA gene. Both sharks showed granulomas in connective tissues of the gonads without central necrosis or surrounding fibrous capsules, which is unlike the typical mycobacterial granulomas seen in teleosts. This study reveals that elasmobranchs can be aquatic hosts of M.marinum. Because M.marinum is a representative waterborne NTM and a potential zoonotic agent, cautious and intensive research is needed to overcome a lack of data on the relationship between NTM and the aquatic environment in association with this subclass of Chondrichthyes.

S2.1d Incidence of mixed fungal infections in post-COVID-19 outbreak of Mucormycosis

S2.1 Update on Mucormycosis, September 21, 2022, 3:00 PM - 4:30 PM IntroductionPost-COVID-19 rhino orbital mucormycosis has emerged as an important life-threatening complication adding to mortality. Fungal infections are a major health challenge, especially in the immunocompromised.Mucormycosis is a severe, frequently fatal fungal infection that has a unique predisposition to infect patients with diabetes. The most probable reasons for the emergence of these cases could be the extensive use of steroids in the management of coronavirus disease 2019 (COVID-19) patients and extensive dysregulated immune response due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. A prompt diagnosis is vital for the effective management of invasive rhino-orbital fungal infections due to their propensity for angioinvasion and destructive spread with brain involvement.Materials and MethodsA total of 150 surgical pathology specimens received with a clinical suspicion of invasive fungal infection during the post-COVID-19 outbreak of mucormycosis were retrieved from the archives of the Department of histopathology. The cases were reviewed for the presence of Aspergillus fruiting bodies by senior pathologists and microbiologists on a multi-headed microscope. The morphological features of the fruiting bodies were noted and correlated with the fungal KOH and culture. The tissue reaction pattern, presence of oxalate crystals, and morphology of the fungal hyphae were also noted in each case showing Aspergillus fruiting bodies.ResultsA total of 8 out of 150 cases (5.3%) showed the presence of Aspergillus fruiting bodies. The histopathological diagnosis given in these 8 cases were—Aspergillus (1), combined Aspergillus and Mucorales (7). Two types of fungal hyphae were noted in all seven cases of combined infection. Granulomatous tissue reaction was noted in two out of seven cases of combined infection. Calcium oxalate crystals were noted in the single case of Aspergillosis and were absent in all cases of mixed infection.ConclusionTo conclude Aspergillus fruiting bodies are found in a small but significant number of cases of post-COVID-19 Rhino-Orbital invasive mold infections so while reporting the surgical specimens with clinical suspicion of post-COVID-19 mucormycosis one should be aware of the possibility of mixed fungal infections and look for Aspergillus fruiting bodies as a tell-tale sign of mixed Mucorales and Aspergillus infection. However, their presence does not estimate the true incidence of mixed fungal infections for which immunohistochemistry and polymerase chain reaction are needed.

Pathological complete remission of relapsed tumor by photo-activating antibody-mimetic drug conjugate treatment.

Antibody-mimetic drug conjugate is a novel noncovalent conjugate consisting of an antibody-mimetic recognizing a target molecule on the cancer cell surface and low-molecular-weight payloads that kill the cancer cells. In this study, the efficacy of a photo-activating antibody-mimetic drug conjugate targeting HER2-expressing tumors was evaluated in mice, by using the affibody that recognize HER2 (ZHER2:342 ) as a target molecule and an axially substituted silicon phthalocyanine (a novel potent photo-activating compound) as a payload. The first treatment with the photo-activating antibody-mimetic drug conjugates reduced the size of all HER2-expressing KPL-4 xenograft tumors macroscopically. However, during the observation period, relapsed tumors gradually appeared in approximately 50% of the animals. To evaluate the efficacy of repeated antibody-mimetic drug conjugate treatment, animals with relapsed tumors were treated again with the same regimen. After the second observation period, the mouse tissues were examined histopathologically. Unexpectedly, all relapsed tumors were eradicated, and all animals were diagnosed with pathological complete remission. After the second treatment, skin wounds healed rapidly, and no significant side effects were observed in other organs, except for occasional microscopic granulomatous tissues beneath the serosa of the liver in a few mice. Repeated treatments seemed to be well tolerated. These results indicate the promising efficacy of the repeated photo-activating antibody-mimetic drug conjugate treatment against HER2-expressing tumors.

DRUG-INDUCED SARCOIDOSIS-LIKE REACTION IN THE ORAL CAVITY: A CASE REPORT

Drug-induced sarcoidosis-like reaction (DISR) is almost indistinguishable from sarcoidosis, and it manifests as a systemic granulomatous tissue reaction occurring in a temporal association with initiation of an offending drug. This study presents a rare case of DISR with oral involvement. A 63-year-old woman with a history of rheumatoid arthritis who has been treated with adalimumab presented with multiple ulcerative nodules on the hard palate, with 15 days of duration. Imaging exams did not exhibit any alteration. Blood tests and serological investigations were negative. An incisional biopsy was performed. Microscopic examination demonstrated a granulomatous inflammatory process in the connective tissue, consisting of multiple granulomas, without evidence of caseating necrosis or microorganisms. Histochemical reactions were negative for acid-fast bacilli and fungi, and immunohistochemical assessment for CD3, CD20, and CD68 highlighted the presence of normal lymphocytes and histiocytes. Adalimumab was ceased and after 17 months complete resolution of the lesions was observed.

Histopathology of the fish infected with the epizootic ulcerative syndrome in Eastern Nepal

Epizootic ulcerative syndrome (EUS) is the major disease of fish which causes high mortality of fish in eastern Nepal since its initial outbreak. Of the 445 EUS infected fish samples, the suspected fungus was identified in eight spp. during the five years study period following standard methods to isolate, culture and identification. The sections of muscles, livers, and kidneys of infected fish samples showed the outbreak of EUS due to the presence of Aphanomyces spp. A complete loss of epidermis and the underlying musculature was replaced by granulomatous and inflammatory tissues. In some areas, myonecrosis and fungal hyphae, black stained with GMS, reflected a positivity for the presence of fungus. Pathogenicity test in Heteropneustes fossilis showed some lesions and 43.33% mortality when isolated zoospores were injected into experimental fish samples.

The cardiac sarcoidosis consortium: elucidating a mysterious disease through collaborative research

Cardiac sarcoidosis (CS) is an inflammatory disease of unknown aetiology that can lead to life-threatening arrhythmias, heart failure, and death. The hallmark pathophysiology involves the development of noncaseating granulomas in cardiac tissue disrupting normal electrical signalling and ultimately impairing cardiac pump function. Advanced cardiac imaging has improved the clinician’s ability to detect the disease, and there has been a significant rise in the number of patients diagnosed with this disorder in the last 20 years. Critical knowledge gaps remain in the domains of aetiology, genetic basis, and immunological mechanisms. There is also uncertainty as to the most appropriate diagnostic criteria, risk stratification, and treatments. The CS literature is mostly comprised of case reports and small retrospective studies; high-quality data from randomized controlled trials are lacking. After collaborating on a multicentre analysis of safety and efficacy of implantable cardioverter defibrillator (ICD) in CS,1 the founding members [Dr Thomas Crawford and Dr Frank Bogun (University of Michigan), Dr William Sauer (then at the University of Colorado), and Dr Kenneth Ellenbogen and Dr Jordana Kron (Virginia Commonwealth University)] established an international, prospective registry, the Cardiac Sarcoidosis Consortium (CSC). The consortium identified five primary aims (Figure 1). The CSC has advocated for inclusion of CS sessions at major national and international meetings and proposed and championed the development of the first CS-specific guidelines, which resulted in the 2014 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated with Cardiac Sarcoidosis.2 Since the inception of the CSC, we have witnessed an increase in academic interest in CS at national meetings and in research publications.

Impact of systemic health on treatment outcomes in endodontics.

The healing of periapical lesions after root canal treatment (RCT) is not the result of the curative action of the treatment. The process of healing begins with inflammation, and is resolved by the clearance of the immunogen that induces the immune response. Then, the periapical tissue itself carries out the healing of the periapical lesion, by repair or by a combination of repair and regeneration, depending on the host's reparative response working properly. The ultimate objective of RCT is to achieve wound healing by removing the source of bacterial antigens and toxins, allowing chronic inflammatory tissue to become reparative tissue. Some systemic conditions increase the susceptibility of the host to infection or impair the tissue reparative response, maintaining the inflammatory process and periapical bone resorption after RCT. This can cause the failure of RCT and even the need for extraction of the affected tooth. To analyse the scientific literature on the possible influence of systemic conditions on the treatment outcomes in endodontics, as well as to discuss the biological mechanisms that may be involved. The search was carried out in PubMed, SCOPUS and EMBASE. The inclusion criteria established were original scientific articles reporting data about some systemic condition in relation to treatment outcomes in endodontics, including clinical studies and studies carried out in animal models. Systemic factors (age, nutrition, stress, hormones, smoking habits), and systemic diseases, such as diabetes, cardiovascular diseases, osteoporosis, HIV infection, inflammatory bowel disease, and others, can influence or interfere in the repair of periapical tissues after RCT. Some of these systemic diseases can alter bone turnover and fibroblast function, preventing or delaying periapical wound healing. Others can alter the microvasculature, reducing nutrients and oxygen supply to periapical tissues. As a result, these systemic conditions can decrease the success rate of RCT and provoke incomplete wound healing (typically granulomatous tissue formation) in the periapical region. The results of this narrative review show worse success rate of RCT, with higher percentage of postoperative radiolucent periapical lesions and higher proportion of non-retained teeth (RFT), associated with several systemic conditions, such as smoking habits and diabetes.

A retrospective study on Schistosoma spindale infection in domestic ruminants, Andhra Pradesh, India.

The present study was undertaken to determine the prevalence of Schistosoma spindale infection in domestic ruminants in Krishna district, Andhra Pradesh by coprological and necropsy examination. Examination of 177 buffaloes, 283 sheep and 166 goats faecal samples (n = 626) revealed 2.25, 2.82 and 1.80% of S. spindale infection, respectively. Necropsy examination of 21 buffaloes, 185 sheep and 217 goats revealed 14.2, 1.08 and 3.68% of S. spindale infection, respectively. Overall, microscopic examination of faecal smears revealed 2.39% (n = 15) prevalence of S. spindale infection in ruminants in the study area, while 3.07% (n = 13) of ruminants were found to be positive for S. spindale during postmortem examination. Adult worms collected from the mesenteric veins were processed and identified as S. spindale. Grossly, the infected livers were found with petechial haemorrhages, cirrhotic changes and pinpoint granulomas in parenchymatous tissue. Histological sections of livers revealed microgranulomas with infiltration of mononuclears, eosinophils and fibroblast cells surrounding the Schistosome ova. The intestinal mucosa was thickened, edematous and haemorrhagic with copious mucous exudates. Cut section of infected intestines revealed severe inflammatory reactions in the mucosa and sub mucosa and granulomatous changes surrounding the Schistosoma eggs.

Panhypopituitarism as the first manifestation of sarcoidosis: case report

Sarcoidosis is a systemic inflammatory disease of unknown etiology characterized by the formation of noncaseating granulomas in various organs and tissues and the activation of T-cells at the site of granulomatous inflammation with the release of various chemokines and cytokines [1]. The incidence on average ranges from 10 to 20 per 100,000 population [2]. Most often in patients with sarcoidosis, lesions of the lungs and intrathoracic lymph nodes are detected. Significantly less often (in about 5-20% of patients) damage to the nervous system is noted [6,7,9]. In 9-18% of patients with neurosarcoidosis, involvement of the pituitary gland, pituitary infundibulum and hypothalamus is found, which is manifested by a variety of clinical symptoms [8,10]. We observed a patient with sarcoidosis whose disease debuted with clinical symptoms of hypogonadism, followed by the development of signs of secondary hypothyroidism, adrenal insufficiency, and diabetes insipidus, which was initially regarded as panhypopituitarism against the background of a hypothalamic lesion of unknown origin. Later, additional examination revealed signs of intrathoracic lymphadenopathy and focal changes in the lung parenchyma on CT, as well as skin lesions. Despite the biochemical compensation of hypopituitarism, the clinical efficacy of hormonal therapy with cabergoline, testosterone, hydrocortisone and levothyroxine sodium was insufficient, and the patient's condition improved after the addition of immunosuppressive and anti-inflammatory therapy with methotrexate and methylprednisolone.

Itraconazole, a cytochrome P450 inhibitor, enhanced the efficacy of praziquantel against Schistosoma mansoni infection and alleviated liver injury in mice

Treatment of schistosomiasis is heavily reliant on the single antischistosomal drug praziquantel (PZQ). The use of synergistic drug-drug interactions is one possible solution, which could be used to mitigate PZQ's poor and variable bioavailability. Itraconazole (ITZ), a triazole antifungal agent, is a potent CYP3A inhibitor that can cause significant drug-drug interactions when used with CYP3A substrates. This study investigates the effect of ITZ as adjuvant therapy with PZQ on worm load, egg deposition and maturation, and the consequent histopathology and biochemical abnormalities in the liver during the immature and mature stages of Schistosoma mansoni (S. mansoni) infection. S. mansoni-infected mice were divided into five groups of eight−ten mice each: (I) infected untreated, (II) infected and treated with PZQ 3 weeks PI, (III) infected and treated with both ITZ and PZQ 3 weeks PI, (IV) infected and treated with PZQ 7 weeks PI, and (V) infected and treated with both ITZ and PZQ 7 weeks PI. All mice were killed by rapid decapitation 9 weeks PI. Data revealed that ITZ in combination with PZQ at both immature and mature stages improved the parasitological criteria of cure, and greatly reduced inflammation, granuloma and fibrotic tissue formation, and apoptosis versus PZQ alone. Furthermore, it showed the greatest impact on improving liver injury and oxidative stress markers. Notably, the effect was considerably stronger at the mature stage of S. mansoni infection. These findings support the notion that ITZ increased PZQ's antischistosomal activity by inhibiting CYP450 expression, potentially reducing PZQ metabolism and increasing systemic exposure.