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Abstract Background Ethacrynic acid (EA) is a loop diuretic that is approved orally and parenterally to manage edema-associated diseases. Nevertheless, it was earlier reported that it is also associated with bleeding upon its parenteral administration. In this report, we investigated the effects of EA on human factor XIIIa (FXIIIa) of the coagulation process using a variety of techniques. Methods A series of biochemical and computational methods have been used in this study. The potency and efficacy of human FXIIIa inhibition by EA was evaluated using a bisubstrate-based fluorescence trans-glutamination assay under near physiological conditions. To establish the physiological relevance of FXIIIa inhibition by EA, the effect on FXIIIa-mediated polymerization of fibrin(ogen) as well as the formation of fibrin(ogen) – α2-antiplasmin complex was evaluated using SDS-PAGE experiments. The selectivity profile of EA against other coagulation proteins was assessed by evaluating EA’s effect on human clotting times in the activated partial thromboplastin time (APTT) and the prothrombin time (PT) assays. We also used molecular modeling studies to put forward a putative binding mode for EA in the active site of FXIIIa. Results involving EA were the average of at least three experiments and the standard error ± 1 was provided. In determining the inhibition parameters, we used non-linear regression analysis. Results FXIIIa is a transglutaminase that works at the end of the coagulation process to form an insoluble, rigid, and cross-linked fibrin rich blood clot. In fact, inhibition of FXIIIa-mediated biological processes has been reported to result in a bleeding diathesis. Inhibition of FXIIIa by EA was investigated given the nucleophilic nature of the thiol-containing active site of the enzyme and the Michael acceptor-based electrophilicity of EA. In a bisubstrate-based fluorescence trans-glutamination assay, EA inhibited FXIIIa with a moderate potency (IC 50 ~ 105 µM) and efficacy (∆Y ~ 66%). In SDS-PAGE experiments, EA appears to significantly inhibit the FXIIIa-mediated polymerization of fibrin(ogen) as well as the formation of fibrin(ogen) – α2-antiplasmin complex which indicates that EA affects the physiological functions of FXIIIa. Interestingly, EA did not affect the clotting times of human plasma in the APTT and the PT assays at the highest concentration tested of 2.5 mM suggesting the lack of effects on the coagulation serine proteases and potentially the functional selectivity of EA with respect to the clotting process. Molecular modeling studies demonstrated that the Michael acceptor of EA forms a covalent bond with catalytic residue of Cys314 in the active site of FXIIIa. Conclusions Overall, our studies indicate that EA inhibits the physiological function of human FXIIIa in vitro which may potentially contribute to the bleeding complications that were reported with the association of the parenteral administration of EA.

Purpose: The aim of the present study was to establish the role of platelets and activated factor XIIIa (FXIIIa) in the structuring of the fibrin network as well as to clarify the effect of network compaction on clot lysis., Methods: Turbidimetry was used for the one-stage clotting test where platelet-free plasma (PFP) is regarded as single factor-deficient plasma (platelets as lacking factor) and autologous platelet-rich plasma (PRP) as deficiency corrected plasma. Structural features of the developed and subsequently lysed fibrin network, formed under static and flow conditions, were visualized by confocal microscopy., Results: Thrombin-initiated plasma clotting revealed changes in the shape of the absorption curve, more pronounced in the presence of platelets. These changes correlate with the transformation of the fibrin scaffold during clot maturing. With the combined action of platelets, thrombin and Ca2+, plasma clotting passes through two phases: initial formation of a platelet-fibrin network (first peak in the polymerization curve), and then the compaction of fibrin, driven by FXIIIa (the second peak) which can be further modulate by the contractile action of platelets. These structural changes, mediated by platelets and FXIIIa, have been shown to determine subsequent clot lysis., Conclusions: Platelet aggregates serve as organizing centers that determine the distribution of fibrin in clot volume. The openwork structure of the platelet-transformed fibrin provides the necessary prerequisites for its timely lysis. The revealed aspects of the interaction of platelets and FXIIIa, which accompanies the maturation of a fibrin clot, may lead to new approaches in the pharmacological correction of disorders associated with both thrombotic episodes and bleeding tendency., (© 2024 The Author(s).)

Background: Ethacrynic acid (EA) is a loop diuretic that is approved orally and parenterally to manage edema-associated diseases. Nevertheless, it was earlier reported that it is also associated with bleeding upon its parenteral administration. In this report, we investigated the effects of EA on human factor XIIIa (FXIIIa) of the coagulation process using a variety of techniques. Methods: A series of biochemical and computational methods have been used in this study. The potency and efficacy of human FXIIIa inhibition by EA was evaluated using a bisubstrate-based fluorescence trans-glutamination assay under near physiological conditions. To establish the physiological relevance of FXIIIa inhibition by EA, the effect on FXIIIa-mediated polymerization of fibrin(ogen) as well as the formation of fibrin(ogen) – α2-antiplasmin complex was evaluated using SDS-PAGE experiments. The selectivity profile of EA against other coagulation proteins was assessed by evaluating EA's effect on human clotting times in the activated partial thromboplastin time (APTT) and the prothrombin time (PT) assays. We also used molecular modeling studies to put forward a putative binding mode for EA in the active site of FXIIIa. Results involving EA were the average of at least three experiments and the standard error ± 1 was provided. In determining the inhibition parameters, we used non-linear regression analysis. Results: FXIIIa is a transglutaminase that works at the end of the coagulation process to form an insoluble, rigid, and cross-linked fibrin rich blood clot. In fact, inhibition of FXIIIa-mediated biological processes has been reported to result in a bleeding diathesis. Inhibition of FXIIIa by EA was investigated given the nucleophilic nature of the thiol-containing active site of the enzyme and the Michael acceptor-based electrophilicity of EA. In a bisubstrate-based fluorescence trans-glutamination assay, EA inhibited FXIIIa with a moderate potency (IC50 ~ 105 µM) and efficacy (∆Y ~ 66%). In SDS-PAGE experiments, EA appears to significantly inhibit the FXIIIa-mediated polymerization of fibrin(ogen) as well as the formation of fibrin(ogen) – α2-antiplasmin complex which indicates that EA affects the physiological functions of FXIIIa. Interestingly, EA did not affect the clotting times of human plasma in the APTT and the PT assays at the highest concentration tested of 2.5 mM suggesting the lack of effects on the coagulation serine proteases and potentially the functional selectivity of EA with respect to the clotting process. Molecular modeling studies demonstrated that the Michael acceptor of EA forms a covalent bond with catalytic residue of Cys314 in the active site of FXIIIa. Conclusions: Overall, our studies indicate that EA inhibits the physiological function of human FXIIIa in vitro which may potentially contribute to the bleeding complications that were reported with the association of the parenteral administration of EA. [ABSTRACT FROM AUTHOR]

Maximum clot firmness (MCF) is the main parameter of thromboelastography (TEG) reflecting the stability of a clot. In this work, we looked for markers that can influence the enhancement of MCF and detec­ted molecular markers and blood clotting parameters that can be involved in such mechanisms. Blood samples of pregnant women with placental disorders were collected in the Kyiv Perinatal Center. TEG was performed on whole blood in EXTEM and INTEM tests. APTT, INR, fibrinogen concentration and platelet aggregation were measured using traditional laboratory approaches. D-dimer was detected in sandwich ELISA using monoclonal antibodies III-3B and II-4D. The relative cross-linking activity of factor XIIIa was measured by the direct quantification of the cross-linked γ-chain of fibrin using Western-Blotting with monoclonal antibody II-4D. D-dimer and fibrinogen concentrations, clotting time in the APTT test, INR and rate of platelet aggregation did not correlate with the MCF. However, we found positive correlations of MCF with factor XIIIa activity: 0.51 and 0.87 for EXTEM and INTEM, respectively. These data indicate that for normal and slightly increased fibrinogen concentrations, fibrin clot firmness will depend mostly on the activity of factor XIIIa. Thus the direct determination of factor XIIIa activity in blood plasma of patients can be relevant for predicting the risk of intravascular coagulation. Evaluation of the content and activity of individual clotting factors or other components of the coagulation system can be useful additions to the TEG diagnostics and should not be neglected.

The ability to design artificial extracellular matrices as cell-instructive scaffolds has opened the door to technologies capable of studying the fate of cells in vitro and to guiding tissue repair in vivo. One main component of the design of artificial extracellular matrices is the incorporation of biochemical cues to guide cell phenotype and multicellular organization. The extracellular matrix (ECM) is composed of a heterogeneous mixture of proteins that present a variety of spatially discrete signals to residing cell populations. In contrast, most engineered ECMs do not mimic this heterogeneity. In recent years, photo-deprotection has been used to spatially immobilize signals. However, this approach has been limited mostly to small peptides. Here we combine photo-deprotection with enzymatic reaction to achieve spatially controlled immobilization of active bioactive signals that range from small molecules to large proteins. A peptide substrate for transglutaminase factor XIII (FXIIIa) was caged with a photo-deprotectable group, which was then immobilized to the bulk of a cell-compatible hydrogel. With focused light, the substrate can be deprotected and used to immobilize patterned bioactive signals. This approach offers an innovative strategy to immobilize delicate bioactive signals, such as growth factors, without loss of activity and enables in situ cell manipulation of encapsulated cells.

Background: Dermatophytosis has assumed epidemic proportions with rising resistance, recalcitrance and recurrence, especially in tropical regions. While various factors contribute to high prevalence worldwide, yet little is known about the interactions between host defence mechanisms and dermatophytes, particularly in chronic and recalcitrant dermatophytosis., Objectives: We aimed to compare the population of various immune cells in specimens of chronic recurrent dermatophytosis and those with acute superficial dermatophytosis., Methods: We investigated the density of various immune cells-Langerhans cells (CD1a+), macrophages (CD68+), dermal dendrocytes (Factor XIIIa+) in the skin of chronic dermatophytosis patients and those with successfully resolved lesions (controls)., Results: Langerhans cells were significantly decreased in the epidermis of patients, both in affected and unaffected areas in comparison with controls. In the dermis, however, no differences in the density of immune cells (macrophages and fibroblasts) were observed., Limitations: The limited sample size and immune cells evaluated could be expanded further in future research., Conclusion: These results indicate that the decreased number of Langerhans cells could be a potential risk factor for the development of chronic and recurrent dermatophytosis., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Introduction: The ever-growing number of COVID-19 patients stresses upon the need to identify effective yet readily available predictors of disease severity to ensure better clinical outcomes. D-dimer is a fibrin specific degradation product derived by enzymatic action of plasmin on factor XIIIa cross-linked fibrin. It serves as an ideal marker for activation of coagulation and fibrinolytic pathways. Identification of coagulopathy as an important complication in COVID-19 patients has brought to focus D-dimer as a possible predictor of clinical severity in patients. Aim: In this study, we analysed the role of D-dimer levels in assessing the clinical severity of the COVID-19 patients. Materials and Methods: We enrolled 217 in-patients of Tirunelveli Medical College in this single centre observational study and classified them into asymptomatic, mild, moderate and severe according to “Clinical Management Protocol: COVID 19”, by the Ministry of Health and Family Welfare and Director General of Health Services. D-dimer was estimated in the separated plasma, using latex based assay using semi-automated coagulation analyser. Data were presented as percentages for categorical variables and median±Inter Quartile Range (IQR) for continuous variables. Chi-square test was used to compare the D-dimer values between symptomatic and asymptomatic groups. A value of p

Introduction: The ever-growing number of COVID-19 patients stresses upon the need to identify effective yet readily available predictors of disease severity to ensure better clinical outcomes. D-dimer is a fibrin specific degradation product derived by enzymatic action of plasmin on factor XIIIa cross-linked fibrin. It serves as an ideal marker for activation of coagulation and fibrinolytic pathways. Identification of coagulopathy as an important complication in COVID-19 patients has brought to focus D-dimer as a possible predictor of clinical severity in patients. Aim: In this study, we analysed the role of D-dimer levels in assessing the clinical severity of the COVID-19 patients. Materials and Methods: We enrolled 217 in-patients of Tirunelveli Medical College in this single centre observational study and classified them into asymptomatic, mild, moderate and severe according to “Clinical Management Protocol: COVID 19”, by the Ministry of Health and Family Welfare and Director General of Health Services. D-dimer was estimated in the separated plasma, using latex based assay using semi-automated coagulation analyser. Data were presented as percentages for categorical variables and median±Inter Quartile Range (IQR) for continuous variables. Chi-square test was used to compare the D-dimer values between symptomatic and asymptomatic groups. A value of p<0.05 was considered statistically significant. Results: Among the 217 cases, 88.9% were asymptomatic cases, 8.8% presented with mild clinical severity and 2.3% had moderate clinical presentation. In our study population, the Mean±SD and Median±IQR of D-dimer values (in ng/mL) were 223.4±230.6 and 157.0±187.7, respectively. The mean D-dimer value was found to increase as the category of our study group ascended from asymptomatic patients to mild and moderate clinical cases. It was noted that 91.1% of the cases who had D-dimer values <500 ng/mL were asymptomatic. Also, the odds of patients with high levels of D-dimer being clinically symptomatic was 5.5 times more than the odds of patients with D-dimer levels <500 ng/mL. Conclusion: Elevation of D-dimer levels associated with the severity of clinical course of patients infected with SARS CoV-2 when compared to patients with mild or asymptomatic clinical presentations. [ABSTRACT FROM AUTHOR]

A biopsy diagnosis of conventional (common) type of benign fibrous histiocytoma (BFH) is usually easy. However, there are many other histopathologic variants, that may cause difficulties to make an accurate diagnosis. The author describes a 53-year old women, who presented with a protuberated ulcerated skin tumor arising on the left shoulder. It consisted of a highly cellular mass of proliferating spindle-shaped cells with a fascicular growth pattern, that was confined to dermis. The cells were relatively uniform with a slightly increased mitotic rate and proliferation activity. Immunohistochemically, the tumor expressed vimentin, Factor XIIIa and alpha-SMA, while it was negative for CK5/6, CK7, BerEP4, p63, EMA, S-100, melan A, HMB-45, MSA, h-caldesmon and CD34. A diagnosis of ulcerated cellular BFH was made. Although BFH is a very frequent cutaneous tumor, its less common cellular variant may result in diagnostic pitfalls. The purpose of this paper was to point out that even such „banal" and prognostically favourable cutaneous lesion sometimes requires a complex differential diagnostic approach in biopsy practice. [ABSTRACT FROM AUTHOR]

Transglutaminases are a class of enzymes that catalyze the formation of a protein:protein cross-link between a lysine and a glutamine residue. These cross-links play important roles in diverse biological processes. Analysis of cross-linking sites in target proteins is required to elucidate their molecular action on target protein function and the molecular specificity of different transglutaminase isozymes. Mass-spectrometry using settings designed for linear peptide analysis and software designed for the analysis of disulfide bridges and chemical cross-links have previously been employed to identify transglutaminase cross-linking sites in proteins. As no control peptide with which to assess and improve the mass spectrometric analysis of TG cross-linked proteins was available, we developed a method for the enzymatic synthesis of a well-defined transglutaminase cross-linked peptide pair that mimics a predicted tryptic digestion product of collagen I. We then used this model peptide to determine optimal score thresholds for correct peptide identification from y- and b-ion series of fragments produced by collision-induced dissociation. We employed these settings in an analysis of fibrinogen cross-linked by the transglutaminase Factor XIIIa. This approach resulted in identification of a novel cross-linked peptide in the gamma subunit. We discuss the difference in behavior of ions derived from different cross-linked peptide sequences and the consequent demand for a more tailored mass spectrometry approach for cross-linked peptide identification compared to that routinely used for linear peptide analysis.

Objectives: Interplay of Factor XIIIa (FXIIIa), a transglutaminase, responsible for cross-linking of matrix proteins, Matrix Metalloproteinase-9 (MMP-9), a gelatinase, and Vascular Endothelial Growth Factor (VEGF), an angiogenic inducer, were studied in relation to fibrogenesis and disease progression in oral submucous fibrosis (OSMF)., Material and Methods: Immunohistochemical expression of markers was studied in 60 formalin-fixed paraffin-embedded tissue blocks of OSMF and 20 normal oral mucosal tissues. FXIIIa was studied quantitatively while MMP-9 and VEGF were assessed semi-quantitatively. Expression was compared with histopathological grades of OSMF., Results: FXIIIa expression significantly increased in OSMF (p-value 0.000). However, expression decreased and cells became quiescent with increasing grades (p-value 0.000). MMP-9 (p-value epithelium 0.011, p-value connective tissue 0.000) and VEGF expression (p-value epithelium 0.000, connective tissue 0.000) increased in OSMF. A negative correlation between FXIIIa and MMP-9 (-0.653) in early grade (p-value of 0.021) and a positive correlation between FXIIIa and VEGF (0.595) (p-value of 0.032) was found in the moderate grade OSMF. Regression analysis showed a significant association (p<0.01) of FXIIIa in OSMF and with increasing grades of OSMF., Conclusion: FXIIIa may play a crucial role in initiation of fibrosis in OSMF. MMP-9 may have a diverse role to play in OSMF as a regulator of fibrosis. VEGF may show an angio-fibrotic switch and contribute to fibrosis in OSMF. These cytokines may show altered function and can contribute to fibrosis and chronicity of disease due to changes in the microenvironment. Tissue stiffness in OSMF itself creates an environment that enhances the chronicity of the disease., (Copyright © 2023 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Medallion‐like dermal dendrocyte hamartoma is a rare congenital lesion that is more commonly seen in females. It often presents at birth on the neck or upper trunk as a well‐circumscribed, atrophic patch with wrinkling of the overlying skin. Clinically, the differential diagnosis includes atrophoderma, anetoderma, and congenital atrophic dermatofibrosarcoma protuberans. Histologic findings show epidermal atrophy and dermal spindle cell proliferation that is CD34 positive, along with Factor XIIIa in the original reports. Due to this CD34 positivity, another name for the lesion is plaque‐like CD34+ dermal fibroma. We present a unique patient case as he is male and the lesion is located on his abdomen. Further reports and studies need to be done for thorough understanding of this neoplasm. [ABSTRACT FROM AUTHOR]

Juvenile xanthogranuloma (JXG) belongs to the group of non-Langerhans cell histiocytosis. JXG is typically factor XIIIa- and CD68-positive. Nonlipidized JXG (NJXG) is a rare, mononuclear variant of JXG that shows few or absence of foam cells or Touton giant cells in the histiocytic infiltrate. Herein, we describe an unusual case of NJXG in a 7-year-old boy presenting with a 1-month history of a flesh-colored nodule on the forehead. The lesion was factor XIIIa-positive and CD68-negative but CD163-positive. Our case illustrates that CD163, a more specific marker of macrophage and monocyte differentiation, is a valuable marker for the diagnosis of NJXG.

Cellular fibrous histiocytoma, a variant of fibrous histiocytoma, is a designation used for lesions showing increased cellularity with a fascicular growth pattern and frequent extension into the subcutis. Here we describe a case of cellular fibrous histiocytoma showing repeated recurrence in a 36-year-old woman who initially presented with a 2-cm cutaneous tumor on her right elbow. Histopathologically, the first resected specimen demonstrated irregularly arranged collagen fibers mixed with scattered proliferating plump to spindle-shaped fibrohistiocytes. However, examination of the resected specimens obtained after recurrence showed that the cellularity had increased, the spindle-shaped cells showing monomorphic proliferation with a fascicular and storiform growth pattern extending into the subcutis, as well as an increase of Ki-67 positivity. Since the lesion showed repeated relapse within a short period, we performed wide-field resection of the tumor with a 3-cm margin. Currently, 48 months after surgery, there has been no local recurrence or metastasis, but continuous strict follow-up will be necessary.

BACKGROUND: Pityriasis alba affects 1% of the world population and about 9.9% of the children in Brazil. However, its etiology remains uncertain. OBJECTIVE: The objective of the present study was to evaluate the immunoexpression of factor XIIIa in dermal dendrocytes of skin lesions of pityriasis alba. METHOD: Twenty patients with pityriasis alba and 20 patients with atopic dermatitis underwent biopsy. The dermal dendrocytes marked by factor XIIIa were counted by means of immunohistochemical analysis. RESULTS: The mean amount of dermal dendrocytes found in the patients with pityriasis alba was 2, whereas in the patients with atopic dermatitis it was 4, with a statistically significant difference between them. A cutoff point of 3 cells/square inch was established to differentiate pityriasis alba from atopic dermatitis, with 80% sensibility and 90% specificity. CONCLUSION: We believe that pityriasis alba and atopic dermatitis should be considered different clinical forms within the spectrum of atopic disease, in which sun radiation plays an important role by modulating the progression of the disease.

Dermatofibromas are most frequently encountered in women on the lower extremities, often after minor trauma. A recurrent lesion of the right lower eyelid developed in a 64-year-old woman. It harbored “monster cells” that were large, with either multiple nuclei or a single, large, convoluted, and hyperchromatic nucleus. The presence of these cells does not signify a malignant transformation. The background cells were either histiocytoid (many were adipophilin positive), spindled cells, or dendritiform cells without mitoses. Factor XIIIa, CD68, and CD163 immunostaining was positive, and a subpopulation of CD1a + Langerhans cells was intermixed. Facial and eyelid dermatofibromas are more likely to recur and deserve wider, tumor-free surgical margins. Their microscopic differential diagnosis includes a cellular scar, peripheral nerve tumor, atypical fibrous xanthoma, and dermatofibrosarcoma protuberans. [ABSTRACT FROM AUTHOR]

Calcifying fibrous tumor is a very rare benign mesenchymal tumor which shows a predilection for soft tissue, mesentery and peritoneum. Up to date only 7 cases have been reported in the literature confined to the gastric wall. We report a rare case of a calcifying fibrous tumor of the stomach in a 60-year-old man who presented with dyspepsia, flatulence and feeling weight. A clinical and laboratory investigation was performed with normal results. Gastroscopy revealed a bulge in the gastric body measuring 1 cm with normal overlying mucosa, and mucosal biopsies showed chronic gastritis. Endoscopic ultrasound of the gastric bulge showed a 1 × 0.8 cm hypoechoic lesion involving the gastric wall. After the above finding a wedge resection of the stomach was performed. Microscopically the lesion consisted of well-circumscribed hypocellular hyalinized fibrosclerotic tissue with lympoplasmatic infiltrates, lymphoid aggregates and psammomatous calcifications. Lesional cells were positive for vimentin and factor XIII and negative for actin, desmin, S100p, CD117, CD34, CD31 and ALK-1. The lesion involved the muscularis propria with variable submucosal extension. Calcifying fibrous tumor has shown an excellent prognosis with recurrences being rare and showing the same morphology as the primary lesion.

BACKGROUND: Few studies have evaluated the ultrastructure of the superficial skin nerves in urticaria. OBJECTIVE: The objective of this study was to describe findings in superficial skin nerves in cases of drug-induced acute urticaria. METHODS: Seven patients with drug-induced acute urticaria were included in the study. Skin biopsies were obtained from the urticarial lesion and from the apparently normal skin. The 14 fragments collected were processed for immunogold electron microscopy using single stains for antitryptase and anti-FXIIIa antibodies, as well as double immunogold labeling for both. RESULTS: Some sections showed mast cells in the process of degranulation. Following double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were found together throughout the granules in mast cells, indicating that tryptase and FXIIIa are located inside each one of the granules of these cells. Interestingly, we found strong evidence of the presence of tryptase and factor XIIIa in the superficial skin nerves of these patients, both in cases of urticarial lesions (wheals) and in the apparently normal skin. CONCLUSIONS: Tryptase and FXIIIa are present in the superficial nerves of the skin in drug-induced acute urticaria. This is the first report of tryptase and FXIIIa expression in the superficial skin nerves of patients with urticaria. Tryptase may be participating in neural activation in these patients, while FXIIIa may be present in the nerves to guarantee the functional integrity of structures.FUNDAMENTOS: Poucos autores têm estudado a ultraestrutura dos nervos superficiais na urticária. OBJETIVO: Descrever os achados nos nervos cutâneos superficiais em casos de urticária aguda induzida por medicamentos. MÉTODOS: Sete pacientes com urticária aguda induzida por medicamentos foram incluídos no estudo. Foram obtidas biopsias da pele da lesão urticariforme e da pele aparentemente normal. Os 14 fragmentos coletados foram processados usando imunomarcação com ouro para anticorpos anti-triptase e anti-FXIIIa separadamente, além da dupla imunomarcação com ambos anticorpos. A seguir as amostras foram submetidas à análise por microscopia imunoeletrônica. RESULTADOS: Alguns cortes demonstraram mastócitos em processo de degranulação. Após a imunomarcação dupla, partículas de ouro de 10 nm (FXIIIa) e partículas de ouro de 15 nm (Triptase) apresentavam-se juntas em grânulos de mastócitos indicando que a triptase e o FXIIIa se localizam dentro de cada um dos grânulos dessas células. Curiosamente, foi encontrada uma forte evidência da presença da triptase e do fator XIIIa nos nervos superficiais dos pacientes avaliados, tanto em lesões urticadas, como na pele aparentemente normal. CONCLUSÕES: A triptase e o FXIIIa estão presentes nos nervos superficiais da pele na urticária aguda medicamentosa. Este é o primeiro relato da expressão de triptase e de FXIIIa nos nervos superficiais na urticária. A triptase poderia estar participando da ativação neural nos pacientes estudados. O FXIIIa poderia estar presente nos nervos, com a finalidade de manter a integridade funcional dessas estruturas.

The aim of the present study was to compare quantitatively the distribution of dendritic cell subpopulations in chronic periodontitis and gingivitis. Fourteen biopsies from patients with chronic periodontitis and fifteen from patients with gingivitis were studied. An immunoperoxidase technique was used to quantify the number of Langerhans' cells (CD1a) and interstitial dendritic cells (factor XIIIa) in the oral and sulcular and junctional/pocket epithelia and in the lamina propria. A greater number of factor XIIIa+ dendritic cells in the lamina propria and CD1a+ dendritic cells in the oral epithelium were observed in gingivitis compared to the periodontitis group (p = 0.05). In the sulcular and junctional/pocket epithelia and in the lamina propria, the number of CD1a+ dendritic cells was similar in the gingivitis and periodontitis groups. In conclusion, the number of Langerhans' cells in the oral epithelium and interstitial dendritic cells in the lamina propria is increased in gingivitis compared to periodontitis, which may contribute to the different pattern of host response in these diseases.

Background: Leprosy is manifested in varied forms based on the immune status of the patient giving rise to the polar and borderline spectrum of tuberculoid (TT) and lepromatous leprosy (LL). The present study was conducted to assess the macrophage activation in the spectrum of leprosy using CD1a and Factor XIIIa immunohistochemical markers and to correlate the macrophage expression with the morphological spectrum and bacillary index., Methodology: The present study was an observational study., Results: The present study consisted of 40 biopsy-proven leprosy cases, in which a majority were males, and the most common age group was 20-40 years. The most common type encountered was borderline tuberculoid (BT) leprosy. Expression of epidermal dendritic cells and intensity of staining by CD1a was higher in TT (seven of 10 cases (70%)) when compared to LL (one of three cases (33%)). Similarly, Factor XIIIa showed higher expression of dermal dendritic cells in 90% of TT when compared to LL which was seen in 66%., Conclusion: The increased number and strong intensity of dendritic cells in the tuberculoid spectrum may indirectly indicate macrophage activation and possibly account for the low bacillary index., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, K et al.)

This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL ( n = 27), OL ( n = 20), and inflammatory fibrous hyperplasia ( n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.

FUNDAMENTOS: Leishmaniose tegumentar é doença parasitária infecciosa que apresenta aspectos imunológicos relevantes. OBJETIVO: Estudar a histopatologia e aspectos imuno-histoquímicos de 21 biópsias de leishmaniose tegumentar. MÉTODOS: Anticorpo policlonal anti-Leishmania foi utilizado para identificação das leishmânias. A classificação histopatológica adotada foi em grupos padrões de I a V. Foram analisados os dendrócitos dérmicos FXIIIa+, células de Langerhans CD1a+, macrófagos CD68+, linfócitos B CD20+ e T CD3+. As células FXIIIa+ foram quantificadas na derme papilar e comparadas a peles normais obtidas de área não exposta à luz solar, sendo o número de células FXIIIa+ avaliado estatisticamente através do teste de Mann-Whitney. As demais células foram contadas semiquantitativamente. RESULTADOS: Entre os grupos histopatológicos, predominaram os I e II. Não houve diferença estatisticamente significante (p=0,157) entre o número de células FXIIIa+ na leishmaniose e na pele normal. Não foi observada diferença si ificante entre a presença das células CD1a+, CD68+, CD20+ e CD3+, quando comparadas entre si ou com as células FXIIIa+. CONCLUSÃO: Não houve diferença no número de células dendríticas FXIIIa+ entre a leishmaniose e pele normal. No entanto, sugere-se que mais estudos sejam necessários para se entender o papel dessas células na leishmaniose.BACKGROUND: Mucocutaneous leishmaniasis is a parasitic infectious disease with relevant immunological aspects. OBJECTIVE: To study the histopathological and immunohistochemical aspects of 21 leishmaniasis tegumentary biopsies. METHODS: Polyclonal anti-Leishmania antibody was used to confirm the presence of Leishmania amastigotes. Histopathological classification comprised I-V standard groups. The immunopathological pattern was evaluated as to the presence of FXIIIa+ dermal dendrocytes, CD1a+ Langerhans cells, CD68+ macrophages, CD20+ B lymphocytes, and CD3+ T lymphocytes. The FXIIIa+ cells were quantified and compared to specimens of normal skin obtained from unexposed areas. The other cells were counted in a semi-quantitative way. The number of FXIIIa+ cells was statistically analyzed using the Mann-Whitney test. RESULTS: Among the histopathological groups, I and II standards prevailed. The FXIIIa+ cells were observed for different aspects and compared to normal skin, without significant statistical differences (p = 0.157). There was no relation between the amount of CD1a+, CD68+, CD20+ and CD3+ cells when compared to each other or to FXIIIa+ cells. CONCLUSION: There was no difference between the number of FXIIIa+ cells in leishmaniasis and in normal skin. However, more studies are needed in order to understand the role of FXIIIa+ cells in leishmaniasis.

Sebaceous carcinoma is a rare but serious malignancy that may be difficult to diagnose when poorly differentiated. Other epithelial tumors with clear cell change may mimic sebaceous carcinoma. Few useful or specific immunohistochemical markers for sebaceous differentiation are available. Nuclear staining with factor XIIIa (clone AC-1A1) was recently found to be a highly sensitive marker of sebaceous differentiation. We evaluated nuclear factor XIIIa (AC-1A1) staining in sebaceous neoplasms vs. other cutaneous clear cell tumors. We stained 27 sebaceous proliferations: sebaceous hyperplasia (7), sebaceous adenoma (8), sebaceoma (5), sebaceous carcinoma (7). We also stained 67 tumors with clear cell change: basal cell carcinoma (8), squamous cell carcinoma (8), hidradenoma (7), desmoplastic trichilemmoma (2), trichilemmoma (10), trichilemmal carcinoma (3), clear cell acanthoma (9), atypical fibroxanthoma (1), syringoma (8), trichoepithelioma (1), metastatic renal cell carcinoma (2), and nevi with balloon cell change (8). Nuclear factor XIIIa (AC-1A1) staining was present in 100% of sebaceous proliferations; 96% displayed strong staining. Non-sebaceous clear cell tumors were negative or only weakly positive with factor XIIIa (AC-1A1) in 95.5%; only 4.5% showed strong staining. This suggests that strong nuclear factor XIIIa (AC-1A1) staining is a sensitive and specific marker of sebaceous neoplasms vs. other clear cell tumors. [ABSTRACT FROM AUTHOR]