Macrophages CD163+ and Factor XIIIa+ Provide a First-Line Defence against Proliferative Verrucous Leukoplakia Antigens.

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.

Immunopathological characterization of human cutaneous leishmaniasis lesions caused by Leishmania (Viannia) spp. in Amazonian Brazil.

American cutaneous leishmaniasis (ACL) is a chronic infectious disease caused by different protozoan species of Leishmania, and it is endemic in both tropical and subtropical countries. Using immunohistochemistry, we investigate the density of CD68+, lysozyme+, CD1a+, factor XIIIa+, CD4+, CD8+, CD56+, interferon (IFN)-γ+, and inducible NO synthase (iNOS+) cells. These cells were analyzed from 22 biopsy samples obtained from the lesions of ACL patients, whose infection was caused by Leishmania (Viannia) spp. Histopathological analysis showed dense mononuclear inflammatory infiltration in the dermis, which was composed of lymphocytes, macrophages, plasma cells, and discrete tissue parasitism. Granulomatous reactions were also present in the majority of cases. The density of the activated macrophages was higher than that of inactivated macrophages in the lesions. The density of Langerhans cells (CD1a+) was lower than that of dermal dendrocytes (factor XIIIa+). The density of CD8+ T lymphocytes was higher than that of CD4+ T lymphocytes. The cellular density of these immunological markers in relation to the species of Leishmania demonstrated that L. (Viannia) sp. lesions had higher IFN-γ expression than that Leishmania (Viania) braziliensis lesions. The evaluation of these markers, according to disease progression, did not reveal any significant differences. L. (Viannia) sp. infection leads to a favorable immune response in the host, as predominantly represented by lysozyme+, factor XIIIa+, CD8+ T cells, and the expression of (IFN)-γ+ at the lesion site.

Association between the Val34Leu polymorphism in blood coagulation factor XIII-A and intracerebral hemorrhage: a meta-analysis.

Although the Val34Leu polymorphism in blood coagulation factor XIII-A (FXIII-A) has been implicated in the pathogenesis of intracerebral hemorrhage (ICH), the results of research conducted thus far have been inconclusive. In this meta-analysis, we have assessed the association between the FXIII-A Val34Leu polymorphism and ICH risk. Published reports pertaining to this association were retrieved from the PubMed database, and the data from these studies were pooled and statistically analyzed with Stata 12.0. Summary odds ratios (OR) and 95% confidence intervals (95%CI) were calculated according to a fixed-effect or a random-effect model (as appropriate). The initial search identified 520 articles, only seven of which (retrospective studies) met the inclusion criteria and were included in this meta-analysis. These studies comprised 727 ICH patients and 1968 controls. The results of a combined analysis showed no significant association between the FXIII-A Val34Leu polymorphism and ICH risk in the overall population (Leu/Leu vs Val/Val: OR = 1.41, 95%CI = 0.82-2.43; Val/Leu vs Val/Val: OR = 1.08, 95%CI = 0.89-1.30; dominant model: OR = 1.14, 95%CI = 0.95-1.36; recessive model: OR = 0.72, 95%CI = 0.43-1.22). The results of this meta-analysis suggest that the FXIII-A Val34Leu polymorphism is not associated with ICH risk in a Caucasian population. Further large and well-designed studies must be conducted to confirm this preliminary conclusion.

Langerhans cells (CD1a and CD207), dermal dendrocytes (FXIIIa) and plasmacytoid dendritic cells (CD123) in skin lesions of leprosy patients.

The clinical course of infection with Mycobacterium leprae varies widely and depends on the pattern of the host immune response. Dendritic cells play an important role in the activation of the innate and adaptive immune system and seem to be essential for the development of the disease. To analyze the presence of epidermal dendritic cells (CD1a and CD207), plasmacytoid dendritic cells (CD123) and dermal dendrocytes (factor XIIIa) in lesion fragments of leprosy patients, skin samples from 30 patients were studied. These samples were submitted to immunohistochemistry against CD1a, CD207, FXIIIa, and CD123. The results showed a larger number of Langerhans cells, detected with the CD1a or CD207 marker, dermal dendrocytes and plasmacytoid dendritic cells in patients with the tuberculoid form. A positive correlation was observed between the Langerhans cell markers CD1a and CD207 in both the tuberculoid and lepromatous forms, and between Langerhans cells and dermal dendrocytes in samples with the tuberculoid form. The present results indicate the existence of a larger number of dendritic cells in patients at the resistant pole of the disease (tuberculoid) and suggest that the different dendritic cells studied play a role, favoring an efficient immune response against infection with M. leprae.

Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions.

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.

Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions

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. .

Relationship between chemokines and dendritic cells in human chronic periodontitis.

BACKGROUND: The purpose of this study was to evaluate the relationship between chemokines and dendritic cells (DCs) in human chronic periodontitis (CP). METHODS: Gingival samples were obtained from 23 individuals with CP, and six samples of normal mucosa (NM) overlapping the third molar were used to control for the chemokine levels. Periodontal examination was conducted. Immunohistochemistry was performed for Factor XIIIa(+) and cluster of differentiation (CD)1a(+) immature DCs and CD83(+) mature DCs. Levels of the CC chemokine ligand (CCL)2, CCL3, CCL5, CCL19, CCL20, and CXC chemokine ligand (CXCL)8 were measured in gingival tissues using enzyme-linked immunosorbent assay. Inflammatory infiltrate, DCs, chemokines, classification of human CP, and clinical parameters were correlated and compared. RESULTS: The expression of CCL2 and CCL20 was positively correlated with increased densities of CD1a(+) DCs. CCL3 and CXCL8 were positively related to the clinical attachment level. CCL3, CCL5, CCL19, and CXCL8 levels increased in the gingival samples of patients with CP compared with NM, whereas CCL20 levels increased in advanced CP compared with mild-moderate CP. CONCLUSIONS: More CD1a(+) immature DCs are related to CCL2 and CCL20. CCL3 and CXCL8 chemokines are related to a greater severity of human CP.

Interferon-γ, interleukins-6 and -4, and factor XIII-A as indirect markers of the classical and alternative macrophage activation pathways in chronic periodontitis.

BACKGROUND: Macrophages account for 5% to 30% of the inflammatory infiltrate in periodontitis and are activated by the classic and alternative pathways. These pathways are identified by indirect markers, among which interferon (IFN)-γ and interleukin-6 (IL)-6 of the classic pathway and IL-4 of the alternative pathway have been studied widely. Recently, factor XIII-A (FXIII-A) was reported to be a good marker of alternative pathway activation. The aim of this study is to determine the macrophage activation pathways involved in chronic periodontitis (CP) by the detection of the indirect markers IFN-γ, IL-6, FXIII-A, and IL-4. METHODS: Biopsies were taken from patients with CP (n = 10) and healthy individuals (n = 10) for analysis of IFN-γ, IL-6, IL-4, and FXIII-A by Western blot (WB), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). The same biopsies of healthy and diseased gingival tissue were used, and the expressions of these markers were compared between healthy individuals and those with CP. RESULTS: The presence of macrophages was detected by CD68+ immunohistochemistry and their IFN-γ, IL-6, IL-4, and FXIII-A markers by WB, IHC, and ELISA in all samples of healthy and diseased tissue. IL-6, IL-4, and FXIII-A were significantly higher in patients with CP, whereas FXIII-A was higher in healthy individuals. CONCLUSION: The presence of IFN-γ, IL-6, IL-4, and FXIII-A in healthy individuals and in patients with CP suggests that macrophages may be activated by both classic and alternative pathways in health and in periodontal disease.

Decreased CD1a(+) , CD83(+) and factor XIIIa(+) dendritic cells in cervical lymph nodes and palatine tonsils of AIDS patients.

AIMS: The purpose of this study was to quantify and compare the density of dendritic cells (DCs) in cervical lymph nodes (LNs) and palatine tonsils (PTs) of AIDS and non-AIDS patients. METHODS AND RESULTS: Factor XIIIa, CD1a and CD83 antibodies were used to identify migratory DCs by immunohistochemistry in LNs and PTs of 32 AIDS patients and 21 HIV-negative control patients. Quantification was performed by the positive pixel count analytical method. AIDS patients presented a lower density of factor XIIIa(+) cells (P < 0.001), CD1a(+) cells (P < 0.05) and CD83(+) cells (P < 0.001) in cervical LNs and PTs compared to the non-AIDS control group. CONCLUSION: Overall depletion of DCs in lymphoid tissues of AIDS patients may be predictive of the immune system's loss of disease control.

Ultrastructure of vascular permeability in urticaria.

BACKGROUND: Few studies have addressed the ultrastructure of vascular permeability in urticaria. OBJECTIVES: To describe the types of endothelial cell organelles involved in vascular permeability in drug-induced acute urticaria (DIAU). METHODS: Seven patients with DIAU were enrolled in the study. Biopsies of urticarial lesions and apparently normal skin were performed. The 14 collected fragmentswere processed with immunogold electron microscopy using single stains for tryptase and factor XIIIa (FXIIIa) and double immunogold labeling for both tryptase and FXIIIa. RESULTS: Some sections demonstrated mast cells in the degranulation process, in both anaphylactic and piecemeal degranulation. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (tryptase) gold particles wereboth present, covering the granules in the mast cells, indicating that both tryptase and FXIIIa were localized within the granules of these cells. Interestingly, we found strong evidence of the presence of caveolae and vesico-vacuolar organelles (VVOs) in the endothelial cells of the biopsies. In addition to these findings, we were able to demonstrate the presence of tryptase and FXIIIa in the endothelial celIs, in urticarial lesions and in apparently normal skin. CONCLUSIONS: VVOs are present in the endothelial cells of post-capillary venules in DIAU. This is the first report on the expression of FXIIIa and tryptase in the cytoplasm of endothelial cells in urticaria.

Comparison of the distribution of dendritic cells in peri-implant mucosa and healthy gingiva.

PURPOSE: The host response to infection differs between peri-implantitis and periodontitis, but the mechanisms underlying these differences are not understood. In this study, the distribution of dendritic cell subpopulations in healthy peri-implant mucosa (HPIM) was compared to that of healthy gingiva (HG). MATERIALS AND METHODS: HPIM and HG specimens were obtained from nonsmoking, systemically healthy subjects. Immunohistochemistry was used to quantify the number of Langerhans cells (LCs) (CD1a+) and interstitial dendritic cells (IDCs) (factor XIIIa+) in the oral epithelium, sulcular/junctional epithelia, and lamina propria without inflammatory infiltration and with inflammatory infiltration. RESULTS: Fourteen HPIM and 13 HG specimens were obtained from subjects aged 29 to 55 years. The lamina propria of the HPIM had fewer LCs than that of the HG (HPIM: 7.99 ± 10.76, HG: 25.68 ± 16.98; P = .003). There was no significant difference in the number of CD1a+ cells in the oral epithelium or the sulcular/junctional epithelia between the HPIM and the HG (P ≥ .23). A greater number of IDCs was observed in the lamina propria with inflammatory infiltration of the HPIM compared to the HG (HPIM: 57.02 ± 35.70, HG: 33.89 ± 26.98; P = .06). CONCLUSIONS: In the lamina propria of HPIM, fewer LCs and more IDCs were observed. These differences may be associated with reduced stimulation of the innate and acquired immune responses initiated by LCs and the greater matrix remodeling of peri-implant tissue associated with IDCs.

Dermal dendritic cell population and blood vessels are diminished in the skin of systemic sclerosis patients: relationship with fibrosis degree and disease duration.

Recent studies have suggested that the number of dermal dendritic cells is altered in the skin of patients with scleroderma and that these cells may have an important role in the pathogenesis of this disease. There is also a belief that insufficient blood flow to the affected organs may also be responsible for the disease. Our aim was to quantify CD34+ cells, factor XIIIa cells, and blood vessels in the skin of patients with systemic sclerosis and to correlate these data with fibrosis degree and duration of disease. Paraffin-embedded skin sections from patients with systemic sclerosis and from healthy subjects were immunolabelled with antibodies against CD34+ and factor XIIIa. Cells and blood vessels were quantified in the papillary and reticular dermis. Both, the number of CD34+ cells and factor XIIIa cells in the skin of patients with systemic sclerosis were reduced. The reduction of these cell types preceded the appearance of intense fibrosis, suggesting that fibrosis is not responsible of this phenomenon. Blood vessel volume and surface density were also reduced in the skin of systemic sclerosis patients. This reduction was also noted early in the evolution of the disease. Our results suggest that CD34+ cells and factor XIIIa cells may contribute to normal regulation of extracellular matrix assembly. We confirmed the observation that capillary density is diminished in scleroderma skin.

Dermal dendrocytes FXIIIA+ phagocytizing extruded mast cell granules in drug-induced acute urticaria.

BACKGROUND: Few authors have been attempting between mast cells and dermal dendrocytes interactions on urticaria. OBJECTIVE: To describe the extruded mast cell granules and dermal dendrocytes in drug-induced acute urticaria. METHODS: Seven patients with drug-induced acute urticaria were enrolled in the study. We token skin biopsies of urticaria lesion and perilesional skin. The 14 fragments collected were processed to immunogold electron microscopy using single stains to tryptase and FXIIIa, besides double immunogold labeling with both. RESULTS: Some sections demonstrated mast cells in degranulation process, both in anaphylactic and piecemeal degranulation types. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were present together over the granules in mast cells indicating that tryptase and FXIIIa are each localized within the granules of these cells. Interestingly, we found a strong evidence of than the exocytosed mast cell granules contents both FXIIIa and tryptase immunolabeled are phagocytized by dermal dendrocytes. CONCLUSIONS: The current observations provide morphological evidence that the exocytosis-phagocytosis mechanisms of mast cell granules represents one pathophysiological example of mast cells-dermal dendrocytes interactions in urticaria.

Presencia de marcadores de las vías de activación de los macrófagos en periodontitis crónica / Presence of markers of activation pathways of macrophages in chronic periodontitis

La periodontitis crónica es una patología infecciosa, causada por un complejo de especies bacterianas, que afecta principalmente los tejidos de inserción de los dientes. La respuesta inmune-inflamatoria producida se caracteriza por la presencia de un infiltrado inflamatorio, en el cual los macrófagos representan entre 5 al 30 por ciento. Es sabido que los macrófagos se activan mediante dos vías: Clásica y Alterna, caracterizadas por la presencia de marcadores indirectos: IFN-y e IL-6 para la vía clásica e IL-4 para la vía alterna, ampliamente abordados. Recientemente, se ha descrito a la subunidad A del factor XIII de la coagulación (FXIII-A) como un buen marcador de la vía alterna. El objetivo de este estudio consiste en determinar la presencia de IFN-y, IL-6, FXIII-A e IL-4 como marcadores de las vías de activación de los macrófagos, en pacientes con periodontitis crónica. Para tal efecto, se realizó inmunohistoquímica y Western-Blot para los cuatro marcadores junto a CD-68, marcador de macrófagos, en 18 biopsias de tejido periodontal sano y 18 con periodontitis crónica. Se detectó la presencia de IFN-y, IL-6, IL-4 y FXIII-A junto a CD68+, en todas las muestras de pacientes sanos y con periodontitis. Los resultados obtenidos sugieren que al estar presente IFN-y, IL-6, IL-4 y FXIII-A, los macrófagos se activarían a través de ambas vías, lo cual, produciría una respuesta tanto proinflamatoria (Th1) como antinflamatoria (Th2). Son necesarios más estudios para determinar si existe una vía preferencial de activación.

Periodontitis is a chronic infectious disease caused by a bacterial species complex, which affects mainly the insertion tissues of the teeth. The immune-inflammatory response produced is characterized by an inflammatory infiltrate in which macrophages represent between 5 to 30 percent. It is known and has been widely discussed that macrophages are activated in two ways: Classical and Alterna, characterized by the presence of indirect markers: IFN-y and IL-6 for the classical pathway and IL-4 for the alternative pathway. Recently the subunit A of the clotting factor XIII (FXIII-A) has been described as a good marker of the alternative pathway. The objective of this study is to determine the presence of IFN-y, IL-6, IL-4 and FXIII-A as markers of the macrophage activation pathways in patients with chronic periodontitis. To this end, we performed immunohistochemistry and Western blot for the four markers with CD68 macrophage marker, in 18 healthy periodontal tissue biopsies and 18 with chronic periodontitis. We detected the presence of IFN-y, IL-6, IL-4 and FXIII-A with CD68 +, in all samples of healthy patients and periodontitis. The results suggest that when present, IFN-y, IL-6, IL-4 and FXIII-A, activate macrophages through both routes, which would produce a proinflammatory response (Th1) as antiinflammatory (Th2). Further studies are necessary to determine whether there is a preferential pathway activation.

Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria.

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.

Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria / Estudo de microscopia imunoeletrônica dos nervos superficiais da pele na urticária aguda induzida por medicamentos

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.

Efecto del polimorfísmo factor XIII VAL34LEU sobre terapia trombólitica en pacientes con infarto agudo del miocardio con elevación del ST / Effect of factor XIII VAL34LEU polymorphism on thrombolytic therapy in patients with acute ST elevation myocardial infarction

Dos polimorfismos pueden tener un importante papel protector contra el infarto de miocardio, debido a que se asocian a una notable disminución de los niveles plasmáticos del factor VII y de la propensión a la trombosis. Objetivo: 1-. Determinar la presencia del polimorfismo Val34leu del Factor XIII en pacientes con infarto del miocardio que ingresan a la unidad de cuidados coronarios (UCC) del HMPC y reciben terapia trombolítica; 2-. Contrastar el efecto de la terapia trombolítica en pacientes con presencia de la mutación y aquellos que no la presentan. Métodos: Se realizó un estudio de campo, descriptivo y correlacional, desde mayo a septiembre del 2007, en la unidad de cuidados coronarios del HMPC-Caracas. La población fue seleccionada mediante criterios de AHA: SCA con elevación del ST, susceptibles a recibir terapia trombolítica. La muestra definitiva, quedo conformada por 30 pacientes. La eficacia de la fibrinólisis fue evaluada por criterios clínicos, electro cardiográfico y enzimático. Una disminución del ST mayor de 50 % a los 90 min y una elevación temprana de las enzimas cardiacas antes de las 12 h fueron considerados criterios de reperfusión. El ADN genómico fue evaluado mediante reacción en cadena de polimerasa. Resultados: El polimorfismo se presento en 39 % de los pacientes estudiados. Se demostró la asociación entre polimorfismo y niveles de fibrinógeno. Conclusiones: Los valores de fibrinógeno estaban disminuidos en la población con polimorfismo en comparación con la que no lo presentaba. La respuesta terapéutica a la terapia trombolítica se relaciono con el fibrinógeno(AU)

Two polymorphisms may have an important protective role against myocardial infarction, because it is associated with a significant decrease in plasma levels of factor VII and the propensity to thrombosis. Objective: 1 -. To determine the presence of Factor XIII Val34Leu polymorphism in patients with myocardial infarction admitted to coronary care unit (CCU) of the HMPC and receives thrombolytic therapy, 2 -. To compare the effect of thrombolytic therapy in patients with presence of the mutation and those without. Methods: We conducted a field study, descriptive, correlation, from May to September 2007 in the coronary care unit of HMPC-Caracas. The population was selected by AHA criteria: ST elevation ACS, likely to receive thrombolytic therapy. The final sample was composed of 30 patients. The effectiveness of fibrinolysis was assessed by clinical, electro cardiograph and enzyme. ST A decrease greater than 50% at 90 min and an early elevation of cardiac enzymes before 12 h reperfusion criteria were considered. DNA was assessed by polymerase chain reaction. Results: The polymorphism was present in 39% of the patients studied. Demonstrated the association between polymorphism and fibrinogen levels. Conclusions: Fibrinogen levels were decreased in the population with polymorphism in comparison with which it had not. The therapeutic response to thrombolytic therapy was associated with fibrinogen(AU)

Performance of two commercial ELISAs for detecting IgA anti-human and anti-guinea pig tissue transglutaminase antibodies.

BACKGROUND: Sensitivity and specificity of anti-human tissue transglutaminase antibodies (anti-htTGA) seem to be superior to those of anti-tissue transglutaminase of guinea pig (anti-gptTGA) for screening patients with celiac disease (CD), but there are still controversies. The aim of this study was to evaluate the performance of two INOVA ELISA kits to detect IgA anti-htTGA and anti-gptTGA in patients with and without CD. METHODS: The study groups were comprised of 49 anti-endomysial antibody (EMA)-positive untreated-CD, and 123 controls (EMA-negative treated CD, EMA-negative chronic diarrhea, autoimmune hepatitis, inflammatory bowel disease and healthy people). RESULTS: The agreement between the two ELISAs was statistically significant in all study groups and there was no significant difference between them (92.7% agreement; kappa = 0.70; kappa p = 0.001; McNemar p = 1). All patients with serum reactivity of more than 100 units had histologic diagnosis of CD. In seven of 10 patients with treated-CD who had control biopsies, villous atrophy was still present in four who tested positive by both kits. Two of three celiacs with histologic remission tested positive for both anti-tTGA. CONCLUSIONS: the anti-gptTGA and anti-htTGA determination were equally efficient in identifying patients with untreated-CD with high titers of EMA. Whatever the anti-tTGA ELISA used, the reactivity above 100 units was always related to active CD diagnosed by histologic alterations in intestinal biopsies. The anti-tTGA reactivity by both kits was not only similar in determining histologic activity in the follow-up of CD after a gluten free diet, but also in identifying positive sera from the control groups, regardless if CD has been confirmed by duodenal biopsies.

Factor XIIIa+ dermal dendrocyte parasitism in American tegumentary leishmaniasis skin lesions.

Dendritic cells belong to a family of antigen-presenting cells that are localized at the entry sites, such as skin and mucosa. Dendritic cells are related to immune surveillance function. The role of Langerhans cells in the pathogenesis of skin infectious diseases is well studied; however, there are few articles addressing involvement of factor XIIIa-positive dermal dendrocytes (FXIIIa+ DD) in such processes. FXIIIa+ DDs are bone marrow-monocytic lineage-derived cells and members of the skin immune system. Due to their immune phenotype and functional characteristics, they are considered complementary cells to Langerhans cells in the process of antigen presentation and inducing immune response. To verify the interaction between FXIIIa+ DD and Leishmania amastigotes, 22 biopsies of American tegumentary leishmaniasis (ATL) skin lesions were subjected to double staining technique with anti-factor XIIIa and anti-Leishmania antibodies. FXIIIa+ DDs were hypertrophic and abundant in the cutaneous reaction of ATL. FXIIIa+ DDs harboring parasites were observed in 11 of 22 skin biopsies. The data obtained suggest that FXIIIa+ DD plays a role in the pathogenesis of ATL skin lesion as host cell, immune effector, and/or antigen-presenting cell.

CD1a and factor XIIIa immunohistochemistry in leprosy: a possible role of dendritic cells in the pathogenesis of Mycobacterium leprae infection.

Leprosy is a curable chronic granulomatous infectious disease caused by the bacillus Mycobacterium leprae. This organism has a high affinity for skin and peripheral nerve cells. In the evolution of infections, the immune status of patients determines the disease expression. Dendritic cells are antigen-presenting cells that phagocytose particles and microorganisms. In skin, dendritic cells are represented by epidermal Langerhans cells and dermal dendrocytes, which can be identified by expression of CD1a and factor XIIIa (FXIIIa). In the present study, 29 skin samples from patients with tuberculoid (13 biopsies) and lepromatous (16 biopsies) leprosy were analyzed by immunohistochemistry using antibodies to CD1a and FXIIIa. Quantitative analysis of labeling pattern showed a clear predominance of dendritic cells in tuberculoid leprosy. Difference between the number of positive cells of immunohistochemistry for the CD1a and FXIIIa staining observed in this study indicates a role for dendritic cells in the cutaneous response to leprosy. Dendritic cells may be a determinant of the course and clinical expression of the disease.