Unveiling the Enigma: Exploring capsular contracture-Unraveling its link with autoimmune disorders and comprehensive examination of predisposing factors.

Introduction: Breast augmentation, a popular cosmetic surgery using devices like silicone implants, can lead to a common issue called capsular contracture (CC). This condition involves the formation of fibrous tissue around the implants and can be influenced by variables like immunological and bacterial factors. This study aimed to explore the impact of autoimmune diseases (ADs) on CC along with other factors influencing future clinical decisions. Methods: A systematic review of electronic databases was conducted using PubMed, Web of Science, Scopus, EMBASE, and involving adult patients (>18) with CC and ADs after breast surgery using MeSH terminology using a broad search strategy. All searches were performed and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and duplicates were removed with Rayyan. Two independent investigators extracted and assessed the data involving demographics and baseline data related to CC and AD. Results: The incidence of CC varied (2.3%-4.1%). Subglandular placement and older device age raised risk. SERI Surgical Scaffold complications included necrosis, seroma, hematoma, implant loss, and infection; CC was associated with necrosis. Natrelle 410 implants showed lower 10-year CC risk than round gel implants. Acellular dermal matrix implant-based breast reconstruction with radiotherapy (RT) correlated with 20.7% post-RT CC. Previous research demonstrated no significant connection between silicone gel implants and ADs. Biofilm, surgical site infection, implant features, and interventions emerged as frequent CC risk factors. Conclusion: Finding appropriate techniques to reduce the risk factors associated with CC together with providing comprehensive patient counseling on these factors will definitely improve the patient-centered outcome of breast implant surgery.

Prostaglandin E2/leukotriene B4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection.

BACKGROUND: Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. METHODS: C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. RESULTS: Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E2 (PGE2), but reduced leukotriene B4 (LTB4) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE2 production is associated with diminished parasite killing. CONCLUSIONS: These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE2/LTB4 axis, which may represent an important mechanism on establishment of the infection.

Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils.

Neutrophils are considered the host's first line of defense against infections and have been implicated in the immunopathogenesis of Leishmaniasis. Leishmania parasites are inoculated alongside vectors' saliva, which is a rich source of pharmacologically active substances that interfere with host immune response. In the present study, we tested the hypothesis that salivary components from Lutzomyia longipalpis, an important vector of visceral Leishmaniasis, enhance neutrophil apoptosis. Murine inflammatory peritoneal neutrophils cultured in the presence of SGS presented increased surface expression of FasL and underwent caspase-dependent and FasL-mediated apoptosis. This proapoptosis effect of SGS on neutrophils was abrogated by pretreatment with protease as well as preincubation with antisaliva antibodies. Furthermore, in the presence of Leishmania chagasi, SGS also increased apoptosis on neutrophils and increased PGE(2) release and decreased ROS production by neutrophils, while enhancing parasite viability inside these cells. The increased parasite burden was abrogated by treatment with z-VAD, a pan caspase inhibitor, and NS-398, a COX-2 inhibitor. In the presence of SGS, Leishmania-infected neutrophils produced higher levels of MCP-1 and attracted a high number of macrophages by chemotaxis in vitro assays. Both of these events were abrogated by pretreatment of neutrophils with bindarit, an inhibitor of CCL2/MCP-1 expression. Taken together, our data support the hypothesis that vector salivary proteins trigger caspase-dependent and FasL-mediated apoptosis, thereby favoring Leishmania survival inside neutrophils, which may represent an important mechanism for the establishment of Leishmania infection.

Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E2 production in murine macrophages.

BACKGROUND: Sand fly saliva contains molecules that modify the host's hemostasis and immune responses. Nevertheless, the role played by this saliva in the induction of key elements of inflammatory responses, such as lipid bodies (LB, also known as lipid droplets) and eicosanoids, has been poorly investigated. LBs are cytoplasmic organelles involved in arachidonic acid metabolism that form eicosanoids in response to inflammatory stimuli. In this study, we assessed the role of salivary gland sonicate (SGS) from Lutzomyia (L.) longipalpis, a Leishmania infantum chagasi vector, in the induction of LBs and eicosanoid production by macrophages in vitro and ex vivo. METHODOLOGY/PRINCIPAL FINDINGS: Different doses of L. longipalpis SGS were injected into peritoneal cavities of C57BL/6 mice. SGS induced increased macrophage and neutrophil recruitment into the peritoneal cavity at different time points. Sand fly saliva enhanced PGE2 and LTB4 production by harvested peritoneal leukocytes after ex vivo stimulation with a calcium ionophore. At three and six hours post-injection, L. longipalpis SGS induced more intense LB staining in macrophages, but not in neutrophils, compared with mice injected with saline. Moreover, macrophages harvested by peritoneal lavage and stimulated with SGS in vitro presented a dose- and time-dependent increase in LB numbers, which was correlated with increased PGE2 production. Furthermore, COX-2 and PGE-synthase co-localized within the LBs induced by L. longipalpis saliva. PGE2 production by macrophages induced by SGS was abrogated by treatment with NS-398, a COX-2 inhibitor. Strikingly, SGS triggered ERK-1/2 and PKC-α phosphorylation, and blockage of the ERK-1/2 and PKC-α pathways inhibited the SGS effect on PGE2 production by macrophages. CONCLUSION: In sum, our results show that L. longipalpis saliva induces lipid body formation and PGE2 production by macrophages ex vivo and in vitro via the ERK-1/2 and PKC-α signaling pathways. This study provides new insights regarding the pharmacological mechanisms whereby L. longipalpis saliva influences the early steps of the host's inflammatory response.

O desenvolvimento de Leishmania (Viannia) braziliensis no flebotomíneo Lutzomyia (Nyssomyia) intermedia e a influência da alimentação sanguínea em animais domésticos / The development of Leishmania (Viannia) braziliensis in the sand flies Lutzomyia (Nyssomyia) intermedia and the influence of the sanguineous feeding in domestic animals

Este estudo teve como objetivo entender a interação entre a Leishmania (V.) braziliensis e seu vetor Lutzomyia (N.) intermedia, ambos provenientes de uma área endêmica para Leishmaniose Tegumentar Americana (LTA), e também analisar a influência da alimentação e realimentação com sangue de animais domésticos. Flebotomíneos foram capturados e submetidos à infecção artificial com amastigotas de L. braziliensis e demonstrou-se o padrão de desenvolvimento do parasito em L. intermedia. Após cada alimentação artificial, os intestinos médios dos insetos foram analisados para observar a presença, localização, morfologia e densidade dos parasitos. Numa primeira etapa, flebotomíneos foram submetidos a uma alimentação com sangue de camundongo e amastigotas de L. braziliensis. Após diferentes dias de infecção, o intestino médio de cada flebotomíneo foi dissecado e observou-se que houve uma queda da infecção de 86,5 (por cento) no 1º dia para 42,9 (por cento) no 10º dia após alimentação sangüínea. Na etapa seguinte, foram feitas infecções usando sangue de diferentes animais (homem, boi, carneiro, porco, galinha, camundongo, cão, jegue e cavalo) Observou-se que no 5º dia 100 (por cento) dos flebotomíneos submetidos a alimentação com sangue de boi estavam infectados. Porém, quando utilizamos sangue de jegue, este número caiu para 33,3 (por cento). Na última etapa, foram feitas alimentações infectivas seguidas de realimentações para observar a influência do segundo repasto sanguíneo no desenvolvimento da L. braziliensis no vetor. Primeiramente, os flebotomíneos foram alimentados com sangue de camundongo e amastigotas e, em seguida, realimentados no 4º dia com sangue de diferentes animais domésticos saudáveis. O intestino médio de cada flebotomíneo foi dissecado no 7º dia e observou-se um aumento no número de parasitos dentro flebotomíneo. Quanto à posição ocupada pelos parasitos dentro de seu vetor, foi constatada a preferência da L. braziliensis pela região pilórica em todos...

O desenvolvimento de Leishmania (Viannia) braziliensis no flebotomíneo Lutzomyia (Nyssomyia) intermedia e a influência da alimentação sanguínea em animais domésticos

Este estudo teve como objetivo entender a interação entre Leishmania (V.) braziliensis e seu vetor Lutzomyia (N.) intermedia, ambos provenientes de uma área endêmica para Leishmaniose Tegumentar Americana (LTA), e também analisar a influência da alimentação e realimentação com sangue de animais domésticos. Flebotomíneos forma capturados e submetidos à infecção artificial com amastigotas de L. braziliensis e demonstrou-se o padrão de desenvolvimento do parasito em L. intermedia. Após cada alimentação artificial, o intestino médio dos insetos foram analisados para observar a presença, localização, morfologia e densidade dos parasitos. Numa primeira etapa, flebotomíneos foram submetidos a uma alimetação com sangue de camundongo o amastigotas de L. braziliensis. Após diferentes dias de infecção com sangue, o intestino médio de cada flebotomíneo foi dissecado e observou-se que houve uma queda da infecção de 86,5 porcento no primeiro dia para 42,9 porcento no décimo dia após alimentação sangüínea

Na etapa seguinte, foram feitas infecções usando sangue de diferentes animais (homem, boi, carneiro, porco, galinha, camundongo, cão, jeugue e cavalo). Observou-se que no quinto dia 100 porcento dos flebotomíneos utilizados submetidos a alimentação com sangue de boi estavam infectados. Porém, quando utilizamos sangue de jegue, este número caio para 33,3 porcento. Na última etapa, foram feitas alimentações infectivas seguidas de realimentações para observar a influência do segundo repasto sanguíneo no desenvolvimento da L. braziliensis no vetor. Primeiramente, os realimentados no quarto dia com sangue de diferentes animais domésticos saudáveis. Ointestino médio de cada flebotomíneo foi dissecado no sétimo dia e obdervou-se um aumento no número de parasitos dentro flebetomíneo. Quanto à posição ocupada pelos parasitos dentro de seu vetor, foi constatada a preferência da L. brazilienses pela região pilórica em todos os experimentos, e quanto às diferented formas, observou-se a presença de formas metacíclicas em todos experimentos, contudo ocorreu o predomínio de promastigotas haptomonas e nectomonas

O desenvolvimento de Leishmania (Viannia) braziliensis no flebotomíneo Lutzomyia (Nyssomyia) intermedia e a influência da alimentação sanguínea em animais domésticos / The development of Leishmania (Viannia) braziliensis in the sandfly Lutzomyia (Nyssomyia) intermedia and the influence of blood meal in livestock

Este estudo teve como objetivo entender a interação entre Leishmania (V.) braziliensis e seu vetor Lutzomyia (N.) intermedia, ambos provenientes de uma área endêmica para Leishmaniose Tegumentar Americana (LTA), e também analisar a influência da alimentação e realimentação com sangue de animais domésticos. Flebotomíneos forma capturados e submetidos à infecção artificial com amastigotas de L. braziliensis e demonstrou-se o padrão de desenvolvimento do parasito em L. intermedia. Após cada alimentação artificial, o intestino médio dos insetos foram analisados para observar a presença, localização, morfologia e densidade dos parasitos. Numa primeira etapa, flebotomíneos foram submetidos a uma alimetação com sangue de camundongo o amastigotas de L. braziliensis. Após diferentes dias de infecção com sangue, o intestino médio de cada flebotomíneo foi dissecado e observou-se que houve uma queda da infecção de 86,5 porcento no primeiro dia para 42,9 porcento no décimo dia após alimentação sangüínea. Na etapa seguinte, foram feitas infecções usando sangue de diferentes animais (homem, boi, carneiro, porco, galinha, camundongo, cão, jeugue e cavalo). Observou-se que no quinto dia 100 porcento dos flebotomíneos utilizados submetidos a alimentação com sangue de boi estavam infectados. Porém, quando utilizamos sangue de jegue, este número caio para 33,3 porcento. Na última etapa, foram feitas alimentações infectivas seguidas de realimentações para observar a influência do segundo repasto sanguíneo no desenvolvimento da L. braziliensis no vetor. Primeiramente, os realimentados no quarto dia com sangue de diferentes animais domésticos saudáveis. Ointestino médio de cada flebotomíneo foi dissecado no sétimo dia e obdervou-se um aumento no número de parasitos dentro flebetomíneo. Quanto à posição ocupada pelos parasitos dentro de seu vetor, foi constatada a preferência da L. brazilienses pela região pilórica em todos os experimentos, e quanto às diferented formas, observou-se a presença de formas metacíclicas em todos experimentos, contudo ocorreu o predomínio de promastigotas haptomonas e nectomonas.

Lutzomyia longipalpis salivary gland homogenate impairs cytokine production and costimulatory molecule expression on human monocytes and dendritic cells.

In this report, we describe an investigation of the effects of Lutzomyia longipalpis sand fly salivary gland homogenates (SGH) on cytokine production and expression of costimulatory molecules on human monocytes, macrophages (Mphis), and dendritic cells (DCs). SGH of L. longipalpis induced an increase in interleukin-6 (IL-6), IL-8 and IL-12p40 production but a decrease in tumor necrosis factor alpha and IL-10 production by lipopolysaccharida (LPS)-stimulated monocytes. We also examined the expression of costimulatory molecules on the surface of monocytes, Mphis, and DCs. Whereas SGH affected the expression of these molecules on monocytes and Mphis, it had little effect on these molecules on DCs. However, when DCs were generated from human monocytes in the presence of SGH, SGH inhibited the expression of costimulatory molecules. In addition, a decrease in the maturation of DCs induced by CD40L was observed in the presence of SGH. Finally, preincubating SGH with human sera containing anti-SGH-specific antibodies abolished the effects of SGH on cytokine production by LPS-stimulated monocytes.

Abortive infection of Lutzomyia longipalpis insect vectors by aflagellated LdARL-3A-Q70L overexpressing Leishmania amazonensis parasites.

Leishmania donovani ADP-ribosylation factor-like protein 3A (LdARL-3A) is a small G protein isolated from the protozoan parasite L. donovani with no defined physiological function. Previously [Cuvillier, A., Redon, F., Antoine, J.-C., Chardin, P., DeVos, T., and Merlin, G. (2000) J Cell Sci 113: 2065-2074] we have shown that overexpression in L. amazonensis promastigotes of the mutated protein LdARL-3A-Q70L, which remains constitutively associated with GTP, leads to the disappearance of the flagellum but does not impair cell viability or growth. Here we report that parasites overexpressing LdARL-3A-Q70L can invade in vitro cultivated macrophages to the same extent as control cells, demonstrating that the flagellum is not necessary for attachment to or engulfment into macrophages. These infections are productive because amastigotes differentiate and multiply. However, aflagellated LdARL-3A-Q70L-overexpressing Leishmania promastigotes could not survive in experimentally infected Lutzomyia longipalpis insect vectors, in contrast to untransfected or native LdARL-3A-overexpressing cells. Overexpression of the native and mutated proteins did not modify in vitro procyclic to metacyclic lipophosphoglycan maturation or differentiation from procyclic to metacyclic promastigotes, nevertheless there is a block in transmission of Leishmania. Better understanding of LdARL-3A pathways, notably those regarding flagellum biogenesis, may lead to the future development of Leishmania-specific drugs, which may stop parasite transmission in nature without affecting other species.

Frequency of Infection of Lutzomyia Phlebotomines with Leishmania braziliensis in a Brazilian endemic area as assessed by pinpoint capture and polymerase chain reaction

Leishmania infected of Lutzomyia spp. are rare in endemic areas. We tested the hypothesis that there is clustering of infected vectors by combining pinpoint capture with sensitive L. braziliensis kDNA minicircle specific PCR/dot blot in an endemic area in the State of Bahia. Thirty out of 335 samples (10 to 20 sand flies/sample; total of 4,027 female sand flies) were positive by PCR analysis and dot blot leading to a underestimated overall rate of 0.4 percent positive phlebotomines. However, 83.3 percent of the positive samples were contributed by a single sector out of four sectors of the whole studied area. This resulted in a rate of 1.5 percent Leishmania positive phlebotomines for this sector, far above rates of other sectors. Incidence of American cutaneous leishmaniasis cases for this sector was about twice that for other sectors. Our results show that there is a non-homogeneous distribution of Leishmania-infected vectors. Such a clustering may have implications in control strategies against leishmaniasis, and reinforces the necessity of understanding the ecological and geographical factors involved in leishmanial transmission

Surto de leishmaniose tegumentar americana em Canoa, Santo Amaro, Bahia, Brasil / An outbreak of American cutaneous leishmaniasis in Canoa, Santo Amaro, Bahia, Brazil

Em 1993, um surto leishmaniose tegumentar americana (LTA) foi detectado no povoado rural de Canoa, município de Santo Amaro, Bahia. Um estudo observacional prospectivo delineou-se, com objetivo de determinar as taxas de freqüência e caracterizar clinicamente a doença. Foram acompanhados 555 indivíduos, registrando-se 29 casos de LTA, 11 casos sugestivos de LTA pregressa e 529 sadios. Desses 529 sadios, 65 apresentaram reaçäo de Montenegro positiva sem qualquer evidência presente ou passada de doença. A prevalência de LTA no período de estudo foi de 5,2 por cento (29/555). A leishmania envolvida foi caracterizada como Leishmania braziliensis e o vetor, Lutzomyia intermedia. Foram detectados cäes e equídeos infectados por leishmania. O acometimento de crianças menores de 10 anos, o acometimento igual entre os sexos e um componente de agregaçäo familiar sugerem um padräo de transmissäo peri ou intradomiciliar