Psoriase e comorbidades metabólicas / Psoriasis and metabolic comorbidities

A psoríase é uma doença inflamatória crônica, caracterizada por um ciclo evolutivo acelerado dos queratinócitos, associado a uma ativação imune desordenada. Diversos estudos associam a doença à comorbidades metabólicas, as quais aumentam o risco de o paciente desenvolver eventos cardiovasculares. Diante de tal panorama, este estudo comparou a frequência de fatores de riscos e comorbidades em 80 psoriáticos tratados no ambulatório do Instituto Lauro de Souza Lima, Bauru-SP. A análise dos dados revelou uma correlação significativa entre as variáveis: Pressão Arterial e Dislipidemia com IMC, elevação dos níveis glicêmicos; Obesidade abdominal e Dislipidemia com Alteração dos níveis de triglicerídeos. Em conjunto, nossos resultados identificaram fatores agravantes capazes de cooperar negativamente na qualidade de vida dos pacientes, aumentando o risco de morbidade e mortalidade.

Avaliação dos efeitos da isotretinoína oral em pacientes com acne: revisão bibliográfica / Assessment of the effects of oral isotretinoin in patients with ace: Literature review

A acne é uma doença inflamatória que acomete principalmente os folículos sebáceos presentes no rosto, tórax e costa. Seu tratamento inicialmente limita-se ao uso de soluções desengordurantes, antissépticas e esfoliantes tópicas, capazes de controlar a oleosidade. No entanto, os casos mais graves requerem o uso de drogas farmacológicas como antibiótico sistêmico, terapias hormonais e administração de isotretinoína oral. Visto a efetividade deste medicamento, reunimos informações atuais sobre a isotretinoína e relatamos as principais alterações laboratoriais encontradas.

Acne is an inflammatory disease that affects the sebaceous follicles present on the face, chest and coast. His treatment was initially limited to the use of degreasing solutions, antiseptic and topical exfoliants, can control the oiliness. However, more severe cases require the use of pharmaceutical drugs such as systemic antibiotics, hormonal therapy and administration of oral isotretinoin. Since the effectiveness of this product, we gather current information about isotretinoin and report the main laboratory abnormalities found.

Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy

Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. lepraewas lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy.

Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy.

Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy.

Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy

Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties of M. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy

Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection.

Conflicting findings about the association between leprosy and TLR1 variants N248S and I602S have been reported. Here, we performed case-control and family based studies, followed by replication in 2 case-control populations from Brazil, involving 3162 individuals. Results indicated an association between TLR1 248S and leprosy in the case-control study (SS genotype odds ratio [OR], 1.81; P = .004) and the family based study (z = 2.02; P = .05). This association was consistently replicated in other populations (combined OR, 1.51; P < .001), corroborating the finding that 248S is a susceptibility factor for leprosy. Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs) carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when stimulated with Mycobacterium leprae but not with lipopolysaccharide or PAM3cysK4. The same effect was observed after infection of PBMCs with the Moreau strain of bacillus Calmette-Guerin but not after infection with other strains. Finally, molecular dynamics simulations indicated that the Toll-like receptor 1 structure containing 248S amino acid is different from the structure containing 248N. Our results suggest that TLR1 248S is associated with an increased risk for leprosy, consistent with its hypoimmune regulatory function.

Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection

Conflicting findings about the association between leprosy and TLR1 variants N248S and I602S have been reported. Here, we performed case-control and family based studies, followed by replication in 2 case-control populations from Brazil, involving 3162 individuals. Results indicated an association between TLR1 248S and leprosy in the case-control study (SS genotype odds ratio [OR], 1.81; P = .004) and the family based study (z = 2.02; P = .05). This association was consistently replicated in other populations (combined OR, 1.51; P < .001), corroborating the finding that 248S is a susceptibility factor for leprosy. Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs) carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when stimulated with Mycobacterium leprae but not with lipopolysaccharide or PAM3cysK4. The same effect was observed after infection of PBMCs with the Moreau strain of bacillus Calmette-Guerin but not after infection with other strains. Finally, molecular dynamics simulations indicated that the Toll-like receptor 1 structure containing 248S amino acid is different from the structure containing 248N. Our results suggest that TLR1 248S is associated with an increased risk for leprosy, consistent with its hypoimmune regulatory function.

Stereotactic body radiation therapy for locally recurrent, previously irradiated nonsquamous cell cancers of the head and neck.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for patients with recurrent, previously irradiated head and neck cancer; however, data are limited predominantly to squamous cell carcinomas. Herein, we report the efficacy of SBRT in recurrent, nonsquamous cell cancers of the head and neck (NSCHNs). METHODS: In all, 34 patients with pathologically proven NSCHN were re-irradiated with SBRT to a median dose of 40 Gy in 5 fractions (interquartile range, 30-44 Gy). Toxicity and quality of life were followed prospectively. RESULTS: Median follow-up was 10 months (absolute range, 0-55 months). The 6-month/1-year local control rate was 77/59%, with a 6-month/1-year overall survival of 76/59%. Local control was significantly improved for tumors <25 mL (p = .030). Acute/late grade 3 toxicity was 15/6%, with no grade 4-5 toxicity. CONCLUSIONS: SBRT for previously irradiated, locally recurrent NSCHN provides promising local control, especially for tumors <25 mL, with minimal toxicity. The optimal dose for larger tumors remains to be defined.

Quantificação dos níveis séricos de leptina na Hanseníase / Quantification of serum leptin levels in leprosy

A leptina é uma adipocina com semelhanças estruturais e funcionais às citocinas pró-inflamatórias, contribuindo para a diferenciação de células Th1, e parece estar envolvida na resposta imune a agentes infecciosos. Na hanseníase, doença infecciosa crônica causada pelo Mycobacterium leprae, cujas manifestações clínicas dependem da resposta imune do hospedeiro, não há relatos sobre o papel da leptina. Neste estudo piloto foram quantificados os níveis séricos de leptina em pacientes recém-diagnosticados com as diferentes formas clínicas da doença, pacientes hansenianos em reação tipo 1 e 2,contatos de pacientes hansenianos e controles saudá-veis (237 amostras de soros: 165 homens e 72 mulheres).No sexo masculino, as formas TT e BB apresentaram concentrações próximas àquelas observadas nos controles enquanto os grupos I, BT, BV, VV, reação do tipo1 e 2 apresentaram médias inferiores à observada nos controles e contatos, sendo que nos BV e VV foram observados os menores níveis de leptina. No sexo feminino verificamos uma grande variação entre os valores observados nos diferentes grupos. O grupo BV apresentou níveis maiores de leptina enquanto os grupos I, TT, BT e BB apresentaram média próxima àquela observada nos contatos e controles. Pacientes do grupo VV e em reação tipo 1 e 2 apresentaram médias inferiores ao observado nos contatos e controles. As diferenças observadas tanto em homens quanto em mulheres não foram estatisticamente significantes. Em nossos achados há uma tendência a níveis mais baixos de leptina nas formas multibacilares, contudo, estes resultados não permitem associação desses níveis com qualquer forma clínica da hanseníase.

Leptin, an adipokine with structural and functional similaritiesto proinflammatory cytokines that contributesto the differentiation of T helper-1 cells, seems to beinvolved in the immune response to infectious agents.In leprosy, a chronic infectious disease caused by Mycobacteriumleprae, whose clinical manifestations depend on the host immune response, there are no reports onthe role of leptin. In this pilot study the serum leptin levelswere quantified in newly diagnosed patients withdifferent clinical forms of leprosy, patients with type 1and 2 reaction, contacts of leprosy patients and healthycontrols (237 serum samples:165 men and 72 women).In males, TT and BB patients showed concentrations closeto those observed in controls while groups I, BT, BV,VV, type 1 and 2 reactional patients had lower means incomparison to controls and contacts, whereas in BV andVV patients it were observed the lowest levels of leptin.In females, we found a wide variation between the valuesobserved in the different groups. The BV group hadhigher levels of leptin while groups I, TT, BT and BB hadaverages closed to that observed in contacts and controls.The differences observed in both men and womenwere not statistically significant. Our findings show atendency to lower levels of leptin in multibacillary patients,however, these results do not allow any associationof leptin with leprosy clinical forms.