Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease.

The joint disease called pararamosis is an occupational disease caused by accidental contact with bristles of the caterpillar Premolis semirufa. The chronic inflammatory process narrows the joint space and causes alterations in bone structure and cartilage degeneration, leading to joint stiffness. Aiming to determine the bristle components that could be responsible for this peculiar envenomation, in this work we have examined the toxin composition of the caterpillar bristles extract and compared it with the differentially expressed genes (DEGs) in synovial biopsies of patients affected with rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteins identified, 129 presented an average of 63% homology with human proteins and shared important conserved domains. Among the human homologous proteins, we identified seven DEGs upregulated in synovial biopsies from RA or OA patients using meta-analysis. This approach allowed us to suggest possible toxins from the pararama bristles that could be responsible for starting the joint disease observed in pararamosis. Moreover, the study of pararamosis, in turn, may lead to the discovery of specific pharmacological targets related to the early stages of articular diseases.

Human Chondrocyte Activation by Toxins From Premolis semirufa, an Amazon Rainforest Moth Caterpillar: Identifying an Osteoarthritis Signature.

Pararamosis is a disease that occurs due to contact with the hairs of the larval stage of the Brazilian moth Premolis semirufa. Envenomation induces osteoarticular alterations with cartilage impairment that resembles joint synovitis. Thus, the toxic venom present in the caterpillar hairs interferes with the phenotype of the cells present in the joints, resulting in inflammation and promoting tissue injury. Therefore, to address the inflammatory mechanisms triggered by envenomation, we studied the effects of P. semirufa hair extract on human chondrocytes. We have selected for the investigation, cytokines, chemokines, matrix metalloproteinases (MMPs), complement components, eicosanoids, and extracellular matrix (ECM) components related to OA and RA. In addition, for measuring protein-coding mRNAs of some molecules associated with osteoarthritis (OA) and rheumatoid arthritis (RA), reverse transcription (RT) was performed followed by quantitative real-time PCR (RT-qPCR) and we performed the RNA-sequencing (RNA-seq) analysis of the chondrocytes transcriptome. In the supernatant of cell cultures treated with the extract, we observed increased IL-6, IL-8, MCP-1, prostaglandin E2, metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-13), and complement system components (C3, C4, and C5). We noticed a significant decrease in both aggrecan and type II collagen and an increase in HMGB1 protein in chondrocytes after extract treatment. RNA-seq analysis of the chondrocyte transcriptome allowed us to identify important pathways related to the inflammatory process of the disease, such as the inflammatory response, chemotaxis of immune cells and extracellular matrix (ECM) remodeling. Thus, these results suggest that components of Premolis semirufa hair have strong inflammatory potential and are able to induce cartilage degradation and ECM remodeling, promoting a disease with an osteoarthritis signature. Modulation of the signaling pathways that were identified as being involved in this pathology may be a promising approach to develop new therapeutic strategies for the control of pararamosis and other inflammatory joint diseases.

2-Phthalimidethanol and 2-phthalimidethyl nitrate inhibit mechanical allodynia, neutrophil recruitment and cytokine and chemokine production in a murine model of articular inflammation.

BACKGROUND: Phthalimide analogs have been shown to exhibit anti-inflammatory, analgesic and immunomodulatory activities in different preclinical assays. This study aimed to investigate the potential role of 2-phthalimidethanol (PTD-OH) and 2-phthalimidethyl nitrate (PTD-NO) in a murine model of antigen-induced articular inflammation. METHODS: Articular inflammation was induced by intra-articular injection of methylated bovine serum albumin (mBSA) in the knee joint of immunized male C57BL/6J mice. The animals were pre-treated with PTD-OH or PTD-NO (500mg/kg, per os, - 1h). Nociceptive threshold was measured using an electronic von Frey apparatus. The total number of leukocytes in the synovial cavity was determined. Concentrations of tumor necrosis factor (TNF)-α and CXCL-1 and myeloperoxidase (MPO) activity were determined in periarticular tissue. RESULTS: Both PTD-OH and PTD-NO inhibited at similar extent the mechanical allodynia, neutrophil recruitment to the synovial cavity and periarticular tissue and TNF-α and CXCL-1 production induced by intra-articular challenge with mBSA in immunized mice. CONCLUSIONS: PTD-OH and PTD-NO exhibit a marked activity in a murine model of antigen-induced articular inflammation in immunized animals. These results reinforce the interest in the investigation of phthalimide analogs devoid of the glutarimide ring as candidates to analgesic and anti-inflammatory drugs.

Artropatias iatrogênicas droga-induzidas / Iatrogenic drug-induced arthropathy

Um grupo de pacientes idosos apresenta várias doenças, levandoa consumir inúmeras drogas. Por outro lado, o metabolismo dessasdrogas se encontra bastante alterado pelas condições especiais doprocesso de envelhecimento. Portanto, um determinado sintoma aser combatido pode não ser causado pela devida doença, mas sim,por algum tipo de droga que o paciente esteja usando. Este capítulotem como escopo enumerar as síndromes reumáticas que podem seruma conseqüência das várias drogas administradas aos idosos.

Osteoarticular complications related to HIV infection and highly active antiretroviral therapy.

With the significant increase in life expectancy for HIV-infected patients in the era of high potency antiretroviral therapy, major metabolic changes have been observed due to the prolonged period of the viral infection and the treatment itself. Osteoarticular changes resulting from these processes are mainly reported in long term HIV-infected patients receiving high potency antiretroviral therapy and include osteopenia/osteoporosis, osteonecrosis, carpal tunnel syndrome and adhesive capsulitis of the shoulder.

Osteoarticular complications related to HIV infection and highly active antiretroviral therapy

With the significant increase in life expectancy for HIV-infected patients in the era of high potency antiretroviral therapy, major metabolic changes have been observed due to the prolonged period of the viral infection and the treatment itself. Osteoarticular changes resulting from these processes are mainly reported in long term HIV-infected patients receiving high potency antiretroviral therapy and include osteopenia/osteoporosis, osteonecrosis, carpal tunnel syndrome and adhesive capsulitis of the shoulder.

Manifestaciones osteomioarticulares de causa tóxico-farmacológica / Osteomyoarticular manifestations due to toxico-pharmacological cause

Los autores hacen referencia a productos industriales y farmacológicos que pueden inducir osteomioartropatias tóxicas. Al respecto detallan aspectos patogénicos y las medidas a tomar

Manifestaciones osteomioarticulares de causa tóxico-farmacológica / Osteomyoarticular manifestations due to toxico-pharmacological cause

Los autores hacen referencia a productos industriales y farmacológicos que pueden inducir osteomioartropatias tóxicas. Al respecto detallan aspectos patogénicos y las medidas a tomar (AU)

Role of rifampicin in arthralgia induced by pyrazinamide

Arthralgia during daily treatment with chemotherapy regimens containing pyrazinamide was found to be considerably less in patients who received rifampicin concomitantly...