Books on the topic 'Bone inhibition'

Psoriatic arthritis (PsA) is associated with a distinct pattern of bone pathology, which influences the clinical picture of the disease. High-resolution computed tomography (CT) has contributed to understanding structural bone changes in PsA. Periarticular bone erosions in PsA are characterized by periosteal responses around the cortical break, distinguishing them from bone erosions in rheumatoid arthritis. Furthermore, a large number of enthesophytes can be found in CT studies of joints of PsA patients and in psoriasis patients without clinical arthritis. This latter observation supports the idea that articular changes start in psoriasis before joint disease commences. Moreover, enthesophytes are not influenced by methotrexate treatment and tumour necrosis factor inhibition. Finally, studies of systemic bone loss by high-resolution CT revealed significant alterations of the bone architecture in PsA but not in patients with skin disease only. In summary, CT has made valuable contributions in understanding the structural bone changes in PsA.

Metastatic spread of cancer to bone is frequent and causes pain, disability, and functional limitation. New understanding of the homing method of cancer cells to bone and the mechanism of cancer production of pain raise possible new treatment strategies. Non-surgical treatments such as chemotherapy and hormone therapy are effective in early disease. Bisphosphonates and inhibition of osteoprotegerin prevent progression of bone lesions and avoid pain, radiation, and surgery. Radiotherapy arrests disease and relieves pain in many cases. Surgery is needed when the bone is weak or fractured. It effectively relieves pain and preserves function. It usually requires replacing or bypassing the deficient bone with site-specific reconstructive surgery. Surgery should be selected based on projections of patient survival. New tools to make these projections have been validated and are now available. New targeted drug therapies appear to be changing metastatic bone disease into a more chronic condition. This will alter the management of local disease in many histological subtypes of metastatic cancers.

Highly active antiretroviral therapy remains the mainstay of treatment for patients chronically infected with HIV. Novel drugs, both within existing classes and new ones, are in various stages of development and testing. New medications within existing classes of antiretroviral agents are in clinical trials and will likely offer activity against resistant HIV-1 strains and provide alternatives for combination pill therapy. Novel therapeutics including oral attachment inhibitors and monoclonal antibody treatments continue to show efficacy against HIV-1 and progress in clinical trials. Tenofovir alafenamide is a prodrug that produces higher intracellular levels of tenofovir diphosphate with likely less renal and bone toxicity. Among traditional classes of HIV treatment, both doravirine (a non-nucleoside reverse transcriptase inhibitor) and cabotegravir (an integrase strand inhibitor) are newer agents with activity against resistant virus. Maturation inhibitors are a new class of treatment that block protease cleavage, leading to the release of an immature virion.

This chapter provides a brief summary of the immune pathogenesis of atherosclerosis, highlighting shared features with inflammatory pathways in rheumatoid arthritis (RA) described in detail in Chapter 25.4. RA constitutes a prototype autoimmune disease primarily affecting the joints but also the heart and vessels associated with increased cardiovascular mortality. Recent years have produced a wealth of novel insights into the diversity of immune cell types which either propagate or dampen inflammation in atherogenesis. Expansion of this inherent anti-inflammatory component carried by regulatory T cells may constitute a new therapeutic target to harness the progression of atherosclerotic cardiovascular disease. Among the various inflammatory mediators involved in RA pathology, cytokines (tumour necrosis factor-α‎ and interleukin-6) have gained major interest as therapeutic targets with approved therapies available. In light of the many common features in the pathogenesis of RA and atherosclerosis, these biologics are currently being evaluated in cardiovascular patients. The recently published CANTOS trial showed that IL-1 inhibition reduced adverse cardiovascular events in patients with coronary artery disease demonstrating that inflammation is a genuine therapeutic target. The near future will provide more information whether inflammation is a bona fide cardiovascular risk factor based on completion of several clinical trials using anti-inflammatory approaches in patients with both cardiovascular disease and rheumatoid arthritis.

Listeriosis occurs in a variety of animals including humans, and most often affects the pregnant uterus, the central nervous system (CNS) or the bloodstream. During pregnancy, infection spreads to the foetus, which will either be born severely ill or die in-utero. In non-pregnant animals, listeriosis usually presents as meningitis, encephalitis. In humans, infection most often occurs in the immunocompromised and elderly, and to a lesser extent the pregnant woman, the unborn, or the newly delivered infant. Infection can be treated successfully with antibiotics, however 20–40% of human cases are fatal..In domestic animals (especially in sheep and goats) listeriosis usually presents as encephalitis, abortion, or septicaemia, and is a cause of considerable economic loss.The genus Listeria comprises six species of Gram-positive bacteria. Almost all cases of listeriosis are due to Listeria monocytogenes although up to 10% of cases in sheep are due to Listeria ivanovii.Listeriae are ubiquitous in the environment worldwide, especially in sites with decaying organic vegetable material. Many animals carry the organism in the faeces without serious infection. The consumption of contaminated food or feed is the principal route of transmission for both humans and animals, however other means of transmission occur.Human listeriosis is rare (<1 to > 10 cases per million people in North America and Western Europe), but because of the high mortality rate, it is amongst the most important causes of death from food-borne infections in industrialized countries. In the UK, human listeriosis is the biggest single cause of death from a preventable food-borne disease. Listeriosis in domestic animals is a cause of considerable economic loss. Control measures should be directed towards both to exclude Listeria from food or feed as well as inhibiting its multiplication and survival. Silage which is spoiled or mouldy should not be used, and care should be taken to maintain anaerobic conditions for as long as possible.Dietary advice is available for disease prevention, particularly targeted at ‘at risk’ individuals to modify their diet to avoid eating specific foods such as soft cheese and pâté.

O vírus da dengue (DENV), o vírus da Zika (ZIKV) e o vírus da chikungunya (CHIKV) são espécies que apresentam relevância clínica para a saúde pública. Porém, ainda não existe um tratamento específico ou vacina disponível para esses arbovírus. Nesse contexto, é fundamental encontrar novos alvos terapêuticos que possam auxiliar estratégias e tratamentos mais eficientes. A metodologia de codon usage tem demonstrado bons resultados para encontrar alvos para terapias que visam inibidores de tradução. Este estudo buscou analisar o uso de códons e o equilíbrio entre a abundância relativa dos RNAs transportadores (tRNAs) para encontrar alvos terapêuticos que irão estimular novas alternativas de tratamento para infecções causadas pelos DENV, ZIKV e CHIKV. Para tanto, foi replicada uma estratégia computacional, assumindo uma terapia hipotética de inibição seletiva de tRNA (Selective Transport RNA Inhibition Therapy - STRIT), onde foi estabelecido um índice de potencial terapêutico (T-score) para encontrar potenciais espécies de tRNA que poderiam ser inibidas seletivamente para atenuar a replicação viral na célula hospedeira. Foram identificados os cinco códons com maior frequência relativa vírus/hospedeiro (mais relevantes para o vírus) nas seis espécies de arbovírus, notando que todos terminam com purinas A ou G. Os códons GGA (Glicina), AGA (Arginina) e ATA (Isoleucina) são relevantes em todos os flavivirus (ZIKV, DENV-1, DENV-2, DENV-3, DENV-4), mas não no alphavirus CHIKV, onde os códons ACG (Treonina) e CCG (Prolina) são os mais relevantes. Posteriormente, selecionando os cinco códons com maiores T-score nas seis espécies virais (30 códons em total) encontramos apenas 11 códons diferentes, todos terminados com A ou G. Agrupados segundo o nucleotídeo na primeira posição do códon estes 11 códons são: (AGA, ACA, ATA, ACG), (GGA, GCA, GTA, GCG), (CTA, CCG) e (TGG). No agrupamento, notamos outro fato intrigante: que 10 dos 11 códons mais bem ranqueados por T-score, terminam com GA, CA, TA ou CG. Nosso método identificou as espécies de tRNA (através da identificação do códon cognato com maior T-score), cuja inibição funcional por qualquer método específico a anticódon, poderia ter potenciais efeitos terapêuticos em células infectadas pelo vírus da Dengue, Zika e Chikungunya causando a inibição da tradução das proteínas do vírus sem ter um efeito deletério na sobrevivência das células hospedeiras durante o período da infeção. A predominância absoluta dos nucleotídeos A e G na terceira posição dos 11 códons com maior T-score, que por sua vez indica uma preferência dos arbovírus por 11 espécies de tRNA com C ou T na primeira posição do anticódon, abre um novo espaço de pesquisa na interação vírus-hospedeiro.

Influenza is a highly infectious, acute illness which has affected humans and animals since ancient times. Influenza viruses form the Orthomyxoviridae family and are grouped into types A, B, and C on the basis of the antigenic nature of the internal nucleocapsid or the matrix protein. Infl uenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals, and birds, occasionally producing devastating pandemics in humans, such as in 1918 when it has been estimated that between 50–100 million deaths occurred worldwide.There are two important viral surface glycoproteins, the haemagglutinin (HA) and neuraminidase (NA). The HA binds to sialic acid receptors on the membrane of host cells and is the primary antigen against which a host’s antibody response is targeted. The NA cleaves the sialic acid bond attaching new viral particles to the cell membrane of host cells allowing their release. The NA is also the target of the neuraminidase inhibitor class of antiviral agents that include oseltamivir and zanamivir and newer agents such as peramivir. Both these glycoproteins are important antigens for inducing protective immunity in the host and therefore show the greatest variation.Influenza A viruses are classified into 16 antigenically distinct HA (H1–16) and 9 NA subtypes (N1–9). Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. Each virus possesses one HA and one NA subtype.Last century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, occurred on three occasions, 1918 (H1N1), 1957 (H2N2) and 1968 (H3N2), resulting in pandemics. The frequent epidemics that occur between the pandemics are as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Epidemics throughout the world occur in the human population due to infection with influenza A viruses, such as H1N1 and H3N2 subtypes, or with influenza B virus. Phylogenetic studies have led to the suggestion that aquatic birds that show no signs of disease could be the source of many influenza A viruses in other species. The 1918 H1N1 pandemic strain is thought to have arisen as a result of spontaneous mutations within an avian H1N1 virus. However, most pandemic strains, such as the 1957 H2N2, 1968 H3N2 and 2009 pandemic H1N1, are considered to have emerged by genetic re-assortment of the segmented RNA genome of the virus, with the avian and human influenza A viruses infecting the same host.Influenza viruses do not pass readily between humans and birds but transmission between humans and other animals has been demonstrated. This has led to the suggestion that the proposed reassortment of human and avian influenza viruses takes place in an intermediate animal with subsequent infection of the human population. Pigs have been considered the leading contender for the role of intermediary because they may serve as hosts for productive infections of both avian and human viruses, and there is good evidence that they have been involved in interspecies transmission of influenza viruses; particularly the spread of H1N1 viruses to humans. Apart from public health measures related to the rapid identification of cases and isolation. The main control measures for influenza virus infections in human populations involves immunization and antiviral prophylaxis or treatment.