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This review article focuses on intranasal immunisation against influenza, although it also encompasses antigen uptake and processing in the nasopharyngeal passages, host defence from influenza and current influenza vaccination practices. Improvement of current vaccination strategies is clearly required; current procedures involve repeated annual injections that sometimes fail to protect the recipient...
Reactive arthritis follows infections of the urogenital or enteric tract with bacteria such as Chlamydia, Yersinia, Shigella, Salmonella or Campylobacter. Typically, one knee or ankle are affected for weeks to several months, with up to 20% of patients experiencing a chronic course of more than 1 year. The acute arthritis is treated nonspecifically with nonsteroidal anti-inflammatory drugs (NSAIDs),...
Aspirin (ASA)-sensitive asthma is characterised by a typical sequence of symptoms, including intense eosinophilic inflammation of nasal and bronchial tissues. It is more commonly found in non-atopic, middle-aged female asthmatic patients with chronic rhino-sinusitis and/or nasal polyps. The lysine-aspirin bronchoprovocation test has become a widely used diagnostic test. When ASA-sensitive asthma is...
Immune-mediated uveitis is a collective term referring to a group of potentially blinding intraocular inflammations which may coexist with systemic inflammatory diseases. T lymphocytes appear to play an important pathogenic role in uveitis, and these cells are therefore the logical target of drug therapy. Corticosteroids act nonspecifically, but are highly effective in controlling the inflammation...
Recent studies strongly suggest that cerebral ischaemia initiates a focal inflammatory response that results in significant secondary injury to brain tissue, thereby extending the ultimate size of a stroke. Factors involved in this cascade include the release of cytokines that cause a pro-inflammatory and prothrombotic state on cerebral vessel endothelium, the expression of leucocyte adhesion molecules,...
Allergen-specific immunotherapy is widely used to treat allergic diseases, and current research is now focusing on the development of therapeutic vaccines acting on the IgE immune response following allergen challenge. The IgE immune response is dependent on genetic and environmental factors; production of IgE results from complex interactions among B cells, T cells, mast cells, basophils, surface...
α1-Antitrypsin (A1AT) deficiency is inherited as an autosomal codominant disorder characterised by reduced levels of A1AT in the serum. Low levels of A1AT in blood perfusing the lung cause low levels in the lung interstitium, making it susceptible to proteolytic damage from resident neutrophil elastase. A ‘protective threshold’ serum A1AT level of 11 μmol/L has been identified by epidemiological studies...
Phosphodiesterases (PDEs) are involved in the regulation of intracellular levels of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These enzymes hydrolyse the cyclic nucleotides to the corresponding nucleoside 5′-monophosphates. Nine PDE subtypes have been identified; these differ in their substrate specificity and mode of activation. The type...
Adrenal androgens dehydroepiandrosterone (DHEA; prasterone) and its sulphated form (DHEA-S) are among the most abundant hormonal steroids in men and nonpregnant women. Deficiencies of these adrenal androgens are associated with autoimmune disorders such as rheumatoid arthritis (RA). Recent studies from our laboratory have also identified low levels of adrenal androgens in the serum and synovial fluid...
The treatment of chronic obstructive pulmonary disease (COPD) is receiving increasing attention since the burden of this disease is expected to rise on a global scale in the coming decades. Preventing deterioration of lung function parameters has been the main goal of research in COPD management. In practice, however, the success of drug treatment is not dependent on lung function only, but also relies...
The main cause of Addison’s disease is an autoimmune organ-specific destruction of the cells in the adrenal cortex by an autoreactive process of activated immune cells directed against the steroid-synthesising enzyme 21-hydroxylase. The diagnosis of Addison’s disease is suspected in a patient presenting with symptoms of fatigue, bodyweight loss, anorexia, salt craving, and signs of low blood pressure...
Intravenously administered alteplase (recombinant tissue plasminogen activator; rtPA) is the only medical treatment that has been approved for the management of acute ischaemic stroke. Although rtPA has demonstrated efficacy in improving outcomes of patients with a wide range of neurological impairments, it cannot be given with impunity. Thrombolytic therapy is associated with a considerable risk...
In some patients with Crohn’s disease the anorectal complications are the major cause of symptoms and morbidity. Anorectal Crohn’s disease may be present in patients with intestinal Crohn’s disease, may be the initial manifestation of the disease, or rarely occurs without involvement of Crohn’s disease elsewhere in the intestinal tract. The pathogenesis of these anorectal complications remains to...
Multiple sclerosis is now a treatable disease and several immunomodulating therapies exist, but their clinical efficacy is moderate and treatment failure during the course of the disease is an increasing problem. As agents with different targets are available, the question was raised whether combination of these therapies would: (i) be safe; (ii) result in reduction of adverse effects; and (iii) provide...
▴ Lanoteplase is a recombinant plasminogen activator, which when administered as a single bolus intravenous injection, displays thrombolytic activity. ▴ In the phase II In TIME trial, lanoteplase dose-de-pendently increased reperfusion rates at 60 and 90 minutes in patients with acute myocardial infarction and at 90 (but not 60) minutes lanoteplase 120 kU/kg was significantly superior to alteplase...
Cytomegalovirus (CMV) infection in solid organ transplantation is associated with significant morbidity and mortality. Primary infection, secondary infection or superinfection may occur in this setting. Progression to disease may ensue with development of symptoms, with or without organ involvement. The mainstay of treatment of CMV disease is intravenous ganciclovir. Aside from protective organ matching...
Significant advances have been made in the field of liver-directed gene therapy. Many diseases are potential targets for gene therapy, including diseases that have exclusive liver involvement and those with systemic manifestations as a result of defective protein synthesis from the liver. Examples are Crigler-Najjar syndrome type 1, α1-antitrypsin deficiency and haemophilia A and B. Strategies for...
The activation of dominant oncogenes and inactivation of tumour suppressor genes may result in cancer. These genetic events may represent novel targets for cancer therapy. Antisense nucleic acids can be used to modulate the expression of selected genes, and to suppress malignant behaviour in cancer cells. Nevertheless, in practice, the selection of suitable antisense targets still remains a trial-and-error...
Hepatitis B virus (HBV) infection is still an important cause of cirrhosis, hepatocellular carcinoma and acute liver failure worldwide, and orthotopic liver transplantation (OLT) is the only effective treatment for many of these conditions. Until recently, however, OLT in patients with HBV infection was associated with a high rate of graft loss due to viral recurrence. The use of long term passive...
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