Journal of internal medicine
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Obesity induces an inflammation state that is implicated in many clinically important complications, including insulin resistance, diabetes, atherosclerosis and non-alcoholic fatty liver disease. Although the cause and the molecular participants in this process remain incompletely defined, adipose tissue has a central role. ⋯ More recently a critical role for immune cells, specifically mononuclear phagocytes, in generating the obesity-induced inflammation has been identified. Defining the molecular and cellular components of obesity-induced inflammation offers the potential of identifying therapeutic targets that can ameliorate the complications associated with obesity.
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An increasing body of evidence suggests the likelihood of a link between arterial and venous disease. According to the results of recent studies, atherosclerosis and venous thromboembolism (VTE) share common risk factors, including age, obesity, diabetes mellitus and metabolic syndrome. ⋯ Several recent studies have consistently shown that patients with VTE of unknown origin are at a higher risk of cardiovascular diseases, including atherosclerotic complications, than patients with secondary VTE and matched control individuals. Future studies are needed to clarify the nature of this association, to assess its extent and to evaluate its implications for clinical practice.
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Vaccine-induced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines. However, for highly variable viruses such as HIV-1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV-1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and entry. ⋯ The primary challenge in the development of an HIV-1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers. Here, we describe neutralizing determinants on the viral envelope glycoproteins that are defined by their function in receptor binding or by rare neutralizing antibodies isolated from HIV-infected individuals. We also describe the nonvariable cellular receptors involved in the HIV-1 entry process, or other cellular proteins, and ongoing studies to determine if antibodies against these proteins have efficacy as therapeutic reagents or, in some cases, as vaccine targets to interfere with HIV-1 entry.
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Tuberculosis (TB) continues to kill more than 2 million people globally each year. Annual TB case notification rates have risen up to fourfold since the mid-1980s, with the highest rate of 1000/100,000 around Cape Town, South Africa. ⋯ The rising incidence of TB has been attributed to HIV co-infection especially in developing countries. The threat of drug resistance arising from ineffective TB treatment programmes is looming and could potentially lead to loss of any gains made in controlling the disease globally.
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An increased understanding of the genetic, molecular and cellular mechanisms responsible for the development of polycystic kidney disease has laid out the foundation for the development of rational therapies. Many animal models where these therapies can be tested are currently available. This review summarizes the rationale for these treatments, the results of preclinical trials and the prospects for clinical trials, some already in early phases of implementation.