The presence of inadequately controlled hypertension in a diabetic patient with clinical signs of renal involvement portends a poor prognosis. Initial assessment should include ruling out factors which may exacerbate the hypertension and careful assessment of the stage of hypertension, renal function and amount of proteinuria. Intensive treatment requires finding a combination of medications which will reduce not only blood pressure but also proteinuria. It is suggested that treatment should be started with an ACE inhibitor or an AT1 receptor blocker often in a fixed combination with a low-dose thiazide diuretic. Calcium channel blockers and beta-blockers may be added if required as second or third-line agents. In patients not responding to this combination, the dosages of the ACE inhibitor or AT1 blocker should be titrated upwards in order to obtain the maximal therapeutic effect. However, if this is still insufficient, dual blockade of the RAS should be considered and even an aldosterone receptor blocker may need to be added to the therapeutic regimen. It should be remembered that such a patient requires close monitoring in order to be sure that he is compliant with respect to the prescribed treatment and that there are no side-effects such as hyperkalaemia.
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http://dx.doi.org/10.1111/j.1466-5468.2004.1180g.x | DOI Listing |
Int J Mol Sci
December 2024
Molecular Genetics, The Weizmann Institute of Science, Rehovot 7610001, Israel.
Interleukin-18 (IL-18) serves a dual function in the immune system, acting as a "double-edged sword" cytokine. Depending on the microenvironment and timing, IL-18 can either drive harmful inflammation or restore immune homeostasis. Pathologies characterized by elevated IL-18, recently proposed to be termed IL-18opathies, highlight the therapeutic potential for IL-18 blockade.
View Article and Find Full Text PDFKaohsiung J Med Sci
January 2025
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
SET domain bifurcated histone lysine methyltransferase 1 (SETDB1/ESET), a pivotal H3K9 methyltransferase, has been extensively studied since its discovery over two decades ago. SETDB1 plays critical roles in immune regulation, including B cell maturation, T-cell activity modulation, and endogenous retrovirus (ERV) silencing. While essential for normal immune cell function, SETDB1 overexpression in cancer cells disrupts immune responses by suppressing tumor immunogenicity and facilitating immune evasion.
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January 2025
Thoracic and GI Malignancies Branch, National Institutes of Health, 10 Center Drive, 2B50C, Bethesda, MD, 20892, USA.
Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type in the world and is associated with an overall poor prognosis. The protein methyltransferase SET and MYND domain-containing 3 (SMYD3), which trimethylates H3K4, activates gene transcription and enhances several oncogenic pathways, including epithelial-mesenchymal transition and cell cycle related pathways, in various cancer types. It was also recently shown that SMYD3 is overexpressed in HPV-negative HNSCC, and represses the expression of type I IFN response genes, contributing to resistance to anti-PD-1 checkpoint blockade in this disease.
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Light Chain Bioscience - Novimmune SA, Geneva, Switzerland.
Curr Cancer Drug Targets
January 2025
Division of Pharmacology, Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, 700114, India.
Immune checkpoint blockade (ICB) has fundamentally transformed cancer treat-ment by unlocking the potency of CD8+ T cells by targeting the suppression of the CTLA-4 and PD-1/PD-L1 pathways. Nevertheless, ICBs are associated with the risk of severe side effects and resistance in certain patients, driving the search for novel and safer immune check-point modulators. Monoamine Oxidase A (MAO-A) plays an unexpected role in the field of cancer.
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