Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low-density lipoprotein (LDL) pathway in systemic lupus erythematosus (SLE) patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the LDL lipidic structure. LDE was labeled with (14)C-cholesteryl ester ((14)C-CE), then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched and followed rigorous selection criteria of conditions that interfere in the lipid profile. Blood samples were collected in pre-established intervals after infusion for radioactivity measurement. Fasting lipoproteins were determined in the beginning of kinetic studies. Fractional clearance rate (FCR) of (14)C-CE was significantly different in the three groups (P = 0.03). In fact, a greater FCR of (14)C-CE was observed in CDP compared to NO THERAPY (0.076 +/- 0.037 versus 0.046 +/- 0.021 h(-1); P < 0.05) and to CONTROL (0.0516 +/- 0.0125 h(-1); P < 0.05). Accordingly, a significant lower total and LDL cholesterol were observed in CDP (156 +/- 16 and 88 +/- 16 mg/dl) compared to NO THERAPY (174 +/- 15 and 108 +/- 17 mg/dl; P < 0.05) and to CONTROL (200 +/- 24 and 118 +/- 23 mg/dl; P < 0.05). In contrast, no difference in (FCR) of (14)C-CE of NO THERAPY and CONTROL groups was observed. This is the first in vivo demonstration that LDE removal by LDL receptor from plasma is increased in SLE patients taking CDP with a consequent beneficial decrease in LDL-c levels.
Lupus 2007
PMID:Chloroquine increases low-density lipoprotein removal from plasma in systemic lupus patients. 1743 34

Rheumatoid arthritis is a chronic inflammatory disease. Established treatment is limited because of the clinical response or the induction of adverse effects. New biological agents evaluated for treatment of rheumatoid arthritis have shown varied clinical success. These agents target cytokines such as tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1 or IL-6, or cell surface molecules such as CD4, CD5, CD7, IL-2 receptor, CDw52 or CD54. Amongst these new drugs, only a few have shown clinical effectiveness in double-blind placebo-controlled trials. These include the primatised nondepleting anti-CD4 monoclonal antibody (mAb) CE9.1 (keliximab), the TNFalpha-blocking mAbs cA2 (infliximab) and CDP-571, the human recombinant soluble TNFalpha receptors p55 (lenercept) and p80, as well as the human recombinant IL-1 receptor antagonist protein, anakinra. Thus, only these agents qualify for evaluation of combination treatment in rheumatoid arthritis. Rationales for combination therapy include: combining drugs with different sites of action to increase efficacy or with different toxicities to minimise risk; combining drugs with different kinetics, thus improving clinical activity; using a combination of drugs for the prevention of tachyphylaxis; or using a second drug which helps to prevent or delay the development of resistance to the first one. In addition, combination therapy could help to prevent or minimise adverse effects caused by treatment with biological agents. Based on knowledge from trials with biological agents, and on the different properties attributed to the established disease-modifying antirheumatic drugs (DMARDs) in ex vivo and in vitro studies, we propose evaluation of the following combination regimens involving biological agents. First, biological agents targeting TNFalpha (such as the mAbs cA2 or CDP-571, or the TNFalpha receptor p55-IgG1 fusion protein) given as a single infusion for rapid clinical response could be followed by continuation treatment with methotrexate, possibly combined with chloroquine, azathioprine or cyclosporin. Combination of specific anti-TNFalpha strategies with sulfasalazine should be avoided because of the induction of double-stranded DNA antibodies seen after TNFalpha blockade in vivo and reports on a systemic lupus erythematosus-like syndrome as an adverse effect during treatment with biological agents directed against TNFalpha or with sulfasalazine. Alternatively, continuous inhibition of TNFalpha or IL-1 with TNFalpha receptor p80-IgG1 fusion protein or IL-1 receptor antagonist, respectively, could be combined with methotrexate, with the disadvantage of a slower initial improvement of clinical symptoms. Combination regimens with the primatised CD4 mAb could include methotrexate as concomitant medication, with chloroquine or sulfasalazine as additional medication. Importantly, combination of different biological agents might induce more severe adverse effects than seen with monotherapy. Thus, protocols involving combinations of biological agents with established DMARDs promise better acceptance than combinations of 2 new and as yet unestablished drugs with possibly synergistic adverse effects because of their antigenic properties.
 ...
PMID:Biological agents in rheumatoid arthritis: which ones could be used in combination? 1802 May 67

Our improved tools to identify the aetiologies in patients with multiple abnormalities resulted in the finding that some patients have more than a single genetic condition and that some of the diagnoses made in the past are acquired rather than inherited. However, limited knowledge has been accumulated regarding the phenotypic outcome of the interaction between different genetic conditions identified in the same patients. We report a newborn girl with brachytelephalangic chondrodysplasia punctata (BCDP) as well as frontonasal dysplasia, ptosis, bilateral hearing loss, vertebral anomalies, and pulmonary hypoplasia who was found, by whole exome sequencing, to have a de novo pathogenic variant in RAF1 (c.770C>T, [p.Ser257Leu]) and a likely pathogenic variant in SIX2 (c.760G>A [p.A254T]), as well as maternal systemic lupus erythematosus (SLE). This case shows that BCDP is most probably not a diagnostic entity and can be associated with various conditions associated with CDP including maternal SLE.
 ...
PMID:Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants. 3250 14