Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liposomes have been suggested as carriers for corticosteroids in the local treatment of arthritis by intra-articular injection. The long chain 21-esters of cortisol such as the palmitate or octanoate are taken up and retained by liposomes in higher concentration than cortisol itself. Differential scanning calorimetry has been used to show that the cortisol ester is anchored in the liposome phospholipid bilayer by the acyl side chain. In addition, the limiting concentration of cortisol-21-palmitate which can be incorporated into dipalmitolyl phosphatidylcholine liposomes has been measured by observing changes in the DSC spectrum at different steroid concentrations. Steroid in excess of this concentration limit forms a separate phase which can be identified by nuclear magnetic resonance. For optimum effect, the treatment of arthritis with liposomes must be carried out with liposomes containing steroid below the limiting concentration.
 ...
PMID:Interaction of cortisol-21-palmitate with liposomes examined by differential scanning calorimetry. 2 61

Cell wall lytic enzyme (Kyowa lytic no. 2 enzyme) liberated arthritogenic hydrosoluble peptidoglycans from both arthritogenic and non-arthritogenic bacterial cell walls. From these cell walls, mutanolysin (peptidoglycan-degrading enzyme) also liberated hydrosoluble peptidoglycans which, however, lacked arthritogenicity. Based on the chemical composition of these peptidoglycans, it was suggested that their arthritis-inducing ability depends on a relatively long chain of glycan units that consists of repeated units of N-acetylglucosaminyl-N-acetylmuramic acid. However, the glycan chain lengths on these peptidoglycans appeared to be related to their adjuvancy rather than to an antigen(s) responsible for development of arthritis in rats.
 ...
PMID:Preparation of arthritogenic hydrosoluble peptidoglycans from both arthritogenic and non-arthritogenic bacterial cell walls. 30 40

Eicosapentaenoic acid (EPA), a long chain fatty acid of the n-3 series, is found in marine foods. Beneficial effects of these foods containing EPA on factors associated with cardiovascular disease risk and arterial thrombosis have been demonstrated. More recently, studies have suggested that EPA may also have a favourable effect on other human diseases such as arthritis, renal disorders, psoriasis and possibly also cancer. EPA is metabolized in a manner generally similar to that of arachidonic acid (AA) although some significant differences between the two are apparent. The metabolic fate of dietary EPA in human subjects is reviewed herein with inclusion of information from animal studies where human data is not available. The metabolism of EPA in the phospholipids of human platelets is emphasized to some extent. Effects of EPA on AA metabolism are also described.
 ...
PMID:Health effects and metabolism of dietary eicosapentaenoic acid. 284 41

Certain dietary-induced changes in tissue levels of polyunsaturated fatty acids are known to modify inflammatory reactions, possibly through changes in the synthesis of mediators of inflammation derived from fatty acids, including prostaglandins and leukotrienes. We have therefore examined the effects of a fish oil diet, enriched in highly unsaturated (delta-17) long chain fatty acids, on collagen arthritis. Weanling female Sprague-Dawley rats were maintained on a diet with fat provided by either fish oil (containing 14.5% 5, 8, 11, 14, 17-eicosapentaenoic acid; EPA) or, as a control, beef tallow (containing less than 0.05% EPA). They were immunized with native chick type II collagen emulsified in incomplete Freund's adjuvant 5 to 6 wk later. There was an increased incidence of arthritis in the rats receiving the fish oil compared with the group receiving the beef diet (88 vs 61%, p less than 0.001), but there was no significant difference in the severity of joint inflammation of arthritic rats in the two groups. The mean serum titer of IgG antibodies to type II collagen, measured by an enzyme-linked immunosorbent assay (ELISA), was decreased in the group receiving the fish oil (p less than 0.001), whereas the hemagglutinating antibody titer and delayed-type hypersensitivity to collagen were similar in the two groups. Primary synovial explant cultures from fish oil-treated rats produced only 21 to 24% as much PGE2 as beef tallow-treated controls, and this reduction in the experimental group was not accompanied by any detectable increase in PGE3, the E-prostaglandin derived from the arachidonic acid analogue, EPA, in fish oil. These data demonstrate that inductive mechanisms in collagen arthritis can be altered by diet-induced changes in tissue fatty acid composition without essential fatty acid deficiency. The reason(s) for this effect is unknown, but it is possible that changes in the cyclooxygenase or lipoxygenase products of polyunsaturated fatty acids are involved.
 ...
PMID:Dietary fish oil augments the induction of arthritis in rats immunized with type II collagen. 658 Dec 27

Rheumatoid arthritis (RA) is a heterogeneous disorder with a spectrum of clinical severity ranging from mild arthritis to a crippling joint disease with involvement of internal organs. Carnitine is essential for muscle energy production and is required for the transport of long chain fatty acids and the acyl coenzyme A derivatives across the inner mitochondrial membrane. The levels of malondialdehyde (MDA), an index of lipid peroxidation, and the antioxidants copper-zinc superoxide dismutase (CuZnSOD), glutathione (GSH), ceruloplasmin (CP), catalase (CAT), and carnitine were assessed in 42 patients with RA and 24 control subjects. While plasma carnitine and erythrocyte CuZnSOD levels were significantly lower in the patients with RA compared with the control group (p<0.01 and p<0.001, respectively), the CAT level was not different from controls (p>0.05). Plasma MDA, CP, and erythrocyte GSH levels were significantly higher than in the control group (p<0.001, p<0.001 and p<0.01, respectively). MDA levels showed a positive correlation with CP and GSH levels (r=0.716, p<0.001 and r=0.492, p<0.01, respectively). However, MDA, GSH, and CP demonstrated a negative correlation with carnitine (r=-0.719, p<0.001; r=-0.559, p<0.01, and r=-0.635, p<0.001, respectively) in the patient group but not in controls. There was also a significant positive correlation between CP and GSH levels (r=0.561, p<0.01). However, neither CuZnSOD nor CAT levels demonstrated correlation withcarnitine, MDA, GSH, or CP levels. It was interesting that CAT activity was not altered and CuZnSOD activity decreased when compared with the control group. These results suggest that while CP, MDA and GSH levels increased, carnitine and CuZnSOD levels decreased, but CAT activity was unchanged.
 ...
PMID:Carnitine and antioxidants levels in patients with rheumatoid arthritis. 985 15

Tissue lipogenesis is variably controlled by substrate supply and hormones. The possibility that nitric oxide (NO) might regulate lipogenesis derives from the action of NO on coenzyme A (CoA) to produce metabolically inactive S-nitrosoCoA. The effect of the nitric oxide donor S-nitrosoglutathione (GSNO) on long chain fatty acid and cholesterol synthesis was measured in isolated cultured rat hepatocytes. [1-14C] Butyrate was used as substrate to measure 14C incorporation into lipids as butyrate is twice as effective as acetate in hepatic lipogenesis and is ketogenic via the Lynen cycle. NO very significantly (P < 0.01) impaired long chain fatty acid and cholesterol synthesis an observation dependent upon time of exposure (3 h pre-incubation or 6 h continuous exposure) and concentration of GSNO (500 microM to 2.0 mM). Decrease in hepatic lipogenesis was paralleled by decrease in ketogenesis. ATP levels remained unchanged following short-term exposure to GSNO. Exposure of hepatocytes to GSNO together with 2.0 mM glutathione significantly diminished the inhibition of lipogenesis induced by GSNO alone. Impairment of lipogenesis by GSNO appears not to be limited by energy supply and now adduced, but not proven, to be operative via the degree of inactivation of cytosolic CoA. NO control of lipogenesis could be clinically important where NO production is increased as in demyelinating diseases, chronic arthritis or colitis and in wasting diseases such as AIDS.
 ...
PMID:Inhibition of hepatocyte lipogenesis by nitric oxide donor: could nitric oxide regulate lipid synthesis? 1499 78

Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the sigma(B) and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids.
 ...
PMID:The Staphylococcus aureus response to unsaturated long chain free fatty acids: survival mechanisms and virulence implications. 1918 15