Burden and Disease Characteristics of Psoriatic Arthritis at a Tertiary Center.

BACKGROUND: Psoriatic arthritis (PsA) has a detrimental influence on the quality of life (QoL). The goal of this study was to evaluate the QoL of patients with PsA and its determinants at the King Abdulaziz University Hospital in Jeddah, Saudi Arabia. METHODS:  A cross-sectional study was conducted on 60 PsA patients. A questionnaire was used to collect data about their demographics. Assessment of health-related quality of life (HRQOL) was done by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and the FACIT-General (FACIT-G) scales were used to assess fatigue. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity. RESULTS: The mean age of the patients was 50.33 ± 11.15 years and 78.3% were females. The mean HRQOL, FACIT-G, FACIT, and BASDAI scores were 59.99 ± 34.67, 28.18 ± 5.95, 20.01 ± 9.68, and 4.05 ± 2.54, respectively. The HRQOL scores were found to have a highly significant negative correlation with both the FACIT and BASDAI scores, as well as the patients' age and BMI. The FACIT-G scores and the BASDAI scores, as well as the BASDAI scores and the FACIT scores, were found to have a strong positive correlation with age and BMI. CONCLUSION: PsA has a significant detrimental influence on QoL, with a link between QoL and disease activity and fatigue. A greater understanding of QoL issues will help improve the quality of care.

Prevalence of androgen deficiency in chronic spinal cord injury patients suffering from erectile dysfunction.

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVES: To estimate the prevalence of biochemical androgen deficiency in Iranian spinal cord injured men suffering from erectile dysfunction (ED) and to determine factors related to this problem. SETTING: An andrology clinic of a teaching hospital in Tehran. METHODS: Men, 18 years of age and older, with chronic (>2 years) spinal cord injury (SCI) suffering from ED were recruited. Demographic data, hormonal and lipid levels, injury variables and drug history were obtained from the medical records. The relationships between biochemical androgen deficiency (unequivocally low serum testosterone levels) and patient characteristics, injury variables and laboratory data were determined. RESULTS: Out of 319 patients, 32.6% had total testosterone deficiency and 29.1% had biochemical androgen deficiency. Of those with biochemical androgen deficiency, 93.5 and 85.7% had luteinizing hormone (LH) and follicle stimulating hormone (FSH) within or below the normal ranges, respectively. Opioid use, triglyceride (TG) and total cholesterol (TC) were associated with biochemical androgen deficiency. Significant correlations between total testosterone level and sex hormone binding globulin (r=0.3, P<0.001), LH (r=0.2, P=0.02), TC (r=-0.1, P=0.04) and TG (r=-0.3, P<0.001) were found. CONCLUSION: A substantial proportion of our patients with chronic SCI and ED had biochemical androgen deficiency. Opioid use, TG and TC levels were associated with biochemical androgen deficiency in our studied population. Standard screening of androgen deficiency and testosterone replacement therapy are recommended in men with chronic SCI suffering from ED. SPONSORSHIP: Tehran University of Medical Sciences.

Apolipoprotein AII enrichment of HDL enhances their affinity for class B type I scavenger receptor but inhibits specific cholesteryl ester uptake.

Apolipoproteins of high density lipoprotein (HDL) and especially apolipoprotein (apo)AI and apoAII have been demonstrated as binding directly to the class B type I scavenger receptor (SR-BI), the HDL receptor that mediates selective cholesteryl ester uptake. However, the functional relevance of the binding capacity of each apolipoprotein is still unknown. The human adrenal cell line, NCI-H295R, spontaneously expresses a high level of SR-BI, the major apoAI binding protein in these cells. As previously described for murine SR-BI, free apoAI, palmitoyl-oleoyl-phosphatidylcholine (POPC)-AI, and HDL are good ligands for human SR-BI. In vitro displacement of apoAI by apoAII in HDLs or in Lp AI purified from HDL by immunoaffinity enhances their ability to compete with POPC-AI to bind to SR-BI and also enhances their direct binding capacity. The next step was to determine whether the higher affinity of apoAII for SR-BI correlated with the specific uptake of cholesteryl esters from these HDLs. Free apoAII and, to a lesser extent, free apoAI that were added to the cell medium during uptake experiments inhibited the specific uptake of [(3)H]cholesteryl esters from HDL, indicating that binding sites on cells were the same as cholesteryl ester uptake sites. In direct experiments, the uptake of [(3)H]cholesteryl esters from apoAII-enriched HDL was highly reduced compared with the uptake from native HDL. These results demonstrate that in the human adrenal cell line expressing SR-BI as the major HDL binding protein, efficient apoAII binding has an inhibitory effect on the delivery of cholesteryl esters to cells.

Developmental and pharmacological regulation of apolipoprotein C-II gene expression. Comparison with apo C-I and apo C-III gene regulation.

Increased plasma triglyceride concentrations are often observed in metabolic disorders predisposing to coronary heart disease. Among the major determinants of plasma triglyceride metabolism are the apolipoproteins (apos) of the C class, C-I, C-II, and C-III. Whereas physiological concentrations of apo C-II are required for lipolysis of triglycerides by lipoprotein lipase (LPL), overexpression of all 3 C apolipoproteins leads to hypertriglyceridemia. In the present study, we investigated apo C-II gene regulation under conditions associated with profound changes in plasma triglyceride metabolism, ie, during postnatal development and after treatment with the triglyceride-lowering fibrate drugs, and compared its expression to that of apo C-I and apo C-III. Whereas the expression of both apo C-I and apo C-III is low in fetal liver, increases gradually after birth, and attains maximal levels after weaning, apo C-II gene expression is already detectable in the fetal liver, increases rapidly immediately after birth, and remains elevated throughout suckling. Thus, the increased ingestion of lipids during suckling is met by an earlier induction of apo C-II, the obligatory activator for LPL, compared with apo C-III and apo C-I, which antagonize triglyceride catabolism. Treatment of rats with fibrates decreased apo C-II gene expression in the liver, but not in the intestine, whereas apo C-I gene expression did not change. The decrease of liver apo C-II mRNA levels after fenofibrate occurred in a time- and dose-dependent manner and was reversible but appeared less pronounced than the decrease of apo C-III mRNA. Apo C-II mRNA levels were not affected after treatment with BRL49653, a peroxisome proliferator-activated receptor (PPAR)gamma-specific ligand, suggesting that fibrates act on apo C-II expression via PPARalpha. Addition of fenofibric acid to primary rat and human hepatocytes resulted in a decrease of apo C-II expression. In conclusion, fibrates decrease gene expression of apo C-II and apo C-III, but not apo C-I, in rat and human hepatocytes. This decrease of apo C-II and apo C-III gene expression, together with a lowered apo C-III to apo C-II ratio, should result in an improved clearance of triglyceride-rich remnant lipoproteins from plasma, without hampering triglyceride lipolysis by LPL.

Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages.

Peroxisome proliferator-activated receptors (PPARs) have been implicated in metabolic diseases, such as obesity, diabetes, and atherosclerosis, due to their activity in liver and adipose tissue on genes involved in lipid and glucose homeostasis. Here, we show that the PPARalpha and PPARgamma forms are expressed in differentiated human monocyte-derived macrophages, which participate in inflammation control and atherosclerotic plaque formation. Whereas PPARalpha is already present in undifferentiated monocytes, PPARgamma expression is induced upon differentiation into macrophages. Immunocytochemistry analysis demonstrates that PPARalpha resides constitutively in the cytoplasm, whereas PPARgamma is predominantly nuclear localized. Transient transfection experiments indicate that PPARalpha and PPARgamma are transcriptionally active after ligand stimulation. Ligand activation of PPARgamma, but not of PPARalpha, results in apoptosis induction of unactivated differentiated macrophages as measured by the TUNEL assay and the appearance of the active proteolytic subunits of the cell death protease caspase-3. However, both PPARalpha and PPARgamma ligands induce apoptosis of macrophages activated with tumor necrosis factor alpha/interferon gamma. Finally, PPARgamma inhibits the transcriptional activity of the NFkappaB p65/RelA subunit, suggesting that PPAR activators induce macrophage apoptosis by negatively interfering with the anti-apoptotic NFkappaB signaling pathway. These data demonstrate a novel function of PPAR in human macrophages with likely consequences in inflammation and atherosclerosis.

Fish-eye disease: structural and in vivo metabolic abnormalities of high-density lipoproteins.

Fish-eye disease (FED) in humans is characterized by corneal opacities and markedly decreased plasma concentrations of high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) AI, and apo All, but no tendency to precocious atherosclerosis is present. To elucidate this paradox, the structure of HDL, the potential of serum to promote cholesterol efflux from cultured cells, and the in vivo metabolism of HDL were examined in a 53-year-old woman with a FED syndrome in association with a markedly decreased lecithin:cholesterol acyltransferase (LCAT) activity in HDL due to a mutation of the LCAT gene (Arg158 --> Cys). HDLs isolated by ultracentrifugation were small and enriched in unesterified cholesterol and phospholipids at the expense of cholesteryl esters and proteins. The apolipoprotein content showed an enrichment in apo E and apo AIV, whereas apo AI and apo All were dramatically reduced. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting using specific antibodies showed that the apo E was free or covalently bound to apo All. These particles analyzed by electron microscopy were small and round lipoproteins with a size similar to the smallest fraction of normal HDL3. The potential capacity of the serum to promote efflux from the cells was approximately 40% of control serum levels, but FED HDLs were as efficient as control HDLs in promoting cholesterol efflux from cells. To assess the metabolism of HDL apolipoproteins, in vivo apolipoprotein kinetic studies were performed using endogenous labeling techniques in the patient with FED and three control subjects. All subjects were administered D3-labeled leucine by primed constant infusion for up to 10 hours. The fractional synthetic rates (FSRs) of apo AI and apo All in the patient were 0.674 and 0.594 per day, clearly higher than in controls, 0.210 +/- 0.053 and 0.148 +/- 0.014 per day for apo AI and apo All, respectively. Apo AI and apo All production rates in the patient with FED were normal, 11.32 and 2.62 mg/kg x d, respectively, as compared with those in normal subjects, 11.45 +/- 1.23 and 2.68 +/- 0.17 mg/kg x d. These data established that hypoalphalipoproteinemia in FED was caused by marked hypercatabolism of apo AI and apo All. This hypercatabolism could be the consequence of structural abnormalities due to the selective LCAT deficiency. In conclusion, two steps of reverse cholesterol transport, cholesterol efflux and apo-HDL metabolism, appeared particularly efficient. This efficiency could participate in the absence of premature atherosclerosis in FED patients as regards the low HDL level.

Interstitial fluid apolipoprotein A-II: an association with the occurrence of myocardial infarction.

A sample of male patients aged 25-64 years, survivors of myocardial infarction (MI) taken from the Lille MONICA register, and age-matched control subjects from the general population were recruited in Lille and its surroundings in the North of France. Diabetics and subjects taking hypolipidemic drugs were excluded from the analysis, so that 73 MI and 144 control subjects were included. Lipids, apolipoprotein (apo) A-I, apo A-II, apo A-IV and apo B, and apo A-I-containing particles such as lipoproteins containing both apo A-I and apo A-II (LpA-I:A-II) and those containing apo A-I but not apo A-II (LpA-I) were measured in interstitial fluid by applying mild suction, and in plasma. Univariate analysis showed that plasma triglycerides, very low density lipoprotein (VLDL)-cholesterol and apo B were significantly higher, while high density lipoprotein (HDL)-cholesterol, apo A-I, LpA-I and LpA-I:A-II were lower in MI survivors compared to controls after adjustment for age, body mass index (BMI), alcohol and tobacco consumption. In interstitial fluid, cholesterol and apo A-II were higher in MI than in controls before adjustment for covariates. However, after adjustment, triglycerides became significant while cholesterol and apo A-II remained significantly higher in MI, at 43.8 and 7.5 mg/dl, respectively, than in control subjects, at 38.6 and 5.9 mg/dl, respectively. Taking into account only the plasma parameters, the multivariate analysis reveals that triglycerides and apo A-I appear to be independent factors indicative of the presence of a MI. When plasma and interstitial fluid parameters were taken together in the multivariate analysis, the measurement of apo A-II in interstitial fluid increased the level of prediction of MI over the information provided by the plasma parameters. These data raise the possibility that interstitial fluid apo A-II levels may be associated with the occurrence of MI.