Current Drug-Scams News Results

Effect of etanercept on serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor in patients with rheumatoid arthritis.

Scand J Rheumatol. 2009 Nov-Dec; 38(6): 439-44
Klimiuk PA, Sierakowski S, Domyslawska I, Chwiecko J

OBJECTIVE: Endothelium and adhesion molecules are engaged in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to analyse the effect of etanercept on the levels of soluble cell adhesion molecules (sCAMs) and vascular endothelial growth factor (VEGF) in patients with active RA. METHODS: Patients were receiving 50 mg/week of subcutaneous etanercept and 10-25 mg/week of methotrexate (MTX). Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 18 RA patients (prior to injection) at 0, 3, 6, 9, and 12 months. RESULTS: A decrease in serum levels of sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01), and VEGF (p<0.001) was observed in RA patients after 3 months of treatment with etanercept. Six months of therapy with etanercept prolonged the suppression of serum sICAM-1 (p<0.01) and even more remarkably diminished sVCAM-1, sE-selectin, and VEGF (in all cases p<0.001) concentrations as compared to baseline (month 0). Treatment also effectively diminished sICAM-1, sVCAM-1, and VEGF levels at months 9 and 12 (in all cases p<0.001), and less significantly sE-selectin (p<0.05 at month 9 and p<0.01 at month 12). The Disease Activity Score including a 28-joint count (DAS28) measured at 3, 6, 9, and 12 months decreased significantly compared to baseline (in all cases p<0.001). CONCLUSION: Our study shows that, besides a rapid suppression of disease activity, serum sCAM and VEGF concentrations are downregulated following anti-tumour necrosis factor alpha (TNFalpha) therapy combined with MTX. Prolonged treatment with etanercept sustained or even more remarkably diminished the sCAM and VEGF serum concentrations.

Immune activation in advanced cancer patients treated with recombinant IL-21: multianalyte profiling of serum proteins.

Cancer Immunol Immunother. 2009 Jun; 58(6): 843-54
Dodds MG, Frederiksen KS, Skak K, Hansen LT, Lundsgaard D, Thompson JA, Hughes SD

PURPOSE: Recombinant interleukin-21 (rIL-21) is an immune stimulating cytokine recently tested in two Phase 1 trials for immune responsive cancers. A secondary objective of these trials was to characterize pharmacodynamic responses to rIL-21 in patients. Here, we report the effects of systemic rIL-21 on serum markers of immune stimulation. EXPERIMENTAL DESIGN: Recombinant IL-21 was administered by intravenous bolus injection at dose levels from 1 to 100 microg/kg using two distinct treatment regimens: thrice weekly ('3/w') for 6 weeks; or once daily for five consecutive days followed by nine dose-free days ('5 + 9'). In the absence of dose limiting toxicity, additional cycles of dosing were initiated immediately following the nine dose-free days. An array of 70 different proteins was profiled in subject serum samples from several time points during the course of the study. Hierarchical clustering analysis was performed on a normalized subset of these data. RESULTS: Systemic administration of rIL-21 affected the serum levels of several cytokines, chemokines, acute-phase proteins and cell adhesion proteins. The magnitude and duration of response were dose dependent for a subset of these biomarkers. The 5 + 9 dosing regimen generally produced cyclic changes that were of greater magnitude, as compared to a more chronic stimulation with the 3/w dosing regimen. Despite these differences, rIL-21 effects on many analytes were similar between regimens when averaged over the time of treatment. Based on similar temporal, between-subject and dose response changes, groups of analytes were identified that exhibited distinct components of the rIL-21-mediated immune activation. Biomarkers indicative of lymphocyte activation (increased IL-16, decreased RANTES), acute phase response (increased CRP, ferritin), myeloid activation (increased MDC, MIP-1 alpha), and leukocyte chemotaxis/trafficking (increased sCAMs, MCP-1) were strongly modulated in subjects treated with rIL-21. CONCLUSIONS: Administration of rIL-21 resulted in activation of multiple cell types and immune response pathways. The changes observed in serum proteins were consistent with coincident processes of lymphoid and myeloid cell activation and trafficking, and acute phase response.

Calcium-dependent and -independent binding of soybean calmodulin isoforms to the calmodulin binding domain of tobacco MAPK phosphatase-1.

J Biol Chem. 2007 Mar 2; 282(9): 6031-42
Rainaldi M, Yamniuk AP, Murase T, Vogel HJ

The recent finding of an interaction between calmodulin (CaM) and the tobacco mitogen-activated protein kinase phosphatase-1 (NtMKP1) establishes an important connection between Ca(2+) signaling and the MAPK cascade, two of the most important signaling pathways in plant cells. Here we have used different biophysical techniques, including fluorescence and NMR spectroscopy as well as microcalorimetry, to characterize the binding of soybean CaM isoforms, SCaM-1 and -4, to synthetic peptides derived from the CaM binding domain of NtMKP1. We find that the actual CaM binding region is shorter than what had previously been suggested. Moreover, the peptide binds to the SCaM C-terminal domain even in the absence of free Ca(2+) with the single Trp residue of the NtMKP1 peptides buried in a solvent-inaccessible hydrophobic region. In the presence of Ca(2+), the peptides bind first to the C-terminal lobe of the SCaMs with a nanomolar affinity, and at higher peptide concentrations, a second peptide binds to the N-terminal domain with lower affinity. Thermodynamic analysis demonstrates that the formation of the peptide-bound complex with the Ca(2+)-loaded SCaMs is driven by favorable binding enthalpy due to a combination of hydrophobic and electrostatic interactions. Experiments with CaM proteolytic fragments showed that the two domains bind the peptide in an independent manner. To our knowledge, this is the first report providing direct evidence for sequential binding of two identical peptides of a target protein to CaM. Discussion of the potential biological role of this interaction motif is also provided.

Thieves target Medicare plan. New drug plan invites scams, state officials say.

S C Nurse. 2006 Jan-Mar; 13(1): 27
Osby L

The unbearable lightness of "light" cigarettes: a comparison of smoke yields in six varieties of Canadian "light" cigarettes.

Can J Public Health. 2005 May-Jun; 96(3): 167-72
Gendreau PL, Vitaro F

BACKGROUND: Labelling cigarettes as "light" or "mild" is claimed to be one of the biggest marketing scams in Canadian history. Arguably, such labelling implies that these varieties of cigarettes are less harmful than "regular" cigarettes. In Canada, a food product can be labelled "light" if there is a 25% reduction from the "reference food" and if the constituent being reduced is clearly identified (e.g., light in fat). Cigarette labelling does not comply with these regulations, however. To examine whether or not some tobacco constituents meet the 25% reduction criterion, we compared yields of 41 toxic and/or carcinogenic smoke constituents in six varieties of "light" cigarettes to the yields of "regular" cigarettes. We selected cigarettes from the two most popular Canadian brands, Du Maurier and Players. METHODS: Using a set of data provided by Imperial Tobacco Canada and made available to the public by the Government of British Columbia, we compared yields measured under a laboratory protocol (modified ISO) that was designed to provide a more rigorous evaluation of the differences between varieties of cigarettes and a more accurate assessment of smokers' potential smoke intake than the traditional protocol (standard ISO). FINDINGS: For all six varieties of "light" cigarettes, the yields of nicotine were higher by an average of 5% (range: 1% to 13%). The 25% reduction criterion was not met for any variety of "light" cigarettes concerning yields of tar. For all cigarettes tested, yields of tar were reduced on average by only 16% (range: 5% to 22%). For carbon monoxide (CO), only Player's Smooth Light had an over 25% reduction (30%) compared with Player's Regular. Conversely, yield of CO was 24% higher for Du Maurier Lights compared with Du Maurier Regular. As for the other smoke constituents, the majority (75%) were not reduced by 25% or more in "light" cigarettes, and a sizeable proportion of yields (e.g., acrylonitrile, benzene, chromium, m+p cresol, mercury, nickel, toluene) were larger in these varieties of cigarettes. Only yields of formaldehyde, crotonaldehyde, 1-aminonaphtalene, and proprionaldehyde were systematically reduced in all varieties of "light" cigarettes. CONCLUSION: The six varieties of "light" cigarettes examined in this study do not differ substantially from "regular" cigarettes in terms of smoke yields. We argue that the modified ISO protocol should be implemented for a more valid comparison of potential smoke yields in all varieties of cigarettes and that labelling based on this protocol should be promoted.

Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids.

Nutr Metab Cardiovasc Dis. 2004 Aug; 14(4): 180-5
Eschen O, Christensen JH, De Caterina R, Schmidt EB

BACKGROUND AND AIM: Long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against atherosclerotic disease, and serum levels of soluble cellular adhesion molecules (sCAMs) possibly reflect the inflammatory process underlying atherosclerosis. We studied the effect of n-3 PUFA dietary supplementation on the serum levels of sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), and the correlation between sCAMs and the fatty acid composition of granulocyte membranes. METHODS AND RESULTS: Sixty healthy volunteers were randomly assigned to receive a daily supplement of n-3 PUFA 6.6 g, n-3 PUFA 2.0 g, or olive oil for 12 weeks in a double blind design. A significant negative correlation was found between serum sICAM-1 levels and the DHA content of granulocyte membranes at entry. After supplementation with 6.6 g of n-3 PUFA, there was a significant decrease only in sP-selectin, which a gender subanalysis showed to be more marked in men. Among the women, there was a significant decrease in sICAM-1 in the PUFA 2.0 g group and a significant increase in sVCAM-1 in the PUFA 6.6 g group. CONCLUSIONS: The results indicate that high-dose supplementation with n-3 PUFA decreases sP-selectin levels in healthy subjects, thus suggesting a decrease in platelet reactivity or endothelial activation. However, the effect of n-3 PUFA on sCAMs is complex and may depend on gender and n-3 PUFA dose.

Cell adhesion molecules as a marker reflecting the reduction of endothelial activation induced by glucocorticoids.

Shock. 2004 Apr; 21(4): 311-4
Leone M, Boutière-Albanèse B, Valette S, Camoin-Jau L, Barrau K, Albanèse J, Martin C, Dignat-George F

In vitro, steroids down-regulate the expression of cell adhesion molecules (CAMs) in endothelial cells stimulated by lipopolysaccharide. Low-dose hydrocortisone is a new treatment of patients with septic shock, a state that is characterized by an endothelial injury. The aim of the present study was to investigate whether the plasma levels of soluble CAMs, reflecting in vivo endothelial activation, could be modulated in patients with septic shock treated by hydrocortisone. This was a prospective and observational study conducted in the intensive care unit at a university hospital. The subjects included 40 patients with septic shock (American College of Chest Physicians Consensus Conference/Society of Critical Care Medicine definition); 45 healthy blood donors served as controls. The patients receiving the standard care ("reference group") during the first 6 months were compared with the patients receiving the hydrocortisone therapy ("hydrocortisone group") for the next 6 months. Measurements of sCAMs were performed on days 1 and 3 of the disease. On day 1, sE-selectin, sP-selectin, sVCAM-1, and sICAM-1 were significantly elevated in patients with septic shock compared with healthy donors. sE-selectin levels significantly decreased between days 1 and 3 in the "hydrocortisone group," whereas there was no significant change in the "reference group". Surprisingly, sICAM-1 levels significantly increased between days 1 and 3 only in patients treated by hydrocortisone. No significant changes were observed for sP-selectin and sVCAM-1 levels in the two groups. In patients with septic shock, glucocorticoids differently affected the pattern of evolution of sCAMs, with sE-selectin being decreased and sICAM-1 being increased. Expression of sP-selectin and sVCAM-1 was not affected.

Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects.

Cardiovasc Res. 2003 Feb; 57(2): 563-71
van Dam B, van Hinsbergh VW, Stehouwer CD, Versteilen A, Dekker H, Buytenhek R, Princen HM, Schalkwijk CG

OBJECTIVE: In a combination of in vivo and in vitro studies, we investigated mechanisms via which alpha-tocopherol, a lipid soluble form of vitamin E, can directly affect endothelial activation as induced by H(2)O(2) and TNFalpha. METHODS: We measured effects of alpha-tocopherol on H(2)O(2)-induced lipid peroxidation as determined with a fluorescent C-11 BODIPY(581/591) probe and on adhesion molecule expression in cultured endothelial cells. In 20 healthy volunteers treated with increasing doses of alpha-tocopherol up to 800 IU/ml for 12 weeks, plasma levels of soluble cell adhesion molecules (sCAMs) and C-reactive protein were measured. RESULTS: We showed that alpha-tocopherol protects cultured endothelial cells against H(2)O(2)-induced lipid peroxidation, while TNFalpha did not induce lipid peroxidation. Moreover, alpha-tocopherol attenuated H(2)O(2)-, but not TNFalpha-induced increases in adhesion molecule expression. In healthy persons, alpha-tocopherol decreased plasma levels of sE-selectin from 65+/-6 to 60+/-6 ng/ml (P=0.002), sVCAM from 893+/-31 to 853+/-23 ng/ml (P=0.022), and sICAM from 483+/-21 to 463+/-16 ng/ml (P=0.048). C-Reactive protein, as a sensitive marker of low grade inflammation, was not significantly affected. CONCLUSION: alpha-Tocopherol specifically inhibits lipid peroxidation-induced endothelial activation in vitro. The observed vitamin E-induced decrease in sCAMs in control subjects suggests that lipid peroxidation can take place in healthy individuals. Although vitamin E supplementation may be especially effective in specific groups of patients exposed to increased oxidative stress, our study suggests that vitamin E supplementation can be of benefit in healthy individuals as well.

Watch out for these drug scams.

Med Econ. 2002 Mar 8; 79(5): 81-4
Egerton J

Reduced levels of TNF alpha in hypercholesterolemic individuals after treatment with pravastatin for 8 weeks.

Atherosclerosis. 2001 Aug; 157(2): 411-5
Solheim S, Seljeflot I, Arnesen H, Eritsland J, Eikvar L

BACKGROUND: cellular adhesion molecules (CAMs) expressed on the endothelial surface play a key role in the inflammatory process of atherosclerosis, and increased expression of CAMs has been shown in hypercholesterolemic individuals. The expression of CAMs is mediated by several cytokines including tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6). The aim of the present study was to assess the influence of pravastatin 40 mg per day on selected soluble CAMs; intercellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), E-selectin, P-selectin and some circulating markers of inflammation; C-reactive protein (CRP) and the cytokines TNF alpha and IL-6. 40 non-diabetic men, age below 70 years, with serum total cholesterol 6--10 mmol/l combined with HDL-cholesterol < or =1.2 mmol/l were included. The study was randomized, double blinded, placebo controlled, cross over designed with 8 weeks intervention periods. Fasting blood samples were drawn after 8 and 16 weeks. RESULTS (MEDIAN VALUES): significant reduction of total cholesterol was achieved after treatment with pravastatin (7.8 on placebo vs. 5.7 mmol/l on pravastatin). TNF alpha was significantly reduced after treatment with pravastatin (1.33 on placebo vs. 1.10 pg/ml on pravastatin, P=0.032), whereas no differences in the levels of the measured sCAMs, CRP and IL-6 were found. Subgroup analysis among smokers versus non-smokers showed a significant reduction in the level of TNF alpha only among the smokers. CONCLUSION: hypercholesterolemic individuals treated with pravastatin 40 mg per day for 8 weeks showed a statistically significant reduction in the levels of TNF alpha as compared with placebo.

Circulating levels of soluble E-selectin, ICAM-1 and VCAM-1 in bullous pemphigoid during low-dose methotrexate therapy. A prospective study.

Exp Dermatol. 2000 Oct; 9(5): 336-40
Dahlman-Ghozlan K, Heilborn JD, Stephansson E

Soluble iso-forms of cellular adhesion molecules (sCAMs) have been described and reported to be elevated in various inflammatory diseases. Elevated levels of sE-selectin have recently been detected and found to correlate with the number of blisters in bullous pemphigoid (BP) during oral corticosteroid therapy. In this prospective study we analysed levels of sCAMs in 10 elderly BP patients during low-dose oral pulse methotrexate monotherapy. We used standardised ELISA kits for soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin on 65 sera from 10 patients and 19 controls. Results were correlated with clinical parameters. Before therapy, we found significant elevation of sE-selectin (P=0.004) and sVCAM-1 (P=0.002) but not of sICAM-1. sE-selectin levels decreased during the efficient therapy and correlated with the number of blisters. Our results further support the proposition that sE-selectin might be a future clinical and predictive tool; but whether the elevation of sVCAM-1 also might reflect the disease activity in BP needs more investigation. The findings also indicate that BP might be more a cellularly mediated disease where interactions of different adhesion molecules play a crucial role.

Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation.

Circulation. 2000 Jul 11; 102(2): 191-6
Devaraj S, Jialal I

BACKGROUND: Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects. Thus, we tested whether (1) postsecretory modifications of LDL (glycation and oxidation), monocyte proatherogenic activity, and circulating levels of soluble cell adhesion molecules (sCAMs) are more pronounced in DM2-MV than in DM2 and control subjects and (2) RRR-alpha-tocopherol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group). METHODS AND RESULTS: Although LDL glycation was increased in both diabetic groups compared with control subjects, AT therapy had no significant effect on glycation. AT therapy significantly decreased LDL oxidizability in all 3 groups. Diabetic monocytes released significantly more superoxide anion (O(2)(-)) and interleukin-1beta (IL-1beta) and exhibited greater adhesion to endothelium than control subjects. AT therapy significantly decreased the release of O(2)(-), IL-1beta, tumor necrosis factor-alpha, and monocyte-endothelium adhesion in all 3 groups. There was no significant difference between the 2 diabetic groups for any of the above parameters. sICAM levels were significantly elevated in both diabetic groups compared with controls. AT therapy resulted in a significant decrease in sCAMs. CONCLUSIONS: This is the first demonstration of increased IL-1beta secretion and increased adhesion of monocytes to endothelium from normotriglyceridemic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.

South African public sceptical about new AIDS "cure".

BMJ. 1999 Mar 20; 318(7186): 757
Sidley P

Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion.

Arterioscler Thromb Vasc Biol. 1998 May; 18(5): 723-31
Abe Y, El-Masri B, Kimball KT, Pownall H, Reilly CF, Osmundsen K, Smith CW, Ballantyne CM

Hypertriglyceridemia may contribute to the development of atherosclerosis by increasing expression of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as markers for CAMs. In this study, we examined the association between sCAMs and other risk factors occurring with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels, and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhesion in vitro. Compared with normal control subjects (n=20), patients with hypertriglyceridemia and low HDL (n=39) had significantly increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316+/-28.8 versus 225+/-16.6 ng/mL), sVCAM-1 (743+/-52.2 versus 522+/-43.6 ng/mL), and soluble E-selectin (83+/-5.9 versus 49+/-3.6 ng/mL). ANCOVA showed that the higher sCAM levels in patients occurred independently of diabetes mellitus and other risk factors. In 27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for > or =7 months, triglyceride level was reduced by 47+/-4.6%, sICAM-1 level was reduced by 9+/-3.4% (P=.02), and soluble E-selectin level was reduced by 16+/-3.2% (P<.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that disorders in triglyceride and HDL metabolism influence CAM expression and treatment with fish oils may alter vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1 at the concentration seen in patients significantly inhibited adhesion of monocytes to interleukin-1-stimulated cultured endothelial cells under conditions of flow by 27.5+/-7.2%. Thus, elevated sCAMs may negatively regulate monocyte adhesion.

Defrauding AIDS patients: federal felony statute may be necessary to curb multiplying scams.

Healthspan. 1993 Jul-Aug; 10(7): 14-6
Margolis RE