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At least 217 records · Page 12Linked to original sources

Long-term moderate magnesium-deficient diet shows relationships between blood pressure, inflammation and oxidant stress defense in aging rats.

Epidemiological and experimental studies have indicated a relationship among aging, dietary Mg, inflammatory stress, and cardiovascular disease. Our aim in the present study was to investigate possible links between dietary Mg, oxidant stress parameters, and inflammatory status with aging in rats. We designed a long-term study in which rats were fed for 22 months with moderately deficient (150 mg/kg), standard (800 mg/kg), or supplemented (3200 mg/kg) Mg diets. Comparisons were made with young rats fed with the same diets for 1 month. Compared to the standard and supplemented diets, the Mg-deficient diet significantly increased blood pressure, plasma interleukin-6, fibrinogen, and erythrocyte lysophosphatidylcholine, particularly in aging rats, it decreased plasma albumin. The impairment of redox status was indicated by increases in plasma thiobarbituric acid reactive substances and oxysterols and an increased blood susceptibility to in vitro free-radical-induced hemolysis. We concluded that Mg deficiency induced a chronic impairment of redox status associated with inflammation which could significantly contribute to increased oxidized lipids and promote hypertension and vascular disorders with aging. Extrapolating to the human situation and given that Mg deficiency has been reported to be surprisingly common, particularly in the elderly, Mg supplementation might be useful as an adjuvant therapy in preventing cardiovascular disease.

Animals↗

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.

Adult↗

Comparative study of the anti-inflammatory effect of two intravenous immunoglobulin preparations manufactured by different processes.

Intravenous immunoglobulin (IVIG) is increasingly used in the treatment of diverse immune-mediated disorders. Since several preparations of IVIG are available for therapy, it is possible that different manufacturing processes might influence clinical efficacy of IVIG. An insight into the mechanisms of action of such different IVIG preparations is therefore necessary that will provide further guidelines for the utility of IVIG preparations in autoimmune and inflammatory diseases. Since endothelial cells (EC) influence the inflammatory process via production of cytokines, chemokines and expression of adhesive molecules, we analyzed the anti-inflammatory effect on EC of two IVIG preparations: caprylated IVIG (IVIG-C) versus solvent/detergent-treated IVIG (IVIG-SD) preparation. We found that both IVIG preparations inhibit in an equivalent manner, the expression of different pro-inflammatory factors such as IL-6, IL-8, GM-CSF, IL-1beta and TNF-alpha and the adhesion molecules ICAM-1 and VCAM-1. Our results thus suggest that the caprylate while inactivating the virus and enhancing the yield of IgG during IVIG formulation, does not modulate the immunomodulatory properties of IVIG at EC level and that the two preparations show similar anti-inflammatory effects.

Caprylates↗

Long-term treatment of atopic dermatitis with pimecrolimus cream 1% in infants does not interfere with the development of protective antibodies after vaccination.

OBJECTIVE: We investigated whether treatment of atopic dermatitis with pimecrolimus cream 1% in infants affects the development of a normal antibody response to vaccinations. METHODS: In all, 91 patients participated in a 1-year, open-label extension to a 1-year double-blind study: 76 used pimecrolimus twice daily at the first signs or symptoms of the disease until clearance for 2 years and 15 only in the second year. Serum concentrations of antibodies against tetanus, diphtheria, measles, and rubella were measured at months 18 and 24. RESULTS: The seropositivity rates of 93.6% for tetanus, 88.6% for diphtheria, 88.5% for measles, and 84.4% for rubella were comparable with those reported in literature. Seropositivity was not significantly affected by the use of pimecrolimus at the time of vaccinations (+/- 28 days). CONCLUSIONS: Treatment of atopic dermatitis with pimecrolimus cream 1% in early childhood does not appear to interfere with the development of a normal immune response to vaccinations.

Administration, Cutaneous↗

Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a two-year study.

OBJECTIVE AND METHODS: The safety and efficacy of treatment with pimecrolimus cream 1% was evaluated for up to 2 years in infants and young children with atopic dermatitis. Ninety-one patients participated in a 1-year, open-label extension to a 1-year double-blind study. Of these, 76 received pimecrolimus for 2 years. Pimecrolimus was applied twice daily at the first signs or symptoms of the disease until clearance. Outcome measures included the incidence of adverse events and the Eczema Area and Severity Index (EASI). RESULTS: No patient discontinued because of adverse events. The incidence of systemic and skin infections did not increase over time. Over the 2-year period, 2 patients experienced an episode of clinically diagnosed eczema herpeticum. In patients receiving pimecrolimus for 2 years, the mean decrease in EASI score from baseline was 68.7% at 3 months and 70.8% at 24 months. CONCLUSION: Treatment with pimecrolimus cream 1% for up to 2 years was well tolerated and resulted in a marked and sustained improvement of atopic dermatitis.

Administration, Cutaneous↗

Acne in recipients of renal transplantation treated with sirolimus: clinical, microbiologic, histologic, therapeutic, and pathogenic aspects.

We evaluated the clinical characteristics of sirolimus-induced acne in 80 recipients of renal transplantation. It developed in 36 of 48 (75%) men and 2 of 32 (6%) women. Lesion locations and clinical, bacteriologic, and histologic features differentiated sirolimus-induced acne from acne vulgaris, but therapeutic management was similar. The main limitation for this study was the absence of a control group without sirolimus. Epidermal growth factor inhibition by sirolimus is a plausible explanation for this acne.

Acne Vulgaris↗

Proceedings of the 4th Georg Rajka International Symposium on Atopic Dermatitis, Arcachon, France, September 15-17, 2005.

The 4th Georg Rajka International Symposium on Atopic Dermatitis presented a comprehensive view of our current understanding and management of atopic dermatitis (AD). These proceedings highlight contributions related to the history of AD doctrines; genetic and epigenetic background; epidemiology; maturation of the immune system; infection and innate-adaptive immunity; epidermal inflammation, including neurogenic inflammation and pruritus; animal models; skin barrier; evidence-based therapy and education programs; prognostic and severity markers; and allergy testing. Several studies in animal models and human subjects point to impaired skin barrier function as a primary defect that facilitates the effect of environmental factors and immune dysregulation found in AD. The new frontier in AD therapy should, in the near future, reflect our better understanding of the skin barrier. The influence of environmental factors on the skin and other epithelial barriers in the perinatal period needs to be better understood to implement appropriate prevention programs.

Animals↗

Tachon's syndrome (suracute back and/or thoracic pain following local injections of corticosteroids). A report of 318 French cases.

OBJECTIVES: To assess the frequency, features, and outcome of excruciating lumbar, dorsal, and/or thoracic pain following injections of local corticosteroids in rare instances. METHODS: A questionnaire mailed to 500 French rheumatologists. RESULTS: Three hundred and eighteen cases were reported by 92 rheumatologists (one event per 8000 injections or 6.5 years of practice), following injections into lumbar epidural space (39%), an upper limb (30%), a lower limb (mostly the heel) (24%), or other locations (7%), of cortivazol (67%), hydrocortisone (25%), betamethasone (7%), or paramethasone (1%). Symptoms occurred 1-5 min (78%) or less than 1 min (22%) after injection, and highly acute axial pain usually lasted for less than 5 min (34%) or 5-15 min (51%). In addition to pain in lumbar (84%) and/or dorsal regions (25%) [often preceded or associated with thoracic pain (36%)], other signs were: anxiety (87%), shortness of breath (64%), facial flushing (64%), diffuse sweating (41%), agitation (29%), transient cough (23%), abdominal pain (20%), transient hypertension (15%), paleness (10%), hypotension (8%), diarrhoea (3%) and headache (3%). None of these patients was known to be allergic, and urticaria developed in only 2%. Outcome was favourable in all cases (even though 4/318 patients were transiently hospitalised) with an overall duration of 25 +/- 71 min. Another injection was performed later in 146/318 cases (46%), but Tachon's syndrome recurred in only 20 of these 146 patients (14%). CONCLUSION: The outcome of this impressive syndrome seems excellent. Tachon's syndrome might be the venous counterpart of Nicolau's syndrome (injection of corticosteroids in an artery).

Adrenal Cortex Hormones↗

Effect of aqueous extract of Ajuga iva supplementation on plasma lipid profile and tissue antioxidant status in rats fed a high-cholesterol diet.

The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL(2)-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney. Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.

Ajuga↗

Changes in serum lipoprotein lipids and their fatty acid compositions and lipid peroxidation in growing rats fed soybean protein versus casein with or without cholesterol.

OBJECTIVE: We compared the effects of diets based on soybean protein and casein supplemented or not supplemented with 0.1% cholesterol on plasma lipoprotein lipid amounts and their fatty acid compositions, lecithin:cholesterol acyl-transferase activity, and lipid peroxidation. METHODS: The composition and concentration of lipid and apolipoprotein in different lipoprotein classes, plasma LCAT activity, and lipid peroxidation were determined in rats fed 20% highly purified soybean protein or casein with or without 0.1% cholesterol for 2 mo. RESULTS: Soybean protein and casein diets with or without cholesterol had similar plasma total cholesterol concentrations. Soybean protein consumption diminished very low-density lipoprotein particle number, as measured by diminished contents of very low-density lipoprotein triacylglycerol, phospholipid, and apolipoprotein-B100. Lecithin:cholesterol acyl-transferase activity was not significantly modified by either protein. The soybean protein diet decreased the linoleate desaturation index (20:4[omega-6]/18:2[omega-6]) in liver and high-density lipoprotein fraction 2-3-phospholipids but enhanced red blood cell resistance against free radical attack. Addition of cholesterol to both protein diets decreased concentrations of high-density lipoprotein fraction 2-3 cholesterol. Lecithin:cholesterol acyl-transferase activity tended to be greater after cholesterol feeding, likely due to the enhanced high-density lipoprotein fraction 2-3 apolipoprotein-AI, a cofactor activator for lecithin:cholesterol acyl-transferase. Regardless of dietary protein source, cholesterol supplementation decreased the linoleate desaturation index in liver and plasma lipoprotein lipids and red blood cell resistance to free radical attack. CONCLUSIONS: Our results suggest that the dietary protein origin affects lipid peroxidation and polyunsaturated fatty acid biosynthesis and distribution among liver and different lipoprotein lipid classes, but plays only a minor role in the regulation of plasma and lipoprotein cholesterol concentrations. Providing dietary cholesterol (0.1%) with casein or soybean protein attenuates the effects of these proteins, with the exception of plasma cholesterol.

Animals↗

Changes in lipid metabolism and antioxidant defense status in spontaneously hypertensive rats and Wistar rats fed a diet enriched with fructose and saturated fatty acids.

OBJECTIVE: Larger doses of fructose and saturated fat have been associated with oxidative stress and development of hypertension. The effects of modest amounts of fructose and saturated fatty acids on oxidative stress are unknown. METHODS: To increase knowledge on this question, 10-wk-old spontaneously hypertensive rats and Wistar rats were fed for 8 wk with a control diet or an experimental diet enriched with fructose (18%) and saturated fatty acids (11%; FS diet). The total antioxidant status of organs and red blood cells was assayed by monitoring the rate of free radical-induced red blood cell hemolysis. Sensitivity of very low-density lipoprotein and low-density lipoprotein (VLDL-LDL) to copper-induced lipid peroxidation was determined as the production of thiobarbituric acid-reactive substances. Antioxidant enzymes and vitamins were also measured to establish the oxidative stress effect. RESULTS: The FS diet did not affect blood pressure in either strain, but it increased plasma insulin concentrations only in Wistar rats without affecting those of glucose of either strain. The FS diet significantly enhanced plasma and VLDL-LDL triacylglycerol concentrations without affecting concentrations of VLDL-LDL thiobarbituric acid-reactive substances. The decreased content of arachidonic acid and total polyunsaturated fatty acids in VLDL-LDL by the FS diet may have prevented lipid peroxidation in this fraction. Moreover, FS consumption by both strains was accompanied by a significant increase in total antioxidant capacity of adipose tissue, muscle, heart, and liver. This may have resulted from increased tissue ascorbic acid levels and glutathione peroxidase and glutathione reductase activities in tissues. CONCLUSIONS: These findings clearly indicate that the FS diet did not alter blood pressure of spontaneously hypertensive rats and Wistar rats. The FS diet resulted in hypertriglyceridemia but increased the total antioxidant status, which may prevent lipid peroxidation in these rats.

Animals↗

Fructose-enriched diet modifies antioxidant status and lipid metabolism in spontaneously hypertensive rats.

OBJECTIVE: High-fructose consumption in industrial countries has been shown to induce metabolic abnormalities or syndrome X. Changes in antioxidant defense are unknown in hypertension associated with metabolic disorders induced by high-fructose feeding. METHODS: Twenty spontaneously hypertensive rats were assigned to one of two groups; one received a fructose-enriched diet (60% fructose) and the other a starch diet. After a 13-wk diet period, total antioxidant status was assessed in the blood and liver by monitoring the rate of free radical-induced red blood cell hemolysis. Antioxidants (enzymes and vitamins) were determined in blood and liver. Gene expression of antioxidant enzymes (copper/zinc superoxide dismutase and glutathione peroxidase) were also investigated in hepatic tissue. RESULTS: Fructose-fed rats showed blood pressure values similar to that of control rats but had increased glycemia and insulinemia. The antioxidant capacity in the blood of the fructose-fed group represented by copper/zinc superoxide dismutase and glutathione peroxidase activities and ascorbic acid was lower. However, the fructose diet enhanced the total antioxidant capacity of liver correlated with increased antioxidant enzyme activities and retinol concentrations. Gutathione peroxidase mRNA expression was decreased in livers of spontaneously hypertensive rats fed the fructose diet. CONCLUSION: Fructose feeding negatively affects antioxidant capacity in the blood of hypertensive rats but improves this capacity in the liver.

Animals↗

Five labdane diterpenoids from the seeds of Aframomum zambesiacum.

Five labdane diterpenoids, (3-5), zambesiacolactone A (7) and zambesiacolactone B (8), were isolated from the seeds of Aframomum zambesiacum (Baker) K. Schum., along with five known labdanes and a linear sesquiterpene, nerolidol. Their structures were elucidated by spectroscopic analysis. Their antiplasmodial activity was evaluated in vitro against Plasmodium falciparum. Compound 3 was the most active with an IC(50) value of 4.97 microM.

Animals↗

Tyrosine phosphatase MptpA of Mycobacterium tuberculosis inhibits phagocytosis and increases actin polymerization in macrophages.

Protein tyrosine phosphatases from several microorganisms have been shown to play a role as virulence factors by modifying the phosphorylation/dephosphorylation equilibrium in cells of their host. Two tyrosine phosphatases, MptpA and MptpB, secreted by Mycobacterium tuberculosis, have been identified. Expression of MptpA is upregulated upon infection of monocytes, but its role in host cells has not been elucidated. A eukaryotic expression vector containing the mptpA cDNA has been transfected into macrophages. We report that MptpA reduced phagocytosis of mycobacteria, opsonized zymosan or zymosan, but had no effect on phagocytosis of IgG-coated particles. We also noted that the presence of F-actin at the surface of phagosomes containing opsonized zymosan was significantly increased in cells expressing MptpA. In the presence of recombinant MptpA, the process of actin polymerization at the surface of isolated phagosomes was increased; this was not the case in the presence of the phosphatase-dead mutant MptpA(C11S). MptpA had no effect when IgG-coated particles were present inside isolated phagosomes. These results indicate that, like other tyrosine phosphatases of pathogens, MptpA plays a role in phagocytosis and actin polymerization. However, MptpA had no effect on IgG particles, suggesting that its putative substrate(s) is not linked to the signaling pathways of Fcgamma receptors.

Actins↗

Dynamic modes of the cortical actomyosin gel during cell locomotion and division.

Tight regulation of the contractility of the actomyosin cortex is essential for proper cell locomotion and division. Enhanced contractility leads, for example, to aberrations in the positioning of the mitotic spindle or to anomalous migration modes that allow tumor cells to escape anti-dissemination treatments. Spherical membrane protrusions called blebs occasionally appear during cell migration, cell division or apoptosis. We have shown that the cortex ruptures at sites where actomyosin cortical contractility is increased, leading to the formation of blebs. Here, we propose that bleb formation, which releases cortical tension, can be used as a reporter of cortical contractility. We go on to analyze the implications of spontaneous cortical contractile behaviors on cell locomotion and division and we particularly emphasize that variations in actomyosin contractility can account for a variety of migration modes.

Actomyosin↗

Efficient priming of simian/human immunodeficiency virus (SHIV)-specific T-cell responses with DNA encoding hybrid SHIV/hepatitis B surface antigen particles.

Recent efforts to design an human immunodeficiency virus type 1 (HIV-1) vaccine candidate have focused on means of eliciting anti-viral T-cell responses. We tried to improve the immunogenicity of DNA vaccines by designing hybrid DNA constructs encoding hepatitis B surface antigen (HBsAg) fused to antigenic domains of simian/human immunodeficiency virus (SHIV 89.6P). Immunisation with hybrid DNA induced both effector and long-lasting precursor T-cells. Following boosting with a recombinant modified vaccinia Ankara (rMVA) producing full-length SIV and HIV antigens, it appeared that priming with hybrid DNA had increased virus-specific T-cell responses in terms of both the number of virus-specific IFN-gamma-secreting T-cells and virus-specific lymphoproliferation. After intrarectal challenge with SHIV 89.6P, immunised animals demonstrated early control of SHIV 89.6P replication and stable CD4+ T-cell counts.

AIDS Vaccines↗