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A new approach to encapsulating nonsteroidal anti-inflammatory drugs. III. Coating acidic as well as basic nonsteroidal anti-inflammatory drugs with cellulose derivatives having different functional groups.

Acidic and basic nonsteroidal anti-inflammatory drugs were encapsulated with cellulose derivatives having different functional groups, acidic (carboxymethyl cellulose), basic (chitosan), and neutral (hydroxypropylmethyl cellulose). The properties of the microcapsules were studied and the interaction of the drugs with chitosan was assessed.

Anti-Inflammatory Agents, Non-Steroidal↗

Nutritional modulation of the inflammatory response in inflammatory bowel disease--from the molecular to the integrative to the clinical.

Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD). Both total parenteral and enteral nutrition provide important supportive therapy for IBD patients, but in adults these are not useful for primary therapy. Dietary intervention with omega-3 polyunsaturated fatty acids contained in fish oil may be useful for the care of IBD patients, and recent studies have stressed the role of PPAR on NFkappaB activity on the potential beneficial effect of dietary lipids on intestinal function.

Enteral Nutrition↗

[Pharmacological study of 9 alpha-fluoro-11 beta, 17, 21-trihydroxy-16 beta-methylpregna-1, 4-diene-3,20-dione-17-benzoate (betamethasone-17-benzoate, MS-1112), a local anti-inflammatory agent. (1). Its anti-inflammatory and other pharmacological properties].

The anti-inflammatory activity and the other pharmacological properties of MS-1112, a new steroid compound, were examined and compared with other glucocorticoid analogues such as hydrocortisone acetate (Hydr), betamethasone 17-valerate (Val) and dexamethasone (Dexa). Systemically administered MS-1112 and glucocorticoids had a significant effect in inhibiting rat paw edema induced by various phlogistic stimulations and increasing vascular permeabilities and granuloma formation by cotton pellet or granuloma pouch. The order of those inhibiting activity was, in general, Dexa greater than MS-1112 greater than Val greater than Hydr. Concomitantly, Xthymolysis and adrenal weight suppression and reduced rate of body weight gain after multiple systemical administration were also observed. Locally administered MS-1112 caused an inhibiting activity, without systemic side-effects. This activity was approximately 3 to 5 times more potent than that of Dexa in rat carrageenin paw edema and cotton pellet granuloma. MS-1112 was less active than Dexa in glycogen liver deposition activity and in the depression of plasma level of corticosterone but more active than Val and Hydr. In the dose administered, MS-1112 had neither androgenic and anabolic nor estrogenic and anti-estrogenic activity. From this data, it concluded that MS-1112 is a very potent agent applicable regarding permeability and retention of steroids in a local site.

Administration, Topical↗

[Recent aspects of acute and chronic inflammatory polyneuropathies: Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy].

INTRODUCTION: In last decade many advances have occurred in knowledge of pathogenic, in the different types of clinic expression and in the therapy of both acute and chronic polyneuritis. OBJECTIVE: To review the recent advances in the childhood expression of these disorders. DEVELOPMENT AND CONCLUSIONS: Into the broad term of Guillain-Barré syndrome (GBS) several types are considered: demyelinating, motor sensory axonal and motor axonal, and the Miller Fisher syndrome (MFS). Diagnostic criteria, clinical and neurophysiological are explained. The actual modes of treatment are reviewed, especially immunoglobulins and plasmapheresis. The chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disease in childhood but it is necessary think on it when a picture of demyelinating polyneuropathy that seems the more frequent Charcot Marie Tooth type 1 polyneuropathy, because the treatment of CIDP changes radically the prognosis. Last advances of pathogenic, diagnostic criteria and treatment with corticosteroids, immunoglobulins and plasmapheresis are reviewed.

Guillain-Barre Syndrome↗

Anti-inflammatory and combined anti-inflammatory/analgesic medication in the early management of iliotibial band friction syndrome. A clinical trial.

Forty-three athletes presenting with unilateral iliotibial band friction syndrome (ITBFS) were randomly divided into three groups for the first 7 days of treatment (placebo-controlled, double-blind): 1--placebo (N = 13); 2--anti-inflammatory medication (N = 14) (Voltaren; Geigy); and 3--analgesic/anti-inflammatory combined medication (N = 16) (Myprodol; Rio Ethicals). All subjects rested from day 0 to day 7 and all groups received the same physiotherapy outpatient treatment programme from day 3 to day 7. On days 0, 3 and 7 the subjects performed a functional treadmill running test (maximum 30 minutes) during which they reported pain (scale 0-10; 0 = no pain, 10 = unbearable pain) each minute. Total running distance, total running time and the area under the pain v. time curve was calculated. Daily 24-hour recall pain scores were also recorded. The 24-hour recall pain scores decreased significantly for all the groups over the treatment period. This method of assessing efficacy of treatment therefore failed to show differences between groups. In contrast, during the running test only group 3 improved their total running time and distance from day 0 to day 7, whereas in all the groups the area under the pain v. time curve decreased from day 0 to day 7. All the other groups improved total running time and running distance from day 3 to day 7. All three treatment modalities are effective in the early treatment of ITBFS but physiotherapy in combination with analgesic/anti-inflammatory medication is superior.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Studies on phytohemagglutinin-induced peritonitis of mice: dynamics of inflammatory responses and influence of anticomplementary agents and anti-inflammatory drugs.

The intraperitoneal injection of phytohemagglutinin in the mouse resulted in the marked accumulation of leukocytes, especially macrophages, in the peritoneal cavity between 8 and 36 h after the injection. Parallel to the accumulation of macrophages, exudation of plasma proteins into the peritoneal cavity was observed. When the effect of anticomplementary agents (FUT-175 and K-76 COONa) and anti-inflammatory drugs (indomethacin and dexamethasone) on phytohemagglutinin-induced peritonitis was examined, FUT-175, K-76 COONa and indomethacin suppressed only the plasma protein exudation. On the other hand, dexamethasone suppressed both the accumulation of macrophages and the plasma protein exudation.

Animals↗

Production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha by inflammatory granuloma fibroblasts.

The formation of hepatic granulomas around persistently deposited Schistosoma mansoni eggs leads to parenchymal damage, ongoing fibrosis, and ultimate loss of liver function. In this study, the production of macrophage inflammatory protein-1 alpha (MIP-1) and monocyte chemoattractant protein-1 (MCP-1) by granuloma fibroblasts was examined to establish the potential contribution of intragranuloma fibroblasts to the maintenance of the chronic inflammation. Isolated fibroblasts from dispersed acute infection hepatic granulomas were grown in tissue culture for 3 to 4 weeks and used on the third or fourth passage. We initially surveyed fibroblasts for production of MIP-1 and MCP-1 by reverse transcription-polymerase chain reaction (RT-PCR) after stimulation with interleukin (IL)-1, tumor necrosis factor, interferon (IFN)-gamma, IL-4, or IL-10: cytokines found within the granuloma. These studies demonstrated constitutive expression of MCP-1 and differential up-regulation of MIP-1 on cytokine stimulation. Protein expression was then verified by immunohistochemical localization of MIP-1 and MCP-1 in paraformaldehyde-fixed fibroblasts and by direct quantitation of MIP-1 and MCP-1 in culture supernatants by specific ELISAs. These studies demonstrated constitutive expression of MCP-1 in unstimulated and cytokine-stimulated granuloma fibroblasts. In contrast, IL-1 (0.1 to 2.5 ng/ml), IFN-gamma (10 micrograms/ml), and IL-10 (2.5 to 10 ng/ml) were able to induce the significant production of MIP-1 by the granuloma fibroblasts. Interestingly, normal noninflammatory fibroblasts from uninfected mice showed no significant production of MIP-1 or MCP-1 in response to these cytokines. These results suggest that granuloma fibroblasts may be phenotypically altered compared with normal fibroblasts and have a significant role in leukocyte recruitment, granuloma growth, and maintenance of the egg-induced lesion.

Animals↗

Endoscopic ultrasonography in inflammatory bowel disease, paracolorectal inflammatory pathology, and extramural abnormalities.

Endoscopic ultrasound (EUS) is easy to perform, noninvasive, and well tolerated in individuals with inflammatory bowel disease. In the anorectal region, the examination takes minimal preparation and has become a routine procedure in the diagnosis and therapeutic follow-up of malignant and nonmalignant disorders. Topics discussed in this article include techniques, abscesses, and fistulas.

Abscess↗

Malignant inflammatory histiocytoma (inflammatory fibrous histiocytoma): report of a patient with four lesions.

A patient with four subcutaneous inflammatory fibrous histiocytomas is presented. Three of these tumors developed synchronously. The neoplasms were examined by light and electron microscopy and were composed of well differentiated histiocytes, multinucleated histiocytes, and less differentiated cells. The ultrastructural findings support the histiocytic nature of this particular tumor.

Female↗

Inflammatory mediators in chronic inflammatory bowel diseases.

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unknown etiology. They are characterized by an activation of intestinal mononuclear cells. Cytokines play a crucial role in the regulation of the functions of these cells. An increased synthesis of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha), which are primarily synthesized by activated monocytes/macrophages has been described in patients with IBD. The synthesis of interleukin-2 (IL-2) and of interferon gamma (IFN gamma), which are produced by lymphocytes, on the other hand, has been found to be decreased. The published data are, however, not quite consistent. In patients with IBD there is not only a stimulation of the local cytokine production in the gut. The blood levels and the synthesis of the cytokines IL-1, IL-6 and TNF alpha by peripheral blood mononuclear cells are also increased, in particular in patients with Crohn's disease. Drugs, which are commonly used for the treatment of IBD impair the synthesis of these cytokines in monocytes/macrophages.

Colitis, Ulcerative↗

Effects of modulation of inflammatory and immune parameters in patients with rheumatic and inflammatory disease receiving dietary supplementation of n-3 and n-6 fatty acids.

To describe the rationale and status of n-3 and n-6 fatty acid dietary supplementation in patients with inflammatory disease. The most recent literature is reviewed with a focus on rheumatoid arthritis (RA) as most investigations have described the use of n-3 supplements in this disease entity. Investigations from Europe, the United States, and Australia have described consistent improvement in tender joint scores with many investigators also observing improvements in morning stiffness. A meta analysis has confirmed the predictable improvement in tender joints. Recent studies also suggest that some patients with RA are able to discontinue nonsteroidal antiinflammatory drugs (NSAIDs) while receiving n-3 fatty acids. A large number of peer reviewed publications from around the world have established the utility of dietary supplementation with n-3 fatty acids in reducing tender joint counts and morning stiffness in patients with RA. Some patients are also able to discontinue NSAIDs while on these supplements.

Animals↗

[Persistent inflammatory reaction at the injection site of Il-2 with lymphoma-like inflammatory infiltrates].

Interleukin-2 (Il-2) is widely used for treatment of carcinomas, leukemia, and melanoma. Adverse drug effects of Il-2 include various systemic and generalized cutaneous drug reactions. In the following we report on a persistent inflammatory reaction at the injection site of Il-2. A patient received chemoimmuno-therapy for treatment of metastasizing melanoma, including subcutaneous application of recombinant interleukin-2 (Proleukin((R))). Within a few days reddish nodules developed at the injection sites that persisted after cessation of Il-2 injections for two years until final lethal outcome. Histologic examination revealed a lobular panniculitis expressing atypical lymphocytes and multinucleated histiocytes.

Aged↗

Expression of tumor necrosis factor-alpha in regenerating muscle fibers in inflammatory and non-inflammatory myopathies.

The expression level of tumor necrosis factor (TNF)-alpha is elevated in idiopathic inflammatory myopathies and Duchenne muscular dystrophy (DMD), but the precise role of TNF-alpha is unknown. To elucidate the possible role of TNF-alpha, we investigated the expression of TNF-alpha and its receptor in polymyositis (PM), dermatomyositis (DM), and DMD using in situ hybridization (ISH) and immunohistochemistry. We showed that TNF-alpha mRNA and protein were present in muscle fibers. TNF-alpha-positive fibers were observed in all cases of PM, DM and DMD, but were rare or absent in neurogenic disorders and normal controls. The proportion of TNF-alpha-positive fiber showed a significant positive correlation with the proportion of regenerating fibers that were positive for the developmental form of myosin heavy chain (MHC-d). The number of TNF receptor-positive fibers was small. Some muscle fibers expressed both TNF-alpha and its receptor simultaneously. Our results indicate that TNF-alpha is produced and expressed by muscle fibers and associated with muscle regeneration.

Adolescent↗

The expression of P-selectin in inflammatory and non-inflammatory lung tissue.

An initial attachment of leucocytes to blood vessel walls is mediated by selectins. A feature of adhesion mediated by P-selectin is the "rolling" of leucocytes on the endothelium. The time dependent expression of p-selectin in lung tissue was investigated in five groups of cases with different causes of death: carbon-monoxide and cyanide intoxication (n = 11), drowning (n = 5), hanging (n = 9), pneumonia (n = 13) and polytrauma with blunt thorax trauma (n = 14). In paraffin-embedded archival specimens immunostaining was achieved using an adapted APAAP-immunoperoxidase technique together with a wet autoclave method. P-selectin detection was scored by a semiquantitative method evaluating the intensity and incidence of positively stained endothelial cells. The distribution pattern of endothelial P-selectin of blood vessels in cases of pneumonia and septic shock were heterogenius and weak. In one case with lung contusion (survival time 3 h) moderate infiltrates of granulocytes were found near to septal and subpleural hemorrhages. In these inflammatory areas the positive endothelial immunostaining of small vessels was often weaker than in other lung segments or compared to the intensely stained platelets in corresponding vessels.

Carbon Monoxide Poisoning↗

Cyclophilin A may contribute to the inflammatory processes in rheumatoid arthritis through induction of matrix degrading enzymes and inflammatory cytokines from macrophages.

Cyclophilin A (CypA) levels increase in the sera and synovial fluids of rheumatoid arthritis (RA) patients, but the cell types expressing CypA and the function of CypA in the pathogenesis of RA are not known yet. Immunohistochemistry analyses revealed high level CypA staining in the macrophages in the lining layers of human RA and osteoarthritis synovium. Low level CypA staining was also detected in endothelial cells, lymphocytes, and smooth muscle cells in RA synovium. Further investigation of the CypA function using monocyte/macrophage cell lines revealed that CypA induced expression of cytokine/chemokines such as TNF-alpha, IL-8, MCP-1, and IL-1beta and matrix metalloproteinase (MMP)-9 through a pathway that is dependent on NFkappaB activation. Furthermore, MMP-9 staining pattern overlapped with that of CypA in both RA and OA synovium. Our data suggest that CypA may stimulate macrophages to degrade joint cartilage via MMP-9 expression and promote inflammation via pro-inflammatory cytokine secretion.

Animals↗

Treatment with an acetylcholinesterase inhibitor in Alzheimer patients modulates the expression and production of the pro-inflammatory and anti-inflammatory cytokines.

Elevated levels of cytokines have been detected in brains of Alzheimer's disease (AD) patients, and altered peripheral levels of IL-1beta, TNFalpha and IL-6 have been reported in these patients. We studied the ability of PBMC from patients with AD, matched with a control group, to release pro- and anti-inflammatory cytokines, and the effect of AChEI treatment on cytokine release. Our data indicates that AChEI treatment down-regulates IL-1, IL-6 and TNF, and up-regulates the expression and production of IL-4 in PBMC in AD patients, and that AChEI leads to the remodelling of the cytokine network, probably acting on the lymphocytic cholinergic system.

Aged↗

The inflammatory response following delivery is amplified in women who previously suffered from major depression, suggesting that major depression is accompanied by a sensitization of the inflammatory response system.

BACKGROUND: There is now evidence that some patients with major depression show an activation of the inflammatory response system (IRS). This study was carried out to examine whether major depression may induce sensitization with increased IRS responses to the stress of child birth. METHODS: Serum concentrations of interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), sgp130 (the IL-6 signal transducing protein) and the sIL-1R antagonist (sIL-1RA) were determined in 16 and 50 women with and without a lifetime history of major depression, respectively. Blood was collected 3-6 days before delivery and 1 and 3 days after delivery. On each occasion the women completed the Zung Depression Rating Scale (ZDS). RESULTS: Serum IL-6, sIL-6R, sIL-1RA were significantly higher 1 and 3 days after delivery than before. Women who had suffered from a lifetime history of major depression had greater increases in serum IL-6 and sIL-1RA in the early puerperium than women without a lifetime history. Women who had suffered from a lifetime history of major depression had significantly higher IL-6, and sIL-1RA concentrations 1 and 3 days after delivery than women with a negative life-time history. CONCLUSIONS: The responses of IL-6 and sIL-1RA following delivery are amplified in women who previously suffered from major depression. The results suggest that major depression is accompanied by a sensitization of the IRS.

Adult↗

IL-1 receptor type I gene expression in the amygdala of inflammatory susceptible Lewis and inflammatory resistant Fischer rats.

Lewis (LEW/N) and Fischer (F344/N) rats have different responses to inflammatory and behavioral stressors due to differences in hypothalamus-pituitary-adrenal (HPA) axis function. For example, LEW/N rats are more sensitive to restraint, inflammation and experimentally induced autoimmunity due to decreased HPA activity. The HPA axis response to peripheral inflammation is mediated, at least in part, by IL-1beta and its receptor, IL-1 type I (IL-1RI). Here, we studied the distribution of IL-1RI mRNA in the brains of LEW/N and F344/N rats, and demonstrated that IL-1RI mRNA expression has significantly increased in the basolateral nucleus (BLA) of the amygdala of LEW/N rats. These findings suggest that strain-specific HPA axis responses may be mediated by extrahypothalamic pathways.

Amygdala↗