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PubMed2006

Inflammation in metabolic syndrome and type 2 diabetes: Impact of dietary glucose.

Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose-induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.

Cytokines↗
PubMed1985

Suppressive effect of inflammation and other forms of stress on the binding of prolactin by rat liver.

We have found that in female rats a variety of stressful stimuli, including sc inflammation, skin incision, endotoxin injection, and cold exposure, cause a significant decrease (30-86%) in the capacity of the hepatic cell membranes to specifically bind [125I]ovine PRL. Stress-induced decrease in food intake was not a factor in these studies, as nourishment was given only by tube feeding. Neither sc inflammation nor cold exposure affected hepatic binding of [125I]insulin. Further, the induction of inflammation in lactating rats and rats bearing 7,12-dimethylbenz[a]anthracene-induced mammary carcinomas did not affect the binding of PRL by the lactating or malignant mammary tissue. The suppressive effect of inflammation on hepatic binding of PRL was demonstrable in adrenalectomized-ovariectomized rats, in hypophysectomized rats receiving hormone replacement, and in adrenalectomized rats that had undergone partial chemical sympathectomy. We conclude that sc inflammation, as well as other forms of stress, decreases hepatic binding of PRL, but does not affect hepatic binding of insulin or mammary binding of PRL. The decrease in hepatic PRL binding is not mediated by a hormone secreted by the adrenals, ovaries, or pituitary, or by catecholamines, but could be mediated by another plasma factor or by peripheral dopaminergic neurons. Stress-induced decrease in hepatic PRL binding, or a related decrease in the binding of other polypeptide hormones, could play a role in the physiological response to stress.

Adrenalectomy↗
PubMed2003

The effects of preoperative inflammation on the analgesic efficacy of intraarticular piroxicam for outpatient knee arthroscopy.

UNLABELLED: We conducted a double-blinded study in 90 patients undergoing elective arthroscopic knee surgery to determine whether there is a role of inflammation in the analgesic efficacy of intraarticular piroxicam. Standardized general anesthetic techniques were used for all patients. At the end of the operation, after harvesting synovial biopsies, patients were randomized into three intraarticular groups equally. Group 1 received 25 mL saline, Group 2 received 25 mL 0.25% bupivacaine, and Group 3 received 25 mL 0.25% bupivacaine and piroxicam 20 mg. After microscopic examination of the synovial materials, the patients were divided into two subgroups, inflammation positive (I+) and inflammation negative (I-). Preoperatively and postoperatively at 1, 2, 4, and 6 h, pain levels, analgesic duration, and postoperative analgesic consumption were recorded. Analgesic duration was significantly longer in the I+ subgroup than the I- subgroup of Group 3 (P < 0.05). Pain scores at 1, 2, and 4 h postoperatively were significantly lower in the I+ subgroup than the I- subgroup of Group 3 (P < 0.05), whereas there were no significant differences among the subgroups of Group 1 and 2. We concluded that preoperative inflammation is one of the most important determinants of analgesic efficacy of intraarticular piroxicam. IMPLICATIONS: Intraarticular administration of piroxicam along with bupivacaine improves postoperative analgesia in synovial inflammation before surgery.

Adult↗
PubMed2002

Effect of Sho-saiko-to extract on hepatic inflammation and fibrosis in dimethylnitrosamine induced liver injury rats.

Sho-saiko-to extract, a Chinese herbal medicine, is widely used for treatment of chronic hepatitis in Japan. However, it is not clear what conditions Sho-saiko-to extract improves hepatic inflammation and fibrosis. We therefore induced various stages of liver injury in model rats and administered Sho-saiko-to extract. We then evaluated the liver inflammation and liver fibrosis-improving effects of Sho-saiko-to extract. The liver injury model rats were produced by administration of various doses of dimethylnitrosamine (DMN) and Sho-saiko-to extract was administered to these rats. Then the liver inflammation and fibrosis-improving effects of Sho-saiko-to extract were evaluated according to L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), liver retinoid levels, levels of hydroxyproline, Transforming Growth Factor-beta (TGF-beta), and the liver fibrosis area. These indicators depended on the total doses of DMN. The ability of Sho-saiko-to extract to improve liver inflammation and fibrosis was limited to the following levels of the respective parameters: AST levels (234-264 U/l), ALT levels (208-232 U/l), TGF-beta levels (1102-1265 pg/g liver tissue), hydroxyproline levels (633-719 nmol/g liver tissue), and liver fibrosis area (9.7-10.6 times for normal rat). These findings suggested that Sho-saiko-to extract is effective in the treatment of liver inflammation and fibrosis up to a certain degree of severity, but it produces no improvement in more severe cases.

Animals↗
PubMed1985

Analysis of the factor(s) involved in pathogenesis of zymosan-induced inflammation in rats.

The role of mast cell degranulation in increased vascular permeability in zymosan-air-pouch inflammation, an experimental model of inflammation induced by zymosan in rats, was investigated. The complement in the inflammatory pouch fluid was exhausted, and mast cells in the pouch wall subcutaneous tissues were degranulated. The histamine level in the pouch fluid was elevated immediately after application of zymosan in the preformed air-pouch and then quickly declined. Plasma exudation into the pouch fluid changed in close parallel with the change of histamine level. Application of compound 48/80 in the air-pouch also brought about liberation of histamine from mast cells, accompanied with elevation of vascular permeability similar to that observed in the zymosan-air-pouch inflammation. However, the amount of the plasma exudation in the zymosan-air-pouch inflammation was about twice as high as that induced by compound 48/80, though the quantity of histamine liberated in the two cases was almost equal. Rats depleted of histamine and serotonin were incapable of responding to compound 48/80, but zymosan still induced increased vascular permeability. A combination treatment with pyrilamine and methysergide did not abolish plasma exudation caused by zymosan, but brought about complete blockade of the vascular permeability response to compound 48/80. These results suggest that some mechanisms independent of degranulation of mast cells are responsible in part for the initial sudden elevation of vascular permeability in zymosan-induced inflammation.

Animals↗
PubMed1993

Neurogenic inflammation and sensitivity to environmental chemicals.

Neurogenic inflammation as a pathway distinct from antigen-driven, immune-mediated inflammation may play a pivotal role in understanding a broad class of environmental health problems resulting from chemical exposures. Recent progress in understanding the mediators, triggers, and regulation of neurogenic inflammation is reviewed. Evidence for and speculations about a role for neurogenic inflammation in established disorders such as asthma, rhinitis, contact dermatitis, migraine headache, and rheumatoid arthritis are presented. The sick building syndrome and multiple chemical sensitivity syndrome have been defined as clinical entities in which exposure to chemical inhalants gives rise to disease. Current data on the existence of chemical irritant receptors in the airway and skin are discussed; neurogenic inflammation arising from stimulation of chemical irritant receptors is a possible model to explain many of the aspects of chemical sensitivities.

Air Pollutants↗
PubMed2005

Monitoring urinary orosomucoid in acute inflammation: observations on urinary excretion of orosomucoid, albumin, alpha1-microglobulin, and IgG.

BACKGROUND: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (alpha(1)-acid glycoprotein), albumin, alpha(1)-microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. METHODS: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgery-induced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. RESULTS: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for alpha(1)-microglobulin, 33-fold for albumin, and 26-fold for IgG. CONCLUSIONS: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically relevant real-time observation of changes in acute inflammatory processes. Orosomucoid in urine may be a more informative marker than albumin for inflammation.

Acute Disease↗
PubMed2002

Alterations in airway inflammation and lung function during corticosteroid therapy for atopic asthma.

INTRODUCTION: Although corticosteroid therapy for asthma improves lung function and reduces airway inflammation, the relation between these two events is unclear. This article investigates associations between changes in bronchial inflammation and lung function during high-dose inhaled corticosteroid therapy for asthma. METHODS: Nine subjects with atopic asthma received high-dose inhaled fluticasone propionate (FP), 2,000 microg/d for 8 weeks. Fiberoptic bronchoscopy with endobronchial biopsies, spirometry, and histamine provocation challenge were performed on each subject at baseline, after 2 weeks, and again after 8 weeks of therapy. Spearman rank correlation coefficients between changes in parameters of bronchial inflammation and lung function were computed. RESULTS: As expected, significant down-regulation of airway inflammation and improvements in lung function were observed after both short-term and long-term therapy with high-dose inhaled FP. During corticosteroid therapy, changes in lymphocyte and macrophage numbers in bronchial biopsy specimens were closely correlated. Changes in EG1+ eosinophils were associated with changes in EG2+ eosinophils after 8 weeks of therapy. Although changes in airway inflammation and changes in lung function were not closely associated after 2 weeks of therapy, changes in eosinophils (EG1) in bronchial biopsy specimens correlated with changes in bronchodilator response (r = 0.77, p = 0.016) after 8 weeks of therapy. CONCLUSION: In patients with atopic asthma, changes in bronchial eosinophils and lung function during steroid therapy are closely related but do not occur simultaneously.

Administration, Inhalation↗
PubMed2004

Characteristics of airway inflammation and bronchodilator reversibility in COPD: a potential guide to treatment.

STUDY OBJECTIVES: The management of stable patients with COPD depends on the severity of symptoms and airflow limitation. Regarding inflammation, corticosteroids are the only medications that are recommended for use, and only under restricted circumstances. Corticosteroids tend to undertreat or overtreat patients with COPD when only clinical manifestations and the findings of simple spirometry are considered. Accordingly, our aim was to survey the characteristics of airway inflammation in stable COPD patients, and to assess the interrelations among inflammatory cells, inflammatory mediators, bronchodilator reversibility, and pulmonary function. Factors related to airway inflammation and bronchodilator reversibility may be important in the management of stable COPD patients. METHODS: A total of 88 stable patients with smoking-related COPD were recruited into the study. All patients were steroid-free, and had been treated with theophylline, oral beta(2)-agonist agents, anticholinergic agents, and possibly mucolytic agents. Bronchodilator tests and sputum induction were performed to evaluate bronchodilator reversibility, and numbers of inflammatory cells and mediators (eg, interleukin [IL]-8, eotaxin, and regulated on activation, normal T cells expressed and secreted [RANTES]). RESULTS: Thirty-one of 48 patients (64.6%) who had bronchodilator reversibility, and 19 of 40 patients (47.5%) without bronchodilator reversibility had sputum eosinophilia (median, 8.0% and 7.0%, respectively). FEV(1) showed a significant inverse correlation with the number of sputum neutrophils. The correlation coefficient for postbronchodilator FEV(1) vs the percentage of neutrophils in patients with nonreversible COPD was higher than that in those with reversible COPD. The levels of IL-8 were closely associated with the percentage of neutrophils. The sputum concentrations of IL-8 and albumin were significantly higher in patients with nonreversible COPD than in those with reversible COPD. A significant inverse correlation was found between bronchodilator response (ie, DeltaFEV(1) and DeltaFVC) and prebronchodilator FEV(1). CONCLUSIONS: Eosinophilic inflammation may play a substantial role in COPD, while neutrophils and IL-8 may have a great influence on nonreversible obstructive airways. The assessment of airway inflammation and bronchodilator responses can help the selection of specific therapies and the prediction of clinical outcomes for COPD patients.

Aged↗
PubMed2000

Nitric oxide synthase 2 and cyclooxygenase 2 interactions in inflammation.

Nitric oxide (NO) and prostaglandin (PG) E2 produced by NO synthase type 2 (NOS2) and cyclooxygenase type 2 (COX2), respectively, are important mediators in inflammation. There is much information regarding their roles in models of inflammation in mice and in humans with diseases such as rheumatoid arthritis (RA). A variety of stimuli including cytokines, microbial components, immune complexes, and mechanical stress can induce both NOS2 and COX2 mRNA transcription and protein synthesis and enhance inflammation. This has been demonstrated in both mice and humans. NOS2-specific inhibitors reduce inflammation in mice, and COX2-specific inhibitors reduce inflammation in mice and in humans. There is significant cross-talk between PGE2/NO and COX2/NOS2. Treatments that inhibit both NOS2 and COX2 should provide the most potent antiinflammatory effects.

Animals↗
PubMed2004

Time course of systemic markers of inflammation in patients presenting with acute coronary syndromes.

Inflammation within coronary plaques may cause an acute coronary syndrome by promoting rupture and erosion. It was the aim of this study to examine whether markers of inflammation derive from a cardiac or extracardiac source and how their levels develop over time. Blood samples were taken from patients with acute coronary syndromes (ACS) with proven atherosclerotic lesion(s) of the left coronary artery (n=13) and from control patients without coronary artery disease (n=13). Blood was taken from the femoral vein and the coronary sinus vein before and after coronary angioplasty (day 0) and on days 1 and 120. Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1 ra) and soluble CD40 ligand (sCD40L) were higher in ACS patients as compared to controls and remained elevated up to day 120. In the long-term time course these markers of inflammation and plaque remodeling slightly decreased in ACS patients. There were no statistically significant differences detectable in the levels of TNF-alpha, IL-6, IL-1 beta, IL-10, IL-1 ra, sCD40L and monocyte chemoattractant protein-1 (MCP-1) in the blood of ACS patients taken from a cardiac source as compared to an extracardiac source (coronary sinus vs. femoral vein). This study demonstrates the importance of a systemic inflammatory condition in patients with ACS, in whom markers of inflammation are increased as compared to controls. During long-term follow-up the pro-inflammatory activity remains elevated in ACS patients, supporting the concept of a systemic rather than a local vascular inflammation contributing to the development of atherosclerosis.

Acute-Phase Reaction↗
PubMed2005

Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation.

Transgenic overexpression of NMDA NR2B receptors in forebrain regions increased behavioral responses to persistent inflammatory pain. However, it is not known whether inflammation leads to the upregulation of NR2B receptors in these regions. Here, we show that peripheral inflammation increased the expression of NMDA NR2B receptors and NR2B receptor-mediated synaptic currents in the anterior cingulate cortex (ACC). In freely moving mice, the increase in NR2B receptors after inflammation contributed to enhanced NMDA receptor-mediated responses in the ACC. Inhibition of NR2B receptors in the ACC selectively reduced behavioral sensitization related to inflammation. Our results demonstrate that the upregulation of NR2B receptors in the ACC contributes to behavioral sensitization caused by inflammation.

Animals↗
PubMed2001

Low-grade systemic inflammation in overweight children.

OBJECTIVE: Human adipose tissue expresses and releases the proinflammatory cytokine interleukin-6, potentially inducing low-grade systemic inflammation in persons with excess body fat. To limit potential confounding by inflammation-related diseases and subclinical cardiovascular disease, we tested the hypothesis that overweight is associated with low-grade systemic inflammation in children. DESIGN AND SETTING: The third National Health and Nutrition Examination Survey, 1988-1994, a representative sample of the US population. PARTICIPANTS: A total of 3512 children 8 to 16 years of age. OUTCOME MEASURES: Elevated serum C-reactive protein concentration (CRP; >/=.22 mg/dL) and white blood cell count (10(9) cells/L). RESULTS: Elevated CRP was present in 7.1% of the boys and 6.1% of the girls. Overweight children (defined as having a body mass index or a sum of 3 skinfolds (triceps, subscapula, and supra-iliac) above the gender-specific 85th percentile) were more likely to have elevated CRP than were their normal-weight counterparts. After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) was 3.74 (95% confidence interval [CI]: 1.66-8.43) for overweight boys and the OR was 3.17 (95% CI: 1.60-6.28) for overweight girls, based on the body mass index. Based on the sum of 3 skinfolds, these ORs were 5.11 (95% CI: 2.36-11.06) and 2.89 (95% CI: 1.49-5.59) for boys and girls, respectively. Overweight was also associated with statistically significant higher white blood cell counts. The results were similar when restricted to healthy, nonsmoking, nonestrogen-using children. CONCLUSIONS: In children 8 to 16 years of age, overweight is associated with higher CRP concentrations and higher white blood cell counts. These findings suggest a state of low-grade systemic inflammation in overweight children. inflammation, obesity, children.

Adipose Tissue↗
PubMedDate not supplied

Changes in serum ovotransferrin levels in chickens with experimentally induced inflammation and diseases.

A competitive enzyme immunoassay was developed to measure the changes in serum levels of ovotransferrin (OTF) during inflammation and infectious diseases in chickens. The assay is based on the competition of serum OTF with a fixed concentration of biotin-labeled OTF to bind to a rabbit anti-chicken transferrin antibody immobilized on microtiter wells. After several washing steps, the antibody-bound biotinylated OTF is probed with streptavidin-horseradish peroxidase conjugate (HRP) followed by a colorimetric detection of the HRP activity. The relative changes in the optical density of color are plotted against the competing concentrations of OTF with logarithmic regression to generate a standard curve that is used to determine the concentrations of OTF in unknown samples. Serum had no effect on the measurement of OTE By this method, the time course changes of serum OTF levels in 4-wk-old male broiler chickens that were subjected to inflammation by croton oil injection were measured. The results showed croton oil-induced inflammation elevated serum OTF levels at 16 hr postinjection. OTF levels reached a peak by 72 hr, remained high through 120 hr, and returned to a basal level of olive oil-injected controls by 240 hr. There were no changes in serum OTF levels at any of the above time points in olive oil-injected control chickens. For studies with poultry diseases, specific-pathogen-free (SPF) male chickens were challenged with known bacterial and viral pathogens, and serum was collected at the height of the infection, i.e., 7 days after the challenge. Compared with uninjected controls, the SPF chickens challenged with Escherichia coli, fowl poxvirus, respiratory enteric orphan virus, infectious bursal disease virus, infectious bronchitis virus, or infectious laryngotracheitis virus had higher levels of OTF in serum. Inflammation-induced changes in serum OTF levels were also evident in the changes in the density of a 65-kD band protein corresponding to OTF. These results demonstrate that serum OTF may be a nonspecific clinical marker of inflammation associated with traumatic or infectious avian diseases.

Animals↗
PubMed2005

Alpha2-macroglobulin expression in the liver in response to inflammation is mediated by the testis.

Earlier studies have shown that germ cells or germ cell-conditioned media are capable of regulating alpha2-macroglobulin (alpha2-MG, a non-specific protease inhibitor) expression by Sertoli cells and hepatocytes cultured in vitro. These results illustrate a possible physiological link between testes and liver regarding alpha2-MG production. Using a series of surgical procedures including castration, hemicastration, and hepatectomy coupled with Northern blot and immunoblot analyses, we report herein that the surge in alpha2-MG expression in the liver in response to inflammation is indeed regulated, at least in part, by the testis via testosterone. It was found that hepatectomy induced at least a tenfold increase in the steady-state mRNA and protein production of alpha2-MG in the liver. However, castration induced a mild but not statistically significant induction of alpha2-MG in the liver in contrast to sham operation or hemicastration alone, when hemicastration alone could induce liver alpha2-MG production by almost fourfold. Perhaps most important of all, hepatectomy accompanied by castration significantly reduced the liver alpha2-MG response to the surgery-induced inflammation compared with hepatectomy alone, illustrating that the removal of the testicles can induce a loss of signal communications between the testis and the liver, rendering a significant loss of the alpha2-MG response to experimentally induced inflammation in the liver. Interestingly, this lack of response of the liver to surgery-induced inflammation regarding alpha2-MG production following castration could be restored, at least in part, by using testosterone implants placed subdermally 6 days prior to orchiectomy. Collectively, these results illustrate that a physiological link does indeed exist between the testis and the liver, and that testes per se can influence the liver in vivo alpha2-MG expression in response to inflammation possibly via testosterone or testosterone-induced biological factor(s).

Animals↗
PubMed2006

Chronic local inflammation in mice results in decreased TRH and type 3 deiodinase mRNA expression in the hypothalamic paraventricular nucleus independently of diminished food intake.

During illness, changes in thyroid hormone metabolism occur, known as nonthyroidal illness and characterised by decreased serum triiodothyronine (T3) and thyroxine (T4) without an increase in TSH. A mouse model of chronic illness is local inflammation, induced by a turpentine injection in each hind limb. Although serum T3 and T4 are markedly decreased in this model, it is unknown whether turpentine administration affects the central part of the hypothalamus-pituitary-thyroid axis (HPT-axis). We therefore studied thyroid hormone metabolism in hypothalamus and pituitary of mice during chronic inflammation induced by turpentine injection. Using pair-fed controls, we could differentiate between the effects of chronic inflammation per se and the effects of restricted food intake as a result of illness. Chronic inflammation increased interleukin (IL)-1beta mRNA expression in the hypothalamus more rapidly than in the pituitary. This hypothalamic cytokine response was associated with a rapid increase in local D2 mRNA expression. By contrast, no changes were present in pituitary D2 expression. TSHbeta mRNA expression was altered compared with controls. Comparing chronic inflamed mice with pair-fed controls, both preproTSH releasing hormone (TRH) and D3 mRNA expression in the paraventricular nucleus were significantly lower 48 h after turpentine administration. The timecourse of TSHbeta mRNA expression was completely different in inflamed mice compared with pair-fed mice. Turpentine administration resulted in significantly decreased TSHbeta mRNA expression only after 24 h while later in time it was lower in pair-fed controls. In conclusion, central thyroid hormone metabolism is altered during chronic inflammation and this cannot solely be attributed to diminished food intake.

Abscess↗
PubMed2005

Local simvastatin effects on mandibular bone growth and inflammation.

BACKGROUND: Simvastatin has been shown to increase bone growth when applied topically to murine bone; however, it causes considerable soft tissue inflammation at high doses (2.2 mg), making future clinical use problematic. This study evaluated the effect of lower simvastatin doses and cyclooxygenase (COX) synthase inhibitors on tissue inflammation and bone growth in rats and gene expression in mice. METHODS: Adult female rats were untreated or treated with a single dose of 0.1, 0.5, 1.0, 1.5, or 2.2 mg simvastatin in methylcellulose gel in a polylactic acid membrane (SIM) on the lateral aspect of the mandible. The contralateral mandible side was implanted with methylcellulose gel/polylactic acid membrane alone (GEL), and five rats in each dose pairing were evaluated histomorphometrically after 3, 7, and 24 days. Subsequent rats were similarly treated with 0.5 mg simvastatin (optimal dose) and daily intraperitoneal injections of COX-2 inhibitor (NS-398; 1 mg/kg x 7 days; N = 16), general COX inhibitor (indomethacin; 1 mg/kg x 7 days; N = 16), or no inhibitor (N = 10) and evaluated histomorphometrically after 7 or 24 days by analysis of variance (ANOVA). Gene arrays were also used to evaluate osteogenic gene expression from 0.5 mg simvastatin in murine calvaria (N = 12). RESULTS: There was a 45% increase in bone area with 0.5 mg simvastatin versus gel control (P <0.001; similar to the 2.2-mg dose), and clinical swelling was reduced compared to the high simvastatin dose (P <0.05). The 0.1-mg simvastatin dose failed to stimulate significant bone growth. NS-398 and indomethacin reduced inflammation and bone growth. Simvastatin significantly upregulated procollagen, fibronectin, and matrix metalloproteinase-13 genes. CONCLUSION: Reducing the simvastatin dose from 2.2 to 0.5 mg reduced inflammation to a more clinically acceptable level without sacrificing bone-growth potential, but COX-associated inflammation appears to be necessary for in vivo bone growth.

Animals↗
PubMed1988

Nimesulide. A preliminary review of its pharmacological properties and therapeutic efficacy in inflammation and pain states.

Nimesulide is a new non-steroidal anti-inflammatory analgesic agent given orally or rectally on a twice daily basis in a number of inflammatory and pain states. Although still at an early stage of clinical assessment, preliminary evidence suggests that nimesulide 200 to 400mg daily is significantly more effective than placebo in reducing the pain, fever and inflammatory symptoms of chronic rheumatoid arthritis or osteoarthritis, respiratory tract infections, otorhinolaryngological diseases, soft tissue and oral cavity inflammation, dysmenorrhoea, phlebitis/thrombosis, urogenital disease and postoperative pain states. In a number of comparative studies, nimesulide has also been shown to be more effective than piroxicam (in osteoarthritis), paracetamol (acetaminophen) [in respiratory tract inflammation], benzydamine or naproxen (in otorhinolaryngological disease), phenylprenazone (in laryngotracheitis/bronchitis, respiratory inflammation and otorhinolaryngological disease), Serratia peptidases (in postoperative or dental pain, trauma and phlebitis), ketoprofen (in postoperative dental pain) and mefenamic acid (in dysmenorrhoea). In addition, the efficacy of nimesulide has been observed to be comparable with that of aspirin, with or without vitamin C, and mefenamic acid (in respiratory tract infection), ibuprofen (in soft tissue disease), naproxen (in respiratory tract inflammation, dysmenorrhoea and postoperative pain states), suprofen and paracetamol (in postoperative pain states), benzydamine (in genitourinary tract inflammation) and dipyrone, paracetamol or diclofenac (in fever). The safety profile of nimesulide has yet to be fully established, although initial evidence suggests the usual adverse effects associated with non-steroidal anti-inflammatory drugs occur, possibly with a lower incidence of gastrointestinal problems than with other members in its therapeutic class. Nimesulide, therefore, appears to offer a useful alternative to other non-steroidal anti-inflammatory drugs in the treatment of patients with inflammatory conditions and/or pain and fever states. However, further definition of its efficacy and tolerability is clearly required, particularly in comparison with established or other new drugs in its therapeutic class.

Anti-Inflammatory Agents, Non-Steroidal↗