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Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed classes of drugs worldwide. Due to their excellent effects for analgesic, anti-inflammatory and antipyretic, most elder population used frequently for osteoarthritis. Gastrointestinal symptoms and ulceration associated with NSAIDs are common. Such ulcers may cause pain, bleeding, or perforation. It leads to other medical problems. The aim of this study was to examine the utilizations of medical resources associated with inpatients with NSAID related peptic ulcer disease and compared to non-NSAID related peptic ulcer disease. The study used the database from a teaching hospital in southern Taiwan. Inpatients who were identified ICD-9 CM codes as peptic ulcer diseases from January 1st of 2008 to December 31 of 2008 were included in this study. We also examined the indications for usage of NSAIDs, the date of prescription before the index date. The results showed 17.6% of inpatients with peptic ulcer disease related to NSAIDs. Inpatients with NSAIDs related peptic ulcer disease compared with inpatients with non-NSAIDs related peptic ulcer disease had significant difference in age and comorbidity. Although rapid urease test positive rate for Helicobacter pylori was higher in group of non-NSAID related peptic ulcer disease, it seemed underestimate because of the test number of patients was low. The average total direct medical cost of inpatients with NSAID related peptic ulcer was NT$ 36,491 and non-NSAID related peptic ulcer was NT$ 37,266.1. There were no significant difference in medical costs of standard care , intensive care , blood products,endoscopy, endoscopic hemostasis, surgery, CT scan , ultrasound, laboratory tests,medications, doctor¡¦s service between the two groups. Diagnostic and therapeutic procedures were no statistically significant difference, including blood transfusion,CT scan, endoscopic hemostasis, surgery, symptoms presentations, and intensive care. In this study, the duration for using NSAID was within 30 days for inpatients associated with NSAID related peptic ulcer, which had a substantial excess numbers of ulcer hospitalization. Since the common disease for using NSAID is osteoarthritis,which is very popular in elderly, therefore, we suggested that the policy makers of the National Health Insurance should be aware that preventive usage of proton pump inhibitors for the elder population who need frequent use of NSAIDs might decrease NSAID related ulcer complications.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to suppress bone formation when administered before, but not if administered after, an acute bout of mechanical load in rats. The NSAID ibuprofen inhibits cyclooxygenase-2 enzyme, effectively reducing loading induced prostaglandin E2. Whether this affects eventual bone mass gains after multiple sessions of a more physiological mechanical loading regimen is unclear. Therefore, the aim of this study was to test the hypothesis that gains in bone mass and size will be diminished in adult rats given ibuprofen before, but not after, each exercise bout during 20 days of simulated resistance training (SRT). Virgin female Sprague-Dawley rats (5-mo-old, n=29) completed 9 SRT sessions using stimulated muscle contractions under anesthesia at 75% peak isometric strength on alternate days; each of 20 contractions included 1 sec isometric + 1 sec eccentric contraction. Animals were blocked assigned by body weight to one of three groups: 1) ibuprofen (30mg/kg) before exercise, placebo after (I:P)(n=9), 2) placebo before, ibuprofen after (P:I)(n=10) and 3) placebo before and after (P:P)(n=10). In vivo pQCT scans measured changes in total volumetric bone mineral density (vBMD) and total bone mineral content (BMC) at the proximal tibia (cancellous), and total vBMD, total BMC and total area at midshaft tibia on days -7 and 21. Dynamic histomorphometry on both midshaft tibiae (exercised and non-exercised legs) determined mineralizing surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR) on the periosteal surface. There were no differences in body weights among groups at baseline or at day 21. There were significant gains due to SRT, but not ibuprofen treatment in total BMC (+10.50 ± S.D. +8.15%) and total vBMD (+5.29 ± 3.41%) at the proximal tibia. The midshaft tibia exhibited significant gains in total vBMD (6.68 ± 3.03%), total BMC (19.18 ± 5.51%) and total area (11.68 ± 5.49%) due solely to SRT. Furthermore, there were significant increases in periosteal BFR (pre 21.89 µm3/µm2/d ±2.63; post 717.81 µm3/µm2/d ±100.57) at the midshaft tibia in the exercised vs. non-exercised legs in all groups but no effect of ibuprofen regimen was detected on these indices of bone formation. In the context of robust increase in BFR and bone mass within this simulated resistance protocol, we were unable to detect any impact of ibuprofen administration on the response to bone loading.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for systemic control of acute and chronic pain and inflammation (Lin et ah, 2000:1129), but usage problems and side-effects that occur during the post-marketing phase of these drugs are well documented (Thiefin & Beaugerie, 2005:287). Following the demonstration of the value of anti-inflammatory therapy in diseases like rheumatoid arthritis (Boardman & Dudley Hart, 1967:268), new NSAIDs appeared on the market (Dieppe et al., 2004:867), and the indications steadily broadened from inflammatory diseases to almost any painful condition. Studies have indicated that NSAID-associated serious upper gastro-intestinal (GI) adverse events result in 103 000 hospitalisations (Bombardier, 2002:4) and 165 000 deaths per year in the United States. A study in South Africa in 2002 indicated that NSAID utilisation contributed considerably to the total cost of all medicine items from a medicine claim database in the private health care sector (Joubert, 2002:260). The objective of this study was to determine the prevalence and cost of non-steroid anti-inflammatory drugs in a section of the private health care sector, and specifically to determine the prevalence, usage and cost of Coxib (Specific cyclo-oxygenase-2 inhibitor) medicine items before and after the withdrawal of Vioxx® from the market in September 2004 (Merck, 2004). Data from two medicine claim databases for the years 2004, 2005 and 2006 (medicine claim database I) and the years 2005 and 2006 (medicine claim database M), were analysed by means of a retrospective drug utilisation review (DUR) study. The usage of Coxib medicine items was determined, and compared for the periods before and after the withdrawal of Vioxx® in September 2004. It was found that between 9 and 10.5 per cent of prescriptions dispensed through both medicine claim database I and medicine claim database M during the study period were NSAID prescriptions. NSAID medicine items on medicine claim database I represented between 3.9 % (R25 942 986) and 2.9 % (R8 073 034) of the total cost of all medicine items claimed from 2004 to 2006. NSAIDs represented 3.1 % (R58 290 412) and 2.8 % (R57 752 267) of the cost of all medicine items claimed through medicine claim database M during 2005 and 2006 respectively, indicating similar trends in the two medicine claim databases. The prevalence of Coxibs on medicine claim database I decreased from almost 20 % (47 938) in 2004 to 8.4 % (13 276) in 2005, but showed an increase again to 10.9 % (12 355) in 2006. The prevalence of both cyclo-oxygenase (COX) inhibitors, and Coxibs demonstrated a change during 1 September 2004 to 31 December 2004 when COX-inhibitors showed an increase in use, while Coxibs showed and almost equal but opposite trend with a decrease in use. This could possibly be related to perceptions of providers and public with regard to Coxibs and their related safety after the withdrawal of Vioxx® on 30 September 2004 (Merck, 2004) and other Coxibs such as Bextra® (FDA, 2005) in 2005 in USA. It is concluded that most patients who were using Coxibs before the withdrawal of Vioxx®, substituted Coxibs for COX-inhibitors, that are known for their possible gastro-intestinal side-effects. Recommendations for future research regarding NSAID use were also made, and included an investigation of the usage of Coxibs in different age groups, as well as the combination of NSAIDs with gastro-protective medicines in long-term use. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for systemic control of acute and chronic pain and inflammation (Lin et ah, 2000:1129), but usage problems and side-effects that occur during the post-marketing phase of these drugs are well documented (Thiefin & Beaugerie, 2005:287). Following the demonstration of the value of anti-inflammatory therapy in diseases like rheumatoid arthritis (Boardman & Dudley Hart, 1967:268), new NSAIDs appeared on the market (Dieppe et al., 2004:867), and the indications steadily broadened from inflammatory diseases to almost any painful condition. Studies have indicated that NSAID-associated serious upper gastro-intestinal (GI) adverse events result in 103 000 hospitalisations (Bombardier, 2002:4) and 165 000 deaths per year in the United States. A study in South Africa in 2002 indicated that NSAID utilisation contributed considerably to the total cost of all medicine items from a medicine claim database in the private health care sector (Joubert, 2002:260). The objective of this study was to determine the prevalence and cost of non-steroid anti-inflammatory drugs in a section of the private health care sector, and specifically to determine the prevalence, usage and cost of Coxib (Specific cyclo-oxygenase-2 inhibitor) medicine items before and after the withdrawal of Vioxx® from the market in September 2004 (Merck, 2004). Data from two medicine claim databases for the years 2004, 2005 and 2006 (medicine claim database I) and the years 2005 and 2006 (medicine claim database M), were analysed by means of a retrospective drug utilisation review (DUR) study. The usage of Coxib medicine items was determined, and compared for the periods before and after the withdrawal of Vioxx® in September 2004. It was found that between 9 and 10.5 per cent of prescriptions dispensed through both medicine claim database I and medicine claim database M during the study period were NSAID prescriptions. NSAID medicine items on medicine claim database I represented between 3.9 % (R25 942 986) and 2.9 % (R8 073 034) of the total cost of all medicine items claimed from 2004 to 2006. NSAIDs represented 3.1 % (R58 290 412) and 2.8 % (R57 752 267) of the cost of all medicine items claimed through medicine claim database M during 2005 and 2006 respectively, indicating similar trends in the two medicine claim databases. The prevalence of Coxibs on medicine claim database I decreased from almost 20 % (47 938) in 2004 to 8.4 % (13 276) in 2005, but showed an increase again to 10.9 % (12 355) in 2006. The prevalence of both cyclo-oxygenase (COX) inhibitors, and Coxibs demonstrated a change during 1 September 2004 to 31 December 2004 when COX-inhibitors showed an increase in use, while Coxibs showed and almost equal but opposite trend with a decrease in use. This could possibly be related to perceptions of providers and public with regard to Coxibs and their related safety after the withdrawal of Vioxx® on 30 September 2004 (Merck, 2004) and other Coxibs such as Bextra® (FDA, 2005) in 2005 in USA. It is concluded that most patients who were using Coxibs before the withdrawal of Vioxx®, substituted Coxibs for COX-inhibitors, that are known for their possible gastro-intestinal side-effects. Recommendations for future research regarding NSAID use were also made, and included an investigation of the usage of Coxibs in different age groups, as well as the combination of NSAIDs with gastro-protective medicines in long-term use. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most used drugs in equine medicine, mainly used to treat inflammation, endotoxemia, pain or fever. NSAIDs inhibit cyclooxygenases which induce to synthesize prostanoids. But NSAIDs have side effects to renal functions too. Objectives: The current study was carried out to investigate the effects of the most common used NSAIDs on urinary parameters in horses. Materials and Methods: Thirty healthy horses were used as a control group and 20 horses with left dorsal displacement, left ventral impaction or lameness of using either flunixin meglumine (FM), metamizole (MZ) or phenylbutazone (PHZ) have been assigned to groups 1, 2 or 3, respectively. Creatinine, urea nitrogen, glucose, protein and electrolytes were measured in serum and urine including GGT using an automatic analyzer. Fractional excretions (FE) of sodium, chloride, potassium, calcium, magnesium and inorganic phosphate, in addition to urinary protein (U-Pro):U-Cr and urinary gamma glutamyl transferase (U-GGT):U-Cr ratios were calculated. Urinary mucus and IgA concentrations were measured and their ratios to the urinary creatinine were calculated. The data were statistically analyzed using Shapiro-Wilks test, descriptive statistics, Kruskal-Wallis one-way analysis of variance and Dunn’s test. Significance was set at P £ 0.05. Results: The FEMg was significantly higher in group 3 (P < 0.033) compared to the control group. The U-GGT:U-Cr ratio was also significantly higher in group 3 (P < 0.001) compared with the control group. The U-Pro:U-Cr ratio was significantly higher in groups 1 and 2 (P < 0.007 and P < 0.001, respectively) than in the control group. PHZ group had a significantly increase in mucus:U-Cr ratio (P < 0.005). Significant increases were observed regarding the IgA:U-Cr ratio in groups 1 (P < 0.007) and 2 (P < 0.014). Conclusions: Long-term use of PHZ has an influence on the renal ascending limb of the loop of Henle, and all these drugs could have effects on the proximal tubules. Phenylbutazone causes an increase in urinary mucus secretion, probably as a protective mechanism against the necrotic effect in renal pelvis of PHZ. Parameters such as U-Pro:U-Cr and U-GGT:U-Cr ratios and FEMg are helpful in detecting these renal abnormalities.

Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.

L'objectiu principal d'aquestaTesi Doctoral és el desenvolupament de diferents estratègies per disminuir els límits de detecció de l’electroforesicapil•lar per a la determinació de compostos farmacèutics i els productes de cura personal. Aquestes estratègies es basen en les tècniques de preconcentració electroforètiques i cromatogràfiques, i l'ús de l’espectrometria de masses com a sistema de detecció. Com a tècniques de preconcentració electroforètiques s'han estudiat les tècniques de samplestacking i sweeping, i com a tècnica de preconcentració cromatogràficas’ha avaluat l'acoblament en línia entre l'extracció en fase sòlida i l'electroforesicapil•lar (In-line SPE-CE). Entre elsPPCPs, aquesta tesi doctoral es centra específicament en els antiinflamatoris no esteroïdals(AINE), els parabens i els filtres ultraviolats. Un altre dels objectius d'aquestaTesi Doctoral és estudiarl’aplicabilitat de les metodologies desenvolupades per a l'anàlisi de mostres ambientals per determinar PPCP. / The main objective of this Doctoral Thesis is the development of different strategies to decrease the detection limits of capillary electrophoresis for the determination of pharmaceutical and personal care products. These strategies are based on electrophoretic and chromatographic preconcentration techniques, and the use of mass spectrometry as a detection system. The electrophoretic preconcentration techniques studied included sample stacking techniques and sweeping while the chromatographic preconcentration technique evaluated was in-line coupling between solid phase extraction and capillary electrophoresis. With respect to PPCPs, this Doctoral Thesis focuses specifically on non-steroidal anti-inflammatory drugs (NSAIDs), parabens and UV-filters. Another objective of this Doctoral Thesis is to study the suitability of the developed methodologies for the determination of PPCPs in environmental samples.

L’apparition de plusieurs maladies, telles que le cancer, le diabète, l'hypertension artérielle et la propagation d'infections de type virus mutagènes peuvent être liées à la qualité et au mode de vie que nous menons aujourd’hui. En effet, plusieurs études sur les facteurs déclenchant ces maladies dites "morbides" à long ou à court terme, sont liées au stress et à la qualité des aliments consommés, qu'ils soient d'origine végétale ou animale. Ces maladies deviennent un phénomène courant, elles touchent différentes races et toutes les catégories de la société. D'après les recherches ethnobotaniques, les substances d’origine naturelle, ont permis à des civilisations de survivre à des maladies mortelles. A titre d'exemple, on retrouve ainsi des références à des périodes de fièvre paludique en Chine et à des symptômes de cette maladie dans le «Huangdi Neijiang» Le Canon de Médecine datant des environs du premier siècle avant notre ère, plus de 2000 ans, qui relate de l'emploi de plantes médicinales, pour soulager les fièvres (Desgrouas et al., 2014).Vers 186 avant J.-C. apparaît, dans certaines régions de Chine, l'utilisation en tisane, du Qing hao su, appelé plus tard artémisinine en Occident et extrait d'une plante médicinale utilisée comme antipyrétique appelée "Qing hao", Artemisia annua ou Armoise annuelle. L'artemisinine bloque une enzyme qui permet au parasite de pomper le calcium et l'empêche ainsi de se développer. Au jour d'aujourd'hui l’Artemisinin-based combination therapy, en français Thérapie combinée à base d'artémisinine et en sigle ACT, est une thérapie et une prévention tertiaire dans les cas de paludisme simple.Dans cette optique notre étude vient s'ajouter à une longue série d'études menées sur les plantes médicinales et les substances naturelles extraites. Elle a pour objectif de révéler de nouvelles biomolécules, de mettre en évidence leurs activités biologiques grâce à des techniques de biotechnologies d'une part. D'autre part ces investigations permettront de valoriser les ressources naturelles qui se distinguent par leur endémicité.Pour se faire, notre choix s'est porté sur deux plantes médicinales endémiques à l'Algérie Cyclamen africanum Boiss. & Reuter et Zygophyllum cornutum Coss. , après une recherche ethnobotanique sur la pharmacopée traditionnelle du Nord de l'Afrique, et qui a révélé l’efficacité de ces plantes dans les problèmes inflammatoires minimes chez les autochtones, nous avons entrepris des investigations pharmaco- biochimiques.Ces dernières nous ont permis d'isoler : cinq composés à partir de l'extrait méthanolique des racines de l'espèce Cyclamen africanum Boiss. & Reuter, deux nouvelles saponines triterpéniques de type Oleanane, Afrocyclamin A et B (1, 2), ainsi que trois saponines triterpénoïdes connus sous le nom de lysikokianoside (3), deglucocyclamin I (4) et de son dérivé d'acide dicrotalique (5); et Sept saponosides connus à partir de l'extrait méthanolique de la plante entière de Zygophyllum cornutum Coss., ces saponosides sont de type ursane, ce type de triterpène est rapporté dans cette espèce pour la première fois et peuvent être considérés comme un marqueur chimio-taxonomique (chemotype) du genre Zygophyllum. Les structures ont été élucidées, sur la base de l'analyse des spectres de l'expérience RMN-1D et RMN- 2D (COSY, TOCSY, NOESY, HMBC et HSQC) et spectrométrie de masse en source FAB mode ion négatif. Des activités biologiques, des fractions saponosidiques Fr.1 et Fr.2, ont été testées sur des lignées de Rats mâles et femelles, de la race Winstar pour évaluer l'activité anti inflammatoire.La fraction saponosidique Fr.1 de Cyclamen africanum à la dose 5 mg, a montré un effet significatif sur l'inflammation causé par la carragénine, en réduisant l'oedème et la réponse immunitaire, qui s'est traduite par la concentration des protéines de la réponse inflammatoire (PRI) à travers leurs action sur les pro-médiateurs de l'inflammation (COX-2, PGE2, TNF -α, iNOS). / The appearance of several diseases, such as cancer, diabetes, high blood pressure and spread of infections mutagenic virus type can be linked to the quality and lifestyle that we lead today. Indeed, several studies on the factors triggering these so-called "morbid" long-or short-term illnesses are related to stress and quality of food consumed, whether of plant and animal origin. These diseases are becoming a common occurrence, they affect different races and all classes of society. According ethnobotanical research, naturally occurring substances, allowed civilizations to survive deadly diseases. For example, we thus find references to periods of malarial fever in China and one of the symptoms of this disease in the "Huangdi Neijiang" The Canon of Medicine dating from around the first century BC, more than 2000 years, which relates to the use of herbal medicines to relieve fevers (Desgrouas et al., 2014).Around 186 BC appears, in some parts of China, the use in herbal tea, Qing hao su, later known as artemisinin in the West and extracted from a medicinal plant used as antipyretic called "Qing hao" Artemisia annua or annual wormwood. Artemisinin blocks an enzyme which enables the parasite to pump calcium and prevents it from developing. As of today the Artemisinin-based combination therapy in French Combination therapy of artemisinin and ACT acronym, is a therapy and tertiary prevention in cases of uncomplicated malaria.From this perspective our study adds to a long series of studies on medicinal plants and natural substances extracted. It aims to reveal new biomolecules, highlighting their biological activities through techniques of biotechnology on the one hand. Moreover, these investigations will develop natural resources that are characterized by endemic.To do this, our choice is focused on two endemic medicinal plants in Algeria Cyclamen africanum Boiss. & Reuter and Zygophyllum cornutum Coss. After an ethnobotanical research on traditional medicine in Northern Africa, which showed the effectiveness of these plants in minimal inflammatory problems among Aboriginal, we undertook biochemical pharmacological investigations.The latter allowed us to isolate, five compounds from the methanol extract of the roots of the species Cyclamen africanum Boiss. Reuter & two new oleanane triterpene saponins type, Afrocyclamin A and B (1, 2) and three triterpenoid saponins known lysikokianoside of (3), deglucocyclamin I (4) and its derivative dicrotalique acid (5) September and known from the methanol extract saponins from the whole plant of Zygophyllum cornutum Coss. these saponins are ursane type, type triterpenes are reported in this species for the first time and can be considered a chemotherapy marker Taxonomic (chemotype) of Zygophyllum kind. The structures were elucidated on the basis of the analysis of NMR spectra of the experience-1D and 2D-NMR (COSY, TOCSY, NOESY, HSQC and HMBC) and mass spectrometry method negative ion FAB source. The biological activities of saponosidiques FR.1 and Fr.2 fractions were tested on lines of male and female rats of the Winstar rats to evaluate the anti-inflammatory activity. The saponosidique fraction FR.1 Cyclamen africanum the 5 mg dose, showed a significant effect on inflammation caused by carrageenan, reducing edema and immune response, which resulted in the concentration of protein the inflammatory response (PRI) through their action on the pro-inflammatory mediators (COX-2, PGE2, TNF -α, iNOS). The fraction of Fr.2 saponosidique Zygophyllum dose 20 mg did not show a significant effect on inflammation in general.