Aqueous extract of the bark of Uncaria tomentosa, an amazonian medicinal plant, promotes gastroprotection and accelerates gastric healing in rats.

ETHNOPHARMACOLOGICAL IMPORTANCE: Uncaria tomentosa Willd. DC., is used in the Amazonian region of South America, wherein ethnic groups use the plant to treat diseases, including gastric disorders. However, despite its widespread popular use, this species has yet to be assessed for its anti-ulcer effects. AIM OF THE STUDY: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects. MATERIALS AND METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses. RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1ß and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects. CONCLUSION: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.

Nimbolide attenuates complete Freund's adjuvant induced arthritis through expression regulation of toll-like receptors signaling pathway.

Nimbolide is an active constituent of Azadirachta indica and is known for its anti-inflammatory, anti-oxidant, immune-modulatory, and anti-cancer effects. Few studies suggest that nimbolide treatment influences the responses to rheumatoid arthritis, but the underlying molecular mechanisms involved are not yet well established. Therefore, the present study was designed to determine the effect of nimbolide on expression regulation of toll-like receptors to attenuate rheumatoid arthritis. The rheumatoid arthritis model was established by injecting complete Freund's adjuvant (CFA) intra-dermally into the sub-plantar region of the left hind paw of rats. Nimbolide (20 mg/kg) and piroxicam (10 mg/kg) were given to arthritic rats. Rats treated with nimbolide showed a significant reduction in inflammatory cells, rheumatoid factor, ESR, and improved the body weight. The results indicated that nimbolide possesses the capacity to attenuate rheumatoid arthritis by downregulating toll-like receptors, IL-17, IL-23, HSP70, and IFN-γ expression levels. Nimbolide treatment showed significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to piroxicam, which is a standard non-steroidal anti-inflammatory drug used for the treatment of rheumatoid arthritis. It can be concluded that nimbolide can be considered as a potential candidate for therapeutic targeting of the toll-like receptors pathway in rheumatoid arthritis.

Anti-inflammatory and Immunomodulatory Potency of Selenium-Enriched Probiotic Mutants in Mice with Induced Ulcerative Colitis.

Selenium-enriched Lactobacillus plantarum and Bifidobacterium longum mutants were used as a protector against Piroxicam-induced ulcerative colitis (UC). In this study, 32 BALB/c male mice were distributed to four groups: the control group, the Piroxicam group which was given 0.8 mg Piroxicam, SP and SB groups which were given 0.8 mg Piroxicam, and plus Lactobacillus plantarum and Bifidobacterium longum selenium-enriched mutants, respectively. Bodyweight; serum content of IgG, IgM, TNF-α, IL-2, IL-6, and IL-10; CBC; myeloperoxidase enzyme activity; histopathological examination of colon and spleen; and expression of TNF-α, IL-2, IL-6, and IL-10 genes in colon and spleen with qRT-PCR were determined. Bodyweight was found to reduce in the Piroxicam group and then recovery in the SB group. Serum content of IgG, IL-2, and IL-10 reduced in the Piroxicam group, whereas IgG, TNF-α, and IL-6 increased in the Piroxicam group in comparison to the other groups. Myeloperoxidase activity witnessed a significant increase in the Piroxicam group compared with the other groups. No significant differences were observed between all groups in measurements of red cells, hemoglobin, neutrophil, monocyte, eosinophil, and basophil in blood. Meanwhile, the white blood cells and platelets recorded the highest and lowest value, respectively, in the Piroxicam group. The colon of the Piroxicam group showed a noticeably massive infiltration of inflammatory cells in the lamina propria. These inflammations were mildly reduced in the SP group, while the reduction in the SB group was significant. In the Piroxicam group, splenic parenchyma saw an increase in the number of melanomacrophages, while hypertrophic plasma cells were observed in the SP group. The spleen of the SB group exhibits a nearly normal form. TNF-α and IL-6 genes had significantly upregulated in the colon of the Piroxicam group compared to the control group, while they were significantly downregulated in the SB group. In contrast, IL-2 and IL-10 genes had upregulated in the colon of the SB group compared to the control groups, while they had downregulated in the Piroxicam group. The expression of these genes had not recorded significant differences between all groups in the spleen. Therefore, this study recommends Bifidobacterium longum selenium-enriched mutants as anti-inflammatory and immunomodulatory supplements.

Analgesic Effect of Topical Piroxicam vs Phytotherapy Gel in the Treatment of Acute Soft Tissue Injuries: A Randomized Controlled Noninferiority Study.

OBJECTIVE: The study compared the efficacy and tolerability of piroxicam gel and a new topical combination of medicinal plant products (Soulagel®; Belpharma Tunisia) to treat pain caused by soft tissue injuries. METHODS: Patients (n = 1,525) were assigned to receive piroxicam gel or Soulagel. Efficacy assessments included a change of at least 50% in the pain-on-movement visual numeric scale rating from emergency department discharge (baseline) to day 7 final assessment, as well as the time required to reach pain resolution criteria, the need for rescue analgesia, patients' satisfaction, and the rate of adverse effects. RESULTS: At day 7, 1,216 patients (79.7%) achieved at least 50% reduction in visual numeric scale rating from baseline: 623 patients (82.4%) in the Soulagel group vs 593 patients (77.1%) in the piroxicam group (P = 0.01). Time to decrease pain on movement by 50% was significantly higher with piroxicam gel than with Soulagel (34 ± 1 vs 33 ± 1 days, respectively; P = 0.54). At day 7, 96.4% of patients in the Soulagel group declared being "very satisfied" to "satisfied," vs 68% in the piroxicam group (P < 0.001). There were no major adverse events in either group. CONCLUSIONS: Soulagel is not inferior to piroxicam gel for managing pain related to a soft tissue injuries. Further studies will help ascertain whether this new gel offers an alternative treatment option for this common emergency department condition.

Gastroprotective and gastric healing effects of the aqueous extract of Casearia sylvestris in rodents: Ultrasound, histological and biochemical analyzes.

ETHNOPHARMACOLOGICAL IMPORTANCE: Casearia sylvestris Sw. (Salicaceae) is a native plant from the Americas, where it is also known as "guaçatonga" or "erva-de-bugre." Although its leaves have been commonly used to treat inflammation and gastrointestinal disorders in South America, the antiulcer effects of an aqueous extract from this medicinal plant, similar to popular use, have not to be investigated yet. AIM OF THE STUDY: This study evaluated the hypothesis that the aqueous extract a of C. sylvestris (AEC) prevents the gastric ulcers and accelerates the healing of ulcers already installed, by assessing ultrasound imaging, histological and biochemical analyses. MATERIALS AND METHODS: Rats (females) were treated with AEC (3, 30 or 300 mg/kg) prior to the ethanol or piroxicam-induced gastric ulcers. The healing effect of AEC (300 mg/kg) was examined in 80% acetic acid-induced ulcer in rats, whereas the quality of healing was evaluated in recurrent 10% acetic acid-induced ulcer in mice with recurrence induced by interleukin 1ß. To assess the responses of the lesions, in addition to the classical methods used to analyze gastroprotection (ex vivo), we also measured the gastric wall thickness (in vivo) using ultrasonography. After euthanasia, the extent of ulcer was determined and the levels of reduced glutathione (GSH), lipid hydroperoxides (LOOH), nitrate, and the activities of myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase (NAG), superoxide dismutase (SOD), and glutathione S-transferase (GST) were measured. The antisecretory activity of AEC was also examined based on pylorus ligated rats. Furthermore, gastric tissue samples were analyzed histologically, and phytochemical analyses of the C. sylvestris extract were parallelly performed. RESULTS: The AEC (30 or 300 mg/kg) prevented ulcers in the ethanol- and piroxicam-induced acute. Moreover, the AEC at a dose of 300 mg/kg also accelerated the gastric healing of acetic acid-induced ulcer in rats by 48% and the ultrasonography records shown a decrease in the wall thickness and the extent of edema of ulcerous lesions promoted by the extract. The gastric healing effect of AEC was also accompanied by reduced MPO and NAG activities at acetic acid-induced ulcer in rats; as well as was by the reduction in the nitrate and LOOH levels, the increase in mucin and SOD activity, and by a partial recovery of GSH levels. The AEC (300 mg/kg) minimized the ulcer recurrence in mice exposed to IL-1ß, but the extract administration did not change pH or peptic activity of gastric juice in pylorus ligated rats. CONCLUSION: The results of this study provide convincing evidence for the therapeutic efficacy of C. sylvestris with respect to gastroprotection and indicate that ultrasound examination would be a potentially promising approach for evaluating gastroprotective effects in vivo. Collectively, our findings indicate that the gastric the gastroprotective and healing effects of aqueous extract C. sylvestris involve a reduction in acid secretion, promotion of the antioxidant system, reductions in the migration of neutrophils and mast cells, with a consequent lower inflammatory response, and the preservation of mucin.

[A rare side effect of mesotherapy: Nicolau syndrome]. / Un effet indésirable rare de la mésothérapie : la dermite de Nicolau.

BACKGROUND: Nicolau's livedoid dermatitis is associated with drug-induced embolism in the cutaneous arterial bed, generally as a result of accidental intra-arterial injection. Herein, we report a case that is somewhat surprising because of its late onset following mesotherapy injections. CASE REPORT: A 53-year-old man, with a history solely of tendinopathy for which he underwent mesotherapy sessions, consulted for livedoid lesions of the front of the knee with central necrosis. History-taking revealed a final course of mesotherapy three weeks earlier for patellar tendinitis below the left kneecap; intradermal injection of procaine and piroxicam had been unusually and intensely painful. The remainder of the clinical examination revealed additional livedoid lesions on the outside of the left ankle as well as purpuric lesions on the pads of the toes on the left foot. Laboratory tests revealed nothing of note. Skin biopsies of the livedoid circumference of the lesion showed arteriolar emboli of an amorphous material within the dermis obliterating the arteriolar lumen. The clinical appearance of skin lesions after mesotherapy led us to a diagnosis of Nicolau livedoid dermatitis. DISCUSSION: Nicolau dermatitis is a rare skin complication described as occurring mainly as a result of intramuscular injections. The reported case is special because it comprises Nicolau dermatitis arising out of a session of mesotherapy employing an intradermal injection. However, there are only very few cases in which subcutaneous injections have induced Nicolau dermatitis. The pathophysiology is not well known, but several mechanisms are involved: arterial ischaemia by vasospasm or thrombosis. In this case, the semiotic appearance of the lesions and histological analysis militate in favour of accidental injection of a skin product into an arteriole, resulting in obliteration of the latter. Mesotherapy can induce Nicolau dermatitis.

Non-steroidal anti-inflammatory drugs (NSAIDs) and hypertension treatment intensification: a population-based cohort study.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to antagonize the effects of antihypertensive drugs, and these associations can lead to an increase in arterial blood pressure. However, the impact of NSAIDs on hypertension treatment management in large-scale populations remains poorly evaluated. We examined whether the introduction of NSAID into the treatment regimen would induce an intensification of hypertension treatment (defined as the introduction of a new antihypertensive drug). METHODS: We conducted a cohort study involving 5,710 hypertensive subjects included in the French health insurance system database who had been treated and stabilized with their antihypertensive therapy and not exposed to any NSAID between 1 April 2005 and 1 April 2006. The maximum follow-up duration was 4 years. RESULTS: Adjusted hazard ratios (HR) for hypertension treatment intensification were 1.34 [95 % confidence interval (CI) 1.05-1.71] for NSAIDs in general, 1.79 (95 % CI 1.15-2.78) for diclofenac and 2.02 (95 % CI:1.09-3.77) for piroxicam. There were significant interactions between NSAIDs and angiotensin converting enzyme inhibitors (ACEIs; HR 4.09, 95 % CI 2.02-8.27) or angiotensin receptor blockers (ARBs; HR 3.62, 95 % CI 1.80-7.31), but not with other antihypertensive drugs. CONCLUSIONS: Exposure to NSAIDs leads to an intensification of hypertension treatment, especially in patients treated with ACEIs or ARBs. Renin-angiotensin system blockers should be avoided whenever NSAIDs are prescribed.

Safety of subcutaneous microinjections (mesotherapy) in musicians.

OBJECTIVE: Determine the safety and tolerance of mesotherapy as a technique for the treatment of musculoskeletal complaints in musicians. METHOD: 67 patients (55.2% women) were subjected to a total of 267 mesotherapy sessions. A mesotherapy needle or normal needle was used randomly. The drugs employed were thiocolchicoside and diazepam as muscular relaxants, pentoxifylline or buflomedil as vasodilators, and piroxicam as an anti-inflammatory, as directed. A visual analogue scale was used to quantify the pain produced by the microinjections as well as the degree of immediate and midterm side effects as reported on a standard questionnaire. RESULTS: A mean of 155.5 microinjections were performed per session, of which 45.6% were perceived as painful by the patient with a mean severity of 4.3 out of 10. The pain reduced to 0.5 out of 10 after 24 hours. The most sensitive areas were the levator scapulae and splenius muscles. Systemic symptoms were reported by 5.99% of the musicians after the mesotherapy sessions (muscular weakness 1.5%, rash 1.5%, drowsiness 1.1% and itching 1.1%, being the most frequent). The mean severity of these symptoms was 2.77 out of 10. In all cases the symptoms had completely disappeared after 24 hours. No patient referred to signs of local or systemic infection. CONCLUSIONS: The application of drugs by means of subcutaneous injections (mesotherapy) in musicians is a technique that is safe, well tolerated, and without any severe complications.

Are traditional NSAIDs prescribed appropriately among French elderly with osteoarthritis? Results from the CADEUS cohort.

AIM: To describe the inappropriate use of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) in elderly subjects in the CADEUS cohort using the Beers 2003 criteria modified by recommendations from the French Medicines Agency. METHODS: Of the 23,217 subjects in the CADEUS cohort, 1,851 were ≥65 years old, had bee diagnosed with osteoarthritis (OA), and had been dispensed a tNSAID at least once in the 6 months before the index date. Data were obtained from the French national reimbursement database and from patient and prescriber questionnaires. The Beers criteria for inappropriate use were modified to include all tNSAIDs, and long-term high-dose use was defined as having been dispensed at least five dispensations for tNSAID over a 6-month period with a gap of <45 days between each dispensation and when the gap was >45 days, medicine availability >50% [i.e., defined daily dose (DDD) delivered/theoretical DDD] for the gap. RESULTS: The most frequently dispensed tNSAIDs were piroxicam (25%), diclofenac (24%), ibuprofen (18%), ketoprofen (18%), and naproxen (10%). Of the study population, 1.5% were dispensed indomethacin; 15%, two tNSAIDs; 15%, a tNSAIDs with a platelet aggregation inhibitor; 4.6%, a tNSAID with low-dose aspirin; 0.2%, a tNSAID with vitamin K antagonists. The analysis revealed that 18% of the study population were high-dose and long-term users of tNSAIDs and that 70% of these were dispensed a proton pump inhibitor. CONCLUSIONS: The most common inappropriate tNSAID dispensation was the co-prescription of two different tNSAIDs within 1 month or of a platelet aggregation inhibitor. The real-life consequences of our results need to be ascertained, and it would be interesting to update the Beers criteria.

Gastro-protective effect of Crossopteryx febrifuga in Wistar rats.

Preparations of Crossopteryx febrifuga (Afzel.) Benth. (Rubiaceae) are widely used in Northern Nigeria in the therapeutic management of trypanosomiasis, malaria and painful inflammatory disorders. Previous studies have shown that the methanolic stem bark extract of Crossopteryx febrifuga possesses significant analgesic and anti-inflammatory properties possibly mediated via Non-selective inhibition of cyclo-oxygenase pathways. In the present study, the methanolic stem bark extract of Crossopteryx febrifuga was evaluated against ethanol- and piroxicam-induced ulceration in rats. Histopathological studies of the rat stomach tissues were also carried out in order to determine its safety profile on the gastrointestinal tract (git). The extract (25, 50 and100 mg extract/kg body weight) significantly (P<0.05) and dose-dependently reduced ulcer index induced by ethanol (24 - 92%) and piroxicam (81.81- 98.60%). Histopathology of the rat stomach tissues from control and extract-treated groups at 25 mg/kg body weight extract showed mild inflammation characterized by infiltration of inflammatory cells, while the extract treated groups at 50 and 100mg/kg body weight and 200 mg misoprostol/kg body weight group showed no obvious lesions. These results showed that the extract had no deleterious effects and was cytoprotective on the gastrointestinal tract (git). It can thus be developed as a safe alternative to conventional non-steroidal anti-inflammatory drugs (NSAIDs) for the management of painful inflammatory disorders.

Effects of D-002, a product isolated from beeswax, on gastric symptoms of patients with osteoarthritis treated with piroxicam: a pilot study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are indicated for treatment of rheumatoid arthritis and osteoarthritis, but often induce gastric adverse experiences (AE), including gastric ulcers and complications. Inhibitors of proton pump and H(2) antagonists are very effective for duodenal ulcer; meanwhile, cytoprotective drugs are more effective for gastric ulcer. D-002 is a mixture of higher aliphatic alcohols obtained from beeswax, wherein triacontanol is the most abundant. D-002 induces anti-ulcer effects through a cytoprotective mechanism, being more effective in protecting against ethanol- and NSAID-induced ulcers. The present double-blind, placebo-controlled clinical study was undertaken to investigate the effects of D-002 on gastric symptoms associated to piroxicam use on patients suffering osteoarthritis. Fifty-nine patients, all taking piroxicam, 20 mg/day, were randomized to placebo or D-002 (40 or 100 mg/day) for 14 days. The primary efficacy variable was the reduction on the frequency of patients with gastric AE compared with placebo. Pain evolution was investigated to discard any influence on D-002 on the analgesic effect of piroxicam. The frequency of patients treated with D-002, 40 and 100 mg/day, reporting acidity [0 of 18 (0%) and 1 of 21 (4.8%), respectively] was lower (P < .05) than in placebo [6 of 20 (30%)]. Also, the frequency of patients treated with 100 mg/day reporting some gastric AE [5 of 21 (23.8%)] was lower (P < .05) than in placebo [13 of 20 (65.0%)]. The analgesic effect of piroxicam was unaffected with D-002. Treatment was well tolerated. Two patients discontinued from the study because of gastrointestinal AE: one in the placebo group and the other treated with D-002, 40 mg/day. Other three patients discontinued because of other AE: mildly uncontrolled hypertension (one in the placebo group, one treated with D-002, 40 mg/day) and headache (one treated with D-200, 100 mg/day). It is concluded that D-002 could be useful for controlling gastric AE of patients treated with NSAIDs, although further studies with a larger sample size and longer follow-up are needed for definitive conclusions.

Modelling therapeutic strategies in the treatment of osteoarthritis: an economic evaluation of meloxicam versus diclofenac and piroxicam.

OBJECTIVE: To assess the economic efficiency of meloxicam, a cyclo-oxygenase (COX)-2 selective inhibitor, versus diclofenac and piroxicam in the UK for the treatment of patients with osteoarthritis and the impact on the NHS budget of substituting nonselective NSAIDs with meloxicam. Methods and perspective: A decision analytical model was used to compare the effects of 4 weeks' treatment of osteoarthritis with meloxicam (7.5 mg/day), diclofenac (100 mg/day) and piroxicam (20 mg/day). The decision tree was derived by combining best practice and clinical reality. Analysis was from the NHS perspective. The study considered only the direct costs. These included costs for drug acquisition and management of all adverse events, both serious gastrointestinal events requiring hospitalisation, and non-serious events that required maintenance. Resource use and treatment costs were obtained from local and published sources. A range of sensitivity analyses was carried out. RESULTS: Based on two 4-week large-scale trials, the Meloxicam Large-scale International Study Safety Assessment (MELISSA) and Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trials, and a decision analytical model, the findings suggested that meloxicam had the lowest cost per patient ( pound 30 versus pound 35 for piroxicam and pound 51 for diclofenac [costs presented as 1998 values except for drug costs which were in 2000 values]). The results of the Monte Carlo probabilistic sensitivity analysis, using 4000 samples, suggested that meloxicam was the optimal strategy in the drug treatment of patients with osteoarthritis compared with nonselective NSAIDs both individually and as a group. The cost savings were due to lower levels of serious adverse events accompanied by fewer days in intensive care units and shorter overall duration of hospital stay observed with meloxicam compared with diclofenac and piroxicam in the 4-week trials. CONCLUSIONS: Based on the 4-week trial period, meloxicam was predicted to be the lowest cost drug therapy, and thus the optimal drug therapy, in the management of patients with osteoarthritis compared with nonselective NSAIDs such as diclofenac and piroxicam. Applying the cost savings per patient derived from the model, switching patients from piroxicam and diclofenac to meloxicam would indicate a cost saving of over pound 25 million per annum. Models such as this can facilitate better clinical guidance and is a useful way of assessing treatment outcomes.

A randomized controlled trial comparing topical piroxicam gel with a homeopathic gel in osteoarthritis of the knee.

OBJECTIVE: : To evaluate the efficacy and safety of a homeopathic gel vs an NSAID (piroxicam) gel in the treatment of osteoarthritis of the knee. METHOD: : One hundred and eighty-four out-patients with radiographically confirmed symptomatic osteoarthritis of the knee were entered into a pragmatic, randomized, double-blind controlled trial and treated with 1 g of gel three times daily for 4 weeks. Main outcome measures were pain on walking as a Visual Analogue Score (VAS) and a single-joint Ritchie index. RESULTS: : One hundred and seventy-two of the 184 enrolled patients had endpoints for the main outcome parameters. The pain reduction was 16.5 mm VAS in the homeopathy group (n = 86) and 8.1 mm in the piroxicam group (n = 86); the difference between treatment groups was 8.4 mm (95% confidence interval 0.8-15.9), and after adjustment for pain at baseline it was 6.8 mm (95% confidence interval -0.3 to 13.8). There was no significant difference between treatment groups in the single-joint Ritchie index (P = 0.78). Adverse events occurred in 28 patients (12 homeopathy group, 5 withdrawn; 16 piroxicam group, 9 withdrawn); 18 of the events involved a local reaction (7 homeopathy group, 2 withdrawn; 11 piroxicam group, 5 withdrawn). CONCLUSION: : The homeopathic gel was at least as effective and as well tolerated as the NSAID gel. The presence of a clinically relevant difference between treatment groups cannot be excluded. The homeopathic gel supplemented by simple analgesics if required may provide a useful treatment option for patients with osteoarthritis.

The economic consequences of NSAID-induced gastropathy: the French context.

The costs of treating gastroduodenal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are shown to increase the total cost of NSAID treatment to the Assurance-Maladie, the French national health insurance system. This increased cost is termed the iatrogenic cost factor, and is defined as the ratio of the shadow price of an NSAID to its reimbursed cost. The shadow price is calculated from estimates of the incidence of NSAID-induced gastropathies, the cost of the drug, and the hospital and ambulatory costs of treating the gastropathies. The resulting iatrogenic cost factors are estimated as 1.36 for naproxen, 1.48 for sulindac, 1.65 for diclofenac, 1.67 for piroxicam, 2.00 for ketoprofen, and 2.12 for etodolac.

Measurement of renal functions by double isotope techniques in elderly patients during tenoxicam therapy.

Four elderly patients (aged 68-87 yr) with osteoarthritis were treated with 20 mg of tenoxicam (a new non-steroidal anti-inflammatory drug) daily for at least 12 weeks. Tenoxicam did not appear to have any harmful effect on glomerular filtration rate and effective renal plasma flow, as measured by a single intravenous injection of 51Cr-EDTA and 125I-iodohippurate. Plasma concentration of tenoxicam indicated good compliance, and no evidence of unexpected accumulation of tenoxicam in the plasma was observed during 12 weeks of medication.

A double-blind, placebo-controlled study comparing three single-dose regimens of piroxicam with ibuprofen in patients with primary dysmenorrhea.

Sixty-eight women with primary dysmenorrhea were randomly assigned to one of five four-times-daily treatment groups for a minimum of three days and a maximum of five days. Three of the groups received different initial single-daily doses of piroxicam, which were followed on each treatment day with placebo for the second through fourth doses, namely, piroxicam 20 mg daily for five days (piroxicam 20 mg for five days); piroxicam 40 mg on Day 1, followed by piroxicam 20 mg on Days 2 through 5 (piroxicam 40 mg for one day); and piroxicam 40 mg on Days 1 and 2, followed by piroxicam 20 mg on Days 3 through 5 (piroxicam 40 mg for two days). The fourth group received ibuprofen 400 mg four times per day, and the fifth group received placebo four times per day. Patients determined the severity of overall discomfort and pelvic-abdominal pain at baseline and prior to each dose using a four-point numerical scale. Supplemental ibuprofen, 400 mg four times per day, was provided for those patients requiring additional pain relief. Patients also made a global determination of overall relief at the end of the study. At 24 hours, the results revealed that piroxicam 40 mg for two days, piroxicam 20 mg for five days, and ibuprofen provided significantly more relief of overall discomfort compared with placebo (p = 0.003, p = 0.018, and p = 0.026, respectively). All four active treatment groups also experienced significantly more relief of pelvic-abdominal pain compared with placebo: piroxicam 40 mg for two days followed by three days of 20 mg (p = 0.002), piroxicam 40 mg for one day followed by four days of 20 mg (p = 0.023), piroxicam 20 mg for five days (p = 0.012), and ibuprofen (p = 0.011). A significantly smaller percentage of patients treated with piroxicam 40 mg for two days required supplemental medication as compared with those treated with piroxicam 20 mg for five days (p = 0.035) and patients treated with placebo (p = 0.010). A greater amount of overall relief was obtained by patients treated with piroxicam 40 mg for two days compared with patients treated with piroxicam 40 mg for one day (p = 0.041) and placebo-treated patients (p = 0.001). It was concluded that single daily doses of piroxicam 20 mg and 40 mg were as effective as ibuprofen, 400 mg four times per day, for the relief of primary dysmenorrhea.