Administration Of Piroxicam Research Articles

Comparison of Analgesic Effect of Piroxicam and Transcutaneous Electrical Nerve Stimulation Therapy on Pain associated with Orthodontic Separator Placement: A Single Blind Randomized Controlled Trial

Aims and objectives: To assess and compare the efficacy of transcutaneous electrical nerve stimulation (TENS) therapy and preemptive piroxicam administration in reducing the severity of pain after orthodontic separator placement. Materials and methods: It was a randomized, single-blind, parallel arm trial. Subjects of either gender between 18 and 30 years of age, scheduled to undergo regular orthodontic therapy with placement of two separators in each arch, were selected for this trial. The sample size consisted of 60 patients from whom prior informed consent was obtained. They were assigned randomly into two categories of 30 subjects each. • Group I: Subjects were given piroxicam (20 mg) 1 hour before separator placement. • Group II: Subjects were given TENS therapy immediately after separator placement. The treatment was administered by the coinvestigator, so as to blind the principal investigator to the treatment group. Perceived pain was evaluated on chewing and fitting back teeth together at 2-, 6-, 24-, and 48-hour intervals, using the visual analog scale (VAS). Results: Descriptive statistical analysis revealed that the VAS scores in the piroxicam group were marginally higher than the TENS group at all intervals, except at 2 hours. The difference was, however, statistically insignificant. Conclusion: The findings of this single blind randomized, controlled trial (RCT) suggest that TENS therapy is as effective as 20 mg piroxicam administered preemptively, in controlling pain felt due to separator placement. The TENS offers several advantages over piroxicam, as it is devoid of the inherent side effects of nonsteroidal antiinflammatory drugs (NSAIDs) like an inhibitory effect on orthodontic tooth movement and also gastric irritation. Therefore, the use of TENS is recommended over NSAIDs for the successful management of orthodontic pain, which is so critical both from the patient’s and from the clinician’s perspective.

Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin.

BackgroundTransitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans.Hypothesis/ObjectivesWe hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept.AnimalsFourteen client‐owned dogs were prospectively enrolled.MethodsTumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia.ResultsA 90‐minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days).Conclusions and Clinical ImportanceTavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.

Clinical outcome of partial cystectomy for transitional cell carcinoma of the canine bladder.

Canine transitional cell carcinoma (TCC) of the bladder has historically been treated with a combination of chemotherapy, cyclooxygenase inhibitors and radiation therapy. While surgery has been used to treat TCC of the bladder, its efficacy has yet to be established. Thirty-seven client owned dogs that underwent partial cystectomy +/- various nonsurgical treatments for TCC were retrospectively evaluated. The overall median progression-free interval (PFI) was 235 days and the median survival time (ST) was 348 days. Prognostic factors identified on univariate analysis significant for ST were age, tumor location, full thickness excision and frequency of piroxicam administration. Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration. The median ST with partial cystectomy and daily piroxicam therapy, with or without chemotherapy, was 772 days. Dogs with non-trigonal bladder TCC treated with full thickness partial cystectomy and daily piroxicam (+/- chemotherapy) may have improved outcome compared to dogs treated with medical therapy.

Study of illness anorexia in birds by concentrating on roles of central and peripheral cyclooxygenases-1 and cyclooxygenases-2

Prostaglandin E2 (PGE2) is one of the major mediators involved in illness anorexia in rodents. Cyclooxygenases (COX), the important enzymes in prostaglandin synthesizing pathway, have two main isoforms named COX-1 and COX-2. Lipopolysaccharides (LPS) are components of the cell wall of gram-negative bacteria which are used as a standard model of infection. Here, we evaluated the interaction between central and peripheral COX-1 and COX-2 with LPS in neonatal broilers. In the central experiments, the following drugs were injected intracerebroventricularly (ICV): LPS (100 ng), piroxicam, a selective inhibitor of COX-1 (10, 50, 100 μg), nimesulide, a selective inhibitor of COX-2 (1, 5, 10, 20 μg), and LPS plus piroxicam and LPS plus nimesulide (100 ng and 50 μg, respectively). For peripheral experiments, either the solvent or LPS were injected intraperitoneally 30 min after piroxicam or nimesulide administration. Food intake was assessed at 30 to 360 min post-injections in 3 h fasted chicks. In both central and peripheral administrations, LPS, piroxicam, and nimesulide either alone or in combination suppressed food intake. Injection of LPS plus COX-1 and COX-2 inhibitors also exacerbated food intake suppression. Our results showed that COXs are not involved in the illness anorexia in neonatal chicks. The other pathways such as Cox-PGD2 might be involved and requires more studies. It seems that administration of COXs inhibitors such as aspirin or indomethacin might not recommended for improvement of the illness anorexia in infectious diseases of neonatal chicks.

Effects of piroxicam administration on pregnancy outcome in intrauterine insemination (IUI) cycles: a randomized clinical trial

Background: Uterus contractibility is considered a powerful prognostic factor in predicting the embryo transfer outcome. Moreover, uterine contractions are known to be stimulated by prostaglandins which are produced by cyclooxygenase from arachidonic acid. As such, suppressing the inflammatory response and contractions using anti-inflammatory and relaxant agents is expected to result in increased success rate of embryo transfer and artificial insemination. Objective: To investigate the effect of piroxicam administration on the success rate in intrauterine insemination (IUI) cycles in patients presenting with unexplained infertility. Materials and Methods: This randomized, placebo-controlled clinical trial included 260 women with unexplained infertility undergoing IUI cycles. Patients were randomly assigned to receive either piroxicam ten mg/day on days 4-6 after IUI or placebo (control group). The main outcome measures were number of IUI cycles, pregnancy, abortion, and multiple pregnancy rates. Results: The pregnancy rate was found to be 25 (19.2%) and 16 (12.3%) in piroxicam and control groups, respectively (p = 0.039). Five patients (3.8%) in piroxicam group experienced twin pregnancy whereas only three patients (2.3%) in control group had twin pregnancy (p = 0.361). The pregnancy rate per cycle was also significantly higher in those who received piroxicam as compared to controls (11.16 vs. 6.66; p = 0.021). Conclusion: Administration of piroxicam after IUI is associated with decreased number of cycles, as well as increased pregnancy rate and pregnancy rate per cycle in IUI cycles. However, piroxicam did not have any effect on abortion, multiple pregnancy, and ongoing pregnancy rates.

Solid Lipid Nanoparticles Incorporated Transdermal Patch for Improving the Permeation of Piroxicam

Aim: Piroxicam is class II drug and has low oral bioavailability owing to low aqueous solubility. Long-term administration of piroxicam is reported to produce gastrointestinal toxicity. The objective of this study was to improve the permeation of piroxicam by incorporating as piroxicam loaded solid lipid nanoparticles (pirox-SLNs) into a transdermal patch. Method: Pirox-SLN’s (average particle size 248.87 ± 6.481 nm and entrapment efficiency 84.48% ± 1.08%) upon optimization, were prepared by pre-emulsion sonication method and were incorporated into ethyl cellulose and polyvinyl pyrrolidone matrix patch prepared by solvent evaporation method. Results& Discussion: The prepared transdermal patches were evaluated for thickness, weight variation, flatness, folding endurance, and drug content which were found to 0.31 ± 0.04 mm, 0.17 ± 0.03 g, 99.5% ± 0.3%, 35 ± 1.34 and 95.74 ± 0.4, respectively. Ex-vivo skin permeation of the prepared formulation was studied on rat skin and the drug release from patch incorporated with SLNs was found 66.6% up to 24 h, significantly less as compared to plain piroxicam patch having release of 88.01%, however, the slow release from the SLN patch was attributed due to slow release of the drug from SLN. Ex-vivo skin permeation studies on pirox-SLN containing patches showed satisfactory flux (17.16 μg/cm2/h) compared with that of plain piroxicam patches (4.6 μg/cm2/h). The skin irritation test showed that the prepared transdermal patch were free of skin irritants. Conclusion: It was concluded that SLN’s can be successfully used as a carrier for enhancing transdermal permeation of piroxicam and thus the bioavailability.

Mixed Epigastric Axial Pattern Flap Following Cutaneous Hemangiosarcoma Excision in a Male Dog

Background: Axial pattern flaps use direct cutaneous arteries to enable closure of a skin defect using a large skin segment. Caudal epigastric axial pattern flaps are highly versatile owing to their wide arc of rotation, which includes the preputial area. The presence of abundant loose and elastic skin allows wider flaps. Hemangiosarcoma (HSA) is a malignant neoplasm of endothelial cells with aggressive local behavior and high metastatic rate; the lungs are the most common site of metastasis. This case report aims to describe the use of a caudal epigastric artery-based flap, with preservation of some cranial epigastric artery branches for penis sparing, following resection of a hemangiosarcoma in the right inguinal region of a male dog.Case: An eight-year-old male Pitt Bull dog was referred with a 15 cm, ulcerated hemangiosarcoma in the right inguinal region, near the prepuce. A similar tumor had been removed from the same location two years before. Previous treatment with oral prednisone did not provide satisfactory results. The patient was suffering from intense chronic blood loss andbacterial infection of the tumor tissue. Thoracic radiographs revealed multiple metastatic nodules. Only mild regenerative anemia was found in blood tests. Considerable reductions in tumor size and in the ulcerated surface, decrease in bleeding, and recovery of appetite were observed after 7 days of administration of piroxicam and cephalexin. Surgical resectionof the tumor was performed as a palliative treatment with a minimal safety margin of 2 cm, which spared the penis. An epigastric skin flap incorporating the second mammary gland was performed preserving branches of cranial epigastric arteries, and was rotated 160° to cover the defect created in the right inguinal region and on the body of the penis. A small suture dehiscence, necrosis of the distal border of the flap, seroma, and multidrug-resistant Escherichia coli infection were observed in the postoperative period. Administration of penicillin V and topical collagenase, placement of a passive drain, and a second surgical procedure to correct the dehiscence were necessary to solve postoperative complications. Piroxicam based metronomic chemotherapy was maintained continuously, as the patient would exhibit worsening of overall condition upon discontinuation of medication. One hundred days after the initial presentation, the animal was euthanized owing to the presence of an osteolytic lesion on the vertebral bodies of L3-L4 and L5-L6, which were suggestive of discosponlylitis or axial bone metastasis.Discussion: Since lung metastases were present, penectomy and uretrostomy were not considered an option, and a pallia tive surgical treatment was performed. In this case report, cranial and caudal epigastric flap presented few complications. Caudal epigastric blood vessels are robust and abundant. Distal necrosis was considered a minor complication and was in accordance with others reports. The multidrug resistant infection was considered a nosocomial infection that arised from a long hospital stay. By inhibiting cyclooxygenase, piroxicam decreases angiogenesis, increases apoptosis, and prolongs disease-free intervals with mild toxicity. An excellent response to preoperative administration of piroxicam was crucial when choosing the postoperative protocol. A signifcant tumor size reduction and a decrease in chronic bleeding associated to improvement in general health were observed with the piroxicam-based treatment. To our knowledge, this is the frst report of a mixed (cranial and caudal) epigastric artery skin flap. This type of flap was considered a good option for correction of large defects in the inguinal region and for preservation of the prepuce and penis.Keywords: hemangiosarcoma, cranial, caudal, penis, sparing.

The nonsteroidal antiinflammatory drug piroxicam reverses the onset of depressive-like behavior in 6-OHDA animal model of Parkinson’s disease

Depression is one of the most common psychiatric symptoms in patients with Parkinson’s disease (PD). Some authors have reported that depression is characterized by activation of the inflammatory response. Animal models of PD also present with depressive-like behavior, such as increased immobility time in the modified forced swim test and anhedonia-like behavior in the sucrose preference test. Considering the potential neuroprotective effect of nonsteroidal antiinflammatory drugs in neurodegenerative diseases, the objective of the present study was to investigate the effects of piroxicam on depressive-like behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN). Antidepressant-like effects were observed after prolonged administration of piroxicam for 21days. In the forced swim test, the 6-OHDA+saline group exhibited significant reductions in swimming time and increased immobility time compared with the sham+saline. In the sucrose preference test, the 6-OHDA+piroxicam group exhibited no reduction of sucrose preference compared with the sham+saline, with significant effects of treatment and time and a significant treatment×time interaction. 5-Hydroxytryptamine (5-HT) levels significantly decreased in the hippocampus in the 6-OHDA+saline group and not changed in the 6-OHDA+piroxicam group when compared with the sham+saline on day 21. In conclusion, 21-day treatment with piroxicam reversed the onset of depressive-like behavior and prevented the reduction of hippocampal 5-HT levels.

Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice.

Osteoporosis and fractures are common complications of inflammatory bowel disease. The pathogenesis is multifactorial and has been partly attributed to intestinal inflammation. The aim of this study was to evaluate bone status and assess the association between bone loss and gut inflammation in an experimental colitis model. Colitis was induced in interleukin-10 knockout mice (PAC IL-10 k.o.) by peroral administration of piroxicam for 12 days. The degree of colitis was assessed by clinical, macroscopic, and microscopic evaluation. Trabecular and cortical bone microarchitecture of tibia were determined using micro-computed tomography. Moreover, the serum levels of bone formation and bone resorption biomarkers were measured, and inflammatory protein profiling was performed on colons. PAC IL-10 k.o. mice developed severe colitis, characterized by hyperplasia and focal transmural inflammation, which was consistent with Crohn's disease-like pathology. The gut inflammation was accompanied by a 14% and 12% reduction in trabecular thickness relative to piroxicam-treated wild type and untreated wild type mice, respectively (P < 0.001). The trabecular bone structure was also changed in PAC IL-10 k.o. mice, whereas no differences in cortical bone geometry were observed. The trabecular thickness was inversely correlated with serum levels of CTX (r = -0.93, P = 0.006). Moreover, numerous inflammatory mediators, including RANKL and osteoprotegerin, were significantly increased in the colon of PAC IL-10 k.o. mice. PAC IL-10 k.o. mice develop bone loss and changed trabecular structure, as a result of increased bone resorption. Thus, the PAC IL-10 k.o. model could be a useful experimental model in preclinical research of inflammatory bowel disease-associated bone loss.

Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a "brake" on neuronal excitability in ischemic stroke.

Our previous studies indicated an increase in extracellular γ-aminobutyric acid (GABA) in rodent's ischemic brain after Piroxicam administration, leading to alleviation of glutamate mediated excitotoxicity through activation of type A GABA receptor (GABAA). This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

Alleviation of glutamate mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism.

Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P < 0.01) reduction in cerebral infarct volume and potentiation of the intrinsic antioxidant status. High-performance liquid chromatography of brain cortex and striatum revealed changes in extracellular concentrations of neurotransmitters which were found to be 0.519 ± 0.44 pmole/mg (GABA); 1.18 ± 0.28 pmole/mg (glutamate), and 0.63 ± 0.21 pmole/mg (serotonin), respectively. Hydroxyl radical (·OH) adduct of salicylate in the frontal cortex and striatum in control, untreated, and treated groups was found to be 0.261 ± 0.06, 0.68 ± 0.52, and 0.401 ± 0.68 pmole/mg, respectively. After stroke, the extracellular level of glutamate in rat brain increases continuously as compared to that of control group. However, piroxicam administration in stroke rat significantly reduced (P < 0.05) elevated extracellular cerebral glutamate. This indicates that piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism.

Protective effect of antioxidant rich aqueous curry leaf (Murraya koenigii) extract against gastro-toxic effects of piroxicam in male Wistar rats

Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide), a classical non-steroidal anti-inflammatory drug (NSAID) is orally administered to arthritic patients. Inhibition of prostaglandin E2 (PGE2) synthesis and subsequent free hydroxyl radical generation in vivo exert gastro-toxic side effects on piroxicam treatment. Leaves of curry plant are rich in antioxidants with prolific free radical scavenging activities. This led us to investigate the efficiency of the use of curry leaves in ameliorating piroxicam induced gastric damage. Piroxicam was orally (30 mg per kg body weight) administered in male albino Wistar rats to generate gastric ulcers. These rats were orally fed with graded doses of aqueous extract of curry or Murraya koenigii leaves (Cu LE) prior to piroxicam administration. Oxidative stress biomarkers, activities of antioxidant and pro-oxidant enzymes, mucin content and nature, PGE2 level, activities of mitochondrial enzymes and histomorphology of gastric tissues were studied. Piroxicam treatment altered all the above mentioned parameters whereas, curry leaf extract pre-treated animals were protected against piroxicam induced alterations. Hence, the protective action of the antioxidant rich Cu LE was investigated to propose a new combination therapy or dietary management to arthritic patients using piroxicam.

P023 Therapy with FREMS (Frequency Rhythmic Electrical Modulation System)

Background: Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation with unknown etiology. Interleukin-10 Knockout (IL-10 KO) Mice are known to develop intestinal inflammation that resemble CD. We investigated if a human adipose-derived stem cells (h-ASCs) are capable to attenuated colon inflammation in IL-10 KO mice. Methods: h-ASCs were isolated from adipose tissues obtained from human donors. Colitis was induced in the mice by administration of piroxicam orally. Mice treated with intraperitoneal h-ASCs injection (5×105 cells) or normal saline as control after induction of colitis. All mice were euthanized 14 days after colitis. Histopathologic score and level of inflammation related cytokines were evaluated. Comparisons were made between h-ASCs treated or control non-treated IL-10 KO mice and wild type littermate. Results: The flow cytometry showed higher expression of CD105, CD73, CD90, CD44, however, hematopoietic stem cell markers such as CD45, CD34 and CD31 were not expressed in ADSC. Clinical score was lower in h-ASCs treated IL-10 KO mice than in control. Histopathologic assesment of large intestine showed lower inflammatory cells infiltration and less mucosal damage in h-ASCs treated mice than in control. Tissue score was lower in h-ASCs treated IL-10 KO mice than in control. The level of Monocyte chemoattractant protein-1 and Toll-like receptor 4 expression in the large intestine was lower and anti human IL-10 and anti mouse IL-4 in the serum was higher in h-ASCs treated mice. Conclusions: These findings suggested that administration of h-ASCs show beneficial effect on T-cell induced spontaneous colitis model and emerge a therapeutic option in inflammatory bowel disease.

P022 Therapeutic effect of adipose tissue-derived stem cell in Interleukin-10 knockout mice

Background: Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation with unknown etiology. Interleukin-10 Knockout (IL-10 KO) Mice are known to develop intestinal inflammation that resemble CD. We investigated if a human adipose-derived stem cells (h-ASCs) are capable to attenuated colon inflammation in IL-10 KO mice. Methods: h-ASCs were isolated from adipose tissues obtained from human donors. Colitis was induced in the mice by administration of piroxicam orally. Mice treated with intraperitoneal h-ASCs injection (5×105 cells) or normal saline as control after induction of colitis. All mice were euthanized 14 days after colitis. Histopathologic score and level of inflammation related cytokines were evaluated. Comparisons were made between h-ASCs treated or control non-treated IL-10 KO mice and wild type littermate. Results: The flow cytometry showed higher expression of CD105, CD73, CD90, CD44, however, hematopoietic stem cell markers such as CD45, CD34 and CD31 were not expressed in ADSC. Clinical score was lower in h-ASCs treated IL-10 KO mice than in control. Histopathologic assesment of large intestine showed lower inflammatory cells infiltration and less mucosal damage in h-ASCs treated mice than in control. Tissue score was lower in h-ASCs treated IL-10 KO mice than in control. The level of Monocyte chemoattractant protein-1 and Toll-like receptor 4 expression in the large intestine was lower and anti human IL-10 and anti mouse IL-4 in the serum was higher in h-ASCs treated mice. Conclusions: These findings suggested that administration of h-ASCs show beneficial effect on T-cell induced spontaneous colitis model and emerge a therapeutic option in inflammatory bowel disease.

English

NSAIDs are frequently used for relief of inflammation and Antihistaminics are indicated for simultaneous administration for allergic manifestations. Opioids analgesics have been reported to interact with Antihistaminics. To explore the interacting potentiality, in the present study the effects of combined treatment with NSAIDs and antihistaminics were examined in rats. Anti-inflammatory effect was evaluated by Carrageenan induced hind paw oedema in rats. NSAIDs like aspirin, ibuprofen and piroxicam were selected for study on per se and on concurrent administration with Antihistaminics such as Promethazine, Cetrizine and Astemizole. All NSAIDs protected animals show anti-inflammatory activity. Aspirin shows highly significant potentiation of anti-inflammatory effect at all dose level, however ibuprofen and piroxicam show highly significant anti-inflammatory effect at higher doses only and on concurrent administration of antihistaminics, aspirin, piroxicam and ibuprofen with all antihistaminics produced highly significant potentiation except ibuprofen with Cetrizine produced significant potentiation of anti-inflammatory response at higher doses only.

Effects of Diclofenac, Piroxicam and α-Tocopherol on Monoamine-lymphopoietic Interfacing in Mice

The non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac (CAS 15307-79-6) and piroxicam (CAS 36322-90-4) were shown in previous works to induce bone marrow lymphopoiesis. The present work aimed at evaluating the extent to which lymphopoietic effects of the above mentioned drugs as well as their interactions with alpha-tocopherol (CAS 10191-41-0) may be reflected in changes in the tissue levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT). The study was performed in male adult mice. The doses were given once daily for 7 days. The evaluations were performed in 2 phases. First, dose-response relationships of each of diclofenac, piroxicam and alpha-tocopherol were evaluated using bone marrow lymphocytes counts and monoamines levels in plasma, brain and spleen. Then, interactions of alpha-tocopherol (10 mg/kg) with diclofenac (20 mg/kg) and piroxicam (3 mg/kg), respectively, were evaluated. The interaction evaluations included effects on bone marrow lymphocytes count, monoamines levels in plasma, brain, spleen and thymus, as well as spleen weight. The obtained findings revealed that diclofenac, piroxicam and alpha-tocopherol decreased NE and DA levels in plasma, brain and spleen. There was some correlation between the decrease in plasma NE and the bone marrow lymphopoiesis. Pre-administration of alpha-tocopherol failed to maintain monoamines levels at the range of normal values in plasma, brain and spleen of NSAIDs-treated mice except splenic DA levels. In addition, the decrease in NE level induced by administration of piroxicam or diclofenac, either alone or together with a-tocopherol, corresponded to the increase in bone marrow lymphopoiesis. The present work suggests that the diclofenac- and piroxicam-induced bone marrow lymphopolesis as well as their respective interactions with alpha-tocopherol are associated with parallel changes in monoamines levels, especially those of NE and 5-HT.

Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin

Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.

Effectiveness of piroxicam and ibuprofen premedication on orthodontic patients' pain experiences

To compare the effectiveness of preoperative administration of ibuprofen and piroxicam on orthodontic pain experienced after separator placement. Ninety patients aged between 13 years 9 months and 18 years 2 months who were to undergo fixed appliance orthodontic treatment were enrolled in this double-blind, parallel-arm, prospective study. Patients were evenly and randomly distributed to any of three experimental groups, as follows: (1) administration of placebo, (2) administration of 400 mg ibuprofen, and (3) administration of 20 mg piroxicam; medications were administered 1 hour before separator placement. The pain perceived was recorded by the patients on a linear and graded Visual Analogue Scale at time intervals of 2 hours; 6 hours; nighttime on the day of appointment; 24 hours after the appointment; and 2 days, 3 days, and 7 days after separator placement during each of the four activities (viz, chewing, biting, fitting front teeth, and fitting back teeth). The results revealed that preoperative administration of 20 mg of piroxicam 1 hour prior to separator placement resulted in a significant decrease in pain levels at 2 hours, 6 hours, nighttime, and 24 hours and on the second and third days after separator placement, compared to patients on a placebo or ibuprofen. Premedication with 20 mg of piroxicam results in significantly decreased pain experienced, compared to premedication with 400 mg of ibuprofen or placebo. Usage of 20 mg of piroxicam 1 hour prior to separator placement is recommended.

Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia-reperfusion injury

The present study was aimed to assess the effect of protein carbonylation (PC) in hepatic cells and effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on indicators of tissue damage induced by liver ischemia-reperfusion injury (LIRI). Warm ischemia was performed by partial vascular occlusion during 90 min in Wistar rats. In serum, we determined the catalytic activity of Alanine Aminotransferase, Aspartate Aminotransferase, Lacticate Dehydrogenase, and Ornithine Carbamoyltransferase. In liver samples, we studied cellular alterations by means of histologic studies, lipid peroxidation, PC by immunohistochemistry, apoptosis and reactive oxygen species in bile by electron paramagnetic resonance. Based on PC data, sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were the first to exhibit LIRI-associated oxidative damage and prior to parenchymal cells. Administration of piroxicam or meloxicam during the pre-ischemic period produced a highly significant decrease in all studied injury indicators. No significant differences were revealed between the protective action of the two drugs. The data shown here suggest the potential use of NSAIDs such as piroxicam or meloxicam in minimizing ischemic event-caused damage in liver. We also propose that PC may be employed as an adequate tool to assess tissue damage after oxidative stress.

Comparison of oral versus sublingual piroxicam during postoperative pain management after lower third molar extraction

In this study, 53 patients received piroxicam, administered orally or sublingually, after undergoing removal of symmetrically positioned lower third molars, during two separate appointments. This study used a randomized, blind, cross-over protocol. Objective and subjective parameters were recorded for comparison of postoperative results for 7 days after surgery. Patients treated with oral or sublingual piroxicam reported low postoperative pain scores. The patients who received piroxicam orally took a similar average amount of analgesic rescue medication compared with patients who received piroxicam sublingually (p>0.05). Patients exhibited similar values for mouth opening measured just before surgery and immediately following suture removal 7 days later (p>0.05), and showed no significant differences between routes of piroxicam administration for swelling control during the second or seventh postoperative days (p>0.05). In summary, pain, trismus and swelling after lower third molar extraction, independent of surgical difficulty, could be controlled by piroxicam 20mg administered orally or sublingually and no significant differences were observed between the route of delivery used in this study.