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The Journal of Headache and Pain Dec 2017Hemicrania continua (HC), paroxysmal hemicrania (PH) and short lasting neuralgiform headache attacks (SUNCT and SUNA) are rare syndromes with a difficult therapeutic... (Review)
Review
BACKGROUND
Hemicrania continua (HC), paroxysmal hemicrania (PH) and short lasting neuralgiform headache attacks (SUNCT and SUNA) are rare syndromes with a difficult therapeutic approach. The aim of this review is to summarize all articles dealing with treatments for HC, PH, SUNCT and SUNA, comparing them in terms of effectiveness and safety.
METHODS
A survey was performed using the pubmed database for documents published from the 1st January 1989 onwards. All types of articles were considered, those ones dealing with symptomatic cases and non-English written ones were excluded.
RESULTS
Indomethacin is the best treatment both for HC and PH. For the acute treatment of HC, piroxicam and celecoxib have shown good results, whilst for the prolonged treatment celecoxib, topiramate and gabapentin are good options besides indomethacin. For PH the best drug besides indomethacin is piroxicam, both for acute and prolonged treatment. For SUNCT and SUNA the most effective treatments are intravenous or subcutaneous lidocaine for the acute treatment of active phases and lamotrigine for the their prevention. Other effective therapeutic options are intravenous steroids for acute treatment and topiramate for prolonged treatment. Non-pharmacological techniques have shown good results in SUNCT and SUNA but, since they have been tried on a small number of patients, the reliability of their efficacy is poor and their safety profile mostly unknown.
CONCLUSIONS
Besides a great number of treatments tried, HC, PH, SUNCT and SUNA management remains difficult, according with their unknown pathogenesis and their rarity, which strongly limits the studies upon these conditions. Further studies are needed to better define the treatment of choice for these conditions.
Topics: Amines; Analgesics; Anticonvulsants; Cyclohexanecarboxylic Acids; Female; Fructose; Gabapentin; Humans; Indomethacin; Lamotrigine; Lidocaine; Male; Neuralgia; Paroxysmal Hemicrania; Reproducibility of Results; SUNCT Syndrome; Surveys and Questionnaires; Topiramate; Triazines; Trigeminal Autonomic Cephalalgias; gamma-Aminobutyric Acid
PubMed: 28730562
DOI: 10.1186/s10194-017-0777-3 -
Heliyon Jul 2019The organic molecule tenoxicam and similar derivatives, piroxicam and isoxicam have been studied by quantum chemical theory (DFT), FT-Raman and FT-IR. By FMOs energies...
The organic molecule tenoxicam and similar derivatives, piroxicam and isoxicam have been studied by quantum chemical theory (DFT), FT-Raman and FT-IR. By FMOs energies the charge transfer inside the molecules are obtained. The UV-Vis spectra of the compounds are simulated to study the electronic transition in the target molecules. By using natural bond orbital (NBO), charge delocalization analyzes arising from hyper conjugative interactions and the stability of the molecules are obtained. First order hyperpolarizability of piroxicam is higher than that of isoxicam and tenoxicam. The reactive areas are thoroughly studied by MEP. Prediction of Activity Spectra gives activities, anti-inflammatory, CYP2C9 substrate and gout treatment. Docked ligands form a stable complex with the receptors.
PubMed: 31388594
DOI: 10.1016/j.heliyon.2019.e02175 -
Canadian Journal of Veterinary Research... Apr 2020The objective of this study was to evaluate taurolidine as a therapy for transitional cell carcinomas in canine patients. Transitional cell carcinoma (TCC) is the most...
The objective of this study was to evaluate taurolidine as a therapy for transitional cell carcinomas in canine patients. Transitional cell carcinoma (TCC) is the most common cancer of the urinary bladder in dogs and accounts for approximately 2% of reported malignancies in this species. There is no cure for this neoplasm and most dogs are lost from complications associated with progression of the local disease. Taurolidine has been shown to have anti-tumor and antiangiogenic effects against a variety of neoplasms in human and animal models. Four canine TCC cell lines were treated with various concentrations of taurolidine, mitoxantrone, and piroxicam alone. In addition, combinations of taurolidine/mitoxantrone, taurolidine/piroxicam, mitoxantrone/piroxicam, and taurolidine/mitoxantrone/piroxicam were assessed. Susceptibility of the TCC cell lines was based on a 72-hour growth inhibition assay using resazurin with absorbance measured at λ530/590. The ability of taurolidine to induce apoptosis was evaluated on 2 of the cell lines with an Annexin-V/propidium iodide assay. All cell lines were susceptible to treatment with taurolidine, mitoxantrone, and piroxicam alone. The results of the combination therapies of the 3 drugs were dependent on cell line and concentration and revealed no change in cell growth inhibition, a subadditive relationship, or a synergistic relationship. Taurolidine induced apoptosis in a concentration- and time-dependent fashion. Taurolidine alone showed significant effects on cell viability in canine TCC cell lines and these effects can be potentially enhanced with the addition of mitoxantrone and/or piroxicam.
Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Transitional Cell; Cell Line; Cell Survival; Dog Diseases; Dogs; Drug Synergism; Mitoxantrone; Piroxicam; Taurine; Thiadiazines
PubMed: 32255906
DOI: No ID Found -
Polymers Jan 2023Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present...
Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxicam nanosuspension (PRX NS) was prepared by an anti-solvent precipitation technique and optimized using a full-factorial design. Herein, the nanosuspension was prepared using polymer polyvinylpyrrolidone (PVP) K30 and Poloxamer 188 as a stabilizer to improve the solubility and in vitro bioavailability of the drug. Nine formulations were prepared based on 3 full-factorial experimental designs to study the effect of the formulation variables such as concentration of poloxamer 188 (%) (X) and stirring speed (rpm) (X) as a process variable on the response of particle size (nm) and solubility (µg/mL). The prepared NS was characterized by phase solubility, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), particle size, zeta potential, entrapment efficiency, and percent drug release. DSC and XRPD analysis of freeze-dried NS formulation showed conversion of PRX into a less crystalline form. NS formulations showed a reduction in the size from 443 nm to 228 nm with -22.5 to -30.5 mV zeta potential and % drug entrapment of 89.76 ± 0.76. TEM analysis confirmed the size reduction at the nano level. The solubility was increased from 44 μg/mL to 87 μg/mL by altering the independent variables. The solubility of PRX NS in water was augmented by 14- to 15-fold (87.28 μg/mL) than pure PRX (6.6 μg/mL). The optimized formulation (NS9) at drug-to-stabilizer concentration exhibited a greater drug release of approximately 96.07% after 120 min as compared to the other NS formulations and pure PRX (36.78%). Thus, all these results revealed that the prepared NS formulations have improved the solubility and in vitro dissolution compared to the pure drug. Furthermore, an increase in the drug release was observed from the NS than that of the pure PRX. All these outcomes signified that the prepared PRX NS showed an increase in solubility and in vitro dissolution behavior; which subsequently would aid in attainment of enhanced bioavailability.
PubMed: 36771784
DOI: 10.3390/polym15030483 -
Biological Trace Element Research Jan 2023Selenium-enriched Lactobacillus plantarum and Bifidobacterium longum mutants were used as a protector against Piroxicam-induced ulcerative colitis (UC). In this study,...
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.
Topics: Mice; Male; Animals; Colitis, Ulcerative; Interleukin-10; Selenium; Peroxidase; Tumor Necrosis Factor-alpha; Piroxicam; Interleukin-2; Interleukin-6; Colon; Anti-Inflammatory Agents; Probiotics; Immunoglobulin G; Disease Models, Animal
PubMed: 35190960
DOI: 10.1007/s12011-022-03154-1 -
Avicenna Journal of Phytomedicine Nov 2014The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative...
OBJECTIVE
The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative stress and gastro-toxicity in Wistar rats.
MATERIALS AND METHODS
Thirty healthy male and female Albino Wistar rats (190-220 g) were grouped into six (n = 5) with designated treatments including: Normal saline, piroxicam (20 mg/kg), extract (200 and 400 mg/kg) alone and both doses of the extract co-administered with piroxicam. The drugs were administered orally to all the rats for fourteen consecutive days and on the fifteenth day, they were euthanized with chloroform inhalation. Blood samples and the stomachs were isolated for evaluation of the oxidative stress biomarkers and gastro integrity, respectively.
RESULTS
The results of the study revealed that the levels of oxidative stress markers didn't differ significantly between the groups receiving the extract alone, the extract in combination or piroxicam alone. Gross and histological observations of the stomach showed gastric mucosal changes and mild atrophic lesions in the piroxicam group only.
CONCLUSION
This study illustrates the interaction of Khaya senegalensis and piroxicam results in the gastro-protective beneficial effects. The extract's outcome on various prostaglandin levels and synthesis is being considered towards possible elucidation regarding the exact mechanism of cytoprotection.
PubMed: 25386401
DOI: No ID Found -
Gut Microbes 2023Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel...
Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesized that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive (AIEC)], might explain this inconsistent NSAIDs/IBD correlation. Using mice, we found that NSAID aggravated colitis in AIEC-colonized animals. This was accompanied by activation of the NLRP3 inflammasome, Caspase-8, apoptosis, and pyroptosis, features not seen in mice exposed to AIEC or NSAID alone, revealing an AIEC/NSAID synergistic effect. Inhibition of NLRP3 or Caspase-8 activity ameliorated colitis, with reduction in NLRP3 inflammasome activation, cell death markers, activated T-cells and macrophages, improved histology, and increased abundance of cluster XIVa species. Our findings provide new insights into how NSAIDs and an opportunistic gut-pathobiont can synergize to worsen IBD symptoms. Targeting the NLRP3 inflammasome or Caspase-8 could be a potential therapeutic strategy in IBD patients with gut inflammation, which is worsened by NSAIDs.
Topics: Animals; Mice; Anti-Inflammatory Agents, Non-Steroidal; Caspase 8; Colitis; Gastrointestinal Microbiome; Inflammasomes; Inflammatory Bowel Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; Caspase Inhibitors; Escherichia coli
PubMed: 36656595
DOI: 10.1080/19490976.2022.2163838 -
Molecules (Basel, Switzerland) Dec 2021The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the...
The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes , , , and as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and and downregulated . They inhibited and and their effect on and depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only and were not upregulated in tumors, nor was in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, and were upregulated, while , and were downregulated in tumors. Tumor and increased along with advancing T and and along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating and interfering with NF-κB signaling.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Caco-2 Cells; Chemokines; Colorectal Neoplasms; Female; HCT116 Cells; Humans; Macrophages; Male; Meloxicam; Piroxicam
PubMed: 34885960
DOI: 10.3390/molecules26237375 -
IUBMB Life Dec 2014Oxicams are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) structurally related to the enolic acid class of 4-hydroxy-1,2-benzothiazine carboxamides. They are... (Review)
Review
Oxicams are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) structurally related to the enolic acid class of 4-hydroxy-1,2-benzothiazine carboxamides. They are used clinically to treat both acute and chronic inflammation by inhibiting the activity of the two cyclooxygenase (COX) isoforms, COX-1 and COX-2. Oxicams are structurally distinct from all other NSAIDs, exhibiting a novel binding pose in the COX active site. The 4-hydroxyl group on the thiazine ring partners with Ser-530 via hydrogen bonding while two coordinated water molecules mediate a polar interaction between the oxicam and COX. The rotation of Leu-531 in the complex opens a new pocket, which is not used for binding other NSAIDs to the enzyme. This structure provides the basis for understanding documented structure-activity relationships within the oxicam class. In addition, from the oxicam template, a series of potent microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors represents a new direction for drug development. Here, we review the major route of oxicam synthesis and structure-activity for COX inhibition, as well as recent advances in oxicam-mediated mPGES-1 inhibition.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Inflammation; Intramolecular Oxidoreductases; Meloxicam; Piroxicam; Prostaglandin-E Synthases; Thiazines; Thiazoles
PubMed: 25537198
DOI: 10.1002/iub.1334 -
ACS Omega Nov 2023Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints,...
Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints, disability, and even premature death. Markers of inflammation are highly expressed in synovium fluid and serum of arthritic patients and play an important role in the pathophysiology of RA. These transcription factors promote the fabrication of type I interferons and inflammatory cytokines. In RA, degradation of synovial cartilage and bone results from stimulation of proinflammatory cytokines. Citronellol (Ct), a monoterpene alcohol, is found in citrus fruits and essential oils of many aromatic plants. It possesses numerous pharmacological properties such as antioxidant activity and potential antinociceptive and anti-inflammatory effects. Keeping in view the significant anti-inflammatory role of Ct, a trial of 28 days was conducted. Ct was administered orally at three different doses (25, 50, and 100) mg/kg in Freund's adjuvant-induced arthritic rats, and the results were compared with piroxicam, chosen as the standard drug. The antiarthritic activity of the compound was evaluated through measurements of arthritic scoring and plethysmometry before and after treatment. The blood biochemical and hematological parameters and histopathological analyses were performed. Additionally, qPCR was conducted to analyze the mRNA expression levels of TNF-α, IL-1β, NF-κB, MMP3, IL-6, and IL-4 in the blood. ELISA was performed to evaluate the levels of PGE2. The results demonstrated that Ct showed significant results at all doses, but the highest dose proved to be most significant in terms of decreasing arthritic scoring and paw edema, indicating the antiarthritic potential of Ct. Furthermore, the compound was found to downregulate all the proinflammatory cytokines (TNF-α, IL-1β, NF-κB, MMP3, and IL-6) and upregulate the anti-inflammatory cytokine (IL-4). The levels of PGE2 were also reduced which further supported the antiarthritic effects of Ct and validated it as a potential antiarthritic candidate.
PubMed: 38046326
DOI: 10.1021/acsomega.3c06374