393 research outputs found
Cytoprotection and healing: Two unequal brethren
The promotion of the concept of cytoprotection has fostered hopes that the use of co-prescribed mucosal protective agents would revolutionize the prevention of NSAID-induced ulcers and supply the basis for novel ulcer therapy. Prostaglandins do not, however, accelerate ulcer healing when applied at doses that exert an unequivocal cytoprotective activity. Attempts have therefore been made in recent years to create new less-toxic NSAIDs, such as combined lipoxygenase/cyclo-oxygenase inhibitors, NSAIDs coupled to an NO donor and so-called COX-2 inhibitors. All these preparations do in fact exert a diminished gastrointestinal toxicity. There is however increasing evidence accumulating from studies performed in and outside our laboratories that in chromic ulcer models their increased gastrointestinal tolerance is not necessarily reflected by non-interference with ulcer healing. It is thus mandatory to distinguish between cytoprotective and healing properties of drugs interfering with the cyclo-oxygenase pathwa
The Effects of a Human Hand on a Wireless Mouse Antenna
In this paper, Finite Difference Time Domain (FDTD) method is used to analyze the effect of a human hand on a wireless mouse antenna. The need for this analysis is based on the fact that human tissues are dielectric in nature and they can, therefore, be treated as electromagnetic absorbers. In the first part, hand effect on reflection coefficient, input resistance, bandwidth and radiation efficiency are studied. In the second part, the variation of radiation efficiency with the position of the hand from the antenna feed point is estimated. The Method of Moments is used to validate the results. Keywords: Wireless mouse, Antenna dipole, Electromagnetic Field, FDTD, Efficiency
N K1 Receptors M ed iated Release of 6-Keto-PG F1 from the Ex Vivo Perfused Canine IIeum1
ABSTRACT ABBREVIATiONS: EGTA, ethyleneglycol-bis- ( -aminoethyl ether)N,N,N',N'-tetra-acetic acid; L-NAME, N#{176}'-L-arginine methyl ester LT, leukotnene; ANOVA, analysis of variance; AlA, radioimmunoassay; GC-MS, gas chromatography-mass spectrometry
Rationale and evidence for the incorporation of heparin to the diclofenac epolamine medicated plaster
The nonsteroidal anti-inflammatory drug (NSAID) diclofenac epolamine (DHEP) formulated as a topical patch has demonstrated efficacy and safety in the localized treatment of acute pain from minor strains, sprains, and contusions, and for epicondylitis and knee osteoarthritis. The glycosaminoglycan heparin enhances the activity of topical NSAIDs formulated as a medicated plaster, even in the absence of any significant release of heparin. Therefore, DHEP Plus, a new formulation of the DHEP medicated plaster containing a small amount of heparin sodium as excipient has been developed.
Methods: We reviewed the pivotal and supportive studies of the clinical development program of the new patch and evaluated the role of heparin as an enhancer in the treatment of localized pain/inflammation of musculoskeletal structures, associated with post-traumatic and/or rheumatic conditions.
Results: The data were consistent with the concept that heparin increased the clinical activity of the DHEP Plus medicated plaster versus the reference DHEP medicated plaster through improved bioavailability due to enhanced movement of diclofenac from the plaster. Both DHEP formulations have the same dissolution profile, indicating that heparin does not change the physical and chemical characteristics of the plaster. Permeation testing showed that heparin is not released from the DHEP Plus medicated plaster. Efficacy studies showed that the DHEP Plus medicated plaster was significantly more effective in reducing pain than the reference marketed DHEP medicated plaster.
Conclusions: The benefit/risk assessment of DHEP Plus 180 mg medicated plaster is favorable, with a safety profile equal to placebo and improved efficacy over the reference marketed DHEP medicated plaster
Submucosal diclofenac for acute postoperative pain in third molar surgery: A randomized, controlled clinical trial
Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) for relief of inflammatory pain. A recent formulation combines this drug with hydroxypropyl-β-cyclodextrin (HPβCD) to improve its solubility and to enable subcutaneous administration. Previous studies confirmed the efficacy of this combination. This study’s aim was to evaluate the efficacy, safety, and local tolerability of diclofenac HPβCD administered as a local submucosal injection prior to lower third molar surgery. We conducted a prospective, randomized, double-blind, placebo-controlled, parallel-group phase II single-center study. Seventy-five patients requiring mandibular third molar surgery were randomized into 1 of 5 groups: 5 mg/1 mL diclofenac HPβCD, 12.5 mg/1 mL diclofenac HPβCD, 25 mg/1 mL diclofenac HPβCD, 50 mg/1 mL diclofenac HPβCD, or 1 mL placebo. The respective study drug was injected into the mucosal tissue surrounding the surgical site prior to surgery following achievement of local anesthesia. The primary outcome measure was the area under the curve (AUC) of cumulative pain scores from end of surgery to 6 h postsurgery. This demonstrated a global treatment effect between the active groups and placebo, hence confirming the study drug’s efficacy (P = 0.0126). Secondary outcome measures included the time until onset of pain and the time until patients required rescue medication, both showing statistical significance of the study drug compared to placebo (P < 0.0161 and P < 0.0001, respectively). The time until rescue medication ranged between 7.8 h (for 25 mg/1 mL diclofenac HPβCD) and 16 h (for 50 mg/1 mL diclofenac HPβCD). Interestingly, the 5-mg/1-mL solution appeared superior to the 12.5-mg/1-mL and 25-mg/1-mL solutions (time until rescue medication = 12.44 h). A total of 14% of patients experienced minor adverse drug reactions (ADRs), of which 2 cases demonstrated flap necrosis. These resolved without further intervention. The study results overall indicate efficacy, safety, and relative tolerability of diclofenac HPβCD used locally as a submucosal injection prior to third molar surgery (ClinicalTrials.gov NCT01706588)
Ketorolak-dekstran konjugati: sinteza, in vitro i in vivo vrednovanje
Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.U radu je opisana sinteza konjugata dektrana i protuupalnog lijeka ketorolaka (KD). Konjugati su pripravljeni da bi se povećala topljivost ketorolaka u vodi i smanjila njegova nusdjelovanja u gastrointestinanom traktu. Ketorak je prvo preveden u N-acilimidazolni derivat (KAI) koji je kondenziran s polimernim nosačem, dekstranom različitih molekulskih masa (40000, 60000, 110000 i 200000). IR-spektri potvrdili su nastajanje esterske veze. Udio ketorolaka u konjugatu određen je UV-spektrofotometrijskom analizom. Molekulske mase određene su mjerenjem viskoznosti koristeći Mark-Howink-Sakurada jednadžbu. Hidroliza in vitro praćena je u puferskim otopinama (pH 1,2, 7,4 i 9) i u 80% V/V humanoj plazmi (pH 7,4). Pri pH 9 primjećeno je značajno brže oslobađanje ketorolaka iz KD nego u puferskoj otopini pH 7,4 i krvnoj plazmi. Oslobađanje je prati kinetiku prvog reda. In vivo biološka ispitivanja na miševima i štakorima ukazuju da konjugati imaju analgetsko i protuupalno djelovanje, a značajno smanjeno ulcerogeno djelovanje
Healing Potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration.
<p>Abstract</p> <p>Background</p> <p>The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, <it>Picrorhiza kurroa </it>in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE<sub>2</sub>) and EGF during the process.</p> <p>Methods</p> <p>Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose) were treated up to 7 days with different doses of the methanol extract of <it>P. kurroa </it>rhizomes (designated as PK). The healing capacity of the most effective dose of PK (20 mg/kg, p. o. × 3 d) was compared with that of omeprazole (Omez) (3 mg/kg, p. o. × 3 d). The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1<sup>st </sup>and 3<sup>rd </sup>day of ulceration. The stomach tissues of the mice were used for the biochemical analysis.</p> <p>Results</p> <p>The macroscopic indices revealed maximum ulceration on the 3<sup>rd </sup>day after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (<it>P </it>< 0.01), and 76.3% respectively (<it>P </it>< 0.001), compared to the untreated ulcerated mice.</p> <p>Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS) (32.7%, <it>P </it>< 0.05) and protein carbonyl (37.7%, <it>P </it>< 0.001), and increased mucin (42.2%, <it>P </it>< 0.01), mucosal PGE<sub>2 </sub>(21.4%, <it>P </it>< 0.05), and expressions of COX-1 and 2 (26.9% and 18.5%, <it>P </it>< 0.05), EGF (149.0%, <it>P </it>< 0.001) and VEGF (56.9%, <it>P </it>< 0.01). Omez reduced the TBARS (29.4%, <it>P </it>< 0.05), and protein carbonyl (38.9%, <it>P </it>< 0.001), and increased mucin (38.3%, <it>P </it>< 0.01), without altering the other parameters significantly.</p> <p>Conclusion</p> <p>PK (20 mg/kg, p. o. × 3 days) could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.</p
A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality
The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19
Dental calculus and isotopes provide direct evidence of fish and plant consumption in Mesolithic Mediterranean
In this contribution we dismantle the perceived role of marine resources and plant foods in the subsistence economy of Holocene foragers of the Central Mediterranean using a combination of dental calculus and stable isotope analyses. The discovery of fish scales and flesh fragments, starch granules and other plant and animal micro-debris in the dental calculus of a Mesolithic forager dated to the end of the 8th millenium BC and buried in the Vlakno Cave on Dugi Otok Island in the Croatian Archipelago demonstrates that marine resources were regularly consumed by the individual together with a variety of plant foods. Since previous stable isotope data in the Eastern Adriatic and the Mediterranean region emphasises that terrestrial-based resources contributed mainly to Mesolithic diets in the Mediterranean Basin, our results provide an alternative view of the dietary habits of Mesolithic foragers in the Mediterranean region based on a combination of novel methodologies and data
Ajustamento de observações: uma interpretação geométrica para o método dos mínimos quadrados
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