betadex and Chronic-Disease

The clinical effects of piroxicam-beta-cyclodextrin (PBC) in sachet form have been surveyed in patients with osteoarthritic or acute pain in western countries, but scarcely studied in those with chronic low back pain (LBP), and never investigated in the field of postural sway. The aim of this study was to evaluate the clinical effects of PBC in sachet form prescribed in patients with chronic backache in local Asian when compared with those of plain piroxicam.. After randomized allocation and experimental exclusion, a total of 42 eligible patients were randomized into two groups, the sachet group (n = 23) and the piroxicam tablet group (n = 19). Both groups were administered the same dosage, orally per day (daily dose = 20 mg). The duration of trial was 28 days. Efficacy was assessed with pain score, disability index and postural sway.. The patients in sachet group showed greater improvement in pain score and disability index than those who took piroxicam tablets. There were significantly lower sway velocity and intensity at almost all different conditions than baseline profiles in both groups (P < 0.05). However, there was no significant difference of sway velocity and intensity in the piroxicam tablets group with regard to eyes open or eyes closed in 20 degrees dorsiflexion.. Piroxicam-beta-cyclodextrin (PBC) sachet may have greater improvement in the treatment of chronic LBP and possess the extended effects on postural abnormality relevant to chronic LBP.

Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Chronic Disease; Dosage Forms; Drug Combinations; Female; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Piroxicam; Postural Balance; Tablets; Young Adult

Piroxicam-beta-cyclodextrin (PBC) is the first nonsteroidal anti-inflammatory drug (NSAID), in which the active substance is complexed with the cyclic oligosaccharide cyclodextrin, which acts as an artificial receptor. This complex allows single molecules of the NSAID to be released adjacent to the gastrointestinal mucosa, instead of crystals. Since the piroxicam is immediately bioavailable in this formulation, the onset of action is similar to that of a parenteral drug. Since the time contact with gastric mucosa is reduced, the risk of direct-contact gastric irritation is also reduced. There is good evidence that PBC is beneficial in managing acute non-specific back pain (BP) but sufficient evidence on chronic BP is lacking.. Thirty-one eligible patients aged 18-85 years, resistant to previous therapy with different NSAIDs, were treated with PBC 20 mg once daily in a 40-day open-label noncomparative study. The patients experienced chronic BP defined as pain between the occipital region and gluteal fold, lasting for at least 6 weeks but not more than 6 months. Efficacy was assessed by changes in pain intensity, paravertebral tonus, functional impairment and morning stiffness using a 4-point numerical rating scale. Patients also self-assessed nocturnal and diurnal pain using the visual analogue scale. Tolerability was assessed by adverse events and routine laboratory evaluations. Global assessment of efficacy and tolerability by physician and patients was performed at the last visit.. Using intention-to-treat analysis, all efficacy assessments demonstrated statistically significant improvements over baseline at each follow-up. 90.3% of the patients evaluated the efficacy of PBC as improved or greatly improved, and investigators rated the treatment as improved or greatly improved in 87.1% of patients. Remission was achieved in 19.3% of the patients. Tolerability was also rated highly, with 83.9% of the patients characterizing PBC treatment as good or very good, and the investigators rated the treatment as good or excellent in 87.1% of the patients. Drug related adverse events were reported in 9.7% of patients and prompted discontinuation of the study medication in 3.2% of patients. No serious adverse events were reported.. These results suggest that the newly developed dosage form of piroxicam is effective and well tolerated in the treatment of patients with chronic BP. Thus, PBC, may be an important new treatment option in this condition. (Tab. 3, Fig. 3, Ref. 36.).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Back Pain; beta-Cyclodextrins; Chronic Disease; Cyclodextrins; Drug Combinations; Female; Humans; Male; Middle Aged; Piroxicam

To compare the absorption and clinical effect of spironolactone from an inclusion complex with beta-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease.. Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5-7 and 12-14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study.. The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6beta-hydroxyl 7alpha-thiomethyl spironolactone and 7alpha-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD.. Better absorption of spironolactone from the spironolactone: beta-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.

Topics: beta-Cyclodextrins; Biological Availability; Canrenone; Chronic Disease; Cross-Over Studies; Cyclodextrins; Diuresis; Diuretics; Female; Humans; Liver Diseases; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Spironolactone; Treatment Outcome; Water-Electrolyte Balance

A study was carried out to assess the analgesic efficacy and the safety of piroxicam and to compare them with those of a piroxicam derivative, piroxicam beta-cyclodextrin, in chronic pain caused by arthritis of the neck and lower back. The drugs in question were administered for two weeks at the dose of 20 mg/die per os to 63 patients, 32 of whom were treated with the original molecule and the remaining subjects with its derivative. The study protocol scheduled assessments of pain and its reduction at baseline and after three, seven, and fourteen days of treatment. At the end of the two weeks of treatment, the drugs' efficacy and safety were evaluated. The results confirmed piroxicam's efficacy and safety in pain of the neck and lower back caused by osteoarthritis and did not show any differences, for the parameters examined, between the original molecule and its derivative.

Topics: Adult; Aged; beta-Cyclodextrins; Cervical Vertebrae; Chronic Disease; Cyclodextrins; Drug Evaluation; Female; Humans; Joint Diseases; Lumbar Vertebrae; Male; Middle Aged; Pain; Piroxicam; Randomized Controlled Trials as Topic

Inflammation is a common cause of many acute and chronic inflammatory diseases. A major limitation of existing anti-inflammatory therapeutics is that they cannot simultaneously regulate pro-inflammatory cytokine production, oxidative stress, and recruitment of neutrophils and macrophages. To overcome this limitation, nanoparticles (NPs) with multiple pharmacological activities are synthesized, using a chemically modified cyclic oligosaccharide. The manufacture of this type of bioactive, saccharide material-based NPs (defined as LCD NP) is straightforward, cost-effective, and scalable. Functionally, LCD NP effectively inhibits inflammatory response, oxidative stress, and cell migration for both neutrophils and macrophages, two major players of inflammation. Therapeutically, LCD NP shows desirable efficacies for the treatment of acute and chronic inflammatory diseases in mouse models of peritonitis, acute lung injury, and atherosclerosis. Mechanistically, the therapeutic benefits of LCD NP are achieved by inhibiting neutrophil-mediated inflammatory macrophage recruitment and by preventing subsequent pro-inflammatory events. In addition, LCD NP shows good safety profile in a mouse model. Thus, LCD NP can serve as an effective anti-inflammatory nanotherapy for the treatment of inflammatory diseases mainly associated with neutrophil and macrophage infiltration.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; beta-Cyclodextrins; Biological Transport; Chronic Disease; Inflammation; Macrophages; Mice; Nanoparticles; RAW 264.7 Cells

Chronic stress is a risk factor for depression, and chronic stress can induce cognitive impairments associated with prefrontal cortical dysfunction, which are also major components of depression. We have previously shown that 5 wk chronic intermittent cold (CIC) stress induced a reversal-learning deficit in rats, associated with reduced serotonergic transmission in the orbitofrontal cortex (OFC) that was restored by chronic treatment with a selective serotonin reuptake inhibitor (SSRI). However, the mechanisms underlying the beneficial cognitive effects of chronic SSRI treatment are currently unknown. Thus, the purpose of this study was to investigate the potential modulatory influence specifically of 5-HT2A receptors (5-HT2ARs) in the OFC on reversal learning, and their potential contribution to the beneficial cognitive effects of chronic SSRI treatment. Bilateral microinjections of the selective 5-HT2AR antagonist, MDL 100,907 into OFC (0.02-2.0 nmol) had a dose-dependent detrimental effect on a reversal-learning task, suggesting a facilitatory influence of 5-HT2ARs in the OFC. In the next experiment, rats were exposed to 5 wk CIC stress, which compromised reversal learning, and treated chronically with the SSRI, citalopram (20 mg/kg.d) during the final 3 wk of chronic stress. Chronic citalopram treatment improved reversal learning in the CIC-stressed rats, and bilateral microinjection of MDL 100,907 (0.20 nmol, the optimal dose from the preceding experiment) into OFC once again had a detrimental effect on reversal learning, opposing the beneficial effect of citalopram. We conclude that 5-HT2ARs in the OFC facilitate reversal learning, and potentially contribute to the beneficial cognitive effects of chronic SSRI treatment.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Attention; beta-Cyclodextrins; Chronic Disease; Citalopram; Cognition; Fluorobenzenes; Male; Microinjections; Pharmaceutical Vehicles; Piperidines; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Reversal Learning; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Set, Psychology; Stress, Psychological

Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-alpha1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4+/-1.1-, 3.2+/-0.9-, and 3.4+/-1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of beta-methyl cyclodextran (betaMCD) had significantly reduced growth factor expression (1.3+/-0.3, vs betaMCD untreated being 6.4+/-1.1-fold increase) upon stimulation with KAT Abs. Depletion of cholesterol on NHBE cells upon treatment with betaMCD also resulted in decreased partitioning of caveolin in the membrane fraction indicating a decrease in raft-domains. In conclusion, our results demonstrate an important role for lipid raft-mediated ligation of Abs to KAT on the epithelial cell membrane, which results in the upregulation of growth factor cascades involved in the pathogenesis of BOS following human lung transplantation.

Topics: Antibodies; beta-Cyclodextrins; Bronchiolitis Obliterans; Cells, Cultured; Chronic Disease; Fibroblast Growth Factor 2; Graft Rejection; Humans; Lung Transplantation; Membrane Microdomains; Platelet-Derived Growth Factor; Respiratory Mucosa; Tubulin; Vascular Endothelial Growth Factor A

The case of a 53-year-old woman is described, who since the age of 38 years had been suffering from a unilateral headache that was at first remitting, but then evolved into an unremitting course. The headache was burning in quality, located in the left forehead and face, and was accompanied by mild ipsilateral autonomic symptoms. The clinical picture, as well as the absolute response to indomethacin, suggested a diagnosis of hemicrania continua. The presence of mild gastric discomfort on continuous indomethacin administration made us transfer the patient to another NSAID (piroxicam-beta-cyclodextrin). With this drug, complete relief and good tolerability was obtained.

Topics: beta-Cyclodextrins; Chronic Disease; Cyclodextrins; Drug Combinations; Female; Humans; Indomethacin; Middle Aged; Migraine Disorders; Piroxicam; Stomach Diseases