Lack of interaction of buprenorphine with flunitrazepam metabolism

OBJECTIVE: The authors' goal was to determine if the reported clinical adverse interaction of flunitrazepam and buprenorphine was caused by inhibition of drug metabolism. METHOD: Inhibition of flunitrazepam metabolism by buprenorphine and norbuprenorphine were determined in three human liver microsome preparations carrying the CYP2C19*1/*1 allele. Omeprazole metabolism mediated by CYP2C19 and CYP3A4 was used as a control reaction. Apparent K(i) values were determined. RESULTS: Norbuprenorphine did not inhibit the metabolism of flunitrazepam or omeprazole. Buprenorphine inhibited the formation of CYP3A4-mediated pathways of 3-hydroxyflunitrazepam and omeprazole sulfone formation (K(i) 118 and 16 microM) in human liver microsomes. Corresponding values were 38 and 90 microM in cDNA-expressed CYP3A4 microsomes. Projected in vivo inhibition of CYP3A4-mediated metabolism of flunitrazepam by buprenorphine is 0. 1%-2.5%. Estimated inhibition of buprenorphine N-dealkylation by flunitrazepam in vivo is 0.08%. CONCLUSIONS: The clinical interaction of flunitrazepam and buprenorphine is likely based on a pharmacodynamic mechanism.     

Resection of clinically localized segments of painful retinaculum in the treatment of selected patients with anterior knee pain

We reviewed the long-term results of 25 patients who had localized soft tissue resections for refractory anterior retinacular knee pain. Patients completed visual analog scales to determine their activity and pain level changes, subjective assessment of their results, and whether they would have the surgery again under the same circumstances. Five of the 25 patients (20%) had had no knee surgery before the soft tissue excision, with the rest having had an average of two prior operations (range, 1 to 6). Subjectively, 22 patients (88%) noted moderate-to-substantial improvement after surgery; 3 patients (12%) declared no long-term benefit. All 25 patients stated that they would repeat the surgery under the same circumstances. Five patients (20%) noted a decrease in their results over time, but only two patients (8%) decreased their job level after surgery because of their knee pain. The average activity level dropped 60% after knee symptoms developed and increased 40% after surgery. Pain levels decreased 50% after surgery. The patients with the best overall results had lesions that were in the medial, inferomedial, or inferolateral retinaculum. The histologic results of the specimens included fibrosis, vascular proliferation, and small nerves with decreased myelin (neuromata). Our results show that specific soft tissue excision of painful tissue can often lead to successful clinical outcomes.     

Isoflavone Genistein Induces Fluid Secretion and Morphological Changes in the Uteri of Post-Pubertal Rats

A reported increase in the incidence of infertility following high genistein intake could be related to alteration in the normal fluid volume and morphology of the uterus in adult female. In view of this, we investigated the effect of this compound on fluid secretion, fluid volume and morphology of the uterus in post-pubertal rats. Methods: Ovariectomised SD rats were treated with 17-β oestradiol (E) (0.8 X 10^-4 mg/kg/day) and genistein (0.5, 5, 10, 25, 50 and 100 mg/kg/day) for three days. Following drug treatment, in-vivo uterine perfusion was performed and the rate of fluid secretion and the volume of fluid in the uterus were determined via changes in weight (μl/min) and F-dextran concentration of the perfusate respectively. The animals were then sacrificed and the uteri were removed for weight determination, morphological analyses and proliferative cell nuclear antigen (PCNA) expression analyses by Western blotting. Results: Subcutaneous genistein treatment resulted in a dose-dependent increase in fluid secretion rate, fluid volume and uterine wet weight. Treatment with 100 mg/kg/day genistein resulted in a remarkable increase in the rate of uterine fluid secretion, the volume of the uterine luminal fluid as well as the circumference of the uterine and uterine glandular lumen suggesting an excessive fluid accumulation. Meanwhile, there were evidence of glandular hyperplasia and an increase in the expression of PCNA following treatment with 50 and 100 mg/kg/day genistein. Conclusion: High genistein intake could potentially cause adverse effects on the uterus by inducing excessive fluid secretion and accumulation as well as hyperplasia.     

Effects of Al-dopant at Ni or Co sites in LiNi0.6Co0.3Ti0.1O2 on interlayer slabs (Li–O) and intralayer slabs (TM–O) and their influence on the electrochemical performance of cathode materials

In order to satisfy the energy demands of the electromobility market, further improvements in cathode materials are receiving much attention, especially high energy density cathode materials for Li-ion batteries (LIBs). In this work, the self-propagating combustion (SPC) method is use to synthesise undoped LiNi_0.6Co_0.3Ti_0.1O₂ (LNCT), novel nano-sized Al-doped LiNi_0.6Co_0.3−xAl_xTi_0.1O₂ (LCA) and LiNi_0.6−xCo_0.3Al_xTi_0.1O₂ (LNA) (x = 0.01) cathode materials. LNCT, LCA and LNA were annealed at 700 °C for 24 h. Following the synthesis, the phase, chemical structure and purity of the materials were analysed using X-ray diffraction (XRD). Based on the XRD results, all materials exhibit a single-phase structure with rhombohedral layered structure. Based on the HRTEM and EDX results, all samples exhibit polyhedral-like shapes, while the Al-doped samples display smaller crystallite sizes compared to the undoped sample. As for the electrochemical performances, the initially discharged capacity of LCA (238.6 mA h g⁻¹) is higher than that of LNA (214.7 mA h g⁻¹) and LNCT (150.5 mA h g⁻¹). However, LNA has a lower loss of capacity after the 50^th cycle compared to the LCA sample, which makes it a more excellent candidate for electrochemical applications. The main reason for the excellent electrochemical behaviour of LNA is due to lower cation mixing. Furthermore, Rietveld refinements reveal that the LNA sample has a longer atomic distance of Li–O and shorter TM–O in the cathode structure, which makes Li⁺ ion diffusion more efficient, leading to excellent electrochemical performance. These findings further proved the potential of the novel nano cathode material of LiNi_0.6−xCo_0.3Al_xTi_0.1O₂ (LNA) to replace the existing commercialized cathode materials for rechargeable Li-ion batteries.

Al substitute into Ni site increase Li–O and reduce M–O atomic distance lead to excellent cycleability with high energy density.     

The Influence of Different Nonsteroidal Anti-Inflammatory Drugs on Alveolar Bone in Rats: An Experimental Study

The aim

The aim of this study was to investigate the effect of dexketoprofen trometamol, meloxicam, diclofenac sodium on any untreated alveolar bone when they are used as drugs for another indication.

Materials and Methods

Twenty eight male Spraque-Dawley rats were randomized into four groups as dexketoprofen trometamol (Group I), meloxicam (Group II), diclofenac sodium (Group III) and control group. Nonsteroidal anti-inflammatory drugs (NSAID) were administered after a fibula fracture for 10 days. Untreated alveolar bone was histopathologically examined for spongious bone density, osteoclastic density and osteoblastic density.

Results

Spongious bone density was lower in study groups (Group I, group II and group III) than the control group (p<0.05). In contrast, the increase in osteoclastic density was observed in other groups apart from the control group (p<0.05). Osteoblastic density was evaluated and it was determined that group II and group III had lower results than the control group (p<0.05) but group I was equal to the control group.

Conclusion

This study showed that systemically administrated NSAIDs have the potential to affect untreated alveolar bone. This should also be considered in long term use of NSAIDs.Key Words: Non-steroidal anti-inflammatory agents, bone remodeling, osteoblast, osteoclast, maxillary bone     

Microclimate and development of pressure ulcers and superficial skin changes

This study aims to evaluate the microclimate and development of pressure ulcers and superficial skin changes. A prospective cohort study was conducted in an acute care ward in Indonesia. Risk factors for pressure ulcers and superficial skin changes were identified based on the Bergstrom Braden conceptual model. Microclimate data were collected every 3 days for 15 days while the development of pressure ulcers and superficial skin changes was observed every day. Pressure ulcers and superficial skin changes were developed in 20 of the 71 participants. Total mean difference in skin temperature was higher for patients with pressure ulcers and superficial skin changes (0·9 ± 0·6°C) compared with controls (0·6 ± 0·8°C) (P = 0·071). Binary logistic regression predictor values for pressure ulcers and superficial skin changes were 0·111 for type of sheet and 0·347 for Braden Scale results. In conclusion, difference in skin temperature seems to be a predictor for pressure ulcer development and superficial skin changes, while synthetic fibre sheets are able to maintain a beneficial microclimate.