Encapsulation in lipospheres of the complex between butyl methoxydibenzoylmethane and hydroxypropyl-beta-cyclodextrin

The aim of this study was to investigate the incorporation into lipospheres of the complex between hydroxypropyl-β-cyclodextrin (HP-β-CD) and the sunscreen agent, butyl methoxydibenzoylmethane (BMDBM) and to examine the influence of this system on the sunscreen photostability. The formation of the inclusion complex was confirmed by thermal analysis and powder X-ray diffraction. Lipid microparticles loaded with free BMDBM or its complex with HP-β-CD were prepared using tristearin as the lipid material and hydrogenated phosphatidylcholine as the emulsifier. The obtained lipospheres were characterized by scanning electron microscopy and differential scanning calorimetry. The microparticle size (15–40 μm) was not affected by the presence of the complex. Release of BMDBM from the lipospheres was lower when it was incorporated as inclusion complex rather than as free molecule. Unencapsulated BMDBM, its complex with HP-β-CD, the sunscreen-loaded lipospheres or the lipoparticles containing the BMDBM/HP-β-CD complex, were introduced into a model cream (oil-in-water emulsion) and irradiated with a solar simulator. The photodegradation studies showed that all the examined systems achieved a significant reduction of the light-induced decomposition of the free sunscreen agent (the BMDBM loss decreased from 28.9 to 17.3–15.2%). However, photolysis experiments performed during 3 months storage of the formulations, demonstrated that the photoprotective properties of the HP-β-CD complex and of BMDBM alone-loaded lipospheres decreased over time, whereas the microencapsulated HP-β-CD/BMDBM complex retained its photostabilization efficacy. Therefore, incorporation in lipid microparticles of BMDBM in the cyclodextrin complex form is more effective in enhancing the sunscreen photostability than the complex alone or the liposphere-entrapped free BMDBM.     

Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial

OBJECTIVE: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain. METHODS: This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity >or= 40 on a 100-mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily.Main outcome measures: The co-primary efficacy variables were pain and physical function subscales of the WOMAC Osteoarthritis Index and subject global assessment of disease activity. RESULTS: Mean changes in WOMAC Osteoarthritis Index pain and physical function subscales were significantly different between tramadol ER and placebo, overall (p 相似文献   

Population-Based Geospatial and Molecular Epidemiologic Study of Tuberculosis Transmission Dynamics,Botswana, 2012–2016

Tuberculosis (TB) elimination requires interrupting transmission of Mycobacterium tuberculosis. We used a multidisciplinary approach to describe TB transmission in 2 sociodemographically distinct districts in Botswana (Kopanyo Study). During August 2012–March 2016, all patients who had TB were enrolled, their sputum samples were cultured, and M. tuberculosis isolates were genotyped by using 24-locus mycobacterial interspersed repetitive units–variable number of tandem repeats. Of 5,515 TB patients, 4,331 (79%) were enrolled. Annualized TB incidence varied by geography (range 66–1,140 TB patients/100,000 persons). A total of 1,796 patient isolates had valid genotyping results and residential geocoordinates; 780 (41%) patients were involved in a localized TB transmission event. Residence in areas with a high burden of TB, age <24 years, being a current smoker, and unemployment were factors associated with localized transmission events. Patients with known HIV-positive status had lower odds of being involved in localized transmission.     

Effect of methylguanidine in carrageenan-induced acute inflammation in the rats

In vitro and in vivo studies have demonstrated that methylguanidine, an inhibitor of nitric oxide synthase (NOS), is also able to reduce tumour necrosis factor-alpha (TNF-alpha) release. In the present study, we evaluated the anti-inflammatory potential of methylguanidine treatment in two models of acute inflammation (carrageenan-induced paw edema and pleurisy) where oxyradical, nitric oxide (NO) and prostaglandins play a crucial role in the inflammatory processes. Our data show that methylguanidine, given intraperitoneally at the dose of 30 mg/kg, inhibits the inflammatory response reducing significantly (P<0.05) paw swelling, pleural exudates formation, mononuclear cell infiltration and histological injury. Furthermore, our data suggests that there is a significant (P<0.05) reduction in the activity and expression both of the inducible NOS (iNOS) and of cyclooxygenase-2 in lung tissue of pleurisy model. Methylguanidine is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) synthase immunoreactivity in the inflamed lung tissues. Treatment with aminoguanidine, the reference drug, significantly reduced all the evaluated pro-inflammatory parameters in carrageenan-treated rats. Taken together, the present results demonstrate that methylguanidine exerts potent anti-inflammatory effects that could be, in part, related to an inhibition of the expression/activity of the iNOS and cyclooxygenase-2 and, another part, may be related to a reduction of TNF-alpha release.     

Improvement in solubility and dissolution rate of flavonoids by complexation with beta-cyclodextrin

The inclusion into the beta-cyclodextrin is used to improve pharmacokinetic characteristics of hesperetin and naringenin. Solubility of hesperetin and naringenin with increasing concentrations of beta-cyclodextrin grows as long as the temperature increased. Stability constants were determined by the solubility method by Higuchi and Connors at different temperatures, and the thermodynamic parameters were calculated for inclusion complex formation in aqueous solution. The solid complexes were obtained in a molar ratio of 1:1 and their dissolution behavior at different pH was examined.     

DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders

Journal of Autism and Developmental Disorders - Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin...     

Estimating determinants of dentist productivity: new evidence

Objective: Productivity (output per unit of input) is a major driver of dental service capacity. This study uses 2006‐2007 data to update available knowledge on dentist productivity. Methods: In 2006‐2007, the authors surveyed 1,604 Oregon general dentists regarding hours worked, practice size, payment and patient mix, prices, dentist visits, and dentist characteristics. Effects of practice inputs and other independent variables on productivity were estimated by multiple regression and path analysis. Results: The survey response rate was 55.2 percent. Dentists responding to the productivity‐related questions were similar to dentists in the overall sampling frame and nationwide. Visits per week are significantly positively related to dentist hours worked, number of assistants, hygienists, and number of operatories. Dentist ownership status, years of experience, and percentage of Medicaid patients are significantly positively related to practice output. The contributions of dentist chairside time and assistants to additional output are smaller for owners, but the number of additional dentist visits enabled by more hygienists is larger for owners. Conclusion: As in earlier studies of dental productivity, the key determinant of dentist output is the dentist's own chairside time. The incremental contributions of dentist time, auxiliaries, and operatories to production of dentist visits have not changed substantially over the past three decades. Future studies should focus on ultimate measures of output – oral health – and should develop more precise measures of the practice's actual utilization of auxiliaries and their skill and use of technology.     

Cerebrospinal fluid B lymphocyte identification for diagnosis and follow‐up in human African trypanosomiasis in the field

Objectives In human African trypanosomiasis (HAT, sleeping sickness), staging of disease and treatment follow‐up relies on white cell count in the cerebrospinal fluid (CSF). As B lymphocytes (CD19 positive cells) are not found in the CSF of healthy individuals but occur in neurological disorders such as multiple sclerosis, B lymphocyte count may be useful for field diagnosis/staging and therapeutic follow‐up in HAT. Methods Seventy‐one HAT patients were diagnosed and 50 were followed‐up 6–24 months after treatment. White cell counts were used for conventional staging (stage 1, ≤5 cells/μl CSF, n = 42; stage 2, ≥20 cells/μl, n = 16) and intermediate stage (6–19 cells/μl, n = 13). Slides containing 1 μl of CSF mixed with Dynabeads^® CD19 pan B were examined microscopically to detect B cell rosettes (bound to at least four beads). Results Stage 1 patients exhibited zero (n = 37) or one CSF rosette/μl (n = 5), contrary to most stage 2 patients (14/16: ≥2 rosettes/μl). Intermediate stage patients expressed 0 (n = 9), 1 (n = 3) or 2 (n = 1) rosettes/μl of CSF. During follow‐up, rosette counts correlated with white cell count staging but were much easier to read. Conclusion B cell rosettes being easily detected in the CSF in field conditions may be proposed to replace white cell count for defining HAT stages 1 and 2 and limit uncertainty in treatment decision in patients with intermediate stage.