Abstract:

Objective and design: Ebselen, an organoselenium compound is able to modulate the inflammatory response in rodents. In the present study, the anti-inflammatory and antinociceptive activity of diaryl diselenides and ebselen was studied.¶Materials: Adult male Wistar rats and albino mice were treated with diaryl diselenides and ebselen in different doses.¶Methods: Carrageenin-induced paw edema, tail-flick, formalin, acetic acid-induced abdominal writhing and capsaicin models of pain were carried out. Data were analyzed by ANOVA followed by Duncan's multiple range when appropriate.¶Results: In all models, the most promising profile was displayed by diphenyl diselenide, which produced anti-inflammatory and antinociceptive activity significantly higher than ebselen. Diphenyl diselenide also produced dose-dependent antinociception when assessed in acetic acid-induced abdominal constriction, tail-flick test or formalin and capsaicin-induced nociception.¶Conclusion: The data presented here provide evidence that administration of diphenyl diselenide produced anti-inflammatory and antinociceptive activity.

Amacrine cells are interneurons that make lateral and vertical connections in the inner plexiform layer of the retina. Amacrine cells have no axon and their dendrites function as both presynaptic and postsynaptic sites. GABAergic amacrine cells constitute 80% of the amacrine cell population in goldfish retina and mediate lateral inhibition between neighboring amacrine cells. Their light-evoked responses consist of regenerative action potentials and excitatory postsynaptic potentials (EPSPs). These depolarizing voltage changes induce Ca²⁺ influx into dendrites, which triggers transmitter release from the storage site in the dendrite. Thus, it is crucial to know how and where Ca²⁺ influx is caused in amacrine cells.

Purpose. The aim of the study was to investigate the effect of histidine on the stability and physical properties of a fully human anti-IL8 monoclonal antibody (ABX-IL8) in aqueous and solid forms.

Methods. Using a fractional factorial design, we tested many excipients, including histidine, sucrose, and other commonly used excipients, on the stability and physical properties of the antibody in both liquid and lyophilized forms. Antibody stability and physical properties were evaluated using size-exclusion high-performance liquid chromatography (SEC-HPLC), sodium dodecyl sulfate-polyacryla- mide gel electrophoresis (SDS-PAGE), and a viscometer. Residual moisture content was determined by coulometric Karl Fischer titrator. Differential scanning calorimetry (DSC) was used to detect the glass transition temperatures (T_g) of the solid cakes and melting temperatures (T_m) of the antibody in liquid formulations. Fourier-transform infrared (FTIR) spectroscopy was used to examine the overall secondary structure.

Results. Increasing the histidine concentration in the bulk solution inhibited the increases of high-molecular-weight (HMW) species and aggregates upon lyophilization and storage. In addition, histidine bulk enhanced solution stability of the antibody under freezing and thermal stress conditions, as evidenced by the lower levels of aggregates. Furthermore, histidine reduced viscosity of the antibody solution, which is desirable for the manufacture of the dosage form. However, high concentrations of histidine in liquid formulations led to coloration of the solution and high levels of aggregates on storage at elevated temperature (40°C) after the formulations were exposed to stainless steel containers during bulk freezing-thawing.

Conclusions. Histidine enhanced the stability of ABX-IL8 in both aqueous and lyophilized forms. Histidine also improved the physical properties such as reducing the solution viscosity. Liquid formulations containing high concentrations of histidine should not be stored in stainless steel tanks at elevated temperatures.

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease that affects males. It is caused by the expansion of a polyglutamine (polyQ) tract in androgen receptors. Female carriers are usually asymptomatic. No specific treatment has been established. Our transgenic mouse model carrying a full-length human androgen receptor with expanded polyQ has considerable gender-related motor impairment. This phenotype was abrogated by castration, which prevented nuclear translocation of mutant androgen receptors. We examined the effect of androgen-blockade drugs on our mouse model. Leuprorelin, a lutenizing hormone–releasing hormone (LHRH) agonist that reduces testosterone release from the testis, rescued motor dysfunction and nuclear accumulation of mutant androgen receptors in male transgenic mice. Moreover, leuprorelin treatment reversed the behavioral and histopathological phenotypes that were once caused by transient increases in serum testosterone. Flutamide, an androgen antagonist promoting nuclear translocation of androgen receptors, yielded no therapeutic effect. Leuprorelin thus seems to be a promising candidate for the treatment of SBMA.

The spatial and temporal coupling between the hands is known to be very robust during movements which use homologous muscles (in-phase or symmetric movements). In contrast, movements using nonhomologous muscles (antiphase or asymmetric movements) are less stable and exhibit a tendency to undergo a phase transition to in-phase movements as movement frequency increases. The instability during antiphase movements has been modeled in terms of signal interference mediated by the ipsilateral corticospinal pathways. In this study we report that participants in whom distal ipsilateral motor-evoked potentials could be elicited with transcranial magnetic stimulation (TMS), exhibited higher variability during a bimanual circling task than participants whose ipsilateral pathways could not be transcranially activated. These results suggest that ipsilateral control of the limb affects the level of bimanual coupling, and may contribute to uncoupling phenomena observed during asymmetric coordination.

Effective cancer vaccines targeted against specific antigens have eluded researchers for decades. When combined with a drug, one such vaccine now shrinks tumors in a mouse model of promyelocytic leukemia ( pages 1413–1417 ).

We studied the effects of oral treatment with extracts from Rhodiola rosea (50 mg/kg) and Rhodiola crenulata (50 mg/kg) roots on the duration of exhaustive swimming and ATP content in mitochondria of skeletal muscles in rats. Treatment with R. rosea extract significantly (by 24.6%) prolonged the duration of exhaustive swimming in comparison with control rats and rats treated with R. crenulata. R. rosea extract activated the synthesis or resynthesis of ATP in mitochondria and stimulated reparative energy processes after intense exercise. Experiments proved different pharmacological characteristics of R. rosea and R. crenulata: R. rosea is most effective for improving physical working capacity.

Objective: Cancer survival information is available for only few populations in developing countries. Data on survival of oral cancer patients registered by the Bombay population-based cancer registry, India, during 1992–1994 is presented in this paper. Methods: Vital status of the patients was established by matching against death certificates, reply paid postal enquiries, telephone enquiries, scrutiny of hospital records and house visits. Of the 1808 eligible cases for analysis, 1204 (66.6%) were dead; and 604 (33.4%) were alive at last follow-up, of whom 136 were lost to follow-up during the first 5-years after diagnosis. Observed and relative survival rates are presented and hazard ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazard model. Results: The overall 5-year observed and relative survival rates were 30.5% and 39.7%, respectively. Survival steadily declined with advancing age and advanced clinical stages. Five-year observed survival was 59.1% for localised cancer, 15.7% for cancers with regional extension and 1.6% for those with distant metastasis. Those with tongue, buccal mucosa and retromolar trigone cancers had poor survival rates. Conclusions: Our study shows that detecting oral cancer in early stages, when these are amenable to single modality therapies, offers the best chance of long-term survival. However, primary prevention by tobacco/alcohol control measures is important in the long-term perspective.