Characterization of the binding of [3H]-SB-204269, a radiolabelled form of the new anticonvulsant SB-204269, to a novel binding site in rat brain membranes

1. SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2,2-dimethyl-2H-benzol[b]pyran-3R-ol, hemihydrate) shows potent anticonvulsant activity in a range of animal seizure models, with a lack of neurological or cardiovascular side-effects. The profile of the compound suggests that it may have a novel mechanism of action. This study describes the characteristics of a binding site for [³H]-SB-204269 in rat forebrain membranes.
2. Specific [³H]-SB-204269 binding was saturable and analysis indicated binding to a homogenoeous population of non-interacting binding sites with a dissociation constant (K_D) of 32±1 nM and a maximum binding capacity (B_max) of 253±18 fmol mg⁻¹ protein. Kinetic studies indicated monophasic association and dissociation. Binding was similar in HEPES or Tris-HCl buffers and was unaffected by Na⁺, K⁺, Ca²⁺ or Mg²⁺ ions. Specific binding was widely distributed in brain, but was minimal in a range of peripheral tissues.
3. Specific [³H]-SB-204269 binding was highly stereoselective, with a 1000 fold difference between the affinities of SB-204269 and its enantiomer SB-204268 for the binding site. The affinities of analogues of SB-204269 for binding can be related to their activities in the mouse maximal electroshock seizure threshold (MEST) test of anticonvulsant action.
4. None of the standard anticonvulsant drugs, phenobarbitone, phenytoin, sodium valproate, carbamazepine, diazepam and ethosuximide, or the newer anticonvulsants, lamotrigine, vigabatrin, gabapentin and levetiracetam, showed any affinity for the [³H]-SB-204269 binding site. A wide range of drugs active at amino acid receptors, Na⁺ or K⁺ channels or various other receptors did not demonstrate any affinity for the binding site.
5. These studies indicate that SB-204269 possesses a specific CNS binding site which may mediate its anticonvulsant activity. This binding site does not appear to be directly related to the sites of action of other known anticonvulsant agents, but may have an important role in regulating neuronal excitability.

     

The effectiveness of an integrated pain management program for older persons and staff in nursing homes

This study examined the effects of an 8-week integrated pain management program (IPMP) on enhancing the knowledge and attitude toward pain management among staff; and improving the pain, quality of life, physical and psychosocial functions, and use of non-drug therapies for the elderly in nursing homes. Nursing home staff (N=147) and residents (N=535) were recruited from ten nursing homes. Nursing homes were randomly assigned into an experimental group (N=296) with IPMP or control group (N=239) without IPMP. The IPMP consisted of pain education for staff and physical exercise and multisensory stimulation art and craft therapy for residents. Data were collected before and after the IPMP. The staff demonstrated a significant improvement in knowledge and attitude to pain management, with the survey score increasing from 8.46±3.74 to 19.43±4.07 (p<0.001). Among the residents, 74% had experienced pain within the previous 6 months, with pain intensity of 4.10±2.20. Those in the experimental group showed a significantly better reduction in pain scores than the control group, from 4.19±2.25 to 2.67±2.08 (p<0.001). Group differences were also found in psychological well-being, including happiness, loneliness, life satisfaction and depression (p<0.05), and the use of non-drug methods (p<0.05). These results suggested that IPMP is beneficial for staff, and is effective in reducing geriatric pain and negative impacts. Management support and staff involvement in the program are important for its long-term continuation.     

An Analytical Study on Reasoning of Extreme Learning Machine for Classification from Its Inductive Bias

Since extreme learning machine (ELM) was proposed, hundreds of studies have been conducted on this subject in various areas, from theoretical researches to practical applications. However, there are very few papers in the literature to reveal the reasons why in ELM classification the class with the highest output value is being chosen as the predicted class for a given input. In order to give a clear insight into this question, this paper analyzes the rationality of ELM reasoning from the perspective of its inductive bias. The analysis results show that the choice of highest output in ELM is reasonable for both binary and multiclass classification problems. In addition, to deal with multiclass problems ELM uses the well-known one-against-all strategy, in which unclassifiable regions may exist. This paper also gives a clear explanation on how ELM resolves the unclassifiable regions, through both analysis and experiments.     

Performances of the Amplified Mycobacterium Tuberculosis Direct Test in non respiratory specimens (study about 1538 samples)

From March 1998 to August 2009, 1538 non-respiratory samples collected from 1182 patients, were tested using the Gen-Probe Amplified Mycobacterium Direct Test™ (AMTD). After decontamination procedure, every sample was tested by AMTD and by culture on solid and liquid media. The “Gold-standard” was considered by the combination of culture results and clinical diagnosis. Tuberculosis was present in 17,59 % (208 patients). For theses 1538 non-respiratory samples (225 culture positive samples, 248 AMTD positive), 279 corresponded to tuberculosis. After resolving the discordant results, the sensitivity, specificity, positive and negative values were 89, 99, 99,6 and 97,3 %.     

Evaluation of the SD BIOLINE TB Ag MPT64 Rapid® for the diagnosis of tuberculosis

The purpose of this study was to evaluate the SD Bioline Ag MPT64 Rapid^® for identification of the Mycobacterium tuberculosis complex. The method uses an immunochromatographic assay and needs 100 μl of sample taken from liquid culture or colonies suspended. The sensitivity was determined using 99 strains of M. tuberculosis complex and the specificity using 10 nontuberculous mycobacteria and 85 strains other than mycobacteria genus. The test showed excellent sensitivity (99%) and specificity (100%). This technique displays several advantages and is destined to spread in all laboratories and particularly in endemic areas.