Noni as an anxiolytic and sedative: A mechanism involving its gamma-aminobutyric acidergic effects

Noni (Morinda citrifolia) is increasing in worldwide popularity as a food or dietary supplement with versatile health benefits. The aim of this study was to investigate the effects of Noni fruit on anxiety symptoms in vitro. To this end, a competitive GABAa receptor-binding assay was developed. Our preliminary study indicates that the methanol crude extract of Noni fruit showed significant affinity to the gamma-aminobutyric acid A (GABAa) inhibitory neurotransmitter receptors, and displayed 75% binding inhibition of the agonist radioligand [3H] muscimol at a concentration of 100 microg/ml. Further experiments demonstrated that the MeOH extract, and its BuOH and H2O partitions, exhibited IC50 values of 22.8, 27.2, and 17.1 microg/ml, respectively, in the GABAa-binding assay. Experimental results with Noni fruit indicate the presence of competitive ligand(s), which may bind to the GABAa receptor as an agonist, and thus induce its anxiolytic and sedative effects. The study provides an in vitro rationale for one of Noni's versatile and traditional uses. In addition, an HPLC fingerprint profile of the methanolic extract of Noni fruit has been established for quality control purpose.     

A 45‐bp Insertion/Deletion Polymorphism of Uncoupling Protein 2 in Relation to Obesity in Tongans

We compared the current prevalence of increased BMI and type 2 diabetes in a representative group of Tongan subjects with measurements made in 1973, and we determined the distribution and possible interrelations with the UCP2 insertion/deletion (ins/del) polymorphism of these variables. We documented the BMI, glucose tolerance, and standard lipid variables in 1012 Tongan subjects (429 men and 583 women, ages 15 to 85 years) during 1998 and 2000 and compared the BMI findings with those of the 1973 survey. We also genotyped for the UCP2 ins/del polymorphism, assessed its association with obesity and type 2 diabetes, and compared its prevalence with those reported for other ethnic populations. The mean BMI ± SD was greatly increased in both men (30.2 ± 5.4 kg/m²) and women (33.8 ± 6.2 kg/m²), representing increases since 1973 of 11.9% and 19.4%, respectively. The genotype frequencies were 97% for the del/del genotype and 3% for the ins/del genotype; we found no ins/ins homozygotes. This distribution is strikingly different from those reported for white, South Indian, Pima Native‐American, and Asian populations (49 to 77% for del/del genotype). We conclude that there is a marked prevalence of obesity in Tonga, a prevalence that has increased since 1973. We also conclude that there is a unique, near‐uniform distribution of the UCP2 45‐bp ins/del polymorphism in Tongans. This may be the result of a founder effect and may be relevant to the prevalence of obesity and type 2 diabetes in Tonga.     

Direct phage to intrabody screening (DPIS): demonstration by isolation of cytosolic intrabodies against the TES1 site of Epstein Barr virus latent membrane protein 1 (LMP1) that block NF-kappaB transactivation

The expression of intracellular antibodies (intrabodies) in eukaryotic cells has provided a powerful tool to manipulate microbial and cellular signaling pathways in a highly precise manner. However, there have been several technical issues that have restricted their more widespread use. In particular, single-chain antibodies (sFv) have been reported to fold poorly in the reducing environment of the cytoplasm and as such there has been a reluctance to use sFv-phage libraries as a source of intrabodies unless a pre-selection step to identify these rare sFvs from natural libraries or libraries of engineering sFvs that could fold properly in the absence of disulfide bonds were used. Here, we investigated whether target specific sFvs that are isolated from a 15 billion member non-immune human sFv-phage display library could be directly screened in pools as intrabodies without prior knowledge of their individual identity or purity within pools of antigen-specific sFvs. As the target, we used a synthetic transformation effector site 1 (TES1) polypeptide comprising the membrane-most proximal 34 amino acid residues of the carboxy-terminal cytoplasmic tail of the oncogenic latent membrane protein 1 (LMP1) of Epstein Barr virus, which serves as a docking site for adapter proteins of the tumor necrosis factor (TNF) receptor (TNFR)-associated factor (TRAF) family. Anti-TES1 sFvs, initially identified by phage ELISA screens, were grouped into pools according to the absorbance reading of the antigen-specific phage ELISA assays and then transferred as pools into eukaryotic expression vectors and expressed as cytoplasmic intrabodies. Using the pooling strategy, there was no loss of individual anti-TES1 sFvs in the transfer from prokaryotic to eukaryotic expression vectors. In addition, the initial assignments into sFv pools based on phage ELISA readings allowed the segregation of individual anti-TES1 sFvs into discrete or minimally overlapping intrabody pools. Further assessment of the biological activity of the anti-TES1 intrabody pools demonstrated that they were all able to selectively block F-LMP1-induced NFkappaB activity that was mediated through the TES1-site and to bind LMP1 protein with high efficiency. This direct phage to intrabody screening (DPIS) strategy should allow investigators to bypass much of the in vitro sFv characterization that is often not predictive of in vivo intrabody function and provide a more efficient use of large native and synthetic sFv phage libraries already in existence to identify intrabodies that are active in vivo.     

Nonlinearity in normal human EEG: cycles,temporal asymmetry,nonstationarity and randomness,not chaos

Two-hour vigilance and sleep electroencephalogram (EEG) recordings from five healthy volunteers were analyzed using a method for identifying nonlinearity and chaos which combines the redundancy–linear redundancy approach with the surrogate data technique. A nonlinear component in the EEG was detected, however, inconsistent with the hypothesis of low-dimensional chaos. A possibility that a temporally asymmetric process may underlie or influence the EEG dynamics was indicated. A process that merges nonstationary nonlinear deterministic oscillations with randomness is proposed for an explanation of observed properties of the analyzed EEG signals. Taking these results into consideration, the use of dimensional and related chaos-based algorithms in quantitative EEG analysis is critically discussed. Received: 25 September 1994 / Accepted in revised form: 10 July 1996     

The spectral dynamics and its applications in EEG

The method of spectral dynamics is introduced to process slow changes in EEG. This method is based on evaluation of distance between EEG spectra. The typical application field is pharmaco-EEG after single dose drug administration, where distances between pre and post drug EEG spectra are computed. The distance between two spectra may be, however, defined in several different ways. The paper deals with the well known L _p metrics and with the metrics that plays an important role in discriminating stationary processes with different spectra. The L _p and metrics are non-equivalent and their properties, consistency and robustness, are studied in a simple statistical model.     

Blood pressure changes during running in humans: the "beat" phenomenon

In 20 runners the intra-arterial blood pressure changes determined by a long-distance run and by a maximal bicycle ergometric test were recorded by means of the portable Oxford system. A peculiar pattern of the phasic waves was observed throughout the run: continuous rhythmic pulse pressure oscillations ranging in frequency between 4 and 28/min and unrelated to respiration were detected. The shape of these oscillations prompted us to investigate whether they were due to a "beat" phenomenon, that is, to the combined effect of two waves with a nearly equal frequency. To test this hypothesis, during the run 10 athletes carried a fluid-filled container around the chest. The pressure waves recorded in the container were added by computer to those recorded intra-arterially during bicycle ergometry. The resultant harmonic showed a pattern similar to that recorded in the athlete's radial artery during running. Conversely, by subtracting the pressure waves recorded in the container from those simultaneously recorded at the radial artery during running, nearly flat tracings were obtained. The source of the beat phenomenon has therefore been identified in the wave, which generates inside the aorta and the great vessels at each foot-strike shock.