Dermatoglyphic asymmetry in healthy and pathological subjects

The amount of asymmetry in various digital and palmar characters found in healthy and pathological individuals (presenting Cooley's anemia, cleft lip, cleft palate and breast cancer) was examined. Males with cleft palate presented higher asymmetry index values than did healthy males. No great differences were found in the other pathologies, while different behaviour in the two sexes was noted. Work supported by M.U.R.S.T. 60%     

Mapped distribution of pattern reversal VEPs to central field and lateral half-field stimuli of different spatial frequencies

Visual evoked potentials (VEPs) to pattern reversal vertical bar stimuli of 3 different sizes (1, 2, 4 c/deg) were recorded from 19 scalp derivations in 50 controls. The stimuli were presented on a full-field (FF) screen of 24° visual angle, and on left and right half-fields (HF) of 12° radius. In 15 controls partial HF stimuli were presented on the central 3 and 6° and as hemiannular stimuli of 12° with occlusion of the central 3 and 6°.An antero-posterior polarity reversal of the N1-P1-N2 sequence was observed for FF VEPs. A tangential polarity reversal was observed for HF VEPs. Also with central or hemiannular stimuli polarity reversals of all VEP components were observed within the scalp.Variants of VEP distribution, absence of prominence of some of the ipsi- or contralateral VEP components were observed in 8–40% of controls.The FF and HF VEP distribution, and the variant VEP asymmetries were partly dependent on the pattern spatial frequency.     

Effects of chlorpromazine on pattern and flash ERGs and VEPs compared to oxazepam and to placebo in normal subjects

Antidopaminergic drugs delay the pattern-reversal VEP (P-VEP) and the flash VEP (F-VEP) and, in separate studies, reductions in the amplitude and increases in the latencies of scotopic ERGs have been reported. This study investigated the effects of chlorpromazine (CPZ) on the pattern ERG (P-ERG), P-VEP, flash ERGs and VEPs and oscillatory potentials (OPs). Normal volunteers (N = 15) were administered a placebo, or a single dose of CPZ 100 mg or oxazepam (OZP) 15 mg at weekly intervals, in a double-blind crossover design. A gold foil-ipsilateral ear derivation and an Oz′-Fz derivation were used for the ERG and VEP recordings, respectively. The latencies of ‘mixed’ and cone ERGs were significantly prolonged after CPZ compared to both placebo and to OZP. Amplitudes of rod- and cone-dominated ERGs were reduced following CPZ administration. All components of the OPs were significantly delayed after CPZ administration. No significant intertreatment differences were found in the F-VEP results. The P-ERG P50 peak and the P-VEP N70 and P100 peaks were significantly delayed after CPZ in the case of 28′ checks but not 55′ checks. Retinocortical times and P-ERG and P-VEP amplitudes were not significantly affected. In contrast to CPZ, the administration of OZP had virtually no significant effects compared to placebo. These findings suggest that the antidopaminergic CPZ has a primary effect on retinal electrophysiology. Similar findings have been reported in Parkinson's disease and in animal models.     

Stumbling corrective responses in healthy human subjects to rapid reversal of treadmill direction.

The kinematics of stumbling and recovery induced by a rapidly reversing treadmill is described for eight healthy adults. Stability was achieved in approximately 400 ms following treadmill reversal (initiated at heel-strike) and the ensuing stumble. It appeared to be accomplished primarily by rapid flexion of the thigh and knee of the stance limb, which prevented damage to the knee joint and lowered the trunk, and by extension of the contralateral joints (swing limb), which contacted the ground presumably to deliver an impulsive thrust to counter the backward lean of the trunk. The movements of the ankle also contributed to the recovery from the stumble, but its movements were markedly more variable among the subjects than those of the thigh and knee. The observed kinematics to some extent resembled a crossed-extension reflex, which may have been triggered by muscle, joint, cutaneous or vestibular afferents. These data should provide a baseline by which to compare groups in which recovery from stumbling is known to be deficient (e.g., the elderly).     

Locomotion pattern and foot pressure adjustments during gentle turns in healthy subjects

People suffering from locomotor impairment find turning manoeuvres more challenging than straight-ahead walking. Turning manoeuvres are estimated to comprise a substantial proportion of steps taken daily, yet research has predominantly focused on straight-line walking, meaning that the basic kinetic, kinematic and foot pressure adaptations required for turning are not as well understood. We investigated how healthy subjects adapt their locomotion patterns to accommodate walking along a gently curved trajectory (radius 2.75 m). Twenty healthy adult participants performed walking tasks at self-selected speeds along straight and curved pathways. For the first time for this mode of turning, plantar pressures were recorded using insole foot pressure sensors while participants’ movements were simultaneously tracked using marker-based 3D motion capture. During the steady-state strides at the apex of the turn, the mean operating point of the inside ankle shifted by 1 degree towards dorsiflexion and that for the outside ankle shifted towards plantarflexion. The largest change in relative joint angle range was an increase in hip rotation in the inside leg (>60%). In addition, the inside foot was subject to a prolonged stance phase and a 10% increase in vertical force in the posteromedial section of the foot compared to straight-line walking. Most of the mechanical change required was therefore generated by the inside leg with hip rotation being a major driver of the gentle turn. This study provides new insight into healthy gait during gentle turns and may help us to understand the mechanics behind some forms of impairment.     

Clinical evaluation of VEPs to interleaved checkerboard reversal stimulation of central,hemi- and peripheral fields

The VEPs of 195 patients referred for supportive evidence of multiple sclerosis or optic neuritis were studied by a new method of interleaved checkerboard reversal stimulation of different areas of the visual field. In the first group of 95 patients checks of 40′ subtense reversed in the whole field (28° × 20°), alternately in the left and right hemifields and alternately in the central (5° radius) and peripheral fields. In the second group of 100 patients checks reversed in the whole field and in interleaved mode in 3 visual field areas, comprising the central (4° radius) and left and right hemisurround fields.In the first group abnormal responses were recorded from 52 eyes and there was partial disagreement among the stimulus conditions in 10 of the 52. Abnormalities were seen uniquely to central field stimulation in 3 eyes but never to whole field stimulation alone. In the second group abnormal responses were recorded in 58 eyes, again never uniquely to whole field stimulation, while abnormalities confined to one or two areas of the visual field were seen in 24, providing evidence of peripheral field involvement alone in 8 eyes.In the first group, waveforms created from the sum of the left and right hemifield and central and peripheral field responses showed quite close conformity to the whole field VEP, although amplitudes were significantly lower and latencies significantly shorter. In 7 eyes responses would have been differently classified (normal or abnormal) using the sum as compared with the whole fields. The sum of the 3 interleaved stimuli was less reliable, its morphology often not closely approximating whole field responses.It is suggested that interleaved stimulation of two or more areas of the visual field is a sensitive and reliable method which reduces the time necessary to perform the test and helps control the patients' concentration, fixation and alertness. Whole field stimulation is probably necessary only in patients with severely degraded responses.     

Intraobserver reliability of posturography in healthy subjects

Reliability of posturography is essential for the identification of intervention effects in any setting (e.g., sport, rehabilitation). The purpose was to establish the intraobserver reliability of a posturographic method in asymptomatic subjects (n?=?30). Intraclass correlation coefficients (relative reliability) for every parameter and all test positions (ALL_mean) ranged from 0.78 (95% CI: 0.53–0.90) to 0.95 (95% CI: 0.89–0.97). Absolute reliability, quantified by using the coefficient of variation, ranged between 3.5 and 19.8. Reliability of single test positions is much lower. The posturographic system showed good relative and satisfactory absolute intraobserver reliability for ALL_mean.     

Existence of anti-thyroglobulin IgG in healthy subjects

An autoantibody, anti-thyroglobulin IgG, was detected in a large proportion of healthy subjects. Sera were collected from 232 healthy subjects aged 7-83 yr, who had no apparent symptoms with normal serum levels of thyroid-stimulating hormone, confirming the absence of Graves' disease and chronic thyroiditis. Anti-thyroglobulin IgG in serum was measured by a novel enzyme immunoassay, the principle of which has been shown to provide 3,000 to 10,000-fold higher sensitivity than the conventional methods. Anti-thyroglobulin IgG was demonstrated in 38% of the healthy subjects (15% of those aged 7-19 yr and 69% of those aged 20-39 yr), and the serum concentration of anti-thyroglobulin IgG was assessed to be 2 micrograms/l - 38 mg/l.     

Ranges of phenotypic flexibility in healthy subjects

Background

A key feature of metabolic health is the ability to adapt upon dietary perturbations. A systemic review defined an optimal nutritional challenge test, the “PhenFlex test” (PFT). Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Furthermore, it was demonstrated that quantification of PFT response was more sensitive as compared to fasting markers in demonstrating reduced phenotypic flexibility in metabolically impaired type 2 diabetes subjects.

Methods

This study aims to demonstrate that quantification of PFT response can discriminate between different states of health within the healthy range of the population. Therefore, 100 healthy subjects were enrolled (50 males, 50 females) ranging in age (young, middle, old) and body fat percentage (low, medium, high), assuming variation in phenotypic flexibility. Biomarkers were selected to quantify main processes which characterize phenotypic flexibility in response to PFT: flexibility in glucose, lipid, amino acid and vitamin metabolism, and metabolic stress. Individual phenotypic flexibility was visualized using the “health space” by representing the four processes on the health space axes. By quantifying and presenting the study subjects in this space, individual phenotypic flexibility was visualized.

Results

Using the “health space” visualization, differences between groups as well as within groups from the healthy range of the population can be easily and intuitively assessed. The health space showed a different adaptation to the metabolic PhenFlex test in the extremes of the recruited population; persons of young age with low to normal fat percentage had a markedly different position in the health space as compared to persons from old age with normal to high fat percentage.

Conclusion

The results of the metabolic PhenFlex test in conjunction with the health space reliably assessed health on an individual basis. This quantification can be used in the future for personalized health quantification and advice.

     

Pharmacokinetics of fexofenadine enantiomers in healthy subjects

Fexofenadine, a substrate of P-glycoprotein and an organic anion transporter polypeptide, is commonly used to assess P-glycoprotein activity in vivo. The purpose of this study was to elucidate the pharmacokinetics of each fexofenadine enantiomer. After a single oral dose of racemic fexofenadine (60 mg), the plasma and urine concentrations of fexofenadine enantiomers were measured over the course of 24 h in six healthy subjects. The mean plasma concentration of R(+)-fexofenadine was higher than that of S(-)-fexofenadine. The area under the plasma concentration-time curve (AUC(0-infinity)) and the maximum plasma concentration (C(max)) of R(+)-fexofenadine were significantly greater than those of the S(-)-enantiomer (P = 0.0018 and 0.0028, respectively). The R/S ratios of AUC and C(max) of fexofenadine were 1.75 and 1.63, respectively. The oral clearance and renal clearance of S(-)-fexofenadine were significantly greater than that of R(+)-fexofenadine (P = 0.0074 and 0.0036). On the other hand, the stereoselective metabolism of fexofenadine using recombinant CYP3A4 was investigated; however, fexofenadine enantiomers were not metabolized by CYP3A4. Fexofenadine is transported by both P-glycoprotein and OATP and is not metabolized by intestinal CYP3A. Our findings suggest that the affinity of P-glycoprotein for S(-)-fexofenadine is greater than its affinity for the R(+)-enantiomer. Thus, P-glycoprotein is likely to have chiral discriminatory abilities.     

Pole reversal and the development of cell asymmetry during division in cryptomonad flagellates

Summary A unique form of cell division is reported for the cellsKomma caudata andCryptomonas ovata (Cryptophyceae). During cytokinesis, the posterior tail-like region of each daughter cell develops from the anterior region of the parental cell. This process, termed pole reversal, involves a major realignment in overall cell polarity as well as alterations to cytoplasmic and surface components. Pole reversal may be a consequence of flagellar apparatus transformation and reorientation during division, and pole reversal may facilitate the development of the asymmetric cell shape in daughter cells.