[The influence of procaine electrophoresis and mesotherapy on the indices of body components and biochemical characteristics in the subjects above 30 years of age].

This study has demonstrated the effectiveness of a 2% procaine solution given with a view to improving metabolic parameters of aging, such as the body weight and composition along with the lipid profile in the patients varying in age from 30 years to 75 years. The study involved 95 patients treated with a 2% procaine solution that was administered by different methods (electrophoresis and mesotherapy) into several points of the collar region and upper back. The control group was comprised of the patients who received placebo by means of galvanization and mesotherapy. The results of the study indicate that the introduction of a 2% procaine solution in the treatment of metabolic disorders effectively improves selected metabolic characteristics of ageing and thereby helps to reduce the biological age in comparison with the control patients treated with placebo.

[The influence of different massage techniques on the characteristics of biological age in the subjects above the age of 30 years].

This paper is designed to demonstrate the efficacy of different massage modalities used to decrease the biological age in relatively healthy subjects between 30 and 69 years of life. The study involved 78 subjects (67 women and 11 men). Each of them underwent a course of 10 sessions of massage of the collar and upper back regions for the prevention of premature ageing and the reduction of the biological age. Cryomassage was performed with the use of cryocare packs and vacuum massage on the Cerri apparatus (Italy). The control group was comprised of the subjects given no treatment. The main characteristics measured before and after therapy included biomarkers of ageing and biological age. The results of the study indicate that both cryogenic and vacuum massage effectively improves certain biomarkers of ageing; namely, such treatment reduces systolic, diastolic, and pulse pressure, increase pulmonary vital capacity and breath holding time in expiration, improves the sense of equilibrium, self-assessment of health condition, and concentration of attention. Taken together, these effects contribute to the reduction of the biological age of the subjects and prevent their premature ageing to a greater extent than in the untreated persons.

[The influence of procaine electrophoresis and mesotherapy on the characteristics of biological age].

The assessment of the biological age is needed to estimate the level of health and the efficacy of measures being undertaken to slow down the ageing processes and prolong the active life of the patients. Earlier studies have demonstrated the improvement of both physical health and psychic status of the elderly patients following intravenous administration of procaine. The objective of the present work was to evaluate effect of various methods of administration of a 2% procaine solution on the biological age. A total of 95 subjects at the age between 30 and 75 years were enrolled in the study. The procaine solutions were applied to the collar region. The patients of group 1 were treated with 2% procaine electrophoresis, those in group 2 with procaine galvanization with the same parameters. Mesotherapy using the 2% procaine solution was given to the patients of group 3. It was substituted by placebo (0.9% physiological solution) in the patients of group 4 (controls). The study revealed the most significant decrease of the biological age (calculated as described by L. M. Belozerova) in the patients treated with procaine electrophoresis (91% improvement). The mesotherapeutic administration of procaine also produced the beneficial effect (59% improvement). Neither procaine galvanization nor placebo mesotherapy caused any significant change of the variables characterizing the biological age.

[The application of a pulsed low-frequency electrostatic field for the prevention of premature ageing].

This paper demonstrates the effectiveness of the application of a pulsed low-frequency electrostatic field (PLFESF) in order to prevent premature ageing. The study involved 50 subjects. PLFESF therapy was conducted using the DEEP OSCILLATION-200 apparatus with the applicator moved 9.5 cm along the massage lines in the dorsal collar region during 15 minutes. The therapeutic course included 10 sessions of massage at regular intervals every other day. The control subjects did not receive PLFESF therapy. The analysis of the results obtained revealed the influence of effective PLFESF therapy on various biomarkers of ageing which gives reason to recommend this technique for the application for the normalization of hemodynamic parameters, the correction of asthenic-neurotic disorders, the improvement of the patients' well-being and, as a result, the reduction of the biological age and the prevention of premature ageing.

Smaller gray matter volumes in frontal and parietal cortices of solvent abusers correlate with cognitive deficits.

BACKGROUND AND PURPOSE: Abuse of toluene-containing organic solvents by inhalation is a prevalent practice among adolescents. Long-term abuse of toluene causes cognitive deficits. The mechanism of cognitive deficits induced by long-term toluene abuse has not yet been defined. In the current study, we assessed the effects of chronic toluene abuse on cortical gray matter volume and the association between cognitive impairment and cortical gray matter volume distribution in chronic toluene abusers. MATERIALS AND METHODS: Fifteen toluene abusers and 20 healthy control subjects matched in sex, age, education level, and handedness were investigated by structural MR imaging. The cognitive states of the subjects were assessed by using the third edition of the Wechsler Intelligence Scale for Children (WISC-III). The voxel-based comparison and correlation analyses of MR images were performed by using SPM5 software. RESULTS: The voxel-based morphometric analysis revealed that toluene abusers had significantly lower gray matter volumes in the bilateral frontotemporal and right parietal cortices. In addition, the lower gray matter volumes in the frontal and parietal regions correlated with the duration of toluene abuse. There was a positive correlation between the WISC performance scale scores and gray matter volumes in the frontal and parietal cortices of the abusers. CONCLUSIONS: The results of the current study demonstrate that chronic toluene abusers have smaller gray matter volumes than nonabusers in various regions of the brain. Moreover, the cognitive deficits are associated with the lower gray matter volumes in the frontal and parietal cortices of chronic toluene abusers.

The emotional control of action: ERP evidence.

It is known that unpleasant emotions can modulate the speed of involuntary movements, yet the effects of aversive stimulation on voluntary motor acts have not been systematically investigated. The effects of aversive stimulation on subsequent movement-related cortical activity were examined using a task invalving compatible and incompatible movements. Negative shifts in the timing of two motor event-related potentials were found subsequent to aversive stimulation for compatible movements only. With analogy to the Fear-Potentiated Startle Reflex, a reactive mechanism affecting covert action, these Fear-Potentiated Movement-Related Potentials (FPMPs) reflect preparation for overt actions performed to cope with particular types of danger. Further analysis revealed a positive deflection in the left frontal cortex prior the execution of incompatible movements, which may reflect inhibitory suppression of externally-triggered imitative tendencies.

Gene expression in autonomic areas of the medulla and the central nucleus of the amygdala in rats during and after space flight.

During space flight astronauts show vestibular-related changes in balance, eye movements, and spontaneous and reflex control of cardiovascular, respiratory and gastrointestinal function, sometimes associated with space motion sickness. These symptoms undergo compensation over time. Here we used changes in the expression of two immediate-early gene (IEG) products to identify cellular and molecular changes occurring in autonomic brainstem regions of adult male albino rats killed at different times during the Neurolab Space Mission (STS-90). Both direct effects of gravitational changes, as well as indirect effects of gravitational changes on responses to light exposure were examined. Regions under the direct control of vestibular afferents such as the area postrema and the caudal part of the nucleus of the tractus solitarius (NTSC) were both directly and indirectly affected by gravity changes. These areas showed no changes in the expression of IEG products during exposure to microgravity with respect to ground controls, but did show a significant increase 24 h after return to 1 G (gravity). Exposure to microgravity significantly inhibited gene responses to light exposure seen after return to 1 G. A similar direct and indirect response pattern was also shown by the central nucleus of the amygdala, a basal forebrain structure anatomically and functionally related to the NTS. The rostral part of the NTS (NTSR) receives different afferent projections than the NTSC. This region did not show any direct gravity-related changes in IEG expression, but showed an indirect effect of gravity on IEG responses to light. A similar pattern was also obtained in the intermediate reticular nucleus and the parvocellular reticular nucleus. Two other medullary reticular structures, the dorsal and the ventral medullary reticular nuclei showed a less well defined pattern of responses that differed from those seen in the NTSC and NTSR. The short- and long-lasting molecular changes in medullary and basal forebrain gene expression described here are thought to play an important role in the integration of autonomic and vestibular signals that ultimately regulate neural adaptations to space flight.

Short-term (Fos) and long-term (FRA) protein expression in rat locus coeruleus neurons during the neurolab mission: contribution of altered gravitational fields, stress, and other factors.

Changes in immediate-early gene (IEG) expression during and after space flight were studied in the rat locus coeruleus (LC) during the NASA Neurolab mission. The LC sends widespread projections throughout the brain and releases the neuromodulator norepinephrine. LC neurons respond to natural vestibular stimulation; their firing rate also increases during waking and decreases or ceases during sleep. LC neurons express IEGs such as c-fos after activation. Adult male albino Fisher 344 rats were killed at four mission time points, and the number of Fos- and Fos-related antigen (FRA)-positive LC cells were counted in flight and ground-based control rats. Half of the subjects at each time point were exposed to light for 60 min prior to killing to standardize their sleep-waking state. FRA-expressing cells were more numerous than Fos-expressing cells in both flight- and ground-based subjects. The difference between FRA- and Fos-expressing cells within individuals was significantly larger 24 h after landing in subjects exposed to both space flight and light pulse than in all other subjects at any mission time point. Fos and FRA responses scaled in proportion to the maximum response observed in any single individual showed similar patterns of variation. Analysis of the scaled and combined responses showed that LC IEG levels responded to both gravity changes and light pulses. Subjects exposed to either single stimulus had equivalent responses, significantly greater than those of control subjects maintained in dim light. The combination of gravity change and light pulse gave significantly higher LC responses than either stimulus alone 24 h after takeoff, and to a lesser extent after 12 days in space; the highest responses were obtained 24 h after landing. By 14 days after landing, animals exposed to space flight and light pulse responded no differently than ground-based subjects. No difference in LC IEG expression was clearly attributable to changes in the sleep-waking state of subjects. Activity of noradrenergic LC neurons has been previously shown to modulate IEG expression in target structures. The increased IEG LC activity (seen most especially 24 h after landing) may reflect large-scale activation of noradrenergic neurons that may serve as a trigger for molecular changes in target structures, and be critical for adaptation to gravity changes.

Gene expression in rat vestibular and reticular structures during and after space flight.

Space flight produces profound changes of neuronal activity in the mammalian vestibular and reticular systems, affecting postural and motor functions. These changes are compensated over time by plastic alterations in the brain. Immediate early genes (IEGs) are useful indicators of both activity changes and neuronal plasticity. We studied the expression of two IEG protein products [Fos and Fos-related antigens (FRAs)] with different cell persistence times (hours and days, respectively) to identify brainstem vestibular and reticular structures involved in adaptation to microgravity and readaptation to 1 G (gravity) during the NASA Neurolab Mission (STS-90). IEG protein expression in flight animals was compared to that of ground controls using Fisher 344 rats killed 1 and 12 days after launch and 1 and 14 days after landing. An increase in the number of Fos-protein-positive cells in vestibular (especially medial and spinal) regions was observed 1 day after launch and 1 day after landing. Fos-positive cell numbers were no different from controls 12 days after launch or 14 days after landing. No G-related changes in IEG expression were observed in the lateral vestibular nucleus. The pattern of FRA protein expression was generally similar to that of Fos, except at 1 day after landing, when FRA-expressing cells were observed throughout the whole spinal vestibular nucleus, but only in the caudal part of the medial vestibular nucleus. Fos expression was found throughout the entire medial vestibular nucleus at this time. While both Fos and FRA expression patterns may reflect the increased G force experienced during take-off and landing, the Fos pattern may additionally reflect recent rebound episodes of rapid eye movement (REM) sleep following forced wakefulness, especially after landing. Pontine activity sources producing rhythmic discharges of vestibulo-oculomotor neurons during REM sleep could substitute for labyrinthine signals after exposure to microgravity, contributing to activity-related plastic changes leading to G readaptation. Reticular structures exhibited a contrasting pattern of changes in the numbers of Fos- and FRA-positive cells suggestive of a major influence from proprioceptive inputs, and plastic re-weighting of inputs after landing. Asymmetric induction of Fos and FRAs observed in some vestibular nuclei 1 day after landing suggests that activity asymmetries between bilateral otolith organs, their primary labyrinthine afferents, and vestibular nuclei may become unmasked during flight.

Human pitch perception is reflected in the timing of stimulus-related cortical activity.

'Pitch' refers to a sound's subjective highness or lowness, as distinct from 'frequency,' which refers to a sound's physical structure. In speech, music and other natural contexts, complex tones are often perceived with a single pitch. Using whole-head magnetoencephalography (MEG) and stimuli that dissociate pitch from frequency, we studied cortical dynamics in normal individuals who extracted different pitches from the same tone complexes. Whereas all subjects showed similar spatial distributions in the magnitude of their brain responses to the stimuli, subjects who heard different pitches exhibited contrasting temporal patterns of brain activity in their right but not their left hemispheres. These data demonstrate a specific relationship between pitch perception and the timing (phase) of dynamic patterns of cortical activity.

Transferring an inborn auditory perceptual predisposition with interspecies brain transplants.

Inborn species' perceptual preferences are thought to serve as important guides for neonatal learning in most species of higher vertebrates. Although much work has been carried out on experiential contributions to the expression of such preferences, their neural and developmental correlates remain largely unexplored. Here we use embryonic neural transplants between two bird species, the Japanese quail and the domestic chicken, to demonstrate that an inborn auditory perceptual predisposition is transferable between species. The transfer of the perceptual preference was dissociated from changes to the vocalizations of the resulting animals (called chimeras), suggesting that experiential differences in auditory self-stimulation cannot explain the perceptual change. A preliminary localization of the effective brain region for the behavioral transfer by using a naturally occurring species-cell marker revealed that it is not contained within the major avian auditory pathways. To our knowledge, this is the first demonstration that abstract aspects of auditory perception can be transferred between species with transplants of the central nervous system.

Learning and memory.

Memory is one of the most fundamental mental processes. Neuroscientists study this process by using extremely diverse strategies. Two different approaches aimed at understanding learning and memory were introduced in this symposium. The first focuses on the roles played by synaptic plasticity, especially in long-term depression in the cerebellum in motor learning, and its regulatory mechanism. The second approach uses an elegant chick-quail transplantation system on defined brain regions to study how neural populations interact in development to form behaviorally important neural circuits and to elucidate neurobiological correlates of perceptual and motor predispositions.

Temporal patterns of human cortical activity reflect tone sequence structure.

Despite growing interest in temporal aspects of auditory neural processing, little is known about large-scale timing patterns of brain activity during the perception of auditory sequences. This is partly because it has not been possible to distinguish stimulus-related activity from other, endogenous brain signals recorded by electrical or magnetic sensors. Here we use amplitude modulation of unfamiliar, approximately 1-minute-long tone sequences to label stimulus-related magnetoencephalographic neural activity in human subjects. We show that temporal patterns of activity recorded over particular brain regions track the pitch contour of tone sequences, with the accuracy of tracking increasing as tone sequences become more predictable in structure. In contrast, temporal synchronization between recording locations, particularly between sites over the left posterior hemisphere and the rest of the brain, is greatest when sequences have melody-like statistical properties, which may reflect the perceptual integration of local and global pitch patterns in melody-like sequences. This method is particularly well suited to studying temporal neural correlates of complex auditory sequences (such as speech or music) which engage multiple brain areas as perception unfolds in time.

Eugenics and individual phenotypic variation: to what extent is biology a predictive science?

Eugenics, in whatever form it may be articulated, is based on the idea that phenotypic characteristics of particular individuals can be predicted in advance. This paper argues that biology's capacity to predict many of the characteristics exhibited by an individual, especially behavioral or cognitive attributes, will always be very limited. This stems from intrinsic limitations to the methodology for relating genotypes to phenotypes, and from the nature of developmental processes which intervene between genotypes and phenotypes. While genetic studies may generate valid population predictions for conditions which impact human health, neither genetics nor developmental biology are likely to generate useful individual predictions about variation in non-disease-related human behavioral and cognitive phenotypes in the foreseeable future.

Changes in multiple brain regions underlie species differences in a complex, congenital behavior.

The evolutionary brain modifications that produce any complex, congenital behavioral difference between two species have never been identified. Evolutionary processes may (i) alter a single, "higher" brain area that generates and/or coordinates the diverse motor components of a complex act; (ii) separately change independent, "lower" brain areas that modulate the fine motor control of the individual components; or (iii) modify both types of areas. This study explores the brain localization of a species difference in one such behavior, the crowing of chickens (Gallus gallus domesticus) and Japanese quail (Coturnix coturnix japonica). Two major subcomponents of the behavioral difference can be independently transferred with interspecies transplantation of separate brain regions, despite the fact that these components, sound and patterned head movement, occur together in a highly integrated fashion. To our knowledge, this is the first experimental demonstration that species differences in a complex behavior are built up from separate changes to distinct cell groups in different parts of the brain and that these cell groups have independent effects on individual behavioral components.

Mean genes and the biology of aggression: a critical review of recent animal and human research.

Recent genetic work has suggested that abnormalities in serotonin biochemistry are directly causally linked to aggressive behavior, and there appears to be a consensus in the psychiatric literature that low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid are specifically associated with impulsive violent behavior. We review the limitations of the genetic studies and conduct a meta-analysis of 39 studies linking 5-HIAA to aggression in humans. No differences in mean 5-HIAA levels were found between groups of violent impulsive psychiatric patients and groups of subjects diagnosed with other psychiatric or medical conditions not considered to involve violence once these levels had been corrected for three nonpsychiatric sources of variation (age, sex and height). However, mean 5-HIAA levels in both of these groups were lower than the mean corrected level in groups of normal healthy volunteers. The results confirm an association between low 5-HIAA levels and psychiatric disorders, but fail to support any specific relationship between low 5-HIAA levels and impulsive aggression or criminality. It is premature and misleading to speak of "mean genes" (Hen 1996) or a specific neurochemistry of aggressive behavior.

The development of a species difference in the local distribution of brain estrogen receptive cells.

Estrogen receptors (ER) are crucial for estrogen-dependent brain differentiation and for estrogen-dependent neural functions of vertebrates. ER are expressed in a area-specific pattern in the vertebrate brain. The mechanisms that lead to the area-specific expression of ER are unknown. Here we use a species difference in the ER distribution between quail and chick and isochronic and isotopic quail to chick transplants to investigate mechanisms underlying the development of area-specific expression of ER. The entire neural tube rostral to the 6th somite (n = 2) or rostral to the otic capsules (n = 4) were transplanted at the second day of incubation (E2). In immunocytochemical stainings with the ER antibody H222Sp gamma, there is a defined cluster of intensely immunostained cells in the ventrolateral preoptic area of adult quails (the QERN). At the time of grafting, the entire brain primordium lacks ER. The QERN expresses ER as early as E13. The homologous area of the chicken brain does not differentiate cells that contain ER at any stage after ER are first detectable in the chicken brain at E11. In contrast, quail-chick chimeras develop the QERN phenotype in the ventrolateral preoptic area similar to quails. This implies that some signal which commits cells to the QERN phenotype (ER expression) is present in the quail brain primordium rostral to the otic capsules by embryonic day 2, and that this signal is unaffected by subsequent exposure to the global chick environment.

The effect of running on serum and red cell ferritin. A longitudinal comparison.

It is unclear whether running can affect iron stores. Results using the serum ferritin assay (SER FER) have been conflicting. Decreased red cell ferritin (RBC FER) values (< or = 4 ag/RBC) occur in iron depleted or inflammatory states. We compared the longitudinal changes of hemoglobin (Hb), SER FER, RBC FER, % saturation of total iron binding capacity (% sat TIBC), and daily dietary intake in 27 runners during a training program. These parameters were measured at days 0, 49 (range 48-52), and 115 (range 85-120). No significant changes occurred in the SER FER, % sat TIBC and Hb determinations throughout the study. Overall the RBC FER values trended down (mean values 11.7 ag/RBC to 7.7 ag/RBC; p = 0.06). Fifteen runners (56%) acquired RBC FER values in the iron deficient range (mean 6.8 ag/RBC to 2.4 ag/RBC; p < 0.05). These values differed significantly from the remaining 12 runners (mean 17.3 ag/RBC to 14.7 ag/RBC). The decline in RBC FER into the iron deficient range was primarily seen in a subset of runners who began with a RBC FER value < or = 10 ag/RBC (positive predictive value 0.79) and was independent of iron intake. We conclude that ferritin can be affected by running as recognized by the red cell ferritin assay. Moreover our results suggest that this decrease in red cell ferritin is likely a function of defective iron utilization rather than total body iron deficiency. A potential consideration is that this fall may occur as a result of repetitive running-associated injury and inflammation.

Double modulation of 5-fluorouracil in the treatment of advanced colorectal carcinoma: report of a trial with sequential methotrexate, intravenous (loading dose) folinic acid, 5-fluorouracil, and a literature review.

5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FU's potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FU's cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600 mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29%). These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.