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Precise determinations of C and D periods by flow cytometry in Escherichia coli K-12 and B/r.

The C and D cell cycle periods of seven Escherichia coli K-12 strains and three E. coli B/r strains were determined by computer simulation of DNA histograms obtained by flow cytometry of batch cultures grown at several different generation times. To obtain longer generation times two of the K-12 strains were cultivated at several different dilution rates in glucose-limited chemostats. The replication period (C period) was found to be similar in K-12 and B/r strains grown at similar generation times. At generation times below 60 min the C period was constant; above 60 min it increased linearly with increasing generation time. The period from termination of replication to cell division (D period) was more variable. It was much shorter in B/r than in K-12 strains. Like the C period it was relatively constant at generation times below 60 min and it increased with increasing generation times at longer generation times. In glucose-limited chemostats good correlation was found between D periods and generation times, whereas batch cultures exhibited carbon-source-dependent variations. Chemostat cultures showed cell cycle variations very similar to those obtained in batch cultures. These flow cytometric determinations of cell cycle periods confirm earlier determinations of the C period and establish that the D period also varies with generation time in slowly growing cultures. In addition they extend the range of growth rates at which cell cycle periods have been determined in E. coli K-12.

Cell Cycle↗

[Serovars, antimicrobial resistance and conjugative R plasmids of Salmonella isolated from human during the period of 1966-1986 in Tokyo. Research Group for Infectious Enteric Diseases].

We examined 4,739 isolates of Salmonella isolated from patients with gastroenteritis during the period of 1966-1986 in Tokyo for the incidences of serovars, antibiotic resistance and conjugative R plasmids. The period of study was divided into three: 1966-73 (early period), 1974-79 (middle period), and 1980-86 (late period). The predominant serovars were S. typhimurium (34.3%), Infantis (5.6%), Panama (4.9%) in the middle period, S. typhimurium (31.7%), Paratyphi B (9.4%), Litchfield (7.3%) in the late period. These results were consistent with serovars of isolates from healthy citizens. The frequency of resistant isolates was as high as 86.9% in the early period, mostly streptomycin (SM)- and tetracycline (TC)-resistant isolates, but decreased significantly in the middle and the late periods, to 53.3 and 39.4%, respectively. The percentages of ampicillin (ABPC)-, chloramphenicol (CP)-, and kanamycin (KM)-resistant isolates increased in the late period. Strains carrying conjugative R plasmids were isolated as frequently as 57.8% of the total isolates in 1973, but as less frequently as 6.7% in 1981 indicating that the rate was roughly proportional to the incidence of the drug resistant isolates. The rate, however, increased gradually after 1981. The predominant resistance pattern of the R plasmids was TC-resistance in the early period, gradually changed into multiple and finally to AP-, CP-, KM-, SM-, TC- and sulfonamides-resistance in the late period.

Conjugation, Genetic↗

Intersegmental coordination of the leech swimming rhythm. I. Roles of cycle period gradient and coupling strength.

The isolated leech nervous system generates a metachronally coordinated rhythmic output that is the neuronal correlate of swimming activity. We investigated two factors that contribute to intersegmental coordination: the swim-cycle periods expressed by segmental ganglia and the strength of neuronal coupling between ganglia. To determine the regional variation in swim-cycle periods, we severed both of the lateral intersegmental connectives. We left intact the median connective, which conveys tonic excitation but little phasic information. We obtained a reduction in intersegmental coupling strength by severing a single lateral intersegmental connective. Cycle periods were manipulated by cooling restricted sections of the nerve cord. Our experiments revealed an anterior-posterior gradient of cycle periods in ganglia of the isolated nerve cord; that is, chains of ganglia obtained from the anterior nerve cord exhibited longer cycle periods than those obtained from the posterior end of the cord. This gradient extends posteriorly to approximately ganglion 12 and may reverse posterior to ganglion 13. Increasing local cycle periods by cooling restricted sections of the nerve cord caused delay in activity cycles in the cooled ganglia, relative to the cycles of ganglia at the control temperature. This finding demonstrates that the observed gradient in cycle period provides for smaller intersegmental phase lags than would occur if there were no period gradients. Reduction of coupling strength by severing a lateral connective led to altered phase relationships across the lesion, both at the motor and oscillator levels. For those ganglion chains in which the anterior ganglia had greater periods, the reduced coupling led to reduced or even reversed phase relationships across the lesion but left unchanged the phase lag between the ends of the chain. In contrast, reduced coupling between halves of a chain in which the posterior ganglia had greater cycle periods led to increased phase lags across the lesion and between the ends. These altered phase relationships arise from a relative increase in the contribution of period differences when coupling strength is decreased. We conclude that the anterior-to-posterior progression of neuronal activity in the isolated leech nerve cord during swimming activity is provided by the intersegmental coupling signals. Furthermore, the period gradient expressed in our preparations acts to provide for smaller phase lags than would be generated by these coupling signals in the absence of such a gradient.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Properties of delay-period neuronal activity in the monkey dorsolateral prefrontal cortex during a spatial delayed matching-to-sample task.

The dorsolateral prefrontal cortex (PFC) has been implicated in visuospatial memory, and its cellular basis has been extensively studied with the delayed-response paradigm in monkeys. However, using this paradigm, it is difficult to dissociate neuronal activities related to visuospatial memory from those related to motor preparation, and few studies have provided evidence for the involvement of PFC neurons in visuospatial memory of a sensory cue, rather than in motor preparation. To extend this finding, we examined neuronal activities in the dorsolateral PFC while a rhesus monkey performed a spatial delayed matching-to-sample (SDMTS) task, which allows us to adequately access visuospatial memory independent of any sensorimotor components. The SDMTS task required the subject to make a lever-holding NOGO response or a lever-releasing GO response when a visuospatial matching cue (white spot, one of four peripheral locations, 15 degrees in eccentricity) matched or did not match a sample cue (physically the same as the matching cue) that had been presented prior to a delay period (3 s). Thus, the SDMTS task requires the subject to remember visuospatial information regarding the sample cue location during the delay period and is suitable for accessing visuospatial memory independent of any sensorimotor components, such as motor preparation, for directed movements. Of a total of 385 task-related neurons, 184 showed a sustained increase in activity during the delay period ("delay-period activity"). Most of these neurons (n = 165/184, 90%) showed positional delay-period activity, i.e., delay-period activity where the magnitude differed significantly with the position of the sample cue. This activity appears to be involved in visuospatial memory and to form a "memory field." To quantitatively examine the properties of positional delay-period activity, we introduced a tuning index (TI) and a discriminative index (DI), which represent the sharpness of tuning and the discriminative ability, respectively, of positional delay-period activity. Both TI and DI varied among neurons with positional delay-period activity and were closely related to the time from the onset of the sample cue to the onset of positional delay-period activity; positional delay-period activity with sharper tuning and a greater discriminative ability had a slower onset. Furthermore, at the population level, both TI and DI were increased during the delay period in the neuronal population with a high DI value. These results extend previous findings to suggest that integrative, convergent processes of neuronal activities for increasing the accuracy of visuospatial memory may occur in the dorsolateral PFC. Thus, a critical role of the dorsolateral PFC in visuospatial memory may be to sharpen it to guide behaviors/decisions requiring accurate visuospatial memory.

Animals↗

[Factors related to the slowdown in the reduction of the tuberculosis incidence rate in Osaka City--structure of the high incidence rate of tuberculosis in Osaka City analyzed by administrative-ward group, five-year period and age group].

The tuberculosis incidence rate in Osaka City is the highest in Japan. We analyzed the incidence rate in Osaka City in five-year period from 1978 to 1997, namely, 1978-1982 (period I), 1983-1987 (period II), 1988-1992 (period III), and 1993-1997 (period IV). Until the first half of 1980, the tuberculosis incidence rate in Osaka City had been dropping every year, but the rate of decline has been slowed substantially or even stopped since 1983. The incidence rate ratio of Osaka City compared with the national rate was 2.0 to 2.3 from 1970 to 1975, but it has been increasing from 1983 and is now higher than 3. We divided 24 wards of Osaka City into five groups based on selected employment indicators of population 15 years of age and over of 1995 National Census. Group A consists of two wards characterized by extremely high unemployment rate, Group B of four wards by high unemployment rate and high rate of manufacturing workers, Group C of six wards by high rate of non-manufacturing workers (tertiary industry workers), Group D of five wards by high rate of manufacturing workers, and Group E of seven wards by residential areas. The incidence rate of Group A had been declining during periods I and II but started to rise after period III. The rates of Group B and C had been declining from period I to II but the decline slowed down substantially even for every age class in periods III and IV. The incidence rates of Groups D and E have been falling. The incidence rate of the 50-69 year-old age group has been increasing substantially. The proportion of newly registered patients in Group A to all patients of Osaka City increased from 25.2% in period I to 32.7% in period IV. The number of newly registered patients of the 40-69 age class in Group A accounted for 45.1% of that in Osaka City in period IV. The slowdown in the reduction of the tuberculosis incidence rate has occurred not in all, but in only a few wards and it is a typical phenomenon of the middle-aged in those wards. It would be worth investigating whether a substantial decline in the tuberculosis incidence rate in Osaka City cannot be achieved by means of uniform control measures for all wards. Intensified tuberculosis control measures should focus on patients in specific wards and age groups.

Adolescent↗

Cardiac ATP breakdown and mechanical function during recurrent periods of anoxia.

The effect of repeated short anoxic or ischemic periods on ATP breakdown and cardiac function remains controversial. To analyze this issue further and to study the regulation of adenine nucleotide breakdown during recurrent cardiac anoxia, we compared two different protocols of intermittent anoxia. Four rat hearts, perfused according to Langendorff, were exposed to 12 periods of anoxia, each lasting 1 minute, with reoxygenation periods of 3 minutes (protocol A). A second group of 8 hearts were made anoxic for 6 periods of anoxia, each lasting 1 minute, followed by 6 periods of anoxia, each lasting 2 minutes, with the same reoxygenation periods (protocol B). Adenosine production was studied with high performance liquid chromatography, ventricular contraction was monitored using a force transducer. During anoxia a substantial vasodilation and immediate fall in strength of ventricular contraction occurred. They were most pronounced during the first anoxic period and during the change from 1 to 2 minute periods of anoxia. Adenosine production was about 1 nmol/min during the first 1-minute anoxic period, decreasing during the following 1-minute anoxic periods. During the first 2-minute anoxic period, a new and much higher adenosine peak was observed (6 nmol/min), decreasing during the following 2-minute anoxic periods. Total purine release followed a pattern similar to that of adenosine. The concentration of ATP at the end of protocol B was 18.5 mumol/g dry tissue, which is significantly lower than that in protocol A (21.6 mumol/g). The results show that ATP breakdown during intermittent anoxia gradually decreases, notwithstanding the presence of substantial amounts of ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Periodic breathing in preterm infants: incidence and characteristics.

The prevalence and characteristics of periodic breathing in preterm infants were measured by 24-hour impedance pneumograms in 66 preterm infants before discharge from the nursery. Four periodic breathing parameters (percentage of periodic breathing per quiet time, number of episodes of periodic breathing per 100 minutes of quiet time, mean duration of periodic breathing, and longest episode of periodic breathing) were compared to data available from healthy term infants and from term infants who subsequently died of sudden infant death syndrome (SIDS). Periodic breathing was found in all preterm infants studied and mean periodic breathing parameter values (12.0%, 8.6 episodes, 1.2 minutes, and 7.3 minutes, respectively) in our preterm population were substantially higher than values from healthy term infants and SIDS victims. Most periodic breathing parameters decreased significantly in infants studied at 39 to 41 weeks' postconceptional age compared with earlier postconceptional age groups. No relationship was found between central apneas of greater than or equal to 15 seconds' duration and postconceptional age or any periodic breathing parameter. Periodic breathing is a common respiratory pattern in preterm infants that is usually not of pathologic significance. Associations between elevated levels of periodic breathing and respiratory dysfunction or SIDS should be made with caution.

Apnea↗

[Epidemiology of chronic renal insufficiency treated by dialysis in a region in France. Changes in a 12-year period].

Between January 1976 and December 1987, 278 patients (172 men, 106 women) aged over 15 and living in a region of some 400,000 inhabitants were treated with dialysis for end-stage chronic renal failure (CRF). The annual incidence of new cases treated was evaluated separately for 3 consecutive 4-year periods: 1976-79 (period A), 1980-83 (period B) and 1984-87 (period C). The incidence rose from 4.6-4.9 in periods A and B to 7.8/100,000 in period C, i.e. a 38 per cent progression. At the start of dialysis the mean age of women did not significantly vary throughout the 3 periods, whereas it increased significantly in men during period C. There was a significant increase of primary glomerulonephritis (GN) throughout the 3 periods: 1.25, 1.70 and 2.35/100,000 respectively; this disease accounted for 27.3, 34.6 and 30.6 per cent of all causes of CRF. Similarly, the incidence of secondary nephropathy (diabetes, amyloidosis) treated with dialysis increased from 0.6 (A) to 1.0 (B) and 1.9/100,000 (C) (P less than 0.05 with period A). The same happened with polycystic kidney: 0.25, 0.65 and 0.93/100,000. During period C, when 95 per cent of primary GN were diagnosed histologically, igAGN (13 per cent), diabetes (13 per cent) and polycystic kidney (12 per cent) were the main causes of CRF. During the whole 12-year period under study, when 80 per cent of primary GN were diagnosed, the prevalence of causes of CRF varied according to the patients' age. In patients under 65 at the start of dialysis primary GN were the principal causes of CRF (36.8 per cent, including 15.5 per cent of IgAGN), followed by secondary nephropathies (20.3 per cent, including 10.7 per cent of diabetes), chronic interstitial nephropathies (18.7 per cent, including 9.6 per cent of reflux nephropathy), hereditary nephropathies (14.4 per cent, including 10.7 per cent of cystic kidney) and vascular nephropathies (7 per cent). Above the age of 65, the principal causes of CRF were chronic interstitial nephropathies (27.7 per cent, including 8.9 per cent of drug-induced nephropathy), followed by secondary nephropathies (20 per cent, including 6.7 per cent of amyloidosis and 11.1 per cent of diabetes), vascular nephropathies (20 per cent), primary GN (12.2 per cent), and hereditary nephropathies (12.2 per cent) including 11.1 per cent of polycystic kidney).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Development of species identification in ducklings. XIII: A comparison of malleable and critical periods of perceptual development.

The present experiments sought to determine the relationship of the malleable period--when the mallard duck embryo is most susceptible to alien forms of maternal auditory stimulation--to the critical period, when the embryo must hear its own vocalizations in order to respond normally to the species-typical maternal call after hatching. It was found that a preference for either a wood duck or a chicken maternal call could be induced in devocalized mallard duck embryos by exposing them to either alien call some time between day 24, 0600 to day 26, 0600 hrs. Further experiments showed the height of the malleable period to be between day 24, 1400 hrs and day 25, 0800 hrs of embryonic development. Since the embryonic critical period for maintenance of the species-typical maternal auditory preference spans day 24, 0800 hrs to day 26, 0800 hrs, the malleable period for the induction of a preference for species-atypical maternal stimulation falls inside the critical period. While it is often assumed that malleable and critical periods overlap, this is the first behavioral study to actually demonstrate the temporal relationship of the two periods. It would seem important to further examine malleable and critical periods of development in a broader array of developmental contexts and species to determine whether malleable periods for atypical or abnormal development and critical periods for species-typical or normal development always coincide.

Acoustic Stimulation↗

Differentiation of periodic from nonperiodic low-frequency heart rate fluctuations.

Periodic low-frequency (LF) fluctuations of heart rate (HR) may be of diagnostic and prognostic value in diverse pathologic cardiopulmonary conditions. Two principal components of LF HR rate variations may be distinguished: periodic fluctuations and nonperiodic, nonstationary changes. The frequency content of these two components may overlap considerably. In order to avoid a tedious work-intensive visual analysis an efficient computer-based method for detection, differentiation, and quantitation of these signals is required. Two methods for separating periodic from nonperiodic HR changes are presented, namely, detrending and bandwidth (BW) calculation. A group of healthy individuals was evaluated in order to assess these methods in individuals with significant LF periodic episodes (15 patients) contrasted to those without LF periodic episodes (94 patients). The commonly used method of detrending consists of a fitted polynomial which by subtraction removes low frequencies originating from nonstationary changes without affecting periodic fluctuations. We found, however, that the frequencies involved in nonstationary and periodic fluctuations often overlap and thus the detrending method may not be highly efficient. In a second method we postulated different shapes for power spectrum curves of periodic and nonperiodic episodes. This latter method is based on BW calculation of the LF component of the R-R power spectrum and proved to be more efficient in detecting periodic episodes. It showed higher significance levels for the difference between the periodic and nonperiodic groups when the BW or the ratio between peak power and BW in the LF range was used. This new, alternative detection method may be employed in further studies which seek to elucidate the clinical relevance of the LF range and, in particular, the mechanisms for such long-wavelength periodic fluctuations.

Adolescent↗

Histochemical procedures for the simultaneous visualization of neutral sugars and either sialic acid and its side chain O-acyl variants or O-sulphate ester. I. Methods based upon the selective periodate oxidation of sialic acids.

Five new methods, based upon the selective oxidation of sialic acid residues with 0.4 mM periodic acid in approximately 1 M hydrochloric acid at 4 degree C for 1 h (PA), have been devised for the simultaneous visualization of neutral sugars and either sialic acid and its side chain O-acyl variants or O-sulphate ester. In the first of these, the selective periodate oxidation-borohydride reduction-saponification-selective periodate oxidation-Thionin Schiff-saponification-borohydride reduction-periodic acid-Schiff (PA-Bh-KOH-PA-T-KOH-Bh-PAS) technique, sialic acids with O-acyl substituents at C7, C8 or C9 (or which have two of three side chain O-acyl substituents) stain blue while neutral sugars with periodate-sensitive vicinal diols (hexose, 6-deoxyhexose, and N-acetylhexosamine) stain magenta. The second method, the saponification-selective periodate oxidation-Thionin Schiff-saponification-borohydride reduction-periodic acid-Schiff (KOH-PA-T-KOH-Bh-PAS), stains all sialic acids blue and neutral sugars magenta. In the third procedure, the selective periodate oxidation-Thionin Schiff-borohydride reduction-periodic acid-Schiff-saponification (PA-T-Bh-PAS-KOH) method, sialic acids without side chain substituents (or which have an O-acyl substituent at C7) stain blue and neutral sugars stain magenta. In the fourth method, the saponification-selective periodate oxidation-borohydride reduction-Alcian Blue pH 1.0-periodic acid-Schiff (KOH-PA-Bh-AB1.0-PAS) technique, O-sulphate esters stain aquamarine blue and neutral sugars stain magenta. In all of these techniques mixtures of the components stain in various shades of purple.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evidence of phase transitions in heart period dynamics.

Complexity measures of non-linear dynamics are a useful tool for quantifying observed stretching, folding, scaling and mixing processes in the Takens-reconstructed state space of heart period dynamics. Although such measures are not suited to provide evidence of deterministic chaos or to estimate true fractal dimensions and Lyapunov spectra in heart period time series, they allow the classification of RR dynamics and the identification of changes in RR complexity (RRC). The aim of this study was to develop appropriate measures and examine their utility in identifying the physiological effect of changes between the sleeping and waking state. Twenty-four hour electrocardiography (EEG) recordings and diaries noting their waking/sleeping period were obtained from 78 healthy subjects, aged 20 to 55 years. The approximate information dimension (ApD1) and the approximate Kolmogorov entropy (ApEn), introduced by Pincus, Kaplan and others, were modified in order to allow the calculation of strictly local values. That is, the local or pointwise dimensions and entropies were calculated for each reference vector with respect to its symmetric neighbourhood in time. For each subject the values for the local measures were averaged for 10-min periods, resulting in 144 global values over 24 h. Similarly, low- and high-frequency spectral parameters were calculated. All measures were examined and compared for the waking and the sleeping periods. All complexity measures as well as to a lesser degree high-frequency power showed a linear dependency on mean RR interval with a large individual variation. For the RRC measures this linear correlation was separated into two different clusters corresponding to the sleeping and waking periods. In almost all cases the correlation was greater in the waking period. In particular, in many cases no correlation was observed in the sleeping period. However, the r values for LF were appreciably lower and indicated solely a weak relationship to the RR interval in the waking period. Analysis of variance combining mean RR interval with RRC or spectral parameters singly and in couples revealed that the best separation with respect to physiological state could be achieved with the complexity measures, in particular with ApEn. The results show evidence of at least two dynamical regimes (phases) of heart period dynamics and a close but different functional relationship within the phases between RR interval and RR complexity. The separation between these regimes and the relatively sudden shift from one regime to the other suggest the existence of a phase transition with respect to waking and sleeping periods in terms of synergetics.

Adult↗

Detecting periodic patterns in unevenly spaced gene expression time series using Lomb-Scargle periodograms.

MOTIVATION: Periodic patterns in time series resulting from biological experiments are of great interest. The commonly used Fast Fourier Transform (FFT) algorithm is applicable only when data are evenly spaced and when no values are missing, which is not always the case in high-throughput measurements. The choice of statistic to evaluate the significance of the periodic patterns for unevenly spaced gene expression time series has not been well substantiated. METHODS: The Lomb-Scargle periodogram approach is used to search time series of gene expression to quantify the periodic behavior of every gene represented on the DNA array. The Lomb-Scargle periodogram analysis provides a direct method to treat missing values and unevenly spaced time points. We propose the combination of a Lomb-Scargle test statistic for periodicity and a multiple hypothesis testing procedure with controlled false discovery rate to detect significant periodic gene expression patterns. RESULTS: We analyzed the Plasmodium falciparum gene expression dataset. In the Quality Control Dataset of 5080 expression patterns, we found 4112 periodic probes. In addition, we identified 243 probes with periodic expression in the Complete Dataset, which could not be examined in the original study by the FFT analysis due to an excessive number of missing values. While most periodic genes had a period of 48 h, some had a period close to 24 h. Our approach should be applicable for detection and quantification of periodic patterns in any unevenly spaced gene expression time-series data.

Algorithms↗

Follower neurons in lobster (Panulirus interruptus) pyloric network regulate pacemaker period in complementary ways.

Distributed neural networks (ones characterized by high levels of interconnectivity among network neurons) are not well understood. Increased insight into these systems can be obtained by perturbing network activity so as to study the functions of specific neurons not only in the network's "baseline" activity but across a range of network activities. We applied this technique to study cycle period control in the rhythmic pyloric network of the lobster, Panulirus interruptus. Pyloric rhythmicity is driven by an endogenous oscillator, the Anterior Burster (AB) neuron. Two network neurons feed back onto the pacemaker, the Lateral Pyloric (LP) neuron by inhibition and the Ventricular Dilator (VD) neuron by electrical coupling. LP and VD neuron effects on pyloric cycle period can be studied across a range of periods by altering period by injecting current into the AB neuron and functionally removing (by hyperpolarization) the LP and VD neurons from the network at each period. Within a range of pacemaker periods, the LP and VD neurons regulate period in complementary ways. LP neuron removal speeds the network and VD neuron removal slows it. Outside this range, network activity is disrupted because the LP neuron cannot follow slow periods, and the VD neuron cannot follow fast periods. These neurons thus also limit, in complementary ways, normal pyloric activity to a certain period range. These data show that follower neurons in pacemaker networks can play central roles in controlling pacemaker period and suggest that in some cases specific functions can be assigned to individual network neurons.

Animals↗

Differential effects of amino acids on the period of the circadian rhythm from the Aplysia eye.

The effect of continuous treatments of single L-amino acids (0.1mM) on the free running rhythm from the isolated Aplysia eye was examined. A variation in the change in free running period produced by different amino acids was observed. Two well-known precursors of neurotransmitters (tyrosine, tryptophan) had the largest effects. These amino acids lengthened the period ca. 1.7 h. Another group of amino acids (alanine, threonine, proline) lengthened the period by about 1 h. Smaller effects were produced by aspartic acid and leucine and no effects were caused by lysine, glycine, valine, and serine. Phenylalanine may shorten the period a small amount. Glucose (5mM) lengthens the period a small amount (0.4 h), decreases the effect of tyrosine somewhat, and has no effect on the lengthening of the period produced by tryptophan. Three amino acids not involved in protein synthesis (ornithine, beta-alanine, citrulline) had at most small effects on the free running period. Also, D-tryptophan lengthened the period by 0.6 h but the effect of D-tryptophan was considerably smaller than the effect of L-tryptophan. A few of the amino acids had small short-term effects on spike rate and longer-term effects on the amplitudes of the rhythms but these effects did not correlate with the effects of the amino acids on the free running period. Though continuous treatments of certain amino acids lengthened the periods, shorter treatments (tryptophan, 6 h) did not phase-shift the rhythm. Since eyes maintained in a commonly used culture medium have longer periods than eyes in a simple seawater medium, the amino acids of the culture medium must be responsible, at least in part, for the lengthening effect of the culture medium. The mechanism of action of the amino acids is unknown. The magnitude of the effects did not correlate with physical-chemical properties of the amino acids nor with whether the amino acids were "essential" or "nonessential." The effects of the amino acids may be mediated by their effects on neurotransmitter and/or protein synthesis.

Amino Acids↗

Potential bias in pharmacoepidemiological studies due to the length of the drug free period: a study on antidepressant drug use in adults in the Netherlands.

PURPOSE: The aim of this study was to evaluate the effect of the length of the drug free period on incidence measurements as well as on cohort characteristics in users of antidepressants. METHODS: The study population consisted of patients aged 18 years or older who filled a prescription for an antidepressant drug in the Netherlands, between October 2001 and September 2002. One-year incidence of antidepressant drug use was estimated using drug free periods varying in length from 1 month to 9 years. In addition, we evaluated what effect the drug free period has on cohort characteristics by comparing a cohort of first time antidepressant drug users defined using a 9-year drug free period with cohorts using 6, 12 and 24 months drug free period. RESULTS: When using a 6-month drug free period the measured incidence was about 32 per 1,000 individuals (95%CI: 31.3, 32.6) while the measured incidence was 27.5 (95%CI: 26.9, 28.1), 23.5 (95%CI: 22.9, 24.0) and 17.2 (95%CI: 16.7, 17.7) per 1,000 individuals when using a 12-month, 24 month respectively a 9-year drug free period. Furthermore, the prevalence of characteristics in inception cohort studies changes when using different drug free periods. CONCLUSION: Altering the drug free period from a short to a longer one results in decreased incidence. Furthermore, for inception cohorts where first time drug use is an inclusion criterion the drug free period can influence the prevalence of cohort characteristics and for short drug free periods give biased estimates.

Adolescent↗

Correlation of C0 and C2 levels with lipid profiles in adolescent renal transplant recipients in the early and late posttransplant periods.

Hyperlipidemia is a frequent complication after renal transplantation. Cyclosporine therapy is an important cause of hyperlipidemia. It is still controversial whether C0 or C2 is the most effective way to monitor blood cyclosporine concentrations to guide dosages. We sought to evaluate the relationship of C0 or C2 to serum lipid levels in the early and late posttransplant periods among adolescent renal transplant recipients. The posttransplantation charts of 26 adolescent renal transplant recipients were evaluated retrospectively. Serum C0 and C2 levels and serum lipid (triglyceride and total cholesterol) levels were analyzed both in the early (first 6 months) and the late (thereafter) posttransplant periods. Hypertriglyceridemia and hypercholesterolemia were defined as levels above the 95th percentile adjusted for age and gender. To evaluate the influence of C0 and C2 levels on serum lipids, we excluded one patient with familial hyperlipidemia. In addition, serum lipid levels of the remaining 25 patients were excluded in acute rejection periods and when the serum creatinine levels were above 2.5 mg/dL, representing chronic allograft nephropathy. Concurrently recorded serum C0 and C2 levels were present for only 21 patients. Overall, we evaluated the records of 245 visits for these 21 patients. The incidence of hyperlipidemia decreased in the late posttransplant period, being significant for hypercholesterolemia. C2 had strong negative correlation with serum lipids; it was significant for total cholesterol in the early posttransplant period (r=-0.542, P=.005), but weaker in the late posttransplant and whole posttransplant periods. Thus correlation of C2 with serum lipids showed differences during posttransplant follow-up. C0, on the other hand, was positively correlated with total cholesterol levels in all periods, being significant for the whole posttransplant period (r=0.293, P=.000) and for the late posttransplant period (r=0.196, P=.025). Although not statistically significant, C0 levels were higher among hypertriglyceridemic or hypercholesterolemic episodes both in the early and the late posttransplant periods. When only the C0 levels of all 25 patients were analyzed (789 visits), C0 and serum cholesterol levels were positively correlated both in the early and the late posttransplant periods (P=.013, r=0.198 and P=.000, r=0.177, respectively). We concluded that C0 has a more predictable correlation with serum cholesterol levels after renal transplantation in adolescent patients.

Adolescent↗

Adrenergic sensitivity of neurons with non-periodic firing activity in rat injured dorsal root ganglion.

In this study, we compared the sensitivity of non-periodically and periodically active neurons in chronically compressed dorsal root ganglion in rats to norepinephrine and sympathetic stimulation. Forty-nine of 58 (84.5%) neurons with non-periodic activity showed responses to norepinephrine, whereas only five of 48 (10.4%) neurons with periodic activity displayed any response. The dose-response relationship of norepinephrine to the irregular burst pattern neurons shifted towards the left significantly compared to that of the periodic activity neurons. Responses to norepinephrine became apparent in eight neurons after their periodic firing activity was transformed into the non-periodic firing activity through the increase in Ca(2+). Changes in the time-response curves indicate a higher sensitivity of irregular burst pattern neurons to sympathetic stimulation than the periodic activity neurons. Finally, deterministic dynamics contained within the interburst interval series for non-periodic activity were identified. From these results, we suggest that the non-periodic activity neurons have a higher adrenergic sensitivity than those displaying periodic activity, and that this sensitivity may depend on the deterministic chaos within its firing dynamic system.

Action Potentials↗