Clinical and pathological study of an outbreak of obstructive urolithiasis in feedlot cattle in southern Brazil

The epidemiology, clinical picture and pathology of an outbreak of urolithiasis in cattle in southern Brazil are described. The disease occurred in August 1999 in a feedlot beef cattle herd. Five out of 1,100 castrated steers were affected. Clinical signs included colic and ventral abdominal distension. White, sand-grain-like mineral deposits precipitated on the preputial hairs. Affected cattle died spontaneously 24-48 hrs after the onset of the clinical signs. Only one animal recovered after perineal urethrostomy. Necropsy findings included calculi blocking the urethral lumen of the distal portion of the penile sigmoid flexure, urinary bladder rupture with leakage of urine into the abdominal cavity and secondary fibrinous peritonitis. Daily water intake was low since water sources were scarce and not readily available. The animals were fed rations high in grains and received limited amounts of roughage. Biochemical analysis revealed that the calculi were composed of ammonium phosphate. A calcium-phosphorus imbalance (0.4:0.6) was detected in the feedlot ration. For the outbreak, it is suggested that contributing factors to urolith formation include insufficient fiber ingestion, low water intake and high dietary levels of phosphorus. No additional cases were observed in that feedlot after preventive measures were established. Similar dietary mismanagement in fattening steers has been associated with obstructive urolithiasis in feedlot beef cattle in other countries.

Rapid eye movement (REM) sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7) activity

Rapid eye movement (REM) sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase) controls acetylcholine (Ach) availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two additional groups, a home-cage control (N = 6) and a large platform control (N = 6), were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000 g supernatant) Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8). There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2). Our results suggest that REM sleep deprivation changes Ach availability at the level of its receptors through a decrease in Achase activity

Cardiovascular and respiratory changes during slow-wave sleep in rats are associated with electrocorticogram desynchronization

In awake rats a single recurrent larger tidal volume (deep breaths) occurs at regular intervals, followed by oscillations in arterial pressure and heart rate. In the present study we recorded the changes in blood pressure, heart rate and ventilation during the wakefulness-sleep cycle identified by electrocorticographic records in order to determine whether the deep breaths and cardiovascular oscillations were associated with changes in the electrocorticogram. During several episodes of slow-wave sleep (SWS) in 7 rats the deep breaths and oscillations in arterial pressure and heart rate were preceded by SWS desynchronization. The interval between deep breaths during SWS was 71 ± 4 s, the period between initial desynchronization and the generation of deep breaths was 3.98 ± 0.45 s and the duration of SWS desynchronization was 11 ± 0.65 s. Hypotension (-16 ± 1 mmHg) and tachycardia (+15 ± 5 bpm) were observed during deep breaths in the SWS state. These data indicate that the oscillations in arterial pressure and heart rate during SWS are associated with deep breaths, which in turn are preceded by desynchronization of the electrocorticogram in this state of sleep

Neuroethologic differences in sleep deprivation induced by the single- and multiple-platform methods

It has been proposed that the multiple-platform method (MP) for desynchronized sleep (DS) deprivation eliminates the stress induced by social isolation and by the restriction of locomotion in the single-platform (SP) method. MP, however, induces a higher increase in plasma corticosterone and ACTH levels than SP. Since deprivation is of heuristic value to identify the functional role of this state of sleep, the objective of the present study was to determine the behavioral differences exhibited by rats during sleep deprivation induced by these two methods. All behavioral patterns exhibited by a group of 7 albino male Wistar rats submitted to 4 days of sleep deprivation by the MP method (15 platforms, spaced 150 mm apart) and by 7 other rats submitted to sleep deprivation by the SP method were recorded in order to elaborate an ethogram. The behavioral patterns were quantitated in 10 replications by naive observers using other groups of 7 rats each submitted to the same deprivation schedule. Each quantification session lasted 35 min and the behavioral patterns presented by each rat over a period of 5 min were counted. The results obtained were: a) rats submitted to the MP method changed platforms at a mean rate of 2.62 ± 1.17 platforms h-1 animal-1; b) the number of episodes of noninteractive waking patterns for the MP animals was significantly higher than that for SP animals (1077 vs 768); c) additional episodes of waking patterns (26.9 ± 18.9 episodes/session) were promoted by social interaction in MP animals; d) the cumulative number of sleep episodes observed in the MP test (311) was significantly lower (chi-square test, 1 d.f., P<0.05) than that observed in the SP test (534); e) rats submitted to the MP test did not show the well-known increase in ambulatory activity observed after the end of the SP test; f) comparison of 6 MP and 6 SP rats showed a significantly shorter latency to the onset of DS in MP rats (7.8 ± 4.3 and 29.0 ± 25.0 min, respectively; Student t-test, P<0.05). We conclude that the social interaction occurring in the MP test generates additional stress since it increases the time of forced wakefulness and reduces the time of rest promoted by synchronized sleep.

Effect of SX-3228, a selective ligand for the BZ1 receptor, on sleep and waking during the light-dark cycle in the rat

The effects of the benzodiazepine1 (BZ1) receptor agonist SX-3228 were studied in rats (N = 12) implanted for chronic sleep procedures. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228, sc, to rats 1 h after the beginning of the light phase of the light-dark cycle induced a significant reduction of rapid-eye-movement sleep (REMS) during the third recording hour. Moreover, slow wave sleep (SWS) was increased during the fourth recording hour after the two largest doses of the compound. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228 one hour after the beginning of the dark period of the light-dark cycle caused a significant and maintained (6-h recording period) reduction of waking (W), whereas SWS and light sleep (LS) were increased. REMS values tended to increase during the entire recording period; however, the increase was statistically significant only for the 1.0 mg/kg dose during the first recording hour. In addition, a significant and dose-related increase of power density in the delta and the theta regions was found during nonREM sleep (LS and SWS) in the dark period. Our results indicate that SX-3228 is a potent hypnotic when given to the rat during the dark period of the light-dark cycle. Moreover, the sleep induced by SX-3228 during the dark phase closely resembles the physiological sleep of the rat.

Electrolocation-communication discharges of the fish Gymnotus carapo L. (Gymnotidae: Gymnotiformes) during behavioral sleep

Technical problems have hampered the study of sleep in teleosts. The electrical discharges of Gymnotus carapo L. (Gymnotidae: Gymnotiformes) were monitored to evaluate their ease and reliability as parameters to study sleep. The discharges were detected by electrodes immersed in a glass aquarium and were recorded on a conventional polygraph. G. carapo showed conspicuous signs of behavioral sleep. During these periods, opercular beat rates were counted, electric discharges recorded, and the "sharp discharge increase" (SDI) of the orienting reflex was investigated. All 20 animals monitored maintained electrical discharges during behavioral sleep. The discharge frequencies during sleep (50.3 ± 10.4 Hz) were not significantly different from those observed when the fish was awake and inactive (57.2 ± 12.1 Hz) (Wilcoxon matched-pairs signed-ranks test, P>0.05). However, the SDI, which was prevalent in the awake fish, was not observed during periods of behavioral sleep. Additional observations showed that the species had cannibalistic habits. When presented with electrical discharges from a conspecific, the sleeping fish showed an initial decrease or pause in discharge frequency, while the awake fish did not have this response. We conclude that the electrical discharges of G. carapo were not conspicuous indicators of behavioral sleep. Discharges may have been maintained during sleep for sensory purposes, i.e., conspecific detection and avoidance of cannibalistic attacks.

Sleep patterns and sleep-related complaints of Brazilian interstate bus drivers

Sleep-related complaints have become a highlight for physicians as well as public health administrators. Studies of sleep patterns and sleep-related complaints of shift workers have been useful in minimizing reduction in the quality of life due to the warping of the sleep-wake cycle. The objective of the present study was to assess patterns of sleep, sleep-related complaints as well as physical activity and scoring rates for depression and anxiety in interstate bus drivers. Data were obtained with a sleep questionnaire, with the Beck inventory for depression, and the State-Trait Anxiety Inventory (STAI). A total of 400 interstate bus drivers from the northern, southern, central-western and south-eastern regions of Brazil were interviewed. Sixty percent of the subjects interviewed presented at least one sleep-related complaint, 16% admitted to have dozed at the wheel while on duty, and 41% stated that they exercised on a regular basis. Other sleep disturbance complaints reported were: sleep latency 29'17"; physical fatigue, 59.8%; mental fatigue, 45.4%; sleepiness, 25.8%; irritability, 20.6%; insomnia, 37.5%, respiratory disturbances, 19.25% and snoring, 20.75%. Scores for anxiety and depression were not in the pathological range. The present data reinforce the view that bus drivers are generally discontent with shift work and its effects on sleep. Consequently, it is very important to establish an appropriate work schedule for drivers, besides implementing photo-therapy and physical activities in order to minimize sleepiness when driving.

Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei) are involved in the generation of rapid eye movement (REM) sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase), the enzyme which inactivates acetylcholine (Ach) in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase) are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex) after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1) were assayed photometrically. The results (mean ± SD) obtained showed a statistically significant (Student t-test) increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025) and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05). Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05) and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05) were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity induced by REM sleep deprivation was specific to the pons, a brain region where cholinergic neurons involved in REM generation are located, and also to brain regions which receive cholinergic input from the pons (the thalamus and medulla oblongata). During REM sleep extracellular levels of Ach are higher in the pons, medulla oblongata and thalamus. The increase in Achase activity in these brain areas after REM sleep deprivation suggests a higher rate of Ach turnover.

Fighting by sleep-deprived rats as a possible manifestation of panic: effects of sodium lactate

Increased fighting is an effect of desynchronized sleep deprivation (DSD) in rats, and recently this behavior has been suggested to be spontaneous panic and equivalent to panic disorder. In the present study we tested this hypothesis by evaluating the effect of sodium lactate on this aggressiveness, because this substance is recognized to induce spontaneous panic attacks in patients. A total of 186 male albino Wistar rats, 250-350 g, 90-120 days of age, were submitted to DSD (multiple platform method) for 0, 4, or 5 days. At the end of the deprivation period the rats were divided into subgroups respectively injected intraperitoneally with 1.86, 2.98 and 3.72 g/kg of 1 M sodium lactate, or 1.86 and 3.72 g/kg of 2 M sodium lactate. The control animals were submitted to the same procedures but received equivalent injections of sodium chloride. Regardless of DSD time, sleep-deprived animals that received sodium lactate presented a significantly higher mean number of fights (0.13 ± 0.02 fights/min) and a longer mean time spent in confrontation (2.43 ± 0.66 s/min) than the controls (0.01 ± 0.006 fights/min and 0.12 ± 0.07 s/min, respectively; P<0.01, Student t-test). For the sodium lactate group, concentration of the solution and time of deprivation increased the number of fights, with the mean number of fights and mean duration of fighting episodes being greater with the 2.98 g/kg dose using 1 M lactate concentration. These results support the hypothesis that fighting induced by DSD is probably a spontaneous panic manifestation. However, additional investigations are necessary in order to accept this as a promising animal model for studies on panic disorder.

Scintigraphy and Doppler ultrasonography for the evaluation of obstructive urinary calculi

Forty-seven patients with unilateral obstructive calculi (12 males and 35 females) were submitted to 99mTc-diethylene triamine pentaacetic acid (DTPA) or 99mTc-dimercaptosuccinic acid (DMSA) scans for assessment of renal function. The scans revealed unilateral functional deficit in 68 and 66% of the patients, respectively. A calculus size of 1.1 to 2.0 cm was significantly associated with deficit detected by DTPA, but duration of obstruction and calculus localization were not. After relief of the obstruction, the mean percent renal function of the affected kidney was found to be significantly increased from 25 ± 12% to 29 ± 12% in DTPA and from 21 ± 15% to 24 ± 12% in DMSA. Initial Doppler ultrasonography performed in 35 patients detected an increased resistive index in 10 (29%). In the remaining patients with a normal resistive index, ureteral urinary jet was observed, indicating partial obstruction. The high frequency of renal function impairment detected by DTPA and of tubulointerstitial damage detected by DMSA as well as the slight amelioration of unilateral renal function after relief of obstruction suggest that scintigraphy assessment may help evaluate the unilateral percentage of renal function and monitor renal function recovery when it occurs. The presence of a urinary jet detected by Doppler ultrasonography further indicates the severity of obstruction and the recovery prognosis.

The brain decade in debate: VII. Neurobiology of sleep and dreams

This article is a transcription of an electronic symposium held on February 5, 2001 by the Brazilian Society of Neuroscience and Behavior (SBNeC) during which eight specialists involved in clinical and experimental research on sleep and dreaming exposed their personal experience and theoretical points of view concerning these highly polemic subjects. Unlike most other bodily functions, sleep and dreaming cannot, so far, be defined in terms of definitive functions that play an ascribable role in maintaining the organism as a whole. Such difficulties appear quite clearly all along the discussions. In this symposium, concepts on sleep function range from a protective behavior to an essential function for maturation of the nervous system. Kleitman's hypothesis [Journal of Nervous and Mental Disease (1974), 159: 293-294] was discussed, according to which the basal state is not the wakeful state but sleep, from which we awake to eat, to protect ourselves, to procreate, etc. Dreams, on the other hand, were widely discussed, being considered either as an important step in consolidation of learning or simply the conscious identification of functional patterns derived from the configuration of released or revoked memorized information.

Sawtooth waves during REM sleep after administration of haloperidol combined with total sleep deprivation in healthy young subjects

We sought to examine the possible participation of dopaminergic receptors in the phasic events that occur during rapid eye movement (REM) sleep, known as sawtooth waves (STW). These phasic phenomena of REM sleep exhibit a unique morphology and, although they represent a characteristic feature of REM sleep, little is known about the mechanisms which generate them and which are apparently different from rapid eye movements. STW behavior was studied in 10 male volunteers aged 20 to 35 years, who were submitted to polysomnographic monitoring (PSG). On the adaptation night they were submitted to the first PSG and on the second night, to the basal PSG. On the third night the volunteers received placebo or haloperidol and spent the whole night awake. On the fourth night they were submitted to the third PSG. After a 15-day rest period, the volunteers returned to the sleep laboratory and, according to a double-blind crossover randomized design, received haloperidol or placebo and spent the whole night awake, after which they were submitted to the fourth PSG. The volunteers who were given haloperidol combined with sleep deprivation exhibited an elevation of the duration and density of the STW, without significant alterations of the other REM sleep phasic phenomena such as rapid eye movement. These findings suggest that sawtooth waves must have their own generating mechanisms and that the dopaminergic receptors must exert a modulating role since REM sleep deprivation, as well as administration of neuroleptics, produces supersensitivity of dopaminergic receptors.

Effects of aerobic exercise training on heart rate variability during wakefulness and sleep and cardiorespiratory responses of young and middle-aged healthy men

The purpose of the present study was to evaluate the effects of aerobic physical training (APT) on heart rate variability (HRV) and cardiorespiratory responses at peak condition and ventilatory anaerobic threshold. Ten young (Y: median = 21 years) and seven middle-aged (MA = 53 years) healthy sedentary men were studied. Dynamic exercise tests were performed on a cycloergometer using a continuous ramp protocol (12 to 20 W/min) until exhaustion. A dynamic 24-h electrocardiogram was analyzed by time (TD) (standard deviation of mean R-R intervals) and frequency domain (FD) methods. The power spectral components were expressed as absolute (a) and normalized units (nu) at low (LF) and high (HF) frequencies and as the LF/HF ratio. Control (C) condition: HRV in TD (Y: 108, MA: 96 ms; P<0.05) and FD - LFa, HFa - was significantly higher in young (1030; 2589 ms²/Hz) than in middle-aged men (357; 342 ms²/Hz) only during sleep (P<0.05); post-training effects: resting bradycardia (P<0.05) in the awake condition in both groups; VO2 increased for both groups at anaerobic threshold (P<0.05), and at peak condition only in young men; HRV in TD and FD (a and nu) was not significantly changed by training in either groups. The vagal predominance during sleep is reduced with aging. The resting bradycardia induced by short-term APT in both age groups suggests that this adaptation is much more related to intrinsic alterations in sinus node than in efferent vagal-sympathetic modulation. Furthermore, the greater alterations in VO2 than in HRV may be related to short-term APT.

Sleep-wake pattern of medical students: early versus late class starting time

The sleep-wake cycle of students is characterized by delayed onset, partial sleep deprivation and poor sleep quality. Like other circadian rhythms, the sleep-wake cycle is influenced by endogenous and environmental factors. The aim of the present study was to determine the effects of different class starting times on the sleep-wake pattern of 27 medical students. The data were collected during two medical school semesters having different class starting times. All subjects answered the Portuguese version of the Horne and Östberg Morningness/Eveningness Questionnaire, the Pittsburgh Sleep Quality Index (PSQI) and kept a sleep diary for two weeks during each semester. Better sleep quality (PSQI = 5.3 vs 3.4), delayed sleep onset (23:59 vs 0:54 h) and longer sleep duration (6 h and 55 min vs 7 h and 25 min) were observed with the late schedule. We also found reduced sleep durations during weekdays and extended sleep durations during weekends. This pattern was more pronounced during the semester with the early class schedule, indicating that the students were more sleep deprived when their classes began earlier in the morning. These results require further investigation regarding the temporal organization of our institutions.

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 ± 6.24%) in sputum whereas neutrophils (63.3 ± 4.66%) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 ± 330.7 pg/ml) and plasma (716.6 ± 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 ± 105.2 pg/ml) and TNF-alpha (308.8 ± 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 ± 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.