Influence of Timed Nutrient Diet on Depression and Light Sensitivity in Seasonal Affective Disorder

Seasonal Affective Disorder (SAD) patients crave and eat more carbohydrates (CHO) in fall‐winter when depressed, especially in the evenings, and feel energetic thereafter. Evening CHO‐rich meals can phase delay circadian rhythms, and glucose increases retinal response to light. We studied timed CHO‐ or protein‐rich (PROT) diet as a putative therapy for SAD. Unmedicated, DSM‐IV‐diagnosed depressed women with SAD (n=22, 19–63 yrs) in the follicular phase of the menstrual cycle (present in 19) were randomized to nine days of eating ～1600 kcal of either CHO before 12:00 h (n=9), CHO after 18:00 h (n=6), or PROT after 18:00 h (n=7); only water was allowed for the rest of the day. Measurements included the depression questionnaire SIGH‐SAD (with 21‐item Hamilton depression subscale), Eating Behavior Questionnaire (DEBQ), percentage fat (by bioimpedancemetry), clinical biochemistry (glucose, cholesterol, triglycerides, TSH, T4, cortisol), and electroretinogram (ERG). No differential effects of diet were found on any of the studied parameters (except DEBQ). Clinically, participants improved slightly; the 21‐HDRS score (mean±SD) decreased from 19.6±6.4 to 14.4±7.4 (p=.004). Percent change correlated significantly with menstrual day at diet onset (mood improved the first week after menstruation onset), change in available sunshine (more sunlight, better mood), and initial percentage fat (fatter patients improved more). Scotopic ERG amplitude was diminished after treatment (p=.025, three groups combined), probably due to greater exposure to sunshine in 14/22 subjects (partial correlation analysis significant). Keeping in mind the limitations of this ambulatory study (i.e., inability to control outdoor light exposure, small number of participants, and briefness of intervention), it is suggested that the 25% clinical improvement (of the order of magnitude of placebo) is not related to nutrient diet or its timing, but rather to natural changes during the menstrual cycle, available sunshine, and ease of dieting for fatter patients.     

Effect of pedal rate on diurnal variations in cardiorespiratory variables

Recently, it was observed that the freely chosen pedal rate of elite cyclists was significantly lower at 06:00 than at 18:00 h, and that ankle kinematics during cycling exhibits diurnal variation. The modification of the pedaling technique and pedal rate observed throughout the day could be brought about to limit the effect of diurnal variation on physiological variables. Imposing a pedal rate should limit the subject's possibility of adaptation and clarify the influence of time of day on physiological variables. The purpose of this study was to determine whether diurnal variation in cardiorespiratory variables depends on pedal rate. Ten male cyclists performed a submaximal 15 min exercise on a cycle ergometer (50% W_max). Five test sessions were performed at 06:00, 10:00, 14:00, 18:00, and 22:00 h. The exercise bout was divided into three equivalent 5 min periods during which different pedal rates were imposed (70 rev · min^-1, 90 rev · min^-1 and 120 rev · min^-1). No significant diurnal variation was observed in heart rate and oxygen consumption, whatever the pedal rate. A significant diurnal variation was observed in minute ventilation (p=0.01). In addition, the amplitude of the diurnal variation in minute ventilation depended on pedal rate: the higher the pedal rate, the greater the amplitude of its diurnal variation (p=0.03). The increase of minute ventilation throughout the day is mainly due to variation in breath frequency (p=0.01)—the diurnal variation of tidal volume (all pedal rate conditions taken together) being non-significant—but the effect of pedal rate×time of day interaction on minute ventilation specific to the higher pedal rate conditions (p=0.03) can only be explained by the increase of tidal volume throughout the day. Even though an influence of pedal rate on diurnal rhythms in overall physiological variables was not also evidenced, high pedal rate should have been imposed when diurnal variations of physiological variables in cycling were studied.     

Oxidative stress implication in a new phenotype of amyotrophic quadricipital syndrome with cardiac involvement due to lamin A/C mutation

This study aimed at evaluating OS in an amyotrophic quadricipital syndrome with cardiac impairment in a family of 80 members with a mutation in lamin A/C gene. Twelve patients had cardiac involvement (5 cardiac and skeletal muscles impairment). OS was evaluated in blood samples (thiobarbituric acid-reactive substances (TBARS), carbonylated proteins (PCO)) 6 “affected patients” with phenotypic and genotypic abnormalities without heart failure and 3 “healthy carrier” patients. OS was higher in affected patients than in healthy, as shown by the higher TBARS and PCO values. Patients with cardiac and peripheral myopathy exhibited a higher OS than patients with only cardiac disease (TBARS: 1.73 ± 0.05 vs. 1.51 ± 0.04 mmol/l (p = 0.051), PCO: 2.73 ± 0.34 vs. 0.90 ± 0.10 nmol/mg protein (p = 0.47)), and with healthy carriers patients (TBARS: 1.73 ± 0.05 vs. 1.16 ± 0.14 mmol/l (p = 0.05), PCO: 2.73 ± 0.34 vs. 0.90 ± 0.20 nmol/mg protein (p = 0.47)).

OS may thus contribute to the degenerative process of this laminopathy. ROS production occurs, prior to heart failure symptoms. We suggest that the extent activation may also promote the variable phenotypic expression of the disease.     

More prominent reactivity in mood than activity and sleep induced by differential light exposure due to seasonal and local differences

The aim of this study was to investigate how mood, work time, light exposure, activity, and sleep indices are affected by the differences of latitude and season in healthy volunteers. Twenty-four subjects (38.92±11.32 yrs) in Rochester, Minnesota, USA (latitude 44°1'N) and 30 subjects (47.03±16.32 yrs) in San Diego, California, USA (latitude 32°43'N) completed a 1 yr protocol measuring daily logs including daily work time and sleep diary; the Center for Epidemiologic Studies Depression Scale (CES-D); the eight-item atypical subscore of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder version (SIGH-SAD); and actigraphic measures of light exposure and sleep for one-week in each solstice of summer and winter. Higher scores of CES-D (p=0.038) and the eight-item atypical subscore of SIGH-SAD (p=0.009), and longer indoor (p=0.001) and shorter outdoor (p=0.002) work times were observed during winter than summer only in Rochester, with no differences in San Diego. The mesor of light was decreased in both Rochester (p≤0.001) and San Diego (p=0.004) during winter compared to summer, with no differences in the mesors (24 h means) of activity and sleep. The eight-item atypical subscore of SIGH-SAD was significantly negatively correlated with the mesor of light (p=0.034). Sleep indices showed no significant differences between two locales or two seasons. A more prominent depressive mood in Rochester than San Diego during winter can be explained by decreased light exposure of healthy subjects in Rochester. Despite a significant difference of mood and light exposure between the two seasons in Rochester, there were no differences in activity or sleep. Therefore, mood might be more reactive than activity and sleep in the seasonal variation induced by differential light exposure.     

Circadian variation in oxidative stress markers in healthy and type II diabetic men

Seven clinically healthy, nondiabetic (ND) and four Type II diabetic (D) men were assessed for circadian rhythms in oxidative “stress markers.” Blood samples were collected at 3h intervals for ∼27 h beginning at 19:00h. Urine samples were collected every 3 h beginning with the 16:00h-19:00h sample. The dark (sleep) phase of the light-dark cycle extended from 22:30h to 06:30h, with brief awakening for sampling at 01:00h and 04:00h. Subjects were offered general hospital meals at 16:30h, 07:30h, and 13:30h (2400 cal in total/24 h). Serum samples were analyzed for uric acid (UA) and nitrite (NO) concentrations, and urine samples were assayed for 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), and 8-isoprostane (ISP). Data were analyzed statistically both by the population multiple-components method and by the analysis of variance (ANOVA). The 24h mean level of UA and NO was greater in D than in ND subjects (424 vs. 338 μmol/L and 39.2 vs. 12.7 μM, respectively). A significant circadian rhythm in UA (p=0.001) and NO (p=0.048) was evident in ND but not in D (p=0.214 and 0.065). A circadian rhythm (p=0.004, amplitude=8.6 pmol/kgbw/3h urine vol.) was also evident in urine 8-OHdG of ND but not of D. The 24h mean levels of ND and D were comparable (76.8 vs. 65.7 pmol/kgbw/3h urine vol.). No circadian rhythm by population multiple-components was evident in MDA and ISP levels of ND subjects, or in 8-OHdG, MDA, and ISP in D. However, a significant time-effect was demonstrated by ANOVA in all variables and groups. The 24h mean of MDA and ISP in D was significantly greater than in ND (214 vs. 119 nmol/3h urine vol. and 622 vs. 465 ng/3h urine vol.). The peak concentrations of the three oxidative “stress markers” in urine, like those of serum NO, occurred early in the evening in both groups of men. This observation suggests a correlation between increased oxidative damage and increased rate of anabolic-catabolic events as evidenced by similarities in the timing of peak NO production and in parameters relevant to metabolic functions.     

Effect of Ramadan on the diurnal variation in short-term high power output

This study examined the effects of Ramadan fasting on anaerobic performances and their diurnal fluctuations. In a balanced and randomized study design, 12 subjects were measured for maximal power (P_max; force-velocity test), peak power (P_peak), and mean power (P_mean) with the Wingate test at 07:00, 17:00, and 21:00 h on four different occasions: one week before Ramadan (BR), the second week of Ramadan (SWR), the fourth week of Ramadan (ER), and two weeks after Ramadan (AR). There was an interval of 28 h between any two successive tests. Oral temperature was measured before each test. Under each condition, the results showed a time-of-day effect on oral temperature. Analysis of variance revealed a significant (Ramadan×time-of-day of test) interaction effect on P_max. This variable improved significantly from morning to evening before Ramadan (1.1±0.2 W · kg^-1), during the second week of Ramadan (0.6±0.2 W · kg^-1), and two weeks after the end of Ramadan (0.9±0.2 W · kg^-1). However, daily fluctuations disappeared during the fourth week of Ramadan. For P_peak and P_mean, there was no significant Ramadan×test-time interaction. These variables improved significantly from morning to evening before Ramadan ([1±0.3 W · kg^-1] for P_peak and [1.7±1.6 W · kg^-1] for P_mean) and in the second week of Ramadan ([0.9±0.6 W · kg^-1] for P_peak and [1.7±1.5 W · kg^-1] for P_mean). However, they were not affected by time-of-day in the fourth week of Ramadan. Considering the effect of Ramadan on anaerobic performances, in comparison with before Ramadan, no significant difference was observed during Ramadan at 07:00 h. The variables were significantly lower in the second week of Ramadan and in the fourth week of Ramadan at 17:00 h and 21:00 h. P_mean was not affected during the second week of Ramadan. In conclusion, the time-of-day effect on anaerobic power variables tends to disappear during Ramadan. In comparison with the period before Ramadan, anaerobic performances were unaffected in the morning but impaired in the evening during Ramadan.     

Measuring activity patterns using actigraphy in multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease resulting in impairments in motor and mental performance and restrictions in activities. Self-report instruments are commonly used to measure activity patterns; alternatively, actigraphs can be placed on several parts of the body. The aims of this study were to evaluate the superiority and specificity of actigraph placement (wrist vs. ankle) in subjects with MS and healthy controls and explore the relationship between self-report and objective activity patterns. A total of 19 subjects with definite MS and 10 healthy volunteers wore actigraphs on the non-dominant wrist and ankle for three days while they kept a log to register performed activities every .5 h. Wrist and ankle actigraphs produced similar activity patterns during the most active hours (09:00-20:30 h) (ANOVA, time×location interaction: F=.901, df=23, p=.597) in individuals with MS and healthy controls (between subjects factor F=3.275, p=.083). Wrist placement of the actigraphs was better tolerated than ankle placement. Wrist actigraph data corresponded to a higher degree with self-reported activities of the upper limbs in the early afternoon, whereas ankle data seem to reflect better whole body movements in the later afternoon/early evening. Overall, actigraph data correlated moderately with self-reported activity (r=.57 for ankle and r=.59 for wrist). The regression model revealed that self-reported activities explained 44% of the variance in ankle and 50% of wrist data. Wrist and ankle actigraphs produce similar activity patterns in subjects with MS and in healthy controls; however, the placement of actigraphs on the wrist is better tolerated. Ankle actigraphs reflect general movement but underestimate upper body activity. Subjective registration of activity level partly matches with objective actigraph measurement. A combination of both objective and subjective activity registration is recommended to evaluate the physical activity pattern of subjects with MS.     

Attenuated feeding responses to circadian and palatability cues in mice lacking neuropeptide Y

Neuropeptide Y (NPY) is a potent orexigenic peptide that is implicated in the feeding response to a variety of stimuli. The current studies employed mice lacking NPY (Npy−/−) and their wild-type (Npy+/+) littermates to investigate the role of this peptide in the feeding response to circadian and palatability cues. To investigate the response to a circadian stimulus, we assessed food intake during the 4-h period following dark onset, a time of day characterized by maximal rates of food consumption. Compared to Npy+/+ controls, intake of Npy−/− mice was reduced by 33% during this period (0.6 ± 0.1 g versus 0.9 ± 0.1 g; p ≤ 0.05). In contrast, intake did not differ between genotypes when measured over a 24-h period (3.7 ± 0.2 g versus 3.5 ± 0.3 g; p = ns). Furthermore, reduced dark cycle 4 h food intake in Npy−/− mice was not evident after a 24-h fast (1.4 ± 0.1 g for both genotypes; p = ns), despite a pronounced delay in the initiation of feeding (636 ± 133 s versus 162 ± 29 s; p ≤ 0.05). To investigate the role of NPY in the feeding response to palatability cues, mice were presented with a highly palatable diet (HP) for 1 h each day (in addition to having ad libitum access to chow) for 18 days. Npy+/+ mice rapidly increased daily HP intake such that by the end of the first week, they derived a substantial fraction of daily energy from this source (41 ± 3%). By comparison, HP intake was markedly reduced in Npy−/− mice during the first week (24 ± 7% of daily energy intake, p ≤ 0.05 versus Npy+/+), although it eventually increased (by Day 9) to values comparable to those of Npy+/+ controls. These experiments suggest that NPY contributes to the mechanism whereby food intake increases in response to circadian and palatability cues and that mechanisms driving food intake in response to these stimuli differ from those activated by energy restriction.     

Effects of a five-hour exposure of arm and leg to a slightly cool thermal environment in the afternoon on the body temperature rhythm

The purpose of this study was to determine whether the different thermal conditions of the arm and leg due to wearing different types of clothing during the afternoon could modulate the circadian rhythm of body temperature and subjective sleep quality. Six healthy female volunteers were studied twice with two types of clothing, leaving the arm and leg covered or uncovered. The environmental chamber was controlled at 24 ± 0.5°C and 50 ± 5% RH during wakefulness and 28 ± 0.5°C and 50 ± 5% RH during night sleep. One type of clothing consisted of long-sleeved shirts and full-length trousers (Type L, 989 g, 0.991 clo); the other type was of half-sleeved shirts and knee-length trousers (Type H, 750 g, 0.747 clo). One testing session lasted for 16 h from 14:00 to 06:00 h the next morning. Subjects wore Type L or Type H clothing during the afternoon exposure (14:00 - 19:00), and Type L clothing during the evening (19:00 - 22:30 h) and the night sleep (22:30 - 06:00 h). Results were as follows. (1) When wearing Type H rather than Type L clothing, skin temperatures of the arm and leg were significantly lower during the time of exposure, and increased more after the evening. (2) Rectal temperature was not significantly different between the two types of clothing except during the early part of the exposure period, but it decreased during the evening by a significantly greater amount when wearing Type H clothing. (3) Subjective sleep quality was not significantly different between the two clothing types. These results suggest that afternoon exposure of the arm and leg to a slightly cool environment does not have a strong after-effect on the body temperature and subjective sleep quality.     

Morning melatonin has limited benefit as a soporific for daytime sleep after night work

Exogenous melatonin administration in humans is known to exert both chronobiotic (phase shifting) and soporific effects. In a previous study in our lab, young, healthy, subjects worked five consecutive simulated night shifts (23:00 to 07:00 h) and slept during the day (08:30 to 15:30 h). Large phase delays of various magnitudes were produced by the study interventions, which included bright light exposure during the night shifts, as assessed by the dim light melatonin onset (DLMO) before (baseline) and after (final) the five night shifts. Subjects also ingested either 1.8 mg sustained-release melatonin or placebo before daytime sleep. Although melatonin at this time should delay the circadian clock, this previous study found that it did not increase the magnitude of phase delays. To determine whether melatonin had a soporific effect, we controlled the various magnitudes of phase delay produced by the other study interventions. Melatonin (n=18) and placebo (n=18) groups were formed by matching a melatonin participant with a placebo participant that had a similar baseline and final DLMO (±1 h). Sleep log measurements of total sleep time (TST) and actigraphic measurements of sleep latency, TST, and three movement indices for the two groups were examined. Although melatonin was associated with small improvements in sleep quality and quantity, the differences were not statistically significant by analysis of variance. However, binomial analysis indicated that melatonin participants were more likely to sleep better than their placebo counterparts on some days with some measures. It was concluded that, the soporific effect of melatonin is small when administered prior to 7 h daytime sleep periods following night shift work.     

SLEEP LOGS OF YOUNG ADULTS WITH SELF-SELECTED SLEEP TIMES PREDICT THE DIM LIGHT MELATONIN ONSET

The purpose of this study was to determine whether a sleep log parameter could be used to estimate the circadian phase of normal, healthy, young adults who sleep at their normal times, and thus naturally have day-to-day variability in their times of sleep. Thus, we did not impose any restrictions on the sleep schedules of our subjects (n=26). For 14 d, they completed daily sleep logs that were verified with wrist activity monitors. On day 14, salivary melatonin was sampled every 30 min in dim light from 19:00 to 07:30h to determine the dim light melatonin onset (DLMO). Daily sleep parameters (onset, midpoint, and wake) were taken from sleep logs and averaged over the last 5, 7, and 14 d before determination of the DLMO. The mean DLMO was 22:48±01:30 h. Sleep onset and wake time averaged over the last 5 d were 01:44±01:41 and 08:44±01:26 h, respectively. The DLMO was significantly correlated with sleep onset, midpoint, and wake time, but was most strongly correlated with the mean midpoint of sleep from the last 5 d (r=0.89). The DLMO predicted using the mean midpoint of sleep from the last 5 d was within 1 h of the DLMO determined from salivary melatonin for 92% of the subjects; in no case did the difference exceed 1.5 h. The correlation between the DLMO and the score on the morningness-eveningness questionnaire was significant but comparatively weak (r=-0.48). We conclude that the circadian phase of normal, healthy day-active young adults can be accurately predicted using sleep times recorded on sleep logs (and verified by actigraphy), even when the sleep schedules are irregular.     

Impact of vitamin E supplement in standard laboratory animal diet on microvascular manifestation of ischemia/reperfusion injury

Aimed at improving animal fertility and health, diets for farm and laboratory animals have over the last few years been supplemented with increasing amounts of the antioxidant vitamin E. We now demonstrate by intravital microscopy that feeding hamsters with a vitamin E-supplemented “standard” rodent diet (60 ppm vitamin E) significantly reduces the microvascular manifestations of ischemia/reperfusion injury when compared to animals fed a nonsupplemented diet. Postischemic leukocyte adhesion to venular endothelium was reduced from 770 ± 204 cells/mm² at 24 h after reperfusion in control animals on the nonsupplemented diet to 403 ± 105 cells/mm² in animals on the “standard” rodent diet (means ± SD, N = 7 animals per group, p < 0.01). Animals on the nonsupplemented diet showed a dramatic loss of capillary perfusion density until 7 days after reperfusion (to 21 ± 13% of preischemic baseline values), whereas this loss was significantly attenuated (to 71 ± 12% of preischemic values, p < 0.01) in animals on the “standard” rodent diet. No difference in the extent of reperfusion injury was seen between animals on the “standard” rodent diet and animals on diets with substantially higher vitamin E supplements (300 ppm–30.000 ppm). Besides underscoring the benefit of vitamin E in reducing the extent of ischemia/reperfusion injury, this study raises the concern that vitamin E supplements in “standard” laboratory animal diets may have a far-reaching impact on biomedical research by jeopardizing established animal models of disease.     

Autoantibodies against oxidized LDL are associated with severe chest pain attacks in patients with coronary heart disease

Autoantibodies against oxidized low-density lipoprotein (oxLDL) predict the progression of atherosclerosis. Several studies have shown that oxLDL is present in atherosclerotic lesions and that several factors present in active atherosclerotic plaques can oxidatively modify LDL. Oxidation of LDL induces production of autoantibodies against oxLDL (oxLDLab) that can be measured using an EIA test. Our aim was to see whether oxLDLab are associated with severe chest pain attacks in coronary heart disease (CHD) patients. Patients having two- or three-vessel CHD, as assessed by coronary angiography, and their siblings were recruited into the study (n = 568, mean age 55.8 years, range 29.3–83.2 years). Nondiabetic patients having a history of severe chest pain attacks had significantly higher oxLDLab levels (0.611 ± 0.56) than those who did not have a history of severe chest pain attacks (0.487 ± 0.40) (p = 0.027), even though age, cholesterol level, body mass index, and blood pressure were similar in both groups. However, no difference was found in oxLDLab levels in diabetic patients with or without a history of severe chest pain attacks. Increased levels of oxLDL autoantibodies are associated with severe chest pain attacks in nondiabetic patients with CHD.     

Reproductive phase dependent circadian variations of plasma melatonin, testosterone, thyroxine and corticosterone in Indian palm squirrel, Funambulus pennanti

To explain the complex mechanism of environmental influence along with internal hormonal (factors) milieu on daily variations in the circulating levels of melatonin, testosterone, thyroxine and corticosterone were analyzed with the help of inferential statistics (Cosinor rhythmometry) in a seasonally breeding tropical rodent, F. pennanti during the reproductively active (RAP) and inactive phases (RIP). Plasma melatonin, thyroxine and corticosterone levels exhibited a significant circadian oscillation during both the active and inactive phases of the annual reproductive cycle. Melatonin showed higher amplitude during RIP in the circulating plasma. Testosterone presented a peak level during evening hours (16:00 - 18:00 h) during RAP only. The phase of thyroxine was noted ∼09:76 h and ∼10.35 h during active and inactive phases, respectively. Corticosterone showed a peak level at ∼12.00 h during both phases of the reproductive cycle. Further, in this tropical rodent, the minimum difference in photoperiod (∼3 - 4 hours) and maximum variation in temperature (max. 18°C - min. 10°C during RIP and max. 45°C - min. 32°C during RAP) and humidity (85% during RIP and 35% during RAP) regulated the diurnal rhythm of circulating melatonin circadian rhythm by ∼1 hour phase advance during RIP. In conclusion, the studied hormonal rhythms may be part of an integrative system to coordinate reproduction and physiological processes successfully with environmental factors.     

Effects of oven- or freeze-drying on chemical composition and NIR spectra of pasture silage

In order to assess effects of drying method on chemical composition and NIR spectra of pasture silage, 20 samples of silages from permanent pastures of different qualities were subsampled and dried either by forced draught oven at 65°C or freeze-dried. Samples were analysed for crude protein (CP), crude fibre (CF), neutral detergent fibre (NDF), acid detergent fibre (ADF), gross energy (GE) and in vitro digestible organic matter in the dry matter (DOMD) and composition expressed on a dry-matter (DM) basis, either obtained as oven 105°C DM (DM_105°) or toluene DM (DM_tol). Effects of the drying method on chemical composition were estimated by paired comparisons. Near-infrared reflectance (NIR) spectra were taken and the difference spectra between treatments for each sample were plotted in order to visually inspect effects of treatments, either as log 1/R or transformed by their first derivative. Principal components explaining spectral variability were computed and samples graphically displayed according to the eigenvalues of the first (1 and 2), or second (2 and 3) pairs of principal components. Oven-drying resulted in a reduction in CP (p<0.02) content and an increase in CF (p<0.1), NDF (p<0.001) and ADF (p<0.06) content of silages, when expressed on a DM_105° basis. When expressed on a DM_tol basis, a reduction in CP (p<0.02) and DOMD (p<0.06) content was observed with oven drying, but fibre fractions were not affected (p>0.1). Effects of the drying treatment were visually apparent on NIR spectra when plotted as log 1/R against wavelengths, mainly as a baseline shift. Difference spectra (OD − FD), both as log 1/R and its first derivative, showed consistent absorption bands, indicative of different molecular responses of OD and FD silages to incident light. Plotting samples according to eigenvalues of the first two or second two principal components suggests that drying methods affect the distribution of samples. This is also indicative of an effect of drying treatment on spectral features and reinforces the general advice that sample processing should be consistent in order to avoid adding errors to NIR analysis.     

Clara cell protein (CC16) in serum and bronchoalveolar lavage fluid of subjects exposed to asbestos

The Clara cell protein (CC16) is a small and readily diffusible protein of 16kDa secreted by bronchiolar Clara cells in the distal airspaces. These epithelial cells are altered in several pulmonary pathological processes induced by various lung toxicants. In the search for a new biomarker of asbestos-induced lung impairment, we used a sensitive immunoassay to determine the levels of CC16 in bronchoalveolar fluid (BALF) and serum of subjects exposed to asbestos compared with a group of healthy controls. In the BALF of asbestos-exposed subjects there was an insignificant trend towards CC16 elevation compared with controls, with a (mean ±SD of 0.81 ±0.65mg l^-1 for asbestos-exposed subjects (n = 23) versus 0.39 ±0.19mg l^-1 for controls (n = 11) (p = 0.09). In serum, CC16 concentration was significantly increased among asbestos-exposed subjects, with values of 27.2 ±24.0 µg l^-1 for asbestos-exposed subjects (n = 34) versus 16.1 ±7.6 µg l^-1 for controls (n = 34) (p = 0.01). Regarding the effects of smoking, there were significant differences between generally lower CC16 levels in serum and BALF (p = 0.05 and 0.001, respectively) of smokers compared with the higher levels in non-smokers. Serum CC16 levels positively correlated with those in BALF, which is consistent with a diffusional transfer of CC16 from the bronchoalveolar space into the serum. No association, however, emerged between the levels of CC16 in serum or BALF and either the duration of asbestos exposure or the severity of the lung impairment as assessed by chest X-ray. These findings suggest that exposure to asbestos elicits early changes in the local and, importantly, also the systemic levels of CC16. This pneumoprotein therefore appears as a promising non-invasive biomarker of asbestos-induced lung injury and occupational disease in both smoking and non-smoking exposed subjects.     

24-hour, weekly, and annual patterns in traumatic and non-traumatic surgical pediatric emergencies

24 h patterns with high frequency components in the incidence of pediatric trauma were validated and quantified in one of our earlier studies. Herein, we further explored the temporal—high frequency, 24 h, weekly (7 d), hemi-weekly (3.5 d), and annual - patterns in traumatic (1990-1997; n=15,110 events) and non-traumatic pediatric surgical emergencies (PSE) (1992-2001; n=5,593 events) as well as automobile accidents (AA) (1990-1997; n=67,712) in the County of Vaud, Switzerland. The latter served as a reference system of human adult activity and risk. Two-way ANOVA, χ2, correlation, and cosinor analyses were used as statistical tools. A 24 h pattern, reproducible from year to year, was validated in traumatic and non-traumatic PSE and AA. The 24 h patterns were not correlated and differed from one another in terms of their acrophase (peak time) and amplitude. A gender-related difference was found only in the non-traumatic time series for weekly (7 d) and hemi-weekly (3.5 d) patterns. The latter were detected in boys but not girls. No statistically significant difference was found in the acrophase and amplitude between boys and girls in the temporal patterns of other periods. An annual pattern was validated in automobile accidents (acrophase: 4th of September ±37 d (SD)) and pediatric trauma (acrophase: 14th of June ±10 d), but not in non-traumatic PSE. These results suggest that environmental modulations differ between the incidence of traumatic and non-traumatic PSE. Presumably, the two phenomena involve different aspects of the temporal organization and/or different levels of susceptibility of a set of biological rhythms to environmental factors.     

Expression of angiotensin type 1 and 2 receptors in brain after transient middle cerebral artery occlusion in rats

Angiotensin II (Ang II) type 2 receptors (AT2Rs) have been associated with apoptosis. We hypothesized that AT2Rs are increased in stroke and may contribute effects of stroke to the brain. To test this, we have examined the expression of Ang II type 1 receptor (AT1R), AT2R and Ang II levels in the brain 24 h after transient middle cerebral artery occlusion (MCAO). The densities of AT1R and AT2R were measured by quantitative autoradiography (n=6). The levels of Ang II were measured by radioimmunoassay (RIA) (n=6) and by immunohistochemistry (n=3). AT1R levels on autoradiography showed a significant decrease (0.87±0.06 to 1.39±0.07 fmol/mg, p<0.01) in the ventral cortex of the stroke side compared to the cortices of non-stroke (NS) rats (n=4). There was no significant difference on ATIR in the contralateral verbal cortex of the stroke rats compared to NS control. In contrast, levels of AT2R in the ventral cortex of both the stroke and the contralateral sides were significantly increased (0.77±0.06, p<0.05 and 0.91±0.05, p<0.01 compared to 0.60±0.03 fmol/mg tissue, respectively). RIA showed that Ang II in the ventral cortex of both the stroke and the contralateral sides were significantly increased (241.63±47.72, p<0.01 and 165.51±42.59, p<0.05 compared to 76.80±4.10 pg/g tissue, respectively). Also, Ang II in the hypothalamus was significantly increased (179.50±17.49 to 118.50±6.65 pg/g tissue, p<0.05). Immunohistochemistry confirmed the increase of Ang II. These results demonstrate that brain Ang II and AT2Rs are increased whereas AT1Rs are decreased after transient MCAO in rats. We conclude that in stroke, Ang II and AT2R are activated and may contribute neural effects to brain ischemia.     

Seasonality on Mood and Length of Menstrual Cycle in Tropical Young Women

In order to know whether seasonal variations affect mood and the length of the menstrual cycle in tropical young women, we have conducted a survey with 200 female students in Hanoi, Vietnam. We used the Vietnamese-translated Self-rating Depression Scale (SDS) for the measurements of their mood. Each of them was given a calendar (from September, 1999 to August, 2000) and was instructed to circle the first day of their menstruation, each month. The results showed that there existed a high prevalence of summer Seasonal Affective Disorder (SAD) and that the length of the menstrual cycle was affected by seasonal change. The average lengths of menstrual cycles were 30.7 ± 0.3 days (mean ± SEM) which is longer than in American young women. The higher occurrence of summer SAD seems to be related to the high ambient temperature during summer in the tropics, influencing their mood.     

Daily rhythms of nonshivering thermogenesis in common spiny mice Acomys cahirinus under short and long photoperiods

Daily rhythms of nonshivering thermogenesis NST were studied in common spiny mice Acomys cahirinus, acclimated to different photoperiod regimes (16L:8D and 8L:16D) at a constant ambient temperature of 26°C. Noradrenaline NA (1.5 mg/kg subcutaneous) was injected at: 06:00, 12:00, 18:00 and 24:00 h (±15 min). NST was measured as the ratio between the maximal oxygen consumption (VO₂) as response to NA — VO₂NA and VO₂ measured at 26°C — VO_{2 min}. Rectal temperatures T_bNA and T_{b min} respectively were recorded at the end of VO₂ measurements. Significant variations in T_{b min}, T_bNA, and NST were revealed, under the two different photoperiod regimes. Significant differences in VO_{2 min}, NST, T_{b min} and T_bNA were also recorded within each photoperiod acclimation group. These results suggest that daily and photoperiod depended variations in the brown adipose tissue activity, presumably emerge from amount of unoccupied receptors or changes in the receptors affinity to NA.