Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.     

Ultradian rhythms in waking behavior of rhesus monkeys

The behavior of seven individually housed adult male rhesus monkeys was recorded by time-lapse video, 10 hr per day, for up to 5 days. Recordings were analyzed in 50 sec intervals for the presence or absence of 5 behavior, viz., ingestion, locomotion, exploration, self-grooming, and resting. Analyses were based on the number of 50 sec intervals per 5 min epoch in which each of these behaviors occurred. Variance spectra were computed on each behavior for each animal, and the significance of a prospectively predicted behavioral cyclicity in the frequency band of 12–18 cycles/day was explored with t tests for the group of monkeys. All 5 behaviors exhibited a statistically significant spectral peak as predicted. Significant cross-spectral relationships were found reflecting temporal relationships between ingestion, locomotion, exploration, and resting. The first 3 were in phase with one another and out-of-phase (reciprocal) with resting. Locomotion tended to precede exploration, and exploration to precede ingestion. These results suggest that the 12–24 cycles/day orality rhythm described earlier in monkeys is not discrete, but is one component of a more general 12–18 cycles/day behavioral cycle involving locomotion, exploration, and rest as well. Self-grooming, while perhaps cyclic, was not significantly related to the orality-locomotion-exploration complex.     

Gender differences in the circadian temperature rhythms of healthy elderly subjects: relationships to sleep quality

Body core temperature and subjective sleep quality were measured in 22 healthy elderly men and women while they lived at home and continued their normal daily activities. The acrophase of body temperature was phase-advanced by an average of 1.25 h in the older women compared to the age-matched men. Habitual bedtimes did not differ between men and women, but usual wakeup time and average sleep duration did: women awakened earlier and slept for shorter durations. Women were also less satisfied with their sleep than were the men. For the group, the acrophase of body temperature was significantly positively correlated with habitual bedtime and wakeup time. These data support the notion that age-related changes in the circadian timing system are, in large part, gender-dependent. The findings are also consistent with the hypothesis that alterations in sleep timing and quality that typically accompany aging are closely tied to age-related changes in circadian physiology.     

Long-term follow-up of periodic limb movements in sleep in older adults

STUDY OBJECTIVES: The goal of this study was to examine the natural history of periodic limb movements in sleep (PLMS) in older adults. DESIGN: Prospective, longitudinal design. SETTING: San Diego area. PARTICIPANTS: Community-dwelling older adults. INTERVENTIONS: NA MEASUREMENTS AND RESULTS: Subjects participated in follow-up visits every few years. Sleep disorders were assessed at each visit using sleep questionnaires and overnight sleep recordings. Changes in PLMS over time were examined as well as variables that were associated with change. Average PLMS did not change over time, although there was considerable variability within the sample. In women, changes in PLMS were associated with changes in sleep-disordered breathing. This relationship was not found in men. CONCLUSIONS: Although the prevalence of PLMS is high for older adults, the severity of the disorder does not progressively worsen with increasing age.     

Periodic limb movements in sleep in community-dwelling elderly.

The prevalence of periodic limb movements in sleep (PLMS) in a randomly selected elderly sample is reported. In San Diego, 427 elderly volunteers aged 65 yr and over were recorded in their homes. Forty-five percent had a myoclonus index, MI greater than or equal to 5. Correlates of PLMS included dissatisfaction with sleep, sleeping alone and reported kicking at night. Although statistically significant, the strengths of the associations between interview variables and myoclonus indices were all small. No combination of demographic variables and symptoms allowed highly reliable prediction of PLMS.     

A critical role for Fas ligand in the active suppression of systemic immune responses by ultraviolet radiation

Induction of antigen-specific suppression elicited by environmental insults, such as ultraviolet (UV)-B radiation in sunlight, can inhibit an effective immune response in vivo and may contribute to the outgrowth of UV-induced skin cancer. Although UV-induced DNA damage is known to be an initiating event in the immune suppression of most antigen responses, the underlying mechanism(s) of such suppression remain undefined. In this report, we document that Fas ligand (FasL) is critical for UV-induced systemic immune suppression. Normal mice acutely exposed to UV exhibit a profound suppression of both contact hypersensitivity and delayed type hypersensitivity (DTH) reactions and the development of transferable antigen-specific suppressor cells. FasL-deficient mice exposed to UV lack both transferable suppressor cell activity and primary suppression to all antigens tested, with the exception of the DTH response to allogeneic spleen cells. Interestingly, suppression of this response is also known to occur independently of UV-induced DNA damage. Delivery of alloantigen as protein, rather than intact cells, restored the requirement for FasL in UV-induced immune suppression of this response. These results substantiate that FasL/Fas interactions are essential for systemic UV-induced suppression of immune responses that involve host antigen presentation and suggest an interrelationship between UV-induced DNA damage and FasL in this phenomenon. Collectively, our results suggest a model whereby UV-induced DNA damage disarms the immune system in a manner similar to that observed in immunologically privileged sites.     

p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas.

PURPOSE: The purpose is to investigate whether aggressive basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ from nonaggressive BCC and SCC with respect to the p53 mutation spectrum and whether specific mutations can serve as prognostic indicators of tumor aggressiveness. EXPERIMENTAL DESIGN: We analyzed 342 tissues from patients with aggressive and nonaggressive BCCs and SCCs for p53 mutations by single-strand conformation polymorphism and nucleotide sequencing. RESULTS: p53 mutations were detected in 33 of 50 aggressive BCCs (66%), 37 of 98 nonaggressive BCCs (38%), 28 of 80 aggressive SCCs (35%), 28 of 56 nonaggressive SCCs (50%), and 3 of 29 samples of sun-exposed skin (10%). About 71% of the p53 mutations detected in aggressive and nonaggressive BCCs and SCCs were UV signature mutations. The frequency of CC to TT mutations in aggressive (36%) and nonaggressive SCCs (39%) was 2-fold higher than in aggressive (18%) and nonaggressive (14%) BCCs. In contrast, aggressive BCCs had a higher frequency (24%) of transversions than nonaggressive BCCs (8%) and aggressive (14%) and nonaggressive (11%) SCCs did. CONCLUSIONS: Our results indicate that UV radiation is responsible for the induction of p53 mutations and perhaps for the initiation of both aggressive and nonaggressive BCCs and SCCs. Although some differences in p53 mutation frequency, types of mutation, and hot spots were seen between aggressive and nonaggressive BCCs and SCCs, these factors do not constitute as clear-cut diagnostic or prognostic indicators of tumor aggressiveness. Tumor aggressiveness may be attributable to other genetic changes or events that occur during tumor progression.