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Selected AbstractsInterferon-,-dependent inhibition of late allergic airway responses and eosinophilia by CD8+,, T cellsIMMUNOLOGY, Issue 2 2007Susumu Isogai Summary We have previously shown that CD8+,, T cells decrease late allergic airway responses, airway eosinophilia, T helper 2 cytokine expression and increase interferon-, (IFN-,) expression. We hypothesized that the effects of CD8+,, T cells were IFN-, mediated. Brown Norway rats were sensitized to ovalbumin on day 1. Cervical lymph node CD8+,, T cells from sensitized animals were treated with antisense oligodeoxynucleotide (5 µmol/l) to inhibit IFN-, synthesis or control oligodeoxynucleotide and 3·5 × 104 CD8+,, T cells were injected intraperitoneally into sensitized recipients on day 13. Rats were challenged with aerosolized ovalbumin on day 15 and lung resistance was monitored over an 8 hr period, after which bronchoalveolar lavage was performed. Control oligodeoxynucleotide treated ,, T cells decreased late airway responses and eosinophilia in bronchoalveolar lavage. There was a complete recovery of late airway responses and a partial recovery of airway eosinophilia in recipients of antisense oligodeoxynucleotide treated cells. Macrophage ingestion of eosinophils was frequent in rats administered ,,T cells but reduced in recipients of antisense oligodeoxynucleotide treated cells. These results indicate that CD8+,, T cells inhibit late airway responses and airway eosinophilia through the secretion of IFN-,. Defective or altered ,, T-cell function may account for some forms of allergic asthma. [source] Melatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in ratsJOURNAL OF PINEAL RESEARCH, Issue 3 2006Göksel Abstract:, Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12-hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU. [source] Daily variation in the concentration of 5-methoxytryptophol and melatonin in the duck pineal gland and plasmaJOURNAL OF PINEAL RESEARCH, Issue 4 2002Jolanta B. Zawilska The duck pineal gland rhythmically produces two 5-methoxyindole compounds, i.e. 5-methoxytryptophol and melatonin. 5-Methoxytryptophol levels are low at night and high during the day, while melatonin concentrations are high at night and low during the day. The melatonin rhythm reflects oscillations in the activity of serotonin N -acetyltransferase (AA-NAT; a penultimate and key regulatory enzyme in the melatonin biosynthetic pathway). The activity of hydroxyindole- O -methyltransferase (HIOMT; an enzyme involved in the synthesis of both 5-methoxytryptophol and melatonin) does not exhibit any significant rhythmic changes throughout the 24-hr period. Plasma levels of melatonin exhibited daily changes that were parallel to fluctuations in pineal melatonin content. Although plasma concentrations of 5-methoxytryptophol were low in ducks, they showed daily variations. The mean 5-methoxytryptophol concentration between zeitgeber time 9 (ZT9) and ZT15 was 2.4-times higher than the mean value for samples collected between ZT18 and ZT3. These findings indicate that in the duck the pineal production of 5-methoxytryptophol and melatonin may be inversely correlated. [source] Melatonin disrupts circadian rhythms of glutamate and GABA in the neostriatum of the awake rat: a microdialysis studyJOURNAL OF PINEAL RESEARCH, Issue 4 2000B. Marquez de Prado The purpose of this study was to investigate possible circadian changes in extracellular concentrations of glutamate (GLU) and ,-aminobutyric acid (GABA), and the influence of melatonin on the levels of these neurotransmitters in the neostriatum of awake rats using in vivo microdialysis. At the same time, the concentrations of the amino acids taurine (TAU), glutamine (GLN) and arginine (ARG), as well as dopamine (DA) and its metabolites 3, 4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA), were measured in the extracellular fluid. When dialysates were collected over a 24-hr period (6 hr dark, 12 hr light, 6 hr dark), both GLU and GABA, without the infusion of melatonin, exhibited statistically significant rhythms, with higher levels of these constituents during the dark and lower levels during the day. Perfusion with melatonin (for 19 consecutive hours) prevented the daytime reductions in both GLU and GABA. Of the amino acids measured in the dialysates collected from the neostriatum of non-perfused rats, only ARG exhibited a significant change during the light:dark cycle; again, lowest concentrations were measured during the day. While melatonin perfusion did not statistically significantly influence neostriatal levels of TAU and ARG, GLN levels continued to drop during the infusion of the indoleamine. Dialysate concentrations of DA, DOPAC and HVA exhibited circadian rhythms which were not influenced by melatonin perfusion. The findings indicate there are differential effects of melatonin on extracellular neurotransmitter concentrations in the neostriatum of the awake rat. The results also suggest that the day:night variations in GLU and GABA may relate to daily changes in endogenous melatonin production, while DA and its metabolites are minimally influenced by this secretory product. [source] Alcohol Deprivation Effect Is Prolonged in the Alcohol Preferring (P) Rat After Repeated DeprivationsALCOHOLISM, Issue 1 2000Zachary A. Rodd-Henricks Background: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of ethanol/total fluid intake and the voluntary intake of ethanol solutions over baseline drinking conditions when ethanol access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. The current study examined the effects of initial deprivation length and number of deprivation exposures on the ADE in alcohol-preferring (P) rats. Methods: Adult female P rats received 24-hr free-choice access to 10% (v/v) ethanol and water for 6 weeks. Rats were then randomly assigned to five groups deprived of ethanol for O (control), 2, 4, 6, or 8 weeks (W). All deprived groups were then given 24-hr access to ethanol for 2 weeks before bbeing deprived of ethanol for another 2 weeks. Results: After the initial ethanol deprivation period, the deprived groups displayed a similar 2-fold ADE (e.g., 4-W group; 4.6 ± 0.5 for baseline vs. 10.5 ± 0.3 g/kg/day for the 1st reinstatement day) during the initial 24-hr period. Ethanol consumption began to return to control levels 48 (7.1 ± 0.4 g/kg/day) and 72 (6.4 ± 0.4 g/kg/day) hrs later. In addition, each deprived group showed increases in the ratio of ethanol/total fluid intake upon reinstatement, and there was a tendency for sustained higher ethanol intake ratlos during the first 3 postexposure days for the 4-, 6-, and 8-W grups, but only during the first 2 reinstatement days for the 2-W group. The second deprivation did not increase the magnitude of the ADE over that observed in the first deprivation during the initial 24-hr period of re-exposure, but it did prolong the duration of the ADE into the 2nd and 3rd reinstatement day for the 2-, 4-, and 6-W groups and into the 5th reinstatement day for the 8-W group. Conclusions: Equivalent robust ADEs can be seen in P rats with deprivation periods of 2,8 W, which suggests that the ADE has a rapid onset and is not affected by the durations of deprivation that were tested. The duration of the ADE was prolonged in P rats exposed to a second deprivation period, suggesting that factors associated with the ADE phenomenon could be strengthened by repated deprivations. [source] Methodological issues related to exhaled nitric oxide measurement in children aged four to six yearsPEDIATRIC PULMONOLOGY, Issue 2 2005Edward Napier MBBS Abstract This study was designed to test five methodological issues related to measurement of fractional exhaled nitric oxide (FENO) in children aged 4,6 years using commercially available apparatus. Participants attended two randomly selected schools. A respiratory questionnaire was completed. Measurements of FENO were made on successive days, using a NIOX® analyzer employing standard or modified methodologies. Ninety-one children participated in the study (mean age, 5.3 years; 46 boys). Using a standard methodology (n,=,61), FENO was successfully measured in 28 (46%) children, 1/12 aged 4 years, 12/25 aged 5 years, and 15/24 aged 6 years (trend test P,=,0.01). On the first assessment, FENO could be determined in more boys than girls (64% vs. 30%, respectively, P,=,0.008), but this gender difference was not apparent on the second assessment. Exhaled NO was reproducible over a 24-hr period; the mean difference between repeated measurements of natural log (ln) FENO was 0.016 parts per billion (ppb) (95% confidence limits, ,0.479, 0.511), n,=,20. Data from 35 assessments showed that values of FENO did not alter over nine individual, successive measurements. Use of a modified methodology in 30 children increased success in obtaining FENO, but these values were unreliable. In conclusion, measurements of FENO can be obtained in the majority of 5- and 6-year-old but not 4-year-old children. Exhaled NO measurements were reproducible over a 24-hr interval, and did not change over up to nine expiratory maneuvers in these young children. Pediatr Pulmonol. 2005; 40:97,104. © 2005 Wiley-Liss, Inc. [source] Daily computer usage correlated with undergraduate students' musculoskeletal symptoms,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 6 2007Che-hsu (Joe) Chang PT Abstract Background A pilot prospective study was performed to examine the relationships between daily computer usage time and musculoskeletal symptoms on undergraduate students. Methods For three separate 1-week study periods distributed over a semester, 27 students reported body part-specific musculoskeletal symptoms three to five times daily. Daily computer usage time for the 24-hr period preceding each symptom report was calculated from computer input device activities measured directly by software loaded on each participant's primary computer. General Estimating Equation models tested the relationships between daily computer usage and symptom reporting. Results Daily computer usage longer than 3 hr was significantly associated with an odds ratio 1.50 (1.01,2.25) of reporting symptoms. Odds of reporting symptoms also increased with quartiles of daily exposure. Conclusions These data suggest a potential dose,response relationship between daily computer usage time and musculoskeletal symptoms. Am. J. Ind. Med. 50:481,488, 2007. © 2007 Wiley-Liss, Inc. [source] Intra-community coalitionary lethal attack of an adult male southern muriqui (Brachyteles arachnoides)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 10 2009M.G. Talebi Abstract We report on the first evidence of intra-community coalitionary lethal aggression in muriquis (Brachyteles). The event occurred in southern muriquis (Brachyteles arachnoides) during a long-term study (>15 years) of two social groups inhabiting mostly pristine Atlantic forest habitat in the Parque Estadual Carlos Botelho, southern Sćo Paulo State, Brazil. The attack took place deep in the core area of the Group Caetź home range. Tense agonistic behaviors and vocalizations preceded the lethal coalitionary attack, and the tension increased over a 36,48,hr period. One adult female and two unidentified individuals also took part in a coalition led by six adult males. The members of the coalition collectively approached, embraced, immobilized and repeatedly bit the entire body of an adult male, resulting in severe bleeding injuries and the victim's death in less than 1,hr after the attack commenced. Combined ecological, behavioral and spatial data related to the event indicate that this was an intra-community attack and suggest social tensions related to mating competition as the proximate trigger of the coalitionary killing. The attack resembled those reported for chimpanzees, with clear numeric superiority and a low risk of injury to aggressors, resulting in the death of a lone conspecific victim. This observation (n=1) is suggestive of a capacity for escalated aggression in muriquis and reinforces arguments for the potential adaptive significance of intra-community aggression in male philopatric societies, as reported for spider monkeys and chimpanzees. These characteristics challenge the view of the muriquis as a peaceful primate and support the general hypothesis that imbalances of power contribute to intra-specific killing in primates, such as chimpanzees and humans. Am. J. Primatol. 71:860,867, 2009. © 2009 Wiley-Liss, Inc. [source] Mothers' maximum drinks ever consumed in 24 hours predicts mental health problems in adolescent offspringTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 9 2010Stephen M. Malone Background:, The maximum number of alcoholic drinks consumed in a single 24-hr period is an alcoholism-related phenotype with both face and empirical validity. It has been associated with severity of withdrawal symptoms and sensitivity to alcohol, genes implicated in alcohol metabolism, and amplitude of a measure of brain activity associated with externalizing disorders in general. In a previous study we found that the maximum number of drinks fathers had ever consumed in 24 hrs was associated with externalizing behaviors and disorders in preadolescent and adolescent children. The purpose of the present study was to determine whether maternal maximum consumption has similar correlates. Method:, We examined associations between maternal maximum consumption and alcohol dependence, respectively, and disruptive disorders and substance-related problems in two large independent population-based cohorts of 17-year-old adolescents. Results:, Maximum consumption was associated with conduct disorder, disruptive disorders in general, early substance use and misuse, and substance disorders in adolescent children regardless of sex. Associations were consistent across cohorts, providing internal replication. They also paralleled our previous findings regarding paternal status. They could not be explained by maternal alcohol dependence, effects of drinking during pregnancy, or paternal maximum consumption. They were not simple artifacts of the fact that maximum consumption is a continuous measure while alcohol dependence is dichotomous. Conclusions:, Despite deriving from a single question about lifetime behavior, parental maximum consumption appears to reflect vulnerability for mental health problems, especially substance-related ones, more directly than a diagnosis of alcohol dependence. [source] Pharmacokinetics, biodistribution, and antitumor efficacy of a human glandular kallikrein 2 (hK2)-activated thapsigargin prodrugTHE PROSTATE, Issue 4 2006Samuel Janssen Abstract BACKGROUND Prostate cancer cells secrete unique proteases such as prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) that represent targets for the activation of prodrugs as systemic treatment of metastatic prostate cancer. Previously, a combinatorial peptide library was screened to identify a highly active peptide substrate for hK2. The peptide was coupled to an analog of the potent cytotoxin thapsigargin, L12ADT, to generate an hK2-activated prodrug that was efficiently hydrolyzed by purified hK2, stable to hydrolysis in human and mouse plasma in vitro and selectively toxic to hK2 producing prostate cancer cells in vitro. METHODS In the current study, toxicology, pharmacokinetics, prodrug biodistribution, and antitumor efficacy studies were performed to evaluate the hK2-activated prodrug in vivo. RESULTS The single intravenous maximally tolerated dose of prodrug was 6 mg/kg (i.e., 3.67 µmole/kg) which produced peak serum concentration of ,36 µM and had a half-life of ,40 min. In addition, over a 24 hr period <0.5% of free L12ADT analog was observed in plasma. The prodrug demonstrated significant antitumor effect in vivo while it was being administered, but prolonged intravenous administration was not possible due to local toxicity to tail veins. Subcutaneous administration of equimolar doses produced lower plasma AUC compared to intravenous dosing but equivalent intratumoral levels of prodrug following multiple doses. CONCLUSIONS The hK2-activated prodrug was stable in vivo. The prodrug, however, was rapidly cleared and difficult to administer over prolonged dosing interval. Additional studies are underway to assess antitumor efficacy with prolonged administration of higher subcutaneous doses of prodrug. Second-generation hK2-activated thapsigargin prodrugs with increased half-lives and improved formulations are also under development. © 2005 Wiley-Liss, Inc. [source] The sleep of co-sleeping infants when they are not co-sleeping: Evidence that co-sleeping is stressfulDEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2002Melissa Hunsley Abstract Co-sleeping proponents consider the practice to be "natural" and a potential protection against sudden infant death syndrome (SIDS); others consider the practice of an infant sleeping in the parents' bed for prolonged periods at night to place an infant at risk for harm or death. For this study, co-sleeping was investigated from a different perspective, that is, as a significant early experience to investigate as it may have implications for the infant's development. The sleep of 101 normal, full-term infants was recorded nonintrusively in the home for 24 hr periods when they were 5 weeks and 6 months old. Infants were assigned to three groups: short-term co-sleepers, long-term co-sleepers, and non-co-sleepers. Their sleep states and wakefulness were compared at the two ages and over age. At 5 weeks and 6 months, the long-term co-sleeping infants differed significantly from the non-co-sleepers on a number of measures: At 5 weeks, they showed more quiet sleep and longer bouts of quiet sleep; and at 6 months, they also showed less active sleep, fewer arousals in active sleep, and less wakefulness. Each of these differences indicates a markedly lower arousal level in the long-term co-sleeping infants. This sleep pattern has been repeatedly found to be an indicator of stress. We infer that a major source of stress for these infants is the experience of sleep disturbance documented for infants when they were co-sleeping. Based on extensive evidence for long-term effects of early stress, we conclude that co-sleeping should have significant implications for infants' neurobehavioral development. © 2002 John Wiley & Sons, Inc. Dev Psychobiol 40: 14,22, 2002 [source] | |||||||||||||