望江南总蒽醌苷抗肿瘤作用的研究

探讨望江南总蒽醌苷(CSAG)的抗肿瘤作用及其作用机制.利用MTT法检测望江南总蒽醌苷对肝癌细胞HepS、肺癌细胞(A549)、小鼠肉瘤(S180)腹水型肿瘤细胞等肿瘤细胞和人正常肝细胞L-02增殖的影响;实体瘤称重法测定CSAG对肝癌(HepS)实体瘤的抑制情况,将接种肿瘤的小鼠分成5组,每组6只小鼠,雌雄各半,给药12 d,停药后24 h处死动物,秤鼠体重,剥离出肿瘤,秤瘤重,测定生化指标.结果显示,CSAG对以上肿瘤细胞的增殖均有抑制作用,对肝癌细胞荷瘤小鼠肿瘤生长具有明显的抑制作用;同时可增加胸腺指数和脾指数.因此,CSAG具有明显的抗肿瘤效果,其抗肿瘤作用可能与提高机体免疫力和诱导细胞凋亡有关.     

Can Marmoset Mothers Count to Three? Effect of Litter Size on Mother–Infant Interactions

Harper (Parental Care in Mammals, Plenum Press, New York, 1981, p. 158) proposed that ‘there may be lower and upper limits for frequency or intensity of offspring stimulation that, on average, serve as reliable boundaries, below or above which it would be uneconomical to invest at all or at current levels.‘ This proposition was tested in captive common marmosets by comparing the responses of marmoset mothers exposed to differing number of infants. Fifteen common marmoset (Callithrix jacchus) litters (seven twin and eight triplet litters) from 11 different dams were observed for 6–12, 30‐min sessions over days 1–4 following birth. Mothers nursed smaller infants less frequently (F = 4.208, df = 1, 22; p = 0.052) regardless of litter size. The percent time mothers spent transporting (nursing and carrying) each infant was less for triplets than twins (F = 11.785, df = 1, 12; p = 0.005). Average transport bout length was significantly shorter for smaller infants (F = 7.566, df = 1, 22; p = 0.012) and was half as long for triplet infants as for twins (F = 10.733, df = 1, 7; p = 0.013). Twice as many transport bouts for triplets included maternal harassment of infants, than for twins (F = 42.742, df = 1, 24; p = 0.0001). Infant‐initiated transfers to the mother were more common for triplets than for twins (Mann–Whitney U = 79.50, p = 0.006). The overall maternal carrying score (% carry × number of infants carried) was lower for triplet litters than for twin litters (F = 15.38, df = 1, 3; p = 0.029); i.e. mothers of triplets did not, overall, invest in more carrying and nursing than did mothers of twins but instead invested less. These findings suggest that, as opposed to the strong attraction to infants that is common for many primates, the marmoset mother's tolerance for carrying infants does not increase with increasing infant stimuli present; rather, marmoset mothers will only tolerate a limited amount of time transporting and nursing infants, regardless of litter size. This limited tolerance may be due to the species’ small body size and anti‐predator strategies (e.g. concealment) that make infant care incompatible with other essential activities, such as foraging.     

Intraruminal Fluid Administration to Goats: Effects of Handling and Fluid Temperature

Physiological stress response to intraruminal fluid administration was studied in 5 female goats. The fluid was given through a stomach tube. The water was cold (10°C) or warm (38°C) and in an amount of 7.5-10% of body weight. Plasma concentrations of adrenaline, noradrenaline and Cortisol increased significantly after both treatments. Adrenaline and noradrenaline responses were greater and more longlasting after cold water administration, but there was no difference in Cortisol response between cold and warm water. Haematocrit and plasma protein concentrations increased also and the effects of cold water lasted longer. Blood pressure showed a sharp rise of short duration and was independent of water temperature. The immediate tachycardie response was similar with both treatments, but cold water caused an additional peak 15 min later. The cooling did not increase plasma histamine level. The results suggest that stomach intubation and administration of water into the rumen leads to strong activation of hormonal and cardiovascular stress parameters even in goats well adapted to handling. Low temperature of the fluid further heightens the effect. Warming of fluids to near body temperature before their administration is thus recommended.     

Effects of Acute Lorazepam Administration on Aminergic Activity in Normal Elderly Subjects: Relationship to Performance Effects and Apolipoprotein Genotype

The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.     

Traditional Living Habits of the Taz Tundra Population: A Paleoparasitological Study

An excavation of the Vesakoyakha II–IV and Nyamboyto I burial grounds was conducted during the 2014 field season, and soil samples from intact burials dating from the 19th and 20th centuries, respectively, were analyzed to determine interactions between parasites and host/vectors. Considering the discovery of Diphyllobothrium sp. and Taenia sp. eggs in soil samples from the pelvic region, diphyllobothriasis was the most frequent helminthic infection among the Taz Nenets. The Nyamboyto Nenets mainly consumed uncooked fish, while the Vesakoyakha Nenets had a bigger variety in food choices, including reindeer meat. Nenets children were given raw fish from early childhood. The paleoparasitological results corroborate rare ethnographic records about the consumption of uncooked reindeer cerebrum which led to beef tapeworm helminthiases. This is the first parasitological report of helminthic diseases among the Taz Nenets, and, as such, it provides insight into their subsistence activities and food patterns and broadens our understanding of their health condition.     

Administration of Thimerosal to Infant Rats Increases Overflow of Glutamate and Aspartate in the Prefrontal Cortex: Protective Role of Dehydroepiandrosterone Sulfate

Thimerosal, a mercury-containing vaccine preservative, is a suspected factor in the etiology of neurodevelopmental disorders. We previously showed that its administration to infant rats causes behavioral, neurochemical and neuropathological abnormalities similar to those present in autism. Here we examined, using microdialysis, the effect of thimerosal on extracellular levels of neuroactive amino acids in the rat prefrontal cortex (PFC). Thimerosal administration (4 injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15) induced lasting changes in amino acid overflow: an increase of glutamate and aspartate accompanied by a decrease of glycine and alanine; measured 10–14 weeks after the injections. Four injections of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate and aspartate concentrations at microdialysis time (but based on thimerosal pharmacokinetics, could have been effective soon after its injection). Application of thimerosal to the PFC in perfusion fluid evoked a rapid increase of glutamate overflow. Coadministration of the neurosteroid, dehydroepiandrosterone sulfate (DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate and aspartate; the steroid alone had no influence on these amino acids. Coapplication of DHEAS with thimerosal in perfusion fluid also blocked the acute action of thimerosal on glutamate. In contrast, DHEAS alone reduced overflow of glycine and alanine, somewhat potentiating the thimerosal effect on these amino acids. Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders. DHEAS may partially protect against mercurials-induced neurotoxicity.     

Effects of Prenatal and Postnatal Exposure to GSM-Like Radiofrequency on Blood Chemistry and Oxidative Stress in Infant Rabbits, an Experimental Study

We aimed to investigate the potential hazardous effects of prenatal and/or postnatal exposure to 1800 MHz GSM-like radiofrequency radiation (RFR) on the blood chemistry and lipid peroxidation levels of infant rabbits. A total of 72 New Zealand female and male white rabbits aged 1-month were used. Thirty-six female and 36 male were divided into four groups which were composed of nine infants: (i) Group 1 were the sham exposure (control), (ii) Group 2 were exposed to RFR, 15 min daily for 7 days in the prenatal period (between 15th and 22nd days of the gestational period) (prenatal exposure group). (iii) Group 3 were exposed to RFR 15 min/day (14 days for male, whereas 7 days for female) after they reached 1-month of age (postnatal exposure group). (iv) Group 4 were exposed to RFR for 15 min daily during 7 days in the prenatal period (between 15th and 22nd days of the gestational period) and 15 min/day (14 days for male, whereas 7 days for female) after they reached 1-month of age (prenatal and postnatal exposure group). Results showed that serum lipid peroxidation level in both female and male rabbits changed due to the RFR exposure. However, different parameters of the blood biochemistry were affected by exposure in male and female infants. Consequently, the whole-body 1800 MHz GSM-like RFR exposure may lead to oxidative stress and changes on some blood chemistry parameters. Studies on RFR exposure during prenatal and postnatal periods will help to establish international standards for the protection of pregnants and newborns from environmental RFR.     

Serum NGF,BDNF and IL-6 Levels in Postpartum Mothers As Predictors of Infant Development: The Influence of Affective Disorders

Background

Early adverse experiences are associated with increased risk of developing psychiatric disorders, although little is known about the neurobiological mediators involved. The mechanisms by which early environmental influences may mediate vulnerability in the development of offspring await further investigation. The present study correlated the NGF, BDNF, IL-6 and cortisol levels of mothers with postpartum affective disorders (PPAD) with infant development.

Methods

A longitudinal study was performed with 152 pregnant women and their infants. Between 60 and 120 days after delivery, women were interviewed and provided biological samples for biochemical analysis, and the infants were examined for neurobiological-motor development.

Results

Overall, the mothers'' history of affective disorders, PPAD and anxiety disorder were associated with infant motor development. Using an adjusted linear regression analysis, PPAD (p = 0.049), maternal anxiety disorder (p = 0.043), NGF level (p = 0.034) and infant cortisol level (p = 0.013) were associated with infant motor development. Using a factorial analysis of primary components, two components were retained. The psychological factor was characterized by a positive loading of a history of affective disorder, PPAD and anxiety disorder. For the biological factor, infant cortisol adhered negatively with infant motor development, but NGF was positively associated. The psychological factor had a negative association, but the biological factor had a positive association with infant motor development.

Conclusions

There are few studies that have focused on the relationship of biomarkers and infant neurodevelopment. Our study points that psychological and biological factors are associated with infant motor development, however the causal relationship between these factors is still to be defined.     

Effects of Age and Gender on Sleep Habits and Sleep Trouble for Aged People

The healthy 455 subjects above 60 years of age were questioned on their sleep habit inventory and the morningness-eveningness questionnaire. We analyzed the effects of age and sex on sleep habits and sleep-related trouble. Bedtimes on weekdays and weekends became earlier with aging, and women went to bed significantly later than men did. The length of sleep on weekdays slightly increased with aging, and it was longer for men than for women. The number of urinations and awakenings during nocturnal sleep and the amount of daytime napping increased with aging. The score on morningness-eveningness shifted toward the morning type with aging. In comparison with men, women had significantly longer sleep latency; and a higher percentage of subjects who reported that they sleep for only a short time, have sleep trouble, have received medical treatment for their sleep trouble, and take sleep medication. From these results, we deduced that the phase of sleep shifted forward in subjects above 60 years of age, and they showed frequent interruptions during nocturnal sleep and long daytime napping. We discussed the factor of gender difference in sleep in relation to social and cultural factors, particularly the household activities of women.     

Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions

Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-related quality of life and performance status were maintained longer in the bevacizumab group and the glucocorticoid requirement was lower. Here, we construct a clinical-scale model of GBM whose predictions uncover a new pattern of recurrence in 11/70 bevacizumab-treated patients. The findings support an exception to the Folkman hypothesis: GBM grows in the absence of angiogenesis by a cycle of proliferation and brain invasion that expands necrosis. Furthermore, necrosis is positively correlated with brain invasion in 26 newly-diagnosed GBM. The unintuitive results explain the unusual clinical effects of bevacizumab and suggest new hypotheses on the dynamic clinical effects of migration by active transport, a mechanism of hypoxia-driven brain invasion.     

Effects of Neonatal Melatonin Administration on the Extra-Hypothalamic Regions in Rat Brains: Effects on the Serotonergic System

The effects of 100g melatonin injection at postnatal day 5 (PD 5) on the development of the central serotonergic systems in male and female rats were investigated. The contents of serotonin (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) were measured in several extra-hypothalamic regions at 3, 10 and 42 weeks of age. The neonatal melatonin administration increased both 5-HT and 5-HIAA levels in the striatum throughout the examined period. In the hippocampus, an increase in 5-HIAA contents by neonatal melatonin administration was found at 3 weeks but not 10 or 42 weeks of age. There were no significant differences in the effects of melatonin between male and female rats. These results indicated that exogenous melatonin administration during the early neonatal period influenced the development of the serotonergic systems in extrahypothalamic regions including the hippocampus and the striatum.     

Longitudinal Analysis of the Premature Infant Intestinal Microbiome Prior to Necrotizing Enterocolitis: A Case-Control Study

Necrotizing enterocolitis (NEC) is an inflammatory disease of the newborn bowel, primarily affecting premature infants. Early intestinal colonization has been implicated in the pathogenesis of NEC. The objective of this prospective case-control study was to evaluate differences in the intestinal microbiota between infants who developed NEC and unaffected controls prior to disease onset. We conducted longitudinal analysis of the 16S rRNA genes of 312 samples obtained from 12 NEC cases and 26 age-matched controls with a median frequency of 7 samples per subject and median sampling interval of 3 days. We found that the microbiome undergoes dynamic development during the first two months of life with day of life being the major factor contributing to the colonization process. Depending on when the infant was diagnosed with NEC (i.e. early vs. late onset), the pattern of microbial progression was different for cases and controls. The difference in the microbiota was most overt in early onset NEC cases and controls. In proximity to NEC onset, the abundances of Clostridium sensu stricto from Clostridia class were significantly higher in early onset NEC subjects comparing to controls. In late onset NEC, Escherichia/Shigella among Gammaproteobacteria, showed an increasing pattern prior to disease onset, and was significantly higher in cases than controls six days before NEC onset. Cronobacter from Gammaproteobacteria was also significantly higher in late onset NEC cases than controls 1-3 days prior to NEC onset. Thus, the specific infectious agent associated with NEC may vary by the age of infant at disease onset. We found that intravenously administered antibiotics may have an impact on the microbial diversity present in fecal material. Longitudinal analysis at multiple time points was an important strategy utilized in this study, allowing us to appreciate the dynamics of the premature infant intestinal microbiome while approaching NEC at various points.     

Safety of Ferric Carboxymaltose Immediately after Infliximab Administration,in a Single Session,in Inflammatory Bowel Disease Patients with Iron Deficiency: A Pilot Study

AimTo obtain preliminary safety and efficacy data on intravenous (IV) administration of infliximab (IFX) and ferric carboxymaltose (FCM) to inflammatory bowel disease (IBD) patients in a single treatment session.MethodsA two-phase non-interventional, observational, prospective pilot study was performed to evaluate safety and efficacy of FCM given immediately after IFX. IBD patients were recruited consecutively in the outpatient clinic in two groups. Control group patients (n = 12) received FCM on a separate day from IFX. Subsequently, single-session group patients (n = 33) received FCM after IFX on the same day. All patients received 5mg/kg IFX and 1000mg FCM for iron-restricted anemia (IRA) or 500mg FCM for iron deficiency without anemia. Safety assessment was performed by recording adverse events (AEs) during and immediately after infusion, 30 minutes afterwards, and via follow-up at 7 days and 8 weeks. For efficacy assessment, hematological parameters were assessed prior to FCM infusion (pre-FCM) and after 8 weeks. Economic impact of FCM given immediately after IFX was assessed.ResultsAll 45 patients (35 Crohn´s disease, 10 ulcerative colitis) received IFX 5mg/kg. 21 patients received 500mg FCM and 24 received 1000mg. FCM administration immediately after IFX corrected iron deficiency or IRA as shown by increases in hematological parameters. No AEs were reported during the safety evaluation at the end of FCM or IFX administration, 30 minutes, 7 days and 8 weeks afterwards, in either control or single-session groups. Total cost per patient for single-session administration was 354.63€; for patients receiving IFX and FCM on separate days, it was 531.94€, giving a 177.31€ per-patient cost saving.ConclusionSingle-session administration of FCM after IFX was safe and effective in IBD patients and can offer a good cost-benefit ratio and improve treatment adherence. To our knowledge, this study is the first to evaluate FCM and IFX administration in a single treatment session.     

Baseline Plasma GABA: Its Relationship to the Adverse Effects of Acute Lorazepam Administration on Cognition in the Elderly

The GABA system is an active target for drugs to treat a variety of disorders and the availability of an indirect measure of central GABA activity would not only enhance psychiatric research, but also permit assessment of the pharmacodynamic effects of drugs designed to act on this system. The relationships between plasma baseline pre-drug GABA concentrations and cognitive impairments induced by an acute oral dose of lorazepam (0.5 and 1.0 mg) were investigated in 22 healthy elderly individuals. Partial correlations controlling for plasma lorazepam concentrations revealed no significant relationship between baseline plasma GABA levels and lorazepam-induced impairments on tests of cognitive functioning. Plasma GABA concentration does not appear to be a useful marker of susceptibility to benzodiazepine-induced cognitive toxicity in the elderly. Other approaches to estimating central GABA activity should be pursued.     

Effects of Nucleotides Supplementation of Infant Formulas on Plasma and Erythrocyte Fatty Acid Composition: A Meta-Analysis

Objective

Nucleotides (NTs) have been added to infant formulas for several years due to their health benefits. However, studies have reported inconsistent findings regarding the association between NTs and fatty acid (FA) composition. A meta-analysis was performed to assess the effects of NTs supplementation of infant formula on erythrocyte and plasma FA composition.

Methods

Randomized controlled trials that evaluated the association between NTs supplementation and FA composition and were published before October 2014 were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using Q and I ² tests.

Results

Eight studies (364 infants) were included in the meta-analysis. NTs supplementation did not affect the concentrations of total saturated FAs (SMD= 0.05; 95% CI= -0.23–0.32; P = 0.75) or total monounsaturated FAs (SMD= -0.01; 95% CI= -0.28–0.27; P = 0.95) in erythrocyte membranes. Erythrocyte total n-3 (SMD= 0.15; 95% CI= -0.11–0.41; P = 0.27) and n-6 PUFA (SMD= -0.16; 95% CI= -0.42–0.10, P = 0.22) concentrations did not increase with NTs supplementation. The concentrations of erythrocyte n-3 PUFA (18:3, 20:5, 22:5, and 22:6) and n-6 PUFA (18:2, 20:3, 20:4, and 22:4) were not affected by NTs supplementation. NTs significantly increased plasma concentrations of 18:2 n-6 (SMD= 0.90; 95% CI= 0.47–1.33; P < 0.0001), 20:3 n-6 (SMD= 0.56; 95% CI= 0.14–0.97; P = 0.009), and 20:4 n-6 PUFA (SMD= 0.92; 95% CI= 0.50–1.35; P < 0.0001), and significantly decreased the concentration of plasma 18:3 n-3 PUFA (SMD= -0.60; 95% CI -1.12 to -0.09; P = 0.02). No effect was obtained on plasma 20:2 n-6 PUFA concentrations (SMD= 0.06; 95 % CI, -1.03 to -0.2; P = 0.93).

Conclusions

Our meta-analysis revealed that NTs supplementation significantly increased plasma 18:2 n-6, 20:3 n-6, and 20:4 n-6 PUFA concentrations in infants, but did not affect erythrocyte FA composition.