Neurobehavioral Biomarkers of Aging：Influence of Genotype and Dietary Restriction

Because of the importance of central nervous system(CNS) functions to productive capacity and quality oflife, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes.The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole.Age-related behavioral changes,the products of CNS aging,have content and predictive validity with respect to human functional capacities and may ,therefore,represent important “neurobehavioral“ markers of functional aging.This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity.Studies conducted in the authors‘ laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns,and hypothetical and empirical examples of these pitfalls are described and discussed.In spite of those concerns,it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.     

Research Progress on Prevention and Treatment of Glucolipid Metabolic Disease with Integrated Traditional Chinese and Western Medicine

Hyperlipidemia,type 2 diabetes mellitus,nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients.In addition,these diseases are closely related in pathophysiological settings.However,increasing of the disease incidence,lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattern of the single disease,single target therapy,that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine(WM).On the basis of the combination of the advantages of integrated Chinese medicine(CM) and WM,with unified understanding of such diseases,the new concept of glucolipid metabolic disease(GLMD) is introduced.In this new concept,disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD.The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance,oxidative stress,inflammation and intestinal flora imbalance.In the core pathogenic perspective of CM,it can be explained as "Gan(Liver) Shi Shu Xie"(dysfunction of Gan in metabolism and emotion regulation) that will lead to the occurence/production of endogenous dampness and phlegm,blood stasis and turbid.This leads to the new concept of "Liver-based regulatory system for metabolic homeostasis" to be introduced further.The comprehensive prevention and control strategy "Tiao Gan Qi Shu Hua Zhuo"(modulating Gan,trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness).Its representative formula Fufang Zhenzhu Tiaozhi Capsule(复方贞术调脂胶囊) is innovated under such rationales.Comment for some commonly-used CM GLMD therapeutic drugs was presented.High-level evidence-based and epidemiological and mechanism studies should be carried out to further interpret and explain of the scientific connotation of GLMD.     

Biogenic Amines as Biomarkers for Neurotoxicity

There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity.To investigate these neurochemical endpoints ,two prototype neurotoxicants were evaluated in experimental animals.One agent,reserpine, was used to assess developmental neurotoxicity and administered prenatally ,while the other ,MDMA, was used in the adult animal.The neurochemical biomarkers measured were dopamine,serotonin,and their metabolite(DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques.A review of the background, experimental design,and results are presented in this article.Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity.These neurochemical biomarkers can be correlated with neuropathological and behavioral biomarkers to aid in the understanding of mechanisms of neurotoxicity.     

Circadian rhythm: a new clue for neuropsychological dysfunction after cardiac surgery

In the recent editorial comment, DubouleI emphasized .that ＂animal development is, in fact, nothing but time＂.That a circadian timing system is apparently universal in biology is the evidence for the important physiological role that rhythmicity plays. It is by the circadian rhythm that we could choose the optimal time to give therapeutic settings, such as antihypertensive drugs, adjusting sleep disorders and hormone in order to improve the prognosis. Besides the physiological action, there is pathological significance for circadian rhythm. In the recent years, more and more evidences have been found that the mechanisms of many diseases are associated with rhythm disturbance.[第一段]     

Blood Oxidant/Antioxidant Status in overfed Aging Rats: Comparative Effects of Sunflower and Olive-Linseed Mixture Oil Rich Diets

Obesity,one of the most common health problems,is associated with glucose and lipid metabolism abnormalities,increased cardiovascular risk and oxidative stress[1].Aging is also associated with an increase in oxidative stress[2].Considering that older adults are already at risk for oxidant stress,the additional metabolic perturbations of obesity aggravated the susceptibility to oxidant stress.Modulating age-related oxidative stress via dietary interventions could reduce free radical production and significantlyimprove health in aging.     

Neurotoxicity and Biomarkers of Lead Exposure:a Review

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups： biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer＇s disease, Parkinson＇s disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.     

Increased serum levels of C-reactive protein and matrix metalloproteinase-9 in obstructive sleep apnea syndrome

Background Obstructive sleep apnea syndrome （OSAS）, characterized by intermittent hypoxia/reoxygenation （IHR）, has been identified as an independent risk factor for cardiovascular diseases （CVD）. The CVD biomarkers associated with OSAS have not been thoroughly investigated. Methods Fifty-one men with OSAS recently diagnosed by polysomnography were classified into two groups according to the severity of apnea： moderate to severe OSAS group （n=- 28） and mild OSAS group （n=- 23）. Twenty-five obese men, of comparable age and body mass index （BMI）, without OSAS were chosen as control subjects. Serum metabolic variables, C-reactive protein （CRP） and matrix metalloproteinase-9 （MMP-9） were measured. Spearman correlation and regression analysis were performed. Results Serum concentrations of CRP and MMP-9 were significantly higher in 51 OSAS patients than in 25 control subjects. Levels of CRP and MMP-9 were significantly higher in patients with moderate to severe OSAS than in patients with mild OSAS or in obese control subjects. A positive correlation was found between levels of CRP and MMP-9 in OSAS patients. Regression analysis showed that after adjusting for age and BMI, apnea/hypopnea index （AHI） significantly correlated with serum concentrations of CRP and MMP-9 in patients with OSAS. Conclusions AHI, mirroring the frequency of IHR, was a predictor of enhanced circulating CVD biomarkers MMP-9 and CRP. Our data support the theory that IHR contributes to the upregulation of the inflammatory factors in OSAS patients.[第一段]     

多环芳烃接触者P21蛋白跟踪研究

Polycyclic Aromatic Hydrocarbons(PAHs),first determined as a sort of chemical carcinogen, can exist in chemical substance such as coal tar pitch (CTP) and coke oven volatiles (COV). The carcinogenesis of PAHs has been confirmed by epidemiological studies among high risk population and animal experiments. The excessive mortality of lung cancer has been found in workers exposed to CTP and COV. Lung cancer can be induced in rats or mice with CTP by inspiring CTP fog or intratracheal instillations. The latest advance in the study of molecular biology has been applied to the fields of occupational cancer prevention and diagnosis. The study of the amount, effect, and injury of carcinogen with biomarkers has become one of the imporant methods for the early detection for occupational lung cancer.     

An Association between Immunosenescence and CD^4＋CD25^＋ Regulatory T Cells： A Systematic Review

Objective Age-related increment of the prevalence of CD4^＋CD25^＋ regulatory T （Treg） cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8＋ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^＋CD25^＋ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease （AD） and Parkinson disease （PD）. The impaired condition of CD4＋ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.     

Atherosclerosis, vascular aging and therapeutic strategies

<正>With the arrival of the era of global population aging,we strive for healthy aging and a healthy senior life rattier than simple prolongation of the physical age.For the past 50 years,cardiovascular diseases (CVD) have been the most common cause of death among the elderly people globally.In China,there has been an exponential increase in the incidence of heart disease and stroke in the elderly population.Atherosclerosis is the pathological change in the coronary artery disease,stroke,and peripheral vascular disease.Despite the significant benefit demonstrated,control of classic risk factors alone,such as lifestyle change or drug therapy, was shown to have limitations in reducing the incidence of cardiovascular events.Vascular aging has been shown to be an important independent predictor of CVD events.Interventions targeting vascular aging have emerged as a new paradigm in conjunction with control of risk factors for the prevention of CVD.Vascular aging and atherosclerosis are two distinct pathological changes and difficult to distinguish clinically.Recent research with Chinese medicine(CM) has shown encouraging observations,linking the clinical benefit of delaying vascular aging and treating atherosclerosis.These results demonstrate great potential of CM in the prevention and treatment of CVD.     

REVIEW Risk Assessment of the Mycotoxin Ochratoxin A

Ochratoxin A (OA) is a mycotoxin which has been found to occur in foods of plant origin, in edible animal tissues, as well as in human blood sera and tissues. The ability of OA to move up the food chain is aided by its long half-life in certain edible animal species. In this report, an evaluation of the health risks to Canadians due to the presence of OA in food products is presented. The first part of the report deals with the physicochemical aspects, mycology, laboratory production, analytical methods, and natural occurrence in plant products, animal products, and human tissues. The stability of OA in foods and feeds, the effects of food processing, and the removal from foods and feeds by physicochemical means are also discussed. From these data, the worst case estimate for the daily exposure of Canadians to OA, from the consumption of pork-based food products and cereal foods, is approximately 5 ng OA/kg body wt (mean of eaters) for young children, the highest consumption group on a body weight basis. The second part of the report deals with the metabolic disposition as well as the available toxicity database for OA in laboratory animals, farm animals, and humans. The major target for OA toxicity in all mammalian species tested is the kidney, and endemic nephropathies affecting livestock as well as humans have been attributed to OA. OA is also teratogenic, and in the fetus the major target is the developing central nervous system. Recent studies have provided "clear evidence" of the carcinogenicity of OA in two rodent species. OA was found to be nonmutagenic in various microbial and mammalian gene mutation assays, but weak genotoxic activity to mammalian cells was noted. In addition, OA was found to suppress immune function. Based on the NTP carcinogenicity study with OA in rats, the estimated tolerable daily intake in humans ranges from 0.2 to 4.2 ng OA/kg body wt, depending on the method of extrapolation used. In view of the toxic properties of OA, it is recommended that exposure to OA be kept to a minimum. In Canada, further monitoring programs are required to better define the overall residue profile of OA in cereal grains, animal feeds, animal food products, and human blood. Such data are required to better assess dietary exposure and to ascertain the need for regulatory controls or other control mechanisms. (c)1989 Academic Press, Inc.     

The Problem of Helio-Gerontology： The New Scientific Point of View at the Processes of Aging and Water-Holographic Prevention

The author＇s hypothesis for amount of the solar activity during prenatal development of human organism, detecting gene expression responsible for the level of metabolism and the fact that age processes can restrict man lifespan was investigated. The prenatal period of each person development proceeds in continuous interaction with heliogeophysical environment, depending on individual helio-magnetosensitivity of an organism. Heliogeophysical impact was estimated with the use computer program HELIOS （Ru Reg.Cert. 970125, 24.08.1997）. There was a task in view： to develop new generation ofhelio-protectory means for people with high heliosensitivity and high risk of accelerated aging. Such means were created and patented in Russia （patent RU 2342149, 27.12.2008） and they were named helio-geroprotectors. Tests on bio-objects have shown high efficiency of such protectors on water and-holographic basic, increase in level steroid hormones, anabolic processes and reduction of speed of aging estimated on relation of stable isotopes of carbon 13C/12C in tissues （wool） in males-rats （n = 30）, born at high activity of the Sun and using special informational light-hologram （patent RU 2239860, 10.11.2004） or for drink within one month water helio-protectors. Change of the level of isotope 13C in tissues （hairs）, which content was detected by mass-spectrometer Delta and the vector of correlation of the decreasing or increasing of this isotope with sun＇s protons streams may be a new marker of rate of human aging and criteria of helio-gero-protectors efficiency. New helio-biophysical horizons of non-medical decrease in rate of human aging are designated.     

Efficacy of polyphenolic ingredients of Chinese herbs n treating dyslipidemia of metabolic syndromes

There is an increasing interest and popularity of Chinese herbal medicine worldwide, which is accompanied by increasing concerns about its effectiveness and potential toxicity. Several ingredients, such as polyphenolic compounds berberine, flavonoids, and curcumin, have been studied extensively by using various animal models. Effectiveness of treatment and amelioration of metabolic syndromes, including insulin resistance and dyslipidemia, has been demonstrated. This review summarizes the major checkpoints and contributing factors in regulation of exogenous and endogenous lipid metabolism, with particular emphasis centered on triglyceride-rich and cholesterol-rich lipoproteins. Available experimental evidence demonstrating the lipid-lowering effect of berberine, flavonoids and curcumin in cell culture and animal models is compiled, and the strengths and shortcomings of experimental designs in these studies are discussed.     

Energy Balance and Physical Activity

The prevalence of obesity is increasing in most parts of the world and becoming one of the major global public health problems.Although the components of energy balance have not been adequately estimated over time,available evidence suggests that the increase in obesity is the result of reduced physical activity.Increases in physical activity have been showen to be strongly associated with improving physical fitness and body composition,with probably a positive effect on resting metabolic rate.The Surgeon General‘s Report on physical Activity and Health advocates that 30 min of regular,moderate-intensity physical activity is associated with decreases in the risk of chronic diseases and may contribute to quality of life.However,the small changes that contribute 10 min for 3 times a day for 3 times a day for aerobic training,or one set instead of three sets of repetitions on resistance training will provide individuals training,or one set instead of three sets of repetitions on resistance training will provide individuals with health benefits.Indeed,nutrition and physical activity should be considered an integral part of fitness and good health,and should be encouraged in all age groups,particularly early in life,The question is no longer centerd around the health benefit of increasing physical activity,but rather creating self awareness and behavior changes in individuals,Hence,effective intervention programs are needed that foster long term changes in physical activity.Among various interventions,the Nutrifit program was recently conducted in Thailand and found to improve health related fitness in children,The development of more effective interventions and approaches is a major challege in this field today.     

Awakening concentration of desflurane is decreased in patients with obstructive jaundice

BACKGROUND： Some studies suggest that behavioral complications of cholestasis, such as fatigue and pruritus, may be associated with altered neurotransmission in the brain. Because inhaled anesthetics primarily act on ion channels and receptors on the neuronal cell membrane and alter synaptic transmission in the central nervous system,     

BENEFICIAL EFFECT OF AN ACTH-（4-9） ANALOG（ORG2766）IN THE TREATMENT OF EXPERIMENTAL CORTEX LESION IN RATS

This paper reports that lesions of the medial frontal cortex(MFC)caused behavioral deficit in rats and that this deficit could be attenuated by a well formulated treatment with Org2766,an analog of ACTH-(4-9).Wistar rats were distributed in 3groups:MFC lesion treated with saline(M-N);MFC lesion treated with Org2766(M-O);and sham-operation treated with saline (S).Repeated Org2766 or saline injection commenced from the day of surgery and lasted for 13 days.After surgery,the rats were trained in a passive avoidance task and then in an ac-tive avoidance task. MFC lesions were found to be strongly associated with behavioral deficits.The M-N group rats displayed poor retention of the passive avoidance response and showed much slower learning of the active avoidance task as compared to S group rats.The rseult showed that chronic Org2766 administration improved the behavioral performance of both tasks in MFC lesioned rats.The also revealed that the superoxide dismutase (SOD)activity was significantly increased in the M-O group as compared to the M-N group 15 days after surgery.The possible mechanisms related to the beneficial effect of Org2766 on cortex damage are discussed.     

Associated risk factors of knee osteoarthritis: a population survey in Taiyuan, China

Background Since knee osteoarthritis （KOA） is one of the common diseases, identification of its associated risk factors is of preventive significance. This investigation was designed to investigate the prevalence of KOA in Taiyuan, and identify the associated risk factors of KOA. Methods A population sample was surveyed of 2188 adults aged from 35 to 64 years, living in 6-story buildings without elevators. The protocol of Asia Pacific League of Associations for Rheumatology （APLAR） Community Oriented Program for Control of Rheumatic Diseases （COPCORD） core questionnaire was implemented. The data on knee pain and KOA were collected and analyzed. Variables such as sex, age, body mass index （BMI）, waist circumference （WC）, education level, and smoking history, were included in binary logistic regression model for further analysis. Results The prevalence rates of knee pain and KOA were 13.6% and 10.9%, respectively, significantly higher than those in Shantou of south China and similar to those in Beijing of north China. The prevalence of KOA was significantly higher in women than in men （18.3% versus 8.7% and 15.1% versus 6.3%）, with a tendency of increase with age. The prevalence was increased more obviously in women after 40 years old and in men after 45 years old. BMI in KOA group was significantly higher than that in non-KOA group. Binary Logistic regression revealed that age, sex, and BMI were significantly associated with KOA, whereas no significant correlation was seen between KOA and other factors such as climbing stairs, WC, time length of occupation service, education level, smoking history and religious belief. Conclusion Geography, age, sex, and BMI might be the risk factors of KOA, but climbing stairs, WC, time length of occupation service, education level, smoking history and religious belief are not correlated with KOA. Prevention of KOA should be initiated before the middle-age, especially in female adults, and weight control is necessary. Other factors might also contribute to the development of KOA, but further study is needed to elucidate the role of these factors.     

Correlation of serum cholesteryl ester fatty acid composition with susceptibility to atherosclerosis in different species.

Fatty acid composition of serum cholesteryl esters (CEs) in Chinese and 9 species of laboratory animals was analysed. Polyunsaturated fatty acids (PUFAs) were the predominant fatty acids in CEs. A close correlation between PUFAs to saturated fatty acids ratio (P/S) in CEs and susceptibility to atherosclerosis (AS) was observed in different species. Animals with high P/S such as mice (13.0), tree shrews (9.0) and rats (9.0) were AS-resistant, and those with low P/S such as rabbits (2.9) were susceptible to AS. The P/S value in men (4.9) was between those of the above two kinds of animals, and similar to those of pigs (4.2) and monkeys (3.7). Marked physiological significance of the rich PUFAs in CEs may be expected. As the main constituent of low density lipoprotein (LDL), CEs may provide PUFAs for cells efficiently via LDL receptor. It is assumed that PUFAs in CEs may play an important role in the metabolism of cholesterol and the development of AS by regulating LDL receptor activity, platelet function and prostaglandin metabolism.

     

Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata （L,） Stapf in rats

OBJECTIVE： In continuation to the growing evidence for therapeutical potential of Desmostachya bipinnata （Linn） Stapf, the current pharmacological study was carried out to evaluate the diuretic and laxative activity of its hydro-alcoholic extract in rats. METHODS： The hydro-alcoholic extract of D. bipinnata whole plant was prepared by using Sox- hlet extractor and subjected to analysis by standard preliminary phytochemical tests. Evaluation of both diuretic and laxative activity was carried out using standard methods as reported earlier. Frusemide （20 mg/kg） was served as positive control for diuretic activity and sennosides （10 mg/kg） served as negative control for laxative activity. RESULTS： The hydro-alcoholic extract showed significant diuretic activity and was found to be the most potent in increasing the urinary output at 500 mg/kg when the effect was compared with that of the standard frusemide （P〈0.01）. Moreover, this extract was found to be most effective in increasing urinary electrolyte concentration （Na＋, K＋, and Cl-） at both doses tested. Whereas the results for laxative activity showed minimal increase of feces output at the dose of 500 mg/kg and the increase was negligible when compared with that of the standard drug sennosides. CONCLUSION： Altogether, the above significant findings validate and support its folkloric diuretic use and lend pharmacological credence to the ethno-medical use of this plant in traditional system of medicine, which demands further studies to investigate its active constituents, as well as its use and safety.