Nuclear bodies in rat hepatocytes: Dynamics of appearance and formation during aging and functional loads

Department of Pathomorphology, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR D. S. Sarkisov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 2, pp. 203–208, February, 1992.     

The Heritability of Depression Symptoms in Elderly Danish Twins: Occasion-Specific Versus General Effects

Depression symptomatology was assessed up to four times at 2-year intervals on a sample of 2100 Danish twins initially aged 70 years and older. Data were analyzed using the biometric growth model approach proposed by Neale and McArdle (2000). Results show that occasion-specific depression is moderately and equally heritable in men and women (occasion-specific estimates of heritability ranged from 22% to 37%). Estimates of phenotypic variance, genetic variance, and heritability did not vary systematically across waves. In the best-fitting growth model, depression symptomatology was accounted for by two factors: (1) a level (i.e., average) effect that was highly heritable (estimate of 69% in women and 64% in men) and reflected overall vulnerability, and (2) a residual effect that was nonheritable and reflected occasion-specific circumstances that could either exacerbate or moderate inherited vulnerability. Attempts to identify specific genetic contributions to depression might profitably focus on average levels across multiple assessments, while attempts to identify specific environmental effects might profitably focus on deviations about this average.     

Effect of age on serum immunoglobulin G subclass antibody responses to inactivated influenza virus vaccine

We previously reported an age-associated impairment of serum immunoglobulin G (IgG) antibody responses to inactivated influenza virus vaccine. The present study extends these observations by examining the IgG subclass distribution of vaccine responses measured by enzyme linked immunosorbent assay in healthy adults aged <40 (young), 40–64 (middle-aged), and ?65 (elderly) years. Serological responses in all age groups showed antibodies that were predominantly IgG1 and secondarily IgGS. Influenza antigen-specific IgG4 titers did not change following vaccination, and antibodies of the IgG2 subclass were not detected in any serum specimens. Aging was associated with a significant impairment of IgG1, but not of IgGS, antibody production. Relative differences in the magnitude and frequency of response between IgG1 and IgGS subclasses, which were present in young and middle-aged adults (viz., IgG1 > IgGS), were less apparent in the elderly. This observation was confirmed in a second analysis of IgG subclass-specific responses in a separate cohort of elderly vaccinees. These results suggest that the age-related impairment of humoral responses to inactivated influenza virus vaccine is primarily accounted for by differences in IgG1 antibody production, and that IgGS antibodies make up a larger proportion of the overall serologic response in the elderly than they do in younger persons. © 1994 Wiley-Liss, Inc.     

The effects of nifedipine on platelet aggregation and plasma 6-keto-PGF1α, and its interaction with indomethacin

Summary Pre-incubation of human platelets with nifedipine in vitro or treatment of normal volunteers with nifedipine, 30 mg daily for one week, did not alter ADP induced aggregation measured by whole blood aggregometry. 6-oxo-Prostaglandin F₁ remained undetectable in plasma following oral administration of nifedipine to normal volunteers. The hypotensive response to intravenous nifedipine administration was similar in spontaneously hypertensive rats pretreated with indomethacin or placebo. These results conflict with previous reports that nifedipine alters platelet aggregation and prostaglandin metabolism.     

Pharmacokinetics and effects on blood pressure of a single oral dose of milrinone in healthy subjects and in patients with renal impairment

Summary Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30–63 ml/min) and 7 patients with severe renal impairment (CRI II, creatinine clearance 9–29 ml/min). All except one of the patients with renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t_1/2) was 0.94 h. In CRI the mean plasma t_1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6–8 h after dosing, with the maximal decrease at 2–3 h (healthy subjects 118/71107/56, CRI 159/95136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2–6 h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled.The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.     

Effects of fenflumizole on aggregation ex vivo of human platelets and formation of thromboxane B2 and 6-keto-prostaglandin-F_{1\alpha }

Summary Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl)imidazole), a new non-steroidal anti-inflammatory drug, was given to healthy subjects in single oral doses of 0.1, 1 and 2 mg/kg. The effect of the drug was followed for up to 8 h by repeated tests of arachidonic acid-induced platelet aggregation and was related to its concomitant plasma concentration. Fenflumizole reversibly inhibited platelet aggregation and the degree of inhibition was found to be linearly correlated with the log plasma concentration. There was depression of the formation of thromboxane B₂ and 6-keto-prostaglandin F₁ (the stable metabolites of thromboxane A₂ and prostacyclin) in clotted whole blood measured by radioimmunoassay after fenflumizole 1 mg/kg. This effect was directly related to the concentration of the drug in plasma, the maximum effect being reached at fenflumizole concentrations >200 ng/ml. EC₅₀-values for inhibition of the formation of thromboxane B₂ and 6-keto-prostaglandin were approximately 20 and 40 ng/ml, respectively. The results suggest that orally administered fenflumizole is a potent inhibitor of platelet aggregation and prostanoid formation.     

基于“正虚邪滞”理论探讨肺癌自噬机制及中药干预进展

自噬是一种细胞自我保护和自我更新机制,与肺癌的发生发展密切相关,有利自噬可以减缓肺癌进展,而不利自噬能够促进肺癌进展,故调节自噬水平在肺癌治疗中具有重要意义。“正虚邪滞”是王永炎院士“虚气留滞”理论的延伸,是指因肺脾肾气亏虚,引发津液代谢异常,导致痰瘀阻滞的病理过程,以肺脾肾气亏虚为本、痰瘀阻滞为标,是肺癌的关键病机。肺癌的自噬机制与“正虚邪滞”有着相互贯通之处,肺脾肾气亏虚是肺癌有利自噬减弱的关键因素,进而抑制了肿瘤细胞凋亡,并导致有害物质蓄积;痰瘀阻滞是肺癌不利自噬增强的直接因素,进而促进了正常细胞自噬性死亡,削弱了免疫细胞对肿瘤细胞的免疫抑制作用,导致肿瘤细胞增殖和迁移。正虚与邪滞相合,致使自噬状态向着不利的方向不断发展,最终导致肺癌持续进展。因此,中医干预肺癌自噬机制需以扶正抗邪为原则,补益正气以治其本,祛痰化瘀以治其标,增强有利自噬的同时抑制不利自噬,将自噬水平调节到最佳状态,从而抑制肿瘤细胞增殖和迁移,促进肺癌的缓解。通过分析现有文献可知,目前通过自噬途径治疗肺癌的中医药以中药单体为主,中医药干预肺癌自噬的作用主要集中在促进自噬激活层面,这可能是因为藉由肺脾肾气亏虚引发的有利自噬减弱是肺癌发展的根本原因。     

Beneficial Effects of a Mixture of Algae and Extra Virgin Olive Oils on the Age-Induced Alterations of Rodent Skeletal Muscle: Role of HDAC-4

Aging is associated with a progressive decline in skeletal muscle mass, strength and function (sarcopenia). We have investigated whether a mixture of algae oil (25%) and extra virgin olive oil (75%) could exert beneficial effects on sarcopenia. Young (3 months) and old (24 months) male Wistar rats were treated with vehicle or with the oil mixture (OM) (2.5 mL/kg) for 21 days. Aging decreased gastrocnemius weight, total protein, and myosin heavy chain mRNA. Treatment with the OM prevented these effects. Concomitantly, OM administration decreased the inflammatory state in muscle; it prevented the increase of pro-inflammatory interleukin-6 (IL-6) and the decrease in anti-inflammatory interleukin-10 (IL-10) in aged rats. The OM was not able to prevent aging-induced alterations in either the insulin-like growth factor I/protein kinase B (IGF-I/Akt) pathway or in the increased expression of atrogenes in the gastrocnemius. However, the OM prevented decreased autophagy activity (ratio protein 1A/1B-light chain 3 (LC3b) II/I) induced by aging and increased expression of factors related with muscle senescence such as histone deacetylase 4 (HDAC-4), myogenin, and IGF-I binding protein 5 (IGFBP-5). These data suggest that the beneficial effects of the OM on muscle can be secondary to its anti-inflammatory effect and to the normalization of HDAC-4 and myogenin levels, making this treatment an alternative therapeutic tool for sarcopenia.     

Three-Year Follow-Up of the POIBA Intervention on Childhood Obesity: A Quasi-Experimental Study

Childhood obesity has increased worldwide over the past four decades. This quasi-experimental study aimed to assess the effectiveness of a multicomponent and multilevel school-based intervention (POIBA) at 3 years of follow-up. The nutrition intervention focused on food groups, food pyramid, nutrients, portions, and balanced menus. In total, 3624 children participated in the study. Anthropometric measurements and information on food frequency and behavior, physical activity, and daily screen use were collected in the intervention (IG) and comparison group (CG). Positive unadjusted changes toward adherence to recommendations were found for water, meat, sweets, and fried potato consumption, proper breakfast, not having dinner in front of the TV, out-of-school physical activity, and daily screen use. Three scores were used to calculate the proportion of children making more than one change to improve healthy habits regarding physical activity (global Activity score), nutrition (global Nutrition score), and both (global score). Students exposed to the intervention had a significantly better global Activity score (16.2% IG vs. 11.9% CG; p = 0.012) and Global score (63.9% IG vs. 58.5% CG; p = 0.025). Intervention effects on obesity incidence at 3-year follow-up lost significance but maintained the positive trend. In conclusion, school-based interventions including a family component could be useful to address the childhood obesity problem.