The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys

Infection with human or simian immunodeficiency virus (SIV) is characterized by the rapid turnover of both viral particles and productively infected cells. It has recently been reported that the clearance of SIV in vivo is exceedingly fast, with half-lives on the order of minutes. The underlying mechanism or site responsible for this rapid clearance, however, remains unknown. To investigate this issue, we chose to infuse infectious SIVmac239 grown from autologous peripheral blood mononuclear cells that were radioactively labeled by [(35)S]methionine and [(35)S]cysteine. This approach eliminates from the viral membrane alloantigens that may have a significant impact on viral clearance. In addition, this approach also permits identification of the sites of viral clearance by measuring the radioactive intensity, even if degradation of SIV RNA occurs in tissues. We now report that the half-life of infused SIV in blood is extremely close to estimates from a previous study, in which unlabeled SIV grown in a heterologous cell line was used. The allogeneic effect due to the presence of human antigens on the surfaces of virions may, therefore, play a minimal role in the high rate of virion clearance. Moreover, close to 30% of infused radioactivity was found in the liver and measureable amounts were detected in the lungs (5.4%), lymph nodes (3.0%), and spleen (0.4%). The detection of a significant proportion of infused virus in the liver suggests that viral clearance from circulation is mediated by a common, nonspecific mechanism, such as the phagocytic functions of the reticuloendothelial system. The rapid clearance and degradation of exogenously infused virions may pose a major obstacle for gene therapy with viral vectors, unless strategies to overcome the rapid in vivo elimination of these particles are developed.     

Effect of redox-modified fibrinogen on blood leukocyte functions

The influence of oxidized fibrinogen on the intensity of luminol-dependent chemilumin escence of blood leukocytes, stimulated by opsonized zymosan was studied. It was shown that the introduction of fibrinogen modified by UV-irradiation in to a suspension of cells resulted in a significant increase in the intensity of the luminol-dependent chemiluminescence of leukocytes. It was suggested that oxidized fibrinogen can influence blood leukocytes, enhancing their functional activity.     

Heparin clearance during activation of the anticoagulation system in animals

Retarded heparin-35S clearance from the blood stream during activation of the blood anticoagulation system was observed. Under these conditions the half-life of heparin-35S increased from 1.6 h in control animals to 2.35 h in the animals after intravenous injection of a threshold dose of thrombin causing activation of the anticoagulation system. Retarded heparin-35S clearance from the blood stream during activation of the blood anticoagulation system is accompanied by increase of its absorption in the liver and in the auricular atrii.     

Changes in cell respiration of postural muscle fibers under long-term gravitational unloading after addition of succinate into diet

The intensity of cell respiration of the rat m. soleus, gastrocnemius c.m., and tibialis anterior fibers during 35-day gravitational unloading, with the addition of succinate in the diet at a dosage rate of 50 mg per 1 kg animal weight has been investigated. The gravitational unloading was modeled by antiorthostatic hindlimb suspension. The intensity of cell respiration was estimated by polarography. It was shown that the rate of oxygen consumption by soleus and gastrocnemius fibers on endogenous and exogenous substrates and with the addition of ADP decreases after the unloading. This may be associated with the transition to the glycolytic energy pathway due to a decrease in the EMG activity. At the same time, the respiration rate after the addition of exogenous substrates in soleus fibers did not increase, indicating a disturbance in the function of the NCCR-section of the respiratory chain and more pronounced changes in the structure of muscle fibers. In tibialis anterior fibers, no changes in oxygen consumption velocity were observed. The introduction of succinate to the diet of rats makes it possible to prevent the negative effects of hypokinesia, although it reduces the basal level of intensity of cell respiration.     

Comparative characterization of the lipoprotein spectrum and status of free radical processes in the blood of rabbits exposed to external gamma-irradiation and cholesterol administration]

Characteristic of lipoprotein spectrum and state of free-radical processes in the animals under action of ionizing radiation and cholesterin diet are comparatively studied. The content of lipids in the blood serum increases on the 5th day after irradiation and then decreases on the 15th and 30th days. Cholesterin diet increases the content of cholesterin under practically unchanged content of triglycerides in the blood serum in all the terms of investigations. Total decrease of the intensity of induced chemiluminescence of the blood serum and erythrocytes after irradiation is shown. Peroral introduction of cholesterin evokes differently directed changes in the light sum of chemiluminescence--a decrease in erythrocytes and increase in the blood serum.     

Kidney function and sulfate uptake and loss in the freshwater bivalve Toxolasma texasensis

Toxolasma texasensis acclimated to an artificial pondwater (PW) maintained a concentration of SO4 in the blood of about 1-2 mmol l(-1) . The anion transport inhibitor DIDS (5,5'-diisothiocyanatostilbene 2, 2'-disulfonic acid) reduced the uptake of 35SO4 from the bathing medium by 54%. The clearance of polyethylene glycol (PEG) injected into the blood of T. texasensis ranged between 0.8 and 1.3 ml g(-1) dry tissue h(-1), and provided an estimate of renal filtration in PW-acclimated animals. The clearance of radioactive 35SO4 simultaneously injected into the same animal was about 16% of the PEG clearance, suggesting that sulfate was being reabsorbed by the kidney. Para-aminohippuric acid was cleared about 4.6 times faster than PEG, indicating that this organic acid was subjected to secretion in addition to filtration. When the normal osmotic gradient was abolished by acclimating T. texasensis to 10% seawater (SW), the PEG clearance decreased to 0.17 ml g(-1) dry tissue h(-1). Sulfate clearance in animals acclimated to PW or 10% SW was the same. However, in mussels acclimated to 10% SW, the calculated amount of SO4 reabsorbed was significantly reduced relative to mussels acclimated to PW. T. texasensis conserved SO4 when acclimated to PW, and reduced reabsorption when acclimated to the sulfate-rich 10% SW. When mussels acclimated to 10% SW were returned to PW, there was a transient increase in sulfate clearance during the first 8 h because filtration exceeded reabsorption.     

鳜鱼头肾的组织发生及成鱼头肾B淋巴细胞的分布

通过整体连续切片,研究了鳜鱼不同发育时期的头肾结构,并利用原位PCR方法检测了B淋巴细胞在鳜鱼头肾中的分布。在孵化后第1d观察到了肾组织,主要由肾小管组成。尔后头肾的发育经历了三个结构和功能的转变。第一个阶段为孵化后第1d到第7d,头肾作为滤过性器官存在,由肾小管及少量淋巴细胞组成。第二个阶段从第8d到第36d,是一个功能混合型阶段,头肾中既有肾小管,又有造血组织;随时间推移,肾小管数量减少,淋巴细胞数量剧增。紧接着进入第三个阶段：肾小管完全消失,头肾中开始出现大量的嗜铬细胞,头肾作为淋巴-肾上腺组织而存在。肾上腺首先出现在头肾前端,随发育成熟,集中分布于头肾门静脉周围。IgM在鳜头肾中大量表达,IgM分泌细胞分布于整个头肾组织,在血管周围有集中趋势[动物学报51(3)：440—446,20051。     

Effect of acidification of the duodenal contents on splanchnic circulation and metabolism

Portal vein (PF) and superior mesenteric artery blood flows (SMAF), arterial and portal venous oxygen concentrations were measured in dogs before and after duodenal introduction of 3 ml/kg 0.1 mol HCl. The duodenal acidification increased PF by 30% and SMAF by 35%. The change of mesenteric oxygen utilisation, from 0.80 +/- 0.10 to 0.81 ml/kg was not significant. It is concluded that the circulatory changes after acidification of the duodenal contents are not secondary to a metabolic effect.     

Studies on the relationship between the estrous cycle of BALB/c mice and their resistance to Paracoccidioides brasiliensis infection

A relationship between the estrous cycle and non-specific host resistance to Paracoccidioides brasiliensis yeast cells was examined by using both sexes of adult BALB/c mice. They were divided into 6 groups, including a male group and females at proestrus, estrus, metestrus-I, metestrus-II and diestrus. The mice received yeast cells through three different inoculation routes; intravenous, intraperitoneal and intratracheal. In all of the inoculation routes, the clearance of the yeast cells was influenced by the estrous cycle. The female mice at estrus, which might have high blood estrogen levels, showed a marked clearance of the yeast cells from the blood, peritoneal cavity and lungs. These results suggested that non-specific host resistance to the yeast cells was enhanced by estrogen. All female groups inoculated by the three routes showed higher clearance of the yeast cells than the male group.     

头端延髓腹外侧区注射5—羟色胺对应激性高血粘度...

Experiments were carried out on 62 wistar rats. The hyperviscosity and elevation of blood pressure were induced by hanging and restraining the rats with their four limbs tied on a frame. It was found that microinjection of 5-HT (25 micrograms/10 microliters) into the 4th ventricle of the brain or bilateral microinjection of 5-HT (4 micrograms/0.5 microliters/site) into rostral ventrolateral medulla (rVLM) reduced stress-induced hyperviscosity (p < 0.01) and elevation of blood pressure (p < 0.01). The effect of 5-HT injected into the 4th ventricle or rVLM was blocked by bilateral microinjection of cinanserine (4 micrograms/0.5 microliter/site) into rVLM. These results suggest that microinjection of 5-HT into 4th ventricle and rVLM could reduce stress-induced hyperviscosity and elevation of blood pressure and these effects were probably mediated via 5-HT receptors in the rVLM.     

Early effect of Crotalus durissus terrificus venom on kidney circulation

Local blood flow was measured in renal cortex (1 mm below cortical surface) by means of the hydrogen clearance method in urethanized rats. Recording of blood pressure from femoral artery was performed. Crotalus durissus terrificus venom injection (one mg/kg i.v.) significantly decreased cortical blood flow at 10 min, without a significant arterial pressure modification. Posterior injection of mannitol 200 mg induced a significant increase in cortical blood flow, although initial values were not reached. Electron microscopy showed thromboses in the glomerular capillaries 35 minutes after venom injection. It is suggested that the precocious effect of this venom on renal cortical blood flow may be instrumental in the development of the renal acute insufficiency induced by Crotalus durissus terrificus venom.     

Manifestation of active and passive defensive behavior in juvenile rats

The dynamics of freezing and flight reactions in juvenile rats was investigated. The rats were tested on the 20th, 25th, 35th, and 40th postnatal days. A sound of 6-sec duration (bell) was used as a threatening stimulus. The following parameters were recorded: number of rearing reactions and defecations within 5 min prior to stimulation, reactions to the bell, latent periods and durations of freezing reactions, freezing posture rigidity, and time of recovery of movements after freezing. It was shown that the intensity of freezing reduced in the period from the 20th to 35th postnatal day. The flight reactions were highest on the 25th and 40th days. Correlations between freezing indices and numbers of rearing and defecation reactions were different in rats of all age groups. The results suggest that the structure of defensive behavior changes with maturation of principal defensive reactions in rats within the first 40 postnatal days.     

The circadian rhythm of the adrenal glucocorticoid function in female rats selected for the reaction of the estrous cycle to constant illumination

Studies have been made of the circadian rhythms of a glucorticoid hormone, corticosterone, in the adrenals and blood serum in female Wistar rats from two substrains selected for high (ESTH) and low (ESTL) ability to develop permanent oestrus under constant illumination. Significant changes in parameters of the circadian rhythm of the hormone were observed in animals of the 26th generation of selection. Total alleviation of corticosterone rhythm in the blood was on observed in ESTL rats, while in ESTH animals maximum level of the hormone in the blood was shifted to the dark time. Comparison of a high corticosterone content of the adrenals in ESTL rats with a low concentration in the blood plasma indicates the increase in metabolic clearance of the hormone in animals from this strain. It is suggested that the decreased corticosteroid production in the adrenals of ESTH rats facilitates the development of permanent oestrus under constant illumination.     

Porphyromonas gingivalis surface components induce interleukin-1 release and tyrosine phosphorylation in macrophages

Abstract (1 → 3)-β- d -Glucans have a variety of biological and immunopharmacological properties, and they are used clinically as biological response modifiers (BRMs). Clinically, these glucans have often been used for long periods by multiple dosing. During studies on the clearance and metabolism of the glucans in mice, we have found that, in the case of a single dose, the glucan was cleared from blood eventually, and remained constant in the organs for at least one month. Here, we investigated the clearance of glucans from the blood following multiple dosing using MRL lpr/lpr mice with an autoimmune disease. Two kinds of glucans, GRN from Grifola frondosa and SSG from Sclerotinia sclerotiorum , were administered to the mice once a week for more than 35 weeks (250 μg/week/mouse by the intraperitoneal route). Examination of the blood clearance of the glucans in these mice revealed that the glucan concentrations were always high (about 20 μg/ml for GRN and 200 μg/ml for SSG). It is also shown that the glucans were significantly deposited in the liver and spleen of these mice. These findings suggest that administration of a large quantity of the glucan saturated the reticuloendothelial system, resulting in circulation of the glucan in the blood.     

Stimulation of physiological functions in cooled rats without rewarming after introducing ethylenediaminetetraacetate into lateral ventricles of the brain

On cooling the animals to the rectum temperature from approximately 37 to 24-28 degrees C the decreases were shown to occur in the frequency and amplitude of respiration motions, in the intensity of muscle electrical activity (thermoregulation muscle tone and cold muscle shivering), in the frequency of heart contractions. In 3-8 min after introducing ethylenediaminetetraacetate into a lateral ventricle of the rat brain the frequency and the amplitude of respiration motions increased statistically reliable and so did the intensity of thermoregulation muscle tone and cold muscle shivering (judging from the total muscle electrical activity). The doses of EDTA, which caused this effect, were by a factor of 30 - 100 less than the doses, which caused a similar stimulation of the functions in cooled animals after introduction into the blood.     

Fatty acids in the milk of goats after cessation of lactation

Regular hand milking of six goats was discontinued after 32-35 weeks of lactation. A few days after milking out ceased, the concentration of triglyceride in peripheral blood plasma increased. Over a period of weeks, the concentration of triglyceride in small samples of fluid taken from the teat canal fell gradually. Lipase activity of the milk fluid was temporarily reduced shortly after milking out ended, but, despite this, its concentration of free fatty acids increased. It is suggested that free fatty acids are released during clearance of milk triglyceride from residual fluid in the mammary gland after cessation of lactation.     

Lipid peroxidation and regulation of it in rat blood and liver under the experimental alimentary radionuclide effect

Effect of alimentary radionuclide load (137Cs, 700 Bq for animal per day during 7, 14 and 22 days) on the lipid peroxidation intensity and blood and liver enzymatic and non-enzymatic antioxidant system in the Wistar male-rats was investigated. It was found that considerable change of antioxidant system activity in plasma and erythrocytes of experimental animals was already noticeable on the 7th day of radionuclide load. After 22 days of experiment the reliability of glutathione-dependent antioxidant system in blood was essentially decreased and lipid hydroperoxide content was increased. The increase of lipid peroxidation intensity was also found in the experimental animals liver but at the same time the activities of all studied enzymes of antioxidant system were significantly higher than they were in the control rats.     

Stimulation of thermoregulatory and respiratory functions with the help of EDTA and EGTA during deep hypothermia in rats

Influence of EDTA (C10H14N2Na2O8.2H2O) and EGTA (C14H24N2O10) on physiological functions homoiothermic organisms at deep hypothermia, was studied. White rats during cooling were in special sections without rigid fixing of head and limbs. In reply to intravenous introduction of EDTA and EGTA solutions, similar answers of the organisms were observed: raised breathing frequency and amplitude, intensity of electrical activity of muscles; these signs of activation of physiological functions lasted 8-10 minutes. Besides, of the 20th-30th minute after introduction of the second dose of preparations (at rectal temperature 17.1 +/- 0.5 degrees C), the secondary activation respiratory and thermoregulatory functions were registered. The termination of the cold shivering in experiments with introduction of EDTA and EGTA solutions occurred at lower temperatures in rectum and in a brain (16.7-17.3 degrees and 17.8-18.2 degrees C, resp.) than in control experiments (18.7 +/- 0.6 degrees C and 20.2 +/- 1.5 degrees C). The authors suppose that the activation of the thermoregulatory and respiratory functions is caused by a decrease in concentration of ions Ca2+ in the blood plasma.     

Pharmacokinetics of the antitumor antibiotic bleomycetin in cancer patients given the preparation by different methods

The pharmacokinetics of bleomycetin, a new antitumor antibiotic prepared in the USSR, was studied microbiologically. The less the extent of the main tumor in the patients, the higher the antibiotic blood levels in them. This might be associated with the adsorption capacity of the tumor tissue. The dependence of the bleomycetin kinetics on the intensity of renal clearance was shown. The characteristics of the drug distribution in the blood after intravenous, intramuscular and intrapleural administration are presented.     

Inclusion of the calcium-regulating hormones,cortisol, and blood electrolytes into early adaptive responses of the body

Comparative study of calcium-regulating hormones, cortisol and electrolytes content in blood as well as of the cardiac contractions and respiration rate before and in early terms (the 5th min., the 45th min., the 5th hour) of the motor activity maximal limitation (immobilisation) was performed in rats. It as ascertained that the maximal, limitation of motor activity even at the earliest stages are accompanied with activation of the adaptive accessory responses as well as with a significant increase in content of calcium, sodium and potassium in the blood, along with a relatively minor decrease in content of parathyroid hormone, thereocalcitonine and phosphorus. Possible mechanisms of the revealed changes as well as the role of the above endogenic factors in the organism's early adaptive responses, were discussed.