Experimental and epidemiological estimation of seasonal and climato-geographical features of non-specific resistance of the organism to influenza

One and the same series of live influenza vaccine from the strains B/Dushanbe/66 and B/Leningrad/67 or A2/Moscow/21/65 administered intranasally to non-immune persons in Leningrad and 'krasnodar in winter caused an increase in body temperature in 6.7-8% of vaccinated subjects, but in summer in 0.8%. In the transitional seasons of the year (in May and in October), 6.3-16.8% of reactions were observed in Murmansk and 0.1% in Krasnodar. An increase in antibodies in the vaccinated in Leningrad and Arkhangelsk in winter was observed 1.5 times more frequently than in summer. In Krasnodar, seroconversion occurred in only 5.7% in May and october, but in 31.3% in January; in Murmansk in 41.2-48% in May and in 75.6-78.8% in October. The seasonal as well as latitudinal and climatic differences in reactogenicity and antigenic activity of the vaccine can be explained by seasonal oscillations in non-specific resistance of people of influenza viruses. The importance of this factor in the mechanism of seasonal occurrence of influenza is discussed.     

Neuroactive steroids in the brain and age and sex specificity of behavior and anxiety: An experimental study

Changes in the brain’s neuroactive steroid levels, behavior in the open field, and the anxious-phobic status of male and female rats in the course of development have been studied. An increase in the motor and exploratory activity and emotionality in rats of both sexes in the pubertal period and a decrease in their values in mature and old animals have been detected. Anxiety has no sexual dimorphism in adult animals; it is significantly higher in males than in females in the prepubertal and pubertal periods of development and is higher in old females than in males of the same age. An increase in the level of corticosterone in some brain structures in maturing and old rats has been found; the testosterone concentration increases in one-month-old and adult animals but decreases in old individuals, while the estradiol concentration in all studied brain structures of male and female rats was low in all periods of postnatal life. Correlation analysis has shown modulation by steroid hormones of the changes in behavioral responses during development.     

Right atrial predominance of atrial natriuretic peptide secretion in isolated perfused rat atria.

In order to investigate the regulatory mechanism for the atrial release of atrial natriuretic peptide (ANP), a perfused rabbit atrial model was devised. In the present experiments, the effect of a reduction in atrial distension on the immunoreactive ANP (irANP) secretion was investigated and compared in the perfused right and left atria of rats. Elevations in right and left atrial pressure resulted in proportional increases in the volume of atrial distension-reduction which was larger in the right than in the left atria. The basal rate of irANP secretion was higher in the right than in the left atria. Increases in the volume of atrial distension-reduction resulted in proportional increases in irANP secretion in both atria. Increment in irANP secretion in response to a reduction in atrial distension was significantly higher in the right than in the left atria. Higher rate of irANP secretion in response to unit volume change was observed in the right atria. Increases in the volume of atrial distension-reduction resulted in accentuated irANP responses in the right atrium. IrANP content was significantly higher in the right than in the left atria. The results suggest that the right atrium is a predominant site in ANP secretion in rats.     

HIV epidemics in Africa: what explains the variations in HIV prevalence?

There are large differences in the prevalence of HIV infection between different regions in sub-Saharan Africa, ranging from less than 10% in pregnant women in most of West Africa, to over 25% in pregnant women in large cities in Eastern and Southern Africa. These differences in HIV prevalence are in many instances due to differences in rate of spread of the virus. The multicenter study on factors determining the differential spread of HIV in four African cities tried to identify factors that could explain differences in spread of HIV between different regions in sub-Saharan Africa. The study was conducted in four cities, including two cities with a relatively low HIV prevalence (Cotonou in Bénin and Yaoundé in Cameroon) and two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia). The difference in HIV prevalence between the four cities could not be explained by differences in sexual behavior. Any differences in sexual behavior were outweighed by differences in factors that influence HIV transmission, i.e. male circumcision and HSV-2 infection. These findings have important implications for the design of interventions.     

Seroprevalence of Neospora caninum and Toxoplasma gondii antibodies in the South American opossum (Didelphis marsupialis) from the city of São Paulo, Brazil

Antibodies to Neospora caninum and Toxoplasma gondii were assayed in sera of 396 opossums (Didelphis marsupialis) from the city of S?o Paulo, Brazil. Antibodies to N. caninum were assayed using the indirect immunofluorescent antibody test (IFAT). Antibodies (IFAT, approximately 1:25) to N. caninum were found in 84 opossums (D. marsupialis) in titers of 1:25 in 46, 1:50 in 20, 1:100 in 17, and 1:400 in 1. Antibodies to T. gondii were assayed with the modified agglutination test (MAT) and the IFAT. Antibodies to T. gondii (MAT, approximately 1:25) were found in 82 (20.4%) of the 396 opossums, in titers of 1:25 in 24, 1:50 in 26, 1:100 in 18, 1:200 in 13, and 1:800 in 1. The IFAT antibodies to T. gondii were found in 148 of 396 opossums, in titers of 1:16 in 41, 1:32 in 23, 1:64 in 13, 1:128 in 6, 1:256 in 20, 1:512 in 17, 1:1,024 in 10, 1:2,048 in 10, 1:4,096 in 7, and 1:8,192 in 1. This is the first report of N. caninum and T. gondii infections in D. marsupialis.     

Intercellular communication in in vivo- and in vitro-produced bovine embryos.

In vivo bovine embryos were obtained by nonsurgical flushing of uterine horns of cows submitted to superovulatory treatment, while in vitro embryos were generated from oocytes collected from slaughtered donors. Lucifer Yellow injected into single blastomeres did not diffuse into neighboring cells until the morula stage in in vivo embryos and the blastocyst stage in in vitro embryos. In both cases diffusion was limited to a few cells. In contrast, diffusion was extensive in microsurgically isolated inner cell mass (ICM) but absent in the trophectoderm (TE). At the blastocyst stage, diffusion was always more extensive in in vivo than in in vitro embryos. Ultrastructural analyses confirmed these functional observations, and gap junction-like structures were observed at the blastocyst stage. These structures were diffuse in the ICM of in vivo embryos, scarce in the ICM of in vitro embryos and in the TE of in vivo embryos, and not observed in the TE of in vitro embryos. Blastomeres at all stages of development from the 2-cell stage to the blastocyst stage in in vitro embryos and at the morula and blastocyst stage in in vivo embryos were electrically coupled, and the junctional conductance (Gj) decreased in in vitro embryos from 4.18 +/- 1.70 nS (2-cell stage) to 0.37 +/- 0.12 nS (blastocyst stage). At each developmental stage, in vivo embryos showed a significantly (P < 0. 05) higher Gj than in vitro-produced embryos. Moreover, a significantly (P < 0.01) higher Gj was found in isolated ICM than in the respective blastocyst in both in vivo- and in vitro-produced embryos (3.5 +/- 1.4 vs. 0.7 +/- 0.3 and 2.6 +/- 1.6 vs. 0.37 +/- 0. 12 nS, respectively). The electrical coupling in absence of dye coupling in the early bovine embryo agrees with observations for embryos from other phyla. The late and reduced expression of intercellular communicative devices in in vitro-produced embryos may be one of the factors explaining their developmental low efficiency.     

Natural incidence of interruptions in the internal elastic lamina of caudal and renal arteries of the rat

Interruptions in the internal elastic lamina (IEL) have been quantified by light microscopy in the caudal arteries of different strains of rats and in caudal and renal arteries of (i) male and female virgin rats up until 2 years of age, (ii) repeatedly bred rats and (ii) hypertensive rats. Results showed that gaps in the IEL exist in caudal arteries of adult males in all strains studied, but to a lesser extent in the hairless mutant. In the virgin Wistar rat these interruptions in the IEL form with age in both caudal and renal arteries, and are more numerous (i) in the male than in the female in both arteries, and (ii) in the caudal than in the renal artery in both sexes. Repeated breeding in the Wistar rat abolishes the sex difference in incidence of IEL gaps in both renal and caudal arteries. The Sprague-Dawley breeder rat is more susceptible than the Wistar breeder to their formation in the renal artery. Hypertension in the male consistently increases the formation of IEL gaps in the renal but not in the caudal artery. The importance of local factors, e.g. hemodynamics, in the formation of these defects in the IEL, and their possible relationship with the development of arteriosclerosis is discussed.     

Production of tumor necrosis factor in cells of hibernating ground squirrels Citellus undulatus during annual cycle

TNF production has been studied in peritoneal macrophages and splenic T cells of Arctic Yakutian ground squirrel (Citellus Undulatus Pallas) in hibernating and awake animals in winter and in prehibernating autumn as well as in active euthermic spring-summer animals. A high level of TNF production in macrophages of ground squirrel is observed over the active period and during arousals in winter. There are no significant season variations in TNF production in splenic T lymphocytes of ground squirrels. This suggests the major role of activated macrophages in the arousals of hibernating animals. T lymphocyte proliferation in ground squirrels in the active period is higher than in winter, and the most significant seasonal variations are found in T cell mitogenic response, which increases in spring-summer period. Evidence is presented that functional activity of macrophages of squirrel in autumn has much in common with that in winter rather than in spring-summer period.     

Effects of sex factors and hemispheric localization on the involvement of serotonin from the frontal cortex, striatum, and nucleus accumbens into the processing of novel and repeatedly presented information in rats

The effects of novel or relevant (a single exposure to experimental chamber) and irrelevant (20 exposures to experimental chamber) stimuli on the levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex, striatum, and nucleus accumbens in the left and right hemispheres were studied in male and female rats. It was found that 5-HT and 5-HIAA contents in the frontal cortex changed in response to neither relevant nor irrelevant stimuli. However, there were hemispheric difference in 5-HT and 5-HIAA in the frontal cortex of intact animals. The level of 5-HT in males and the level of 5-HIAA in females were higher in the left frontal cortex. In females, the level of 5-HIAA in the left striatum decreased in response to the novel stimulus. Sex differences in: a) 5-HT metabolism (increase in the level of 5-HIAA in males and increase in 5-HT in females) and b) lateralization (the striatal 5-HT metabolism in males changed bilaterally and only in the left hemisphere in females) were observed in reactions to irrelevant stimuli. Both in male and female rats, serotonin content in the nucleus accumbens changed only in response to the irrelevant stimuli. The 5-HT level increased in the left and right hemispheres independently of sex, but hemispheric difference was revealed only in females, in which the serotonin level was higher in the left nucleus accumbens. It is concluded that serotonergic neurotransmitter mechanisms are involved in hemispheric and sex differences in selective attention.     

Saccade latency during probability presentation of the visual targets in man

The latent periods of saccadic eye movements in response to peripheral visual stimuli were measured in 8 right-handed healthy subjects using Posner's paradigm "COST-BENEFIT". In 6 subjects, the saccade latency in response to visual target presented in expected location in valid condition was shorter than that in neutral condition ("benefit"). Increase in saccade latency in response to the visual target presented in unexpected location in valid condition versus neutral condition took place only in 4 subjects ("cost"). A decrease in left-directed saccade latency in response to expected target presented in the left hemifield and increase in saccade latency in response to unexpected left target in comparison with analogous right-directed saccades were observed in valid condition. This phenomenon can be explained by the dominance of the right hemisphere in the processes of spatial orientation and "disengage" of attention.     

Role of calcium in secretion of chorionic gonadotropin by first trimester human placenta.

The role of calcium in regulation of secretion of human chorionic gonadotropin (hCG) by first trimester human placental minces in vitro has been investigated. Depletion of calcium in the medium by addition of EGTA resulted in a drastic decrease in the levels of immunoreactive hCG in the medium with consequent of accumulation of hCG in the tissue. Addition of A 23187 which is a calcium ionophore resulted in a dose dose dependent increase in the hCG in the medium and this stimulatory response could not be observed in the absence of calcium. Use of lanthanum (a calcium antagonist) in place of calcium in the medium used resulted in a significant decrease in the levels of hCG in the medium. Addition of veratridine (a sodium channel activator) stimulated hCG secretion in a dose dependent manner. These results suggest that calcium is essential for normal secretion of hCG by human placenta.     

Galanin and its binding sites in the brain of eels subjected to different osmolar conditions

A galanin (GAL)-like peptidergic system was investigated in the brain of Anguilla anguilla subjected to hyperosmolar and hypoosmolar conditions, by using antisera raised against porcine 1-29 GAL. A group of immunoreactive perikaria was identified in the periventricular hypothalamus, in the ventral thalamus, in the pretectal areas and in the optic tectum. Immunoreactive perikaria were present in the nucleus lateralis of the torus semicircularis in seawater (SW) adapted eels, and were absent in the freshwater (FW) adapted eels. Galaninergic fibres were observed in many areas of the brain. The immunoreactive perikaria and fibres, when localised in the same areas, were more strongly labelled and numerous in the SW adapted eels in comparison to the FW adapted animals. GAL-specific binding sites, investigated by autoradiography using iodinated porcine GAL, occurred in several regions of the brain, in particular in the dorsal telencephalon, in the dorsal thalamus and in the torus semicircularis, where a high density of binding sites was observed in the SW adapted eels. Conversely, a higher density of binding sites was observed in the caudal substantia reticularis and in the corpus cerebelli in the FW adapted eels. We conclude that different distributions and intensity in immunoreactive elements occur in response to the two environmental conditions.     

Chemoattractant-elicited increases in Dictyostelium myosin phosphorylation are due to changes in myosin localization and increases in kinase activity

We previously reported (Berlot, C. H., Spudich, J. A., and Devreotes, P. N. (1985) Cell 43, 307-314) that cAMP stimulation of chemotactically competent Dictyostelium amoebae causes transient increases in phosphorylation of the myosin heavy chain and 18,000-dalton light chain in vivo and in vitro. In this report we investigate the mechanisms involved in these changes in phosphorylation. In the case of heavy chain phosphorylation, the amount of substrate available for phosphorylation appears to be the major factor regulating the in vitro phosphorylation rate. Almost all heavy chain kinase activity is insoluble in Triton X-100, and the increase in the heavy chain phosphorylation rate in vitro parallels an increase in Triton insolubility of myosin. Changes in heavy chain phosphatase activity are not involved in the changes in the in vitro phosphorylation rate. In the case of light chain phosphorylation, increases in the vitro phosphorylation rate occur under conditions where the amount of substrate available for phosphorylation is constant and phosphatase activity is undetectable, implicating light chain kinase activation as the means of regulation. The specificity of the myosin kinases operating in vivo and in vitro was explored using phosphoamino acid and chymotryptic phosphopeptide analysis. The light chain is phosphorylated on serine both in vivo and in vitro, and phosphopeptide maps of the light chain phosphorylated in vivo and in vitro are indistinguishable. In the case of the heavy chain, both serine and threonine are phosphorylated in vivo and in vitro, although the cAMP-stimulated increases in phosphorylation occur primarily on threonine. Phosphopeptide maps of the heavy chain show that the peptides phosphorylated in vitro represent a major subset of those phosphorylated in vivo. The kinetics of the transient increases in myosin phosphorylation rates observed in vitro can be predicted quantitatively from the in vivo myosin phosphorylation data assuming that there is a constant phosphatase activity.     

Protein synthesis in skeletal muscle of the perfused rat hemicorpus compared with rates in the intact animal.

The rate of protein synthesis was measured in muscles of the perfused rat hemicorpus, and values were compared with rates obtained in whole animals. In gastrocnemius muscle of fed rats the rate of synthesis measured in the hemicorpus was the same as that in the whole animal. However, in plantaris, quadriceps and soleus muscles rates were higher in the hemicorpus than those in vivo. In the hemicorpus, starvation for 1 day decreased the rate of protein synthesis in gastrocnemius and plantaris muscles, in parallel with decreases in the RNA content, but the soleus remained unaffected. Similar effects of starvation were observed in vivo, so that the relationships between rates in vivo and in the hemicorpus were the same as those in fed rats. Proteins of quadriceps and plantaris muscles were separated into sarcoplasmic and myofibrillar fractions. The rate of synthesis in the sarcoplasmic fraction of the hemicorpus from fed rats was similar to that in vivo, but synthesis in the myofibrillar fraction was greater. In the plantaris of starved rats the rates of synthesis in both fractions were lower, but the relationships between rates measured in vivo and in the perfused hemicorpus were similar to those seen in fed rats. The addition of insulin to the perfusate of the hemicorpus prepared from 1-day-starved animals increased the rates of protein synthesis per unit of RNA in gastrocnemius and plantaris muscles to values above those seen in fed animals when measured in vivo or in the hemicorpus. Insulin had no effect on the soleus. Overall, the rates of protein synthesis in the hemicorpus differed from those in vivo. However, the effect of starvation when measured in the whole animal was very similar to that measured in the isolated rat hemicorpus when insulin was omitted from the perfusate.     

Hypothalamic luteinizing hormone-releasing hormone (LHRH) and LH secretion in aging female rats

Age-related changes in hypothalamic luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH) secretion were studied in young (6 months), middle-aged (12 months) and old (18 months) female rats. The LHRH levels in the mid-hypothalamic area were higher in intact middle-aged and old females than in young ones. Additionally, there was no age difference in the hypothalamic LHRH levels in male rats. In order to clarify the significance of this age-related increase in female rats, we examined the effects of progesterone treatment in estrogen-primed ovariectomized young and old rats on the LHRH levels in the median eminence (ME) and on plasma LH levels. We found phasic changes in ME-LHRH and plasma LH levels in estrogen-primed rats following progesterone treatment in rats of both ages, but the progesterone-induced change in ME-LHRH levels tended to be delayed in old rats compared with young females. This delay may correspond to the delayed onset, slow and low magnitude of plasma LH increase in old females. The ME-LHRH levels were generally higher in old rats than in young rats. Nevertheless, we found that the increase in plasma LH in response to progesterone treatment in estrogen-primed ovariectomized females was smaller in old rats than young rats. These results suggest that the LHRH secretory mechanism changes with age in female rats. Such alterations may result in the accumulation of LHRH in the mid-hypothalamic area and an increase in ME-LHRH.     

Nicotine increases dopamine clearance in medial prefrontal cortex in rats raised in an enriched environment

Environmental enrichment results in differential behavioral and neurochemical responsiveness to nicotine. The present study investigates dopamine clearance (CL_DA) in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in rats raised in enriched (EC) or impoverished conditions (IC) and administered nicotine (0.4 mg/kg) or saline. Baseline CL_DA in striatum or mPFC was not different between EC and IC. Across repeated DA application, striatal CL_DA increased in saline-control EC and IC. CL_DA increased in mPFC in saline-control IC; CL_DA did not change in saline-control EC. Thus, enrichment differentially alters dynamic responses of the dopamine transporter (DAT) to repeated DA application in mPFC, but not in striatum. In EC, nicotine increased mPFC CL_DA compared to saline-control, but had no effect on CL_DA in IC; nicotine had no effect in striatum in EC or IC. Compared to respective saline-controls, nicotine increased dihydroxyphenylacetic acid content in striatum and mPFC in EC, but not in IC. Nicotine also had no effect on DA content in striatum or mPFC in EC or IC. Results indicate that enrichment eliminated the dynamic response of mPFC DAT to repeated DA application in saline-control and augmented the nicotine-induced increase in DAT function in mPFC, but not in striatum.     

Ciprofloxacin: in vivo genotoxicity studies.

The fluoroquinolone ciprofloxacin is widely used in antimicrobial therapy. It inhibits the bacterial gyrase and in high concentrations in vitro also the functionally related eukaryotic topoisomerase-II, which resulted in genotoxic effects in several in vitro tests. In order to evaluate the relevance of these findings, ciprofloxacin was tested in vivo for genotoxic activity using the following test systems: micronucleus test in bone marrow of mice, cytogenetic chromosome analysis in Chinese hamster, dominant lethal assay in male mice and UDS tests in primary rat and mouse hepatocytes in vivo. These results are compared with already published in vitro and in vivo studies with ciprofloxacin. All in vivo genotoxicity revealed no genotoxic effect for ciprofloxacin. In addition, ciprofloxacin was found to be non-carcinogenic in two rodent long-term bioassays. Therefore, ciprofloxacin is considered to be safe for therapeutic use.     

Effect of dietary fibres on constituents of complex carbohydrates in streptozotocin induced diabetic rat tissues

The effect of dietary fibres on constituents of complex carbohydrates in various tissues of streptozotocin induced diabetic rats is presented by analysing different constituents of complex carbohydrates in presence and absence of dietary fibre. Wheat bran was effective in preventing the decrease (14%) in total sugars in spleen and an increase in total sugars in stomach (33%) during diabetes. Decrease in uronic acid content during diabetes in spleen was prevented to the extent of 25% by the presence of wheat bran in the diet. The other parameters which were affected by the presence of wheat bran in the diet during diabetes are amino sugar (brain and stomach), sulphates (liver) and protein (lungs and stomach). Guar gum was effective in preventing the decrease in total sugar content in spleen by 28% and sulphate content in liver by 14% during diabetes. Variation in protein content in lungs was observed in diabetes. The results indicated beneficial role of dietary fibres like wheat bran and guar gum on complex carbohydrates to varying extents in different tissues.     

Effect of a cholesterol-biosynthesis inhibitor on the fatty acid composition of phospholipids in the serum and tissues of rats

1. Changes produced by a cholesterol-biosynthesis inhibitor, trans-1,4-bis-(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride (AY-9944), in the total fatty acids in the liver and brain, and in phospholipids in the serum, liver, heart, brain and lungs from male rats, have been studied. 2. Treatment with AY-9944 produced the following changes in the fatty acid composition: (a) a marked decrease in the percentage of linoleic acid and an increase in oleic acid in the total fatty acids in the liver; (b) in the serum, an overall decrease in the percentage of linoleic acid in neutral lipids and phospholipids; (c) an increased content of linoleic acid in the beta-acyl chain of phosphatidylcholines in the liver and in sphingomyelins in the brain and lungs; (d) an increased content of palmitic acid and oleic acid in the beta-acyl chain of phosphatidylcholine in the liver, heart and lungs; (e) an increased content of phosphatidylcholines and sphingomyelins, together with an increased percentage of saturated fatty acids in these phosphatides in the lungs. 3. Changes in the phosphatides and the production of foam cells in the lungs suggest that AY-9944 may be of use in the study of the alveolar membrane.     

The fatty acid composition of the tissues of streptozotocin-diabetic rats

The authors studied acute changes in the fatty acid composition of the tissues of streptozotocin-diabetic rats. They found that streptozotocin diabetes led to changes in the total lipids fatty acid spectrum in serum and in tissues (liver, adipose tissue, renal cortex diaphragm). After only 7 days' diabetes there was an increase in the percentual proportion of saturated fatty acids and a decrease in the amount of polyene fatty acids in the serum and in all the above tissue of diabetic animals. Palmitic acid (16:0) participated in the increase in the proportion of saturated fatty acids in all the given tissues, while stearic acid (18:0) played a role in the increase in the renal cortex and the serum. Among the monoene acids, there was a drop in the proportion of palmitoleic acid (16:1) in the adipose tissue and serum and in the amount of oleic acid (18:1) in the renal cortex, liver and muscle. Linoleic acid (18:2) played a role in the decrease in the proportion of polyene acids in all the given tissues and the serum, while arachidonic acid (20:4) was involved in the drop in the renal cortex, liver and muscle. The results show that diabetes leads to changes in the fatty acid composition of the renal cortex and muscle, as well as of the liver and adipose tissue. At present it is not yet clear whether there is an absolute decrease in the proportion of essential fatty acids, or whether diabetes is characterized by an increase in the amount of lipids in both serum and tissues.