The immunomodulating action of aminoglycoside antibiotics via different administration technics]

It was shown that intramuscular administration of aminoglycosides such as gentamicin and amikacin had an immunosuppressive action in healthy animals. Administration of the antibiotics entrapped in erythrocyte shades increased the immune response. The immunostimulating effect was higher when the aminoglycosides entrapped in allogenic erythrocytes were administered. After the routine administration of the antibiotics they were detected in the blood and urine within the first hours after the administration. After administration of the antibiotics entrapped in erythrocyte shades their detection was later in time. When the aminoglycosides entrapped in allogenic erythrocytes were administered they were not detected in the biological fluids.     

Effects of human growth hormone on erythrocyte insulin binding in growth hormone deficient children

In this paper, the effect of acute human growth hormone (GH) administration on erythrocyte insulin binding in GH deficient children (N = 6) was studied. Following GH (0.25 U/kg) administration, the blood levels of GH peaked within 4 to 8 h and returned to basal levels 24 h later. However, the changes in somatomedin activity, free fatty acid (FFA), urea, blood glucose and 125I-insulin binding to erythrocyte were observed around 24 h following the injection, and there was a converse relationship between maximum percent 125I-insulin binding (IBmax) and FFA (P less than 0.02). By Scatchard analysis it was found that the decrease in IBmax is mainly due to the change in the number of insulin receptors. These results suggest that GH may possibly affect the insulin binding to erythrocyte indirectly through metabolic changes as a result of hormonal changes in GH deficient children.     

Erythropoietin attenuates cachectic events and decreases production of interleukin-6, a cachexia-inducing cytokine

In cancer cachexia, erythropoietin often yields beneficial therapeutic effects by improving patient's metabolic and exercise capacity via an increased erythrocyte count. However, erythropoietin also has counter-regulatory effects against pro-inflammatory cytokines, which are postulated to be mediators of cancer cachexia. We investigated the mechanisms by which erythropoietin improves the cachectic condition. In this study, 100 Units/day of erythropoietin were administered intraperitoneally to BALB/c male mice, carrying a subclone of colon 26 adenocarcinoma, beginning on the day after tumor inoculation and continuing until they died. Erythropoietin administration attenuated the decline in body weight, as well as the decline in fat and muscle weights, of tumor-bearing mice, but improved the survival of cachectic mice. Mice receiving erythropoietin had increased erythrocyte and platelet counts, but significantly decreased white blood cell count. In addition, erythropoietin administration significantly decreased interleukin-6 levels, not only in serum but also in the inoculated tumor. These results indicate that the positive therapeutic effects of erythropoietin on cancer cachexia are due, not only to improving metabolic and exercise capacity via an increased erythrocyte count, but also to attenuation of cachectic manifestations by decreased production of the cachexia-inducing cytokine, interleukin-6.     

Haematological changes in experimental hydralazine-induced collagen-like syndrome in guinea pigs.

Haematological studies were carried out in hydralazine-induced collagen-like syndrome in guinea pigs. 37.5 per cent of animals were found to be LE-positive. It was found that long-term administration of hydralazine caused a decrease of erythrocyte count, a decrease of haemoglobin concentration and a decrease of haemoglobin content in individual red blood cell as well as a decrease of a single erythrocyte volume. A significant leukopenia was shown in LE-positive subgroup of hydralazine-treated guinea pigs. The obtained results confirmed the similarity of hydralazine syndrome to systemic lupus erythematosus.     

Erythrocyte pyrimidine 5'-nucleotidase inhibition by acute lead exposure in neonatal rats

Inhibition by lead of erythrocyte pyrimidine 5'-nucleotidase (P5N) is thought to contribute to morphological abnormalities observed in red blood cells (RBC) of lead-exposed subjects. However, neither the mechanism of lead inhibition of P5N nor the relationship of this inhibition to blood lead levels attained in exposed subjects is known. In the present investigation, acute in vivo and in vitro lead acetate effects on erythrocyte P5N from 21-day-old rat pups were determined and were related to blood lead concentrations ascertained by atomic absorption spectrophotometry. Acute lead administration to rat pups resulted in a 16% to 21% reduction in erythrocyte P5N, with mean blood lead levels ranging from 77 to 108 micrograms/dl 24 hours later. Inhibition of erythrocyte P5N was linearly related to blood lead level (r = -0.67, P less than 0.05) following acute lead administration. Lead acetate addition to RBC preparations from 21-day-old rats resulted in concentration-dependent P5N inhibition which was comparable to that produced following acute in vivo exposure. The results indicate that acute P5N inhibition in lead-treated neonatal rats is due to noncompetitive P5N inhibition by lead. The inhibition of P5N produced by acute lead treatment is linearly related to blood lead concentrations.     

Cytotoxic effect of poly-dispersed single walled carbon nanotubes on erythrocytes in vitro and in vivo

Single wall Carbon Nanotubes (SWCNTs) are hydrophobic and do not disperse in aqueous solvents. Acid functionalization of SWCNTs results in attachment of carboxy and sulfonate groups to carbon atoms and the resulting acid functionalized product (AF-SWCNTs) is negatively charged and disperses easily in water and buffers. In the present study, effect of AF-SWCNTs on blood erythrocytes was examined. Incubation of mouse erythrocytes with AF-SWCNTs and not with control SWCNTs, resulted in a dose and time dependent lysis of erythrocyte. Using fluorescence tagged AF-SWCNTs, binding of AF-SWCNTs with erythrocytes could be demonstrated. Confocal microscopy results indicated that AF-SWCNTs could enter the erythrocytes. Treatment with AF-SWCNTs resulted in exposure of hydrophobic patches on erythrocyte membrane that is indicative of membrane damage. A time and dose dependent increase in externalization of phosphatidylserine on erythrocyte membrane bilayer was also found. Administration of AF-SWCNTs through intravenous route resulted in a transient anemia as seen by a sharp decline in blood erythrocyte count accompanied with a significant drop in blood haemoglobin level. Administration of AF-SWCNTs through intratracheal administration also showed significant decline in RBC count while administration through other routes (gavage and intra-peritoneal) was not effective. By using a recently developed technique of a two step in vivo biotinylation of erythrocytes that enables simultaneous enumeration of young (age <10 days) and old (age>40 days) erythrocytes in mouse blood, it was found that the in vivo toxic effect of AF-SWCNTs was more pronounced on older subpopulation of erythrocytes. Subpopulation of old erythrocytes fell after treatment with AF-SWCNTs but recovered by third day after the intravenous administration of AF-SWCNTs. Taken together our results indicate that treatment with AF-SWCNTs results in acute membrane damage and eventual lysis of erythrocytes. Intravenous administration of AF-SWCNTs resulted in a transient anemia in which older erythrocytes are preferably lysed.     

Ethological and haematological response of catfish,Heteropneustes fossilis,exposed to exogenous urea

Exposure of the airbreathing catfish,Heteropneustes fossilis to a sublethal concentration (200 mg/l) of urea resulted in blanching of skin, increased mucus secretion, hyperexcitability and higher rate of surfacing and gill ventilation. These changes were more pronounced during the first eight days of exposure as compared to the later period. A progressive increase in haematocrit, erythrocyte count, percentage of immature erythrocytes, mean corpuscular volume and erythrocyte sedimentation rate was observed during the 20 day exposure period. White blood cell-thrombocyte count registered a sharp decline initially upto 6 days but steadily increased afterwards. Initial decrease in the total leucocyte count was found to be mainly due to the decline in the number of lymphocytes and thrombocytes while the percentage of granulocytes (neutrophils and eosinophils) and monocytes showed a reverse trend.     

Influence of prednisolone on cells erythroid series in the bone marrow of rabbits immunized with diphtheria toxoid]

The bone marrow reaction to prednisolone showed significant changes after the administration of the antigen: there proved to be a significant reduction of the erythrocyte count, hemoglobin content and of hematocrite. The mean erythrocyte volume increased. Along with this there was a reduction of the number of basophilic and polychromatophilic erythroblasts and an increase in number of proerythroblasts. The degree of depression of the red series of the bone marrow (induced by prednisolone) was much less in case of combined administration of prednisolone and diphtheria toxoid.     

Erythrocyte pyrimidine 5′-nucleotidase inhibition by acute lead exposure in neonatal rats

Inhibition by lead of erythrocyte pyrimidine 5′-nucleotidase (P5N) is thought to contribute to morphological abnormalities observed in red blood cells (RBC) of lead-exposed subjects. However, neither the mechanism of lead inhibition of P5N nor the relationship of this inhibition to blood lead levels attained in exposed subjects is known. In the present investigation, acute in vivo and in vitro lead acetate effects on erythrocyte P5N from 21-day-old rat pups were determined and were related to blood lead concentrations ascertained by atomic absorption spectrophotometry. Acute lead administration to rat pups resulted in a 16% to 21% reduction in erythrocyte P5N, with mean blood lead levels ranging from 77 to 108 μg/dl 24 hours later. Inhibition of erythrocyte P5N was linearly related to blood lead level (r = ?0.67, P < 0.05) following acute lead administration. Lead acetate addition to RBC preparations from 21-day-old rats resulted in concentration-dependent P5N inhibition which was comparable to that produced following acute in vivo exposure. The results indicate that acute P5N inhibition in lead-treated neonatal rats is due to noncompetitive P5N inhibition by lead. The inhibition of P5N produced by acute lead treatment is linearly related to blood lead concentrations.     

Haematological values during normal reproduction of the maternal and the fetal rabbit

1. Haematological values of non-pregnant/non-lactating, pregnant as well as lactating rabbits and 28-day-old fetuses were measured. 2. The haemoglobin content in does decreased during the observed periods from 122 +/- 8 g/l to 100 +/- 11 g/l. In 28-day-old fetuses it was 85 +/- 0 g/l. 3. The erythrocyte count in 28-day-old fetuses was 2.4 X 10(12)/l. In the does, the erythrocyte count was 5.2 X 10(12)/l in week 4 of gestation. The erythrocyte volume in fetuses was about 45% higher than that of the doe. 4. In fetuses the leucocyte count was approximately one ninth that of the mother in week 4 of gestation (0.41 +/- 0.08 X 10(9)/l vs 3.8 +/- 0.4 X 10(9)/l).     

Testosterone action on erythropoiesis does not require its aromatization to estrogen: Insights from the testosterone and estrogen treatment of two aromatase-deficient men

Androgens act on erythropoiesis, but the relative role of testosterone (T) and estradiol (E₂) on erythropoietic parameters in men is a poorly investigated issue. In order to evaluate separately the effects on erythropoiesis of high-dose T administration alone and of physiological dose of E₂ administration alone two adult men with aromatase deficiency were assessed before and during each treatment. Blood cell count, hemoglobin (Hb), hematocrit (Hct), erythrocyte mean cell volume (MCV), erythrocyte mean corpuscular hemoglobin (MCH), erythrocyte mean corpuscular hemoglobin concentration (MCHC), serum ferritin, iron and total iron-binding capacity (TIBC), serum erythropoietin, serum total testosterone and estradiol were evaluated. Hb, Hct and red cell count rose during testosterone treatment, consistently with the increase in circulating testosterone, but failed to increase during estradiol treatment. A decrease in Hb, Hct and red cell count was recorded in one of the two subjects during estradiol treatment, with a concomitant decrease in serum testosterone. Circulating T alone is capable of and sufficient to influence erythropoiesis, especially at supraphysiological dosage, while circulating E₂ have not the same effect on erythropoietic parameters, suggesting the hypothesis that the erythropoietic changes induced by androgens are not mediated via its aromatization to estrogens.     

Effects of pyrazidol on resistance of animals to hypobaric hypoxia]

The influence of monoamine oxidase type A inhibitor pyrazidol on rats sensitivity to hypobaric hypoxia was investigated. Preliminary pyrazidol administration shows evident protective effect under hypoxia. It increases animals survival at the altitude of 12,000 m above the sea level, prevents lungs affection and erythrocyte membrane destabilization at the altitude of 9,000 m during 3 hours. Plasma total peroxidase activity, extraerythrocyte hemoglobin concentration and free iron content were used as the indexes of erythrocyte membrane stability reflecting the organism state under stress effects.     

Some selected peripheral blood and haemopoietic system indices in Wistar rats with chronic vanadium intoxication

1. Wistar rats of both sexes received vanadium in drinking water in the amount of 23-29 mg/kg body weight in the form of ammonium metavanadate (AMV) for a period of 2, 4 and 8 weeks. 2. Animals treated in this way ate less food and drank less AMV solution as compared with the amount of water consumed by the controls; they suffered from diarrhoea, and owing to this the increment in body weight was reduced. 3. Vanadium decreased erythropoiesis and maturation of red blood cells, which was expressed by a reduced erythrocyte count and haemoglobin level and increased reticulocyte and polychromatophilic erythrocyte count in the peripheral blood. 4. The composition percentage of the bone marrow cells and the peripheral blood leukocyte count did not undergo noticeable changes under the influence of vanadium.     

Endotoxin-induced changes in the rabbit's blood picture

The authors studied changes in the rabbit's blood picture in the first 24 hours after the administration of three different doses of endotoxin. The most pronounced changes were observed in the white blood component, particularly the granulocytes, which almost vanished from the blood stream immediately after the endotoxin was injected. In 24 hours granulocytopenia was succeeded by marked granulocytosis. Changes in the lymphocytes were smaller; the lymphocyte count fell slightly about 3 hours after the injection of endotoxin, but by 24 hours it was almost normal again. The platelet count also fell after the administration of endotoxin, but the red blood picture remained virtually the same.     

Experimental studies on anaemia in sheep infected with Dictyocaulus filaria

The pathogenesis of Dictyocaulus filaria induced anaemia was experimentally investigated. Nineteen Dorset-Muzaffarnagri male lambs were divided into two groups of 13 and six. The lambs in the former group received a primary infection dose of 2000 D. filaria infective larvae, whereas animals in the latter group were kept as uninfected controls. The haematological alterations and faecal larval output were monitored weekly until day 220 post-infection. The infection caused an increase in erythrocyte sedimentation rate (ESR) and total leukocyte count (TLC). However, a decrease in packed cell volume (PCV), haemoglobin, total erythrocyte count (TEC) and blood pH was observed in acute infection. The shape and size of the erythrocytes, serum bilirubin level, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) remained unaffected In carriers, except for TEC, the values of these parameters returned to near-normal levels. The analysis of the results suggests that the infected animals developed a normocytic normochromic anaemia which persisted during the later stage of infection.     

Interferon-inducing activity of hydroxybenzylamine derivative]

Interferon-inducing activity of the interferon inductor savrats, an oxybenzylamine derivative of was studied. It was shown on experimental animals that along with its low toxicity, savrats had a high interferon inducing capacity. There were early and late peaks of interferon production (4-8 and 48-96 hours later, respectively) depending on the route of the inductor administration. It was noted that for optimization of the schemes for using interferon inductors, careful choosing of the drug pairs participating in the induction and employment of various routes for administration of the same drug are required.     

Physical exercise effect on erythrocyte metabolism

A group of 27 canoeists from the national team and 35 subjects beginning training in a sports discipline were subjected to investigations for determination of glucose utilization by erythrocytes, and the level of lactic acid in these cells and in serum. Furthermore, erythrocyte count and haematocrit value were determined in them. Both groups performed submaximal and maximal work on cycle ergometer. In the trained sportsmen the erythrocyte count and haematocrit value were higher already before exercise. During the exercise the increase in these values, as well as the rise in erythrocyte and serum lactic acid levels were again greater than in untrained freshmen. This difference was caused by the fact that the trained sportsmen performed twice as much work. Glucose utilization by erythrocytes (in vitro) was greatest after maximal exercise in both groups. The differences observed between both groups became manifest during exercise with a greater rise in glucose utilization by the erythrocytes obtained from the trained group. Fifteen minutes after the exercise this utilization fell in both groups below the value obtained before exercise. During the same time erythrocyte count and haematocrit returned to their initial levels.     

Some aspects of neurophysiological basis of insecticide action.

When the insecticide parathion was administered to awake, unrestrained rats with chronically implanted brain electrodes, it was observed that the latency of the averaged flash-evoked potential in the visual cortex and superior colliculus was increased and the amplitude was decreased 2 to 4 hours later with responses returning to pretreatment levels about 8 hours after administration. Similarly, after administration of several dose levels of parathion in the rat, durations of phases of the maximal electroshock seizure (MES) pattern were altered to the greatest extent 4 hours later, but effects disappeared at 24 hours. These effects of parathion on the MES and evoked potentials coincided with a fall in blood and brain acetylcholinesterase (AChe) activities but disappeared after AChe inhibition had reached its peak and stabilized. Brain AChe activities required 2 to 4 weeks for recovery whereas blood AChe activity recovered in 1 week following inhibition by parathion (at least 2 mg/kg body weight). Studies in the monkey demonstrated similar results. Because these measurements of central nervous system function returned to normal despite continued inhibition of AChe activity, the results are interpreted to mean either that adaptation of evoked potentials or MES responses to prolonged AChe inhibition can occur in the rat and monkey after parathion administration or that some of the effects of parathion do not depend on AChe inhibition. Administration of DDT (100 mg/kg by mouth) to awake, unrestrained rats markedly increased the amplitude of spontaneous electrical activity in the cerebellum, whereas there was much less effect on electrical activity recorded simultaneously in the occipital cortex, reticular formation, and medial geniculate body. Similarly, DDT administration had marked effects on the averaged, sound evoked potential recorded in the cerebellum; DDT caused the appearance and increased the amplitude of an early component of this response not usually present during control recordings. Sound-evoked potentials recorded simultaneously from the frontal and occipital cortex and reticular formation were affected less or were decreased in amplitude by administration of DDT.     

Effect of erythrocyte breakdown products on mast cells and erythropoietin formation]

Experiments were conducted on CBA mice and albino rats. A study was made of the effect of erythrocyte destruction products (EDP) on the content of hemopoietic colony-forming units (CFU), differentiation of stem cells and the erythropoietin production. It was shown that 3 or 4 EDP injections to normal mice or to lethally irradiated (1000 rad) mice after the transplantation of bone marrow cells caused no changes in the CFU level of stem cells differentiation. In case of a daily (for 3 days) administration of EDP to mice before the irradiation (1000 rad) and bone marrow transplantation there was observed an increase of the colonies count in the recipients' spleen on account of the erythroid colonies. EDP injection caused no changes in the erythropoietic activity of the blood serum. A possible role of erythrocyte destruction products in the mechanism of erythropoiesis autoregulation is discussed.     

The effects of thyroid scintigraphy studies on oxidative damage in patients

The majority of radiation injury in cells depends on oxidative stress. Irradiation and absorbed doses, duration of the irradiation and the susceptibility of the tissue against radiation are the factors that cause variations on living cells. The aim of this study was to investigate gamma radiation-induced oxidative damage in erythrocytes after thyroid scintigraphy with Tc-99m pertechnetate. Fifteen patients (8 women and 7 men) who performed thyroid scintigraphy with Tc-99m pertechnetate were included in this study. The median age was 52 +/- 8 years (range 33-65). The blood samples were taken from patients just before, 1 hour after and three hours after injection of radiopharmaceutical. Malondialdehyde (MDA) and antioxidant enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) levels were measured to evaluate the gamma radiation induced oxidative damage. No difference was detected in any final measurement activities of erythrocyte antioxidant enzyme such as SOD and GPX in the direct comparison between the before and after injection of the radiopharmaceutical groups, except erythrocyte CAT activities measured 1 hour after and 3 hours after injection of the radiopharmaceutical (p < 0.05). MDA levels were decreased 1 hour after and 3 hours after injection of the radiopharmaceutical.