Impulse Flow in Sympathetic Efferents of the Abdominal Aortic Nerve after Intrathecal Administration of the Substrate and Inhibitor of Nitric Oxide Synthase

Experiments were performed on rats anesthetized with urethane and nembutal. Intrathecal administration of a nitric oxide inhibitor L-NAME (60 mg) into the cerebrospinal fluid of the thoracic spinal cord was followed by a 40–45% decrease in tonic activity of efferent fibers of the abdominal aortic nerves. L-NAME reduced a reflex increase in the rate of efferent impulses, which was induced by tetanic stimulation of afferent C-fibers in the mesenteric nerve. Administration of L-arginine into the cerebrospinal fluid of the spinal cord (80 mg/20 ml) was accompanied a long-term increase in tonic activity of efferent fibers of the abdominal aortic nerves (by 15–20%). These changes reflect a prolonged activating effect of L-arginine on sympathetic structures. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 3, pp. 249–253, March, 2009     

Exogenous ghrelin improves blood flow distribution in pulmonary hypertension-assessed using synchrotron radiation microangiography

Ghrelin has cardioprotective properties and, recently, has been shown to improve endothelial function and reduce endothelin-1 (ET-1)-mediated vasoconstriction in peripheral vascular disease. Recently, we reported that ghrelin attenuates pulmonary hypertension (PH) caused by chronic hypoxia (CH), which we hypothesized in this study may be via suppression of the ET-1 pathway. We also aimed to determine whether ghrelin’s ability to prevent alterations of the ET-1 pathway also prevented adverse changes in pulmonary blood flow distribution associated with PH. Sprague–Dawley rats were exposed to CH (10% O₂ for 2 weeks) with daily subcutaneous injections of ghrelin (150 μg/kg) or saline. Utilizing synchrotron radiation microangiography, we assessed pulmonary vessel branching structure, which is indicative of blood flow distribution, and dynamic changes in vascular responsiveness to (1) ET-1 (1 nmol/kg), (2) the ET-1_A receptor antagonist, BQ-123 (1 mg/kg), and (3) ACh (3.0 μg kg⁻¹ min⁻¹). CH impaired blood flow distribution throughout the lung. However, this vessel “rarefaction” was attenuated in ghrelin-treated CH-rats. Moreover, ghrelin (1) reduced the magnitude of endothelial dysfunction, (2) prevented an increase in ET-1-mediated vasoconstriction, and (3) reduced pulmonary vascular remodeling and right ventricular hypertrophy—all adverse consequences associated with CH. These results highlight the beneficial effects of ghrelin for maintaining optimal lung perfusion in the face of a hypoxic insult. Further research is now required to establish whether ghrelin is also an effective therapy for restoring normal pulmonary hemodynamics in patients that already have established PH.     

Antitumor and antimetastatic activity of fucoidan,a sulfated polysaccharide isolated from the Okhotsk sea <Emphasis Type="Italic">Fucus evanescens</Emphasis> brown alga

Antitumor and antimetastatic activities of fucoidan, a sulfated polysaccharide isolated from Fucus evanescens (brown alga in Okhotsk sea), was studied in C57Bl/6 mice with transplanted Lewis lung adenocarcinoma. Fucoidan after single and repeated administration in a dose of 10 mg/kg produced moderate antitumor and antimetastatic effects and potentiated the antimetastatic, but not antitumor activities of cyclophosphamide. Fucoidan in a dose of 25 mg/kg potentiated the toxic effect of cyclophosphamide. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 675–677, June, 2007     

In vivo validation of Aloe ferox (Mill). Elephantorrhiza elephantina Bruch. Skeels. and Leonotis leonurus (L) R. BR as potential anthelminthics and antiprotozoals against mixed infections of gastrointestinal nematodes in goats

Aloe ferox (Mill)., Elephantorrhiza elephantina Bruch. Skeels. and Leonotis leonurus (L) R. BR. are some of the plants used by farmers in the Eastern Cape Province to control worms in goats, but information on their efficacy is lacking. The study was conducted to determine efficacy of these plants on gastrointestinal nematodes in natural mixed infections in goats. Forty-eight male goats aged 8–12 months were divided into eight groups (Treatments A–H) of six animals each, balanced in terms of liveweight and worm egg count. Treatments A to F received plant extracts, three animals in each group receiving doses of 250 mg/kg and the other three receiving 500 mg/kg at concentration of 100 mg/ml, while those in G and H received Valbazen? (11.36% albendazole) at 10 mg/kg, and 0.5 ml/kg distilled water, respectively per os. Faecal samples were collected on days 0, 3, 6 and 9 for faecal egg counts (FEC), and body weights recorded on days 1 and 9. Results showed significant reductions (P < 0.05) in strongyle eggs by A. ferox extract at dose levels of 500 mg/kg on days 3, 6 and 9, while reductions in Eimeria spp. oocysts were observed on days 3, 6 and 9 for animals that received 500 mg/kg doses. E. elephantina caused significant reduction (P < 0.05) of Trichuris spp. eggs on days 3 and 6, respectively at 250 mg/kg dose level, whereas L. leonurus also caused significant reduction (P < 0.05) in FEC of Trichuris spp. and Eimeria spp. oocysts at 250 mg/kg dose level on day 9. Albendazole caused reductions (P < 0.05) in strongyle eggs on days 3 and 6, Trichuris spp. on days 3, 6 and 9, and on coccidia, it caused a reduction (P > 0.05) on day 1, whereas on days 6 and 9, there was an increase. On total mixed infections, highest FECR% were observed with the extract of A. ferox on days 3 (53%), 6 (54%) and 9 (58%) at 500 mg/kg,whereas albendazole had efficacy levels of 39%, 44% and 29% on days 3, 6 and 9, respectively. Body weight of goats from days 1 to 9 were not significant different from the control. The study revealed efficacy of A. ferox, E. elephantina and L. leonurus against gastrointestinal parasites at high doses (500 mg/kg), showing that the plants have the potential to be used as anthelminthics.     

UHF-dielectrometry of the urine in prognosis of aggregation stability

The hypothermic effects of 5-HT_1A serotonin receptor agonist 8-OH-DPAT after intranasal, intraperitoneal, and subcutaneous administration were compared. In a dose of 1 mg/kg 8-OH-DPAT induced similar thermal reactions after administration by all three routes. In a dose of 0.5 mg/kg 8-OH-DPAT caused no appreciable changes in body temperature after intraperitoneal injection and decreased it after subcutaneous and intranasal administration. No genotypic differences in the effects of 5-HT_1A receptor agonist administered by different routes were detected in four inbred mouse strains. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 413-415, October, 2008     

Effect of radioprotector indralin on carboplatinum hemotoxicity

A decrease in carboplatinum hemotoxicity was detected in experiments on C57Bl mice treated with the drug in combination with indralin (urgent radioprotector). Carboplatinum in a dose of 125 mg/kg, injected intraperitoneally, caused 80–100% death; the median term of death was 6 days (3–17). Single oral dose of indralin (100 mg/kg) during the 1st min or 15 min after carboplatinum injection (125 mg/kg) increased animal survival by 40.0–46.7% by day 20 of the experiment primarily during the period of manifest hemotoxicity (days 7–17), indralin injected 1, 2, or 4 h after carboplatinum exhibited no chemoprotective effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 422–424, April, 2006     

Improved efficacy of tetracycline by acaciasides on <Emphasis Type="Italic">Dirofilaria immitis</Emphasis>

The discovery of Wolbachia, a bacterial endosymbiont that occurs in the filarial parasite and its sensitivity to tetracycline, has fostered a new initiative in the development of suitable antifilarial drugs. The present study is an attempt to investigate whether adding acaciasides (saponins from Acacia auriculiformis) to the standard dose of tetracycline would further improve the efficacy of tetracycline treatment against Dirofilaria immitis microfilariae in vivo. Treatment of microfilaremic adult dogs (body weight range 8–12 kg) with tetracycline at 10 mg/kg/day for 40 days resulted in 72% and 83% reduction in mf count on days 15 and 30, respectively, and the maximum reduction in mf count (91%) was achieved on day 75 post-treatment. However, treatment with tetracycline (10 mg/kg/day for 40 days) followed by acaciasides (10 mg/kg/day for 7 days) resulted in almost 100% clearance of mf at a faster rate on day 45 post-treatment and ensured long-term (until 4 months post-treatment) protection against microfilaremia. Data from polymerase chain reaction analysis reveals that compared to untreated dogs, in treated dogs, there was marked reduction in Wolbachia specific wsp markers in fast depleting mf population. The present data indicate that prior tetracycline treatment enhances microfilaricidal activity of saponins. This effect may be additive or synergistic as the worms are weakened by Wolbachia depletion, and these weakened microfilariae are possibly killed by the saponins. S. Datta and S. Maitra have contributed equally in this paper.     

Antithrombogenic and Antiplatelet Activities of Extract from <Emphasis Type="Italic">Maackia amyrensis</Emphasis> Wood

Antithrombogenic and antiplatelet effects of a new drug, containing isoflavonoids (extract from the wood of Maackia amyrensis, a Far Eastern plant), were studied. A course (200 mg/kg intragastrically during 14 days) of Maackia amyrensis extract prevented intravascular clotting, initiated by application of 10% iron chloride solution on the vessel. The drug increased antiaggregant activity of the vascular wall and potentiated endothelium-dependent vasodilatation in ovariectomied rats. The reference drug ethinylestradiol (25 μg/kg intragastrically during 14 days) potentiated the antiaggregant effect of the endothelium, but was inferior to Maackia amyrensis extract in the capacity to induce endothelium-dependent vasodilatation in ovariectomied rats. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 2, pp. 164-167, February, 2009     

Tactile impairments cannot explain the effect of age on a grasp and lift task

This experiment addressed the often-posed theory that age-related declines in manual dexterity result from diminished tactile function. We measured the time ’young’ subjects (n=33; mean=45 years) and ’old’ subjects (n=33; mean=74 years) needed to grip (thumb and index finger), lift, and transport a small metal sphere when vision was permitted and when blindfolded. Subjects began each trial by reaching for the sphere and were instructed to complete the entire task quickly. In the absence of visual information, placement of the finger and thumb for a secure grip and lift cannot be performed efficiently without tactile information. If age-related tactile changes are functionally significant for this task, then without visual information the ’old’ group should show a disproportionate increase in the duration of the grip and lift phase of the task compared to the ’young’ group. Perceptual thresholds for tactile pressure stimuli (Semmes-Weinstein filaments) confirmed well-known age-related changes. Age and vision effects were manifest mainly during the grip-lift phase (time from object contact to lift-off from its support surface), with the expected finding that the ’old’ group required more time than ’young’ group, regardless of visual condition. The main finding was that the ’grip-lift’ duration in the ’no-vision’ condition was about twice the duration observed in the ’vision’ condition for both age groups (ratios of 2.1 and 2.3 for ’young’ and ’old’, respectively). This similar relative slowing for the two groups fails to support the hypothesis that old adults’ ability to grip and lift the object was limited by changes in the availability or use of tactile information. Received: 30 September 1997 / Accepted: 26 January 1998     

Ratio between the contents of 11-dehydrocorticosterone and corticosterone after acute and repeated stress: Effect of dehydroepiandrosterone sulfate

Acute stress was accompanied by reduction of 11-dehydrocorticosterone to corticosterone in male rats. The reverse reaction predominated during repeated stress and increased after administration of dehydroepiandrosterone sulfate. Treatment with μ-opioid receptor antagonist naltrexone in a dose of 0.1 mg/kg 20 min before administration of dehydroepiandrosterone sulfate abolished this effect. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 158–161, August, 2004     

Effectiveness evaluation of several cattle anthelmintics via the fecal egg count reduction test

Utilizing groups of cograzed, naturally infected beef-type heifers, three fecal egg count reduction tests were conducted in the later months of 2007 at the University of Arkansas. Each test was 28 days in length consisting of individual animal fecal nematode egg counts and coprocultures. Both original and generic ivermectin injectable formulations were used in two of the tests at 0.2 mg/kg BW, with FECR percentages never exceeding 90% in either test. Oral fenbendazole was evaluated at 5 and 10 mg/kg BW, with FECR%'s exceeding 90% on all occasions, but with a precipitous drop when recently treated animals were treated at the lower dose. Evaluated in one test, injectable moxidectin given at 0.2 mg/kg BW resulted in egg count reductions of 96–92% (days 7 to 28). Also evaluated in one test, albendazole delivered orally at 10 mg/kg BW was 98% and 97% effective at 17 and 28 days post-treatment. For all tests, coprocultures conducted post-treatment contained only Cooperia spp. larvae (benzimidazole use), relatively unmodified percentages of Cooperia spp. and Haemonchus spp. larvae (ivermectin use), and primarily Cooperia spp. larvae with a small percentage of Haemonchus spp. larvae (moxidectin use).     

Impact of chronic intermittent external compressions on forearm blood flow capacity in humans

During dynamic exercise, the vasculature embedded within skeletal muscle intermittently collapses due to increased intramuscular pressure (IMP). The aim of this study was to ascertain whether oscillations in IMP during muscle contractions independently contribute to exercise training-induced increases in blood flow capacity (BFC). Based on IMP measurements during handgrip exercise, we attempted to mimic the action of repeated vascular compressions by using external inflatable cuffs. Thus, 24 healthy young male subjects underwent a 4-week program (5 days/week, 1 h/day) of application of external compressions of the non-dominant forearm, while the dominant limb served as an internal control. To evaluate the impact of compression pressures of different magnitudes, subjects were randomly assigned to one of three groups: 50, 100 and 150 mmHg of external compression. Prior to the intervention and after 2 and 4 weeks of treatment, we measured peak forearm blood flow (PBF) (Doppler ultrasound) and calculated peak vascular conductance (PVC) following 10 min of forearm ischemia. In the 50 and 100 mmHg groups, application of intermittent compressions did not alter PBF in either control or intervention forearms. In the 150 mmHg group, there was a trend (P = 0.04) for greater increases in PBF from baseline after 4 weeks in the intervention forearm compared to the control forearm (delta PBF: 4.2 ± 2.5 vs. −2.1 ± 2.0 (ml(100 ml)⁻¹ min⁻¹), in the intervention and control forearms, respectively), but the changes in PVC were not significant (P = 0.1). These findings suggest that repeated oscillations in IMP contribute minimally to exercise-induced increase in forearm BFC in healthy young humans.     

Analysis of NM23 Protein and Components of Plasminogen Activation System in Tumors of Patients with Stomach Cancer with Consideration for Disease Clinical Picture and Morphology

Immunohistochemical analysis of the expression and distribution of nm23 protein and biochemical analysis of the main components of plasminogen activation system in tumors were carried out in stomach cancer patients. The data indicate that the expression of nm23 protein in malignant epithelial gastric tumors is heterogeneous, characterized by cytoplasmic and nuclear immunoreactivity. Reduced expression of the marker is more typical of poorly or undifferentiated tumors. The expression of nm23 protein positively correlated with tPA level (r _s = 0.4; p = 0.01) and did not correlate with the content of uPA and PAI-1 in tumors. High PAI-1 values in tumors (>0.5 ng/mg protein) significantly correlated with lower 3-year overall survival of stomach cancer patients. These data confirm the role of the studied proteins in invasion and metastases of malignant tumors and suggest a relationship between changes in the expression of nm23 protein and mechanisms of stomach cancer progress. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 12, pp. 686–690, December, 2008     

<Emphasis Type="Italic">In Vivo</Emphasis> Effect of Selective Macrophage Suppression on the Development of Intrahepatic Cholestasis in Mice

We studied the role of selective suppression of liver Kupffer cells (gadolinium chloride, 14 mg/kg intravenously) in the development of intrahepatic cholestasis in CBA/C57Bl/6 mice after intraperitoneal injection of α-naphthylisothiocyanate in a single dose of 200 mg/kg. Pretreatment with gadolinium chloride increased the severity of cholestasis and signs of liver damage. Gadolinium accumulation in the liver peaked after 24 h and was accompanied by a decrease in activities of cathepsin D and cathepsin B and concentration of matrix metalloprotease-2. Our results confirm the hypothesis that normal function of Kupffer cells and extracellular matrix plays an important role in cholestasis. Administration of gadolinium chloride serves as a convenient model to study the side effects, toxicity, and safety of lanthanides as nanoparticles. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 10, pp. 376–380, October, 2008     

Study of cholesterol-lowering effect and safety of simvaglisin on rabbit model of hypercholesterolemia

Using rabbit model of experimental hypercholesterolemia we showed that the hypocholesterolemic effect of simvaglisin, a complex preparation containing simvastatin and glycyrrhizic acid, in doses corresponding to 40, 66.5, and 100 mg/kg/day simvastatin is equal to the hypocholesterolemic effect of 200 mg/kg/day simvastatin alone. The total blood cholesterol decreased by 39, 36, 47, and 38% (p<0.05), respectively, after 20-day course of the preparation. Myotoxicity of simvaglisin evaluated by serum creatine phosphokinase was lower than that of simvastatin. After 30-day treatment, this parameter was lower by 26, 24, and 29% (p<0.05) than the corresponding parameter for simvastatin. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 285–287, March, 2008     

Cell microvesicles during experimental endotoxemia

The dynamics of microvesicle formation in arterial blood in generalized Schwartzman phenomenon was studied. Successive (with 24-h interval) intravenous injections of endotoxin to rabbits in a dose of 1 mg/kg and 3 mg/kg caused an increase in the content of microvesicles in the blood, some of them containing ecto-5′-nucleotidase. Biphasic changes in arterial blood clotting time and erythrocyte hemolysis were observed. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 11, pp. 517–520, November, 2006     

Morphometric changes, biochemical values, and kidney morphology of male West African Dwarf goats exposed to 2,4-dichlorophenoxyacetic acid (2,4-D)

This study investigated the morphometric changes, biochemical parameters, and kidney morphology of male West African Dwarf goats exposed to graded levels of 2,4-dichlorophenoxyacetic acid (2,4-D). Four groups of five goats were used for this experiment. Goats in three of the groups were exposed to oral administration of 2,4-D as follows: group A, low dose (75 mg/kg body weight); group B, medium dose (100 mg/kg body weight); and group C, high dose (125 mg/kg body weight); every 72 h for a period of 112 days. The group D goats served as the control and received no 2,4-D treatment. Morphometric changes, biochemical parameters, and histomorphological features of the kidney of goats exposed to 2,4-D were compared with control goats. Exposing male goats to 2,4-D treatment led to reduction in mean body weights (p < 0.05), mean blood glucose (p < 0.05), and mean total serum protein (p < 0.05) concentrations. The histomorphology of the kidney sections of the 2,4-D-treated goats was that of subacute to chronic exudative glomerulonephritis; and the severity of lesions increased with higher 2,4-D concentration. It was concluded that exposing male West African Dwarf goats to varied concentrations of 2,4-D herbicide resulted in reduction in weight gain, changes in blood glucose and total serum protein concentrations, as well as glomerular, tubular, and interstitial lesions in the kidney.     

Antiplasmodial activity of Xanthium strumarium against Plasmodium berghei-infected BALB/c mice

The present work was undertaken to evaluate the antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant Xanthium strumarium in Plasmodium berghei-infected BALB/c mice along with phytochemical screening and acute toxicity test to support its traditional medicinal use as a malaria remedy. The ethanolic leaves extract of X. strumarium (ELEXS) 150, 250, 350 and 500 mg/kg/day demonstrated dose-dependent chemosuppression during early and established infection long with significant (p < 0.001) repository activity. The oral administration of 500 mg/kg/day concentration showed a maximum of 88.6% chemosuppression during early infection, which was more than that of the standard drug chloroquine (5 mg/kg/day) with 88.3% chemosuppression. However, 60% mortality has been found in this group. The LD₅₀ of ELEXS was found to be 1.5 g/kg/mouse. The administration of 350 mg/kg/day concentration of extract have been found to exert 90.40% chemosuppression during repository infection, which was well comparable to standard drug pyrimethamine (1.2 mg/kg/day) exerting 92.91% chemosuppression. The extract has been found to enhance mean survival time of mice from 21 to 26 days with 250 and 350 mg/kg/day concentrations, while 150 mg/kg/day concentration has been found to sustain all the mice up to 29 days which was similar to the employed standard drug chloroquine (5 mg/kg/day). All these findings support the ethanopharmacological use of X. strumarium as malarial remedy and indicate the potential of plant for active antiplasmodial components.     

Behavioral Changes in Rats Induced by a Dipeptidyl Peptidase IV Inhibitor Methionyl-2(S)-Cyanopyrrolidine: Experimental Model of Anxiety-Depression Disorder

Administration of a synthetic dipeptidyl peptidase IV inhibitor methionyl-2(S)-cyanopyrrolidine (1 mg/kg) to rats during the early postnatal period was followed by the development of behavioral changes in young and adult animals. The degree of anxiety in the elevated plus maze increased in treated rats at the age of 1–2 months. Depressive behavior in the forced swimming test was typical of animals aging 2–3 months. Diazepam reduced the severity of anxiety in treated rats. Melipramine had a normalizing effect on swimming behavior. A novel prolyl endopeptidase inhibitor benzyloxycarbonylmethionyl-2(S)-cyanopyrrolidine had the antidepressant properties. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 3, pp. 254–260, March, 2009     

The effects of dietary enzyme on some blood biochemical parameters of the cultured great sturgeon Huso huso juveniles

In this study the effects of dietary exogenous enzyme (Kemin?; 0, 250, 500, 750 and 1,000 mg/kg) on certain blood biochemical parameters (total protein, glucose, cholesterol) and serum magnesium in cultured great sturgeon (Huso huso) juveniles were determined. Juveniles (mean weight 10.2 ± 0.8 g) were fed three times a day at 5–10% body weight for 46 days. Serum total protein concentration remained unaffected except in fish fed with 750 mg/kg enzyme which was significantly higher than the other treatments. Although dietary enzyme did not affect the glucose level in juveniles fed with 1,000 mg/kg enzyme, its level decreased significantly in other groups. Serum cholesterol of the fish decreased in all treatments except in fish fed 750 mg/kg dietary enzyme. Magnesium levels were higher in the groups that received 500–750 mg/kg dietary enzyme.