scholarly journals Renal hemodynamic and excretory responses to intra-arterial infusion of peroxynitrite in anesthetized rats

2009 ◽  
Vol 296 (1) ◽  
pp. F170-F176 ◽  
Author(s):  
Luis C. Matavelli ◽  
Philip J. Kadowitz ◽  
L. Gabriel Navar ◽  
Dewan S. A. Majid

Peroxynitrite (ONOO−) is formed endogenously by the reaction of nitric oxide (NO) and superoxide (O2−). To examine the hypothesis that OONO− cause renal vasodilation at low concentrations but cause vasoconstriction at higher concentrations, we examined renal responses to intra-arterial infusion of incremental doses of OONO− (10, 20, and 40 μg·kg−1·min−1; 45 min each) in anesthetized rats. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearance. In control rats ( n = 6), low dose (10 μg·kg−1·min−1) of OONO− increased RBF by 10 ± 3% and GFR by 15 ± 5%. The higher doses (20 and 40 μg·kg−1·min−1) mostly reversed these responses which were −7 ± 4 and −27 ± 7% ( P < 0.05) in RBF and −0.1 ± 4.8 and −14 ± 12% in GFR, respectively. There were no appreciable changes in urine flow (V) and sodium excretion (UNaV) during OONO− infusion. However, in rats pretreated with NO synthase (NOS) inhibitor, l-NAME (50 μg·kg−1·min−1; n = 5), these doses of ONOO− significantly reduced RBF (−26 ± 7, −27 ± 6, and −44 ± 3%) and GFR (−21 ± 6, −25 ± 8, and −32 ± 12%) with variable increases in V or UNaV. Long-term infusion of OONO− (10 μg·kg−1·min−1 for 75 min) in another set of control rats ( n = 5) also showed similar vasodilator and hyperfiltration responses. These data indicate that ONOO− acts as an oxidant at high concentration but provides renoprotective function at low concentration that depends on intact NOS activity.

2010 ◽  
Vol 29 (5) ◽  
pp. 523-531 ◽  
Author(s):  
Mirella Falconi ◽  
Michela Ortolani ◽  
Gabriella Teti ◽  
Michela Zago ◽  
Giovanna Orsini ◽  
...  

The purpose of this study was to evaluate the cytotoxicity of low doses and long-term exposure to 2-hydroxyethylmethacrylate (HEMA) on the protein expression of human gingival fibroblasts (HGFs). Human gingival fibroblasts were exposed to different concentrations of HEMA ranging from 0.5 mmol/L to 3 mmol/L for periods of time from 72 hours to 2 weeks. A significant decrease in the expression of procollagen α1 type I protein was observed 72 hours after treatment of cells with 3 mmol/L HEMA. Although low concentrations of the monomer after 2 weeks of exposure to HEMA did not appear to induce any marked changes in the morphology or viability of cells, the expression of procollagen α1 type I protein and its messenger RNA (mRNA) markedly decreased. In conclusion, our data demonstrated that cell viability and morphology assays could be deficient parameters in evaluating the biocompatibility of dental resin materials.


1982 ◽  
Vol 93 (3) ◽  
pp. 866-874 ◽  
Author(s):  
M C Kielian ◽  
R M Steinman ◽  
Z A Cohn

The long-term exposure of macrophages to low concentrations of a number of polyanions leads to their accumulation in high concentration within secondary lysosomes. This was associated with enlargement of the lysosomes, the presence of membranous whorls, and intense toluidine blue staining of the organelles at pH 1.0. After the ingestion of a particulate load by these cells, newly formed phagocytic vacuoles failed to fuse with polyanion-laden lysosomes. The lack of fusion was evident in both fluorescence and electron micrographic studies which followed the transfer of acridine orange or Thorotrast from 2 degrees lysosomes to phagosomes. Agents that inhibited phagosome-lysosome (P-L) fusion included molecules containing high densities of sulfate, sulfonate, or carboxylate residues. Dextran sulfate (DS) in microgram/ml quantities was an excellent inhibitor, whereas nonsulfated dextran (D) was without effect at 1,000-fold higher concentrations. In contrast to their effects on P-L fusion, polyanions failed to influence the fusion of pinocytic vesicles with 2 degrees lysosomes. The uptake, intravacuolar distribution, and intralysosomal digestion of fluid-phase pinocytic markers were unaltered in lysosomes containing either D or DS. Furthermore, subcellular fractionation studies showed that the fluid-phase pinocytic marker HRP was efficiently transferred from pinosomes to large, dense 2 degrees lysosomes containing DS.


1996 ◽  
Vol 271 (2) ◽  
pp. R333-R338 ◽  
Author(s):  
T. E. Scammell ◽  
J. K. Elmquist ◽  
C. B. Saper

The labile gas nitric oxide (NO) mediates a wide variety of thermoregulatory processes including vasomotor control, brown fat thermogenesis, and neuroendocrine regulation. Additionally, during endotoxemia, NO modulates the release of cytokines and hypothalamic peptides. To determine the role of NO in thermoregulation and fever, we intravenously injected the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and measured its effects on body temperature during normal thermoregulation and endotoxemia in awake, unrestrained rats. L-NAME produced a stereoselective, dose-dependent hypothermia that lasted up to 4 h after bolus intravenous injection. Intravenous lipopolysaccharide (LPS) produced fever in a dose-dependent manner, which was preceded by hypothermia at higher doses alpha-LPS. NOS inhibition reduced the febrile response to LPS and produced marked hypothermia with a low dose of LPS. These findings indicate that NO may play an important role in thermoregulation and suggest that NO is required for the production of fever.


2017 ◽  
Vol 25 (1) ◽  
pp. 51
Author(s):  
T. Eve ◽  
L. Nief ◽  
S. Gonçalves ◽  
C. Fontfreyde ◽  
S. Jurjanz

<p>The ingestion of 3 hay types by growing rabbits and the consequences on animal performance were studied in a first part. Two kinds of hay from high nature value grasslands [CFP (<em>Colchico-Festucetum pratensis</em>) and SBR (<em>Senecioni-Brometum racemosi</em>)] differentiated by their botanical composition were compared to a classical agricultural hay (control). The 3 hays, offered <em>ad libitum</em>, were ingested at 30.6, 34.8 and 36.1 g/kg body weight (BW) respectively for SBR, CFP and the control, where the consumption of SBR hay was significantly lower. (P&lt;0.01). The type of hay distributed did not affect the consumption of commercial feed or growth (44 g/kg BW and 36 g/d, respectively). The effect of meadow saffron concentration (<em>Colchicum autumnale</em>) in CFP hay was tested at 3 doses (absence, 2.75 and 15% of the distributed hay mass) with respect to their effect on ingestion and animal health. Again, no effect of the presence of meadow saffron (MeS) in the hay on these parameters was observed, even at the highest dose. However, during this second part, rabbits preferred to consume meadow saffron instead of the rest of the distributed hay (hardly any MeS was refused by rabbits at the representative dose, whereas 12% of the rest of the hay was refused, and 3.4 and 20% respectively at the maximal dose). The intake of the toxic alkaloid colchicine corresponded to 30 to 44% of the median lethal doses (LD<sub>50</sub>) at the representative and maximal doses respectively. The real exposure of the rabbits was probably lower, as the absorption of ingested colchicine is reported to be around 50% of the LD<sub>50</sub> values which are established after an intravenous injection. Nevertheless, the absence of any effect should be interpreted with caution. The colchicine content of MeS varied greatly depending on the time of harvest and the parts of the plant taken into consideration. A late harvest (mid-June or later) would ensure (very) low concentrations of colchicine in the aerial parts of MeS. The presence of cloves on this plant should be completely avoided, due to the very high concentration of colchicine in the seeds. Moreover, long term exposure of the animals to this toxic plant may increase the risk of adverse effects. The study shows that hay distribution can aid digestion without altering the animal’s performance. Moreover, the valorisation of hay from high nature value grasslands would not only add real value to the commercialisation of rabbit meat by commercial breeders, but also to pet owners on the condition that hay quality would be guaranteed.</p>


2019 ◽  
Vol 34 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Juan Carlos Bazo-Alvarez ◽  
Tim P Morris ◽  
James R Carpenter ◽  
Joseph F Hayes ◽  
Irene Petersen

Background: Antipsychotics are often prescribed for long-term periods, however, most evidence of their impact on body weight comes from short-term clinical trials. Particularly, impact associated with dosage has been barely studied. Aims: The aim of this study was to describe the short- and long-term change in body weight of people initiated on high or low doses of the three most commonly prescribed second-generation antipsychotics. Methods: Retrospective cohorts of individuals with a diagnosed psychotic disorder observed from 2005 to 2015 in the UK primary care. The exposure was the first prescription of olanzapine, quetiapine or risperidone. The main outcome was change in body weight four years before and four years after initiation of antipsychotic treatment, stratified on sex and ‘low’ or ‘high’ dose. Results: In total, 22,306 women and 16,559 men were observed. Olanzapine treatment was associated with the highest change in weight, with higher doses resulting in more weight gain. After 4 years, given a high dose of olanzapine (> 5 mg), women gained on average +6.1 kg; whereas given a low dose (⩽ 5 mg), they gained +4.4 kg. During the first six weeks of olanzapine treatment, they gained on average +3.2 kg on high dose and +1.9 kg on low dose. The trends were similar for men. Individuals prescribed risperidone and quetiapine experienced less weight gain in both the short- and long-term. Conclusions: Olanzapine treatment was associated with the highest increase in weight. Higher doses were associated with more weight gain. Doctors should prescribe the lowest effective dose to balance mental-health benefits, weight gain and other adverse effects.


Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.


2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.


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