170 Short-term Exposure to High Glucose Alters Acetylcholine Sensitivity and Maximal Relaxation in Male and Female Rat Pudendal Artery, Respectively, Which is Reversed With Testosterone Incubation

2018 ◽  
Vol 15 (2) ◽  
pp. S51-S52
Author(s):  
N.S. Klee ◽  
C. Webb
2021 ◽  
pp. 074823372110105
Author(s):  
Roberta Tassinari ◽  
Andrea Martinelli ◽  
Mauro Valeri ◽  
Francesca Maranghi

Synthetic amorphous silica (SAS) nanomaterial – consisting of aggregates and agglomerates of primary silicon dioxide (SiO2) particles in the nanorange (<100 nm) – is commonly used as excipient in pharmaceuticals, in cosmetics and as food additive (E551). The available data suggest that SAS nanoparticles (NP) after intravenous (IV) exposure persist in liver and spleen; however, insufficient data exist to verify whether SAS may also induce adverse effects. The aim of the present study was to verify the potential long-term effects of SAS NP (NM-203) on spleen and liver as target organs following short-term exposure. Adult male and female Sprague-Dawley rats were treated by IV injection in the tail vein with a single (1-day) dose (SD) and repeated (5-day) doses (RD) of 20 mg/kg bw per day of SAS dispersed in sterile saline solution as vehicle. Histopathological examinations of target organs were performed after 90 days. Tissue biodistribution and full characterization of NM-203, primary particle size 13–45 nm, was performed within the framework of the Nanogenotox project. No mortality or general toxicity occurred; histopathological analysis showed splenomegaly in the RD group accompanied by inflammatory granulomas in both sexes. Granulomas were also present in liver parenchyma in the RD (both sexes) and SD groups (male only). The histopathological results indicated that SAS NP have the potential to persist and induce sex-specific chronic inflammatory lesions in spleen and liver upon short-term treatment. Overall, the data showed that the widespread use of silica in drugs might elicit chronic reactions in spleen and liver prompting to the need of further investigations on the safety of SAS NP.


2014 ◽  
Vol 61 (5) ◽  
pp. 457-470 ◽  
Author(s):  
Shiva PD Senthil Kumar ◽  
Minqian Shen ◽  
Elizabeth G Spicer ◽  
Ashley J Goudjo-Ako ◽  
Justin D Stumph ◽  
...  

2020 ◽  
pp. 803-812
Author(s):  
S SEELEY ◽  
M D’SOUZA ◽  
T STOOPS ◽  
B RORABAUGH

Methylphenidate is commonly used for the treatment of attention deficit hyperactivity disorder. The cardiovascular safety of methylphenidate has been a subject of debate with some studies indicating that methylphenidate increases the likelihood of experiencing a myocardial infarction. However, it is unknown whether methylphenidate worsens the extent of injury during an ischemic insult. The purpose of this study was to determine whether short term exposure to methylphenidate increases the extent of myocardial injury during an ischemic insult. Male and female rats received methylphenidate (5 mg/kg/day) or saline for 10 days by oral gavage. Hearts were subjected to 20 min of ischemia and 2 h of reperfusion on a Langendorff isolated heart apparatus on day 11. Cardiac contractile function was monitored via an intraventricular balloon and myocardial injury was assessed by triphenyltetrazolium chloride staining. Methylpheni-date significantly increased locomotor activity in male and female rats, confirming absorption of this psychostimulant into the central nervous system. Male hearts had significantly larger infarcts than female hearts, but methylphenidate had no impact on infarct size or postischemic recovery of contractile function in hearts of either sex. These data indicate that methylphenidate does not increase the extent of injury induced by an ischemic insult.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Adedotun O. Afolayan ◽  
Temitope I. Borokini ◽  
Gloria O. Afolayan

Raphia hookeri fruits are used for fishing in Nigeria due to their ichthyotoxic properties. This study investigated the toxic effects of R. hookeri on the reproductive capacity of Clarias gariepinus. The results from both short-term (96-hour test) and long-term (3-month sublethal test) bioassays revealed a linear relationship between R. hookeri extract dose and negative effects on the catfish. The percentage survival of both sexes of the catfish decreased with increasing extract concentration at short-term exposure, with LC50 values of 600 mg/L and 800 mg/L for male and female, respectively. At long-term exposure, the reproductive capacity of 10–12-month-old male and female brood-stocks diminished at relatively higher concentrations of R. hookeri fruit extract, with the gravid females producing fewer and mostly unviable eggs. The fruit extract also affected the eggs’ hatchability and fry survival when the exposed gravid females were treated with pituitary hormone and sperms from unexposed males, while the exposed males were unable to sexually stimulate female brooders. Sperms and pituitary hormone from exposed males were infertile, leading to low percentage of hatched eggs and mortality of the few hatched fries within 24 hours. These results confirmed the ethnobotanical use of this fruit extract for fishing in Nigeria.


2020 ◽  
Vol 122 (5) ◽  
pp. 151558
Author(s):  
Julia Matuszewska ◽  
Kamil Ziarniak ◽  
Monika Dudek ◽  
Paweł Kołodziejski ◽  
Ewa Pruszyńska-Oszmałek ◽  
...  

2000 ◽  
Vol 1 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Marwan Hamaty ◽  
Cristina B. Guzmán ◽  
Mary F. Walsh ◽  
Ann M. Bode ◽  
Joseph Levy ◽  
...  

Impaired vascular endothelium-dependent relaxation and augmented contractile responses have been reported in several models of long-term hyperglycemia. However, the effects of short-term ambient hyperglycemia are poorly understood. Since oxidative stress has been implicated as a contributor to impaired vascular function, we investigated the following:Aims: (1) the effects of high glucose exposurein vitro(7 – 10 days) on vascular relaxation to acetylcholine (Ach) and contractility to norepinephrine (NE) and KCl; (2) if NO-dependent cGMP generation is affected under these conditions; and (3) aortic redox status.Methods: Non-diabetic rat tail artery rings were incubated in normal (5mM) (control NG) or high (20mM) glucose buffer (control HG). Vascular responses to Ach, NE and KCl were compared to those of streptozotocin (SZ) diabetic animals in the same buffers (diabetic NG, diabetic HG). Ach stimulated cGMP levels were quantitated as an indirect assessment of endothelial nitric oxide (NO) production and oxidative stress evaluated by measuring vascular glutathione and oxidized glutathione.Results: Rings from diabetic rats in NG showed impaired relaxation to Ach (P= 0.002) but relaxed normally, when maintained in HG. Similarly, contractile responses to NE were attenuated in diabetic rings in NG but similar to controls in HG. HG markedly augmented maximal contraction to KCl compared to control and diabetic vessels in NG (P< 0.0001). Diabetic vessels in a hyperosmolar, but normoglycemic, milieu respond like those in HG.in vitro, HG for 2 hours changed neither relaxation nor contractile responses to NE and KCl in control rings. Basal cGMP levels were lower in aortae from diabetic animals pre-incubated in NG than in HG/LG or in control rings in NG (P< 0.05). cGMP responses to Ach were exaggerated in diabetic vessels in HG (P= 0.035vs. control NG,P= 0.043vs. diabetic NG) but not different between control and diabetic rings in NG. Vessels from diabetic animals had lower levels of GISH (P< 0.0001) and higher levels of GSSG (P< 0.0001) indicating oxidative stress.Conclusions: Our data indicate that endothelium dependent relaxation is altered early in the diabetic state and that increased NO responses may compensate for augmented oxidative stress but the lack of effect of short-term exposure of normal vessels to HG suggests that short-term hyperglycemiaper sedoes not cause abnormal vascular responses.


1976 ◽  
Vol 36 (01) ◽  
pp. 221-229 ◽  
Author(s):  
Charles A. Schiffer ◽  
Caroline L. Whitaker ◽  
Morton Schmukler ◽  
Joseph Aisner ◽  
Steven L. Hilbert

SummaryAlthough dimethyl sulfoxide (DMSO) has been used extensively as a cryopreservative for platelets there are few studies dealing with the effect of DMSO on platelet function. Using techniques similar to those employed in platelet cryopreservation platelets were incubated with final concentrations of 2-10% DMSO at 25° C. After exposure to 5 and 10% DMSO platelets remained discoid and electron micrographs revealed no structural abnormalities. There was no significant change in platelet count. In terms of injury to platelet membranes, there was no increased availability of platelet factor-3 or leakage of nucleotides, 5 hydroxytryptamine (5HT) or glycosidases with final DMSO concentrations of 2.5, 5 and 10% DMSO. Thrombin stimulated nucleotide and 5HT release was reduced by 10% DMSO. Impairment of thrombin induced glycosidase release was noted at lower DMSO concentrations and was dose related. Similarly, aggregation to ADP was progressively impaired at DMSO concentrations from 1-5% and was dose related. After the platelets exposed to DMSO were washed, however, aggregation and release returned to control values. Platelet aggregation by epinephrine was also inhibited by DMSO and this could not be corrected by washing the platelets. DMSO-plasma solutions are hypertonic but only minimal increases in platelet volume (at 10% DMSO) could be detected. Shrinkage of platelets was seen with hypertonic solutions of sodium chloride or sucrose suggesting that the rapid transmembrane passage of DMSO prevented significant shifts of water. These studies demonstrate that there are minimal irreversible alterations in in vitro platelet function after short-term exposure to DMSO.


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