scholarly journals Fluoropolymer-based Emulsions for the Intravenous Delivery of Sevoflurane

2008 ◽  
Vol 109 (4) ◽  
pp. 651-656 ◽  
Author(s):  
Jonathan P. Fast ◽  
Mark G. Perkins ◽  
Robert A. Pearce ◽  
Sandro Mecozzi

Background The intravenous delivery of halogenated volatile anesthetics has been previously achieved using phospholipid-stabilized emulsions, e.g., Intralipid. However, fluorinated volatile anesthetics, such as sevoflurane, are partially fluorophilic and do not mix well with classic nonfluorinated lipids. This effect limits the maximum amount of sevoflurane that can be stably emulsified in Intralipid to 3.5% vol/vol. This is a significant limitation to the potential clinical use of Intralipid-based emulsions. Methods The authors prepared a 20% vol/vol sevoflurane emulsion using a novel fluorinated surfactant and tested its effectiveness and therapeutic index by administering it to male Sprague-Dawley rats via intravenous injection into the jugular vein. The median effective dose to induce anesthesia (ED50), the median lethal dose (LD50), and the therapeutic index (LD50/ED50) were determined. Anesthesia was measured by loss of the forepaw righting reflex. Results The ED50 and LD50 values were found to be 0.41 and 1.05 ml emulsion/kg body weight, respectively. These lead to a therapeutic index of 2.6, which compares favorably with previously determined values of emulsified isoflurane, as well as values for propofol and thiopental. Conclusions A novel semifluorinated surfactant was able to considerably increase the maximum amount of stably emulsified sevoflurane compared with Intralipid. These formulations can be used to rapidly induce anesthesia with bolus dosing from which recovery is smooth and rapid.

Author(s):  
Redzuan Nul Hakim Abdul Razak ◽  
Suzanah Abdul Rahman ◽  
Asmah Hanim Hamdan ◽  
Roszaman Ramli ◽  
Muhammad Lokman Md Isa ◽  
...  

Aquilaria malaccensis or commonly known as ‘gaharu’ is a species of Aquilaria genus and belongs to the Thymelaeaceae family. It is widely distributed in Malaysia, Indonesia, and the Borneo Islands. Traditionally, its leaves were used to relieve bruises and studies have shown that they function as an antioxidant, aphrodisiac, and tranquilizer. Despite its proven beneficial medicinal properties, information regarding its toxicity is limited. Therefore, we performed a safety evaluation on the aqueous A. malaccensis leaves extract (AMAE) in Sprague Dawley rats. The assessment of acute toxicity based on the Organization for Economic Cooperation and Development (OECD) Guideline 420 revealed that AMAE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 2000 mg/kg body weight. In the sub-acute toxicity, all doses did not significantly modify the body weight and food and water intake. In male rats treated with 2000 mg/kg, there was a significant reduction in the relative weight of liver. Not only that, an increase in alkaline phosphatase and alanine transaminase was also observed in different groups among the female rats. A significant decrease in the creatinine level was also seen among male rats administered with different doses of AMAE. In both sexes, histopathological analysis had shown abnormalities in the liver and kidney of rats treated at the dose of 2000 mg/kg. In conclusion, the 50% lethal dose (LD50) of AMAE was estimated to be greater than 2000 mg/kg. In sub-acute duration, the findings suggested that AMAE administered orally is slightly toxic at higher doses (2000 mg/kg) and could provoke functional and structural changes in the kidney and liver of rats. Thus, the extract should be used with caution.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Liang ◽  
Jing Ma ◽  
Bo Wei

AbstractTo investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.


1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.


2008 ◽  
Vol 198 (3) ◽  
pp. 617-624 ◽  
Author(s):  
Alaa E S Abdel-Razik ◽  
Ellen J Forty ◽  
Richard J Balment ◽  
Nick Ashton

Urotensin II (UTS) is a potent vasoactive peptide that was originally identified in teleost fish. Mammalian orthologues of UTS and its receptor (UTSR) have been described in several species, including humans and rats. We have shown previously that bolus injections of UTS caused a decrease in urine flow and sodium excretion rates in parallel with marked reductions in renal blood flow (RBF) and glomerular filtration rate (GFR). The aim of this study was to determine the effect of UTS infusion at a dose that has minimal impact upon renal haemodynamics in order to identify a potential direct tubular action of UTS. Infusion of rat UTS (rUTS) at 0.6 pmol/min per 100 g body weight in male Sprague–Dawley rats, which had no effect on RBF and caused a 30% reduction in GFR, resulted in a significant increase in the fractional excretion of sodium (vehicle 2.3±0.6 versus rUTS 0.6 pmol 4.5±0.6%, P<0.05) and potassium. At the higher dose of 6 pmol/min per 100 g body weight, haemodynamic effects dominated the response. rUTS induced a marked reduction in RBF and GFR (vehicle 1.03±0.06 versus rUTS 6 pmol 0.31±0.05 ml/min per 100 g body weight, P<0.05) resulting in an anti-diuresis and anti-natriuresis, but no change in fractional excretion of sodium or potassium. Uts2d and Uts2r mRNA expression were greater in the renal medulla compared with the cortex. Together, these data support an inhibitory action of Uts2d on renal tubule sodium and potassium reabsorption in the rat, in addition to its previously described renal haemodynamic effects.


1998 ◽  
Vol 274 (2) ◽  
pp. R412-R419 ◽  
Author(s):  
Barry E. Levin ◽  
Richard E. Keesey

Among outbred Sprague-Dawley rats, approximately one-half develop diet-induced obesity (DIO) and one-half are diet resistant (DR) on a diet relatively high in fat and energy content (HE diet). Here we examined the defense of body weight in these two phenotypes. After HE diet for 13 wk, followed by chow for 6 wk, DR rats gained weight comparably but their plasma leptin levels fell to 54% of chow-fed controls. When a palatable liquid diet (Ensure) was added for 13 wk, other DR rats became obese. But when switched to chow, their intakes fell by 60%, and body and retroperitoneal (RP) fat pad weights and plasma leptin and insulin levels all declined for 2 wk and then stabilized at control levels after 6 wk. In contrast, comparably obese DIO rats decreased their intake by only 20%, and their weights plateaued when they were switched to chow after 13 wk on HE diet. When a subgroup of these DIO rats was restricted to 60% of prior intake, their weights fell to chow-fed control levels over 2 wk. But their leptin and insulin levels both fell disproportionately to 30% of controls. When no longer restricted, their intake and feed efficiency rose immediately, and their body and RP pad weights and leptin and insulin levels rose to those of unrestricted DIO rats within 2 wk. Thus diet and genetic background interact to establish high (DIO) or low (DR) body weight set points, which are then defended against subsequent changes in diet composition and/or energy availability. If leptin affects energy homeostasis, it does so differentially in DIO vs. DR rats since comparably low and high levels were associated with differing patterns of weight change between the two phenotypes.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 321
Author(s):  
Kokila Vani Perumal ◽  
Nor Liyana Ja’afar ◽  
Che Norma Mat Taib ◽  
Nurul Husna Shafie ◽  
Hasnah Bahari

Obesity is one of the risk factors associated with cardiovascular diseases, hypertension, abnormal liver function, diabetes, and cancers. Orlistat is currently available to treat obesity, but it is associated with adverse side effects. Natural resources are widely used for obesity treatment. Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. The rats’ obesity was induced by a high-fat (HF) diet made up of 50% standard rat pellet, 20% milk powder, 6% corn starch, and 24% ghee and a cafeteria (CAF) diet such as chicken rolls, salty biscuits, cakes, and cheese snacks. A hot aqueous method for the extraction of E. tapos shells was applied by using 500 mL of distilled water for about 24 h. Various dosages of E. tapos shell extract (10 mg/kg, 100 mg/kg, and 200 mg/kg) were used. At the end of the study, body weight, caloric intake, organ weight, lipid profile, lipoprotein lipase (LPL) activity, and histopathology analysis were carried out. E. tapos shell extract treated groups showed a reduction in body weight, positive lipid-lowering effect, decrements in triglyceride accumulation and LPL activity, and positive improvement in histopathology analysis. A dose of 200 mg/kg showed the most effective result compared to 10 mg/kg and 100 mg/kg doses.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Saira Tanweer ◽  
Tariq Mehmood ◽  
Saadia Zainab ◽  
Zulfiqar Ahmad ◽  
Muhammad Ammar Khan ◽  
...  

Purpose Innovative health-promoting approaches of the era have verified phytoceutics as one of the prime therapeutic tools to alleviate numerous health-related ailments. The purpose of this paper is to probe the nutraceutic potential of ginger flowers and leaves against hyperglycemia. Design/methodology/approach The aqueous extracts of ginger flowers and leaves were observed on Sprague Dawley rats for 8 weeks. Two parallel studies were carried out based on dietary regimes: control and hyperglycemic diets. At the end of the experimental modus, the overnight fed rats were killed to determine the concentration of glucose and insulin in serum. The insulin resistance and insulin secretions were also calculated by formulae by considering fasting glucose and fasting insulin concentrations. Furthermore, the feed and drink intakes, body weight gain and hematological analysis were also carried out. Findings In streptozotocin-induced hyperglycemic rats, the ginger flowers extract depicted 5.62% reduction; however, ginger leaves extract reduced the glucose concentration up to 7.11% (p = 0.001). Similarly, ginger flowers extract uplifted the insulin concentration up to 3.07%, while, by ginger leaves extract, the insulin value increased to 4.11% (p = 0.002). For the insulin resistance, the ginger flower showed 5.32% decrease; however, the insulin resistance was reduced to 6.48% by ginger leaves (p = 0.014). Moreover, the insulin secretion increased to 18.9% by flower extract and 21.8% by ginger leave extract (p = 0.001). The feed intake and body weight gain increased momentously by the addition of ginger flowers and leaves; however, the drink intake and hematological analysis remained non-significant by the addition of ginger parts. Originality/value Conclusively, it was revealed that leaves have more hypoglycemic potential as compared to flowers.


2015 ◽  
Vol 70 (5-6) ◽  
pp. 151-157 ◽  
Author(s):  
Ye Pan ◽  
Peng Lü ◽  
Lijing Yin ◽  
Keping Chen ◽  
Yuanqing He

Abstract Two-dimensional gel electrophoresis (2-DE) was used to detect fluoride-induced alterations in the proteome of the rat hippocampus. Male Sprague-Dawley rats (n=30) were subjected to treatments three weeks after weaning. Animals of the first group were injected intraperitoneally (i.p.) with aqueous NaF (20 mg/kg/body weight/day), the second group, injected with physiological saline, served as the control. After 30 days, the body weight of the fluoride-treated rats was lower than that of the control, and F– levels in serum were higher than in the control. The hippocampus was subjected to proteomic analysis, and the fluoride-treated group was found to contain 19 up-regulated and eight down-regulated proteins. The proteins, identified by mass-spectroscopic analysis of their fragments obtained after digestion, were found to be involved in amino acid biosynthesis, the insulin signaling pathway and various other crucial functions. Our results also provide useful information on the mechanism of the reduction of the learning ability and memory induced by F.


2021 ◽  
Vol 10 ◽  
Author(s):  
Kazunari Kadokura ◽  
Tsuyoshi Tomita ◽  
Kohei Suruga

Abstract The fish paste product, fish balls ‘tsumire’, is a traditional type of Japanese food made from minced fish as well as imitation crab, kamaboko and hanpen. Although tsumire is known as a high-protein and low-fat food, there is a lack of scientific evidence on its health benefits. Hence, we aimed to investigate the effects of tsumire intake on organ weight and biomarker levels in Sprague–Dawley rats for 84 d as a preliminary study. Six-week-old male Sprague–Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5 % dried tsumire. Throughout the administration period, we monitored their body weight and food intake; at the end of this period, we measured their organ weight and analysed their blood biochemistry. No significant differences were observed with respect to body weight, food intake, organ weight and many biochemical parameters between the two groups. It was found that inorganic phosphorus and glucose levels were higher in group II rats than in group I rats. On the other hand, sodium, calcium, amylase and cholinesterase levels were significantly lower in group II than in group I. Interestingly, we found that the levels of aspartate aminotransferase, alanine transaminase, lactate dehydrogenase and leucine aminopeptidase in group II were significantly lower than in group I, and that other liver function parameters of group II tended to be lower than in group I. In conclusion, we consider that the Japanese traditional food, ‘tsumire,’ may be effective as a functional food for human health management worldwide.


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