Sargassum muticum is a successful invasive Phaeophyte macroalga, which has colonized from Norway ... more Sargassum muticum is a successful invasive Phaeophyte macroalga, which has colonized from Norway to the Mediterranean in Europe and from Alaska to the Bay of Mexico on the American Atlantic coast. It is also being evaluated as a commercial crop within its native range, SE Asia. Understanding its reproductive tolerance will improve our understanding of its invasive potential and allow optimal germling production for commercial cultivation. Egg liberation, fertilization and germling production were monitored in fertile branchlets collected from Great Cumbrae, Scotland, UK. These were incubated under a range of conditions as follows: photon flux densities (20-150 μmol photons m −2 s −1), salinity (0-70 psu), temperature (10-30°C) and desiccation in either the sun (5-60 min) or the shade (15-120 min). The optimum conditions to maximize germling production were found to be a 15-30 min desiccation period in the shade, followed by immersion into normal salinity seawater at 20°C and 50-100 μmol photons m −2 s −1. This information could be useful for the development of a cultivation industry within its native range. An interactive effect was seen between temperature and light intensity with germling production favoured in high light and low temperature (10-15°C, 100-150 μmol photons m −2 s −1) and vice versa (25-30°C, 20-50 μmol photons m −2 s −1). Whilst its salinity and desiccation tolerance agree with previous investigations 40 years ago, the lower temperature optimum of 20°C (previously 25°C) may indicate selection for lower temperature reproduction within the UK population. This may accelerate its invasion northward into Scotland.
Rats were treated with nitrogen-containing phenanthrene (3,4-, 5,6-, or 7,8-benzoquinoline) or an... more Rats were treated with nitrogen-containing phenanthrene (3,4-, 5,6-, or 7,8-benzoquinoline) or anthracene (acridine or quinacrine) derivatives at a dose of 75 mg/kg, daily for 3 days. The hepatic drug metabolizing enzyme response ranged from no induction (quinacrine) through low (5,6-benzoquinoline), intermediate (acridine), and high (3,4-benzoquinoline) magnitude increases of only phase II enzymes, to induction of both phase I and phase II enzymes (7,8-benzoquinoline). The phase I enzyme response of 7,8-benzoquinoline was an induction of CYP1A. All three benzoquinolines, but neither anthracene derivative, elevated NAD(P)H quinone oxidoreductase activity. A similar pattern but of lesser magnitude was seen with glutathione S-transferase activity. 3,4-Benzoquinoline was the only agent to significantly increase microsomal epoxide hydrolase activity (2.3fold). Both 3,4-and 7,8-benzoquinoline increased UDP-glucuronosyltransferase activity toward 4-nitrophenol (40% and 70%, respectively), but only the 3,4isomer increased activity toward morphine (75%), diclofenac (75%), and testosterone (23%), and only the 7,8-isomer increased activity toward chloramphenicol (105%). 3,4-Benzoquinoline elevated the hepatic mRNA concentration of UGT2B1 but not UGT1*6. Acridine treatment increased UDP-glucuronosyltransferase activity toward morphine (47%), 1-naphthol (28%), testosterone (19%), and estrone (19%). Quinacrine failed to elevate any UDP-glucuronosyltransferase activity and depressed activities toward testosterone and estrone by 20%. This study shows that some tricyclic aromatic compounds containing a single heterocyclic nitrogen atom have the potential for use as chemoprotective agents based upon their ability to selectively induce only phase II enzymes.
International journal of surgery case reports, 2014
de Garengeot's hernia is very rare. Richter's hernia is responsible for 10% of acute stra... more de Garengeot's hernia is very rare. Richter's hernia is responsible for 10% of acute strangulated hernias. A 91-year-old woman with three days of abdominal distention was found on computed tomogram to have an incarcerated femoral hernia. Operation revealed a de Garengeot's hernia combined with a Richter's hernia of small bowel. Primary repair was performed along with appendectomy. We discuss these rare hernias, not previously reported in combination, and options for management. Combined de Garengeot's and…
Background. Postoperative abdominal adhesions are a major cause of morbidity and mortality. We pr... more Background. Postoperative abdominal adhesions are a major cause of morbidity and mortality. We previously demonstrated the inhibitory effect of sunitinib, a receptor tyrosine kinase inhibitor, on adhesion formation in a murine model, and now investigate its effects in a rabbit model. Methods. Forty New Zealand White rabbits underwent a standard adhesion procedure. Preoperatively, animals were randomized to treatment with sunitinib or saline (control). Animals were treated with a total of 11 daily doses, 1 preoperative and 10 postoperative. One group of 20 animals (group 1) was humanely killed on postoperative day 10, and the other (group 2) on postoperative day 30. After killing, adhesions were scored and abdominal wounds were collected for tensile strength and microvessel density measurements. Results. Sunitinib-treated animals in group 1 had a mean tenacity score of 1.67 ± 0.29 compared with 3.60 ± 0.16 in control animals (P < .01). Similarly, the mean tenacity scores for sunitinib-treated and control animals in group 2 were 0.20 ± 0.20 and 2.70 ± 0.37, respectively (P < .01). The mean uterine involvement scores for sunitinib-treated and control animals in group 1 were 1.44 ± 0.29 and 3.70 ± 0.15, respectively (P < .01), and in group 2 were 0.10 ± 0.10 and 2.70 ± 0.45, respectively (P < .01). There were no differences in ultimate or modular wound tensile strength between sunitinib-treated and control animals. Conclusion. Sunitinib significantly reduces postoperative adhesions in a rabbit model. This therapy may improve postoperative adhesion-related morbidity and mortality.
Background: Parenteral nutrition (PN), including intravenous lipid administration, is a life-savi... more Background: Parenteral nutrition (PN), including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO) has been associated with the development of liver disease, while the administration of intravenous fish oil (FO) has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease. Methods: We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD)), PN plus intravenous FO (OmegavenH; Fresenius Kabi AG, Bad Homburg VDH, Germany), PN plus intravenous SO (IntralipidH; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL), or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling. Results: The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macroand microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors. Conclusions: Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo.
Interest in pharmacological intervention to combat metabolic syndrome and its complications is in... more Interest in pharmacological intervention to combat metabolic syndrome and its complications is increasing as the prevalence of obesity is reaching epidemic proportions. The potential efficacy of drugs is often tested in animal models; however, the method of drug delivery is frequently overlooked and may act as a confounder due to stress. We hypothesized that long-term orogastric gavage would negatively influence the development of hepatic steatosis and the metabolic syndrome in a murine model of diet-induced obesity. C57BL/6J male mice were fed a high fat diet and were gavaged with a vehicle once or twice daily for 9 weeks. A group without orogastric gavaging served as control. A similar experiment was performed using leptin deficient ob/ob mice that were fed a standard diet for 4 weeks. Food intake was monitored, insulin resistance determined, and steatosis was assessed by histology and quantified via magnetic resonance spectroscopy. After 9 weeks, control C57BL/6J mice exhibited significantly more weight gain, insulin resistance and hepatic steatosis, compared to mice that were gavaged daily, or twice daily. This effect was likely due to decreased food consumption associated with gavage-induced stress. In contrast, the phenotype of leptin deficient ob/ob mice was not affected by orogastric gavage. Therefore, we concluded that orogastric gavage may lead to increased stress, thereby affecting food intake and the development of diet-induced obesity in a murine model. The effects of what may seem to be trivial laboratory routines, such as orogastric gavage, should be taken into account when designing animal studies for drug development.
Rats treated with quinoline, and to a lesser extent, isoquinoline (75 mg/kg, daily for 3 days) sh... more Rats treated with quinoline, and to a lesser extent, isoquinoline (75 mg/kg, daily for 3 days) showed induction of phase II drug metabolizing enzyme activities without inducing either cytochrome P450 concentration or CYP1A-, CYP2B-, CYP2E-, and CYP3A-selective activities. Elevations of UDP-glucuronosyltransferase activities towards 4-nitrophenol, 1-naphthol, and morphine elicited by quinoline (1.9- to 2.7-fold), were greater than those elicited by isoquinoline (1.4- to 1.8-fold). UDP-glucuronosyltransferase activities towards estrone and testosterone were not increased by either compound. Microsomal epoxide hydrolase activity was increased only by quinoline (2.7-fold). NAD(P)H quinone oxidoreductase activity was increased 2-fold by quinoline and isoquinoline. Cytosolic glutathione S-transferase (GST) activity was increased similarly (approximately 20%) by both agents. Similar treatment of rats with either quinine (75 mg/kg) or chloroquine (150 mg/kg) increased 1-naphthol glucuronidation and GST (quinine only) activities. At 75 mg/kg, chloroquine did not affect any phase II enzyme activities but caused a minor elevation of a phase I enzyme, CYP1A; ascertained from an elevation of 7-ethoxyresorufin deethylase activity and a small hypsochromic shift to the absorbance maximum of the cytochrome P450 CO-complex. With quinoline and isoquinoline treatments (n = 14), the correlation coefficients (R) between microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities towards 4-nitrophenol and morphine were 0.96 and 0.92 respectively, suggesting a highly coordinated induction. The highest NAD(P)H quinone oxidoreductase correlations were with microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities towards 4-nitrophenol and morphine (R approximately 0.78). Correlation coefficients between GST and microsomal epoxide hydrolase and NAD(P)H quinone oxidoreductase activities were approximately 0.49. Quinoline and isoquinoline, nitrogen heterocyclic analogs of naphthalene, join the list of simple nitrogen-containing polycyclic aromatic agents capable of selective induction of phase II drug metabolizing enzymes. The position of the single heterocyclic nitrogen atom in the bicyclic ring influences the magnitude and breadth of the induction response. The addition of bulky ring substituents (quinine, chloroquine) reduced the induction response.
Sargassum muticum is a successful invasive Phaeophyte macroalga, which has colonized from Norway ... more Sargassum muticum is a successful invasive Phaeophyte macroalga, which has colonized from Norway to the Mediterranean in Europe and from Alaska to the Bay of Mexico on the American Atlantic coast. It is also being evaluated as a commercial crop within its native range, SE Asia. Understanding its reproductive tolerance will improve our understanding of its invasive potential and allow optimal germling production for commercial cultivation. Egg liberation, fertilization and germling production were monitored in fertile branchlets collected from Great Cumbrae, Scotland, UK. These were incubated under a range of conditions as follows: photon flux densities (20-150 μmol photons m −2 s −1), salinity (0-70 psu), temperature (10-30°C) and desiccation in either the sun (5-60 min) or the shade (15-120 min). The optimum conditions to maximize germling production were found to be a 15-30 min desiccation period in the shade, followed by immersion into normal salinity seawater at 20°C and 50-100 μmol photons m −2 s −1. This information could be useful for the development of a cultivation industry within its native range. An interactive effect was seen between temperature and light intensity with germling production favoured in high light and low temperature (10-15°C, 100-150 μmol photons m −2 s −1) and vice versa (25-30°C, 20-50 μmol photons m −2 s −1). Whilst its salinity and desiccation tolerance agree with previous investigations 40 years ago, the lower temperature optimum of 20°C (previously 25°C) may indicate selection for lower temperature reproduction within the UK population. This may accelerate its invasion northward into Scotland.
Rats were treated with nitrogen-containing phenanthrene (3,4-, 5,6-, or 7,8-benzoquinoline) or an... more Rats were treated with nitrogen-containing phenanthrene (3,4-, 5,6-, or 7,8-benzoquinoline) or anthracene (acridine or quinacrine) derivatives at a dose of 75 mg/kg, daily for 3 days. The hepatic drug metabolizing enzyme response ranged from no induction (quinacrine) through low (5,6-benzoquinoline), intermediate (acridine), and high (3,4-benzoquinoline) magnitude increases of only phase II enzymes, to induction of both phase I and phase II enzymes (7,8-benzoquinoline). The phase I enzyme response of 7,8-benzoquinoline was an induction of CYP1A. All three benzoquinolines, but neither anthracene derivative, elevated NAD(P)H quinone oxidoreductase activity. A similar pattern but of lesser magnitude was seen with glutathione S-transferase activity. 3,4-Benzoquinoline was the only agent to significantly increase microsomal epoxide hydrolase activity (2.3fold). Both 3,4-and 7,8-benzoquinoline increased UDP-glucuronosyltransferase activity toward 4-nitrophenol (40% and 70%, respectively), but only the 3,4isomer increased activity toward morphine (75%), diclofenac (75%), and testosterone (23%), and only the 7,8-isomer increased activity toward chloramphenicol (105%). 3,4-Benzoquinoline elevated the hepatic mRNA concentration of UGT2B1 but not UGT1*6. Acridine treatment increased UDP-glucuronosyltransferase activity toward morphine (47%), 1-naphthol (28%), testosterone (19%), and estrone (19%). Quinacrine failed to elevate any UDP-glucuronosyltransferase activity and depressed activities toward testosterone and estrone by 20%. This study shows that some tricyclic aromatic compounds containing a single heterocyclic nitrogen atom have the potential for use as chemoprotective agents based upon their ability to selectively induce only phase II enzymes.
International journal of surgery case reports, 2014
de Garengeot's hernia is very rare. Richter's hernia is responsible for 10% of acute stra... more de Garengeot's hernia is very rare. Richter's hernia is responsible for 10% of acute strangulated hernias. A 91-year-old woman with three days of abdominal distention was found on computed tomogram to have an incarcerated femoral hernia. Operation revealed a de Garengeot's hernia combined with a Richter's hernia of small bowel. Primary repair was performed along with appendectomy. We discuss these rare hernias, not previously reported in combination, and options for management. Combined de Garengeot's and…
Background. Postoperative abdominal adhesions are a major cause of morbidity and mortality. We pr... more Background. Postoperative abdominal adhesions are a major cause of morbidity and mortality. We previously demonstrated the inhibitory effect of sunitinib, a receptor tyrosine kinase inhibitor, on adhesion formation in a murine model, and now investigate its effects in a rabbit model. Methods. Forty New Zealand White rabbits underwent a standard adhesion procedure. Preoperatively, animals were randomized to treatment with sunitinib or saline (control). Animals were treated with a total of 11 daily doses, 1 preoperative and 10 postoperative. One group of 20 animals (group 1) was humanely killed on postoperative day 10, and the other (group 2) on postoperative day 30. After killing, adhesions were scored and abdominal wounds were collected for tensile strength and microvessel density measurements. Results. Sunitinib-treated animals in group 1 had a mean tenacity score of 1.67 ± 0.29 compared with 3.60 ± 0.16 in control animals (P < .01). Similarly, the mean tenacity scores for sunitinib-treated and control animals in group 2 were 0.20 ± 0.20 and 2.70 ± 0.37, respectively (P < .01). The mean uterine involvement scores for sunitinib-treated and control animals in group 1 were 1.44 ± 0.29 and 3.70 ± 0.15, respectively (P < .01), and in group 2 were 0.10 ± 0.10 and 2.70 ± 0.45, respectively (P < .01). There were no differences in ultimate or modular wound tensile strength between sunitinib-treated and control animals. Conclusion. Sunitinib significantly reduces postoperative adhesions in a rabbit model. This therapy may improve postoperative adhesion-related morbidity and mortality.
Background: Parenteral nutrition (PN), including intravenous lipid administration, is a life-savi... more Background: Parenteral nutrition (PN), including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO) has been associated with the development of liver disease, while the administration of intravenous fish oil (FO) has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease. Methods: We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD)), PN plus intravenous FO (OmegavenH; Fresenius Kabi AG, Bad Homburg VDH, Germany), PN plus intravenous SO (IntralipidH; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL), or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling. Results: The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macroand microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors. Conclusions: Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo.
Interest in pharmacological intervention to combat metabolic syndrome and its complications is in... more Interest in pharmacological intervention to combat metabolic syndrome and its complications is increasing as the prevalence of obesity is reaching epidemic proportions. The potential efficacy of drugs is often tested in animal models; however, the method of drug delivery is frequently overlooked and may act as a confounder due to stress. We hypothesized that long-term orogastric gavage would negatively influence the development of hepatic steatosis and the metabolic syndrome in a murine model of diet-induced obesity. C57BL/6J male mice were fed a high fat diet and were gavaged with a vehicle once or twice daily for 9 weeks. A group without orogastric gavaging served as control. A similar experiment was performed using leptin deficient ob/ob mice that were fed a standard diet for 4 weeks. Food intake was monitored, insulin resistance determined, and steatosis was assessed by histology and quantified via magnetic resonance spectroscopy. After 9 weeks, control C57BL/6J mice exhibited significantly more weight gain, insulin resistance and hepatic steatosis, compared to mice that were gavaged daily, or twice daily. This effect was likely due to decreased food consumption associated with gavage-induced stress. In contrast, the phenotype of leptin deficient ob/ob mice was not affected by orogastric gavage. Therefore, we concluded that orogastric gavage may lead to increased stress, thereby affecting food intake and the development of diet-induced obesity in a murine model. The effects of what may seem to be trivial laboratory routines, such as orogastric gavage, should be taken into account when designing animal studies for drug development.
Rats treated with quinoline, and to a lesser extent, isoquinoline (75 mg/kg, daily for 3 days) sh... more Rats treated with quinoline, and to a lesser extent, isoquinoline (75 mg/kg, daily for 3 days) showed induction of phase II drug metabolizing enzyme activities without inducing either cytochrome P450 concentration or CYP1A-, CYP2B-, CYP2E-, and CYP3A-selective activities. Elevations of UDP-glucuronosyltransferase activities towards 4-nitrophenol, 1-naphthol, and morphine elicited by quinoline (1.9- to 2.7-fold), were greater than those elicited by isoquinoline (1.4- to 1.8-fold). UDP-glucuronosyltransferase activities towards estrone and testosterone were not increased by either compound. Microsomal epoxide hydrolase activity was increased only by quinoline (2.7-fold). NAD(P)H quinone oxidoreductase activity was increased 2-fold by quinoline and isoquinoline. Cytosolic glutathione S-transferase (GST) activity was increased similarly (approximately 20%) by both agents. Similar treatment of rats with either quinine (75 mg/kg) or chloroquine (150 mg/kg) increased 1-naphthol glucuronidation and GST (quinine only) activities. At 75 mg/kg, chloroquine did not affect any phase II enzyme activities but caused a minor elevation of a phase I enzyme, CYP1A; ascertained from an elevation of 7-ethoxyresorufin deethylase activity and a small hypsochromic shift to the absorbance maximum of the cytochrome P450 CO-complex. With quinoline and isoquinoline treatments (n = 14), the correlation coefficients (R) between microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities towards 4-nitrophenol and morphine were 0.96 and 0.92 respectively, suggesting a highly coordinated induction. The highest NAD(P)H quinone oxidoreductase correlations were with microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities towards 4-nitrophenol and morphine (R approximately 0.78). Correlation coefficients between GST and microsomal epoxide hydrolase and NAD(P)H quinone oxidoreductase activities were approximately 0.49. Quinoline and isoquinoline, nitrogen heterocyclic analogs of naphthalene, join the list of simple nitrogen-containing polycyclic aromatic agents capable of selective induction of phase II drug metabolizing enzymes. The position of the single heterocyclic nitrogen atom in the bicyclic ring influences the magnitude and breadth of the induction response. The addition of bulky ring substituents (quinine, chloroquine) reduced the induction response.
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