The use of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis.
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Biomedical subjects
Publications and source records attributed to G Guy.
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We conducted a study to evaluate the effects of intramuscular fat levels on the sensory characteristics of duck breast meat. Combining duck genotypes (Muscovy, Pekin, and their crossbreed hinny and mule ducks) and feeding levels (overfeeding between 12 and 14 wk of age vs. ad libitum feeding) enabled us to obtain a wide range of lipid levels in breast muscle. The average values were between 2.55 and 6.40 g per 100 g of muscle. Breast muscle from overfed ducks showed higher lipid and lower water levels than breast muscle from ducks fed ad libitum. Muscle from the overfed ducks was also paler in color and exhibited greater yellowness and cooking loss values. Juiciness was judged lower and flavor more pronounced in overfed ducks. Muscovy ducks exhibited higher breast weight and lower lipid levels than the other genotypes. At the other extreme, Pekin ducks exhibited the highest lipid levels and the lowest breast weights; values for these criteria were intermediate in hinny and mule ducks. Breast muscle of Muscovy ducks was paler, less red, and more yellow than that of other genotypes. Breast muscle of Pekin ducks exhibited the lowest values for lightness, yellowness, and energy necessary to shear meat, as well as the highest cooking loss values, and was judged more tender, juicy and less stringy than that of other genotypes. In contrast, scores for breast muscle of Muscovy ducks were the lowest for tenderness, juiciness, and flavor, and the highest for stringiness. Breast muscle of hinny and mule ducks scored the highest values for redness. Hinny ducks also scored the highest values for flavor. Genotype exerted a higher effect on the sensory quality of breast muscle than did feeding levels. Finally, increasing lipid levels in breast muscle increased lightness, yellowness, cooking loss, tenderness, and flavor, with correlation coefficients of 0.49, 0.47, 0.54, 0.43, and 0.28, respectively. However, breast meat color and tenderness were mainly influenced by genotype.
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Overfeeding of some waterfowl species results in obesity, which is mainly characterized by a dramatic hepatic steatosis induced by strong accumulation of lipids synthesized from dietary glucose in the liver. In mammals, fructose is known to be able to raise plasma triacylglycerol concentrations significantly; consequently, this may induce obesity. The aim of this study was to assess the effect of partial replacement of dietary glucose provided by corn starch with fructose on metabolism and fatty liver production in the Mule ducks. On the basis of 9.5 kg maize (132,920 kJ) given twice a day for 14 days, a supplementation of 9,800 kJ was provided in form of glucose, sucrose or high fructose corn syrup (HFCS: 50 % glucose, 42 % fructose and 8 % other saccharides). Fatty liver weight in ducks fed with glucose supplementation was 499 +/- 21 g. Sucrose or HFCS supplementation brought about a significant increase in liver weight (+ 18.7 % and + 16.3 % vs. glucose supplementation respectively, p < 0.05). These results suggest that the dietary fructose favors the liver steatosis by increasing hepatic lipogenesis. Postprandial plasma insulin concentrations were similar in ducks fed diets with or without fructose, suggesting that the effect of fructose on liver steatosis is not mediated by insulin.
The Mule duck develops a fatty liver in response to overfeeding, which results from a dramatic increase in de novo liver lipogenesis, and thus raises questions regarding the role of glucokinase (GK), a key enzyme regulating carbohydrate metabolism in mammals. However, the presence of GK in avian species is still a matter of debate. The aim of the present study was to characterize a GK-like protein (using an immunological technique) and a GK-like activity (using an enzymatic assay) in duck liver and to measure their respective variations during various stages of overfeeding. Duck liver protein cross-reacted with antibodies directed against mammalian GK yielding a band at 50 kDa, i.e., the same molecular weight as mammalian GK. The intensity of the signal varied significantly between overfed and control ducks but in opposing ways according to the GK antibodies used, which suggests the presence of 2 isoforms of GK in the duck liver as in mammals. Enzymatic analysis demonstrated the presence of glucose phosphorylation activity sensitive to high and low glucose concentrations (high/low ratio between 1.7 and 3.7) in the soluble and particulate fractions of liver homogenates. Glucokinase-like activity per milligram protein was strongly induced by overfeeding, and plasma insulin levels increased concomitantly. More than 80% of total GK-like activity was concentrated in the soluble component from 1 to 13 d of overfeeding. These results suggest that a GK-like enzyme may actively contribute to glucose disposal throughout the overfeeding period in Mule ducks fed a carbohydrate-rich diet.
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Susceptibility to fear and stress has often been studied in birds using selection experiments. Crosses between different species of the same genus have also been used to study the type of transmission observed for "fixed action patterns." In this experiment we used a cross between two species (male muscovy and female pekin ducks) to study the genetic transmission of various characteristics of fear reactions and adrenal activity. Males of the three genetic types (two parental species and the hybrid) were submitted to tonic immobility and fear of man tests. Blood was collected for corticosterone assay before and after physiological stress or injection of 5 microg/kg of immediate synacthen (ACTH agonist). The muscovy duck showed lower levels of fear reactions than the pekin duck in the majority of behavioral tests (six of eight). Corticosterone levels were also nearly always the lowest in muscovy ducks (five of six). Generally speaking, the muscovy duck appeared to be less fearful and less susceptible to stress than the pekin duck. The mule duck was similar to one parent, midway between the two, or showed heterosis for fear of man at 10 weeks of age (more fearful than the two parents). Corticosterone levels were midway between the two parents in the mule duck with only one exception, i.e., where the pekin duck was dominant. The existence of heterosis for fear is surprising, as this character is classically considered to be submitted to stabilizing selection. The transmission of corticosterone levels and other fear characteristics is, however, compatible with stabilizing selection. The results are discussed in terms of adaptability.
When overfed at their maximum (intensive overfeeding) or at only 80% (moderate overfeeding) of food intake capacity, Mule ducks developed strong liver steatosis, whereas Pekin ducks showed very marked extrahepatic fattening. During overfeeding, evolution of plasma glucose and triacylglycerol concentrations suggested a very strong increase in the hepatic lipogenesis as well as genotype- and diet-independent lipoprotein secretion. In contrast, lipoprotein-lipase activity was dependent on alimentary status (the intensive overfeeding induces the highest activities), and Pekin ducks showed higher lipoprotein-lipase activity than Mule ducks, which could favor extrahepatic fattening to the detriment of hepatic steatosis. In Pekin ducks, plasma pancreatic hormone concentrations are related to diet levels and blood sugar. With similar food intake, Mule ducks (moderately overfed) showed global blood insulin lower than that of Pekin ducks (intensively overfed) despite similar blood sugar levels, suggesting a trend towards reduced pancreas response to glucose in Mule ducks. This may result from their lower lipoprotein-lipase activity as previously shown in these two ducks overfed at only 60% of their maximal food intake capacity (unpublished results). These results suggest that high plasma insulin concentrations may be necessary to induce an optimum lipoprotein-lipase activity in overfed ducks.
1. The effects of the force-feeding procedure and its different components on various physiological indicators of acute and chronic stress were investigated in male mule ducks before and during a 12-d cramming period. 2. The highest concentration of corticosterone were measured after injection of ACTH agonist, during the pre-experimental period when the ducks were still housed in collective floor pens and at the time of transfer. 3. During the cramming period, corticosterone measured before and after force-feeding did not differ significantly though there was a non-significant trend towards an increase in certain cases. 4. The different components of force-feeding, including manipulation, intubation, force-feeding with a standard or a large amount of food had no significant effect upon corticosterone concentrations. 5. There was no indication from ACTH agonist challenge either of a change in adrenal sensitivity or a change in its responsiveness. 6. The heterocyte-lymphocyte ratio measured before and at the end of the cramming period did not differ significantly. 7. In conclusion, we observed no significant indication that force-feeding is perceived as an acute or chronic stress by male mule ducks, in our experimental conditions. Nevertheless, it remains to be shown that their adrenocorticotropic axis is responsive to acute stressors.
Cranial dermal sinus, usually associated with dermoid cyst, is the persistance of an abnormal embryonal communication between the skin and the central nervous system. It may be the source of intracranial infection, most often a meningitis and rarely an abscess formation. Two cases of little girls (18 months and 2 years) having dermal sinus with dermoid cyst revealed by cerebellar abscess formations are reported. In the first case there were multiple cerebellar abscesses with hydrocephalus leading to a raised intracranial pressure. In the second case there was an abscess formation adjacent to the dermoid cyst. CT scan showed cysts and abscesses but MRI, achieved in the second case, was useful in demonstrating the sinus tract as well as the associated cyst and abscess. The two patients underwent a posterior fossa surgery with antibiotic therapy. In the first case abscess drainage and ventricular external drainage were necessary before sinus and cyst excision. Two months after surgery the two patients were neurologically intact and developping well. Surgery with total excision of dermal sinus and dermoid cyst, even sometimes difficult, must be preferred to the simple abscess drainage and antibiotic therapy.
In response to overfeeding, the Landes goose develops a fatty liver that is twice as large as that of the Poland goose, despite similar food intake. The role of hepatic lipogenesis in the genetic susceptibility to fatty liver was assessed in male overfed geese of the two breeds. For a similar hepatic protein content, total activities of malic enzyme, glucose-6-phosphate dehydrogenase, acetyl-Coa-carboxylase and fatty acid synthase, and specific activity and mRNA level of malic enzyme were about two-fold higher in the Landes goose. In the Poland goose, the weight of the fatty liver was correlated positively with the specific activity of ME and the VLDL concentration, which was not the case in the Landes breed. These results show that: (1) hepatic lipogenesis remains very active until the end of the overfeeding period; (2) the pentose-phosphate pathway may function in birds, contrary to what is assumed usually; (3) the level of hepatic lipogenesis is a major factor in the susceptibility to hepatic steatosis in different breeds of geese; and (4) ME activity may be a limiting factor of lipid synthesis in the less susceptible Poland breed.
Biochemical mechanisms which may control fat deposition in liver and/or peripheral tissues have been studied in Poland and Landes geese. Post-prandial plasma substrates and post-heparin lipoprotein-lipase (LPL) activity were measured in 10-week-old animals. At 23 weeks of age, geese were overfed for 14 days then slaughtered. Hepatic steatosis was more important in Landes geese, while muscle and subcutaneous adipose tissue were less developed. In this breed, fatty liver weight negatively scaled to LPL activity, suggesting that a low LPL activity is a limiting factor of peripheral fat deposition. Consequently, non-catabolized VLDL may return to liver and increase hepatic steatosis. In Poland geese, such a mechanism does not exist. On the other hand, fatty liver weight was positively correlated to very low density lipoproteins (VLDL) and triacylglycerols measured in overfed Poland geese, suggesting that lipids synthetized by liver are better transferred from liver to extrahepatic tissues. Kinetics of post-prandial plasma glucose, triacylglycerols, phospholipids and uric acid were similar in the two breeds. However, the marked decrease in post-prandial plasma glycerol in Poland geese suggests that an extrahepatic tissue lipolysis inhibition could contribute to the higher peripheral fattening in overfed Poland geese and could be a limiting factor of hepatic steatosis in this breed.
1. Selected Fat or Lean chickens differ in their plasma glucose insulin relationship: in the fed or fasted state, Fat chickens have a lower glycaemia associated with normal or higher insulinaemia, depending upon the difference in glycaemia. 2. Conversely, chickens selected for low fasting glycaemia (LG) are fattier than their counterparts selected for high fasting glycaemia (HG), although the divergence in fat content is lower than in the Fat-Lean model. 3. The plasma glucose insulin relationship has been investigated in males of the HG and LG lines in the F4 and F5 generations. 4. A difference in glycaemia is suggested during embryonic development and was present at hatching and later on in the fasted or the fed state; insulinaemia did not differ. 5. During refeeding after an overnight fast, glycaemia differed between lines (except at intermediate times); cumulative food intake and insulinaemia were similar. 6. During a glucose tolerance test, glucose disposal rate and insulinaemia were rather similar. 7. Exogenous insulin exerted a very similar hypoglycaemic effect in both lines. 8. Other variables (body temperature, plasma concentrations of potassium and alpha NH2-non protein nitrogen) did not differ between HG and LG chickens. 9. In conclusion, HG and LG chickens do not exhibit any differences in glucose disposal rate, insulinaemia (in various nutritional conditions) or sensitivity to exogenous insulin, which contrasts with Fat or Lean chickens and may explain why HG and LG chickens have diverged to a lesser extent in fat content.
OBJECT: The authors present a retrospective analysis of 248 immunocompetent patients with primary intracerebral lymphoma treated at 19 French and Belgian medical centers between January 1980 and December 1995. METHODS: This study involved 127 female and 121 male patients with a median age of 61 years (range 2-88 years). All tumors available for review were classic diffuse non-Hodgkin's lymphoma, for which the phenotype was determined in 220 patients: 212 (96.4%) were B-cell and eight (3.6%) were T-cell type tumors. According to the Revised European-American classification of lymphoid neoplasms, most lesions were diffuse large cell tumors (62%). A total of 196 tumors were reviewed in 127 patients for whom preoperative computerized tomography and magnetic resonance studies were available. There was a single lesion in 66% of the cases, with a supratentorial location in 87%. Tumor location in the basal ganglia, corpus callosum, or fornix, infiltration of the periventricular ependyma, or a mirror pattern, were strongly suggestive of a lesion of lymphomatous origin. The histological diagnosis was obtained after surgical resection in 116 patients, with the remainder undergoing biopsy sampling only. Of the 248 patients studied, 129 (52%) received chemotherapy plus radiation therapy, 60 (24%) received radiation therapy alone, 35 (14%) received chemotherapy alone, and 24 (10%) received no postsurgical treatment. CONCLUSIONS: Using univariate analysis, the authors determined prognostic factors that were significantly associated with a favorable impact on survival including age younger than 60 years, radiation therapy (without evidence of a dose-response relationship), radiation therapy combined with chemotherapy, and chemotherapy consisting of anthracycline. Partial surgical resection was an unfavorable prognostic factor. Multivariate analysis was used to confirm the independent prognostic value of radiation therapy, age, chemotherapy consisting of anthracyclines or methotrexate, and partial surgical resection. This European survey provides a reasonable basis for the treatment of primary intracerebral lymphoma with the following sequence: stereotactic biopsy sampling, chemotherapy with a methotrexate- and anthracycline-based regimen, followed by cranial irradiation.
BACKGROUND: The authors have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this study, this method was used to provide localized and sustained delivery of 5-fluorouracil (5-FU) after the surgical resection of glioblastoma. This antimetabolite and radiosensitizing drug was selected in an attempt to decrease the rate of local recurrence of the tumor. METHODS: Eight patients with newly diagnosed glioblastoma were included in the study and 2 increasing amounts of 5-FU were studied (70 mg and 132 mg). After surgical resection of the tumor, poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres with an average dimension of 45 microm were implanted in the wall of the surgical bed. External beam radiation (59.4 grays) was initiated before the seventh postsurgical day. Patients were followed by clinical examination, magnetic resonance imaging, and 5-FU assays in the blood and cerebrospinal fluid (CSF). RESULTS: 5-FU assays confirmed sustained concentrations in the CSF for at least 1 month. Concentrations of 5-FU in the blood were lower and transitory. Systemic tolerance to the treatment was good; one case of recurrent brain swelling was observed at the higher dose studied. At the time of last follow-up the overall median survival time was 98 weeks from the time of implantation and 2 patients had achieved disease remission at 139 and 153 weeks, respectively. CONCLUSIONS: This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5-FU-loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197-9, this issue].
1. Changes in plasma corticosterone concentrations according to puncture sites and various challenges including injections of an ACTH agonist (Immediate Synacthen) were investigated in male mule ducks. 2. Lower concentrations were measured in samples drawn by puncture from the occipital sinus than at a wing vein site. 3. Immobilisation and a single intramuscular injection of saline solution (1 ml, 0.9%) had no effect on plasma corticosterone after 15 min. 4. A single intramuscular injection of ACTH (5 microg/kg body weight) produced a rise (P<0.05) in corticosterone. Maximum concentrations were measured after 10 min and, in the absence of further sampling, a return to initial levels was observed by 1 h. 5. On the other hand, repeated bleedings following ACTH challenge maintained higher corticosterone concentrations. 6. A single intramuscular injection of ACTH at doses ranging between 0.625 to 20 microg/kg body weight increased corticosterone concentrations (P<0.05) in a dose-dependent manner, with the responses plateauing at doses of 1.25 microg/kg and higher.
In response to overfeeding for the production of "foie gras," the Poland goose differs from the Landes goose by a lesser susceptibility to hepatic steatosis, resulting in a lower accumulation of hepatic triacylglycerol (TG), together with a greater exportation of hepatic phospholipid (PL) in very low density lipoproteins (VLDL) and high density lipoproteins (HDL) (Fournier et al., 1997). A study was designed 1) to compare the liver composition in overfed and nonoverfed geese of the two breeds of geese and 2) to determine whether the differential channelling of lipids in response to overfeeding is reflected in the PL and fatty acid profiles of the different hepatic lipids, whether stored or secreted. In nonoverfed geese, there were no breed-related differences in liver weight (approximately 90 to 100 g), hepatic lipid content (3 to 4%), and lipid and PL composition. However, plasma VLDL and HDL of the Landes breed contained a higher phosphatidylcholine (PC) to phosphatidylethanolamine (PE) ratio than those of the Poland breed (20.7 and 33.8 vs 12.6 and 25.6 in VLDL and HDL, respectively). After 14 d of overfeeding, hepatic PL profiles were identical in the two breeds and similar to that in control livers; choline-containing PL accounted for 95% of total PL. In contrast, plasma HDL concentrations of the Landes geese were lower than those of the Poland geese (9.4 vs 12.9 g/L) and their PC:PE (13.6%) and PL-polyunsaturated fatty acids (PUFA) content (25%) were decreased compared with the Poland geese (21.2 and 30%). It is likely that the higher susceptibility to fatty liver of the Landes breed involves a differential channelling of PL, resulting in a greater hepatic retention of PC and PUFA that are necessary for plasma membrane growth and cell hypertrophy.