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91.
The latency, the rise time and the influence of the acoustic reflex on sound transmission were investigated in the adult rat during ketamin anesthesia. This was done by recordings of the cochlear microphonics (CM) and electromyographic (EMG) recordings of the reflex responses of the tensor tympani muscle. The acoustic reflex was elicited by contralateral acoustic stimuli of which the intensity and frequency was varied. Ipsilaterally, the effect on sound transmission was determined by estimating the change in amplitude of the CM's of ipsilateral administered subliminal stimuli. It was shown that both the tensor tympani muscle and the stapedius muscle contribute in the reflex. The latency as well as the rise time of the reflex determined by CM recordings showed to be short (minimal values: 12 and 7 ms respectively). The mean latency of the tensor tympani muscle reflex, measured by EMG, was about 7 ms. The attenuation of 0.25-8 kHz tone bursts upto 115 dB SPL is limited to a mean maximum of 15 dB SPL. The maximal attenuation was shown to occur at 1 kHz. Frequencies above 2 kHz appeared to be the best elicitor of the middle ear muscle reflex.  相似文献   
92.
Female sex hormones and platelet/endothelial cell interactions   总被引:2,自引:0,他引:2  
The effects of estradiol and progesterone added to the growth medium of human umbilical vein endothelial cells for 72 h on the formation and release of prostacyclin were investigated. The influence on collagen-induced platelet aggregation and on the platelet formation of thromboxane A2 following aggregation, of the growth medium collected before and after thrombin stimulation of the endothelial cells, was studied simultaneously. Under basal conditions, endothelial cells grown with progesterone released significantly less prostacyclin into the growth medium than did controls (p less than 0.05). Following thrombin stimulation, endothelial cells grown with estradiol (p less than 0.05) or a combination of estradiol and progesterone (p less than 0.01) contained significantly less prostacyclin than controls. No significant effects on the platelet aggregation or platelet thromboxane formation could be found. This study indicates a lowering effect of both female sex hormones on the endothelial cell prostacyclin formation and release. This may be of significance for the increased risk of vascular disease in pregnant women and oral contraceptive users, but can hardly explain the consequences of the hormonal loss occurring at the menopause.  相似文献   
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'Active suppression', a mechanism of transplantation tolerance, can spread to newly introduced minor antigens once these antigens are linked to tolerizing antigens. We explored whether this suppression can extend to major histocompatibility (MHC) antigens and whether this phenomenon can be demonstrated once tolerance is induced to a MHC antigen. Mice were tolerized using donor bone marrow plus CD4 and CD8 monoclonal antibodies. The following strain combinations were used: AKR (H-2k) into CBA (H-2k), a multiple minor difference and B6 (H-2b) into B6(bm12) (H-2b), a MHC class II difference. Tolerance was tested by a donorskingraft. CBA mice tolerant to AKR received a second skin carrying either AKR antigens plus additional multiple minor antigens [F1(AKRxBalb.K)] or carrying additional minors and a MHC class I antigen (B10.AKM-H2M). B6(bm12) (H-2b) tolerant to B6 (H-2b) were grafted with skin from a Balb.B donor (Balb minors linked to the tolerizing class II antigen) or from a B10.A(3R) strain (a MHC class I antigen linked to the tolerizing class II antigen). CBA mice tolerant to AKR accepted F1(AKRxBalb.K) skin, whereas F1(CBAxBalb.K) were rejected. Rejection of B10.AKM/H2M skin by tolerant mice was delayed as compared with nontolerant mice. Tolerant and nontolerant B6(bm12) mice rejected Balb.B skin and B10.A(3R) skin within the same time. Thus, in this model, suppression was linked to minors. Alloreactivity against minors and majors could be suppressed. Suppression linked to a class II antigen could not be demonstrated.  相似文献   
94.
S Hunskaar  O G Berge  K Hole 《Pain》1986,25(1):125-132
It is assumed that the mild analgesia produced by acetylsalicylic acid (ASA) and indomethacin is due to a common mode of action, namely inhibition of the cyclo-oxygenase reaction in the synthesis of prostaglandins. It has, however, been difficult to separate the influence of the anti-inflammatory activity from pure analgesia in standard animal tests using a fully developed inflammatory state. In the present experiments a modification of the formalin test in mice is used. Licking of the injected paw is recorded after the injection of a small nociceptive amount of formalin (20 microliters, 1%). The results show that the response to formalin is biphasic with an early (0-5 min) and a late (20-30 min) phase of high licking activity. ASA had a dose-dependent antinociceptive effect during both the early and the late phases. In contrast, antinociceptive effect of indomethacin was found only during the late phase. On the basis of these results it may be suggested that inhibition of the cyclo-oxygenase reaction has no major effect on the early phase in the formalin test. This also suggests that ASA and indomethacin are antinociceptive through partially different modes of action. In addition to an anti-inflammatory effect common to both drugs, ASA may have a direct antinociceptive action.  相似文献   
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Background: Obesity is a global pandemic leading to increased mortality and increased risk of cardiovascular disease. Bariatric surgery is an established treatment of obesity leading to weight loss and reduction of mortality. To further elucidate how bariatric surgery improves metabolic control, we explored the fatty acid (FA) profiles in morbidly obese subjects treated with lifestyle intervention and subsequent bariatric surgery.

Methods: The intervention group consisted of 34 morbidly obese patients scheduled for bariatric surgery and the control group of 17 non-obese patients scheduled for elective laparoscopic procedures. The intervention group had to undergo lifestyle changes preoperatively. Fasting blood samples were drawn at admission, after lifestyle intervention and 1 year after bariatric surgery.

Results: At admission, the morbidly obese patients had significantly higher levels of monounsaturated FAs (MUFAs) and lower levels of n-6 polyunsaturated FAs (PUFAs) and n-3 PUFAs than healthy controls (all p-values <.05). In the intervention group, there was a significantly lower level of total FAs after lifestyle intervention, and from admission to 1 year after surgical intervention (both, p?<?.05), primarily reflecting a lower proportion of saturated FAs (SFAs). Following bariatric surgery, but not after lifestyle changes, there was an increase in the proportion of n-3 PUFA (p?<?.05) reaching levels not significantly different from healthy controls.

Conclusions: Our findings suggest that a reduced proportion of the proposed anti-atherogenic n-3 PUFAs characterizes morbidly obese individuals, and that this FA profile is reversed by bariatric surgery, but not by lifestyle intervention.  相似文献   
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OBJECTIVE—Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these processes.RESEARCH DESIGN AND METHODS—We examined fatty acid and glucose metabolism and gene expression in cultured human skeletal muscle cells from control and type 2 diabetic individuals after 4 days of preincubation with EPA or TTA.RESULTS—Type 2 diabetes myotubes exhibited reduced formation of CO2 from palmitic acid (PA), whereas release of β-oxidation products was unchanged at baseline but significantly increased with respect to control myotubes after preincubation with TTA and EPA. Preincubation with TTA enhanced both complete (CO2) and β-oxidation of palmitic acid, whereas EPA increased only β-oxidation significantly. EPA markedly enhanced triacylglycerol (TAG) accumulation in myotubes, more pronounced in type 2 diabetes cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO2 formation) was enhanced and lactate production decreased after chronic exposure to EPA and TTA, whereas glucose uptake and storage were unchanged. EPA and especially TTA increased the expression of genes involved in fatty acid uptake, activation, accumulation, and oxidation.CONCLUSIONS—Our results suggest that 1) mitochondrial dysfunction in diabetic myotubes is caused by disturbances downstream of fatty acid β-oxidation; 2) EPA promoted accumulation of TAG, enhanced β-oxidation, and increased glucose oxidation; and 3) TTA improved complete palmitic acid oxidation in diabetic myotubes, opposed increased lipid accumulation, and increased glucose oxidation.Type 2 diabetes is characterized by hyperglycemia, reduced ability to oxidize fat, and accumulation of triacylglycerol (TAG) in skeletal muscle fibers. The increased deposition of intramyocellular TAG (imTAG) has received special interest, because several studies have demonstrated a positive association between insulin resistance and imTAG storage (1,2). Accumulation of imTAG depends on the availability and uptake of fatty acids, the rate of fatty acid oxidation, and the rate of synthesis and hydrolysis of TAG. Increased availability of plasma free fatty acid (FFA) during lipid infusion or high-fat feeding is associated with development of insulin resistance and accumulation of imTAG in vivo (3). Moreover, studies have shown impaired capacity for fatty acid oxidation in skeletal muscle from insulin-resistant/type 2 diabetic individuals (4,5), and reduced mitochondrial fatty acid oxidation in skeletal muscle and myotubes is associated with increased deposition of imTAG (68). Fatty acids may promote insulin resistance via intracellular intermediates such as acyl-CoA, diacylglycerol (DAG), and ceramides, interfering with insulin signaling and glucose metabolism (9).Previous studies have demonstrated positive effects on skeletal muscle insulin sensitivity of mono- and polyunsaturated fatty acids (PUFAs) compared with saturated fatty acids (1012). Very long–chain ω-3 fatty acids, including eicosapentaenoic acid (EPA), may protect against skeletal muscle insulin resistance caused by high-fat feeding in vivo (1,13). PUFAs may also promote increased TAG accumulation without impairing insulin-stimulated glucose uptake in myotubes (10,11). The sulfur-substituted fatty acid analog tetradecylthioacetic acid (TTA) is a pan–peroxisome proliferator–activated receptor (pan-PPAR) activator that reduces plasma lipids and enhances hepatic fatty acid oxidation in rodents (14). Dual and pan-PPAR agonists are currently being developed for treatment of type 2 diabetes (15), and TTA has been shown to improve glucose metabolism in insulin-resistant rats (16) and to stimulate mitochondrial proliferation in rat skeletal muscle (17). We have recently demonstrated that TTA may increase fatty acid oxidation in human myotubes similar to the PPARδ-specific agonist GW501516 (18).Skeletal muscle metabolism is influenced by physical activity, hormonal status, and muscle fiber type, rendering it difficult to determine the impact of EPA and TTA on basal and insulin-stimulated intermediary metabolism. Cultured human myotubes display the morphological, metabolic, and biochemical properties of adult skeletal muscle (19) and offer a unique model to distinguish between genetic and environmental factors in the etiology of insulin resistance (20). We and others have reported several potential intrinsic deficiencies in myotubes from individuals with type 2 diabetes, including lower basal palmitate oxidation (21) and impaired insulin-stimulated glucose metabolism (20,22). It is unknown whether EPA or TTA may improve insulin resistance or other characteristics of type 2 diabetes, such as decreased lipid oxidation in myotubes.To identify the potential effects of EPA and TTA on the intermediary energy metabolism and insulin resistance, we compared the effect of TTA, EPA, and oleic acid in myotubes established from obese individuals with type 2 diabetes and obese healthy subjects.  相似文献   
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