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101.
Purpose To investigate the impact of a change in the proportions of lipid, surfactant and co-solvent on the solubilisation capacity
of self-emulsifying formulations of danazol during in vitro dispersion and digestion studies and correlation with in vivo bioavailability in beagle dogs.
Methods Formulations from within the phase diagram of the pseudo-ternary system composed of soybean oil:maisine 35-1 (1:1 w/w), Cremophor
EL and ethanol were assessed in vitro on dispersion and digestion. The relative bioavailability of danazol after administration of a series of these formulations
was also determined.
Results All formulations formed microemulsions in the presence of water and no drug precipitation was observed on dispersion. In contrast,
drug solubilisation was markedly affected by lipase-mediated digestion and a reduction in lipid (and increase in surfactant)
content resulted in increased drug precipitation. Consistent with these data, the bioavailability of danazol decreased significantly
when the lipid content in the formulations was reduced.
Conclusion A rank-order correlation was observed between the patterns of solubilisation obtained during in vitro digestion and the in vivo performance of self-emulsifying formulations of danazol. In general a decrease in the lipid content and an increase in the
proportions of surfactant and co-solvent resulted in reduced danazol bioavailability. 相似文献
102.
Lemaure B Touché A Zbinden I Moulin J Courtois D Macé K Darimont C 《Phytotherapy research : PTR》2007,21(8):724-730
Cyperus rotundus L. (Cyperaceae; C. rotundus) is an Indian medicinal plant demonstrated to exert multiple health benefits. The purpose of the present study was to test the biological efficacy of C. rotundus tubers extract on weight control in obese Zucker rats. It was demonstrated that administration of 45 or 220 mg/kg/day of C. rotundus tubers hexane extract for 60 days in Zucker rats induced a significant reduction in weight gain without affecting food consumption or inducing toxicity. In vitro, 250 microg/mL of this extract was able to stimulate lipolysis in 3T3-F442 adipocytes suggesting that this medicinal plant contains activators of beta-adrenoreceptors (AR). The binding assay performed on the rat beta3-AR isoform, known to induce thermogenesis, demonstrated that C. rotundus tubers extract can consistently and effectively bind to this receptor. These data suggest that the effect on weight gain exerted by C. rotundus tubers extract may be mediated, at least partially, through the activation of the beta3-AR. In conclusion, C. rotundus tubers extract prove to be a new herbal supplement for controlling body weight preferentially in beta3-AR sensitive species. 相似文献
103.
George Wolf 《Nutrition reviews》2009,67(9):551-554
A white adipose-tissue-specific intracellular phospholipase, which releases arachidonic acid from position sn-2 of phospholipids, was recently discovered and named AdPLA. When AdPLA was induced by feeding or by insulin treatment, the arachidonic acid released from phospholipids acted as a precursor for the formation of prostaglandin E2 (PGE2 ). Subsequent activation of the prostaglandin receptor EP3 caused decreased levels of cAMP that led to decreased lipolysis and increased adiposity. Ablation of AdPLA in knockout mice resulted in the reverse sequence of events, with a decline in arachidonic acid release and prostaglandin synthesis and an increase in levels of cAMP, leading to increased lipolysis and a decline in adiposity, even though food intake was not affected. The newly discovered AdPLA enzyme in white adipose tissue functions as a regulator of lipolysis by acting as an antilipolytic agent mediated by increased PGE2 formation and decreased intracellular cAMP. 相似文献
104.
Sandqvist M Johanson EH Ahrén B Axelsen M Schmelz M Smith U Jansson PA 《European journal of clinical investigation》2006,36(6):383-388
BACKGROUND: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. SUBJECTS AND METHODS: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. RESULTS: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. CONCLUSIONS: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients. 相似文献
105.
From its initial implication in the development of cachexia in the early 1980s, it is now almost 15 years ago that tumour necrosis factor-alpha (TNF-alpha) was first shown to be involved in the development of insulin resistance in obesity. Since the original findings in mice, a wealth of data has been obtained in a variety of settings and species. This intensive research has demonstrated both similarities and differences between rodents and humans regarding the molecular mechanisms and metabolic consequences of TNF-alpha overexpression. This review will focus on the role of TNF-alpha in human white adipose tissue with particular emphasis on its regulation of lipolysis - an important pathway in adipocytes which is linked to insulin-resistant phenotypes in obesity and the metabolic syndrome. 相似文献
106.
Alison Kang MD Mikaela Kislevitz BSN RN Christine Wamsley BA Jennifer Barillas BS John Hoopman CMLSO Jeffrey Kenkel MD Suzanne Kilmer MD 《Journal of Cosmetic Dermatology》2023,22(11):3017-3025
Background
Laser hyperthermia-induced lipolysis is a non-invasive method of localized fat treatment. Non-invasive approaches could be an option for a growing number of patients who are risk-averse and are seeking out non-invasive alternatives to surgical procedures such as liposuction. This study evaluated the safety and efficacy of a 1060 nm diode laser for the non-invasive fat reduction of the flanks.Methods
A total of 30 subjects were enrolled in this prospective, single center study. Subjects received one 25-min treatment with a 1060 nm diode laser to both flanks. Follow-up visits were conducted at 6 and 12 weeks after the last treatment. Ultrasound adipose thickness, body weight, and circumference measurements were taken at baseline and at the 6- and 12-week follow-up visits. Subject satisfaction was assessed using a self-assessment of fat reduction, pain, and tolerability scales, and a subject satisfaction questionnaire. Safety was assessed via the presence or absence of any adverse events.Results
The average age of subjects was 47.3 years. A total of 27 subjects completed the treatment and returned for both follow-up visits. An adipose reduction of 7.57 ± 1.15% at 6 weeks post-treatment (p < 0.0001) was measured using ultrasound. High subject satisfaction was seen, with 74% of subjects reporting being either “satisfied” or “very satisfied” with their results on a 5-point Likert Scale. Eighty-two percent of subjects stated they would recommend the treatment to their friends. All subjects had either mild or moderate pain, with 52% of subjects rating their pain as “mild” (1–3), while 48% rated their pain as moderate (4–7) on the Wong-Baker Scale.Conclusions
A single treatment with a 1060 nm diode laser was both safe and effective in reducing unwanted fat in the flanks without any unanticipated adverse events. Subjects described their treatment pain as mild or moderate and were highly satisfied with their treatment outcomes. 相似文献107.
Sonja Grunewald Marc Oliver Bodendorf Jan C. Simon Uwe Paasch 《Journal der Deutschen Dermatologischen Gesellschaft》2011,9(2):146-159
New trends in dermatological laser therapy during the last years are based on new wavelengths, concepts and treatment combinations resulting in a variety of new dermatologic indications. Fractional laser therapy of chronic actinic damage of the skin has been introduced and already represents a standard technique. The concept of fractional non‐ablative and ablative laser treatment has been shown to be safe and effective. Also pigmented and vascular skin changes can be treated by this method. New, very promising concepts for laser epilation include linear scanned as well as low fluence laser systems. The first enable very short treatment times for large areas; the latter are the basis for the growing market of laser epilation devices for home use. Nevertheless, the potential of low fluence laser devices for long‐term hair reduction has not been tested so far. Furthermore, no data exist on side effects resulting from repetitive application of laser light to melanocytic lesions. Laser lipolysis has been introduced as the latest, minimally invasive way of removing small localised fat deposits. The new procedure may have a great potential for liposculpture; its further development should be thoughtfully observed. The latest innovations for precise ablation are ultra‐short pulsed laser systems. Femtosecond lasers avoid thermal damage at the border areas of ablation zones. 相似文献
108.
G Marchini B Persson N Jonsson C Marcus 《Acta paediatrica (Oslo, Norway : 1992)》1995,84(11):1284-1288
The present study investigated possible interactions between body temperature, lipolysis and thyrotropin (TSH), the only hormone with a documented lipolytic effect in vitro in newborn infants. Healthy infants were either nursed in the usual way ( n = 18) or protected from a decrease in body temperature ( n = 17) during the first postnatal hour. The infants'axillary temperatures were measured immediately after birth and after 10 and 60 min. Blood samples were collected from the umbilical vein and from the infants 10 and 60 min after birth for analysis of TSH, glycerol, free fatty acids, 3-OH-butyric acid and glucose. We found that the mean (±SD) infant axillary temperature was 37.6 ± 0.4o C immediately after birth. In the routinely nursed infants, body temperature decreased to 37.0 ± 0.5o C at 10 min ( p = 0.01) and to 36.6 ± 0.4o C at 60 min ( p = 0.01); the cold-protected infants maintained their fetal temperature at 60 min of age. There was a four-fold increase in plasma TSH levels at 10 min, independent of the infant's body temperature, and the hormone level remained invariably high at 60 min. Plasma glycerol levels increased progressively at 10 min ( p = 0.01) and 60 min ( p = 0.01) in both infant groups, but were higher ( p = 0.02) in the routinely nursed infants at 60 min. No significant relationship was found between TSH and glycerol levels. Infant body temperature did not affect the levels of free fatty acids, 3-OH-butyric acid or glucose. We conclude that the change in environmental temperature as a result of extrauterine adaptation causes thermal stimulation of the infant's body surface which leads to activation of the hypothalamic-pituitary TSH axis, resulting in maximal TSH release, and thus to induction of the lipolytic process. A decrease in body temperature may be an additive stimulus for further enhancement of lipolysis. 相似文献
109.
Hasengschwandtner F 《Journal of Cosmetic Dermatology》2005,4(4):308-313
The medicine Lipostabil N has been in widespread use in Europe since 2002 by doctors working in the field of esthetics to achieve a reduction in the volume of smaller fat deposits by means of injections into the subcutaneous fatty tissue. The lipases released from the adipocytes by means of phosphatidylcholine produce a local breakdown of fat that is then discharged over the liver and metabolized via beta-oxidation. The medicine has been authorized for intravenous use in the prophylaxis and therapy of fat embolisms and liver diseases. 相似文献
110.
Martinez A Chiolero R Bollman M Revelly JP Berger M Cayeux C Tappy L 《Clinical physiology and functional imaging》2003,23(5):286-292
To evaluate the role of adipose tissue in the metabolic stress response of critically ill patients, the release of glycerol and lactate by subcutaneous adipose tissue was assessed by means of microdialysis in patients with sepsis or circulatory failure and in healthy subjects. Patients with sepsis had lower plasma free fatty acid concentrations and non-significant elevations of plasma glycerol concentrations, but higher adipose-systemic glycerol concentrations gradients than healthy subjects or patients with circulatory failure, indicating a stimulation of subcutaneous adipose lipolysis. They also had a higher lipid oxidation. Lipid metabolism (adipose-systemic glycerol gradients, lipid oxidation) was not altered in patients with circulatory failure. These observations highlight major differences in lipolysis and lipid utilization between patients with sepsis and circulatory failure. Hyperlactataemia was present in both groups of patients, but the adipose-systemic lactate concentration gradient was not increased, indicating that lactate production by adipose tissue was not involved. This speaks against a role of adipose tissue in the development of hyperlactataemia in critically ill patients. 相似文献