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Biomedical subjects

C M Williams

Publications and source records attributed to C M Williams.

At least 19 recordsLinked to original sources

Comparison of four carbon dioxide resurfacing lasers. A clinical and histopathologic evaluation.

BACKGROUND: Several high-energy, pulsed and scanned carbon dioxide (CO2) lasers are currently available for cutaneous resurfacing. Although each laser system adheres to the same basic principles of selective photothermolysis, there are significant differences between lasers with respect to tissue dwell time, energy output, and laser beam profile. These differences may result in variable clinical and histologic tissue effects. OBJECTIVE: The purpose of this study was to examine the in vivo clinical and histopathologic effects of four different high-energy, pulsed or scanned CO2 resurfacing lasers. METHODS: A prospective study using four different CO2 resurfacing lasers (Coherent UltraPulse, Tissue Technologies TruPulse, Sharplan FeatherTouch, and Luxar NovaPulse) was performed. The cheeks of seven patients were divided into four quadrants. Each quadrant was randomly assigned to receive treatment with one of four CO2 lasers. Skin biopsies were obtained intraoperatively from each quadrant, after each of three laser passes, and at 1 and 3 months postoperatively. Blinded clinical assessments of each laser quadrant were made at 1, 3, and 6 months postoperatively by three physicians. Degree of lesional improvement as well as erythema severity, re-epithelialization rates, and presence of side effects were recorded. Blinded histologic examination of laser-treated quadrants was performed to determine the amount of tissue ablation, residual thermal damage, inflammation, and new collagen synthesis. RESULTS: The four CO2 lasers produced equivalent clinical improvement of rhytides and scars. Re-epithelialization occurred in all laser quadrants by day 7. Postoperative erythema was most intense in the quadrants treated by UltraPulse and NovaPulse; however, overall duration of erythema was equivalent for all four laser systems (3 months). Postinflammatory hyperpigmentation was the most frequently encountered side effect and occurred with equal frequency in each quadrant. No scarring, hypopigmentation, or infections were observed. After one laser pass, histologic examination revealed partial ablation of the epidermis with the TruPulse laser and complete epidermal ablation using the UltraPulse, NovaPulse, and FeatherTouch laser systems. The greatest degree of residual thermal damage was seen after FeatherTouch and NovaPulse laser irradiation. New collagen formation was greatest in the UltraPulse and FeatherTouch laser-irradiated quadrants. CONCLUSIONS: Equivalent clinical results were observed using the FeatherTouch, NovaPulse, TruPulse, and UltraPulse CO2 lasers. While postoperative erythema intensity differed between laser systems, total duration of erythema was equivalent. The four lasers under study resulted in minimal residual thermal damage and stimulated new collagen formation within 6 months after treatment.

Adult

Hyperphagia in pre-fed rats following oral delta9-THC.

Using a pre-feed paradigm, the effects of orally-administered delta9-tetrahydrocannabinol (THC) on low baseline levels of nocturnal feeding were assessed. Following 2-h access to a palatable wet mash diet at dark onset, adult male Lister hooded rats (Charles River) were treated with either sesame seed oil vehicle or delta9- tetrahydrocannabinol (0.063, 0.12, 0.25, 0.5, 1.0, or 2.0 mg/kg). One hour later, rats were allowed ad libitum access to standard chow, and intakes were monitored over the subsequent 24 h. Doses of 0.5, 1.0, and 2.0 mg/kg produced substantial hyperphagia during the first hour of testing. Subsequently, rats compensated for their overconsumption so that 24-h intakes were similar in all conditions. The data confirm anecdotal reports of the orexigenic actions of exogenous cannabinoids and suggest a critical role for endogenous cannabinoid systems in the regulation of appetite.

Administration, Oral

Differences in postprandial lipaemic response between Northern and Southern Europeans.

Postprandial lipaemic responses to two test meals were investigated in 30 Northern (15 British and 15 Irish), and 30 Southern (Greeks from Crete) healthy male Europeans. The meals were a saturated fatty acid (SFA) meal, which resembled the fatty acid composition of an average UK diet, and a monounsaturated fatty acid (MUFA) meal in which the fat consisted of olive oil. Habitual diets of the two groups differed, with higher total fat, (P < 0.03) and MUFA (P < 0.0001) and lower polyunsaturated fatty acid (PUFA) (P < 0.0001) intakes in Southern than Northern Europeans. Levels of total MUFA (P < 0.02) and oleic acid (P < 0.004) were also higher in adipose tissue of Southern in comparison to Northern Europeans. In both European groups there were no significant differences in postprandial triglyceride response between the two meal types, SFA or MUFA. However, Northern and Southern Europeans showed significant differences in their patterns of postprandial response in plasma triglycerides (P < 0.0001), apolipoprotein B-48 (P < 0.0001), NEFA (P < 0.0001), insulin (P < 0.0007), and factor VII activity (P-0.03). In the case of NEFA, areas under the response curve were higher following the SFA than the MUFA meal for both groups, (P < 0.003) and were greater in Southern than Northern Europeans (P < 0.002) and apo B-48 responses were lower (P < 0.005). Some of these differences may reflect differences in fasting levels since fasting apolipoprotein B-48 levels were lower (P < 0.01) and fasting NEFA (P < 0.02) and insulin (P < 0.005) were higher in the Southern than in the Northern Europeans. In addition, 9 h postprandial post-heparin lipoprotein lipase activity was lower in the Southern than in the Northern Europeans (P < 0.0006). This is the first report of differences in postprandial lipid, factor VII and insulin responses in Southern and Northern Europeans which may be of importance in explaining the different susceptibilities of these two populations to risk of coronary artery disease.

Adipose Tissue

Dietary interventions affecting chylomicron and chylomicron remnant clearance.

Interest in effects of diet on postprandial lipoproteins has increased in recent years as a result of accumulating evidence for adverse cardiovascular consequences of elevated concentrations of triglyceride rich lipoproteins. Particular attention has been given to ability of different fatty acids to modulate postprandial lipoprotein responses because of evidence for both harmful and protective cardiovascular properties of the saturated, monounsaturated and omega-6 and omega-3 polyunsaturated fatty acid (PUFA) classes. Evidence for direct atherogenic properties of chylomicron remnants has led to attempts to monitor effects of diet specifically on this lipoprotein class. Limitations in the methods employed to measure chylomicron remnants and the small number of human studies which have evaluated effects of meal, and background diet, fatty acid composition, makes it difficult to draw definitive conclusions at the present time. However consideration of data from both animal and human studies tends to support the conclusion that diets, and meals, rich in PUFA (particularly long chain omega-3 PUFA), result in attenuated postprandial responses of the intestinally-derived lipoproteins. Attenuated responses to high PUFA meals appear to be due to greater rates of clearance and greater activation of lipoprotein lipase (LPL). Attenuated responses to high PUFA background diets may be due to adaptive changes involving both accelerated rates of clearance in peripheral tissues and liver, as well as decreased output of the competitor for chylomicron clearance, very low density lipoprotein (VLDL).

Animals

The effect of test meal monounsaturated fatty acid: saturated fatty acid ratio on postprandial lipid metabolism.

Epidemiological evidence shows that a diet high in monounsaturated fatty acids (MUFA) but low in saturated fatty acids (SFA) is associated with reduced risk of CHD. The hypocholesterolaemic effect of MUFA is known but there has been little research on the effect of test meal MUFA and SFA composition on postprandial lipid metabolism. The present study investigated the effect of meals containing different proportions of MUFA and SFA on postprandial triacylglycerol and non-esterified fatty acid (NEFA) metabolism. Thirty healthy male volunteers consumed three meals containing equal amounts of fat (40 g), but different proportions of MUFA (12, 17 and 24% energy) in random order. Postprandial plasma triacylglycerol, apolipoprotein B-48, cholesterol, HDL-cholesterol, glucose and insulin concentrations and lipoprotein lipase (EC 3.1.1.34) activity were not significantly different following the three meals which varied in their levels of SFA and MUFA. There was a significant difference in the postprandial NEFA response between meals. The incremental area under the curve of postprandial plasma NEFA concentrations was significantly (P = 0.03) lower following the high-MUFA meal. Regression analysis showed that the non-significant difference in fasting NEFA concentrations was the most important factor determining difference between meals, and that the test meal MUFA content had only a minor effect. In conclusion, varying the levels of MUFA and SFA in test meals has little or no effect on postprandial lipid metabolism.

Adult

Effect of olive oil on immune function in middle-aged men.

Consumption of diets rich in monounsaturated fatty acids (MUFAs) has been linked with a low prevalence of atherosclerosis and there has been great interest in the effects of MUFAs on lipoprotein metabolism. Less attention has been paid to the effects of MUFAs on the immune system, yet cells of the immune system are an inherent part of the inflammatory events involved in atherosclerosis and several animal studies showed that olive oil has some potent immunomodulatory actions. We therefore considered it important to investigate the effects of chronic consumption of MUFAs on several immune cell functions in healthy humans. Healthy middle-aged males entered a double-blind, randomized, controlled trial in which they consumed either a MUFA diet or a control diet for 2 mo. There was a significant decrease in the expression of intercellular adhesion molecule 1 by peripheral blood mononuclear cells from subjects consuming the MUFA diet. Consumption of the MUFA diet did not affect natural killer cell activity or proliferation of mitogen-stimulated leukocytes. The effects of a MUFA-rich diet on adhesion molecule expression may have implications for the influence of dietary fat on inflammatory diseases, including atherosclerosis.

Adult

Effect of long-term olive oil dietary intervention on postprandial triacylglycerol and factor VII metabolism.

Although the beneficial effects of Mediterranean-type diets, which are rich in olive oil, a good source of monounsaturated fatty acids (MUFAs), are generally accepted, little is known about the effects of long-term dietary MUFA intake on postprandial lipoprotein metabolism and hemostasis. This study used a single-blind, randomized, crossover design to investigate the relative effects of a long-term dietary olive oil intervention and a control [saturated fatty acid (SFA)-enriched] diet on postprandial triacylglycerol metabolism and factor VII activity. The postprandial response to a standard test meal was investigated in 23 healthy men who adhered to both diets for 8 wk. cis-MUFAs were successfully substituted for SFAs in the MUFA diet without affecting total dietary fat or energy intakes. The long-term dietary MUFA intervention significantly reduced plasma and LDL-cholesterol concentrations (P = 0.01). Postprandial triacylglycerol concentrations were significantly greater in the early postprandial period after the MUFA diet (P = 0.003). Postprandial factor VII activation and the concentration of the factor VII antigen were significantly lower after the MUFA diet (P = 0.04 and P = 0.006, respectively). This study showed that isoenergetic substitution of MUFAs for SFAs reduces plasma cholesterol and reduces the degree of postprandial factor VII activation. The alterations in the postprandial triacylglycerol response suggest a greater rate of dietary fat absorption and postprandial triacylglycerol metabolism after a diet rich in MUFAs. This study presents new insights into the biochemical basis of the beneficial effects associated with long-term dietary MUFA consumption, which may explain the lower rates of coronary mortality in Mediterranean regions.

Adult

Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats.

The addition of oligofructose as a dietary fiber decreases the serum concentration and the hepatic release of VLDL-triglycerides in rats. Because glucose, insulin, insulin-like growth factor I (IGF-I) and gut peptides [i.e., glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)]) are factors involved in the metabolic response to nutrients, this paper analyzes their putative role in the hypolipidemic effect of oligofructose. Male Wistar rats were fed a nonpurified diet with or without 10% oligofructose for 30 d. Glucose, insulin, IGF-I and GIP concentrations were measured in the serum of rats after eating. GIP and GLP-1 contents were also assayed in small intestine and cecal extracts, respectively. A glucose tolerance test was performed in food-deprived rats. Serum insulin level was significantly lower in oligofructose-fed rats both after eating and in the glucose tolerance test, whereas glycemia was lower only in the postprandial state. IGF-I serum level did not differ between groups. GIP concentration was significantly higher in the serum of oligofructose-fed rats. The GLP-1 cecal pool was also significantly higher. In this study, we have shown that cecal proliferation induced by oligofructose leads to an increase in GLP-1 concentration. This latter incretin could be involved in the maintenance of glycemia despite a lower insulinemia in the glucose tolerance test in oligofructose-fed rats. We discuss also the role of hormonal changes in the antilipogenic effect of oligofructose.

Animals

P- and E-selectins are required for the leukocyte recruitment, but not the tissue swelling, associated with IgE- and mast cell-dependent inflammation in mouse skin.

Many studies, in both experimental animal and human systems, have indicated that P- and/or E-selectins may contribute importantly to the leukocyte recruitment that occurs in association with mast cell-dependent inflammatory responses. We used mice that genetically lack P-selectin (P -/-), E-selectin (E -/-), or both selectins (P/E -/-) to investigate the possible roles of these selectins in the IgE- and mast cell-dependent recruitment of neutrophils to the skin of mice. We found that a lack of either or both selectins had little or no effect on the extent of mast cell degranulation or the tissue swelling associated with these reactions. Moreover, a lack of either P- or E-selectin alone did not reduce the neutrophil infiltration at the reaction sites. However, mice lacking both P- and E-selectins exhibited an almost complete ablation of IgE- and mast cell-dependent neutrophil recruitment. These findings show that P- and E-selectins can express overlapping functions in leukocyte recruitment associated with IgE- and mast cell-dependent cutaneous late-phase reactions in mouse skin, and that a lack of both selectins results in a virtual elimination of IgE-dependent leukocyte recruitment.

Animals

Effects of probiotics and prebiotics on blood lipids.

Since the early work of Mann and Spoerry, probiotics in the form of fermented milk products have been reputed to have cholesterol-lowering properties in humans. However, studies conducted since the early 1970s have produced equivocal findings, with interpretation of the outcomes complicated by use of excessive quantities of product, inadequate sample sizes, failure to control nutrient intake and energy expenditure and variations in baseline blood lipids. More recent studies are of better quality, but fail to provide convincing evidence that 'live' fermented milk products have cholesterol-lowering efficacy in man. Future studies using probiotics should ensure adequate sample sizes sufficient to detect relatively small changes in blood cholesterol and should be conducted over longer periods of time. The recent introduction of the concept of prebiotics has directed attention towards the possibility that alterations in gut microflora induced by the fermentation of non-digestible components of the diet may also have the potential to influence systemic lipid metabolism. This possibility has been strengthened by the observation that in animals, dietary oligofructosaccharides cause suppression of hepatic triglyceride and VLDL synthesis, resulting in marked reductions in triglyceride, and to a lesser extent cholesterol, levels. Evidence for similar effects in humans is sparse and more studies are needed, particularly with respect to effects on postprandial triglyceride concentrations.

Animals

The effects of cyclosporin A, dexamethasone and other immunomodulatory drugs on induced expression of IL-3, IL-4 and IL-8 mRNA in a human mast cell line.

We examined by RT-PCR the effect of a number of immunomodulatory compounds on cytokine gene expression at the level of mRNA in the HMC-1 human leukemic mast cell line. Resting cells expressed relatively low constitutive levels of mRNA for the cytokine genes IL-3, IL-4 and IL-8, and mRNA levels for each of these cytokines were significantly enhanced after 4-h stimulation with the calcium ionophore ionomycin. Treatment of the cells with the immunosuppressant CsA at 10(-5) M produced a significant inhibition of ionomycin-induced expression of IL-3, IL-4 and IL-8 mRNA, and at 10(-6) M produced a significant inhibition of induced expression of IL-3 and IL-8 but not IL-4. At both concentrations of CsA, expression of IL-3 was inhibited to a greater extent than that of the other two cytokines. Treatment of the cells with the corticosteroid DEX at 10(-5) M but not 10(-6) M significantly reduced the ionomycin-induced expression of IL-3 but not IL-4 or IL-8 mRNA. Progesterone and methotrexate were both inactive in modulation of induced cytokine expression in this cell line. In conclusion, this study shows that cytokine expression, particularly of IL-3, is inhibited in a human mast cell line by CsA and DEX. These findings may be relevant to the anti-allergic action of these drugs.

Adjuvants, Immunologic

Tumour necrosis factor-alpha expression and cell recruitment in Sephadex particle-induced lung inflammation: effects of dexamethasone and cyclosporin A.

1. Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with diverse properties consistent with a possible role in inflammatory disease. We investigated whether TNF-alpha is induced during the progression of lung inflammation elicited by a particulate non-antigenic stimulus, and whether pharmacological control of TNF-alpha expression influences recruitment of specific inflammatory cell types. 2. A single intravenous injection of Sephadex particles into rats led to extensive granulomatous inflammation in lung alveolar and bronchial tissue that peaked in intensity after 24-72 h. Mononuclear cells were the principal component of granulomas, but neutrophils and eosinophils were also abundant. Numbers of mononuclear cells, neutrophils and eosinophils recovered by bronchoalveolar lavage (BAL) peaked at 72 h, 48 h and 72 h, respectively. 3. Messenger RNA encoding TNF-alpha was induced in lung epithelial cells, lung granulomas and BAL cells 6 h after Sephadex administration and remained elevated for 72 h before declining to baseline by 7 days. In BAL cell populations TNF-alpha protein was localized to mononuclear cells at all times points pre- and post-Sephadex administration. 4. Treatment of rats with dexamethasone significantly reduced the Sephadex-induced recruitment of mononuclear cells, neutrophils and eosinophils into the bronchoalveolar cavity, and significantly reduced TNF-alpha mRNA expression by BAL cells. 5. Treatment of rats with cyclosporin A was without effect on Sephadex-induced elevations of mononuclear cell numbers and expression of TNF-alpha, but did reduce significantly recruitment of neutrophils and eosinophils to BAL cell populations. 6. These results show that a sequential asthma-like recruitment of neutrophils, eosinophils and mononuclear cells into lung tissue can be induced by single exposure to a non-antigenic stimulus. Pharmacological and histological studies reveal that mononuclear cell mobilization relates closely to induced TNF-alpha expression, whereas mobilization of neutrophils and eosinophils appears secondary to expression of the cytokine.

Animals