Skin Ultrasound in Kaposi Sarcoma. / Ecografía cutánea en el sarcoma de Kaposi.

The use of ultrasound imaging has recently been increasing in numerous dermatologic diseases. This noninvasive technique provides additional details on the structure and vascularization of skin lesions. Kaposi sarcoma is a vascular tumor that typically arises in the skin and mucosas. It can spread to lymph nodes and internal organs. We performed B-mode and color Doppler ultrasound studies in 3 patients with a clinical diagnosis of Kaposi sarcoma confirmed by histological examination. We found differences in the ultrasound pattern between nodular and plaque lesions, in both B-mode and color Doppler. We believe that skin ultrasound imaging could be a useful technique for studying cutaneous Kaposi sarcoma, providing additional information on the structural and vascular characteristics of the lesion.

Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats.

Alkaline phosphatase (AP) inactivates bacterial lipopolysaccharide and may therefore be protective. The small intestine and colon express intestinal (IAP) and tissue nonspecific enzyme (TNAP), respectively. The aim of this study was to assess the therapeutic potential of exogenous AP and its complementarity with endogenous enzyme protection in the intestine, as evidenced recently. IAP was given to rats by the oral or intrarectal route (700U/kgday). Oral budesonide (1mg/kgday) was used as a reference treatment. Treatment with intrarectal AP resulted in a 54.5% and 38.0% lower colonic weight and damage score, respectively, and an almost complete normalization of the expression of S100A8, LCN2 and IL-1ß (p<0.05). Oral AP was less efficacious, while budesonide had a more pronounced effect on most parameters. Both oral and intrarectal AP counteracted bacterial translocation effectively (78 and 100%, respectively, p<0.05 for the latter), while budesonide failed to exert a positive effect. AP activity was increased in the feces of TNBS colitic animals, associated with augmented sensitivity to the inhibitor levamisole, suggesting enhanced luminal release of this enzyme. This was also observed in the mouse lymphocyte transfer model of chronic colitis. In a separate time course study, TNAP was shown to increase 2-3 days after colitis induction, while dextran sulfate sodium was a much weaker inducer of this isoform. We conclude that exogenous AP exerts beneficial effects on experimental colitis, which includes protection against bacterial translocation. AP of the tissue-nonspecific isoform is shed in higher amounts to the intestinal lumen in experimental colitis, possibly aiding in intestinal protection.

Effects of flavonoids and other polyphenols on inflammation.

Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.

Bovine glycomacropeptide ameliorates experimental rat ileitis by mechanisms involving downregulation of interleukin 17.

BACKGROUND AND PURPOSE: Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action. EXPERIMENTAL APPROACH: We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction. KEY RESULTS: BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP.

The bisphosphonate alendronate improves the damage associated with trinitrobenzenesulfonic acid-induced colitis in rats.

BACKGROUND AND PURPOSE: The nitrogen-containing bisphosphonates are drugs used successfully in the treatment of osteoporosis. They act inhibiting farnesyl diphosphate synthase. This mechanism may also produce anti-inflammatory effects. The therapeutic activity of alendronate was tested in vivo using a model of inflammatory bowel disease. EXPERIMENTAL APPROACH: The trinitrobenzenesulfonic acid model of colitis in the rat was used. Rats were treated orally with alendronate and its efficacy compared with that of oral sulphasalazine or vehicle, starting 2 h after colitis induction. The status of the animals was assessed 5 days later. KEY RESULTS: Alendronate treatment (25 or 75 mg kg(-1) day(-1)) resulted in a decrease in the colonic damage score and loss of body weight (at 25 mg kg(-1) day(-1) only). This was associated to a dramatic reduction in the mRNA levels of interleukin 1 beta (IL-1 beta), monocyte chemoattractant protein 1 (MCP-1) and interleukin 1 receptor antagonist (IL-1 ra). The magnitude of the beneficial effect was comparable to that of sulphasalazine (at a 6-20 fold higher dose). Thus sulphasalazine post-treatment reduced the mRNA levels of IL-1 beta/IL-1 ra and MCP-1 to the same extent as alendronate and additionally lowered colonic alkaline phosphatase activity, but failed to affect body weight loss or colonic damage score. Alendronate failed to exert beneficial effects when administered intraperitoneally. CONCLUSIONS AND IMPLICATIONS: Oral but not intraperitoneal alendronate significantly protected the colon in experimental rat colitis. Inflammatory bowel disease patients might benefit from exposure to oral alendronate.

Effects of farm management practices and transport duration on stress response and meat quality traits of suckling goat kids.

Studies aimed to assess up to what extent farming and transport previous to slaughtering might affect physiology and meat quality in young goat kids are needed, with the ultimate purpose of promoting practices that minimize stress in these animals. In this regard the effects of on-farm management and transport duration on some physiological responses and meat quality parameters in goat kids were assessed. Two farms representing 'high' and 'low' welfare-friendly management practices were selected. In total, 32 suckling kids were withdrawn from each farm, transported by road for 2 or 6 h, and then slaughtered. Blood samples were collected both on-farm and in the slaughterhouse, and biochemistry, cell counts and haematocrit were determined. After slaughtering, carcass quality parameters were measured. Longissimus dorsi muscle was dissected and pH, colour parameters, water holding capacity and shear force were measured throughout 8-day ageing period. Results indicate that, regardless its duration, transport caused significant effects on some blood parameters suggesting stress in live animals, like glucose, cortisol or creatine kinase. Despite the marked stress status in animals, this condition was not decisively reflected on L. dorsi quality parameters, but some effects were observed regarding fat cover in carcasses and colour parameters. The results suggest that postmortem changes throughout ageing were more decisive in terms of meat quality than stressful management either on-farm or during transport.

Changes in lipid composition and desaturase activities of duodenal mucosa induced by dietary fat.

In the present work we have studied the effects of feeding either olive or sunflower oil on lipid composition and desaturase activities of duodenal mucosa microsomes. Duodenal microsomes prepared from dogs fed the sunflower oil diet showed higher percentages of saturated, of linoleic and of n - 3 polyunsaturated fatty acids as well as lower levels of oleic, dihomo-gamma-linolenic and arachidonic acids in phosphatidylcholine and phosphatidylethanolamine than those prepared from animals fed the olive oil diet. In sphingomyelin, the dietary supplementation did not produce significant differences between the two groups. The cholesterol/phospholipid molar ratio was higher in the sunflower oil group than in the olive oil group. The in vitro delta 9-desaturase activity was higher in microsomes from the olive oil dogs. The delta 6-desaturase activity was similar in microsomes from the two groups and lower than that found for delta 9-desaturase activity. Desaturase activities were higher in duodenal microsomes than those previously found for liver microsomes.

Lipid composition of liver microsomes in rats fed a high monounsaturated fatty acid diet.

The fatty acid and cholesterol contents of tissue membranes are the determinants of membrane stability and functionality. This study was designed to evaluate the influence of a high monounsaturated fatty acid diet on the fatty acid composition of rat liver microsomes and on their cholesterol and lipid phosphorus content. Weanling animals were fed for 5 weeks with high fat diets containing olive oil or corn oil. Saturated fatty acids were increased and oleic acid decreased in microsomal total phospholipids and in the three major phosphoglycerides, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), of rats fed corn oil as compared to the olive oil group. The percentage of linoleic acid was higher in the corn oil group, but only for total phospholipids and PC. Linoleic and alpha-linolenic metabolites were significantly increased in total phospholipids of olive oil-fed animals with respect to those fed corn oil. These changes were responsible for the low unsaturation index found in microsomal phospholipids of the corn oil group. The diet did not affect the microsome cholesterol or the lipid phosphorus content. These results show that, in olive oil-fed rats, the cholesterol content and the degree of unsaturation of liver microsomes was similar to that observed in weanling animals; this probably suggests an adequate maintenance of functionality of membranes in olive oil-fed animals.

Effect of dietary (n-9), (n-6) and (n-3) fatty acids on membrane lipid composition and morphology of rat erythrocytes.

Studies focused on the intake of different dietary fats have shown changes in membrane lipid composition and, as a result, alterations in membrane physical properties. These changes affect erythrocyte morphology, receptor activity and oxygen transport, among others. Here, we compare the effects of diets exclusively differing in the type of fat (olive oil rich in monounsaturates, sunflower oil rich in n-6 polyunsaturates and fish oil rich in n-3 polyunsaturates) on fatty acid composition of plasma and erythrocyte membranes and erythrocyte morphology under scanning electron microscopy in rats. Monounsaturates are highest in animals fed olive oil diets; as are linoleic and arachidonic acids in sunflower oil-fed animals and n-3 PUFAs in fish oil-fed animals. The lowest levels of arachidonic acid are found in fish oil-fed animals and so are n-3 PUFAs in sunflower oil-fed animals. Our results show that sunflower oil-fed animals present lower discocyte, the major cell shape related to tissue oxygen supply, and higher codocyte percentages than olive oil- and fish oil-fed groups. Echinocyte percentage is higher in fish oil-fed animals with respect to the other two groups. The collective data indicate that olive oil elevates monounsaturates and the number of discocytes, pointing out a possible beneficial aspect of this dietary fat.

Modulation of glucose transporters in rat diaphragm by sodium tungstate.

Oral administration of sodium tungstate is an effective treatment for diabetes in animal models. We examined the effects of 6 weeks of oral administration of tungstate on glucose transporters (GLUT) in streptozotocin-induced diabetic rat diaphragm. Diabetes decreased GLUT4 expression while tungstate treatment normalized not only GLUT4 protein but also GLUT4 mRNA in the diabetic rats. Furthermore, treatment increased GLUT4 protein in plasma and internal membranes, suggesting a stimulation of its translocation to the plasma membrane. Tungstate had no effect on healthy animals. There were no differences in the total amount of GLUT1 transporter in any group. We conclude that the normoglycemic effect of tungstate may be partly due to a normalization of the levels and subcellular localization of GLUT4, which should result in an increase in muscle glucose uptake.

Reactivators of organophosphorus-inhibited acetylcholinesterase. 1. Imidazole oxime derivatives.

4-[(Hydroxyimino)methyl]-3-methylimidazolium iodides were prepared and tested for their reactivating potency on acetylcholinesterase inhibited by tetraethyl pyrophosphate (TEPP). The in vitro testing revealed that the new compounds are weak reactivators of the phosphorylated electrophorus acetylcholinesterase.

Effects of dietary fatty acids on lipid metabolism in streptozotocin-induced diabetic rats.

We measured the activity of liver delta9- and delta6-desaturases and examined plasma and liver microsome phospholipid fatty acid composition in control and diabetic rats fed a basal diet supplemented with 5% (by weight) olive oil (OO), sunflower oil (SO), or fish oil (FO), respectively. Plasma glucose, cholesterol, triacylglyceride, and phospholipid levels were also measured. An increase in plasma and liver microsome oleic acid and a decrease in arachidonic acid were found in diabetes. In the liver, docosahexaenoic acid levels were higher in diabetic versus control rats. Diabetes increased liver delta9-desaturase in OO-fed rats and did not modify delta6-desaturase activity in OO- or SO-fed rats. Both enzymatic activities were decreased in diabetic rats fed the FO diet. As a main conclusion, it appears that diet-induced alterations in membrane composition provide a mechanism for improving the diabetic condition in animals and overcoming the effect of insulin deficiency on desaturase activities. Plasma cholesterol was not modified either by diabetes or by diet. In diabetes, OO-fed rats showed the lowest levels of triglycerides. Plasma phospholipids were significantly higher in OO-fed versus FO-fed rats. These findings suggest that OO contributes to a better control of the hypertriglyceridemia accompanying diabetes as compared with the other two diets in this rat model.

Detection of anti-interferon-gamma autoantibodies in subjects infected by Mycobacterium tuberculosis.

SETTING: Among the cytokines involved in defensive mechanisms against Mycobacterium tuberculosis infection, special attention has been given to interferon-gamma (IFN-gamma); a local synthesis of this cytokine as well as IL-2 (type 1 cytokines) at the site of disease in patients with tuberculous pleuritis has been demonstrated. Moreover, high levels of IgG autoantibodies against IFN-gamma have been shown in several clinical situations. It has been suggested that these antibodies could serve to limit the intensity or duration of the immune response or be able to interfere with the pathophysiological effects of IFN-gamma. OBJECTIVE: To investigate the potential role of anti-IFN-gamma antibodies in the course of M. tuberculosis infection. DESIGN: Investigation of the presence of these antibodies in sera from healthy and ill subjects infected with M. tuberculosis in relation to the extent of the disease and the presence of IFN-gamma in sera by enzyme-linked-immunosorbent assay (ELISA). In order to investigate the presence of these antibodies at the site of infection we included 12 pleural fluids from tuberculosis patients and 9 pleural fluids from other origins. RESULTS: In the course of M. tuberculosis infection the production of anti-IFN-gamma IgG antibodies is induced, being particularly higher in healthy skin test converters. Among tuberculosis patients, the presence of anti-IFN-gamma autoantibodies is significantly associated with detectable levels of the cytokine in sera. Levels of anti-IFN-gamma antibodies in moderately advanced and far advanced tuberculosis patients are significantly greater than in healthy individuals. These antibodies increase at the site of infection. CONCLUSION: Anti-IFN-gamma antibodies must be considered as a new element in the immune response to M. tuberculosis. It would be of great interest to investigate this point especially at the site of infection.

Amylin and food intake in mice: effects on motivation to eat and mechanism of action.

Amylin is a hormone produced by the pancreatic islets of Langerhans. Amylin decreased food pellet consumption. Amylin also decreased lever pressing for milk solution whether or not the mice were prefed. Amylin did not produce a conditioned taste aversion in a two bottle test, whereas lithium chloride did. In addition, L-arginine, a precursor for nitric oxide synthesis, was demonstrated to inhibit the ability of amylin to decrease food intake. Amylin did not alter nitric oxide synthase activity in the fundus of the stomach. These studies demonstrated that amylin inhibits food intake at a higher range of doses than is typical of anorectic agents such as cholecystokinin. Amylin does not appear to decrease food intake by reducing the release of nitric oxide but may affect appetite by modulating serum glucose levels when co-released with insulin.

Influence of casein and casein hydrolysate diets on nutritional recovery of starved rats.

BACKGROUND: The aim of this study was to compare the effects of two diets, which differed in their protein source (casein and casein hydrolysate), on the nutritional recovery and intestinal repair of undernourished rats at weaning after a 3-day fasting period. Profound alterations in gut structure and signs of malnutrition appeared after the starvation period. METHODS: The casein hydrolysate was prepared by enzymatic hydrolysis and ultrafiltration. Rats were refed the casein-based or the casein hydrolysate-based diet for 96 hours. Normal-fed male Wistar rats at weaning were given the casein diet for 7 days and were used as controls. Liver acetylcholinesterase, glutamate dehydrogenase activities, serum amino acid profiles, jejunal oligosaccharidases, alkaline phosphatase, and leucine aminopeptidase activities were studied. Intestinal permeability to intact proteins was also tested by using ovalbumin and measuring its concentration in serum. RESULTS: Intestinal and liver enzyme activities and serum amino acid profiles reached normal values after 96 hours of refeeding, regardless of the diet used. Glutamate dehydrogenase activity remained higher in both diet groups. Intestinal permeability to ovalbumin remained significantly increased only in the group refed the casein diet. CONCLUSIONS: Our results show that 4 days of refeeding are sufficient for complete intestinal recovery after fasting, provided the dietary protein source is a casein hydrolysate. We suggest that patients with malnutrition or malabsorption syndrome should be fed formula composed of enzymatic protein hydrolysates (because of their low antigenicity) rather than enteral formulas composed of intact proteins.

Nitric oxide synthase inhibition and food intake: effects on motivation to eat and in female mice.

Recent studies have demonstrated that nitric oxide may play an important role in the regulation of food intake. The studies reported here extend these findings by demonstrating that NG-nitro-arginine-methylester, N-Arg(ME), a nitric oxide synthase inhibitor, decreased intake of a highly palatable substance (i.e., milk), though at a higher dose than necessary for decreasing consumption of food pellets. N-Arg(ME) failed to inhibit lever press for milk reward in nonprefed mice, but decreased lever pressing in prefed mice. N-Arg(ME) decreased food intake in female mice, being most potent in proestrus. These studies suggest that nitric oxide synthase inhibition decreases food intake without inducing aversion or illness.

Effect of dietary nucleotides on intestinal repair in rats with experimental chronic diarrhea.

Nucleic acid synthesis in tissues of rapid growth is preferentially done using dietary purines and pyrimidines via the salvage pathway. In the case of a low protein intake, dietary nucleotides may be semiessential for cell replication of gut, lymphocytes, and bone marrow, and especially in those intestinal diseases in which the mucosa is altered, dietary nucleotides may have a role in intestinal development. The effect of dietary nucleotides on intestinal weight and length, gut mucosal weight, intestinal protein and DNA contents, and lactase, maltase, and intestinal mucosal activities was assessed in a controlled way. Weanling (21-day-old) rats were separated into two groups of 36, each receiving blindly a basal diet containing glucose polymers (C) or a basal diet with lactose as the main carbohydrate (L) for 15 days. Those fed with L developed a syndrome of chronic diarrhea and malnutrition. Ten rats of each group were sacrificed at that time. The rest of the animals of each group were separated into two subgroups. The first was fed with the C diet and the second with the C diet supplemented with 50 mg/100 g of each of the following nucleotides: AMP, GMP, CMP, UMP, and IMP (CN). Thus the subgroups CC, CN, LC, and LN were formed. Rats were sacrificed after 4 weeks and gut separated into three segments corresponding to duodenum, jejunum, and ileum. Analysis of variance was used to compare the effect of diet or segments. DNA and lactase, maltase, and sucrase activities increased in the LN group with respect to LC especially in jejunum and ileum but there were not any differences between CC and CN.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative voltammetric studies of immunoglobulins and DNP-labelled immunoglobulins.

A comparative electrochemical study of human immunoglobulins IgG(1) and IgG(3) carried out at a hanging mercury drop electrode shows that mechanisms other than the reduction of interchain disulphide linkages are responsible for the cathodic peaks observed for such proteins. Considering that the nature of the electrochemical process observed for immunoglobulins are poorly defined and not fully understood, a new approach to the electrochemical determination of such proteins, involving the use of 2,4-dinitrophenol (DNP) as a label, has been developed. Dynamic linear ranges of nearly two magnitudes and detection limits below 10(-10) M were achieved.

Alterations in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA concentration in cultured chick aortic smooth muscle cells.

We observed and compared alterations in 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase at the transcriptional level in unsynchronized, three-passage cultures of smooth-muscle cells from the aorta of chicks fed on a control diet (C-SMC) and those of chicks fed on a similar diet plus cholesterol (Ch-SMC). Alterations in reductase mRNA concentrations in senescent cultures were much lower. We used a modification of the competitive (c) reverse transcription polymerase chain reaction method, using a Thermus thermophilus DNA polymerase (Tth pol) to quantify the very scarce species of HMG-CoA reductase mRNA in samples of cytoplasmic SMC mRNA. We cloned and sequenced a 199 bp cDNA fragment of chicken HMG-CoA reductase, which encoded a region of 66 amino acids belonging to the catalytic domain of the enzyme. HMG-CoA reductase mRNA concentrations from young C-SMC cultures rose 3.89-fold 4 h after the change of medium and returned to base levels between 8 to 12 h afterward. Concentrations in Ch-SMC cultures increased less (2.36-fold) 8 h after the change to fresh medium. Increases in reductase mRNA in senescent cultures of Ch-SMC and C-SMC measured under similar conditions were only 1.28- and 1.39-fold, respectively.