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Aline de Piano*, Débora Estadella, Lila M. Oyama, Eliane B Ribeiro, Ana R Dâmaso and Claudia M da Penha Oller do Nascimento
Department of Biosciences, Graduate Program in Nutrition, Nutrition Physiology, Federal University of São Paulo, Brazil
Received Date: June 25, 2014; Accepted Date: August 01, 2014; Published Date: August 05, 2014
Citation: de Piano A, Estadella D, Oyama LM, Ribeiro EB, Dâmaso AR, et al. (2014) Nonalcoholic Fatty Liver Disease (NAFLD), a Manifestation of the Metabolic Syndrome: New Perspectives on the Nutritional Therapy. Endocrinol Metab Synd 3:135. doi: 10.4172/2161-1017.1000135
Copyright: © 2014 de Piano A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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NAFLD; Nutrition; Fatty acids; Intestinal microbiota; Vitamin D
Nonalcoholic fatty liver disease (NAFLD) is defined as the abnormal accumulation of lipids, primarily in the form of triglycerides in individuals who do not consume significant amounts of alcohol (≤ 20 g ethanol/d) [1]. NAFLD is characterized by a spectrum of disease varying from simple steatosis through to steatohepatitis with fibrosis and scarring, which can lead to cirrhosis [2].
The prevalence of individuals diagnosed with NAFLD varies from 10-39% of the world population. The disease can be associated with other co-morbidities and affects 50% of diabetics, 57 to 74% of obese people, and 90% of morbidly obese people. In the pediatric population, NAFLD affects 2.6% of eutrophic children and up to 60% of obese children and adolescents [3-5]. NAFLD is currently recognized as a clinically emergent problem among obese patients [6,7].
NAFLD is a multifactorial disease and is the hepatic manifestation of metabolic syndrome. The pathogenesis of NAFLD involves complex mechanisms and has been extensively discussed in the literature. Insulin resistance (IR), inflammatory states, nutrients, genetic factors and lifestyle all play key roles in its development [8]. The central mechanism responsible for NAFLD is insulin resistance, which causes an influx of free fatty acids into hepatocytes, elevates de novo hepatic lipogenesis that can exceed the rate of β-oxidation of fatty acids and causes very low density lipoprotein (VLDL) exportation, ultimately resulting in hepatic fat accumulation [7]. This disequilibrium, caused by hepatic lipid influx, can induce reactive oxygen species (ROS) production, which increases oxidative stress and activates stellar hepatic cells. Molecular lipotoxicity can occur once the influx of free fatty acids activates complex intracellular pathways, including the c-jun N-terminal Kinase enzyme and the Tolllike 4 receptor (TLR-4). Moreover, increased lipid peroxidation leads to the generation of ROS, which are toxic mediators that ultimately promote mitochondrial dysfunction in hepatocytes [9,10].
Visceral adipose tissue accumulation, which contributes to inflammatory pathways and the development of peripheral insulin resistance, has also been explored as a potential mechanism for developing NAFLD [11]. Inflammatory cells, such as macrophages, infiltrate visceral adipose tissue, which increases inflammatory adipokine secretion, leptin, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and angiotensinogen as well as reduces adiponectin production [12]. When the tissue becomes insulin-resistant, it induces major lipolytic activity and increases the levels of free fatty acid influx into the portal vein, potentially causing hepatotoxicity. Small intestinal bacterial overgrowth (SIBO) may also promote the progression of NAFLD into nonalcoholic steatohepatitis by enhancing intestinal permeability and favoring absorption of endotoxins with pro-inflammatory and pro-fibrogenetic effects on the liver [13]. It is worthwhile to consider that the microbiota and nutrients involved in intestinal health can inform strategies for NAFLD treatment.
Several studies have reported the important role that dietary composition plays in the development and progression of NAFLD [14-16]. A high-fat diet converts the pathology from bland NASH with fibrosis, which leads to cirrhosis in humans [17]. It has been proposed that the levels and types of fatty acid composition, especially saturated and trans fatty acids, promote the accumulation of free fatty acids (FFA) in hepatocytes, which causes apoptosis by diverse inflammatory pathways. These may include microbiota modification, insulin resistance, and ROS-induced stress that affect the mitochondrial membranes, endoplasmic reticulum and lysosomes (see review Estadella et al., [10]).
Lipid peroxidation increases the levels of reactive oxygen species, which may be partially responsible for hepatocyte dysfunction. Antioxidant nutrients reportedly exert an important role in reducing ROS production [18]. Moreover, mono and polyunsaturated fatty acids can play a protective role in NAFLD development, mainly because n-3 PUFAs (polyunsaturated fatty acids) have many beneficial effects on most metabolic syndrome features and have anti-inflammatory properties [19].
The objective of this review was to elucidate the influence and role of dietary composition, including the type of consumed fatty acids, antioxidant nutrients, pre and probiotics and vitamin D in the nutritional treatment and prevention of NAFLD.
NAFLD and Lipids
Fatty acids are an essential constituent of the cell membrane, as they modulate the activity of membrane-bound transporters and enzymes, modify membrane fluidity, serve as intracellular messengers and alter intracellular functions. One animal study reported that dietary lipids can change both the chemical composition and lateral organization of rat hepatocyte plasma membranes [20].
In humans, dietary fat intake may play a critical role in the development of NAFLD. It is now clear that both the levels of lipids introduced and the types of fatty acids ingested affect the development of the disease [21].
The lipid metabolic perturbations in NAFLD are complex and may be more fully explored. The evaluation of the amounts and quality of different lipid classes, comparison of fatty acid distribution and comprehension of the functions fatty acids have in different NAFLD mechanisms can be an important tool for NAFLD treatment [21]. Recently, lipotoxicity and plasma lipidome have emerged as novel targets for potential therapeutic strategies [21,22]. The possible mechanisms by which lipids affect NAFLD treatment will be further explored in the present review.
NAFLD and mono and polyunsaturated fatty acids
Diet composition may directly and indirectly influence the NAFLD pathways. Dyslipidemia is considered a risk factor for NAFLD development [23]. Several studies have demonstrated that a high intake of monounsaturated fat improves postprandial glucose, decreases oxidized low density lipoprotein (LDL), LDL cholesterol, and triacylglycerol concentrations, particularly for a diet in which monounsaturated fats replace both saturated fat and high levels of carbohydrates [8,24-26].
A recent study has demonstrated that in only 6 weeks, an oliveoil rich diet, the Mediterranean diet, which contains high levels of monounsaturated fatty acids, promotes a decrease in hepatic steatosis accompanied by an improvement in peripheral insulin sensitivity and a reduction in circulating insulin concentrations [27]. These authors also suggested that an increased intake of monounsaturated fatty acids (MUFAs) and omega-3 PUFAs, particularly as a replacement for saturated fat and as a higher proportion of the diet than carbohydrate intake, is beneficial for NAFLD patients. Some studies suggest that insulin resistance may be accompanied by a change in the composition of fatty acids in the blood and tissues, with deficiency of omega 3polyunsaturated fatty acids. Moreover, there have been promising results in animal models and humans with the use of omega 3 in NAFLD [28,29].
The beneficial effects of supplementing with omega 3 can be partially explained by the increase in the plasma levels of adiponectin as well as the increased synthesis of adiponectin in the adipose tissue and the restored expression of hepatic peroxisome proliferator-activated receptor alpha (PPAR-α), promoting a reduction in the cholesterol levels and accumulation of triacylglycerol [30].
Several authors have shown that n-3 PUFA may have beneficial effects in preventing the complications of lipotoxicity that are primarily caused by excess saturated and trans fatty acids. PUFA dietary intake has beneficial effects on intra-hepatic fat accumulation in patients with NAFLD [19,21,31]. In a study on a pediatric NAFLD population, n3- docosahexaenoic acid treatment for 6 months improved the fatty liver and insulin sensitivity [29].
Omega 3 (n-3) PUFAs, especially eicosapentaenoic acid (C20:5n3, EPA) and docosahexaenoic acid (C22:6n3, DHA), exert protective roles in the inflammatory pathways involved in NAFLD development and progression [19].
The omega-3 (n-3) fatty acids are essential, polyunsaturated fatty acids (PUFAs) that cannot be synthesized in vivo. Instead, they are consumed in the diet, especially from fish oil, flaxseed and some nuts. These fatty acids, which are derived from α-linolenic acid and mainly occur as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are anti-inflammatory. The other key group of PUFAs, n-6 fatty acids, is predominantly found in grain and derived from linolenic acid; arachidonic acid is proinflammatory and prothrombotic [28].
Omega-6 (n-6) and omega-3 (n-3) fatty acids (PUFAs) are competitively metabolized by the same pathway. In this way, the ratio of n-6 to n-3 should be approximately 3:1; however, there is no consensus on the adequate ratio for achieving beneficial effects in NAFLD. Although this ratio has not been established, it is strong confirmation that a low total level of n-3 is found in NAFLD and is associated with steatosis, increased oxidative stress and progression of the disease [28].
Briefly, the n-6 and n-3 fatty acids compete for enzymes involved the in chain desaturation and elongation reactions. Although these enzymes have higher affinity for the n-3 family, the conversion of alphalinolenic acid in PUFA-LC is strongly influenced by the levels of linoleic acid in the diet. Thus, the ratio between the daily intake of food sources of fatty acids n-6 and n-3 is important in human nutrition [32-34].
Studies have revealed a significant reduction in the mortality rate of patients with cardiovascular disease, inflammation, and symptoms resulting from asthma when the ratio of linoleic/alpha-linoleic in the diet is 4:1; the symptoms were intensified for a ratio of 10:1 [32-34].
Moreover, there was a study in which the exposure of human hepatocytes to different mixtures of linoleic and alpha-linoleic affected the transcription levels of a selection of genes encoding regulatory proteins that are involved in several stages of fatty acid metabolism. This effect strongly depends on the ratio of n6/n3 fatty acids, revealing the importance of ingesting not only appropriate levels of fatty acids but also an appropriate ratio of n6 and n3 fatty acids [35].
Arachidonic acid, di-homo-gamma-linoleic acid (20:3 n-6), and eicosapentaenoic acid (20:5 n-3) are precursors of series 1, 2 and 3 prostanoids and series 4, 5 and 6 leukotrienes, respectively. Cyclooxygenase (COX), which converts these free fatty acids in cyclic endoperoxides, produces prostaglandins and thromboxane, the prostanoids. Lipoxygenase (LOX), which is also linked with the production of lipoxins 1,9, contributes to the production of leukotrienes [36].
Increased levels of fish oil decrease the levels of arachidonic acid in the inflammatory cell membranes, resulting in less substrate availability for the synthesis of eicosanoids that are derived from arachidonic acid. Additionally, EPA inhibits arachidonic acid release from phospholipids, which is mediated by phospholipase A2, and competitively inhibits the COX-mediated oxygenation of arachidonic acid. Thus, n-3 fatty acids have important anti-inflammatory properties, including decreasing the production of series 2 prostaglandins and thromboxanes [37].
The excessive production of series 2 prostanoids may be related to immune disorders, cardiovascular disease, and inflammation. Thus, people are encouraged to increase their intake of n-3 fatty acids to increase the production of series 3 prostanoids [36].
Alterations in the liver long chain polyunsaturated fatty acids (LCPUFA) status in NAFLD are characterized by significant depletion of the n-3 LCPUFA content and an increased in the n-6/n-3 LCPUFA ratio, which can favor the development of NAFLD [38
Studies investigating whether dietary n-3 LCPUFA supplementation triggers an antioxidant response that prevents liver steatosis have demonstrated that supplementation results in a reduction in the hepatic lipid content; increased insulin sensitivity; and decreased levels of serum transaminase, TNF-alpha, soluble TNF receptor 1 and 2, and oxidative stress markers, with improvement of hepatic steatosis. These outcomes are mediated by either n-3 LCPUFA derived resolvins and protectins and/or direct PPAR-a-dependent factor nuclear kappa B (NF-kB) and inhibition of the activator protein 1 (AP-1) [39-41].
Omega-3 fatty acids are key regulators of the transcription of hepatic genes, such as PPARa and sterol regulatory element binding protein-1 (SREBP-1). PPARa reduces plasma lipids and increases mitochondrial beta oxidation, and omega-3 fatty acids activate this transcription factor, improving the expression of genes associated with fatty acid and lipid metabolism [42]. The SREBP-1 influences the genes involved in fatty acid and cholesterol synthesis, reducing endogenous lipid production and improving peripheral insulin sensitivity [28]. Moreover, the levels of omega 3 fatty acids in the diet can substantially influence the stimulation of adiponectin, an anti-inflammatory adipokine, gene expression [43].
EPA and DHA promote decreases in the levels of anti-inflammatory and inflammation resolving resolvins and protectins [37]. The resolvins and protectins are new families of locally acting mediators that are derived from essential fatty acids. The synthesis of resolvins and protectins involves the COX and LOX pathways, and their biological effects of have been widely evaluated in cell culture and animal models as anti-inflammatory and inflammation resolving; for example, they inhibit the transendothelial migration of neutrophils, preventing the infiltration of neutrophils into sites of inflammation and inhibiting IL-1β production. Furthermore, protectin D1 specifically inhibits the synthesis of TNF-alpha and IL-1 β [37].
Several studies have confirmed that n-3 fatty acids are involved in the regulation of hepatic gene expression, cell membrane composition, insulin sensitivity, anti-inflammatory effects, and the reduction of TNFalpha levels, decreasing liver steatosis [19,21,28,31,44,45].
NAFLD, intestinal health and inflammatory pathways
Multi-targeted therapy could optimally treat NAFLD patients. Recently, interesting nutritional strategies like the use of dietary supplements, such as probiotics and long chain omega-3 polyunsaturated fatty acids, have been adopted in NAFLD treatment [28,46,47].
Among the pathogenic factors leading to NAFLD, crosstalk between the gut and liver is critical [48]. Currently, specific nutrients that are capable of increasing the intestinal permeability to bacterial endotoxins promote the inflammatory response of liver cells, leading to a profibrogenic state [49]. A recent study utilizing animal models [50] demonstrated that restoring the gut microflora is critical to protecting the liver from fat accumulation, which reinforces that nutrients that act on inflammatory pathways to improve gut health and promote adequate microbiota colonization, such as pro and prebiotics and vitamin D, should be considered in NAFLD treatment.
NAFLD: Probiotics and Prebiotics
The human gut contains substantial microorganisms, including bacteria, archaea, viruses, and some unicellular eukaryotes, called microbiota, which may provide energy, nutrients, and immunological protection that benefit the host [51].
The intestinal flora is important to normal gut function and maintenance of health, and the dietary composition can influence the intestinal colonization. In healthy adults, 80% of the identified fecal microbiota can be classified into the following three dominant phyla: Bacteroidetes, Firmicutes and Actinobacteria. The Firmicutes to Bacteroidetes ratio is important in the human gut microbiota composition [52]. Studies have demonstrated that human obesity is associated with low levels of intestinal Bacteriodetes and high levels of Firmicutes, favoring the development of metabolic syndrome and NAFLD [53,54].
Several mechanisms have been proposed that link the gut flora to obesity; for example, the gut microbiota increase energy extraction from indigestible dietary polysaccharides and elevate plasma lipopolysaccharide levels, resulting in chronic low-grade inflammation. Additionally, the gut microbiota in regulate the host genes that control metabolic processes [55,56].
Inflammatory process
Germ-free mice are protected from obesity and metabolic syndrome. There may be complex mechanisms for the potential increased energy harvest from the diet through dietary-induced or genetically induced obese microbiota [57]. However, experimental protocols that colonize germ-free mice with selective human flora are essential for investigating the influence of diets and other confounding factors on the microbiota and their consequent implications for the host metabolism [58].
The quality of the diet influences the gut microbiota composition. Diet explains 57% of the bacterial variation in the gut while genetic background only accounts for 12% of the variation in animals, suggesting the importance of diet in determining the composition of the gut microbiota [59].
Cani et al. [55] found that mice treated with a high-fat diet have a significant change in the composition of their dominant bacterial populations within the gut microflora, including a decrease in the number of Bifidobacteria, Eubacterium rectal-Clostridium coccoides group and Bacteroides, favoring an increase in the gram-negative to gram-positive ratio. This change in the gut microflora composition was associated with a significant increase in plasma lipopolysaccharide (LPS) levels accompanied by an increase in the intestinal permeability and a reduction in the expression of genes coding for tight junction proteins [60,61]. These studies demonstrate the possible pathways that are responsible for the gut microbiota in metabolic endotoxemia, inflammation, obesity, liver hepatic triacylglycerol accumulation, insulin resistance and type 2 diabetes [62,63].
Increasing evidence suggests the gut microbiota in humans controls obesity and visceral fat storage [64]. Small intestinal bacterial overgrowth (SIBO), a common condition in obese individuals, is mainly stimulated by slowing of the oro-coecal transit time, may promote NAFLD progression to nonalcoholic steatohepatitis by enhancing intestinal permeability and favoring absorption of endotoxins with proinflammatory and pro-fibrogenetic effects on the liver [65].
In previous clinical studies performed by our research group, we found a positive correlation between the calories derived from SFA intake and visceral fat in NAFLD patients [66,67]. Moreover, we recently demonstrated a positive correlation between the plasma endotoxin concentration and pro-inflammatory cytokines, especially IL-6, and insulin resistance in obese adolescents. After long-term (one year) interdisciplinary therapy, endotoxemia, pro-inflammatory status and insulin resistance were decreased [68]. These results demonstrate the efficiency of lifestyle changes (i.e., nutritional modification) in reducing the pro-inflammatory state of obese individuals [69].
An increase in serum LPS has been associated with the proinflammatory state, development of insulin resistance and type 2 diabetes. LPS stimulates Toll-like receptors in the cell membranes, which activate specific kinases and lead to insulin resistance [68].
These pathways also activate NF-ĸB, which results in the expression of inflammatory genes. Similar to LPS, saturated fatty acids are also recognized by membrane receptors that trigger proinflammatory signaling pathways [56,62,63,68].
The bacterial metabolities, TMAO (trimethylamine-N-oxide) and SCFA (short chain fatty acids) are markers of risk for disease and have varied effects on metabolism [51].
TMAO is a phospholipid that is integral to cell membranes and is present in foods with higher fat contents that are associated with the atheroprogression process, which is influenced by the microbiota composition [51]. This phospholipid is a new biomarker for developing CVD as well as a novel biomarker for food choice behavior. In fact, NAFLD has recently been associated with the pro atherogenic state [70].
The SCFAs produced by microbiota fermentation are acetate, propionate and butyrate, which are used as an energy source for colonocytes, and the overproduction of SCFAs could increase the liver lipogenesis because they are a lipogenic substrate [71]. Indeed, SCFAs are affected by the gut microbiota composition and influence the regulation of blood lipids as well as affect pathways related to food intake and lipid metabolism. The intestinal microbiota break down indigestible polysaccharides (i.e., fiber) to short-chain fatty acids (SCFAs) providing 80 to 200 kcal per day or approximately 4–10% of the daily energy intake in normal adults [72].
The mechanisms supporting that the absence of adequate gut microbiota is associated with the development of obesity and NAFLD are related, in part, to the effect of healthy microbiota on the reduction of hepatic de novo lipogenesis as well as to the inhibition of triacylglycerol storage in the white adipose tissue. The latter effect is thought to be caused by an excessive production of FIAF (fasting-induced adipocyte factor) or angiopoetin-like protein 4 (ANGPTL4) in the intestines of the germ-free mice [73].
FIAF is a circulating lipoprotein lipase inhibitor produced by the intestines, liver and adipose tissue. FIAF inhibits lipoprotein lipase (LPL), blocking the disassociation of fatty acids from triacylglycerols for uptake into tissues as well as upregulating fatty acid oxidation and uncoupling proteins, potentially reducing the fat storage in germ-free mice [74]. FIAF also plays a role in the metabolic adaption to fasting via PPAR activation [75].
Several systems in people can be affected by bacterial components and metabolities of the gut microbiota detecting, especially in the case of the development of metabolic diseases [51]. The gut microbiota can directly and indirectly affect the host's health through bacterial components and metabolites.
The probiotics promote gastrointestinal health and beneficial consequences for the liver.
In colonic epithelia, probiotics stimulate mucin production and improve the self-protecting properties of the intestinal epithelium by stimulating tight junctions, which competitively exclude microbial pathogens. Indeed, the tight junction proteins remain intact and, thereby, prevent both the uptake of macromolecules and translocation of viable organisms to mesenteric lymph nodes and the liver [76].
Moreover, the integrity of the intestinal barrier decreases the LPS exposure and proinflammatory signaling, improving the antiinflammatory cytokines, such as interleukin-10, which results in less vulnerability to hepatotoxins and limits intestinal bacteria overgrowth (IBO) and LPS production [76]. Altogether, probiotic supplementation is an important tool for treating NAFLD patients.
Corroborating these findings, studies have demonstrated that gut microbiota manipulation with probiotics in rodents with fatty livers reduces intestinal inflammation and improves the function of the epithelial barrier [60,61]. Hence, probiotics could be used to treat NAFLD human patients [13].
Loguercio and colleagues [77] showed that probiotics may reduce NAFLD liver injury and improve liver function tests. Another study found that treatment with 500 million Lactobacillus bulgaricus and Streptococcus thermophiles/day in adults with biopsyproven NAFLD promotes a significant reduction of the levels of liver transaminases [78].
These data suggest that the diet composition has an important role on the development and treatment of NAFLD [67]. Additionally, it is essential to consider the use of probiotics to treat and prevent NAFLD [62].
To further elucidate the role of the gut microbiota and gut-liver-axis both in causing or worsening obesity itself and/or related complications including NAFLD and NASH, robust, well-designed studies should be performed. These studies should focus on the mechanisms involved in the possible imbalances of the numerous metabolic, toxic, and immunological actors participating in the gut-liver-axis. The probioticmediated gut microbiota modulation is a promising tool for treating NAFLD, NASH, and obesity due to the safety, tolerability and efficacy of this treatment method [78,79].
Using probiotics as an intervention for intestinal microbiota can modulate the expression of nuclear receptors, improving insulin resistance in the liver and adipose tissue as well as protecting against the development of NAFLD. Randomized placebo controlled trials on the use of probiotics in NAFLD are ongoing in humans [46-48].
Prebiotics are beneficial, non-digestible food ingredients that affect the host by selectively stimulating growth and/or modifying the metabolic activity of select intestinal bacteria [80]. Various fermented ingredients are classified as prebiotics, including inulin-type fructans and galactans [81].
The main health effects of prebiotics are due to three principal mechanisms that include selective modulation of the gut microbiota to reduce inflammation; improvement of glucoregulation and modification of lipid metabolism including reduced de novo fatty acid synthesis and SCFA production; and reduction of body fat [81,82].
Modulation of the gut microbiota is linked to improvement in the glucose, energy intake, insulin, satiety hormones, hepatic cholesterol, and triacylglycerol accumulation. Prebiotics have been reported as a potential therapeutic approach for reducing the risk of obesity and altering the composition of the gut microbiota (Figure 1) [78].
Prebiotic fibers have a bifidogenic effect and are associated with reduced LPS levels. As stated before, LPS, also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; LPS are found in the outer membrane of gramnegative bacteria, act as endotoxins and elicit strong immune responses in animals [83].
Jumpertz et al. [84] reported that the stool energy in proportion to the ingested calories is positively correlated with the abundance of the phylum Bacteroidetes and negatively correlated with the abundance of the phylum Firmicutes in the feces of people.
Dysbiosis in the gut microbiota refers to a condition with microbial imbalances in the bowel that may activate hepatic de novo lipogenesis by increasing the expression of lipogenic enzymes, acetyl co-A carboxylase (ACC), and fatty acid synthase (FAS) [64].
A recent study in obese rats showed that prebiotic fibers improve or normalize gut microbiota dysbiosis by decreasing Firmicutes and increasing Bacteroidetes phylae [82].
Finally, prebiotic induced changes in the gut microbiota also influence the production of the gut trophic hormone, glucagonlike peptide-2, which could potentially decrease the lipid and LPS concentrations due its effects on the intestinal permeability and epithelial tight junctions [85].
Prebiotic-rich diets may ameliorate NAFLD by attenuating de novo fatty acid synthesis as has been shown in animal models [86-89]. Fiordaliso et al. [89] verified that animals treated with oligofructose (OFS) have a modified liver capacity that can synthesize triacylglycerols from free fatty acids in isolated hepatocytes.
However, in another animal model of germ-free mice, there was a doubling of the hepatic triacylglycerol content and a concomitant increase in the hepatic mRNA levels of sterol-responsive elementbinding protein (SREBP-1) and carbohydrate-responsive elementbinding protein (ChREBP), both of which are positive regulators of the aforementioned lipogenic enzymes [90,91].
Moreover, prebiotics associated with probiotics promote the production of short chain fatty acids (SCFA), leading to the growth of indigenous bifidobacteria and/or lactobacilli and lowering the luminal pH, which in turn prevents the growth of pathogens [92]. Acetate, propionate and butyrate are the main SCFAs produced in the large intestine. As described previously, although the greater part of butyrate is metabolized by colonocytes, propionate and acetate are delivered to the liver via the portal vein [93].
Butyrate is a major metabolite in the colonic lumen arising from bacterial fermentation of dietary fiber and is a critical mediator of the colonic inflammatory response. This SCFA is associated with the inhibition of HMG-CoA reductase, an enzyme involved in the metabolic pathway that produces cholesterol. Studies have shown that a diet enriched with prebiotic fibers promotes an increase in the ratio of propionate to acetate, decreasing lipogenesis as propionate inhibits lipogenesis, whereas acetate promotes the process [88,93].
Animals receiving a high fat diet and prebiotic treatment have decreased steatosis, fat storage in the white adipose tissue, systemic inflammation, and insulin resistance [93,94]. Prebiotic treatment in people results in a reduction in BMI, waist circumference, fat mass, and insulin resistance [81,95].
Prebiotic fiber supplementation is associated with reduced body weight or attenuated weight gain in lean, high-fructose fed high-fat, high-sucrose fed and genetically obese rodent models [96].
Although the majority of animal studies use a 10% inulin dose by weight with a minimum 4 week supplementation period, Sugatani et al. [97] reported reductions in the liver TAG and cholesterol in cafeteria diet-fed rats supplemented with 5% synthetic inulin for 3 weeks. In comparison, improvements in serum and liver lipids with prebiotic doses are reported to be as high as 20% [87]. The minimum inulin dose and necessary duration has not been fully defined and requires further study.
Human studies assessing the effects of prebiotic fiber supplementation on NAFLD patients are lacking; however, we can verify clinical protocols to identify the effects of prebiotic fiber supplementation on serum lipids. Parnell and Reimer [98] reported significant weight loss following 3 months of oligofructose supplementation in overweight and obese adults. Other possible mechanisms for the action of prebiotics in humans include improvements in glycemia and modifications to plasma glucagon-like peptide-1, peptide YY and ghrelin [82].
In summary, the prebiotic-induced, gut-mediated changes in luminal and peripheral metabolism include a reduction in bacteriaderived hepatotoxins, improved gut epithelial barrier, reduced inflammation, decreased de novo lipogenesis, modified appetite and satiety, and improved glycemic control [82] (Figure 1).
Recent studies suggest that vitamin D is associated with obesity, diabetes, cardiovascular diseases, metabolic syndrome and NAFLD [99-101]. In a multiple logistic regression analysis study, performed on Korean men, the tertiles with lower 25(OH)D(3) levels presented with a significantly increased risk for NAFLD compared with the highest tertile, even after adjusting for the body mass index and metabolic syndrome. Accordingly, individuals with higher serum 25(OH)D3 presented with a significantly reduced risk for NAFLD independent of obesity and metabolic syndrome [99]. Additionally, inadequate 25(OH) D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D (>30 ng/mL), insufficient (15–30 ng/mL) or deficient (<15 ng/mL) [102].
In a recent meta-analysis, the vitamin D role in the pathogenesis of NAFLD was discussed. Deficiency of vitamin D, considering a cut-off serum level ranging from 12 to 30 ng/mL, was associated with a higher NAFLD risk. The normal range of vitamin D remains controversial; however, the most recent Institute of Medicine (IOM) Committee report endorses the use of 20 ng/mL [103].
The lower 25(OH) D concentrations in overweight and obese individuals needs to be confirmed and the possible reasons for differences in these concentrations must be studied in more detail to better manage the vitamin D status [104]. To prevent and treat vitamin D deficiency by maintaining serum 25(OH)D levels above 30 ng/mL, the Endocrine Society Guidelines recommend 400-1000 UI for children and 1000-2000 UI for adults [105].
The vitamin D is a hormone implicated in several aspects of metabolism and the human immune system [106]. This vitamin can be obtained from exogenous sources and can be synthetized in the skin by conversion of 7-two hydroxylation in the liver and kidney, generating active vitamin D (vitamin D, 1,25(OH)2D3) [107]. The hepatocytes are exclusively responsible for 25-hydroxylation, which is mediated by CYP27A1 and CYP2R1, two cytochromes expressed in the liver [108]. Barchetta et al. [109] demonstrated that the expression of these cytochromes in NASH patients is lower than in the control group, but this difference was not significant.
Moreover, liver vitamin D receptor (VDR) expression has a strong association with the NASH diagnosis independent of BMI, insulin resistance or adiponectin, suggesting a loss in the hydroxylation of hepatocytes and the hepatoprotective role of vitamin D [109]. The VDR is expressed in many tissues, such as the liver, pancreas, and several immune cells, and its expression is most abundant on the epithelial cells of the gastrointestinal tract. The VDR modulates the expression of several other genes that are involved in converting dehydrocholesterol to previtamin D3 by ultraviolet radiation [107]. The VDR is expressed by macrophages; 1,25(OH)2D3 upregulates the inhibitor of nuclear factor (NF)-κB (IκB-alpha) by increasing mRNA stability and decreasing IκB-alpha phosphorylation, suggesting that 1,25(OH)2D3 has an antiinflammatory effect on macrophages [110].
Vitamin D increases the VDR expression in the rat ileum and liver as well as in the ileum of humans [111]. The VDR stabilizes tight junctions in the intestinal epithelial cells [112], suggesting a possible reduction of LPS action and the proinflammatory process.
There is a negative correlation between VDR expressions on hepatocytes with the NAFLD activity score in humans [109]. In an animal study performed in rats fed on a high-fat/high-fructose corn syrup diet alone or with vitamin D depletion, the vitamin deficient group presented with significantly greater hepatic steatosis, lobular inflammation and higher hepatic messenger mRNA levels for TLR2, TLR4 and TLR9 and other proinflammatory and oxidative stress markers compared to the control group.
Vitamin D deficiency can exacerbate NAFLD through TLR activation accompanied by increased inflammation and oxidative stress [113]. In a recent investigation developed by our research group, vitamin D3 supplementation for a high fatty diet exerts an anti-inflammatory effect once it decreases the IL-6 production in epididymal adipose tissue in mice as well as in 3T3-L1 adipocytes stimulated with LPS [114].
Another study developed in human adipocytes and in 3T3-L1 adipocytes reported decreases in the levels of inflammatory markers such as IL-6, MCP-1, and IL-1β (mRNA and protein levels) after 1,25-dihydroxyvitamin D3 (1,25-(OH)(2) D(3) treatment. In basal and TNF-α-stimulated conditions, this treatment decreased the expression of the proinflammatory marker in 3T3-L1 and human adipocytes. Finally, the 1,25-(OH)(2) D(3) treatment promoted improvement in glucose uptake and AKT phosphorylation. These data support the involvement of the vitamin D receptor gene and NF-κB in NAFLD, suggesting that low-grade inflammation could be linked to vitamin D deficiency [115].
The effects of 1,25(OH)2D3-VDR have not yet been fully defined, but it appears that vitamin D, likely cooperating with other regulators, exerts immunoregulation, antimicrobial defense, xenobiotic detoxification, anti-cancer actions, control of insulin secretion and, possibly, cardiovascular effects [110]. Indeed, the influence of vitamin D in the NAFLD mechanisms should be further explored [99].
The biovailability of vitamin D is disturbed by obesity, wherein adiposity is associated with lower bioavailability of this vitamin, leading to impairment in insulin secretion and sensitivity [104]. Corroborating this finding, an investigation of two common VDR polymorphisms suggested that 2 major VDR gene polymorphisms may be linked to insulin secretion and resistance [107].
Pancreatic insulin secretion is inhibited by vitamin D deficiency, suggesting a role for this vitamin in the regulation of endocrine pancreatic function, especially in the β cell [116]. It is already known that 1,25(OH)2D3 directly influences β cell insulin secretion through the induction of increases in the intracellular free calcium concentration through voltage-dependent Ca2+ channels [117]. This mechanism is implicated in insulin cascade signaling, which exerts a fundamental role in preventing several diseases, such as NAFLD.
A study on young adults showed that the prevalence of metabolic syndrome components is significantly lower across quintiles of vitamin D intake, reinforcing the usefulness of vitamin D intake [100]. Vitamin D intake may modulate the risks of metabolic syndrome and, as cited previously, vitamin D is involved in the promotion of calcium influx, regulation of insulin secretion and glucose uptake [100].
Based on these findings, measuring vitamin D levels may be an important strategy in NAFLD treatment, and vitamin D supplementation may be associated with an adequate n3/n6 ratio and pre and probiotics, contributing to healthy gut microbiota [103] (Figures 2 and 3).
Figure 2: Beneficial pathways of dietary composition (omega 6/omega 3 ratio) in the nutritional treatment and prevention of NAFLD. PPAR (proliferator-activated receptor), SREBP-1 (sterol regulatory element binding protein-1), VDR (Vitamin D Receptor), COX (cyclooxygenase), LOX (lipoxygenase), NFκB (nuclear factor kappa B), IκB-α (nuclear factor – kappa-B inhibitor alpha), IL-1β (Interleukin-1 beta), TNF- α (tumor of necrosis factor alpha).
Finally, another possible mechanism linking vitamin D, the PUFAs and NAFLD has been studied. Researchers have identified several additional nutritional lipids as candidate, low-affinity VDR ligands that may function locally in high concentrations. The novel putative VDR ligands include w3- and w6-essential polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and arachidonic acid. The ligand binding of VDR triggers tight association between VDR and its heterodimeric partner, retinoid X receptor (RXR), and only the VDRRXR heterodimer can penetrate the deep groove of DNA and recognize vitamin D responsive elements (VDREs) in the DNA sequence of vitamin D-regulated genes. These VDR-RXR controlled genes encode proteins that determine bone growth and remodeling, intestinal calcium absorption, phosphate homeostasis, the mammalian hair cycle, cell proliferation, and lipid detoxification [110]. The n-3 PUFAs, such as DHA and EPA, and n-6 PUFAs, such as linoleic acid and arachidonic acid, compete with titrated 1,25(OH)2D3 for binding to VDR with affinities for the receptor that are four orders of magnitude lower than that of the 1,25(OH)2D3 hormonal ligand. Nevertheless, the authors concluded that high local concentrations of PUFAs could be present in select cells or tissues and, if VDR is expressed, result in VDR-mediated anti-proliferation/ pro-differentiation effects, which may partially explain the chemoprotective nature of diets rich in PUFAs [110].
New perspectives on the nutritional treatment and prevention of NAFLD
Knowledge of the inflammatory pathways involved in the development of NAFLD and new studies in nutrition, which reveal the strong positive influence of bioactive compounds in these inflammatory processes, are essential for guiding treatment and prevention recommendations. Based on these findings, we suggest the follow steps for NAFLD treatment:
Analyzing the dietary intake using different tools, such as the 24- hour recall, three-day food diary, food frequency and diet history, focusing on verifying the w3/w6 ratio, pre and probiotics and vitamin D ingestion;
The nutritional plan must be designed based on reducing the saturated and trans fatty acids and substituting monounsaturated and polyunsaturated fatty acids, corresponding to the following: saturated fat <7%, monounsaturated fat 10% and polyunsaturated fat 10% of the total energetic value. Supplementation with w3 (1 g/fish oil) is beneficial at a suggested ratio of n-6 to n-3 of approximately 3:1;
Considering that dietary composition can influence the health of gut microbiota, the dietary plan should include daily alimentary sources of probiotics and a prebiotic-rich diet, such as with a 10% of inulin dose by weight with a minimum 4 week supplementation period. However, the optimal dose of pre and probiotics need to be further investigated.
Performing a serum analysis of vitamin D to verify possible deficiency and determine the necessary vitamin D supplementation;
Based on the cut-off serum level, 12 to 30 ng/mL of vitamin D was associated with an increased NAFLD risk, and the recommended vitamin D was 400-1000 UI for children and 1000-2000 UI for adults to correct the deficiency status and promote NAFLD improvement.
Altogether, these guidelines are important for nutritional therapy. Finally, the multidisciplinary team should always look for joint strategies and treat all aspects of the disease in question as well as delve deeper into promising areas such as nutrigenomics and translational investigations, which improve our understanding of the interaction between potential bioactive components and track the triggering of these comorbidities, all of which are new strategies for the treatment of NAFLD.
The authors gratefully acknowledge all agencies which supported this work: FAPESP (2010/20079-2), CAPES (007419/2011-21), and CNPq (161433/2011-1).


text:
First we went to my parents for me to help a friend get some painting done. My mom and sister watched the girls while I went to paint. We came home for three days and then left to go to a week of church camp. It was a great week, with great weather and lots of fun with cousins, friends and grandparents. I worked in the kitchen as a cook all week with my sister Valerie and two other ladies. We had a great time and were totally exhausted by Wednesday! I don't remember which day it was, but one morning three of us cooks, and Kate too, went back to our cabins after breakfast and took naps!
Callie and her friend Katie (in the pink jacket) during the memory work "contest"
We got home from camp Saturday morning, we were gone pretty much the whole day on Sunday and then Monday my sister Alyson's baby Finally decided to come into this world. He's been a bit of a stinker. First he wanted to come too early, then he decided to come after the due date! My sister is quite the trooper. Deklan Ray Sparks arrived around 2:30 PM. He weighed........9 lbs and 15 oz!! AND he was 22 inches long. One of my friends said she gave birth to a toddler!! LOL
In the midst of all this excitement, a very special purchase and subsequent delivery was made. The girls have been saving for quite some time for Julie and Ivy. Now to those of you who do not have little girls, those are American Girl dolls. Julie and Ivy are dolls that represent the 70's. Julie has long blonde hair and Ivy is her Chinese friend. Very appropriate, yes? I have been very proud of how hard they have both worked to earn these dolls and how patient they have been. Here they are before taking all of their cash to the bank.
Do you think they were excited?
We have doll pictures and baby pictures to share, but it will have to wait. :) I'm going to bed!

subset: commoncrawl


text: Siemens selling defense electronics unit: Siemens AG said Tuesday it has hired U.S. investment bank Morgan Stanley & Co. to sell its defense electronics unit in an effort to focus on its profitable businesses. Siemens said Morgan Stanley will seek to sell or find a joint-venture partner for its defense electronics business. Siemens did not specify how much it seeks. Siemens has been under pressure from investors since November, when it warned that it would not report a profit this fiscal year.


text:
Deep Dark Chocolate Truffle Bars
- 1 (16.5-ounce) roll refrigerated sugar cookie dough, well chilled
- 1 1/2 cups semi-sweet chocolate chips
- 1 (14-ounce) can of sweetened condensed milk
- 1/2 cup white chocolate chips
- 1 tablespoon shortening
Preheat oven to 350 degrees F. Spray a 13×9 inch pan with non-stick spray.
Cut cookie dough into 1/4 inch slices. Arrange slices in bottom of the prepared pan. With floured fingers, press dough evenly to form a crust in bottom of the pan. Bake for 15-18 minutes or until deep golden brown (dough will appear puffed). Cool Completely.
Combine semi-sweet chocolate chips and sweetened condensed milk in medium saucepan over low heat; stir until smooth and chips are melted. Remove from heat and pour over crust.
Combine White chocolate chips and shortening in small sauce pan over low hear. Stir until melted and smooth. Drizzle over Chocolate layer.
Refrigerate for 1-2 hours or until set. Cut into bars or squares.
Yield: 36 squares


text:
Coming June 9, 2016, Here & Now listeners and visitors will experience our stories and journalism online in a whole new way.
On Friday we heard music from the Lickets, Steve Earle and more.
As opposition leaders close in on Tripoli, American business and consulting firms that work in the country are keeping a close eye developments there. We take a look at one Boston-based firm that Libya hired to improve its image after sanctions were dropped in 2004.
As the fight for control of Libya continues, world markets are fluctuating as they traders to determine how Libya's political future will affect its oil future. We examine Libya's oil reserves and how important they are to world oil production.
A bill to strip most collective bargaining rights from public sector unions in Wisconsin is a step closer to passage, after a late night vote to pass Republican Governor Scott Walker's controversial budget repair bill.
When Josh Fox was offered $100,000 for the natural gas drilling rights to his property in Pennsylvania, he resisted. Instead, he picked up a camera and traveled the country to find out more about what could happen on his land if he signed on the dotted line. His documentary "Gasland" is now up for an Oscar.
"The Social Network," is up for a handful of Oscars this weekend. The movie's Nine Inch Nails soundtrack also got an Oscar nod for the soundtrack, in part thanks to an unusual handmade synthesizer called the Swarmatron. We speak with the Swarmatron's creators, you can also hear samples of the instrument's sounds.


text:
30 avril 2017
Two dated Suzhou 'golden bricks', Qing dynasty, Qianlong period, dated 1749 and 1784
Lot 292. Two dated Suzhou 'golden bricks', Qing dynasty, Qianlong period, dated 1749 and 1784. Estimate 6,000 — 8,000 GBP. Photo: Sotheby's. each of square form, inscribed to the side with a date and place of manufacture, the brick of dark grey tone, later mounted on simple wood bases to form a table. Quantity: 4. Tile: 72 by 70 by 10 cm, 28 1/4 by 27 1/2 by 4 in., and 68.5 by 66 by 8 cm, 27 by 26 by 3 1/8 in. Sotheby's. Important Chinese Art, London, 10 May 2017,... [Lire la suite]
30 avril 2017
600-year-old rare lacquer dish leads Sotheby's Chinese Art Sales in London
Lot 138. A Magnificent and Extremely Rare Large Carved Cinnabar Lacquer Dish, Late Yuan-Early Ming Dynasty, 44.5cm. Est. £400,000-600,000 / HK$3,860,000-5,790,000. Lot sold 1,568,750 GBP. Photo: Sotheby's LONDON.- Following an outstanding year in Chinese art, Sotheby's Important Chinese Art auction in London on 10 May 2017 showcases a selection of notable Chinese ceramics and works of art across the disciplines of imperial porcelain, lacquer, jade and Buddhist sculpture. Skilfully crafted and spanning... [Lire la suite]
23 janvier 2017
Galerie Lamy. Stand 43b. Brafa Art Fair, 21-29 janvier 2017
Pair of large baluster-shaped jars with lids, China, Kangxi period (1662-1722). Blue and white porcelain painted with figures, flower pots and floral decorations. H 56 cm. Courtesy Galerie Lamy. Literature: exhibition catalogue 'The Age of Gallantry', The Chinese porcelain New York, 1995, n° 100 (similar pair) Pair of spaniels, China, Qianlong period (1711-1799); Polychrome porcelain. H 16.5 cm and 17 cm. Courtesy Galerie Lamy. Provenance: Hodroff collection 4041 ... [Lire la suite]
22 janvier 2017
Galerie Bertrand de Lavergne. Stand 3c. Brafa Art Fair, 21-29 janvier 2017
Chinese incense burner, Blue and white and copper-red porcelain on a celadon ground, China, Kangxi period (1662-1722). H 15.5 cm. Courtesy Galerie Bertrand de Lavergne Decorated in light relief with two deer and two cranes in a landscape. Pair of incense boxes shaped as quails. Cloisonné enamel, China, Qianlong period (1736-1795). Total H 24 cm. Courtesy Galerie Bertrand de Lavergne They stand on a later wooden lotus shaped base Set of Chinese snuff bottles. Blue-and-white... [Lire la suite]
28 décembre 2016
A large Chinese dish decorated in the famille rose palette for the Persian market, Qianlong period (1736-1795), circa 1740
A large Chinese dish decorated in the famille rose palette for the Persian market, Qianlong period (1736-1795), circa 1740. © Galerie Nicolas Fournery 2016 Of octogonal form, painted in the famille rose palette, the wide rim moulded in eight planes sloping inwards, with angles clearly showing where they radiate towards the points on the rim. Decorated with eight sepia roundels, each gilded with one of two alternating flowers and set within an irregular border of sepia scrollwork, heightened with thick icy-pink... [Lire la suite]
25 décembre 2016
A rare pair of famille rose sconces, Qianlong period (1735-96)
Lot 358. A rare pair of famille rose sconces, Qianlong period (1735-96). Estimate USD 30,000 - USD 50,000 © Christie's Images Ltd 2016. Each richly enameled with a young man gallantly offering the protection of his parasol to a lady 5 ½ in. (31.8 cm.) high Note: The very rare sconce form, intended for brass or silver candle arms, found in two Pronk-related special order designs. VOC archives note "...sconces...according to the wooden moulds". Christie's. Chinese Export... [Lire la suite]
24 décembre 2016
A large famille rose three-piece garniture, Qianlong period (1735-96)
Lot 357. A large famille rose three-piece garniture, Qianlong period (1735-96). Estimate USD 30,000 - USD 50,000 © Christie's Images Ltd 2016. Molded with panels of mountainous landscape alternating with bird and flower vignettes, all on a patterned ground strewn with peony and prunus - 25 ½ in. (63.5 cm.) high, the vase and cover Christie's. Chinese Export Art, 18 January 2017, New York, Rockefeller Center
06 décembre 2016
A Chinese Imari Cornelius Pronk plate, Qianlong period, circa 1735
Lot 30. A Chinese Imari Cornelius Pronk plate, Qianlong period, circa 1735. Estimate € 1000-1500. Lot sold € 1,700. Photo Vellinghuiis AAG. With a decor designed by Cornelis Pronk (1691-1759) called the "Umbrella Ladies' along the edge eight cartouches at the rear insects. Diam. 23.4 cm Provenance: - Auction AAG, Amsterdam, April 2, 2012, lot 198 - Private collection, Netherlands Vellinghuiis AAG. THE ASIAN ART SALE, Monday, November 28, 2016, 14 h
04 décembre 2016
A very rare pair of imperial inscribed cloisonné enamel peach-shaped wall vases, Qianlong period (1736-1795)
Lot 3333. A very rare pair of imperial inscribed cloisonné enamel peach-shaped wall vases, Qianlong period (1736-1795). Estimate: HKD 800,000 - HKD 1,000,000 (USD 103,606 - USD 129,508). Price Realised HKD 1,000,000 (USD 129,528) © Christie's Images Limited 2016. Each vase is of peach shape with a gilt flat back, decorated in brightly coloured enamels with leafy branches bearing blossoming peach flowers, on a graduating pistachio-green, white, pink and red ground, superimposed with... [Lire la suite]
16 novembre 2016
A cinnabar lacquer 'dragons' quatrelobed box and cover, Qianlong period (1736-1795)
Lot 36. A cinnabar lacquer 'dragons' quatrelobed box and cover, Qianlong period (1736-1795). Estimate HK$ 250,000 - 350,000 (€30,000 - 42,000). © Bonhams 2001-2016 Of quatrefoil shape, finely carved on the cover with three five-clawed dragons in flight chasing a flaming pearl above turbulent waves, framed within a key-fret and leaf lappet border, the body further carved with the Eight Treasures in relief emerging from raging waves, all bordered by key-fret scrolls at the rim and foot, the interior and base... [Lire la suite]


text:
This factor was absolutely relevant for the band to adopt a more profound progressive vibe, adding colorfulness and sophistication to the existing muscle.
The band also changed labels (from DERAM to POLYDOR), and why not, the name, after dropping the article "THE".
Listening music while travelling also decreases the boredom.
Find and download latest Mp4/3gp Videos of your favorite songs from Mobi Mast on Hamari Web Directory.
For example the following request body forces the GSA to re-index a file at the location It has to be mentioned that those ACLs do not propagate back to the real permissions set on the filesystem/wiki entry/…
but as the GSA supports document previews as known from the Internet wide search engine, this might be enough to leak confidential data to internal attackers.
One of the main interfaces for the indexing is available through the TCP ports 1992 where external applications can indicate changes of the documents via HTTP and HTTPS respectively (also called Feeders by Google).
You can set this configuration for the duration of a single session by running a command-line switch.
The powerful presence of African-American singer John L.
WATSON and two guitarists provided a tight muscle to the band's sound, reflected in the first two studio efforts "Fully Interlocking" (1968) and "Theraposa Blondi" (1970).
The GSA is used by companies to apply the Google search algorithms to their internal documents without publishing them to cloud providers.
To accomplish this task, the GSA provides multiple interfaces including a search interface, an administrative interface and multiple interfaces to index the organization's data.


text:
Tuesday, July 30, 2013
Rob is stuck! He must continue treatment in order to keep the pain at bay, but the chemo makes his life hardly worth living. I hate this beast. I hate what it is doing to his body, his spirit, his future.
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text:
A lot of Jacksonville State fans are planning to attend the season opener against Ole Miss. Here is a preview of them by Parish Alford which was part of an article on www.nola.com:
Quarterback status: Nathan Stanley is the starter. He has scant game experience but has shown a nice touch with deep balls. His decision-making improved, and he won the job on his own merit, not based solely on the fact that his chief competitor, redshirt freshman Raymond Cotton, missed a handful of practices with shoulder soreness and may need surgery.
Injuries: Cotton has a torn labrum in his throwing shoulder, but the tear is in the back of the labrum, not the front. That makes the pain tolerable. Surgery is likely, but it's not clear at this point whether that will be in the summer or after the season.
Spring strengths: Defensive line. Rebels are two deep with four senior tackles. Kentrell Lockett is a senior playmaker at one defensive end. Junior college transfer Wayne Dorsey is capable at the other end, but like all newcomers, he'll have a period of acclimation.
Spring weaknesses: Offensive line. Left tackle Bradley Sowell developed into a pretty good pass blocker as the season went on last year. Right tackle Bobby Massie started only four games. Three new starters from guard to guard, and depth is thin. Key is guard Rishaw Johnson. He has a physical streak that the tackles haven't shown. Johnson was expected to be a starter last year but struggled with off-field problems, and was eventually suspended.
Player who will make a splash: Receiver Jesse Grandy. Returned a couple of kicks for touchdowns last year but was used sparingly in the passing game. Very fast and showed dependable hands in the spring. He'll make catches downfield, but there was great emphasis in the spring in getting the ball in his hands quickly with short passing.
Player who will be missed most: Dexter McCluster. Perhaps the top athlete among football players in the SEC last season. Rushed for 1,000 yards in roughly five games. First player in SEC history to rush for more than 1,000 yards and have more than 500 receiving yards in the same season. Replacing him will be done by committee. The top three backs - Brandon Bolden, Enrique Davis and Rodney Scott.
-- Parrish Alford
Monday, May 3, 2010
An Early Look At Ole Miss
Posted by JSU Gamecock Sports at 3:28 PM
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Lytiga W01 Extended Medium Fonts
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@import url(//db.onlinewebfonts.com/c/15615ad28376d69f1be47fb26044301e?family=LytigaW01-ExtendedMedium);#3 Use font-face declaration Fonts.(http | https)
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Copyright (c) 2012 by Andriy Konstantynov. All rights reserved.
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Mondo Redondo NF
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Nick's FontsAuthor
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Storm Sans W01 Bold Italic
Monotype Imaging Inc.Trademark
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Alpsoft Gezit Bold
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3.00 April 3, 2009Company
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Crillee Italic Inline Shad Std
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text: I had to get gas and also wanted a drink, and I was in a huge wet soggy diaper. I decided I'd change into a fresh diaper and go out. It was so fun! I had maybe a 1/3 full bladder at the register, so I peed. It was so cool! I peed in front of everyone, and nobody noticed! Once I got in my truck I tried crapping my pants but nothing came out D=. Anyway, just another little story.


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The Faithfull Bypass Loppers have a powerful ratcheting action that enables easy cutting of large branches. The non-stick coating on the cutting blades resists rust and reduces friction. The oval profile of the strong moulded steel handles enhances rigidity and provides extra strength. They are fitted with soft comfortable non-slip rubber grips that minimise fatigue.
Size: 76cm (30in).Cutting Capacity: 45mm.
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There is no individual thing in nature which is not surpassed in strength and power by some other thing, but any individual thing being given, another and stronger is also given, by which the former can be destroyed. There is always a bigger fish. Every part is important, each comprising the whole. We suffer in so far as we are a part of nature, which part cannot be conceived by it alone without the other parts. The force by which man perseveres in existence is limited, and infinitely surpassed by the power of external causes. The power by which individual things and consequently man preserve their being is the actual power of God or nature, not in so far as it is infinite, but in so far as it can be manifested by the actual essence of man. The power therefore of man, in so far as it is manifested by his actual essence, is part of the infinite power of God or nature, that is to say, part of his essence. Hence it follows that man is always necessarily subject to passions, and that he follows and obeys the common order of nature, accommodating his self to it as far as the nature of things requires. If the power of man is but an expression of the infinite power of God, by better understanding the powers of our own minds, we can better understand the power of God, and hence become more like him.
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Interferon alfa-2b injection may cause or worsen the following conditions that may be serious or life-threatening: infections mental illness, including depression, mood and behavior problems, or thoughts of hurting or killing yourself or others ischemic disorders Interferon alfa 2b is an antiviral or antineoplastic drug, that was originally discovered in the laboratory of Charles Weissmann at the University of Zurich, developed at Biogen, and ultimately marketed by Schering-Plough under the tradename Intron-A. Pegylated interferons are powerful drugs that treat viral hepatitis. What is the difference between Peginterferon alfa 2a and alfa 2b?Pegylated interferon is a modified form of the drug that is able to stay in the body longer, which provides better treatment. The main goal of the development of the HSA-free formulation was to identify a stable interferon alfa-2b solution free of human serum albumin and remains essentially free from visible particles. Regimen details: Interferon alpha2b. 3 million IU.Formulation available IntronA (interferon alfa-2b). This is an unlicensed indication. IntronA is available as the following multi-dose pre-filled pens Interferon Alpha 2B is used for hairy cell leukemia, malignant melanoma, follicular lymphoma, kaposis sarcoma caused by aids, chronic hepatitis b or c and other conditions. interferon alfa-2b treated patients and month after treatment, twice weekly for the. six of 12 controls by week 52. Interferon second month, every month for the next four.TABLE II Progression ofacute non-A, non-B hepatitis to. Interferon alfa-2b is a prescription medication used to treat chronic hepatitis B, chronic hepatitis C, certain type of genital warts, hairy cell leukemia, malignant melanoma, AIDS-related Kaposis sarcoma, and follicular lymphoma. Overview. SYNOPSIS. PharmaCompass Interferon Alfa-2B InformatioALL API SUPPLIERS. 4. View All Suplliers of Interferon Alfa-2B. This page contains brief information about recombinant interferon alfa-2b and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.
Recombinant interferon alfa-2b is approved to treat What are the possible side effects of interferon alfa-2b (Intron A)? Get emergency medical help if you have any of these signs of an allergic reaction: hives difficulty breathing swelling of your face, lips, tongue, or throat. Methods 1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 10001200 mg/day orally, peginterferon alfa-2b 15 g/kg each week plus 800 mg/day ribavirin, or peginterferon 1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 10001200 mg/day orally, peginterferon alfa-2b 15 g/kg each week plus 800 mg/day ribavirin, or peginterferon Interferon alfa-2b reviews. Read drug prescription. It is very important to know about what medicine is given by the doctor, for what condition, and when it needs to be taken in what dose. Interferon alfa-2b may also be used for other purposes not listed in this medication guide. What is the most important information I should know about interferon alfa-2b? Interferon alfa-2b is often used in combination with another drug called ribavirin (Rebetol). INTERFERON ALFA-2B. Therapeutic use. Anti-Inflammatory.Alfaferone (Interferon Alfa-2b). Full match. Anti-Inflammatory Antimicrobial Antiproliferative Antitumour Antiviral Immunomodulating Immunostimulants. Medscape - Indication-specific dosing for Intron A, Interferon alfa-2b ( interferon alfa 2b), frequency-based adverse effects, comprehensive interactions, contraindications, pregnancy lactation schedules, and cost information.
An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile.Comment in. Interferon alfa for chronic hepatitis C infection. Description of the drug Interferon Alfa-2b. - patient information, description, dosage and directions.3) Permanently discontinue interferon alfa-2b if severe adverse reactions persist or if they recur in patients receiving a reduced dose. Interferon alfa-2b is also used to treat some infections caused by viruses, such as the hepatitis C virus.Interferon alfa-2b is a form of interferon alfa (a substance normally made by cells in the immune system) and is made in the laboratory. Interferon alfa-2b may also be used for purposes not listed in this medication guide. You should not use interferon alfa-2b if you have autoimmune hepatitis, or severe liver problems from causes other than hepatitis B or C. Interferon alfa-2b, homeopathic remedy made by Remedia Homeopathy in its own laboratories. Highest quality due to own laboratories and 250 years of experience.Interferon alfa-2b: potencies in stock. Click on a potency to view more information and to order. Medication guide intron. A (In-tron-aye) (Interferon alfa-2b, recombinant). had a serious allergic reaction to another alpha interferon product or are allergic to any of the ingredients in INTRON A. See the end of this Medication Guide for a complete list of ingredients. Interferon alfa-2 concentrated solution. EUROPEAN PHARMACOPOEIA 6.0. rhombohedral crystals, the majority having a maximum dimension when measured from corner to corner through the crystal greater than 10 m but rarely exceeding 40 m. Interferon alpha 2b (human leukocyte clone hif-sn 206 protein moiety reduced). A type I interferon consisting of 165 amino acid residues with arginine in position 23.Interferon Alfa-2b, Recombinant (10000000 unit) Water (1 ml). Liquid Powder, for solution. INTERFERON ALFA-2B. CLASS: Interferon. INDICATIONS: Patients 1 year of age: Chronic hepatitis B. CYT-15 Human interferon-alpha 2B. Description: Interferon-alpha 2B (IFN- alpha 2B) is produced by macrophages and has antiviral activities.The interferon-alpha 2B gene was obtained from human leukocytes. The IFN- alpha 2B is purified by proprietary chromatographic techniques. Interferon Alfa-2B Humano Recombinante pharmaceutical active ingredients containing related brand and generic drugs: Active ingredient is the part of the drug or medicine which is biologically active. Interferon is a protein that occurs naturally in the body in small amounts. Your injection will be a protein that is synthetically produced in a large dose. Administration. It is given as a subcutaneous (under the skin) injection most often in the abdomen or thigh. Interferon alfa-2b has been available in the European Union (EU) for the treatment of various diseases for a number of years.The replacement interferon alfa-2b acts in same way as naturally produced interferon alpha. Interferon alfa-2b is used to treat hairy cell leukemia, malignant melanoma, follicular lymphoma, Kaposis sarcoma caused by AIDS, and certain types of genital warts. Interferon alfa-2b is also used to treat chronic hepatitis B or C in adults Interferon Alfa-2b (Ifn Alpha 2B): Symptoms Workup Diagnosis Treatment Complications Causes Epidemiology Incidence Prognosis Check at SYMPTOMA.com. Pegylated Interferon alfa-2a (Pegasys) Relapse Rates in Genotype 1 Chronic Hepatitis C Patients Depend on Weight-based Ribavirin Dosage 4/07/09.FDA Requires Updated Labeling for Interferon Alpha Products Due to Recently Identified Safety Issues 9-04-2009. Human recombinant Interferon alpha 2b (IFN-2b). Interferon- (INF-), also known as leukocyte interferon, comprises a grope of related but distinct proteins that share over 95 amino acid sequence homology. WHO International Standard INTERFERON ALPHA 1/8, (HUMAN rDNA derived). NIBSC code: 95/572 Instructions for use (Version 5.0, Dated 16/04/2013). 1. INTENDED USE This material is the 1. Alpha interferons, including INTRON.Interferon alfa-2b, recombinant for Injection has been classified as an alfa interferon and is a water-soluble protein with a molecular weight of 19,271 daltons produced by recombinant DNA techniques. While in the combined treatments with interferon alfa-2a or -2b plus ribavirin, there was a highly significant increase in the sperm abnormalities, chromosomal aberrations, number of implantation, dead and live embryos when compared with the control. SYNONYM(S): IFN, alpha interferon COMMON TRADE NAME(S): INTRON-A CLASSIFICATION: biological response modifier1.BC Cancer Agency Cancer Drug Manual Developed: 1994 Revised: 1 June 2015. Page 1 of 12. Interferon alfa-2b. Interferon alfa-2b. Very Low Risk for breastfeeding. Compatible.Alpha-Interferon is a cytokine with antiviral, antiproliferative and immunomodulatory properties with is produced by leukocytes and lymphoblasts that are obtained by recombinant DNA engineering. interferon alfa 2b.A request for the patient identified below has been made for the dispensing of Intron A interferon alfa 2b. Based on recent clinical information, we require more information before this prescription can be paid by the patients health benefit plan. Overview. Interferon alfa-2b. Product attributes. Analyte data.Attributes. Technical name. Interferon alfa-2b. Related products. DESCRIPTION. INTRON A (Interferon alfa-2b) for intramuscular, subcutaneous, intralesional, or intravenous Injection is a purified sterile recombinant interferon product. INTRON A recombinant for Injection has been classified as an alpha interferon and is a Peginterferon alfa-2bs wiki: Pegylated interferon alfa-2b, sold under the brand name is PegIntron among others, is a medication used to treat hepatitis C andThe basic mechanism works such that PEG-interferon alpha-2b will bind to its receptor, interferon-alpha receptor 1 and 2 (IFNAR1/2). Interferon alfa-2b is made from human proteins. Interferons help the body fight viral infections. Interferon alfa-2b is used to treat hairy cell leukemia, malignant melanoma, follicular lymphoma, Kaposis sarcoma caused by AIDS, and certain types of genital warts. This mini review focuses on human interferon alpha-2b (hIFN. -2b) as therapeutic protein for cancer treatment.R. C. Flanigan, S. E. Salmon, B. A. Blumenstein et al Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer, The New Anterferon Suppository--Recombinant Human Interferon alpha 2b (rIFN a2b, rDNA Origin) Suppository.Chinese phoneticize: Chongzu Ren Ganraosu alpha 2b Shuan. [COMPOSITION]. Recombinant Human Interferon alpha 2b. [DESCRIPTION]. [Description] Recombinant Human Interferon alfa-2b is a sterile protein product for injection.
rHuIFN alfa-2b is produced by recombinant DNA technology by Yeast carrying a human interferon alfa-2b gene. Interferons (IFNs) are a group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells. In a typical scenario 12. Recombinant interferon alpha-2b: Pharmaco-clinical summary.Interferon alfa-2 concentrated solution. 1997. p.1031-5. 20. DAndrea M, Tarnowski S, Clark A, inventors Interferon Sciences Inc as-signee. Russias first pegylated interferon alpha with the original structure of the molecule. Prescribed to patients with chronic hepatitis C. Launched in 2013. Genferon ( interferon alfa-2b taurine benzocaine).


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Film: 2267
Feature Comedy | 1900 | Silent | B/W
Williamson of the Brighton Pioneers.
A man is so absorbed in reading his book that he pours his coffee into his hat and trips over the maid. In the street, he walks around unaware that he is causing trouble. First in his dining room his wife points to the clock and gives him his hat but he just wants to carry on reading. A Victorian dining and his breakfast on the table. he pours his coffee and milk into his hat while reading then, realising his mistake, tips it out onto the carpet and splashes the wall. Outside the maid washes the step. Still reading, he trips over her, hurting her arm. He carries on, Two girls in pinafores turn a skipping rope as one jumps in the middle but our man walks right into it. The girls run off. he, still reading, walks into a donkey and the man on the cart behind hits him with a sack. walking down a wide boulevard. he dodges other walkers until finally he walks right into a steam roller, which runs right over him. A cyclist spots him flat on the road and, with the help of another pumps him up with a bicycle pump and brings him back to his feet. he shakes their hands, gets his book and goes on his way. The cyclists roar with laughter.
To request more details on this film, please contact us quoting Film number 2267.


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One of the purposes of conferences, I think, is to facilitate serendipity. Like when a not-very-enlightening presentations leads, almost despite itself, to a very enlightening Q-and-A. Or when two very different takes on the same concept help you nail down what makes you uneasy about both.After an earnest but not terribly helpful discussion of one college's attempt to move to the "Learning College" model - again, an entire session based on one college - a surprisingly lively discussion ensued in which I saw that the critical mind is not dead.
Dean Dad
From Confessions of a Community College Dean, in which a veteran of cultural studies seminars in the 1990's moves into academic administration and finds himself a married suburban father of two. Foucault, plus lawn care.
Most Recent Articles
March 3, 2008
March 2, 2008
The League for Innovation conference has a very different feel than the conferences I used to attend in my scholarly discipline. It makes sense, given that it serves such a different purpose, but I was surprised at how immediately noticeable the difference was.
February 29, 2008
This story made me smile. Someone out there in the real world actually knows how to use a semicolon!Never mind that the use is inelegant; it's technically correct, unpretentious, and practical.
February 27, 2008
This weekend, TW and I are flying out to Denver, where I'll be attending and blogging the League for Innovation in the Community College conference. It's my first 'roving reporter' gig, which I think means I have to buy a brown fedora and a tan trenchcoat. (Any regular correspondents or commenters who plan to be there and want to arrange a meetup, shoot me an email!) I'll be posting my reports on my IHE site, so readers who usually read me on my original site will have a chance to check that out.
February 27, 2008
A canny correspondent writes:I work for a community college system and am working on an Ed.D. in leadership. I am casting around for research questions and wondered if you had any thoughts regarding useful research questions centering around community colleges, systems and educational leadership.Ooh, I like that.
February 26, 2008
A new correspondent writes:I am currently an associate professor at a community college. I have applied for several positions in four year institutions. My applications are in and now I am waiting to see if I will get any interviews. I'm a perfect fit for several of the positions I've applied for and, I think, a decent fit for the others, so I am expecting to interview at several institutions.Here are my questions:
February 24, 2008
As my college stares down the barrel of a nasty external funding cut for the coming fiscal year, and a strong likelihood of another one after that, it's becoming clear to me that higher ed is in a really lousy position for dealing with recessions.
February 21, 2008
The Girl is the cutest, most angelic looking three year old on the planet.But don't be fooled.Yesterday morning, as The Wife and I were upstairs getting ready, and The Boy and The Girl were downstairs, finishing their breakfast:TB: *Mo-ooooommmmm*!TW (sighing): What?TB: TG said I *suck*!DD: (stifled laugh)TW: TG, did you say that?TG (brightly): Sow-wy!TW was mortified, but I was a little proud. TG may look like a girlie girl, but she takes no crap. Over time, this will be a good thing.
February 20, 2008
A new correspondent writes:I read your blog daily and know there are many wise readers who help those seeking knowledge. I am in search!Our Biology instructor is taking a class to the gulf coast for a week long Marine Biology trip. They will spend one night in a hotel both coming and going to the coast. While there, the students will be staying in apartment-style housing where everyone will have their own bed. However, at the hotel, that option is not available.
February 19, 2008
A new correspondent writes:


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|1,291 sq. ft.
|Property type
|Minimum Stay
|3 - 7 nights
Set in a traditional Andalusian style complex, close to all shops, supermarkets and restaurants, this very light, spacious, and well furnished, first floor 2 bedroom apartment has the following accommodation.
There is a spacious open plan living and dining area. Leading off the hallway is the spacious kitchen with all the facilities required. The master bedroom is accessed off the lounge and has a large en suite bathroom and extensive wardrobes, there is access to the south facing terrace off this bedroom, The second bedroom has two single beds and extensive wardrobe space. The bathroom is adjacent to this bedroom. The South facing dining terrace is accessed off the lounge.
There is an underground garage for those wishing to hire a car.
In the complex itself, you have a large communal pool, set to the side of this is a shaded children´s pool. A short walk away is a communal heated pool. The complex has the benefit of 24 hour security.
The apartment was lovely and clean and within a great complex. The complex is situated about a 20 minute walk from the beach and resort centre but had a great selection of restaurants within a 5 minute walk. The pools within the complex are great and our children (aged 5 and 9) had a fab time. Claire as a host was very responsive to messages and provided all the information we needed. We would have no hesitation in recommending this villa.
A lovely light and spacious very comfortable property with fabulous views. A very clean and well equipped apartment situated in well maintained gardens with two amazing swimming pools, one of which has a life guard on duty for most of the opening time. Close to many amenities and a wonderful base to visit the area which has so much to offer. We had a wonderful time and would highly recommend it.
Lovely, spacious apartment (with air con!!) within a beautifully maintained and extremely secure complex. Lovely views of the mountains from the balcony. Choice of pools was great and the gardens were fab. Location was really handy, near to the supermarket (note that it's closed on Sundays!) and several eateries. It's also within walking distance of the town centre/marina/beaches ... just remember to get a taxi back up the hill ... it's definitely worth it!! Can definitely recommend Astral (the ship shaped) cocktail bar on the beach ... amazing cocktails!! Gutted I didn't get to spend the day at the Ocean Club ... but there's always next year!! Can definitely recommend this apartment/location for all ages groups. A truly relaxing/fun holiday!!
Great apartment, extremely secure and clean complex with beautiful grounds. Fab choice of pools! Really convenient location, near supermarket (but be aware supermarket is closed on Sundays!) Market day down the road on Saturdays. There's a huge choice of cafes/restaurants/bars on your walk into town ... but do get a taxi back (it's really cheap and worth it!!) Beaches are great ... alas didn't get to try out the Ocean Club (this time!!) ... but managed to pop in the ship-shaped cocktail bar on the beach a few times ... their cocktails are definitely recommended! A very easy holiday for all age groups ... everything's on your doorstep ... no car required. Great fun!! We'll be back Marbella x
I recently returned from this beautiful apartment after a 10 day stay with friends and family. We all had an amazing week and the photo's really don't do justice to this lovely place, the choice of three pools and its surroundings were ideal, its a great location for restaurants and bars with everything on the doorstep, the port within easy reach. Claire was most helpful throughout, arranging our transfers and recommending places to visit. We hope to return next year if not sooner!
We took a holiday this property at the end of March 15 and spent a wonderful week at this lovely apartment. Excellent location for shops restaurants and supermarket short walk to main port. Look forward to returning again soon.
A perfect place to stay for exploring the coast of the Costa del Sol and Puerto Banus. This very popular development built in the traditional Andalusian style, lies on the edge of Puerto Banus. The port itself is just a 10 minute walk away. The apartment itself is located on the first floor and is very light and spacious. The area is well served by supermarkets, shops, restaurants, cafe´s and bars, the nearest supermarket being 100 metres away, all that you require is on your doorstep.
This is a very vibrant area, extremely popular with all age groups due to its fantastic location.
Puerto Banus has something to offer all everyone. If it is a relaxing holiday you are looking for, there are many beaches within walking distance, including Plaza Beach, Mistral, Buddah and the famous Ocean Club. Should you wish to hire a car, it is well situated for exploring the Southern Coast of Spain and it´s many white villages and the major cities of Granada and Seville, the tax free haven of Gibraltar is a mere 45 minute drive.
This part of the Costa Del Sol enjoys a unique micro climate averaging 320 days of sunshine a year. You can travel to the ski slopes of Sierra Nevada in 2 hours. You are in the middle of the famous Golf Valley offering something to all levels of golfers.
You can dine to your hearts content, every dining experience is available from traditional Spanish to the more sophisticated venues. A must see attraction is the Port itself, this should be visited both during the day and also in the evening.
For those of you wishing to experience something more lively, the nightlife of Puerto Banus is for you.
|No additional mandatory fees
|Damage Deposit
A security deposit of 25% is required to secure the booking.
The balance to be paid 8 weeks prior to arrival.
A refundable security deposit of 250 euros is required with the final payment, this is paid back to you within 7 days of your departure.


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This is a pretty easy to follow sonatina with clear exposition, development, and recapitulation sections. Okay, let's start out the harmonic analysis.
Exposition ms.1-15
First Tonal Area: C Major
ms.1-3 I
ms.4 V, HC
ms.5 I
ms.6 I, V6/V
ms.7 V, vi6, V64, V/V, transition
Second Tonal Area: G Major
ms.8 I
ms.9 V6
ms.10 I
ms.11 V43
ms.12 I6
ms.13 IV
ms.14 V
ms.15 I, PAC
Development ms.16-19
New Key: c minor
ms.16 V42
ms.17 i6
ms.18 V65, i
ms.19 V, HC
Retransition ms.20-23
ms.20 V7
ms.21 i64
ms.22 V6
ms.23 V
Recapitulation ms.24-end
First Tonal Area: C Major
ms.24-26 I
ms.27 V
ms.28-29 I
ms.30 V7, HC
ms.31 I, transition
Second Tonal Area (transposed to tonic key)
ms.32 V6
ms.33 I
ms.34 V43
ms.35 I6
ms.36 IV
ms.37 V
ms.38 I, PAC
Pretty simple right?
Now, to answer questions c, d, and e...
The theme from the first tonal area is "explored" in the development. Really all that happens here is that Clementi takes the first theme, which is in major, and makes it minor, pretty straightforward. The harmonic motion is also simple it goes D,T,D,T, and then back to Dominant one last time ending on a half cadence.
Nothing really drastic happens when the two themes return in the recapitulation. The first theme is in its original key but is lowered by an octave. The second theme is also the same...minus the it being transposed to the tonic key part.
Yep, this is a sonatina. And yes, a sonatina is a basically a shortened sonata. And yeah, it does have an abbreviated development section. Is there really anything else to say? Well, I suppose you could say that if this were a sonata then perhaps the development section would have elaborated a bit more on the first theme, as well as developed the second theme, and maybe even the development section could make up it's own theme for itself! yay for run-on sentences.
Thursday, April 17, 2008
I will shoot this piece in the face if I have to listen to it one more time.
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