Optimization of parameters affecting on CHO cell culture producing recombinant erythropoietin.

Several factors may affect erythropoietin (EPO) sugar structures including designing cell culture procedure, pH, concentration of additives, dissolved oxygen, and other physicochemical parameters. In this study, we investigated the influence of changes in effective parameters and compounds on the growth rate of Chinese hamster ovary cell (CHO) cells producing recombinant EPO. Cell culture was performed at different temperature, buffering conditions, and varied concentrations of additives such as pyruvic acid, insulin, GlutaMAX, and sodium butyrate. Results indicated that the optimal temperature and pH were 37 °C and 7.2, respectively. Also, optimal concentrations for pyruvic acid, butyrate, glutamate, and insulin were obtained to be 20 mM, 1 mM, 2 mM, and 40 µg/mL, respectively. Then, cell culture was performed in microcarrier-coated spinner flasks under the optimized condition. The results showed recombinant human EPO (rhEPO) production with adequate purity. Optimization of physicochemical conditions and culture media are important factors to improve the quantity and quality of protein products. This study showed that cell growth and recombinant EPO protein production significantly increased under the optimized conditions. The results of this research can also be used in scale-up to increase the efficiency of EPO production. Abbreviations: EPO: erythropoietin; CHO cell: Chinese hamster ovary cell; rhEPO: recombinant human EPO; DMEM: modified eagle's medium; FBS: fetal bovine serum; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; IGF-1: insulin-like growth factor 1.

Garlic Dermatitis on the Neck of an Infant Treated for Nasal Congestion.

The health benefits of garlic (Allium sativum) as a naturopathic remedy have been well documented, but topical application of garlic has been linked to allergic and irritant contact dermatitis. We present a case of severe irritant contact dermatitis due to application of a fresh garlic necklace to the neck of infant for treatment of nasal congestion.

Post-prandial glucose and insulin responses of hummus alone or combined with a carbohydrate food: a dose-response study.

OBJECTIVES: Pulses are low glycemic index (GI) foods and have been associated with reduced risk of heart disease, diabetes and some cancers. However the blood glucose and insulin responses of hummus, a food containing chickpea, have not been thoroughly tested. METHODS: Ten healthy subjects each consumed 11 breakfast study meals in randomized order over a period of 15 weeks. Hummus was consumed alone at three doses (2.7 g, 10.8 g and 25 g available carbohydrate [avCHO] portions) and with 50 g avCHO from white bread at three doses (2.7 g, 5.4 g and 10.8 g avCHO portions). The responses elicited by hummus alone were compared with 25 g avCHO portions of white bread, while those after hummus plus white bread were compared with 50 g avCHO from white bread. Plasma glucose and serum insulin responses were monitored over two hours and the GI and insulin index (II) calculated using standard methodology. RESULTS: The GI and II of hummus were 15 ± 3 and 52 ± 13, respectively, and were significantly lower than white bread (P < 0.05). The glucose and insulin incremental area under the curve (IAUC) for hummus alone were significantly lower than white bread except for insulin IAUC of hummus 25 g avCHO. The peak rise of blood glucose and insulin after hummus were significantly lower than after white bread. Glucose and insulin IAUC after adding hummus to bread did not differ significantly from white bread alone. However the blood glucose 45 min after adding 25 g avCHO from hummus to white bread was significantly lower while at 120 min it was significantly higher than after white bread alone. CONCLUSIONS: This study demonstrated that, similar to chickpeas, hummus has a very low GI and II. Postprandial glucose responses were 4 times less than that of white bread and did not compromise insulin levels.

Obstacles hindering the mainstream practice of teledermatopathology.

BACKGROUND: Teledermatopathology has the potential to link underserved areas to experts across the country and assist in making quick diagnoses, which may improve health care costs and delivery. Despite these potential benefits, teledermatopathology is not used routinely for primary diagnosis in the United States. OBJECTIVE: To assess the current status of and address the potential for improving health care by the use of teledermatolopathology for primary diagnosis. METHODS: Current available literature and online resources were reviewed to address 3 major variables that hinder the widespread use of teledermatopathology: diagnostic accuracy, licensure requirements, and reimbursement. RESULTS: Recent studies show similar diagnostic accuracy for this technology compared to conventional microscopy. State-to-state variation and ambiguity in laws serve as the biggest hurdles to the widespread use of teledermatopathology. More states are recognizing the importance of the implementation of specific laws regarding telemedicine. More studies are required to evaluate the systems that offer specific telemedicine licenses, in addition to those that pay for telemedicine services specifically. LIMITATIONS: This study reviewed current legislation concerning teledermatopathology; these laws are subject to revision. CONCLUSION: Improving diagnostic accuracy and limiting variations in policy and reimbursement may encourage more pathologists to use teledermatopathology technology.

Low profile multi-layered invisibility carpet cloak using quantum dot core-shell nanoparticles.

In this paper, a method to reduce the profile of layered carpet cloaks is proposed. We analytically prove and numerically demonstrate that using a Low Index Material (LIM), a material with a relative dielectric constant smaller than 1, in construction of carpet cloaks can remarkably reduce their profiles. Using the proposed technique, a carpet cloak consisting of alternating LIM and silicon layers is designed to provide invisibility at visible wavelengths. The designed cloak has a profile that is 2.3 times smaller than a carpet cloak without LIM layers. To realize low index materials at optical wavelengths, silver-coated CdSe/CdS quantum dots dispersed in a polymer host are used. Quantum dots are utilized to compensate the loss of Silver and to achieve a low index medium with neglectable loss. The designed low profile carpet cloak is numerically analyzed showing a good performance for a wide range of incident angles which is the advantage of the proposed structure in comparison with metasurface-based carpet cloaks which work only for a very narrow range of incident angles.

Gut microbiota, diet, and heart disease.

Modulation of the gut microbiota is an area of growing interest, particularly for its link to improving and maintaining the systemic health of the host. It has been suggested to have potential to reduce risk factors associated with chronic diseases, such as elevated cholesterol levels in coronary heart disease (CHD). Diets of our evolutionary ancestors were largely based on plant foods, high in dietary fiber and fermentable substrate, and our gut microbiota has evolved against a background of such diets. Therapeutic diets that mimic plant-based diets from the early phases of human evolution may result in drug-like cholesterol reductions. In contrast, typical Western diets low in dietary fiber and fermentable substrate, and high in saturated and trans fatty acids, are likely contributors to the increased need for pharmacological agents for cholesterol reduction. The gut microbiota of those consuming a Western diet are likely underutilized and depleted of metabolic fuels, resulting in a less than optimal gut microbial profile. As a result, this diet is mismatched to our archaic gut microbiota and, therefore, to our genome, which has changed relatively little since humans first appeared. While the exact mechanism by which the gut microbiota may modulate cholesterol levels still remains uncertain, end products of bacterial fermentation, particularly the short chain fatty acids (i.e., propionate), have been suggested as potential candidates. While more research is required to clarify the potential link between gut microbiota and CHD risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber, and fermentable substrate would be a useful strategy for improving systemic health, possibly by altering the gut microbiota.

The application of the glycemic index and glycemic load in weight loss: A review of the clinical evidence.

Obesity is rapidly becoming a global epidemic. As it is a significant risk factor for several chronic diseases, including type 2 diabetes and cardiovascular disease, it is imperative to study dietary and lifestyle approaches that help reduce its prevalence. Recently, due to its possible link to appetite control and metabolism, several clinical studies have assessed the effect of low glycemic index (GI) and glycemic load (GL) diets on weight loss. To determine the application of GI/GL in the prevention and treatment of obesity, we searched several databases and identified 23 clinical trials that examined low GI/GL diets and weight loss as the primary outcome measure. In general, these studies showed much inconsistency in their findings. While a few studies found significantly greater weight loss on the low GI/GL diets, most of the other studies showed a non-significant trend that favored low GI/GL diets; suggesting that factors other than GI/GL may play a role. It would be helpful if a pooled analysis were undertaken to clarify the current findings and outline the limitations of these studies. There is also a need for more long-term randomized, controlled trials that not only focus on weight loss but also on weight maintenance and body composition.

Health effects of mixed fruit and vegetable concentrates: a systematic review of the clinical interventions.

Diets rich in fruits and vegetables (FV) have been associated with a reduced risk of chronic disease, including cardiovascular disease. Unfortunately, public health campaigns to increase FV intake have had limited success. A number of mixed concentrated FV products have been studied, which may help certain individuals improve nutrient status. However, the possible health benefits of FV supplements have not been systematically reviewed. We, therefore, undertook a systematic search of MEDLINE and EMBASE to identify clinical interventions that examined the effect of commercially available concentrated mixed FV supplements on cardiovascular disease risk factors. Twenty-two reports, which used commercially available products, were identified. None of the studies reported any serious adverse effects. Overall, daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods (ß-carotene, vitamins C and E) and folate. Functional changes, such as reduced serum homocysteine and markers of protein, lipid, and DNA oxidation, were also reported; in addition, the health advantages on markers of inflammation, immunity, and endothelial function are promising. Limitations of the available studies were related to the diversity of studies conducted with respect to design and study population and the variability in the measured outcomes and assays utilized. While mixed FV supplements may serve as an efficacious complement for individuals who have difficulty achieving their daily FV intake requirement, further research on additional retail preparations is warranted. Key teaching points: Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables. Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins (ß-carotene, vitamins C and E) and folate and reduce homocysteine and markers of oxidative stress. Mechanistic studies and larger, randomized, placebo-controlled double-blind trials in both healthy and high-risk populations are necessary to better understand the health effects of these supplements.

Nuts, metabolic syndrome and diabetes.

The ability of nuts to improve the blood lipid profile and reduce the risk of CHD is now well established. The interest that health effects of nuts have gained recently has brought the possible benefits of consuming nuts, such as improvement in the conditions of the metabolic syndrome, and their potential to prevent and control diabetes into focus. Results from cohort studies have associated nut consumption with a reduced risk of developing diabetes and CVD. However, few randomised controlled trials have assessed the effect of nuts on diabetes control, and those that have been undertaken have shown improvements in blood lipids but not in the glycaemic control. Diabetes agencies are increasingly recognising the importance of controlling postprandial glycaemia fluctuations. Acute feeding studies indicate that nuts have minimal effects on rising postprandial blood glucose levels when eaten alone, and diminish the postprandial glycaemic response when consumed with high-glycaemic index carbohydrate foods in both normoglycaemic and type 2 diabetic individuals. Nuts have a healthy nutritional profile, high in MUFA and PUFA, are a good source of vegetable protein and are rich in fibre, vitamins and minerals. Incorporation of nuts in the diet may therefore improve the overall nutritional quality of the diet. While more research is required to establish the ability of nuts to improve glycaemic control in the long run, early data indicate that the inclusion of nuts in the diets of individuals with diabetes and the metabolic syndrome is warranted, in view of their potential to reduce CHD risk.

The glycemic index: physiological significance.

The glycemic index (GI) is a physiological assessment of a food's carbohydrate content through its effect on postprandial blood glucose concentrations. Evidence from trials and observational studies suggests that this physiological classification may have relevance to those chronic Western diseases associated with overconsumption and inactivity leading to central obesity and insulin resistance. The glycemic index classification of foods has been used as a tool to assess potential prevention and treatment strategies for diseases where glycemic control is of importance, such as diabetes. Low GI diets have also been reported to improve the serum lipid profile, reduce C-reactive protein (CRP) concentrations, and aid in weight control. In cross-sectional studies, low GI or glycemic load diets (mean GI multiplied by total carbohydrate) have been associated with higher levels of high-density lipoprotein cholesterol (HDL-C), with reduced CRP concentrations, and, in cohort studies, with decreased risk of developing diabetes and cardiovascular disease. In addition, some case-control and cohort studies have found positive associations between dietary GI and risk of various cancers, including those of the colon, breast, and prostate. Although inconsistencies in the current findings still need to be resolved, sufficient positive evidence, especially with respect to renewed interest in postprandial events, suggests that the glycemic index may have a role to play in the treatment and prevention of chronic diseases.

Effect of novel maize-based dietary fibers on postprandial glycemia and insulinemia.

BACKGROUND: Postprandial hyperglycemia has been associated with increased oxidative stress and the development of diabetes, heart disease and all-cause mortality. OBJECTIVE: To assess the effect of novel maize-based dietary fibers on postprandial glycemia and to assess the correlation between a rapid in vitro digestibility system and the blood glucose response. METHODS: In a clinical study, 12 healthy volunteers were fed seven test beverages containing maize-based fiber ingredients (25g total carbohydrate) along with 2 control meals on separate occasions in random order. Capillary blood samples were obtained and the relative glycemic and insulinemic responses were assessed by calculating the incremental area under the 2 h blood response curves. In vitro digestibility studies of the test fibers and control were also undertaken to determine if these correlated with the clinical findings. RESULTS: All test fibers resulted in significantly lower glycemic and insulinemic responses for the incremental area under the curve (iAUC) and at all time points compared with the control (P < 0.05). The in vitro digestibility curves were comparable to the cumulative in vivo iAUCs. In vitro data expressed as percent digestion correlated significantly with the in vivo iAUC for the first 30min of the test meal (P < 0.05). CONCLUSION: These novel maize-based dietary fibers all produce lower postprandial glycemic and insulinemic responses than the control. While further assessment is necessary in beverage and foods containing these fibers, they may be effective in applications for dietary strategies to control diabetes and other chronic diseases. In addition, the in vitro digestibility assay correlated well with in vivo data and may be useful in guiding product development.

Acute effects of raisin consumption on glucose and insulin reponses in healthy individuals.

Raisins are popular snacks with a favourable nutrient profile, being high in dietary fibre, polyphenols and a number of vitamins and minerals, in addition to being rich in fructose. In light of evidence demonstrating improvements in glycaemic control with moderate fructose intake and low-glycaemic index (GI) fruits, our aim was to determine the GI, insulin index (II) and postprandial responses to raisins in an acute feeding setting. A total of ten healthy participants (four male and six female) consumed breakfast study meals on four occasions over a 2- to 8-week period: meal 1: white bread (WB) (108 g WB; 50 g available carbohydrate) served as the control and was consumed on two separate occasions; meal 2: raisins (R50) (69 g raisins; 50 g available carbohydrate); and meal 3: raisins (R20) (one serving, 28 g raisins; 20 g available carbohydrate). Postprandial glucose and insulin were measured over a 2 h period for the determination of GI, glycaemic load (GL) and II. The raisin meals, R50 and R20, resulted in significantly reduced postprandial glucose and insulin responses when compared with WB (P < 0·05). Furthermore, raisins were determined to be low-GI, -GL and -II foods. The favourable effect of raisins on postprandial glycaemic response, their insulin-sparing effect and low GI combined with their other metabolic benefits may indicate that raisins are a healthy choice not only for the general population but also for individuals with diabetes or insulin resistance.

Effect of a 6-month vegan low-carbohydrate ('Eco-Atkins') diet on cardiovascular risk factors and body weight in hyperlipidaemic adults: a randomised controlled trial.

OBJECTIVE: Low-carbohydrate diets may be useful for weight loss. Diets high in vegetable proteins and oils may reduce the risk of coronary heart disease. The main objective was to determine the longer term effect of a diet that was both low-carbohydrate and plant-based on weight loss and low-density lipoprotein cholesterol (LDL-C). DESIGN, SETTING, PARTICIPANTS: A parallel design study of 39 overweight hyperlipidaemic men and postmenopausal women conducted at a Canadian university-affiliated hospital nutrition research centre from April 2005 to November 2006. INTERVENTION: Participants were advised to consume either a low-carbohydrate vegan diet or a high-carbohydrate lacto-ovo vegetarian diet for 6 months after completing 1-month metabolic (all foods provided) versions of these diets. The prescribed macronutrient intakes for the low-carbohydrate and high-carbohydrate diets were: 26% and 58% of energy from carbohydrate, 31% and 16% from protein and 43% and 25% from fat, respectively. PRIMARY OUTCOME: Change in body weight. RESULTS: 23 participants (50% test, 68% control) completed the 6-month ad libitum study. The approximate 4 kg weight loss on the metabolic study was increased to -6.9 kg on low-carbohydrate and -5.8 kg on high-carbohydrate 6-month ad libitum treatments (treatment difference (95% CI) -1.1 kg (-2.1 to 0.0), p=0.047). The relative LDL-C and triglyceride reductions were also greater on the low-carbohydrate treatment (treatment difference (95% CI) -0.49 mmol/L (-0.70 to -0.28), p<0.001 and -0.34 mmol/L (-0.57 to -0.11), p=0.005, respectively), as were the total cholesterol:HDL-C and apolipoprotein B:A1 ratios (-0.57 (-0.83, -0.32), p<0.001 and -0.05 (-0.09, -0.02), p=0.003, respectively). CONCLUSIONS: A self-selected low-carbohydrate vegan diet, containing increased protein and fat from gluten and soy products, nuts and vegetable oils, had lipid lowering advantages over a high-carbohydrate, low-fat weight loss diet, thus improving heart disease risk factors. TRIAL REGISTRATION: clinicaltrials.gov (http://www.clinicaltrials.gov/), #NCT00256516.

Session 4: CVD, diabetes and cancer: A dietary portfolio for management and prevention of heart disease.

CHD is the leading cause of worldwide mortality. The prevalence of heart disease has been linked to the adoption of a sedentary lifestyle and the increased dietary dependence on saturated fats from animal sources and the intake of refined foods. Elevated blood cholesterol level is one of the major risk factors for CHD. While cholesterol-lowering drug therapy (statins) has been effective in reducing the risk of heart disease, there are those individuals who are unwilling or because of muscle pains or raised levels of liver or muscle enzymes are unable to take cholesterol-lowering medication. Fortunately, there is evidence linking a number of dietary components to CHD risk reduction. The strength of this evidence has prompted various regulatory bodies to advocate diet as the first line of defence for primary prevention of heart disease. It was therefore decided to combine four dietary components that have been shown to lower blood cholesterol concentrations (nuts, plant sterols, viscous fibre and vegetable protein) in a dietary portfolio in order to determine whether the combined effect is additive. In a metabolically-controlled setting this dietary portfolio has proved to be as effective as a starting dose of a first-generation statin cholesterol-lowering medication in reducing the risk of CHD. The dietary portfolio has also been shown to be effective in sustaining a clinically-significant effect in the long term under a 'real-world' scenario. However, success of the diet depends on compliance and despite the accessibility of the foods adherence has been found to vary greatly. Overall, the evidence supports the beneficial role of the dietary portfolio in reducing blood cholesterol levels and CHD risk.

Health benefits of nuts in prevention and management of diabetes.

The effects of tree nuts on risk factors for coronary heart disease (CHD), in particular blood lipids, have been investigated in a number of studies and the beneficial effects are now recognized. The beneficial effects of nuts on CHD in cohort studies have also been clearly demonstrated. However, while there is also reason to believe the unique micro- and macronutrient profiles of nuts may help to control blood glucose levels, relatively few studies have investigated their role in diabetes control and prevention. Nuts are low in available carbohydrate, have a healthy fatty acid profile, and are high in vegetable protein, fiber and magnesium. Acute feeding studies indicate that when eaten alone nuts have minimal effects on raising postprandial blood glucose levels. In addition, when nuts are consumed with carbohydrate rich foods, they blunt the postprandial glycemic response of the carbohydrate meal. Despite the success of these acute studies, only a limited number of trials have been conducted with nuts in type 2 diabetes. These studies have either been of insufficient duration to observe changes in HbA1c, as the standard measure of glycemic control, or have been underpowered. Therefore, more long-term clinical trials are required to examine the role of nuts on glycemic control in patients with prediabetes and diabetes. Overall, there are good reasons to justify further exploration of the use of nuts in the prevention of diabetes and its micro- and macrovascular complications.

The effect of physiological concentrations of sex hormones, insulin, and glucagon on growth of breast and prostate cells supplemented with unmodified human serum.

The majority of cell culture studies have assessed the effect of hormones on cancer cell growth using media supplemented with charcoal-treated fetal bovine serum (CTS). We aimed to determine whether using a system more reflective of the human condition by changing the charcoal-treated serum to an untreated pooled human serum (PHS) resulted in the same hormone responses in breast and prostate cell lines. MCF-7 breast cancer, MCF-10A non-transformed breast, and LNCaP prostate cancer cell lines supplemented with PHS were treated with high and low physiological concentrations of six hormones (17ß-estradiol, dehydroepiandosterone (DHEA), dihydrotestosterone (DHT), testosterone, insulin, and glucagon). Cell growth was measured after 72 h of incubation. All hormones stimulated growth of MCF-7 cells (p < 0.05). MCF-10A cell growth was inhibited by DHEA, DHT, and testosterone (p < 0.05), unaffected by 17ß-estradiol and glucagon, and stimulated by insulin (p < 0.05). LNCaP cell growth was stimulated by the highest concentration of DHEA and DHT (p < 0.05) and inhibited by the highest concentration of 17ß-estradiol (p < 0.05), while insulin and testosterone, had no effect. Overall, PHS lowered the magnitude of the effect of hormones on cell growth in comparison to CTS. Due to the presence of all serum constituents, our model represents a more appropriate physiological environment for determining the effect of hormones on cancer cell growth. Further studies are required to determine the mechanisms by which added hormones interact with the constituents of untreated human serum.

The effect of a plant-based low-carbohydrate ("Eco-Atkins") diet on body weight and blood lipid concentrations in hyperlipidemic subjects.

BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.

Nutritional considerations for older adults with type 2 diabetes.

As Western populations age, the burden of associated chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer will increase dramatically. In the United States in the next 50 years, it is projected that the percentage of adults with type 2 diabetes will exceed 30%, with the vast majority older than 65 years. It is therefore important to determine the best possible dietary and lifestyle modifications to prevent and control this disease and its associated complications. Although few data are available regarding the optimal nutritional regimen for the elderly with type 2 diabetes, as a general rule, the use of nutrient-dense, low glycemic index, high-dietary fiber foods with possibly higher protein intake is recommended.