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Title:
Long-term consumption of a carbohydrate-restricted diet does not induce deleterious metabolic effects
Authors:
Grieb, Pawe\l; K\lapcińska, Barbara; Smol, Ewelina; Pilis, Tomasz; Pilis, Wies\law; Sadowska-Kr\c epa, Ewa; Sobczak, Andrzej; Bartoszewicz, Zbigniew; Nauman, Janusz; Stańczak, Kinga; Langfort, Józef; Grieb Pawe\land K\lapcińska, Barbara; Smol, Ewelina; Pilis, Tomasz; Pilis, Wies\law; Sadowska-Kr\c epa, Ewa; Sobczak, Andrzej; Bartoszewicz, Zbigniew; Nauman, Janusz; Stańczak, Kinga; Langfort, Józef
Abstract:
Carbohydrate (CHO)-restricted diets have been recommended for weight loss and to prevent obesity, but their long-term effects have not been fully elucidated. This study was designed to evaluate the effect of long-term (\textgreater1 year) consumption of a low-CHO high-fat diet (“The optimal diet,” developed by Dr Kwaśniewski referenced herein) on lipid profile, glycemic control, and cardiovascular disease risk factors in healthy subjects. Of 31 “optimal” dieters enrolled in the study (17 women and 14 men, aged 51.7 ± 16.6 years), 22 declared adherence to the diet for more than 3 years. Average energy intake and principal nutrients consumed were assessed from 6-day dietary records provided by the participants. In most dieters, concentrations of $\beta$-hydroxybutyrate, free fatty acids, total cholesterol, and low-density lipoprotein cholesterol exceeded the upper limits of the reference ranges for nonstarved subjects. The metabolic profiles of most subjects were positive for several indicators, including relatively low concentrations of triacylglycerols, high levels of high-density lipoprotein cholesterol (HDL-C), and normal ratios of low-density lipoprotein cholesterol/HDL-C and total cholesterol/HDL-C. In most subjects, plasma concentrations of glucose, insulin, glucagon, cortisol, homocysteine, glycerol, and C-reactive protein were within reference ranges. Notably, in all but one subject, the homeostasis model assessment index of insulin resistance remained below the threshold for diagnosis of insulin resistance. These results indicate that long-term (\textgreater1 year) compliance with a low-CHO high-fat “optimal diet” does not induce deleterious metabolic effects and does not increase the risk for cardiovascular disease, as evidenced by maintenance of adequate glycemic control and relatively low values for conventional cardiovascular risk factors.
Published:
2008-12
Title:
Perspectives for metabolomics in human nutrition: an overview
Authors:
Koulman A; Volmer DA
Abstract:
Metabolomics describes the measurement of the full complement of the products of metabolism in a single biological sample and correlating these metabolomic profiles with known physiological or pathological states. The metabolome offers the possibility of finding unique fingerprints responsible for different phenotypes. Analytical techniques such as nuclear magnetic resonance or mass spectrometry measure thousands of compounds within the metabolome simultaneously, and appropriate data mining and database tools allow the finding of significant correlations among the measured metabolomes. The first direct outcome of nutritional metabolomics will be the discovery of biomarkers, which can reveal changes in health and disease, but also indicate short-term and long-term dietary intake. The concerted actions of nutrigenomics and metabolomics will play a crucial role in understanding how specific interactions of single nucleotide polymorphisms influence a person's response to a diet. Finally, systems biology approaches to human nutrition combine transcriptomics, proteomics and metabolomics, with the aim of understanding how diets interact within the human being.
Published:
2008-12
Title:
Sudden cardiac death in association with the ketogenic diet
Authors:
Bank, Ilana M.; Shemie, Sam D.; Rosenblatt, Bernard; Bernard, Chantal; Mackie, Andrew S.
Abstract:
The ketogenic diet is a high-fat, low-carbohydrate, adequate-protein diet that is used to decrease the frequency of seizures in patients who have refractory epilepsy. Despite its positive effects in some patients, there are potential adverse effects. Two complications related to the ketogenic diet are selenium deficiency, which has been associated with impaired myocardial function, and QT prolongation as documented on electrocardiography. Reported here are two cases of death in a child on the ketogenic diet for seizure control. In case 1, the child who died of complications related to torsade de pointes, with documented QT prolongation; post mortem examination revealed selenium-deficiency cardiomyopathy. In case 2, a child experienced QT prolongation while on the ketogenic diet and later died suddenly at home. Both children exhibited selenium deficiency. These two cases suggest that patients on the ketogenic diet require monitoring of the QT interval by electrocardiography, myocardial function by echocardiography, and selenium levels before and during the ketogenic diet.
Published:
2008-12
Title:
Undescended testes: a consensus on management
Authors:
Ritzén, E Martin
Abstract:
The mode of treatment best for undescended testes is controversial, and local traditions often override knowledge gained from randomized controlled studies. In order to reach a consensus within the Nordic countries on the current state-of-the-art of treatment, a group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for 2 days. Before the meeting, reviews of the literature had been prepared by the participants. Judging from published meta-analyses, hormonal treatment has low efficacy. Although 15-20% of retained testes descend during hormonal treatment, one-fifth of these re-ascend later on. Also, treatment with human chorionic gonadotropin (hCG) may be harmful to future spermatogenesis through increased apoptosis of germ cells. Orchiopexy, on the contrary, results in about 95% anatomical success, with a low (about 1%) risk of complications. The optimal time for orchiopexy has also been debated. However, a recent randomized controlled study shows that surgery at 9 months of age is followed by a better post-operative growth of the testes than surgery at 3 years, which supports previous arguments for early surgery. The unanimous conclusion of the group was that surgery is generally the preferred mode of treatment, rather than hCG or GnRH treatments. Orchiopexy should be performed between 6 and 12 months of age, or soon after diagnosis, if that occurs later. If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery. Referral should be to paediatric rather than general surgeons/urologists if the boy is less than 1 year old, if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.
Published:
2008-12
Title:
[Ketogenic diets: additional benefits to the weight loss and unfounded secondary effects]
Authors:
Pérez-Guisado, Joaquin
Abstract:
It is also necessary to emphasize that as well as the weight loss, ketogenic diets are healthier because they promote a non-atherogenic lipid profile, lower blood pressure and diminish resistance to insulin with an improvement in blood levels of glucose and insulin. Such diets also have antineoplastic benefits, do not alter renal or liver functions, do not produce metabolic acidosis by Ketosis, have many neurological benefits in central nervous system, do not produce osteoporosis and could increase the perfomance in aerobic sports.
Published:
2008-12
Title:
Alzheimer's disease is type 3 diabetes-evidence reviewed
Authors:
de la Monte, Suzanne M; Wands, Jack R
Abstract:
Alzheimer's disease (AD) has characteristic histopathological, molecular, and biochemical abnormalities, including cell loss; abundant neurofibrillary tangles; dystrophic neurites; amyloid precursor protein, amyloid-beta (APP-Abeta) deposits; increased activation of prodeath genes and signaling pathways; impaired energy metabolism; mitochondrial dysfunction; chronic oxidative stress; and DNA damage. Gaining a better understanding of AD pathogenesis will require a framework that mechanistically interlinks all these phenomena. Currently, there is a rapid growth in the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration, but this surge of new information is riddled with conflicting and unresolved concepts regarding the potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity to AD pathogenesis. Herein, we review the evidence that (1) T2DM causes brain insulin resistance, oxidative stress, and cognitive impairment, but its aggregate effects fall far short of mimicking AD; (2) extensive disturbances in brain insulin and insulin-like growth factor (IGF) signaling mechanisms represent early and progressive abnormalities and could account for the majority of molecular, biochemical, and histopathological lesions in AD; (3) experimental brain diabetes produced by intracerebral administration of streptozotocin shares many features with AD, including cognitive impairment and disturbances in acetylcholine homeostasis; and (4) experimental brain diabetes is treatable with insulin sensitizer agents, i.e., drugs currently used to treat T2DM. We conclude that the term "type 3 diabetes" accurately reflects the fact that AD represents a form of diabetes that selectively involves the brain and has molecular and biochemical features that overlap with both type 1 diabetes mellitus and T2DM.
Published:
2008-11
Title:
An uncertain revolution: Why the rise of a genetic model of mental illness has not increased tolerance
Authors:
Schnittker, Jason
Abstract:
This study uses the 2006 replication of the 1996 General Social Survey Mental Health Module to explore trends in public beliefs about mental illness in the USA. Drawing on three models related to the framing of genetic arguments in popular media, the study attempts to address why tolerance of the mentally ill has not increased, despite the growing popularity of a biomedical view. The key to resolving this paradox lies in understanding how genetic arguments interact with other beliefs about mental illness, as well as the complex ideational implications of genetic frameworks. Genetic arguments have contingent relationships with tolerance. When applied to schizophrenia, genetic arguments are positively associated with fears regarding violence. Indeed, in this regard, attributing schizophrenia to genes is no different from attributing schizophrenia to bad character. However, when applied to depression, genetic arguments are positively associated with social acceptance. In addition to these contingencies, genetic explanations have discontinuous relationships with beliefs regarding treatment. Although genetic arguments are positively associated with recommending medical treatment, they are not associated with the perceived likelihood of improvement. The net result of these assorted relationships is little change in overall levels of tolerance over time. Because of the blunt nature of the forces propelling a biomedical viewdincluding the growing popularity of psychiatric medicationsdaltering beliefs about the etiology of mental illness is unlikely, on its own, to increase tolerance.
Published:
2008-11
Title:
Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors:
Nettleton JA; Diez-Roux A; Jenny NS; Fitzpatrick AL; Jacobs DR Jr.
Abstract:
Background: Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes.Objective: With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation.Design: Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant.Results: After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller ([beta] +/- SE: -0.07 +/- 0.03, P = 0.006). Categorical analysis showed that participants consuming >/=1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length.Conclusions: Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations. © American Society for Nutrition
Published:
2008-11
Title:
Does the effectiveness of the ketogenic diet in different epilepsies yield insights into its mechanisms?
Authors:
Hartman, Adam L.
Abstract:
The ketogenic diet (KD) has been used successfully in a variety of epilepsy syndromes. This includes syndromes with multiple etiologies, including Lennox-Gastaut syndrome and infantile spasms; developmental syndromes of unknown etiology, such as Landau-Kleffner syndrome; and idiopathic epilepsies, such as myoclonic-astatic (Doose) epilepsy. It also includes syndromes where genetics play a major role, such as Dravet syndrome, tuberous sclerosis, and Rett syndrome. Study of the KD in humans and animals harboring various genetic mutations may yield insights into the diet's mechanisms. Comparison of the diet's effectiveness with other treatments in specific syndromes may be another useful tool for mechanistic studies. The diet's utility in epilepsy syndromes of various etiologies and in some neurodegenerative disorders suggests it may have multiple mechanisms of action.
Published:
2008-11
Title:
Double-Blind Comparison of First- and Second-Generation Antipsychotics in Early-Onset Schizophrenia and Schizo-affective Disorder: Findings From the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study
Authors:
Sikich, Linmarie; Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E.; Michael, Emily; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K.; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.
Abstract:
Published:
2008-11
Title:
Efficiency of facultative frugivory in the nectar-feeding bat Glossophaga commissarisi: the quality of fruits as an alternative food source
Authors:
Kelm, Detlev H.; Schaer, Juliane; Ortmann, Sylvia; Wibbelt, Gudrun; Speakman, John R.; Voigt, Christian C.
Abstract:
The efficiency of food exploitation correlates positively with the extent of dietary specialization. Neotropical nectar-feeding bats (Glossophaginae) have one of the most specialized diets among mammals, as floral nectar constitutes a sugar-rich and highly digestible but protein and fiber depleted food source. However, dietary constraints, such as a temporary scarcity of nectar, or protein demands may sometimes require the uptake of alternative food items. We investigated the influence of a diet switch from nectar to fruit on intestinal morphology, body mass, and energy budget in the nectar-feeding bat Glossophaga commissarisi and quantified feeding efficiency. We hypothesized that these nectar specialists depend on a constant supply of nectar, if they were lacking the ability for morphological and physiological plasticity in response to a fiber-rich diet. Although capable of harvesting infructescences of Piper hispidum, G. commissarisi was less efficient in extracting energy from fruits (48% digestive efficiency of total fruit energy content) than from nectar (c. 99% digestive efficiency). The intestinal morphology and organ masses did not change after bats were switched from nectar to fruits. Captive bats exhibited lower daily energy expenditures and flight activity when feeding on fruits than during nectarivory. Possibly, this may have been a deliberate regulation to balance reduced feeding efficiency, or simply the consequence of extended digestive pauses. The low digestibility of Piper, in combination with slow digestion and the bats' inability for morphological and physiological plasticity may cause nectar-feeders to reduce their maximum energy expenditure when feeding on fruits. We argue that although fruits may substitute for nectar, they may cause restricted maximum energy assimilation compared with nectar.
Published:
2008-11
Title:
Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet
Authors:
Bough, Kristopher
Abstract:
The efficacy of the ketogenic diet (KD) develops gradually over a period of 1-3 weeks, suggesting that adaptive changes in gene expression are involved in its anticonvulsant effects. Previously, microarrays were employed to define patterns of gene expression in the hippocampus of rats maintained on either a KD or a control diet for 3 weeks. The density of mitochondria in hippocampal tissue was assessed by electron microscopy. Levels of selected energy metabolites, enzyme activities, and the effect of low glucose on synaptic transmission were also investigated in hippocampal tissue taken from either KD- or control-fed animals. We found a coordinated up-regulation of transcripts encoding energy metabolism enzymes and a dramatic 46% increase in the density of mitochondria observed in neuronal processes. These changes were accompanied by an increased phosphocreatine (PCr):creatine (Cr) energy-store ratio. Consistent with heightened energy reserves, hippocampal synaptic transmission in KD-fed animals was maintained approximately 50% longer compared to controls after exposure to a mild metabolic stressor. Taken together, several lines of evidence indicate that the KD enhances energy production in the brain. As a consequence, brain tissue appears to become more resistant to metabolic stress. It is proposed...that the observed KD-induced enhancements in energy metabolism help to compensate for the metabolic deficits exhibited (interictally) within epileptic foci and transient failures of gamma-aminobutyric acid (GABA) ergic inhibition, which would otherwise favor the initiation and propagation of seizure activity.
Published:
2008-11
Title:
Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans
Authors:
Yeo, Wee Kian; Lessard, Sarah J.; Chen, Zhi-Ping; Garnham, Andrew P.; Burke, Louise M.; Rivas, Donato A.; Kemp, Bruce E.; Hawley, John A.
Abstract:
We have previously reported that 5 days of a high-fat diet followed by 1 day of high-carbohydrate intake (Fat-adapt) increased rates of fat oxidation and decreased rates of muscle glycogenolysis during submaximal cycling compared with consumption of an isoenergetic high-carbohydrate diet (HCHO) for 6 days (Burke et al. J Appl Physiol 89: 2413-2421, 2000; Stellingwerff et al. Am J Physiol Endocrinol Metab 290: E380-E388, 2006). To determine potential mechanisms underlying shifts in substrate selection, eight trained subjects performed Fat-adapt and HCHO. On day 7, subjects performed 1-h cycling at 70% peak O2 uptake. Muscle biopsies were taken immediately before and after exercise. Resting muscle glycogen content was similar between treatments, but muscle triglyceride levels were higher after Fat-adapt (P < 0.05). Resting AMPK-alpha1 and -alpha2 activity was higher after Fat-adapt (P = 0.02 and P = 0.05, respectively), while the phosphorylation of AMPK's downstream target, acetyl-CoA carboxylase (pACC at Ser221), tended to be elevated after Fat-adapt (P = 0.09). Both the respiratory exchange ratio (P < 0.01) and muscle glycogen utilization (P < 0.05) were lower during exercise after Fat-adapt. Exercise increased AMPK-alpha1 activity after HCHO (P = 0.03) but not Fat-adapt. Exercise was associated with an increase in pACC at Ser221 for both dietary treatments (P
Published:
2008-11
Title:
KetoCalculator: a web-based calculator for the ketogenic diet
Authors:
Zupec-Kania, Beth
Abstract:
The classic ketogenic diet (KD) is a mathematically calculated diet with specific daily goals of fat, protein, and carbohydrate. Precise quantities of foods are then derived from these values which result in meal plans for the individual patient. The algebraic algorithm to determine a single meal requires approximately 35 calculations. This process is time consuming given that each individual requires many meals for variety and satisfaction. Computer applications can process multiple calculations in seconds. In 1997, a program was designed by this author with LifeTime Computing, a computer software company. This program was rebuilt into digital format in 2002, given the title KetoCalculator, and made available to registered dietitians on the World Wide Web (Zupec-Kania, 2002).
Published:
2008-11
Title:
Ketogenic ratio, calories, and fluids: do they matter?
Authors:
Wirrell, Elaine C.
Abstract:
The ketogenic diet (KD) traditionally was initiated using specified ketogenic ratios, limited calories, and fluids. Recent work has shown that lower ketogenic ratio diets are frequently as efficacious as higher ones and result in fewer adverse effects. In animals, calorie restriction is anticonvulsant. In children, however, the need for calorie restriction is less clear, but avoidance of excessive calories may improve efficacy of the diet. There is no evidence that fluid restriction is a necessary component of the KD. Given the higher risk of nephrolithiasis, adequate fluid intake should be encouraged.
Published:
2008-11
Title:
Long-term health consequences of epilepsy diet treatments. [Review] [15 refs]
Authors:
Vining, Eileen P. G.
Abstract:
The ketogenic diet (KD) typically provides a marginally healthy diet and in recent years has been used for more protracted courses of therapy. This results in concern about the impact of the diet on the general health of the child. Studies have demonstrated poor growth, dyslipidemia, kidney stones, and numerous other problems seen less frequently. Major areas of concern are reviewed as well as some emerging evidence of more beneficial long-term health consequences beyond the expected control of seizures. [References: 15]
Published:
2008-11
Title:
Long-term management of the ketogenic diet: seizure monitoring, nutrition, and supplementation
Authors:
Zupec-Kania, Beth; Zupanc, Mary L.
Abstract:
The ketogenic diet (KD) is a medical nutrition therapy (MNT) for the treatment of epilepsy. As such, it can affect the outcome of an individual's health and chronic medical condition. The components of MNT which have been established by the American Dietetic Association as core guidelines for nutrition care include a diet history, assessment, diet therapy and a follow-up plan of care (American Dietetic Assoc 2002). We have utilized these guidelines in designing our approach to KD therapy in our pediatric population. Many of the practices described here have been adopted from our practical experience.
Published:
2008-11
Title:
Palaeoenvironmental and cultural dynamics of the coast of Málaga (Andalusia, Spain) during the Upper Pleistocene and early Holocene
Authors:
Cortés-Sánchez, Miguel; Morales-Muñiz, Arturo; Simón-Vallejo, María D.; Bergadà-Zapata, M. Mercè; Delgado-Huertas, Antonio; López-García, Pilar; López-Sáez, José A.; Lozano-Francisco, M. Carmen; Riquelme-Cantal, José A.; Roselló-Izquierdo, Eufrasia; Sánchez-Marco, Antonio; Vera-Peláez, José L.
Abstract:
The impact of late Upper Pleistocene climate change in the western Mediterranean region has been mainly documented through marine records. Archaeological and geomorphological continental records now available for the coast of Málaga complement these records for the second part of the last major glacial episode and the early stages of the Holocene. This paper provides an overview of the archaeological, chronological and palaeoenvironmental data from the end of the Middle Palaeolithic period to the Epipalaeolithic. Sequences from the two major sites, Nerja and Bajondillo, indicate a mosaic-type response of ecosystems to the rapidly shifting conditions of the Last Glacial episode. Terrestrial mammals, for example, show no major variations from present-day communities. Plant remains in contrast, demonstrates the existence of localised refuge areas for species that would not otherwise have survived in the more widely prevailing climatic conditions of the time, whereas remains of fish and, secondarily, birds demonstrate the existence of communities without any present-day analogues combining Mediterranean and Boreal (i.e., northern Atlantic) taxa. From an archaeological standpoint, the major cultural shift is the onset of marine fishing, beginning in the Solutrean. This coincided with the end of the Last Glacial Maximum (LGM) episode. The faunal record also testifies to the rising importance of marine resources more generally. Although the data have not been used systematically to test the validity of the Broad Spectrum Revolution (BSR) hypothesis, the hints for it in the area seem compelling from the start of the Solutrean onwards.
Published:
2008-11
Title:
Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets
Authors:
Seyfried, Thomas N.; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy
Abstract:
Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.
Published:
2008-11
Title:
The Isolation and Characterization of Murine Macrophages
Authors:
Zhang, Xia; Goncalves, Ricardo; Mosser, David M.
Abstract:
Macrophages are mononuclear phagocytes that are widely distributed throughout the body. These cells can contribute to development and homeostasis and participate in innate and adaptive immune responses. The physiology of macrophages can vary tremendously depending on the environment in which they reside and the local stimuli to which they are exposed. Macrophages are prodigious secretory cells, and in that role can promote and regulate immune responses and contribute to autoimmune pathologies. Macrophages are highly phagocytic, and in this capacity have long been considered to be essential immune effector cells. The important roles of macrophages in maintaining homeostasis and in contributing to tissue remodeling and wound healing is sometimes overlooked because of their vital role in host defense.
Published:
2008-11
Title:
The ketogenic diet: uses in epilepsy and other neurologic illnesses
Authors:
Barañano, Kristin W.; Hartman, Adam L.
Abstract:
The ketogenic diet is well established as therapy for intractable epilepsy. It should be considered first-line therapy in glucose transporter type 1 and pyruvate dehydrogenase deficiency. It should be considered early in the treatment of Dravet syndrome and myoclonic-astatic epilepsy (Doose syndrome). Initial studies indicate that the ketogenic diet appears effective in other metabolic conditions, including phosphofructokinase deficiency and glycogenosis type V (McArdle disease). It appears to function in these disorders by providing an alternative fuel source. A growing body of literature suggests the ketogenic diet may be beneficial in certain neurodegenerative diseases, including Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these disorders, the ketogenic diet appears to be neuroprotective, promoting enhanced mitochondrial function and rescuing adenosine triphosphate production. Dietary therapy is a promising intervention for cancer, given that it may target the relative inefficiency of tumors in using ketone bodies as an alternative fuel source. The ketogenic diet also may have a role in improving outcomes in trauma and hypoxic injuries.
Published:
2008-11
Title:
The usefulness of Conners' Rating Scales-Revised in screening for attention deficit hyperactivity disorder in children with intellectual disabilities and borderline intelligence
Authors:
Deb, S.; Dhaliwal, A.-J.; Roy, M.
Abstract:
BACKGROUND: Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) are believed to be common in children with intellectual disabilities (ID). Conners' Rating Scales are widely used for screening ADHD among children who do not have ID, but little is known about their usefulness among children with ID. AIMS: To find cut-off scores for the Conners' Parent Rating Scales-Revised (CPRS-R) and the Conners' Teacher Rating Scale-Revised (CTRS-R) that will give optimum levels of sensitivity and specificity for screening for ADHD among children with ID and borderline intelligence. METHOD: Receiver operating characteristic analysis was used to compare a clinical diagnosis of ADHD according to the Diagnostic and Statistical Manual 4th revision-Text Review criteria with scores according to the CPRS-R and the CTRS-R. RESULTS: Among children with ID, a CPRS-R total score of 42 provided a sensitivity of 0.9 and a specificity of 0.67 with an area under the curve of 0.84. Similarly, a CTRS-R total score of 40 provided a sensitivity of 0.69 and a specificity of 0.67 with an area under the curve of 0.71. There was poor concordance between the CPRS-R and the CTRS-R total scores (Intraclass Correlation; ICC = 0.17). There were statistically significant differences in the total score of the CPRS-R and most of its sub-scores between children with ID with and without ADHD. The CTRS-R total score and its sub-scores did not show any statistically significant difference between two groups. Factor analysis showed three clinically distinct factors for both the CPRS-R and the CTRS-R items, although the CPRS-R factors were better and had less item overlap than the CTRS-R factors. CONCLUSIONS: The CPRS-R scores may distinguish between children with ID with and without ADHD but not the CTRS-R scores. Many items in the CPRS-R and the CTRS-R are not applicable to children with severe and profound ID who do not have speech. The CPRS-R and the CTRS-R scores did not correlate with each other. There is a need to develop an ADHD screening instrument specifically for children with ID.
Published:
2008-11
Title:
A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma
Authors:
Bergmark, Claes; Dewan, Asheesh; Orsoni, Alexina; Merki, Esther; Miller, Elizabeth R.; Shin, Min-Jeong; Binder, Christoph J.; Hörkkö, Sohvi; Krauss, Ronald M.; Chapman, M. John; Witztum, Joseph L.; Tsimikas, Sotirios
Abstract:
Published:
2008-10
Title:
Effectiveness of anastrozole and cyproterone acetate in two brothers with familial male precocious puberty
Authors:
Eyssette-Guerreau, Stéphanie; Pinto, Graziella; Sultan, Ariane; Le Merrer, Martine; Sultan, Charles; Polak, Michel
Abstract:
Testotoxicosis is a rare form of precocious puberty caused by a constitutively activating mutation in the luteinizing hormone receptor (LHR) gene. Symptoms include rapid virilization, accelerated growth and reduced adult height. We describe a rare association of testotoxicosis with a metaphyseal chondrodysplasia called cartilage-hair hypoplasia (CHH) and report two brothers with testotoxicosis after 4 years of treatment. The brothers had a T577I mutation in the LHR gene. One brother also presented CHH. The older brother was treated with ketoconazole, then with the aromatase inhibitor anastrozole and the anti-androgen cyproterone acetate. The younger brother received this combination as first-line therapy. Clinical improvements included reductions in growth velocity and bone maturation rate, which should result in taller adult stature. Tolerance was good. CONCLUSION: Combined treatment with anastrozole and cyproterone acetate is effective in improving the prognosis of adult height in testotoxicosis.
Published:
2008-10
Title:
Home use of vegetable oils, markers of systemic inflammation, and endothelial dysfunction among women
Authors:
Esmaillzadeh, Ahmad; Azadbakht, Leila
Abstract:
BACKGROUND: Most knowledge about adverse health effects of trans fats was mainly derived from studies done in Western populations of European or American origins; few data are available in the understudied region of the Middle East. OBJECTIVE: We assessed the association between consumption of partially hydrogenated vegetable oils (PHVOs) and non-HVOs and circulating concentrations of inflammatory markers among Tehrani women aged 40-60 y. DESIGN: Usual dietary intakes were assessed with a food-frequency questionnaire among 486 apparently healthy women. PHVOs (commonly used for cooking in Iran) were considered as PHVOs category. Sunflower oil, corn oil, canola oil, soybean oil, and olive oil were defined as non-HVOs. Anthropometric measurements were done, and fasting blood samples were taken to measure inflammatory markers. RESULTS: The energy-adjusted daily intakes (mean +/- SD) of PHVOs and non-HVOs were 23 +/- 11 and 22 +/- 10 g/d, respectively. After control for potential confounders, women in the highest quintile of PHVO intake had higher plasma concentrations of C-reactive protein (CRP; percentage difference from lowest quintile: 45%; P for trend: <0.01), tumor necrosis factor-alpha (TNF-alpha; 66%; P for trend: <0.01), interleukin-6 (72%; P for trend: <0.05), and soluble intercellular adhesion molecule-1 (sICAM-1; 22%; P for trend: <0.01) than did women in the lowest quintile. In contrast, higher consumption of non-HVOs was associated with lower circulating concentrations of CRP (percentage difference between top and bottom quintiles: -23%; P for trend: 0.05), TNF-alpha (-29%; P for trend: <0.01), serum amyloid A (-24%; P for trend: <0.01), and sICAM-1 (-19%; P for trend:
Published:
2008-10
Title:
Nutritional and dietary influences on attention deficit hyperactivity disorder
Authors:
Sinn, Natalie
Abstract:
An abundance of research has investigated causes and treatments for attention deficit hyperactivity disorder (ADHD). The research includes identification of suboptimal levels of nutrients and sensitivities to certain foods and food additives. This review gives an overview of this research and provides an up-to-date account of clinical trials that have been conducted with zinc, iron, magnesium, Pycnogenol, omega-3 fatty acids, and food sensitivities. A literature search was conducted using PubMed, ISI Web of Knowledge, and Google Scholar and included studies published before April 2008. Although further research is required, the current evidence supports indications of nutritional and dietary influences on behavior and learning in these children, with the strongest support to date reported for omega-3s and behavioral food reactions.
Published:
2008-10
Title:
Psychopharmacological and other treatments in preschool children with attention-deficit/hyperactivity disorder: current evidence and practice
Authors:
Ghuman, Jaswinder K.; Arnold, L. Eugene; Anthony, Bruno J.
Abstract:
OBJECTIVE: This article reviews rational approaches to treating attention-deficit/hyperactivity disorder (ADHD) in preschool children, including pharmacological and nonpharmacological treatments. Implications for clinical practice are discussed. DATA SOURCES: We searched MEDLINE, PsychINFO, Cumulative Index to Nursing & Allied Health, Educational Resources Information Center, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects for relevant literature published in English from 1967 to 2007 on preschool ADHD. We also reviewed the references cited in identified reports. STUDY SELECTION: Studies were reviewed if the sample included at least some children younger than 6 years of age or attending kindergarten, the study participants had a diagnosis of ADHD or equivalent symptoms, received intervention aimed at ADHD symptoms, and included a relevant outcome measure. DATA EXTRACTION: Studies were reviewed for type of intervention and outcome relevant to ADHD and were rated for the level of evidence for adequacy of the data to inform clinical practice. CONCLUSIONS: The current level of evidence for adequacy of empirical data to inform clinical practice for short-term treatment of ADHD in preschool children is Level A for methylphenidate and Level B for parent behavior training, child training, and additive-free elimination diet.
Published:
2008-10
Title:
Soft drink consumption linked with fatty liver in the absence of traditional risk factors
Authors:
Assy, Nimer; Nasser, Gattas; Kamayse, Iad; Nseir, William; Beniashvili, Zaza; Djibre, Agness; Grosovski, Maria
Abstract:
BACKGROUND: Little is known about dietary habits and their relationships with liver disease in nonalcoholic fatty liver disease (NAFLD) patients, particularly in the absence of obesity, diabetes or hyperlipidemia. OBJECTIVE: To assess the association between soft drink consumption and the presence of fatty liver in NAFLD patients who do not have classic risk factors. METHODS: Three hundred ten patients with NAFLD diagnosed by ultrasound were assessed for 36 months in a cross-sectional manner. Thirty-one patients (10%) who had NAFLD without classic risk factors were compared with 30 healthy controls. Physical activity was assessed during the preceding week and year, and every six months for 36 months. Data on daily dietary intake of food and soft drink, and the source of added sugar were collected during two seven-day periods, at the beginning of the study, and within two weeks after the metabolic tests by using a validated food questionnaire given by a trained dietician. Insulin resistance and lipid peroxidation were assessed by homeostasis model assessment-insulin resistance index (HOMA-IRI) and malondialdehyde (MDA) levels, respectively. RESULTS: Eighty per cent of patients (25 of 31) consumed an excessive amount of soft drink beverages (more than 50 g/day of added sugar) for 36 months, compared with 20% in healthy controls (P<0.001). Twenty per cent of patients consumed one drink per day, 40% consumed two to three drinks per day, and 40% consumed more than four drinks per day for most days during 36 months. The most common soft drinks consumed were regular Coca-Cola (40% of patients), Diet Coke (40%) and flavoured fruit juices (20%). Ultrasound findings revealed mild fatty liver in 44% of cases (n=14), moderate fatty liver in 38% (n=12), and severe fatty liver in 18% (n=5). HOMA-IRI and MDA levels were significantly higher in patients with NAFLD than in healthy controls (HOMA-IRI, 3.7 versus 1.7, P<0.001; and MDA, 420±300 μmol/mL versus 200±100 μmol/mL; P
Published:
2008-10
Title:
The effect of glucose ingestion on inflammation and oxidative stress in obese individuals
Authors:
Manning, Patrick J.; Sutherland, Wayne H. F.; Walker, Robert J.; de Jong, Sylvia A.; Berry, Elizabeth A.
Abstract:
Ingestion of 75 g glucose during an oral glucose tolerance test (OGTT) increases systemic inflammation and oxidative stress in healthy subjects and patients with type 2 diabetes mellitus, but the effect in overweight/obese nondiabetic individuals is uncertain. The aim of the present study was to determine the effect of an OGTT on plasma concentrations of inflammatory cytokines and peroxides in 33 subjects with body mass index >27 kg/m(2). After an overnight fast, blood samples were taken from participants immediately before and at 30, 60, 90, and 120 minutes after ingestion of 75 g glucose. Plasma glucose, insulin, free fatty acid, interleukin (IL)-6, tumor necrosis factor alpha, and peroxides were measured during the tests. Plasma IL-6 concentrations decreased (13%) significantly (P
Published:
2008-10
Title:
An emerging risk factor for obesity: does disequilibrium of polyunsaturated fatty acid metabolism contribute to excessive adipose tissue development?
Authors:
Ailhaud, Gérard; Guesnet, Philippe; Cunnane, Stephen C.
Abstract:
A positive energy balance (energy intake>energy expenditure), in which total fat intake plays an important role, is commonly regarded as a major factor contributing to obesity. Adipose tissue development, i.e. both size (hypertrophy) and number (hyperplasia), is stimulated by high dietary fat intake during early postnatal development, a susceptibility that now appears to continue well into adulthood. Recent human and animal studies suggest that by altering rates of adipocyte differentiation and proliferation, differences in the composition of dietary fat may also contribute to adipose tissue development. At least in rodent models, the relative intake of n-6 to n-3 PUFA is clearly emerging as a new factor in this development. In these models, higher linoleate intake raises tissue arachidonic acid, which increases prostacyclin production and, in turn, stimulates signalling pathways implicated in adipogenesis. Signalling pathways stimulated by arachidonic acid probably include phospholipase and/or cyclo-oxygenase activation and may be linked as much to relatively low intake of n-3 PUFA as to excessive dietary linoleate. One factor potentially contributing to oversight about the apparent role of dietary n-6 PUFA (especially excess dietary linoleate) in adipose tissue development is the historical overestimation of linoleate requirements and the enthusiasm for higher intake of ‘essential fatty acids’. More research is needed to address whether disequilibration of dietary PUFA intake contributes to the risk of obesity in humans.
Published:
2008-09
Title:
Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome
Authors:
Volek, Jeff S.; Fernandez, Maria Luz; Feinman, Richard D.; Phinney, Stephen D.
Abstract:
Abnormal fatty acid metabolism and dyslipidemia play an intimate role in the pathogenesis of metabolic syndrome and cardiovascular diseases. The availability of glucose and insulin predominate as upstream regulatory elements that operate through a collection of transcription factors to partition lipids toward anabolic pathways. The unraveling of the details of these cellular events has proceeded rapidly, but their physiologic relevance to lifestyle modification has been largely ignored. Here we highlight the role of dietary input, specifically carbohydrate intake, in the mechanism of metabolic regulation germane to metabolic syndrome. The key principle is that carbohydrate, directly or indirectly through the effect of insulin, controls the disposition of excess dietary nutrients. Dietary carbohydrate modulates lipolysis, lipoprotein assembly and processing and affects the relation between dietary intake of saturated fat intake and circulating levels. Several of these processes are the subject of intense investigation at the cellular level. We see the need to integrate these cellular mechanisms with results from low-carbohydrate diet trials that have shown reduced cardiovascular risk through improvement in hepatic, intravascular, and peripheral processing of lipoproteins, alterations in fatty acid composition, and reductions in other cardiovascular risk factors, notably inflammation. From the current state of the literature, however, low-carbohydrate diets are grounded in basic metabolic principles and the data suggest that some form of carbohydrate restriction is a candidate to be the preferred dietary strategy for cardiovascular health beyond weight regulation.
Published:
2008-09
Title:
Lamotrigine does not prolong QTc in a thorough QT/QTc study in healthy subjects
Authors:
Dixon, Ruth; Job, Sarah; Oliver, Ruth; Tompson, Debra; Wright, John G.; Maltby, Kay; Lorch, Ulrike; Taubel, Jorg
Abstract:
METHODS Healthy subjects received a single oral dose of moxifloxacin (400 mg) or placebo in crossover design, followed by a dose-escalating regimen of lamotrigine (n = 76) over a 77-day period, or matched placebo (n = 76). Blood samples were taken for determination of moxifloxacin and lamotrigine concentrations and digital 12-lead ECGs were recorded. The relationships between individual QT values and respective individual moxifloxacin or lamotrigine concentrations were explored using population pharmacokinetic–pharmacodynamic (PK–PD) modelling. RESULTS Moxifloxacin was associated with a maximum mean increase from baseline in QTcF of 14.81 ms [90% confidence interval (CI) 13.50, 16.11] 2.5 h after dosing. Steady-state exposure to lamotrigine (50, 150 or 200 mg b.d.) was not associated with an increase in QTc interval. Small reductions in QTcF (maximum mean difference from placebo -7.48 ms, 90% CI -10.49, -4.46) and small increases in heart rate (maximum mean difference from placebo 5.94 bpm, 90% CI 3.81, 8.06) were observed with lamotrigine 200 mg b.d. vs. placebo. No effect of lamotrigine on QRS duration or blood pressure was observed. No outliers with QTcF > 450 ms, or with an increase from baseline of >60 ms were observed in the lamotrigine group. PK–PD modelling indicated statistically significant decreases in individually corrected QT intervals for lamotrigine and statistically significant increases in individually corrected QT intervals for moxifloxacin over the concentration ranges studied. CONCLUSIONS Therapeutic doses of lamotrigine (50–200 mg b.d.) were not associated with QT prolongation in healthy subjects.
Published:
2008-09
Title:
Similar numbers but different repertoires of olfactory receptor genes in humans and chimpanzees
Authors:
Go, Yasuhiro; Niimura, Yoshihito
Abstract:
Animals recognize their external world through the detection of tens of thousands of chemical odorants. Olfactory receptor (OR) genes encode proteins for detecting odorant molecules and form the largest multigene family in mammals. It is known that humans have fewer OR genes and a higher fraction of OR pseudogenes than mice or dogs. To investigate whether these features are human specific or common to all higher primates, we identified nearly complete sets of OR genes from the chimpanzee and macaque genomes and compared them with the human OR genes. In contrast to previous studies, here we show that the number of OR genes ( approximately 810) and the fraction of pseudogenes (51%) in chimpanzees are very similar to those in humans, though macaques have considerably fewer OR genes. The pseudogenization rates and the numbers of genes affected by positive selection are also similar between humans and chimpanzees. Moreover, the most recent common ancestor between humans and chimpanzees had a larger number of functional OR genes (>500) and a lower fraction of pseudogenes (41%) than its descendents, suggesting that the OR gene repertoires are in a phase of deterioration in both lineages. Interestingly, despite the close evolutionary relationship between the 2 species, approximately 25% of their functional gene repertoires are species specific due to massive gene losses. These findings suggest that the tempo of evolution of OR genes is similar between humans and chimpanzees, but the OR gene repertoires are quite different between them. This difference might be responsible for the species-specific ability of odor perception.
Published:
2008-09
Title:
An isoenergetic high-protein, moderate-fat diet does not compromise strength and fatigue during resistance exercise in women
Authors:
Dipla, Konstantina; Makri, Maria; Zafeiridis, Andreas; Soulas, Dimitrios; Tsalouhidou, Sofia; Mougios, Vassilis; Kellis, Spyros
Abstract:
Resistance exercise is recommended to individuals following high-protein diets in order to augment changes in body composition. However, alterations in macronutrient composition may compromise physical performance. The present study investigated the effects of an isoenergetic high-protein diet on upper and lower limb strength and fatigue during high-intensity resistance exercise. Ten recreationally active women, aged 25-40 years, followed a control diet (55, 15 and 30 % of energy from carbohydrate, protein and fat, respectively) and a high-protein diet (respective values, 30, 40 and 30) for 7 d each in a random counterbalanced design. Each participant underwent strength testing of upper limb (isometric handgrip strength and endurance) and lower limb (four sets of sixteen maximal knee flexions and extensions on an isokinetic dynamometer) before and after applying each diet. Body weight, body fat and RER were significantly reduced following the high-protein diet (P
Published:
2008-08
Title:
Carbohydrate restriction as the default treatment for type 2 diabetes and metabolic syndrome
Authors:
Feinman, Richard D.; Volek, Jeff S.
Abstract:
Dietary carbohydrate restriction in the treatment of diabetes and metabolic syndrome is based on an underlying principle of control of insulin secretion and the theory that insulin resistance is a response to chronic hyperglycemia and hyperinsulinemia. As such, the theory is intuitive and has substantial experimental support. It has generally been opposed by health agencies because of concern that carbohydrate will be replaced by fat, particularly saturated fat, thereby increasing the risk of cardiovascular disease as dictated by the so-called diet-heart hypothesis. Here we summarize recent data showing that, in fact, substitution of fat for carbohydrate generally improves cardiovascular risk factors. Removing the barrier of concern about dietary fat makes carbohydrate restriction a reasonable, if not the preferred method for treating type 2 diabetes and metabolic syndrome. We emphasize the ability of low carbohydrate diets to improve glycemic control, hemoglobin A1C and to reduce medication. We review evidence that such diets are effective even in the absence of weight loss.
Published:
2008-08
Title:
Cholesterol does not cause coronary heart disease in contrast to stress
Authors:
Rosch, Paul J.
Abstract:
The belief that coronary atherosclerosis is due to high cholesterol from increased saturated fat intake originated from experiments in herbivorous animals. It was reinforced by reports allegedly demonstrating this sequence of events in various populations but ignoring contradictory data. The idea has been perpetuated by powerful forces using similar tactics to preserve the profit and the reputations of those who promote this doctrine. Opponents find it difficult to publish their scientifically supported opinions. The advent of statins has further fuelled this fallacious lipid hypothesis, despite compelling evidence that their effect is not due to cholesterol lowering and that serious side effects have been suppressed and alleged benefits have been hyped. The adverse effects of the cholesterol campaign on health, quality of life, the economy and medical research are inestimable. It is imperative that public health officials, physicians and patients are apprised of proof that it is misguided, malicious and malignant.
Published:
2008-08
Title:
Heated palm oil causes rise in blood pressure and cardiac changes in heart muscle in experimental rats
Authors:
Leong, Xin Fang; Aishah, A.; Nor Aini, U.; Das, Srijit; Jaarin, Kamsiah
Abstract:
BACKGROUND: Palm oil used worldwide contains considerable amounts of antioxidants, namely, vitamin E and carotenes. The purpose of the study was to observe the effect of heated palm oil on blood pressure and observe the cardiac histological changes in rats. METHODS: Forty male Sprague Dawley rats were divided equally into four groups and given treatment as follows: (i) basal diet (control group); (ii) basal diet fortified with 15% weight/weight (w/w) fresh palm oil (FPO); (iii) basal diet fortified with 15% w/w palm oil heated five times (5HPO); (iv) basal diet fortified with 15% w/w palm oil heated ten times (10HPO). Treatment duration was 16 weeks. Blood pressure was measured at baseline and at monthly intervals for 4 months using the tail-cuff method. After 16 weeks of study, the rats were killed and the hearts were taken out. The specimens were sectioned longitudinally and stained with hematoxylin and eosin for light microscopy. RESULTS: The FPO group did not show any significant changes in blood pressure and histological study. There was a significant increase (p
Published:
2008-08
Title:
Relation of dietary and other lifestyle traits to difference in serum adiponectin concentration of Japanese in Japan and Hawaii: the INTERLIPID Study
Authors:
Nakamura Y; Ueshima H; Okuda N; Higashiyama A; Kita Y; Kadowaki T; Okamura T; Murakami Y; Okayama A; Choudhury SR; Rodriguez B; Curb JD; Stampler J
Abstract:
BACKGROUND: In initial analyses, we found significant differences between serum adiponectin in Japanese living in Japan and Hawaii. OBJECTIVE: We investigated whether differences in dietary and other lifestyle factors explain higher serum adiponectin concentrations in Japanese in Japan compared with Japanese emigrants living a Western lifestyle in Hawaii. DESIGN: Serum adiponectin and nutrient intakes were examined by standardized methods in men and women aged 40-59 y from 2 population samples, one Japanese American in Hawaii (99 men, 104 women), the other Japanese in central Japan (124 men, 125 women). Multiple linear regression models were used to assess the role of dietary and other lifestyle traits in accounting for serum adiponectin difference between Hawaii and Japan. RESULTS: Mean adiponectin was significantly higher in Japan than in Hawaii (10.5 +/- 5.5 mug/mL compared with 6.7 +/- 3.2 mug/mL in men, P = 0.002; 12.9 +/- 5.9 mug/mL compared with 9.4 +/- 4.2 in women, P
Published:
2008-08
Title:
The fallacies of the lipid hypothesis
Authors:
Ravnskov, Uffe
Abstract:
Most researchers to-day consider that a high intake of saturated fat and elevated LDL cholesterol are the most important causes of atherosclerosis and coronary heart disease. The lipid hypothesis has dominated cardiovascular research and prevention for almost half a century although the number of contradictory studies may exceed those that are supportive. The harmful influence of a campaign that ignores much of the science extends to medical research, health care, food production and human life. There is an urgent need to draw attention to the most striking contradictions, many of which may be unknown to most doctors and researchers.
Published:
2008-08
Title:
The fallacies of the lipid hypothesis
Authors:
Ravnskov, Uffe
Abstract:
Most researchers to-day consider that a high intake of saturated fat and elevated LDL cholesterol are the most important causes of atherosclerosis and coronary heart disease. The lipid hypothesis has dominated cardiovascular research and prevention for almost half a century although the number of contradictory studies may exceed those that are supportive. The harmful influence of a campaign that ignores much of the science extends to medical research, health care, food production and human life. There is an urgent need to draw attention to the most striking contradictions, many of which may be unknown to most doctors and researchers.
Published:
2008-08
Title:
The ketogenic diet increases mitochondrial glutathione levels
Authors:
Jarrett, Stuart G.; Milder, Julie B.; Liang, Li-Ping; Patel, Manisha
Abstract:
The ketogenic diet (KD) is a high-fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. We sought to determine whether the KD improves mitochondrial redox status. Adolescent Sprague-Dawley rats (P28) were fed a KD or control diet for 3 weeks and ketosis was confirmed by plasma levels of beta-hydroxybutyrate (BHB). KD-fed rats showed a twofold increase in hippocampal mitochondrial GSH and GSH/GSSG ratios compared with control diet-fed rats. To determine whether elevated mitochondrial GSH was associated with increased de novo synthesis, the enzymatic activity of glutamate cysteine ligase (GCL) (the rate-limiting enzyme in GSH biosynthesis) and protein levels of the catalytic (GCLC) and modulatory (GCLM) subunits of GCL were analyzed. Increased GCL activity was observed in KD-fed rats, as well as up-regulated protein levels of GCL subunits. Reduced CoA (CoASH), an indicator of mitochondrial redox status, and lipoic acid, a thiol antioxidant, were also significantly increased in the hippocampus of KD-fed rats compared with controls. As GSH is a major mitochondrial antioxidant that protects mitochondrial DNA (mtDNA) against oxidative damage, we measured mitochondrial H2O2 production and H2O2-induced mtDNA damage. Isolated hippocampal mitochondria from KD-fed rats showed functional consequences consistent with the improvement of mitochondrial redox status i.e. decreased H2O2 production and mtDNA damage. Together, the results demonstrate that the KD up-regulates GSH biosynthesis, enhances mitochondrial antioxidant status, and protects mtDNA from oxidant-induced damage.
Published:
2008-08
Title:
Vitamin D deficiency in children and its management: review of current knowledge and recommendations
Authors:
Misra, Madhusmita; Pacaud, Danièle; Petryk, Anna; Collett-Solberg, Paulo Ferrez; Kappy, Michael
Abstract:
Given the recent spate of reports of vitamin D deficiency, there is a need to reexamine our understanding of natural and other sources of vitamin D, as well as mechanisms whereby vitamin D synthesis and intake can be optimized. This state-of-the-art report from the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society was aimed to perform this task and also reviews recommendations for sun exposure and vitamin D intake and possible caveats associated with these recommendations.
Published:
2008-08
Title:
Consumption of repeatedly heated soy oil increases the serum parameters related to atherosclerosis in ovariectomized rats
Authors:
Adam, Siti Khadijah; Das, Srijit; Soelaiman, Ima Nirwana; Umar, Nor Aini; Jaarin, Kamsiah
Abstract:
Repeated heating of soy oil may promote lipid peroxidation. Oxidized unsaturated fatty acids may contribute to the pathogenesis of atherosclerosis, especially in estrogen-deficient states. This study was performed to explore the deleterious effects of repeatedly heated soy oil on the development of atherosclerosis using ovariectomized rats, which represent an estrogen-deficient state. Twenty-four female Sprague-Dawley rats were ovariectomized and were divided equally into four groups. The control group was fed with 2% cholesterol diet without any oil. The three treatment groups each received 2% cholesterol diet fortified with fresh, once-heated or five-times-heated (repeatedly heated) soy oil, respectively. Serum thiobarbituric acid reactive substances (TBARS), lipid profile and homocysteine levels were measured prior to ovariectomy and at the end of four months. Ovariectomized rats treated with repeatedly heated soy oil showed significant increases in lipid peroxidation and low-density lipoprotein (LDL) levels. Treatment with once-heated or repeatedly heated soy oil caused a significant increase in total cholesterol, while fresh soy oil caused significant reduction in homocysteine level as compared to other groups. Repeatedly heated soy oil caused significant increases in TBARS and LDL as compared to fresh oil. The higher level of homocysteine in the ovariectomized rats fed with repeatedly heated oil, as compared to those fed with fresh oil, also suggests the repeatedly heated oil contributes to the development of atherosclerosis. Importantly, the protective effect of the soy oil may be lost once it was being repeatedly heated. In conclusion, the consumption of repeatedly heated oil may predispose to atherosclerosis in estrogen-deficient states.
Published:
2008-07
Title:
Dietary habits of Mongolian people, and their influence on lifestyle-related diseases and early aging
Authors:
Komatsu, Fumio; Kagawa, Yasuo; Kawabata, Terue; Kaneko, Yoshinori; Purvee, Baatar; Otgon, Jugder; Chimedregzen, Ulziiburen
Abstract:
Mongolians are known to have relatively short life expectancy. In order to examine the role of dietary habits in the early aging of Mongolians, the food intake inquiry, anthropometric measurements and blood clinical tests were performed for 365 healthy inhabitants in Murun, a northern Mongolia city, and compared to those of Japanese. Murun inhibitants were found to have a characteristic dietary habit of taking large amounts of meat, milk, dairy products and wheat flour products, in contrast little vegetables, fruits and fishes. The daily calorie intake of the adults was estimated to be 2,525 kcal, and the fat/total calorie ratio was calculated 33.7%, about 1.3-fold higher than that of Japanese. The intake ratio of fatty acid from the Mongolian foods, saturated : mono-unsaturated : poly-unsaturated fatty acids (PUFA) ratio, was 10.3 : 7.8 : 3.0. Results of blood clinical tests showed significantly higher levels of serum triglycerides, low-density lipoprotein cholesterol (LDL) and homocysteine, and lower levels of high-density lipoprotein cholesterol (HDL), n-3 PUFA, folic acid and adiponectin, in comparison with those of Japanese. In addition, the Mongolians were also found to have significantly high levels of oxidative stress markers, such as serum malondialdehyde-modified LDL (MDA-LDL), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum reactive oxygen metabolites (ROM). The serum ROM level in the Mongolians seemed to associate with their body fat ratio (p<0.05), and was significantly inverse-correlated to handgrip strength (p
Published:
2008-07
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