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Title:
Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration
Authors:
Nakashima, Yutaka; Fujii, Hiroshi; Sumiyoshi, Shinji; Wight, Thomas N.; Sueishi, Katsuo
Abstract:
OBJECTIVE: The present study was designed to clarify the morphological features of early human atherosclerosis and to determine whether specific extracellular matrix proteoglycans play a role in early atherogenesis. METHODS AND RESULTS: Step and serial sections were obtained from right coronary arteries with no or early atherosclerosis. Atherosclerosis was classified into 4 grades according to the amount of lipid deposition. Coronary arteries with Grade 0 showed diffuse intimal thickening (DIT) with no lipid deposits. The extracellular matrix proteoglycans, biglycan and decorin, were localized in the outer layer of DIT. Most cases of Grade 1 and Grade 2 exhibited fatty streaks with extracellular lipids colocalizing with biglycan and decorin in the outer layer of the intima. As lipid grades increased, macrophages increased in number and were present in the deeper layers. Most cases of Grade 3 exhibited pathologic intimal thickening (PIT) with extracellular lipids underneath a layer of foam cell macrophages. CONCLUSIONS: In early human coronary atherosclerosis, fatty streaks develop via extracellular deposition of lipids associated with specific types of proteoglycans in the outer layer of preexisting DIT. As the amount of the lipid increases in fatty streaks, macrophages infiltrate toward the deposited lipid to form PIT with foam cells.
Published:
2007-05
Title:
Evidence against enhanced glutamate transport in the anticonvulsant mechanism of the ketogenic diet
Authors:
Bough, Kristopher J.; Paquet, Maryse; Paré, Jean-François; Hassel, Bjørnar; Smith, Yoland; Hall, Randy A.; Dingledine, Raymond
Abstract:
Excessive glutamatergic neurotransmission is considered an underlying factor of epilepsy. Energy-dependent glutamate transporters clear extracellular glutamate to limit neuronal excitability. Evidence suggests that reduced expression and/or activity of glutamate transporters contribute to hyperexcitability and progressive seizure activity in rats. By comparison, treatment with the anticonvulsant ketogenic diet (KD) results in increased mRNA expression of the neuronal glutamate transporter EAAC1, elevated energy reserves, and an increased resistance to seizures in rats. The goal of the current study was to determine whether the expression and/or re-uptake activity of glutamate transporters were elevated in hippocampal tissue of rats after KD treatment. Rats were fed either a ketogenic- or control diet for 4-5 weeks. Western blot analysis showed that protein levels of EAAC1, GLT-1 and GLAST glutamate transporters were not changed in hippocampus, cerebral cortex, or cerebellum after KD. Electron microscopic evidence indicated that the KD did not affect hippocampal EAAC1 distribution. In addition, the re-uptake activity of (3)H-glutamate into hippocampal proteoliposomes was similar in both KD and control tissue extracts. These multiple studies suggest that the anticonvulsant nature of the KD does not stem from enhanced glutamate re-uptake.
Published:
2007-05
Title:
How does the health and well-being of young Australian vegetarian and semi-vegetarian women compare with non-vegetarians?
Authors:
Baines, Surinder; Powers, Jennifer; Brown, Wendy J.
Abstract:
OBJECTIVE: To compare the sociodemographic characteristics, health status and health service use of vegetarians, semi-vegetarians and non-vegetarians. DESIGN: In cross-sectional data analyses of the Australian Longitudinal Study on Women's Health in 2000, 9113 women (aged 22-27 years) were defined as non-vegetarians if they reported including red meat in their diet, as semi-vegetarians if they excluded red meat and as vegetarians if they excluded meat, poultry and fish from their diet. RESULTS: The estimated prevalence was 3% and 10% for vegetarian and semi-vegetarian young women. Compared with non-vegetarians, vegetarians and semi-vegetarians were more likely to live in urban areas and to not be married. Vegetarians and semi-vegetarians had lower body mass index (mean (95% confidence interval): 22.2 (21.7-22.7) and 23.0 (22.7-23.3) kg m(-2)) than non-vegetarians (23.7 (23.6-23.8) kg m(-2)) and tended to exercise more. Semi-vegetarians and vegetarians had poorer mental health, with 21-22% reporting depression compared with 15% of non-vegetarians (P
Published:
2007-05
Title:
How does the health and well-being of young Australian vegetarian and semi-vegetarian women compare with non-vegetarians?
Authors:
Baines, Surinder; Powers, Jennifer; Brown, Wendy J.
Abstract:
OBJECTIVE: To compare the sociodemographic characteristics, health status and health service use of vegetarians, semi-vegetarians and non-vegetarians. DESIGN: In cross-sectional data analyses of the Australian Longitudinal Study on Women's Health in 2000, 9113 women (aged 22-27 years) were defined as non-vegetarians if they reported including red meat in their diet, as semi-vegetarians if they excluded red meat and as vegetarians if they excluded meat, poultry and fish from their diet. RESULTS: The estimated prevalence was 3% and 10% for vegetarian and semi-vegetarian young women. Compared with non-vegetarians, vegetarians and semi-vegetarians were more likely to live in urban areas and to not be married. Vegetarians and semi-vegetarians had lower body mass index (mean (95% confidence interval): 22.2 (21.7-22.7) and 23.0 (22.7-23.3) kg m(-2)) than non-vegetarians (23.7 (23.6-23.8) kg m(-2)) and tended to exercise more. Semi-vegetarians and vegetarians had poorer mental health, with 21-22% reporting depression compared with 15% of non-vegetarians (P
Published:
2007-05
Title:
The Neuropharmacology of the Ketogenic Diet
Authors:
Hartman, Adam L.; Gasior, Maciej; Vining, Eileen P. G.; Rogawski, Michael A.
Abstract:
The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. The pattern of protection of the ketogenic diet in animal models of seizures is distinct from that of other anticonvulsants, suggesting that it has a unique mechanism of action. During consumption of the ketogenic diet, marked alterations in brain energy metabolism occur, with ketone bodies partly replacing glucose as fuel. Whether these metabolic changes contribute to acute seizure protection is unclear; however, the ketone body acetone has anticonvulsant activity and could play a role in the seizure protection afforded by the diet. In addition to acute seizure protection, the ketogenic diet provides protection against the development of spontaneous recurrent seizures in models of chronic epilepsy, and it has neuroprotective properties in diverse models of neurodegenerative disease.
Published:
2007-05
Title:
The role of apoptosis in therapy and prophylaxis of epithelial tumours by nonsteroidal anti-inflammatory drugs (NSAIDs)
Authors:
Fecker, L. F.; Stockfleth, E.; Nindl, I.; Ulrich, C.; Forschner, T.; Eberle, J.
Abstract:
In addition to having anti-inflammatory activities, nonsteroidal anti-inflammatory drugs (NSAIDs) also inhibit neoplastic cell proliferation by inducing apoptosis. Diclofenac is the anti-neoplastic compound in diclofenac 3% gel (Solaraze) used for topical treatment of actinic keratosis (AK). Main target of NSAIDs seems to be the inhibition of cyclo-oxygenase-2 (COX-2), which is overexpressed in several epithelial tumours and catalyses the synthesis of prostaglandins. The precise mechanism of action of diclofenac in cutaneous cells is still unclear, but induction of apoptosis is a key effect of anti-neoplastic drugs, including NSAIDs. In this paper we give an overview of the anti-tumoural activities of NSAIDs with emphasis on induction of apoptosis. Cyclo-oxygenase-2-mediated synthesis of prostaglandin E(2) (PGE(2)) leads to activation of mitogen-activated protein kinase (MAPK), as well as phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Induction of the anti-apoptotic Bcl-2 and Mcl-1, as well as activation of the caspase-8 inhibitor cFLIP have been reported. In addition, altered lipid concentrations in the cytoplasmic membrane may modulate death receptor activities. Downregulation of both the intrinsic mitochondrial and the extrinsic pathways have been reported. Our data demonstrate induced apoptosis and activation of the caspase cascade in three of four cutaneous squamous cell carcinoma (SCC) cell lines, after treatment with diclofenac plus hyaluronic acid and diclofenac alone; one cell line remained nonresponsive. The effects were less pronounced in normal keratinocytes and cytotoxic effects were not seen. Detailed analysis of apoptosis pathways employed by diclofenac in these cells may help to improve therapeutic strategies and to overcome possible mechanisms that are involved in nonresponsiveness.
Published:
2007-05
Title:
[Failure to thrive and psychomotor regression revealing vitamin B12 deficiency in 3 infants]
Authors:
Mathey, C.; Di Marco, J.-N.; Poujol, A.; Cournelle, M.-A.; Brevaut, V.; Livet, M.-O.; Chabrol, B.; Michel, G.
Abstract:
The newborn's vitamin B12 storage exclusively comes from placenta transfer, later from animal food. We relate 3 observations of infants (3-11-13 months) with failure to thrive, anorexia, vomiting and for the two olders refusal of weaning, associated with psychomotricity regression and hypotony. Blood cell count showed a macrocytosis without anemia (case 2-3) and a severe microcytic anemia for the first case caused by a mild alpha-thalassemia, with megaloblastic bone marrow. Vitamin B12 levels were very low associated with increased methylmalonic acid and homocysteine serum levels which confirm the diagnostic . Cerebral imaging showed diffuse cortical atrophy. Cobalamin deficiency was caused by strict vegetarian diets mothers of breastfed infants (cases 2-3) and for younger by mother's unrecognized pernicious anemia. 3 mothers had no anemia and normal B12 's levels at diagnosis. Vitamin B12 supply lead to a rapid clinical and hematologic improvement. In two cases, neurologic recovery was incomplete. About one hundred case of B12 deficiency 's infant are reported, 2/3 are breast-fed by vegetarian mothers, and 1/4 have mothers with pernicious anemia. The failure to thrive is due to anorexia, refusal of weaning and partial villous atrophy. Neurologic manifestations are secondary to cerebral disorders, sometimes revealed by an exposure to anesthetic nitrous oxyd. The macrocytic anemia is inconstant. The etiologic research of developmental delay in an infant may include vitamin B12's deficiency, even if there is no haematologic signs, especially if breast-fedding 's mothers is vegetarian.
Published:
2007-05
Title:
[Tinnitus and diabetes]
Authors:
Holcát, M.
Abstract:
Tinnitus is the perception of sound in the absence of corresponding external sound(s). Tinnitus can be perceived in one or both ears or in the head. It is usually described as an unpleasant noise, but in some patients it takes the form of a ringing, buzzing, hissing, humming, or whistling sound, or as ticking, clicking, roaring, tunes, songs, or beeping. It is estimated that 1 out of every 5 people experience some degree of tinnitus. Tinnitus is not itself a disease but an unwelcome symptom. It can be accompanied by audiometric evidence of deafness which occurs in association with both conductive and sensorineural hearing loss resulting from a range of underlying causes, including ear infections, foreign objects orwax in the ear, and injury from loud noises. Tinnitus is also a side-effect of some metabolic disorders, medications, and may also result from an abnormally low level of serotonin or high level of insulin. As mentioned above, some foods are found by some people to make their tinnitus worse. The inner ear, like the brain, is totally lacking in energy reserves. Its metabolism depends directly on the supply of oxygen and glucose from the blood supply. Alterations in glucose metabolism therefore have great potential for disturbing the workings of the inner ear. Because tinnitus is often defined as a subjective phenomenon, it is difficult to measure using objective tests. Although there is no specific cure for tinnitus, those affected can learn techniques to successfully manage their tinnitus to the point where it is no longer a problem for them.
Published:
2007-05
Title:
Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inflammatory Response, Oxidative Stress, and Aging
Authors:
Uribarri, Jaime; Cai, Weijing; Peppa, Melpomeni; Goodman, Susan; Ferrucci, Luigi; Striker, Gary; Vlassara, Helen
Abstract:
Background Oxidative stress (OS) and inflammatory mediators increase with aging. The levels of advanced glycation endproducts (AGEs), prooxidant factors linked to chronic diseases such as diabetes, cardiovascular disease, and renal disease, also increase with aging. AGEs are readily derived from heat-treated foods. We propose that the excess consumption of certain AGEs via the diet enhances OS and inflammatory responses in healthy adults, especially in elderly persons. Methods We examined 172 young (60 years old) healthy individuals to determine whether the concentration of specific serum AGEs (Nε-carboxymethyl-lysine [CML] or methylglyoxal [MG] derivatives) were higher in older compared to younger persons and whether, independent of age, they correlated with the intake of dietary AGEs, as well as with circulating markers of OS and inflammation. Results Body weight, body mass index (BMI), and serum AGE, CML, and MG derivatives were higher in older participants, independent of gender. Serum CML correlated with levels of 8-isoprostanes (r =0.448, p =.0001) as well as with Homeostasis Model Assessment index (HOMA), an index of insulin resistance (r = 0.247, p = .044). The consumption of dietary AGEs, but not of calories, correlated independently with circulating AGEs (CML: r =0.415, p = .0001 and MG: r = 0.282, p = .002) as well as with high sensitivity C-reactive protein (hsCRP) (r = 0.200, p = .042). Conclusions Circulating indicators of AGEs (CML and MG derivatives), although elevated in older participants, correlate with indicators of inflammation and OS across all ages. Indicators of both AGEs and OS are directly influenced by the intake of dietary AGEs, independent of age or energy intake. Thus, reduced consumption of these oxidants may prove a safe economic policy to prevent age-related diseases, especially in an aging population.
Published:
2007-04
Title:
Comparison of uptake between PureSorb-Q40 and regular hydrophobic coenzyme Q10 in rats and humans after single oral intake
Authors:
Nukui, Kazuki; Yamagishi, Toshihiko; Miyawaki, Hiromi; Kettawan, Aikkarach; Okamoto, Tadashi; Sato, Kiyoshi
Abstract:
Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant and essential component of the mitochondrial electron transfer system in the body, and is in wide use as a functional food material and cosmetic raw material. However, as CoQ10 is extremely lipid-soluble, absorption by the body is not easy. In general, people use soft-gel capsules in which CoQ10 is suspended in oil, and take these capsules with food. PureSorb-Q40 (P40) was developed to improve CoQ10 processability and absorption when taken without food, and the present study compared the effects of food on absorption between P40 and conventional lipid-soluble CoQ10 in rats and humans. The results of a rat study showed higher uptake when P40 was administered in the fasting state or with food compared to lipid-soluble CoQ10. The results of a human study showed that uptake was favorable when P40 was administered in the fasting state, and even when administered postprandially, a significant difference was noted in uptake rate up to 6 h after intake and uptake volume up to 8 h after intake when compared to lipid-soluble CoQ10. These results show that any CoQ10 product using P40 can be quickly and reliably absorbed by the body regardless of dosage form or intake time.
Published:
2007-04
Title:
Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects
Authors:
Rungapamestry, Vanessa; Duncan, Alan J.; Fuller, Zoë; Ratcliffe, Brian
Abstract:
The isothiocyanate, sulforaphane, has been implicated in the cancer-protective effects of brassica vegetables. When broccoli is consumed, sulforaphane is released from hydrolysis of glucoraphanin by plant myrosinase and/or colonic microbiota. The influence of meal composition and broccoli-cooking duration on isothiocyanate uptake was investigated in a designed experiment. Volunteers (n 12) were each offered a meal, with or without beef, together with 150 g lightly cooked broccoli (microwaved 2.0 min) or fully cooked broccoli (microwaved 5.5 min), or a broccoli seed extract. They received 3 g mustard containing pre-formed allyl isothiocyanate (AITC) with each meal. Urinary output of allyl (AMA) and sulforaphane (SFMA) mercapturic acids, the biomarkers of production of AITC and sulforaphane respectively, were measured for 24 h after meal consumption. The estimated yield of sulforaphane in vivo was about 3-fold higher after consumption of lightly cooked broccoli than fully cooked broccoli. Absorption of AITC from mustard was about 1.3-fold higher following consumption of the meat-containing meal compared with the non meat-containing alternative. The meal matrix did not significantly influence the hydrolysis of glucoraphanin and its excretion as SFMA from broccoli. Isothiocyanates may interact with the meal matrix to a greater extent if they are ingested pre-formed rather than after their production from hydrolysis of glucosinolates in vivo. The main influence on the production of isothiocyanates in vivo is the way in which brassica vegetables are cooked, rather than the effect of the meal matrix.
Published:
2007-04
Title:
Efficacy and tolerability of the ketogenic diet according to lipid:nonlipid ratios--comparison of 3:1 with 4:1 diet
Authors:
Seo, Joo Hee; Lee, Young Mock; Lee, Joon Soo; Kang, Hoon Chul; Kim, Heung Dong
Abstract:
PURPOSE: The ketogenic diet (KD) has been considered a highly potent antiepileptic treatment for intractable childhood epilepsy. In this study, we compared the antiepileptic efficacy and diet tolerability of two different diets with lipid:nonlipid ratios of 3:1 and 4:1. METHODS: Seventy-six patients with refractory childhood epilepsy were randomly placed into two groups and were started on KD diets with nonlipid:lipid ratios of either 3:1 or 4:1. Antiepileptic efficacy and diet tolerability were evaluated 3 months after initiating the diet. Patients showing seizure-free outcome with the 4:1 diet were changed to the 3:1 diet, and those without a seizure-free outcome on the 3:1 diet were changed to the 4:1 diet, for three more months, after which time their progress was monitored. RESULTS: (1) Antiepileptic efficacy was higher for the 4:1 than the 3:1 diet (p < 0.05). Twenty-two (55.0%) of 40 patients on the 4:1 diet and 11 (30.5%) of 36 patients on the 3:1 diet became seizure free. Seizure reduction of over 90% was observed in 2 (5.0%) patients on the 4:1 diet, and 2 (5.6%) on the 3:1 diet. (2) Dietary tolerability was better for the 3:1 than the 4:1 diet. Gastrointestinal symptoms were observed in 5 (13.9%) patients with the 3:1 diet and 14 (35.0%) patients with the 4:1 diet (p
Published:
2007-04
Title:
Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study
Authors:
Kimura, Yasumi; Kono, Suminori; Toyomura, Kengo; Nagano, Jun; Mizoue, Tetsuya; Moore, Malcolm A.; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Yasunami, Yohichi; Maekawa, Takafumi; Takenaka, Kenji; Ichimiya, Hitoshi; Imaizumi, Nobutoshi
Abstract:
High intake of red meat has been associated with increased risk of colorectal cancer in Western countries. There has been much interest in the role of n-3 polyunsaturated fatty acids (PUFA) in colorectal cancer prevention, but epidemiological findings are limited and inconsistent. The objective of our study was to examine associations of meat, fish and fat intake with risk of colorectal cancer, paying particular attention to the subsite within the colorectum. Data were from the Fukuoka Colorectal Cancer Study, a population-based case-control study, covering 782 cases and 793 controls. Diet was assessed by interview, using newly developed personal-computer software for registering semiquantitative food frequencies. The intake of beef/pork, processed meat, total fat, saturated fat or n-6 PUFA showed no clear association with the overall or subsite-specific risk of colorectal cancer. There was an almost significant inverse association between n-3 PUFA and the risk of colorectal cancer; the covariate-adjusted odds ratio for the highest (median 3.94 g/day) versus lowest (median 1.99 g/day) quintile of energy-adjusted intake was 0.74 (95% confidence interval 0.52-1.06, trend P=0.050). The consumption of fish and fish products was similarly inversely related to the risk although the association was not statistically significant. These associations were more evident for distal colon cancer; adjusted odds ratio for the highest versus lowest quintile of n-3 PUFA intake was 0.56 (95% confidence interval 0.34-0.92, trend P=0.02). Our findings do not support the hypothesis that consumption of red meat increases colorectal cancer risk but do suggest that high intake of fish may decrease the risk, particularly of distal colon cancer.
Published:
2007-04
Title:
Protein intake during energy restriction: effects on body composition and markers of metabolic and cardiovascular health in postmenopausal women
Authors:
Mahon, Anne K.; Flynn, Michael G.; Stewart, Laura K.; McFarlin, Brian K.; Iglay, Heidi B.; Mattes, Richard D.; Lyle, Roseann M.; Considine, Robert V.; Campbell, Wayne W.
Abstract:
OBJECTIVE: The primary aim of this study was to assess the effects of dietary protein intake on energy restriction (ER)-induced changes in body mass and body composition. Clinical markers of metabolic and cardiovascular diseases were also measured. DESIGN: 54 postmenopausal women, age 58 +/- 2 y, body mass index 29.6 +/- 0.8 kg/m(2), were assigned to one of four groups. For 9 weeks, three ER groups ate a 1000 kcal/d lacto-ovo vegetarian basal diet plus 250 kcal/d of either beef (BEEF, n = 14), chicken (CHICKEN, n = 15), or carbohydrate/fat foods (CARB (lacto-ovo), n = 14), while a control group (CON, n = 11) consumed their habitual diets. RESULTS: Energy intake was lower in the ER groups compared to CON (BEEF, 1114 +/- 155 kcal/d, CHO: PRO: FAT, 46:24:30 % of energy intake; CHICKEN, 1098 +/- 203 kcal/d, 51:25:24; CARB 1158 +/- 341 kcal/d, 59:17:24; CON, 1570 +/- 633 kcal/d, 47:20:33), but did not differ among ER groups. For all ER subjects combined, body mass (-6.7 +/- 2.4 kg, 9 %), fat mass (-4.6 +/- 1.9 kg, 13 %), and fat-free mass (-2.1 +/- 1.1 kg, 5 %) decreased. These responses did not differ among the ER groups, except for body mass (CHICKEN -7.9 +/- 2.6 kg(a); BEEF -6.6 +/- 2.7 kg(a,b); CARB -5.6 +/- 1.8 kg(b); CON -1.2 +/- 1.2 kg(c); values with a difference superscript differ, p
Published:
2007-04
Title:
Soy consumption, markers of inflammation, and endothelial function: a cross-over study in postmenopausal women with the metabolic syndrome
Authors:
Azadbakht, Leila; Kimiagar, Masoud; Mehrabi, Yadollah; Esmaillzadeh, Ahmad; Hu, Frank B.; Willett, Walter C.
Abstract:
OBJECTIVE: To determine the effects of soy consumption on markers of inflammation and endothelial function in postmenopausal women with the metabolic syndrome. RESEARCH DESIGN AND METHODS: This randomized cross-over clinical trial included 42 postmenopausal women with the metabolic syndrome. Participants were randomly assigned to consume a control diet (Dietary Approaches to Stop Hypertension [DASH]), soy protein diet, or soy nut diet, each for 8 weeks. Red meat in the DASH diet (one serving/day) was replaced by soy protein in the soy protein diet and by soy nut in the soy nut diet. RESULTS: For nitric oxide levels, the difference from the control diet was 9.8% (P < 0.01) on the soy nut and -1.7% (P = 0.10) on the soy protein diets. The difference from the control diet for serum E-selectin was -11.4% (P < 0.01) on the soy nut consumption and -4.7% (P = 0.19) on the soy protein diet. Soy nut consumption reduced interleukin-18 compared with the control diet (difference from the control diet: -9.2%, P < 0.01), but soy protein did not (difference from the control diet: -4.6%, P = 0.14). For C-reactive protein, the difference from the control diet was -8.9% (P < 0.01) on the soy nut diet and -1.6% (P
Published:
2007-04
Title:
The Foreign Policy of the Calorie
Authors:
Cullather, Nick
Abstract:
Published:
2007-04
Title:
The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid
Authors:
Gasior, Maciej; French, Amy; Joy, Michelle T.; Tang, Rebecca S.; Hartman, Adam L.; Rogawski, Michael A.
Abstract:
BACKGROUND: Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet. The anticonvulsant mechanism of acetone is unknown, but it is metabolized to several bioactive substances that could play a role. METHODS: Acetone and its major metabolites-acetol, 1,2-propanediol, methylglyoxal, and pyruvic acid-were assessed for anticonvulsant activity in two mouse seizure models. Various doses of the substances administered intraperitoneally were characterized for their ability to elevate the threshold for clonic seizures induced by intravenous infusion of pentylenetetrazol (PTZ) and for protection against tonic seizures induced by subcutaneous bolus administration of 4-aminopyridine (4-AP). The inverted-screen test was used to assess acute neurological toxicity. RESULTS: Acetone (1-32 mmol/kg, i.p.), in a dose-dependent fashion, elevated the PTZ threshold and conferred protection against 4-AP seizures (ED(50), 26.3 mmol/kg). Effective doses of acetone (10-32 mmol/kg) did not cause motor impairment in the inverted-screen test (TD(50), 45.7 mmol/kg). In doses 10-fold greater than the minimally effective dose of acetone (3.2 mmol/kg), the metabolites acetol, 1,2-propanediol, and pyruvic acid were inactive in the PTZ model. At higher doses that produced motor impairment, acetol and 1,2-propanediol (but not pyruvic acid) did elevate the PTZ threshold. Methylglyoxal had both proconvulsant and anticonvulsant actions, and had substantial toxicity, producing respiratory distress, motor impairment, and death. None of the acetone metabolites protected against 4-AP seizures. CONCLUSIONS: This study confirms the broad-spectrum anticonvulsant properties of acetone and indicates that the seizure protection conferred is unlikely to result from its major metabolic products.
Published:
2007-04
Title:
Aging gracefully: a retrospective analysis of functional status in Okinawan centenarians.
Authors:
Willcox, D. Craig; Willcox, Bradley J.; Shimajiri, Sanae; Kurechi, Sayuri; Suzuki, Makoto
Abstract:
OBJECTIVE: This study retrospectively explored the late-life functional status of Okinawan centenarians. METHODS: Activities of daily living were measured retrospectively at five time points (10, 5, 3, and 1 year prior and present) for 22 centenarians in relation to seven physical, two sensory, and two cognitive functions using the Inoue Index. RESULTS: In all, 82% of individuals were still functioning independently at a mean age of 92 years and almost two-thirds were still functioning independently at a mean age of 97 years. CONCLUSION: Preliminary analyses suggest high functional status in Okinawan centenarians throughout their 90 s. The genetic and environmental factors contributing to this successful aging phenomenon deserve further investigation.
Published:
2007-03
Title:
Low-carbohydrate diets cause obesity, low-carbohydrate diets reverse obesity: a metabolic mechanism resolving the paradox
Authors:
Mobbs, Charles V.; Mastaitis, Jason; Yen, Kelvin; Schwartz, Joseph; Mohan, Vinuta; Poplawski, Michal; Isoda, Fumiko
Abstract:
High-fat diets produce obesity in part because, per calorie, glucose produces greater post-prandial thermogenesis than lipids, an effect probably mediated by glucose-sensing neurons. A very low-carbohydrate/high-fat/high-protein Atkins-type diet produces obesity but is marginally ketogenic in mice. In contrast, high-sucrose/low-fat diets, and very low-carbohydrate/high-fat/low-protein (anti-epileptic) ketogenic diets reverse diet-induced obesity independent of caloric intake. We propose that a non-ketogenic high-fat diet reduces glucose metabolism and signaling in glucose-sensing neurons, thereby reducing post-prandial thermogenesis, and that a ketogenic high-fat diet does not reduce glucose signaling, thereby preventing and/or reversing obesity.
Published:
2007-03
Title:
Reduced auditory acuity in rat pups from excess and deficient omega-3 fatty acid consumption by the mother
Authors:
Church, Michael W.; Catherine Jen, K.-L.; Stafferton, Tina; Hotra, John W.; Adams, Brittany R.
Abstract:
Abstract: Consumption of the nutrients omega-3 fatty acids (ω-3 FA) during pregnancy and lactation is considered beneficial to fetal and infant development. It may also reduce the incidence and severity of preterm births by prolonging gestational length. However several recent human and animal studies have reported that over-supplementation with ω-3 FA, especially in the form of fish oil, can have adverse effects on fetal and infant development and the auditory brainstem response (ABR). Our goal was to assess further the effects of ω-3 FA excess and deficiency during pregnancy and lactation on the offspring''s auditory acuity as evidenced by their ABR thresholds. Female Wistar rats were given diets that were either deficient, adequate (control) or excess in ω-3 FA from day 1 of pregnancy through lactation. The offspring were ABR-tested at the postnatal age of 24 days. The rat pups in the Excess treatment condition had significantly elevated (worse) ABR thresholds, postnatal growth restriction, and a trend for increased postnatal mortality in comparison to the Control group. The Deficient group was intermediate. In conclusion, excess or deficient amounts of ω-3 FA during pregnancy and lactation in the laboratory rat adversely affected the offspring''s auditory acuity. Postnatal thriving was also adversely affected. Consuming or administering large or inadequate amounts of ω-3 FA during pregnancy and lactation seems inadvisable because of the potential for adverse effects on infant development.
Published:
2007-03
Title:
The ketogenic diet: one decade later
Authors:
Freeman, John M.; Kossoff, Eric H.; Hartman, Adam L.
Abstract:
The ketogenic diet, a high fat, adequate protein, low carbohydrate diet, has, during the past decade, had a resurgence of interest for the treatment of difficult-to-control seizures in children. This review traces its history, reviews its uses and side effects, and discusses possible alternatives and the diet's possible mechanisms of action. Finally, this review looks toward possible future uses of the ketogenic diet for conditions other than epilepsy.
Published:
2007-03
Title:
The metabolic syndrome in polycystic ovary syndrome
Authors:
Essah, Paulina A.; Wickham, Edmond P.; Nestler, John E.
Abstract:
Approximately one-third to one-half of all women and adolescent girls with polycystic ovary syndrome (PCOS) has the metabolic syndrome, associated with increased risk for cardiovascular disease and type 2 diabetes. Evidence suggests that insulin resistance is the likely link between PCOS and the metabolic syndrome. Early screening for impaired glucose tolerance, even in adolescents, is recommended. Lifestyle modification with increased physical activity and weight reduction remains first-line therapy. Insulin-sensitizing drugs may also ameliorate features of the metabolic syndrome in PCOS but long-term prospective studies are needed to determine the role of these drugs in the prevention of the metabolic syndrome.
Published:
2007-03
Title:
[Vegetarian diets; effect on health]
Authors:
de Luis Román, D.; Aller, R.; Castaño, O.
Abstract:
Vegetarian diets are those diets mainly based on the consumption of vegetable product, but that also permit consumption of eggs and milk. The American Dietetic Association made a declaration on these vegetarian diets in which they stated that . Some studies have shown beneficial results in obesity, cancer, Parkinson disease, hypertension, type 2 diabetes mellitus and urinary stones, compared with the omnivorous. The possible theoretical benefits in some diseases has been seen in the medical practice (diabetes mellitus, obesity, cardiovascular risk). However more studies are needed in the case of Parkinson's disease and rheumatoid arthritis.
Published:
2007-03
Title:
‘Mealthy’ food: meat as a healthy and valuable source of micronutrients
Authors:
Nohr, D.; Biesalski, H. K.
Abstract:
Over the last two or three decades meat and especially liver have been looked upon as unhealthy food with high fat content and carcinogenic potential. In addition, its content of highly valuable micronutrients has mostly been ignored. As a result, the mean uptake and serum levels of several micronutrients in the population are below the recommended levels. In the meantime, the contamination of liver with heavy metals and other contaminants has fallen far below the allowed thresholds and sometimes even below the detection limit while its content of micronutrients like iron, folate, selenium or zinc are still high. As a further advantage, the bioavailability of many micronutrients often is better from meat and liver then from plant sources. Considering these advantages and the low content of contaminants in meat and liver leads us to propose that meat – including liver – should be a regular part of a mixed and balanced healthy diet along with vegetables and fruits as the major components to ensure an optimal supply of micronutrients.
Published:
2007-03
Title:
Bite forces and evolutionary adaptations to feeding ecology in carnivores
Authors:
Christiansen, Per; Wroe, Stephen
Abstract:
The Carnivora spans the largest ecological and body size diversity of any mammalian order, making it an ideal basis for studies of evolutionary ecology and functional morphology. For animals with different feeding ecologies, it may be expected that bite force represents an important evolutionary adaptation, but studies have been constrained by a lack of bite force data. In this study we present predictions of bite forces for 151 species of extant carnivores, comprising representatives from all eight families and the entire size and ecological spectrum within the order. We show that, when normalized for body size, bite forces differ significantly between the various feeding categories. At opposing extremes and independent of genealogy, consumers of tough fibrous plant material and carnivores preying on large prey both have high bite forces for their size, while bite force adjusted for body mass is low among specialized insectivores. Omnivores and carnivores preying on small prey have more moderate bite forces for their size. These findings indicate that differences in bite force represent important adaptations to and indicators of differing feeding ecologies throughout carnivoran evolution. Our results suggest that the incorporation of bite force data may assist in the construction of more robust evolutionary and palaeontological analyses of feeding ecology.
Published:
2007-02
Title:
Increased lean red meat intake does not elevate markers of oxidative stress and inflammation in humans
Authors:
Hodgson, Jonathan M.; Ward, Natalie C.; Burke, Valerie; Beilin, Lawrence J.; Puddey, Ian B.
Abstract:
Red meat intake has been associated with increased risk of coronary heart disease and type 2 diabetes, but it remains uncertain whether these associations are causally related to unprocessed lean red meat. It has been proposed that iron derived from red meat may increase iron stores and initiate oxidative damage and inflammation. We aimed to determine whether an increase in unprocessed lean red meat intake, partially replacing carbohydrate-rich foods, adversely influences markers of oxidative stress and inflammation. Sixty participants completed an 8-wk parallel-designed study. They were randomized to maintain their usual diet (control) or to partially replace energy from carbohydrate-rich foods with approximately 200 g/d of lean red meat (red meat) in isoenergetic diets. Markers of oxidative stress and inflammation were measured at baseline and at the end of intervention. Results are presented as the mean between-group difference in change and [95% CI]. Red meat, relative to control, resulted in: higher protein [5.3 (3.7, 6.9) % of energy], lower carbohydrate [-5.3 (-7.9, -2.7)% of energy], and higher iron [3.2 (1.1, 5.4) mg/d] intakes; lower urinary F2-isoprostane excretion [-137 (-264, -9) pmol/mmol creatinine], lower leukocyte [-0.51 (-0.99, -0.02)x10(9)/L] counts, and a trend for lower serum C-reactive protein concentrations [-1.6 (-3.3, 0.0) mg/L, P=0.06]; and no differences in concentrations of plasma F2-isoprostanes [-12 (-122, 100) pmol/L], serum gamma-glytamyltransferase [-0.8 (-3.2, 1.5) U/L], serum amyloid A protein [-1.4 (-3.4, 0.5) mg/L], and plasma fibrinogen concentrations [-0.08 (-0.40. 0.24) g/L]. Our results suggest that partial replacement of dietary carbohydrate with protein from lean red meat does not elevate oxidative stress or inflammation.
Published:
2007-02
Title:
Poor iron status is more prevalent in Hispanic than in non-Hispanic white older adults in Massachusetts
Authors:
Seaverson, Erin L.; Buell, Jennifer S.; Fleming, Diana J.; Bermudez, Odilia I.; Potischman, Nancy; Wood, Richard J.; Chasan-Taber, Lisa; Tucker, Katherine L.
Abstract:
Iron status and dietary correlates of iron status have not been well described in Hispanic older adults of Caribbean origin. The aim of this study was to evaluate iron status and describe dietary components and correlates of iron status in Hispanic older adults and in a neighborhood-based comparison group of non-Hispanic white older adults. Six hundred four Hispanic and non-Hispanic white adults (59-91 y of age) from the Massachusetts Hispanic Elders Study were included in the analysis. We examined physiological markers of iron status as well as dietary factors in relation to iron status. Dietary intake was assessed by FFQ. Our results revealed that Hispanics had significantly lower geometric mean serum ferritin (74.1 microg/L vs. 100 microg/L; P<0.001), lower hemoglobin concentrations (137+/-13 vs. 140+/-12 g/L; P<0.01), higher prevalence of anemia (11.5 vs. 7.3%; P<0.05), and suboptimal hemoglobin concentrations (<125 g/L) for this age group (21.4 vs. 13.3%; P<0.05). Iron deficiency anemia was higher (7.2% vs. 2.3%; P
Published:
2007-02
Title:
Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces
Authors:
Duncan, Sylvia H.; Belenguer, Alvaro; Holtrop, Grietje; Johnstone, Alexandra M.; Flint, Harry J.; Lobley, Gerald E.
Abstract:
Weight loss diets for humans that are based on a high intake of protein but low intake of fermentable carbohydrate may alter microbial activity and bacterial populations in the large intestine and thus impact on gut health. In this study, 19 healthy, obese (body mass index range, 30 to 42) volunteers were given in succession three different diets: maintenance (M) for 3 days (399 g carbohydrate/day) and then high protein/medium (164 g/day) carbohydrate (HPMC) and high protein/low (24 g/day) carbohydrate (HPLC) each for 4 weeks. Stool samples were collected at the end of each dietary regimen. Total fecal short-chain fatty acids were 114 mM, 74 mM, and 56 mM (P < 0.001) for M, HPMC, and HPLC diets, respectively, and there was a disproportionate reduction in fecal butyrate (18 mM, 9 mM, and 4 mM, respectively; P < 0.001) with decreasing carbohydrate. Major groups of fecal bacteria were monitored using nine 16S rRNA-targeted fluorescence in situ hybridization probes, relative to counts obtained with the broad probe Eub338. No significant change was seen in the relative counts of the bacteroides (Bac303) (mean, 29.6%) or the clostridial cluster XIVa (Erec482, 23.3%), cluster IX (Prop853, 9.3%), or cluster IV (Fprau645, 11.6%; Rbro730 plus Rfla729, 9.3%) groups. In contrast, the Roseburia spp. and Eubacterium rectale subgroup of cluster XIVa (11%, 8%, and 3% for M, HPMC, and HPLC, respectively; P
Published:
2007-02
Title:
The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study
Authors:
Tendler, David; Lin, Sauyu; Yancy, William S.; Mavropoulos, John; Sylvestre, Pam; Rockey, Don C.; Westman, Eric C.
Abstract:
Nonalcoholic fatty liver disease is an increasingly common condition that may progress to hepatic cirrhosis. This pilot study evaluated the effects of a low-carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five patients with a mean body mass index of 36.4 kg/m(2) and biopsy evidence of fatty liver disease were instructed to follow the diet (
Published:
2007-02
Title:
Understanding the recent evolution of the human genome: insights from human-chimpanzee genome comparisons
Authors:
Kehrer-Sawatzki, Hildegard; Cooper, David N.
Abstract:
The sequencing of the chimpanzee genome and the comparison with its human counterpart have begun to reveal the spectrum of genetic changes that has accompanied human evolution. In addition to gross karyotypic rearrangements such as the fusion that formed human chromosome 2 and the human-specific pericentric inversions of chromosomes 1 and 18, there is considerable submicroscopic structural variation involving deletions, duplications, and inversions. Lineage-specific segmental duplications, detected by array comparative genomic hybridization and direct sequence comparison, have made a very significant contribution to this structural divergence, which is at least three-fold greater than that due to nucleotide substitutions. Since structural genomic changes may have given rise to irreversible functional differences between the diverging species, their detailed analysis could help to identify the biological processes that have accompanied speciation. To this end, interspecies comparisons have revealed numerous human-specific gains and losses of genes as well as changes in gene expression. The very considerable structural diversity (polymorphism) evident within both lineages has, however, hampered the analysis of the structural divergence between the human and chimpanzee genomes. The concomitant evaluation of genetic divergence and diversity at the nucleotide level has nevertheless served to identify many genes that have evolved under positive selection and may thus have been involved in the development of human lineage-specific traits. Genes that display signs of weak negative selection have also been identified and could represent candidate loci for complex genomic disorders. Here, we review recent progress in comparing the human and chimpanzee genomes and discuss how the differences detected have improved our understanding of the evolution of the human genome.
Published:
2007-02
Title:
A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder
Authors:
Reimherr, Frederick W.; Williams, Erika D.; Strong, Robert E.; Mestas, Ruth; Soni, Poonam; Marchant, Barrie K.
Abstract:
BACKGROUND: The realization that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood has led to increased frequency of diagnosis and treatment in adults. Osmotic release oral system (OROS) methylpheni-date is a long-acting stimulant demonstrated to be effective in the treatment of children and adolescents with ADHD. METHOD: Forty-seven adults entered and 41 completed this double-blind, placebo-controlled, crossover trial of OROS methylphenidate. Each double-blind arm lasted 4 weeks; data were collected from August 2004 through December 2005. Subjects met both DSM-IV-TR and Utah Criteria for ADHD in adults. Outcome measures included the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the adult ADHD-Rating Scale (ADHD-RS), and the Clinical Global Impressions-Improvement scale (CGI-I). At baseline, subjects were categorized as having significant emotional symptoms with the WRAADDS and/or significant oppositional-defiant symptoms using a self-report scale assessing the DSM-IV criteria for oppositional defiant disorder. RESULTS: 17% of the sample (N = 8) had ADHD alone, 38% (N = 18) had ADHD plus significant emotional symptoms, and 40% (N = 19) had ADHD with both significant emotional and oppositional symptoms. At a mean +/- SD dose of 64.0 +/- 23.3 (0.75 mg/kg), OROS methylphenidate proved superior to placebo for all clinical measures: total WRAADDS score decrease of 42% versus 13%, respectively, p
Published:
2007-01
Title:
Anticonvulsant mechanisms of the ketogenic diet
Authors:
Bough, Kristopher J.; Rho, Jong M.
Abstract:
The ketogenic diet (KD) is a broadly effective treatment for medically refractory epilepsy. Despite nearly a century of use, the mechanisms underlying its clinical efficacy remain unknown. In this review, we present one intersecting view of how the KD may exert its anticonvulsant activity against the backdrop of several seemingly disparate mechanistic theories. We summarize key insights gleaned from experimental and clinical studies of the KD, and focus particular attention on the role that ketone bodies, fatty acids, and limited glucose may play in seizure control. Chronic ketosis is anticipated to modify the tricarboxcylic acid cycle to increase GABA synthesis in brain, limit reactive oxygen species (ROS) generation, and boost energy production in brain tissue. Among several direct neuro-inhibitory actions, polyunsaturated fatty acids increased after KD induce the expression of neuronal uncoupling proteins (UCPs), a collective up-regulation of numerous energy metabolism genes, and mitochondrial biogenesis. These effects further limit ROS generation and increase energy production. As a result of limited glucose and enhanced oxidative phosphorylation, reduced glycolytic flux is hypothesized to activate metabolic K(ATP) channels and hyperpolarize neurons and/or glia. Although it is unlikely that a single mechanism, however well substantiated, will explain all of the diet's clinical benefits, these diverse, coordinated changes seem poised to stabilize synaptic function and increase the resistance to seizures throughout the brain.
Published:
2007-01
Title:
Carbohydrate intake and HDL in a multiethnic population
Authors:
Merchant, Anwar T.; Anand, Sonia S.; Kelemen, Linda E.; Vuksan, Vlad; Jacobs, Ruby; Davis, Bonnie; Teo, Koon; Yusuf, Salim; SHARE and SHARE-AP Investigators
Abstract:
BACKGROUND: Ethnic differences in serum lipids are not explained by genetics, central adiposity, lifestyle, or diet, possibly because dietary carbohydrate has not been considered. OBJECTIVE: The aim was to evaluate the relation between carbohydrate intake and HDL and triacylglycerol concentrations in a multiethnic population. DESIGN: We conducted a population-based cross-sectional study of 619 Canadians of Aboriginal, South Asian, Chinese, and European origin with no previously diagnosed medical conditions. Energy-adjusted carbohydrate intake was measured by a validated food-frequency questionnaire. RESULTS: South Asians consumed the most carbohydrate, followed by European, Aboriginal, and Chinese persons. Mean (95% CI) HDL concentrations in the lowest and highest categories of carbohydrate intake after adjustment for age, sex, ethnicity, physical activity, smoking, the waist-to-hip ratio, body mass index, alcohol intake, and intakes of total energy, protein, and fiber were 1.21 mmol/L (1.16, 1.27 mmol/L) and 1.08 mmol/L (1.02, 1.13 mmol/L), respectively, and HDL cholesterol was significantly (P
Published:
2007-01
Title:
Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group
Authors:
Bondy, Carolyn A
Abstract:
OBJECTIVES The objective of this work is to provide updated guidelines for the evaluation and treatment of girls and women with Turner syndrome (TS). PARTICIPANTS The Turner Syndrome Consensus Study Group is a multidisciplinary panel of experts with relevant clinical and research experience with TS that met in Bethesda, Maryland, April 2006. The meeting was supported by the National Institute of Child Health and unrestricted educational grants from pharmaceutical companies. EVIDENCE The study group used peer-reviewed published information to form its principal recommendations. Expert opinion was used where good evidence was lacking. CONSENSUS: The study group met for 3 d to discuss key issues. Breakout groups focused on genetic, cardiological, auxological, psychological, gynecological, and general medical concerns and drafted recommendations for presentation to the whole group. Draft reports were available for additional comment on the meeting web site. Synthesis of the section reports and final revisions were reviewed by e-mail and approved by whole-group consensus. CONCLUSIONS We suggest that parents receiving a prenatal diagnosis of TS be advised of the broad phenotypic spectrum and the good quality of life observed in TS in recent years. We recommend that magnetic resonance angiography be used in addition to echocardiography to evaluate the cardiovascular system and suggest that patients with defined cardiovascular defects be cautioned in regard to pregnancy and certain types of exercise. We recommend that puberty should not be delayed to promote statural growth. We suggest a comprehensive educational evaluation in early childhood to identify potential attention-deficit or nonverbal learning disorders. We suggest that caregivers address the prospect of premature ovarian failure in an open and sensitive manner and emphasize the critical importance of estrogen treatment for feminization and for bone health during the adult years. All individuals with TS require continued monitoring of hearing and thyroid function throughout the lifespan. We suggest that adults with TS be monitored for aortic enlargement, hypertension, diabetes, and dyslipidemia.
Published:
2007-01
Title:
Clinical aspects of the ketogenic diet
Authors:
Hartman, Adam L.; Vining, Eileen P. G.
Abstract:
The ketogenic diet remains a valuable therapeutic option for patients with intractable epilepsy. Clinical aspects of the diet's success may provide insights into epileptogenesis and anticonvulsant action. The diet's efficacy has been established primarily through large case series. The diet has been used successfully in patients with many different epilepsy syndromes in countries around the world. Potential adverse effects can be avoided with careful attention during the diet's initiation and maintenance phases. In the last decade, variations to the classical ketogenic diet have been utilized. Ketogenic diets now are being used for diseases other than epilepsy. This critical analysis of the diet should provide the impetus for further clinical and basic research into the diet's application and mechanisms of action.
Published:
2007-01
Title:
Combined B12 and Iron Deficiency in a Child Breast-Fed by a Vegetarian Mother
Authors:
H, Fadyl; S, Inoue
Abstract:
Combined B12 and Iron Deficiency in a Child Breast-Fed by a Vegetarian Mother
Published:
2007-01
Title:
Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence: The COMBINE Study: A Randomized Controlled Trial
Authors:
Frances, R.J.
Abstract:
Objectives To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. Design, Setting, and Participants Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. Interventions Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. Main Outcome Measures Percent days abstinent from alcohol and time to first heavy drinking day. Results All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n=302), CBI plus medical management and placebos (n=305), or both naltrexone and CBI plus medical management (n=309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n=305), a significant naltrexone ϫ behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P=.02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n=157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n=153) or placebo plus medical management and CBI (n=156) (73.8 and 79.8, respectively; PϽ.001). One year after treatment, these between-group effects were similar but no longer significant. Conclusions Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.
Published:
2007-01
Title:
Evaluation and Management of the Fat Leg Syndrome
Authors:
Warren, Anne; Janz, Brian; Borud, Loren; Slavin, Sumner
Abstract:
Learning Objectives:After studying this article, the participant should be able to: 1. Discuss the initial evaluation of a patient presenting with lower extremity enlargement. 2. Distinguish underlying medical conditions causing lower extremity enlargement, including lymphedema and lipedema. 3. Disc
Published:
2007-01
Title:
Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells
Authors:
Wu, Min; Neilson, Andy; Swift, Amy L.; Moran, Rebecca; Tamagnine, James; Parslow, Diane; Armistead, Suzanne; Lemire, Kristie; Orrell, Jim; Teich, Jay; Chomicz, Steve; Ferrick, David A.
Abstract:
Published:
2007-01
Title:
Phylloquinone intake and risk of cardiovascular diseases in men
Authors:
Erkkilä, Arja T.; Booth, Sarah L.; Hu, Frank B.; Jacques, Paul F.; Lichtenstein, Alice H.
Abstract:
BACKGROUND AND AIMS: Dietary patterns high in fruits and vegetables have been associated with lower risk of cardiovascular diseases. It is difficult to assess whether individuals are following a dietary pattern recommended for cardiovascular disease prevention in large population based studies. Therefore, the association between phylloquinone (vitamin K(1)) intake, derived mainly from green vegetables, and risk of cardiovascular diseases [total and fatal coronary heart disease (CHD), non-fatal myocardial infarction, total and ischemic stroke] was prospectively assessed. METHODS AND RESULTS: The study was conducted in 40,087 men who participated in the Health Professionals' Follow-up Study during 1986-2000. There were 1857 CHD events and 617 strokes. After adjustment for lifestyle factors, the relative risks of total CHD events in increasing quintile categories of phylloquinone intake were 1 (reference), 0.84, 0.87, 0.82 and 0.84, respectively (P for trend 0.05). However, the risk of CHD events and strokes did not remain significantly associated with phylloquinone intake after adjustment for lifestyle and other dietary factors. CONCLUSION: These results suggest that although not an independent risk factor, high phylloquinone intake may be a marker of dietary patterns associated with lower CHD risk and useful when used within that context.
Published:
2007-01
Title:
The effects of a low-carbohydrate ketogenic diet and a low-fat diet on mood, hunger, and other self-reported symptoms
Authors:
McClernon, F. Joseph; Yancy, William S.; Eberstein, Jacqueline A.; Atkins, Robert C.; Westman, Eric C.
Abstract:
OBJECTIVE: To investigate the effects of weight loss diets on mood, food cravings, and other self-reported symptoms. RESEARCH METHODS AND PROCEDURES: Mood and other symptoms were evaluated by participant self-report using the Atkins Health Indicator Test (AHIT) in individuals undergoing weight loss following either a low-carbohydrate, ketogenic diet (LCKD) or a low-fat diet (LFD). Participants were 119 overweight community volunteers randomized to an LCKD or an LFD. An additional 51 participants who had completed an earlier trial contributed data for the psychometric analyses but were not included in the prospective analyses. Self-reported symptom levels on seven scales factor-analytically derived from the AHIT (negative affect, fatigue, somatic symptoms, physical effects of hunger, insomnia, hunger, and stomach problems) were acquired during 12 visits. RESULTS: After adjusting for the change in BMI over the course of the trial, participants experienced significant improvements in most symptoms regardless of diet. Diet group x visit interactions were observed for negative affect [F(9,803) = 2.30, p = 0.015] and hunger [F(9,803) = 3.62, p
Published:
2007-01
Title:
The influence of a cooked-meat meal on estimated glomerular filtration rate
Authors:
Preiss, David J.; Godber, Ian M.; Lamb, Edmund J.; Dalton, R. Neil; Gunn, Ian R.
Abstract:
BACKGROUND: Chronic kidney disease (CKD) is an important but under-recognized condition. Recent national guidelines have recommended that biochemistry laboratories report estimated GFR (eGFR) to improve diagnosis of CKD and facilitate disease staging and management. Previous reports have suggested that intake of large amounts of cooked meat can lead to a significant increase in serum creatinine concentration. METHODS: Participants (n = 32), consisting of 17 healthy volunteers and 15 outpatients, were recruited. Measurement of serum creatinine (kinetic Jaffe method, enzymatic, isotope-dilution mass spectrometry [IDMS]) and cystatin C, and calculation of eGFR were carried out before (i) and after a meal containing cooked meat (ii) and a meat-free meal (iii). RESULTS: Following intake of cooked meat, median serum creatinine concentration (kinetic Jaffe) increased from 80.5 micromol/L preprandially to 101.0 micromol/L 1-2 h postprandially (P<0.0001), and 99.0 micromol/L 3-4 h postprandially (P<0.0001). Median eGFR decreased from 84.0 mL/min/1.73 m2 preprandially to 59.5 mL/min/1.73 m2 1-2 h postprandially (P<0.0001), and 64.0 mL/min/1.73 m2 3-4 h postprandially (P
Published:
2007-01
Title:
Vegetarian diet and cholesterol and triglycerides levels
Authors:
De Biase, Simone Grigoletto; Fernandes, Sabrina Francine Carrocha; Gianini, Reinaldo José; Duarte, João Luiz Garcia
Abstract:
OBJECTIVE: Compare levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) among vegetarians and omnivores. METHODS: Blood samples were collected from 76 individuals--both males and females--separated in four different diet groups: omnivores, lacto-ovo vegetarians, lacto vegetarians, and restricted vegetarians (or vegans). Dosing was done for: TC, LDL, HDL and TG. RESULTS: Significant difference was reported for TC, LDL and TG levels among the samples. Higher levels were reported by omnivores, with decreased levels for vegetarians as animal products were restricted, with lowest levels having been reported by vegans. Mean and standard deviation for TC were 208.09 +/- 49.09 mg/dl in the group of omnivores, and 141.06 +/- 30.56 mg/dl in the group of vegans (p < 0.001). LDL values for omnivores and vegans were respectively: 123.43 +/- 42.67 mg/dl and 69.28 +/- 29.53 mg/dl (p < 0.001). As for TG, those values were 155.68 +/- 119.84 mg/dl and 81.67 +/- 81.90 mg/dl (p
Published:
2007-01
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