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We have recently noted that cells treated with fish oil and n-3-fatty acids show slower DNA replication rates than cells treated with a control emulsion or corn oil only. However, it is not clearly understood how such an effect is induced. Fish oil and its metabolites are known to have several modulating effects on signal transduction pathways. Alternatively, they may influence DNA replication by interacting directly with nuclear components. To investigate this problem in greater detail, we have studied the kinetics of DNA synthesis in a cell-free system derived from HeLa cells. Nuclei and cytosolic extract were isolated from cells synchronized in early S phase after treatment with control emulsion, corn oil, or fish oil, respectively. The nuclei were reconstituted with cytosolic extract and a reaction mixture containing bromodeoxyuridine (BrdU) triphosphate to label newly synthesized DNA. The rate of DNA synthesis was measured by bivariate DNA/ BrdU analysis and flow cytometry. We show that fish oil-treated cytosol inhibits the elongation of newly synthesized DNA by ~80% in control nuclei. However, nuclei treated with fish oil escape this inhibitory effect. We also show that addition of nuclear extract from fish oil-treated cells reverses the inhibitory effect seen in the reconstitution system of control nuclei and fish oil-treated cytosol. These results indicate that polyunsaturated fatty acids can modulate DNA synthesis through cytosolic as well as soluble nuclear factors. n-3 fatty acids; cell cycle kinetics; flow cytometry; S phase; cell-free system

Fish oils (FOs) have been noted to reduce growth and proliferation of certain tumor cells, effects usually attributed to the content of polyunsaturated fatty acids of the n-3 family, which are thought to modulate cellular signaling pathways. We investigated the influence of FO on cell cycle kinetics of cultured Chinese hamster ovary cells. Exponentially growing cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) and analyzed by flow cytometry after 5-day treatment with exogenous fat. Bivariate BrdU-DNA analysis indicated slower progression through S phase and thus longer S phase duration time in FO- but not corn oil-treated or control cells. We hypothesize that FO treatment might interfere with spatial/temporal organization of replication origins. Therefore, we mapped the well-characterized replication origin ori-[beta] downstream of the dihydrofolate reductase gene with the nascent strand length assay. Three DNA marker segments with known positions relative to this origin were amplified by PCR. By quantitatively assessing DNA length of the fragments in all fractions containing these markers, the location of ori-[beta] was established. In control or corn oil-treated cells, the location of ori-[beta] was consistent with previous studies. However, in FO-treated cells, DNA replication appears to start from a new site located farther upstream from ori-[beta], suggesting a different replication initiation pattern. This study suggests novel mechanism(s) by which fats affect cell proliferation and DNA replication in mammalian cells. cell cycle kinetics; n-3 fatty acids; dietary fat; cancer; deoxyribonucleic acid replication; Chinese hamster ovary cells; dihydrofolate reductase

Experimental studies of rats treated with cytokines such as tumor necrosis factor and interleukin-1 (IL-1) and those treated with endotoxins suggest an enhancement of plasma insulin, resistance to insulin, glucose flux in fed state and decrease in plasma zinc in injured state due to IL-1. The response of these rats to endotoxins or cytokines in relation to protein metabolism is complex and varies with food content in the body. These impairments during metabolism can be rectified by using the IL-1 receptor antagonist, in conjunction with a proper nutritional diet.

The estimation of cell cycle kinetics and protein dynamics in tumor affected rats, administered with pulse doses of 5-bromo-2'-deoxyuridine (Brd URd) and tracer-C14 leucine, indicates the antitumor effect of tumor necrosis factor (TNF) and the regulatory role of protein degradation in tumor growth phenomenon. Cell cycle kinetic variables are evaluated in terms of number of cells involved in DNA synthesis and the time duration of DNA synthesis, which are measured as a result of bivariate Brd Urd/DNA flow cytometric analysis. The rate of intracellular protein accumulation decreases as a result of enhanced tumor proteolysis initiated by TNF.

Context: Weight regain (WR) after bariatric surgery is emerging as a common clinical problem due to the increase in the number of procedures performed. Early interventions are necessary to curtail the potential recurrence of comorbid conditions. However, it is often difficult to recognize WR early enough to introduce mitigating measures because there are no current guidelines for timely diagnosis and assessment of the severity of this condition.Objective: We present a practical approach for the early recognition of WR, based on 11-year follow-up data from our multiethnic bariatric surgery patient population.Methods: We classify WR according to the rate of increase in weight relative to nadir weight, normalized per 30-day interval. We also review pertinent literature about the etiologic factors contributing to WR after bariatric surgery.Results: According to our algorithm, mild, moderate, and rapid WR are defined as weight increases of 0.2% to <0.5%, 0.5% to 1.0%, and more than 1.0% of nadir weight per 30 days, respectively. Treatment options, including dietary counseling, use of antiobesity medication, and consideration of surgical revision, are described. A case is presented to illustrate the utility of timely identification of WR and the importance of collaboration between bariatric surgeons, obesity medicine specialists, and dietitians.Conclusion: Our approach emphasizes the importance of regular long-term follow-up for all bariatric surgery patients. [ABSTRACT FROM AUTHOR]

Objective: Weight recidivism following Roux-en-Y gastric bypass (RYGB) is common and is associated with recurrence of comorbidities. Studies with long-term follow-up of recidivism quantified by weight regain (WR) are lacking. A retrospective review of all RYGB at our center from 2004 to 2015 was performed to examine the effects of race and type 2 diabetes on WR following RYGB.Methods: Multivariable linear mixed models were used for the effects of time and race on weight, WR relative to nadir weight (WR/nadir), and WR relative to maximal weight loss, and Cox regressions were used for low, moderate, and high WR/nadir.Results: A total of 1,395 participants were identified. The sample was limited to African American (AA), Caucasian American (CA), and Hispanic American (HA) participants. The effects of time (P < 0.0001), race (P < 0.0001), and race × time interaction (P = 0.0008) on weight trajectory were significant. AA had significantly more WR than CA (P < 0.01). AA and HA had a higher hazard ratio for having low, moderate, and rapid WR/nadir.Conclusions: Racial disparities after RYGB include WR and particularly affect AA. Understanding the etiologic factors that contribute to these disparities is important to optimize the long-term clinical outcomes of bariatric surgery. [ABSTRACT FROM AUTHOR]

Phenylpropanolamine (PPA) hydrochloride is a synthetic drug that is included in many over-the-counter diet aids and in some cold medicines. The federal Food and Drug Administration (FDA) has issued three reports that have concluded that PPA is both safe and effective. However, there has been some concern about possible adverse reactions, particularly the elevation of blood pressure (the pressor effect) from the use of these medications. This possibility is particular distressing in that hypertension is a common problem in the obese, which is the intended population for much of the use of PPA. The current study examines the effect of PPA on 881 healthy individuals of various body weight. Immediate and sustained release capsules in varying dosages were compared against placebos ("sugar pills"). Although a significant short-term increase in blood pressure was detected in the first 6 hours after its administration, the effect was not considered clinically relevant. The pressor effect was more marked in the first six hours after administration and was more pronounced in those individuals receiving the sustained-released capsules. Baseline measures of blood pressure, body weight and treatment were also independently related to changes in blood pressure within the test group., ABSTRACT: Phenylpropanolamine (PPA) is frequently used in over-the-counter diet aids and cold medicines. In view of concern about the safety of this sympathomimetic agent, we undertook a double-blind, multicenter clinical trial to determine the factors that influence the pressor effect of short-term oral administration of PPA in healthy individuals. Eight hundred eighty-one healthy individuals in four categories of body weight were randomized to receive placebo capsules three times per day (n=286), a 75-mg sustained-release PPA hydrochloride preparation once per day (n=296) followed by two doses of placebo capsules, or a 25-mg immediate-release PPA hydrochloride preparation three times per day (n=299). The median age of the study population was 28 years, 56% were men, 73% were white, and 47% were in excess of 30% above their ideal body weight. Measurements of pulse rate and supine and standing blood pressure were made 11 times during the day of PPA administration. A statistically significant but clinically unimportant pressor effect for the short-term administration of PPA was observed. The effect occurred in the first 6 hours after administration and was greater in the sustained-release group. Significant independent determinants of the pressor effect of PPA were baseline diastolic blood pressure, baseline body weight, and treatment.

Abstract: Objective: High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity. Methods: Obese subjects (29.0–44.6kg/m2) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12weeks. Results: The age range of subjects was 21–62years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2h oral glucose tolerance test did not differ (P>0.05) between diets after 12weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet. Conclusions: Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets. [Copyright &y& Elsevier]