Glenn R. Krakower

Probiotic Yogurt for the Treatment of Minimal Hepatic Encephalopathy

OBJECTIVES:Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence.METHODS:Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence.RESULTS:Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71% vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed.CONCLUSIONS:This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence.

Leptin: a significant indicator of total body fat but not of visceral fat and insulin insensitivity in African-American women.

The recently cloned adipose tissue hormone leptin has been proposed to be involved in the neuroendocrine regulation of adiposity and its metabolic sequelae. Visceral fat is known to predict reduced insulin sensitivity and associated adverse metabolic profiles. In this study, we report the first evaluation of the relationships between leptin levels and total body fat, visceral fat, and insulin sensitivity in a cohort of premenopausal African-American women. Thirty-four subjects were analyzed for total fat mass and visceral fat by dual-energy X-ray absorptiometry and computerized axial tomography, respectively. Insulin sensitivity (SI) was assessed using Bergmans minimal model. Results showed that fasting leptin levels strongly correlated with total body fat mass (r = 0.797, P < 0.001). Correlations of leptin with visceral fat (r = 0.54, P < 0.001) and SI (r = −0.419, P = 0.02) were dependent on total body fat. In conclusion, leptin levels reflect total body fat mass, and although visceral fat is known to predict reduced insulin sensitivity independently, leptin did not. Our data thus suggest that diverse mechanisms are responsible for the regulation of total body versus visceral fat distribution, with its metabolic and health risks.

Regional adipocyte precursors in the female rat. Influence of ovarian factors.

A flow cytometric immunofluorescence procedure utilizing a specific antibody to rat adipose tissue lipoprotein lipase (LPL) was developed to quantify differentiated and undifferentiated preadipocytes present in the adipose tissue vascular stroma. This method is highly sensitive and specific for cells capable of synthesizing LPL in significant quantities. Pubescence in female rats was associated with an increase in differentiated preadipocytes and in fat cell number with enlargement of the fat depots in the perirenal, parametrial, and the subcutaneous dorsal and femoral regions. A concomitant decline in the percentage of undifferentiated preadipocytes occurred in all but the femoral depot. Ovariectomy reduced pubertal adipose growth in the femoral and parametrial but not the dorsal or perirenal regions. Furthermore, the femoral undifferentiated preadipocyte pool was not preserved in the ovariectomized animals. Thus, ovarian factors influence the pubescence-associated regional preadipocyte differentiation and conversion to adipocytes. The femoral depot contains an ovarian-dependent infinite pool of fat cell precursors. These features could account for the association between ovarian hormones and body fat topography.

Separation and identification of subpicomole amounts of methotrexate polyglutamates in animal and human biopsy material.

Abstract A rapid, quantitative procedure for separating methotrexate (MTX) polyglutamates utilizing molecular-sieve column chromatography has been developed. MTX polyglutamates were separated in 25 min and detected by a radioassay with a sensitivity of 0.1 pmol MTX, allowing analysis on 2 to 5 mg of tissue. This technique has been used to demonstrate and quantitate the levels of MTX polyglutamates in liver, kidney, and brain tissues of rats treated with weekly low doses of MTX, and in liver and red cells of patients with acute leukemia treated with weekly low doses of MTX.

Effects of Obesity on Lipid Metabolism

Obesity is a complex, heterogeneous disorder whose etiologic mechanisms are influenced by genetic, environmental, and neuroendocrine factors (1,2). Not only is obesity associated with excess body fat, but the biology of obesity is also influenced by size, location, and metabolism of the adipose tissue, as well as hormonal and neuroendocrine factors, all interacting to contribute to the associated health risks. Cardiovascular outcome is the sum total of multiple components, one of which is disturbances in lipid metabolism. Although the mechanisms behind the biology of these associations have been poorly understood, we now have the tools to study the underlying factors, in terms of both the genetic and neuroendocrinologic influences. This chapter describes the health risks associated with obesity and especially with abdominal/visceral obesity, with particular regard to effects on serum lipids and lipoproteins, and their relationship to insulin resistance and progression toward noninsulin-dependent diabetes mellitus (NIDDM).