Are hepatic steatosis and carotid intima media thickness associated in obese patients with normal or slightly elevated gamma-glutamyl-transferase?

<p>Abstract</p> <p>Background</p> <p>Hepatic steatosis (HS) has been associated with obesity and metabolic syndrome (MS), conditions carrying a high risk of coronary artery disease. We aimed to determine whether HS was an independent factor of atherogenic risk beyond its association with MS and its components.</p> <p>Methods</p> <p>We assessed the circulating levels of the heat shock protein-70 (HSP-70), a chaperone involved in inflammation, endoplasmic reticulum stress and apoptosis at liver and endothelial level and the gamma-glutamyl transferase activity (γ-GT) correlating them to carotid intima-media thickness (IMT), along with lipid profile, HOMA, C-reactive protein, fibrinogen, ferritin, adiposity type as well as spleen volume in 52 obese pts with grade 1, 128 with grade 2, and 20 with grade 3 of HS evaluated by sonography.</p> <p>Results</p> <p>Patients with different grade of HS demonstrated overlapping HSP-70 levels; similarly performed obese subjects regarding IMT. Using multiple regression analysis, IMT was predicted by age, visceral adiposity and by HOMA (β = 0.50, <it>p </it>< 0.0001, β = 0.30, <it>p </it>= 0.01 and β = 0.18, <it>p </it>= 0.048 respectively, while the severity of HS was predicted by visceral and subcutaneous adiposity and HOMA (β = 0.50, <it>p </it>< 0.0001 and β = 0.27, <it>p </it>= 0.001 and β = 0.18, <it>p </it>= 0.024, respectively).</p> <p>Conclusion</p> <p>In our series of patients with normal or mild elevation of γ-GT, the severity of HS does not entail higher IMT, which may be linked to MS stigmata.</p

Enhanced serum concentrations of transforming growth factor-beta1 in simple fatty liver: is it really benign?

<p>Abstract</p> <p>Background</p> <p>Inside the spectrum of non-alcoholic fatty liver disease, simple fatty liver is generally thought of as being "non progressive", differently from non-alcoholic steatohepatitis, which increases in severity due to the presence of apoptosis/inflammation and fibrosis. The "benignity" of fatty liver is widely accepted but conceptually difficult to maintain because the mechanisms underlying this entity are the same ones that determine the more severe form.</p> <p>Findings provide evidence that iron overload is associated with increased liver damage and collagen deposition. Transforming growth factor-beta1 released by hepatic stellate cells during chronic liver injury plays a critical role in liver apoptosis and fibrogenesis.</p> <p>Objective</p> <p>To verify whether both the forms of non-alcoholic fatty liver disease were really dissimilar, evaluating the serum profile of two key parameters, indexes of severity.</p> <p>Methods</p> <p>A total of 123 patients (57 females) participated, forming three groups: forty five patients with fatty liver, 42 patients with non-alcoholic steatohepatitis and 36 with chronic hepatitis C. All had a biopsy-proven diagnosis.</p> <p>Measurements</p> <p>Serum concentrations of transforming growth factor-beta1 and ferritin.</p> <p>Results</p> <p>High concentrations of transforming growth factor-beta1 were noticed in patients suffering from both fatty liver and non-alcoholic steatohepatitis, 129.1 (45.4) versus 116.8 (42.2) ng/mL, P = 0.2; they were significantly superior to those of chronic hepatitis C patients 87.5 (39.5) ng/mL, P < 0.001. Ferritin levels were on average above normal values and similar in the three groups (P = 0.9), also when adjusted for gender (P = 0.5) and age (P = 0.3).</p> <p>Conclusion</p> <p>No difference between serum concentrations of transforming growth factor-beta1 and ferritin in fatty liver and non-alcoholic steatohepatitis suggests that these forms share more common aspects, regarding their progression, than previously thought.</p

Plasma immunoreactive thyrotropin releasing hormone (TRH) values in normal newborns

The study reported here extends investigation on the pituitary thyroid axis in newborn infants, including the assay of plasma immunoreactive TSH levels at different intervals after delivery. Blood samples were collected at birth and after 30, 60, 120 minutes, 6, 24 and 48 hours. Plasma TRH levels were also estimated in normal adult subjects and pregnant women. No significant difference was observed with regard to sex, pregnancy or age, except for a marked increase in newborn infants after delivery. Plasma TRH values, already moderately high at birth (mean 46 pg/ml, range 34-57) reached rapidly a peak of 78 pg/ml (range 60-93) 30 minutes after delivery, decreased rapidly between 30 minutes and 2 hours post-partum, then fell gradually to normal range at 24 hours. A comparison of plasma TRH and TSH levels measured simultaneously suggests that the acute TSH surge at delivery is mediated by TRH secretion

Automated determination of neutrophil volume as screening test for late-onset sepsis in very low birth infants.

The diagnosis of sepsis is often a difficult issue for the neonatologist. Clinical signs and symptoms are poorly specific, and the quest for the optimal laboratory assay is still open. C-reactive protein (CRP) requires serial determinations to be of practical value,1 interleukins have not yet entered the routine clinical use, total white blood cells or absolute neutrophil counts alone have not enough sensitivity or specificity. Current hematology analyzers can determine white blood cell subpopulations based on their physical characteristics (eg, volume and granularity). In particular, mean neutrophil volume (MNeV) and its standard deviation (neutrophil distribution width) have been previously used to diagnose sepsis in an adult population with encouraging results.We investigated these same parameters in screening for late-onset neonatal sepsis, defined as a systemic infection, validated by a positive blood culture, diagnosed beyond the third day of life. When taken together, CRP and MNeV represent a powerful rapid combination both to suspect or exclude late onset sepsis. Neutrophil distribution width did not prove to be of any practical help in our neonatal series, possibly because the resting neutrophil population in the newborn is already more heterogeneous in size and shape than in the adult

Serum Bcl-2 concentrations in overweight-obese subjects with nonalcoholic fatty liver disease

AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL) and 41 with nonalcoholic steatohepatitis (NASH)

Altered glucoregulatory response to physiological infusions of epinephrine and glucagon in hyperthyroidism.

To study the mechanism of altered glucose homeostasis in hyperthyroidism, the effects of a 2-h physiological infusion of epinephrine (0.05 microgram/kg x min) or glucagon (3 ng/kg x min) on glucose kinetics and glucoregulatory hormones were determined in nine normal subjects and five untreated hyperthyroid patients. Under basal conditions, hyperthyroid patients exhibited increased glucose turnover (2.2 +/- 0.09 vs. 1.62 +/- 0.1 mg/kg x min in normals), a modest hyperglycemia, hyperglucagonemia, and normal levels of plasma insulin, cortisol, and GH. In normal subjects, epinephrine induced a sustained increase in plasma glucose (45 mg/dl), reflecting a transient 100% rise in glucose output, and a sustained 28% decrease in glucose clearance. In hyperthyroid patients, the rise in plasma glucose was significantly lower (22 mg/dl) due to a smaller but sustained increase in glucose output (45%) and the lack of a fall in glucose clearance. Plasma insulin rose to a peak 80% higher than baseline in hyperthyroid patients, whereas in normals it initially declined and then rose to levels 50% higher than basal. Plasma glucagon displayed only minor changes in both groups. Glucagon infusion induced similar increments in plasma glucagon levels in the two groups (120-150 pg/ml). Insulin, cortisol, and GH remained unchanged. Plasma glucose rose by 4 mg/dl in hyperthyroid patients and by 11 mg/dl in normal subjects. The net increments were significantly lower in the former group (P < 0.05-0.01). Glucose output increased by 40% in normals and returned to baseline by 75 min, whereas it increased by only 15% in hyperthyroid patients and remained above baseline until the end of the infusion. Glucagon had no appreciable effect on glucose clearance in either group. We conclude that hyperthyroidism is characterized by 1) increased glucose turnover and hyperglucagonemia in the basal state, 2) a reduced glucemic response to physiological infusions of epinephrine and glucagon, 3) a sustained response of glucose production to epinephrine and glucagon, and 4) the lack of epinephrine-induced suppression of glucose clearance, presumably due to an exaggerated response of insulin secretion to epinephrine

Myeloperoxidase, but not C-reactive protein, predicts cardiovascular risk in peripheral arterial disease.

AIMS: The prognostic role of inflammation in peripheral arterial disease (PAD) remains to be conclusively established. Accordingly, in these patients we investigated the impact of myeloperoxidase (MPOx) and C-reactive protein on the incidence of myocardial infarction and stroke. METHODS AND RESULTS: Of 156 PAD patients, 10 had a myocardial infarction and seven a stroke, during follow-up. We used the receiver operating characteristic curve analysis and the bootstrap approach to identify the MPOx, C-reactive protein, and ankle brachial index (ABI) threshold levels that provided the best cut-off to predict the outcome. For MPOx a cut-off > or =183.7 pM was independently associated with a poor outcome (HR = 6.80, 95% CI 1.20-38.69, P = 0.031). The result remained unmodified when MPOx was used as a continuous variable (HR = 1.03, 95% CI 1.01-1.05, P = 0.031). Conversely, C-reactive protein was not a prognostic determinant in our series (HR = 0.88, 95% CI 0.60-1.29, P = 0.514). Kaplan-Meier curves for the four groups of patients delineated according to ABI and MPOx values identified using the bootstrap approach showed that the addition of MPOx measurement to ABI improved the ability to identify patients at risk for myocardial infarction and stroke. CONCLUSION: In PAD, MPOx, but not C-reactive protein, predicts an increased risk of major cardiovascular events, and adds to the prognostic value of ABI, currently the most powerful prognostic indicator in these patients