An assessment of serum leptin levels in patients with chronic viral hepatitis: a prospective study

<p>Abstract</p> <p>Background</p> <p>The role of leptin in the course of liver disease due to chronic viral hepatitis (CVH) remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and C (CHC) and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment.</p> <p>Methods</p> <p>We studied 50 (36 men) consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17 men) healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment.</p> <p>Results</p> <p>A significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy.</p> <p>Conclusion</p> <p>Our data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.</p

The role of folate metabolism-related gene polymorphisms in the development of meningiomas

Meningiomas are (usually) slow-growing benign tumors, and several factors have been implicated in their development. Increasing age, previous exposure to ionizing radiation, endogenous hormone status and history, hormone replacement therapy, genetic variants and polymorphisms are the main factors that have been proven or assumed to be involved in meningioma formation. The complex genetic background supporting the pathogenesis of meningiomas includes a large number of mutations and polymorphisms that might be actively involved in tumor development, progression and recurrence. The aim of this mini-review is to summarize the current data concerning the role of folate metabolism-related gene polymorphisms in the development of meningiomas

The involvement of substance P in the induction of aggressive behavior

Aggression is a complex social behavior that involves a similarly complex neurochemical background. The involvement of substance P (SP) and its potent tachykinin receptor (NK1) in the induction of both defensive rage and predatory attack appears to be a consistent finding. However, an overall understanding of the nature of the SP involvement in the induction of aggressive behavior has not yet been fully achieved. The aim of this review is to summarize and present the current knowledge with regards to the role of SP in the induction of aggressive behavior and to synopsize: (a) its biochemical profile, and (b) the exact anatomical circuits through which it mediates all types of aggressive behavior. Future studies should seriously consider the potential use of this knowledge in their quest for the treatment of mood and anxiety disorders

The regulatory role of neurotensin on the hypothalamic-anterior pituitary axons: emphasis on the control of thyroid-related functions

Neurotensin (NT) is a 13 amino acid neurohormone and/or neuromodulator, located in the synaptic vesicles and released from the neuronal terminals in a calcium-dependent manner. This peptide is present among mammalian and nonmammalian species, mainly in the central nervous system and the gastrointestinal tract. Due to its neuroendocrine activity, NT has been related to the pathophysiology of a series of disorders, such as schizophrenia, drug-abuse, Parkinson's disease, cancer, stroke, eating disorders and other neurodegenerative conditions. Moreover, NT participates in the physiology of pain-induction, central blood pressure control and inflammation. NT also plays an important interactive role in all components of the hypothalamic-anterior pituitary circuit, which is mediated by an endocrine, paracrine or/and autocrine manner, towards most of the anatomical regions that define this circuit. A considerable amount of data implicates NT in thyroid-related regulation through this circuit, the exact mechanisms of which should be further investigated for the potential development of more targeted approaches towards the treatment of thyroid-related endocrine diseases. The aim of this study was to provide an up-to-date review of the literature concerning the regulatory role of NT on the hypothalamic-anterior pituitary axons, with an emphasis on the control of thyroid-related functions

Genetic basis and gene therapy trials for thyroid cancer

Gene therapy is regarded as one of the most promising novel therapeutic approaches for hopeless cases of thyroid cancer and those not responding to traditional treatment. In the last two decades, many studies have focused on the genetic factors behind the origin and the development of thyroid cancer, in order to investigate and shed more light on the molecular pathways implicated in different differentiated or undifferentiated types of thyroid tumors. We, herein, review the current data on the main genes that have been proven to (or thought to) be implicated in thyroid cancer etiology, and which are involved in several well-known signaling pathways (such as the mitogen-activated protein kinase and phosphatidylinositol-3-kinase/Akt pathways). Moreover, we review the results of the efforts made through multiple gene therapy trials, via several gene therapy approaches/strategies, on different thyroid carcinomas. Our review leads to the conclusion that future research efforts should seriously consider gene therapy for the treatment of thyroid cancer, and, thus, should: (a) shed more light on the molecular basis of thyroid cancer tumorigenesis, (b) focus on the development of novel gene therapy approaches that can achieve the required antitumoral efficacy with minimum normal tissue toxicity, as well as (c) perform more gene therapy clinical trials, in order to acquire more data on the efficacy of the examined approaches and to record the provoked adverse effects

Effects of gestational and lactational choline deprivation on brain antioxidant status, acetylcholinesterase, (Na(+),K(+))- and Mg(2+)-ATPase activities in offspring rats

BACKGROUND: Choline plays an important role in brain development. Choline-deficient diet (CDD) is known to produce (among other effects) a decrease in acetylcholine in rat brains. The aim of our study was to investigate how CDD administration during gestation and lactation could affect total antioxidant status (TAS) and activities of acetylcholinesterase (AChE), (Na(+),K(+))- and Mg(2+)-ATPase in the brains of both male and female newborn and suckling (21-day-old) rats. METHODS: Three different experiments were performed. Whole brains were obtained from: (a) newborn rats following gestational CDD (experiment I); (b) 21-day-old rats following gestational but not lactational CDD (experiment II); and (c) 21-day-old rats following gestational and lactational CDD (experiment III). Enzyme activities and TAS were measured spectrophotometrically. RESULTS: In choline-deprived (CD) newborn rats, TAS and AChE and Na(+),K(+)-ATPase activities were significantly reduced by 23%, 24% and 50%, respectively, in the brains of both sexes. Gestational CDD caused only a decrease in TAS (-27%, p&lt;0.001) in suckling rat brains in both sexes. No changes were observed for the other enzyme activities. Moreover, gestational and lactational CDD also led only to a decrease in TAS (-24%, p&lt;0.001) in the suckling rat brains of both sexes. Mg(2+)-ATPase activities showed no changes after any of the experimental procedures. CONCLUSIONS: Our data suggest that the lower enzyme activities in newborn CD brains were restored to normal after 21 days of either normal or CDD lactation, possibly due to novel synaptogenesis, endogenous neuroregulation, and/or to other substances acquired by lactation. The increase in homocysteine concentration due to choline deficiency reported in the literature may be the cause of the low antioxidant capacity observed in offspring rat brains. Brain Na(+),K(+)-ATPase inhibition (induced by CDD) could result in modulations of neural excitability, metabolic energy production and neurotransmission

Choline deprivation: an overview of the major hepatic metabolic response pathways

Choline (Ch) is an important nutrient that is involved in many physiological functions. Deprivation of Ch (CD) may lead to hepatocellular modifications and/or even hepatic tumorigenesis and it can be a frequent problem in clinical settings; it can accompany various common pathological (alcoholism and malnutrition) or physiological states (pregnancy and lactation). The aim of this review is to provide an up-to-date overview of the major metabolic pathways involved in the hepatic response toward the experimentally or clinically induced CD, and to shed more light on the implicated (and probably interrelated) mechanisms responsible for the observed hepatocellular modifications and/or carcinogenesis

Equilibrated diet restores the effects of early age choline-deficient feeding on rat brain antioxidant status and enzyme activities: the role of homocysteine, L-phenylalanine and L-alanine

Choline is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions, that affect the developing brain. The aim of this study was to: (a)examine the effects of early age choline deficient diet (CDD) administration on the total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase in the rat brain, (b)investigate the effect of feeding restoration into an equilibrated diet on the above parameters, and (c)study the role of homocysteine (Hcy), L: -phenylalanine (Phe) and L: -alanine (Ala) in certain of the above effects. Male and female Wistar rats were continuously kept off choline (Ch) during their gestational period of life, as well as during the first 6 weeks of their post-gestational life. The animals were sacrificed by decapitation and their whole brains were rapidly removed and homogenated. Their enzyme activities were measured spectrophotometrically. Moreover, in vitro experiments were conducted in order to estimate the effects of Hcy (0.3 mM), Phe (1.2 mM) and/or Ala (1.2 mM) on the above parameters. The administration of CDD led to a statistically significant decrease of the rat brain TAS (-29%, p &lt; 0.001) and to a significant increase of both AChE (+20%, p &lt; 0.001) and (Na(+),K(+))-ATPase (+35%, p &lt; 0.001) activities. Mg(2+)-ATPase activity was found unaltered. Equilibrated diet, administered to early age CDD-treated rats of both sexes for an additional period of 18 weeks, restored the above parameters to control levels. Moreover, the in vitro experiments showed that Hcy could simulate these changes (at least under the examined in vitro conditions), while both Phe and Ala act protectively against the CDD-induced effects on the examined rat brain enzyme activities. The effects of early age CDD-feeding on the examined parameters are proved to be reversible through restoration to equilibrated diet, while our data suggest a role for Hcy (as a causative parameter for the CDD-induced effects) and a possible protective role for Phe and Ala (in reversing the observed CDD-induced effects)

Neuronal tumour necrosis factor-alpha and interleukin-1beta expression in a porcine model of intracerebral haemorrhage: Modulation by U-74389G

Tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) are important mediators of intracerebral haemorrhage (ICH) inflammatory response. Lazaroids, established antioxidants and neuroprotectants, have been studied in several brain pathologies. The present study was designed to investigate: a) TNF-alpha and IL-1beta changes, in neurons and b) U-74389G effects, 4 and 24h after haematoma induction in a porcine model of intracerebral haemorrhage. In twenty male landrace pigs (swines) aged 135-150 days old, autologous whole blood was injected around the right basal ganglia territory; in ten of the pigs the lazaroid compound U-74389G was administered. Brain TNF-alpha and IL-1beta immunopositive neurons were determined by immunoarray techniques at 4 and 24h timepoints. After the haematoma induction the number of TNF-alpha immunopositive neurons ipsilateral to the haematoma was significantly higher compared to the contralateral site at 4h (p<0.0005), while U-74389G significantly reduced the number of TNF-alpha immunopositive neurons, ipsilateral to the haematoma, at 4h (p=0.002); at 24h, TNF-alpha immunopositive neurons were found significantly lower in the control group ipsilateral to the haematoma in comparison to 4h timepoint(p<0.0005). The number of IL-1beta immunopositive neurons at 4h after the hematoma induction was significantly higher ipsilateral to the haematoma site (p<0.0005). U-74389G had no statistical significant effect. TNF-alpha and IL-1beta, increase in neurons, 4h after the haematoma induction, ipsilateral to the haematoma site. The administration of the antioxidant compound U-74389G, results in early (at 4h) decrease of TNF-alpha immunopositive neurons but shows no statistical significant effect to IL-1beta immunopossitive neurons