WITHDRAWN: Assessment of the activity of posaconazole against azole-resistant Aspergillus species studied in an in vitro pharmacokinetic/pharmacodynamic model.

Ahead of Print article withdrawn by publisher.

Effects of gestational thiamine-deprivation and/or exposure to ethanol on crucial offspring rat brain enzyme activities.

Objective: The fetal alcohol spectrum disorder (FASD) is a group of clinical conditions associated with the exposure to ethanol (EtOH). We have recently examined the effects of a moderate maternal exposure to EtOH on crucial brain enzyme activities in offspring rats, and discussed the translational challenges arising when attempting to simulate any of the clinical conditions associated with FASD.

Materials And Methods: In this current study, we: (i) address the need for a more consistent and reliable experimental platform that could simulate milder cases of FASD complicated by simultaneous thiamine-deprivation during gestation and (ii) explore the effects of such a moderate maternal exposure pattern to EtOH and a thiamine-deficient diet (TDD) on crucial enzyme activities in the offspring rat brains.

The impact of low alcohol consumption on the liver and inflammatory cytokines in diabetic rats.

Background: Diabetes mellitus (DM) and alcohol consumption is still one of the important research models that simulate variable clinical conditions and metabolic diseases, such as alcoholic liver diseases.

Objectives: The aim of this study was to evaluate the long-term cumulative effects of low alcohol consumption on the liver tissue, biochemical assays and some inflammatory cytokines in experimentally-induced DM rats.

Material And Methods: Ethanol was administered in the drinking water (3% v/v) for 30 days to adult male Sprague-Dawley rats, with or without DM induced by streptozocin injection.

"Extracellular matrix remodelling in the liver of rats subjected to dietary choline deprivation and/or thioacetamide administration".

Choline deprivation is a recognized experimental approach to nonalcoholic steatohepatitis, while thioacetamide (TAA)-induced liver fibrosis resembles alcoholic liver fibrogenesis. In order to elucidate the effect of TAA on liver extracellular matrix composition under choline deprivation due to choline-deficient diet (CDD) administration, we evaluated the transcriptional and immunohistochemical (IHC) pattern of major hepatic matrix metalloproteinases (namely, MMP-2, -9) and their tissue inhibitors (TIMP-1, -2) in adult male albino Wistar rats at 30, 60 and 90 days. In the CDD+TAA group, IHC showed an early progressive increase in MMP-2 expression, while MMP-9 initially exhibited a significant increase followed by a gradual decrease; TIMP-1 and TIMP-2 IHC expressions showed gradual increase throughout the experiment.

Addressing the Challenges of Tuberculosis: A Brief Historical Account.

Tuberculosis (TB) is a highly contagious disease that still poses a threat to human health. (MTB), the pathogen responsible for TB, uses diverse ways in order to survive in a variety of host lesions and to subsequently evade immune surveillance; as a result, fighting TB and its associated multidrug resistance has been an ongoing challenge. The aim of this review article is to summarize the historical sequence of drug development and use in the fight against TB, with a particular emphasis on the decades between World War II and the dawn of the twenty first century (2000).

Oral Candida in Patients with Fixed Orthodontic Appliance: In Vitro Combination Therapy.

Background: Fixed orthodontic appliance (FOA) increases the cariogenic microorganisms of mouth including candida. The aim was to evaluate the pharmacodynamic effects of some antibacterial drugs in combination with most applicable antifungal agents on candida isolated from patients with FOA.

Methods: Three antifungal agents (amphotericin B (AMB), ketoconazole (KET), and itraconazole (ITZ)) and three antibacterial drugs (ciprofloxacin (CIP), doxycycline (DOX), and metronidazole (MET)) with serial concentrations have been used and microdilution broth method has been done for single and combination therapy, then fungal growth was assessed spectrophotometrically, and the combinations were evaluated by bliss independent analysis.

Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation.

Gestational exposure to cadmium alters crucial offspring rat brain enzyme activities: the role of cadmium-free lactation.

The present study aimed to shed more light on the effects of gestational (in utero) exposure to cadmium (Cd) on crucial brain enzyme activities of Wistar rat offspring, as well as to assess the potential protective/restorative role that a Cd-free lactation might have on these effects. In contrast to earlier findings of ours regarding the pattern of effects that adult-onset exposure to Cd has on brain AChE, Na(+),K(+)- and Mg(2+)-ATPase activities, as well as in contrast to similar experimental approaches implementing the sacrificing mode of anaesthesia, in utero exposure to Cd-chloride results in increased AChE and Na(+),K(+)-ATPase activities in the newborn rat brain homogenates that were ameliorated through a Cd-free lactation (as assessed in the brain of 21-day-old offspring). Mg(2+)-ATPase activity was not found to be significantly modified under the examined experimental conditions.

Experimentally-induced Wernicke's encephalopathy modifies crucial rat brain parameters: the importance of Na+, K+ -ATPase and a potentially neuroprotective role for antioxidant supplementation.

Wernicke's encephalopathy (WE) is a serious neuropsychiatric syndrome caused by chronic alcoholism and thiamine (T) deficiency. Our aim was to shed more light on the pathophysiology of WE, by introducing a modified in vivo experimental model of WE and by focusing on changes provoked in the total antioxidant status (TAS) and three crucial brain enzyme activities in adult rats. Rats were placed on ethanol (EtOH) consumption (20 % v/v) for a total of 5 weeks.

Modulation of crucial adenosinetriphosphatase activities due to U-74389G administration in a porcine model of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) represents a partially-understood cerebrovascular disease of high incidence, morbidity and mortality. We, herein, report the findings of our study concerning the role of two important adenosinetriphosphatases (ATPases) in a porcine model of spontaneous ICH that we have recently developed (by following recent references as well as previously-established models and techniques), with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates that the examined ICH model does not cause a decrease in Na(+),K(+)-ATPase activity (the levels of which are responsible for a very large part of neuronal energy expenditure) in the perihematomal basal ganglia territory, nor a change in the activity of Mg(2+)-ATPase.

Hepatic injury due to combined choline-deprivation and thioacetamide administration: an experimental approach to liver diseases.

Background: The induction of prolonged choline-deprivation (CD) in rats receiving thioacetamide (TAA) is an experimental approach of mild hepatotoxicity that could resemble commonly presented cases in clinical practice (in which states of malnutrition and/or alcoholism are complicated by the development of other liver-associated diseases).

Aim: The present study aimed to investigate the time-dependent effects of a 30-, a 60- and a 90-day dietary CD and/or TAA administration on the adult rat liver histopathology and the serum markers of hepatic functional integrity.

Methods: Rats were divided into four main groups: (a) control, (b) CD, (c) TAA and (d) CD + TAA.

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.

Short-term exposure to nickel alters the adult rat brain antioxidant status and the activities of crucial membrane-bound enzymes: neuroprotection by L-cysteine.

Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation) and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of short-term Ni-administration (as NiCl(2), 13 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase, and Mg(2+)-ATPase; in addition, the potential effect of the co-administration of the antioxidant L-cysteine (Cys, 7 mg/kg) on the above parameters was studied. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Ni), C (Cys), and D (Ni and Cys).

Choline-deprivation alters crucial brain enzyme activities in a rat model of diabetic encephalopathy.

Diabetic encephalopathy describes the moderate cognitive deficits, neurophysiological and structural central nervous system changes associated with untreated diabetes. It involves neurotoxic effects such as the generation of oxidative stress, the enhanced formation of advanced glycation end-products, as well as the disturbance of calcium homeostasis. Due to the direct connection of choline (Ch) with acetylcholine availability and signal transduction, a background of Ch-deficiency might be unfavorable for the pathology and subsequently for the treatment of several metabolic brain diseases, including that of diabetic encephalopathy.

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).

Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats.

Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase of adult rats.

Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na(+),K (+))- and Mg(2+)-ATPase: modulation by L-cysteine.

Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L: -cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase. Thirty-eight male Wistar rats were divided into six groups: C(A) (8-week-control), C(B) (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), D(A) (8-week-diabetic), D(B) (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated).

Effects of adult-onset choline deprivation on the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase in crucial rat brain regions.

Choline (Ch) plays an important role in brain neurotransmission, while Ch-deprivation (CD) has been linked to various pathophysiological states. Prolonged ingestion of Ch-deficient diet (CDD) is known to produce CD causing a reduction of rat brain acetylcholine (ACh) levels, as well as memory and growth disorders. The aim of this study was to investigate the effect of a 2-month adult-onset CD on the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-ATPase in crucial brain regions of male rats.

The neuroprotective role of L-cysteine towards the effects of short-term exposure to lanthanum on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase.

Lanthanum (La) is a rare earth element that is widely used for industrial, medical and agricultural purposes. Its neurotoxic effects are linked to its physical and chemical properties and its interaction with certain trace elements and membrane-bound enzymes. The aim of this study was to investigate the effects of short-term La-administration (as LaCl(3), 53 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase, as well as the potential effect of the co-administration of the antioxidant L: -cysteine (Cys, 7 mg/kg) on the above parameters.

Effects of short-term exposure to manganese on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na,K)-ATPase and Mg-ATPase: modulation by L-cysteine.

Manganese (Mn) is an essential metalloenzyme component that in high doses can exert serious oxidative and neurotoxic effects. The aim of this study was to investigate the potential effect of the antioxidant L-cysteine (Cys, 7 mg/kg) on the adult rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase induced by short-term Mn administration (as Mn chloride, 50 mg/kg). Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Mn), C (Cys) and D (Mn and Cys).