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SUMMARY The airway epithelium may modulate smooth muscle responsiveness via the release of biologically active substances, such as nitric oxide (NO) and prostaglandins. Based on regional differences in structure and function described for... more
SUMMARY The airway epithelium may modulate smooth muscle responsiveness via the release of biologically active substances, such as nitric oxide (NO) and prostaglandins. Based on regional differences in structure and function described for the airway epithelium, we performed a comparative study on the responsiveness of sheep isolated, epithelium‐intact or ‐denuded, first‐ to fourth‐order bronchi to acetylcholine (ACh). We performed contractility studies using KCl or cholinergic stimuli in the presence or absence of NO or prostaglandin‐related drugs in epithelium‐intact and epithelium‐denuded bronchial strips obtained from all four airway regions. We also studied the expression of NO synthase (NOS), using the NADPH‐diaphorase staining technique, and the effect of airway epithelium removal on the synthesis of NO metabolites in the different bronchi orders. There was no difference in the response of first‐ to fourth‐order epithelium‐intact bronchi to ACh (1 nmol/L–100 mmol/L) or KCl (5–...
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The effect of in vivo fentanyl treatment on synaptic transmission was studied in the CA1 area of the rat hippocampus. Animals were treated either with saline or fentanyl (4 x 80 microg/kg, s.c./15 min). Intracellular in vitro recordings... more
The effect of in vivo fentanyl treatment on synaptic transmission was studied in the CA1 area of the rat hippocampus. Animals were treated either with saline or fentanyl (4 x 80 microg/kg, s.c./15 min). Intracellular in vitro recordings were obtained, 24 h after treatment, from CA1 pyramidal neurons. No difference in pyramidal neuron basic membrane properties or postsynaptic membrane excitability was observed between neurons from saline- and fentanyl-treated animals. The peak amplitude of fast (f-) and slow (s-) components of IPSPs elicited in standard ACSF and the peak amplitude and rate of rise of isolated f- and s-IPSPs elicited in the presence of antagonists (CNQX, 10 microM; AP-5, 10 microM; CGP 55845, 1 microM; and bicuculline methochloride, 10 microM), in response to various stimulus intensities, was smaller in fentanyl-treated animals. Conversely, the rising slope of excitatory responses was similar in neurons from saline- and fentanyl-treated animals. Furthermore, in fentanyl-treated animals, lower stimulus strengths were required to elicit subthreshold excitatory responses of the same amplitude suggesting that acute exposure to fentanyl increases susceptibility of pyramidal neurons to presynaptic stimulation. GABA immunohistochemistry revealed lower GABA content in processes and neuronal somata suggesting diminished GABA release onto pyramidal neurons. We conclude that acute in vivo exposure to fentanyl is sufficient to induce long-lasting reduction in GABA-mediated transmission, rather, than enhanced excitatory transmission or modulation of the intrinsic excitability of pyramidal neurons. These findings provide evidence regarding the mechanisms involved in the early stages of tolerance development towards the analgesic effects of opioids.
Research Interests: Neuroscience, Electrophysiology, Long Term Potentiation, Biology, Neuropharmacology, and 15 moreImmunohistochemistry, Medicine, Hippocampus, In Vitro, Animals, Male, Neuronal Plasticity, Inhibition, GABA, Fentanyl, Neurosciences, Bicuculline, Hyperalgesia, Excitatory Postsynaptic Potentials, and Electric stimulation
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The drug discovery process is a rigorous and time-consuming endeavor, typically requiring several years of extensive research and development. Although classical machine learning (ML) has proven successful in this field, its computational... more
The drug discovery process is a rigorous and time-consuming endeavor, typically requiring several years of extensive research and development. Although classical machine learning (ML) has proven successful in this field, its computational demands in terms of speed and resources are significant. In recent years, researchers have sought to explore the potential benefits of quantum computing (QC) in the context of ML, leading to the emergence of Quantum Machine Learning (QML) as a distinct research field. The objective of the current study is twofold: first, to present a review of the proposed QML algorithms for application in the drug discovery pipeline, and second, to compare QML algorithms with their classical and hybrid counterparts in terms of their efficiency. A query-based search of various databases took place, and five different categories of algorithms were identified in which QML was implemented. The majority of QML applications in drug discovery are primarily focused on the...
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In recent years, machine learning has penetrated a large part of our daily lives, which creates special challenges and impressive progress in this area. Nevertheless, as the amount of daily data is grown, learning time is increased.... more
In recent years, machine learning has penetrated a large part of our daily lives, which creates special challenges and impressive progress in this area. Nevertheless, as the amount of daily data is grown, learning time is increased. Quantum machine learning (QML) may speed up the processing of information and provide great promise in machine learning. However, it is not used in practice yet, because quantum software and hardware challenges are still unsurmountable. This paper provides current research of quantum computing and quantum machine learning algorithms. Also, the quantum vendors, their frameworks, and their platforms are presented. A few fully implemented versions of quantum machine learning are presented, which are easier to be evaluated. Finally, QML's challenges, and problems are discussed.
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Exposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c-fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or... more
Exposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c-fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or repeated amphetamine (1 mg/kg, i.p.) administration induced c-fos expression additionally in the nucleus accumbens. An -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(f)quinoxaline (NBQX), blocked expression of conditioned activity, and prevented the increase in c-fos expression in mPFC, implicating mPFC AMPAergic transmission in the conditioned component of behavioural sensitization to amphetamine. NBQX failed to block the expression of amphetamine-conditioned place preference, a measure of conditioned reward, or conditioned c-fos expression in the amygdala, an area implicated in the expression of conditioned place preference. These findings indicate that the conditioned components o...
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ABSTRACT Ιnformation on the role of adiponectin in human ovarian steroidogenesis is limited. The present study aimed to investigate the effect of different doses of adiponectin on the secretion of estradiol and progesterone by human... more
ABSTRACT Ιnformation on the role of adiponectin in human ovarian steroidogenesis is limited. The present study aimed to investigate the effect of different doses of adiponectin on the secretion of estradiol and progesterone by human luteinized granulosa cells in culture. Granulosa cells, obtained from women undergoing in vitro fertilization (IVF) treatment, were pre-incubated for 24 h and then cultured for 48 h. Adiponectin was used in 3 doses, i.e., 5, 10, and 100 μg/ml alone and in combinations with FSH (10 and 100 ng/ml). Estradiol and progesterone were measured by radioimmunoassays in culture supernatants at 24 h and 48 h. Adiponectin after 48 h of culture stimulated the secretion of estradiol and, to a lesser extent, progesterone in a dose-dependent manner. FSH showed a variable effect on steroidogenesis. However, when the low dose FSH was combined with adiponectin, estradiol, and progesterone secretion were increased disproportionally to the dose of adiponectin. With the high dose FSH, the positive effect of adiponectin on FSH-induced estradiol secretion was less pronounced, while the effect on progesterone secretion was negligible. This study shows for the first time a stimulatory effect of adiponectin on the secretion of estradiol and progesterone by human luteinized granulosa cells in vitro. It is suggested that adiponectin plays a paracrine role in human ovarian steroidogenesis by sensitizing the granulosa cells to FSH.
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To investigate the differential localization of somatotropin release-inhibitory factor (SRIF) receptor subtypes (sst2A and sst2B) and their possible colocalization with reduced nicotinamide adenine dinucleotide phosphate... more
To investigate the differential localization of somatotropin release-inhibitory factor (SRIF) receptor subtypes (sst2A and sst2B) and their possible colocalization with reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase in the rat and rabbit retina. Polyclonal antibodies raised against sst2A and sst2B receptors were applied to 10- to 14-microm cryostat sections of rat and rabbit retinas fixed in paraformaldehyde. NADPH-diaphorase reactivity was assessed histochemically. Double labeling was performed for sst2A or sst2B receptors with NADPH-diaphorase, and with markers for the cell types present in the retina (protein kinase C [PKC], tyrosine hydroxylase; [TH], calbindin, and recoverin). sst2A immunoreactivity was detected in rod bipolar cells and colocalized with NADPH-diaphorase in the rabbit, but not the rat, retina. sst2B was present only in photoreceptor cells of the rat and colocalized with NADPH-diaphorase. These results suggest that SRIF, acting through sst...
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SummaryStudies on bovine oocytes have revealed that the activation of adenosine monophosphate activated protein kinase (AMPK) by millimolar concentrations of metformin controls nuclear maturation. Tuberous sclerosis complex 2 (TSC2) has... more
SummaryStudies on bovine oocytes have revealed that the activation of adenosine monophosphate activated protein kinase (AMPK) by millimolar concentrations of metformin controls nuclear maturation. Tuberous sclerosis complex 2 (TSC2) has been identified as a downstream target of AMPK. The objective of this study was to investigate the effects of addition of low concentrations of metformin (1 nM to 10 μM) on the percentage of cultured cumulus–oocyte complexes (COC) giving rise to cleavage-stage embryos and AMPK-mediated TSC2 activation. Metformin was supplemented either throughout in vitro embryo production (IVP) or only during in vitro fertilization (IVF). COC were matured in vitro, inseminated, and presumptive zygotes cultured for a further 72 h post insemination before the percentage of COC that gave rise to zygotes and early embryo development was assessed. The presence of TSC2 in bovine embryos and its possible AMPK-induced activation were assessed by immunocytochemistry. Metform...
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Despite the rapid development of new pharmacological and surgical modalities, the treatment of retinal disease all too often results in poor final visual acuity. The primary pathologic mechanism underlying suboptimal visual acuity... more
Despite the rapid development of new pharmacological and surgical modalities, the treatment of retinal disease all too often results in poor final visual acuity. The primary pathologic mechanism underlying suboptimal visual acuity following retinal disease is cell death. It is induced by a variety of stimuli including ischemia, inflammation, and oxidative stress. New neuroprotective strategies have recently being examined for the prevention of retinal cell death, yet there is still a need for pharmacological agents that are efficacious and lack adverse effects. These could possibly be employed alone or in combination with disease-specific treatments. The neuropeptide somatostatin and its sst(2) receptor selective analogues have been shown to inhibit the ischemia-induced neovascularization in models of retinal ischemia, and to protect from ischemia-induced cell death. The aim of this review is threefold: a) to address the functional role of somatostatin and its receptors in retinal circuitry, b) to present recent evidence supporting the neuroprotective role of somatostatin in experimental models of retinal disease and c) to present the clinical studies that have been performed to date and support the use of somatostatin and its analogues as therapeutics in ophthalmology.
Research Interests: Medicine, Neuroprotection, Somatostatin, Therapeutics, Humans, and 15 moreAnimals, Cell Death, Retinal, CNV, Nitric Oxide Synthase, CME, Ocular Blood Flow, Retinal Diseases, Somatostatin Receptor, Neuropeptide, Adverse effect, Cystoid Macular Edema, Choroidal Neovascularization, Pharmacology and pharmaceutical sciences, and endothelial growth factor
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Research Interests: Endocrinology, Hippocampus, Brain, Internal Medicine, Caudate Nucleus, and 15 moreAnimals, Male, Frontal Cortex, Cyclic peptides, Article, Analysis of Variance, Group, Autoradiography, Immunoassay, Controlled Study, Citalopram, Animal Experiment, Control Group, desipramine, and Antidepressive agents
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The aim of this study was to examine the ability of somatostatin receptor (sst(1)) to regulate the release of somatostatin in rat retina. Immunohistochemistry studies were performed to locate the somatostatin neurons, and radioligand... more
The aim of this study was to examine the ability of somatostatin receptor (sst(1)) to regulate the release of somatostatin in rat retina. Immunohistochemistry studies were performed to locate the somatostatin neurons, and radioligand binding to ascertain the presence of sst(1). The neuronal release of somatostatin was examined ex vivo in rat retinal explants in the presence of KCl (50 and 100 mM), and absence of Ca(++) (EGTA; 10 mM). Somatostatin levels, quantified by radioimmunoassay, were increased in the presence of KCl (100 mM, 151%) and attenuated in the absence of Ca(++) (31%). CH275 (sst(1) agonist) reduced the somatostatin levels in a concentration-dependent manner (10(-5)-10(-7) M), and this effect was reversed by NVP-SRA 880 (sst(1) antagonist;10(-5) M). MK678 (sst(2) agonist; 10(-5) M) had no effect. These data suggest an autoreceptor role for sst(1) in retina.
Research Interests: Endocrinology, Psychology, Cognitive Science, Chemistry, Neuropharmacology, and 15 moreMedicine, Nucleus Accumbens, Internal Medicine, Female, Animals, Male, Microdialysis, Rats, Radioligand Assay, Basal ganglia, Pyridines, Neurosciences, Agonist, Pharmacology and pharmaceutical sciences, and In Vitro Techniques
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The role of somatostatin and its mechanism of action in the retina remains an important target for investigation. Biochemical and pharmacological studies were engaged to characterize the somatostatin receptors in the rabbit retina, and... more
The role of somatostatin and its mechanism of action in the retina remains an important target for investigation. Biochemical and pharmacological studies were engaged to characterize the somatostatin receptors in the rabbit retina, and their coupling to G‐proteins. The ability of selective ligands to inhibit [125I]Tyr11‐somatostatin‐14 binding to rabbit retinal membranes was examined. The sst2 analogues SMS201–995, MK678, and BIM23014, displayed IC50 values of 0.28 ± 0.12, 0.04 ± 0.01 and 1.57 ± 0.39 nm, respectively. The sst1 analogue CH275 moderately displaced the [125I]Tyr11‐somatostatin‐14 binding, while selective analogues for sst3, sst4 and sst5 had minimal effect. Immunoblotting and/or immunohistochemistry studies revealed the presence of the pertussis toxin sensitive Gi1/2, and Go proteins, as well as Gs. Somatostatin‐14 and MK678 stimulated GTPase activity in a concentration‐dependent manner with EC50 values of 42.8 ± 16.8 and 70.0 ± 16.5 nm, respectively, thus supporting t...
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Research Interests: Endocrinology, Biology, Immunohistochemistry, Medicine, Retinal Pigment Epithelium, and 15 moreCell Culture, Biological Sciences, Humans, Internal Medicine, Nitric oxide, Nitric Oxide Synthase, Radioligand Assay, Receptor, Radioimmunoassay, Cell Membrane, binding sites, reverse transcriptase polymerase chain reaction, Medical and Health Sciences, Cell culture techniques, and Nitric oxide synthase type II
Exposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c‐fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or... more
Exposure to an environment, previously conditioned to amphetamine (1 mg/kg, i.p.), induced locomotor activity and c‐fos expression (a marker for neuronal activation) in the mouse medial prefrontal cortex (mPFC) and amygdala; acute or repeated amphetamine (1 mg/kg, i.p.) administration induced c‐fos expression additionally in the nucleus accumbens. An α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)‐receptor antagonist, 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo(f)quinoxaline (NBQX), blocked expression of conditioned activity, and prevented the increase in c‐fos expression in mPFC, implicating mPFC AMPAergic transmission in the conditioned component of behavioural sensitization to amphetamine. NBQX failed to block the expression of amphetamine‐conditioned place preference, a measure of conditioned reward, or conditioned c‐fos expression in the amygdala, an area implicated in the expression of conditioned place preference. These findings indicate that the conditioned components ...
Research Interests: Neuroscience, Cognitive Science, Chemistry, Medicine, Nucleus Accumbens, and 15 moreMice, Animals, Male, Amphetamine, Amygdala, Neurons, European, Neurosciences, Choice Behavior, Dextroamphetamine, Medial Prefrontal Cortex, Gene Expression Regulation, Motor activity, Conditioned place preference, and NBQX
Background Chronic airway diseases, like asthma or COPD, are characterized by excessive acetylcholine release and airway remodeling. The aim of this study was to investigate the long-term effect of muscarinic agonists on the phenotype and... more
Background Chronic airway diseases, like asthma or COPD, are characterized by excessive acetylcholine release and airway remodeling. The aim of this study was to investigate the long-term effect of muscarinic agonists on the phenotype and proliferation of rabbit tracheal airway smooth muscle cells (ASMCs). Methods ASMCs were serum starved before treatment with muscarinic agonists. Cell phenotype was studied by optical microscopy and indirect immunofluorescence, using smooth muscle α-actin, desmin and SM-Myosin Heavy Chain (SM-MHC) antibodies. [N-methyl-3H]scopolamine binding studies were performed in order to assess M3 muscarinic receptor expression on isolated cell membranes. Contractility studies were performed on isolated ASMCs treated with muscarinic agonists. Proliferation was estimated using methyl-[3H]thymidine incorporation, MTT or cell counting methods. Involvement of PI3K and MAPK signalling pathways was studied by cell incubation with the pathway inhibitors LY294002 and P...
Research Interests: Bioinformatics, Endocrinology, Plasticity, Life Sciences, Medicine, and 15 moreInternal Medicine, Biomedical Research, Animals, Proliferation, Acetylcholine, Mechanisms, Phenotype, Kinase, Activation, Cell Proliferation, Rabbits, Contractile Proteins, Cardiovascular medicine and haematology, Muscarinic Agonist, and Muscarinic Antagonist
Research Interests: Neuroscience, Behavioral Sciences, Long Term Potentiation, Biology, Medicine, and 15 moreMemory, Hippocampus, Animals, Object Recognition, Male, ERK, Neurons, Neuronal Differentiation, MAPK, Exploratory Behavior, Alzheimers Disease, Neurosciences, Neurite Outgrowth, Medical and Health Sciences, and In Vitro Techniques
Research Interests: Molecular Biology, Biology, Medicine, Cell Culture, Biological Sciences, and 15 moreGreece, Herpes Simplex, Cell line, Humans, Kidney, Animals, Incidence, Antibody, Immunoassay, Enzyme Linked Immunosorbent Assay, General Population, Enzyme Immunoassay, Cricetinae, Medical and Health Sciences, and Blood Donor
Background—Standard treatment of inoperable hepatocellular carcinoma has not been established. Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours.Aims—To assess the presence of... more
Background—Standard treatment of inoperable hepatocellular carcinoma has not been established. Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours.Aims—To assess the presence of somatostatin receptors in human liver and to treat advanced hepatocellular carcinoma with the somatostatin analogue, octreotide.Methods—Somatostatin receptors were measured in liver tissue homogenates from patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Fifty eight patients with advanced hepatocellular carcinoma were randomised to receive either subcutaneous octreotide 250 μg twice daily, or no treatment. Groups were comparable with respect to age, sex, Okuda classification, presence of cirrhosis, and liver biochemistry and virology.Results—Various amounts of somatostatin receptors were identified in liver tissue of all patients including those with hepatocellular carcinoma. Treated patients had an increased median surviva...