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Journal Article 2011; 32(5): 607-615 PubMed PMID: 22167139 Citation  Keywords:  Animals, Humans, Neurosecretory Systems:physiology, Receptors, G-Protein-Coupled:physiology, Signal Transduction:physiology,.   

: Within the last two decades of studies in the ever-expanding field of GPCR signaling, challenging insights were adopted. Growing evidence now asists the shift from classical linear model of signaling towards a considerably complex network of signaling pathways with many shared proteins and cross-talks. Considering the extensive and intriguing network of pathways activated by these receptors, it is apparent that multi-level system of regulation must exist to rigorously modulate the amplitude, duration and spatial aspects of the GPCR signaling. This review summarizes the principal mechanisms of GPCR regulation and gives the overview of recent advances in this field of research....

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Journal Article 2011; 32(4): 371-379 PubMed PMID: 21876496 Citation  Keywords:  Autonomic Nervous System:physiology, Blood Glucose:metabolism, Diabetes Mellitus:physiopathology, Homeostasis:physiology, Humans, Models, Biological, Neurosecretory Systems:physiology,.   

: The objective of this article is to review the mechanisms which the body uses to regulate its function. The author considers, in particular, the nature and structure of the physiological systems with a specific focus upon the systemic regulation of blood glucose and highlights an innovative technology, based upon the top-down cognitive approach, which incorporates a unique mathematical model of the physiological systems and autonomic nervous system. Most systems biology is a development of the prevailing reductionist biomedical paradigm. It adopts a bottom-up approach seeking systemic justification for biochemical and biophysical research findings. By contrast the 'top-down' approach considers the neural regulation of the physiological systems and the neurological, cognitive and biochemical consequences of systemic dysfunction i.e. the consequences of sensory input upon the neural regulation of the body's systems, organs, and its cellular and molecular biochemistry. In conclusion, the evidence suggests that the onset and progression of Diabetes Mellitus cannot be accurately assessed by individual biomedical indices but instead that the regulation of blood glucose is one of a number of inter-related physiological systems which act in a coordinated manner in order to maintain the body's physiological stability....

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Journal Article 2011; 32(4): 442-448 PubMed PMID: 21876493 Citation  Keywords:  Adolescent, Adult, Dehydroepiandrosterone Sulfate:blood, Female, Humans, Hydrocortisone:blood, MMPI, Male, Middle Aged, Personality:physiology, Pituitary-Adrenal System:physiology, Retrospective Studies, Stress, Psychological:physiopathology, Type A Perso.   

OBJECTIVES: Dehydroepiandrosterone-sulphate (DHEAS) physiologic relevance remains controversial. However, several central nervous system and behavioural effects of DHEAS have been described. We explored the relation between DHEAS and both pituitary-adrenal axis reactivity and personality in human subjects.

DESIGN: We studied 120 consecutive patients assisted at the out patient endocrine department of a public central hospital before medical treatment. Personality was evaluated with the Minnesota Multiphasic Personality Inventory (MMPI) and the pituitary-adrenal axis reactivity was assessed with the CRH test.

RESULTS: Baseline DHEAS was inversely related to peak/basal cortisol (parcial r=-0.454, p<0.05) response to CRH infusion. DHEAS reactivity in the CRH test was directly related to the Deviant Behaviour triad (BD) (r=0.257, p<0.05) and type A personality (AP) (r=0.295, p<0.05). Basal ACTH was directly related to baseline DHEAS (r=0.366, p<0.001) and together with age and gender explained 34% of DHEAS variability.

CONCLUSIONS: DHEAS may be a protective factor against an excessive cortisol response when people are under stress situations. Personality may be related to DHEAS reactivity....

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Case Reports 2011; 32(3): 238-241 PubMed PMID: 21712786 Citation  Keywords:  Atrophy, Brain:diagnostic imaging, Fatal Outcome, Female, Humans, Hydrocortisone:blood, Hypokalemia:etiology, Magnetic Resonance Imaging, Middle Aged, Pituitary ACTH Hypersecretion:pathology, Tomography, X-Ray Computed,.   

: We present a 56-year-old patient with cyclic Cushing's disease (CCD) observed for 28 months, who presented clinically and biochemically with alternating episodes of hyper-, normo- and hypocortisolemia. The course of the disease was fatal, the patient died due to severe hypokalemia....

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Journal Article 2011; 32(3): 313-316 PubMed PMID: 21712774 Citation  Keywords:  Amyloid Precursor Protein Secretases:biosynthesis, Amyloid beta-Peptides:biosynthesis, Amyloid beta-Protein Precursor:biosynthesis, Aspartic Acid Endopeptidases:biosynthesis, Cell Line, Cells, Cultured, DNA:biosynthesis, Humans, Luciferases:genetics, RNA,.   

OBJECTIVE: The effect of SUMO on the promoter activity and mRNA expression of BACE gene was investigated to find the connection between sumoylation and APP processing.

METHODS: The BACE promoter activity was measured by reporter gene analysis and BACE mRNA level was investigated using real-time RT-PCR method.

RESULTS: BACE gene promoter activity was inhibited by the over-expression of SUMO proteins and was blocked by disrupting the SP1 site. Endogenous BACE mRNA level was also negatively regulated by the induction of SUMO proteins. Using a specific inhitor of SP1, BACE promoter activity was coordinately inhibited.

CONCLUSIONS: SUMO negatively regulates the BACE expression and SP1 is involved in the process....

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Journal Article 2011; 32(3): 279-285 PubMed PMID: 21712772 Citation  Keywords:  Adult, Anxiety:psychology, Cognition:physiology, Data Interpretation, Statistical, Depression:psychology, Female, Humans, Hypothyroidism:blood, Male, Memory, Short-Term:drug effects, Neuropsychological Tests, Pilot Projects, Psychomotor Performance:physio.   

OBJECTIVE: The purpose of our pilot study was to explore the relationship between serum thyroid stimulating hormone (TSH) levels during overt hypothyroidism (OH) and hypothyroid-related neuropsychological symptoms. We hypothesized that TSH level may reflect the degree of 'brain hypothyroidism' such that an inverse correlation may exist between serum TSH and cognitive function in patients experiencing overt hypothyroidism (OH), and sought to explore this hypothesis.

METHODS: Eleven thyroidectomized patients underwent neuropsychological and thyroid function testing while overtly hypothyroid, and again following thyroid hormone replacement. Their test performance was compared with that of eleven healthy controls at a similarly separated two points in time, and the change over time for the patient group and the controls was likewise assessed and compared. The patients' neuropsychological test scores were then correlated with their serum TSH levels while hypothyroid.

RESULTS: The patients' performance while hypothyroid was worse than that of the controls in only one neurocognitive measure--Working Memory Index. The subjects improved similarly or to a greater degree than the controls, when the subjects were thyroid hormone replaced, on all but one neurocognitive measure - Thurstone Word Fluency. TSH level during hypothyroidism was inversely proportional to the patients' performance on these same two measures, but no others.

CONCLUSION: Serum TSH level during hypothyroidism was inversely proportional to performance on the only two neurocognitive measures evidencing an adverse effect from hypothyroidism in our cohort. This suggests that serum TSH level may reflect the severity of 'brain hypothyroidism' during the overt stage of this condition....

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Comparative Study 2011; 32(2): 164-169 PubMed PMID: 21552200 Citation  Keywords:  Acetaminophen:therapeutic use, Acetic Acid:adverse effects, Analgesics, Non-Narcotic:therapeutic use, Analgesics, Opioid:therapeutic use, Animals, Celecoxib, Codeine:therapeutic use, Cyclooxygenase 2 Inhibitors:therapeutic use, Data Interpretation, Statis.   

OBJECTIVES: There is good evidence that opioids can potentiate analgesic activity of some older non-opioid analgesics (such as paracetamol or ibuprofen) but it is not known whether this also holds true for newer non-opioid analgesics that selectively inhibit cyclooxygenase 2 (coxibs). This study was undertaken to determine the nature of the interaction between codeine and celecoxib or etoricoxib in peritoneal irritation-induced visceral pain in mice. For comparison, interactions of codeine with paracetamol and ibuprofen were also tested using the same method.

MATERIAL AND METHODS: A small volume of a weak acetic acid (0.6%) was injected into the peritoneal cavity and the number of writhes (contractions of abdominal muscles) was counted. All drugs were given orally. Their interaction was characterized using isobolographic analysis.

RESULTS: Codeine, etoricoxib, celecoxib, ibuprofen and paracetamol all independently produced dose-dependent suppression of writhing. The isobolographic analysis carried out using equipotent dose ratios showed that the interactions between codeine and etoricoxib or celecoxib were sub-additive or additive, respectively. This was in contrast to combinations of codeine with ibuprofen or paracetamol, which were supra-additive. Interaction indexes γ, determined as a ratio between experimental and theoretical ED50 values of the mixture, were as follows: 2.7 for codeine + etoricoxib, 0.62 for codeine + celecoxib, 0.43 for codeine + ibuprofen and 0.33 for codeine + paracetamol.

CONCLUSIONS: These and other results suggest that opioids do not seem to potentiate analgesic effects of selective COX-2 inhibitors, in contrast to nonselective COX inhibitors or paracetamol....

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Journal Article 2011; 32(2): 187-192 PubMed PMID: 21552198 Citation  Keywords:  Aging:metabolism, Animals, Animals, Newborn, Atrial Natriuretic Factor:metabolism, Cells, Cultured, Cochlea:cytology, Ear, Inner:physiology, Models, Animal, Rats, Rats, Sprague-Dawley, Receptors, Atrial Natriuretic Factor:metabolism, Stria Vascularis:cyto.   

OBJECTIVE: Atrial natriuretic peptide (ANP) regulates the homeostasis of body fluid and blood pressure as a neuropeptide in the central nervous system. To assess the possible physiological role in the inner ear, we investigated the expression of ANP in primary culture of marginal cells, and then we detected the expression of ANP and its receptor (NPR-A) in cochlear tissues derived from neonatal and adult rats of various ages.

METHODS: Marginal cells were isolated from cochlear stria vascularis of the neonatal rats. The cultured cells were subsequently characterized by morphology, immunocytochemistry, and scanning electron microscope (SEM) analysis. In order to examine the expression of ANP in marginal cells as well as in the developing rats' cochleae, immunocytochemistry and reverse-transcription polymerase chain reaction (RT-PCR) were applied respectively.

RESULTS: The present study demonstrated typical characteristics of marginal cells, including cobblestone, polygonal monolayer, pleomorphic growth pattern and the expression of cell type-specific marker, and SEM analysis. Subsequently, immunoreactive product of ANP were found in cultured marginal cells. The mRNAs encoding ANP and NPR-A receptor was expressed in rats' cochleae from postembryonic stage to early postnatal period. During the maturation stage, ANP expression was gradually down-regulated, while the expression of NPR-A receptor was relatively stable.

CONCLUSION: ANP might be synthesized and secreted by marginal cells of stria vascularis, and could play an important role in modulating the microenvironment of the inner ear. In addition, ANP might contribute to development and growth process of cochlea....

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