Symptoms In Healthy Individuals Research Articles

Phenylthiocarbamide taste sensitivity is associated with sinonasal symptoms in healthy adults.

The bitter taste receptor T2R38, expressed in the tongue and nasal epithelium, has been shown to trigger sinonasal innate immunity contributing to the prevention of gram-negative upper airway bacterial infections. Common polymorphisms of the T2R38 gene, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been linked to differences in sinonasal innate immune response, with specific genotypes significantly more common in medically recalcitrant chronic rhinosinusitis patients. The purpose of this study was to examine this association between T2R38 function and sinonasal infection or symptoms in a healthy population. A survey of the frequency of sinus infections, as well as other nasal symptoms such as colds, allergies, and overall nasal quality of life (nQOL), was administered to healthy adult participants. nQOL was measured using a 0 to 3 scale of worsening symptoms. A PTC compound taste strip was administered with T2R38 taste sensitivity classified as extremely, somewhat, or not sensitive. Among 217 participants (55% female, 70% Caucasian, 42% age 21 to 25 years), 30% did not detect bitterness (nontasters), 34% were moderate tasters, and 36% were "supertasters," experiencing a strong, unpalatable bitterness. Supertasters were associated with less frequent sinus infections (p = 0.04), and PTC sensitivity was predictive of nasal symptoms: Supertasters had the best nQOL scores, followed by moderate tasters and nontasters (means: 0.65, 0.81, 1.00, respectively; p = 0.014 for trend). There were no significant associations with other variables. This study provides evidence that T2R38 functionality in the tongue correlates with nasal symptoms in healthy individuals.

The intentionality bias and schizotypy

The "intentionality bias" refers to our automatic tendency to judge other people's actions to be intentional. In this experiment we extended research on this effect in two key ways. First, we developed a novel nonlinguistic task for assessing the intentionality bias. This task used video stimuli of ambiguous movements. Second, we investigated the relationship between the strength of this bias and schizotypy (schizophrenia-like symptoms in healthy individuals). Our results showed that the intentionality bias was replicated for the video stimuli and also that this bias is stronger in those individuals scoring higher on the schizotypy rating scales. Overall these findings lend further support for the existence of the intentionality bias. We also discuss the possible relevance of these findings for our understanding of certain symptoms of schizophrenic illness.

The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies.

A number of studies have indicated that antagonists of the N-methyl-d-aspartate subtypes of glutamate receptors can cause schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in individuals with schizophrenia. These findings have led to the glutamate hypothesis of schizophrenia. Here we review the evidence for this hypothesis in postmortem studies of brain tissue from individuals affected by schizophrenia, summarizing studies of glutamate neuron morphology, of expression of glutamate receptors and transporters, and of the synthesizing and metabolizing enzymes for glutamate and its co-agonists. We found consistent evidence of morphological alterations of dendrites of glutamatergic neurons in the cerebral cortex of subjects with schizophrenia and of reduced levels of the axon bouton marker synaptophysin. There were no consistent alterations of mRNA expression of glutamate receptors, although there has been limited study of the corresponding proteins. Studies of the glutamate metabolic pathway have been limited, although there is some evidence that excitatory amino acid transporter-2, glutamine synthetase, and glutaminase have altered expression in schizophrenia. Future studies would benefit from additional direct examination of glutamatergic proteins. Further advances, such as selective testing of synaptic microdomains, cortical layers, and neuronal subtypes, may also be required to elucidate the nature of glutamate signaling impairments in schizophrenia.

Does a standardised exercise protocol incorporating a cognitive task provoke postconcussion-like symptoms in healthy individuals?

To explore whether an exercise protocol, alone and in combination with two selected cognitive tasks related to working memory, provokes postconcussion-like symptoms in healthy individuals. Prospective single cohort semi-randomised crossover repeated measures (time×condition) design. 36 healthy individuals completed three submaximal exercise protocol conditions, namely: exercise alone, exercise with the paced auditory serial addition task, and exercise with Tetris. Self-reported symptoms were measured before exercise and 1-min and 15-min after the cessation of each exercise protocol using the Sports Concussion Assessment Tool 2-Postconcussion symptoms scale. Analysis of variance indicated a significant increase in symptom scores over time (p<0.001), but no effect between conditions (p=0.371) or a significant time×condition interaction (p=0.444). The combination of working memory tasks and a symptom provoking submaximal exercise protocol did not have an additional effect on the provocation of self-reported symptoms in healthy individuals. Furthermore, the two distinct methods of cognitive load delivery, controlled (paced auditory serial addition task) and pragmatic (Tetris), did not lead to a differential symptom response. These findings provide an initial insight into the scientific foundations for the symptom provocation model that is integral to the currently accepted clinical postconcussion return-to-play protocol.

Effects of acute phencyclidine administration on arginine metabolism in the hippocampus and prefrontal cortex in rats

Phencyclidine (PCP), a non-competitive N-methyl-d-aspartate glutamate receptor antagonist, induces schizophrenic symptoms in healthy individuals, and altered arginine metabolism has been implicated in schizophrenia. The present study investigated the effects of a single subcutaneous injection of PCP (2, 5 or 10 mg/kg) on arginine metabolism in the sub-regions of the hippocampus and prefrontal cortex in male young adult Sprague-Dawley rats. Animals' general behaviour was assessed in the open field apparatus 30 min after the treatment, and the brain tissues were collected at the time point of 60 min post-treatment. Behaviourally, PCP resulted in reduced exploratory activity in a dose-dependent manner, and severe stereotype behaviour and ataxia at the highest dose. Neurochemically, PCP significantly altered the nitric oxide synthase and arginase activities, the l-arginine, agmatine, spermine, glutamate and GABA levels, and the glutamine/glutamate and glutamate/GABA ratios in a dose-dependent and/or region-specific manner. Cluster analyses showed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which changed as a function of PCP mainly in the hippocampus. Multiple regression analysis revealed significant neurochemical-behavioural correlations. These results demonstrate, for the first time, that a single acute administration of PCP affects animals' behaviour and arginine metabolism in the brain.

A Homeopathic Perspective on Obstetrics and Gynecology Research

Objectives: Homeopathy is an alternative medicine which reacts based on the principal as ‘likes cures likes’. Small amount and much diluted medicine of original substance that produces signs and symptoms in healthy individuals can treat disease with similar signs and symptoms. Many studies have confirmed the positive effects of homeopathic medicines. Homeopathy is a perfect complement to the science of midwifery. Many women’s health problems are easily treated with homeopathic medicines. The objective of current study is to visualize and analyze the scientific activities by leading countries in the field of Homeopathy and Midwifery. Materials and Methods: All papers entitled Homeopathy in the database of Web of Science were extracted and went under contain analysis. Databases of Science Citation Index Expanded SCI-E) and Social Science Citation Index SSCI) from Web of Science were used to obtain all row data. Results: Retrieving of data led a total number of 1830 papers entitled homeopathy. The contain analysis of extracted papers showed that only 2% of them was in the subject area of Obstetrics & Gynecology. England was the leading country regarding to producing and publishing papers in the field of homeopathy followed by USA and Germany respectively. Conclusion: Regarding to the effective role of homeopathy on Obstetrics & Gynecology, the portion of performed research activities in the subject area of homeopathy seems to be very redundant and small.

The Pharmacokinetic Evaluation Of Oral Administered Carbon Monoxide Instilled In a Liquid Formulation (CO-LF) To Rats To Determine Carbon Monoxide Hemoglobin Levels With Potential Efficacy In Patients With Sickle Cell Disease (SCD)

There is a large published literature presenting information regarding the toxicology of CO in humans. There is information showing that CO-Hb levels below 15% are not associated with clinical adverse signs or symptoms in healthy individuals and smokers have CO-Hb levels around 6%, but may be above 10% on occasion.It has also been found that CO at low levels may have positive effects in SCD. It has been reported that non-toxic levels of CO extend the red cell life span in SCD patients (Beutler E, 1975.). Further, CO might play a role in preventing sickle cell formation by preventing the polymerization of hemoglobin (Sirs JA, 1963), and it has been reported that CO might have a preventative effect on the occurrence of clinical symptoms of SCD (Yallop D et al, 2007). Inhaled CO administered in low concentrations to transgenic sickle mice for one hour per day, 3 days per week for 10 weeks, was non-toxic and substantially decreased white cell counts and cellular inflammatory signals (Beckman J et al, 2009).This research program hypothesizes that CO, when administered orally at non-toxic levels, results in CO-Hb levels that will result in benefit to patients with SCD through two mechanisms: reducing the sickling phenomenon of red cells and by reducing the inflammatory response in these patients. It also hypothesizes that the safest and most efficient mode of administration of CO is by the oral route via a solution with a known dose of CO. MethodsThe carbon monoxide (CO) is obtained from a commercial source. The liquid formulation (LF) is composed of a mixture of the following components: water, proteins, lipids and carbohydrates ( PLC Mixture). The CO is instilled into this LF and tested for CO concentration. The principle of the method used for CO measurement is to allow the CO and added Hb to interact and to measure the CO-Hb formed by using the dithionite reduction method employing a spectrophotometer. (A.H. Chalmers 1991).The container is weighed before and after CO instillation to determine the occurrence of CO gas leakage.The container for the CO-LF is of low gas permeability. Once CO instillation in the LF is complete, the containers of CO-LF are sealed and labeled. The prepared containers are stored at 2-8°C for no longer than 72 hours.The CO content in blood is expressed as ‘%' of total hemoglobin (CO-Hb) and mg/L in the CO-LF.CO-LF was administered via esophageal-placed gavage using Sprague-Dawley rats with jugular venous catheters. ResultsIn the first study, there were 5 groups of 4 non-anemic rats studied, with each group comprising of a different LF made with the following percent of PLC Mixture combined with water: 50% PLC Mixture, 20% PLC Mixture, 10% PLC Mixture, 5% PLC Mixture, and 0% PLC Mixture (water only).Two 3 mL doses of CO-LF were administered to each rat one hour apart. Data generated showed levels of CO-Hb at baseline varying between 0 and 1.1 %. After the administration of the test article, the highest CO-Hb levels were 6.1% in one animal at 1 hour after the first dose, and 9.6% one hour after the second dose in one animal.The levels of CO-Hb fell at different rates depending upon the dose and formulation. The PK data for the first study is shown in Table 1. Differences among the test articles were not statistically different.Table 1PK Data for the CO-LF Non-Anemic Rat Studies.ExperimentTerminal half-life (hours)AUC 0-inf (h-%)0% (water only)0.510.0855% PLC Mixture0.650.07610% PLC Mixture0.810.0720% PLC Mixture0.50.0950% PLC Mixture0.640.11The PK parameters evaluated over 24 hours were not impacted by the administered PLC Mixture, but animals receiving CO-50% PLC Mixture showed an initial fall to baseline levels, then a second rise in CO-Hb levels peaking in one animal at 3.1% at 48 hours. Such late increments were not seen with other CO-LF's.The second PK study was comprised of 2 groups of 4 anemic rates, and employed CO-0% and CO-10% PLC Mixture. This study was carried out on rats made anemic by blood draw to an estimated 50% blood volume. The PK characteristics show data similar to that seen in non-anemic rats. ConclusionThis research has documented the feasibility in a proof-of-concept rat model that orally administered CO via a CO liquid formulation can produce CO-Hb levels that would be expected to impact the pathophysiology of the Sickle Cell Disease-associated micro-vasculature. The terminal half-life of orally administered CO in the rat is similar to that reported via inhaled CO. Disclosures:Gomperts:Hillhurst Biopharmaceuticals Inc: Equity Ownership, Patents & Royalties. Forman:Hillhurst Biopharmaceuticals Inc: Equity Ownership, Patents & Royalties.

Ketamine increases striatal dopamine release and hyperlocomotion in adult rats after postnatal functional blockade of the prefrontal cortex

Schizophrenia is a complex psychiatric disorder that may result from defective connectivity, of neurodevelopmental origin, between several integrative brain regions. Different anomalies consistent with brain development failures have been observed in patients’ left prefrontal cortex (PFC). A striatal dopaminergic functional disturbance is also commonly acknowledged in schizophrenia and could be related to a dysfunctioning of dopamine–glutamate interactions. Non-competitive NMDA antagonists, such as ketamine, can induce psychotic symptoms in healthy individuals and worsen these symptoms in patients with schizophrenia. Our study set out to investigate the consequences of neonatal functional blockade of the PFC for dopaminergic and behavioral reactivity to ketamine in adult rats. Following tetrodotoxin (TTX) inactivation of the left PFC at postnatal day 8, dopaminergic responses induced by ketamine (5mg/kg, 10mg/kg, 20mg/kg sc) were monitored using in vivo voltammetry in the left part of the dorsal striatum in freely moving adult rats. Dopaminergic responses and locomotor activity were followed in parallel. Compared to PBS animals, in rats microinjected with TTX, ketamine challenge induced a greater release of dopamine in the dorsal striatum for the highest dose (20mg/kg sc) and the intermediate dose (10mg/kg sc). A higher increase in locomotor activity in TTX animals was observed only for the highest dose of ketamine (20mg/kg sc). These data suggest transient inactivation of the PFC during early development results in greater behavioral and striatal dopaminergic reactivity to ketamine in adulthood. Our study provides an anatomo-functional framework that may contribute toward a better understanding of the involvement of NMDA glutamatergic receptors in schizophrenia.

Systemic inflammation, depression and obstructive pulmonary function: a population-based study

BackgroundLevels of Interleukin-6 (IL-6) and C-creative protein (CRP) indicating systemic inflammation are known to be elevated in chronic diseases including chronic obstructive pulmonary disease (COPD) and depression. Comorbid depression is common in patients with COPD, but no studies have investigated whether proinflammatory cytokines mediate the association between pulmonary function and depressive symptoms in healthy individuals with no known history of obstructive pulmonary diseases.MethodsIn a population-based sample (n = 2077) of individuals aged 55 and above with no known history of obstructive pulmonary disease in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the relationships between IL-6 and CRP, depressive symptoms (GDS-15 ≥5) and obstructive pulmonary function (FEV1% predicted and FEV1/FVC% predicted).ResultsHigh serum levels of IL-6 and CRP were associated with greater prevalence of depressive symptoms (p < 0.05). High IL-6, high CRP and depressive symptoms were independently associated with decreased FEV1% predicted and FEV1/FVC% predicted after adjusting for smoking status, BMI and number of chronic inflammatory diseases. Increasing grades of combination of inflammatory markers and/or depressive symptoms was associated with progressive increases in pulmonary obstruction. In hierarchical models, the significant association of depressive symptoms with pulmonary obstruction was reduced by the presence of IL-6 and CRP.ConclusionsThis study found for the first time an association of depressive symptoms and pulmonary function in older adults which appeared to be partly mediated by proinflammatory cytokines. Further studies should be conducted to investigate proinflammatory immune markers and depressive symptoms as potential phenotypic indicators for chronic obstructive airway disorders in older adults.

‘New Homeopathic Medicines’ database: A project to employ conventional drugs according to the homeopathic method of treatment

IntroductionSamuel Hahnemann systematized the homeopathy and the effects of the drugs on the state of human health describing a primary action of the drug followed by a secondary and opposite action of the organism. Seeking to employ such secondary action or vital reaction of the organism as a therapeutic method, he formulated the principle of similitude, namely the administration to sick individuals of the drugs that cause similar symptoms in healthy individuals. In modern pharmacology, this secondary action is known as rebound effect or paradoxical reaction of the organism. Besides causing severe and fatal iatrogenic events when appearing after the discontinuation of palliative modern drugs, the rebound effect might waken a healing reaction if the very same drugs involved are employed according to the principle of similitude. MethodologyUsing as database The United States Pharmacopeia Dispensing Information (USP DI) a homeopathic materia medica and repertory with 1251 modern drugs was compiled. A third volume presents the scientific basis of the principle of similitude in accordance with the study of the rebound effect. ResultsThe complete database composed of three eBooks can be freely accessed at http://www.newhomeopathicmedicines.com, allowing anyone to put this proposal into practice immediately. ConclusionIn this way, the therapeutic scope of homeopathy could be broadened through the addition of hundreds of new medicines that could be employed for various diseases and various modern clinical syndromes. Further validation could be achieved by multidisciplinary collaboration.

Injured brain regions associated with anxiety in Vietnam veterans

Anxiety negatively affects quality of life and psychosocial functioning. Previous research has shown that anxiety symptoms in healthy individuals are associated with variations in the volume of brain regions, such as the amygdala, hippocampus, and the bed nucleus of the stria terminalis. Brain lesion data also suggests the hemisphere damaged may affect levels of anxiety. We studied a sample of 182 male Vietnam War veterans with penetrating brain injuries, using a semi-automated voxel-based lesion-symptom mapping (VLSM) approach. VLSM reveals significant associations between a symptom such as anxiety and the location of brain lesions, and does not require a broad, subjective assignment of patients into categories based on lesion location. We found that lesioned brain regions in cortical and limbic areas of the left hemisphere, including middle, inferior and superior temporal lobe, hippocampus, and fusiform regions, along with smaller areas in the inferior occipital lobe, parahippocampus, amygdala, and insula, were associated with increased anxiety symptoms as measured by the Neurobehavioral Rating Scale (NRS). These results were corroborated by similar findings using Neuropsychiatric Inventory (NPI) anxiety scores, which supports these regions' role in regulating anxiety.In summary, using a semi-automated analysis tool, we detected an effect of focal brain damage on the presentation of anxiety. We also separated the effects of brain injury and war experience by including a control group of combat veterans without brain injury. We compared this control group against veterans with brain lesions in areas associated with anxiety, and against veterans with lesions only in other brain areas.

Effects of Resistant Potato Starches on Gastrointestinal Symptoms and Function

The gastrointestinal functions of fiber include stool bulking, increased stool frequency and decreased gastrointestinal transit time. The purpose of this study is to determine the effects of two resistant potato starches (RS4) on bowel movement frequency and gastrointestinal symptoms in healthy individuals. Biscotti and Koolaid , fortified at 30 g/d of fiber from RS4a or RS4b, and control foods, were incorporated into the diets of healthy individuals (n 22) for 15-day periods in a three-phase, randomized, crossover design with 7-day washouts. Participants completed a daily diary of bowel movement frequency andgastrointestinal symptom intensity,with “0” being free of symptoms, “1” mild symptoms and “10” severe symptoms, throughout each treatment period. Daily bowel movement frequency showed a trend to increase from the control period 0.89 0.50 to 1.01 0.58 (p 0.06) for RS4a, and 1.01 0.53 (p 0.11) for RS4b. Mean participant symptom score showed no significant differences in bloating between treatments (Control: 0.47 0.81; RS4a: 0.64 1.26; RS4b: 0.69 0.99). A increase in flatulence was found for both RS4a (1.95 1.69; p 0.05) and RS4b (1.96 1.08; p 0.05) compared to the control (1.25 1.01) with no difference between RS treatments. Cramping was an uncommon symptom (Control: 0.33 0.61; RS4: 0.45 1.14; RS2: 0.36 0.63), aswas intestinal noise (Control: 0.24 0.35; RS1: 0.37 0.87; RS2: 0.22 0.33) with no significant differences between treatments. The intake of resistant potato starch at 30 g per day is well tolerated with only mild flatulence reported as a symptom.

15:00 SHINING LIGHT ON SLEEP-WAKE AND CORTICAL GAMMA OSCILLATIONS IN SCHIZOPHRENIA: THE ROLE OF PARVALBUMIN GABA NEURONS

Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and exacerbates pre-existing symptoms in patients with schizophrenia. PCP also induces behavioral and cognitive abnormalities in non-human animals, and PCP-treated animals are considered a reliable pharmacological model of schizophrenia. However, the exact neural mechanisms by which PCP modulates behavior are not known. During the last decade several studies have indicated that disturbed activity of the prefrontal cortex (PFC) may be closely related to PCP-induced psychosis. Systemic administration of PCP produces long-lasting activation of medial PFC (mPFC) neurons in rats, almost in parallel with augmentation of locomotor activity and behavioral stereotypies. Later studies have showed that such PCP-induced behavioral abnormalities are ameliorated by prior administration of drugs that normalize or inhibit excess excitability of PFC neurons. Similar activation of mPFC neurons is not induced by systemic injection of a typical psychostimulant such as methamphetamine, even though behavioral hyperactivity is induced to almost the same level. This suggests that the neural circuits mediating PCP-induced psychosis are different to those mediating methamphetamine-induced psychosis. Locally applied PCP does not induce excitation of mPFC neurons, indicating that PCP-induced tonic excitation of mPFC neurons is mediated by inputs from regions outside the mPFC. This hypothesis is strongly supported by experimental results showing that local perfusion of PCP in the ventral hippocampus, which has dense fiber projections to the mPFC, induces tonic activation of mPFC neurons with accompanying augmentation of behavioral abnormalities. In this review we summarize current knowledge on the neural mechanisms underlying PCP-induced psychosis and highlight a possible involvement of the PFC and the hippocampus in PCP-induced psychosis.

Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia

Non-competitive antagonists of the N-methyl- d-aspartate receptor (NMDA) such as phencyclidine (PCP) elicit schizophrenia-like symptoms in healthy individuals. Similarly, PCP dosing in rats produces typical behavioral phenotypes that mimic human schizophrenia symptoms. Although schizophrenic behavioral phenotypes of the PCP model have been extensively studied, the underlying alterations of intrinsic neuronal properties and synaptic transmission in relevant limbic brain microcircuits remain elusive. Acute brain slice electrophysiology and immunostaining of inhibitory neurons were used to identify neuronal circuit alterations of the amygdala and hippocampus associated with changes in extinction of fear learning in rats following PCP treatment. Subchronic PCP application led to impaired long-term potentiation (LTP) and marked increases in the ratio of NMDA to 2-amino-3(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor-mediated currents at lateral amygdala (LA) principal neurons without alterations in parvalbumin (PV) as well as non-PV, glutamic acid decarboxylase 67 (GAD 67) immunopositive neurons. In addition, LTP was impaired at the Schaffer collateral to CA1 hippocampal pathway coincident with a reduction in colocalized PV and GAD67 immunopositive neurons in the CA3 hippocampal area. These effects occurred without changes in spontaneous events or intrinsic membrane properties of principal cells in the LA. The impairment of LTP at both amygdalar and hippocampal microcircuits, which play a key role in processing relevant survival information such as fear and extinction memory concurred with a disruption of extinction learning of fear conditioned responses. Our results show that subchronic PCP administration in rats impairs synaptic functioning in the amygdala and hippocampus as well as processing of fear-related memories.

Impact of sex, age, race, ethnicity and aspirin use on bleeding symptoms in healthy adults

Comparing a patient's bleeding symptoms with those of healthy individuals is an important component of the diagnosis of bleeding disorders, but little is known about whether bleeding symptoms in healthy individuals vary by sex, race, ethnicity, age, or aspirin use. OBJECTIVES, PATIENTS/METHODS: We developed a comprehensive, ontology-backed, Web-based questionnaire to collect bleeding histories from 500 healthy adults. The mean age was 43 years (range 19-86 years), 63% were female, 19% were Hispanic, 37% were African-American, 43% were Caucasian, 8% were Asian, and 4% were multiracial. 18 of the 36 symptoms captured occurred with < 5% frequency, and 26% of participants reported no bleeding symptoms (range 0-19 symptoms). Differences in sex, race, ethnicity, aspirin use and age accounted for only 6-13% of the variability in symptoms. Although men reported fewer symptoms than women (median 1 vs. 2, P < 0.01), there was no difference when sex-specific questions were excluded (median 1 for both men and women, P = 0.50). However, women reported more easy bruising (24% vs. 7%, P < 0.01) and venipuncture-related bruising (10% vs. 3%, P = 0.02). The number of symptoms did not vary by race or age, but epistaxis was reported more frequently by Caucasians than by African-Americans (29% vs. 18%, P = 0.02), and epistaxis frequency decreased with age (odds ratio 0.97 per year, P < 0.01). Paradoxically, infrequent aspirin users reported more bruising and heavy menses than frequent users (21% vs. 8%, P = 0.01, and 56% vs. 38%, P = 0.03, respectively). Our findings provide a contemporaneous and comprehensive description of bleeding symptoms in a diverse group of healthy individuals. Our Web-based system is freely available to other investigators.

Duodenal chemosensing: Master control for epigastric sensation?

2005; 438: 932–6. 3 Fidler IJ, Ellis LM. Neoplastic angiogenesis: not all blood vessels are created equal. N. Engl. J. Med. 2004; 351: 215–6. 4 Yoshiji H, Yoshii J, Ikenaka Y et al. Suppression of the renin-angiotensin system attenuates vascular endothelial growth factor-mediated tumor development and angiogenesis in murine hepatocellular carcinoma cells. Int. J. Oncol. 2002; 20: 1227–31. 5 Mas VR, Maluf DG, Archer KJ, Yanek KC, Fisher RA. Angiogenesis soluble factors as hepatocellular carcinoma noninvasive markers for monitoring hepatitis C virus cirrhotic patients awaiting liver transplantation. Transplantation. 2007; 84: 1262–71. 6 Uematsu S, Higashi T, Nouso K et al. Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma. J. Gastroenterol. Hepatol. 2005; 20: 583–8. 7 Desnoyers LR, Pai R, Ferrando RE et al. Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models. Oncogene. 2008; 27: 85–97. 8 Yoshiji H, Kuriyama S, Yoshii J et al. Synergistic effect of basic fibroblast growth factor and vascular endothelial growth factor in murine hepatocellular carcinoma. Hepatology. 2002; 35: 834–42. 9 Dempke WC, Heinemann V. Resistance to EGF-R (erbB-1) and VEGF-R modulating agents. Eur. J. Cancer. 2009; 45: 1117–28. 10 Poon RT, Ng IO, Lau C et al. Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma. Am. J. Surg. 2001; 182: 298–304. 11 Paez-Ribes M, Allen E, Hudock J et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009; 15: 220–31. 12 Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008; 359: 378–90. 13 Jie SH, Li HY, Tian Y et al. Berberine inhibits angiogenic potential of Hep G2 cell line through VEGF down-regulation in vitro. J. Gastroenterol. Hepatol. 2011; 26: 179–85. 14 Jun T, Yibin F, Saiwah T et al. Berberine and coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J. Ethnopharmacol. 2009; 126: 5–17. 15 Kuo CL, Chi CW, Liu TY. The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett. 2004; 203: 127–37.

Gastric secretion

This review summarizes the past year's literature regarding the regulation of gastric exocrine and endocrine secretion at the central, peripheral, and cellular levels. Gastric acid secretion is an intricate and dynamic process that is regulated by neural (efferent and afferent), hormonal (e.g., gastrin), and paracrine (e.g., histamine, ghrelin, somatostatin) pathways as well as mechanical (e.g., distension) and chemical (e.g., protein, glutamate, coffee, and ethanol) stimuli. Secretion of hydrochloric acid by the parietal cell involves recruitment and fusion of HK-adenosine triphosphatase (HK-ATPase)-containing cytoplasmic tubulovesicles with the apical membrane with subsequent electroneutral transport of hydronium ions in exchange for potassium; the source of the latter is the potassium channel, KCNQ1. Concomitantly, chloride exits via the cystic fibrosis transmembrane regulator. Inhibition of the HK-ATPase by proton pump inhibitors leads to a compensatory hypergastrinemia which, if prolonged, results in parietal and enterochromaffin-like cell hyperplasia. The clinical consequence is rebound acid secretion which may induce dyspeptic symptoms in healthy individuals and exacerbate reflux symptoms in patients with gastroesophageal reflux disease. We continue to make progress in our understanding of the regulation of gastric acid secretion in health and disease. A better understanding of the pathways and mechanisms regulating acid secretion should lead to improved management of patients with acid-induced disorders as well as those who secrete too little acid.

Differences in responsiveness of mediodorsal thalamic and medial prefrontal cortical neurons to social interaction and systemically administered phencyclidine in rats

Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and behavioral abnormalities with corresponding symptoms of schizophrenia in non-human animals. Our previous studies showed that systemically administered PCP produces tonic activation of neurons in the medial prefrontal cortex (mPFC) of rats and that this activation is mainly via excitatory inputs from regions outside the mPFC. Such long-lasting activation of PFC neurons is now considered to be a pivotal factor in PCP-induced behavioral abnormalities. Although our previous study identified the ventral hippocampus as a possible source of the excitatory inputs, it is not the only source innervating the mPFC. Several regions such as the thalamus also have monosynaptic projections to the mPFC. Recently, increased c-fos expression by systemic PCP administration was reported in the mediodorsal nucleus of the thalamus (MD) and the centromedial nucleus of the thalamus (CM), which have strong reciprocal innervations with the mPFC. However, few studies have reported effects of PCP on the firing activity of MD/CM neurons in unanesthetized animals. In the current study in freely moving rats, we examined effects of systemically administered PCP on the spontaneous firing activity of the MD/CM, after identifying the response properties of recorded neurons in social interaction with an unfamiliar partner. About 30% of MD/CM neurons recorded exhibited tonic excitation following systemic PCP administration, whereas only a few neurons (7%) were inhibited by PCP. The proportion of MD neurons activated by systemic PCP administration was about half of that in the mPFC. Although the proportion of neurons responsive to social interaction did not differ between the two regions (40%), neurons activated during social interaction in the mPFC (90%) were more likely to be affected by systemic PCP administration than those in the MD/CM (45%). These results suggest that neurons responsive to social interaction in the mPFC may be differently affected by PCP than those in the MD/CM.

Effect of day-to-day variations in adrenal cortex hormone levels on abdominal symptoms

IntroductionThe hypothalamic-pituitary-adrenal axis is known to be related to abdominal symptoms, and the relationship between abdominal pain and cortisol secretory patterns has been previously investigated using a cross-sectional approach. Here, we investigated the effect of day-to-day variations in salivary cortisol and dehydroepiandrosterone-sulfate levels on abdominal symptoms in healthy individuals.MethodsEleven college students (4 males and 7 females) participated in this study. The participants were asked to collect their saliva immediately after awakening and before bedtime for eight consecutive days. They also completed a questionnaire about abdominal symptoms before bedtime. The linear mixed model was applied to analyze the effects of the day-by-day variability or the 8-day average adrenal hormone level (at awakening, before bedtime, slope from awakening to bedtime) on abdominal symptoms.ResultsThe day-to-day variability of cortisol levels before bedtime was negatively related with loose stool, while the day-to-day variability of the cortisol slope was positively correlated with loose stool. A low 8-day average dehydroepiandrosterone-sulfate level at awakening was positively related with frequent bowel movements, loose stool, and long bouts of severe abdominal pain. Likewise, a low 8-day average dehydroepiandrosterone-sulfate slope was positively related with long bouts of abdominal pain.ConclusionsLow cortisol levels before bedtime and a steeper diurnal cortisol slope during the day may be related to bouts of diarrhea during the day.

Validating Novel Targets for Pharmacological Interventions in Schizophrenia

Validating Novel Targets for Pharmacological Interventions in Schizophrenia