bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases food intake and body weight
Authors: Aja Susan , Landree Leslie E. , Kleman Amy M. , Medghalchi Susan M. , Vadlamudi Aravinda , McFadden Jill M. , Aplasca Andrea , Hyun Jayson , Plummer Erica , Daniels Khadija , Kemm Matthew , Townsend Craig A. , Thupari Jagan N. , Kuhajda Francis P. , Moran Timothy H. , Ronnett Gabriele V.
Published: December 2007

Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1–56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.
Impaired acid secretion in cortical collecting duct intercalated cells from H-K-ATPase-deficient mice: role of HKα isoforms
Authors: Lynch I. Jeanette , Rudin Alicia , Xia Shen-Ling , Stow Lisa R. , Shull Gary E. , Weiner I. David , Cain Brian D. , Wingo Charles S.
Published: December 2007

Two classes of H pumps, H-K-ATPase and H-ATPase, contribute to luminal acidification and HCO3transport in the collecting duct (CD). At least two H-K-ATPase α-subunits are expressed in the CD: HKα1and HKα2. Both exhibit K dependence but have different inhibitor sensitivities. The HKα1H-K-ATPase is Sch-28080 sensitive, whereas the pharmacological profile of the HKα2H-K-ATPase is not completely understood. The present study used a nonpharmacological, genetic approach to determine the contribution of HKα1and HKα2to cortical CD (CCD) intercalated cell (IC) proton transport in mice fed a normal diet. Intracellular pH (pHi) recovery was determined in ICs using in vitro microperfusion of CCD after an acute intracellular acid load in wild-type mice and mice of the same strain lacking expression of HKα1, HKα2, or both H-K-ATPases (HKα1,2). A-type and B-type ICs were differentiated by luminal loading with BCECF-AM and peritubular chloride removal from CO2/HCO3-buffered solutions to identify the membrane locations of Cl/HCO3exchange activity. H-ATPase- and Na/H exchange-mediated H transport were inhibited with bafilomycin A1(100 nM) and EIPA (10 μM), respectively. Here, we report 1) initial pHiand buffering capacity were not significantly altered in the ICs of HKα-deficient mice, 2) either HKα1or HKα2deficiency resulted in slower acid extrusion, and 3) A-type ICs from HKα1,2-deficient mice had significantly slower acid extrusion compared with A-type ICs from HKα1-deficient mice alone. These studies are the first nonpharmacological demonstration that both HKα1and HKα2contribute to H secretion in both A-type and B-type ICs in animals fed a normal diet.
Subthreshold K+ Channel Dynamics Interact With Stimulus Spectrum to Influence Temporal Coding in an Auditory Brain Stem Model
Authors: Day Mitchell L. , Doiron Brent , Rinzel John
Published: December 2007

Neurons in the auditory brain stem encode signals with exceptional temporal precision. A low-threshold potassium current, IKLT, present in many auditory brain stem structures and thought to enhance temporal encoding, facilitates spike selection of rapid input current transients through an associated dynamic gate. Whether the dynamic nature of IKLT interacts with the timescales in spectrally rich input to influence spike encoding remains unclear. We examine the general influence of IKLT on spike encoding of stochastic stimuli using a pattern classification analysis between spike responses from a ventral cochlear nucleus (VCN) model containing IKLT, and the same model with the IKLT dynamics removed. The influence of IKLT on spike encoding depended on the spectral content of the current stimulus such that maximal IKLT influence occurred for stimuli with power concentrated at frequencies low enough (<500 Hz) to allow IKLT activation. Further, broadband stimuli significantly decreased the influence of IKLT on spike encoding, suggesting that broadband stimuli are not well suited for investigating the influence of some dynamic membrane nonlinearities. Finally, pattern classification on spike responses was performed for physiologically realistic conductance stimuli created from various sounds filtered through an auditory nerve (AN) model. Regardless of the sound, the synaptic input arriving at VCN had similar low-pass power spectra, which led to a large influence of IKLT on spike encoding, suggesting that the subthreshold dynamics of IKLT plays a significant role in shaping the response of real auditory brain stem neurons.
Vestibular Nuclei and Cerebellum Put Visual Gravitational Motion in Context
Authors: Miller William L. , Maffei Vincenzo , Bosco Gianfranco , Iosa Marco , Zago Myrka , Macaluso Emiliano , Lacquaniti Francesco
Published: December 2007

Animal survival in the forest, and human success on the sports field, often depend on the ability to seize a target on the fly. All bodies fall at the same rate in the gravitational field, but the corresponding retinal motion varies with apparent viewing distance. How then does the brain predict time-to-collision under gravity? A perspective context from natural or pictorial settings might afford accurate predictions of gravity's effects via the recovery of an environmental reference from the scene structure. We report that embedding motion in a pictorial scene facilitates interception of gravitational acceleration over unnatural acceleration, whereas a blank scene eliminates such bias. Functional magnetic resonance imaging (fMRI) revealed blood-oxygen-level-dependent correlates of these visual context effects on gravitational motion processing in the vestibular nuclei and posterior cerebellar vermis. Our results suggest an early stage of integration of high-level visual analysis with gravity-related motion information, which may represent the substrate for perceptual constancy of ubiquitous gravitational motion.
DynamicI-VCurves Are Reliable Predictors of Naturalistic Pyramidal-Neuron Voltage Traces
Authors: Badel Laurent , Lefort Sandrine , Brette Romain , Petersen Carl C. H. , Gerstner Wulfram , Richardson Magnus J. E.
Published: December 2007

Neuronal response properties are typically probed by intracellular measurements of current-voltage ( I-V) relationships during application of current or voltage steps. Here we demonstrate the measurement of a novel I-V curve measured while the neuron exhibits a fluctuating voltage and emits spikes. This dynamic I-V curve requires only a few tens of seconds of experimental time and so lends itself readily to the rapid classification of cell type, quantification of heterogeneities in cell populations, and generation of reduced analytical models. We apply this technique to layer-5 pyramidal cells and show that their dynamic I-V curve comprises linear and exponential components, providing experimental evidence for a recently proposed theoretical model. The approach also allows us to determine the change of neuronal response properties after a spike, millisecond by millisecond, so that postspike refractoriness of pyramidal cells can be quantified. Observations of I-V curves during and in absence of refractoriness are cast into a model that is used to predict both the subthreshold response and spiking activity of the neuron to novel stimuli. The predictions of the resulting model are in excellent agreement with experimental data and close to the intrinsic neuronal reproducibility to repeated stimuli.
Pulmonary Ventilatory Functions and Obesity in Kuwait
Authors: Al-Bader Wafaa R. , Ramadan J. , Nasr-Eldin A. , Barac-Nieto M.
Published: December 2007

Objective: To study the relationship between obesity and pulmonary ventilatory functions in Kuwaiti adults. Subjects and Methods: A total of 200 male and 180 female Kuwaiti adults aged 20–65 years were investigated in six medical centers from April 2004 to March 2006. Parameters measured included forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1 as a percentage of FVC (FEV%); body mass index (BMI in kg/m2) and waist-to-hip ratio (W/H). Results: For the whole group, males or females, BMI (kg·m2) and W/H were poor individual predictors of pulmonary ventilatory functions. However, central adiposity (W/H) was associated with restrictive respiratory impairment (10.6–13.9% decrease in FEV1 and 10–12.3% decrease in FVC), independent of sex, age or height. In obese females and males (BMI >30), increasing severity of obesity was significantly associated (p < 0.05, R2 >0.06) associated with increasing restrictive respiratory impairment (8.7–14.4% decrease in FEV1 and 8–11.7% decrease in FVC), with no evidence of obstructive disease (FEV1/FVC >0.8). Conclusion: In adult Kuwaiti males and females, increase in body fat at BMI >30 or W/H >1 was associated with a restrictive effect on pulmonary ventilation.
Prevalence and Antimicrobial Susceptibility Pattern of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae in the United Arab Emirates
Authors: Al-Zarouni Mansour , Senok Abiola , Rashid Fatima , Al-Jesmi Shaikha Mohammed , Panigrahi Debadatta
Published: December 2007

Objective: To investigate the prevalence and antibiotic susceptibility pattern of extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaecae among patients in the United Arab Emirates. Materials and Methods: A total of 130 Enterobacteriaceaecomprising of Escherichia coli (n = 83), Klebsiella pneumoniae (n = 45) and Klebsiella oxytoca (n = 2) was studied. Of these 130 isolates, 64 were from urine. ESBL screening was by disc diffusion and confirmatory tests for ESBL phenotype were conducted using BD Phoenix™ ESBL System and cephalosporin/clavulanate combination discs. Susceptibility to a panel of antibiotics was evaluated. Results: Of the 130 isolates, 53 (41%) were identified as having ESBL phenotype; of these, 32 (60%) were E. coli, 20 (36%) K. pneumoniae and 2 (4%) K. oxytoca. ESBL phenotype was seen in 100% of endotracheal tubes isolates, 20 (31%) from urine, 7 (58%) from blood and 4 (80%) from catheter tips. Amikacin susceptibility was 100%. Over 90% of ESBL isolates showed resistance to aztreonam and cephalosporins. All Klebsiella isolates were carbapenem sensitive. One ESBL isolate showed intermediate resistance to imipenem and meropenem (both MIC 8 µg/ml), cefotetan (MIC 32 µg/ml) and piperacillin/tazobactam (MIC 32 µg/ml). MIC for the carbapenems was lower in non-ESBL isolates (0.034 µg/ml) than ESBL isolates (0.071 µg/ml). Resistance to gentamicin, ciprofloxacin and piperacillin/tazobactam was higher in ESBL than non-ESBL isolates (p < 0.05). Conclusion: A high prevalence of ESBL-producing bacteria exists among in-patients in the United Arab Emirates. Amikacin and carbapenems remain the most effective drugs, but the presence of carbapenem-resistant ESBL-producing E. coli and occurrence of multidrug resistance are of concern. Continued surveillance and judicious antibiotic usage are recommended.
Is Combined Pretransplantation Seropositivity of Kidney Transplant Recipients for Cytomegalovirus Antigens (pp150 and pp28) a Predictor for Protection against Infection?
Authors: Essa S. , Pacsa A. , Said T. , Nampoory M.R.N. , Raghupathy R. , Johny K.V. , Al-Nakib W. , Al-Mosawy M.
Published: December 2007

Objective: This study was aimed at detecting antibodies to the antigens which may contribute to protection against cytomegalovirus (CMV) infection after organ transplantation. Materials and Methods: A total of 203 kidney transplant patients were enrolled in the study. Based on CMV antigenemia assay, 23 patients were antigen-positive and of the remaining 180 antigen-negative patients, 46 were selected as controls matched for age, gender and source of kidney. The 69 kidney recipients (KR) had CMV antibody due to previous infection and were followed up for a period of 6 months after transplantation for the development of active CMV infections by the antigenemia assay. Antibody responses to five CMV-related peptide antigens (pp65, gB, pp150, pp28 and pp38) were investigated by enzyme immunoassay and their presence was correlated with the results of the CMV antigenemia assay. Results: Of the five CMV-related peptide antigens, only gB antigen showed response to the antibody in 10/23 (43.5%) antigen-positive patients and 9/46 antigen-negative patients and the difference was statistically significant (p = 0.048). On the other hand, there was no significant difference in antibody responses between the antigen-positive and antigen-negative KR to the other four CMV peptide antigens (p > 0.05). However, among the antigen-positive KR there was only 1 patient who had antibodies to both pp150 and pp28 antigen, while among the antigen-negative KR, 22 of 46 (47.8%) had the antibodies (p < 0.001). Conclusion: The findings suggest that the combined presence of antibodies against the pp150 and pp28 antigens may indicate a lower risk of CMV reactivation after kidney transplantation.
Pooled Analysis of 2,408 Cases of Acute Adult Purulent Meningitis from Turkey
Authors: Arda Bilgin , Sipahi Oguz Resat , Atalay Sabri , Ulusoy Sercan
Published: December 2007

Objectives: The aim of this study was to systematically review the Turkish literature of acute adult purulent meningitis. Materials and Methods: The published series of three national databases and two international databases were searched to perform the review. In addition to the databases, abstracts of congresses held between 1994 and 2003 by the Turkish Clinical Microbiology and Infectious Diseases Association, Turkish Microbiology Association, and the Antibiotic and Chemotherapy Association were searched for reports about acute purulent meningitis. Results: Data for 2,408 patients with a diagnosis of acute purulent meningitis were obtained from 30 reports. In terms of clinical findings, 1,254 of 1,570 (79.8%) had fever (>38°C), 1,408 of 1,595 (88.2%) headache, 1,403 of 1,562 (89.8%) stiffness of the neck, and 649 of 784 (82.7%) leukocytosis (>10,000/mm3). Cerebrospinal fluid culture yielded a pathogen in 873 of 2,260 (38.6%) patients. The most common pathogen was Streptococcus pneumoniae, followed by Neisseria meningitidis and Staphylococcus aureus. Overall mortality was 425 of 2,408 (17.6%). Pathogen-specific mortality was 60 of 202 (29.7%) for S. pneumoniae and 6 of 100 (6%) for N. meningitidis. Conclusion: Meningitis is a serious, life-threatening disease. More preventive measures should be sought to further decrease the mortality and morbidity related to acute purulent meningitis.
Morphometric Study of a Horseshoe Kidney
Authors: Oktem Hale , Gozil Rabet , Calguner Engin , Bahcelioglu Meltem , Mutlu Serdar , Kurkcuoglu Ayla , Yucel Deniz , Senol Eyup , Babus Tevfik , Kadıoglu Dural
Published: December 2007

Objective: To describe a horseshoe kidney, a congenital anomaly of the upper urinary tract. Clinical Presentation: A case study of horseshoe kidney harvested from a 62-year-old cadaver at Gazi University Medical School is presented. Results: The right and left kidneys were fused at their lower poles by a parenchymal isthmus located ventral to the abdominal aorta and formed a U-shape with two unequal arms.The isthmus of the ectopic kidney was placed obliquely to the left at the level of the fourth and fifth lumbar vertebra. The left kidney was larger and longer than the right one. The kidneys were supplied by three renal arteries arising from the abdominal aorta. Two arteries on the right side supplied blood of the two kidneys, while the third artery that directly originated from the aorta, above the origin of inferior mesenteric artery, supplied the isthmus. Venous drainage of the both kidneys and the isthmus were drained by three veins that opened independently into the inferior vena cava. The right ureter was duplicated in origin. Conclusion: This report shows that knowledge of anomalies such as this is very important in planning and conducting surgical procedures.
Ewing’s Sarcoma as Second Malignant Neoplasm after Retinoblastoma: A Case Report
Authors: Mittal Rakesh , Al Awadi Shafika , Sahar Omar , Behbehani A.M.
Published: December 2007

Objectives: To report a case of a child with the hereditary form of unilateral retinoblastoma (RB), who developed Ewing’s sarcoma of the right fibula 3 years after the enucleation of the right eye. Case Presentation and Intervention: The child was diagnosed as a case of RB of the right eye at the age of 9 months. He was fully investigated and found to have locally advanced RB with bone marrow involvement (Reese-Ellsworth stage IVA). Enucleation was recommended to the family, but they refused. The patient received chemotherapy and diode laser thermotherapy in Kuwait and the UK. He had a local relapse after 11 months and subsequently underwent enucleation of the right eye. After 3 years, he was investigated for a small swelling in his right lower leg. After extensive investigations, it was reported as Ewing’s sarcoma. He was treated with chemotherapy, surgery (complete excision of the fibula) and high-dose chemotherapy followed by autologous stem cell transplantation. The child is now nearly 2 years after completing the treatment and is disease free. Conclusions: This case confirms the increased risk of a second malignant neoplasm (SMN) in children with hereditary RB. These children need a very close follow-up for the early diagnosis of SMNs or even subsequent malignancies.
From Neuroendocrinology to Neuroimmunomodulation – A Tribute to Prof. Dr. Samuel McCann
Authors: Bornstein Stefan R.
Published: December 2007

One of the leading experts in the field of Neuroendocrinology and Neuroimmunmodulation, Samuel Mac Donald McCann, known by all his friends as ‘Don’, passed away in 2007. This article pays tribute to his outstanding scientific contribution and a glimpse on his fascinating personality. A member of the National Academy of Sciences of the United States and pioneer in the field of neuroendocrine regulation, he identified numerous hormones and peptides and set the stage for basic concepts in physiology and clinical medicine.
Vasoactive Intestinal Peptide Regulates Th17 Function in Autoimmune Inflammation
Authors: Leceta Javier , Gomariz Rosa P. , Martinez Carmen , Carrión Mar , Arranz Alicia , Juarranz Yasmina
Published: December 2007

An imbalance of pro-inflammatory and anti-inflammatory cytokines, autoreactive and inflammatory T helper 1 (Th1) cells, and regulatory T (Treg) cells results in the loss of immune tolerance and the subsequent appearance of inflammatory autoimmune diseases. On the other hand, hormones and neuropeptides are endogenous factors controlling the immune homeostasis that have been proposed as therapeutic agents in different autoimmune disorders. Among them, the vasoactive intestinal peptide (VIP) has been shown to downregulate the inflammatory response and to alter the Th1/Th2 balance in favor of anti-inflammatory Th2 immune responses. Recent studies have revealed a greater diversification of the T cell effector repertoire with the identification of Th17 cells. This subpopulation has been shown to be pathogenic in several autoimmune diseases previously attributed to the Th1 lineage. Arising new data and a critical revision of already published studies indicate that VIP is an immunomodulatory therapeutic agent targeting the Th17/Treg pathway.
Plasma Aminothiol Compounds, but Not Serum Tumor Necrosis Factor Receptor II and Soluble Receptor for Advanced Glycation End Products, Are Related to the Cognitive Impairment in Alzheimer’s Disease and Mild Cognitive Impairment Patients
Authors: Hernanz Angel , De la Fuente Mónica , Navarro Mercedes , Frank Ana
Published: December 2007

Increasing evidence indicates that factors such as oxidative stress, plasma homocysteine increase and glutathione depletion, elevated pro-inflammatory cytokines and advanced glycation end products can play a role in Alzheimer’s disease (AD) pathogenesis. The receptor for advanced glycation end products (RAGE) is a cell surface receptor that has been implicated in neurodegeneration, and a soluble isoform of RAGE (sRAGE) has the ability to prevent the adverse effects of RAGE signaling by acting as a decoy. Twenty-five patients with AD, 26 with mild cognitive impairment (MCI) and 44 age-matched control subjects were studied. All subjects were classified according to their clinical, cognitive and positron emission tomography study. Serum levels of sRAGE and TNF-α receptor II were not significantly different in AD or MCI patients compared to controls. Total plasma levels of glutathione and its metabolite cysteinglycine were decreased in AD and MCI patients compared to the control group. In addition, AD patients presented significantly increased plasma homocysteine compared to those in MCI patients and controls. We found significant positive correlations between sRAGE and glutathione, cysteinglycine and cysteine levels. Moreover, a significant negative correlation between the total score of cognitive impairment and homocysteine levels, and significant positive correlations with glutathione, cysteinglycine and cysteine levels were observed. These findings indicate that plasma aminothiol compounds are associated with AD and MCI patients and with their cognitive status.
Modulation by Astrocytes of Microglial Cell-Mediated Neuroinflammation: Effect on the Activation of Microglial Signaling Pathways
Authors: Tichauer J. , Saud K. , von Bernhardi R.
Published: December 2007

The strong inflammatory response observed in neurodegenerative diseases can depend on the impairment of the endogenous control of microglial activation, triggering the release of potentially detrimental factors such as cytokines, nitric oxide (NO) and superoxide anion (O2–·). Our aim was to study the activation of microglial cells and the transduction pathways involved in their modulation by IL-1β and TNF-α. Microglial and mixed glial cell cultures from neonatal rats were exposed to IFN-γ and/or IL-1β and TNF-α. We analyzed NO secretion and the activation of ERK and STAT1. We found that astrocytes modulated microglial cell activation, decreasing production of NO. IFN-γ induced an 18- to 25-fold increase in NO, associated to a 3- to 5-fold increase in ERK phosphorylation in microglial cultures. IL-1β, but not TNF-α, inhibited IFN-γ-induced production of NO in microglia by 87%. It also reduced IFN-γ-induced phosphoERK (pERK) by 40%, without affecting phosphoSTAT1 (pSTAT1). In contrast, in microglial cultures exposed to media conditioned by astrocytes, IL-1β did not inhibit pERK, whereas it reduced activation of STAT1. Inducible NO synthase expression induced by IFN-γ in microglial cultures was reduced when the activation of ERK was prevented. We propose that IL-1β modulates IFN-γ-induced production of oxidative molecules through cross talk between STAT1 and MAPK pathways, regulating the amplitude and duration of microglial activation. Modulation of ERK was observed at 30 min, whereas inhibition of pSTAT was observed later (at 4 h), indicating that it was an early and transient phenomenon.
NOD Mice Exocrinopathy: Towards a Neuroimmune Link
Authors: Calafat Mario , Larocca Luciana , Roca Valeria , Pérez Leirós Claudia
Published: December 2007

Sjögren’s syndrome (SS) is a chronic autoimmune disorder of exocrine glands characterized as an autoimmune exocrinopathy and more specifically as an autoimmune epithelitis. An impaired balance of neuroimmune interactions mediated by vasoactive intestinal peptide (VIP) in the target organ at early stages of disease is explored by means of the nonobese diabetic (NOD) mouse model of SS. We have previously described a reduced salivary secretion and signaling upon VIP stimulation. The effect reflected a differential regulation of the neural isoform of nitric oxide synthase by calcium calmodulin kinase II and occurred prior to the appearance of detectable levels of cytokines in NOD glands. VIP acting on NOD macrophages treated with lipopolysaccharide promoted anti-inflammatory effects by inhibiting nitric oxide synthase induction as well as IL-12 and TNF-α production, while stimulating IL-10. Here we present evidence on the ability of apoptotic acinar cells from submandibular glands of NOD mice to stimulate nitric oxide in both peritoneal and glandular macrophage pools to a similar extent as lipopolysaccharide + IFN-γ. VIP was not effective to prevent nitrite accumulation and modestly increased IL-10 levels in macrophages coincubated with acinar cells. An enhanced nitrite response of NOD glandular macrophages in basal and stimulated conditions compared to peritoneal cells is also shown.
Effects of Moderate Consumption of Distilled and Fermented Alcohol on Some Aspects of Neuroimmunomodulation
Authors: Diaz Ligia Esperanza , Cano Pilar , Jimenez-Ortega Vanesa , Nova Esther , Romeo Javier , Marcos Asunción , Esquifino Ana Isabel
Published: December 2007

Alcoholic beverages are characterized by their fermented versus distilled origin and also by their degree of alcohol. The toxic effects of chronic alcohol consumption have been widely studied. However, there is less evidence about possible beneficial effects of moderate alcohol intake. This work was aimed at evaluating the effects of moderate alcohol consumption (beer or ethanol) on plasma hormone concentrations, blood and thymus lymphocyte phenotypes and brain neurotransmitter levels. For this purpose, 40 adult Wistar male rats were administered ethanol or beer for 4 weeks (experimental groups). Age-matched rats were administered beer without alcohol or water to be used as controls. Rats were killed by decapitation and plasma from the trunk blood was collected to measure plasma prolactin, growth hormone and ACTH concentrations by homologous specific double antibody radioimmunoassays. Thymus and blood lymphocyte subsets were measured by flow cytometry. Neurotransmitter concentrations [dopamine, γ-aminobutyric acid (GABA) and taurine] were measured by high pressure liquid chromatography in the median eminence and the pituitary. Blood and thymus lymphocyte subsets were not significantly changed by either ethanol or beer consumption, compared to controls. Plasma prolactin levels significantly decreased in ethanol-administered groups (p < 0.05) compared to control animals drinking water, although plasma levels of growth hormone and ACTH were not modified by either alcohol used. Dopamine and GABA concentrations in the median eminence or in the adenohypophysis remained unmodified by moderate beer or ethanol consumption. However, taurine concentration was significantly increased in the pituitary (p < 0.05) in the group drinking ethanol compared to those groups drinking beer with or without alcohol. These data suggest that moderate alcohol consumption may change the regulatory mechanism of prolactin secretion. Whether these modifications have a physiological significance deserves further research.
Neuroimmunomodulation during Exercise: Role of Catecholamines as ‘Stress Mediator’ and/or ‘Danger Signal’ for the Innate Immune Response
Authors: Ortega Eduardo , Giraldo Esther , Hinchado María Dolores , Martín Leticia , García Juan José , De la Fuente Mónica
Published: December 2007

Exercise-induced neuroimmunomodulation is clearly accepted today. The present article reviews the main literature concerning the immunomodulatory capacity of catecholamines on the innate immune response during physical exercise, and presents our laboratory’s latest results on this topic. It is well known that the effects of exercise on the immune system are mediated by the ‘stress hormones and mediators’. Although catecholamines have usually been regarded as immunosuppressors, they may stimulate innate immune response mechanisms (such as phagocytic function) during exercise-induced stress, even without previous antigenic stimulation. The exercise-induced stimulation of the phagocytic response in particular and the innate responses in general have been considered as a prevention strategy of the athlete’s organism in order to prevent the entry and/or maintenance of antigens in a situation where the adaptive immune response seems to be depressed, and thus it has been suggested that catecholamines participate as a ‘stress mediator’ of these effects. Given this hypothesis, it is also suggested here that catecholamines may be the first ‘danger signal’ to the immune system during exercise-induced stress.
Kayexalate Intake (in Sorbitol) and Jejunal Diverticulitis, a Causative Role or an Innocent Bystander?
Authors: Pusztaszeri Marc , Christodoulou Michel , Proietti Stefania , Seelentag Walter
Published: December 2007

Small intestine diverticulosis is a rare entity that is asymptomatic in the majority of cases. However, it may cause serious complications, such as infection, hemorrhage, intestinal obstruction and diverticulitis. Kayexalate (sodium polystyrene sulfonate) in sorbitol has been associated with colonic necrosis and less frequently with upper gastrointestinal injuries in a subset of uremic patients treated for hyperkalemia. We report a case of jejunal diverticulosis with mucosal injury and diverticulitis in a uremic patient treated with Kayexalate and discuss the potential role of Kayexalate in the pathogenesis of diverticulitis.
Cells of Primarily Extravascular Origin in Neointima Formation following Stent Implantation
Authors: Tuleta Izabela , Skowasch Dirk , Peuster Matthias , Nickenig Georg , Bauriedel Gerhard
Published: December 2007

Objectives: In-stent restenosis due to neointima formation is a major limitation following stent implantation. Recently, several studies reported mobilization of primarily extravascular cells to the arterial sites after balloon angioplasty. Therefore, the goal of the present study was to assess the coordinated neointimal expression of endothelial progenitor, dendritic and neural crest-derived cells after stent implantation. Methods: Male minipigs underwent stent implantation in abdominal aortic segments. Animals were sacrificed at 1, 7, 14, 30, 60 or 90 days. Cross sections of the injured vessels were obtained for immunohistochemistry using specific antibodies for the detection of endothelial progenitor (CD133), dendritic (S100) and neural crest-derived cells (GFAP), as well as monocytes/macrophages (CD14) and T lymphocytes (CD3). Results: As a key finding, frequency of CD133, S100, GFAP, CD14 and CD3 (18.5 ± 3.6, 14.9 ± 1.8, 10.6 ± 1.1, 40.2 ± 8.3 and 5.0 ± 0.6%, respectively) in neointima was maximal at day 7. With ongoing neointima enlargement, expression of these cells decreased. In advanced neointima, labeled cells were predominantly localized at luminal and stented sites. Media showed almost no immunoreactivity of the markers studied, whereas adventitial zones of neovascularization revealed some signals. Conclusions: Endothelial progenitor, dendritic, neural crest-derived and inflammatory cells are consistently recruited into arterial neointima, mostly at early time points after stent implantation.
Extracellular Acidification and Hyperkalemia Induce Changes in HERG Inhibition by Ibutilide
Authors: Lin Congrong , Ke Xiaogang , Ranade Vasant , Somberg John
Published: December 2007

Background: A high incidence of proarrhythmia has been reported with ibutilide, especially in patients with underlying heart diseases. Our previous studies have shown that extracellular acidosis and hyperkalemia attenuate the HERG-inhibitory effect of proarrhythmic drugs, e.g. quinidine, but have little impact on the less-proarrhythmic drug amiodarone. We hypothesized that ibutilide would behave like quinidine in the presence of extracellular acidosis and hyperkalemia. Methods and Results: HERG was expressed on Xenopus oocytes, and the two-electrode voltage clamp technique was employed. Our results showed that ibutilide was a potent HERG inhibitor. When extracellular solution contained 5 mM KCl and pH was 7.4, the IC50 of ibutilide was 0.9 ± 0.1 µM. The inhibitory effect of ibutilide was attenuated when extracellular pH decreased to 6.2. There was a significant difference in current inhibition by ibutilide at pH 7.4 versus pH 6.2 (p < 0.01). When the extracellular potassium concentration was increased from 5 to 10 mM, ibutilide produced less current inhibition, and the IC50 was increased to 2.0 ± 0.1 µM. Conclusion: Extracellular acidosis and hyperkalemia attenuate the HERG-inhibitory effect of ibutilide. The differences in HERG inhibition between acidic and hyperkalemic regions compared to normal regions in the myocardium may result in heterogeneity in repolarization, which may contribute to the proarrhythmic toxicity of ibutilide.
A Universal Combination Treatment for Vaginitis
Authors: Bornstein Jacob , Zarfati Doron
Published: December 2007

Background: We compared a novel vaginal tablet consisting of 100 mg of clotrimazole and 100 mg of metronidazole (‘Clo-Met’) to a 100-mg clotrimazole tablet in the treatment of vaginitis. Methods: A multicenter, double-blind, randomized controlled study. Women with vaginal discharge and diagnosed as suffering from vaginitis caused by Trichomonas vaginalis, bacterial vaginosis or Candida albicans, or any combination of the three, and who had not received treatment for vaginitis during the previous month, were studied. Results: 165 patients were enrolled into the study – 84 into the combined therapy group, and 81 into the clotrimazole group. In women with Candida vaginitis, Clo-Met was more effective than clotrimazole treatment (p < 0.012 and p < 0.05, respectively). Conclusion: A combination vaginal tablet consisting of clotrimazole and metronidazole is therapeutically effective in candidal vaginitis. The effectiveness of Clo-Met on bacterial vaginosis, T. vaginalis infection as well as on vaginal infections due to a combination of these microorganisms should be studied further.
Homocysteine, Cystatin C and N-Terminal-Pro Brain Natriuretic Peptide
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: December 2007

Background: There is increasing evidence that vascular disease contributes to cognitive impairment and dementia. Clarification of the role of vascular risk factors in dementia is important because most are modifiable, in contrast to other risk factors such as age and genetics. Methods: In 451 patients with mental illness we have investigated three biochemical markers related to vascular disease, total plasma homocysteine (tHcy), cystatin C, and N-terminal-pro brain natriuretic peptide (NT-proBNP), and their association with vascular disease, diagnoses, and brain imaging findings (CT). Results: Plasma tHcy, serum cystatin C, and serum NT-proBNP showed significantly increased frequencies of elevated levels in patients with vascular disease, in patients with a pathological CT finding indicating cerebrovascular disease, and in patients above 75 years of age. Conclusion: It is possible that the control of conventional vascular risk factors and therapy could be guided by the level of plasma tHcy, serum cystatin C, and serum NT-proBNP. Patients with an elevation of any of these three parameters could be selected for a lower target level of risk factors such as blood pressure, hyperlipidemia etc. than conventional target levels.
Effects of Renal Replacement Therapy on Plasma Lipoprotein(a) Levels
Authors: Rosas Sylvia , Joffe Marshall , Wolfe Megan , Brayman Kenneth , Rader Daniel J.
Published: December 2007

Patients with end-stage renal disease (ESRD) have significantly higher levels of lipoprotein(a) [Lp(a)] when compared to control populations. Elevated levels of Lp(a) may play a role in the high incidence of cardiovascular disease in ESRD. We conducted a prospective study to test the hypothesis that plasma levels of Lp(a) decline rapidly after renal transplantation proportional to the improvement in renal function, but are not affected by hemodialysis. All adults that initiated hemodialysis or received a renal transplant from our institution during a 10-month period were invited to participate in the study. Lp(a) levels were obtained immediately prior to the initiation of renal replacement therapy. In transplant recipients, repeat Lp(a) measures were done at 3 days, 5 days, 1 week, 2 weeks, 3 weeks and 4 weeks post-transplant. In hemodialysis patients, repeat Lp(a) measures were done after 3 months. We used a mixed effects model to analyze the effect of time, race and creatinine on Lp(a) after transplant. Lp(a) levels decreased rapidly after renal transplantation. Mean Lp(a) levels at 2 weeks were 35.3% lower than prior to transplantation. Each reduction of 50% in creatinine was associated with a 10.6% reduction in Lp(a) (p < 0.001). In contrast, there was no significant change in Lp(a) after initiation of hemodialysis. The rapid decrease of Lp(a) levels after renal transplantation provides support for a metabolic role of the kidney in Lp(a) catabolism and suggests that the increase in Lp(a) seen in chronic kidney disease is due to loss of functioning renal tissue.
Juridical works in the oldest catalogue of Leiden University Library (1595)
Authors: Feenstra Robert
Published: December 2007

The first printed catalogue of Leiden University Library (1595, reprint 1995) was omitted in the author's study on Roman law works in XIIIth – XVIth century (manuscript) catalogues in the Northern Netherlands (Tijdschrift voor Rechtsgeschiedenis, 28 (1960), p. 439–507). This gap is now filled by a description of the circa 35 juridical works (of a total of circa 350) listed in this catalogue. Bibliographical references are added for the copies still available (itemized by shelfmarks) as well as for those now missing. Purchase prices and names of donors are given (if known). Some biographical information is supplied for the authors of the works.
Intraseasonal Interactions between Temperature and Vegetation over the Boreal Forests
Authors: Wang Weile , Anderson Bruce T. , Entekhabi Dara , Huang Dong , Su Yin , Kaufmann Robert K. , Myneni Ranga B.
Published: December 2007

This paper uses statistical and analytical techniques to investigate intraseasonal interactions between temperature and vegetation [surrogated by the normalized difference vegetation index (NDVI)] over the boreal forests. Results indicate that interactions between the two fields may be approximated as a coupled second-order system, in which the variability of NDVI and temperature of the current month is significantly regulated by lagged NDVI anomalies from the preceding two months. In particular, the influence from the one-month lagged NDVI anomalies upon both temperature and vegetation variability is generally positive, but the influence from the second-month lagged NDVI anomalies is often negative. Such regulations lead to an intrinsic oscillatory variability of vegetation at growing-season time scales across the study domain. The regulation of temperature variability by NDVI anomalies is most significant over interior Asia (Siberia), suggesting strong vegetation–atmosphere couplings over these regions. Physical mechanisms for these statistical results are investigated further with a stochastic model. The model suggests that the oscillatory variability of the temperature–NDVI system may reflect the dynamic adjustments between the two fields as they maintain a thermal balance within the soil and lower boundary layer of the atmosphere; the particular role vegetation plays in this scenario is mainly to dissipate heat and therefore reduce surface temperatures.
Infants Born to Mothers With Anti-SSA/Ro Autoantibodies: Neonatal Outcome and Follow-up
Authors: Zuppa Antonio Alberto , Fracchiolla Annalisa , Cota Francesco , Gallini Francesca , Savarese Immacolata , D'Andrea Vito , Luciano Rita , Romagnoli Costantino
Published: December 2007

Neonatal lupus syndrome is considered a model of passively acquired autoimmune disease. The first 10 newborns born to mothers with connective tissue disease and positive for anti-SSA/Ro antibodies enrolled in a follow-up program to evaluate the incidence of cardiac, hepatobiliary, hematologic, echoencephalographic, and cutaneous manifestations until 9 months of age are described in this study. No congenital heart block was observed, but only transient rhythm alterations were observed. In all, 1 infant showed typical neonatal lupus syndrome skin lesions at 3 months of age. During the neonatal period, echoencephalographic alterations were found more frequently, whereas at follow-up, hepatic and hematologic alterations were more often observed. In all, 1 baby showed persistent neutropenia. A standard program that enrolls all infants born to mothers with anti-SSA/Ro autoantibodies, who are at risk of developing neonatal lupus syndrome, should also include tests performed some time after birth, as a number of clinical manifestations might appear at a late stage.
Childhood Epilepsy With Occipital Paroxysms: Variations on the Theme
Authors: Shahar Eli , Genizi Jacob
Published: December 2007

This review reports on the various presentations as well as new revealed data relating to the epileptic disorder defined as childhood epilepsy with occipital paroxysms characterized by occipital epileptic discharges recorded by electroencephalography. The initial rigidly delineated subtypes by the International League Against Epilepsy included the following: ( a) Panayiotopoulos syndrome—early-onset seizure disorder presenting with prolonged infrequent, nocturnal autonomic seizures, accompanied by eye deviation and ictal vomiting. ( b) Gastaut syndrome—late-onset type presenting with short diurnal frequent seizures and visual ictal manifestations along with migrainous headaches. A high percentage of children present, however, with mixed clinical phenomena making it difficult to comply with the rigidly segregated syndromes reported by several authorities including our recent report on 28 children of whom 14 showed mixed phenomena. Therefore, childhood epilepsy with occipital paroxysm should be suspected at any age presenting with nocturnal vomiting, autonomic impairment, focal motor fits with head deviation, migraine headaches, and/or visual perturbations.
Why Parents Seek Medical Evaluations for Their Children With Mild Acute Illnesses
Authors: Voigt Robert G. , Johnson Shirley K. , Hashikawa Andrew H. , Mellon Michael W. , Campeau Lynnelle J. , Williams Arthur R. , Yawn Barbara P. , Juhn Young J.
Published: December 2007

The reasons underlying parents' decisions to seek medical evaluations for their mildly ill children are not well understood. This cross-sectional study tracked parents' requests for on-site medical evaluations at a sick child care program. A logistic regression model identified factors associated with parents' decisions to seek medical evaluations for their children based on the data from parent-completed questionnaires. A convenience sample of 196 parents completed all questionnaires; 62 (31.6%) parents sought medical evaluations. Parents were more likely to seek medical evaluations if they were concerned about missing work (odds ratio = 8.6; 95% confidence interval, 3.3-22.0; P = .0001), if they smoked (odds ratio = 3.7; 95% confidence interval, 1.1-12.4; P = .037), or if their spouse's highest educational attainment was some high school (odds ratio = 0.4; 95% confidence interval, 0.1-1.0; P = .044). The data highlight the problems working parents have in accessing health care during usual working hours and the potential value of convenient health care programs.
PEDS: Developmental Milestones—An Accurate Brief Tool for Surveillance and Screening
Authors: Brothers Kyle B. , Glascoe Frances Page , Robertshaw Nicholas S.
Published: December 2007

About 16% of children have developmental-behavioral disabilities but less than one-third of the children are detected by their health care providers, probably because of the use of informal milestones checklists. The goal of this study is to determine the reliability, validity, accuracy, and utility of a new tool, PEDS: Developmental Milestones (PEDS:DM). Data from a nationally representative sample of 1619 children administered developmental diagnostic measures were mined for items that best predicted performance in each developmental domain. A total of 112 met inclusion criteria, that is, sensitivity/specificity ≥ 70%. For each domain/age level (birth to 8 years of age), sensitivity to performance less than or equal to the 16th percentile on diagnostic measures was 83% and specificity was 84%. Reliability was high (test—retest, .98 to .99; interrater, .82 to .96; κ, .81). The readability level was 1.8 grades (range 1.1 to 2.6). The PEDS:DM appears to be a validated, accurate alternative to informal milestones checklists that are a probable contributor to underdetection of children with delays and disabilities.
Common/Unity: An Innovative Program to Address 3 Root Causes of Many of the Social Ills Seen in Adolescents
Authors: Duncan Burris , Harris Gail , Reedy Jessica , Krahe Sue , Gillis Regina , Laguna Michele
Published: December 2007

Multiple community agencies coordinated their individual expertise to develop a comprehensive program for a planned community in a 24-apartment complex for single, young (age range, 18-21 years), homeless mothers and their infants and children. Although objective evaluation of the program proved difficult, “community” was established and lives were changed. The program was designed to address multiple issues faced by teenaged mothers but did not directly address critical factors of youths' internal motivation and decision-making processes. Attempting to reverse major impediments in the lives of young mothers with histories of violence, abuse, unstable early home environments, and lack of education while assuming the sole responsibility of raising a child, advancing their education, and maintaining employment is a daunting task, but a task that deserves our urgent attention.