bluuebunny/crossref_metadata_2025 huggingface dataset:
Promotility Medications – Now and in the Future
Authors: Karamanolis G. , Tack J.
Published: July 2006

Gastrointestinal promotility drugs stimulate smooth muscle contractions to enhance gastric emptying and small and large bowel transit. Currently available drug classes with prokinetic properties include antidopaminergic agents, serotonergic agents, and motilin-receptor agonists. Due to moderate prokinetic effects, poor symptomatic responses and the presence of adverse effects, there is a clear need for new classes of prokinetics. Several newer prokinetic drugs and drug classes are currently under evaluation. Selecting candidate agents and designing the appropriate therapeutic trials is hampered by the lack of insight in the pathophysiology of motility-related symptoms. As gastrointestinal motor disorders are chronic, relapsing, and remitting disorders, it seems desirable that studies with candidate prokinetic drugs establish a long-term efficacy and not only short-term effects on gastrointestinal functions.
Pediatric Gastrointestinal Motility – Future Directions and Challenges
Authors: Youssef Nader N. , Di Lorenzo Carlo
Published: July 2006

The study of gastrointestinal motility has evolved to a sophisticated diagnostic technique that is widely used clinically to further guide management of children with complex gastrointestinal problems. Thorough comprehension requires a multidisciplinary approach with the integration of molecular and cell biology, organ physiology, and clinical observations. During the past decade there has been a dramatic increase in our knowledge of the enteric neuromuscular system. Continued exploration of targeted gene mutations in animal models has the potential of enhancing our understanding of congenital disorders of gastrointestinal motility. Experiments studying polymorphisms in serotonin transporter gene (SERT) and different therapeutic responses to serotonergic agents in adults with irritable bowel syndrome need to be carried out in children with functional bowel disorders. Additional considerations that need to be addressed if advances are to continue include increasing the number of specialists interest in motility disorders and identifying funding sources to support the establishment of research consortiums among pediatric centers.
Use of Endoluminal Ultrasound to Evaluate Gastrointestinal Motility
Authors: Miller Larry , Dai Qing , Korimilli Annapurna , Levitt Barry , Ramzan Zeeshan , Brasseur James
Published: July 2006

The use of high-frequency ultrasound transducers in the gastrointestinal tract (GI) has already yielded remarkable findings concerning the anatomy, physiology and pathophysiology of the GI tract and of various motility disorders. These transducers have made completely invisible portions of the GI tract (the longitudinal smooth muscle, muscles of the upper esophageal sphincter, components of the gastroesophageal junction high-pressure zone, and the muscle of the anal sphincter complex) accessible to investigation. Use of simultaneous ultrasound and manometry has allowed the exploration of the normal physiology of peristaltic contraction. The components of the high-pressure zone of the distal and proximal esophagus have been isolated and the movement of these components has been studied individually and as a group. Various esophageal motility disorders have been investigated including achalasia, scleroderma, Barrett’s esophagus and diffuse esophageal spasm. The possible etiology of the symptoms of esophageal chest pain and heartburn (sustained esophageal contractions of the longitudinal smooth muscle), have been studied. The possible underlying pathophysiology of GERD (the missing gastric clasp and sling fiber pressure profile) has been explored. Three-dimensional high-frequency ultrasound imaging has allowed the peristaltic contraction sequence to be viewed in a completely new and unique manner. The biomechanics of both esophageal contraction and the gastroesophageal junction high-pressure zone have been investigated and the mechanical advantage of esophageal shorting has been studied. The mechanism of action of standard surgical and newer endoscopic therapies for GERD has been defined. Future applications of this technology are limited only by our imagination.
Frequency of Functional Bowel Disorders among Healthy Volunteers in Mexico City
Authors: Schmulson Max , Ortíz Orianna , Santiago-Lomeli Mariana , Gutiérrez-Reyes Gabriela , Gutiérrez-Ruiz María Concepción , Robles-Díaz Guillermo , Morgan Douglas
Published: July 2006

Background: The frequency of functional bowel disorders (FBD) in Mexico using the Rome II criteria is unknown. Methods: The Rome II Modular Questionnaire (RII-MQ) was translated into Spanish in coordination with the Rome Committee and their Latin American program. Volunteers were recruited by advertisement in Mexico City, and administered the RII-MQ. Results:The study population consisted of 324 healthy volunteers, with a mean age of 35.7; 66% were female. The most prevalent disorders were heartburn 35%, irritable bowel syndrome (IBS) 35%, functional bloating 21%, proctalgia fugax 21%, and functional constipation 19%. Based on gender, IBS-C was 4 times more frequent in females than males (19 vs. 4.6%) and functional bloating 3 times more frequent (10 vs. 3.7%). Differences according to occupation included a higher prevalence of ulcer-like dyspepsia (p = 0.04), IBS-C (p = 0.018) and proctalgia fugax (p = 0.034) among students. Conclusions: This is the first study to use RII-MQ to determine the prevalence of FBD in urban Mexico. The prevalence of IBS was significant and is related to a number of factors, including the stress of living in an overpopulated city. Selection bias is likely operative. A community-based study is warranted.
Risk Factors for Short-Term Mortality in Older Subjects with Acute Ischemic Stroke
Authors: Zuliani Giovanni , Cherubini Antonio , Ranzini Monica , Ruggiero Carmelinda , Atti Anna Rita , Fellin Renato
Published: July 2006

Background: Stroke is the third cause of death in older individuals living in Western Countries. The identification of predictors for mortality after stroke has a major importance for clinicians in order to allow the implementation of therapeutic and preventive strategies. Objective: To evaluate the association between clinical and laboratory parameters and 30-days total mortality in a large sample of older patients with stroke. Methods: 469 older patients (median age: 80.0 years) consecutively hospitalized for acute ischemic stroke were enrolled. The data recorded included: (1) clinical features of stroke; (2) routine clinical chemistry analyses; (3) medical history, and (4) 12-lead ECG. All patients underwent computed tomography scan of the brain. Stroke type was classified by the Oxfordshire Community Stroke Project system. Results: 130 subjects died within 30 days after stroke, with an overall mortality of 27.7%. At univariate analysis, altered levels of consciousness (ALC), congestive heart failure, atrial fibrillation, previous stroke, high blood glucose, fibrinogen and blood sedimentation rate levels, higher white blood cell count, lower serum albumin and iron levels were associated with mortality. Multivariate logistic regression analysis indicated that short-term mortality was associated with ALC (OR: 11.80; CI 95%: 5.50–24.00), congestive heart failure (OR: 3.06; CI 95%: 1.04–8.80), and age (OR: 1.04; CI 95%: 1.002–1.09) independent of gender, previous stroke, AF, fasting blood glucose, serum albumin, serum iron, and white blood cell count. In patients with ALC (high-mortality rate: 63.6%), only hyperglycemia (III vs. I tertile, OR: 9.60; CI 95%: 1.65–52.50) was associated with mortality after multivariate adjustment. Conclusion: Our study highlights the role of ALC and congestive heart failure in the short-term prognostic stratification of older patients with acute ischemic stroke. Furthermore, our results support the value of post-stroke hyperglycemia as a marker for short-term mortality also in advanced age, and particularly in the presence of ALC and in nondiabetic individuals.
Search for a Common Cause Factor amongst Cognitive, Speed and Biological Variables Using Narrow Age Cohorts
Authors: Mackinnon Andrew , Christensen Helen , Jorm Anthony F.
Published: July 2006

Background: Cross-sectional studies have demonstrated that age-related effects on many cognitive and biological functioning variables are shared. A number of theories postulate that these associations arise from a common causal mechanism responsible for change across a wide range of functions. However, it has been claimed that the finding of shared variance among variables in these studies may be spurious because most studies have been cross-sectional and based on age-heterogeneous samples. Objective: To examine evidence for changes with age in variance shared by cognitive variables using a narrow-age cohort design. Methods: Three samples of adults with age ranges 20–24 years (n = 2,404), 40–44 years (n = 2,530) and 60–64 years (n = 2,510) were drawn from a population-based study. These groups were supplemented by data from an older sample of individuals (77 years and over) from a second population-based study (n = 374). Four models of the structure of a range of cognitive, speed and biological variables derived from previous cross-sectional research were fitted to data. These models were complete independence of variables within a cohort, a single common factor, multiple independent factors, and a second order factor model. Results: Model fit and the magnitude of loadings from multiple-group confirmatory factor analyses was compared between age groups. The fit for all four models was worse in the 60–64 year age group. Factor loadings on the common factor specified in these models varied between the groups, but the speed factor rather than the biological factor showed increased loadings as a function of age. Conclusions: This narrow age-cohort study did not support the existence of developmental changes in the structure of cognitive and biological variables across the lifespan. Shared variation between measures of cognition and biological function may be an artifact of the research designs that have generated these findings. This casts doubt of the existence of a common causal mechanism. However, it may be that such changes manifest only in later old age.
Entéropathies immunes et auto-immunes
Authors: Sherman Philip M. , Cutz Ernest , Goulet Olivier
Published: July 2006

L’entéropathie auto-immune débute typiquement par une diarrhée prolongée au cours de la première année de la vie. Des anomalies sous-jacentes des fonctions immunitaires, y compris des lymphocytes T régulateurs, doivent être exclues. Le traitement associe la réhabilitation nutritionnelle, l’immunosuppression et, dans certains cas, la greffe de moelle.
Diarrhées persistantes dans les pays en développement
Authors: Bhutta Zulfiqar A.
Published: July 2006

Les affections diarrhéiques sont globalement responsables d’un cinquième de la mortalité totale des enfants de moins de cinq ans, avec un nombre annuel de décès estimé à 2.2 millions. Une proportion significative de ces décès peut être liée à des épisodes de diarrhée persistante (définie comme une diarrhée persistant plus de 15 jours avec altération de la croissance). Il a été démontré que le cadre des diarrhées persistantes rassemblait des enfants chez lesquels la diarrhée était nettement plus sévère. Ces affections sont à l’origine de 36 à 54% de la mortalité totale due à des diarrhées. Bien que la pathogénie exacte de la diarrhée persistante demeure mal élucidée, la plupart des épisodes sont liés à des infections diarrhéiques aiguës antérieures avec prolongation de l’épisode le plus récent. Cette situation peut être liée à plusieurs facteurs propres à l’hôte tel que la préexistence d’une malnutrition, d’une carence en micronutriments et d’une immunodéficience et le traitement inadéquat de l’épisode le plus récent de diarrhée aiguë. La conséquence commune paraît être des lésions persistantes de la muqueuse intestinale qui ne parvient pas à se réparer. Contrairement aux diarrhées persistantes post-infectieuses, certains nourrissons peuvent présenter une diarrhée intraitable sévère due à divers troubles, dont beaucoup ont une base héréditaire. Ils forment aujourd’hui le type dominant de diarrhée prolongée dans les pays industrialisés. La prise en charge d’une diarrhée persistante repose sur une grande vigilance en matière de renutrition et sur l’identification précoce de complications. Bien que divers germes pathogènes aient été associés aux diarrhées persistantes, la place des médicaments antimicrobiens oraux est restreinte dans le traitement de routine de ces affections. L’attention portée à la réhydratation, le dépistage et le traitement appropriés des infections systémiques et la renutrition par la nutrition entérale au moyen d’aliments facilement absorbables sont essentiels pour la prise en charge de ces enfants, fréquemment dans un contexte ambulatoire. L’administration de zinc et de vitamine A peut raccourcir la durée d’une diarrhée persistante et aide également à réduire les récidives. Les stratégies les plus importantes de prévention de ces diarrhées demeurent cependant l’allaitement maternel exclusif au cours des six premiers mois de la vie, poursuivi durant deux ans avec des aliments complémentaires adéquats et une prise en charge optimale des épisodes diarrhéiques aigus.
FDA and CPMP Rulings on Subgroup Analyses
Authors: Maggioni Aldo P. , Darne Bernadette , Atar Dan , Abadie Eric , Pitt Bertram , Zannad Faiez
Published: July 2006

The extent to which subgroup analyses should affect the interpretation and conclusions in a trial report is a contentious matter, and guidelines regarding this issue have been established by the US Food and Drug Administration (FDA) and the EU Committee for Proprietary Medicinal Products (CPMP). ubgroup analyses should be set out in the protocol of clinical trials. The treatment effect itself may vary within a subgroup or covariate. In some cases, interactions are anticipated or are of particular a priori interest; hence a subgroup analysis or a statistical model including interactions is part of the planned analysis. However, subgroup or interaction analyses are often merely exploratory and should be clearly identified as such in the protocol. When exploratory, these analyses should be interpreted cautiously. Market approval of a compound is based on the overall trial results, and, importantly, no drug has so far been approved or not-approved either in the US or in the EU on the basis of subgroup analysis. However, subgroup analysis can influence the approval or can even be required, and therefore it can influence the labelling of the Summary Characteristics of a Product. Two examples in heart failure are given by the Val-HeFT trial comparing valsartan to placebo and the MERIT-HF trial comparing metoprolol to placebo, from which some remarkable regulatory issues arose that were debated by the FDA and CPMP.
Weight Lifting and Aortic Dissection: More Evidence for a Connection
Authors: Hatzaras I. , Tranquilli M. , Coady M. , Barrett P.M. , Bible J. , Elefteriades J.A.
Published: July 2006

Background/Aims: In 2003, we reported on a small number of patients in whom acute aortic dissection appeared to be causally related to intense weight lifting. If additional cases could be identified, the phenomenon of weight lifting induced aortic dissection would be further substantiated. We now report a substantially larger number of cases in which aortic dissection is associated with intense physical exertion. Methods: Additional cases of acute aortic dissection occurring at the time of intense physical exertion were accumulated and analyzed. Cases were culled from retrospective review of a large university data base and from reports forwarded to our attention from around the country. We determined type of activity bringing on symptoms, age and sex of the patients, location of the dissection (ascending or descending aorta), aortic size, therapy, and survival. Results: We identified 31 patients in whom acute aortic dissection occurred in the context of severe physical exertion, predominantly weight lifting or similar activities. All patients except one were males. Mean age was 47.3 (range = 19–76). All except four dissections were in the ascending aorta. Only three patients (9.7%) had a family history of aortic disease. Mean aortic diameter on the initial imaging study was 4.63 cm. Twenty-six of the 31 cases were diagnosed ante-mortem and 5 post-mortem. Overall, 10 of the 31 patients (32.2%) died. Of 24 patients reaching surgical therapy, 20 (83.3%) survived. Conclusion: Weight lifting related acute aortic dissection appears to be a real phenomenon, with increasing evidence for the association of extreme exertion with this catastrophic aortic event. Moderate aortic dilatation confers vulnerability to exertion-related aortic dissection. Individuals with known aortic dilatation should be cautioned to refrain from weight lifting or strenuous exertion. Routine echocardiographic screening of individuals engaging in heavy strength training should be considered, in order to prevent this tragic loss of life.
D2 Lymphadenectomy for Gastric Cancer in Tata Memorial Hospital: Indian Data Can Now Be Incorporated in Future International Trials
Authors: Shrikhande Shailesh V. , Shukla Parul J. , Qureshi Sajid , Siddachari Ravichand , Upasani Vivek , Ramadwar Mukta , Kakade Anagha C. , Hawaldar Rohini
Published: July 2006

Background: While mortality rates after radical gastrectomy have decreased, there is considerable morbidity after D2 lymphadenectomy. In this study, we assessed the perioperative results of D2 gastrectomy for gastric cancer. Materials: Data of 159 patients who underwent D2 gastrectomy for gastric adenocarcinoma at Tata Memorial Hospital was analyzed for interim analysis. The extent of resection, blood loss, transfusions, duration of hospitalization, number of lymph nodes dissected, complications, morbidity and mortality were analyzed. Results: 130 and 29 patients underwent distal and total gastrectomy, respectively (2002–2005) by single specialized surgical unit. Median age was 55 years (range 21–78) and blood loss was 450 ml (range 100–2,200 ml). The median duration of hospitalization was 13 days (range 7–52 days). The median number of dissected lymph nodes was 15 (range 2–46). Minor and major morbidity rate was 4.4 and 4.4% respectively. Mortality rate was 1.25%. Conclusion: Morbidity and mortality following D2 lymphadenectomy is low in this first prospective study from India. With Japan and Western countries having polarized views on D2 lymphadenectomy, future international multicenter trials could also incorporate data such as ours from areas of high incidence of gastric cancer since perioperative outcomes would no longer cloud their results and might provide a better global perspective on D2 lymphadenectomy.
Audit of the Effect of Dialysate Sodium Concentration on Inter-Dialytic Weight Gains and Blood Pressure Control in Chronic Haemodialysis Patients
Authors: Davenport Andrew
Published: July 2006

Background/Aims: Over the last three decades the standard dialysate sodium concentration has increased from 136 to 140 mmol/l (mEq/l) today. There has been great debate as to whether a reduction in dialysate sodium alone can lead to improved blood pressure control, and reduced inter-dialytic weight gain. Methods: An audit was performed in 469 maintenance regular haemodialysis patients who dialysed in seven different centres under the care of one university medical school. Results: Those centres which predominantly used a dialysate sodium of 140 mmol/l (mEq/l) had increased inter-dialytic weight gains, with more difficult blood pressure control, as not only did a greater percentage of patients require anti-hypertensive medication, but also more were prescribed multiple classes of anti-hypertensive agents. There was no difference in the frequency of symptomatic intra-dialytic hypotension. Conclusions: A reduction in dialysate sodium was associated with lower inter-dialytic weight gains, without any additional intra-dialytic hypotensive episodes. Those patients in whom the difference between the time-averaged dialysate sodium concentration and the midweek pre-dialysis serum sodium was positive result had increased inter-dialytic weight gains, compared to those with a negative value. Reduced dialysate sodium alone was not effective in controlling blood pressure without additional proper dietary sodium restriction.
Myeloma Renal Disease: Presentation and Outcome
Authors: Chan Doris T. , Craig Kathrine , Donovan Kieron , Phillips Aled
Published: July 2006

Background: Renal disease can be the first presentation of multiple myeloma (MM) or develop during the disease process. Aim: To define the mode of presentation of MM to nephrologists and determine the association with patient characteristics and outcome. Methods: MM patients referred to a tertiary renal unit were studied retrospectively. Group I presented to nephrologists prior to MM diagnosis (n = 36); group II was referred to nephrology after diagnosis (n = 27), and group III was known only to haematology and never referred (n = 91). Age at presentation, gender, paraprotein type, need for dialysis, haematological and biochemical parameters, and survival were examined. Results: Of the 154 MM patients, 23.4% presented with renal impairment (group I), 17.5% were referred to nephrology after MM diagnosis (group II) and 59.1% did not receive renal input (group III). On presentation, group I had a median serum creatinine (sCr) of 700 (range 341–1,023) µmol/l and 80% required dialysis. Although the median sCr on presentation for group II was 131 (range 103–373) µmol/l, median sCr on renal referral was 554 (range 181–807) µmol/l and 57% needed dialysis. In contrast, the median sCr on presentation for group III was only 99 (range 85–117) µmol/l. Group I was more anaemic (p < 0.001) and had higher β2-microglobulin levels (p < 0.0001) on presentation compared to groups II and III. For groups I and II, the median survival after diagnosis (10.2 vs. 24.7 months, p = 0.11) and renal referral (10.5 vs. 20.0 months, p = 0.68) was not significantly different. Conclusion: Survival in myeloma renal disease remains poor regardless of the mode of presentation to nephrologists.
Erythropoietin in Experimental Acute Renal Failure
Authors: Sharples E.J. , Yaqoob M.M.
Published: July 2006

The haematopoietic factor erythropoietin (EPO) has recently been recognized to play a physiological role in the brain and other tissues. The EPO receptor is present in the glomerulus, mesangial and tubular epithelial cells in the kidney. We have reviewed the experimental use of EPO in animal models of acute renal failure. EPO attenuates the dysfunction and histological changes associated with ischaemia-reperfusion injury, with a reduction in apoptotic cell death. EPO has also shown benefit in animal models of systemic shock and cisplatin-induced nephrotoxicity. In vitro studies have shown that EPO has direct effects on proliferation and cell death in proximal tubular epithelial cells. There is increasingly strong experimental evidence that EPO may be of therapeutic use in acute renal failure, and clinical trials should be undertaken to determine its clinical applications in this field.
Acquired Loss of Erythrocyte Complement Receptor Type 1 in Patients with Diabetic Nephropathy Undergoing Hemodialysis
Authors: Wakabayashi Michiro , Ohi Hiroyuki , Tamano Mariko , Onda Kisara , Fujita Teizo , Tomino Yasuhiko
Published: July 2006

Background: Complement receptor type 1 on erythrocytes (E-CR1) plays important roles not only in the regulation of complement activation, but also the clearance of immune complexes. Reduced E-CR1 was previously found in patients undergoing hemodialysis (HD). We investigated whether the E-CR1level in HD patients with diabetic nephropathy (DMN) is decreased. The levels of decay accelerating factor (DAF) and CD59 on erythrocytes (E) were also determined to ascertain whether the loss of CR1 is a specific phenomenon or other complement regulatory proteins are also affected. Methods: The levels of CR1, DAF, and CD59 on E were analyzed in 176 HD patients with DMN, 101 HD patients with non-diabetes mellitus renal diseases (non-DMN), and 108 healthy individuals. Hind III restriction fragment length polymorphism of intron 27 of the CR1 gene was analyzed. The serum-soluble CR1 levelwas measured by ELISA. Results: The E-CR1 level was significantly lower in the DMN group than the non-DMN group (p < 0.0001) and healthy individuals (p < 0.05). The E-CR1 level was significantly higher in the non-DMN group than in healthy individuals (p < 0.01). The levels of E-DAF and E-CD59 were significantly lower in the DMN group than non-DMN group (DAF, p < 0.01; CD59, p < 0.0001). Within each genotype of the CR1 gene, the E-CR1 level was significantly lower in the DMN group than in the non-DMN group and healthy individuals (non-DMN, p < 0.01; healthy individuals, p < 0.05). The serum-soluble CR1 level was significantly higher in the DMN group than non-DMN group and control group (p < 0.01 each). However, soluble CR1 did not correlate with E-CR1. Conclusion: Acquired loss of E-CR1 was found among HD patients with DMN. From the viewpoint of host defense, it may be a prognostic factor.
Absence of an Interaction between the Rf-1 and Rf-5 QTLs Influencing Susceptibility to Renal Damage in Rats
Authors: van Dijk Sabine J. , Specht Patricia A.C. , Lazar Jozef , Jacob Howard J. , Provoost Abraham P.
Published: July 2006

Background: Previous studies showed that combining the Rf-1 and Rf-3 or Rf-4 QTLs of FHH induced synergistic interactions markedly enhancing renal susceptibility. The present study aimed to determine the presence of such interaction between the Rf-1 and Rf-5 QTLs. Methods: Renal damage susceptibility was assessed in Rf-1B, Rf-1B+5, Rf-1B+4 congenics and ACI control rats in four situations: two-kidney control (2K), unilateral nephrectomy (UNX), L-NAME-induced hypertension (2K+L-NAME) and UNX+L-NAME. Albuminuria (UAV) and systolic blood pressure (SBP) were measured during 18 weeks of follow-up. In separate experiments, renal autoregulation was assessed in 2K rats. Results: In all four situations, Rf-1B+4 rats developed more severe UAV than ACI, Rf-1B and Rf-1B+5. There were no significant differences in UAV between Rf-1B and Rf-1B+5 rats. In the 2K and UNX situation no differences in SBP were noted between all four strains. With 2K+L-NAME and UNX+L-NAME treatment, SBP in double congenics was higher than that of ACI and Rf-1B rats. Renal autoregulation was similarly impaired in all three congenic strains. Conclusion: We conclude that the Rf-5 region, alone or in the presence of Rf-1B, does not affect the development of renal damage. We cannot substantiate that the Rf-5 region contains genes influencing renal damage susceptibility.
Effects of Blocking the Renin-Angiotensin System on Expression and Translocation of Protein Kinase C Isoforms in the Kidney of Diabetic Rats
Authors: Zhang Li , Ma Ji , Gu Yong , Lin Shanyan
Published: July 2006

Background: High glucose and angiotensin II (Ang II) can activate protein kinase C (PKC) in diabetes mellitus. However, it is not clear which isoform of PKC is activated by glucose or Ang II. Our study focused on the effects of angiotensin blockade, using the angiotensin-converting enzyme inhibitor fosinopril, the Ang II receptor blocker irbesartan and their combination, on the expression and translocation of PKC isoforms α and βII in the renal cortex and medulla in diabetes. Methods: Hyperglycemia was induced with streptozotocin and diabetic rats were randomized to 4 groups: diabetic control, irbesartan group (40 mg/kg daily), fosinopril group (40 mg/kg daily) and combination group (irbesartan plus fosinopril, 20 mg/kg daily, respectively); age-matched normal rats served as normal control. After 4 weeks, expression and translocation of PKC-α and -βII in the renal cortex and medulla were assessed by immunohistochemistry and Western immunoblotting. Results: The expression of PKC-α in the membrane and cytosol fractions from the renal cortex was significantly higher in diabetic rats (276.83 ± 32.44% in membrane, 149.04 ± 23.42% in cytosol) than that in normal ones. The expression of PKC-βII in the renal cortex of diabetic rats decreased significantly in the membrane (50.00 ± 11.68%, p < 0.05) and remained unchanged in the cytosol (94.51 ± 11.69%, p > 0.05) compared with normal controls. Treatment with irbesartan, fosinopril and their combination partially corrected the abnormalities mentioned above. For the expression of PKC-α and -βII in the medulla, no difference was detected among the 5 groups. Conclusion: The renin-angiotensin system was implicated in the pathogenesis of diabetic nephropathy by regulating the activation of PKC isoforms.
Effect of Selenium on Cisplatin-Induced Nephrotoxicity in Rats
Authors: Fujieda Mikiya , Naruse Keishi , Hamauzu Tadashi , Miyazaki Eriko , Hayashi Yoshihiro , Enomoto Riyo , Lee Eibai , Ohta Kazuhide , Wakiguchi Hiroshi , Enzan Hideaki
Published: July 2006

Cisplatin (CP), a commonly used antineoplastic drug, is nephrotoxic. CP-induced nephrotoxicity involves oxidative pathways. A deficiency of selenium (Se) reduces glutathione peroxidase (GPx) activity resulting in oxidative stress. We investigated how Se deficiency or oral Se administration influences CP-induced nephrotoxicity. Thirty male Wistar rats were fed a Se-deficient or control diet for 4 weeks. Then they were given intraperitoneal (i.p.) CP alone, i.p. saline alone, or Se by gavage 24 and 1 h prior to i.p. CP. Blood and urine samples were collected and the kidneys were removed 5 days after CP treatment. Urinalysis, renal function, GPx activity, and expression of cellular GPx mRNA were measured. Histology was evaluated by light microscopy with immunohistochemistry for 4-hydroxy-2-nonenal (HNE), vimentin, and heme oxygenase (HO)-1. CP induced renal tubular damage with increased expression of vimentin, HO-1 and HNE staining, which represents lipid peroxidation. Se deficiency exacerbated CP-induced nephrotoxicity as shown by deterioration of the above parameters and depressed GPx activity and expression of GPx mRNA. Se treatment ameliorated CP-induced nephrotoxicity, but did not significantly improve renal function. These findings suggest that Se deficiency increases oxidative stress and enhances CP-induced nephrotoxicity, whereas oral Se treatment partially protects against the nephrotoxicity in rats.
Degeneration in the Brains of Parkinson’s Disease Patients
Authors: Zhang Lihong , Wang Mingwei , Li Qi , Yew D.T. , Wolff Lucille T.
Published: July 2006

Parkinson’s disease is a progressive neurodegenerative disease associated with the loss of the dopaminergic nigrostriatal tract in the basal ganglia. In the present study, we examined Parkinson’s disease-related degeneration that includes but is not limited to the basal ganglia. T1-weighted MRI scans of Parkinson’s disease patients were employed. We found additional atrophy outside of the basal ganglia in 93% of the patients. Our results suggest that future studies should be done to determine how this additional atrophy relates to current pathological models of Parkinson’s disease.
Expression of Nuclear Factor-Kappa B in Early Developing Rhesus Monkey Brains
Authors: Dong Dacui , Zhang Yan , Jiang Yuyun , Hu Yuhui , Liu Zilong , Chan Wood Yee
Published: July 2006

Nuclear factor-kappa B (NF-ĸB) is a transcription factor, which is ubiquitously distributed in the adult nervous system and is thought to be crucially involved in the neuronal and glial functions. However, during development, the spatiotemporal expression pattern of NF-ĸB has not been well characterized, especially in developing primates and humans. In the present study, we used an immunohistochemical method to determine the distribution of NF-ĸB in the developing rhesus monkey (Macaca mulatta) brain at different developmental stages. Immunoreactive products were not observed at 25 days of pregnancy but were detected at 40 days mainly in the perinuclear region, and then, gradually more positive signals were found inside the nucleus of cells in different brain regions. At this stage, when various primitive brain structures had just started to form, a low level of immunoreactivity was detected in the presumptive areas of the thalamus, hypothalamus, caudate nucleus and parietal cortex. The immunoreactive cells were scattered and large, usually with a prominent nucleus. In the developing choroid plexus, moderate immunoreactivity was observed in the epithelial lining of the ventricle and also in the underlying mesenchymal tissues. By 55 days, immunoreactivity became stronger, and brain regions were more easily identified. Both the number of the immunoreactive cells and the intensity of positive signals were increased, and cells were more differentiated. Some of these cells extended cytoplasmic processes. Positive cells were also scattered without any specific pattern of distribution in all the brain regions examined. The columnar epithelium of the choroid plexus showed intense immunoreactivity. Our findings show that NF-ĸB starts to express in many regions of the early developing monkey brain, and the immunoreactivity of NF-ĸB increases with time.
Effects of Traditional Chinese Medicine Radix Astragali, Fructus Aurantii and Rhizoma Cypei Extracts on c-Fos Expression in the Aging Rat Hippocampus Induced by Exercise
Authors: Shi Yan , Yang Weiyi , Zhang Jin-Shan , Leung Tyler C.H. , Yung Ken K.L.
Published: July 2006

Fatigue is a complex interaction between the peripheral systems and the central nervous system and is often a problem in aging individuals. In accordance with the view of traditional Chinese medicine, treatment of fatigue, as induced by heavy exercise, is related to the restoration of Qi in the body. In order to investigate the effects of two formulations of traditional Chinese medicine, namely the Qi-supplementing (QS) medicine containing radix astragaliand the QS formulation plus Qi-rectifying (QR) medicine containing radix astragali, fructus aurantii and rhizoma cypei, which are often used in elderly individuals, aging rats which were exercised for 5 weeks were treated with the above two formulations. Immunocytochemistry revealed that the number of Fos-immunoreactive neurons in the CA1 and CA2 regions of the hippocampus was significantly increased after heavy exercise. Treatment with the QS + QR formulation but not the QS formulation was able to downregulate the number of Fos-immunoreactive neurons in the CA1 and CA2 regions of the hippocampus to the levels of the nonexercise controls. These results indicate that the Chinese medicine formulations, notably the QS + QR formulation, are effective in the restoration of normal levels of Fos protein expression in the central nervous system after heavy exercise. These results have important implications in the treatment of fatigue in aging individuals using formulations of traditional Chinese medicine.
Beneficial Effects of Dietary Vitamins, Lipoic Acid and Carnitine on the Aging Brain
Authors: Ng T.B. , Ye X.Y.
Published: July 2006

A number of vitamins including vitamin A/carotenoids, vitamins C and E and lipoic acid, which have antioxidant activity, are capable of improving cognitive performance in senescent animals and elderly subjects. The B vitamins, folic acid and carnitine also exert beneficial actions on the aging brain.
Bilirubin Kinetic Modeling for Quantification of Extracorporeal Liver Support
Authors: Jung Aleksandra , Krisper Peter , Haditsch Bernd , Stauber Rudolf E. , Trauner Michael , Holzer Herwig , Schneditz Daniel
Published: July 2006

Background/Aim: To provide a measure of treatment dose for extracorporeal liver support (ELS). Methods: The kinetics of conjugated bilirubin were described by a two-compartment model (Vc, Vp) with central elimination (K) and constant generation rate (G). The transfer of solute between compartments was modeled by intercompartmental clearance (Kpc). The central compartment (Vc) was assumed as a constant fraction of total volume (Vc = 0.3*Vt). Results: Eight patients were studied during 35 treatments lasting 6 h each. The average K, Vt, Kpc, G, and mass of conjugated bilirubin removed were 18.6 ± 3.9 ml/min, 9.1 ± 3.8 liters, 103 ± 108 ml/min, 0.33 ± 0.15 mg/min, and 641 ± 275 mg, respectively. The reduction ratio (48 ± 10%) measured as the change in post- to pre-treatment concentrations underestimated the modeled fraction of bilirubin mass removed (54 ± 13%) essentially because of significant conjugated bilirubin appearance during treatments. Conclusions: Kinetic analysis provides an improved measure of treatment dose as generation, distribution, and elimination of conjugated bilirubin are jointly considered.
Plants Beneficial to the Aging Brain
Authors: Ng T.B. , Wang H.X. , Liu F. , Xia L.X.
Published: July 2006

A number of edible plants and/or their constituents have been shown to delay the degenerative changes in the brain associated with aging. These plants included Allium sativum, Aloe vera, Astragalus membranaceus, Boschniakia rossica, Clitoria ternatea, Curcuma phaeocaulis, Capsicum annum, Cyanum wildfordii, Emblica officinals, Ginkgo biloba, Heteropteris aphrodisiaca, Panax ginseng, Pegasus laternarius, Polygonum multiflorum, Ptychopetalum olacoides, Scutellaria baicalensis, Valeriane officinalis, Withania somnifera and Zingiber officinale. Among these plants, the best known are G. biloba and P. ginseng.
Morphological Features of the Esophageal Enteric Nervous System and Its Stereological Changes during Aging
Authors: Wu Mei , Zhang Chen , Timmermans J.-P.
Published: July 2006

Following the enteric nervous system (ENS) of the gastrointestinal tract, the esophageal ENS attracts more and more attention of neuroscience researchers. Despite its continuity with the ENS of the gastrointestinal tract, the esophageal ENS possesses many unique morphological and functional features. This review collates the evidence of recent years, focusing mainly on the morphological features of the esophageal ENS in adult mammals andits stereological and morphological changes during aging.
Winter Birth in Association with a Risk of Brain Tumor among a Finnish Patient Population
Authors: Mainio Arja , Hakko Helinä , Koivukangas John , Niemelä Asko , Räsänen Pirkko
Published: July 2006

The aim of this study was to analyze whether winter birth is related to risk of brain tumor in a clinical sample of patients from northern Finland. The study group comprised 101 patients suffering from a primary brain tumor. When comparing births in winter to births in other seasons, a 1.39-fold (95% CI 1.01–1.77) excess of winter births among patients was observed compared to respective births in the general population (p = 0.026). Especially patients with pituitary adenomas exhibited a 2.5-fold (95% CI 1.5–4.4) excess of winter births. The authors conclude that the season-of-birth effect in brain tumor patients should not be neglected when the actual and important tumorigenesis is investigated.
Frequency of Headache and Migraine in Qatar
Authors: Bener Abdulbari
Published: July 2006

Background: Headache is a worldwide problem that affects all ages. To date there are no epidemiological data regarding headaches in Qatar. Aim: The aim of this study was to use the International Headache Society (IHS) diagnostic criteria to estimate the prevalence of migraine and headache in an adult population. Design: This is a cross-sectional population-based study. Setting: The study was carried out at 12 Primary Health Care Centers during the period from October to December 2004 in Qatar. Subjects: Of the 1,200 subjects who were approached to participate in this study, 913 gave their consent, representing a response rate of 76.1%. Methods: Subjects were selected by a multistage stratified sampling procedure. We used the IHS criteria for migraine. Face-to-face interviews were based on a questionnaire that included variables such as age, sex, socioeconomic status, lifestyle habits, exacerbating factors, warning symptoms, associated features, family history and associated factors. Results: Of the studied subjects, 54.9% were males and 45.1% females. The prevalence of headache and migraine among men was 67.9%, 7.8%, and among women 78.2%, 8.0%, respectively. Subjects aged 25–34 years had higher prevalence of headache comparing to other age groups (27.3%). Prevalence of headache was higher in women. Subjects with less than a high school education had higher frequency of headache (49.1%). The most common warning symptoms prior to headache were abnormal vision (53.0%) and weakness (30.4%). Stress (71.8%) and weather (49.5%) made headache worse in subjects. The majority of the headache sufferers looked for a dark (33.7%) and quiet place (74.5%) to rest. Conclusion: Headachedisorders constitute a public health problem in a newly developed Qatari society, due to fast urbanization. More women suffered from headache and migraine than men. The study revealed that there was a strong association between hemoglobin level and headache and its severity. Furthermore, the prevalence of headache and migraine in Qatar is higher than in Western and African countries.
Obesity, Abdominal Obesity and Alzheimer Disease
Authors: Razay George , Vreugdenhil Anthea , Wilcock Gordon
Published: July 2006

Background/Aims: Obesity has a strong association with vascular and metabolic diseases, which have been linked with Alzheimer disease (AD). While recent studies have reported an association between mid-life obesity and dementia, the role of later-life obesity is less clear. This study investigated the relation between AD, obesity and abdominal obesity at later-life in a case-control study. Methods: Participants were 50 consecutive patients with probable AD from memory disorders clinics in Launceston, Australia, and Bristol, England, and 75 cognitively normal controls. Height and weight [from which body mass index (BMI) was calculated] and hip and waist circumferences (from which waist-hip ratio was calculated) were measured. Participants were classified according to their BMI as: underweight (BMI <20.0 kg/m2); normal weight (BMI 20.0–24.9 kg/m2); overweight (BMI 25–29.9 kg/m2), or obese (BMI ≧30 kg/m2). They were classified as abdominally obese if their waist-hip ratio was >0.9 (men) or >0.8 (women). Results: AD was associated with obesity [OR 9.5, 95% CI 2.4–37.3, p = 0.001], underweight (OR 5.4, CI 0.9–33.7, p = 0.07) and abdominal obesity (OR 2.5, CI 1.1–5.7, p = 0.027) using logistic regression analyses adjusted for age, sex and location. The inclusion of metabolic risk factors in the model increased the ORs for obesity (OR 12.6, CI 2.8–56.5, p = 0.001) and underweight (OR 7.9, CI 1.0–66.3, p = 0.056). Conclusion: AD may be associated with obesity, underweight and abdominal obesity at later life. Larger prospective studies are required to investigate this further.
Normative Auditory Brainstem Response Data for Hearing Threshold in the Rabbit
Authors: Stieve M. , Mojallal H. , Winter M. , Battmer R. , Lenarz T.
Published: July 2006

In an experimental study, we determined the physiological hearing threshold of the rabbit in order to use these data as normative values for further experimental investigations. The aim was to use different acoustic stimuli (click and tone-pip stimuli) with different frequency spectra for air and bone conduction (BC) in order to obtain further information about the optimal form of stimulus when recording auditory evoked potentials in the rabbit. For the investigation, we used 46 female New Zealand rabbits weighing 3.2–4.4 kg and aged 6 months. The equipment used to record brainstem auditory evoked potentials was the Nicolet Viking IV P System (Nicolet Biomedical, Inc.). In accordance with the experimental set-up, the measurements took place under intubation anesthesia, with a total of four repeat measurements performed on each ear at different times. Tone-pip and click stimuli with varying intensities of stimulus, transmitted via air conduction and BC, were applied. The I-IV waves proved the most stable for both stimulus modalities. They were registrable in 98.7% of cases, whereas only 30.2% of the V waves could be recorded. Values averaged from all measurements made throughout the study yielded a potential threshold of 34.8 dB peak equivalent (p.e.) SPL for the click stimulus, 13.8 dB p.e. SPL for the tone-pip stimulus at 8 kHz and 34.2 dB p.e. SPL for the click stimulus transmitted via BC. With regard to latencies, the results indicated a good reproducibility through different stimuli with acceptable standard deviations. The values for physiological hearing threshold obtained here can serve as normative data in subsequent experimental animal studies.
Effect of the Ethnic Factor on Cranial Capacity and Brain Weight of Male Newborns in Northern Iran
Authors: Golalipour Mohammad Jafar , Heydari Kamran
Published: July 2006

Brain weight and cranial capacity are useful in evaluating the health of newborns and providing a baseline to study the changes that might occur to the cranium in later years of life. A total of 419 normal male newborns were evaluated by classic cephalometry. The cranial capacities in the native Fars (n = 203) and Turkman (n = 216) groups were 599 ± 30 and 590 ± 30 ml, respectively (p < 0.05), and brain weights in these two groups were 619.9 ± 34 and 610.8 ± 31 g (p < 0.05). Therefore, an ethnic factor might influence brain weight and the cranial capacity of newborns.
In Long-Term Bedridden Elderly Patients with Dietary Copper Deficiency, Biochemical Markers of Bone Resorption Are Increased with Copper Supplementation during 12 Weeks
Authors: Kawada Etsuo , Moridaira Kazuaki , Itoh Katsuhiko , Hoshino Ayami , Tamura Jun’ichi , Morita Toyoho
Published: July 2006

Background: Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. Method: This study included 10 patients (83.7 ± 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. Results: DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). Conclusions: In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation.