bluuebunny/crossref_metadata_2025 huggingface dataset:
Localized accumulation of angiotensin II and production of angiotensin-(1–7) in rat luteal cells and effects on steroidogenesis
Authors: Pepperell John R. , Nemeth Gabor , Yamada Yuji , Naftolin Frederick , Merino Maricruz
Published: February 2006

These studies aim to investigate subcellular distribution of angiotensin II (ANG II) in rat luteal cells, identify other bioactive angiotensin peptides, and investigate a role for angiotensin peptides in luteal steroidogenesis. Confocal microscopy showed ANG II distributed within the cytoplasm and nuclei of luteal cells. HPLC analysis showed peaks that eluted with the same retention times as ANG-(1–7), ANG II, and ANG III. Their relative concentrations were ANG II ≥ ANG-(1–7) > ANG III, and accumulation was modulated by quinapril, an inhibitor of angiotensin-converting enzyme (ACE), Z-proprolinal (ZPP), an inhibitor of prolyl endopeptidase (PEP), and parachloromercurylsulfonic acid (PCMS), an inhibitor of sulfhydryl protease. Phenylmethylsulfonyl fluoride (PMSF), a serine protease inhibitor, did not affect peptide accumulation. Quinapril, ZPP, PCMS, and PMSF, as well as losartan and PD-123319, the angiotensin receptor type 1 (AT1) and type 2 (AT2) receptor antagonists, were used in progesterone production studies. ZPP significantly reduced luteinizing hormone (LH)-dependent progesterone production ( P < 0.05). Quinapril plus ZPP had a greater inhibitory effect on LH-stimulated progesterone than either inhibitor alone, but this was not reversed by exogenous ANG II or ANG-(1–7). Both PCMS and PMSF acutely blocked LH-stimulated progesterone, and PCMS blocked LH-sensitive cAMP accumulation. Losartan inhibited progesterone production in permeabilized but not intact luteal cells and was reversed by ANG II. PD-123319 had no significant effect on luteal progesterone production in either intact or permeabilized cells. These data suggest that steroidogenesis may be modulated by angiotensin peptides that act in part through intracellular AT1receptors.
Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance
Authors: Bahr Matthias J. , Ockenga Johann , Böker Klaus H. W. , Manns Michael P. , Tietge Uwe J. F.
Published: February 2006

The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels ( P < 0.001) with hepatic venous resistin being higher than arterial levels ( P < 0.001). Circulating resistin was significantly correlated with plasma TNF-α levels ( r = 0.62, P < 0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production ( r = −0.47, P < 0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P < 0.01) and ketone bodies ( r = 0.48, P < 0.001) as well as hepatic ketone body production ( r = 0.40, P < 0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved ( P < 0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis.
Characterization ofl-arginine transport in adrenal cells: effect of ACTH
Authors: Repetto Esteban M. , Pannunzio Vanesa , Astort Francisco , Martinez Calejman Camila , Moreno Marcos Besio , Pignataro Omar P. , Cymeryng Cora B.
Published: February 2006

Nitric oxide synthesis depends on the availability of its precursor l-arginine, which could be regulated by the presence of a specific uptake system. In the present report, the characterization of the l-arginine transport system in mouse adrenal Y1 cells was performed. l-arginine transport was mediated by the cationic/neutral amino acid transport system y+L and the cationic amino acid transporter (CAT) y+in Y1 cells. These Na+-independent transporters were identified by their selectivity for neutral amino acids in both the presence and absence of Na+and by the effect of N-ethylmaleimide. Transport data correlated to expression of genes encoding for CAT-1, CAT-2, CD-98, and y+LAT-2. A similar expression profile was detected in rat adrenal zona fasciculata. In addition, cationic amino acid uptake in Y1 cells was upregulated by ACTH and/or cAMP with a concomitant increase in nitric oxide (NO) production.
Adenosine2Areceptor vasodilation of rat preglomerular microvessels is mediated by EETs that activate the cAMP/PKA pathway
Authors: Carroll Mairéad A. , Doumad Anabel B. , Li Jing , Cheng Monica K. , Falck J. R. , McGiff John C.
Published: February 2006

Dilation of rat preglomerular microvessels (PGMV) by activation of adenosine A2Areceptors (A2AR) is coupled to epoxyeicosatrienoic acid (EET) release. We have investigated the commonality of this signal transduction pathway, i.e., sequential inhibition of Gsα, adenylyl cyclase, PKA, and Ca2+-activated K+(KCa) channel activity, to the vasoactive responses to A2AR activation by a selective A2Aagonist, CGS-21680, compared with those of 11,12-EET. Male Sprague-Dawley rats were anesthetized, and microdissected arcuate arteries (110–130 μm) were cannulated and pressurized to 80 mmHg. Vessels were superfused with Krebs solution containing NG-nitro-L-arginine methyl ester (l-NAME) and indomethacin and preconstricted with phenylephrine. We assessed the effect of 3-aminobenzamide (10 μM), an inhibitor of mono-ADP-ribosyltranferases, on responses to 11,12-EET (3 nM) and CGS-21680 (10 μM) and found that both were inhibited by ∼70% ( P < 0.05), whereas the response to SNP (10 μM) was unaffected. Furthermore, 11,12-EET (100 nM), like cholera toxin (100 ng/ml), stimulated ADP-ribose formation in homogenates of arcuate arteries compared with control. SQ-22536 (10 μM), an inhibitor of adenylyl cyclase activity, and myristolated PKI (14–22) amide (5 μM), an inhibitor of PKA, decreased activity of 11,12-EET and CGS-21680. Incubation of 11,12-EET (3 nM-3 μM) with PGMV resulted in an increase in cAMP levels ( P < 0.05). The responses to both 11,12-EET and CGS-21680 were significantly reduced by superfusion of iberiotoxin (100 nM), an inhibitor of KCachannel activity. Thus in rat PGMV activation of A2AR is coupled to EET release upstream of adenylyl cyclase activation and EETs stimulate mono-ADP-ribosyltransferase, resulting in Gsαprotein activation.
Gamble's “economy of water” revisited: studies in urea transporter knockout mice
Authors: Fenton Robert A. , Chou Chung-Lin , Sowersby Holly , Smith Craig P. , Knepper Mark A.
Published: February 2006

The Gamble phenomenon (initially described over 70 years ago as “an economy of water in renal function referable to urea”) suggested that urea plays a special role in the urinary concentrating mechanism and that the concentrating mechanism depends in some complex way on an interaction between NaCl and urea. In this study, the role of collecting duct urea transporters in the Gamble phenomenon was investigated in wild-type mice and mice in which the inner medulla collecting duct (IMCD) facilitative urea transporters, UT-A1 and UT-A3, had been deleted ( UT-A1/3−/− mice). The general features of the Gamble phenomenon were confirmed in wild-type mice, namely 1) the water requirement for the excretion of urea is less than for the excretion of an osmotically equivalent amount of NaCl; and 2) when fed various mixtures of urea and salt in the diet, less water is required for the excretion of the two substances together than the amount of water needed for the excretion of the two substances separately. In UT-A1/3−/− mice both of these elements of the phenomenon were absent, indicating that IMCD urea transporters play a central role in the Gamble phenomenon. A titration study in which wild-type mice were given progressively increasing amounts of urea showed that the ability of the kidney to reabsorb urea was saturable, resulting in osmotic diuresis above excretion rates of ∼6,000 μosmol/day. In the same titration experiments, when increasing amounts of NaCl were added to the diet, mice were unable to increase urinary NaCl concentrations to >420 mM, resulting in osmotic diuresis at NaCl excretion rates of ∼3,500 μosmol/day. Thus both urea and NaCl can induce osmotic diuresis when large amounts are given, supporting the conclusion that the decrease in water excretion with mixtures of urea and NaCl added to the diet (compared with pure NaCl or urea) is due to the separate abilities of urea and NaCl to induce osmotic diuresis, rather than to any specific interaction of urea transport and NaCl transport at an epithelial level.
AT1receptor-mediated accumulation of extracellular angiotensin II in proximal tubule cells: role of cytoskeleton microtubules and tyrosine phosphatases
Authors: Li Xiao C. , Carretero Oscar A. , Navar L. Gabriel , Zhuo Jia L.
Published: February 2006

Long-term angiotensin II (ANG II) administration is associated with increased ANG II accumulation in the kidney, but intrarenal compartment(s) involved in this response remains to be determined. We tested the hypothesis that 1) extracellular ANG II is taken up by proximal tubule cells (PTCs) through AT1receptor-mediated endocytosis, 2) this process is regulated by cytoskeleton microtubule- and tyrosine phosphatase-dependent mechanisms, and 3) AT1receptor-mediated endocytosis of ANG II has a functional relevance by modulating intracellular cAMP signaling. In cultured PTCs, [125I]Tyr-labeled ANG II and fluorescein labeled-ANG II were internalized in a time-dependent manner and colocalized with the endosome marker Alexa Fluor 594-transferrin. Endocytosis of extracellular ANG II was inhibited by the AT1receptor blocker losartan (16.5 ± 4.6%, P < 0.01 vs. ANG II, 78.3 ± 6.2%) and by the tyrosine phosphatase inhibitor phenylarsine oxide (PAO; 30.0 ± 3.5%, P < 0.05 vs. ANG II). Intracellular ANG II levels were increased by ∼58% (basal, 229.8 ± 11.4 vs. ANG II, 361.3 ± 11.8 pg ANG II/mg protein, P < 0.01), and the responses were blocked by losartan ( P < 0.01), the cytoskeleton microtubule inhibitor colchicine ( P < 0.05), and PAO ( P < 0.01), whereas depletion of clathrin-coated pits with hyperosmotic sucrose had no effect (356.1 ± 25.5 pg ANG II/mg protein, not significant). ANG II accumulation was associated with significant inhibition of both basal (control, 15.5 ± 2.8 vs. ANG II, 9.1 ± 2.4 pmol/mg protein, P < 0.05) and forskolin-stimulated cAMP signaling (forskolin, 68.7 ± 8.6 vs. forskolin + ANG II, 42.8 ± 13.8 pmol/mg protein, P < 0.01). These effects were blocked by losartan and PAO. We conclude that extracellular ANG II is internalized in PTCs through AT1receptor-mediated endocytosis and that internalized ANG II may play a functional role in proximal tubule cells by inhibiting intracellular cAMP signaling.
Effects of water restriction on gene expression in mouse renal medulla: identification of 3βHSD4 as a collecting duct protein
Authors: Cai Qi , Keck Maggie , McReynolds Matthew R. , Klein Janet D. , Greer Kevin , Sharma Kumar , Hoying James B. , Sands Jeff M. , Brooks Heddwen L.
Published: February 2006

To identify novel gene targets of vasopressin regulation in the renal medulla, we performed a cDNA microarray study on the inner medullary tissue of mice following a 48-h water restriction protocol. In this study, 4,625 genes of the possible ∼12,000 genes on the array were included in the analysis, and of these 157 transcripts were increased and 63 transcripts were decreased by 1.5-fold or more. Quantitative, real-time PCR measurements confirmed the increases seen for 12 selected transcripts, and the decreases were confirmed for 7 transcripts. In addition, we measured transcript abundance for many renal collecting duct proteins that were not represented on the array; aquaporin-2 (AQP2), AQP3, Pax-8, and α- and β-Na-K-ATPase subunits were all significantly increased in abundance; the β- and γ-subunits of ENaC and the vasopressin type 1A receptor were significantly decreased. To correlate changes in mRNA expression with changes in protein expression, we carried out quantitative immunoblotting. For most of the genes examined, changes in mRNA abundances were not associated with concomitant protein abundance changes; however, AQP2 transcript abundance and protein abundance did correlate. Surprisingly, aldolase B transcript abundance was increased but protein abundance was decreased following 48 h of water restriction. Several transcripts identified by microarray were novel with respect to their expression in mouse renal medullary tissues. The steroid hormone enzyme 3β-hydroxysteroid dehydrogenase 4 (3βHSD4) was identified as a novel target of vasopressin regulation, and via dual labeling immunofluorescence we colocalized the expression of this protein to AQP2-expressing collecting ducts of the kidney. These studies have identified several transcripts whose abundances are regulated in mouse inner medulla in response to an increase in endogenous vasopressin levels and could play roles in the regulation of salt and water excretion.
Nitric Oxide Potentiates cAMP-Gated Cation Current in Feeding Neurons of Pleurobranchaea californica Independent of cAMP and cGMP Signaling Pathways
Authors: Hatcher Nathan G. , Sudlow Leland C. , Moroz Leonid L. , Gillette Rhanor
Published: February 2006

Critical roles for nitric oxide (NO) in regulating cell and tissue physiology are broadly appreciated, but aspects remain to be explored. In the mollusk Pleurobranchaea, NO synthase activity is high in CNS ganglia containing motor networks for feeding and locomotion, where a cAMP-gated cation current ( INa,cAMP) is also prominent in many neurons. We examined effects of NO on INa,cAMP using voltage-clamp methods developed to analyze cAMP signaling in the live neuron, focusing on the identified metacerebral giant neuron of the feeding network. NO donors enhanced the INa,cAMP response to injected cAMP by an averaged 85%. In dose-response measures, NO increased the current stimulated by cAMP injection without altering either apparent cAMP binding affinity or cooperativity of current activation. NO did not detectably alter levels of native cAMP or synthesis or degradation rates as observable in both current saturation and decay rate of INa,cAMP responses to cAMP injection. NO actions were not exerted by cGMP signaling, as they were not mimicked by cGMP analogue nor blocked by inhibitors of guanylate cyclase and protein kinase G. NO potentiation of INa,cAMP was broadly distributed among many other neurons of the feeding motor network in the buccal ganglion. However, NO did not affect a second type of INa,cAMP found in locomotor neurons of the pedal ganglia. These results suggest that NO acts through a novel mechanism to regulate the gain of cAMP-dependent neuromodulatory pathways that activate INa,cAMP and may thereby affect the set points of feeding network excitability and reactivity to exogenous input.
Estimation of the Voice Source from Speech Pressure Signals: Evaluation of an Inverse Filtering Technique Using Physical Modelling of Voice Production
Authors: Alku Paavo , Story Brad , Airas Matti
Published: February 2006

Objective: The goal of the study is to use physical modelling of voice production to assess the performance of an inverse filtering method in estimating the glottal flow from acoustic speech pressure signals. Methods: An automatic inverse filtering method is presented, and speech pressure signals are generated using physical modelling of voice production so as to obtain test vowels with a known shape of the glottal excitation waveform. The speech sounds produced consist of 4 different vowels, each with 10 different values of the fundamental frequency. Both the original glottal flows given by physical modelling and their estimates computed by inverse filtering were parametrised with two robust voice source parameters: the normalized amplitude quotient and the difference (in decibels) between the levels of the first and second harmonics. Results:The results show that for both extracted parameters the error introduced by inverse filtering was, in general, small. The effect of the distortion caused by inverse filtering on the parameter values was clearly smaller than the change in the corresponding parameters when the phonation type was altered. The distortion was largest for high-pitched vowels with the lowest value of the first formant. Conclusions: The study shows that the proposed inverse filtering technique combined with the extracted parameters constitutes a voice source analysis tool that is able to measure the voice source dynamics automatically with satisfactory accuracy.
Comparison of Speaking Rate, Articulation Rate and Alternating Motion Rate in Dysarthric Speakers
Authors: Nishio Masaki , Niimi Seiji
Published: February 2006

Despite recent indications that speaking rate, articulation rate and alternating motion rate (AMR) are sensitive to the influence of neurological disease on speech production in dysarthric speakers, the relationship among these parameters remains largely questionable. In the current study, speech samples were collected from 62 dysarthric speakers and 34 controls while reading a passage. Acoustic analysis investigated speaking rate, articulation rate and AMR and compared these parameters between the dysarthric and control groups and within the control and dysarthric group. The major findings were: (1) Speaking rate, articulation rate and AMR were all markedly lower in dysarthric speakers than in controls. (2) Marked correlations were recognized between speaking rate, articulation rate and AMR in the dysarthric group. (3) Compared with the speaking rate and articulation rate, AMR is characterized as follows: (i) variation was more limited in controls, and (ii) the control group was clearly distinguishable from the dysarthric group. (4) Unlike in controls, AMR in the dysarthric speakers was notably lower than their articulation rate. We therefore conclude that AMR is a more easily detected sign of abnormal articulation than speaking rate and articulation rate.
Heteromorphic sex chromosome system with an exceptionally large Y chromosome in a catfish Steindachneridion sp. (Pimelodidae)
Authors: Swarça A.C. , Fenocchio A.S. , Cestari M.M. , Bertollo L.A.C. , Dias A.L.
Published: February 2006

The chromosomes and banding patterns of Steindachneridion sp., a large catfish (Pimelodidae), endemic to the Iguaçu River, Brazil, were analyzed using conventional (C-, G-banding) and restriction enzyme banding methods. The same diploid number (2n = 56) as in other members of the genus and the family was found but the karyotype displayed an XX/XY sex chromosome system. The X chromosome was the smallest submetacentric, while the Y was the largest chromosome in the karyotype. Meiotic analysis showed 27 autosomal bivalents plus one heteromorphic XY bivalent during spermatogenesis. Sex chromosomes had no particular pattern after C-banding but G- and restriction enzyme bandings showed specific banding characteristics. The present finding represents the first report of a well-differentiated and uncommon sex chromosome system in the catfish family Pimelodidae.
Antiplatelet Therapy in Stroke Prevention: Present and Future
Authors: Caplan Louis R.
Published: February 2006

White platelet-fibrin thrombi often form on roughened endothelial surfaces and unstable arterial plaques. Agents that reduce the tendency of platelets to aggregate, agglutinate, and secrete and to attach to endothelial surfaces have been explored as agents that prevent brain and heart infarction. Aspirin, ticlopidine, clopidogrel, dipyridamole, cilostazol, and glycoprotein llb/llla inhibitors are all used now and have various different modes of action and functions.
Regional Differences in Incidence and Management of Stroke – Is There Any Difference between Western and Japanese Guidelines on Antiplatelet Therapy?
Authors: Shinohara Yukito
Published: February 2006

Purpose: There have not been many discussions on the differences between the guidelines for the management of stroke used in eastern and western countries. The purpose of this paper was to examine whether or not there are substantial differences between western countries and Japan in the prevalence of stroke and the frequencies of stroke subtypes, as well as in the recommended therapy for secondary prevention of ischemic stroke. Results and Conclusions: Although there are racial differences and differences in approved drugs between the East and West, the prevalence of stroke and the frequencies of stroke subtypes tend to converge throughout the world. However, the ratio of stroke to ischemic heart disease is still different between the East and West. Comparison of various countries’ guidelines shows that recommendations on antiplatelet therapy for secondary prevention of ischemic stroke are fundamentally similar in the East and West, but the recommended doses of antiplatelets, especially aspirin and ticlopidine, are smaller in Japan. Furthermore, Japanese guidelines only recommend the use of antiplatelets (particularly cilostazol) for patients with lacunar infarction with evidence.
Polypill Strategy vs. Prevention Clinics for Stroke Prevention
Authors: Amarenco Pierre
Published: February 2006

Thirty years of clinical trials have demonstrated that stroke can be prevented by reducing blood pressure to less than 140/90 mm Hg or by a further decrease of 10/5 mm Hg when blood pressure is controlled, by reducing LDL cholesterol by at least 1 mmol/l (39 mg/dl), and by inhibiting platelet aggregation. The (too simplistic) concept of the polypill strategy combining pharmacologic agents to achieve these goals is supposed to reduce the risk by 80% overall. However, reducing general salt and sugar intake, giving up smoking, developing prevention clinics with prevention nurses to improve adherence to preventive treatments, as well as decreasing poverty and malnutrition, increasing the level of hygiene, fighting against infectious diseases and financially helping developing countries are all combined necessary approaches to decrease the worldwide burden of stroke and other vascular diseases.
Factor V Kuwait: A Novel Mutation in the Coagulation Factor V Gene Discovered in Kuwait
Authors: Jadaon Mehrez M. , Dashti Ali A. , Lewis Hend L.
Published: February 2006

Objective: It was the aim of this study to report a new point mutation in the clotting factor V gene in the general Arab population. Subjects and Methods: The HR2 haplotype was tested in 288 Arabs living in Kuwait – 188 patients with venous thromboembolic disorders (VTE) and 100 healthy subjects – using polymerase chain reaction and restriction fragment length polymorphism techniques. The presence of the new mutation was verified by DNA sequencing. Results: Two (1.06%) VTE patients had guanine instead of the wild-type adenine at nucleotide number 3935 (A3935G) of the factor V gene. This mutation caused a histidine to arginine change in amino acid number 1254 of the factor V molecule. The new mutation is termed ‘factor V Kuwait’ (His1254Arg) and was absent in the 100 healthy subjects. Conclusion: It appears that factor V Kuwait could be a risk factor for developing VTE in Arabs. A larger study is needed to confirm this observation.
Detection of Serum Antibodies to Hepatitis C Virus in ‘False-Seronegative’ Blood Donors in Oman
Authors: Alnaqy Adel , Al-Harthy Safia , Kaminski Geraldine , Al-Dhahry Said
Published: February 2006

Objective: To detect hepatitis C virus (HCV) antibodies in seronegative donors by disruption of the immune complexes (ICs). Subjects and Methods: HCV antibody detection was carried out on 600 seronegative donors following an IC dissociation assay. Reverse transcription polymerase chain reaction (RT-PCR) was then performed on the positive results. Results: Nine of the 600 samples (1.5%) were positive for IC-dissociated HCV antibodies. Of the 9 only 3 antibody-positive samples had detectable HCV RNA. Conclusion: Screening for antibodies to HCV in combination with PCR appears to be the safest way to reduce the residual risk of HCV in blood transfusion.
Clinical and Neurophysiological Pattern of Guillain-Barré Syndrome in Kuwait
Authors: Nagarajan Venkatesan , Al-Shubaili Asmahan
Published: February 2006

Objective: To study the clinical and neurophysiological pattern of Guillain-Barré syndrome (GBS) in Kuwait. Materials and Methods: The clinical records of consecutive GBS patients admitted to Ibn Sina Hospital, Kuwait, during a 7-year period between 1997 and 2003 were analyzed. Results: Of the 41 cases, 77% were male. The majority of the cases presented during the winter months and a preceding infection was reported in two thirds of them. Proximal lower limb (LL) weakness was the predominant clinical presentation. Nerve conduction studies (NCS) demonstrated a demyelinating pattern in 70%, an axonal pattern in 15%, mixed type in 5% and no abnormality in the remaining 5%. The majority of the patients (73%) improved with one course of intravenous immunoglobulin (IV IG). Mean recovery time (MRT) was 4.4 weeks. Delayed recovery (MRT ≧6 weeks) was noted in patients with predominant distal weakness in the LL (MRT 7.8 weeks; p = 0.001), proximal weakness in the upper limb (UL) (MRT 6 weeks; p = 0.005), autonomic disturbance (MRT 6.5 weeks; p = 0.05), and axonal type GBS (MRT 6 weeks; p = 0.001). Conclusion: The presence of predominant distal weakness in LL, proximal weakness in UL, autonomic disturbance and axonal pattern in NCS predict a poor outcome. Hence we recommend early immunomodulatory therapy in patients presenting with these features.
Neonatal Sepsis 1991–2001: Prevalent Bacterial Agents and Antimicrobial Susceptibilities in Bahrain
Authors: Bindayna Khalid M. , Jamsheer Afaf , Farid Eman , Botta Giuseppe A.
Published: February 2006

Objectives: To investigate the organisms causing neonatal sepsis and their modifications over an extended period, to assess their changing sensitivities to antibiotics and to verify whether the policy for screening pregnant women for group B streptococci (GBS) carriage is desirable in our settings. Subjects and Methods: Medical records of all infants with positive blood culture from the Neonatal Intensive Care Unit at Salmaniya Medical Complex between 1991 and 2001 and Bahrain Defense Force Hospital between 1999 and 2001 were reviewed. Results: Of the 7,978 neonates in both hospitals 335 (4.19%) had culture-proven bacteremia. Gram-positive bacteria were isolated at constant rate over the 11-year period. The main agents isolated were coagulase-negative Staphylococcus (CoNS) in 138 cases (41%), Staphylococcus aureus in 28 newborns (8%) and GBS in 26 patients (7.8%, 0.2/1,000 live births). All of them were sensitive to penicillin G, erythromycin and clindamycin. Gram-negative bacteria were declining but Escherichia coli was isolated in 35 cases (10%). Of special concern is the increasing percentage (5.7%) of Candida isolation. No clear trend toward increasing resistance was observed, although a major difference among the two institutions was evident. Klebsiella and Enterobacter spp. showed resistance to many of the antibiotics tested, thereby posing difficult therapeutic choices. Conclusion: Good quality specimens are essential to evaluate the role of CoNS. The increasing threat of fungal infection must be carefully tackled. Specifically tailored policies for GBS prevention must be defined according to the local epidemiology.
Skeletal Imaging of Gorlin’s Syndrome
Authors: Smith J. , Byun K. , Elgazzar A.H.
Published: February 2006

Objective: To report a case of a patient with many of the common manifestations of Gorlin’s syndrome, a rare inherited condition. Clinical Presentation and Intervention: A 26-year-old female with longstanding left hip pain was referred for bone scintigraphy to find the cause of pain. The findings on bone scintigraphy as well as prior radiographic studies illustrated many of the defining features of Gorlin’s syndrome, i.e. jaw keratocysts, falcine calcifications, short and deformed ribs, Sprengel deformity and a sclerotic bone lesion. The past medical history also revealed dermatologic, cardiac and gynecological findings related to the syndrome. Conclusion: Our case highlights the multisystemic involvement of Gorlin’s syndrome, based particularly on the skeletal findings. Practicing physicians, including imaging specialists, should be familiar with these findings to reach the diagnosis.
Systemic Immunological Response to Exercise in Patients with Chronic Obstructive Pulmonary Disease: What Does It Mean?
Authors: van Helvoort H.A.C. , Heijdra Y.F. , Dekhuijzen P.N.R.
Published: February 2006

Chronic obstructive pulmonary disease (COPD) is no longer seen as a pulmonary disease, but is increasingly associated with systemic effects with important clinical relevance. Systemic immunological changes in COPD patients are characterized by an increased number of circulating inflammatory cells, functional changes of the inflammatory cells, elevated plasma levels of cytokines, and oxidative stress. Physical exercise induces an abnormal systemic inflammatory and oxidative response in COPD patients, which is seen in both the circulation and the peripheral muscles. Although mechanisms and consequences of these effects are not yet fully understood, they could be harmful in COPD patients by inducing damage or functional changes in, for example, skeletal muscles. Whether these changes of the immune system can also affect the susceptibility to infections in these patients is unknown. The concept of COPD as a systemic rather than only a pulmonary disease also opens new perspectives on the development for new therapeutic interventions. The effects of new antioxidative and anti-inflammatory agents are investigated. A better understanding of the complexity of the systemic effects will aid the development of new therapies and management strategies for patients with COPD.
Myocardial Infarction in a Young African-American Male due to Myocardial Bridging
Authors: Balamuthusamy Saravanan , Kosla Sandeep , Benatar Daniel , Arora Rohit R.
Published: February 2006

Myocardial bridging is a clinically uncommon congenital anomaly characterized by tunneling of the coronary artery within the myocardial tissue, usually seen in the left anterior descending artery. Myocardial bridging is associated with altered intracoronary hemodynamics during systole and diastole, determined by the severity and the location of the bridging within the coronary artery. Patients with myocardial bridging may present with angina in the absence of other coronary risk factors which may paradoxically improve with exercise due to an increased intrasystolic pressure, preventing vessel compression. It is uncommon to have bridging in the right coronary artery; it is even more uncommon to have right coronary artery bridging with angina and significant ECG changes. We present a case involving bridging of the right coronary artery with significant symptoms and ECG changes.
Plasma Soluble Adhesion Molecule Levels in Coronary Artery Ectasia
Authors: Yilmaz Hale , Tayyareci Gulsah , Sayar Nurten , Gurkan Ufuk , Tangurek Burak , Asilturk Recep , Ozer Nihat , Aksoy Sukru , Simsek Dilek , Yilmaz Mehmet , Engin Oner , Cagil Aydin
Published: February 2006

Background:Coronary artery ectasia (CAE) is defined as localized or diffuse dilatation of the coronary arteries. There are scarce data about the role of inflammation in CAE. In the present study, the plasma soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) levels in CAE were investigated. Methods: The study population (n = 67) consisted of four groups. Group 1: patients with normal coronary artery (NCA); group 2: patients with isolated ectasia without stenotic lesion; group 3: patients with obstructive coronary artery disease (OCAD) without CAE; group 4: patients with both OCAD and CAE. Results: Plasma concentrations of ICAM-1 and VCAM-1 were higher in patients with isolated ectasia than in cases with NCA (p < 0.001 and p < 0.001, respectively). Compared with OCAD patients, patients with CAE had significantly elevated concentrations of ICAM-1 and VCAM-1 (p < 0.001 and p < 0.05, respectively). The levels of ICAM-1 and VCAM-1 of the CAE and OCAD group were higher than in patients in the OCAD group (p < 0.05 and p < 0.05, respectively). We detected a positive correlation between the presence of CAE and the levels of ICAM-1 and VCAM-1. Multivariate logistic regression analyses revealed a significant independent relation between the presence of CAE and ICAM-1 and VCAM-1. Conclusion: We found elevated plasma levels of ICAM-1 and VCAM-1 in patients with CAE and OCAD + CAE compared with subjects with NCA and OCAD. These data strongly suggest that more severe vascular wall inflammation may play a role in the pathogenesis of CAE.
Delayed Reduction in Left Ventricular Function following Treatment of Non-Hodgkin’s Lymphoma with Chemotherapy and Rituximab, Unrelated to Acute Infusion Reaction
Authors: Kanamori Hiroe , Tsutsumi Yutaka , Mori Akio , Kawamura Takahito , Obara Shinji , Shimoyama Norihiko , Tanaka Junji , Asaka Masahiro , Imamura Masahiro , Masauzi Nobuo
Published: February 2006

We report 3 cases of reduced cardiac function with complications in non-Hodgkin’s lymphoma patients who were treated with rituximab. Patients experienced reduced cardiac functions after the administration of rituximab; there was no evidence of any preceding infusion reactions. Reticulin fiber was observed diffusely in cardiac muscles. Transforming growth factor-β levels were elevated after the administration of rituximab. We believe that continuous elevation of transforming growth factor-β may promote the growth of reticulin fiber in cardiac muscles. Reduction in cardiac functions is a severe complication that must be considered when rituximab is administered.
The Auditory Oddball Paradigm in Patients with Vascular Cognitive Impairment: A Prolonged Latency of the N2 Complex
Authors: van Harten B. , Laman D.M. , van Duijn H. , Knol D.L. , Stam C.J. , Scheltens P. , Weinstein H.C.
Published: February 2006

Objective: The event-related potential (ERP) evoked by the auditory oddball paradigm has been investigated mainly in patients with Alzheimer’s disease and in patients with different causes of subcortical dementia. Subcortical ischemic vascular disease (SIVD) seems to be an important cause of vascular cognitive impairment (VCI) frequently not fulfilling the criteria for dementia. Recognition of VCI is needed in order to provide adequate care and therapy. The aim of this study was to investigate the diagnostic value of the different elements of this response (N1, N2 complex and P3 latencies) in a group of elderly patients with VCI caused by SIVD. Methods: The study population consisted of patients with a clinical and neuropsychological diagnosis of VCI caused by SIVD (n = 38) and healthy control subjects (n = 53) aged 60 years or older. The mean Mini Mental State Examination score of both groups was 27.6, and the mean HIV Dementia Scale score was 6.1 in the patient group and 12.3 in the control group. In all subjects, the ERP was recorded under standardized conditions, and the latencies and amplitudes of N1, N2 and P3 were analyzed by two clinical neurophysiologists in consensus. Both were blinded to the diagnosis. Results: The N2 latency was significantly longer in patients with VCI than in age-matched controls, whereas the latencies of the P3 and N1 were not significantly different. The peak-to-peak amplitude of the N2 complex to the P3 wave was significantly lower in the patient group. White matter abnormalities on MRI were not significantly correlated with the N2 latency. Conclusion: Our findings suggest that the latency of the N2 complex is prolonged and the peak-to-peak amplitude of the N2 complex to the P3 wave is lowered in patients with VCI caused by SIVD.
Involvement of Voltage-Dependent Ca2+ Channel β3 Subunit in the Autonomic Control of Heart Rate Variability
Authors: Wu Tsai-Wen , Ono Kyoichi , Murakami Manabu , Iijima Toshihiko
Published: February 2006

Noradrenaline release from sympathetic nerve terminals is dependent on Ca2+ entry through neuronal voltage-gated N-type Ca2+ channels. The accessory β3 subunits of Ca2+ channels (CaVβ3) are preferentially associated with the α1B subunit to form N-type Ca2+ channels, and are therefore expected to play a functional role in the stimulation-evoked release of noradrenaline. In this study, we employed CaVβ3-null, CaVβ3-overexpressing (CaVβ3-Tg), and wild-type (WT) mice to investigate the possible roles of CaVβ3 in the sympathetic regulation of heart rate in vivo. Telemetry was used to monitor the ECG and both time and frequency domain analyses were carried out to evaluate heart rate variability. In the frequency domain analysis, power spectral density of the RR interval series was computed using the fast Fourier transform algorithm. The resting heart rate was increased in CaVβ3-Tg mice compared with both CaVβ3-null and WT mice. Mice overexpressing CaVβ3 displayed decreased heart rate variability, which was measured by the time domain analysis of the standard deviation of RR intervals. In the frequency domain analysis, CaVβ3-Tg mice showed decreased spectral powers compared with WT and CaVβ3-null mice. Pharmacological blockade of β-adrenergic receptors with metoprolol decreased the heart rate in all genotypes, but the extent of the decrease was most obvious in CaVβ3-Tg mice. On the other hand, the spectral powers were decreased in response to parasympathetic blockade (atropine) in WT and CaVβ3-Tg mice. These results indicate the functional roles of CaVβ3 in regulating sympathetic nerve signaling.
Insulin-Lowering Agents Inhibit Synthesis of Testosterone in Ovaries of DHEA-Induced PCOS Rats
Authors: Misugi Takuya , Ozaki Koji , El Beltagy Khaled , Tokuyama Osamu , Honda Ken-ichi , Ishiko Osamu
Published: February 2006

Background: Insulin-lowering agents are reported to be useful in treating polycystic ovary syndrome (PCOS) anovulation. It has been suggested that lower insulin levels secondarily affect ovarian tissue, although the direct mechanism of action has not yet been verified. Here we investigated if these agents directly affect the ovary. Methods: Thirty female Wister rats were studied. Six control rats were injected subcutaneously with 0.2 ml sesame oil, while 24 rats used as PCOS models were injected subcutaneously with dehydroepiandrosterone (DHEA) and divided into four groups. Six rats were injected with only DHEA, while the remaining 18 rats received metformin, pioglitazone or troglitazone. The ovaries were immunohistochemically stained with anti- testosterone and anti-17β-HSD antibodies, and then evaluated for morphological changes. Results: In the DHEA administration group, the number of atretic follicles significantly increased compared to that of control rats. The insulin-lowering agents did not improve the multicystic appearance. Serum testosterone concentrations significantly increased with DHEA administration, but the increase was inhibited by oral administration of insulin-lowering agents. Testosterone deposits in ovarian tissue were also reduced by feeding rats insulin-lowering agents. Conclusion: Insulin-lowering agents affected ovarian tissue by inhibiting testosterone biosynthesis in vivo.
Vaginal Ultrasonographic and Hysterosonographic Evaluation of the Low Transverse Incision after Caesarean Section: Correlation with Gynaecological Symptoms
Authors: Menada Valenzano Mario , Lijoi Davide , Mistrangelo Emanuela , Costantini Sergio , Ragni Nicola
Published: February 2006

Aim: We investigated whether there is a correlation between morphological changes of the lower uterine segment after caesarean section (CS), visualized by means of either a transvaginal sonography (TVS) or a sonohysterography (SHG), and the frequency of abnormal uterine bleedings reported by the women. Methods: By means of a random selection of our population, anamnesis, medical records, and TVS and SHG images of the lower uterine segment were collected in 217 women (116 with previous CS and 101 with previous vaginal birth), and an observational case-control study was performed. Results: The uterine incision was identified in almost all women after CS (102/116) using TVS. It was observed that abnormal uterine bleeding was significantly more frequent in the CS group in comparison with the group of women who delivered vaginally. A correlation between the presence of abnormal uterine bleeding and the presence of significant sonographic findings in the lower uterine transverse incision in the women after CS was found. In the CS group, TVS findings were confirmed by those obtained by SHG, and, with this technique, a triangular anechoic area at the presumed site of incision (the niche) was identified in 69 of the 116 women (59.5%). Conclusions: In this study, we found a correlation between abnormal uterine bleeding and sonographic findings in women after CS. This correlation appears to be more significant in women who had CS 5–10 years ago. A significant difference exists between the CS group and the group of women who delivered vaginally for both frequency of abnormal uterine bleeding and sonographic findings.
Cognitive Impairment Related to Apathy in Early Huntington’s Disease
Authors: Baudic Sophie , Maison Patrick , Dolbeau Guillaume , Boissé Marie-Françoise , Bartolomeo Paolo , Dalla Barba Gianfranco , Traykov Latchezar , Bachoud-Lévi Anne-Catherine
Published: February 2006

Objective: To investigate the relationships between cognitive impairment and apathy in patients with early Huntington’s disease (HD) and to further explore the influence of depression on the outcome of cognitive changes associated with apathy. Methods: We included 36 early HD patients, among them 20 were apathetic (HDA) and 16 were not (HDnA). The two groups were matched by age, education and severity of disease. Cognitive functions were evaluated by a comprehensive neuropsychological battery that measures memory, attention, executive function, language and visuospatial abilities. Results: The HDA patients had significantly lower scores on memory, attention and executive function tests when compared with the HDnA patients (p values <0.05). We compared the performance of patients with (50%) and without depression on cognitive tasks and showed that depression per se did not influence performance. Finally, the results demonstrate that interactions between apathy and motor disturbance have a significant effect on cognitive impairment in HD. Discussion: The presence of apathy is associated with more severe deficits of attention, executive function and episodic memory in early HD patients. Furthermore, the findings suggest that depression has little or no effect on cognitive deficits. Finally, apathy increased in parallel with both motor and cognitive dysfunction.
The Effects of Methylene Blue on Lung Injury in Septic Rats
Authors: Demirbilek S. , Sizanli E. , Karadag N. , Karaman A. , Bayraktar N. , Turkmen E. , Ersoy M.O.
Published: February 2006

Purpose: We aimed to investigate the effects of methylene blue (MB) on NO production, myeloperoxidase (MPO) activity, antioxidant status and lipid peroxidation in lung injury during different stages of sepsis in rats. Material and Methods: Rats were randomly divided into 4 groups (n = 20): group C, sham operated; group CMB, sham operated and receiving MB (25 mg/kg, i.p.); group S, sepsis; group SMB, sepsis and receiving MB (25 mg/kg, i.p.). Sepsis was induced by cecal ligation and puncture (CLP). The MB dose was administered after CLP. Each group was subdivided into two subgroups (n = 10) which were sacrificed at 9 or 18 h after the surgical procedure. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and MPO activity, total nitrite/nitrate and malondialdehyde (MDA) in the lung tissue were measured. Lung injury was graded from 1 (injury to 25% of the field) to 4 (diffuse injury) by the pathologist. Results: In group SMB, while SOD and CAT increased in both early and late sepsis periods, GSH-PX increased significantly only in the early sepsis period when compared with group S. Increase in lung MPO activity after CLP-induced sepsis was prevented by MB administration. MB significantly decreased to nitrite/nitrate and MDA levels both in early and late sepsis periods when compared with group S (p < 0.05). Group S showed a marked increase in neutrophil infiltration into the interstitial space and thickening of the alveolar septa, whereas the alveolar damage score was lower in the SMB group (p < 0.05). Conclusion: MB reduced the MPO activity and lipid peroxidation by both decreasing oxidative stress and NO overproduction in the lungs, which resulted in the attenuation of lung injury after CLP-induced sepsis in rats.
Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
Authors: Pierson Diane M. , Ionescu Diana , Qing Gefei , Yonan Abdullah M. , Parkinson Kent , Colby Thomas C. , Leslie Kevin
Published: February 2006

Hermansky-Pudlak syndrome (HPS) is a rare heterogeneously inherited autosomal recessive group of disorders presenting with oculocutaneous albinism, bleeding diathesis and pulmonary disease. HPS is thought to occur as a consequence of disturbed formation or trafficking of intracellular vesicles, most importantly, melanosomes, platelet dense granules and lysosomes. The latter finding, in particular, contributes much to the morbidity associated with the disease, as ceroid lipofuscin deposits in lysosomes affect many organ systems. This is especially problematic in the lungs where it is often associated with pulmonary fibrosis and premature death. Currently, there are 7 known HPS genes in humans. In the mouse, at least 16 known HPS genes produce HPS-mutant phenotypes. The HPS gene mutation is considered to be one of the most prevalent single-gene disorders in northwest Puerto Rico, home to the largest cohort of known patients. In HPS, interventions addressing the bleeding diathesis and pulmonary fibrosis are often disappointingly ineffectual. Pirfenidone, a novel compound with documented anti-inflammatory, antioxidant and antifibrotic effects, appears to hold promise in delaying or preventing fibrosis. To date, there has been one successful lung transplant performed on a patient with HPS. We present a patient with HPS and review the current literature on our understanding of this rare disorder.
TICAD after 10 Years: A Preliminary Assessment and Proposals for the Future
Authors: Horiuchi Shinsuke
Published: February 2006

Ten years have passed since the first Tokyo International Conference on African Development (TICAD) was held in 1993. Since then, TICAD II, III, and Ministerial Level Meetings followed with each meeting producing either internationally agreed upon documents or action plans. There are many similar initiatives for development of African countries. In fact, cynics in and out of Africa castigate TICAD and other international initiatives as waste of time and energy because they have not been associated with any useful and concrete projects and the overall growth of Africa. This paper sets out to assess positive contributions that have been made by international initiatives including TICAD. The premise of this paper is that we are all in the game of globalization and development of Africa is a sub-game of globalization. Any game is played by the rules. Functions of international conferences for development could be defined in terms of setting development rules, guiding strategies and providing opportunities to build capacity for development. The paper examines what TICAD has offered to African countries as well as international community over ten years within this simple framework of analysis.