bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical state for overconsolidated unsaturated silty soil
Authors: Estabragh A. R. , Javadi A. A.
Published: April 2008

The critical state concepts have been investigated for an overconsolidated unsaturated silty soil through a comprehensive set of controlled suction triaxial laboratory experiments. The experimental tests were conducted in a specially designed double-walled Bishop and Wesley triaxial cell on samples of unsaturated silty soil. Isotropic loading, unloading, and triaxial drained shear tests were performed on samples of unsaturated silty soil with different overconsolidation ratios at various suctions. The data from the triaxial tests were used in the development of a critical state framework for overconsolidated unsaturated silty soil. The framework is defined in terms of four state variables: mean net stress (p'), deviator stress (q), suction (s), and specific volume (v). The results show that the critical state lines in q:p' space for different soil suctions are not parallel and merge with each other. The slopes and intercepts of these lines are functions of suction. However, the critical state lines are nearly parallel in the v – ln p' plane except under saturation conditions, and the slope and intercept of these lines are also functions of suction.
Production and characterization of polyhydroxyalkanoates inPseudomonas aeruginosaATCC 9027 from glucose, an unrelated carbon source
Authors: Rojas-Rosas Oscar , Villafaña-Rojas Juan , López-Dellamary Fernando A. , Nungaray-Arellano Jesús , González-Reynoso Orfil
Published: April 2008

The production and characterization of polyhydroxyalkanoic acids (PHAs) from glucose in Pseudomonas aeruginosa ATCC 9027 is described. We determined that the synthesis of PHAs was not due to a complete lack of nitrogen source, as previously reported for other microorganisms. The synthesis of PHAs was observed during exponential growth and it depended on the carbon/nitrogen ratio in the culture. More significantly, the specific PHA accumulation rate in this phase was higher than that observed in the storage phase. This phenomenon was a consequence of higher extracellular production rates of gluconate and 2-ketogluconate detected during the storage phase. Therefore, the production of those acids decreased the synthesis of PHAs in P. aeruginosa. The maximum percentage of PHA accumulation obtained was 10.8% of the cell dry matter when all the glucose was consumed. The monomer composition of this PHA consisted only of saturated 3-hydroxy fatty acids (octanoic, decanoic, and dodecanoic acids) as shown by gas chromatography – mass spectroscopy and nuclear magnetic resonance analyses, where 3-hydroxydecanoic acid was the main component because of the high affinity of its PhaC synthase for this monomer. The physical properties of this PHA were determined by differential scanning calorimetry and gel permeation chromatography.
Molecular and biochemical detection of fengycin- and bacillomycin D-producing Bacillus spp., antagonistic to fungal pathogens of canola and wheat
Authors: Ramarathnam Rajesh , Bo Shen , Chen Yu , Fernando W.G. Dilantha , Xuewen Gao , de Kievit Teresa
Published: April 2008

Bacillus species are well known for their ability to control plant diseases through various mechanisms, including the production of secondary metabolites. Bacillus subtilis DFH08, an antagonist of Fusarium graminearum , and other Bacillus spp. that are antagonists of common fungal pathogens of canola were screened for peptide synthetase biosynthetic genes of fengycin and bacillomycin D. Specific polymerase chain reaction (PCR) primers identified B. subtilis strains DFH08 and 49 for the presence of the fenD gene of the fengycin operon. Bacillus cereus DFE4, Bacillus amyloliquefaciens strains DFE16 and BS6, and B. subtilis 49 were identified for the presence of the bamC gene of the bacillomycin D synthetase biosynthetic operon. Both fengycin and bacillomycin D were detected in the culture extract of strain Bs49, characterized through MALDI–TOF–MS (matrix-assisted laser desorption ionization – time of flight – mass spectrometry), and their antifungal activities demonstrated against F. graminearum and Sclerotinia sclerotiorum . This study designed and used specific PCR primers for the detection of potential fengycin- and bacillomycin D-producing bacterial antagonists and confirmed the molecular detection with the biochemical detection of the corresponding antibiotic produced. This is also the first report of a B. cereus strain (DFE4) to have bacillomycin D biosynthetic genes. Bacteria that synthesize these lipopeptides could act as natural genetic sources for genetic engineering of the peptide synthetases for production of novel peptides.
NUMBER THEORETIC PROPERTIES OF WRONSKIANS OF ANDREWS–GORDON SERIES
Authors: MILAS ANTUN , MORTENSON ERIC , ONO KEN
Published: April 2008

For positive integers 1 ≤ i ≤ k, we consider the arithmetic properties of quotients of Wronskians in certain normalizations of the Andrews–Gordon q-series [Formula: see text] This study is motivated by their appearance in conformal field theory, where these series are essentially the irreducible characters of [Formula: see text] Virasoro minimal models. We determine the vanishing of such Wronskians, a result whose proof reveals many partition identities. For example, if Pb(a;n) denotes the number of partitions of n into parts which are not congruent to 0, ±a ( mod b), then for every positive integer n, we have [Formula: see text] We also show that these quotients classify supersingular elliptic curves in characteristic p. More precisely, if 2k + 1 = p, where p ≥ 5 is prime, and the quotient is non-zero, then it is essentially the locus of supersingular j-invariants in characteristic p.
SEMIGROUP PROPERTIES OF N-ARY OPERATIONS ON FINITE SETS
Authors: Butkote R. , Denecke K. , Ratanaprasert Ch.
Published: April 2008

A clone is a set of operations defined on a base set A which is closed under composition and contains all the projection operations. There are several ways to regard a clone as an algebraic structure (see e.g. [3]). If f, g1,…,gn: An→ A are n-ary operations defined on A, then by Sn(f, g1… , gn)(a1… , an) := f(g1(a1,…,an),…,gn(a1,…,an)) for all a1,…, an∈ A an (n + 1)-ary operation on the set On(A) of all n-ary operations can be defined. From this operation one can derive a binary operation + defined by f + g := Sn(f, g,…,g) and obtains a semigroup (On(A);+). The collection of all clones of operations on a finite set forms a complete lattice. This lattice is well-described ([4], [5]) if |A| = 2. If |A| > 2, this lattice is uncountably infinite and very complex. In this paper instead of clones we study semigroups of n-ary operations, i.e. subsemigroups of the semigroup (On(A); +) and their properties. We look for idempotent and regular elements of (On(A); +), consider Green's relations for the semigroup (On(A); +), characterize all constant subsemigroups of (On(A);+), all semilattices, rectangular bands and normal bands contained in (On(A);+).
MINIMALITY AND MAXIMALITY OF ORDERED QUASI-IDEALS IN ORDERED SEMIGROUPS
Authors: Iampan Aiyared
Published: April 2008

The aim of this paper is to study the concept of (0-)minimal and maximal ordered quasi-ideals in ordered semigroups that are studied analogously to the concept of minimal and maximal ordered left ideals in ordered semigroups considered by Cao and Xu [2].
ON THE EDGE-CONNECTIVITY OF CARTESIAN PRODUCT GRAPHS
Authors: Klavžar Sandi , Špacapan Simon
Published: April 2008

A short proof for the closed expression of the edge-connectivity of Cartesian product graphs is given and the structure of minimum edge cuts is described. It is also proved that the connectivity and edge-connectivity of an arbitrary Cartesian power equals its minimum degree.
Salmonella entericaserovar Typhimurium modulates P-glycoprotein in the intestinal epithelium
Authors: Siccardi Dario , Mumy Karen L. , Wall Daniel M. , Bien Jeffrey D. , McCormick Beth A.
Published: April 2008

Studies over the last decade have shown that Salmonella enterica serovar Typhimurium ( S. typhimurium) is able to preferentially locate to sites of tumor growth and modulate (shrink) the growth of many cancers. Given this unique association between S. typhimurium and cancer cells, the objective of this study was to investigate the capacity of this microorganism to modulate the plasma membrane multidrug resistance (MDR) protein P-glycoprotein (P-gp), an ATP-binding cassette transporter responsible for effluxing many cancer drugs. Using an in vitro model of S. typhimurium infection of polarized human cancer intestinal cell lines, we have found that this enteric pathogen functionally downregulates the efflux capabilities of P-gp. Specifically, we show that S. typhimurium infection of human intestinal cancer cells results in the enhanced intracellular accumulation of a number of P-gp substrates that corresponds to the posttranscriptional downregulation of P-gp expression. Furthermore, cells expressing small interfering RNAs against MDR1, the gene encoding P-gp, were significantly more susceptible to the cytotoxic effects of bacterial infection. This result is consistent with our observation that S. typhimurium was significantly less able to invade cells overexpressing MDR1. Taken together, these results reveal a novel role for P-gp in the maintenance of homeostasis in the gastrointestinal tract in regard to bacterial infection. Thus the regulation of P-gp by S. typhimurium has important implications not only for the development of new cancer therapeutics aimed at reversing drug resistance but also in the understanding of how microbes have evolved diverse strategies to interact with their host.
Wave reflection augments central systolic and pulse pressures during facial cooling
Authors: Edwards David G. , Roy Matthew S. , Prasad Raju Y.
Published: April 2008

Cardiovascular events are more common in the winter months, possibly because of hemodynamic alterations in response to cold exposure. The purpose of this study was to determine the effect of acute facial cooling on central aortic pressure, arterial stiffness, and wave reflection. Twelve healthy subjects (age 23 ± 3 yr; 6 men, 6 women) underwent supine measurements of carotid-femoral pulse wave velocity (PWV), brachial artery blood pressure, and central aortic pressure (via the synthesis of a central aortic pressure waveform by radial artery applanation tonometry and generalized transfer function) during a control trial (supine rest) and a facial cooling trial (0°C gel pack). Aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform. Measurements were made at baseline, 2 min, and 7 min during each trial. Facial cooling increased ( P < 0.05) peripheral and central diastolic and systolic pressures. Central systolic pressure increased more than peripheral systolic pressure (22 ± 3 vs. 15 ± 2 mmHg; P < 0.05), resulting in decreased pulse pressure amplification ratio. Facial cooling resulted in a robust increase in AI and a modest increase in PWV (AI: −1.4 ± 3.8 vs. 21.2 ± 3.0 and 19.9 ± 3.6%; PWV: 5.6 ± 0.2 vs. 6.5 ± 0.3 and 6.2 ± 0.2 m/s; P < 0.05). Change in mean arterial pressure but not PWV predicted the change in AI, suggesting that facial cooling may increase AI independent of aortic PWV. Facial cooling and the resulting peripheral vasoconstriction are associated with an increase in wave reflection and augmentation of central systolic pressure, potentially explaining ischemia and cardiovascular events in the cold.
Physical exercise improves plasmatic levels of IL-10, left ventricular end-diastolic pressure, and muscle lipid peroxidation in chronic heart failure rats
Authors: Nunes R. B. , Tonetto M. , Machado N. , Chazan M. , Heck T. G. , Veiga A. B. G. , Dall'Ago P.
Published: April 2008

Chronic heart failure (CHF) is characterized by left ventricular dysfunction, resulting in hemodynamic changes, sustained inflammatory state, as well as increase in oxidative stress. Physical exercise has been described as an important nonpharmacological procedure in the treatment of CHF, contributing to the improvement of the clinical outcomes in this disease. This study evaluated the effects of physical training on hemodynamics, muscle lipid peroxidation, and plasmatic levels of IL-10 in CHF rats. The left coronary artery was ligated to induce CHF, or sham operation was performed in control groups. Rats were assigned to one of four groups: trained CHF (T-CHF, n = 10), sedentary CHF (S-CHF, n = 10), trained sham (T-Sham, n = 10), or sedentary sham (S-Sham, n = 10). Trained animals had carried out a swimming protocol, 60 min/day, 5 days/wk, during 8 wk, whereas sedentary animals remained without training. Eight weeks of physical training promoted an improvement of diastolic function represented by a reduction of the left ventricular end-diastolic pressure in the T-CHF group compared with the S-CHF group ( P < 0.05). Lipid peroxidation evaluated in gastrocnemius muscle using thiobarbituric acid reactive substance assay was higher in the S-CHF group compared with all other groups ( P < 0.05). However, there were no differences between T-CHF compared with S-Sham and T-Sham groups. The plasmatic levels of IL-10 were lower in the S-CHF group compared with all other groups ( P < 0.05). These findings demonstrate that regular physical training using a swimming protocol, with duration of 8 wk, improves the cardiac function and the anti-inflammatory response and reduces muscle cellular damage.
Key aspects of phrenic motoneuron and diaphragm muscle development during the perinatal period
Authors: Mantilla Carlos B. , Sieck Gary C.
Published: April 2008

At the time of birth, respiratory muscles must be activated to sustain ventilation. The perinatal development of respiratory motor units (comprising an individual motoneuron and the muscle fibers it innervates) shows remarkable features that enable mammals to transition from in utero conditions to the air environment in which the remainder of their life will occur. In addition, significant postnatal maturation is necessary to provide for the range of motor behaviors necessary during breathing, swallowing, and speech. As the main inspiratory muscle, the diaphragm muscle (and the phrenic motoneurons that innervate it) plays a key role in accomplishing these behaviors. Considerable diversity exists across diaphragm motor units, but the determinant factors for this diversity are unknown. In recent years, the mechanisms underlying the development of respiratory motor units have received great attention, and this knowledge may provide the opportunity to design appropriate interventions for the treatment of respiratory disease not only in the perinatal period but likely also in the adult.
Increased ventilation does not impair maximal voluntary contractions of the elbow flexors
Authors: Smith Janette L. , Butler Jane E. , Martin Peter G. , McBain Rachel A. , Taylor Janet L.
Published: April 2008

Exercise performance is impaired by increased respiratory work, yet the mechanism for this is unclear. This experiment assessed whether neural drive to an exercising muscle was affected by cortically driven increases in ventilation. On each of 5 days, eight subjects completed a 2-min maximal voluntary contraction (MVC) of the elbow flexor muscles, followed by 4 min of recovery, while transcranial magnetic stimulation tested for suboptimal neural drive to the muscle. On 1 day, subjects breathed without instructions under normocapnia. During the 2-min MVC, ventilation was ∼3.5 times that at rest. On another day, subjects breathed without instruction under hypercapnia. During the 2-min MVC, ventilation was ∼1.5 times that on the normocapnic day. On another 2 days under normocapnia, subjects voluntarily matched their breathing to the uninstructed breathing under normocapnia and hypercapnia using target feedback of the rate and inspiratory volume. On a fifth day under normocapnia, the volume feedback was set to each subject's vital capacity. On this day, ventilation during the 2-min MVC was approximately twice that on the uninstructed normocapnic day (or ∼7 times rest). The experimental manipulations succeeded in producing voluntary and involuntary hyperpnea. However, maximal voluntary force, fatigue and voluntary activation of the elbow flexor muscles were unaffected by cortically or chemically driven increases in ventilation. Results suggest that any effects of increased respiratory work on limb exercise performance are not due to a failure to drive both muscle groups optimally.
Effects of Ephedrine on Human Nasal Ciliary Beat Frequency
Authors: Zhang Luo , Han Demin , Song Xiaohong , Wang Hong , Wang Kuiji , Liu Zhongyan
Published: April 2008

The purpose of this study was to investigate the effects of ephedrine, an α,β-adrenoceptor agonist, on the regulation of human nasal ciliary beat frequency (CBF). Changes in (cultured) human nasal CBF in response to 0.25, 0.5, 1.0 and 2.0% ephedrine were quantified by using high-speed (240 frames per second) digital microscopy combined with a beat-by-beat CBF analysis. At ∼25°C, we found that ephedrine induces an instant and moderate increase in human nasal CBF followed by an inhibitory response. With concentrations ranging from 0.25 to 2.0%, while the increment is independent of ephedrine concentration, the inhibitory effect is dependent on the concentration of ephedrine. Based on these results we propose that the clinically used concentration of ephedrine, 0.5%, has maximum stimulatory effect without obvious inhibitory effect on (cultured) human nasal CBF.
Enhanced Efficacy of Amodiaquine and Chlorpheniramine Combination over Amodiaquine Alone in the Treatment of Acute Uncomplicated Plasmodium falciparum Malaria in Children
Authors: Falade C.O. , Michael S.O. , Oduola A.M.J.
Published: April 2008

Objective: To evaluate the comparative efficacy of amodiaquine (AMQ) alone and the combination of AMQ and chlorpheniramine (CP) in the treatment of acute uncomplicated malaria in children. Subjects: Of the 110 children enrolled in the study, 103 with acute uncomplicated malaria, aged 6 months to 12 years, were evaluated using the 14-day modification of the WHO field test. The patients were randomized to 2 groups. Group 1 received supervised treatment with AMQ alone (10 mg AMQ base/kg daily for 3 days), while group 2 received supervised treatment with AMQ (same dose as group 1) plus CP (AMQCP) for 7 days. Results: Both treatment regimens were well tolerated and no patient was withdrawn as a result of recurrent vomiting or drug-related adverse events. There was no significant difference in mean fever and parasite clearance times. The cure rates at day 7 were 90.2 versus 100% (ρ = 0.027) for AMQ versus AMQCP, while the day 14 cure rates were 85.9 versus 98.1% for AMQ versus AMQCP, respectively (ρ = 0.016). Conclusion: The combination of AMQ plus CP proved significantly more effective than AMQ alone in the treatment of acute uncomplicated falciparum malaria, most probably due to the enhancement of the antimalarial effect of AMQ by CP. The combination of AMQCP could be a better alternative to AMQ alone as a companion drug in artemisinin-based combination therapies.
Study Motives and Career Choices of Iranian Dental Students
Authors: Khami M.R. , Murtomaa H. , Jafarian M. , Vehkalahti M.M. , Virtanen J.I.
Published: April 2008

Objectives: To investigate the study motives and career choices of Iranian senior dental students in relation to their background factors. Subjects and Methods: During the spring term 2005, a questionnaire survey was administered to 327 senior dental students in seven randomly selected state dental schools in Iran. The questionnaire requested information on age, gender, parents’ employment in dentistry, previous education and employment in dental hygiene, study motives, and career choices. Statistical analyses were made using independent sample t test, factor analysis, and binary logistic regression model. Results: Based on the factor analysis, which explained 73% of the total variance, five motive dimensions were identified: altruism and intellectual challenges, characteristics of the profession, social status and security, other person’s recommendation, and failure to be admitted to other study programmes. The mean for the ‘characteristics of the profession’ dimension was lower among the students with at least one parent employed in dentistry (p = 0.03). The ‘altruism and intellectual challenges’ dimension was reported to be more influential by the students with background in dental hygiene (32 students) compared to the others (p < 0.001). Engaging in postgraduate studies was the first career preference of 189 (70%) of the respondents. Those with a background in dental hygiene were less inclined to enter postgraduate courses (p < 0.001), but more eager to be employed in either the public or the private sector (p < 0.001), and to enter the community oral health and research field (p < 0.001) than the others. Conclusion: Personal characteristics and motives of the students play a major role in shaping their career preferences.
Headache as a First Manifestation of Vogt-Koyanagi-Harada Disease
Authors: Kosma Katerina K. , Kararizou Evangelia , Markou Ioannis , Eforakopoulou Evanthia , Kararizos Grigoris , Mitsonis Charalampos , Gkiatas Konstantinos
Published: April 2008

Objectives: To describe headache as an initial presentation of Vogt-Koyanagi-Harada (VKH) disease. Clinical Presentation and Intervention: A 56-year-old man initially presented with a 6-month duration of a continuous, diffuse headache of mild to moderate and sometimes of severe intensity. A CT of the brain was normal. Neurological examination was normal, including absence of symptoms and signs of meningismus. During the last 2 months, an intermittent eye pain, redness, and gradual loss of vision in both eyes was detected and subsequently he had tinnitus, malaise, nausea and mild meningismus. He was diagnosed as having VKH disease. Ophthalmologic examination revealed high intraocular pressure, requiring trabeculectomy with surgical iridectomy. The patient is now being treated with systemic steroids. Conclusion: VKH disease may initially present as sustained headache, without specific ophthalmologic symptoms and it should be considered in the differential diagnosis in patients with atypical but relentless headache.
Epilepsy in a Young Adult Caused by L-2-Hydroxyglutaric Aciduria: A Case Report
Authors: Periasamy Vembu , Rudwan Mohd , Yadav Girish , Khan Riyadh A.
Published: April 2008

Objective: To report the importance of a rare organic acid metabolic disorder, L-2-hydroxyglutaric aciduria, and its characteristic neuroimaging cerebral white matter abnormalities in a case of epilepsy. Subject and Methods: A 19-year-old male presented with an 11-year history consisting of school failures, intellectual deterioration and generalized tonic-clonic convulsions. Results: Neurological examination showed mental subnormality, mild dysarthria and bilateral pyramidal signs. Computed tomography and magnetic resonance imaging (MRI) of the brain showed characteristic white matter lesions, suggestive of L-2-hydroxyglutaric aciduria. The diagnosis of this disease was confirmed by elevated urinary concentrations of L-2-hydroxyglutaric acid. The epilepsy was partially controlled with antiepileptic drugs. Conclusion: This report indicates the importance of routine examination of urinary organic acids in children and young adults presenting with chronic encephalopathy and epilepsy with characteristic MRI white matter lesions. L-2-hydroxyglutaric aciduria should be considered as one of the differential diagnoses of epilepsy.
Clinical Description of Seizures in Patients with Systemic Lupus Erythematosus
Authors: González-Duarte Alejandra , Cantú-Brito Carlos Gerardo , Ruano-Calderón Luis , García-Ramos Guillermo
Published: April 2008

Objective: To evaluate the frequency of and risk factors for epileptic seizures in patients with systemic lupus erythematosus (SLE) in a large cohort series. Methods: One thousand two hundred patients with SLE were analyzed. The type and frequency of risk factors for seizures associated with SLE were studied and compared with two other series reported in the literature. Results: One hundred and forty-two patients had seizures. Seventy-five patients were studied with a mean follow-up of 5 years from the first seizure episode. Fifty-eight (77%) patients had tonic-clonic seizures, 9 (12%) complex partial seizures (PS), 5 (7%) simple partial motor seizures and 3 (4%) secondary tonic-clonic seizures. In 41 (54%) patients, the seizures occurred within the first year of the SLE diagnosis. Recurrence occurred in 40 (53%) patients, and was associated with PS in 14 (35%; p = 0.006) and time of seizures with SLE onset in 5 (12.5%; p = 0.05). Less than one third of the patients had positive antiphospholipid antibodies. A concurrent infection was present in 16 (21%) patients. Conclusions: Epileptic seizures were more common during the first year after SLE diagnosis. Neither infection nor antiphospholipid syndrome was associated with the occurrence of seizures.
Localized Giant Inflammatory Polyposis of the Ileocecum Associated with Crohn’s Disease: Report of a Case
Authors: Fumimoto Yuichi , Tamagawa Koji , Ito Toshinori , Sawa Yoshiki , Nishida Toshirou
Published: April 2008

Although inflammatory polyposis is one of the common complications in patients with inflammatory bowel disease, it is rare that each poly grows up to more than 1.5 cm. We describe a case of localized giant inflammatory polyposis of the ileocecum associated with Crohn’s disease. A 40-year-old man who had been followed for 28 years because of Crohn’s disease was hospitalized for right lower abdominal pain after meals. Barium enema and colonoscopy showed numerous worm-like polyps in the ascending colon which grew up to the hepatic flexure of the colon from the ileocecum, causing an obstruction of the ileocecal orifice. Since histology of a biopsy specimen taken from the giant polyps showed no dysplasia, he was diagnosed with ileus due to the localized giant inflammatory polyposis. A laparoscopically assisted ileocecal resection was performed. The resected specimen showed that the giant polyps grew up into the ileocecum. Histological examination revealed inflammatory polyposis without neoplasm. Generally, conservative treatment is indicated for localized giant inflammatory polyposis because this lesion is regarded as benign. However, occasionally serious complications arise, requiring surgical treatment.
Patient-Reported Outcomes of Deferasirox (Exjade®, ICL670) versus Deferoxamine in Sickle Cell Disease Patients with Transfusional Hemosiderosis
Authors: Vichinsky Elliott , Pakbaz Zahra , Onyekwere Onyinye , Porter John , Swerdlow Paul , Coates Thomas , Lane Peter , Files Beatrice , Mueller Brigitta U. , Coïc Lena , Forni Gian Luca , Fischer Roland , Marks Peter , Rofail Diana , Abetz Linda , Baladi Jean-Francois
Published: April 2008

Background/Aims: There is increasing evidence demonstrating the value of transfusions in sickle cell disease (SCD). However, resultant iron overload can be life threatening if untreated. Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment. Methods: As part of a phase II trial, SCD patient-reported outcomes were evaluated. One hundred and ninety-five patients were randomized (2:1) to receive oral deferasirox (5–30 mg/kg/day) or deferoxamine (20–50 mg/kg, 5 days per week); 121 had previously received deferoxamine. Results: At each time point, significantly more patients who had previously received deferoxamine were ‘satisfied/very satisfied’ with deferasirox, or found treatment to be ‘convenient/very convenient’ compared with deferoxamine (p < 0.001). In these patients, fewer hours were lost from daily activities with deferasirox than deferoxamine treatment. Most patients (77%) preferred deferasirox, and more were willing to continue taking deferasirox than deferoxamine at end-of-study (84 vs. 11%, respectively). Conclusions: Patients with SCD are therefore more satisfied with deferasirox, which has a lower impact on daily activities than deferoxamine. Given the high levels of satisfaction, it is likely that quality of life will be improved. These results also suggest that treatment adherence with deferasirox may be better than with deferoxamine, which should lead to improved long-term outcomes.
Relationship between Theory of Mind and Executive Function in Schizophrenia: A Systematic Review
Authors: Pickup Graham J.
Published: April 2008

Background: There is good agreement that Theory of Mind (ToM) and executive function are impaired to some degree in many patients with schizophrenia. However, few studies have set out to investigate as a primary aim the relationship between these 2 cognitive domains in the disorder. Methods: A systematic review was carried out to identify all published studies in which tests of ToM and executive function were administered to individuals with schizophrenia, and in which the relation between scores was reported. Results: The review revealed 17 relevant studies, of which 8 reported the relation between ToM and executive function using multivariate statistics. These all concurred in showing that ToM ability continued to predict an individual having schizophrenia (rather than being a control participant) once executive function was controlled for. Conclusions: There is very good agreement that ToM and executive function impairments in schizophrenia are independent of one another. Implications are discussed for the putative brain systems involved in the disorder and for its cognitive rehabilitation.
Self-Injurious Behavior in Adolescent Girls
Authors: Ohmann S. , Schuch B. , König M. , Blaas S. , Fliri C. , Popow C.
Published: April 2008

Background: Self-injurious behavior (SIB) is increasingly popular in psychically ill adolescents, especially in girls with posttraumatic stress (PTSD) and personality disorders. Adolescents with SIB frequently exhibit neurofunctional and psychopathological deficits. We speculated that specific neuropsychological deficits and temperamental factors could predispose patients to SIB and prospectively explored adolescent psychiatric patients with and without SIB in order to find out differences in psychopathology, and neuropsychological or temperamental factors. Sampling and Methods: Ninety-nine psychically ill adolescent girls with SIB, aged 12–19 years and treated at our clinic, were prospectively recruited during a period of 5.5 years (1999–2005). The clinical (ICD-10) diagnoses were mainly substance abuse, eating disorders, depression, PTSD and personality disorders. The control group was also prospectively recruited during the same period and consisted of 77 girls with similar diagnoses and ages but no SIB. All patients were subjected to the same selection of clinical and neuropsychological tests, mainly self-rating questionnaires and tests evaluating executive functions. Results: Adolescent girls with psychiatric disease and SIB were more severely traumatized and depressed. They reported severe emotional and behavioral problems and deficits of self-regulation. In addition, their parents more frequently had psychiatric problems. Temperament, intelligence, investigated executive functions and presence of dissociative symptoms were not different in patients with and without SIB. Conclusions: We could not verify our primary hypothesis that SIB is related to specific neuropsychological deficits or temperamental factors. SIB was associated with traumatic experience, depression, problems of self-regulation and parental psychiatric disease. The prevention of SIB should therefore focus on improving affect regulation, the management of emotional distress and problem-solving strategies.
Dihydroartemisinin Potentiates the Cytotoxic Effect of Temozolomide in Rat C6 Glioma Cells
Authors: Huang Xiao-Jia , Li Cheng-Tan , Zhang Wei-Ping , Lu Yun-Bi , Fang San-Hua , Wei Er-Qing
Published: April 2008

Gliomas are the most common primary brain tumor in adults, but the efficacy of chemotherapy is limited. Artemisinin and its analogs, such as dihydroartemisinin (DHA), can kill cancer cells via generating free radicals. In the present study, we determined whether DHA at low concentrations potentiates the cytotoxic effect of temozolomide in rat glioma C6 cells. We found that the IC50 values of DHA and temozolomide for cell viability were 23.4 and 560 µmol/l, respectively. The cytotoxic effect of temozolomide was enhanced by 177% at a nontoxic DHA concentration (1 µmol/l), and by 321% at a low-toxic DHA concentration (5 µmol/l). DHA substantially increased temozolomide-induced apoptosis and necrosis. The generation of intracellular reactive oxygen species (ROS) was increased by temozolomide combined with DHA at noneffective concentrations of both agents. Edaravone (20 µmol/l), a ROS scavenger, reversed the effects of temozolomide/DHA on both ROS generation and cell viability reduction. These results indicate that DHA at low concentrations potentiates the cytotoxic effects of temozolomide in C6 cells partly via generating ROS, suggesting a beneficial combination for the chemotherapy of gliomas.
Role of Angiotensin II on Dihydrofolate Reductase, GTP-Cyclohydrolase 1 and Nitric Oxide Synthase Expressions in Renal Ischemia-Reperfusion
Authors: Seujange Yuyen , Eiam-Ong Somchit , Tirawatnapong Thaweesak , Eiam-Ong Somchai
Published: April 2008

Background: The present study was conducted to investigate the role of renal ischemia-reperfusion (IR) and angiotensin II (ANG II) on mRNA and protein levels of renal dihydrofolate reductase (DHFR), GTP-cyclohydrolase 1 (GTP- CH 1), and endothelial and inducible nitric oxide synthase (eNOS and iNOS, respectively). Methods: Male Wistar rats were sham operated or received IR (30 min occlusion, and reperfusion for 1 day). Each group was treated separately with water, angiotensin-converting enzyme inhibitor (ACEI) and ANG II receptor type 1 blocker (ARB) for 1 day before the sham operation or IR, and continuously for 1 day after the operation. The mRNA and protein levels were detected by RT-PCR and Western blot, respectively. Results: IR decreased DHFR mRNA and protein levels (p < 0.01), both of which were restored by ACEI or ARB, whereas GTP-CH 1 expression was unaltered. IR suppressed eNOS dimer while enhancing the monomer (p < 0.01). IR augmented iNOS mRNA, total iNOS protein and iNOS monomer (all p < 0.01) which were attenuated by ACEI or ARB. Conclusion: Our study is the first to demonstrate that the heightened ANG II in IR, via stimulation of ANG II receptor type 1, suppresses DHFR and eNOS dimer, while activating both iNOS mRNA and protein levels.
Factors that contribute to the immmunogenicity of therapeutic recombinant human proteins
Authors: Mukovozov Ilya , Sabljic Thomas , Hortelano Gonzalo , Ofosu Frederick
Published: April 2008

Use of recombinant human proteins has revolutionized medicine by providing over 200 highly purified hormones and proteins that effectively treat many inherited and acquired peptide hormone and protein deficiencies. With the exception of therapeutic monoclonal antibodies, these biological medicines are synthesized by cultured cells using DNA sequences that would yield proteins with identical amino acid sequences as endogenous human proteins. Therefore, there was the broad expectation that recombinant human biological medicines would be non-immunogenic in patients capable of synthesizing even sub-optimal levels of these therapeutic proteins to which they are innately tolerant. However, the widespread clinical use of recombinant human proteins has demonstrated that nearly all of them are immunogenic. This observation suggests that factors additional to differences in amino acid sequences of endogenous and biotherapeutic proteins contribute to the immunogenicity of therapeutic proteins. The main aim of this review is to summarize some of the factors that are known to contribute to the immunogenicity of recombinant therapeutic proteins.
Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease – The Indian Atherosclerosis Research Study
Authors: Shanker Jayashree , Dash Debabrata , John Shibu , Sannappa Prathima , Rao Veena , Ramanna Jayakumar , Kakkar Vijay , Maitra Arindam
Published: April 2008

Inflammation plays a major role in coronary artery disease (CAD). We investigated the polymorphisms in the interleukin 6 (IL6) gene and their effect on the expression of acute-phase proteins in premature CAD in Asian Indian families. One hundred and ninety affected sibling pairs (ASPs) were genotyped for three tag single nucleotide polymorphisms (SNPs) in the IL6 gene for linkage analysis. We observed suggestive logarithm of odds (LOD) score for one SNP (rs2066992) in a subset of 62 ASPs with the age at onset less than 45 years (LOD score = 1.114, p = 0.011 in linkage analysis; pi = 0.55, p = 0.008 in identity by descent; LOD score = 1.06, p = 0.014 in quantitative trait locus for plasma levels of high sensitivity C-reactive protein, hsCRP). This was followed by sequencing of the promoter region and haplotype analysis in 46 probands and 40 controls. Five out of the eight previously reported promoter SNPs were found to be polymorphic (rs1800797, rs1800796, rs7802307, rs7802308, rs1800795). Two novel sequence variants were also found. One promoter haplotype (GGAAG) was detected with an odds ratio (OR) of 3.676 (p = 0.0017, 95% confidence interval [CI]: 1.68 – 8.045) and population attributable risk of 21.1% (95%CI: 9.2%-31.5%). The plasma levels of both hsCRP and fibrinogen exhibited significant association with these promoter SNP genotypes (p < 0.001). In conclusion, IL6 gene polymorphisms appear to be important genetic factors in premature CAD, and in the regulation of key atherogenic markers in Asian Indian families.
Heparin and low-molecular-weight heparin
Authors: Mulloy Barbara , Barrowcliffe Trevor , Gray Elaine
Published: April 2008

Heparin is one of the oldest biological medicines, and has an established place in the prevention and treatment of venous thrombosis. Low-molecular-weight heparins (LMWH) have been developed by several manufacturers and have advantages in terms of pharmacokinetics and convenience of administration. They have been shown to be at least as effective and safe as unfractionated heparin and have replaced the latter in many indications. In this article the chemistry, mechanisms of action, measurement of anticoagulant activities, and clinical status of heparin and LMWH are reviewed.
Augmentation of Vascular Remodeling by Uncoupled Endothelial Nitric Oxide Synthase in a Mouse Model of Diabetes Mellitus
Authors: Sasaki Naoto , Yamashita Tomoya , Takaya Tomofumi , Shinohara Masakazu , Shiraki Rio , Takeda Masafumi , Emoto Noriaki , Fukatsu Akiko , Hayashi Toshio , Ikemoto Kazuhisa , Nomura Takahide , Yokoyama Mitsuhiro , Hirata Ken-ichi , Kawashima Seinosuke
Published: April 2008

Objective—

Diabetes mellitus is associated with increased oxidative stress, which induces oxidation of tetrahydrobiopterin (BH4) in vessel wall. Without enough BH4, eNOS is uncoupled to L-arginine and produces superoxide rather than NO. We examined the role of uncoupled eNOS in vascular remodeling in diabetes.

Methods and Results—

Diabetes mellitus was produced by streptozotocin in C57BL/6J mice. Under stable hyperglycemia, the common carotid artery was ligated, and neointimal formation was examined 4 weeks later. In diabetic mice, the neointimal area was dramatically augmented. This augmentation was associated with increased aortic superoxide formation, reduced aortic BH4/dihydrobiopterin (BH2) ratio, and decreased plasma nitrite and nitrate (NOx) levels compared with nondiabetic mice. Chronic BH4 treatment (10 mg/kg/d) reduced the neointimal area in association with suppressed superoxide production and inflammatory changes in vessels. BH4/BH2 ratio in vessel wall was preserved, and plasma NOx levels increased. Furthermore, in the presence of diabetes, overexpression of bovine eNOS resulted in augmentation of neointimal area, accompanied by increased superoxide production in the endothelium.

Conclusions—

In diabetes, increased oxidative stress by uncoupled NOSs, particularly eNOS, causes augmentation of vascular remodeling. These findings indicate restoration of eNOS coupling has an atheroprotective benefit in diabetes.
Overexpression of ACE2 Enhances Plaque Stability in a Rabbit Model of Atherosclerosis
Authors: Dong Bo , Zhang Cheng , Feng Jing Bo , Zhao Yu Xia , Li Shu Ying , Yang Ya Pei , Dong Qiu Li , Deng Bi Ping , Zhu Li , Yu Qing Tao , Liu Chun Xi , Liu Bin , Pan Chun Ming , Song Huai Dong , Zhang Ming Xiang , Zhang Yun
Published: April 2008

Objective—

The purpose of this study was to test the hypothesis that ACE2 overexpression may enhance atherosclerotic plaque stability by antagonizing ACE activity and converting angiotensin II to angiotensin 1–7.

Methods and Results—

Atherosclerotic plaques were induced in the abdominal aorta of 114 rabbits by endothelial injury and atherogenic diet. Gene therapy was performed in group A at week 4 and in group B at week 12, respectively. Each group of rabbits were randomly divided into 3 subgroups which received, respectively, a recombinant ACE2 expressing vector (AdACE2), a control vector AdEGFP and AdACE2+A779, an antagonist of angiotensin 1–7 receptor. Local ACE2 overexpression attenuated the progression of lesions from week 4 to week 8, but not progression of plaque size from week 12 to week 16. In group B rabbits, local ACE2 overexpression resulted in stable plaque compositions, ie, fewer macrophages, less lipid deposition and more collagen contents, higher plaque stability scores, decreased angiotensin II levels, and increased angiotensin 1–7 levels in plaque tissues in the AdACE2 subgroup compared with those in the AdEGFP subgroup.

Conclusions—

Overexpression of ACE2 results in stabilized atherosclerotic plaques and the mechanism is probably the conversion of vasoconstrictive angiotensin II to vessel protective angiotensin 1–7.
Ultrasonic Microbubble Destruction Stimulates Therapeutic Arteriogenesis Via the CD18-Dependent Recruitment of Bone Marrow–Derived Cells
Authors: Chappell John C. , Song Ji , Klibanov Alexander L. , Price Richard J.
Published: April 2008

Objective—

We have previously shown that, under certain conditions, ultrasonic microbubble destruction creates arteriogenesis and angiogenesis in skeletal muscle. Here, we tested whether this neovascularization response enhances hyperemia in a rat model of arterial insufficiency and is dependent on the recruitment of bone marrow–derived cells (BMDCs) to treated tissues via a β2 integrin (CD18)-dependent mechanism.

Methods and Results—

Sprague-Dawley rats, C57BL/6 wild-type mice, and C57BL/6 chimeric mice engrafted with BMDCs from either GFP
+
or CD18
−/−
mice received bilateral femoral artery ligations. Microbubbles (MBs) were intravenously injected, and one gracilis muscle was exposed to pulsed 1 MHz ultrasound (US). Rat hindlimbs exhibited significant increases in adenosine-induced hyperemia and arteriogenesis compared to contralateral controls at 14 and 28 days posttreatment. US-MB–treated wild-type C57BL/6 mice exhibited significant arteriogenesis, angiogenesis, and CD11b
+
monocyte recruitment; however, these responses were all completely blocked in CD18
−/−
chimeric mice. The number of BMDCs increased in US-MB–treated muscles of GFP
+
chimeric mice; however, GFP
+
BMDCs did not incorporate into microvessels as vascular cells.

Conclusion—

In skeletal muscle affected by arterial occlusion, arteriogenesis and hyperemia can be significantly enhanced by ultrasonic MB destruction. This response depends on the recruitment, but not vascular incorporation, of BMDCs via a CD18-dependent mechanism.
Coexpression of CLA-1 and Human PDZK1 in Murine Liver Modulates HDL Cholesterol Metabolism
Authors: Komori Hidenori , Arai Hidenori , Kashima Terumi , Huby Thierry , Kita Toru , Ueda Yukihiko
Published: April 2008

Objective—

In rodents scavenger receptor class B type I (SR-BI) is a key molecule for selective uptake of cholesteryl ester from high-density lipoprotein (HDL). This study was aimed to clarify the role of the human SR-BI/CD36 and LIMP-II Analogues-1 (CLA-1) as a molecular target of selective uptake of cholesteryl ester from HDL in vivo.

Methods and Results—

To clarify the function and regulation of CLA-1 in vivo we produced
CLA-1
BAC transgenic mice. In spite of abundant hepatic RNA expression of
CLA-1
,
CLA-1
BAC transgenic mice had no significant effect on mouse HDL cholesterol. Although coexpression of a human scaffolding protein PDZK1 along with CLA-1 enhanced hepatic CLA-1 expression, it did not affect mouse HDL cholesterol levels, either. However, in the presence of human apoA-1, HDL cholesterol level and size were significantly reduced in CLA-1 transgenic mice, and its reduction was more pronounced in
CLA-1/
human
PDZK1
double transgenic mouse.

Conclusions—

We established a mouse model to study human reverse cholesterol transport by expressing
CLA-1
, human
PDZK1
, and human
apoA-I
gene. Our results imply that enhancing CLA-1 expression by human PDZK1 in the liver can modulate HDL cholesterol metabolism and possibly enhance reverse cholesterol transport to prevent the progression of atherosclerosis in human.
Assessment of Intracranial Collateral Flow by Using Dynamic Arterial Spin Labeling MRA and Transcranial Color-Coded Duplex Ultrasound
Authors: Sallustio Fabrizio , Kern Rolf , Günther Matthias , Szabo Kristina , Griebe Martin , Meairs Stephen , Hennerici Michael , Gass Achim
Published: April 2008

Background and Purpose—

To evaluate the potential of a new dynamic MRA sequence (DynAngio) based on arterial spin labeling for the assessment of intracranial collateral flow.

Methods—

Twelve patients with unilateral internal carotid artery obstruction were investigated. Different patterns of collateral flow were compared between DynAngio, transcranial color-coded duplex ultrasound, and time-of-flight MRA.

Results—

There was a good agreement between the methods, with sensitivities between 80% and 90%. Small collateral vessels were detected more frequently with DynAngio compared to time-of-flight MRA.

Conclusion—

DynAngio provides anatomic and similar to transcranial color-coded duplex ultrasound functional information on collateral flow for the assessment of intracranial hemodynamics.
Role of Retrospective Forecasts of GCMs Forced with Persisted SST Anomalies in Operational Streamflow Forecasts Development
Authors: Sankarasubramanian A. , Lall Upmanu , Espinueva Susan
Published: April 2008

Seasonal streamflow forecasts contingent on climate information are essential for water resources planning and management as well as for setting up contingency measures during extreme years. In this study, operational streamflow forecasts are developed for a reservoir system in the Philippines using ECHAM4.5 precipitation forecasts (EPF) obtained using persisted sea surface temperature (SST) scenarios. Diagnostic analyses on SST conditions show that the tropical SSTs influence the streamflow during extreme years, whereas the local SSTs (0°–25°N, 115°–130°E) account for streamflow variability during normal years. Given that the EPF, local, and tropical SST conditions are spatially correlated, principal components regression (PCR) is employed to downscale the GCM-predicted precipitation fields and SST anomalies to monthly streamflow forecasts and to update them every month within the season using the updated EPF and SST conditions. These updated forecasts improve the prediction of monthly streamflows within the season in comparison to the skill of the monthly streamflow forecasts issued at the beginning of the season. It is also shown that the streamflow forecasting model developed using EPF under persisted SST conditions performs well upon employing EPF obtained under predicted SSTs as predictor. This has potential implications in the development of operational streamflow forecasts and statistical downscaling, which requires adequate years of retrospective GCM forecasts for recalibration. Finally, the study also shows that predicting the seasonal streamflow using the monthly precipitation forecasts reproduces the observed seasonal total better than the conventional approach of using seasonal precipitation forecasts to predict the seasonal streamflow.