bluuebunny/crossref_metadata_2025 huggingface dataset:
A Method for Calculating Projected Increases in the Number of Dementia Sufferers
Authors: Jorm A. F. , Korten A. E.
Published: October 2008

A new method of projecting increases in the number of dementia cases is described. This method is based on a statistical analysis of all published prevalence studies which shows that prevalence rate rises exponentially with age. The method can be easily applied to any age-specific population projections. When applied to Australia and New Zealand, the method shows that the increase in dementia will greatly exceed the total population growth rate, and even surpass the expected rise in the elderly group over the next third of a century. The method predicts that the Australian demented population will increase by 136–139% between 1984 and 2021, compared to a general population increase of only 42–54%. Over the period 1982 to 2016, the New Zealand demented population will grow by 96–100% against a rise of 18–26% in the general population. The validity of this method and its implication for future service demands are discussed.
Clomipramine in Obsessional Disorders: A Cautionary Tale
Authors: Morstyn Ron
Published: October 2008

The author examines some dilemmas raised by the increasing use of clomipramine in the treatment of obsessional disorders. He presents a case vignette to illustrate some diagnostic, therapeutic and ethical concerns and suggests that by asking certain questions, pitfalls can be avoided.
Psychosocial Causes of Duodenal Ulcer
Authors: Tennant Chris
Published: October 2008

The evidence that duodenal ulcer is a psychosomatic disorder is reviewed. A variety of both experimental stressors and differing states of emotional arousal (anxiety and anger in particular) are associated with increased acid and pepsin secretion. Furthermore, chronic life stressors predispose to duodenal ulcer, presumably by way of symptomatic anxiety or depression, while poor social support may comprise another risk factor. Subjects with high levels of trait anxiety or neuroticism are more prone to stress-induced anxiety and its physiological consequences. There is minimal acceptable evidence to support more specific personality-related theories, including Type A behaviour, alexithymia or the earlier psycho-analytic theories of Alexander. Nonetheless, it is concluded that Alexander's inclusion of duodenal ulcer as one of a handful of classic psychosomatic disorders has been confirmed. Since some 40% of duodenal ulcer patients relapse in the first year after medical treatment, there may be some role for psychological treatments (especially in the domain of stress/anxiety management) for those patients who relapse and have co-existing high state or trait anxiety or exposure to chronic stressors.
Mania Associated with Small Cell Carcinoma of the Lung
Authors: Collins C. , Oakley-Browne M.
Published: October 2008

This paper describes a case of small cell carcinoma of the lung with ectopic adrenocorticotropic hormone (ACTH) production which presented with mania. The association between manic syndromes and the various forms of glucocorticoid or ACTH excess is discussed.
A Proof of the Beneficial Effects of Psychotherapy, with an Evaluation of Two Competing Models
Authors: Ellard John
Published: October 2008

The heuristic evaluation (HE) of differential strategies (DS) for the dissipation of dysfunctional cognitive and affective psychopathology (DODCAAP) has been addressed with ongoing evaluative modalities (OEM) for many years without an emergent consensus concerning their meaningful effective roles (MER). Their strategic perspectives (SP) have been addressed in this study, and the attention deployment(AD), reactive vigilance (RV), process withdrawal reactivity (PWR) and other ongoing responses to two strategic modalities of intervention are addressed with investigational techniques (IT).
Transcavum interforniceal endoscopic surgery of the third ventricle
Authors: Souweidane Mark M. , Hoffman Caitlin E. , Schwartz Theodore H.
Published: October 2008

Object

Intraventricular anatomy has been detailed as it pertains to endoscopic surgery within the third ventricle, particularly for performing endoscopic third ventriculostomy (ETV) and endoscopic colloid cyst resection. The expanding role of endoscopic surgery warrants a careful appraisal of these techniques as they relate to frequent anatomical variants. Given the common occurrence of cavum septum pellucidum (CSP) and cavum vergae (CV), the endoscopic surgeon should be familiar with that particular anatomy especially as it pertains to surgery within the third ventricle.

Methods

From a prospective database of endoscopic surgical cases were selected those cases in which the defined pathology necessitated surgery within the third ventricle and there was coexistent CSP and CV. Pertinent radiographic studies, operative notes, and archived video files were reviewed to define the relevant anatomy. Features of the intracavitary anatomy were assessed regarding their importance in approaching the third ventricle.

Results

Four cases involving endoscopic surgery within the third ventricle (2 colloid cyst resections and 2 ETVs) were identified in which the surgical objective was accomplished through a septal cavum. In each case the width of the body of the lateral ventricle was reduced and the foramen of Monro was obscured. Because of the ventricular distortion, a stereotactic transcavum route was used for approaching the third ventricle. Entry into the third ventricle was accomplished through an interforniceal fenestration immediately behind the anterior commissure. The surgical goal was met in each case without any neurological change or postoperative morbidity. During the follow-up period, there has been no recurrence of a colloid cyst and no need of a secondary cerebrospinal fluid diversionary procedure.

Conclusions

In the presence of a CSP and CV, endoscopic navigation into the third ventricle can be problematic via a transforaminal approach. Alternatively, a transcavum interforniceal route for endoscopic surgery in the third ventricle is suggested, with the rostral lamina and the anterior commissure as important anatomical landmarks. Endoscopic third ventriculostomy and endoscopic colloid cyst resection performed via a transcavum interforniceal route in patients with a coexistent septal cavum is a feasible and safe option.
Long-term outcomes and prognostic factors in pediatric patients with severe traumatic brain injury and elevated intracranial pressure
Authors: Jagannathan Jay , Okonkwo David O. , Yeoh Hian Kwang , Dumont Aaron S. , Saulle Dwight , Haizlip Julie , Barth Jeffrey T. , Jane John A. , Jane John A.
Published: October 2008

Object

The management strategies and outcomes in pediatric patients with elevated intracranial pressure (ICP) following severe traumatic brain injury (TBI) are examined in this study.

Methods

This study was a retrospective review of a prospectively acquired pediatric trauma database. More than 750 pediatric patients with brain injury were seen over a 10-year period. Records were retrospectively reviewed to determine interventions for correcting ICP, and surviving patients were contacted prospectively to determine functional status and quality of life. Only patients with 2 years of follow-up were included in the study.

Results

Ninety-six pediatric patients (age range 3–18 years) were identified with a Glasgow Coma Scale score < 8 and elevated ICP > 20 mm Hg on presentation. The mean injury severity score was 65 (range 30–100). All patients were treated using a standardized head injury protocol. The mean time course until peak ICP was 69 hours postinjury (range 2–196 hours). Intracranial pressure control was achieved in 82 patients (85%). Methods employed to achieve ICP control included maximal medical therapy (sedation, hyperosmolar therapy, and paralysis) in 34 patients (35%), ventriculostomy in 23 patients (24%), and surgery in 39 patients (41%). Fourteen patients (15%) had refractory ICP despite all interventions, and all of these patients died. Seventy-two patients (75%) were discharged from the hospital, whereas 24 (25%) died during hospitalization. Univariate and multivariate analysis revealed that the presence of vascular injury, refractory ICP, and cisternal effacement at presentation had the highest correlation with subsequent death (p < 0.05). Mean follow-up was 53 months (range 11–126 months). Three patients died during the follow-up period (2 due to infections and 1 committed suicide). The mean 2-year Glasgow Outcome Scale score was 4 (median 4, range 1–5). The mean patient competency rating at follow-up was 4.13 out of 5 (median 4.5, range 1–4.8). Univariate analysis revealed that the extent of intracranial and systemic injuries had the highest correlation with long-term quality of life (p < 0.05).

Conclusions

Controlling elevated ICP is an important factor in patient survival following severe pediatric TBI. The modality used for ICP control appears to be less important. Long-term follow-up is essential to determine neurocognitive sequelae associated with TBI.
Incomplete lateral medullary syndrome in a patient with Chiari malformation Type I presenting with combined trigeminal and vagal nerve dysfunction
Authors: Dahdaleh Nader S. , Menezes Arnold H.
Published: October 2008

The combination of unilateral trigeminal and vagal nerve dysfunction is a rare presentation in patients with Chiari malformation Type I (CM-I). The authors present a case of incomplete lateral medullary syndrome in a patient with CM-I. The patient's symptoms of decreased unilateral facial sensitivity to pain and temperature and her vocal cord dysfunction reversed after posterior fossa decompression and intradural exploration. Although rare, clinicians should be aware of this presentation as part of a protean spectrum of symptoms in patients with CM-I.
Clinical predictors of developmental outcome in patients with cephaloceles
Authors: Lo Benjamin W. Y. , Kulkarni Abhaya V. , Rutka James T. , Jea Andrew , Drake James M. , Lamberti-Pasculli Maria , Dirks Peter B. , Thabane Lehana
Published: October 2008

Object

Cephaloceles represent primary axial mesodermal defects, occurring in 0.8–4 per 10,000 live births. Prior studies have reported posterior location, hydrocephalus, microcephaly, seizure, and presence of brain tissue as poor prognostic markers for neurological outcome. However, these studies were small and the results were analyzed using univariate tests. The purpose of this study was to investigate the potential risk factors for the occurrence of developmental delay in patients with cephaloceles, using both univariate and multivariable regression techniques.

Methods

This is a retrospective cohort study of cephalocele cases treated at the Hospital for Sick Children between 1990 and 2006. Two independent investigators collected the data from the Hospital for Sick Children Encephalocele Database and hospital charts. Developmental assessments were made by general pediatricians and neuropsychologists. Both univariate analysis (α = 0.10) and multivariable logistic regression analysis (α = 0.05) were performed.

Results

Eighty-five cases of cephaloceles were identified. The patient group consisted of 48 boys and 37 girls. Sixty-eight lesions were encephaloceles and 17 were meningoceles. The distribution was as follows: frontal (40 lesions), occipital (33), and parietal (12). Associated conditions included hydrocephalus (23), seizure disorder (17), microcephaly (6), corpus callosal abnormalities (15), heterotopias (9), cerebral dysgenesis (11), and myelomeningocele (1). Evaluation of long-term development revealed that 41 patients (48%) had normal development, 9 (11%) had mild delay, 14 (16%) had moderate delay, and 21 (25%) had severe delay. Hydrocephalus, seizure disorder, microcephaly, presence of associated intracranial abnormalities, and presence of brain tissue were significantly associated with poor outcome on univariate analysis. Multivariable analysis revealed hydrocephalus and presence of intracranial abnormalities to be statistically significant predictors of developmental delay.

Conclusions

To the authors' knowledge, this is one of the largest North American cephalocele series documented. Unlike prior studies, location of the cephaloceles is not a significant predictor of outcome. The multivariable regression analysis demonstrates hydrocephalus and the presence of associated intracranial abnormalities as variables with cumulative predictive effects for developmental delay.
Frontal intradiploic angioleiomyoma
Authors: Vijayasaradhi Mudumba , Uppin Shantiveer Gurulingappa , Sreedhar Vuyyuri , Sundaram Challa , Panigrahi Manas K.
Published: October 2008

A left frontal intradiploic angioleiomyoma in a 10-year-old girl is presented with a review of the literature. The pathological and differential diagnosis and management of this rare lesion is discussed.
Lymphangioma of the skull base bones leading to cerebrospinal fluid rhinorrhea
Authors: Ito Eiji , Saito Kiyoshi , Nagatani Tetsuya , Teranishi Masaaki , Kamei Yuzuru , Yagi Shunjiro , Kawabe Takashi , Niimi Norihiro , Yoshida Jun
Published: October 2008

Lymphangioma localized to the bones of the skull base is rare. The authors report herein the case of a 5-year-old boy who presented with lymphangioma of the bone, localized to the skull base and leading to cerebrospinal fluid (CSF) rhinorrhea with meningitis. Neuroimaging demonstrated lytic destruction with a cyst in the right middle skull base. The patient was successfully treated with resection of the tumor and prevention of CSF leakage. Histopathological examination revealed a lymphangioma. An enlarging lymphangioma can lead to bone destruction. A differential diagnosis of a lytic lesion for a cyst at the skull base is important for proper case management.
Correlation of a preoperative grading scale with progressive spinal deformity following surgery for intramedullary spinal cord tumors in children
Authors: McGirt Matthew J. , Constantini Shlomi , Jallo George I.
Published: October 2008

Object

Postoperative progressive spinal deformity often complicates functional outcome after resection of pediatric intramedullary spinal cord tumors (IMSCTs). The authors propose a preoperative grading scale that correlates with the postoperative development of progressive spinal deformity requiring subsequent fusion.

Methods

The data obtained in 164 patients who underwent resection of an IMSCT at a single institution were retrospectively collected and analyzed to determine the development of progressive spinal deformity requiring fusion. A grading scale (range of scores I–V) was created based on the presence or absence of 4 preoperative variables: preoperative scoliosis, involvement of the thorocolumbar junction, age < 13 years, and number of surgeries for an IMSCT. The grading scale was then retrospectively applied to this series of 164 children to assess the correlation of variables with subsequent spinal deformity.

Results

Nine patients presented with Grade I status, 41 patients with Grade II, 58 patients with Grade III, 44 patients with Grade IV, and 12 patients with Grade V. Overall, 44 patients (27%) developed progressive spinal deformity requiring fusion at a mean follow-up of 5 years after surgery. A higher preoperative grade was associated with an increasing need for subsequent fusion for progressive spinal deformity (Grade I [0%], Grade II [5%], Grade III [26%], Grade IV [40%], and Grade V status [75%]).

Conclusions

Application of this grading scheme to a series of resected pediatric IMSCTs has demonstrated its correlation with the incidence of postoperative progressive spinal deformity requiring fusion. The application of a standardized grading scheme will assist in the process of surgical decision making and postoperative evaluation.
Laparoscopic placement of distal ventriculoperitoneal shunt catheters
Authors: Handler Michael H. , Callahan Brian
Published: October 2008

Object

Ventriculoperitoneal shunts (VPSs) are commonly placed into the peritoneal cavity via a small laparotomy or blindly by using a split trocar. Larger patients require larger incisions, and placement is made more difficult by previous abdominal operations and obesity. For general surgeons, laparoscopy has become the first-choice approach for abdominal procedures, using 1 or several very small incisions. The authors discuss their pediatric series of patients in whom laparoscopy was used to place distal shunt catheters.

Methods

The authors reviewed the medical records accrued over a 9-year period, noting VPS operations performed using laparoscopy. Complications, morbidity, and alterations of planned management were noted.

Results

One hundred thirty-seven VPS operations in 126 patients were identified, 92 performed by the senior author (M.H.H.) alone and 45 conducted with the assistance of a general surgeon. A second port was placed for lysis of adhesions or retrieval of old catheters in 7 cases. There were no immediate complications. The infection rate was 6.6%, comparable with the institutional norm (6.3%) over an 8-year period. There were 3 early failures due to abdominal malabsorption without infection. Five catheters later broke at the level where they were introduced into the abdomen due to shearing by the abdominal trocar.

Conclusions

Laparoscopic placement of distal VPS catheters is relatively safe and allows insertion via inconspicuous incisions. It can allow for inspection or lysis of adhesions and removal of foreign bodies, help determine if and where the abdomen can absorb shunt fluid, and make VPS surgery in the obese patient easier.
Thrombosis associated with ventriculoatrial shunts
Authors: Wilkinson Norka , Sood Sandeep , Ham Steven D. , Gilmer-Hill Holly , Fleming Patricia , Rajpurkar Madhvi
Published: October 2008

Object

In this single-center study, the authors examined the clinical characteristics, risk factors, treatment strategies, and outcomes in patients with thrombosis associated with ventriculoatrial (VA) shunts.

Methods

Inpatient and outpatient charts of patients who underwent treatment and follow-up in the Hematology-Oncology Division at the authors' institution and in whom thrombosis developed secondary to a VA shunt placement were reviewed. A complete thrombophilia work-up was performed in each patient, and these records were also reviewed. Treatment including medical and surgical management was noted and outcome data were recorded.

Results

Resolution of thrombosis was seen after anticoagulation therapy in all patients; this may be an alternative to surgical therapy.

Conclusions

Patients with VA shunts represent a unique group at risk for thrombosis. The duration of anticoagulation therapy must be individualized. However, larger studies are needed to evaluate the efficacy of screening for asymptomatic thrombosis and to investigate the role of prophylactic anticoagulation.
Prevalence and risk factors of Type 2 diabetes in an urbanizing rural community of Bangladesh
Authors: Rahman Md. Mafuzar , Rahim Md. Abdur , Nahar Quamrun
Published: October 2008

This cross-sectional study was carried out to estimate the prevalence of type 2 diabetes mellitus and itsâ risk factors in an urbanizing rural community of Bangladesh. Two villages were randomly selected from the rural areas of Gazipur district and total 975 subjects (>20 years), were included following simple random procedure. Capillary blood glucose levels, fasting blood glucose (FBG) levels and 2-hour after 75 g oral glucose load (OGTT) were measured. Height, weight, waist and hip circumferences and blood pressure were measured. The study population was lean with mean body mass index (BMI) of 20.48. The total prevalence of type 2 diabetes was 8.5%, men showed higher prevalence (9.4%) compare to women (8.0%). Increasing age and higher BMI were found to be significant risk factors following both FBG and OGTT. The study has shown that prevalence of diabetes has increased in the populations who are in transitional stage of urbanization, and may indicate an epidemiological transition due to fast expanding urbanization. Keywords: Bangladesh; Diabetes; RuralDOI: 10.3329/bmrcb.v33i2.1204Bangladesh Med Res Counc Bull 2007; 33: 48-54
Spot urinary protein/osmolality ratio as a predictor for proteinuria of nephrotic range
Authors: Jahan Salma , Islam Md. Saiful , Hossain Md. Moazzam
Published: October 2008

A prospective study was carried out on 50 patients (age 1-15 years) with nephrotic range of proteinuria to determine the correlation of 24-hour urinary total protein with spot urinary protein/creatinine ratio and urinary protein/osmolality ratio. Another 50 patients having no proteinuria grouped as control. Twenty-four hours urine and spot urine were collected from each child and were analyzed for total volume, total protein, creatinine and osmolality level. The average 24-hour urinary total proteins in nephritic patient were 2148.6 Â± 808.7 mg and the spot urinary protein/creatinine and spot urinary protein/osmolality were 3.2332 Â± 0.4293 mg/mg and 3.2418 Â± 0.4393 mg/mOsm respectively. There was a strong positive correlation of the 24-hour urinary total protein with spot urinary protein/creatinine and protein/osmolality ratios (r=0.9846 and 0.9870, p= <0.001). But in control group, these ratios did not show any correlation with 24-hour urinary total protein. These results suggest that in pediatric patients with nephrotic range of proteinuria, the spot urinary protein/osmolality ratio can predict the 24-hour Â urinary total protein excretion like that of spot urinary protein/creatinine ratios. Keywords: Kidney; Proteinuria; UrinaryDOI: 10.3329/bmrcb.v33i2.1207Bangladesh Med Res Counc Bull 2007; 33: 65-68
Antibiotic sterilization of cadaveric homograft aortic valve for clinical use
Authors: Hoque Rezwanul , Rashid Zulfiqar , Sarkar Sunil Kumar
Published: October 2008

DOI: 10.3329/bmrcb.v33i2.1208Bangladesh Med Res Counc Bull 2007; 33: 69-72
Ultrasonography and computer tomography evaluation of hepatocellular carcinoma with cytohistopathological correlation
Authors: Hoque Hasnat Waheedul , Alam Shahinul , Ahsan Sania , Islam Md. Nazrul
Published: October 2008

The prevalence of hepatocellular carcinoma (HCC) in Bangladesh is 35% among all liver diseases. Sonographic examinations were performed for the evaluation of 38 cases of HCC; then, CT examina-tions were done of these cases subsequently. Expert opinion was taken in each case for both modalities. Age, sex, clinical features, location of the hepatic lesion, multiplicity, echo-character, CT density, and, contrast enhancement were evaluated in all cases. Histocytopathology reports were collected from the patients and were correlated with the ultrasonography and CT findings. Thirty five cases were detected as HCC on ultrasonography and 36 cases in CT scan. In ultrasonography, most of the lesions (82.9%) were found in right lobe, maximum lesions (45.7%) were hypoechoic and lesion showed mosaic pattern in 68.6% cases, lateral shadowing in 34.3% and posterior acoustic enhancement in 45.7% cases. Significant difference found between mosaic pattern and lateral shadowing (p<0.05). On CT scan, majority of lesions (50%) were hypodense, 91.7% lesions were contrast enhanced. Pattern of enhancement was mostly heterogeneous. Both of the modalities found sensitive but CT was found more sensitive, specific and accurate than ultrasonography in detecting HCC.Â  Keywords: Computer tomography; Cytohistopathological; Hepatocellular carcinoma; UltrasonographyDOI: 10.3329/bmrcb.v33i2.1209Bangladesh Med Res Counc Bull 2007; 33: 73-77Â
Shear Stress Transmission Model for the Flagellar Rotary Motor
Authors: Mitsui Toshio , Ohshima Hiroyuki
Published: October 2008

Most bacteria that swim are propelled by flagellar filaments, which are driven by a rotary motor powered by proton flux. The mechanism of the flagellar motor is discussed by reforming the model proposed by the present authors in 2005. It is shown that the mean strength of Coulomb field produced by a proton passing the channel is very strong in the Mot assembly so that the Mot assembly can be a shear force generator and induce the flagellar rotation. The model gives clear calculation results in agreement with experimental observations, e g., for the charasteristic torque-velocity relationship of the flagellar rotation.
Pretreatment of Lignocellulosic Wastes to Improve Ethanol and Biogas Production: A Review
Authors: Taherzadeh Mohammad J. , Karimi Keikhosro
Published: October 2008

Lignocelluloses are often a major or sometimes the sole components of different waste streams from various industries, forestry, agriculture and municipalities. Hydrolysis of these materials is the first step for either digestion to biogas (methane) or fermentation to ethanol. However, enzymatic hydrolysis of lignocelluloses with no pretreatment is usually not so effective because of high stability of the materials to enzymatic or bacterial attacks. The present work is dedicated to reviewing the methods that have been studied for pretreatment of lignocellulosic wastes for conversion to ethanol or biogas. Effective parameters in pretreatment of lignocelluloses, such as crystallinity, accessible surface area, and protection by lignin and hemicellulose are described first. Then, several pretreatment methods are discussed and their effects on improvement in ethanol and/or biogas production are described. They include milling, irradiation, microwave, steam explosion, ammonia fiber explosion (AFEX), supercritical CO2 and its explosion, alkaline hydrolysis, liquid hot-water pretreatment, organosolv processes, wet oxidation, ozonolysis, dilute- and concentrated-acid hydrolyses, and biological pretreatments.
Exact and Effective Pair-Wise Potential for Protein-Ligand Interactions Obtained from a Semiempirical Energy Partition
Authors: Carvalho Alexandre R. F. , Puga André T. , Melo André
Published: October 2008

In this work, the partition method introduced by Carvalho and Melo was used to study the complex between Cucurbita maxima trypsin inhibitor (CMTI-I) and glycerol at the AM1 level. An effective potential, combining non-bonding and polarization plus charge transfer (PLCT) terms, was introduced to evaluate the magnitude of the interaction between each amino acid and the ligand. In this case study, the nonbonding–PLCT noncompensation characterizes the stabilization energy of the association process in study. The main residues (Gly29, Cys3 and Arg5) with net attractive effects and Arg1 (with a net repulsive effect), responsible by the stability of protein-ligand complex, are associated with large nonbonding energies non-compensated by PLCT effects. The results obtained enable us to conclude that the present decomposition scheme can be used for understanding the cohesive phenomena in proteins.
Integration of Motor Proteins – Towards an ATP Fueled Soft Actuator
Authors: Kakugo Akira , Shikinaka Kazuhiro , Gong Jian Ping
Published: October 2008

We present a soft bio-machine constructed from biological motors (actin/myosin). We have found that chemically cross-linked polymer-actin complex gel filaments can move on myosin coated surfaces with a velocity as high as that of native Factin, by coupling to ATP hydrolysis. Additionally, it is shown that the velocity of polymer-actin complex gel depends on the species of polycations binding to the F-actins. Since the design of functional actuators of well-defined size and morphology is important, the structural behavior of polymer-actin complexes has been investigated. Our results show that the morphology and growth size of polymer-actin complex can be controlled by changes in the electrostatic interactions between F-actins and polycations. Our results indicate that bio actuators with desired shapes can be created by using a polymer-actin complex.
The Influence of Carbon-Carbon Multiple Bonds on the Solvolyses of Tertiary Alkyl Halides: a Grunwald-Winstein Analysis
Authors: Reis Marina C. , Elvas-Leitão Ruben , Martins Filomena
Published: October 2008

The influence of carbon-carbon multiple bonds on the solvolyses of 3-chloro-3-methylbutyne (1), 2-chloro-2-phenylpropane (2), 2-bromo-2-methyl-1-phenylpropane (3), 4-chloro-4-methyl-2-pentyne (4) and 2-chloro-2-methylbutane (5) is critically evaluated through the extended Grunwald-Winstein equation. Substrates 1, 3 and 5 lead to correlations with unexpected negative sensitivity, h, to changes in the aromatic ring parameter, I. It is claimed that I is not a pure parameter, reflecting also some solvent nucleophilicity, NOTs, character. In substrates 2 and 4 the possibility of rearside solvation is reduced due to steric hindrance and/or cation stabilization and the best found correlations involve only the solvent ionizing power, Y, and I.
Are the Genes nadA and norB Involved in Formation of Aflatoxin G1?
Authors: Ehrlich Kenneth C. , Scharfenstein Leslie L. , Montalbano Beverly G. , Chang Perng-Kuang
Published: October 2008

Aflatoxins, the most toxic and carcinogenic family of fungal secondary metabolites, are frequent contaminants of foods intended for human consumption. Previous studies showed that formation of G-group aflatoxins (AFs) from Omethylsterigmatocystin (OMST) by certain Aspergillus species involves oxidation by the cytochrome P450 monooxygenases, OrdA (AflQ) and CypA (AflU). However, some of the steps in the conversion have not yet been fully defined. Extracts of Aspergillus parasiticus disruption mutants of the OYE-FMN binding domain reductase-encoding gene nadA (aflY) contained a 386 Da AFG1 precursor. A compound with this mass was predicted as the product of sequential OrdA and CypA oxidation of OMST. Increased amounts of a 362 Da alcohol, the presumptive product of NadA reduction, accumulate in extracts of fungi with disrupted aryl alcohol dehydrogenase-encoding gene norB. These results show that biosynthesis of AFG1 involves NadA reduction and NorB oxidation.
A Reconsideration of the Link between the Energetics of Water and of ATP Hydrolysis Energy in the Power Strokes of Molecular Motors in Protein Structures
Authors: Widdas Wilfred F.
Published: October 2008

Mechanical energy from oxygen metabolism by mammalian tissues has been studied since 1837. The production of heat by mechanical work was studied by Fick in about 1860. Prior to Fick’s work, energetics were revised by Joule’s experiments which founded the First Law of Thermodynamics. Fenn in 1923/24 found that frog muscle contractions generated extra heat proportional to the amount of work done in shortening the muscle. This was fully consistent with the Joule, Helmholtz concept used for the First Law of Thermodynamics. The link between the energetics of water and ATP hydrolysis in molecular motors is recommended for reconsideration.
A Crosslinking Analysis of GAP-43 Interactions with Other Proteins in Differentiated N1E-115 Cells
Authors: Ollom Callise M. , Denny John B.
Published: October 2008

It has been suggested that GAP-43 (growth-associated protein) binds to various proteins in growing neurons as part of its mechanism of action. To test this hypothesis in vivo, differentiated N1E-115 neuroblastoma cells were labeled with [35S]-amino acids and were treated with a cleavable crosslinking reagent. The cells were lysed in detergent and the lysates were centrifuged at 100,000 x g to isolate crosslinked complexes. Following cleavage of the crosslinks and analysis by two-dimensional gel electrophoresis, it was found that the crosslinker increased the level of various proteins, and particularly actin, in this pellet fraction. However, GAP-43 was not present, suggesting that GAP-43 was not extensively crosslinked to proteins of the cytoskeleton and membrane skeleton and did not sediment with them. GAP-43 also did not sediment with the membrane skeleton following nonionic detergent lysis. Calmodulin, but not actin or other proposed interaction partners, co-immunoprecipitated with GAP-43 from the 100,000 x g supernatant following crosslinker addition to cells or cell lysates. Faint spots at 34 kDa and 60 kDa were also present. Additional GAP-43 was recovered from GAP-43 immunoprecipitation supernatants with anti-calmodulin but not with anti-actin. The results suggest that GAP-43 is not present in complexes with actin or other membrane skeletal or cytoskeletal proteins in these cells, but it is nevertheless possible that a small fraction of the total GAP-43 may interact with other proteins.
The New Unified Theory of ATP Synthesis/Hydrolysis and Muscle Contraction, Its Manifold Fundamental Consequences and Mechanistic Implications and Its Applications in Health and Disease
Authors: Nath Sunil
Published: October 2008

Complete details of the thermodynamics and molecular mechanisms of ATP synthesis/hydrolysis and muscle contraction are offered from the standpoint of the torsional mechanism of energy transduction and ATP synthesis and the rotation-uncoiling-tilt (RUT) energy storage mechanism of muscle contraction. The manifold fundamental consequences and mechanistic implications of the unified theory for oxidative phosphorylation and muscle contraction are explained. The consistency of current mechanisms of ATP synthesis and muscle contraction with experiment is assessed, and the novel insights of the unified theory are shown to take us beyond the binding change mechanism, the chemiosmotic theory and the lever arm model. It is shown from first principles how previous theories of ATP synthesis and muscle contraction violate both the first and second laws of thermodynamics, necessitating their revision. It is concluded that the new paradigm, ten years after making its first appearance, is now perfectly poised to replace the older theories. Finally, applications of the unified theory in cell life and cell death are outlined and prospects for future research are explored. While it is impossible to cover each and every specific aspect of the above, an attempt has been made here to address all the pertinent details and what is presented should be sufficient to convince the reader of the novelty, originality, breakthrough nature and power of the unified theory, its manifold fundamental consequences and mechanistic implications, and its applications in health and disease.
Lix@C60: Calculations of the Encapsulation Energetics and Thermodynamics
Authors: Slanina Zdeněk , Uhlík Filip , Lee Shyi-Long , Adamowicz Ludwik , Nagase Shigeru
Published: October 2008

Li@C60 and Li@C70 can be prepared and thus, their calculations at higher levels of theory are also of interest. In the report, the computations are carried out on Li@C60, Li2@C60 and Li3@C60 with the B3LYP density-functional theory treatment in the standard 3-21G and 6-31G* basis sets. The computed energetics suggests that Lix@C60 species may be produced for a few small x values if the Li pressure is enhanced sufficiently. In order to check the suggestion, a deeper computational evaluation of the encapsulation thermodynamics is carried out.
A New Phenolic Amide from the Roots of Paris verticillata
Authors: Lee Kyu Ha , Yang Min Cheol , Kim Ki Hyun , Kwon Hak Cheol , Choi Sang Un , Lee Kang Ro
Published: October 2008

A new phenolic amide 8, together with the nine known phenolic compounds 1-7,9 and 10 were isolated from the MeOH extract of the roots of Paris verticillata. Thestructure of the new compound 8 was determined to be 1-N-feruloylaminobutyl-4-ρ-hydroxybenzamide by spectroscopic methods. The isolated compounds were tested forcytotoxicity against four human tumor cell lines using the SRB assay.
Synthesis and Antiplasmodial Activity of 3-Furyl and 3-Thienylquinoxaline-2-carbonitrile 1,4-Di-N-oxide Derivatives
Authors: Vicente Esther , Charnaud Sarah , Bongard Emily , Villar Raquel , Burguete Asunción , Solano Beatriz , Ancizu Saioa , Pérez-Silanes Silvia , Aldana Ignacio , Vivas Livia , Monge Antonio
Published: October 2008

The aim of this study was to identify new compounds active againstPlasmodium falciparum based on our previous research carried out on 3-phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Twelve compounds weresynthesized and evaluated for antimalarial activity. Eight of them showed an IC50 less than 1 μMagainst the 3D7 strain. Derivative 1 demonstrated high potency (IC50= 0.63 μM) and goodselectivity (SI=10.35), thereby becoming a new lead-compound.
Preparation of Second Generation Ionic Liquids by Efficient Solvent-Free Alkylation of N-Heterocycles with Chloroalkanes
Authors: Cravotto Giancarlo , Gaudino Emanuela Calcio , Boffa Luisa , Lévêque Jean-Marc , Estager Julien , Bonrath Werner
Published: October 2008

Non-conventional techniques, such as microwave (MW) and power ultrasound(US) as well as combined MW/US irradiation, have been used to promote one-potsynthesis of second-generation ionic liquids (ILs), cutting down reaction times andimproving yields. However, the use of chloroalkanes in the alkylation of N-heterocyclesrequires more drastic conditions if results are to match those obtained with more reactivealkyl halides. The present paper describes a series of MW- or MW/US-promoted ILpreparations starting from chloroalkanes and classic heterocycles (1-methylimidazole,pyridine and 1-methylpyrrolidine). When reactions were carried out under conventionalheating in an oil bath they required longer reaction times and gave poorer yields. 1H-NMRanalysis and ion-exchange chromatography showed that the present solventless procedureafforded ILs of satisfactory purity. The observed high yields (usually 70-98% isolated),and short reaction times showed that a straightforward access to ILs can be also achievedwith the use of alkyl chlorides, resulting in a considerable reduction of costs.
Reaction of Nitrilimines with 2-Substituted Aza-heterocycles. Synthesis of Pyrrolo[1,2-a]pyridine and Pyrimido[2,1-d]1,2,3,5- tetrazine
Authors: Awadallah Adel M. , Zahra Jalal A.
Published: October 2008

The reaction of nitrilimine 6a with ethyl pyridine-2-acetate (7) gave thecorresponding pyrrolo[1,2-a]pyridine 8, while the reaction of 6b containing an estermoiety afforded the acyclic adduct 9. The reaction of 6a with 2-aminopyrimidine (10)gave the novel unexpected pyrimido[2,1-d]1,2,3,5-tetrazine 11. Acyclic adducts 16 and17 were obtained from the reaction of 6b with 2-cyanomethylbenzimidazole (14) and 2-aminobenzimidazole (15), respectively.
New Di-(β-chloroethyl)-α-amides on N-(meta-Acylaminobenzoyl)- D,L-aminoacid Supports with Antitumoral Activity
Authors: Sunel Valeriu , Popa Marcel , Desbrières Jacques , Profire Lenuta , Otilia Pintilie , Catalina Lionte
Published: October 2008

In order to obtain new compounds with antitumoural action the N-(metaacylaminobenzoyl)-α-acylaminobenzoyl)-α-aminoacids 4-9 were prepared. Thesecompounds were subsequently converted into the corresponding δ2-oxazolin-5-ones 10-15,which in turn were submitted to a ring opening reaction with di-(β-chloroethyl)amine toafford the peptide supported N-mustards 16-21, which showed low toxicity and cytostaticactivity similar to that of sarcolisine against the Ehrlich ascite and Walker 253carcinosarcoma.
First Synthesis and Isolation of the E- and Z-Isomers of Some New Schiff Bases. Reactions of 6-Azido-5-Formyl-2-Pyridone with Aromatic Amines
Authors: Mekheimer Ramadan A. , Hameed Afaf M. Abdel , Sadek Kamal U.
Published: October 2008

Some novel Schiff bases have been prepared by reacting 6-azido-5-formyl-2-pyridone 1 with a series of aromatic amines 2a-f. 5-Arylaminomethylene-6-(E)-aryliminopyridones3a-e were obtained by reaction of 1 with 2a-e at room temperature,whereas with 2f, the 6-azido-5-naphthalen-2-yl-iminomethylpyridone derivative 4 wasformed. On the other hand, heating 1 with 2a-d at 140-150°C yielded two sets of isomericproducts, (E)-3a-d and (Z)-5a-d. Refluxing compounds (Z)-3a,c with hydroxyl-amine inmethanol gave the corresponding hydroxyliminopyridones 8a,c. Heating of (E)-3a-d withexcess POCl3 at reflux did not give the expected tricyclic compound 9, but rather theisomeric products (Z)-5a-d were obtained. The structures of all these products have beencharacterized using IR and 1H- and 13C-NMR spectroscopy.
Antifouling Metabolites from the Mangrove Plant Ceriops tagal
Authors: Chen Jun De , Feng Dan Qin , Yang Zhi Wei , Wang Zhan Chang , Qiu Yan , Lin Yi Ming
Published: October 2008

The new diterpene methoxy-ent-8(14)-pimarenely-15-one (1) and three knownmetabolites: ent-8(14)-pimarene-15R,16-diol (2), stigmasterol (3) and β-sitosterol (4), wereisolated from the roots of the mangrove plant Ceriops tagal. Their structures and relativestereochemistry were elucidated by means of extensive NMR, IR and MS analysis.Compounds 1, 2, 3 and 4 exhibited significant antifouling activities against cyprid larvaeof the barnacle Balanus albicostatus Pilsbry, with EC50 values of 0.32 ± 0.01, 0.04 ± 0.00,4.05 ± 0.15 and 18.47 ± 0.40 μg/cm2, respectively, whereas their toxicities towards cypridswere very low, with LC50 values all above 10 μg/cm2.
Progress in the Studies on Rutaecarpine
Authors: Lee Seung Ho , Son Jong-Keun , Jeong Byeong Seon , Jeong Tae-Cheon , Chang Hyeon Wook , Lee Eung-Seok , Jahng Yurngdong
Published: October 2008

Rutaecarpine is an indolopyridoquinazolinone alkaloid isolated from Evodiarutaecarpa and related herbs, which has shown a variety of intriguing biological propertiessuch as anti-thrombotic, anticancer, anti-inflammatory and analgesic, anti-obesity andthermoregulatory, vasorelaxing activity, as well as effects on the cardiovascular andendocrine systems. Recent progress in the studies on the isolation, synthesis, structureactivityrelationship studies, biological activities and metabolism of rutaecarpine arereviewed.
Synthesis and Properties of a New Water-Soluble Prodrug of the Adenosine A2A Receptor Antagonist MSX-2
Authors: Vollmann Karl , Qurishi Ramatullah , Hockemeyer Jörg , Müller Christa E.
Published: October 2008

The compound L-valine-3-{8-[(E)-2-[3-methoxyphenyl)ethenyl]-7-methyl-1-propargylxanthine-3-yl}propyl ester hydrochloride (MSX-4) was synthesized as an aminoacid ester prodrug of the adenosine A2A receptor antagonist MSX-2. It was found to bestable in artificial gastric acid, but readily cleaved by pig liver esterase.
Design, Synthesis and Applications of Hyaluronic Acid-Paclitaxel Bioconjugates†
Authors: Leonelli Francesca , La Bella Angela , Migneco Luisa Maria , Bettolo Rinaldo Marini
Published: October 2008

Paclitaxel (1a), a well known antitumor agent adopted mainly for the treatmentof breast and ovarian cancer, suffers from significant disadvantages such as low solubility,certain toxicity and specific drug-resistance of some tumor cells. To overcome theseproblems extensive research has been carried out. Among the various proposed strategies,the conjugation of paclitaxel (1a) to a biocompatible polymer, such as hyaluronic acid(HA, 2), has also been considered. Coupling a bioactive compound to a biocompatiblepolymer offers, in general, many advantages such as better drug solubilization, betterstabilization, specific localization and controlled release. Hereafter the design, synthesisand applications of hyaluronic acid-paclitaxel bioconjugates are reviewed. An overview ofHA-paclitaxel combinations is also given.
Novel Prodrugs for Targeting Diagnostic and Therapeutic Radionuclides to Solid Tumors
Authors: Kassis Amin I. , Korideck Houari , Wang Ketai , Pospisil Pavel , Adelstein S. James
Published: October 2008

Most cancer therapeutics (chemo, radiation, antibody-based, anti-angiogenic)are at best partially and/or temporarily effective. In general, the causes for failure can besummarized as: (i) poor diffusion and/or nonuniform distribution of drug/prodrugmolecules in solid tumors; (ii) high drug concentration and retention in normal tissues(leading to side effects); (iii) requirement for plasma-membrane permeability and/orinternalization of drug/prodrug molecules; (iv) low uptake of drug by tumor; (v) lack ofretention of drug within tumor (most have gradient-driven reversible binding); and (vi)multidrug resistance. We are developing an innovative technology that aims to surmountthese problems by actively concentrating and permanently entrapping radioimaging andradiotherapeutic prodrugs specifically within solid tumors. The approach will enablenoninvasive sensing (imaging) and effective therapy of solid tumors, allowing tumordetection, diagnosis, and treatment to be closely coupled (personalized medicine).
Spirowallichiione: A Rearranged Multiflorane from Euphorbia wallichii Hook F. (Euphorbiaceae)
Authors: Ali Muhammad Shaiq , Ahmed Shakeel , Saleem Muhammad
Published: October 2008

Euphorbia wallichii of the family Euphorbiaceae yielded a new rearrangedpentacyclic triterpene of the multiflorane class which we have named spirowallichiione.The structure of this natural spirocompound was elucidated with the aid of modernspectroscopic techniques, including 2D-NMR.
Structure and Catalytic Properties of Carboxylesterase Isozymes Involved in Metabolic Activation of Prodrugs
Authors: Hosokawa Masakiyo
Published: October 2008

Mammalian carboxylesterases (CESs) comprise a multigene family whose geneproducts play important roles in biotransformation of ester- or amide-type prodrugs. Theyare members of an α,β-hydrolase-fold family and are found in various mammals. It has beensuggested that CESs can be classified into five major groups denominated CES1-CES5,according to the homology of the amino acid sequence, and the majority of CESs that havebeen identified belong to the CES1 or CES2 family. The substrate specificities of CES1 andCES2 are significantly different. The CES1 isozyme mainly hydrolyzes a substrate with asmall alcohol group and large acyl group, but its wide active pocket sometimes allows it toact on structurally distinct compounds of either a large or small alcohol moiety. In contrast,the CES2 isozyme recognizes a substrate with a large alcohol group and small acyl group,and its substrate specificity may be restricted by the capability of acyl-enzyme conjugateformation due to the presence of conformational interference in the active pocket. Sincepharmacokinetic and pharmacological data for prodrugs obtained from preclinicalexperiments using various animals are generally used as references for human studies, it isimportant to clarify the biochemical properties of CES isozymes. Further experimentationfor an understanding of detailed substrate specificity of prodrugs for CES isozymes and itshydrolysates will help us to design the ideal prodrugs.
Synthesis and Antimalarial Evaluation of Cyclic β-Amino Acid-Containing Dipeptides
Authors: Sathe Manisha , Thavaselvam D. , Srivastava A. K. , Kaushik M. P.
Published: October 2008

This paper describes an efficient synthesis and the antiparasitic evaluation ofcyclic β-amino acid-containing dipeptides 3.1-3.6 and 4.1-4.5. The antimalarial propertiesof all these dipeptides have been evaluated in vitro against Plasmodium falciparum and invivo against Plasmodium berghai. Compounds 4.4 and 4.5 have been found to be veryeffective in this respect, with IC50 values of 3.87 and 3.64 μg/mL in the in vitro test, while4.5 has also been found to be active in the in vivo evaluation.
Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells
Authors: Lee Jae Joon , Jin Chun Mei , Kim Young Kyoon , Ryu Shi Yong , Lim Sung Cil , Lee Myung Koo
Published: October 2008

The effects of anonaine, an aporphine isoquinoline alkaloid, on dopaminebiosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaineat concentration ranges of 0.01-0.2 μM showed a significant inhibition of dopaminecontent at 24 h, with an IC50 value of 0.05 μM. Anonaine at 0.05 μM inhibited tyrosinehydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities to 38.4-40.2% and 78.4-90.2% of control levels at 12-24 h and 3-6 h, respectively. TH activity wasmore influenced than AADC activity. Anonaine also decreased intracellular cyclic AMPlevels, but not intracellular Ca2+ concentrations. In addition, anonaine (0.05 μM) reducedL-DOPA (50 μM and 100 μM)-induced increases in dopamine content at 24 h. However,anonaine (0.05 μM) did not enhance L-DOPA (50 μM and 100 μM)-induced cell death 476after 24 h. These results suggest that anonaine inhibits dopamine biosynthesis by mainlyreducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells.