bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Review: DSM‐V conduct disorder: research needs for an evidence base
Authors: Moffitt Terrie E. ,   and in alphabetical order, Arseneault Louise , Jaffee Sara R. , Kim‐Cohen Julia , Koenen Karestan C. , Odgers Candice L. , Slutske Wendy S. , Viding Essi
Published: January 2010

This article charts a strategic research course toward an empirical foundation for the diagnosis of conduct disorder in the forthcoming DSM‐V. Since the DSM‐IV appeared in 1994, an impressive amount of new information about conduct disorder has emerged. As a result of this new knowledge, reasonable rationales have been put forward for adding to the conduct disorder diagnostic protocol: a childhood‐limited subtype, family psychiatric history, callous‐unemotional traits, female‐specific criteria, preschool‐specific criteria, early substance use, and biomarkers from genetics, neuroimaging, and physiology research. This article reviews the evidence for these and other potential changes to the conduct disorder diagnosis. We report that although there is a great deal of exciting research into each of the topics, very little of it provides the precise sort of evidence base required to justify any alteration to the DSM‐V. We outline specific research questions and study designs needed to build the lacking evidence base for or against proposed changes to DSM‐V conduct disorder.
Facts, fancies and follies of drug‐induced QT/QTc interval shortening
Authors: Malik Marek
Published: January 2010

Parallels exist between drug‐induced QT/QTc prolongation and shortening. However, these parallels are largely superficial and the experience with drug‐induced QTc prolongation and its potential proarrhythmic link cannot be directly applied to drug‐related QTc shortening. The congenital short QT syndrome (SQTS) is clearly much less prevalent than congenital, long QT syndrome, possibly some 1000 times. If the same discrepancy exists between arrhythmic susceptibility to drug‐induced QTc prolongation and shortening, it is questionable whether regulatory burden should be imposed on drugs that might cause serious arrhythmia, once in many millions of exposures. Further, majority of torsadegenic drugs block the IKr current which is susceptible to the drug blockade because of the corresponding channel geometry. There is no parallel known for drug‐induced QTc shortening. Also, all drugs that prolong QTc interval massively cause torsade de pointes tachycardia in more than exceptional isolated instances. On the contrary, digitalis that causes substantial QTc shortening is not known to trigger frequently ventricular arrhythmias. Moreover, most available population QTc data were obtained with Bazett's correction which produces erroneous QTc shortening at slow heart rates. Safety limits derived from such data are inappropriate. Because practically all new drugs undergo the so‐called thorough QT study, drug‐induced QTc shortening will not go unnoticed for any new pharmaceutical. Describing drug‐related QTc shortening in the label seems sufficient to avoid treatment of the rare SQTS subjects. Intensive investigations of QTc‐shortening drugs (similar to those of drugs with positive thorough QT studies) do not seem to be warranted.

This article is a commentary on Shah, pp. 58–69 of this issue and is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010
Evaluation of Selective Culling of Infected Individuals to Control Tasmanian Devil Facial Tumor Disease
Authors: LACHISH SHELLY , McCALLUM HAMISH , MANN DYDEE , PUKK CHRISSY E. , JONES MENNA E.
Published: January 2010

Abstract:  Sustainable strategies to manage infectious diseases in threatened wildlife are still lacking despite considerable concern over the global increase in emerging infectious diseases of wildlife and their potential to drive populations to extinction. Selective culling of infected individuals will often be the most feasible option to control infectious disease in a threatened wildlife host, but has seldom been implemented or evaluated as a management tool for the conservation of threatened species. The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction by an infectious cancer, devil facial tumor disease (DFTD). We assess the success of an adaptive management trial involving selective culling of infected Tasmanian devils to control DFTD. Demographic and epidemiological parameters indicative of disease progression and impact were compared between the management site and a comparable unmanaged control site. Selective culling of infected individuals neither slowed rate of disease progression nor reduced population‐level impacts of this debilitating disease. Culling mortality simply compensated for disease mortality in this system. Failure of selective culling to impede DFTD progress and reduce its impacts in the managed population was attributed to DFTD's frequency‐dependent nature, its long latent period and high degree of infectivity, and the presence of a cryptic hidden disease reservoir or continual immigration of diseased individuals. We suggest that increasing the current removal rate and focusing removal efforts prior to the breeding season are options worth pursuing for future management of DFTD in this population. On the basis of our experience, we suggest that disease‐management programs for threatened wildlife populations be developed on the principles of adaptive management and utilize a wide variety of strategies with regular reviews and adaptation of strategies undertaken as new information is obtained.
Automated Mapping of Explosives Particles in Composition C‐4 Fingerprints*†‡
Authors: Verkouteren Jennifer R. , Coleman Jessica L. , Cho Inho
Published: January 2010

Abstract:  A method is described to perform automated mapping of hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX) particles in C‐4 fingerprints. The method employs polarized light microscopy and image analysis to map the entire fingerprint and the distribution of RDX particles. This method can be used to evaluate a large number of fingerprints to aid in the development of threat libraries that can be used to determine performance requirements of explosive trace detectors. A series of 50 C‐4 fingerprints were characterized, and results show that the number of particles varies significantly from print to print, and within a print. The particle size distributions can be used to estimate the mass of RDX in the fingerprint. These estimates were found to be within ±26% relative of the results obtained from dissolution gas chromatography/μ‐electron capture detection for four of six prints, which is quite encouraging for a particle counting approach. By evaluating the average mass and frequency of particles with respect to size for this series of fingerprints, we conclude that particles 10–20 μm in diameter could be targeted to improve detection of traces of C‐4 explosives.
Study of Chilean Children’s Dental Maturation*
Authors: Flores Antonieta Pérez , Sanhueza Mario Aguirre , Barboza Patricio , Monti Claudia Fierro
Published: January 2010

Abstract:  In forensic science, determining a person’s chronological age has become a challenge for researchers. Determining age using dental calcification is becoming increasingly important. The objective of this study is to estimate the dental age of the children’s population in Region VIII, Chile. The sample was randomly taken from children under the care of the Faculty of Dentistry at the Universidad de Concepción in Chile. The study encompasses 159 children between 3 and 14 years of age. The dental age was determined following the Demirjian method. The Bland–Altman method was applied to establish the correlation. It was determined that the range between chronological and dental age is similar, and the degree of correlation between both ages is nearly perfect. In conclusion, the degree of correlation between the chronological and dental ages for each gender is also very good although it is slightly higher for females.
Efficacy of a low‐concentration chlorhexidine mouth rinse in non‐compliant periodontitis patients attending a supportive periodontal care programme: a randomized clinical trial
Authors: Escribano Marta , Herrera David , Morante Sergio , Teughels Wim , Quirynen Marc , Sanz Mariano
Published: January 2010

Escribano M, Herrera D, Morante S, Teughels W, Quirynen M, Sanz M. Efficacy of a low‐concentration chlorhexidine mouthrinse in non‐compliant periodontitis patients attending a supportive periodontal care programme: a randomized clinical trial. J Clin Periodontol 2010; 37: 266–275. doi: 10.1111/j.1600‐051X.2009.01521.x.

Objective: To assess the clinical and microbiological efficacy of a 0.05% chlorhexidine and 0.05% cetyl‐pyridinium chloride mouth rinse in supportive periodontal care (SPC) in patients with inadequate plaque control.

Material and Methods: The study was a randomized, double‐blinded, placebo‐controlled clinical trial in patients with moderate to severe chronic periodontitis under SPC with an inadequate plaque control (Turesky index >1). After supragingival prophylaxis and oral hygiene reinforcement, participants rinsed twice a day for 3 months with the test or placebo solutions, in addition to conventional hygiene. Primary clinical outcome variables included plaque and gingival indices. As secondary outcomes, periodontal and microbiological variables were studied. ancova and χ2 tests were used to compare the variables.

Results: Forty‐seven patients (22 placebo and 25 test group) participated. After 3 months, plaque levels increased in the placebo group, while diminished in the test group (p<0.001). Similar effects were found for bleeding on probing. The other clinical parameters did not show significant differences. Microbiological variables demonstrated inter‐group significant reductions in subgingival counts of Fusobacterium nucleatum and Prevotella intermedia and a decrease of the total bacterial counts in saliva.

Conclusions: The tested mouth rinse demonstrated efficacy in reducing plaque and gingivitis, as well as in decreasing the microbial load in saliva and gingival sulcus.
Growth/differentiation factor‐5: a candidate therapeutic agent for periodontal regeneration? A review of pre‐clinical data
Authors: Moore Yolanda R. , Dickinson Douglas P. , Wikesjö Ulf M. E.
Published: January 2010

Moore YR, Dickinson DP, Wikesjö UME. Growth/differentiation factor‐5: a candidate therapeutic agent for periodontal regeneration? A review of pre‐clinical data. J Clin Periodontol 2010; 37: 288–298. doi: 10.1111/j.1600‐051X.2009.01527.x.

Aim: Therapeutic concepts involving the application of matrix, growth and differentiation factors have been advocated in support of periodontal wound healing/regeneration. Growth/differentiation factor‐5 (GDF‐5), a member of the bone morphogenetic protein family, represents one such factor. The purpose of this review is to provide a background of the therapeutic effects of GDF‐5 expressed in various musculoskeletal settings using small and large animal platforms.

Methods: A comprehensive literature search was conducted to identify all reports in the English language evaluating GDF‐5 using the PubMed and Google search engines, and a manual search of the reference lists from the electronically retrieved reports. Two reviewers independently screened the titles and abstracts from a total of 69 reports, 22 of which were identified as pre‐clinical (in vivo) evaluations of GDF‐5. The full‐length article of the 22 pre‐clinical reports was then reviewed.

Results: Various applications including cranial and craniofacial bone formation, spine fusion, long bone fracture healing, cartilage, and tendon/ligament repair using a variety of small and large animal platforms evaluating GDF‐5 as a therapeutic agent were identified. A majority of studies, using biomechanical, radiographic, and histological analysis, demonstrated significant dose‐dependent effects of GDF‐5. These include increased/enhanced local bone formation, fracture healing/repair, and cartilage and tendon/ligament formation. GDF‐5 frequently was shown to accelerate wound maturation. Several studies demonstrated GDF‐5 to be a realistic alternative to autograft bone. Studies using pre‐clinical models and human histology suggest GDF‐5 may also increase/enhance periodontal wound healing/regeneration.

Conclusions: GDF‐5 appears a promising therapeutic agent for periodontal wound healing/regeneration as GDF‐5 supports/accelerates bone and tendon/ligament formation in several musculoskeletal settings including periodontal tissues.
Diagnosis of jaw and dentoalveolar fractures in a traumatized patient with cone beam computed tomography
Authors: Dölekoğlu Semanur , Fişekçioğlu Erdoğan , İlgüy Dilhan , İlgüy Mehmet , Bayirli Gündüz
Published: January 2010

Abstract –  The purpose of this case report is to discuss and illustrate the clinical usage of Cone Beam Computed Tomography (CBCT) for the diagnosis of maxillofacial fractures in a traumatized patient. In this presentation, a 30‐year‐old male patient who was referred to Oral Diagnosis and Radiology Department with a limitation of mouth opening was reported. The history of the patient revealed a traumatic injury on his face because of a fall. The patient was initially examined by a medical practitioner in the emergency department of a public hospital. According to 2D cephalometric analysis, no fracture existed. Panoramic radiograph and postero‐anterior reverse‐town showed bilateral condyle fractures. In addition, a fracture in the left mandibular incisor region could clearly be detected on the panoramic radiograph. For further diagnosis, digital images were taken with CBCT. Cross‐sectional views showed two vertical fracture lines on the alveolar bone between teeth numbers 17, 18 and 14, 15. A palatal root fracture was observed associated with tooth number 18. A fracture line in the left mandibular incisor region as well as bilateral condyle fractures could be seen clearly on CBCT views. CBCT is becoming a popular tool in modern dental practise. In the diagnosis of dentoalveolar fractures, CBCT has made it possible for the practitioner to get more detailed information.
Prevalence of traumatic injuries to maxillary permanent teeth in 9‐ to 14‐year‐old school children in Yazd, Iran
Authors: Navabazam Alireza , Farahani Shokoufeh Shahrabi
Published: January 2010

Abstract –  Aim: Trauma to maxillary anterior teeth is a common reason for emergency room visits among children; therefore, the goal of this study was to evaluate the prevalence and related factors of such trauma among 9‐ to 14‐year‐old children in Yazd.

Materials and methods: A sample of 1440 schoolchildren aged 9–14 years old, consisting of 720 boys and 720 girls, were randomly selected from 24 schools in Yazd. Ellis classification was used to record the dental injuries. Results: The prevalence found was 27.56%. The occurrence of trauma was significantly higher in male patients; furthermore, most of the dental trauma occurred in children between 9 and 10 years of age (47.38%). The most common type of injury was the ‘enamel only’ fracture; falls being the main cause of trauma. The most affected tooth was the maxillary central incisor Conclusions: The prevalence and most common causal factor of traumatic injuries to the maxillary anterior teeth in schoolchildren living in Yazd was approximately the same as that found in other countries.
Genotype Frequencies of Selected Drug Metabolizing Enzymes and ABC Drug Transporters among Breast Cancer Patients on FAC Chemotherapy
Authors: Afsar Nasir Ali , Haenisch Sierk , Mateen Ahmed , Usman Ahmed , Ufer Mike , Ahmed Khwaja Zafar , Ahmad Hakimuddin Razi , Cascorbi Ingolf
Published: January 2010

Abstract:  Polymorphic genes of drug metabolizing enzymes and transporters may influence drug response. With some exemptions, single nucleotide polymorphisms in such genes, however, are not known to be susceptibility factors for breast cancer. This study explored genotype profiles for the breast cancer patients on fluorouracil, doxorubicin and cyclophosphamide (FAC) in a Pakistani set of population and their comparison with HapMap data. Sixty‐eight female breast cancer patients were included. All received FAC chemotherapy. Relevant genotyping was done either through restriction fragment length polymorphism or pyrosequencing. The variant allele frequencies were: 5.1% for CYP2C9*2 (430C>T), 15.4% for CYP2C9*3 (1075A>C), 27.2% for CYP2C19*2 (681G>A), 33.1% for GSTA1*B (‐69C>T, ‐52G>A), 62.5% for ALDH3A1*2 (985C>G), 58.8% and 4.4% for ABCB1 (2677 G>T/A), 64.7% for ABCB1 3435 C>T, and 15.4%, 33.1% and 39.7% for ABCC2 (–24 C>T, 1249 G>A and 3972 C>T). In comparison with HapMap, this first exploration in Pakistani samples shows higher frequency of (i) CYP2C9*3 carriers (p < 0.05) than in Hispanic, Chinese, Japanese and African samples, (ii) ALDH3A1*2 carriers (p < 0.01) than Caucasian, Hispanic, Chinese, Japanese and African samples. For ABC transporters, a higher frequency of variant allele was observed in (iii) ABCB1 2677 G>T/A (p < 0.01) than Caucasian, Hispanic and African, (iv) ABCB1 3435 C>T (p < 0.05) than Chinese, Japanese and African, (v) ABCC2 1249 G>A (p < 0.01) than Hispanic, Chinese and Japanese samples. In conclusion, cyclophosphamide activation and detoxification of reactive intermediates may be altered in the Pakistani. Though carriers of CYP2C19*2 were higher than in Caucasian and Hispanics, they did not reach statistical significance (p = 0.05).
Implantation of Artificial Penile Nodules—A Review of Literature
Authors: Fischer Nicolas , Hauser Stefan , Brede Olivier , Fisang Christian , Müller Stefan
Published: January 2010

Introduction

The implantation of penile nodules under the foreskin is unusual in Western society. This practice is known in Slavic and Asian cultures and occasionally appears in the western world. We review the historical and medical evidence found in world literature to this date.

Aim

We discuss case reports and other literature on penile nodules and evaluate their medical significance.

Main Outcome Measures

Literature search for MEDLINE publications and additional references from non-Medline indexed publications concerning the implantation of foreign bodies under the foreskin.

Methods

Literature search for MEDLINE-indexed papers followed by a manual bibliographic review of cross-references. We extended the search to non-MEDLINE references using an Internet-based search engine. More information was retrieved by contacting different experts. A statistical analysis was applied to the data collected.

Results

There seems to be a predominance of penile bead implantation in Asian countries. The average age of a patient was 25.47 years. The average number of beads implanted was 2.71. There is a higher risk of becoming a sexually transmitted disease.

Conclusions

The prevalence of complications seems to be low. The incidence and severity of early or delayed complications are unknown but are probably underreported. Complications associated with this procedure should be known, especially partner complications. These nodules will possibly be encountered more often in western countries.
Effect of Penile-Extender Device in Increasing Penile Size in Men with Shortened Penis: Preliminary Results
Authors: Nikoobakht Mohammadreza , Shahnazari Alireza , Rezaeidanesh Maedeh , Mehrsai Abdolrasoul , Pourmand Gholamreza
Published: January 2010

Introduction

It has been suggested that the application of penile-extender devices increases penile length and circumference. However, there are a few scientific studies in this field.

Aims

The aim of this study was to assess the efficacy of a penile-extender (Golden Erect®, Ronas Tajhiz Teb, Tehran, Iran) in increasing penile size.

Methods

This prospective study was performed on subjects complaining about “short penis” who were presented to our clinic between September 15, 2008 and December 15, 2008. After measuring the penile length in flaccid and stretched forms and penile circumference, patients were instructed to wear Golden Erect®, 4–6 hours per day during the first 2 weeks and then 9 hours per day until the end of the third month. The subjects were also trained how to increase the force of the device during determined intervals. The patients were visited at the end of the first and third months, and penile length and circumference were measured and compared with baseline.

Main Outcome Measures

The primary end point of the study was changes in flaccid and stretched penile lengths compared with the baseline size during the 3 months follow-up.

Results

Twenty-three cases with a mean age of 26.5 ± 8.1 years entered the study. The mean flaccid penile length increased from 8.8 ± 1.2 cm to 10.1 ± 1.2 cm and 10.5 ± 1.2 cm, respectively, in the first and third months of follow-up, which was statistically significant (P < 0.05). Mean stretched penile length also significantly increased from 11.5 ± 1.0 cm to, respectively, 12.4 ± 1.3 cm and 13.2 ± 1.4 cm during the first and second follow-up (P < 0.05). No significant difference was found regarding proximal penile girth. However, it was not the same regarding the circumference of the glans penis (9.3 ± 0.86 cm vs. 8.8 ± 0.66 cm, P < 0.05).

Conclusion

Our findings supported the efficacy of the device in increasing penile length. Our result also suggested the possibility of glans penis girth enhancement using penile extender. Performing more studies is recommended.
Impact of Dry Ejaculation Caused by Highly Selective α1A-blocker: Randomized, Double-blind, Placebo-controlled Crossover Pilot Study in Healthy Volunteer Men
Authors: Shimizu Fumitaka , Taguri Masataka , Harada Yoshiko , Matsuyama Yutaka , Sase Kazuhiro , Fujime Makoto
Published: January 2010

Introduction

Dry ejaculation with loss of seminal emission is reported in patients who have been administered silodosin, an alpha1A-adrenoceptor antagonist.

Aim

We investigated the impact of dry ejaculation caused by orally administered silodosin on orgasmic function.

Methods

In a double-blind crossover study, 50 healthy volunteer men were randomly assigned to receive either a single dose of 4-mg silodosin or placebo with 3 days of washout before crossover. Subjects masturbated 4 hours after administering agents.

Main Outcome Measures

Numerical rating scale (NRS) score from 0 (highest) to 10 (lowest) for subjective quality of orgasm, the subjective number of contractions of the bulbocavernosus/pelvic floor muscles, and the amount of semen were examined.

Results

After the administration of silodosin, the NRS score worsened by 1.3 points (P = 0.003), the number of contractions of the bulbocavernosus/pelvic floor muscles decreased by about 1 (P = 0.003), and there was a decrease of 1.8 mL in the amount of semen produced (P <0.0001). Eleven men overall (22%) on silodosin administration had less than a 50% decrease from baseline in the amount of semen.

Conclusions

Silodosin may adversely affect the subjective orgasmic function by causing an abnormal ejaculation with decreased (or no) semen discharge and a decrease in the number of bulbocavernosus/pelvic floor muscle contractions. Semen passing through the urethra and sufficient rhythmic contraction of the muscle of the pelvic floor may contribute to the subjective pleasure of orgasm.
The Relaxation Induced by Uroguanylin and the Expression of Natriuretic Peptide Receptors in Human Corpora Cavernosa
Authors: Sousa Clauber M. , Havt Alexandre , Santos Cláudia F. , Arnaud-Batista F.J. , Cunha Karina M.A. , Cerqueira João Batista G. , Fonteles Manassés C. , Nascimento Nilberto R.F.
Published: January 2010

Introduction

Receptors for natriuretic peptides have been demonstrated as potential targets for the treatment of male erectile dysfunction.

Aim

This study investigates the relaxant effects of the atrial natriuretic peptide (ANP) and uroguanylin (UGN), and expression of natriuretic peptide receptors on strips of human corpora cavernosa (HCC).

Main Outcome Measures

Quantitative analysis of natriuretic receptor expression and relaxation of precontracted strips were used to assess the membrane-bound guanylate cyclase–cyclic guanosine monophosphate (cGMP) pathway in HCC strips.

Methods

HCC was obtained from a cadaver donor at the time of collection of organs for transplantation (14–47 years) and strips were mounted in organ baths for isometric studies.

Results

ANP and UGN both induced concentration-dependent relaxation on HCC strips with a maximal response attained at 300 nM, corresponding to 45.4 ± 4.0% and 49 ± 4.8%, respectively. The relaxation is not affected by 30 µM 1H-[1,2,4]oxaolodiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylate cyclase inhibitor), but it is significantly blocked by 10 µM isatin, a nonspecific particulate guanylate cyclase (pGC) inhibitor. UGN was unable to potentiate electrical field stimulation (EFS) or acetylcholine-induced relaxations. The potential role of pGC activation and cGMP generation in this effect is reinforced by the potentiation of this effect by phosphodiesterase-5 inhibitor vardenafil (55.0 ± 7.5-UGN vs. 98.6 ± 1.4%-UGN+vardenafil; P <0.05). The relaxant effect was also partially (37.6%) blocked by the combination iberitoxin-apamin but was insensitive to glybenclamide. The expression of guanylate cyclase receptors (GC-A, GC-B, GC-C) and the expression of the natriuretic peptide “clearance” receptor (NPR-C) were confirmed by real-time polymerase chain reaction. The exposure of HCC strips to ANP (1 µM) and UGN (10 µM) significantly increased cGMP, but not cyclic adenosine monophosphate (cAMP) levels.

Conclusions

UGN relaxes HCC strips by a guanylate cyclase and Kca-channel-dependent mechanism. These findings obtained in HCC reveal that the natriuretic peptide receptors are potential targets for the development of new drugs for the treatment of erectile dysfunction.
Nurse Anesthetist Follow‐up of an Adolescent Female With Gunshot Trauma: A Case Study
Authors: Johnson Carolyn , Lunney Margaret
Published: January 2010

PURPOSE.  This case study was written to demonstrate the usefulness of standardized nursing diagnoses, outcomes, and interventions in nurse anesthetist care of an adolescent trauma patient.

DATA SOURCES.  Literature reviews using Academic Premier, Google Scholar, and CINAHL databases were done to find current, relevant articles concerning evaluation and support of female African‐American adolescents living in socially vulnerable and economically exploited environments.

DATA SYNTHESIS.  A case is presented and evidence from current publications is analyzed to support the diagnosis, outcomes, and interventions.

CONCLUSION.  The investment in extra time, care, and effort sometimes required for the full development of a treatment plan for teenagers who live where they are at high risk for violence and other consequences of stressful environments is a worthwhile one, even if results may require contact over an extended time period.

PRACTICE IMPLICATIONS.  Nurses of all specialty backgrounds need to be concerned with the progress of their patients. Sometimes nurses can best serve their patients by stepping away from the physiological event and focusing instead on responses in the domain of coping and stress tolerance as the root of difficulties.
Immunosuppressive Activity of Buxidin and E‐Buxenone from Buxus hyrcana
Authors: Mesaik M. Ahmed , Halim Sobia A. , Ul‐Haq Zaheer , Choudhary M. Iqbal , Shahnaz Salma , Ayatollahi S. A. M , Murad Shahnaz , Ahmad Aqeel
Published: January 2010

Buxidin (1) and E‐Buxenone (2), steroidal alkaloids from Buxus hyrcana, are found to possess potent immunosuppressive properties. The activity was tested in vitro on oxidative burst, chemotaxis, T‐cell proliferation, and cytokine production. Both compounds showed a significant immunomodulatory activity with clear suppressive effect on oxidative burst and chemotaxis in a dose‐dependent manner. They also exhibited suppressive effect on the phytohemagglutinin‐stimulated T‐cell proliferation. The immunomodulatory activity was further confirmed by the suppression of IL‐2 and IL‐4 production. Furthermore, molecular docking studies were performed to investigate the binding mode of Buxidin (1) and E‐Buxenone (2) with IL‐2. Despite the structural differences between Buxidin (1) and E‐Buxenone (2), docking results revealed that they adopt a similar binding pattern at the active site of the IL‐2. A good agreement between practical and theoretic results indicates that the current docking study could provide an alternate tool for the structural optimization of recently identified ligand as more potent IL‐2 inhibitors.
Microwave‐Assisted Solvent‐Free Synthesis of Bis(dihydropyrimidinone)benzenes and Evaluation of their Cytotoxic Activity
Authors: Azizian Javad , Mohammadi Mohammad K. , Firuzi Omidreza , Mirza Behrooz , Miri Ramin
Published: January 2010

An effective one‐pot synthesis of bis(dihydropyrimidinonoe)benzenes using chlorotrimethylsilane (TMSCl) through Biginelli condensation reaction of terephthalic aldehyde, 1,3‐dicarbonyl compounds and (thio)urea or guanidine under microwave irradiation conditions is described. Excellent yields of the products and simple work‐up are attractive features of this green protocol. Then, the cytotoxic activities of these compounds were evaluated on five different human cancerous cell lines (Raji, HeLa, LS‐180, SKOV‐3 and MCF7). Their cytotoxic study indicated that they possessed a weak to moderate activity. Furthermore, the higher activity of compound 4b bearing sulfur in C2 position of pyrimidinone ring showed the importance of this site for cytotoxic activity of these compounds.
Antiproliferative Activity of Purine Nucleoside Phosphorylase Multisubstrate Analogue Inhibitors Containing Difluoromethylene Phosphonic Acid against Leukaemia and Lymphoma Cells
Authors: Glavaš‐Obrovac Ljubica , Suver Mirjana , Hikishima Sadao , Hashimoto Mariko , Yokomatsu Tsutomu , Magnowska Lucyna , Bzowska Agnieszka
Published: January 2010

Potent inhibitors of purine nucleoside phosphorylase (PNP) are expected to act as selective agents against T‐cell tumours. Five compounds with guanine, three with hypoxanthine, and five with 9‐deazaguanine, all connected by a linker with difluoromethylene phosphonic acid, were studied on their inhibitory potential against human and calf PNPs. Antiproliferative activity of these analogues against lymphocytes as well as lymphoma and leukaemia cells has been also investigated. All tested compounds act as multisubstrate analogue inhibitors of PNP with the apparent inhibition constants in the range 5–100 nm, and also show a slight antiproliferative activity. Analogues with 9‐deazaguanine aglycone have better anti‐leukaemic and anti‐lymphoma activities compared to the guanine and hypoxanthine analogues, and applied in the concentration of 100 μm, caused a statistically significant decrease in the cell viability in all human leukaemia and lymphoma cells used. Despite the high PNP inhibitory potential of tested analogues, no differences were observed between the effects on the growth of tumour cells sensible to the inhibition of PNP, such as human adult T‐cell leukaemia and lymphoma cells, and other investigated cells. Obtained poor effects on cell proliferation could be explained probably by a poor ability of tested compounds to penetrate cell membranes.
Using Ligand‐Based Virtual Screening to Allosterically Stabilize the Activated State of a GPCR
Authors: Taylor Christina M. , Rockweiler Nicole B. , Liu Cassie , Rikimaru Loryn , Tunemalm Anna‐Karin , Kisselev Oleg G. , Marshall Garland R.
Published: January 2010

G‐protein coupled receptors play an essential role in many biological processes. Despite an increase in the number of solved X‐ray crystal structures of G‐protein coupled receptors, capturing a G‐protein coupled receptor in its activated state for structural analysis has proven to be difficult. An unexplored paradigm is stabilization of one or more conformational states of a G‐protein coupled receptor via binding a small molecule to the intracellular loops. A short tetrazole peptidomimetic based on the photoactivated state of rhodopsin‐bound structure of Gtα(340–350) was previously designed and shown to stabilize the photoactivated state of rhodopsin, the G‐protein coupled receptor involved in vision. A pharmacophore model derived from the designed tetrazole tetrapeptide was used for ligand‐based virtual screening to enhance the possible discovery of novel scaffolds. Maybridge Hitfinder and National Cancer Institute diversity libraries were screened for compounds containing the pharmacophore. Forty‐seven compounds resulted from virtually screening the Maybridge library, whereas no hits resulted with the National Cancer Institute library. Three of the 47 Maybridge compounds were found to stabilize the MII state. As these compounds did not inhibit binding of transducin to photoactivated state of rhodopsin, they were assumed to be allosteric ligands. These compounds are potentially useful for crystallographic studies where complexes with these compounds might capture rhodopsin in its activated conformational state.
The Frequency and Functional Impact of Overlapping Hypertension on Hypertrophic Cardiomyopathy: A Single‐Center Experience
Authors: Aslam Farhan , Haque Attiya , Foody JoAnne , Shirani Jamshid
Published: January 2010

J Clin Hypertens (Greenwich)

Between 1995 and 2005, 196 adults with hypertrophic cardiomyopathy (HCM) were evaluated. Among these, 122 (62%, group 1) patients also had systemic hypertension. The clinical presentation, management, outcome, and echocardiographic findings of these patients were compared with 74 (38%, group 2) patients without systemic hypertension. Patients in group 1 were older at the time of HCM diagnosis and had a higher prevalence of diabetes (28% vs 9%; P=.02) and coronary artery disease (40% vs 25%; P=.03). In addition, echocardiography showed a significantly higher prevalence of systolic anterior motion of the anterior mitral valve in association with dynamic left ventricular outflow obstruction (52% vs 19%; P=.02) and mitral annular calcification (27% vs 13%; P=.03) in group 1 patients. Left ventricular wall thickness (17 mm vs 19 mm), end‐diastolic diameter (42 mm vs 42 mm), resting outflow tract gradient >30 mm Hg (17% vs 16%), and ejection fraction (65% vs 64%) were similar in the two groups. HCM frequently coexists with systemic hypertension in the adult population. Presence of systemic hypertension in HCM patients is associated with older age and higher risk of diabetes, coronary artery disease, and noncardiac death.
Cardiac Rehabilitation Programs Improve Metabolic Parameters in Patients With the Metabolic Syndrome and Coronary Heart Disease
Authors: Pérez Ignacio P. , Zapata Maria Á. , Cervantes Carlos E. , Jarabo Rosario M. , Grande Cristina , Plaza Rose , Garcia Sara , Rodriguez Miriam L. , Crespo Silvia , Perea Jesús
Published: January 2010

J Clin Hypertens (Greenwich).

This study was performed to determine the effectiveness of a cardiac rehabilitation and exercise training program on metabolic parameters and coronary risk factors in patients with the metabolic syndrome and coronary heart disease. The study involved 642 patients with coronary heart disease. Of them, 171 (26.7%) fulfilled criteria for the metabolic syndrome. Clinical data, laboratory tests, and exercise testing were performed before and after the program, which lasted 2 to 3 months. Except for waist circumference, there were no significant differences between groups; blood pressure, high‐density lipoprotein cholesterol, triglycerides, and fasting glucose improvements during the follow‐up were higher in patients with the metabolic syndrome (all P<.001). At study end, in patients with the metabolic syndrome, functional capacity increased by 26.45% ( P<.001), as measured by metabolic equivalents, with a slight increase of 1.25% ( P=not significant) in the double product. Patients with the metabolic syndrome who took part in this secondary prevention program reported improvements in cardiovascular risk profile and functional capacity.
IDEC's History: Important Milestones 1963–1978
Authors: Harwood Buie
Published: January 2010

IDEC began to compile its history in 1972, and later had anniversary celebrations at its annual conferences in 1982, 1987, 1992, and 2008. When the first efforts began, members recognized that IDEC had a significant history and that the history was important internally as well as externally to the profession as a whole. Without these early efforts and continuing ones by IDEC members, IDEC would not have its developmental footprint, historical archives, historical identity, or milestone markers charted herein. In essence, its history served as its memory keeper and its foundation for growth.
Glutamate‐mediated astrocyte‐to‐neuron signalling in the rat dorsal horn
Authors: Bardoni Rita , Ghirri Alessia , Zonta Micaela , Betelli Chiara , Vitale Giovanni , Ruggieri Valentina , Sandrini Maurizio , Carmignoto Giorgio
Published: January 2010

By releasing neuroactive agents, including proinflammatory cytokines, prostaglandins and neurotrophins, microglia and astrocytes are proposed to be involved in nociceptive transmission, especially in conditions of persistent, pathological pain. The specific action on dorsal horn neurons of agents released from astrocytes, such as glutamate, has been, however, poorly investigated. By using patch‐clamp and confocal microscope calcium imaging techniques in rat spinal cord slices, we monitored the activity of dorsal horn lamina II neurons following astrocyte activation. Results obtained revealed that stimuli that triggered Ca2+ elevations in astrocytes, such as the purinergic receptor agonist BzATP and low extracellular Ca2+, induce in lamina II neurons slow inward currents (SICs). Similarly to SICs triggered by astrocytic glutamate in neurons from other central nervous system regions, these currents (i) are insensitive to tetrodotoxin (TTX), (ii) are blocked by the NMDA receptor (NMDAR) antagonist d‐AP5, (iii) lack an AMPA component, and (iv) have slow rise and decay times. Ca2+ imaging also revealed that astrocytic glutamate evokes NMDAR‐mediated episodes of synchronous activity in groups of substantia gelatinosa neurons. Importantly, in a model of peripheral inflammation, the development of thermal hyperalgesia and mechanical allodynia was accompanied by a significant increase of spontaneous SICs in dorsal horn neurons. The NMDAR‐mediated astrocyte‐to‐neuron signalling thus represents a novel pathway that may contribute to the control of central sensitization in pathological pain.
Effects of intrauterine undernutrition on hypothalamic Kiss1 expression and the timing of puberty in female rats
Authors: Iwasa T. , Matsuzaki T. , Murakami M. , Fujisawa S. , Kinouchi R. , Gereltsetseg G. , Kuwahara A. , Yasui T. , Irahara M.
Published: January 2010

Recent studies have suggested that intrauterine undernutrition is closely associated with the pathogenesis of diseases after birth. Perinatal undernutrition is known to disturb the development of reproductive function and delay the onset of puberty in some species. Using a rat model, we determined the effects of prenatal undernutrition on the development of the hypothalamic kisspeptin system and evaluated whether the alteration of the kisspeptin system contributes to the delayed onset of puberty induced by prenatal undernutrition. We also evaluated the effects of prenatal undernutrition on the developmental changes in serum leptin levels because leptin was a putative positive regulator of the hypothalamic kisspeptin system. We compared the timing of vaginal opening (VO) and the developmental changes in body weight, hypothalamic Kiss1 mRNA levels, and serum leptin concentrations between offspring with prenatal undernutrition (UN offspring) and normal nutrition (NN offspring). After birth, the UN offspring showed rapid growth and had caught up to body weight of the NN offspring by postnatal day 12. After postnatal day 16, the UN offspring showed significantly lower Kiss1 mRNA levels than the NN offspring, despite their significantly higher serum leptin levels (at days 20 and 28). The timing of VO in the UN offspring was delayed compared with that in the NN offspring, and chronic central injection of kisspeptin normalized the timing of VO in the UN offspring. These results suggest that decreased hypothalamic kisspeptin action contributes to the delayed onset of puberty in prenatally undernourished female rats. Increased leptin resistance in the kisspeptin system might be involved in these alterations.
Statins for Wound Healing
Authors: Gough Nancy R.
Published: January 2010

By inhibiting the production of farnesyl pyrophosphate, statins may promote epithelial wound healing.
Focus Issue: External and Internal Regulators of Immune Responses
Authors: Foley John F. , Gough Nancy R.
Published: January 2010

Host defense mechanisms are modulated by host-derived and pathogen-derived factors.
What Is the Function of the Dendritic Cell Side of the Immunological Synapse?
Authors: Rodríguez-Fernández José Luis , Riol-Blanco Lorena , Delgado-Martín Cristina
Published: January 2010

The immunological synapse organizes signaling responses in dendritic cells as well as in T cells.
Fish Cell Culture: Characteristics of a Continuous Fibroblastic Cell Line from Walleye (Stizostedion vitreum vitreum)
Authors: Kelly R. K. , Miller H. R. , Nielsen O. , Clayton J. W.
Published: January 2010

A cell line (WC-1) was initiated from a dermal tumor from walleye (Stizostedion vitreum vitreum). The fibroblastic cells were propagated in Eagle's minimum essential medium, supplemented with 10% fetal bovine serum, as monolayer cultures that exhibited only slight density-dependent inhibition of mitosis. Cells, which were characterized at passage levels 45–46, grew optimally at 20 to 25 °C, but growth was limited at 10 and 30 °C. The line has a chromosome modal number of 48 or 49. Zymograms for lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) of WC-1 cells and of normal walleye tissue were very similar, indicating that the WC-1 line may be distinguished by these isozymes. Cell cultures supported replication (with resulting cytopathology) of infectious pancreatic necrosis virus (IPNV, strain VR 299) and the amphibian icosahedral cytoplasmic deoxyribovirus LT-1. The WC-1 line which has now been subcultured more than 100 times can properly be regarded as a continuous cell line.Key words: poikilotherm vertebrate cell line, fish virus, amphibian virus, neoplasm, walleye dermal sarcoma, lactate dehydrogenase, malate dehydrogenase, isozyme
Effects of Logging on Macroinvertebrates in Streams With and Without Buffer Strips
Authors: Newbold J. D. , Erman D. C. , Roby K. B.
Published: January 2010

The impact of logging with and without buffer strip protection on stream macroinvertebrates was examined through comparisons of community structure in commercially logged and control watersheds throughout northern California. A nonparametric test of community dissimilarities within matched blocks of two control and one or two treated stations showed significant (P < 0.05) logging effects on unprotected streams when Euclidean distance and mutual information were used as dissimilarity indices, but not when chord distance was used. Shannon diversity in unprotected streams was lower (P < 0.01) than in control (unlogged) streams; densities of total macroinvertebrate fauna and of Chironomidae, Baetis, and Nemoura were higher in unprotected streams than in controls (P < 0.05). Streams with narrow buffer strips (< 30 m) showed significant effects by the Euclidean distance test, but diversity varied widely and was not significantly different from that in either unprotected or control streams. Macroinvertebrate communities in streams with wide buffers (≥ 30 m) could not be distinguished from those of controls by either Euclidean distance or diversity; however, diversity in wide-buffered streams was significantly greater than in streams without buffer strips, indicating effective protection from logging effects.Key words: buffer strips, California, diversity, ecological dissimilarity, invertebrates, logging, streams
Biochemical Genetic Variation in Walleye Pollock, Theragra chalcogramma: Population Structure in the Southeastern Bering Sea and the Gulf of Alaska
Authors: Grant W. S. , Utter F. M.
Published: January 2010

The distributions of biochemical genetic variants were used to examine the genetic relationships among populations of walleye pollock, Theragra chalcogramma, located in the southeastern Bering Sea and the Gulf of Alaska. Enzymatic proteins in tissue samples of fish collected from 14 locations were assayed for electrophoretically detectable variants. Twenty-eight loci were tentatively identified, 8 (28%) of which were polymorphic. Only two loci, ME-2 and 6PG, had variants in great enough frequencies to be of use in distinguishing populations. Significant differences between regions were detected using a log-likelihood test for heterogeneity. Variation in allelic frequencies within each region was minimal. Cluster analysis of genetic similarities between sample pairs revealed two major clusters roughly corresponding to the Bering Sea and the Gulf of Alaska. Our biochemical genetic data suggest that there are no distinct stocks within the southeastern Bering Sea nor within the Gulf of Alaska, but that there are minor genetic differences between fish in these two regions.Key words: Walleye pollock, Theragra chalcogramma; biochemical genetic variation, population structure, eastern Bering Sea, Gulf of Alaska, starch gel electrophoresis
Some Methods of Estimating the Parameters of the Leslie Matrix using Incomplete Population Data
Authors: Aalto Sergei , (Buck) Newsome G. E.
Published: January 2010

Methods of estimating some parameters or elements of a Leslie matrix when data for the modeled population are insufficient, particularly for the young year-classes, are developed. It is shown that the growth rate or dominant eigenvalue, as well as other eigenvalues of the matrix can be obtained and that estimates of the numbers in certain age-classes at future times can be predicted from incomplete data. Methods of dealing with cases where the given data are very restricted and results of computer simulations to test these methods are discussed. The methods are applied in estimating parameters for a population of yellow perch (Perca flavescens) inhabiting Lochaber Lake, Antigonish Co., Nova Scotia.Key words: yellow perch, Perca flavescens; Leslie matrix, population, simulation, modeling
Aluminum Shadowing–Direct Projection Photomicroscopy of Diatom Frustules
Authors: Quackenbush Dale W. , Bothwell Max L. , Bisson Peter A.
Published: January 2010

An aluminum shadowing–direct projection method is described which allows high resolution photomicrographic reproduction of diatom preparations in the 200–800× magnification range. The technique is simple and provides an inexpensive alternative to low magnification scanning electron micrographs. While resolution and depth of field are constrained by the limits of conventional optical microscopy, the shadowing technique permits size determination in three dimensions. In addition, routine diatom identification and enumeration can be done directly from photographic prints, which provide a permanent record for storage.Key words: diatom, microscopy, phytoplankton