bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Holocene history of the southwestern Baltic Sea: the Ancylus Lake stage
Authors: JENSEN JφRN BO , BENNIKE OLE , WITKOWSKI ANDRZEJ , LEMKE WOLFRAM , KUIJPERS ANTOON
Published: June 2010

One of the most discussed stages in the history of the Baltic Sea is the Ancylus Lake phase. This paper presents detailed information from the Darss Sill threshold area as well as the adjacent basins, i.e. the Mecklenburg Bay and Arkona Basin located in the southwesternmost Baltic. The threshold area was transgressed at the Baltic Ice Lake maximum phase and during the following regression about 10.3 ka BP a river valley was incised in the Darss Sill to a level of 23–24 m below present sea level (b.s.l.). Preboreal sediments in the study area show lowstand basin deposition in the Arkona Basin and the existence of a local lake in Mecklenburg Bay. The lowstand system is followed by the Ancylus Lake transgression that reached a maximum level of 19 m b.s.l. Thus, at the maximum level the water depth was about 5 m over the threshold, and the shore level fall during the Ancylus Lake regression must be in the same range. The Darss Sill area is the key area for drainage of the Ancylus Lake, and if the previously suggested regression of 8–10 m in southeastern Sweden is to be achieved, isostatic rebound must also play a role. The existence of the so‐called Dana River in the Darss Sill area cannot be supported by our investigations. We observed no signs of progressive erosion of the Darss Sill area in the Early Holocene, and there are no prograding systems in Mecklenburg Bay that can be related to the Ancylus Lake regression. On the contrary, local lakes developed in Mecklenburg Bay and in the Darss Sill threshold area. In the Darss Sill area, marl was deposited in a lake in the valley that developed after the final drainage of the Baltic Ice Lake. Studies of diatoms and macrofossils, combined with seismic interpretation and radiocarbon dating, provide detailed information about the chronology and the relative shore level of these lake phases as well as about environmental conditions in the lakes.
Inbreeding Depression Accumulation across Life‐History Stages of the Endangered Takahe
Authors: GRUEBER CATHERINE E. , LAWS REBECCA J. , NAKAGAWA SHINICHI , JAMIESON IAN G.
Published: June 2010

Abstract:  Studies evaluating the impact of inbreeding depression on population viability of threatened species tend to focus on the effects of inbreeding at a single life‐history stage (e.g., juvenile survival). We examined the effects of inbreeding across the full life‐history continuum, from survival up to adulthood, to subsequent reproductive success, and to the recruitment of second‐generation offspring, in wild Takahe (
Porphyrio hochstetteri
) by analyzing pedigree and fitness data collected over 21 breeding seasons. Although the effect size of inbreeding at individual life‐history stages was small, inbreeding depression accumulated across multiple life‐history stages and ultimately reduced long‐term fitness (i.e., successful recruitment of second‐generation offspring). The estimated total lethal equivalents (2B) summed across all life‐history stages were substantial (16.05, 95% CI 0.08–90.8) and equivalent to an 88% reduction in recruitment of second‐generation offspring for closely related pairs (e.g., sib–sib pairings) relative to unrelated pairs (according to the pedigree). A history of small population size in the Takahe could have contributed to partial purging of the genetic load and the low level of inbreeding depression detected at each single life‐history stage. Nevertheless, our results indicate that such “purged” populations can still exhibit substantial inbreeding depression, especially when small but negative fitness effects accumulate across the species’ life history. Because inbreeding depression can ultimately affect population viability of small, isolated populations, our results illustrate the importance of measuring the effects of inbreeding across the full life‐history continuum.
Weight issues for people with epilepsy—A review
Authors: Ben‐Menachem Elinor
Published: June 2010

Summary  Weight gain or loss is not an integral part of epilepsy although a sedentary lifestyle can contribute to weight gain. Pharmacological treatment for epilepsy may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. Antiepileptic drugs (AEDs) associated with weight loss are felbamate, topiramate, and zonisamide. AEDs associated with weight gain are gabapentin, pregabalin, valproic acid, and vigabatrin and possibly, carbamazepine. Weight neutral AEDs are lamotrigine, levetiracetam, and phenytoin. In clinical practice it is critical to weigh patients regularly and AED selection should be based on each patient's profile without sacrificing therapeutic efficacy.
Laboratory Models Available to Study Alcohol‐Induced Organ Damage and Immune Variations: Choosing the Appropriate Model
Authors: D’Souza El‐Guindy Nympha B. , Kovacs Elizabeth J. , De Witte Philippe , Spies Claudia , Littleton John M. , De Villiers Willem J. S. , Lott Amanda J. , Plackett Timothy P. , Lanzke Nadine , Meadows Gary G.
Published: June 2010

The morbidity and mortality resulting from alcohol‐related diseases globally impose a substantive cost to society. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, substantial research in the alcohol field is focused on understanding the mechanisms by which alcohol‐related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most studies are performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium “Methods of Ethanol Application in Alcohol Model—How Long is Long Enough” at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol‐induced diseases in humans.
Ethanol Alters Cell Fate of Fetal Human Brain‐Derived Stem and Progenitor Cells
Authors: Vangipuram Sharada D. , Lyman William D.
Published: June 2010

Background:  Prenatal ethanol (ETOH) exposure can lead to fetal alcohol spectrum disorder (FASD). We previously showed that ETOH alters cell adhesion molecule gene expression and increases neurosphere size in fetal brain‐derived neural stem cells (NSC). Here, our aim was to determine the effect of ETOH on the cell fate of NSC, premature glial‐committed precursor cells (GCP), and premature neuron‐committed progenitor cells (NCP).

Methods:  NSC, GCP, and NCP were isolated from normal second‐trimester fetal human brains (n = 3) by positive selection using magnetic microbeads labeled with antibodies to CD133 (NSC), A2B5 (GCP), or PSA‐NCAM (NCP). As a result of the small percentage in each brain, NSC were cultured in mitogenic media for 72 hours to produce neurospheres. The neurospheres from NSC and primary isolates of GCP and NCP were used for all experiments. Equal numbers of the 3 cell types were treated either with mitogenic media or with differentiating media, each containing 0 or 100 mM ETOH, for 120 hours. Expression of Map2a, GFAP, and O4 was determined by immunoflourescence microscopy and western blot analysis. Fluorescence intensities were quantified using Metamorph software by Molecular Devices, and the bands of western blots were quantified using densitometry.

Results:  ETOH in mitogenic media promoted formation of neurospheres by NSC, GCP, and NCP. Under control conditions, GCP attached and differentiated, NSC and NCP formed neurospheres that were significantly smaller in size than those in ETOH. Under differentiating conditions, Map2a expression increased significantly in NSC and GCP and reduced significantly in NCP, and GFAP expression reduced significantly in GCP and NCP, and Gal‐C expression reduced significantly in all 3 cell types in the presence of ETOH compared to controls.

Conclusions:  This study shows that ETOH alters the cell fate of neuronal stem and progenitor cells. These alterations could contribute to the mechanism for the abnormal brain development in FASD.
Effects of Alcohol Cue Exposure on Response Inhibition in Detoxified Alcohol‐Dependent Patients
Authors: Gauggel Siegfried , Heusinger Anne , Forkmann Thomas , Boecker Maren , Lindenmeyer Johannes , Miles Cox W. , Staedtgen Mario
Published: June 2010

Background:  There is evidence that exerting self‐control during alcohol craving can diminish performance on subsequent tasks that require self‐control. Based on the resource depletion model (Muraven and Baumeister, 2000), we examined the influence of alcohol cue exposure on detoxified alcohol‐dependent patients’ ability to inhibit ongoing responses.

Methods:  Twenty alcohol‐dependent patients were randomly assigned to an alcohol‐cue exposure and a control‐cue exposure condition and thereafter had to perform an inhibition task (i.e., stop‐signal task).

Results:  Participants who sniffed alcohol before performing the inhibition task reported a stronger urge to drink alcohol than the control group that sniffed water. Participants who sniffed alcohol were also impaired in their inhibitory performance but not in their noninhibitory performance on the stop‐signal task.

Conclusions:  The urge to drink presumably reduced participants' self‐control, and this interfered with their ability to inhibit responding.
Interactions of Stress and CRF in Ethanol‐Withdrawal Induced Anxiety in Adolescent and Adult Rats
Authors: Wills Tiffany A. , Knapp Darin J. , Overstreet David H. , Breese George R.
Published: June 2010

Background: Repeated stress or administration of corticotropin‐releasing factor (CRF) prior to ethanol exposure sensitizes anxiety‐like behavior in adult rats. Current experiments determined whether adolescent rats were more sensitive to these challenges in sensitizing ethanol withdrawal‐induced anxiety and altering CRF levels in brain during withdrawal.

Methods: Male adult and adolescent Sprague–Dawley rats were restraint stressed (1 hour) twice 1 week apart prior to a single 5‐day cycle of ethanol diet (ED; stress/withdrawal paradigm). Other rats received control diet (CD) and three 1‐hour restraint stress sessions. Rats were then tested 5, 24, or 48 hours after the final withdrawal for anxiety‐like behavior in the social interaction (SI) test. In other experiments, adolescent rats were given two microinjections of CRF icv 1 week apart followed by 5 days of either CD or ED and tested in social interaction 5 hours into withdrawal. Finally, CRF immunoreactivity was measured in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) after rats experienced control diet, repeated ethanol withdrawals, or stress/withdrawal.

Results: Rats of both ages had reduced SI following the stress/withdrawal paradigm, and this effect recovered within 24 hours. Higher CRF doses were required to reduce SI in adolescents than previously reported in adults. CRF immunohistochemical levels were higher in the PVN and CeA of CD‐exposed adolescents. In adolescent rats, repeated ethanol withdrawals decreased CRF in the CeA but was not associated with decreased CRF cell number. There was no change in CRF from adult treatments.

Conclusions: In the production of anxiety‐like behavior, adolescent rats have equal sensitivity with stress and lower sensitivity with CRF compared to adults. Further, adolescents had higher basal levels of CRF within the PVN and CeA and reduced CRF levels following repeated ethanol withdrawals. This reduced CRF within the CeA could indicate increased release of CRF, and future work will determine how this change relates to behavior.
Milk Fat Globule EGF Factor 8 Attenuates Sepsis‐Induced Apoptosis and Organ Injury in Alcohol‐Intoxicated Rats
Authors: Wu Rongqian , Chaung Wayne W. , Zhou Mian , Ji Youxin , Dong Weifeng , Wang Zhimin , Qiang Xiaoling , Wang Ping
Published: June 2010

Background:  Despite advances in our understanding of excessive alcohol‐intake‐related tissue injury and modernization of the management of septic patients, high morbidity and mortality caused by infectious diseases in alcohol abusers remain a prominent challenge. Our previous studies have shown that milk fat globule epidermal growth factor‐factor VIII (MFG‐E8), a protein required to opsonize apoptotic cells for phagocytosis, is protective in inflammation. However, it remains unknown whether MFG‐E8 ameliorates sepsis‐induced apoptosis and organ injury in alcohol‐intoxicated rats. The purpose of this study was to determine whether recombinant murine MFG‐E8 (rmMFG‐E8) attenuates organ injury after acute alcohol exposure and subsequent sepsis.

Methods:  Acute alcohol intoxication was induced in male adult rats by a bolus injection of intravenous alcohol at 1.75 g/kg BW, followed by an intravenous infusion of 300 mg/kg BW/h of alcohol for 10 hours. Sepsis was induced at the end of 10‐hour alcohol infusion by cecal ligation and puncture (CLP). rmMFG‐E8 or vehicle (normal saline) was administered intravenously 3 times (i.e., at the beginning of alcohol injection, the beginning of CLP, and 10 hours post‐CLP) at a dose of 20 μg/kg BW each. Blood and tissue samples were collected 20 hours after CLP in alcoholic animals for various measurements.

Results:  Acute alcohol exposure per se did not affect the production of MFG‐E8; however, it primed the animal and enhanced sepsis‐induced MFG‐E8 downregulation in the spleen. Administration of rmMFG‐E8 reduces alcohol/sepsis‐induced apoptosis in the spleen, lungs, and liver. In addition, administration of rmMFG‐E8 after alcohol exposure and subsequent sepsis decreases circulating levels of TNF‐α and interleukin‐6 and attenuates organ injury.

Conclusions:  rmMFG‐E8 attenuates sepsis‐induced apoptosis and organ injury in alcohol‐intoxicated rats.
The P‐Selectin Gene Polymorphism Val168Met: A Novel Risk Marker for the Occurrence of Primary Ventricular Fibrillation During Acute Myocardial Infarction
Authors: ELMAS ELIF , BUGERT PETER , POPP TATJANA , LANG SIEGFRIED , WEISS CHRISTEL , BEHNES MICHAEL , BORGGREFE MARTIN , KÄLSCH THORSTEN
Published: June 2010

The P‐Selectin Gene Polymorphism Val168Met. Aims: Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death (SCD). Family history of SCD is described as risk factor for primary VF during acute AMI. Genetic factors may be associated with primary VF. We examined polymorphisms in genes related to the activation and adhesion of blood platelets in patients with and without VF in the setting of AMI and among healthy controls.

Methods: Two hundred and forty patients with a history of AMI and 475 healthy controls were studied. Seventy‐three patients (30%) had primary VF during AMI. By using PCR techniques with sequence‐specific primers (PCR‐SSP), we genotyped 5 single nucleotide polymorphisms (SNPs) in P‐selectin (SELP) (V168M, S290N, N592D, V599L, T715P), 2 SNPs (M62I, S273F) in P‐selectin glycoprotein ligand‐1 (SELPLG), 5 SNPs in CD40LG (−3459A>G, −122A>C, −123A>C, 148T>C, intr4–13T>C), the H558R SNP in SCN5A, and rs2106261 in ZFHX3. In addition, length polymorphisms in SELPLG (36bp‐tandem repeat) and CD40LG (CA‐repeat) were genotyped by PCR methods. Results were evaluated by 2‐sided t‐tests, chi‐square tests, and logistic regression analysis.

Results: None of the gene polymorphisms showed significant differences between AMI patients and healthy controls. Among patients with a history of VF, however, the SELP 168M variant showed a significantly higher prevalence (14/73 patients; 19.2%) as compared with patients without VF (13/167 patients; 7.8%; P < 0.01). This association remained significant in a logistic regression analysis after adjustment for age and gender (P = 0.013; odds ratio 2.8; 95% confidence interval 1.2–6.3).

Conclusions: This is the first description of an association of the SELP gene variant 168M with primary VF during acute MI. This variant may be a candidate polymorphism for evaluating the susceptibility for VF in the setting of acute MI. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1260‐1265, November 2010)
The Venture Capital Perspective on Collaboration with Large Corporations/MNEs in London and the South East: Pursuing Extra‐Regional Knowledge and the Shaping of Regional Venture Capital Networks?
Authors: Watkins Andrew
Published: June 2010

A seeming paradox of globalization is that while innovation and the industries and institutions that support it transcend local and national boundaries, high‐tech innovative activity continues to agglomerate in a select number of high‐capacity regions. Research, however, suggests that innovative regions must—through collaborative activity and related networks—both economize regional capacities while remaining open to global knowledge and finance. Collaboration and network formation are viewed as critical in this regard, as the competitive pressures of globalization are forcing firms to adopt collaborative and open innovation practices: forging relationships with external partners. Two important sources of knowledge and finance are regionally concentrated venture capital firms and large corporations, often globe‐straddling multinational enterprises. While collaboration occurs between these two actors, an understanding of the processes and implications has only begun to emerge. Focusing on collaborative venture capital activity in London and the South East, this exploratory paper presents a preliminary understanding as to the role that this particular collaborative activity plays in the pursuit of complementary, extra‐regional knowledge and expertise, and the extent to which this collaboration is recharacterizing the shape of regionally based venture capital networks.
Developmental Validation of Reduced‐Size STR Miniplex Primer Sets*
Authors: Opel Kerry L. , Chung Denise T. , Drábek Jiří , Butler John M. , McCord Bruce R.
Published: June 2010

Abstract:  This paper describes a developmental validation study of three Miniplex sets covering 12 of the 13 CODIS loci. As these new sets will be used for the analysis of degraded and low level DNA, the validation studies were performed using 100–125 pg of DNA, the lowest input level at which peak balance, peak intensity, and allele consistency were stable. To demonstrate the applicability of the Miniplex sets to forensic casework, these validation studies were completed in accordance with the Scientific Working Group on DNA Analysis Methods (SWGDAM). A range of tests were performed including studies of concordance with standard multiplex kits, sensitivity and reproducibility, and PCR amplification conditions. Additionally, studies of mixtures, nonhuman and environmentally degraded DNA, and simulated forensic samples were performed. Our results demonstrate that Miniplex STR amplification procedures are a robust and sensitive tool for the analysis of degraded DNA.
Patient morbidity and root coverage outcome after subepithelial connective tissue and de‐epithelialized grafts: a comparative randomized‐controlled clinical trial
Authors: Zucchelli Giovanni , Mele Monica , Stefanini Martina , Mazzotti Claudio , Marzadori Matteo , Montebugnoli Lucio , De Sanctis Massimo
Published: June 2010

Zucchelli G, Mele M, Stefanini M, Mazzotti C, Marzadori M, Montebugnoli L, de Sanctis M. Patient morbidity and root coverage outcome after subepithelial connective tissue and de‐epithelialized grafts: a comparative randomized‐controlled clinical trial. J Clin Periodontol 2010; 37: 728‐738 doi: 10.1111/j.1600-051X.2010.01550.x.

Aims: The aim of this randomized‐controlled clinical trial was to compare the patient morbidity and root coverage outcomes of a coronally advanced flap (CAF) with connective tissue (CTG) or de‐epithelialized gingival (DGG) grafts.

Methods: Fifty patients with one recession each were treated. In the control group, the CTG was harvested using the trap‐door approach while in the test group the CTG resulted from the de‐epithelialization of a free gingival graft.

Results: No statistically significant differences were demonstrated between groups in patients's pain killer consumption, post‐operative discomfort and bleeding. Lower stress and better ability to chew were demonstrated in the CTG group. Analgesic consumption increased with increasing height of the graft and in the case of dehiscence/necrosis of the primary flap. Pain was negatively correlated with the residual thickness of soft tissue covering the palatal bone. A statistically greater increase in buccal soft tissue thickness was observed in the DGG group.

Conclusions: No differences were demonstrated in the post‐operative pain and root coverage outcome in patients subjected to CAF with CTG or DGG.
Metastatic cutaneous carcinoid tumor mimicking an adnexal poroid neoplasm
Authors: Puri Puja Kumari , Galan Anjela , Glusac Earl J. , Cowper Shawn E.
Published: June 2010

Objective:  Metastatic cutaneous neoplasms may be difficult to differentiate from primary cutaneous neoplasms. Herein, we report an unusual case of metastatic cutaneous carcinoid tumor mimicking an adnexal poroid neoplasm.

Methods:  A 53‐year‐old male man presented with a neoplasm on the vertex of the scalp, clinically resembling a pigmented basal cell carcinoma.

Results:  A shave biopsy was suggestive of an apocrine poroma, however, a metastatic carcinoma could not be excluded. After acquiring additional clinical information and the complete excision of the neoplasm, further immunohistochemical stains supported the diagnosis a metastatic carcinoid tumor.

Conclusion:  To our knowledge, this is the first case of metastatic carcinoid tumor reported that has mimicked a poroid neoplasm.
Resting and post‐exercise serum biomarkers of cardiac and skeletal muscle damage in adolescent runners
Authors: Nie J. , Tong T. K. , George K. , Fu F. H. , Lin H. , Shi Q.
Published: June 2010

This study examined the response of serum biomarkers of cardiac and skeletal muscle damage at rest and after a routine workout of 21 km run in 12 male adolescent (16.2±0.6 years) long‐distance runners. Biomarkers of cardiac [troponins (cTnT, cTnI), creatine kinase MB mass (CK‐Mbmass)] and skeletal muscle [creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hydroxybutyrate dehydrogenase (HBD)] damage were assayed at rest, 2, 4 and 24 h post‐exercise. At rest, cTnT and cTnI were not detectable; however, CK, CK‐MBmass, AST, ALT and HBD were above corresponding clinical cut‐off values. Post‐exercise significant elevations above rest were observed for all biomarkers, except ALT, 2 and 4 h following the run, and remained elevated in cTnI, CK, CK‐MBmass, LDH and AST 24 h post‐workout. A significant increase in data points above clinical cut‐off values from rest to post‐exercise was reported for cTnT, cTnI and CK at 2 and 4 h, and in cTnI and CK 24 h post‐exercise. In conclusion, a 21 km run in adolescent runners increased post‐exercise biomarkers of cardiac and skeletal muscle damage.
Incontinentia pigmenti revisited. A novel nonsense mutation of the IKBKG gene
Authors: Fryssira Helen , Kakourou Talia , Valari Manthoula , Stefanaki Kaliopi , Amenta Stella , Kanavakis Emmanuel
Published: June 2010

Aim:  To describe and evaluate the clinical and molecular findings of patients with incontinentia pigmenti (IP) in Greece.

Methods:  We examined 12 female patients, initially aged 2 weeks to 7 months with clinical diagnosis of IP. Standard tests were performed including skin biopsies and ocular, dental and neurologic examinations. Molecular analysis was carried out on 8 out of 12 cases.

Results:  The initial clinical examination was stage 1 (vesicular lesions), stage 2 (verrucous lesions) or stage 3 (hyperpigmented linear lesions of the trunk/limbs). At the final clinical examination, 10 of our patients had typical vesicular, verrucous or mixed hyper‐hypopigmented skin lesions which had persisted from the neonatal period; seven had delayed dentition or conical teeth; two had developmental delay; one had microcephaly and strabismus and two had scarring alopecia. In seven patients, deletion of exons 4–10 of the IKBKG gene was found. In one patient, skewed X‐inactivation was demonstrated and a novel mutation p.Gln332X was found. The mothers’ DNA analyses were all normal.

Conclusion:  In our sample, all the cases were sporadic and the diagnosis of IP was based mainly on clinical features and confirmed with skin histology. Molecular analysis was used to find the mutations, in some cases to confirm diagnosis and to identify the carriers, which are crucial for prenatal and preimplantation diagnosis.
Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells
Authors: Lou Yi‐Wei , Chen Yi‐Yun , Hsu Shu‐Fan , Chen Ren‐Kun , Lee Chih‐Lei , Khoo Kay‐Hooi , Tonks Nicholas K. , Meng Tzu‐Ching
Published: June 2010

The oxidation and inactivation of protein tyrosine phosphatases is one mechanism by which reactive oxygen species influence tyrosine phosphorylation‐dependent signaling events and exert their biological functions. In the present study, we determined the redox status of endogenous protein tyrosine phosphatases in HepG2 and A431 human cancer cells, in which reactive oxygen species are produced constitutively. We used mass spectrometry to assess the state of oxidation of the catalytic cysteine residue of endogenous PTP1B and show that this residue underwent both reversible and irreversible oxidation to high stoichiometry in response to intrinsic reactive oxygen species production. In addition, our data show that the oxidation of PTP1B is specific to the active site Cys, with the other Cys residues in the protein remaining in a reduced state. Treatment of these cells with diphenyleniodonium, an inhibitor of NADPH oxidases, decreased reactive oxygen species levels. This resulted in inhibition of protein tyrosine phosphatase oxidation, concomitant with decreased tyrosine phosphorylation of cellular proteins and inhibition of anchorage‐independent cell growth. Therefore, our data also suggest that the high level of intrinsic reactive oxygen species may contribute to the transformed phenotype of HepG2 and A431 cells via constitutive inactivation of cellular protein tyrosine phosphatases.
tomocomd‐camps and protein bilinear indices – novel bio‐macromolecular descriptors for protein research: I. Predicting protein stability effects of a complete set of alanine substitutions in the Arc repressor
Authors: Ortega‐Broche Sadiel E. , Marrero‐Ponce Yovani , Díaz Yunaimy E. , Torrens Francisco , Pérez‐Giménez Facundo
Published: June 2010

Descriptors calculated from a specific representation scheme encode only one part of the chemical information. For this reason, there is a need to construct novel graphical representations of proteins and novel protein descriptors that can provide new information about the structure of proteins. Here, a new set of protein descriptors based on computation of bilinear maps is presented. This novel approach to biomacromolecular design is relevant for QSPR studies on proteins. Protein bilinear indices are calculated from the kth power of nonstochastic and stochastic graph–theoretic electronic‐contact matrices, and , respectively. That is to say, the kth nonstochastic and stochastic protein bilinear indices are calculated using and as matrix operators of bilinear transformations. Moreover, biochemical information is codified by using different pair combinations of amino acid properties as weightings. Classification models based on a protein bilinear descriptor that discriminate between Arc mutants of stability similar or inferior to the wild‐type form were developed. These equations permitted the correct classification of more than 90% of the mutants in training and test sets, respectively. To predict tm and values for Arc mutants, multiple linear regression and piecewise linear regression models were developed. The multiple linear regression models obtained accounted for 83% of the variance of the experimental tm. Statistics calculated from internal and external validation procedures demonstrated robustness, stability and suitable power ability for all models. The results achieved demonstrate the ability of protein bilinear indices to encode biochemical information related to those structural changes significantly influencing the Arc repressor stability when punctual mutations are induced.
Symmetrical peripheral digital gangrene following severe Plasmodium falciparum malaria‐induced disseminated intravascular coagulopathy
Authors: Ghafoor Sana ZA , MacRae Eva A , Harding Keith G , Patel Girish K
Published: June 2010

Ghafoor SZA, MacRae EA, Harding KG, Patel GK. Symmetrical peripheral digital gangrene following severe Plasmodium falciparum malaria‐induced disseminated intravascular coagulopathy.

Symmetrical peripheral digital gangrene is a life‐changing complication, caused by a pro‐thrombotic life‐threatening disease, such as disseminated intravascular coagulopathy (DIC) secondary to systemic infection. We describe the unusual case of a woman who developed symmetrical peripheral digital gangrene following DIC because of malaria. While initial treatment led to cure of the infection, in this report we describe also the subsequent management of symmetrical peripheral digital gangrene.
Pelvimetric Dimensions do not Impact upon Nerve Sparing or Erectile Function Recovery in Patients Undergoing Radical Retropubic Prostatectomy
Authors: von Bodman Christian , Matikainen Mika P. , Favaretto Ricardo L. , Matsushita Kazuhito , Mulhall John P. , Eastham James A. , Scardino Peter T. , Akin Oguz , Rabbani Farhang
Published: June 2010

Introduction

The impact of unfavorable pelvic anatomy on the likelihood of having a nerve sparing radical retropubic prostatectomy (RRP) and the potential correlation between pelvic dimensions and recovery of erectile function (EF) after RRP have not been previously evaluated.

Aim

To determine the impact of different pelvic bony and soft tissue dimensions as well as apical prostate depth on the likelihood of performing bilateral nerve sparing and on recovery of EF after RP.

Methods

Between November 2001 and June 2007, 644 potent men undergoing RRP had preoperative MRI where pelvimetry was performed with bilateral nerve sparing in 504 men. Outcomes including varying degrees of recovery of EF (level 1: normal; level 2: partial erections routinely sufficient for intercourse; level 3: partial erections occasionally sufficient for intercourse) were assessed. Median follow-up was 44.1 (interquartile range: 29.2, 65.3) months. We evaluated independent predictors of performing a bilateral nerve sparing procedure and of recovery of EF using multivariable Cox proportional hazards methods.

Main Outcome Measures

Likelihood of performing bilateral nerve sparing as well as recovery of EF after RRP.

Results

Patients with higher clinical stage and biopsy Gleason score are less likely to undergo bilateral nerve sparing. Surgeon is also a factor in the likelihood of having bilateral nerve sparing RRP. On multivariate Cox regression analysis, factors predictive of recovery of EF were age, pretreatment erectile function, surgeon, and modified Charlson score. None of the pelvimetric dimensions were significant predictors of any degree of recovery of EF. However, the study is limited by its retrospective nature and by being based on MRI evaluations useful for cancer staging rather than anatomical evaluation of pelvimetric dimensions.

Conclusions

We did not find unfavorable pelvic anatomy to impact the likelihood of performing a nerve sparing procedure or to be predictive of any degree of recovery of EF after RRP.
Improved Ejaculatory Latency, Control and Sexual Satisfaction When PSD502 is Applied Topically in Men with Premature Ejaculation: Results of a Phase III, Double-Blind, Placebo-Controlled Study
Authors: Carson Culley , Wyllie Michael
Published: June 2010

Introduction

PSD502 is a novel aerosolized, lidocaine-prilocaine, spray being developed for the treatment of lifelong premature ejaculation. The clinical profile of PSD502 is described in one of two double-blind, placebo-controlled, phase III studies.

Aim

To determine the effect of PSD502 on the Index of Premature Ejaculation (IPE) and intravaginal ejaculatory latency (IELT) of men with lifelong PE.

Methods

Men with lifelong PE who documented an IELT ≤ 1 minute with two or more of the first three sexual encounters during a 4-week baseline period were randomized to receive double-blind treatment with PSD502 or placebo for 3 months. Patients completed IPE and Premature Ejaculation Profile questionnaires at entry and monthly visits, and recorded stop-watch timed IELT during each encounter. Safety was assessed by collecting adverse event data and standard safety measures.

Main Outcome Measures

Stopwatch timed IELT recordings and a patient-reported outcome questionnaire the IPE were used in this study to determine the effect of PSD502 applied topically 5 minutes before intercourse.

Results

Two hundred fifty-six men with PE were randomized from 38 centers in the U.S., Canada, and Poland. The geometric mean IELT over the 3-month treatment period increased from a baseline of 0.56 minute and 0.53 minute in the PSD502 and placebo group respectively to 2.60 and 0.80 minute. There were significantly greater increases in the scores for the IPE domains of ejaculatory control, sexual satisfaction and distress in the PSD502 group than in the placebo group, with a mean 5.0 point difference between treatments in change from baseline in the IPE domain for ejaculatory control, 4.6 point difference in change from baseline in the IPE domain for sexual satisfaction, and a 2.5 point difference in change from baseline in the IPE domain for distress. This was supported by improvements in all secondary endpoints.

Conclusion

In this study, PSD502 applied topically to the glans penis 5 minutes before intercourse showed significantly improved ejaculatory latency, ejaculatory control, sexual satisfaction and distress and was shown to be well tolerated by patients and partners.
The Relationship between Androgens, Regulators of Collagen Metabolism, and Peyronie’s Disease: A Case Control Study
Authors: Karavitakis Markos , Komninos Christos , Simaioforidis Vasileios , Kontos Stylianos , Lefakis George , Politis Vasilios , Koritsiadis George , Konstantellou Katerina , Doumanis Gregorios
Published: June 2010

Introduction

Changes in collagen metabolism have been postulated to play a pivotal role in the pathogenesis of Peyronie’s Disease (PD). Androgens such as dehydroepiandrosterone sulfate (DHEA-S) and testosterone influence collagen metabolism by modulating the activity of matrix metalloproteases (MMP) and tissue inhibitors of metalloproteases (TIMP).

Aim

The aim of this study was to evaluate the interrelationship between androgens (DHEA-S and testosterone), key regulators of collagen metabolism such as insulin-like growth factor (IGF) 1 and IGF Binding Protein 3 (IGF-BP3), the MMP/TIMP system, and PD.

Methods

Age matched PD patients (14) and healthy men (10) who acted as controls were recruited. Blood samples were collected from all subjects in the early morning hours after an overnight fast.

Main Outcome Measures

Serum levels of testosterone, sex hormone binding globulin, DHEA-S, 3-α-androstanediol glucuronide, pro-MMP-1, MMP-1, MMP-2, TIMP-1, TIMP-2, IGF-1 and IGF-BP3 were measured in both groups. Statistical methods included univariate, bivariate, and multivariate regression models.

Results

Levels of DHEA-S (114.5 vs. 169.5 µg/dL; p = 0.03), IGF-BP3 (2.96 vs. 3.79 µg/mL; p = 0.01), and TIMP-1 (173.1 vs. 195 ng/mL; p = 0.01) were significantly lower in PD patients. In contrast, the level of TIMP-2 (102 vs. 85 ng/mL; p = 0.001) was significantly lower in the control group. Using stepwise regression analysis, only TIMP-2 (p <0.001) and DHEA-S (p = 0.04) were significantly related to PD in the final model (R2 =0.63). TIMP-1 and DHEA-S (r=0.55, p <0.05) were positively correlated in the PD group, whereas IGF-1 and testosterone (r=−0.54, p <0.05), and IGF-BP3 and testosterone (r=−0.68, p <0.05) were negatively correlated in PD patients.

Conclusions

Our findings suggest that decreased levels of adrenal androgens may be implicated in the pathogenesis of PD. The mechanism and clinical relevance of this observation remain to be established.
The EPIFARM Study: An Observational Study in 574 Community Pharmacies in Spain Characterizing Patient Profiles of Men Asking for Erectile Dysfunction Medication
Authors: Martín Morales Antonio , Ibáñez José , Machuca Manuel , Pol-Yanguas Emilio , Schnetzler Gabriel , Renedo Virginia Pascual
Published: June 2010

Introduction

Community pharmacists may be an important first point of contact for erectile dysfunction (ED) patients, but to date there are no reports of the characteristics of men approaching pharmacists for ED advice or treatment.

Aim

To characterize the profiles of men with and without phosphodiesterase-5 inhibitors (PDE5i) prescription asking for ED treatment at the pharmacy.

Methods

A multicenter, observational, cross-sectional study was conducted in Spanish community pharmacies September–November 2008. Of men asking for ED advice or treatment, each investigator recruited one with and one without PDE5i prescription. Study pharmacists completed a questionnaire of patient demographic, clinical, and behavioural data including the Sexual Health Inventory for Men.

Main Outcome Measures

Demographic characteristics and responses to questionnaires.

Results

Five hundred and seventy-four pharmacists recruited 1,147 patients; 1,113 were included for analysis. There were no statistical differences between the groups regarding weight, hypertension, diabetes mellitus, hypercholesterolemia, dyslipidemia, depression, or stress. There were no statistical differences in severity of ED (P = 0.7892) or proportion of men without ED in each group (P = 0.5755). ED symptoms had been present for a mean of 26 months in both groups before first consultation with a healthcare professional. The visit to the pharmacy was the first discussion about ED for 60.2% of the nonprescription group, and 50% of those who had previously discussed ED had done so with a pharmacist in the first instance. In the nonprescription group, 85.1% of men asked for a PDE5i.

Conclusions

Many men approached a community pharmacist for ED treatment and those with and without a PDE5i prescription had an equivalent ED severity and comorbidity profile. Community pharmacists should be trained in current concepts underlying the diagnosis and management of ED to enable them to educate men and encourage them to seek further medical care, increasing the chance of early detection of undiagnosed comorbidities such as cardiovascular disease.
A Protein Tyrosine Kinase Inhibitor, Imatinib Mesylate (Gleevec), Improves Erectile and Vascular Function Secondary to a Reduction of Hyperglycemia in Diabetic Rats
Authors: Gur Serap , Kadowitz Philip J. , Hellstrom Wayne J.G.
Published: June 2010

Introduction

Erectile dysfunction (ED) afflicts 50% of diabetic men, many of whom experience poor results with phosphodiesterase type 5 inhibitors. The protein tyrosine kinase (PTK) inhibitor imatinib (Gleevec, Novartis Pharmaceuticals, Basel, Switzerland) has therapeutic potential in diabetic men by maintaining β-cell function.

Aim

To determine if imatinib has a beneficial effect on erectile and vascular function in diabetic rats.

Methods

Male Sprague-Dawley rats were divided into six groups: (i) control; (ii) imatinib (50 mg/kg, daily gavage)-treated control; (iii) diabetic; (iv) preventive imatinib (8 weeks); (v) reversal imatinib (4 weeks untreated diabetes and 4 weeks of treatment); and (vi) insulin (8 weeks)-treated diabetic rats.

Main Outcome Measures

After 8 weeks, all groups underwent cavernosal nerve stimulation and measurements of intracavernosal pressure (ICP) and mean arterial pressure (MAP). Contractile and relaxation responses were evaluated using isolated strips of corpus cavernosum smooth muscle (CCSM) and aorta.

Results

Diabetic rats exhibited a 32% decrease in weight and fivefold increase in blood glucose levels. Imatinib-treated diabetic rats gained weight and partially improved blood glucose levels. Diabetic rats displayed a decrease in ICP/MAP. While maximum electrical field stimulation- and acetylcholine (ACh)-induced relaxations in CCSM strips from the diabetics were reduced, preventive imatinib or insulin treatment normalized ICP/MAP ratios and improved relaxation responses. ACh responses in diabetic aortas were diminished by 50.1% and restored by imatinib. While contractile responses to phenylephrine in diabetic CCSM were not altered, there was a significant enhancement (59.4 %) in the aortic contractile response in diabetic rats, which was restored by imatinib and insulin treatment.

Conclusions

In diabetic rats, prolonged therapy with imatinib improves diabetes-related ED and vascular function, which may involve normalization of high glucose levels and restoration of PTK activation. Future studies are needed to elaborate on the actions of imatinib on diabetic vascular complications.
Nicardipine vs. Saline Injection as Treatment for Peyronie’s Disease: A Prospective, Randomized, Single-Blind Trial
Authors: Soh Jintetsu , Kawauchi Akihiro , Kanemitsu Noriyuki , Naya Yoshio , Ochiai Atsushi , Naitoh Yasuyuki , Fujiwara Terufumi , Kamoi Kazumi , Miki Tsuneharu
Published: June 2010

Introduction

Various conservative treatments for Peyronie’s disease (PD) have been attempted over the years. Intralesional verapamil injection has been tested in prospective randomized studies, but the effect of this treatment seems insufficient. Nicardipine is a calcium antagonist alternative to verapamil and is reportedly more effective in vitro.

Aim

The objective of our study was to evaluate the usefulness of intralesional nicardipine injection as a conservative treatment for PD in the transition period of acute and chronic phase.

Methods

Eighty-six patients (age: 38–72 years, mean: 52) were enrolled in this study. A total of 74 patients were assigned randomly to nicardipine group (10 mg diluted in 10 mL of distilled water daily, N=37) and control group (10 mL of saline water, N=37). A total of six injections were administrated biweekly.

Mean Outcome Measure

The subjects were assessed by International Index of Erectile Function (IIEF)-5 and international pain scale. The plaque size was measured by ultrasonography after 20 µg intracavernosal injection of alprostadil (prostaglandin E1). The penile curvature was also measured by taking a photograph at maximum rigidity.

Results

A reduction of pain score was seen throughout the course of treatment in both groups with a significant difference between the nicardipine and control groups (multiple analysis of variance test, P = 0.019). A significant improvement of IIEF-5 score occurred only in the nicardipine group at 48 weeks after the initiation of treatment (P <0.01). The plaque size was significantly reduced at 48 weeks only in the nicardipine group (12 points, P = 0.0004 by paired t-test). The penile curvature was significantly improved in both groups (P <0.01) without significant difference between them (P = 0.14). There were no severe side effects, such as hypotension or other cardiovascular events.

Conclusion

Our findings indicate that intralesional nicardipine injection is clinically effective as a conservative treatment for PD in the transition period of acute and chronic phase.
New Enhancements of the Scrotal One-Incision Technique for Placement of Artificial Urinary Sphincter Allow Proximal Cuff Placement
Authors: Wilson Steven K. , Aliotta Philip J. , Salem Emad A. , Mulcahy John J.
Published: June 2010

Introduction

Urinary incontinence impairs sexual functioning and sexual satisfaction. Traditional artificial urinary sphincter (AUS) implantation requires perineal incision for cuff placement and a second inguinal incision for reservoir and pump placement. We believed AUS could be placed easier and quicker through one scrotal incision.

Aim

In an effort to effect more proximal placement of the cuff while keeping the advantages of the one scrotal incision technique, we report enhancements to the original surgical technique.

Methods

Thirty patients have been operated upon using the enhanced technique. A modification of the SKW retractor system (AMS) facilitates deep bulbar exposure. Twenty patients were first time implantations and 10 were revisions with five of the revisions having had the original AUS placed by traditional two-incision technique. Two of the first time AUS patients received an inflatable penile prosthesis through the same incision.

Main Outcome Measures

We evaluated site of cuff placement, sizes of cuffs used, postoperative continence status.

Results

All of the virgin AUS required dissection of the bulbocavernosus muscle prior to cuff placement. In scrotally placed revisions, replacement cuffs were situated considerably proximal (4.5–7.5 cm) to the original cuff site. The perineal placed revisions were accomplished through a scrotal incision with replacement of two cuffs in the same site and the three other patients immediately distal. No intraoperative complications were seen. One patient developed scrotal hematoma requiring drainage. Only 15 patients are available for follow-up and all are socially continent (one pad or less).

Conclusions

Transscrotal approach is used safely and efficiently for penile implants and AUS implantation. The new enhancements to the one-scrotal incision technique allow more proximal cuff placement as evidenced by the bulbocavernosus muscle dissection and use of larger cuffs. Continence rate is similar to rates achieved with perineal placement of cuff found in the literature.
Sleep-Related Painful Erection in a 50-Year-Old Man Successfully Treated with Cinitapride
Authors: Chiner Eusebi , Sancho-Chust José Norberto , Llombart Mónica , Camarasa Ana , Senent Cristina , Mediero Gabriel , Gómez-Merino Elia
Published: June 2010

Introduction

The sleep-related painful erection (SRPE) is a well-established parasomnia characterized by episodes of penile pain during an erection and typically appears during REM sleep. It is associated with nocturnal awakenings, anxiety, and irritability.

Aim

To report a case study that highlights the successful treatment of SRPE with cinitapride.

Methods

We present a case report of a 50-year-old man suffering from SRPE that was studied by polysomnography.

Results

Severe fragmentation of rapid eye movement (REM) sleep was observed, and nine episodes of sleep-related erections were observed through the night; they were associated with REM sleep, and five of them were classified as SRPE. Cinitapride before the onset of sleep was started. Both the frequency and intensity of SRPE gradually decreased during a period of 6 months with the maintenance of normal sexual function.

Conclusion

Cinitapride can play a role in reducing SRPE at night probably due to central modulation of neurotransmitters mediating erection.