bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostanoids in the Therapy of Glaucoma
Authors: Ishida Naruhiro , Odani‐Kawabata Noriko , Shimazaki Atsushi , Hara Hideaki 
Published: August 2006

ABSTRACTElevated intraocular pressure (IOP) is one of the most important risk factors for the development of glaucoma, which is a progressive optic neuropathy. Lowering IOP is currently the only therapeutic approach to the therapy of glaucoma. Since the use of pilocarpine eye drops for glaucoma treatment was reported in the late 1870s, academic researchers and pharmaceutical companies attempted to discover new drugs with more potent, prolonged, and safer IOP‐reducing effects. These persistent efforts finally paid off, and prostanoids with FP‐receptor agonist activity were found to be very potent IOP‐lowering agents. To date, three prostanoids (latanoprost, travoprost and bimatoprost) have been launched in many countries, and now a new FP‐receptor agonist, tafluprost, is entering clinical development. All of these prostanoids are superior to the β‐adrenoceptor antagonists in their IOP‐lowering efficacy, and no severe side effects have been reported in their long‐term clinical use. In addition, tafluprost may be expected to improve ocular blood flow. Hence, prostanoids currently occupy center stage among glaucoma medications. It cannot be denied that in terms of efficacy, safety, patient compliance, and medical economy prostanoids are currently the first‐line medicines among ocular antihypertensive drugs.
Triflusal: An Antiplatelet Drug with a Neuroprotective Effect?
Authors: González‐Correa José Antonio , De La Cruz José Pedro 
Published: August 2006

ABSTRACTTriflusal is a derivative of salicylic acid with a well‐established platelet aggregation inhibitory profile. Its pharmacokinetic and pharmacodynamic properties differ, however, somewhat from those of acetylsalicylic acid. A number of recent experimental and clinical studies have shown that triflusal is a potentially useful choice in the treatment and prophylaxis of brain ischemia because of its antithrombogenic as well as neuroprotective effects. Its antithrombogenic effect has been demonstrated at the clinical as well as at the experimental level, while its neuroprotective effect has been shown only in experimental models. The drug interferes with thrombogenesis by inhibiting thromboxane synthesis and increasing the levels of cAMP and nitric oxide. Its neuroprotective action is the result of its antioxidant and antiinflammatory effects in brain tissue. From a clinical standpoint triflusal is similar in efficacy to acetylsalicylic acid in preventing stroke, but has less adverse effects, especially it is less likely to cause bleeding. Because of its pharmacodynamic properties and lower rate of adverse reactions, triflusal may be a useful alternative to acetylsalicylic acid in the prevention of stroke.
Pharmacological Profile of U‐37883A, a Channel Blocker of Smooth Muscle‐Type ATP‐Sensitive K+ Channels
Authors: Teramoto Noriyoshi 
Published: August 2006

ABSTRACTU‐37883A (PNU‐37883A, guanidine; 4‐morpholinecarboximidine‐N‐1‐adamantyl‐N′‐cyclohexyl hydrochloride) was originally developed as a potential diuretic with specific binding in kidney and vascular smooth muscle rather than in brain or pancreatic β cells. U‐37883A inhibits ATP‐sensitive K+ channels (KATP channels) in vascular smooth muscle at submicromolar concentrations whilst even at high concentrations (≥10 μM) it has no inhibitory effect at pancreatic, cardiac or skeletal KATP channels. Thus, it is generally thought that U‐37883A is a selective inhibitor of vascular smooth muscle KATP channels.Approximately one decade ago, KATP channels were cloned and found to consist of at least two subunits: an inwardly‐rectifying K+ channel six family (Kir6.x; Kir6.1 and Kir6.2) which forms the ion conducting pore and a modulatory sulphonylurea receptor (SUR.x; SUR1, SUR2A, and SUR2B) that accounts for several pharmacological properties. It is generally believed that different combinations of Kir6.x and SUR.x determine the molecular properties of KATP channels. Thus, Kir6.2/SUR1 channel represents the pancreatic β‐cell KATP channel, Kir6.2/SUR2A channel is thought to represent the cardiac KATP channel, whereas Kir6.1/SUR2B channel is likely to represent the vascular smooth muscle KATP channel.Recent molecular studies have shown that U‐37883A selectively suppresses the activity of recombinant KATP channels which contain Kir6.1 subunits in the channel pore unit. It was thus thought that U‐37883A was a selective pharmacological tool which could be used to investigate the activity of vascular smooth muscle KATP channels. However, due to its multiple pharmacological actions on several ion channels and poor tissue selectivity, U‐37883A should not be viewed as a selective blocker of smooth muscle KATP channels.
Ambrisentan, a Non‐peptide Endothelin Receptor Antagonist
Authors: Vatter Hartmut , Seifert Volker 
Published: August 2006

ABSTRACTIncreasing numbers of experimental investigations and recently also of clinical trials strongly suggest an integral involvement of the endothelin (ET)‐system in the pathophysiology of a variety of disease states, mainly of the cardiovascular system. Ambrisentan (LU 208075), a selective ETA‐receptor antagonist, is an orally active diphenyl propionic acid derivative. It has been shown to have a very promising efficacy to safety ratio in the initial clinical trials. Phase II and Phase III trials with ambrisentan in pulmonary arterial hypertension have been performed. The pharmacological properties and data from the experimental investigations suggest additional possible uses of ambrisentan in the prevention of reperfusion injury after organ transplantation and in restenosis following coronary artery dilatation. Furthermore, the pharmacological profile of ambrisentan indicates that this drug may also be suitable in the treatment of cerebrovascular disorders. In the present article basic investigations, animal studies and clinical trials with ambrisentan are reviewed. This review may help to define pathophysiological conditions, in which ambrisentan could be indicated and further evaluated in appropriate preclinical and clinical trials.
Evaluation of RANK/RANKL/OPG gene polymorphisms in aggressive periodontitis
Authors: Soedarsono N. , Rabello D. , Kamei H. , Fuma D. , Ishihara Y. , Suzuki M. , Noguchi T. , Sakaki Y. , Yamaguchi A. , Kojima T. 
Published: August 2006

Background and Objective:  Aggressive periodontitis (AgP) is a specific type of periodontal disease that is characterized by rapid attachment loss and bone destruction. While attempting to identify genetic polymorphisms associated with AgP, previous research has focused on candidate genes that may be involved in immune responses to microbial infections. In this study, the focus was on single nucleotide polymorphisms (SNPs) in the key mediators of osteoclast differentiation and activation, which involve receptor activator of nuclear factor‐κB (RANK), RANK ligand (RANKL) and osteoprotegrin (OPG), in the Japanese population. The aim of this study was to evaluate the association of RANK/RANKL/OPG gene polymorphisms with AgP in the Japanese population.Material and Methods:  We examined 99 patients with AgP and 89 controls from the Japanese population to explore the possibility of RANK/RANKL/OPG loci as candidate regions associated with the disease. All exons and relevant exon–intron boundaries of these three candidate genes were amplified by polymerase chain reaction (PCR) using 19 primers, followed by direct sequencing. The polymorphisms were identified by comparing the sequences obtained from 48 subjects.Results:  We identified 27 SNPs in RANK, including 10 novel SNPs and seven SNPs each in both RANKL and OPG. A pairwise linkage disequilibrium analysis using the r2 statistic showed that some SNP pairs from the three loci are in tight linkage disequilibrium.Conclusion:  An association analysis with allelotypes showed that SNPs identified in the RANK/RANKL/OPG genes have no significant association with AgP in the Japanese population.
Diagnostic and therapeutic procedures for management of melanoma during pregnancy: risks for the fetus?
Authors: Egberts Friederike , Lischner Stephan , Russo Paul , Kampen W. Uwe , Hauschild Axel 
Published: August 2006

SummaryIn the treatment of malignant melanoma, various stage‐dependent diagnostic and therapeutic procedures are widely accepted.The situation becomes more complicated in pregnant women due to potential hazardous side effects to the fetus. We report on a 36‐year‐old woman, who was admitted with a high‐risk malignant melanoma on the right cheek. Prior to surgery we performed computed tomography (CT)‐scans that were unremarkable with the exception of “two small cysts of the uterus” The primary melanoma was excised and a sentinel node biopsy was performed under general anesthesia using radioactive tracers. Afterwards, adjuvant therapy with interferon alpha 2b was initiated. Five weeks later our patient reported that she was pregnant with twins in their eleventh week of gestation, although she previously denied several questions regarding a potential pregnancy. She declined the offer of an abortion and elected to continue with the interferon treatment against our medical advice. In the 36th week of gestation, she developed regional lymph node metastases. Consequently, labor was induced, resulting in the delivery of healthy twins. Six months later our patient developed lung metastases. Despite several chemotherapy regimens, she died one year later. An interdisciplinary approach to obtaining informed consent and managing female high risk melanoma patients with potential or present pregnancy is presented.
Premature Ejaculation: On Defining and Quantifying a Common Male Sexual Dysfunction
Authors: Broderick Gregory A. 
Published: August 2006

ABSTRACT

Introduction
Premature ejaculation (PE) and its individual and relationship consequences have been recognized in the literature for centuries. PE is one of the most common male sexual dysfunctions, affecting nearly one in three men worldwide between the ages of 18 and 59 years. Until recently, PE was believed to be a learned behavior predominantly managed with psychosexual therapy; however, the past few decades have seen significant advances in understanding its etiology, diagnosis, and management. There is, as yet, no one universally agreed upon definition of PE.

Aim
To review five currently published definitions of PE.

Methods
The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24–26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives.

Main Outcome Measure
Data were utilized from the World Health Organization, the American Psychiatric Association, the European Association of Urology, the Second International Consultation on Sexual Dysfunctions, and the American Urological Association.

Results
The current published definitions of PE have many similarities; however, none of these provide a specific “time to ejaculation,” in part because of the absence of normative data on this subject. While investigators agree that men with PE have a shortened intravaginal ejaculatory latency time (IELT; i.e., time from vaginal penetration to ejaculation), there is now a greater appreciation of PE as a multidimensional dysfunction encompassing several components, including time and subjective parameters such as “control,”“satisfaction,” and “distress.”

Conclusion
There is a recent paradigm shift away from PE as a unidimensional disorder of IELT toward a multidimensional description of PE as a biologic dysfunction with psychosocial components.
Guidelines for the Diagnosis and Management of Premature Ejaculation
Authors: Sharlip Ira D. 
Published: August 2006

ABSTRACT

Introduction
Until recently, premature ejaculation (PE) was believed to have a psychologic etiology requiring psychosexual therapy. Recognition of a neurobiologic component to the etiology of PE has since highlighted the need for diagnostic and management guidelines for this common sexual problem. One major medical organization—the American Urological Association (AUA)—has established such guidelines. In addition, the Second International Consultation on Sexual Dysfunctions (ICSD) in 2003 developed a set of recommendations for PE, as well as for other sexual dysfunctions.

Aim
To review the current guidelines for the diagnosis and treatment of PE.

Methods
The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24–26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives.

Main Outcome Measure
Data from the AUA Guideline on the Pharmacologic Management of Premature Ejaculation and the Second ICSD.

Results
Both documents emphasize the importance of a sexual history in diagnosing PE, and each of these two documents recognizes that diagnosis involves a shortened intravaginal latency time as well as patient reports of poor control over ejaculation and patient distress over the condition.

Conclusions
Condensed guidelines for the diagnosis and treatment of PE are presented. Once diagnosis is suspected, optimal treatment regimens should be established utilizing randomized placebo-controlled trials.
Studies on instant raw tamarind chutney powder
Authors: Jyothirmayi Tummala , Rao Galla Narsing , Rao Dubasi Govardhana 
Published: August 2006

AbstractInstant raw tamarind chutney powder was prepared by mixing the dry raw tamarind powder with a suitable combination of spice powders and salt. The proximate and mineral composition of the dry raw tamarind powder and instant raw tamarind chutney powder were determined. The acid content as tartaric acid was 12.6% and 5.8% in the dry raw tamarind powder and instant chutney powder respectively. Other components in the instant chutney powder and dry raw tamarind powder were: fibre content, 12.7% and 18.7%; protein content, 7.7% and 10.3%; calcium, 64 and 111 mg/100 g; and iron, 9.5 and 4.5 mg/100 g respectively. Storage studies were carried out by packing the powders in polyethylene pouches. The polyphenol content increased in both samples during the storage period. Sensory analyses showed that the instant raw tamarind chutney powder scored 7.2 (above good) even after the 6‐month storage period.
A new ready‐to‐eat dish for a traditional market
Authors: Feliciano Daniel , Albisu Luis Miguel 
Published: August 2006

AbstractConsumption of ready‐to‐eat meals in Spain is limited, although an increasing trend is observed. This paper examines consumers’ reactions to the possible launching of a new ready‐to‐eat roast lamb dish, which could be applied for home consumption or foodservice/catering. This dish is cooked following traditional methods, is appreciated by most consumers and is consumed quite often. A survey has been undertaken to gain information about consumers’ opinions, purchasing habits and consumption of ready‐to‐eat dishes. The consumption of this type of product is strongly related to consumers’ age, education and income. Spanish consumers do not trust ready‐to‐eat dishes because they perceive these dishes as incorrectly processed and containing preservatives. In this study a hypothetical ready‐to‐eat roast lamb dish was also presented to consumers with two non‐traditional side dishes. Consumers tasted the dish, and their preferences were analysed using a conjoint analysis. Results show that some preferences are linked with tradition, whereas others are more innovative and typical of modern‐time behaviour. The right combination of features could be critical for a proper launching process.
Assessing the foodservice potential of muscles from the chuck
Authors: Bratcher Christy L. , Moore Kevin C. , Keene Michael P. , Lorenzen Carol L. 
Published: August 2006

AbstractThe objective of this study was to determine the foodservice potential of muscles from the chuck. US Department of Agriculture Select chucks and briskets (n = 25) were fabricated to produce the following muscles: Complexus (C), Serratus ventralis (SV), Rhomboideus (R) and Pectoralis superficialis (PS). Yield, drip loss, marinade uptake, thiobarbituric acid reactive substances (TBARS) and proximate analysis were performed. Chef focus group (n = 12) determined the desirability for foodservice, and an economic analysis was conducted. SV had the highest yield of the chuck (13%), followed by C (7%) and R (4%). PS was 28% of the brisket. SV had higher drip loss (P < 0.05) than C, and the highest (P < 0.05) marinade uptake. TBARS values were low, with no differences between muscles (P > 0.05). Proximate analysis differed by muscle (P < 0.05). The threshold values for the muscles chosen were $5.51/kg and $6.61/kg for R and C respectively. The breakeven price for R and C combined was $6.06/kg. Other muscles were not perceived as candidates.
Baculovirus-Derived Human Immunodeficiency Virus Type 1 Virus-Like Particles Activate Dendritic Cells and Induce Ex Vivo T-Cell Responses
Authors: Buonaguro L. , Tornesello M. L. , Tagliamonte M. , Gallo R. C. , Wang L. X. , Kamin-Lewis R. , Abdelwahab S. , Lewis G. K. , Buonaguro F. M. 
Published: August 2006

ABSTRACT

We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model based on HIV-1 Pr55

gag

virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A (HIV-VLP
A
s). The HIV-VLP
A
s show the induction in BALB/c mice of systemic and mucosal neutralizing antibodies as well as cytotoxic T lymphocytes, by intraperitoneal as well as intranasal administration. In the present article, the effects of the baculovirus-expressed HIV-VLPs on human immature monocyte-derived dendritic cells (MDDCs) have been evaluated. The HIV-VLPs efficiently induce maturation and activation of MDDCs and are incorporated into MDDCs preferentially via an actin-dependent macropinocytosis and endocytosis. The HIV-VLP-activated MDDCs show enhanced Th1- and Th2-specific cytokine production, and the effects of HIV-VLPs on MDDCs are not mediated through Toll-like receptors 2 and 4 (TLR2 and -4) signaling. Finally, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4
+
T cells in an ex vivo immunization assay. Our results on the interaction and processing of baculovirus HIV-VLPs by MDDCs give an insight into the mechanisms underlying the immune response induced by HIV-VLP
A
s in vivo.
DC-SIGN and CLEC-2 Mediate Human Immunodeficiency Virus Type 1 Capture by Platelets
Authors: Chaipan Chawaree , Soilleux Elizabeth J. , Simpson Peter , Hofmann Heike , Gramberg Thomas , Marzi Andrea , Geier Martina , Stewart Elizabeth A. , Eisemann Jutta , Steinkasserer Alexander , Suzuki-Inoue Katsue , Fuller Gemma L. , Pearce Andrew C. , Watson Steve P. , Hoxie James A. , Baribaud Frederic , Pöhlmann Stefan 
Published: August 2006

ABSTRACTPlatelets can engulf human immunodeficiency virus type 1 (HIV-1), and a significant amount of HIV-1 in the blood of infected individuals is associated with these cells. However, it is unclear how platelets capture HIV-1 and whether platelet-associated virus remains infectious. DC-SIGN and other lectins contribute to capture of HIV-1 by dendritic cells (DCs) and facilitate HIV-1 spread in DC/T-cell cocultures. Here, we show that platelets express both the C-type lectin-like receptor 2 (CLEC-2) and low levels of DC-SIGN. CLEC-2 bound to HIV-1, irrespective of the presence of the viral envelope protein, and facilitated HIV-1 capture by platelets. However, a substantial fraction of the HIV-1 binding activity of platelets was dependent on DC-SIGN. A combination of DC-SIGN and CLEC-2 inhibitors strongly reduced HIV-1 association with platelets, indicating that these lectins are required for efficient HIV-1 binding to platelets. Captured HIV-1 was maintained in an infectious state over several days, suggesting that HIV-1 can escape degradation by platelets and might use these cells to promote its spread. Our results identify CLEC-2 as a novel HIV-1 attachment factor and provide evidence that platelets capture and transfer infectious HIV-1 via DC-SIGN and CLEC-2, thereby possibly facilitating HIV-1 dissemination in infected patients.
Gene-Specific Inhibition of Reovirus Replication by RNA Interference
Authors: Kobayashi Takeshi , Chappell James D. , Danthi Pranav , Dermody Terence S. 
Published: August 2006

ABSTRACT
Mammalian reoviruses contain a genome of 10 segments of double-stranded RNA (dsRNA). Reovirus replication and assembly occur within distinct structures called viral inclusions, which form in the cytoplasm of infected cells. Viral nonstructural proteins μNS and σNS and core protein μ2 play key roles in forming viral inclusions and recruiting other viral proteins and RNA to these structures for replication and assembly. However, the precise functions of these proteins in viral replication are poorly defined. Therefore, to better understand the functions of reovirus proteins associated with formation of viral inclusions, we used plasmid-based vectors to establish 293T cell lines stably expressing small interfering RNAs (siRNAs) specific for transcripts encoding the μ2, μNS, and σNS proteins of strain type 3 Dearing (T3D). Infectivity assays revealed that yields of T3D, but not those of strain type 1 Lang, were significantly decreased in 293T cells stably expressing μ2, μNS, or σNS siRNA. Stable expression of siRNAs specific for any one of these proteins substantially diminished viral dsRNA, protein synthesis, and inclusion formation, indicating that each is a critical component of the viral replication machinery. Using cell lines stably expressing μNS siRNA, we developed a complementation system to rescue viral replication by transient transfection with recombinant T3D μNS in which silent mutations were introduced into the sequence targeted by the μNS siRNA. Furthermore, we demonstrated that μNSC, which lacks the first 40 amino residues of μNS, is incapable of restoring reovirus growth in the complementation system. These results reveal interdependent functions for viral inclusion proteins and indicate that cell lines stably expressing reovirus siRNAs are useful tools for the study of viral protein structure-function relationships.
CD80 and CD86 Control Antiviral CD8
+
T-Cell Function and Immune Surveillance of Murine Gammaherpesvirus 68
Authors: Fuse Shinichiro , Obar Joshua J. , Bellfy Sarah , Leung Erica K. , Zhang Weijun , Usherwood Edward J. 
Published: August 2006

ABSTRACT

The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86
−/−
mice. In the absence of CD80/CD86, primary antiviral CD8
+
T-cell responses and the induction of neutralizing antibodies were severely impaired. During long-term immune surveillance, the virus-specific CD8
+
T cells were impaired in IFN-γ production and secondary expansion and exhibited an altered phenotype. Surprisingly, a low level of viral reactivation in the lung was observed, and this effect was independent of CD28 and CTLA-4. Thus, CD80 and CD86, signaling through CD28 and possibly another unidentified receptor, are required for optimal immune surveillance and antiviral immune responses to murine gammaherpesvirus.