bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a Cyclooxygenase‐2 Inhibitor on Interleukin‐1β–Stimulated Activation of the Transcription Factor Nuclear Factor‐Kappa B in Human Gingival Fibroblasts
Authors: Tipton David A. , Gay Denise C. , DeCoster Vaughn A.
Published: March 2007

Background:In previous work, the cyclooxygenase‐2 inhibitor NS‐398 inhibited interleukin (IL)‐1β–stimulated prostaglandin E2(PGE2) production almost completely while partially inhibiting IL‐6 production in aggressive periodontitis (AgP) human gingival fibroblasts. PGE2and the transcription factor nuclear factor‐kappa B (NF‐κB) regulate IL‐1β–stimulated IL‐6 production. Cytoplasmic NF‐κB is bound to inhibitors (IκB proteins). IL‐1β initiates a cascade resulting in phosphorylation and degradation of IκB, allowing nuclear translocation of NF‐κB and target gene activation. The purpose of this study was to determine whether NS‐398 inhibited phosphorylation of IκB and NF‐κB activation.

Methods:AgP fibroblasts (1 to 2 × 106) were exposed to IL‐1β (1 × 10−11M) with or without NS‐398 (10 nM) in serum‐free medium. The NF‐κB subunit p6‐ and phospho‐IκBα were measured in whole cell, cytoplasmic, or nuclear extracts, using colorimetric assays. Enzyme‐linked immunosorbent assays were used to measure PGE2and IL‐6 production by 2.‐ × 104cells after exposure to IL‐1β with or without NS‐398 in serum‐free medium.

Results:Consistent with previous results, NS‐398 reduced IL‐1β–stimulated PGE2by ∼98% (P<0.001) and IL‐6 by ∼65% (P<0.001). IL‐1β increased nuclear and cytoplasmic p65 (∼8‐fold [P<0.001] and ∼2.5‐fold [P<0.03], respectively) over control levels. NS‐398 reduced IL‐1β–stimulated nuclear and cytoplasmic p65 to control levels. IL‐1β increased phospho‐IκBα in whole cell extracts by a maximum of approximately 9.5 times (P= 0.0001), and this was inhibited significantly by NS‐398 (P≤0.008).

Conclusions:NS‐398 inhibited NF‐κB activation and nuclear p65 levels in human gingival fibroblasts. This seemed to be due to inhibition of the phosphorylation cascade resulting in formation of phospho‐IκBα and free p65. NF‐κB inhibition may be useful in treating inflammatory diseases such as AgP.
Cytokine Profiles in Crevicular Fluid During Orthodontic Tooth Movement of Short and Long Durations
Authors: Ren Yijin , Hazemeijer Heleen , de Haan Bart , Qu Ning , de Vos Paul
Published: March 2007

Background: Orthodontic treatment induces a distortion of the extracellular matrix of the periodontium, resulting in alterations in cytoskeletal configuration. Cytokines are known to facilitate this process by inducing cellular proliferation, differentiation, and stimulation of periodontal remodeling. The aim of the present study was to measure a panel of proinflammatory cytokines (PICs) in crevicular fluid (GCF) samples during tooth movement of short and long durations.

Methods: Twelve patients (11 to 27 years of age) participated in this study: six patients each for tooth movement of short and long duration. GCF sampling was done at different times, ranging from 24 hours to 4 months after force application. The profiles of PICs were analyzed with a multiplex technique.

Results: PICs were elevated significantly in the early stage of tooth movement but at different time points. Interleukin (IL)‐1β and ‐6 and tumor necrosis factor‐alpha (TNF‐α) reached significant levels at 24 hours; IL‐8 reached a significant elevation at 1 month. During the linear stage of tooth movement, all cytokines were diminished to their baseline levels. The results demonstrated that IL‐1β, ‐6, and ‐8 and TNF‐α play a significant role during the early stage of tooth movement but not during the linear stage.

Conclusions: Once the microenvironment of periodontal tissue is activated by an orthodontic force, several key PICs are produced to trigger a cascade of cellular events. The periodontal system stabilizes at a new physiological homeostasis as indicated by the downregulation of the early‐phase PICs.
Nicotine and Lipopolysaccharide Affect Cytokine Expression From Gingival Fibroblasts
Authors: Almasri Amjad , Wisithphrom Kessiri , Windsor L. Jack , Olson Byron
Published: March 2007

Background: This in vitro study investigated the influence of nicotine, lipopolysaccharide (LPS), and a combination of both agents on cytokine expression from human gingival fibroblasts (HGFs).

Methods: HGFs were exposed for 48 hours to 250 μg/ml nicotine, 1 μg/ml Porphyromonas gingivalis LPS, or both. The expression of multiple cytokines was detected in the HGFs conditioned media using cytokine protein arrays.

Results: The untreated HGFs expressed several cytokines, which included relatively high levels of interleukin (IL)‐6, IL‐8, and monocyte chemoattractant protein‐1 (MCP‐1). They also expressed low levels of growth‐regulated oncogene (GRO), IL‐3, and IL‐10. Nicotine had the greatest effect on the expression of GRO‐α, IL‐7, IL‐10, and IL‐1‐ compared to the untreated control. P. gingivalis LPS had the greatest effect on the expression of GRO‐α; IL‐7; IL‐10; and RANTES (regulated on activation, normal T‐cell expressed, and presumably secreted) compared to the untreated control. The combination of both agents had the biggest impact on the expression of GRO‐α, IL‐7, IL‐10, IL‐15, RANTES, and interferon‐γ (IFN‐γ) compared to the untreated control.

Conclusion: HGFs exposed to nicotine, P. gingivalis LPS, or a combination of both agents increased the expression of multiple cytokines.
Treatment of Femoro-Acetabular Impingement: Preliminary Results of Labral Refixation
Authors: Espinosa Norman , Beck Martin , Rothenfluh Dominique A. , Ganz Reinhold , Leunig Michael
Published: March 2007

BACKGROUND:

Recent advances in the understanding of the anatomy and function of the acetabular labrum suggest that it is important for normal joint function. We found no available data regarding whether labral refixation after treatment of femoro-acetabular impingement affects the clinical and radiographic results.

METHODS:

We retrospectively reviewed the clinical and radiographic results of fifty-two patients (sixty hips) with femoro-acetabular impingement who underwent arthrotomy and surgical dislocation of the hip to allow trimming of the acetabular rim and femoral osteochondroplasty. In the first twenty-five hips, the torn labrum was resected (Group 1); in the next thirty-five hips, the intact portion of the labrum was reattached to the acetabular rim (Group 2). At one and two years postoperatively, the Merle d'Aubigné clinical score and the Tönnis arthrosis classification system were used to compare the two groups.

RESULTS:

At one year postoperatively, both groups showed a significant improvement in their clinical scores (mainly pain reduction) compared with their preoperative values (p = 0.0003 for Group 1 and p < 0.0001 for Group 2). At two years postoperatively, 28% of the hips in Group 1 (labral resection) had an excellent result, 48% had a good result, 20% had a moderate result, and 4% had a poor result. In contrast, in Group 2 (labral reattachment), 80% of the hips had an excellent result, 14% had a good result, and 6% had a moderate result. Comparison of the clinical scores between the two groups revealed significantly better outcomes for Group 2 at one year (p = 0.0001) and at two years (p = 0.01). Radiographic signs of osteoarthritis were significantly more prevalent in Group 1 than in Group 2 at one year (p = 0.02) and at two years (p = 0.009).

CONCLUSIONS:

Patients treated with labral refixation recovered earlier and had superior clinical and radiographic results when compared with patients who had undergone resection of a torn labrum. Although the results must be considered preliminary, we now recommend refixation of the intact portion of the labrum after trimming of the acetabular rim during surgical treatment of femoro-acetabular impingement.
Precipitation of Liquid Swine Manure Phosphates Using Magnesium Smelting By‐Products
Authors: Parent Gaétan , Bélanger Gilles , Ziadi Noura , Deland Jean‐Pierre , Laperrière Jean
Published: March 2007

Swine manure contains considerable amounts of total (P) and soluble phosphorus (PO4–P) which may increase the soil P content when applied in excess to crop requirements and, consequently, risk water eutrophication. The feasibility of using magnesium (Mg) from the by‐product of electrolysis and foundries (BPEF) for the removal of P from liquid swine manure was studied by adding up to 3 g of Mg as BPEF per liter of nursery (NU) and grower‐finisher (GF) swine manure in 25‐L plastic buckets. Changes in P and other elements were monitored for up to 360 h. Small amounts of Mg as BPEF (0.5 and 1.0 g Mg L−1 manure) reduced the total P concentration of the liquid fraction by 70 to 95% of both manure types with respect to the control treatment of mixed raw manure. A settling period of 8 h or more was necessary to significantly reduce the liquid fraction's total P concentration for both manure types. Reduction of PO4–P varied from 96 to 100% in the liquid fractions for both manure types, which along with natural settling, explains most of the total P reduction in that fraction. The addition of BPEF did not influence the N content of manure. The low P liquid fraction can be safely applied to saturated P soils whereas the high P solid fraction offers the opportunity of transporting manure to agricultural soils deficient in P. Since N is conserved, both liquid and solid fractions could be valuable fertilizer manure by‐products.
Dissolved Organic Carbon Fluxes under Bare Soil
Authors: Mertens Jan , Vanderborght Jan , Kasteel Roy , Pütz Thomas , Merckx Roel , Feyen Jan , Smolders Erik
Published: March 2007

The flux of dissolved organic carbon (DOC) in soil facilitates transport of nutrients and contaminants in soil. There is little information on DOC fluxes and the relationship between DOC concentration and water flux in agricultural soils. The DOC fluxes and concentrations were measured during 2.5 yr using 30 automatic equilibrium tension plate lysimeters (AETPLs) at 0.4 m and 30 AETPLs at 1.20‐m depth in a bare luvisol, previously used as an arable soil. Average annual DOC fluxes of the 30 AETPLS were 4.9 g C m−2 y−1 at 0.4 m and 2.4 g C m−2 y−1 at 1.2 m depth. The average leachate DOC concentrations were 17 mg C L−1 (0.4 m) and 9 mg C L−1 (1.2 m). The DOC concentrations were unrelated to soil moisture content or average temperature and rarely dropped below 9 mg C L−1 (0.4 m) and 5 mg C L−1 (1.2 m). The variability in cumulative DOC fluxes among the plates was positively related to leachate volume and not to average DOC concentrations at both depths. This suggests that water fluxes are the main determinants of spatial variability in DOC fluxes. However, the largest DOC concentrations were inversely proportional to the mean water velocity between succeeding sampling periods, suggesting that the maximal net DOC mobilization rate in the topsoil is limited. Elevated DOC concentrations, up to 90 mg C L−1, were only observed at low water velocities, reducing the risks of DOC‐facilitated transport of contaminants to groundwater. The study emphasizes that water flux and velocity are important parameters for DOC fluxes and concentrations.
Meta-Analyses of the Effect of Hormone Treatment on Cognitive Function in Postmenopausal Women
Authors: Yesufu Amina , Bandelow Stephan , Hogervorst Eva
Published: March 2007

As we age, most of us experience a certain degree of cognitive decline. In most cases, this decline is gradual. However, in some cases, cognitive impairment is so severe that it can be classified as dementia and this impacts greatly on activities of daily living. Alzheimer's disease, the most common form of dementia, has been linked to the reduction in estrogen levels that comes with aging. More specifically, many researchers have hypothesized that estrogen, and hence estrogen replacement via hormone therapy, could protect against cognitive decline in women. However, recent randomized, controlled trials did not reflect this. In fact, some reports showed that hormone therapy could have detrimental effects on cognitive function in older postmenopausal women. The most publicized of these has been the Women's Health Initiative Memory Study. Studies have thus yielded conflicting results and conclusions. The reasons for this may be due to a number of factors, such as the age of participants, the time of hormone therapy onset (‘window of opportunity’ theory), type of treatment, type of menopause (surgical or natural) and, possibly, genetic risk factors. We performed quantitative and qualitative meta-analyses and reviewed each of these factors in detail. The future may lie in combining these factors in order to fully understand the potential mechanisms behind estrogen and its effect on cognition.
Inherited Thrombophilia and Gestational Venous Thromboembolism
Authors: Zotz Rainer B , Gerhardt Andrea , Scharf Rüdiger E
Published: March 2007

Thromboembolic disease remains a leading cause of maternal mortality during pregnancy and the puerperium. Rational and risk-adapted administration of heparin prophylaxis depends on the identification of those women who have an increased risk of thrombosis and the accurate quantification of this risk. In women without prior thrombosis, the presence of a heterozygous factor V Leiden or heterozygous G20210A mutation in the prothrombin gene is associated with a pregnancy-associated thrombotic risk of approximately 1 in 400. Thus, in pregnant carriers of either one of these mutations, the risk of venous thromboembolism is low. Therefore, no heparin prophylaxis is recommended. A combination of the two genetic risk factors can increase the risk to a modest level of 1 in 25. In all women with prior thrombosis, the authors recommend heparin prophylaxis throughout pregnancy and postpartum for 6 weeks (inconsistent data). However, according to the American College of Chest Physicians recommendations, in the subgroup of women with an episode of prior thrombosis associated with a transient risk factor, such as surgery or trauma, and no additional genetic risk factor, clinical surveillance throughout pregnancy and heparin prophylaxis postpartum is possible. Despite the remarkable progress in risk stratification, the absolute magnitude of risk and the optimum management is, in many cases, an issue of ongoing debate.
Management of Bulimia Nervosa
Authors: Trunko Mary Ellen , Rockwell Roxanne E , Curry Elise , Runfola Cristin , Kaye Walter H
Published: March 2007

Bulimia nervosa is a disorder of complex etiology that tends to occur in young women. These individuals binge eat and purge by vomiting or other means, and often have depression, anxiety, substance abuse and extremes of impulse control. It is thought that binge eating and purging behaviors are, at least in part, a means of coping with dysphoric mood states and interpersonal stress. Bulimic symptoms are not likely to abate without development of new coping skills and behaviors. In the past 25 years, considerable progress has been made in developing specific psychotherapies and medication for the treatment of bulimia nervosa. Despite this progress, many individuals have partial responses to therapy and may remain chronically ill. This complex illness often requires a multidisciplinary team of professionals for effective management and, despite significant advances in treatment, bulimia nervosa continues to present major challenges for providers of care.
Development of quantitative polymerase chain reaction assays for allelic discrimination of gangliosidoses in cats
Authors: Wang Chi-Young J. , Smith Bruce F.
Published: March 2007

Objective—To develop quantitative PCR (qPCR) assays with allele-specific primers to provide a rapid and accurate diagnostic and screening test for the 3 mutations identified as causes of gangliosidoses in domestic cats.

Sample Population—DNA samples obtained from archived feline blood samples submitted for GM1 and GM2 testing.

Procedures—A qPCR assay was developed for each mutation to monitor the efficiency of PCR amplification. Results were determined on the basis of the fluorescent intensity of DNA staining.

Results—Samples from 60 cats were screened by use of the 3 qPCR assays. Of these, 59 qPCR results agreed with the sequence-derived genotypes. The phenotype (affected) for the other cat agreed with results for the qPCR assay, which indicated that interpretation of the sequence-based result was incorrect.

Conclusions and Clinical Relevance—The qPCR assays offer a sensitive, rapid, and reproducible technique for allelic discrimination without the need for complicated processing steps, such as hybridization or sequencing, after PCR procedures. These assays may prove beneficial for a rapid diagnosis of gangliosidoses in cats and could also provide a means for reliable large-scale screening for the carrier state, thereby accelerating the eradication of these debilitating diseases from feline populations.
Evaluation of anticollagen type I antibody titers in synovial fluid of both stifle joints and the left shoulder joint of dogs with unilateral cranial cruciate disease
Authors: de Bruin Tanya , de Rooster Hilde , van Bree Henri , Cox Eric
Published: March 2007

Objective—To evaluate anticollagen type I antibodies in synovial fluid of the affected stifle joint, the contralateral stifle joint, and the left shoulder joint of dogs with unilateral cranial cruciate ligament (CrCL) rupture during an extended period of 12 to 18 months.

Animals—13 client-owned dogs with CrCL rupture and 2 sham-operated dogs.

Procedures—All dogs were examined and arthrocentesis of all 3 joints was performed every 6 months after surgery. Synovial fluid samples were tested for anticollagen type I antibodies by use of an ELISA.

Results—Dogs with partial CrCL rupture had higher antibody titers than dogs with complete rupture. Six of 13 dogs ruptured the contralateral CrCL during the study, whereby higher antibody titers were found for the stifle joints than for the shoulder joint. Seronegative dogs or dogs with extremely low antibody titers and 2 dogs with high antibody titers did not sustain a CrCL rupture in the contralateral stifle joint.

Conclusions and Clinical Relevance—In most dogs that had a CrCL rupture of the contralateral stifle joint, a distinct antibody titer gradient toward the stifle joints was detected, suggesting that there was a local inflammatory process in these joints. However, only a small number of sham-operated dogs were used to calculate the cutoff values used to determine the anticollagen type I antibody titers in these patients. Synovial fluid antibodies against collagen type I alone do not initiate CrCL rupture because not all dogs with high antibody titers sustained a CrCL rupture in the contralateral stifle joint.
Plasma biochemical reference intervals for koi
Authors: Palmeiro Brian S. , Rosenthal Karen L. , Lewbart Gregory A. , Shofer Frances S.
Published: March 2007

Objective—To assess reproducibility of an in-house tabletop biochemical analyzer for measurement of plasma biochemical analytes and establish reference intervals in adult koi.

Design—Prospective study.

Animals—71 healthy adult koi.

Procedures—Plasma was analyzed for concentrations or activities of albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bile acids, BUN, calcium, cholesterol, creatine kinase, γ-glutamyltransferase, globulin, glucose, K, Na, P, total bilirubin, total protein, and uric acid. Duplicate samples were evaluated by use of the intraclass correlation coefficient to determine reproducibility. To assess the magnitude of differences between replicate samples, the absolute mean difference, SD, and minimum and maximum values were calculated for each analyte. Median values and reference intervals were calculated.

Results—Intraclass correlation coefficient values were excellent for all analytes except alanine aminotransferase (good), Na (poor), γ-glutamyltransferase (poor), and P (poor). Reference intervals were established.

Conclusions and Clinical Relevance—The in-house tabletop biochemical analyzer had good precision for measuring most plasma biochemical analytes. Further research and comparison with other reference procedures are needed before reference intervals and precision can be established for globulin, Na, P, K, and albumin. Aquatic veterinarians may be able to use the reference intervals for adult koi as an important diagnostic tool or as part of a fish wellness program, as commonly done in other domestic species.
Pore classification in the characterization of porous materials: A perspective
Authors: Zdravkov Borislav , Čermák Jiří , Šefara Martin , Janků Josef
Published: March 2007

Classification of pores is one of the basic requisites of comprehensive characterization of porous solids. There are various categorizations of pores described in the literature, but it is difficult to give a consistent global classification of porous substances including catalysts, adsorbents, oxides, carbons, zeolites, organic polymers, soils etc. The purpose of each of these classifications is to organize pores in classes by grouping them on the basis of their common characteristics like structure, size, accessibility, shape etc. In this study, a summary of the most used classifications of porous materials is done. Some common properties or behavior for individual classifications could be found, but many differences mainly in pore size are still subject of intensive discussions. Therefore, it is the purpose of this review to provide a general description of the concept and classification of pores in porous solids, to deal with complexity of the matter and to organise our knowledge in decision-making proccesses of pore characteristics determination.
Ultracentrifugation studies of the location of the site involved in the interaction of pig heart lactate dehydrogenase with acidic phospholipids at low pH. A comparison with the muscle form of the enzyme
Authors: Terlecki Grzegorz , Czapińska Elżbieta , Hotowy Katarzyna
Published: March 2007

Lactate dehydrogenase (LDH) from the pig heart interacts with liposomes made of acidic phospholipids most effectively at low pH, close to the isoelectric point of the protein (pH = 5.5). This binding is not observed at neutral pH or high ionic strength. LDH-liposome complex formation requires an absence of nicotinamide adenine dinucleotides and adenine nucleotides in the interaction environment. Their presence limits the interaction of LDH with liposomes in a concentration-dependent manner. This phenomenon is not observed for pig skeletal muscle LDH. The heart LDH-liposome complexes formed in the absence of nicotinamide adenine dinucleotides and adenine nucleotides are stable after the addition of these substances even in millimolar concentrations. The LDH substrates and studied nucleotides that inhibit the interaction of pig heart LDH with acidic liposomes can be ordered according to their effectiveness as follows: NADH > NAD > ATP = ADP > AMP > pyruvate. The phosphorylated form of NAD (NADP), nonadenine nucleotides (GTP, CTP, UTP) and lactate are ineffective. Chemically cross-linked pig heart LDH, with a tetrameric structure stable at low pH, behaves analogously to the unmodified enzyme, which excludes the participation of the interfacing parts of subunits in the interaction with acidic phospholipids. The presented results indicate that in lowered pH conditions, the NADH-cofactor binding site of pig heart LDH is strongly involved in the interaction of the enzyme with acidic phospholipids. The contribution of the ATP/ADP binding site to this process can also be considered. In the case of pig skeletal muscle LDH, neither the cofactor binding site nor the subunit interfacing areas seem to be involved in the interaction.
Dopaminergic Neurotransmission
Authors: Schetz John A. , Sibley David R.
Published: March 2007

Dopamine is a neurotransmitter in the central and peripheral nervous systems where it regulates numerous physiological processes. Within the CNS, dopamine is known to regulate emotion, reward, cognition, memory, endocrine functions, and motor control. Alterations in dopaminergic transmission are known to be involved in the etiology and/or therapy of a number of neurological and psychiatric disorders including Parkinson's disease, Tourette's syndrome, attention deficit hyperactivity disorder, schizophrenia and substance use. One of the hallmarks of these disorders is that they are all treated with drugs that either enhance or impede dopaminergic transmission. Dopamine exerts its effects by binding to and activating five different receptor proteins that are members of the G protein‐coupled receptor (GPCR) family. These five receptors are made up of two subfamilies: D1‐like D2‐like. The D1and D5receptors comprise the D1‐like subfamily while the D2, D3and D4receptors make up the D2‐like subfamily. In general, the D1‐like receptors stimulate the production of the ubiquitous second messenger cAMP whereas D2‐like receptors suppress cAMP production and also couple to additional signaling pathways. Different therapeutic agents are known to selectively activate or inhibit each of the dopamine receptor subtypes. A current goal of medicinal chemists is to develop drugs with even greater selectivity or specific mixed properties for the treatment of brain disorders that are associated with aberrations in various dopaminergic signaling pathways.
Serotonin Systems
Authors: Gray John A. , Roth Bryan L.
Published: March 2007

The serotonin (5‐HT) system is reviewed starting from the early history of 5‐HT. There is a review of the biosynthesis, degradation, and synaptic reuptake of 5‐HT as well as the neuroanatomy of the 5‐HT system. The roles of these pathways in disease and therapeutic interventions are discussed. The focus of this chapter is on the multiple 5‐HT receptors, their history, anatomical and subcellular localization, signaling pathways, and importance in behavior, neuropsychiatric disorders and psychopharmacology.
Ionotropic Glutamate Receptors
Authors: Bleakman David , Alt Andrew , Lodge David , Monaghan Daniel T. , Jane David E. , Nisenbaum Eric S.
Published: March 2007

Since their discovery in the 1950s, ionotropic glutamate receptors represent a class of receptor proteins that mediate fast excitatory transmission in the central nervous system. In this chapter, we describe the extensive studies of agents that act at the various subtypes of ionotropic glutamate receptor and how these agents have been used to delineate the physiological and pathophysiological roles of these receptors.
Neurobiology and Pharmacotherapy of Bipolar Disorder
Authors: Belmaker R. H. , Agam G. , Lenox R. H.
Published: March 2007

Given the complexity of the interaction of the physiological, genetic and environmental factors driving the clinical expression of bipolar disorder phenotypes, its neurobiology is yet to be unraveled and avenues to new pharmacotherapies are just beginning to be explored. The present chapter describes the latest findings from studies of the mechanism of action of our most effective treatments, i.e., lithium and anticonvulsants, as well as ongoing multidisciplinary research in this field utilizing not only genetic, neuroimaging, and peripheral biological markers in patient populations but also postmortem neuroanatomical and neurochemical approaches. The data to‐date do not provide a comprehensive description of the pathophysiology of bipolar disorder or the mechanisms for mood‐stabilization. Enhanced understanding of the long‐term prophylactic action of drugs like lithium in the brain and current advances in the combined use of neuroimaging and genetics will lead to important insights into the neurobiology of the disease and to a rational basis for the development of the novel antibipolar drugs of the future.
Emerging Anxiolytics: Corticotropin‐Releasing Factor Receptor Antagonists
Authors: Grigoriadis Dimitri E. , Hoare Samuel R. J.
Published: March 2007

This chapter describes the potential of the corticotropin‐releasing factor (CRF) system as a target for novel therapeutics in anxiety, depression and stress‐related disorders. CRF is the principle physiological regulator of an organism's response to stress. The authors provide a detailed description of the endogenous receptors and peptide ligands in this family as well as a review of the current non‐peptide small molecule antagonists that may yield the first proof of concept for this system in disease. A detailed analysis of the mechanisms of peptide and non‐peptide interactions with the receptor are presented utilizing various pharmacological and molecular methodologies including radioligand binding, receptor/ligand interactions and mutational studies that have defined specific features of small molecule antagonist interaction with this Class‐B GPCR that differ significantly from the interactions of its endogenous peptides. The findings provide evidence for non‐overlapping sites of action and imply that nonpeptide antagonists act in an allosteric manner to inhibit the function and binding of the endogenous peptides. Current efforts and future strategies for the further development of these novel molecules for neuropsychiatric and stress‐related disorders are discussed.
Dopamine and Glutamate Hypotheses of Schizophrenia
Authors: Moghaddam Bita , Homayoun Houman
Published: March 2007

The original dopamine hypothesis of schizophrenia posits that psychosis is associated with a hyperactive dopamine transmission. This hypothesis has been revised through the years to account for the cognitive and negative symptoms that are increasingly recognized as the core features of schizophrenia. The critical support for this hypothesis stems from the fact that until recently it was assumed that all antipsychotic drugs block dopamine receptors; however, decades of research have failed to provide solid evidence for a primary dopaminergic disruption in schizophrenia. An alternative hypothesis, based on glutamate transmission, was developed after discovering that the psychotomimetic agent phencyclidine is an antagonist of glutamate NMDA receptors. Further clinical and basic research has provided support for the notion that various genetic and cellular susceptibility factors in schizophrenia may converge at the level of NMDA receptor dysfunction. This hypothesis predicts that a disrupted glutamatergic transmission causes the core cognitive deficits of schizophrenia and may lead to a secondary disruption in dopamine transmission that in turn causes psychosis. This hypothesis has provided novel therapeutic targets for schizophrenia that modulate glutamatergic transmission through a number of mechanisms including metabotropic and AMPA receptors and glycine modulatory site on NMDA receptors.
Postmortem Brain Studies: Focus on Susceptibility Genes in Schizophrenia
Authors: Mathew Shiny V. , Mitkus Shruti N. , Lipska Barbara K. , Hyde, Thomas M. , Kleinman Joel E.
Published: March 2007

The discovery of allelic variations in a number of genes that increase the risk for schizophrenia has led to numerous postmortem brain studies designed to elucidate the underlying mechanisms. This review focuses on seven susceptibility genes (COMT, DTNBP1, GRM3, DISC1, NRG1, GAD1 and RGS4) and several of their molecular interactions. Studies of schizophrenia at this genetic/molecular level offer the hope of improved understanding of etiology/pathophysiology and new targets for treatment.
Pharmacotherapy of Schizophrenia
Authors: Sharif Zafar , Miyamoto Seiya , Lieberman Jeffrey A.
Published: March 2007

Antipsychotic medications remain the foundation of pharmacological treatment of schizophrenia. Although there has been significant progress over the past decade resulting in the introduction of several new agents, all currently available antipsychotics modulate brain dopamine systems and can essentially be classified into two groups: conventional (first‐generation) and atypical (second‐generation) antipsychotics. Many of the second‐generation antipsychotics are believed to offer advantages over first‐generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the cIinical use of adjunctive pharmacotherapy to augment the effects of treatment. In addition, the search for novel and nondoparninergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.
Nicotine
Authors: Buchhalter August R. , Fant Reginald V. , Henningfield Jack E.
Published: March 2007

Nicotine pharmacology is of interest due to its importance in understanding structure and function of the nervous system, the potential of nicotinic modulating drugs in treating a wide range of disorders, and due to the public health impact of nicotine‐driven tobacco use and disease. This chapter includes two sections: one on the pharmacology of nicotine and one on the pharmacological treatment of nicotine dependence and withdrawal. Implications for public health policy also are discussed briefly. Topics presented in the pharmacology of nicotine section include nicotine receptors and their functional adaptations, neurosubstrates of nicotine reinforcement and withdrawal, and nicotine pharmacokinetics. Topics presented in the pharmacological treatment section include nicotine and non‐nicotine based pharmacotherapies, their mechanism(s) of action, and pharmacokinetics.
Psychostimulants
Authors: Howell Leonard L. , Kimmel Heather L.
Published: March 2007

Psychstimulants are a broadly defined class of drugs that stimulate the central and peripheral nervous systems as their primary pharmacological effect. The abuse liability of psychostimulants is well established and represents a significant public health concern. An extensive literature documents the critical importance of monoamines (dopamine, serotonin, and norepinephrine) in the behavioral pharmacology and addictive properties of psychostimulants. In particular, dopamine plays a primary role in the reinforcing effects of psychostimulants in animals and humans. However, there is a growing body of evidence that highlights complex interactions among additional neurotransmitter, neuroendocrine, and neuropeptide systems. Cortical glutamatergic systems provide important regulation of dopamine function, and inhibitory amino acid ?‐aminobutyric acid (GABA) systems can modulate basal dopamine and glutamate release. Psychostimulants also activate the hypothalamic‐pituitary axis and thereby engage neuroendocrine systems linked to stress reactivity. Finally, endogenous neuropeptide systems, including opioids and neurotensin, appear to play an important role in the neuropharmacology of psychostimulants. Repeated exposure to psychostimulants can lead to robust and enduring changes in neurobiological substrates and corresponding changes in sensitivity to acute drug effects on neurochemistry and behavior. It is important to emphasize that some neurobiological changes are not evident when drug administration is terminated but actually emerge during the period of drug withdrawal. Significant advances in the understanding of neurobiological mechanisms underlying psychostimulant abuse and dependence have guided pharmacological treatment strategies to improve clinical outcome. In particular, functional agonist treatments may be used effectively to stabilize neurochemistry and behavior. In addition, medications that target glutamatergic and GABAergic function are reasonable candidates that have received significant attention. However, additional clinical studies are required in order to identify safe and efficacious pharmacotherapies.
Marijuana: Pharmacology and Interaction with the Endocannabinoid System
Authors: Wiley Jenny L. , Martin Billy R.
Published: March 2007

Marijuana is one of the most widely used illicit psychoactive substances in the U.S. Recently, negative perceptions of marijuana as an abused substance have been tempered somewhat by the idea that it may also have medicinal properties. Regardless of perception of marijuana, however, investigation of its active substituents and their mechanism of action led to the discovery of an endocannabinoid system that is activated by marijuana as well as by several endogenous cannabinoids, including anandamide and 2‐arachidonylglycerol. In this chapter, we review the pharmacology of marijuana and discuss how its interaction with the endocannabinoid system may have implications for understanding the physiology of this system.
Neuronal Pathways for Pain Processing
Authors: Pasternak Gavril W. , Zhang Yahong
Published: March 2007

Pain remains a prominent factor in all facets of medicine. Pain helps maintain the safety and integrity of subjects by alerting them to potential injury. Pathways that transmit nociceptive stimuli from the periphery to the central nervous system have been studied extensively. However, situations exist where survival may depend upon minimizing or ignoring pain. A major function of the sensory nervous system is its ability to filter sensory input. The vast array of sensation from all modalities makes it essential for the individual to focus upon a selected few and to place others in the background. Thus, it is not surprising that the nervous system has developed a highly complex system to “filter,” or modulate, the perception of pain.
Melatonin Receptors in Central Nervous System
Authors: Dubocovich Margarita L.
Published: March 2007

The functional role of melatonin receptors in the mammalian central nervous system and their therapeutic potential is discussed. Melatonin, dubbed the “hormone of darkness,” is produced primarily in the pineal gland and retina following circadian rhythms with high levels of night. The chapter describes the structure, molecular pharmacology, signaling, and function of the MT1 and MT2 mammalian melatonin receptors. This is followed by discussion of recent advances in the regulation of melatonin receptor sensitivity and its role in circadian rhythm modulation by the circadian timing system. Recent advances in the discovery and development of therapeutic agents targeting melatonin receptors for the treatment of insomnia, circadian rhythm dysfunctions, and depression are also highlighted.
Sedatives and Hypnotics
Authors: Wafford Keith A. , Whiting Paul J.
Published: March 2007

Insomnia is a disorder of significant prevalence. In this chapter we describe current pharmacological treatments for this disorder. We also describe current understanding of the γ‐aminobutyric acid type A neurotransmitter receptor system, through which most currently prescribed hypnotics and sedatives exert their activity. Finally, we discuss the current knowledge of the neural pathways in the brain that mediate sleep. An increased understanding of both the molecular and neural systems that underlie sleep processes will be central to the development of new, improved therapies.
Vapor Sorption and Electrical Response of Au‐Nanoparticle– Dendrimer Composites
Authors: Krasteva N. , Fogel Y. , Bauer R. E. , Müllen K. , Joseph Y. , Matsuzawa N. , Yasuda A. , Vossmeyer T.
Published: March 2007

Films comprising Au nanoparticles and polyphenylene dendrimers (first and second generation) are deposited onto transducer substrates via layer‐by‐layer self‐assembly and characterized by atomic force microscopy and X‐ray photoelectron spectroscopy. Their sorption behavior is studied by measuring the uptake of solvents from the vapor phase with quartz crystal microbalances (QCMs). The resistance of the films is simultaneously monitored. Both sensor types, QCMs and chemiresistors, give qualitatively very similar response isotherms that are consistent with a combination of Henry‐ and Langmuir‐type sorption processes. The sorption‐induced increase in relative differential resistance scales linearly with the amount of analyte accumulated in the films. This result is in general agreement with an activated tunneling process for charge transport, if little swelling and only small changes in the permittivity of the film occur during analyte sorption (a first‐order approximation). The relative sensitivity of the films to different solvents decreases in the order toluene ≈ tetrachloroethylene > 1‐propanol ≫ water. Films containing the larger second‐generation dendrimers show higher sensitivity than films containing first‐generation dendrimers.
Integrated product and process control of Single‐Input‐Single‐Output systems
Authors: Xiao Jie , Huang Yinlun , Qian Yu , Lou Helen H.
Published: March 2007

In many chemical and allied manufacturing systems, product quality is controlled based on postprocess quality inspection on sampled final products. Statistical analysis of the identified quality problems is then utilized to improve process operation, and thus the quality of succeeding products. Although this type of reactive quality control (QC) is necessary, it is not only inefficient because it “waits for” the occurrence of product quality problems, but also ineffective due to usually a significant time lag from problem identification, through solution derivation, to action taking. Furthermore, the derived solutions for problem solving are mostly heuristic in nature. This paper introduces a proactive product QC approach, which is established based on the concept of integrated product and process (IPP) control. Aiming at simultaneous dynamic control of process operation and product manufacturing, this approach ensures all‐time systematic control of both process performance and product quality. From the view point of both process control and product control, it is shown that IPP control can be realized by resorting to a well known scheme, cascade control. The IPP control problem for Single‐Input‐Single‐Output systems can be formulated rigorously, and the control laws can be identified readily. A synthesized IPP control system can effectively reject disturbances on the process and the product, and have excellent set‐point tracking capability, regardless of the type of interaction between the process and the product. The efficacy and attractiveness of the IPP control system design methodology are demonstrated through two types of case studies. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Cover Picture: Interpenetrating Polar and Nonpolar Sublattices in Intermetallics: The NaCd2 Structure (Angew. Chem. Int. Ed. 12/2007)
Authors: Fredrickson Daniel C. , Lee Stephen , Hoffmann Roald
Published: March 2007

The sun and the moon are not quite equal partners; the two clusters shown in the cover picture are more so. They rise and set in several incredibly complex intermetallic phases, such as NaCd2. As explained by R. Hoffmann and co‐workers in their Review on page 1958 ff., an electronic Aufbau based on these clusters generates the full NaCd2 structure in all its glory: the clusters build two interpenetrating networks that strive for the extremes of polarity and nonpolarity. The alchemical image, drawn by Robert Vaughn, is from Elias Ashmole's Theatricum Chemicum Britannicum.
Anastomotic dehiscence after anterior resection of rectum and sigmoid
Authors: Goligher J C , Graham N G , De Dombal F T
Published: March 2007

The incidence of dehiscence of the anastomosis after anterior resection of the sigmoid colon and rectum was studied by digital examination of the rectum, sigmoidoscopy, and radiological examination after a small barium enema in 73 patients who had undergone the operation for carcinoma, villous papilloma, or diverticular disease. Dehiscence was detected in 37 (or 51 per cent) of the entire series, in 19 (or 40 per cent) of the 47 cases treated by high anterior resection, and in 18 (or 69 per cent) of the 26 cases submitted to low anterior resection. The dehiscences were usually much more extensive after low resection. The possible reasons for these differences are discussed. The effect of other factors on the occurrence of dehiscence was examined:— A simultaneous transverse colostomy was performed in 28 of the 68 patients undergoing primary resection. It was used in most cases after low resection, whilst after high resection it was reserved largely for cases with faecal loading. The unfavourable nature of the patients submitted to simultaneous covering colostomy makes it impossible to evaluate the influence of this step on the incidence of dehiscence.A preliminary transverse colostomy was established 14–21 days before resection in 5 patients. Three of these cases developed anastomotic dehiscence after the resection, so that clearly an empty distal colon at the time of resection provides no certain guarantee against breakdown of the suture line.Preoperative administration of bowel antiseptics in the form of phthalylsulfathiazole and neomycin was associated with a significantly lower rate of dehiscence after high anterior resection, but had no obvious beneficial effect on the incidence of this complication after low resection. Though minimal dehiscences, especially after high anterior resection, often pursued an innocuous, subclinical course, major dehiscences endangered the patient's life and prolonged convalescence. There were 2 deaths in this series attributable to dehiscence, a mortality of 2.7 per cent. The mean period in hospital after high anterior resection was 17 days in patients who did not develop dehiscence and 35 days in those who did; and after low anterior resection it was 44 days when dehiscence did not occur and 48 days when it did.
Hiatus Hernia, a follow-up of 53 operations
Authors: Tanner Norman C , Hardy Kenneth J
Published: March 2007

Fifty-three patients having a hiatal hernia repair between 1951 and 1956 are reviewed. Three patients died within 1 year of surgery and were excluded from the assessment of symptoms. Of 41 having an abdominal repair 80 per cent were classed as Visick 1 or 2. The results for anterior repair of the oesophageal hiatus were better than an anterior and posterior repair; posterior repair was the least effective. Six patients required resection for stenosis, and 10 per cent of the group died of a subsequent carcinoma of the cardia.
Idiopathic and drug-induced ulceration of the small intestine
Authors: Davies D R , Brightmore Terence
Published: March 2007

Ulceration of the small intestine is an uncommon lesion of multifactorial origin. The most important factor responsible for the reported increased incidence is the ingestion of enteric-coated potassium chloride. It is desirable that potassium supplements be given in another form, for example as a slow-release preparation. Other drugs which may play a part in the aetiology include corticosteroids and phenylbutazone.

Diagnosis is difficult and ulceration is usually only demonstrated after one of the complications (obstruction, perforation, or haemorrhage) has occurred. It is imperative that a full drug-taking history is obtained.

Laboratory tests are not helpful in diagnosis, but where radiological studies are carried out they often contribute useful information.

If the symptoms of such an ulcer are severe enough to warrant laparotomy, then the treatment of choice is excision of the affected segment followed by end-to-end anastomosis.
Vertebral aneurysm in a case of Ehlers-Danlos syndrome
Authors: Brodribb A J M
Published: March 2007

A case of Ehlers–Danlos syndrome is described with a left vertebral arterial aneurysm.

The occurrence of major arterial lesions with this syndrome is reviewed and the hazards of surgery discussed
Spontaneous rupture of stomach, a rare complication of inguinal hernia
Authors: Gue S
Published: March 2007

Spontaneous rupture of the stomach in the sac of a long-standing large inguinal hernia is described. From a search of the medical literature it is unique.