CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2006
MK Peddyreddy
SUMMARY 1Insulin is the drug of choice in the management of type 1 diabetes mellitus. Approximately 76% of diabetic patients suffer from gastrointestinal disorders. An important area of investigating the inherent effect of insulin on small intestinal transit (SIT) remains unexplored. Hence, the present study was planned to investigate the effects of insulin (2 × 10,6, 2 × 10,3 and 2 U/kg) on small intestinal transit following two different routes of administration in healthy animals. 2Insulin or vehicle was administered subcutaneously or intracerebroventricularly in eight groups of healthy, overnight-fasted mice. Blood glucose (BG) levels were measured 2 min before insulin administration and at the time coinciding with SIT determination. Small intestinal transit was determined 50 min after insulin administration using the charcoal meal method. 3Following subcutaneous administration, the lowest dose of insulin (2 × 10,6 U/kg) produced a significant acceleration in SIT without altering BG levels. However, the highest dose of insulin (2 U/kg) produced an acceleration of SIT that was associated with a significant fall in BG levels. 4Following intracerebroventricular administration, the lowest dose of insulin (2 × 10,6 U/kg) attenuated SIT, without producing any alteration in BG levels, but the highest dose (2 U/kg) mimicked the effects seen following subcutaneous administration. Peripherally administered insulin produced significant acceleration of SIT at lower doses (2 × 10,6 or 2 × 10,3 mU/kg) compared with centrally administered insulin at similar doses. However, at the highest dose of insulin (2 U/kg), both routes (s.c. and i.c.v.) produced acceleration of SIT. 5In the present study, peripherally and centrally administered insulin at 2 × 10,6 U/kg produced contrasting effects on SIT, without any hypoglycaemia. However, 2 U/kg insulin accelerated SIT similarly following both s.c. and i.c.v. administration that was associated with hypoglycaemia in healthy animals. [source]

Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2002
Lan Bao
Abstract Peripheral axotomy-induced sprouting of thick myelinated afferents (A-fibers) from laminae III,IV into laminae I,II of the spinal cord is a well-established hypothesis for the structural basis of neuropathic pain. However, we show here that the cholera toxin B subunit (CTB), a neuronal tracer used to demonstrate the sprouting of A-fibers in several earlier studies, also labels unmyelinated afferents (C-fibers) in lamina II and thin myelinated afferents in lamina I, when applied after peripheral nerve transection. The lamina II afferents also contained vasoactive intestinal polypeptide and galanin, two neuropeptides mainly expressed in small dorsal root ganglion (DRG) neurons and C-fibers. In an attempt to label large DRG neurons and A-fibers selectively, CTB was applied four days before axotomy (pre-injury-labelling), and sprouting was monitored after axotomy. We found that only a small number of A-fibers sprouted into inner lamina II, a region normally innervated by C-fibers, but not into outer lamina II or lamina I. Such sprouts made synaptic contact with dendrites in inner lamina II. Neuropeptide Y (NPY) was found in these sprouts in inner lamina II, an area very rich in Y1 receptor-positive processes. These results suggest that axotomy-induced sprouting from deeper to superficial layers is much less pronounced than previously assumed, in fact it is only marginal. This limited reorganization involves large NPY immunoreactive DRG neurons sprouting into the Y1 receptor-rich inner lamina II. Even if quantitatively small, it cannot be excluded that this represents a functional circuitry involved in neuropathic pain. [source]

,, T-cell anergy in human immunodeficiency virus-infected persons with opportunistic infections and recovery after highly active antiretroviral therapy

IMMUNOLOGY, Issue 4 2000
F. Martini
Summary ,, T lymphocytes recognize non-peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a defective response to non-peptidic antigens was observed in human immunodeficiency virus-positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of ,, T-cell anergy in HIV+ patients with opportunistic infections/co-infections (HIV-OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on ,, T-cell functions. Peripheral ,, T-cell distribution and in vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. ,, T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically, the V,2/V,1 ratio was inverted as a consequence of a decrease in V,2 T-cell number. Moreover, IPP-stimulated V,2 T cells from the HIV-OIC group displayed a major defect in interferon-, (IFN-,) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored ,, T-cell function. Accordingly, in vitro CD45RA depletion resulted in ,, T-cell hyporesponsiveness. Altogether, the incidence of ,, T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore ,, T-cell reactivity, extending the immune recovery to non-peptidic microbial antigens. [source]

Relative frequency of peripheral odontogenic tumors: a study of 45 new cases and comparison with studies from the literature

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 7 2006
Amos Buchner
Background:, Peripheral (extraosseous) odontogenic tumors are rare, and reports in the literature have mainly been single case reports or a small series of cases. The aim of this study was to determine the relative frequency of peripheral (extraosseous) odontogenic tumors relative to one another and relative to their central (intraosseous) counterparts in an oral pathology biopsy service and to compare these data with information available in the literature. Methods:, The files of the Pacific Oral and Maxillofacial Pathology Laboratory of the University of the Pacific, San Francisco, CA, USA, served as the source of material for this study. Files were systematically searched for all cases of peripheral odontogenic tumors (POTs) during a 20-year-period. Results:, There were 91 178 cases accessed in which central and POTs were identified in 1133 (1.24%), central tumors in 1088 (1.2%), and peripheral tumors in 45 (0.05%). Peripheral tumors accounted for 4% of all 1133 central and POTs. Peripheral odontogenic fibroma (PODF) was the most common of the 45 POTs accounting for 51.1% (23 cases) followed by peripheral ameloblastoma (PA) 28.9% (13 cases) and peripheral calcifying cystic odontogenic tumor (PCCOT) 13.3% (six cases). Peripheral calcifying epithelial odontogenic tumor, peripheral ameloblastic fibroma, and peripheral ameloblastic carcinoma were also identified , each comprised 2.2% (one case each). PODF was more common than its central counterpart by a 1.4:1 ratio. This was the only peripheral tumor that was more common than its central counterpart. PA accounted for 9.3% of all ameloblastomas and PCCOT for 26% of all calcifying cystic odontogenic tumors. Conclusion:, There is only scarce information in the literature on the relative frequency of POTs. Additional studies should be conducted to determine the true relative frequency. To ensure accuracy, pathologists with experience in the field of odontogenic tumors should conduct these studies. Intraosseous tumors that perforate through the bone to the gingival tissue, clinically presenting as ,peripheral tumors' should be excluded. [source]

Rapid improvement of autonomic and peripheral neuropathy after liver transplantation: A single case report

LIVER TRANSPLANTATION, Issue 2 2002
Alan John McDougall PhD
Peripheral and autonomic neuropathies are known but often unrecognized associations of cirrhosis from any cause. The pathogenesis of these effects are ill understood. Liver transplantation has been shown to reverse autonomic manifestations, but little evidence exists for an effect on peripheral neuropathy. This case report documents improvement in peripheral and autonomic neuropathy in a 40-year-old man with hepatitis B virus,related cirrhosis. A return to normal neurophysiological function was seen within 9 months of successful liver transplantation, suggesting a metabolic, rather than a structural, cause of such changes in the peripheral nervous system. [source]

CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses

ALLERGY, Issue 9 2010
G. Banfield
To cite this article: Banfield G, Watanabe H, Scadding G, Jacobson MR, Till SJ, Hall DA, Robinson DS, Lloyd CM, Nouri-Aria KT, Durham SR. CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses. Allergy 2010; 65: 1126,1133. Abstract Background:, CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 , ligand interaction may abrogate allergen-induced inflammation. Methods:, Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T-lymphocytes, CCR4+CD3+ and CXCR3+CD3+ cells and examined by in situ hybridization for CCR4, IL-4 and IFN-, mRNA+ cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4+CD4+ cells assessed for actin polymerization in response to the CCR4 ligand macrophage-derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested. Results:, Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3+ T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4+CD3+ protein-positive cells relative to CXCR3+CD3+ cells; CCR4 mRNA+ cells were increased and IL-4 increased to a greater extent than IFN-,. CCR4+CD4+ T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist. Conclusion:, Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses. Blocking CCR4-ligand interaction may provide a novel therapeutic approach in allergic disease. [source]

Maternal allergic disease does not affect the phenotype of T and B cells or the immune response to allergens in neonates

ALLERGY, Issue 7 2010
E. Rindsjö
To cite this article: Rindsjö E, Joerink M, Johansson C, Bremme K, Malmström V, Scheynius A. Maternal allergic disease does not affect the phenotype of T and B cells or the immune response to allergens in neonates. Allergy 2010; 65: 822,830. Abstract Background:, It is hypothesized that the in utero environment in allergic mothers can affect the neonatal immune responses. The aim of this study was to analyse the effect of maternal allergic disease on cord blood mononuclear cell (CBMC) phenotype and proliferative responses upon allergen stimulation. Methods:, Peripheral blood mononuclear cells (PBMC) from 12 allergic and 14 nonallergic mothers and CBMC from their children were analysed. In the mothers, we determined cell proliferation, production of IL-4 and expression of FOXP3 in response to allergen stimulation. In the children, we evaluated cell proliferation and FOXP3 expression following allergen stimulation. Furthermore, expression of different homing markers on T cells and regulatory T cells and maturity of the T cells and B cell subsets were evaluated directly ex vivo. Results:, The timothy- and birch-allergic mothers responded with increased proliferation and/or IL-4 production towards timothy and birch extract, respectively, when compared to nonallergic mothers. This could not be explained by impairment of FOXP3+ regulatory T cells in the allergic mothers. CBMC proliferation and FOXP3 expression in response to allergens were not affected by the allergic status of the mother. Also, phenotype of T cells, FOXP3+ regulatory T cells and B cells was not affected by the allergic status of the mother. Conclusion:, Our results suggest that maternal allergic disease has no effect on the neonatal response to allergens or the phenotype of neonatal lymphocytes. The factors studied here could, however, still affect later development of allergy. [source]

In vitro detection and characterization of drug hypersensitivity using flow cytometry

ALLERGY, Issue 1 2010
M. Martin
Abstract Background:, The lymphocyte transformation test (LTT) is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction's phenotype. However, the LTT includes working with radioactive substances and is considered impracticable for routine laboratory investigation. Objective:, The aim of this study was to assess drug-specific cytokine production by means of flow cytometry as an alternative nonradioactive approach which may be more appropriate for routine testing and may provide in addition more information about the pathophysiology of the reaction than proliferation-based assays, like the LTT. Method:, Peripheral blood mononuclear cells of 19 patients were incubated with culprit drugs (n = 28) or irrelevant antigens (n = 10). Ten healthy persons served as controls for all different drugs (n = 15). Intracellular interleukin (IL)-5, interferon (IFN)-, and IL-10 production was investigated using flow cytometry. Accuracy of the flow cytometry test system was confirmed using different statistical tests, i.e. receiver operating characteristic curve and Mann,Whitney rank test. In addition, drug-specific secretion of IL-5, IL-2 and IFN-, were analysed using enzyme-linked immunosorbent assay (ELISA). Results:, Drug-specific cytokine production could be demonstrated in 75% of the patients using flow cytometry and in 79% using ELISA respectively. Combining ELISA and flow cytometry increased the sensitivity to 100%. Analysis of involved T-cell subsets [e.g. CD4+ or CD8+; T helper (TH) 1 or TH 2] allowed characterization of the in vitro lymphocyte reactivity pattern. Conclusions:, Analysis of drug-specific cytokine production by means of flow cytometry proved a useful and reliable approach for the in vitro detection and characterization of drug hypersensitivities. [source]

Decreased FOXP3 protein expression in patients with asthma

ALLERGY, Issue 10 2009
S. Provoost
Background:, T-regulatory cells (Treg) are important in balancing immune responses and maintaining peripheral tolerance. Current evidence suggests that asthma is characterized by a relative deficiency in Treg, allowing T helper 2 cells to expand. In this study, we aimed to evaluate circulating Treg, defined by the protein FOXP3, in both control subjects and patients with stable asthma. Methods:, Peripheral blood mononuclear cells (PBMC) of control (n = 14) and asthmatic patients (n = 29) were labeled for CD4, CD25, and intracellular FOXP3 and analyzed using flow cytometry. In CD3/CD28 stimulated PBMC, the effects of dexamethasone on the transcription factors T-bet, GATA-3, FOXP3, and RORc2 and representative cytokines were studied. Results:, In control subjects and asthmatic patients, numbers of peripheral blood CD4+CD25high and CD4+CD25highFOXP3+ T-cells were similar. However, FOXP3 protein expression within CD4+CD25high T-cells was significantly decreased in asthmatic patients. There was a tendency for increased FOXP3 expression within CD4+CD25high T-cells in glucocorticosteroid-treated patients when compared to steroid-naive asthmatic patients. In stimulated PBMC, dexamethasone treatment increased the anti-/proinflammatory transcription ratios of FOXP3/GATA-3, FOXP3/T-bet, and FOXP3/RORc2. Conclusion:, Asthmatic patients have decreased FOXP3 protein expression within their CD4+CD25high Treg. Our findings also suggest that treatment with inhaled glucocorticosteroids in asthmatics might increase this FOXP3 protein expression within the CD4+CD25high T-cell population. [source]

Drug-specific in vitro release of IL-2, IL-5, IL-13 and IFN-, in patients with delayed-type drug hypersensitivity

ALLERGY, Issue 9 2009
P. Lochmatter
Background:, The most prevalent drug hypersensitivity reactions are T-cell mediated. The only established in vitro test for detecting T-cell sensitization to drugs is the lymphocyte transformation test, which is of limited practicability. To find an alternative in vitro method to detect drug-sensitized T cells, we screened the in vitro secretion of 17 cytokines/chemokines by peripheral blood mononuclear cells (PBMC) of patients with well-documented drug allergies, in order to identify the most promising cytokines/chemokines for detection of T-cell sensitization to drugs. Methods:, Peripheral blood mononuclear cell of 10 patients, five allergic to ,-lactams and five to sulfanilamides, and of five healthy controls were incubated for 3 days with the drug antigen. Cytokine concentrations were measured in the supernatants using commercially available 17-plex bead-based immunoassay kits. Results:, Among the 17 cytokines/chemokines analysed, interleukin-2 (IL-2), IL-5, IL-13 and interferon-, (IFN-,) secretion in response to the drugs were significantly increased in patients when compared with healthy controls. No difference in cytokine secretion patterns between sulfonamide- and ,-lactam-reactive PBMC could be observed. The secretion of other cytokines/chemokines showed a high variability among patients. Conclusion:, The measurement of IL-2, IL-5, IL-13 or IFN-, or a combination thereof might be a useful in vitro tool for detection of T-cell sensitization to drugs. Secretion of these cytokines seems independent of the type of drug antigen and the phenotype of the drug reaction. A study including a higher number of patients and controls will be needed to determine the exact sensitivity and specificity of this test. [source]

Soluble vascular cell adhesion molecule-1 induces human eosinophil migration

ALLERGY, Issue 5 2009
S. Ueki
Background:, Tissue eosinophilia is one of the hallmarks of allergic diseases and Th2-type immune responses including asthma. Adhesion molecules are known to play an important role in the accumulation of eosinophils in allergic inflammatory foci, and they contribute to eosinophil activation. Elevated levels of the soluble forms of adhesion molecules in the body fluid of asthmatic patients have been observed, although their pathophysiological significance remains to be fully elucidated. Methods:, Peripheral blood eosinophils were purified, and the effect of soluble vascular cell adhesion molecule-1 (sVCAM-1) on eosinophil migration was investigated using in vitro systems. Results:, We found that sVCAM-1 (1 to 10 ,g/ml) induced eosinophil chemotaxis, rather than chemokinesis, in a concentration-dependent fashion. In addition, sVCAM-1 induced cell shape change and actin polymerization, which are necessary for cell movement. Manipulations with very late antigen (VLA)-4-neutralizing antibody and signal inhibitors indicated that the sVCAM-1-induced chemotaxis was mediated through ligand-dependent activation of tyrosine kinase Src, p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase (ERK) MAPK. Rapid phosphorylation of these signaling molecules was observed using a bead-based multiplex assay. Conclusion:, Our results raise the possibility of sVCAM-1 in the fluid phase as a significant contributor to the heightened eosinophilic inflammatory response. [source]

Neural control of the lower urinary tract: Peripheral and spinal mechanisms,

NEUROUROLOGY AND URODYNAMICS, Issue 1 2010
L. Birder
Abstract This review deals with individual components regulating the neural control of the urinary bladder. This article will focus on factors and processes involved in the two modes of operation of the bladder: storage and elimination. Topics included in this review include: (1) The urothelium and its roles in sensor and transducer functions including interactions with other cell types within the bladder wall ("sensory web"), (2) The location and properties of bladder afferents including factors involved in regulating afferent sensitization, (3) The neural control of the pelvic floor muscle and pharmacology of urethral and anal sphincters (focusing on monoamine pathways), (4) Efferent pathways to the urinary bladder, and (5) Abnormalities in bladder function including mechanisms underlying comorbid disorders associated with bladder pain syndrome and incontinence. Neurourol. Urodynam. 29: 128,139, 2010. © 2009 Wiley-Liss, Inc. [source]

Multimodal Analgesia for Chronic Pain: Rationale and Future Directions

PAIN MEDICINE, Issue S2 2009
Charles E. Argoff MD
ABSTRACT Chronic pain is a multifaceted disease requiring multimodal treatment. Clinicians routinely employ various combinations of pharmacologic, interventional, cognitive,behavioral, rehabilitative, and other nonmedical therapies despite the paucity of robust evidence in support of such an approach. Therapies are selected consistent with the biopsychosocial model of chronic pain, reflecting the subjective nature of the pain complaint, and the myriad stressors that shape it. Elucidating mechanisms that govern normal sensation in the periphery has provided insights into the biochemical, molecular, and neuroanatomic correlates of chronic pain, an understanding of which is leading increasingly to mechanism-specific multidrug therapies. Peripheral and central neuroplastic reorganization underlying the disease of chronic pain is influenced by patient-specific emotions, cognition, and memories, further impairing function and idiosyncratically defining the illness of chronic pain. Clinical perceptions of these and related subjective elements associated with the suffering of chronic pain drive psychosocial treatments, including, among other options, relaxation therapies, coping skills development, and cognitive,behavioral therapy. Treatment selection is thus guided by comprehensive assessment of the phenomenology and inferred pathophysiology of the pain syndrome; patient goals, preferences, and expectations; behavioral, cognitive, and physical function; and level of risk. Experiential, practice-based evidence may be necessary for improving patient care, but it is insufficient; certainly, well-designed studies are needed to support therapeutic decision making. This review will discuss the biochemical basis of pain, factors that govern its severity and chronicity, and foundational elements for current and emerging multimodal treatment strategies. [source]

Neurodegeneration and Neuroplasticity in the Peripheral and Central Nervous System

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 12 2009
Roland Pochet Guest Editor The Anatomical Record
No abstract is available for this article. [source]

The Role of Non-Deletional Tolerance Mechanisms in a Murine Model of Mixed Chimerism with Costimulation Blockade

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2005
Sinda Bigenzahn
Peripheral and central clonal deletion are important tolerance mechanisms in models using bone marrow transplantation (BMT) with costimulation blockade (CB). However, since tolerance can be found before peripheral deletion is complete and since elimination of recipient CD4+ cells at the time of BMT prevents tolerance induction, we investigated the potential roles of regulation and anergy in such a murine model. We found that transient elimination of CD25+ cells or neutralization of IL2 immediately after BMT and CB prevented the induction of skin graft tolerance. Cotransfer into SCID mice of CD4+ cells taken from chimeras early after BMT, together with naïve recipient-type CD4+ cells significantly prolonged donor skin graft survival. In contrast, cotransfer of CD4+ cells harvested from chimeras late after BMT did not prolong donor skin graft survival. Besides, depletion of CD25+ cells in established chimeras several months post-BMT did not break tolerance. In vivo administration of recombinant IL2 inhibited chimerism and tolerance neither early nor late post-BMT, arguing against a decisive role for classical anergy. Thus, CD4 cell-mediated regulation contributes significantly to tolerance induction early after BMT, but appears to have no critical role in the maintenance of tolerance. [source]

ASEAN in the Asia Pacific: Central or Peripheral?

ASIAN POLITICS AND POLICY, Issue 4 2010
Julio Santiago Amador III
The Association of Southeast Asian Nations (ASEAN) is an enduring regional organization in the Asia Pacific. However, its claim of being central to any talks on regional architecture is challenged by a multiplicity of external and internal factors. This article assesses ASEAN's centrality by looking into the possible challenges facing it, which inevitably affect its claim to be the central organization in managing the direction of the wider region. It then offers possible ways forward so that ASEAN can retain its leadership and prove to be a credible driver for regional cooperation. [source]

Synthesis of Pyrazoleporphyrins and Pyrazolechlorins by Cyclization of Peripheral ,-Diketone Groups of Porphyrins and Chlorins with Phenylhydrazines.

CHEMINFORM, Issue 20 2004
G. V. Ponomarev
No abstract is available for this article. [source]

Colour contrast sensitivity in cataract and pseudophakia

ACTA OPHTHALMOLOGICA, Issue 5 2000
Björn Friström
ABSTRACT. Purpose: To study the influence of cataract on peripheral and central colour contrast sensitivity. Methods: Peripheral and central colour contrast sensitivity was measured with a computer graphics system along the protan, deutan and tritan axes. Included were 30 patients with cataract divided into three sub-groups: cortical cataract, nuclear sclerosis and posterior subcapsular cataract. Colour contrast was measured before and after cataract operation. Results: There were significant differences in peripheral colour contrast thresholds comparing the preoperative and postoperative results. This difference existed even in patients (n=19) with a pre-operative visual acuity ,0.5 (mean 0.6). The tritan axis was the one most affected by cataract. There was no significant difference between cataract sub-groups. Also, the central colour contrast sensitivity was affected by cataract. Again, the tritan axis was the most affected one. There was no significant difference between the cataract sub-groups. We also found large and significant differences in central colour contrast thresholds between normal subjects and postoperative values from the cataract group in all colour axes. The colour contrast sensitivity was poorer in pseudophakes than in normals. There was a difference between the three groups of different IOL material used (PMMA, acrylic and silicone). The difference was significant in the protan axis, the acrylic group having the best colour contrast sensitivity. Conclusion: Peripheral colour contrast sensitivity was affected by cataract, even when only moderately developed. This finding is of importance and should be considered when the method is used to study other eye diseases e.g. glaucoma. Central colour contrast sensitivity was also affected by cataract. The pseudophakes were found to have poorer colour contrast sensitivity than normals. The material in the IOL seemed to be of importance for colour contrast. [source]

ChemInform Abstract: Large-Scale Synthesis of New Cyclazines, 5-Thia-1,8b-diazaacenaphthylene-3-carboxylic Acid Derivatives Having the Peripheral 12,-Electron Ring System.

CHEMINFORM, Issue 26 2002
Tomomi Ikemoto
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: Results from an international inception cohort study

ARTHRITIS & RHEUMATISM, Issue 3 2008
J. G. Hanly
Objective To examine, in an inception cohort of systemic lupus erythematosus (SLE) patients, the association between neuropsychiatric (NP) events and anti,ribosomal P (anti-P), antiphospholipid (lupus anticoagulant [LAC], anticardiolipin), anti,,2-glycoprotein I, and anti,NR2 glutamate receptor antibodies. Methods NP events were identified using the American College of Rheumatology case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events to SLE was determined using decision rules of differing stringency. Autoantibodies were measured without knowledge of NP events or their attribution. Results Four hundred twelve patients were studied (87.4% female; mean ± SD age 34.9 ± 13.5 years, mean ± SD disease duration 5.0 ± 4.2 months). There were 214 NP events in 133 patients (32.3%). The proportion of NP events attributed to SLE varied from 15% to 36%. There was no association between autoantibodies and NP events overall. However, the frequency of anti-P antibodies in patients with central NP events attributed to SLE was 4 of 20 (20%), versus 3 of 107 (2.8%) in patients with other NP events and 24 of 279 (8.6%) in those with no NP events (P = 0.04). Among patients with diffuse NP events, 3 of 11 had anti-P antibodies (27%), compared with 4 of 111 patients with other NP events (3.6%) and 24 of 279 of those with no NP events (8.6%) (P = 0.02). Specific clinical,serologic associations were found between anti-P and psychosis attributed to SLE (P = 0.02) and between LAC and cerebrovascular disease attributed to SLE (P = 0.038). There was no significant association between other autoantibodies and NP events. Conclusion Clinically distinct NP events attributed to SLE and occurring around the time of diagnosis were found to be associated with anti-P antibodies and LAC. This suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies. [source]

The Use of Midodrine in Patients With Advanced Heart Failure

CONGESTIVE HEART FAILURE, Issue 3 2009
Ramzan M. Zakir MD
In many patients, the treatment of heart failure (HF) cannot be optimized because of pre-existing or treatment-induced hypotension. Midodrine, a peripheral ,1-adrenergic agonist may allow for up-titration of neurohormonal antagonist therapy leading to improved outcomes. Ten consecutive patients with HF due to systolic dysfunction and symptomatic hypotension interfering with optimal medical therapy were started on midodrine. After a 6-month follow-up, a higher percentage of patients were on optimal HF therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker mg % of optimal dose 20% vs 57.5%; P<.001) (,-blockers mg % optimal dose 37.5% vs 75%; P<.001) (spironolactone/eplerenone mg % 43.7% vs 95%; P<.001). This led to an improvement in left ventricular ejection fraction (baseline 24±9.4 vs 32.2±9.9; P<.001) and clinical outcomes, with a significant reduction in total hospital admissions (32 vs 12; P=.02) and total hospital days (150 vs 58; P=.02). [source]

The Problematic Role of Lawyers in the Creativity and Innovation Process

CREATIVITY AND INNOVATION MANAGEMENT, Issue 4 2000
James Tunney
In the literature on creativity and innovation management, the role of law is often peripheral. There is an urgent need to inject law into creativity and innovation management discourse. However there is a deeper reflexive need. Legal systems are in urgent need of reform and repair. They urgently need input from people who genuinely understand about creativity and innovation management in relation to the operation of overall systems. This is a call for a greater dialogue between creativity management and the legal establishment. [source]

Monitoring of monocyte functional state after extracorporeal circulation: A flow cytometry study

CYTOMETRY, Issue 1 2004
Silverio Sbrana
Abstract Background Cardiovascular surgery with cardiopulmonary bypass (CPB) induces systemic inflammation and postoperative complications depending on pro- and anti-inflammatory mechanisms. Activated polymorphonuclear cells and monocytes may be responsible for morbidity associated with CPB. Knowledge of the monocyte functional state in particular may help to develop protective interventions. Methods Samples were drawn from venous peripheral blood (basal condition, at 4 and 24 h after CPB) and coronary blood (before and after cardioplegic arrest) of 14 patients undergoing cardiac surgery. The following phenotypic and functional parameters of the monocyte population were studied by flow cytometry: surface molecules expression (CD18, CD11a, CD11b, CD14, CD15, CD45, HLA-DR, and Toll-like receptor [TLR]-4), myeloperoxidase (MPO) content, and intracellular cytokine production (tumor necrosis factor [TNF]-,, interleukin [IL]-1,, IL-6, and IL-8). Results Cardiac surgery with CPB induced down-modulation of surface molecules expression on peripheral monocytes, especially at 24 h after CPB, for CD18, CD11a, and CD11b (P < 0.003) and for the CD15 adhesive cluster (P = 0.0028) and HLA-DR (P < 0.001). At 4 h after CPB, downregulation was observed for CD14 (P = 0.004), CD45 (P = 0.014), and CD15 (P = 0.0056). A loss of MPO was detected in venous peripheral (at 24 h after CPB, P = 0.01) or coronary (at reperfusion, P < 0.02) blood. The CD15 cluster complex exhibited a down-modulation in coronary blood (at reperfusion, P = 0.0003). Spontaneous intracellular production of IL-1,, IL-6, and IL-8 decreased at 24 h after CPB (P < 0.05). Conclusions The down-modulation of integrins and adhesive receptor expression and the loss of MPO suggest a strong activation and shedding reaction of circulating monocyte after CPB, further exacerbated by contact with coronary ischemic vessels. The changes of differentiation antigens may reflect the appearance of a partially immature population immediately after CPB. The reduced proinflammatory cytokine production, observed at 24 h after CPB, suggests a functional polarization of circulating monocytes. © 2003 Wiley-Liss, Inc. [source]

Xath5 regulates neurogenesis in the Xenopus olfactory placode

DEVELOPMENTAL DYNAMICS, Issue 4 2002
Carole J. Burns
Abstract Helix-loop-helix (HLH) genes function as important regulators of neurogenesis in both the peripheral and central nervous systems. The olfactory system is an ideal tissue in which to study the role of these genes in regulating the acquisition of neuronal cell fate, particularly that of the olfactory receptor neuron (ORN). Here we describe the expression of several basic HLH (bHLH) and repeat HLH (rHLH) factors during olfactory placode development in Xenopus laevis. Our work reveals that a combination of both bHLH and rHLH genes are sequentially expressed within the nascent olfactory placode during normal development. Moreover, overexpression of the bHLH factor, Xenopus atonal homologue 5 (Xath5), promotes olfactory neural fate independent of cellular proliferation within a restricted domain at the anterior of the embryo. Collectively, our data argue that HLH genes are expressed in a cascade during olfactory placode development and that the activity of an atonal homologue, Xath5, can promote ORN fate but only in the appropriate developmental context. © 2002 Wiley-Liss, Inc. [source]

Remodeling of an identified motoneuron during metamorphosis: central and peripheral actions of ecdysteroids during regression of dendrites and motor terminals

DEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002
Laura M. Knittel
Abstract During metamorphosis of the moth Manduca sexta, an identified leg motoneuron, the femoral depressor motoneuron (FeDe MN), undergoes reorganization of its central and peripheral processes. This remodeling is under the control of two insect hormones: the ecdysteroids and juvenile hormone (JH). Here, we asked whether peripheral or central actions of the ecdysteroids influenced specific regressive aspects of MN remodeling. We used stable hormonal mimics to manipulate the hormonal environment of either the FeDe muscle or the FeDe MN soma. Our results demonstrate that motor-terminal retraction and dendritic regression can be experimentally uncoupled, indicating that central actions of ecdysteroids trigger dendritic regression whereas peripheral actions trigger terminal retraction. Our results further demonstrate that discrete aspects of motor-terminal retraction can also be experimentally uncoupled, suggesting that they also are regulated differently. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 99,116, 2002 [source]

Exenatide prevents fat-induced insulin resistance and raises adiponectin expression and plasma levels

DIABETES OBESITY & METABOLISM, Issue 10 2008
L. Li
Background:, Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood. Methods:, In the present study, we examined the effects of exenatide treatment on glucose tolerance (intravenous glucose tolerance test), insulin sensitivity (euglycaemic,hyperinsulinaemic clamps), insulin signalling (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels (visfatin and adiponectin) in high fat,fed rats. Results:, Administration of exenatide (0.5 or 2.0 ,g/kg twice daily × 6 weeks) prevented high-fat diet (HFD),induced increases in body weight, plasma free fatty acids, triglycerides and total cholesterol. Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in exenatide-treated rats, whereas expression and plasma levels of adiponectin increased. Conclusions:, These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat,induced insulin resistance. [source]

The relationship between peripheral glucose utilisation and insulin sensitivity in the regulation of hepatic glucose production: studies in normal and alloxan-diabetic dogs

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2006
M. J. Christopher
Abstract Background Hepatic glucose overproduction (HGP) of diabetes could be primary or could occur in response to the metabolic needs of peripheral (skeletal muscle (SkM)) tissues. This question was tested in normal and diabetic dogs. Methods HGP, SkM glucose uptake (Rdtissue), metabolic clearance of glucose (MCRg) and glycolytic flux (GFexog), and SkM biopsies were measured in the same dogs before and after alloxan-induced diabetes. Normal dogs were exposed to (1) an extended 20-h fast, (2) low- and high-dose glucose infusions (GINF) at basal insulinaemia, and chronic diabetic dogs were exposed to (3) hyperglycaemia, (4) phlorizin-induced normoglycaemia, and (5) poor and good diabetic control. Results (1) Prolonged fast: HGP, Rdtissue, and GFexog fell in parallel (p < 0.05). (2) Low-dose GINF: plasma glucose, insulin, Rdtissue, MCRg, and GFexog were unchanged, but HGP fell by ,40%, paralleling the supplemental GINF. (3) High-dose GINF at basal insulin: plasma glucose doubled and synchronous changes in HGP, Rdtissue, MCRg, and GFexog occurred; ICglucose, G6P, and glycogen were unchanged. (4) Hyperglycaemic diabetes: HGP was raised (p < 0.05), matching urinary glucose loss (UGL) and decreased MCRg, and maintaining normal basal Rdtissue and GFexog. SkM ICglucose was increased and glycogen decreased (both p < 0.05). (5) Phlorizin-induced normoglycaemia in diabetic dogs: HGP rose, matching the increased UGL, while maintaining normal Rdtissue and GFexog. Intramuscular substrates normalised. (6) Whole body and SkM metabolism normalised with correction of the insulin resistance and good diabetic control. Conclusion HGP reflects whether SkM is in a state of relative glucose ,excess' or absolute/relative glucose ,deprivation'. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non-alcoholic fatty liver disease

DIABETIC MEDICINE, Issue 4 2006
G. Targher
Abstract Aims, To estimate the prevalence of cardiovascular disease (CVD) in Type 2 diabetic patients with and without non-alcoholic fatty liver disease (NAFLD), and to assess whether NAFLD is independently related to prevalent CVD. Methods, We studied 400 Type 2 diabetic patients with NAFLD and 400 diabetic patients without NAFLD who were matched for age and sex. Main outcome measures were prevalent CVD (as ascertained by medical history, physical examination, electrocardiogram and echo-Doppler scanning of carotid and lower limb arteries), NAFLD (by ultrasonography) and presence of the metabolic syndrome (MetS) as defined by the World Health Organization or Adult Treatment Panel III criteria. Results, The prevalences of coronary (23.0 vs. 15.5%), cerebrovascular (17.2 vs. 10.2%) and peripheral (12.8 vs. 7.0%) vascular disease were significantly increased in those with NAFLD as compared with those without NAFLD (P < 0.001), with no differences between sexes. The MetS (by any criteria) and all its individual components were more frequent in NAFLD patients (P < 0.001). In logistic regression analysis, male sex, age, smoking history and MetS were independently related to prevalent CVD, whereas NAFLD was not. Conclusions, The prevalence of CVD is increased in patients with Type 2 diabetes and NAFLD in association with an increased prevalence of MetS as compared with diabetic patients without NAFLD. Follow-up studies are necessary to determine whether this higher prevalence of CVD among diabetic patients with NAFLD affects long-term mortality. Diabet. Med. (2006) [source]

Cytology of the central zone of the prostate

DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2003
Lars Egevad M.D., Ph.D.
Abstract The prostate has three anatomical regions: the peripheral, transition, and central zones (CZ). The CZ has distinct histological features, but its cytological morphology has not been described. This study was done on surgical specimens to ensure that samples were representative of the CZ, and that no prostatic intraepithelial neoplasia (PIN) or cancer contaminated the smears. An incision was made in the CZ of 51 prostatectomy specimens, and cells were scraped from cut surfaces. After exclusion of samples contaminated by PIN or cancer or with poor cell yield, 39 Giemsa-stained smears remained for analysis. Large branching epithelial sheets with geographic architecture and crowded nuclei were seen in 97% of smears. Epithelial clusters with elongated palisaded nuclei were identified in 80% of cases, but were always a minor component. Visible nucleoli (97%), cytoplasmic vacuoles (97%), and smooth muscle cells in the background (95%) were common. Blue-green cytoplasmic granules resembling seminal vesicle pigment were seen in 97%. Magenta-colored cytoplasmic pigment, similar to granules seen in other regions of the prostate, was found in 74%. Recognition of CZ epithelium as a benign constituent of prostate cytology is important because elongated cells, crowded nuclei, and visible nucleoli may otherwise be misinterpreted as PIN or cancer. Diagn. Cytopathol. 2003;28:239,244. © 2003 Wiley-Liss, Inc. [source]

Neuropathic pain: symptoms, models, and mechanisms

DRUG DEVELOPMENT RESEARCH, Issue 4 2006
Simon Beggs
Abstract Peripheral neuropathic pain is the most debilitating of all clinical pain syndromes and affects a large and growing number of people worldwide. There are diverse causes for peripheral neuropathic pain, which may be experienced after traumatic nerve injury or from diseases that affect peripheral nerves, such as diabetes, HIV/AIDS, and cancer, and it can also result from toxic chemicals, such as cancer chemotherapy agents. Despite these varying causes, it is clear that neuropathic pain is due to persistent pathological alterations resulting in hyperexcitability in the peripheral and central nervous systems, and it is the neuropathology that must be targeted for effective therapy of which there is none presently available. Mechanistically, neuropathic pain is distinct from acute pain and inflammatory pain, for which many effective therapies are known. In this review, we describe the relationships between clinical symptoms and experimental models of peripheral neuropathic pain, and we provide a framework for understanding the potential mechanisms that involve primary neuronal dysfunction as well as pathological changes in neuron-glial signaling. Drug Dev. Res. 67:289,301, 2006. © 2006 Wiley-Liss, Inc. [source]