Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients

Aims

Our study addressed the influence of early inflammatory stages of diabetic kidney disease: leukocyte adhesion and monocyte activation (as assessed by intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a possible anti-inflammatory counteracting mechanism, were also studied in correlation to the above-mentioned cytokines.

Methods

79 consecutive type 2 diabetic outpatients and 46 controls were included. Routine laboratory analysis, urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and urinary MPC-1 were assessed.

Results

In multiple regression ICAM-1 (p = 0.004) and adiponectin (p = 0.04) were the main determinants of uACR. Plasma adiponectin positively correlated to ICAM-1 (p = 0.03, r = 0.24).In albuminuric patients (uACR ≥30 mg/g) plasma adiponectin was significantly higher compared to normoalbuminuric ones (uACR <30 mg/g). In albuminuric patients the main determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression ICAM-1 is the only one that retains statistical significance (p = 0.02). Urinary MCP-1 did not correlate to uACR.

Conclusions

In our type 2 diabetic patients, plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to adhesion molecule ICAM-1 in our cohort.     

Cauda Equina Intradural Extramedullary Cavernous Haemangioma: Case Report and Review of the Literature

Cavernous haemangioma (cavernoma) is a benign vascular lesion, exceptionally located in cauda equina. We report a case, diagnosed and operated in the Department of Neurosurgery from Pitesti County Emergency Hospital, of a 60-year-old woman with history of lumbar region distress, who presented with low back pain, paravertebral muscle contracture, and bilateral lumbar radiculopathy, with sudden onset after lifting effort. The preoperative diagnosis was done using computed tomography (CT) and magnetic resonance imaging (MRI), and the patient underwent surgery—two level laminectomy, dural incision, and tumor dissection from the cauda equina nerve roots under operatory microscope. Histopathological examination confirmed the positive diagnosis of cavernoma of cauda equina. The patient''s outcome was favorable, without postoperative neurological deficits.     

Arterial calcifications and osteoprotegerin in chronic hemodialysis patients: impact on 6-year survival

International Urology and Nephrology - The association between end-stage renal disease and cardiovascular mortality may be influenced through vascular alterations, in particular atherosclerosis and...     

Fluorescein angiography in diabetic retinopathy

Fluorescein angiography plays an important role in diagnosis, classification and management of diabetic retinopathy. He paper presents angiographic aspects of some patients from "LASER OPTICS" office. An accurate and early diagnosis, and also the evaluation of laser treatment need fluorescein angiography as a useful method in the follow-up of diabetic patient.     

Structural basis for solute transport,nucleotide regulation,and immunological recognition of Neisseria meningitidis PorB

PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 Å resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP–PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction.     

Analogs of methyllycaconitine as novel noncompetitive inhibitors of nicotinic receptors: pharmacological characterization, computational modeling, and pharmacophore development

As a novel approach to drug discovery involving neuronal nicotinic acetylcholine receptors (nAChRs), our laboratory targeted nonagonist binding sites (i.e., noncompetitive binding sites, negative allosteric binding sites) located on nAChRs. Cultured bovine adrenal cells were used as neuronal models to investigate interactions of 67 analogs of methyllycaconitine (MLA) on native alpha3beta4* nAChRs. The availability of large numbers of structurally related molecules presents a unique opportunity for the development of pharmacophore models for noncompetitive binding sites. Our MLA analogs inhibited nicotine-mediated functional activation of both native and recombinant alpha3beta4* nAChRs with a wide range of IC(50) values (0.9-115 microM). These analogs had little or no inhibitory effects on agonist binding to native or recombinant nAChRs, supporting noncompetitive inhibitory activity. Based on these data, two highly predictive 3D quantitative structure-activity relationship (comparative molecular field analysis and comparative molecular similarity index analysis) models were generated. These computational models were successfully validated and provided insights into the molecular interactions of MLA analogs with nAChRs. In addition, a pharmacophore model was constructed to analyze and visualize the binding requirements to the analog binding site. The pharmacophore model was subsequently applied to search structurally diverse molecular databases to prospectively identify novel inhibitors. The rapid identification of eight molecules from database mining and our successful demonstration of in vitro inhibitory activity support the utility of these computational models as novel tools for the efficient retrieval of inhibitors. These results demonstrate the effectiveness of computational modeling and pharmacophore development, which may lead to the identification of new therapeutic drugs that target novel sites on nAChRs.     

Sphincter Defects Are Not Associated With Long-Term Incontinence Following Ileal Pouch-Anal Anastomosis

INTRODUCTION Frequent loose stools test the integrity of sphincter function in patients undergoing ileal pouch-anal anastomosis. The authors hypothesized that women with anal sphincter defects were more likely to experience incontinence episodes than women with intact sphincter muscles following ileal pouch-anal anastomosis.METHODS From 1996 to 1998, 42 women with a mean age of 42 (range, 22–63) years were prospectively evaluated by anorectal manometry and endoanal ultrasound before pouch surgery. Forty women underwent a stapled ileal pouch-anal anastomosis and two underwent a handsewn anastomosis. All patients considered themselves continent of stool before the procedure. A postoperative survey including the Cleveland Clinic Florida scale, Fecal Incontinence Severity Index, and Fecal Incontinence Quality of Life scale was sent to study participants.RESULTS Nineteen women with an obstetrical history had significant sphincter defects associated with significant lower mean resting pressure, mean squeeze pressure, and shorter anal canal length (3 vs. 3.7 cm, P = 0.0007). Thirty-five women (83 percent) responded resulting in a mean follow-up of 62 (range, 49-72) months. Fourteen responders (mean age, 46 years) had sphincter defects but no significant difference was found in Cleveland Clinic Florida scale, Fecal Incontinence Severity Index, or Fecal Incontinence Quality of Life scale scores when compared with those without defects.CONCLUSION Although almost all women reported episodes of seepage, marked sphincter defects associated with low anal pressures and shorter anal canal length did not affect anal function following pouch surgery. This study supports the findings that continent women with significant sphincter defects on ultrasound evaluation may be considered for restorative proctocolectomy.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 22 to 26, 2003.     

Autologous serum utilization in patients with lacrimal hyposecretion and persistent epithelial defects of cornea--clinical study

Autologous serum was supposed to be efficient in the treatment of keratoconjunctivitis sicca and persistent epithelial defects. 14 of 24 eyes of patients with keratoconjunctivitis sicca improved fluorescein and rose Bengal scores. 3 of 6 eyes with persistent epithelial defects healed completely after this treatment and 2 improved fluorescein and rose bengal scores. All patients had been unsuccessfully treated with conventional treatment. Allergic or immune adverse reactions were not present and economical benefit was appreciated by some patients with poor socioeconomic condition.