Increased nitric oxide production during acute rejection in kidney transplantation: a useful marker to aid in the diagnosis of rejection

BACKGROUND: The diagnosis of acute rejection (AR) relies on biopsy (Bx), with all the noninvasive tests failing to show satisfactory predictive value. Nitric oxide (NO) has been shown to play a role in AR. The aim of this study is to analyze the relationship between NO and (1) biopsy-proven allograft rejection and (2) other reasons of allograft dysfunction. PATIENTS AND METHODS: Fifty consecutive renal allograft recipients ages 23-72 yrs who were transplanted were prospectively recruited. Blood samples were collected for 3 months. Endogenous serum nitrate (SNO(3)) levels were measured with Griess reagent in 1178 samples. Biopsies were performed as clinically indicated. Tacrolimus levels, urinary cultures, and renal function tests were done as per unit protocol. RESULTS: Fifty recipients (mean+/-SD age 45.2+/-2.18 yrs, 24 men and 6 women) underwent 68 biopsies. Forty-five Bx (66.2%) showed AR in 19 recipients (mean age 47+/-8) and 23 (33.8%) Bx in 13 recipients (mean age 43+/-12) showed no AR. SNO(3) in AR was (73+/-8.89 micromol/L) compared with negative Bx (45+/-4.5 micromol/L; P<0.05). There was also a significant difference in SNO(3) during AR and other causes of allograft dysfunction; delayed graft function (54+/-7.8 micromol/L), urinary tract infection (44+/-2.9 micromol/L), tacrolimus toxicity (51+/-2.86 micromol/L), and increase in serum creatinine (44+/-2.36 micromol/L). CONCLUSION: There is a significant increase of serum nitrate with episodes of acute rejection compared with other causes of renal dysfunction. SNO(3) can therefore aid in the diagnosis of acute rejection.     

Anesthesia for carbon dioxide laser microsurgery of the larynx

Jet ventilation via the Sanders injector during intravenous general anesthesia provides excellent operative conditions for CO2 laser microsurgery of the larynx. This technique, which includes complete muscle relaxation, is superior to traditional methods of anesthesia because the endotracheal tube is eliminated, thus improving the surgical field and reducing burn hazards owing to ignition of the tube. The laryngoscope has been modified to carry multiple ports into which a 14-gauge needle is inserted and the tip advanced just distal to the vocal cords. This needle is securely attached to the injector and pressure from the oxygen source is adjusted according to the patient's build and total compliance. Satisfactory arterial blood gases, superb operating conditions, safety, and rapid awakening make this the method of choice for most patients.     

Oral human papillomavirus infection in adults is associated with sexual behavior and HIV serostatus

The prevalence and risk factors for oral human papillomavirus (HPV) infection are unknown, despite evidence for an etiological role for HPV in oral cancers. Oral samples from human immunodeficiency virus (HIV)-seronegative (n=396) and HIV-seropositive (n=190) adults were tested for HPV DNA. High-risk HPV infections were present in 2.1% of tonsil and 6.3% of oral-rinse specimens. The prevalence of oral high-risk HPV infection was greater in HIV-seropositive individuals (13.7% vs. 4.5%; P<.001). In multiple logistic regression, odds of oral HPV infection increased with age, male sex, and herpes simplex virus (HSV)-2 seropositivity in HIV-seronegative individuals and with CD4 cell count <200 cells/mL, HSV-2 seropositivity, oral mucosal abnormalities, and >1 oral sex partner during the previous year (odds ratio, 12.8; 95% confidence interval, 3.1-52.7) among HIV-seropositive individuals. HPV type 16, which is present in most HPV-associated tonsillar cancers, was the most prevalent high-risk oral HPV infection.     

Gender differences in sexual biomarkers and behaviors associated with human papillomavirus-16, -18, and -33 seroprevalence

BACKGROUND: The elevated risk for incident head and neck cancer among human papillomavirus (HPV)-16-seropositive individuals has substantiated a role for HPV in the etiology of head and neck cancers. The relationship between HPV seroreactivity and prevalent oral HPV infection in men and women without cancer has yet to be investigated. GOAL: The goal of this study was to evaluate a possible association between oral HPV infection and HPV seroreactivity after adjustment for gender, sexual behaviors, and sexually transmitted disease. STUDY DESIGN: A cross-sectional study of factors associated with HPV-16, -18, and -33 seroreactivity was performed in a population of 586 men and women with and without HIV infection. Antibodies in sera were measured by use of a virus-like protein (VLP)-based enzyme-linked immunosorbent assay. Exfoliated cells from the tonsillar and oral mucosa were analyzed for the presence of 38 mucosal HPV types by polymerase chain reaction. RESULTS: Women had significantly greater seroreactivity for all HPV types investigated when compared with men (odds ratio, 4.3; 95% confidence interval, 3.0-6.0). Seroprevalence was greatest in men and women aged 35 to 45 years. Tonsillar HPV infection, oral sex with men, and HIV infection were independently associated with HPV seroreactivity in men after adjustment for age and number of sexual partners. In women, HSV-2 seropositivity and a history of sexually transmitted diseases were similarly important. Oral and tonsillar HPV infection were not associated with HPV seroreactivity in women. CONCLUSION: HPV seropositivity is associated with sexually transmitted diseases among women and possibly mucosal HPV exposures in men. Tonsillar HPV infection could impact seroprevalence, particularly in men.     

Molecular Dynamics of Sialic Acid Analogues and their Interaction with Influenza Hemagglutinin

Synthetic sialic acid analogues with multiple modifications at different positions(C-1/C-2/C-4/C-8/C-9) are investigated by molecular mechanics and molecular dynamics to determine their conformational preferences and structural stability to interact with their natural receptors. Sialic acids with multiple modifications are soaked in a periodic box of water as solvent. Molecular mechanics and a 2 nanosecond molecular dynamics are done using amber force fields with 30 picosecond equilibrium. Direct and water mediated hydrogen bonds existing in the sialic acid analogues, aiding for their structural stabilization are identified in this study. The accessible conformations of side chain linkages of sialic acid analogues holding multiple substituents are determined from molecular dynamics trajectory at every 1ps interval. Transitions between different minimum energy regions in conformational maps are also noticed in C-1, C-2, C-4, C-8 and C-9 substituents. Docking studies were done to find the binding mode of the sialic acid analogues with Influenza hemagglutinin. This finding provides stereo chemical explanation and conformational preference of sialic acid analogues which may be crucial for the design of sialic acid analogues as inhibitors for different sialic acid specific pathogenic proteins such as influenza toxins and neuraminidases.