Structural, Electronic, and Vibrational Properties of Amino-adamantane and Rimantadine Isomers

We performed a first principles total energy investigation on the structural, electronic, and vibrational propel ties of adamantane molecules, functionalized with amine and ethanamine groups. We computed the vibrational signatures of amantadine and rimanadine isomers with the functional groups bonded to clinic:ill carbon sites By comparing Out results with recent infrared and Raman spectroscopic data, we discuss the possible presence of different isomers in experimental samples.

Characteristics of Acute Kidney Injury in Patients Infected with the 2009 Influenza A (H1N1) Virus

Background and objectives: There have been few studies investigating acute kidney injury (AKI) in patients infected with the 2009 pandemic influenza A (H1N1) virus. Therefore, the objective of this study was to identify the factors associated with AKI in H1N1-infected patients. Design, setting, participants, & measurements: This was a study of 47 consecutive critically ill adult patients with reverse transcriptase-PCR-confirmed H1N1 infection in Brazil. Outcome measures were AKI (as defined by the Risk, Injury, Failure, Loss, and End-stage renal failure [RIFLE] criteria) and in-hospital death. Results: AKI was identified in 25 (53%) of the 47 H1N1-infected patients. AKI was associated with vasopressor use, mechanical ventilation, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and severe acidosis as well as with higher levels of C-reactive protein and lactic dehydrogenase upon intensive care unit (ICU) admission. A nephrology consultation was requested for 16 patients (64%), and 8 (50%) required dialysis. At ICU admission, 7 (15%) of the 25 AKI patients had not yet progressed to AKI. However, by 72 hours after ICU admission, no difference in RIFLE score was found between AKI survivors and nonsurvivors. Of the 47 patients, 9 (19%) died, all with AKI. Mortality was associated with mechanical ventilation, vasopressor use, dialysis, high APACHE II score, high bilirubin levels, and a low RIFLE score at ICU admission. Conclusions: Among critically ill H1N1-infected patients, the incidence of AKI is high. In such patients, AKI is mainly attributable to shock. Clin J Am Soc Nephrol 5: 1916-1921, 2010. doi: 10.2215/CJN.00840110

Severe novel influenza A (H1N1) infection in cancer patients

Patients and methods: Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed. Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died. Results: Eight patients were admitted, with ages ranging from 55 to 65 years old. There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%). Five patients required mechanical ventilation and all died. Four patients had bacterial bronchopneumonia. All deaths occurred due to multiple organ failure. A milder form of lung disease was present in the three cases who survived. Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients. Other lung findings were necrotizing bronchiolitis or extensive hemorrhage. Conclusions: H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death. More data are needed to identify predictors of unfavorable evolution in these patients.

Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs

Introduction: This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated. Methods: Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination. Results: Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination. Conclusion: Renal transplant patients vaccinated against influenza responded with antibody production for in. uenza A virus strains, but not for in. uenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.

Effectiveness of commercial inhibitors against subtype F HIV-1 protease

Subtype F wild type HIV protease has been kinetically characterized using six commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) commonly used for HIV/AIDS treatment, as well as inhibitor TL-3 and acetylpepstatin. We also obtained kinetic parameters for two multi-resistant proteases (one of subtype B and one of subtype F) harboring primary and secondary mutations selected by intensive treatment with ritonavir/nelfinavir. This newly obtained biochemical data shows that all six studied commercially available protease inhibitors are significantly less effective against subtype F HIV proteases than against HIV proteases of subtype B, as judged by increased K(i) and biochemical fitness (vitality) values. Comparison with previously reported kinetic values for subtype A and C HIV proteases show that subtype F wild type proteases are significantly less susceptible to inhibition. These results demonstrate that the accumulation of natural polymorphisms in subtype F proteases yields catalytically more active enzymes with a large degree of cross-resistance, which thus results in strong virus viability.