Multiple Classes of Antiviral Agents Exhibit In Vitro Activity against Human Rhinovirus Type C

Human rhinovirus type C (HRV-C) is a newly discovered enterovirus species frequently associated with exacerbation of asthma and other acute respiratory conditions. Until recently, HRV-C could not be propagated in vitro, hampering in-depth characterization of the virus replication cycle and preventing efficient testing of antiviral agents. Herein we describe several subgenomic RNA replicon systems and a cell culture infectious model for HRV-C that can be used for antiviral screening. The replicon constructs consist of genome sequences from HRVc15, HRVc11, HRVc24, and HRVc25 strains, with the P1 capsid region replaced by a Renilla luciferase coding sequence. Following transfection of the replicon RNA into HeLa cells, the constructs produced time-dependent increases in luciferase signal that can be inhibited in a dose-dependent manner by known inhibitors of HRV replication, including the 3C protease inhibitor rupintrivir, the nucleoside analog inhibitor MK-0608, and the phosphatidylinositol 4-kinase IIIβ (PI4K-IIIβ) kinase inhibitor PIK93. Furthermore, with the exception of pleconaril and pirodavir, the other tested classes of HRV inhibitors blocked the replication of full-length HRVc15 and HRVc11 in human airway epithelial cells (HAEs) that were differentiated in the air-liquid interface, exhibiting antiviral activities similar to those observed with HRV-16. In summary, this study is the first comprehensive profiling of multiple classes of antivirals against HRV-C, and the set of newly developed quantitative HRV-C antiviral assays represent indispensable tools for the identification and evaluation of novel panserotype HRV inhibitors.     

Soluble transferrin receptor as an indicator of iron deficiency in HIV-infected infants

BACKGROUND: Iron deficiency is common in human immunodeficiency virus (HIV)-infected infants in sub-Saharan Africa. It is not known whether soluble transferrin receptor (sTfR) is a good indicator of iron deficiency in infants with HIV. METHODS: We evaluated sTfR as an indicator of iron deficiency in 134 HIV-infected 9-month-old infants in Kampala, Uganda. Ferritin <12 microg/L and microcytic, hypochromic anaemia were used as indicators of iron deficiency, respectively. The presence of inflammation was indicated by C-reactive protein >5 mg/L or alpha1-acid glycoprotein >1 g/L. RESULTS: Receiver operator characteristic curves showed that the area under the curve was 0.67 when sTfR receptor was compared with low ferritin and 0.71 when sTfR was compared with microcytic, hypochromic anaemia. The appropriate calculated cut-offs of sTfR >3.74 microg/mL (43.98 nmol/L) and >3.53 microg/mL (41.55 nmol/L) show adequate specificities of 60% and sensitivities of 63% and 69% for low ferritin and microcytic, hypochromic anaemia, respectively. C-reactive protein and alpha 1-acid glycoprotein were strongly correlated with serum ferritin (r=0.371 and r=0.458, respectively, both p<0.0001) but were not correlated with sTfR (r=0.009 and r= -0.003, respectively, both p=0.9). In all, 78.6% of infants had alpha l-acid glycoprotein >1 g/L and 54.7% had C-reactive protein >5 g/L. CONCLUSIONS: Soluble TfR appears to be an adequate indicator of iron deficiency in HIV-infected infants.     

The natural history of pelvic organ support in pregnancy

 Little is known about the anatomic and physiologic changes in the pelvic floor that occur during pregnancy. The purpose of this study was to prospectively document pelvic organ support throughout pregnancy using the standardized system of the International Continence Society, also known as the Pelvic Organ Prolapse Quantification (POPQ) Staging System. Pelvic organ support evaluations were performed in nulliparous pregnant women presenting for routine obstetric care during each trimester. POPQ stage assignments and POPQ component measurements were compared for first-, second- and third-trimester examinations. Overall POPQ stage was significantly higher in the third trimester than in the first (P=0.001). Individual POPQ points which showed significant differences between the first and third trimesters include Aa, PB, Ap, Ba, Bp, TVL and GH. These findings probably represent normal physiologic changes of the pelvic floor during pregnancy, but suggest that significant changes may be objectively demonstrated prior to delivery. Received: 15 January 2002 / Accepted: 9 September 2002     

Factors affecting attitudes towards medical abortion in Lithuania.

OBJECTIVE: Surgical abortion in Lithuania is governed by a 1994 ministerial decree that made it legal for any woman 16 or older. This article seeks to determine the key demographic factors in Lithuanian attitudes towards medical abortion, which is currently not legal. METHODS: A random sample of the adult population was asked if they supported medical abortion. The dependent variable of attitude towards medical abortion was tested against the eight independent variables reported for each respondent using Chi-square tests and odds ratios. The effects of the variables upon each other were tested with two logistic regression models. RESULTS: Among the respondents, 62.6% supported access to medical abortion. The independent variables of urban/rural residence, employment status and educational level significantly affected opinion. Overall, education level provided the strongest odds ratio for support of medical abortion. CONCLUSION: The majority of the Lithuanian population supports the legalisation of medical abortion. There is somewhat less support for it in rural areas, among those who are least educated and in certain nonworking population groups. Lithuanian policy-makers should consider responding to popular sentiment and legalising medical abortion.