Longitudinal Study of a Human Drug-Induced Model of Autoantibody to Cytoplasmic Rods/Rings following HCV Therapy with Ribavirin and Interferon-α

Background

A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up.

Methodology/Results

597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p<0.0001; HCV versus non-HCV). Anti-RR was present in 38% of 108 patients receiving interferon-α/ribavirin, but none in 26 receiving either interferon-α or ribavirin, or 166 untreated patients (p<0.0001). Other IIF-HEp-2 patterns were more frequently associated with interferon-α treatment alone (52.2%) as compared to interferon-α/ribavirin (25%), ribavirin alone (33.3%), and no therapy (26.5%). Anti-RR frequency was not associated with sex, age, ethnicity, HCV genotype or viral load. Anti-RR occurred only after initiation of treatment, beginning as early as 1 month (6%), but by the sixth month >47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment.

Conclusions

The exquisite association of anti-RR reactivity with combined interferon-α/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy.     

The participation of Wajãpi women from the State of Amapá (Brazil) in the traditional use of medicinal plants – a case study

Background

The purpose of this study was to analyze the importance of traditional medicinal plants use to Wajãpi women in the State of Amapá, Brazil, as well as their practices in the local common illnesses of treatment considering the prevailing practice by non-Indians.

Methods

This study was conducted in the Community of the Wajãpi Indigenous People, a Brazilian territory located in the central western State of Amapá. Wajãpi women were selected for the interview since they have the responsibility to harvest, collect and prepare the preparations. The studied women were residents of four villages. The number of women within these four villages is 24.

Results and conclusions

The findings fell into the following three categories: 1) The daily use of medicinal plants by women and main methods of application. In this category, the botanical families found included Leguminosae-Caesalpinoideae, Anacardiaceae, Meliaceae, and Rubiaceae. The main forms of use found were teas, baths, maceration, in natura, and juices; 2) Through analysis of illness and treatment records, a lack of knowledge integration in the health system was shown to be due to a variety of gaps and the need of health professionals to be more aware about the local culture which they intend to work with, what could decrease the prevailing barriers between the social groups involved; 3) Traditional knowledge and possible sustainability can be fostered by stimulating the transmission of traditional knowledge from generation to generation, therefore reducing the dependence on industrialized medicines and also by maintaining an appreciation of those practices among youngsters, who tend to question them.

     

First assessment of microbial diversity in faecal microflora of Eurasian otter (<Emphasis Type="Italic">Lutra lutra</Emphasis> Linnaeus, 1758) in Portugal

The Eurasian otter (Lutra lutra Linnaeus, 1758), a predator from the Order Carnivora, Family Mustelidae, evolved the ability to swim and forage in water, being an important element of biodiversity. Otters are widely spread through Portugal, and scats have been extensively used in ecology studies; however, valid information on their microbiota is scarce. This work represents a first approach to characterise the otter faecal microflora in samples collected in river stretches of the Sado river basin (Portugal) during winter 2006. Eight sampling stretches of 8 km were selected, and from each, six to eight sampling sites were visited. A total of 31 scats were analysed. The microflora studied included aerobic bacteria, spore-forming anaerobic bacteria and viruses (coronavirus, parvovirus, adenovirus, parainfluenza virus). Bacterial isolates were identified based on morphology and metabolic pathways, and virus detection was performed by polymerase chain reaction. The results revealed the high degree of bacterial diversity in the faecal microflora of L. lutra. A total of 88 Gram-negative (23 genera) and 44 Gram-positive isolates (ten genera) were identified. The identification of four isolates was inconclusive, and their identification was performed by 16S ribosomal ribonucleic acid sequencing, which confirms the need for biochemical testing optimisation regarding animal isolates. None of the scats was positive for virus detection. Identification of otter faecal microflora and of potential pathogens is an important first step towards understanding and monitoring their importance in otter population health.     

Obtaining and selection of hexokinases-less strains of <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> for production of ethanol and fructose from sucrose

Saccharomyces cerevisiae hexokinase-less strains were produced to study the production of ethanol and fructose from sucrose. These strains do not have the hexokinases A and B. Twenty-three double-mutant strains were produced, and then, three were selected for presenting a smaller growth in yeast extract–peptone–fructose. In fermentations with a medium containing sucrose (180.3 g L⁻¹) and with cell recycles, simulating industrial conditions, the capacity of these mutant yeasts in inverting sucrose and fermenting only glucose was well characterized. Besides that, we could also see their great tolerance to the stresses of fermentative recycles, where fructose production (until 90 g L⁻¹) and ethanol production (until 42.3 g L⁻¹) occurred in cycles of 12 h, in which hexokinase-less yeasts performed high growth (51.2% of wet biomass) and viability rates (77% of viable cells) after nine consecutive cycles.     

Origin and function of the two major tail proteins of bacteriophage SPP1

The majority of bacteriophages have a long non-contractile tail (Siphoviridae) that serves as a conduit for viral DNA traffic from the phage capsid to the host cell at the beginning of infection. The 160-nm-long tail tube of Bacillus subtilis bacteriophage SPP1 is shown to be composed of two major tail proteins (MTPs), gp17.1 and gp17.1*, at a ratio of about 3:1. They share a common amino-terminus, but the latter species has approximately 10 kDa more than gp17.1. A CCC.UAA sequence with overlapping proline codons at the 3' end of gene 17.1 drives a programmed translational frameshift to another open reading frame. The recoding event generates gp17.1*. Phages carrying exclusively gp17.1 or gp17.1* are viable, but tails are structurally distinct. gp17.1 and the carboxyl-terminus of gp17.1* have a distinct evolutionary history correlating with different functions: the polypeptide sequence identical in the two proteins is responsible for assembly of the tail tube while the additional module of gp17.1* shields the structure exterior exposed to the environment. The carboxyl-terminal extension is an elaboration present in some tailed bacteriophages. Different extensions were found to combine in a mosaic fashion with the MTP essential module in a subset of Siphoviridae genomes.     

Rapid pre-screening of cervical smears as a method of internal quality control in a cervical screening programme

Objective:  To evaluate the performance of rapid pre-screening (RPS) as a method of internal quality control in the cytopathological examination of cervical smears for cervical cancer screening.
Methods:  The sample consisted of 6135 cervical smears submitted to RPS and routine screening (RS) methods. The smears classified as negative in RPS and RS were considered final diagnoses, and were not, therefore, submitted to any additional review. The smears identified as suspect or unsatisfactory according to RPS were analysed separately by two different cytologists irrespective of the diagnosis reached in RS. Smears considered abnormal or unsatisfactory at RS were also reviewed. When both cytologists issued concordant diagnoses, this was considered the final diagnosis. Discordant results were analysed by a third cytologist and a consensus meeting was held to define the final diagnosis.
Results:  Taking abnormalities detected by RS as the denominator, RPS had a sensitivity of 63.0% for the detection of all abnormal smears and 96.7% for high grade squamous intraepithelial lesion (HSIL). When compared with the final diagnosis, sensitivity of RPS for all abnormal smears was 74.9% and for HSIL 95.0%. Of the 529 abnormal smears confirmed in the final diagnosis, 2.15% were detected only by the RPS.
Conclusion:  RPS is an effective alternative method of internal quality control with high sensitivity for the detection of more severe lesions. It also permits monitoring of the laboratory rate of false-negative results, and allows constant evaluation of the performance both of the pre-screening and RS cytologists.     

Single mitochondrial gene barcodes reliably identify sister-species in diverse clades of birds

Background  

DNA barcoding of life using a standardized COI sequence was proposed as a species identification system, and as a method for detecting putative new species. Previous tests in birds showed that individuals can be correctly assigned to species in ~94% of the cases and suggested a threshold of 10× mean intraspecific difference to detect potential new species. However, these tests were criticized because they were based on a single maternally inherited gene rather than multiple nuclear genes, did not compare phylogenetically identified sister species, and thus likely overestimated the efficacy of DNA barcodes in identifying species.