Safety of the Recombinant Cholera Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy

Introduction

Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.

Methodology/Principal Findings

From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies.

Conclusions/Significance

We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00709410","term_id":"NCT00709410"}}NCT00709410     

Long-Term Effect of Bariatric Surgery on Liver Enzymes in the Swedish Obese Subjects (SOS) Study

Background and Aim

Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim of the present study was to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals.

Methods

The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study designed to compare the long-term effects of bariatric surgery and usual care in obese subjects. A total of 3,570 obese participants with no excess of alcohol consumption at baseline (1,795 and 1,775 in the control and surgery group, respectively) were included in the analyses. Changes in transaminase levels during follow-up were compared in the surgery and control groups.

Results

Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels at 2- and 10- year follow up. The reduction in ALT levels was proportional to the degree of weight loss. Both the incidence of and the remission from high transaminase levels were more favorable in the surgery group compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was lower in the surgery compared to the control group at both 2- and 10-year follow up.

Conclusions

Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals.     

A solanesyl-diphosphate synthase localizes in glycosomes of Trypanosoma cruzi

We report the cloning of a Trypanosoma cruzi gene encoding a solanesyl-diphosphate synthase, TcSPPS. The amino acid sequence (molecular mass approximately 39 kDa) is homologous to polyprenyl-diphosphate synthases from different organisms, showing the seven conserved motifs and the typical hydrophobic profile. TcSPPS preferred geranylgeranyl diphosphate as the allylic substrate. The final product, as determined by TLC, had nine isoprene units. This suggests that the parasite synthesizes mainly ubiquinone-9 (UQ-9), as described for Trypanosoma brucei and Leishmania major. In fact, that was the length of the ubiquinone extracted from epimastigotes, as determined by high-performance liquid chromatography. Expression of TcSPPS was able to complement an Escherichia coli ispB mutant. A punctuated pattern in the cytoplasm of the parasite was detected by immunofluorescence analysis with a specific polyclonal antibody against TcSPPS. An overlapping fluorescence pattern was observed using an antibody directed against the glycosomal marker pyruvate phosphate dikinase, suggesting that this step of the isoprenoid biosynthetic pathway is located in the glycosomes. Co-localization in glycosomes was confirmed by immunogold electron microscopy and subcellular fractionation. Because UQ has a central role in energy production and in reoxidation of reduction equivalents, TcSPPS is promising as a new chemotherapeutic target.     

Surface structure and anatomical aspects of Chinese brake fern (Pteris vittata; Pteridaceae)

The objective of this study was to describe a wide spectrum of surface structural and anatomical details of the Chinese brake fern (Pteris vittata) using scanning electron microscopy (SEM). SEM revealed that the epidermal cells of the pinnae were elongated with raised periclinal and sinuous anticlinal walls. The pinnae were hypostomatous with randomly scattered anomocytic stomatal complexes positioned at the same level as the epidermis. Stomates were large and elliptical (27.4 μm × 10.2 μm). Cross sections from the central regions of the rachis and the stipe revealed V- and U-shaped vascular bundles, respectively. In each vascular bundle, the xylem strands were sea-horse shaped (hippocampus). In contrast, the pinnae possessed a triangular vascular bundle with uniform mesophyll organization comprising of homogenous lobed parenchyma cells. The indumentum consisted of trichomes and scales, which formed various types of vestiture. Trichomes were borne only on the pinnae and scales on the rachis and stipe. The roots developed a dense network of long root hairs averaging 244 μm long, and the xylem consisted of tracheids with scalariform pitting. Sori were submarginal; continuous along both margins of the pinna and were covered with a false indusium. The sporangia were oblong with a short thick stalk and the annulus was positioned vertically resulting in transverse dehiscence of the sporangium. The paraphyses were uniseriate, unbranched, septate and found to be intermixed with the sporangia. The exine of the globose spores was adorned with thick reticulum in which the areoles contained round tubercles. This study describes surface features in detail, which is essential to studies examining the issue of whether morphological characteristics are related to arsenic hyperaccumulation inP. vittata.     

Seed and tuber banks of aquatic macrophytes in the Askö area, northern Baltic proper

Sediment samples from 5 stations in the northern Baltic proper, 6.5 o/oo S, were collected in April 1987 and the emergence of seedlings was recorded over 120 days in a greenhouse at 20°C. Total seedling densities varied from 0 to 3328 m^-2: and of seven species, Zannichellia palustris and Chara spp. were the most abundant among seedlings and sporelings, respectively. Several common macrophytes in the area were rare as seedlings and no seedlings were recorded for the most abundant angiosperms, Potamogeton pectinatus, Potamogeton perfoliatus and Ranunculus baudotii. Except for the few annual species, reproduction by seeds contributed little to the dynamics of the vegetation in the area and no correlation was found between vegetation composition and the seed bank. For perennial species the winter survival of vegetative propagules is the most important factor for vegetation dynamics.     

Different ammonia tolerances may facilitate spatial coexistence of Gammarus roeselii and the strong invader Dikerogammarus villosus

The introduction of invasive species that can replace native species is one of the most critical threats to the biodiversity of aquatic systems. Here we investigated the potential contribution of one factor to the coexistence of the indigenous amphipod Gammarus roeselii and the invasive amphipod Dikerogammarus villosus in the same ecosystem (Lake Constance) within different microhabitats. We quantitatively studied the influence of ambient ammonia concentrations on the distributions of the two amphipod species. We also assessed the ammonia tolerance ranges of both species in laboratory experiments by measuring mortality rate, precopula disruption, egg mortality, and microhabitat choice. The proportion of G. roeselii among the two amphipod species was significantly positively related to the ammonia concentration in the water, which indicated that the distribution of the invasive D. villosus was limited at high ammonia concentrations. Although the mortality rates of the two species did not significantly differ, G. roeselii was more tolerant to ammonia with regard to precopula disruption, egg mortality, and microhabitat choice. The effective ammonia concentrations that led to a significantly reduced direct reproductive success in D. villosus were within the range of the highest field concentrations measured, where only G. roeselii occurred. D. villosus may have a smaller range than the indigenous G. roeselii partially because of its lower tolerance to higher ammonia concentrations, which lead to reduced reproductive success. Beside other habitat parameters differences on ammonia tolerance between the two amphipods might allow their coexistence along a gradient of microhabitats in Lake Constance.     

NMR solution structure and dynamics of motilin in isotropic phospholipid bicellar solution

The structure and dynamics of the gastrointestinal peptide hormone motilin, consisting of 22 amino acid residues, have been studied in the presence of isotropic q=0.5 phospholipid bicelles. The NMR solution structure of the peptide in acidic bicelle solution was determined from 203 NOE-derived distance constraints and six backbone torsion angle constraints. Dynamic properties for the ¹³C-¹H vector in Leu10 were determined for motilin specifically labeled with ¹³C at this position by analysis of multiple-field relaxation data. The structure reveals an ordered -helical conformation between Glu9 and Lys20. The N-terminus is also well structured with a turn resembling that of a classical -turn. The ¹³C dynamics clearly show that motilin tumbles slowly in solution, with a correlation time characteristic of a large object. It was also found that motilin has a large degree of local flexibility as compared with what has previously been reported in SDS micelles. The results show that motilin interacts with the bicelle, displaying motional properties of a peptide bound to a membrane. In comparison, motilin in neutral bicelles seems less structured and more flexible. This study shows that the small isotropic bicelles are well suited for use as membrane-mimetic for structural as well as dynamical investigations of membrane-bound peptides by high-resolution NMR.     

The tyrosine kinase inhibitor genistein increases basal cAMP and potentiates forskolin-induced cAMP accumulation in A549 human airway epithelial cells

Genistein is often used as an inhibitor of tyrosine kinases. A less studied side effect of genistein is an inhibition of cyclic AMP-phosphodiesterase (cAMP-PDE) activity resulting in increased cAMP accumulation. The effect of genistein on intracellular cAMP-levels, basal and forskolin-induced, was studied in A549 human airway epithelial cells and compared with the unspecific PDE inhibitor, isobutylmethylxanthine (IBMX). It was shown that genistein (50 M) increased basal cAMP and potentiated forskolin-induced cAMP accumulation to the same extent as IBMX (100 M). Thus, the use of genistein in studies on signaling transductions may result in erroneous conclusions since increased cAMP may cause or contribute to the observed effects.     

Assessment of angiogenesis-related parameters in juvenile idiopathic arthritis-associated uveitis

Molecular Biology Reports - Juvenile idiopathic arthritis-associated uveitis (JIAU) may run a chronic and treatment-resistant course, and occasionally, alterations of the iris vasculature may be...