Quantifying the venom dose of the spider Cupiennius salei using monoclonal antibodies

The variation in venom dose with prey size of the neotropical wandering spider Cupiennius salei was examined experimentally. Monoclonal antibodies were raised against the venom toxins of C. salei. Mab 9H3, recognizing the main toxin CSTX-1, was used to quantify the venom by enzyme-linked immunosorbent assay (ELISA). Crickets (Acheta domesticus) in four size classes were randomly offered to sixteen mature female spiders at 14 d intervals. The prey items were removed from spiders five minutes after the initial bite and subsequently homogenized for ELISA measurements. The quantity of venom expended was significantly related to the size of prey, ranging from 0.15 μl for the smallest (100–110 mg) to 1.53 μl for the largest (600–660 mg) crickets. Adaptations to prey size were also reflected in capturing behavior. None of the smallest, but almost 50% of the largest crickets were wrapped in silk following the spiders bite. Some other behavioral features may reduce the energetic costs of venom production. In 22% of the smallest crickets no venom was detectable, with the majority showing mechanical damage as a result of fang contact. This indicates, that C. salei does not rely exclusively on its venom when feeding on small prey. Some other aspects such as the site of the bite and the speed of paralyzation and their consequences associated with the amount of venom expended are discussed.     

Severe aortic insufficiency in juvenile chronic arthritis

Valvular heart disease is rare in patients with juvenile chronic arthritis. We describe a 27-year-old woman with the systemic-onset form of juvenile chronic arthritis in whom aortic insufficiency necessitated valve replacement. Nodules were seen on both the aortic and anterior mitral leaflets at surgery, and histopathologic evaluation of the excised aortic leaflets demonstrated nonspecific changes similar to those described in rheumatoid valve disease causing aortic insufficiency in adults with rheumatoid arthritis. We believe that this is the first reported case of aortic insufficiency in systemic-onset juvenile chronic arthritis in which the pathologic condition of the valve can be attributed to the underlying disease.     

Mycobacterium tuberculosis Beijing Lineage Favors the Spread of Multidrug-Resistant Tuberculosis in the Republic of Georgia

High rates and transmission of multidrug-resistant (MDR) tuberculosis (TB) have been associated with the Mycobacterium tuberculosis complex (MTBC) Beijing lineage, pointing to the importance of pathogen genetic factors for the modulation of infection outcome and epidemiology. We present here an in-depth analysis of the population structure of MTBC strains from the Republic of Georgia, a high-incidence setting at the Black Sea Coast. Phylogenetic lineages were identified based on 24-locus MIRU-VNTR (for mycobacterial interspersed repetitive unit-variable number tandem repeat) and spoligotyping analysis. Clusters of strains with identical genotyping profiles were determined as an indicator for the rate of recent transmission. Among the 183 M. tuberculosis isolates investigated, the most prominent lineage found was Beijing (26%), followed by the LAM (18%), Ural (12%), and Haarlem (5%) strains. A closely related previously undefined phylogenetic group (62 strains) showed a genotyping pattern similar to laboratory strain H37RV and was denominated as “Georgia-H37RV-like.” Although isoniazid resistance was found among strains of different lineages, MDR TB was nearly completely restricted to Beijing strains (P < 0.0001). Approximately 50% of the isolates were grouped in clusters, indicating a high rate of recent transmission. Our data indicate that, in addition to the confirmation of the importance of Beijing genotype strains for the TB epidemiology in former Soviet Union countries, a high-population diversity with strains of the LAM, Ural, Haarlem, and a previously undefined lineage represents nearly two-thirds of the strains found in Georgia. Higher rates among previously treated and MDR TB patients point to a higher potential of lineage Beijing to escape therapy and develop MDR TB.Drug-resistant Mycobacterium tuberculosis complex (MTBC) strains have emerged worldwide as a serious threat for tuberculosis (TB) control. Rates of multidrug-resistant (MDR) strains (i.e., resistance at least to isoniazid [INH] and rifampin [RIF]) have reached levels of up to 14% among patients never treated and up to 40% among previously treated patients in several MDR TB “hot spots” such as such as Karakalpakstan (Uzbekistan) and Kazakhstan in Eastern Europe (10, 37). Every year an estimated 489,000 cases of MDR TB arise globally (36). MDR TB is associated with much poorer treatment outcomes than for drug-susceptible TB, with a much higher risk of developing further resistances (2, 7). Prolonged periods of infectivity result in enhanced transmission of drug-resistant strains, further accelerating the rates of drug resistance (3). Even more worrisome is the emergence of a nearly untreatable form of TB, namely, extensively drug-resistant TB (XDR TB), which is defined as MDR plus additional resistance to any fluoroquinolone and at least one of three injectable drugs (i.e., amikacin, kanamycin, or capreomycin). A recent survey confirmed the worldwide presence of XDR strains, with rates of up 15% of MDR TB cases (30).Considering the difficulties and problems associated with the treatment of resistant TB, high levels of MDR and XDR TB have the clear potential to jeopardize TB control on a local or national level. In addition to various measures for strengthening TB control such as rapid case detection, proper treatment, and rapid detection of drug resistance, the long-term effect of the emergence of drug-resistant strains on the worldwide TB epidemic also depends on the relative fitness of the MDR and XDR strains compared to susceptible strains (3).In clinical MTBC strains, drug resistance results from chromosomal mutations in particular genes that confer resistance, which might also have an effect on bacterial fitness (5, 38). Although initial experiments indicated a lower fitness of e.g., INH-resistant strains, recent results confirm that the fitness of resistant strains depends on the kind of mutations, as well on the strain''s genetic background (13). Furthermore, the initial adverse effects on bacterial fitness might be reversed by compensatory mutations occurring during long-term infection and ongoing transmission. In fact, MDR variants have been described to have even an enhanced fitness compared to susceptible progenitor strains (13). If these figures are used in models for prediction of the MDR TB epidemic, it turns out that even in the case of a well-functioning TB control system, small subpopulations of comparatively fit MDR clones might outcompete susceptible and less-fit resistant strains and become the dominant clones in future with dramatic consequences for TB treatment and control (5).The most striking association between a mycobacterial genetic background and drug resistance documented thus far has been described for strains of the so-called Beijing lineage. These strains have been found to be involved in outbreaks and the transmission of MDR TB in several areas of the world (15). In Eastern Europe, a rising number of studies report a clear association between Beijing genotype infection and drug resistance (8, 11, 15, 28). Furthermore, large clusters of dominant clones have been determined that might indicate the development of “highly transmissible” MDR Beijing strains circulating in the community (28). Similar observations have been recently reported from South Africa, where a rapidly spreading highly resistant clone represents nearly half of all cases in the George subdistrict (35).However, the overall picture of the correlation between bacterial genotype disease characteristics is incomplete. The majority of studies focused on particular strain types such as the Beijing genotype only, basically, because they are easy to recognize by applying genotyping techniques such as IS6110 DNA fingerprint and spoligotyping (34). Based on these markers, a variety of strains were not classifiable into phylogenetic lineages or clonal complexes since the genotyping information was not informative, e.g., due to homoplasy (4, 6). Therefore, the presence of particular genotypes might simply be overlooked and, consequently, the association with clinical characteristics could not be investigated or false associations have been obtained. Since this question is of scientific and public health relevance, further studies addressing the population structure of the MTBC applying more appropriate genetic markers are urgently needed. More recently, a new genotyping techniques based on mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing was developed that allows the simultaneous high-resolution discrimination of clinical isolates for epidemiological studies and a valid phylogenetic strain classification (26, 31).In the present study, we used MIRU-VNTR typing and spoligotyping to investigate the population structure of strains obtained from patients living in the Republic of Georgia, where high rates of MDR TB have been recently reported (14, 20). We specifically analyzed the association between Beijing genotype and drug resistance. Furthermore, the data have been used to classify determine the whole variety of strains circulating in Georgia and to describe new clonal complexes and/or phylogenetic lineages. Phylogenetic strain classifications have been correlated with clinical characteristics.     

Agomelatine-induced akathisia with concomitant duloxetine medication: a case report

A 29-year-old depressed, otherwise healthy female patient was treated with agomelatine and duloxetine. She developed subsequent akathisia, which subsided after cessation of agomelatine. As a cause we suggest a pharmacodynamic drug-drug interaction leading to noradrenergic overstimulation. We recommend only gradual dose titration when combining the 2 substances to minimize the risk for side effects.     

Bulkamid (PAHG) in mixed urinary incontinence: What is the outcome?

Introduction and hypothesis

Mixed urinary incontinence (MUI), defined as mixed symptoms of stress urinary incontinence (SUI) and overactive bladder (OAB), is a difficult entity if conservative treatment has failed. Cure rates are low compared with SUI, particularly the OAB component, may deteriorate after sling insertion. Bulking agents pose an appealing alternative for the treatment of MUI. They have shown beneficial effect in small case studies, but larger series are lacking. The aim of this prospective study was an analysis of treatment efficacy and safety profile of the bulking agent, Bulkamid, in female patients with MUI.

Methods

One hundred fifty-four women with MUI symptoms (components of SUI/OAB within the limits of 60–40% either way) received bulking therapy with polyacrylamide hydrogel (Bulkamid). Patients were followed-up 3 months postoperatively. Primary outcome was the domain Incontinence impact on the King’s Health Questionnaire (KHQ). Secondary outcomes were the other KHQ domains, visual analog scale (VAS), and International Continence Society (ICS) standardized pad weight test as objective measurement of incontinence.

Results

Statistically significant improvements were found for all KHQ domains, pad weight test, and the visual analog scale (VAS) before and after bulking. Overall complication rate was 13%.

Conclusions

This study has shown improvement in MUI after bulking therapy according to both subjective and objective outcomes. We can advocate bulking therapy for treating MUI, as it is simple and safe and shows both objective and subjective improvement and relief. Long-term results (up to 1 year) are awaited.