Synthesis of mucoadhesive thiol-bearing microgels from 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate: novel drug delivery systems for chemotherapeutic agents to the bladder

Thiol-bearing microgels have been synthesised from copolymerisation of 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate, and subsequent deprotection using sodium thiomethoxide. The concentration of thiol groups on these microgels could be tailored by use of different molar ratios of the two monomers. These thiol-bearing microgels were shown to adhere to ex vivo porcine urinary bladder, which was correlated with their level of thiolation. By simply mixing solutions of thiol-bearing microgels and doxorubicin, high levels of drug loading into the microgels could be achieved. Thiol-bearing microgels controlled the release of doxorubicin in a time-dependent manner over several hours. These doxorubicin-loaded thiol-bearing microgels could have application in the treatment of early-stage bladder cancers. The method used represents a new ‘bottom-up’ approach for the synthesis of novel mucoadhesive microgels.

A Plant Needs Ants like a Dog Needs Fleas: Myrmelachista schumanni Ants Gall Many Tree Species to Create Housing

Hundreds of tropical plant species house ant colonies in specialized chambers called domatia. When, in 1873, Richard Spruce likened plant-ants to fleas and asserted that domatia are ant-created galls, he incited a debate that lasted almost a century. Although we now know that domatia are not galls and that most ant-plant interactions are mutualisms and not parasitisms, we revisit Spruce`s suggestion that ants can gall in light of our observations of the plant-ant Myrmelachista schumanni, which creates clearings in the Amazonian rain forest called ""supay-chakras,"" or ""devil`s gardens."" We observed swollen scars on the trunks of nonmyrmecophytic canopy trees surrounding supay-chakras, and within these swellings, we found networks of cavities inhabited by M. schumanni. Here, we summarize the evidence supporting the hypothesis that M. schumanni ants make these galls, and we hypothesize that the adaptive benefit of galling is to increase the amount of nesting space available to M. schumanni colonies.

Functional analysis of natriuretic peptide receptors in the bladder of the toad, bufo marinus

This study aimed to localize and characterize natriuretic peptide binding sites in the urinary bladder of Bufo marinus and to then examine the effect of natriuretic peptides on the bladder vascular tone and water reabsorption in isolated perfused bladder preparations. Specific ¹²⁵I-rat atrial natriuretic peptide (¹²⁵I-rANP) binding sites were present on blood vessels, muscle, and epithelium. In tissue sections and/or isolated membranes, the binding was completely displaced by frog ANP, rat ANP, and porcine C-type natriuretic peptide (CNP; membranes only). However, a reduction in binding was observed after incubation with ¹²⁵I-rANP and 1 μM of the natriuretic peptide receptor-C (NPR-C) ligand C-ANF, but residual binding remained suggesting the presence of two distinct binding sites. Electrophoresis of bladder membranes cross-linked to ¹²⁵I-rANP identified two bands at approximately 70 and 140 kDa that correspond to the monomeric mass of NPR-C and the guanylate cyclase receptors, respectively. Furthermore, the presence of natriuretic peptide receptor-A and NPR-C mRNA in the bladder was demonstrated with reverse transcription–polymerase chain reaction. In addition, rat ANP, frog ANP, and porcine CNP stimulated a significant increase in cGMP generation in bladder membrane preparations, which indicated the presence of guanylate cyclase-linked receptors. In perfused bladder preparations, arginine vasotocin increased perfusion pressure and water permeability. The infusion of frog ANP or porcine CNP failed to alter perfusion pressure or water reabsorption in the presence or absence of arginine vasotocin. This study identified a well-developed natriuretic peptide receptor system in the urinary bladder of B. marinus but the function of the receptors remains unclear.

Taxonomy and biology of two new species of gall midge (Diptera: Cecidomyiidae) infesting Sarcocornia quinqueflora (Chenopodiaceae) in Australian salt marshes

Two new species of gall midge associated with two distinct galls on the succulent creeping shrub Sarcocornia quinqueflora are described from salt marshes in south-eastern Australia. The infestations caused by the new species hinder the growth of S. quinqueflora, the seeds of which are the major food of the critically endangered orange-bellied parrot Neophema chrysogaster. Asphondylia floriformis sp. n. Veenstra-Quah & Kolesik transforms leaf segments into flower-like galls, whereas Asphondylia sarcocorniae sp. n. Veenstra-Quah & Kolesik produces simple swellings on branches. Both galls have fungal mycelium growing in the apoplast of the gall tissue and lining the inner surface of the larval chamber where it is presumably grazed by the larva. Descriptions of the larvae, pupae, males, females and the geographical distribution of the two gall midges in south-eastern Australia are given.

New gall midge taxa (Diptera : Cecidomyiidae) from Australian Chenopodiaceae

Five new species and a new genus of gall midge are described from flower galls on native chenopod plants in Eyre Peninsula, South Australia. Asphondylia vesicaria sp. n. induces galls on Atriplex vesicaria; A. mcneilli sp. n. on Sclerolaena diacantha; and A. tonsura sp. n. on Enchylaena tomentosa. Infested flowers develop into galls and produce no seeds. DNA analysis of part of the cytochrome-c oxidase subunit I mitochondrial gene supported the morphological and biological differences between each of the new species and the previously described A. floriformis (Veenstra-Quah & Kolesik) and A. sarcocorniae (Veenstra-Quah & Kolesik) that induce galls on leaves and branches, respectively, of Sarcocornia quinqueflora (Chenopodiaceae) in Australian salt marshes. A new genus, Dactylasioptera gen. n. and two new species of Lasiopterini, D. adentata sp. n. and D. dentata sp. n. are described – both were reared from galls of A. mcneilli and A. tonsura.

Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic progression in transitional cell carcinoma of the bladder

Muscle invasive transitional cell carcinoma (TCC) of the bladder is associated with a high frequency of metastasis, resulting in poor prognosis for patients presenting with this disease. Models that capture and demonstrate step-wise enhancement of elements of the human metastatic cascade on a similar genetic background are useful research tools. We have utilized the transitional cell carcinoma cell line TSU-Pr1 to develop an in vivo experimental model of bladder TCC metastasis. TSU-Pr1 cells were inoculated into the left cardiac ventricle of SCID mice and the development of bone metastases was monitored using high resolution X-ray. Tumor tissue from a single bone lesion was excised and cultured in vitro to generate the TSU-Pr1-B1 subline. This cycle was repeated with the TSU-Pr1-B1 cells to generate the successive subline TSU-Pr1-B2. DNA profiling and karyotype analysis confirmed the genetic relationship of these three cell lines. In vitro, the growth rate of these cell lines was not significantly different. However, following intracardiac inoculation TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2 exhibited increasing metastatic potential with a concomitant decrease in time to the onset of radiologically detectable metastatic bone lesions. Significant elevations in the levels of mRNA expression of the matrix metalloproteases (MMPs) membrane type 1-MMP (MT1-MMP), MT2-MMP and MMP-9, and their inhibitor, tissue inhibitor of metalloprotease-2 (TIMP-2), across the progressively metastatic cell lines, were detected by quantitative PCR. Given the role of MT1-MMP and TIMP-2 in MMP-2 activation, and the upregulation of MMP-9, these data suggest an important role for matrix remodeling, particularly basement membrane, in this progression. The TSU-Pr1-B1/B2 model holds promise for further identification of important molecules.

Natriuretic peptide regulation of the kidney and urinary bladder in the cane toad, Bufo marinus

The natriuretic peptide system of mammals is important in the control of blood volume but its function in non-mammalian animals is unclear. This study identified a functional natriuretic peptide system in an amphibian and showed that the hormones are involved in the control of fluid balance.

Taxonomy of two new species of gall midge (Diptera : Cecidomyiidae) infesting Tecticornia arbuscula (Salicornioideae : Chenopodiaceae) in Australian saltmarshes

Two new species of gall midge associated with two leaf galls on the branched, perennial shrub Tecticornia arbuscula are described from saltmarshes in south-eastern Australia. The infestations caused by the new species hinder the growth of T. arbuscula which can impact on the critically endangered Orange Bellied Parrot (Neophema chrysogaster): T. arbuscula provides perching and roosting sites and the seeds are the major food source for this bird. Asphondylia tecticorniae sp. n. Veenstra & Kolesik transforms leaf segments into single-chambered, spherical galls, whereas Asphondylia peelei sp. n. Veenstra & Kolesik produces a multi-chambered, asymmetrical gall on leaves of the same plant. Both galls have fungal mycelium lining the inner surface of the larval chamber where it is presumably grazed on by the larva. Descriptions of the larvae, pupae, males, females and geographical distribution of the two gall midges in south-eastern Australia are given. Differences in the level of parasitoid infestation of four Asphondylia species feeding on Australian Chenopodiaceae in relation to putative oviposition sites on the host plants are explored.

Herbarium collections - an invaluable resource for gall midge taxonomists

Dasineura tomentosa is a gall midge inducing distinctive galls on Leptospermum laevigatum. An efficient way of determining the geographic distribution of a gall midge is to examine herbarium specimens for the presence of galls inadvertently collected with the plant specimen. Of the 446 herbarium specimens of L. laevigatum examined 40 had galls caused by D. tomentosa, and two of the three galls examined in detail contained a parasitoid wasp. Despite some limitations, herbarium collections are an invaluable resource for insect taxonomists.

Incidence of bladder cancer in Sri Lanka : analysis of the cancer registry data and review of the incidence of bladder cancer in the South Asian population

PurposeTo investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US).Materials and MethodsThe incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data.ResultsA total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC.ConclusionsSri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan.

Kinetics of cellular component in inflammatory response induced by different stimuli in the swim bladder of pacu, Piaractus mesopotamicus Holmberg 1887 (Characidae)

The present study assessed the kinetics of cell accumulation at the site of inflammation induced by thioglycolate, Escherichia coli lipopolysaccharide (LPS) and heat-inactivated Aeromonas hydrophila, in the pacu, Piaractus mesopotamicus (Characidae), swim bladder. A quantitative, as well as qualitative, assessment was done of all the cells present in the exudate at 6, 24, and 48 h (n = 8) after inoculation of inflammatory agents. The results show that the thioglycolate was the irritant to induce higher total inflammatory cell accumulation when compared to the control group, 6 h after insult (P < 0.05). Inoculation of heat-inactivated Aeromonas hydrophila induced progressive accumulation of total inflammatory cells, with cell number peaking after 24 h and being significantly higher than observed in the other groups (P < 0.05). Injection of LPS also induced greater cell accumulation when compared to the control group (P < 0.05), although in lower numbers than those induced by the other two irritants. All irritants injected induced significantly greater accumulation of lymphocytes and thrombocytes when compared to the control group (P < 0.05).

Dose-dependent effect of Resveratrol on bladder cancer cells: Chemoprevention and oxidative stress

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)