Correlation of low molecular weight advanced glycation end products and nitric oxide metabolites with chronic complications in type 1 diabetic patients

Advanced glycation end products (AGEs) are involved in the occurrence of vascular complications in diabetes. The present study was undertaken to investigate the level of low-molecular weight products of AGEs (LMW-AGEs) in relation to microvascular complications in type 1 diabetes, and the possible relationship with nitric oxide (NO) as a marker of endothelial function. Patients with normal renal function (NRF) were classified into two groups: (1) without, and (2) with diabetic neuropathy; and patients with renal impairment also into two groups: (3) diabetic renal disease, and (4) end-stage renal disease. The fluorescence of LMW-AGEs and measurement of NO metabolites was assessed in 277 serum samples. In addition, multiple regression analysis was performed. In group 1, LMW-AGEs level (9.3±1.1 AF%) was higher than in the control group (2.4±0.3 AF%). A trend in the increase of LMW-AGEs with neuropathy (29.7±5.5 AF%, group 2), and further with renal impairment (47.0±8.0, group 3 and 137.8±25.5 AF%, group 4), was observed. In multivariate regression analysis LMW-AGEs were associated with NO metabolites in group 2. In NRF patients, diabetic neuropathy was significantly correlated with LMW-AGEs and NO metabolites, independently of serum creatinine and duration of diabetes. This relationship suggests that the NO and LMW-AGEs’ actions (possibly synergistic) in endothelial activation possess a role in the initiation and development of diabetic microvascular complications.     

The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population

Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.     

Antinociceptive effect of the C-terminus of murine S100A9 protein on experimental neuropathic pain

The synthetic peptide identical to the C-terminus of murine S100A9 protein (mS100A9p) has antinociceptive effect on different acute inflammatory pain models. In this study, the effect of mS100A9p was investigated on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Hyperalgesia, allodynia, and spontaneous pain were assessed to evaluate nociception. These three signs were detected as early as 2 days after sciatic nerve constriction and lasted for over 14 days after CCI. Rats were treated with different doses of mS100A9p by intraplantar, oral, or intrathecal routes on day 14 after CCI, and nociception was evaluated 1h later. These three routes of administration blocked hyperalgesia, allodynia and spontaneous pain. The duration of the effect of mS100A9p depends on the route used and phenomenon analyzed. Moreover, intraplantar injection of mS100A9p in the contralateral paw inhibited the hyperalgesia on day 14 days after CCI. The results obtained herein demonstrate the antinociceptive effect of the C-terminus of murine S100A9 protein on experimental neuropathic pain, suggesting a potential therapeutic use for it in persistent pain syndromes, assuming that tolerance does not develop to mS100A9p.     

On-line near infrared monitoring of glycerol-boosted anaerobic digestion processes: evaluation of process analytical technologies

A study of NIR as a tool for process monitoring of thermophilic anaerobic digestion boosted by glycerol has been carried out, aiming at developing simple and robust Process Analytical Technology modalities for on-line surveillance in full scale biogas plants. Three 5 L laboratory fermenters equipped with on-line NIR sensor and special sampling stations were used as a basis for chemometric multivariate calibration. NIR characterisation using Transflexive Embedded Near Infra-Red Sensor (TENIRS) equipment integrated into an external recurrent loop on the fermentation reactors, allows for representative sampling, of the highly heterogeneous fermentation bio slurries. Glycerol is an important by-product from the increasing European bio-diesel production. Glycerol addition can boost biogas yields, if not exceeding a limiting 5-7 g L(-1) concentration inside the fermenter-further increase can cause strong imbalance in the anaerobic digestion process. A secondary objective was to evaluate the effect of addition of glycerol, in a spiking experiment which introduced increasing organic overloading as monitored by volatile fatty acids (VFA) levels. High correlation between on-line NIR determinations of glycerol and VFA contents has been documented. Chemometric regression models (PLS) between glycerol and NIR spectra needed no outlier removals and only one PLS-component was required. Test set validation resulted in excellent measures of prediction performance, precision: r(2) = 0.96 and accuracy = 1.04, slope of predicted versus reference fitting. Similar prediction statistics for acetic acid, iso-butanoic acid and total VFA proves that process NIR spectroscopy is able to quantify all pertinent levels of both volatile fatty acids and glycerol.     

The diatom flora of the Salton Sea, California

We report on diatom species of the Salton Sea, a highly saline (43 g l^–1) inland lake in California. We identified and photographed all diatom taxa encountered in the phytoplankton and benthos of the Salton Sea and its immediate tributaries. Ninety-four taxa were distinguished based on their morphological features using light- and electron microscopy. In the Salton Sea, there are four general categories of diatom assemblages related to their habitats: (1) A planktonic assemblage composed of Chaetoceros muelleri var. subsalsum, Cyclotella choctawhatcheeana, Cyclotella sp., Cylindrotheca closterium, Pleurosigma ambrosianum, Thalassionema sp.; (2) a benthic assemblage with diatoms that live on the bottom (e.g. genera Caloneis, Diploneis, Entomoneis, Gyrosigma, Plagiotropis, Pleurosigma, Surirella and Tryblionella), or in algal mats (Proschkinia bulnheimii, several species of Navicula and Seminavis gracilenta); (3) an epiphytic community attached to the macroscopic green algae which grow on the rocks and other hard surfaces near shore (e.g. Achnanthes brevipes, Licmophora ehrenbergii, Tabularia parva); and (4) a freshwater assemblage composed of species that get washed in by the rivers and other inflows discharging into the Sea (e.g. Achnanthidium minutissimum, Cocconeis pediculus, Cyclotella atomus, C. scaldensis, Nitzschia elegantula, T. weissflogii). The most striking feature of the phytoplankton is the abundance of species formerly known only from marine environments; this is not surprising given the high salinity and the peculiar history of the lake.     

IGFs, basic FGF, and glucose modulate proliferation and apoptosis induced by IFNgamma but not by IL-1beta in rat INS-1E beta-cells.

We investigated the effects of glucose and beta-cell growth factors (IGF-I, IGF-II, bFGF) on growth and apoptosis in the presence and absence of apoptosis inducing cytokines (IFNgamma, Il-1beta, TNFalpha). Rat INS-1E beta-cell viability was measured by WST-1 viability assay and cell counting, apoptosis by FACS analysis of annexin-V-FITC and fluorescein-dUTP (TUNEL-staining)-positive cells. Glucose alone maintained INS-1E beta-cell viability at high physiological concentrations (6.2-12.5 mmol/l), addition of IGF-II alone or in combination with bFGF further increased these glucose effects. The cytokines IFNg and IL-1beta, but not TNFalpha strongly induced INS-1E beta-cell apoptosis. Interestingly, glucose alone induced apoptosis at extremely low or very high concentrations. In combination with IFNg, low glucose (1.6 mmol/l) increased apoptosis by 25.6% (1SD 5.0%) and high glucose (50 mmol/l) by 22.8% (1SD 2.8%) compared to 12.5 mmol/l glucose. In contrast, glucose failed to modulate IL-1beta-induced apoptosis. Most importantly, IGF-II and bFGF inhibited apoptosis induced by IFNg, but not by IL-1beta. Therefore, IGF signaling, supported by bFGF and optimal glucose levels, maintains beta-cell viability in vitro. Cytokines IFNg and IL-1beta differentially interfere with intracellular signaling cascades stimulated by IGFs and bFGF or glucose, respectively.     

Patterns of MUC1 tissue expression defined by an anti-MUC1 cytoplasmic tail monoclonal antibody in breast cancer.

Our aim was to determine the pattern of expression of MUC1 mucin cytoplasmic tail (MUC1 CT) in breast carcinoma. A total of 98 invasive breast adenocarcinoma tumor samples were assayed by immunohistochemical (IHC) analysis. The pattern of reaction was classified as membrane, cytoplasmic, or mixed. Subcellular fractions were prepared after SDS-PAGE and Western blotting. The antibodies employed were anti-MUC1 CT (CT2 monoclonal antibody, MAb) and C595 MAb against the extracellular MUC1 core protein. With the CT2 MAb, IHC showed a high percentage of positive staining in 93% of specimens, with membrane staining the most common pattern observed. C595 MAb was reactive in 73% of specimens. Similar percentages of membrane and cytoplasmic staining were found, mainly in a mixed pattern. Western blotting showed different bands. With the CT2 MAb, the membrane fraction showed the most intense reaction; a strong band of reaction was detected at approximately <30 kD. With the C595 MAb, in most cases a double band at 200 kD was found. In breast epithelium, the pattern of MUC1 CT expression may constitute an indicator of MUC1 production because it does not depend on glycosylation. The pattern and extension of MUC1 CT positivity do not vary according to the histopathological subtype of the tumor.     

The phlebotomine fauna (Diptera: Psychodidae) of Guaraí, state of Tocantins,with an emphasis on the putative vectors of American cutaneous leishmaniasis in rural settlement and periurban areas

Phlebotomine sandflies were captured in rural settlement and periurban areas of the municipality of Guaraí in the state of Tocantins (TO), an endemic area of American cutaneous leishmaniasis (ACL). Forty-three phlebotomine species were identified, nine of which have already been recognised as ACL vectors. Eleven species were recorded for the first time in TO. Nyssomyia whitmani was the most abundant species, followed by Evandromyia bourrouli, Nyssomyia antunesi and Psychodopygus complexus. The Shannon-Wiener diversity index and the evenness index were higher in the rural settlement area than in the periurban area. The evaluation of different ecotopes within the rural area showed the highest frequencies of Ev. bourrouli and Ny. antunesi in chicken coops, whereas Ny. whitmani predominated in this ecotope in the periurban area. In the rural settlement area, Ev. bourrouli was the most frequently captured species in automatic light traps and Ps. complexus was the most prevalent in Shannon trap captures. The rural settlement environment exhibited greater phlebotomine biodiversity than the periurban area. Ps. complexus and Psychodopygus ayrozai naturally infected with Leishmania (Viannia) braziliensis were identified. The data identified Ny. whitmani as a potential ACL vector in the periurban area, whereas Ps. complexus was more prevalent in the rural environment associated with settlements.     

Radiotherapy setup displacements in breast cancer patients: 3D surface imaging experience

Aim

In this study, we intend to compare two different setup procedures for female breast cancer patients.