Urinary markers of renal inflammation in adolescents with Type 1 diabetes mellitus and normoalbuminuria

Diabet. Med. 29, 1297-1302 (2012) ABSTRACT: Aims Patients with the highest albumin:creatinine ratio within the normal range are at an increased risk for developing microalbuminuria. The mechanistic basis for this is unknown, but may be related to renal inflammation. Our goal was to characterize the urinary excretion of cytokines/chemokines in normoalbuminuric adolescents with Type?1 diabetes to determine whether higher range normoalbuminuria is associated with evidence of renal inflammation. Methods Forty-two urinary cytokines/chemokines were measured in subjects who were screened for the Adolescent Type?1 Diabetes Cardio-Renal Intervention Trial. Urinary cytokines/chemokines were compared across low (n?=?50), middle (n?=?50) or high (n?=?50) albumin:creatinine ratio tertile groups. Results At baseline, participants in the upper tertile were younger and had shorter diabetes duration compared with the other groups. Other clinical characteristics were similar. Urinary levels of interleukin?6, interleukin?8, platelet-derived growth factor-AA and RANTES differed across albumin:creatinine ratio tertiles, with higher values in patients in the middle and high tertiles compared with the lower tertile (ANCOVA P?≤?0.01). Conclusions Within the normal albumin:creatinine ratio range, higher urinary albumin excretion is associated with elevated urinary levels of inflammatory markers. Ultimately, this may provide mechanistic insights into disease pathophysiology and stratify the risk of nephropathy in Type?1 diabetes.     

Blunted IgE-mediated activation of mast cells in mice lacking the Ca2+-activated K+ channel KCa3.1

Mast cell stimulation by Ag is followed by the opening of Ca(2+)-activated K(+) channels, which participate in the orchestration of mast cell degranulation. The present study has been performed to explore the involvement of the Ca(2+)-activated K(+) channel K(Ca)3.1 in mast cell function. To this end mast cells have been isolated and cultured from the bone marrow (bone marrow-derived mast cells (BMMCs)) of K(Ca)3.1 knockout mice (K(Ca)3.1(-/-)) and their wild-type littermates (K(Ca)3.1(+/+)). Mast cell number as well as in vitro BMMC growth and CD117, CD34, and FcepsilonRI expression were similar in both genotypes, but regulatory cell volume decrease was impaired in K(Ca)3.1(-/-) BMMCs. Treatment of the cells with Ag, endothelin-1, or the Ca(2+) ionophore ionomycin was followed by stimulation of Ca(2+)-activated K(+) channels and cell membrane hyperpolarization in K(Ca)3.1(+/+), but not in K(Ca)3.1(-/-) BMMCs. Upon Ag stimulation, Ca(2+) entry but not Ca(2+) release from intracellular stores was markedly impaired in K(Ca)3.1(-/-) BMMCs. Similarly, Ca(2+) entry upon endothelin-1 stimulation was significantly reduced in K(Ca)3.1(-/-) cells. Ag-induced release of beta-hexosaminidase, an indicator of mast cell degranulation, was significantly smaller in K(Ca)3.1(-/-) BMMCs compared with K(Ca)3.1(+/+) BMMCs. Moreover, histamine release upon stimulation of BMMCs with endothelin-1 was reduced in K(Ca)3.1(-/-) cells. The in vivo Ag-induced decline in body temperature revealed that IgE-dependent anaphylaxis was again significantly (by approximately 50%) blunted in K(Ca)3.1(-/-) mice. In conclusion, K(Ca)3.1 is required for Ca(2+)-activated K(+) channel activity and Ca(2+)-dependent processes such as endothelin-1- or Ag-induced degranulation of mast cells, and may thus play a critical role in anaphylactic reactions.     

Management of jute yellow mosaic virus disease through cultural practices

A field experiment was conducted to investigate the effect of some management practices to minimise jute yellow mosaic virus disease. The management practices were employed at natural condition and placed randomly with four replications. The treatments were spraying malathion 57 EC, rouging and field sanitation, top dressing of nitrogenous fertiliser, mulching with straw and untreated control. The highest percentage of mosaic incidence was recorded in control and the lowest incidence was recorded in top dressing of nitrogenous fertiliser. Among the treatments, top dressing of nitrogenous fertiliser showed the best performance in terms of increasing yield (3.05?t/ha). The second highest was obtained in rouging and field sanitation which was statistically similar to spraying malathion 57 EC. The best gross margin ($379.02/ha) and increase of gross margin (63.00%) compared to control were achieved in top dressing of nitrogenous fertiliser with the highest benefit-cost ratio (4.84). However, the treatments were found significantly profitable compared to the control indicating the usefulness of the cultural practices in integrated disease management programme for healthy and profitable jute cultivation.     

A trial of using immunoglobulins of known specificity for preventing hepatitis A in regions with high epidemic activity

The economic effectiveness of immunoglobulin prophylaxis (IGP), carried out among children aged 1-3 at the beginning of a seasonal rise in hepatitis A (HA) morbidity with high coefficients of protection (80-85%), was directly related to the activity of the epidemic process. Preparations with sufficiently high content of antibodies to HA virus sharply decreased the manifestation of this infection. The detection rate of the manifest forms of the infection among children covered by prophylactic measures in the foci of HA was considerably lower than among children who had not received the preparation. IGP exerted no essential influence on the dynamics of the formation of population immunity. A high share of children aged 3-4 years, seropositive to HA virus (up to 90%), validates the inadvisability of carrying out IGP in older groups of children.     

Nitric oxide-induced salt stress tolerance in plants: ROS metabolism,signaling, and molecular interactions

Nitric oxide (NO), a non-charged, small, gaseous free-radical, is a signaling molecule in all plant cells. Several studies have proposed multifarious physiological roles for NO, from seed germination to plant maturation and senescence. Nitric oxide is thought to act as an antioxidant, quenching ROS during oxidative stress and reducing lipid peroxidation. NO also mediates photosynthesis and stomatal conductance and regulates programmed cell death, thus providing tolerance to abiotic stress. In mitochondria, NO participates in the electron transport pathway. Nitric oxide synthase and nitrate reductase are the key enzymes involved in NO-biosynthesis in aerobic plants, but non-enzymatic pathways have been reported as well. Nitric oxide can interact with a broad range of molecules, leading to the modification of protein activity, GSH biosynthesis, S-nitrosylation, peroxynitrite formation, proline accumulation, etc., to sustain stress tolerance. In addition to these interactions, NO interacts with fatty acids to form nitro-fatty acids as signals for antioxidant defense. Polyamines and NO interact positively to increase polyamine content and activity. A large number of genes are reprogrammed by NO; among these genes, proline metabolism genes are upregulated. Exogenous NO application is also shown to be involved in salinity tolerance and/or resistance via growth promotion, reversing oxidative damage and maintaining ion homeostasis. This review highlights NO-mediated salinity-stress tolerance in plants, including NO biosynthesis, regulation, and signaling. Nitric oxide-mediated ROS metabolism, antioxidant defense, and gene expression and the interactions of NO with other bioactive molecules are also discussed. We conclude the review with a discussion of unsolved issues and suggestions for future research.     

Manganese-induced salt stress tolerance in rice seedlings: regulation of ion homeostasis,antioxidant defense and glyoxalase systems

Hydroponically grown 12-day-old rice (Oryza sativa L. cv. BRRI dhan47) seedlings were exposed to 150 mM NaCl alone and combined with 0.5 mM MnSO₄. Salt stress resulted in disruption of ion homeostasis by Na⁺ influx and K⁺ efflux. Higher accumulation of Na⁺ and water imbalance under salinity caused osmotic stress, chlorosis, and growth inhibition. Salt-induced ionic toxicity and osmotic stress consequently resulted in oxidative stress by disrupting the antioxidant defense and glyoxalase systems through overproduction of reactive oxygen species (ROS) and methylglyoxal (MG), respectively. The salt-induced damage increased with the increasing duration of stress. However, exogenous application of manganese (Mn) helped the plants to partially recover from the inhibited growth and chlorosis by improving ionic and osmotic homeostasis through decreasing Na⁺ influx and increasing water status, respectively. Exogenous application of Mn increased ROS detoxification by increasing the content of the phenolic compounds, flavonoids, and ascorbate (AsA), and increasing the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), superoxide dismutase (SOD), and catalase (CAT) in the salt-treated seedlings. Supplemental Mn also reinforced MG detoxification by increasing the activities of glyoxalase I (Gly I) and glyoxalase II (Gly II) in the salt-affected seedlings. Thus, exogenous application of Mn conferred salt-stress tolerance through the coordinated action of ion homeostasis and the antioxidant defense and glyoxalase systems in the salt-affected seedlings.     

Epidemiological Characteristics of Strongyloidiasis in Inhabitants of Indigenous Communities in Borneo Island,Malaysia

Epidemiological study on strongyloidiasis in humans is currently lacking in Malaysia. Thus, a cross-sectional study was carried out to determine the prevalence of Strongyloides stercoralis infection among the inhabitants of longhouse indigenous communities in Sarawak. A single stool and blood sample were collected from each participant and subjected to microscopy, serological and molecular techniques. Five species of intestinal parasites were identified by stool microscopy. None of the stool samples were positive for S. stercoralis. However, 11% of 236 serum samples were seropositive for strongyloidiasis. Further confirmation using molecular technique on stool samples of the seropositive individuals successfully amplified 5 samples, suggesting current active infections. The prevalence was significantly higher in adult males and tended to increase with age. S. stercoralis should no longer be neglected in any intestinal parasitic survey. Combination of more than 1 diagnostic technique is necessary to increase the likelihood of estimating the ‘true’ prevalence of S. stercoralis.     

Application of Cyanidin-3-Glucosides as a functional food ingredient in rice-based bakery products

BackgroundBlack pericarp rice has recently become popular among rice consumers for its diverse health benefits specially anti-cancer effect. Cyanidin-3-Glucosides (C3G), an prominant bioactive component of anthocyanins which is abundantly present in black pericarp rice.ObjectivesWe investigated, how effectively it can be used to fortify Cyanidin-3-Glucosides (C3G) content in red and white pericarp polished rice or rice based bakery products for more nutritional value.MethodIn the present study, we have characterized several black pericarp rice cultivars along with some red pericarp and white pericarp rice cultivars by physicochemical including mineral profiling, and quantified the C3G by UFLC and LCMS.ResultsC3G content was significantly reduced from raw rice to cooked rice condition. All the black pericarp rice cultivars synthesized C3G, while this content was not detected in red and white pericarp rice cultivars. However, when 25% of black pericarp rice were mixed with 75% red or white pericarp polished rice, C3G content was significantly retained in cooked rice conditions. Formulation of rice-based bakery food product using black pericarp rice powder was also remarkably retained the C3G content as compared to that of cooking. Black rice is harder in texture, difficult to digest and needs higher energy for cooking. Therefore, we tried to circumvent these challenges by fortifying 25% of black pericarp rice with white or red pericarp rice.ConclusionFortification of C3G enriched black rice (25%) with red or white pericarp rice (75%) might bring a better nutritional quality in both cooking and baking condition. This may lead a way to the effective management of the non-communicable disease such as cancer for common rice consuming population.     

A multispecific monoclonal antibody G2 recognizes at least three completely different epitope sequences with high affinity

A monoclonal antibody (mAb) G2 possesses an unusual characteristic of reacting with at least three proteins (ATP6V1C1, SEPT3, and C6H10orf76) other than its original antigen, chicken prion protein (ChPrP). The epitopes on ChPrP and ATP6V1C1 have been identified previously. In this study, we identified the epitope in the third protein, SEPT3. Interestingly, there was no amino acid sequence similarity among the epitopes on the three proteins. These epitopes had high binding affinities to G2 (K _D = ～10^?7 M for monovalent binding and K _D = ～10^?9 M for divalent binding), as determined using a SPR biosensor. This is the first report on a three‐in‐one mAb recognizing completely different epitope sequences with high affinity. Additionally, competitive ELISA indicated that the binding sites on G2, specific for the three different epitopes, overlapped, suggesting that the antigen‐binding site may be flexible in the free form and capable of adapting to at least three different conformations to enable interactions with three different antigens.