Reduced Buffering Capacity Research Articles

CHARACTERISTICS OF CHANGES IN QUALITATIVE PROPERTIES OF ORAL FLUID IN CHILDREN WITH CONGENITAL NONUNION OF THE PALATE

According to publications in scientific periodicals, children with congenital malformations of the development are increasingly born, including those with localization on the face, head and neck. Anatomical inferiority of tissues in the area of the slit defect of the palate creates the preconditions for the formation of pathological symptom complex, which contributes to the progression of inflammatory-dystrophic changes in the oral cavity.
 The aim of the study was to study the violations of the qualitative properties of oral fluid in children with congenital nonunion of the palate in the preoperative period.
 For an in-depth examination of 58 children who were under our supervision, a group of 25 patients aged from 4 to 6 years was formed. Of these, 14 had a unilateral cleft and 11 had a bilateral cleft.
 The substrate for the study was unstimulated fraction of oral fluid. The salivation rate was studied, the concentration of hydrogen ions in it, its optical density, viscosity, α-amylase activity, levels of medium weight molecules, sialic acids, total protein, oxyproline were determined. The degree of mineralizing potential was determined by magnesium, calcium and phosphorus.
 At the time of the examination in children with unilateral clefts, a decrease in the amount of oral fluid was found, which was expressed by a decrease in the secretory activity of the large and small salivary glands by 1,3 times. The concentration of ions is visible in it and the activity of α-amylase decreased by 1.3 times. The optical density and viscosity also increased by 1,3 times, the number of medium weight molecules, the level of sialic acid and total protein increased by 1.5 times, and oxyrolin by 1.6 times.
 The analysis of indexes that showed the mineralizing potential of oral fluid mineralizing potential of oral fluid allowed to determine the fact that in patients of this group it decreased by 1,7 times and this occurred against the background of a decrease in calcium and magnesium by 1,5, with an increase in phosphorus by 1.3 times. This imbalance led to falling in calcium-phosphorus ratio by 1,8 times.
 In children with congenital malformations of the palate there is a decrease in the functional activity of large and small salivary glands, reduced buffering capacity of oral fluid, which occurs against the background of falling mineralizing potential of oral fluid, imbalance of calcium, phosphorus and magnesium. This affects the calcium-phosphorus ratio, thus creating optimal conditions for demineralization of tooth hard tissues. Changes in physicochemical and biochemical properties of mixed saliva are determined, which is the basis for the prolongation and progression of pathological processes in the oral cavity that take place in them.
 The complex of treatment-and-prophylactic measures developed by us, aimed at improving the level of components of homeostasis of the oral cavity before surgery, is being tested for the future.

Ocean acidification may mitigate negative effects of warming on carbon burial potential in subtidal unvegetated estuarine sediments

AbstractEstuarine sediments make an important contribution to the global carbon cycle, but we do not know how this will change under a future climate, which is expected to have lower pH oceans and frequent high‐temperature days. Six combinations of warming and partial pressures of CO2(pCO2) were chosen to investigate the combined and individual effects of short‐term pressures on the diel metabolic response of shallow unvegetated sediments ex‐situ. Whereas warming significantly increased respiration, making sediments more heterotrophic, high‐pCO2increased net primary productivity, resulting in less heterotrophic sediments. As a result, warming decreased the carbon burial potential of estuarine sediments and high‐pCO2had the opposite effect. High‐pCO2mitigates the negative effects of warming on benthic metabolism under the combined scenario, with carbon burial similar to that expected under high‐pCO2conditions alone. Climate scenarios also changed the diurnalpCO2variation, with ranges increasing by 33% with warming, and almost doubling under high‐pCO2conditions. An additive response inpCO2variability was observed under the combined scenario, increasing to 2.3× the current diel‐pCO2range, highlighting the reduced buffering capacity of the water associated with a high CO2climate. Future carbon burial and export under increased frequencies of unseasonably warm days projected for mid and end of century (30% and 50% of days‐per‐year, respectively) were estimated with and without ocean acidification. By 2100, warming alone could decrease annual estuarine sediment burial potential by 25%. However, ocean acidification could mitigate the negative effects of more frequent high‐temperature days and increase carbon burial potential over current conditions by ~18%.

Low noncarbonic buffer power amplifies acute respiratory acid-base disorders in patients with sepsis: an in vitro study.

Patients with sepsis have typically reduced concentrations of hemoglobin and albumin, the major components of noncarbonic buffer power (β). This could expose patients to high pH variations during acid-base disorders. The objective of this study is to compare, in vitro, noncarbonic β of patients with sepsis with that of healthy volunteers, and evaluate its distinct components. Whole blood and isolated plasma of 18 patients with sepsis and 18 controls were equilibrated with different CO2 mixtures. Blood gases, pH, and electrolytes were measured. Noncarbonic β and noncarbonic β due to variations in strong ion difference (βSID) were calculated for whole blood. Noncarbonic β and noncarbonic β normalized for albumin concentrations (βNORM) were calculated for isolated plasma. Representative values at pH = 7.40 were compared. Albumin proteoforms were evaluated via two-dimensional electrophoresis. Hemoglobin and albumin concentrations were significantly lower in patients with sepsis. Patients with sepsis had lower noncarbonic β both of whole blood (22.0 ± 1.9 vs. 31.6 ± 2.1 mmol/L, P < 0.01) and plasma (0.5 ± 1.0 vs. 3.7 ± 0.8 mmol/L, P < 0.01). Noncarbonic βSID was lower in patients (16.8 ± 1.9 vs. 24.4 ± 1.9 mmol/L, P < 0.01) and strongly correlated with hemoglobin concentration (r = 0.94, P < 0.01). Noncarbonic βNORM was lower in patients [0.01 (-0.01 to 0.04) vs. 0.08 (0.06-0.09) mmol/g, P < 0.01]. Patients with sepsis and controls showed different amounts of albumin proteoforms. Patients with sepsis are exposed to higher pH variations for any given change in CO2 due to lower concentrations of noncarbonic buffers and, possibly, an altered buffering function of albumin. In both patients with sepsis and healthy controls, electrolyte shifts are the major buffering mechanism during respiratory acid-base disorders.NEW & NOTEWORTHY Patients with sepsis are poorly protected against acute respiratory acid-base derangements due to a lower noncarbonic buffer power, which is caused both by a reduction in the major noncarbonic buffers, i.e. hemoglobin and albumin, and by a reduced buffering capacity of albumin. Electrolyte shifts from and to the red blood cells determining acute variations in strong ion difference are the major buffering mechanism during acute respiratory acid-base disorders.

Influence Of Hypertension On The Physical And Chemical Parameters Of Oral Fluid

On the basis of comparative studies of physicochemical parameters of the oral fluid in patients with normal blood pressure, pre-hypertension, and clinically verified arterial hypertension, a violation of physicochemical parameters of the oral fluid has been identified: reduced rate of salivation, decrease in pH, increase in viscosity and surface tension, and reduced buffering capacity to neutralize acids and bases associated with high blood pressure. Decreased functional activity of the salivary glands may be a potential biomarker of hypertension. To assess their diagnostic value, the physicochemical parameters of oral fluid in the diagnosis of arterial hypertension require further research.

Novel ethanol production using biomass preprocessing to increase ethanol yield and reduce overall costs

BackgroundEthanol biorefineries need to lower their overall production costs to become economically feasible. Two strategies to achieve this are to reduce costs using cheaper feedstocks or to increase the ethanol production yield. Low-cost feedstocks usually have high non-structural components (NSC) content; therefore, a new process is necessary to accommodate these feedstocks and overcome the negative effects of NSC. This study developed a novel ethanol biorefinery process including a biomass preprocessing step that enabled the use of lower-cost feedstocks while improving ethanol production without detoxification (overliming). Two types of poplar feedstocks were used, low-quality whole-tree chips (WTC) and high-quality clean pulp chips (CPC), to determine if the proposed process is effective while using feedstocks with different NSC contents.ResultsTechnical assessment showed that acidic preprocessing increased the monomeric sugar recovery of WTC from 73.2% (untreated) to 87.5% due to reduced buffering capacity of poplar, improved sugar solubilization during pretreatment, and better enzymatic hydrolysis conversion. Preprocessing alone significantly improved the fermentability of the liquid fraction from 1–2% to 49–56% for both feedstocks while overliming improved it to 45%. Consequently, it was proposed that preprocessing can substitute for the detoxification step. The economic assessment revealed that using poplar WTC via the new process increased annual ethanol production of 10.5 million liters when compared to using CPC via overliming (base case scenario). Also, savings in total operating costs were about $10 million per year when using cheaper poplar WTC instead of CPC, and using recycled water for preprocessing lowered its total operating costs by 45-fold.ConclusionsThe novel process developed in this study was successful in increasing ethanol production while decreasing overall costs, thus facilitating the feasibility of lignocellulosic ethanol biorefineries. Key factors to achieving this outcome included substituting overliming by preprocessing, enabling the use of lower-quality feedstock, increasing monomeric sugar recovery and ethanol fermentation yield, and using recycled water for preprocessing. In addition, preprocessing enabled the implementation of an evaporator-combustor downstream design, resulting in a low-loading waste stream that can be treated in a wastewater treatment plant with a simple configuration.

Abstract PO-134: Intracellular calcium regulates androgen receptor expression and basal-luminal features in prostate cancer from African American men

Abstract Background: Disparities in prostate cancer (PrCa) incidence and mortality between African American (AA) and European American (EA) men are partially mediated by underlying disease biology. The goal of this study was to determine how DNA methylation and transcriptomic changes drive PrCa health disparities in AA men. Methods: Transcriptomic alterations potentially mediated by DNA methylation were identified by Illumina arrays and RNA-sequencing in PrCa from 30 AA and 32 EA men. Androgen receptor (AR) protein expression was measured using tissues microarray of matched PrCa tissues from 95 EA and 92 AA men. In vitro, MDA PCa 2a (2a)/MDA PCa 2b (2b) cells derived from an AA man and LNCaP/LaPC-4 cells derived from EA men were stimulated with ionomycin, a calcium ionophore to measure intracellular calcium using fluorescent-based live imaging. Results: Unsupervised hierarchical clustering revealed DNA methylation clusters (Cluster A and Cluster B) with differential methylation of loci that regulate intracellular calcium levels including RYR2, TRPC6, and TRPA1. Increased methylation of calcium regulatory genes in Cluster A was associated with reduced disease-free time (DFT) (21.65 vs 46.71 months, p&amp;lt;0.05) only in AA men with PrCa. RYR2 (-0.122 vs -0.004, p=0.69), TRPC6 (0.006 vs -0.639, p=0.06) and TRPA1 (-0.070 vs -0.269, p&amp;lt;0.05) transcript levels were lower in Cluster A compared to Cluster B. These data suggest DNA methylation can regulate expression of calcium regulating genes. In vitro, we found AA PrCa derived 2b cells have reduced RNA levels of RYR2, TRPV6 and CALB1 compared to EA PrCa derived LNCaP cells. Reduced transcription can result in lower protein expression and thus activity of calcium regulatory genes. To test this, we stimulated cells with ionomycin and found a rapid increase in intracellular calcium in 2a/2b cells (within 60 seconds) compared to LNCaP/LAPC-4 cells (120-300 seconds). This suggests that decreased transcription correlates to reduced buffering capacity of calcium regulatory genes. Others have shown that increased intracellular calcium reduces AR protein levels. Therefore, we analyzed AR protein expression in a subset of tumors from Cluster A and B. AR levels were lower in adjacent non-tumor and tumor tissue in these overlapping samples. AR low PrCa are associated with basal like features and respond poorly to androgen deprivation therapy. Therefore, we analyzed the PAM50 basal/luminal gene sets and AR target genes and found differentially expression of these genes in AA PrCa derived 2b and EA PrCa derived LNCaP cells. Conclusions: Our study shows that AA men with PrCa have epigenetically dysregulated calcium signaling that is associated with worse DFT. Our ongoing work seeks to identify how these alterations regulate AR expression and thus basal/luminal features. Our long- term goal is to establish novel molecular subtypes using calcium-AR-basal/luminal features that can guide design of rationale therapies in a subset of AA men with PrCa. Citation Format: Swathi Ramakrishnan, Xuan Peng, Eduardo C. Gomez, Kristopher Attwood, Ivan V. Maly, Wilma A. Hoffmann, Wendy Huss, Gissou Azabdaftari, Li Yan, Jianmin Wang, Anna Woloszynska. Intracellular calcium regulates androgen receptor expression and basal-luminal features in prostate cancer from African American men [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-134.

The effects of in-vitro pH decrease on the gametogenesis of the red tree coral, Primnoa pacifica.

Primnoa pacifica is the most ecologically important coral species in the North Pacific Ocean and provides important habitat for commercially important fish and invertebrates. Ocean acidification (OA) is more rapidly increasing in high-latitude seas because anthropogenic CO2 uptake is greater in these regions. This is due to the solubility of CO2 in cold water and the reduced buffering capacity and low alkalinity of colder waters. Primnoa pacifica colonies were cultured for six to nine months in either pH 7.55 (predicted Year 2100 pH levels) or pH 7.75 (Control). Oocyte development and fecundity in females, and spermatocyst stages in males were measured to assess the effects of pH on gametogenesis. Oocyte diameters were 13.6% smaller and fecundities were 30.9% lower in the Year 2100 samples. A higher proportion of vitellogenic oocytes (65%) were also reabsorbed (oosorption) in the Year 2100 treatment. Lower pH appeared to advance the process of spermatogenesis with a higher percentage of later stage sperm compared to Control. There was a laboratory effect observed in all measurement types, however this only significantly affected the analyses of spermatogenesis. Based on the negative effect of acidification on oogenesis and increased rate of oosorption, successful spawning could be unlikely in an acidified ocean. If female gametes were spawned, they are likely to be insufficiently equipped to develop normally, based on the decreased overall size and therefore subsequent limited amount of lipids necessary for successful larval development.

Radiotherapy changes salivary properties and impacts quality of life of children with Hodgkin disease

ObjectiveWe aimed to perform a longitudinal investigation of the effects of radiotherapy on salivary flow rate, pH, buffering capacity, and protein composition of saliva and on the quality of life of children with Hodgkin disease. DesignTen children (6–16-year-old) with Hodgkin disease and 10 matched healthy children were investigated. Stimulated and non-stimulated saliva samples were collected at baseline, after 1080 and 2160cGy of radiation, and 1, 2, and 3 months post-radiotherapy. The salivary flow rate was expressed as mL/min. Buffer capacity was determined by titration. Amylase activity, immunoglobulin A, mucin, and lactoferrin concentrations were determined by ELISA. Quality of life was assessed by Quality of Life – Head and Neck module 35 questionnaire. ResultsWe found that radiotherapy caused hyposalivation at 1080cGy and 1 month after radiotherapy and reduced buffering capacity at 2160cGy. Mucin concentration and amylase activity in non-stimulated saliva increased 1 month after radiotherapy. Lactoferrin concentration increased during and after radiotherapy. Immunoglobulin A concentration increased at 1080cGy, 1 and 2 months, for non-stimulated saliva and at 2160cGy and 1 month for stimulated saliva. Children reported more pain after radiotherapy and more xerostomia during radiotherapy. ConclusionWe concluded that the radiotherapy protocol affected the children’s salivary properties and children’s quality of life.

Resilience of Freshwater Communities of Small Microbial Eukaryotes Undergoing Severe Drought Events.

Small and shallow aquatic ecosystems such as ponds and streams constitute a significant proportion of continental surface waters, especially in temperate zones. In comparison with bigger lakes and rivers, they harbor higher biodiversity but they also exhibit reduced buffering capacity face to environmental shifts, such that climate global change can affect them in a more drastic way. For instance, many temperate areas are predicted to undergo droughts with increasing frequency in the near future, which may lead to the temporal desiccation of streams and ponds. In this work, we monitored temporal dynamics of planktonic communities of microbial eukaryotes (cell size range: 0.2–5 μm) in one brook and one pond that experienced recurrent droughts from 1 to 5 consecutive months during a temporal survey carried out monthly for 2 years based on high-throughput 18S rDNA metabarcoding. During drought-induced desiccation events, protist communities present in the remaining dry sediment, though highly diverse, differed radically from their planktonic counterparts. However, after water refill, the aquatic protist assemblages recovered their original structure within a month. This rapid recovery indicates that these eukaryotic communities are resilient to droughts, most likely via the entrance in dormancy. This property is essential for the long-term survival and functional stability of small freshwater ecosystems.

Physical and biogeochemical controls on the variability in surface pH and calcium carbonate saturation states in the Atlantic sectors of the Arctic and Southern Oceans

Polar oceans are particularly vulnerable to ocean acidification due to their low temperatures and reduced buffering capacity, and are expected to experience extensive low pH conditions and reduced carbonate mineral saturations states (Ω) in the near future. However, the impact of anthropogenic CO2 on pH and Ω will vary regionally between and across the Arctic and Southern Oceans. Here we investigate the carbonate chemistry in the Atlantic sector of two polar oceans, the Nordic Seas and Barents Sea in the Arctic Ocean, and the Scotia and Weddell Seas in the Southern Ocean, to determine the physical and biogeochemical processes that control surface pH and Ω. High-resolution observations showed large gradients in surface pH (0.10–0.30) and aragonite saturation state (Ωar) (0.2–1.0) over small spatial scales, and these were particularly strong in sea-ice covered areas (up to 0.45 in pH and 2.0 in Ωar). In the Arctic, sea-ice melt facilitated bloom initiation in light-limited and iron replete (dFe>0.2nM) regions, such as the Fram Strait, resulting in high pH (8.45) and Ωar (3.0) along the sea-ice edge. In contrast, accumulation of dissolved inorganic carbon derived from organic carbon mineralisation under the ice resulted in low pH (8.05) and Ωar (1.1) in areas where thick ice persisted. In the Southern Ocean, sea-ice retreat resulted in bloom formation only where terrestrial inputs supplied sufficient iron (dFe>0.2nM), such as in the vicinity of the South Sandwich Islands where enhanced pH (8.3) and Ωar (2.3) were primarily due to biological production. In contrast, in the adjacent Weddell Sea, weak biological uptake of CO2 due to low iron concentrations (dFe<0.2nM) resulted in low pH (8.1) and Ωar (1.6). The large spatial variability in both polar oceans highlights the need for spatially resolved surface data of carbonate chemistry variables but also nutrients (including iron) in order to accurately elucidate the large gradients experienced by marine organisms and to understand their response to increased CO2 in the future.

Including high-frequency variability in coastal ocean acidification projections

Abstract. Assessing the impacts of anthropogenic ocean acidification requires knowledge of present-day and future environmental conditions. Here, we present a simple model for upwelling margins that projects anthropogenic acidification trajectories by combining high-temporal-resolution sensor data, hydrographic surveys for source water characterization, empirical relationships of the CO2 system, and the atmospheric CO2 record. This model characterizes CO2 variability on timescales ranging from hours (e.g., tidal) to months (e.g., seasonal), bridging a critical knowledge gap in ocean acidification research. The amount of anthropogenic carbon in a given water mass is dependent on the age; therefore a density–age relationship was derived for the study region and then combined with the 2013 Intergovernmental Panel on Climate Change CO2 emission scenarios to add density-dependent anthropogenic carbon to the sensor time series. The model was applied to time series from autonomous pH sensors deployed in the surf zone, kelp forest, submarine canyon edge, and shelf break in the upper 100 m of the Southern California Bight. All habitats were within 5 km of one another, and exhibited unique, habitat-specific CO2 variability signatures and acidification trajectories, demonstrating the importance of making projections in the context of habitat-specific CO2 signatures. In general, both the mean and range of pCO2 increase in the future, with the greatest increase in both magnitude and range occurring in the deeper habitats due to reduced buffering capacity. On the other hand, the saturation state of aragonite (ΩAr) decreased in both magnitude and range. This approach can be applied to the entire California Current System, and upwelling margins in general, where sensor and complementary hydrographic data are available.

Qualidade da silagem de aveia preta sob efeito de estádios fenológicos, tamanhos de partícula e pré-murchamento

ResumoObjetivou-se com esta pesquisa avaliar os efeitos do estádio fenológico, o tamanho de partícula e o pré-murchamento sobre as características de fermentação e valor nutritivo da silagem de aveia preta (Avena strigosa). O experimento foi conduzido durante o período hibernal de 2011, em “latossolo vermelho” de textura argilosa localizado em Renascença, sudoeste do Paraná, Brasil. O delineamento experimental foi inteiramente casualizado em esquema trifatorial (3x2x2) com quatro repetições, sendo os fatores tamanhos médios de partícula: 5; 13 e 22mm; estádios de ensilagem: início do florescimento e florescimento pleno; e manejos: com e sem pré-murchamento. O tamanho de partícula alterou apenas o pH do material ensilado, com melhores resultados com 22mm, sem efeitos na composição bromatológica da silagem produzida. A operação de pré-murchamento é eficiente em restringir a emissão de efluentes no início do florescimento e, também, confere à silagem melhores condições de fermentação, com redução da capacidade tampão de 87,68 para 53,20 meq NaOH 100g MS-1 e do pH de 3,64 para 3,15, os quais garantem melhor preservação do valor nutritivo da forragem, possuindo menores teores de fibra em detergente neutro (FDN) e fibra em detergente acido (FDA), com maior proteína bruta (PB), digestibilidade in vitro da matéria seca (DIVMS) e nutrientes digestíveis totais (NDT). Com o avanço da maturidade, verifica-se elevação nos teores de FDN e FDA e redução nos teores de PB, DIVMS e NDT. A ensilagem em início de florescimento, seguida de pré-murchamento, possui condições adequadas para fermentação e apresenta melhor valor nutritivo

Formation of cytotoxic α-lactalbumin / sodium oleate complexes: Concentration and temperature effects

Cytotoxic complexes may be formed by mixing whey proteins and oleic acid or sodium oleate. The present study investigated the kinetics of complex formation when the whey protein α-lactalbumin (α-LA) is mixed with sodium oleate. Intrinsic fluorescence showed that the complex formed at room temperature during the mixing of α-LA and sodium oleate. However, some of the structural changes brought about by the binding of the sodium oleate can be reversed by dialysis, when loosely bound oleate is removed. During dialysis, solutions with lower protein concentrations had reduced buffering capacity, and so the pH decreased more; this decrease in pH was correlated with a loss of oleate from the complex. The cytotoxicity of all the samples produced in this study was strongly correlated with the amount of oleate bound in the complex, confirming previous studies that suggested that oleic acid is the cytotoxic agent in the complex.

Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3

The herbicide paraquat (PQ) has increasingly been reported in epidemiological studies to enhance the risk of developing Parkinson's disease (PD). Furthermore, case-control studies report that individuals with genetic variants in the dopamine transporter (DAT, SLC6A) have a higher PD risk when exposed to PQ. However, it remains a topic of debate whether PQ can enter dopamine (DA) neurons through DAT. We report here a mechanism by which PQ is transported by DAT: In its native divalent cation state, PQ(2+) is not a substrate for DAT; however, when converted to the monovalent cation PQ(+) by either a reducing agent or NADPH oxidase on microglia, it becomes a substrate for DAT and is accumulated in DA neurons, where it induces oxidative stress and cytotoxicity. Impaired DAT function in cultured cells and mutant mice significantly attenuated neurotoxicity induced by PQ(+). In addition to DAT, PQ(+) is also a substrate for the organic cation transporter 3 (Oct3, Slc22a3), which is abundantly expressed in non-DA cells in the nigrostriatal regions. In mice with Oct3 deficiency, enhanced striatal damage was detected after PQ treatment. This increased sensitivity likely results from reduced buffering capacity by non-DA cells, leading to more PQ(+) being available for uptake by DA neurons. This study provides a mechanism by which DAT and Oct3 modulate nigrostriatal damage induced by PQ(2+)/PQ(+) redox cycling.

The relationship between large artery stiffness, wave reflection and pulsatility in the micro-circulation: new insights into the management of both hypertension and diabetes

Objective: Increased arterial stiffness is associated with a reduced buffering capacity of the large arteries, therefore predisposing the microcirculation to increased flow and pressure pulsatility. However, increased wave reflection may be protective, by reducing the amount of pulsatility transmitted to the microcirculation. The aim of this study was to examine this hypothesis by exploring the relationship between large artery stiffness, wave reflections and pulsatility in the microvasculature. Design and Method: 67 volunteers, aged 64 ± 10 years, not taking any sympathomimetic compounds and free from any acute ocular symptoms participated. Aortic pulse wave velocity (aPWV) and augmentation index (AIx) were recorded using the SphygmoCor system as measures of large artery stiffness and wave reflection, respectively. Retinal artery resistance index (RI), a measure of early retinal organ damage and pulsatility ratio (PR), a measure of retinal artery pulsatility were recorded using doppler ultrasound (Aloca). Results: aPWV was significantly associated with RI (R = 0.43,P = 0.001) and PR (R = 0.54,P = < 0.001) whereas AIx was significantly and inversely related to RI (R = -0.26,P = 0.047) and PR (R = -0.33, P = 0.011, respectively). Stratifying individuals according to tertile of aPWV and AIx revealed that RI and PR were significantly higher in those individuals with high aPWV but low AIx, compared with individuals with low aPWV and high AIx (0.51 ± 0.13 vs 0.37 ± 0.06, P = 0.004,RI; and 2.2 ± 0.61vs1.6 ± 0.20; P = 0.008, PR). Conclusions: Increased large artery stiffness is implicated in microcirculatory damage. However, increased wave reflections may exert a protective effect. Future mechanistic studies linking the macro and micro-circulations may provide important insights into the management of conditions such as hypertension and diabetes.

Effect of Fortification with Various Types of Milk Proteins on the Rheological Properties and Permeability of Nonfat Set Yogurt

Yogurt base was prepared from reconstituted skim milk powder (SMP) with 2.5% protein and fortified with additional 1% protein (wt/wt) from 4 different milk protein sources: SMP, milk protein isolate (MPI), micellar casein (MC), and sodium caseinate (NaCN). Heat-treated yogurt mixes were fermented at 40 degrees C with a commercial yogurt culture until pH 4.6. During fermentation pH was monitored, and storage modulus (G') and loss tangent (LT) were measured using dynamic oscillatory rheology. Yield stress (sigma(yield)) and permeability of gels were analyzed at pH 4.6. Addition of NaCN significantly reduced buffering capacity of yogurt mix by apparently solubilizing part of the indigenous colloidal calcium phosphate (CCP) in reconstituted SMP. Use of different types of milk protein did not affect pH development except for MC, which had the slowest fermentation due to its very high buffering. NaCN-fortified yogurt had the highest G' and sigma(yield) values at pH 4.6, as well as maximum LT values. Partial removal of CCP by NaCN before fermentation may have increased rearrangements in yogurt gel. Soluble casein molecules in NaCN-fortified milks may have helped to increase G' and LT values of yogurt gels by increasing the number of cross-links between strands. Use of MC increased the CCP content but resulted in low G' and sigma(yield) at pH 4.6, high LT and high permeability. The G' value at pH 4.6 of yogurts increased in the order: SMP = MC < MPI < NaCN. Type of milk protein used to standardize the protein content had a significant impact on physical properties of yogurt. Practical Application: In yogurt processing, it is common to add additional milk solids to improve viscosity and textural attributes. There are many different types of milk protein powders that could potentially be used for fortification purposes. This study suggests that the type of milk protein used for fortification impacts yogurt properties and sodium caseinate gave the best textural results.

The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance

Research of the past decade has increased our understanding of the role adipose tissue plays in health and disease. Adipose tissue is now recognized as a highly active metabolic and endocrine organ. Adipocytes are of importance in buffering the daily influx of dietary fat and exert autocrine, paracrine and/or endocrine effects by secreting a variety of adipokines. The normal function of adipose tissue is disturbed in obesity, and there is accumulating evidence to suggest that adipose tissue dysfunction plays a prominent role in the development and/or progression of insulin resistance. Obese individuals often have enlarged adipocytes with a reduced buffering capacity for lipid storage, thereby exposing other tissues to an excessive influx of lipids, leading to ectopic fat deposition and insulin resistance in situations where energy intake exceeds energy expenditure. In addition, adipose tissue blood flow is decreased in obesity. This impairment may affect lipid handling in adipose tissue and, thereby, further contribute to excessive fat storage in non-adipose tissues. On the other hand, adipose tissue hypoperfusion may induce hypoxia in this tissue. Adipose tissue hypoxia may result in disturbances in adipokine secretion and increased macrophage infiltration in adipose tissue, events that are frequently observed in obesity. In this review, it is discussed how enlarged adipocytes, an impaired blood flow through adipose tissue, adipose tissue hypoxia, adipose tissue inflammation and macrophage infiltration are interrelated and may induce insulin resistance.

Locomotor response to levodopa in fluctuating Parkinson’s disease

The aim of this study was to quantify the dynamic response of locomotion to the first oral levodopa administration of the day in patients with fluctuating Parkinson's disease (PD). Stride length, walking speed, cadence and gait variability were measured with an ambulatory gait monitor in 13 PD patients (8 males) with a clinical history of motor fluctuations. The Unified Parkinson's Disease Rating Scale (UPDRS) gait score (part 29) was also determined by a movement disorders specialist from video recordings. Subjects arrived in the morning in an 'off' state (no PD medication) and walked for a maximum length of 100 m. They then took their usual morning dose of oral levodopa and repeated the walking task at 13 min intervals (on average) over a 90 min period. Changes in stride length over time were fit with a Hill (Emax) function. Latency (time until stride length increased 15% of the difference between baseline and maximum response) and the Hill coefficient (shape of the 'off-on' transition) were determined from the fitted curve. Latency varied from 4.7 to 53.3 min post-administration [23.31 min (SD 14.9)], and was inversely correlated with age at onset of PD (R = -0.83; P = 0.0004). The Hill coefficient (H) ranged from a smooth hyperbolic curve (0.9) to an abrupt 'off-on' transition (16.9), with a mean of 8.1 (SD 4.9). H correlated with disease duration (R = 0.67; P = 0.01) and latency (R = 0.67; P = 0.01), and increased with Hoehn & Yahr stage in the 'off' state (P = 0.02) from 5.7 (SD 3.5) (H&Y III) to 11.9 (SD 4.7) (H&Y IV). Walking speed correlated with changes in mean stride length, whereas cadence and gait variability did not. UPDRS gait score also reflected improving gait in the majority of subjects (8), providing clinical confirmation of the objective measures of the locomotor response to levodopa. Increasing abruptness (H) of the 'off-on' transition with disease duration is consistent with results from finger-tapping studies, and may reflect reduced buffering capacity of pre-synaptic nigrostriatal dopaminergic neurons. Ambulatory monitoring of gait objectively measures the dynamic locomotor response to levodopa, and this information could be used to improve daily management of motor fluctuations.

Acetylation of Polyethylenimine Enhances Gene Delivery via Weakened Polymer/DNA Interactions

We previously reported that gene delivery efficiency of 25-kDa, branched polyethylenimine (PEI) increased upon acetylation of up to 43% of the primary amines with acetic anhydride. In the present work, we investigated the effects of further increasing the degree of acetylation and elucidated the source of the higher gene delivery efficiency. Despite reduced buffering capacity, gene delivery activity continued to increase (up to 58-fold in HEK293) with acetylation of up to 57% of primary amines but decreased at higher degrees of acetylation. Characterization of polymer-DNA interactions showed that acetylated polymers bind less strongly to DNA. Further, a fluorescence resonance energy transfer assay showed that increasing acetylation causes polyplexes to unpackage inside cells to a higher degree than polyplexes formed with unmodified PEI. Overall, the data suggest that the increased gene delivery activity may be attributable to an appropriate balance between polymer buffering capacity and strength of polymer/DNA interactions.

Dental Plaque pH and Micro-organisms during Hyposalivation

We have previously reported that minor gland and whole saliva flow rates and salivary proteins showed differences in individuals with primary Sjögren's syndrome or head and neck radiation therapy, compared with controls (Eliasson et al., 2005). We now hypothesize that pH and number of acidogenic micro-organisms in dental plaque as well as saliva buffering capacity also differ in these individuals. Plaque pH was measured by the microtouch method up to 60 min after a sucrose rinse. Plaque collected from the same sites was analyzed for counts of total and acidic micro-organisms. Compared with their controls, the irradiated group but not the Sjögren's syndrome group displayed significantly lower plaque pH, increased numbers of lactobacilli and Candida species, as well as reduced buffering capacity. Stepwise regression tests suggested that the buccal minor-salivary-gland secretion rate in the test groups and counts of mutans streptococci in the controls were of significant importance for dental plaque pH.