Wharton’s jelly or bone marrow mesenchymal stromal cells improve cardiac function following myocardial infarction for more than 32 weeks in a rat model: a preliminary report

The therapeutic effect of mesenchymal stromal cells (MSCs) following myocardial infarction (MI) is small. This may be due to differences in cellular sources and donor age, route of administration, in vitro cellular manipulations and the short time course of follow up in many animal studies. Here, we compared MSCs from two different sources (adult bone marrow or Wharton’s jelly from umbilical cord) for their long-term therapeutic effect following MI in a rat model to evaluate the effect of donor age. MSCs (or control infusions) were given intravenously 24-48 hr after myocardial ischemia (MI) induced by coronary artery ligation. Cardiac function was assessed by ultrasound at time points starting from before MSC infusion through 68 weeks after MI. A significant improvement in ejection fraction was seen in animals that received MSCs in time points 25 to 31 wks after treatment (p <0.01). These results support previous work that show that MSCs can cause improvement in cardiac function and extend that work by showing that the beneficial effects are durable. To investigate MSCs’ cardiac differentiation potential, Wharton’s jelly MSCs were co-cultured with fetal or adult bone-derived marrow MSCs. When Wharton’s jelly MSCs were co-cultured with fetal MSCs, and not with adult MSCs, myotube structures were observed in two-three days and spontaneous contractions (beating) cells were observed in fiveseven days. The beating structures formed a functional syncytium indicated by coordinated contractions (beating) of independent nodes. Taken together, these results suggest that MSCs given 24-48 hr after MI have a significant and durable beneficial effect more than 25 weeks after MI and that MSC treatment can home to damaged tissue and improve heart function after intravenous infusion 24-48 hrs after MI, and that WJCs may be a useful source for off-the-shelf cellular therapy for MI

The effects of dietary fish oil on exercising skeletal muscle vascular and metabolic control in chronic heart failure rats

The ATP-sensitive K+ (KATP) channel is a class of inward rectifier K+ channels that can link cellular metabolic status to vasomotor tone across the metabolic transients seen with exercise. This investigation tested the hypothesis that if KATP channels are crucial to exercise hyperaemia then blockade via glibenclamide (GLI) would lower hindlimb skeletal muscle blood flow (BF) and vascular conductance (VC) during treadmill exercise. In 14 adult male Sprague Dawley rats mean arterial pressure (MAP), blood [lactate], and hindlimb muscle BF (radiolabelled microspheres) were determined at rest (n = 6) or during exercise (n = 8; 20 m min⁻¹, 5% incline) under control (CON) and GLI conditions (5 mg kg⁻¹, i.a). At rest and during exercise, MAP was higher (Rest, CON: 130 ± 6, GLI: 152 ± 8; Exercise, CON: 140 ± 4, GLI: 147 ± 4 mmHg, P < 0.05) and heart rate (HR) was lower (Rest, CON: 440 ± 16, GLI: 410 ± 18; Exercise, CON: 560 ± 4, GLI: 540 ± 10 beats min⁻¹, P < 0.05) with GLI. Hindlimb muscle BF (CON: 144 ± 10, GLI: 120 ± 9 ml min⁻¹ (100 g)⁻¹, P < 0.05) and VC were lower with GLI during exercise but not at rest. Specifically, GLI decreased BF in 12, and VC in 16, of the 28 individual hindlimb muscles and muscle parts sampled during exercise with a greater fractional reduction present in muscles comprised predominantly of type I and type IIa fibres (P < 0.05). Additionally, blood [lactate] (CON: 2.0 ± 0.3; GLI: 4.1 ± 0.9 mmol L⁻¹, P < 0.05) was higher during exercise with GLI. That KATP channel blockade reduces hindlimb muscle BF during exercise in rats supports the obligatory contribution of KATP channels in large muscle mass exercise-induced hyperaemia

Stochastic variation of transcript abundance in C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Transcripts can exhibit significant variation in tissue samples from inbred laboratory mice. We have designed and carried out a microarray experiment to examine transcript variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice and to partition variation into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript abundance between genetically identical mice.</p> <p>Results</p> <p>The nature and extent of transcript variation differs across tissues. Adipose has the largest total variance and the largest within-mouse variance. Liver has the smallest total variance, but it has the most between-mouse variance. Genes with high variability can be classified into groups with correlated patterns of expression that are enriched for specific biological functions. Variation between mice is associated with circadian rhythm, growth hormone signaling, immune response, androgen regulation, lipid metabolism, and the extracellular matrix. Genes showing correlated patterns of within-mouse variation are also associated with biological functions that largely reflect heterogeneity of cell types within tissues.</p> <p>Conclusions</p> <p>Genetically identical mice can experience different individual outcomes for medically important traits. Variation in gene expression observed between genetically identical mice can identify functional classes of genes that are likely to vary in the absence of experimental perturbations, can inform experimental design decisions, and provides a baseline for the interpretation of gene expression data in interventional studies. The extent of transcript variation among genetically identical mice underscores the importance of stochastic and micro-environmental factors and their phenotypic consequences.</p

Selective Pressurized Liquid Extraction of Halogenated Pesticides and Polychlorinated Biphenyls Form Pine Needles.

Pine needles are an ideal matrix for the long-term monitoring of semi-volatile organic compounds in the atmosphere because they are naturally occurring and distributed worldwide. However, typical extraction methods result in the co-elution of matrix-interfering compounds and thus require time-consuming clean-up steps. A selective pressurised liquid extraction method (S-PLE) for extracting current-use pesticides, historic-use pesticides and polychlorinated biphenyls (PCBs) from pine needles that does not require additional clean-up steps was developed and validated. The selective extraction was achieved by packing the extraction vessel with a fat retainer, Florisil, down-stream of the pine needle matrix. A fat to fat-retainer ratio of 0.0057 (corresponding to 35 g of Florisil per 10 g of pine needle sample) was selected to minimise the co-elution of matrix-interfering compounds. Three 5-min extractions were performed using 25:75 (v/v) dichloromethane:n-hexane and a solvent flush of 150%. The mean recovery of spiked current-use pesticides, historic-use pesticides and PCBs using this method was 71%, 72%, and 84%, respectively. The method was validated by comparing target analyte concentrations measured in a pine needle sample using the optimised S-PLE method to those obtained using a conventional PLE method with external clean-up. The method detection limits and reproducibility were similar for the two methods; however, sample preparation time was 67% shorter when using the S-PLE method

Contributions of Long-Range and Regional Atmospheric Transport on Pesticide Concentrations Along a Transect Crossing a Mountain Divide.

Twenty-one halogenated legacy and current-use pesticides and pesticide degradation products were measured in pine needles along a coast-to-coast transect that crossed the Southern Alps of New Zealand. Concentration profiles of nine pesticides were used to determine the influence of geographic sources on the atmospheric pesticide burden at the mountain sites. Pesticide concentration profiles were calculated for each source and mountain site by normalizing concentrations (adjusted for temperature at the site and air–needle partitioning) to the sum of all pesticide concentrations at the site. Each mountain site profile was compared to varying mixtures of the potential source profiles to determine the percent contribution of each source. The highest elevation mountain sites were primarily influenced by long-range, synoptic-scale northwesterly winds. Westerly upslope winds had little influence on any of the mountain sites. Easterly upslope winds from the Canterbury Plains, an agricultural region, strongly influenced the mountain sites within close proximity and had progressively less influence with distance

Trace elements and metal pollution in aerosols at an alpine site, New Zealand: sources, concentrations and implications

Atmospheric aerosol samples were collected at a remote site in New Zealand\u27s Southern Alps. Collected samples were found to be a mixture of New Zealand and Australian sourced sediment, using their trace element signatures. Aerosol concentrations and the relative contribution of different sources was found to be a function of specific air-mass trajectories influencing the study site, dust entrainment rates in source areas and rainfall. Results show that Australian dust is a major source of particulate matter in New Zealand, particularly in remote alpine locations; however, locally derived dust is also important. Metal pollutants, including Pb, Cu and Sn, were enriched in the samples by approximately 15 times and up to \u3e100 times expected natural concentrations, confirming that metal pollution is a ubiquitous component of the atmosphere, even in relatively remote locations. Moreover, pollutants were highly enriched in otherwise clean air, i.e. during and following rainfall. Additionally, high concentrations of elements naturally enriched in sea water, e.g. Sr, Ba and Rb, were deposited alongside mineral dust, reflecting the oceanic origin of air influencing the site and the role of sea spray in contributing aerosol to the atmosphere. These elements experienced the greatest enrichment during rainfall, implying sea spray and pollution become relatively important during otherwise clean air conditions

Using Trace Elements in Particulate Matter to Identify the Sources of Semi-Volatile Organic Contaminants in Air at an Alpine Site.

An approach using trace elements in particulate matter (PM) to identify the geographic sources of atmospherically transported semivolatile organic contaminants (SOCs) was investigated. Daily samples of PM and SOCs were collected with high-volume air samplers from 16 January to 16 February 2009 at Temple Basin, a remote alpine site in New Zealand’s Southern Alps. The most commonly detected pesticides were dieldrin, trans-chlordane, endosulfan I, and chlorpyrifos. Polycyclic aromatic hydrocarbons and polychlorinated biphenyls were also detected. For each sampling day, the relative contribution of PM from regional New Zealand versus long-range Australian sources was determined using trace element profiles and a binary mixing model. The PM approach indicated that endosulfan I, indeno[1,2,3-c,d]pyrene, and benzo[g,h,i]perylene found at Temple Basin were largely of Australian origin. Local wind observations indicated that the chlorpyrifos found at Temple Basin primarily came from the Canterbury Plains in New Zealand

Trace Elements and Metal Pollution in Aerosols at an Alpine Site, New Zealand: Sources, Concentrations, and Implications.

Atmospheric aerosol samples were collected at a remote site in New Zealand\u27s Southern Alps. Collected samples were found to be a mixture of New Zealand and Australian sourced sediment, using their trace element signatures. Aerosol concentrations and the relative contribution of different sources was found to be a function of specific air-mass trajectories influencing the study site, dust entrainment rates in source areas and rainfall. Results show that Australian dust is a major source of particulate matter in New Zealand, particularly in remote alpine locations; however, locally derived dust is also important. Metal pollutants, including Pb, Cu and Sn, were enriched in the samples by approximately 15 times and up to \u3e100 times expected natural concentrations, confirming that metal pollution is a ubiquitous component of the atmosphere, even in relatively remote locations. Moreover, pollutants were highly enriched in otherwise clean air, i.e. during and following rainfall. Additionally, high concentrations of elements naturally enriched in sea water, e.g. Sr, Ba and Rb, were deposited alongside mineral dust, reflecting the oceanic origin of air influencing the site and the role of sea spray in contributing aerosol to the atmosphere. These elements experienced the greatest enrichment during rainfall, implying sea spray and pollution become relatively important during otherwise clean air conditions

Hypertensive disorders of pregnancy increase the risk of developing neovascular age-related macular degeneration in later life

Background: Hypertensive disorders of pregnancy (HDP) and short-term adverse outcomes have long been recognized; however, survivors remain at risk of long-term complications. We investigated whether HDP is associated with the development of choroidal neovascular age-related macular degeneration (CNV AMD). Methods: We identified 31,454 women who experienced HDP based on Utah birth certificates and 62,908 unexposed women matched 2:1 to the exposed. Risk of CNV AMD was estimated using Cox models. Findings: Women with HDP exhibited an 80% higher risk for early CNV AMD (age < 70 y; 95%CI 1.23–2.58). Conclusion: Our findings may have implications forearlier CNV AMD screening and detection