Collagen type XIV is proportionally lower in the lung tissue of patients with IPF

Abnormal deposition of extracellular matrix (ECM) in lung tissue is a characteristic of idiopathic pulmonary fibrosis (IPF). Increased collagen deposition is also accompanied by altered collagen organization. Collagen type XIV, a fibril-associated collagen, supports collagen fibril organization. Its status in IPF has not been described at the protein level yet. In this study, we utilized publicly available datasets for single-cell RNA-sequencing for characterizing collagen type XIV expression at the gene level. For protein level comparison, we applied immunohistochemical staining for collagen type XIV on lung tissue sections from IPF patients and compared it to lung tissue sections from never smoking and ex-smoking donors. Analyzing the relative amounts of collagen type XIV at the whole tissue level, as well as in parenchyma, airway wall and bronchial epithelium, we found consistently lower proportions of collagen type XIV in all lung tissue compartments across IPF samples. Our study suggests proportionally lower collagen type XIV in IPF lung tissues may have implications for the assembly of the ECM fibers potentially contributing to progression of fibrosis.</p

Resting pulmonary haemodynamics and shunting: a comparison of sea-level inhabitants to high altitude Sherpas

The incidence of blood flow through intracardiac shunt and intrapulmonary arteriovenous anastomoses (IPAVA) may differ between Sherpas permanently residing at high altitude (HA) and sea-level (SL) inhabitants as a result of evolutionary pressure to improve gas exchange and/or resting pulmonary haemodynamics. To test this hypothesis we compared sea-level inhabitants at SL (SL-SL; n = 17), during acute isocapnic hypoxia (SL-HX; n = 7) and following 3 weeks at 5050 m (SL-HA; n = 8 non-PFO subjects) to Sherpas at 5050 m (n = 14). inline image, heart rate, pulmonary artery systolic pressure (PASP) and cardiac index (Qi) were measured during 5 min of room air breathing at SL and HA, during 20 min of isocapnic hypoxia (SL-HX; inline image = 47 mmHg) and during 5 min of hyperoxia (inline image = 1.0; Sherpas only). Intracardiac shunt and IPAVA blood flow was evaluated by agitated saline contrast echocardiography. Although PASP was similar between groups at HA (Sherpas: 30.0 ± 6.0 mmHg; SL-HA: 32.7 ± 4.2 mmHg; P = 0.27), it was greater than SL-SL (19.4 ± 2.1 mmHg; P < 0.001). The proportion of subjects with intracardiac shunt was similar between groups (SL-SL: 41%; Sherpas: 50%). In the remaining subjects, IPAVA blood flow was found in 100% of subjects during acute isocapnic hypoxia at SL, but in only 4 of 7 Sherpas and 1 of 8 SL-HA subjects at rest. In conclusion, differences in resting pulmonary vascular regulation, intracardiac shunt and IPAVA blood flow do not appear to account for any adaptation to HA in Sherpas. Despite elevated pulmonary pressures and profound hypoxaemia, IPAVA blood flow in all subjects at HA was lower than expected compared to acute normobaric hypoxia

Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery

Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phase−solubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 × 103 M−1 and 4.27 × 103 M−1. Fourier transforms infrared spectroscopy indicated entrance of an O−CH2 or OCH3−C6H4−OCH3 moiety of Red-Br-Nos in the β-CD or methyl-β- CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD was validated by several spectral techniques. Rotating frame Overhauser enhancement spectroscopy revealed that the Ha proton of the OCH3−C6H4−OCH3 moiety was closer to the H5 proton of β-CD and the H3 proton of the methyl-β-CD cavity. The solubility of Red-Br-Nos in phosphate buffer saline (PBS, pH ∼ 7.4) was improved by ∼10.7-fold and ∼21.2-fold when mixed with β-CD and methyl-β-CD, respectively. This increase in solubility led to a favorable decline in the IC50 by ∼2-fold and ∼3-fold for Red-Br-Nos−β-CD-GGM and Red-Br-Nos−methyl-β-CD-GGM formulations respectively, compared to free Red-Br-Nos−β-CD and Red-Br-Nos−methyl-β-CD in human colon HT-29 cells. GGM-bearing drug complex formulations were found to be highly cytotoxic to the HT-29 cell line and further effective with simultaneous continuous release of Red-Br-Nos from microspheres. This is the first study to showing the preparation of drug-complex loaded GGMS for colon delivery of Red-Br-Nos that warrants preclinical assessment for the effective management of colon cancer

Developmental adaptation to high altitude hypoxia

Experimental studies on animals and humans exposed to hypoxic stress have been reviewed. These data suggest that the influence of hypoxic stress, and the organism's response to it, are greater during growth than during adulthood. The organism's responses include alterations in the quantity and size of the alveolar units of the lungs, enlargement of the right ventricle of the heart, slower somatic growth as measured by birth weight and body size, increased aerobic capacity during maximal work, and greater control of ventilation. It is postulated that the organism is more sensitive to the influence of environmental factors during growth and development than during adulthood. Consequently, adaptive traits acquired during the developmental period have profound, long-term consequences, which are reflected in the physiological and morphological characteristics of the adult organism. It is concluded that the differences between the highland and lowland natives in their physiological performance and morphology are mostly due to adaptations acquired during the developmental period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47840/1/484_2005_Article_BF01553707.pd

Estudio preliminar de la prolificidad y habilidad materna de seis biotipos ovinos en Uruguay. (Preliminary study of prolificacy and maternal ability on six sheep biotypes in Uruguay.).

RESUMEN.Los resultados de las primeras evaluaciones del Proyecto Ovejas Prolíficas de INIA (2008-2011) muestran que la cruza Frisona Milchschaf x Corriedale o Finnish Landrace x Corriedale desteta 60 % más corderos que la Corriedale pura y, por otro lado, la cruza Finnish Landrace x Frisona Milchschaf desteta 85 % más que la Corriedale pura. Sin embargo y bajo lasmismas condiciones productivas, no se conoce el comportamiento al parto y la producción de calostro de estos nuevos biotipos. Para recabar información, se realizó un experimento en INIA La Estanzuela, Colonia, Uruguay (34°S; 57°O) donde se utilizaron 61 borregas de 4-6 dientes nacidas en la primavera del año 2010. Se utilizaron dos razas puras: Corriedale (C.C) y Frisona Milchschaf (M.M) y las cruzas Finnish Landrace x Corriedale (F.C), Frisona Milchschaf x Corriedale (M.C), 3/4 Frisona Milchschaf - 1/4 Finnish Landrace (M.(F.M)) y 7/8 Finnish Landrace - 1/8Corriedale (F.(FxF.C)), apareadas con carneros Texel. El incremento de sangre Finnish en la cruza redundó en un aumento en la prolificidad (2,2; 2,3 y 2,4 para1/4; 1/2 y 7/8 Finnish) con corderos más livianos y menor asistencia al parto. Tanto la media sangre Milchschaf como la pura tuvieron una prolificidad similar e intermedia (1,8 M.C y 1,7 M.M) mientras que la asistencia al parto fue alta. La producción y composición de calostro fue similar entre biotipos a excepción de M.M que produjo más. No existió diferencia en eficiencia placentaria entre biotipos. El peso vivo al nacimiento de los corderos influyó sobre el comportamiento de los mismos en su primera hora de vida, precisamente en el tiempo desde el nacimiento hasta que lograron pararse y mamar..-.-.-.-.-.-.-.-.-.-.-..-.-.-.-SUMMARY.The results of the first evaluation of the Prolific Sheep Project of INIA (2008-2011) demonstrated that the crossbred biotypes Corriedale by East Friesian or Corriedale by Finnish Landrace weaned 60 % more lambs than pure Corriedale and, on the other hand, the crossbred East Friesian by Finnish Landrace weaned 85 % more than pure Corriedale. However, and under the same productive conditions the behavior at lambing and colostrum production of these new biotypes are unknown. In order to find out, an experiment was conducted at INIA La Estanzuela, Colonia, Uruguay (34°S; 57°O) where 61 female lambs 4-6 teeth born in the spring of 2010 were evaluated. Two pure breeds were used: Corriedale (C.C) and East Friesian (M.M), and the crosses Finnish Landrace x Corriedale (F.C), East Friesian x Corriedale (M.C), 3/4 East Friesian - 1/4 Finnish Landrace (M.(F.M)), 7/8 Finnish Landrace - 1/8 Corriedale (F.(FxF.C)), mated with Texel rams. The increase in Finnish blood resulted in more prolificacy (2.2; 2.3 and 2.4 for 1/4; 1/2 and 7/8 Finnish with lighter lambs and less lambing assistance. Both half and pure East Friesian had similar and moderate prolificacy (1.8 M.C and 1.7 M.M) whereas lambing assistancewas high. Colostrum production and composition was similar between biotypes, with the exception of M.M, that produced more. There were no differences in placental efficiency between biotypes. Birth weight of lambs affected their behavior in the first hour of life, specifically the time from birth to first stand up to suckle