Clinical biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism

Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active properties) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surf acta nt proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the surfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta subunit of its receptor (II3rb1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential to propose specific therapeutic procedures: repeated broncho-alveolar ravages, GM-CSF replacement, bone marrow grafting or lung transplantation

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Improved THETA-1 for light olefins oligomerization to diesel: Influence of textural and acidic properties

The increase in diesel demand, especially in Europe, and the need for high fuel quality requirements are forcing refiners to move into additional processes for production of high cetane diesel in order to meet the present market trends. Oligomerization of light olefins into middle distillate range products is a viable option. The fuel produced through this technology is environmentally friendly, free of sulfur and aromatics, and the adequate choice of the heterogeneous catalyst will direct the selectivity towards low branched oligomers, which will result in a high quality product. In this work we show the benefits of combining basic desilication treatments for generation of additional mesoporosity in mono-directional Theta-1 zeolite, with selective acid dealumination steps that restore not only the microporosity to values close to those of the parent samples, but also the total and strong Bronsted acidity. These modified Theta-1 zeolites present an outstanding catalytic behavior for oligomerization of propene, with a largely increased initial activity, a much higher resistance to deactivation with time on stream, and an improved selectivity to products in the diesel fraction, as compared to the original microporous Theta-1.The authors thank BP Products of North America for their financial support and permission to publish this work, and Consolider Ingenio 2010-Multicat, the "Severo Ochoa Program", and MAT2012-31657 for financial support. R. Sanchis is acknowledged for technical support.Martínez, C.; Doskocil, EJ.; Corma Canós, A. (2014). Improved THETA-1 for light olefins oligomerization to diesel: Influence of textural and acidic properties. Topics in Catalysis. 57(6-9):668-682. https://doi.org/10.1007/s11244-013-0224-xS668682576-9Bellussi G, Mizia F, Calemma V, Pollesel P, Millini R (2012) Microporous Mesoporous Mater 164:127–134Bellussi G, Carati A, Millini R (2010) In: Cejka J, Corma A, Zones S (eds) Zeolites and Catalysis. Wiley-VCH Verlag GmbH & Co., Weinheim, pp 449–491Martinez C, Corma A (2011) Coord Chem Rev 255:1558–1580de Klerk A (2005) Ind Eng Chem Res 44:3887–3893de Klerk A (2006) Energy Fuels 20:439–445de Klerk A (2006) Energy Fuels 20:1799–1805Egloff G (1936) Ind Eng Chem Res 28:1461–1467Degnan TF Jr, Smith CM, Venkat CR (2001) Appl Catal A Gen 221:283–294Apelian MR, Boulton JR, Fung AS (1994) US5284989, to Mobil OilQuann RJ, Green LA, Tabak SA, Krambeck FJ (1988) Ind Eng Chem Res 27:565–570Tabak SA, Krambeck FJ, Garwood WE (1986) AIChE J 32:1526–1531Corma A, Martínez C, Doskocil EJ (2013) J Catal 300:183–196Martens JA, Ravishankar R, Mishin IE, Jacobs PE (2000) Angew Chem Int Ed Engl 39:4376–4379Martens JA, Verrelst WH, Mathys GM, Brown SH, Jacobs PA (2005) Angew Chem Int Ed Engl 117(5833–583):6Pater JPG, Jacobs PA, Martens JA (1998) J Catal 179:477–482Tabak SA (1981) US4254295, to Mobil OilOccelli ML, Hsu JT, Galya LG (1985) J Mol Catal A: Chem 32:377–390Tabak SA (1984) US4504693, to Mobil Oil CorpKholer E, Schmidt F, Wernicke HJ, Pontes MD, Roberts HL (1995, Summer) Hydrocarbon Technology InternationalMartens JA, Verduijn JP (1995) WO95/19945, to Exxon Chemical Patents Inc.Verrelst WH (1995) Martens LRM, WO95/22516, to Exxon Chemical Patents Inc.Verrelst WH, Martens LRM (2000) US6143942, to Exxon Chemical Patents Inc.Verrelst WH, Martens LRM, Verduijn JP (2006) US6013851, to Exxon Chemical Patents Inc.Dakka JM, Mathys GMK, Puttemans MPH (2003) WO03/035583 to Exxon-Mobil Chemical LimitedMatias P, Sa CC, Graca I, Lopes JM, Carvalho AP, Ramoa RF, Guisnet M (2011) Appl Catal A 399:100–109Chal R, Gérardin C, Bulut M, van Donk S (2011) ChemCatChem 3:67–81Perez-Ramirez J, Christensen CH, Egeblad K, Groen JC (2008) Chem Soc Rev 37:2530–2542Verboekend D, Perez-Ramirez J (2011) Catal Sci Technol 1:879–890Serrano DP, Escola JM, Pizarro P (2013) Chem Soc Rev 42:4004–4035Verboekend D, Chabaneix AM, Thomas K, Gilson JP, Perez-Ramirez J (2011) Cryst Eng Comm 13:3408–3416Emeis CA (1993) J Catal 141:347–354Perego C, Peratello S (1999) Catal Today 52:133–145Abello S, Bonilla A, Perez-Ramirez J (2009) Appl Catal A Gen 364:191–198Corma A, Martinez C, Doskocil EJ, Yaluris G (2011) WO2011002631A2, to BP Oil International Limited. BP Corporation North America Inc., UKCorma A, Martinez C, Doskocil EJ, Yaluris G (2011) WO2011002630A2, to BP Oil International Limited. BP Corporation North America Inc, UKHan S, Heck RH, DiGuiseppi FT (1993) US5234875, to Mobil Oil CorporationPeratello S, Molinari M, Bellussi G, Perego C (1999) Catal Today 52:271–27

CB2 Cannabinoid Receptors Contribute to Bacterial Invasion and Mortality in Polymicrobial Sepsis

BACKGROUND:Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2) receptors on immune cells. Here we examined the role of CB(2) receptors in regulating the host's response to sepsis. METHODS AND FINDINGS:The role of CB(2) receptors was studied by subjecting CB(2) receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2) receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2) receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF)-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2) receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+) and CD19(+) cells during CLP. CONCLUSIONS:Taken together, our results establish for the first time that CB(2) receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2) receptors may be therapeutically targeted for the benefit of patients suffering from sepsis

Protein disulphide isomerase-mediated grafting of cysteine-containing peptides onto over-bleached hair

The ability of Protein disulphide isomerase (PDI) to promote the grafting of two cysteine-containing peptides onto hair was investigated in order to develop an alternative treatment for over-bleached hair. The studied peptides were designed based on human keratin and human lung surfactant proteins and were linked to a fluorescent dye to facilitate visualisation of the grafting process and to assess hair penetration. The ability of the peptides to restore mechanical and thermal properties lost by repeated bleaching treatments was also studied. After eight bleaching treatments, hair samples displayed 42% less mechanical resistance, coupled with a decrease in α-helix denaturation enthalpies and temperatures. Hair surface damage following bleaching was visualized by scanning electron microscopy. Addition of PDI to the treatment formulations promoted peptide attachment to the hair via disulphide bonds, facilitating their penetration into the hair cortex, as observed by fluorescence microscopy. The proposed peptide treatment resulted in an increase in α-helix denaturation enthalpy in over-bleached hair, as well as an increase in both Young's modulus and tensile strength. Thus, mechanical and thermal properties were improved after the peptide treatment in the presence of PDI; suggesting that the formulations presented in this work are promising candidates for hair-care applications

Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions

The clinical, biochemical and genetic features of the conditions known as estrogen-dependent inherited angioedema, estrogen-associated angioedema, hereditary angioedema with normal C-1 inhibitor, type III angioedema, or factor XII angioedema are reviewed. Discussion emphasizes pathogenesis, diagnosis, and management

Animal Ca2+ release-activated Ca2+ (CRAC) channels appear to be homologous to and derived from the ubiquitous cation diffusion facilitators

<p>Abstract</p> <p>Background</p> <p>Antigen stimulation of immune cells triggers Ca²⁺entry through Ca²⁺release-activated Ca²⁺(CRAC) channels, promoting an immune response to pathogens. Defects in a CRAC (Orai) channel in humans gives rise to the hereditary Severe Combined Immune Deficiency (SCID) syndrome. We here report results that define the evolutionary relationship of the CRAC channel proteins of animals, and the ubiquitous Cation Diffusion Facilitator (CDF) carrier proteins.</p> <p>Findings</p> <p>CDF antiporters derived from a primordial 2 transmembrane spanner (TMS) hairpin structure by intragenic triplication to yield 6 TMS proteins. Four programs (IC/GAP, GGSEARCH, HMMER and SAM) were evaluated for identifying sequence similarity and establishing homology using statistical means. Overall, the order of sensitivity (similarity detection) was IC/GAP = GGSEARCH > HMMER > SAM, but the use of all four programs was superior to the use of any two or three of them. Members of the CDF family appeared to be homologous to members of the 4 TMS Orai channel proteins.</p> <p>Conclusions</p> <p>CRAC channels derived from CDF carriers by loss of the first two TMSs of the latter. Based on statistical analyses with multiple programs, TMSs 3-6 in CDF carriers are homologous to TMSs 1-4 in CRAC channels, and the former was the precursor of the latter. This is an unusual example of how a functionally and structurally more complex protein may have predated a simpler one.</p

Development of environmental tools for anopheline larval control

<p>Abstract</p> <p>Background</p> <p>Malaria mosquitoes spend a considerable part of their life in the aquatic stage, rendering them vulnerable to interventions directed to aquatic habitats. Recent successes of mosquito larval control have been reported using environmental and biological tools. Here, we report the effects of shading by plants and biological control agents on the development and survival of anopheline and culicine mosquito larvae in man-made natural habitats in western Kenya. Trials consisted of environmental manipulation using locally available plants, the introduction of predatory fish and/or the use of <it>Bacillus thuringiensis </it>var. <it>israelensis </it>(<it>Bti</it>) in various combinations.</p> <p>Results</p> <p>Man-made habitats provided with shade from different crop species produced significantly fewer larvae than those without shade especially for the malaria vector <it>Anopheles gambiae</it>. Larval control of the African malaria mosquito <it>An. gambiae </it>and other mosquito species was effective in habitats where both predatory fish and <it>Bti </it>were applied, than where the two biological control agents were administered independently.</p> <p>Conclusion</p> <p>We conclude that integration of environmental management techniques using shade-providing plants and predatory fish and/or <it>Bti </it>are effective and sustainable tools for the control of malaria and other mosquito-borne disease vectors.</p

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized controlled trial

Background - While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss. Methods/Design - Using a two-arm randomized controlled trial, this 6-month study builds upon the community-based progressive resistance training (PRT) programme Lift for Life® to evaluate whether ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, body composition and cardiometabolic health in older adults with type 2 diabetes. Approximately 200 adults aged 50 to 75 years with type 2 diabetes, treated with either diet alone or oral hypoglycaemic agents (not insulin), will be recruited. All participants will be asked to participate in a structured, supervised PRT programme based on the Lift for Life® programme structure, and randomly allocated to receive a whey-protein drink (20 g daily of whey-protein plus 20 g after each PRT session) plus vitamin D supplements (2000 IU/day), or no additional powder and supplements. The primary outcome measures to be collected at baseline, 3 and 6 months will be glycated haemoglobin (HbA1c) and insulin sensitivity (homeostatic model assessment). Secondary outcomes will include changes in: muscle mass, size and intramuscular fat; fat mass; muscle strength and function; blood pressure; levels of lipids, adipokines and inflammatory markers, serum insulin-like growth factor-1 and 25-hydroxyvitamin D; renal function; diabetes medication; health-related quality of life, and cognitive function. Discussion - The findings from this study will provide new evidence on whether increased dietary protein achieved through the ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, muscle mass and size, and cardiometabolic risk factors in older adults with type 2 diabetes