Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review.

Background: Hydroxychloroquine and Azithromycin combination was used rampantly in management of COVID-19 patients in different countries. Present review was conducted to evaluate the efficacy of Hydroxychloroquine and Azithromycin combination compared to the control (standard care) and any adverse effect following this combination use in COVID-19 patients if any. Material and Methods: We included all the systematic review with or without meta-analysis reporting the effect of Hydroxychloroquine (HCQ) and Azithromycin (AZM) combination use in COVID-19 patient using three databases namely PubMed, medline, CINHAL, Web of Science from July 2020 till Jan 2022. Results: The systematic search strategy has identified 104 studies in total, after removal of duplicates only 4 systematic reviews were included in the qualitative synthesis. The various tools for assessing and reporting the data in the reviews were PRISMA, ROBINS-I, Robs2, AMSTAR, MASTER checklists. Mortality among the hydroxychloroquine with azithromycin combination group was significantly higher than among the Standard Care group. The duration of hospital stay in days was shorter in the Standard Care group in comparison with the hydroxychloroquine group or the hydroxychloroquine and azithromycin combination group. Of the 4 systematic reviews included, 3 had low risk of bias and one had unclear risk of bias using the ROBIS tool. Chloroquine or Hydroxychloroquine combination did not shorten the duration of hospital stay. Conclusion: Rampant use of Chloroquine or Hydroxychloroquine alone or with Azithromycin combination caused adverse effects like QT prolongation. Finally, there is no evidence to support use of either Hydroxychloroquine with or without Azithromycin, for the treatment of COVID-19.

Optimization of a near-zero-emission energy system for the production of desalinated water and cooling using waste energy of fuel cells.

In the present study, a biomass-based multi-purpose energy system that can generate power, desalinated water, hydrogen, and ammonia is presented. The gasification cycle, gas turbine, Rankine cycle, PEM electrolyzer, ammonia production cycle using the Haber-Bosch process, and MSF water desalination cycle are the primary subsystems of this power plant. On the suggested system, a thorough thermodynamic and thermoeconomic evaluation has been conducted. For the analysis, the system is first modeled and investigated from an energy point of view, after which it is similarly studied from an exergy point of view before the system is subjected to economic analysis (exergoeconomic analysis). The system is evaluated and modeled using artificial intelligence to aid in the system optimization process after energy, exergy, and economic modeling and analysis. The resulting model is then optimized using a genetic algorithm to maximize system efficiency and reduce system expenses. EES software does the first analysis. After that, it sends the data to MATLAB program for optimization and to see how operational factors affect thermodynamic performance and overall cost rate. To find the best solution with the maximum energy efficiency and lowest total cost, multi-objective optimization is used. In order to shorten computation time and speed up optimization, the artificial neural network acts as a middleman in the process. In order to identify the energy system's optimal point, the link between the objective function and the choice factors has been examined. The results show that increasing the flow of biomass enhances efficiency, output, and cost while raising the temperature of the gas turbine's input decreases cost while simultaneously boosting efficiency. Additionally, according to the system's optimization results, the power plant's cost and energy efficiency are 37% and 0.3950$/s, respectively, at the ideal point. The cycle's output is estimated at 18900 kW at this stage.

Machine learning approach to predict the biofuel production via biomass gasification and natural gas integrating to develop a low-carbon and environmental-friendly design: Thermodynamic-conceptual assessment.

A hybrid energy cycle (HEC) based on biomass gasification can be suggested as an efficient, modern and low-carbon energy power plant. In the current article, a thermodynamic-conceptual design of a HEC based on biomass and solar energies has been developed in order to generate electric power, heat and hydrogen energy. The planned HEC consists of six main units: two electric energy production units, a heat recovery unit (HRU), a hydrogen energy generation cycle based on water electrolysis, a thermal power generation unit (based on LFR field), and a biofuel production unit (based on biomass gasification process). Conceptual analysis is based on the development of energy, exergy and exergoeconomic assessments. Besides that, the reduction rate of pollutant emission through the planned HEC compared to conventional power plants is presented. In the planned HEC, when hydrogen energy is not needed, excess hydrogen is feed into the combustion chamber to improve system performance and reduce the need for natural gas. Accordingly, the rate of polluting gases emitted from the cycle can be mitigated due to the reduction of fossil fuels consumption. Further, based on the machine learning technique (MLT), the level of biofuel produced from the mentioned process is estimated. In this regard, two algorithms (i.e., Support vector machine and Gaussian process regression) have been employed to develop the prediction model. The findings indicated that the considered HEC can produce about 10.2 MW of electricity, 153 kW of thermal power, and 71.8 kmol/h of hydrogen energy. In both training and testing sets, the Support vector machine model exhibits better behavior compared the two Gaussian process regression model. Based on machine learning technique, with increasing gasification pressure, the level of biofuel obtained from the process does not increase significantly.

Simulation of CO2 capture from natural gas by cyclic pressure swing adsorption process using activated carbon.

This work presented modeling and simulation of CO2 from natural gas. One of the most promising technologies is Pressure Swing Adsorption (PSA), which is an energy-efficient and cost-effective process for separating and capturing CO2 from industrial processes and power plants. This paper provides an overview of the PSA process and its application for CO2 capture, along with a discussion of its advantages, limitations, and future research directions. This process is pressure swing adsorption (PSA) with four adsorption beds. The adsorption bed columns fill with activated carbon as adsorbent. In this simulation momentum, mass and energy balance are solved simultaneously. The process was designed with two beds in adsorption conditions and the other two beds in desorption conditions. The desorption cycle includes blow-down and purge steps. The linear driving force (LDF) estimates the adsorption rate in modeling this process. The extended Langmuir isotherm is used for the equilibrium between solid and gas phases. The temperature changes by heat transfer from the gas phase to solid and axial heat dispersion. The set of partial differential equations is solved using implicit finite difference.

Investigations of microwave absorption performance of bi-layer absorber composed of FeWO4 & BiVO4 nanocomposite powder in 2-18 GHz.

Optimization necessitates every feature to be scrutinized associated with enhancement for microwave absorption. So, interplay between simulation and experiment is a significant aspect to find optimal findings in this regard. Herein, microwave absorption characteristics of as-prepared FeWO4 and BiVO4 nanomaterials were investigated by preparing mono layer and bilayer samples. For the bilayer samples, simulation technique was used to regulate microwave absorption efficiency. Using simulation technique, bilayer sample has achieved a minimum reflection loss (RLmin) of -42 dB with BiVO4 as a top layer (0.6 mm thickness) and FeWO4 as a bottom layer (0.8 mm thickness) with effective absorption Bandwidth (EAB) of 13 GHz (15-2 GHz) at 8.2 GHz frequency. The results show that the layered architecture of the absorbent is substantially responsible for its remarkable microwave absorption efficiency. Simulated results of the bilayer sample were also verified with experimental findings. This work provides a facile synthesis route, novel insights into the design of bilayer absorbent as well as simulation and experimental support for high-performance microwave bilayer absorber.

An Epidemiological Study on the Assessment of Cardiovascular Health Status among Adults in an Urban Area of Teliamura Municipality Area, Khowai, Tripura.

BACKGROUND: In India, cardiovascular disease (CVD) is the largest cause of mortality and morbidity in all regions of the country. Now, to reduce the burden of CVD in our country, we first need to assess cardiovascular health status of the adult population. OBJECTIVE: The aim of this study is to assess cardiovascular health status among adults and to find the influence of sociodemographic factors on it. METHODOLOGY: In a cross-sectional study, cardiovascular health status of 100 sampled adult population of urban area of Teliamura Municipality area, Tripura, was assessed using a pre-designed and pre-tested semi-structured schedule from July 2017 to August 2017. Samples were taken from the adult population by simple random sampling. Collected data were compiled and analyzed using the Statistical Package for the Social Sciences (SPSS 16.0.). The Chi-square and Fisher's exact test were applied to find association. RESULTS: The mean age of the study participants was 44.89 (±13.76) years, comprised 52.0% males and 48% females. Hypertension was seen among 58% of the study population and 77% had ideal (<100 mg/dl) level of fasting blood sugar (FBS). The present study showed obesity, hypertension, high level of total cholesterol, high level of FBS was mostly prevalent among 42-61 years age group. Married people were more obese, hypertensive compared to unmarried. CONCLUSION: Middle age group population were worst affected by high blood pressure, high blood sugar, poor body mass index, and poor level of cholesterol. Healthy lifestyle measures might reduce the burden of CVD which could be evaluated in future research.

A cross-sectional study on the prevalence of anxiety among school students in Teliamura municipality area of Tripura.

BACKGROUND: Anxiety in adolescence has been a serious problem nowadays. It is seen that anxiety among students cause many harms to their mental and physical health affecting their career. OBJECTIVE: The objective of this study is to know about the burden of anxiety among school students and to find out the association of different grades of anxiety with sociodemographic characteristics and any other factors. MATERIALS AND METHODS: In a cross-sectional study, 400 school students of Class IX-XII, from four schools of Teliamura Municipality area of Tripura were included during May 2016-June 2016. Required sample from each school was selected by proportion probability sampling. Then, students were selected using systematic random sampling technique until the sample size from each school was reached. Beck anxiety inventory was used to assess the different grades of anxiety among students. RESULTS: Most of the students were suffering from mild anxiety (49.4%) followed by moderate anxiety (43.3%) and severe anxiety (7.3%). The mean anxiety score of the school students was 16.90 ± 9.02. Female students (10.9%) had more severe anxiety compared to male students (3.8%) and this difference of different grades of anxiety with gender was statistically significant. The association of different grades of anxiety with a history of stressful events in the past 6 months was found to be statistically significant. CONCLUSION: Anxiety was present in each age group and females were suffering more with severe anxiety. Future research on academic anxiety should be done to combat against this problem of anxiety among school students.

Knowledge, attitude, and practice regarding household consumption of iodized salt among rural women of Tripura, India: A mixed-methods study.

INTRODUCTION: Iodine is an essential element for thyroid function; it is necessary in minute amounts for normal growth, development, and well-being of all humans. There is gap in the utilization of adequately iodized salt in the rural areas due to nonavailability, poverty, poor knowledge of iodine deficiency diseases, and faulty storage practices. OBJECTIVE: The objective was to find out knowledge, attitude, and practices (KAP) regarding iodized salt consumption and association of sociodemographic factors, if any, among rural women of Tripura. MATERIALS AND METHODS: This community-based study was conducted among 270 rural women residing at Madhupur village, Tripura. A self-made pretested schedule (Cronbach's alpha = 0.7) was used as the study tool to collect information on KAP regarding iodized salt consumption. RESULTS: Majority of the participants belonged to 31-40 years (30.4%), with a mean age of 38.6 (±13.8) years; all were predominantly Hindus (90.4%). Knowledge and attitude regarding iodized salt consumption were significantly associated with age groups ≤36 years, literacy, and general caste (P < 0.05), but practice was not significant (P > 0.05). Good knowledge and attitude regarding use of iodized packed salt were less than half (46.7% and 41.1%, respectively), but higher level (83.3%) of correct practice was found (P > 0.05). CONCLUSION: The existing knowledge and attitude of participants toward iodized salt usage were less, but majority were consuming iodized salt without knowing its benefits. Hence, there is a need to educate rural people through nutrition education or knowledge, with active participation of grassroot level workers in generating awareness about the health benefits of consuming adequately iodized salt.

Awareness, treatment, and control of hypertension among adult population in a rural community of Singur block, Hooghly District, West Bengal.

BACKGROUND: Hypertension is an important treatable public health problem both globally and in India with an increasing prevalence significantly in both urban and rural population. It is one of the leading causes of adult mortality and morbidity, but poorly controlled hypertension remains a major health problem. OBJECTIVE: The objective of this study was to find out awareness, treatment, and control of hypertension among study population and association of hypertension awareness with sociodemographic factors, if any. MATERIALS AND METHODS: This study was conducted from May 2013 to April 2014 in the rural community of Singur block, West Bengal. Data were collected with respect to sociodemographic characteristics as well as records related to hypertension such as awareness, treatment, and control of hypertension. Blood pressure (BP) measurement of individuals aged 20 years and above of both sexes was done. Pearson's Chi-square test was performed to find out the association between the categorical variables. SPSS 19.00 software was used for analysis. RESULTS: Nearly 48.2% of the participants were aware of their elevated BP; 47.1% of the participants were taking pharmacological treatment, mostly allopathic and only 8.8% had their BP under control. A statistically significant association was found between age, education, and socioeconomic status (per capita income) with awareness of hypertension. CONCLUSION: Lack of awareness of the disease and very low rate of control of hypertension among those who were treated became the major issues. These findings emphasize the need for dissemination of knowledge about the disease and counseling of the patients during treatment continuation.

An Epidemiological Study of Blood Pressure and Its Relation with Anthropometric Measurements among Schoolboys of Burdwan Municipal Area, West Bengal.

BACKGROUND: High blood pressure (BP) is often an underdiagnosed problem, because of the asymptomatic nature in early phases of onset during adolescence. This increases the chances of developing complications later during adult life. OBJECTIVE: The objective of this study was to find the relationship of BP with anthropometric measurements among school-going adolescent boys. MATERIALS AND METHODS: It was a cross-sectional study conducted among 894 adolescent schoolboys aged 13 to 18 years from July 2013 to October 2014 in schools of Burdwan Municipal area, West Bengal. The required number of students from each school was determined by proportional probability sampling. Then, the required number of students from each school was selected by systematic random sampling technique. BP and anthropometric measurements such as weight, height, and waist circumference were done using standard guidelines. RESULTS: The mean systolic and mean diastolic BP in the study participants was significantly higher with an increase in weight, height, waist circumference, and body mass index (BMI) (P < 0.05). BP was found to be positively correlated with different anthropometric measurements such as weight, height, waist circumference, and BMI, which were statistically significant. CONCLUSION: Early detection of high BP and application of lifestyle modification among adolescents will be helpful in reducing the burden of high BP in adult life.

Orcinol Glucoside Loaded Polymer - Lipid Hybrid Nanostructured Lipid Carriers: Potential Cytotoxic Agents against Gastric, Colon and Hepatoma Carcinoma Cell Lines.

PURPOSE: Orcinol glucoside (OG) - loaded nanostructured lipid carrier (NLC), coated with polyethylene glycol-25/55-stearate (PEG-25/55-SA), were explored for delivering OG to improve in vitro cytotoxicity against gastrointestinal tract (GIT), colon and hepatoma carcinoma cell lines. It is being expected that the PEGylated formulations would possess the sustainability in withstanding the adverse physiological extremities like the most significant metabolic activities and phase I / II enzymatic activities in the intestines. METHODS: NLCs were prepared using tristearin, oleic acid and PEG-25/55-stearate by hot homogenization-ultrasonic dispersion; characterized by DLS, TEM, SEM, AFM, entrapment efficiency and drug loading capacity studies. RESULTS: NLC diameter ranged from 160 to 230 nm with negative zeta potential of -8 to -20 mV. TEM/SEM and AFM studies suggest spherical and smooth surface morphologies. Differential scanning calorimetry studies reveal the loss of crystallinity when OG was incorporated into the NLC. NLCs showed initial burst release, followed by sustained release of OG. PEG-NLC exhibited superior anticancer activity against GIT and also in hepatoma cancer cell lines. CONCLUSIONS: This is the first report demonstrating a practical approach for possible oral delivery of OG in GIT and targeting hepatoma cancer, warranting further in vivo studies for superior management of GIT cancer.

Paradoxical Bactericidal Effects of Hydrophobic Lung Surfactant Proteins and Their Peptide Mimics Using Liposome Molecular Trojan.

Lung surfactant, besides alveolar stability, also provides defence against pathogens by surfactant proteins (SP), SP-A and SP-D. The hydrophobic proteins SP-B and SP-C enhance surface activity. An unusual and paradoxical effect of bovine LS and synthetic model LS with SP-B/-C was bactericidal to Staphylococcus aureus and Escherichia coli. Bacterial proliferation were investigated with bovine lung surfactant extract (BLES), dipalmitoylphosphatdylcholine, palmitooleylglycerol, in combination with SP-B/-C using standard microbiological colony forming unit (CFU) counts and structural imaging. BLES and other surfactant-SP-B/-C mixtures inhibit bacterial growth in the concentration range of 0 -7.5 mg/mL, at > 10 mg/mL paradoxical growth of both the bacterial species suggest antibiotic resistance. The lipid only LS have no effect on bacterial proliferation. Smaller peptide mimics of SP-B or SP-B1-25, were less efficient than SP-Cff. Ultra structural studies of the bacterial CFU using electron and atomic force microscopy suggest some membrane damage of S. aereus at inhibitory concentration of BLES, and some structural alteration of E. coli at dividing zones, suggesting utilization and incorporation of surfactant lipid species by both bacteria. The results depicted from in vitro studies are also in agreement with protein-protein interactions obtained from PatchDock, FireDock and ClasPro algorithm. The MD-simulation decipher a small range fluctuation of gyration radius of the LS proteins and their peptide mimics. The studies have alarming implications in the use of high dosages (100 mg/mL/kg body weight) of exogenous surfactant for treatment of respiratory distress syndrome, genetic knock-out abnormalities associated with these proteins, and the novel roles played by SP-B/C as bactericidal agents.

Quality of life among geriatric population: A cross-sectional study in a rural area of Sepahijala District, Tripura.

BACKGROUND: Quality of life (QOL) among elderly is an important area of concern which reflects the health status and well-being of this vulnerable population. OBJECTIVES: The objective of this study is to find out different domains of QOL and its association with sociodemographic factors among geriatric population. METHODS:: A community-based cross-sectional study was done among 76 persons aged 60 years and above from August 2016 to October 2016 in rural areas of Madhupur, Sepahijala district, Tripura. The World Health Organization QOL-BREF scale was used and analysis was done using SPSS version 20.0 statistical software. P < 0.05 was considered as statistically significant. RESULTS: The mean QOL score was maximum in social health domain (67.32 ± 15.30), followed by environmental health (51.64 ± 10.11), lowest was in psychological domain (44.29 ± 11.50). Better physical health domain score was found among participants <70 years age. Psychological health was better among Hindu and persons from nuclear family and higher socioeconomic class, whereas male, illiterate, and businessman had better social relationship. Environmental domain score was significantly better among primary educated, businessman, and higher socioeconomic class people. CONCLUSION: The present study revealed social relationship domain had higher mean QOL score in comparison to other domains, but contrastingly psychological domain was affected worst in "old age group." Further research can be done to explore the factors affecting psychological domain.

Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.

Lung surfactant is a complex mixture of lipid and protein, responsible for alveolar stability, becomes dysfunctional due to alteration of its structure and function by leaked serum materials in disease. Serum proteins, cholesterol and low density lipoprotein (LDL) were studied with bovine lipid extract surfactant (BLES) using Langmuir films, and bilayer dispersions using Raman spectroscopy. While small amount of cholesterol (10 wt%) and LDL did not significantly affect the adsorption and surface tension lowering properties of BLES. However serum lipids, whole serum as well as higher amounts of cholesterol, and LDL dramatically altered the surface properties of BLES films, as well as gel-fluid structures formed in such films observed using atomic force microscopy (AFM). Raman-spectroscopic studies revealed that serum proteins, LDL and excess cholesterol had fluidizing effects on BLES bilayers dispersion, monitored from the changes in hydrocarbon vibrational modes during gel-fluid thermal phase transitions. This study clearly suggests that patho-physiological amounts of serum lipids (and not proteins) significantly alter the molecular arrangement of surfactant in films and bilayers, and can be used to model lung disease.

Physicochemical studies on the interaction of serum albumin with pulmonary surfactant extract in films and bulk bilayer phase.

Functionality, structure and composition of the adsorbed films of bovine lipid extract surfactant (BLES), in the absence and presence of bovine serum albumin (BSA), at the air-buffer interface was characterized through surface tension, atomic force microscopy and time of flight secondary ion mass spectrometric methods. Gel and fluid domains of BLES films were found to be altered significantly in the presence of BSA. Differential scanning calorimetric studies on BLES dispersions in presence of BSA revealed that the perturbations of the lipid bilayer structures were significant only at higher amount of BSA. FTIR studies on the BLES dispersions in buffer solution revealed that BSA could affect the lipid head-group hydrations in bilayer as well as the methylene and methyl vibration modes of fatty acyl chains of the phospholipids present in BLES. Serum albumin could perturb the film structure at pathophysiological concentration while higher amount of BSA was required in perturbing the bilayer structures. The studies suggest a connected perturbed bilayer to monolayer transition model for surfactant inactivation at the alveolar-air interface in dysfunctional surfactants.

Molecular dynamics simulations of lung surfactant lipid monolayers.

Pulmonary surfactant provides for a lipid rich film at the lung air-water interface, which prevents alveolar collapse at the end of expiration. The films are likely enriched in the major surfactant component dipalmitoylphosphatidylcholine (DPPC), which, due to its saturated fatty acid chains, can withstand high surface pressures up to 70 mN/m, thereby reducing surface tension in that interface to very low values (close to 1 mN/m). Despite many experimental measurements in situ, as well as in vitro for native lung surfactant films, the exact mechanism by which other fluid lipid components of surfactant, in combination with surfactant proteins, allow for such low surface tension values to be reached is not well understood. We have performed molecular dynamics simulation of films composed of DPPC alone and in mixtures with other fluid and acidic lipid components of surfactant at the high densities relevant to the low surface tension regime. 10-50 ns simulations were performed with the software GROMACS, with 40-64 lipids molecules plus water, using 5 different lipid compositions and 7 different areas per lipid. The primary focus was to learn how differences in lipid composition affect the response of the monolayer to compression, such as the development of curvature or the loss of lipids to the exterior of the monolayer. The systems studied exhibit features of two of the major schools of thought of lung surfactant mechanisms, in that although unsaturated lipids did not appear to prevent the monolayers from achieving high surface pressure, POPG did appear to be selectively squeezed out of the DPPC/POPG monolayers at high lipid densities.

Interfacial organizations of gel phospholipid and cholesterol in bovine lung surfactant films.

Pulmonary surfactants stabilize the lung by way of reducing surface tension at the air-lung interface of the alveolus. 31P NMR, thin-layer chromatography, and electrospray ionization mass spectroscopy of bovine lipid extract surfactant (BLES) confirmed dipalmitoylphosphatidylcholine (DPPC) to be the major phospholipid species, with significant amounts of palmitoyl-oleoylphosphatidylcholine, palmitoyl-myristoylphosphatidylcholine, and palmitoyl-oleoylphosphatidylglycerol. BLES and DPPC spread at the air-water interface were studied through surface pressure area, fluorescence, and Brewster angle microscopy measurements. Langmuir-Blodgett films of monomolecular films, deposited on mica, were characterized by atomic force microscopy. BLES films displayed shape, size, and vertical height profiles distinct from those of DPPC alone. Calcium ions in the subphase altered BLES film domain structure. The addition of cholesterol (4 mol %) resulted in the destabilization of compressed BLES films at higher surface pressures (>40 mN m-1) and the formation of multilayered structures, apparently consisting of stacked monolayers. The studies suggested potential roles for individual surfactant lipid components in supramolecular arrangements, which could be the contributing factors in pulmonary surfactant to attain low surface tension at the air-water interface.

Interactions of serum with lung surfactant extract in the bronchiolar and alveolar airway models.

Lung surfactant (LS) a lipid-protein mixture is secreted by type-II pneumocytes and prevents alveolar collapse as well as maintains upper airway patency. In certain lung pathophysiology dysfunction of the LS occurs due to leakage of serum derived materials interacting with surfactant at the respiratory air-water interface. Bovine lipid extract surfactant (BLES) with and without foetal calf serum (FCS) were studied as models of bronchiolar airway patency using a capillary surfactometer, and in alveolar (terminal) airway using adsorbed Langmuir films in a surface balance. About 5 wt.% of serum was found to maximally decrease airway patency of BLES by 90%, as well as the surface films ability to reach low surface tension below 25 mN/m. In fact, FCS was found to be about 200-fold more potent inhibitor of the surfactant extract compared to a major serum component, albumin. Also serum but not albumin significantly reduced the gel-phase structures found in BLES films under compression at low amounts (5-10 wt.%), and eventually abolished these organized structures as imaged by fluorescence and atomic force microscopy. This fact suggests that serum caused complete molecular re-organization of the surfactant lipids in films at an air-water interface, and the ability of such films to reduce surface tension or maintain airway patency. The study may provide a novel structure-function disruption model for lung surfactant inactivation in the airways in pathophysiology.

An X-ray diffraction study of alterations in bovine lung surfactant bilayer structures induced by albumin.

Lung surfactant (LS) is an extra-cellular lipid-protein system responsible for maintaining low surface tension in the lung and alveolar stability. Serum proteins cause dysfunction of this material, e.g. in adult respiratory distress syndrome (ARDS). BLES is a clinically used LS consisting of most of the lipids and associated proteins from bovine lung lavage. Aqueous phases of BLES at 30% and 70% hydration, with and without 5% by weight of bovine serum albumin (BSA), calculated on the amount of lipids, were studied using X-ray diffraction during cooling from 42 to 5 degrees C. The diffraction curves are consistent with a transition from a lamellar liquid crystalline phase to a gel phase transition at cooling in the interval 30-20 degrees C. The long-spacings correspond to a reduction of the bilayer thickness during this transition. The wide-angle region shows a peak at 4.1 A below 25 degrees C, which is characteristic of the hexagonal chain packing of the gel phase. The perturbation of the bilayers by the presence of BSA seems to induce a significant decrease of the bilayer thickness. Calculations on the observed limits of swelling (taking place in the range 50-60%) indicate that BSA is closely associated with the BLES bilayers, probably due to electrostatic interaction with the cationic surfactant proteins SP-B and SP-C. This study show that the LS lipid structural organizations are extremely susceptible to small amounts of serum albumin, which may have implications in surfactant related lung disease and clinical applications of surfactant therapy.

Probing perturbation of bovine lung surfactant extracts by albumin using DSC and 2H-NMR.

Lung surfactant (LS), a lipid-protein mixture, forms films at the lung air-water interface and prevents alveolar collapse at end expiration. In lung disease and injury, the surface activity of LS is inhibited by leakage of serum proteins such as albumin into the alveolar hypophase. Multilamellar vesicular dispersions of a clinically used replacement, bovine lipid extract surfactant (BLES), to which (2% by weight) chain-perdeuterated dipalmitoylphosphatidycholine (DPPG mixtures-d(62)) had been added, were studied using deuterium-NMR spectroscopy ((2)H-NMR) and differential scanning calorimetry (DSC). DSC scans of BLES showed a broad gel to liquid-crystalline phase transition between 10-35 degrees C, with a temperature of maximum heat flow (T(max)) around 27 degrees C. Incorporation of the DPPC-d(62) into BLES-reconstituted vesicles did not alter the T(max) or the transition range as observed by DSC or the hydrocarbon stretching modes of the lipids observed using infrared spectroscopy. Transition enthalpy change and (2)H-NMR order parameter profiles were not significantly altered by addition of calcium and cholesterol to BLES. (2)H-NMR spectra of the DPPC-d(62) probes in these samples were characteristic of a single average lipid environment at all temperatures. This suggested either continuous ordering of the bilayer through the transition during cooling or averaging of the DPPC-d(62) environment by rapid diffusion between small domains on a short timescale relative to that characteristic of the (2)H-NMR experiment. Addition of 10% by weight of soluble bovine serum albumin (1:0.1, BLES/albumin, dry wt/wt) broadened the transition slightly and resulted in the superposition of (2)H-NMR spectral features characteristic of coexisting fluid and ordered phases. This suggests the persistence of phase-separated domains throughout the transition regime (5-35 degrees C) of BLES with albumin. The study suggests albumin can cause segregation of protein bound-lipid domains in surfactant at NMR timescales (10(-5) s). Persistent phase separation at physiological temperature may provide for a basis for loss of surface activity of surfactant in dysfunction and disease.