Effect of Ambient Temperature on Daily Nebulized Asthma Hospital Visits in a Tropical City of Dhaka, Bangladesh.

The acute effect of temperature on asthma morbidity in Bangladesh is not well understood. As climate varies extensively in different parts of the world, the relation between temperature and asthma might also differ. We investigated the association between temperature and asthma-related hospital visits in the tropical city of Dhaka. We analyzed information from a total of 5989 asthma patients who received ambulatory care in the form of nebulized medication at the National Asthma Center in Mohakhali, Dhaka from February to November 2013. A time-stratified case-crossover study was conducted to estimate the effect of daily temperature, with consideration of delayed effects and possible confounders such as relative humidity and political strikes. An inverse association was observed between temperature and the number of hospital visits. The effect was delayed for approximately a week. A degree centigrade decrease in mean temperature (averaged across lags 0-6) was associated with an increase of approximately 4.5% (95% CI 1.5, 7.5) in all asthma visits. The association was evident in adult males but marginal in elderly males. A positive association (lag 0) was observed among adult females, whereas no association was observed among children. Strikes significantly modified the effect among the elderly. Findings suggest temperature declines affect asthma outcomes in a warm climate, and this effect can be delayed and vary by sex and age group.

Polyamines and its analogue modulates amyloid fibrillation in lysozyme: A comparative investigation.

BACKGROUND: Polyamines can induce protein aggregation that can be related to the physiology of the cellular function. Polyamines have been implicated in protein aggregation which may lead to neuropathic and non neuropathic amyloidosis. SCOPE OF REVIEW: Change in the level of polyamine concentration has been associated with ageing and neurodegeneration such as Parkinson's disease, Alzheimer's disease. Lysozyme aggregation in the presence of polyamines leads to non neuropathic amyloidosis. Polyamine analogues can suppress or inhibit protein aggregation suggesting their efficacy against amyloidogenic protein aggregates. MAJOR CONCLUSIONS: In this study we report the comparative interactions of lysozyme with the polyamine analogue, 1-naphthyl acetyl spermine in comparison with the biogenic polyamines through spectroscopy, calorimetry, imaging and docking techniques. The findings revealed that the affinity of binding varied as spermidine > 1-naphthyl acetyl spermine > spermine. The biogenic polyamines accelerated the rate of fibrillation significantly, whereas the analogue inhibited the rate of fibrillation to a considerable extent. The polyamines bind near the catalytic diad residues viz. Glu35 and Asp52, and in close proximity of Trp62 residue. However, the analogue showed dual nature of interaction where its alkyl amine region bind in same way as the biogenic polyamines bind to the catalytic site, while the naphthyl group makes hydrophobic contacts with Trp62 and Trp63, thereby suggesting its direct influence on fibrillation. GENERAL SIGNIFICANCE: This study, thus, potentiates, the development of a polyamine analogue that can perform as an effective inhibitor targeted towards aggregation of amyloidogenic proteins.

Association between short-term exposure to fine particulate matter and daily emergency room visits at a cardiovascular hospital in Dhaka, Bangladesh.

BACKGROUND: It has been suggested that exposure to fine particulate matter (PM2.5) adversely affects cardiovascular health. However, the effect modifications by individual characteristics and season have been less studied in developing countries where PM2.5 levels are high. OBJECTIVES: To estimate the risks of cardiovascular emergency room visits in relation to daily concentrations of PM2.5 and to assess how these associations can be modified by age, sex, and nutritional status of patients and by season. METHODS: The analytic sample was 6774 adults who visited the emergency room at a cardiovascular disease (CVD) hospital in Dhaka throughout one year (n = 364 days). A time-stratified case-crossover design with conditional Poisson regression analysis was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of visits while adjusting for temperature. Stratification was performed by gender, age (<65 and ≥65 years), BMI (underweight, normal weight, overweight), and season (dry summer: February to April; wet summer: May to October; dry winter: November to January). RESULTS: The mean concentration of PM2.5 was 86.1 µg/m3. An IQR increase (103 µg/m3) in PM2.5 at lag 3 was significantly associated with a 12% (RR: 1.12; 95% CI: 1.01-1.23) increase in CVD emergency room visits. No evidence of association was found for the other lags. Underweight and overweight patients showed evidence of increased risk at lag 2 (RR: 1.31; 95% CI: 1.02-1.67) and lag 4 (RR: 1.20; 95% CI: 1.04-1.39), respectively. CONCLUSION: Increases in the daily concentrations of PM2.5 may lead to more cardiovascular emergency room visits in Dhaka, Bangladesh. Response times from ambient exposure to CVD emergency visits may differ by season and the nutritional status of susceptible individuals, necessitating further research.

Molecular Recognition of tRNA with 1-Naphthyl Acetyl Spermine, Spermine, and Spermidine: A Thermodynamic, Biophysical, and Molecular Docking Investigative Approach.

The role of tRNA in protein translational machinery and the influence of polyamines on the interaction of acylated and deacylated tRNA with ribosomes make polyamine-tRNA interaction conspicuous. We studied the interaction of two biogenic polyamines, spermine (SPM) and spermidine (SPD), with tRNAPhe and compared the results to those of the analogue 1-naphthyl acetyl spermine (NASPM). The binding affinity of SPM was comparable to that of NASPM; both were higher than that of SPD. The interactions led to significant thermal stabilization of tRNAPhe and an increase in the enthalpy of transition. All the interactions were exothermic in nature and displayed prominent enthalpy-entropy compensation behavior. The entropy-driven nature of the interaction, the structural perturbations observed, and docking results proved that the polyamines were bound in the groove of the anticodon arm of tRNAPhe. The amine groups of polyamines were involved in extensive electrostatic, H-bonding, and van der Waals interactions with tRNAPhe. The naphthyl group of NASPM showed an additional stacking interaction with G24 and G26 of tRNAPhe, which was absent in others. The results demonstrate that 1-naphthyl acetyl spermine can target the same binding sites as the biogenic polyamines without substituting for the functions played by them, which may lead to exhibition of selective anticancer cytotoxicity.

Targeting double-stranded RNA with spermine, 1-naphthylacetyl spermine and spermidine: a comparative biophysical investigation.

RNA targeting is an evolving new approach to anticancer therapeutics that requires identification of small molecules to selectively target specific RNA structures. In this report, the interaction of biogenic polyamines spermine, spermidine and the synthetic analogue 1-naphthylacetyl spermine with three double-stranded RNA polynucleotides--poly(I)·poly(C), poly(C)·poly(G), and poly(A)·poly(U)--has been described to understand the structural and thermodynamic basis of the binding and the comparative efficacy of the analogue over the natural polyamines. Circular dichroism spectroscopy, thermal melting experiments, and ethidium bromide displacement assay were used to characterize the interaction. Microcalorimetry studies were performed to deduce the energetics of the interaction and atomic force microscopy experiments done to gain insight into the interaction at the molecular level. The experiments demonstrated structural perturbations in the polynucleotides on binding of the polyamines. Thermal melting studies showed enhanced stabilization of RNA-polyamine complexes with increase in the total standard molar enthalpy of transition. The binding affinity was strongest for poly(I)·poly(C) as revealed by microcalorimetry results and varied as poly(I)·poly(C) > poly(C)·poly(G) > poly(A)·poly(U). The order of affinity for the polyamines was spermine >1-naphthylacetyl spermine > spermidine. Total enthalpy-entropy compensation and high standard molar heat capacity values characterized the interactions. The results of the study on the binding of polyamines to dsRNAs presented here have been compared to those reported earlier with dsDNAs. The present findings advance our knowledge on the mechanism of interaction of polyamines with RNA and may help in the search for analogues that can interfere with biogenic polyamine metabolism and function.

Probing the interaction of spermine and 1-naphthyl acetyl spermine with DNA polynucleotides: a comparative biophysical and thermodynamic investigation.

The interaction of spermine and its analogue, 1-naphthyl acetyl spermine with four double stranded DNA polynucleotides has been studied to understand the structural and thermodynamic basis of the binding. The efficacy and specificity of DNA binding of this analogue has not yet been revealed. The energetics of the interaction was studied by isothermal titration calorimetry and differential scanning calorimetry. Circular dichroism spectroscopy, UV-thermal melting and ethidium bromide displacement assay have been employed to characterize the association. Circular dichroism studies showed that 1-naphthyl acetyl spermine caused a stronger structural perturbation in the polynucleotides. Among the adenine-thymine polynucleotides the alternating polynucleotide was more preferred by naphthyl acetyl spermine compared to the preference of spermine for the homo sequence. The higher melting stabilization revealed by the optical melting and differential scanning calorimetry results suggested that the binding of 1-naphthyl acetyl spermine increased the melting temperature and the total standard molar enthalpy of the transition of adenine-thymine polynucleotides. Microcalorimetry results revealed that unlike spermine the binding of 1-naphthyl acetyl spermine was endothermic. The interaction was characterized by total enthalpy-entropy compensation and high standard molar heat capacity values. There are differences in the mode of association of 1-naphthyl acetyl spermine and spermine. 1-naphthyl acetyl spermine binds with an enhanced affinity with the adenine-thymine hetero polynucleotide. Thus, the result suggests the importance of polyamine analogues and their ability to interfere with normal polyamine interactions.

Binding of the biogenic polyamines to deoxyribonucleic acids of varying base composition: base specificity and the associated energetics of the interaction.

BACKGROUND: The thermodynamics of the base pair specificity of the binding of the polyamines spermine, spermidine, putrescine, and cadaverine with three genomic DNAs Clostridium perfringens, 27% GC, Escherichia coli, 50% GC and Micrococcus lysodeikticus, 72% GC have been studied using titration calorimetry and the data supplemented with melting studies, ethidium displacement and circular dichroism spectroscopy results. METHODOLOGY/PRINCIPAL FINDINGS: Isothermal titration calorimetry, differential scanning calorimetry, optical melting studies, ethidium displacement, circular dichroism spectroscopy are the various techniques employed to characterize the interaction of four polyamines, spermine, spermidine, putersine and cadaverine with the DNAs. Polyamines bound stronger with AT rich DNA compared to the GC rich DNA and the binding varied depending on the charge on the polyamine as spermine>spermidine >putrescine>cadaverine. Thermodynamics of the interaction revealed that the binding was entropy driven with small enthalpy contribution. The binding was influenced by salt concentration suggesting the contribution from electrostatic forces to the Gibbs energy of binding to be the dominant contributor. Each system studied exhibited enthalpy-entropy compensation. The negative heat capacity changes suggested a role for hydrophobic interactions which may arise due to the non polar interactions between DNA and polyamines. CONCLUSION/SIGNIFICANCE: From a thermodynamic analysis, the AT base specificity of polyamines to DNAs has been elucidated for the first time and supplemented by structural studies.

Binding of the anticancer alkaloid sanguinarine with tRNA(phe): spectroscopic and calorimetric studies.

The interaction of the natural plant alkaloid and anticancer agent sanguinarine with tRNA(phe) has been investigated by spectroscopic and calorimetric techniques. Sanguinarine iminium binds to tRNA(phe) cooperatively; alkanolamine does not bind but in presence of large tRNA(phe) concentration, a conversion from alkanolamine to iminium occurs resulting in concomitant binding of the latter. The binding affinity of the iminium to tRNA(phe) obtained from isothermal titration calorimetry was of the order of 10(5) M(-1), which is close to that evaluated from spectroscopy. The binding was driven largely by negative enthalpy and a smaller but favourable positive entropy change. The binding was dependent on the [Na(+)] concentration, but had a larger non-electrostatic contribution to the Gibbs energy. A small heat capacity value and the enthalpy-entropy compensation in the energetics of the interaction characterized the binding of the iminium form to tRNA(phe). This study confirms that the tRNA(phe) binding moiety is the iminium form of sanguinarine.