Do mitochondrial DNA haplogroups play a role in susceptibility to tuberculosis?

BACKGROUND AND OBJECTIVES: Mitochondrial DNA has a unique role in ATP production and subsequent mitochondrial reactive oxygen species (ROS) production in eukaryotic cells and there is a potential role for ROS and oxygen burst against Mycobacterium tuberculosis, an intracellular pathogen. This study aimed to determine whether the frequency of different mitochondrial haplogroups was significantly different in patients with tuberculosis (TB) compared with a normal population. METHODS: Mitochondrial DNA haplogroups M, N, J and K were studied by PCR-restriction fragment length polymorphism and sequencing. Cases were 54 patients with confirmed smear positive pulmonary TB. Controls were 256 healthy persons. RESULTS: There were no statistically significant differences between those with TB and the control group. CONCLUSIONS: There was no statistically significant association between mtDNA haplogroups and the presence of TB infection.     

Fox‐Fordyce Disease Exacerbated by Hyperhidrosis

Abstract: Fox‐Fordyce disease is an uncommon disorder primarily affecting postpubertal females. It is characterized by intensely pruritic, papular eruptions in apocrine‐gland bearing regions. Rarity and scant literature have resulted in a lack of definitive treatment options or pathognomonic diagnostic indicators. We report a 16‐year‐old boy with typical findings of Fox‐Fordyce disease including numerous, grouped, rounded (1–3 mm), skin‐colored papules confined to the axillary and periareolar areas, bilaterally. These lesions started before puberty, and were exacerbated by hyperhidrosis.     

Comparison of In Vitro Deposition of Pharmaceutical Aerosols in an Idealized Child Throat with In Vivo Deposition in the Upper Respiratory Tract of Children

Purpose

Deposition of drug emitted from two commercially available inhalers was measured in an in vitro child oral airway model and compared to existing in vivo data to examine the ability of the child model to replicate in vivo deposition.

Methods

In vitro deposition of drug from a QVAR® pressurized metered dose inhaler (pMDI) and Pulmicort® Turbuhaler® dry powder inhaler (DPI) in an Idealized Child Throat (1) and downstream filter was measured using UV spectroscopy and simulated realistic breathing profiles. Potential effects of ambient relative humidity ranging from 10% to 90% on deposition were also considered.

Results

In vitro QVAR pMDI deposition in the idealized mouth-throat at 50% RH (39.2?±?2.3% of delivered dose) compared well (p?>?0.05) with in vivo extrathoracic deposition in asthmatic children age 8 to 14 (45.8?±?12.3%). In vitro Turbuhaler DPI deposition in the idealized mouth-throat at 50% RH (69.0?±?1.5%) matched in vivo extrathoracic deposition (p?>?0.05) in 6 to 16 year old children with cystic fibrosis (70.4?±?21.2%). The effects of ambient humidity were found to be insignificant for Turbuhaler and minor for QVAR.

Conclusions

The Idealized Child Throat successfully mimics in vivo deposition data in school age children for the inhalers tested, and may provide a standard platform for optimizing pediatric treatment with inhaled pharmaceutical aerosols.     

Congenital heart defects among Down syndrome patients: a clinical profiling

Aim

The incidence of Down syndrome (DS) has been estimated one case in 814 live births in Iranian population. Congenital heart defects (CHDs) are a major cause of morbidity and mortality in DS patients ranges from 40 to 60 %. To the author’s knowledge, there is no data available for the prevalence and types of CHD in patients with DS in south of Iran. Accordingly, this study aimed to determine the prevalence of CHD among DS patients, and to evaluate the 14 clinical features in DS patients with and without CHD.

Subjects and methods

In the current study, a total of 110 patients diagnosed with DS (55 individuals with CHD and 55 without CHD) were included after postnatal cytogenetic analysis. The demographic and clinical features of all subjects were collected using a precodified questionnaire and clinical examination and then were analyzed using SPSS software.

Results

We found that the atrial septal defect (ASD) was the most common defect accounting for 41.82 % of DS followed by patent ductus arteriosis (PDA) (20 %), ventricular septal defect (VSD; 14.54 %), atrioventricular septal defect (AVSD; 12.73 %) and tetralogy of fallot (TOF; 10.91 %) in our population. Indeed, our results showed that pulmonary hypertension and low set ear clinical manifestations were significantly associated with CHD in DS patients (P?<?0.05).

Conclusion

We found that the ASD is the most common CHD seen in DS patients. In addition, our results add to the existing body of evidence that pulmonary hypertension significantly associated with CHD in DS patients. We believe this clinical profiling can become the baseline for intervention in reducing the mortality and morbidity secondary to CHD among DS in our population.

     

Advanced testing method to evaluate the performance of respirator filter media

Filter media for respirator applications are typically exposed to the cyclic flow condition, which is different from the constant flow condition adopted in filter testing standards. To understand the real performance of respirator filter media in the field it is required to investigate the penetration of particles through respirator filters under cyclic flow conditions representing breathing flow patterns of human beings. This article reports a new testing method for studying the individual effect of breathing frequency (BF) and peak inhalation flow rate (PIFR) on the particle penetration through respirator filter media. The new method includes the use of DMA (Differential Mobility Analyzer)-classified particles having the most penetrating particle size, MPPS (at the constant flowrate of equivalent mean inhalation flow rate, MIFR) as test aerosol. Two condensation particle counters (CPCs) are applied to measure the particle concentrations at the upstream and downstream of test filter media at the same time. Given the 10 Hz sampling time of CPCs, close-to-instantaneous particle penetration could be measured. A pilot study was performed to demonstrate the new testing method. It is found that the effect of BF on the particle penetration of test respirator filter media is of importance at all the tested peak inhalation flow rates (PIFRs), which is different from those reported in the previous work.     

Peloruside, Laulimalide, and Noscapine Interactions with Beta-Tubulin

This article reviews the recent findings regarding the binding sites, binding modes and binding affinities of three novel antimitotic drugs peloruside, laulimalide and noscapine with respect to tubulin as the target of their action. These natural compounds are shown to bind to β-tubulin and stabilize microtubules for the cases of peloruside A and laulimalide, and prolong the time spent in pause for noscapine. Particular attention is focused on β-tubulin isotypes as targets for new cancer chemotherapy agents and the amino acid differences in the binding site for these compounds between isotypes. We propose a new strategy for antimitotic drug design that exploits differential distributions of tubulin isotypes between normal and cancer cells and corresponding differential affinities between various drug molecules and tubulin isotypes.     

Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin

Purpose

To explore possible ways in which yew tree tubulin is naturally resistant to paclitaxel. While the yew produces a potent cytotoxin, paclitaxel, it is immune to paclitaxel’s cytotoxic action.

Methods

Tubulin sequence data for plant species were obtained from Alberta 1000 Plants Initiative. Sequences were assembled with Trinity de novo assembly program and tubulin identified. Homology modeling using MODELLER software was done to generate structures for yew tubulin. Molecular dynamics simulations and molecular mechanics Poisson–Boltzmann calculations were performed with the Amber package to determine binding affinity of paclitaxel to yew tubulin. ClustalW2 program and PHYLIP package were used to perform phylogenetic analysis on plant tubulin sequences.

Results

We specifically analyzed several important regions in tubulin structure: the high-affinity paclitaxel binding site, as well as the intermediate binding site and microtubule nanopores. Our analysis indicates that the high-affinity binding site contains several substitutions compared to human tubulin, all of which reduce the binding energy of paclitaxel.

Conclusions

The yew has achieved a significant reduction of paclitaxel’s affinity for its tubulin by utilizing several specific residue changes in the binding pocket for paclitaxel.