Image Analysis Algorithm-Based Platform for Determining Micron and Higher Aggregate Size Distribution of Therapeutic IgG Using Brightfield and Fluorescence Microscope Images

Pharmaceutical Research - A platform for determining size distribution of micron (1–100 μm) and larger (>?100 μm) aggregates of therapeutic IgG has...     

Mitochondrial dysfunction in an animal model of hyperoxaluria: a prophylactic approach with fucoidan

Oxalate/calcium oxalate toxicity is mediated through generation of reactive oxygen species in a process that partly depends upon events that induce mitochondrial damage. Mitochondrial dysfunction is an important event favoring stone formation. The objective of the present study was to investigate whether mitochondria is a target for oxalate/calcium oxalate and the plausible role of naturally occurring glycosaminoglycans from edible seaweed, fucoidan in ameliorating mitochondrial damage. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I: vehicle treated control, Group II: hyperoxaluria was induced with 0.75% ethylene glycol in drinking water for 28 days, Group III: fucoidan from F. vesiculosus (5 mg/kg b.wt, s.c) from the 8th day of the experimental period, Group IV: ethylene glycol+fucoidan treated rats. The tricarboxylic acid (TCA) cycle enzymes like succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase and respiratory complex enzyme activities were assessed to evaluate mitochondrial function. Oxidative stress was assessed based on the activities of antioxidant enzymes, level of reactive oxygen species, lipid peroxidation and reduced glutathione. Mitochondrial swelling was also analyzed. Ultra structural changes in renal tissue were analyzed with electron microscope. Hyperoxaluria induced a decrease in the activities of TCA cycle enzymes and respiratory complex enzymes. The oxidative stress was evident by the decrease in antioxidant enzymes, glutathione and an increase in reactive species and lipid peroxidation in mitochondria. Mitochondrial damage was evident by increased mitochondrial swelling. Administration of fucoidan, decreased reactive oxygen species, lipid peroxidation (P<0.05), mitochondrial swelling and increased the activities of antioxidant enzymes and glutathione levels (P<0.05) and normalized the activities of mitochondrial TCA cycle and respiratory complex enzymes (P<0.05). From the present study, it can be concluded that mitochondrial damage is an essential event in hyperoxaluria, and fucoidan was able to effectively prevent it and thereby the renal damage in hyperoxaluria.     

Subjective social status in association with various health and socioeconomic indicators in Tehran

Aim

Socioeconomic status (SES) is one of the most important determinants of health. Subjective social status (SSS) is a popular SES indicator. The objective of this study is to compare the associations between health and various SES indicators in order to examine whether SSS is a proper SES indicator.

Subject and methods

In this 2013 cross-sectional study, 1,995 Tehrani residents were selected through multi-stage random sampling. The questionnaires included items on subjective and objective SES, self-rated health (SRH) and objective health status. The crude and adjusted associations between health and SES indicators were assessed using bivariate and multiple logistic regressions.

Results

The crude associations between SSS and all assessed health outcomes were significant. After adjustment of the wealth index, consumption, education and occupation, the associations between SSS and SRH (OR?=?0.69, CI 95 %: 0.55–0.86) and having cardiovascular (OR?=?0.73, CI 95 %: 0.58–0.92), musculoskeletal (OR?=?0.81, CI 95 %: 0.70–0.94), asthma and other respiratory diseases (OR?=?0.71, CI 95 %: 0.54–0.92) still remained significant. The adjusted associations between SSS and having hypertension and diabetes were not significant. SSS had a stronger correlation with the wealth index (Spearman r?=?0.42) compared to other SES indicators.

Conclusion

SSS showed a significant association with most of the health outcomes, independent of other SES indicators; therefore, it can be used in health research, though it is not an exact alternative for other objective SES indicators.

     

Selection for high-level resistance by chronic triclosan exposure is not universal

OBJECTIVES: To investigate the effect of triclosan exposure on the antimicrobial susceptibilities of numerically important dental bacteria. METHODS: A gradient plate technique was used to expose Fusobacterium nucleatum, Lactobacillus rhamnosus, Neisseria subflava, Porphyromonas gingivalis, Actinomyces naeslundii, Prevotella nigrescens, Streptococcus oralis, Streptococcus sanguis, Streptococcus mutans and Veillonella dispar repeatedly to escalating, sublethal concentrations of triclosan. Escherichia coli ATCC 8739 was included as an organism showing the triclosan resistance development trait. MIC values towards chlorhexidine, metronidazole and tetracycline were determined before and after biocide exposure. RESULTS: N. subflava, Pr. nigrescens Po. gingivalis and E. coli were highly susceptible to triclosan (MIC range 0.1-3.9 mg/L), whereas the lactobacillus and S. mutans were less susceptible (MIC range 15.6-20.8 mg/L). Triclosan exposure resulted in a highly significant ( approximately 400-fold) reduction in triclosan susceptibility (P < 0.01) for the positive control E. coli, although its MICs towards chlorhexidine, metronidazole and tetracycline were not significantly altered. Minor ( approximately two-fold) decreases in triclosan susceptibility (MIC) occurred for Pr. nigrescens and in S. sanguis and S. oralis (MBC). Mean changes in susceptibilities (MIC and MBC) of the oral species to chlorhexidine, metronidazole and tetracycline did not exceed two-fold, although chlorhexidine MBCs for S. sanguis were markedly, but transiently, increased. CONCLUSIONS: These data fail to demonstrate biologically significant drug resistance in triclosan-exposed bacteria and suggest that markedly decreased triclosan susceptibility, although confirmed for E. coli, is not a universal phenomenon. Other bacteria possibly possess more susceptible targets than FabI that are highly conserved, which may govern triclosan activity.     

Bronchoscopic Lung Volume Reduction: A New Hope for Patients With Severe Emphysema and Air Trapping

Chronic obstructive pulmonary disease (COPD) is common and has significant morbidity and mortality as the fourth leading cause of death in the United States. In many patients, particularly those with emphysema, COPD is characterized by markedly increased residual volume contributing to exertional dyspnea. Current therapies have limited efficacy. Surgical resection of diseased areas of the lung to reduce residual volume was effective in identified subgroups but also had significant mortality in and suboptimal cost effectiveness. Lung-volume reduction, using bronchoscopic techniques, has shown substantial benefits in a broader patient population with less morbidity and mortality. This review is meant to spread the awareness about bronchoscopic lung-volume reduction and to promote its consideration and early referral for patients with advanced COPD and emphysema frequently encountered by both primary care physicians and specialists. A search was conducted on PubMed (MEDLINE), EMbase, and Cochrane library for original studies, using the following keywords: “lung-volume reduction.” “endobronchial valves,” “intrabronchial valves,” “bronchoscopic lung-volume reduction,” and “endoscopic lung-volume reduction.” We included reports from systematic reviews, narrative reviews, clinical trials, and observational studies. Two reviewers evaluated potential references. A total of 27 references were included in our review. Included studies report experience in the diagnosis and bronchoscopic treatment for emphysema; case reports and non-English or non-Spanish studies were excluded.     

Visit‐to‐visit systolic blood pressure variability predicts treatment‐related adverse event of hyponatremia in SPRINT

Hypertension is a common condition and an important cardiovascular risk factor. SPRINT trial showed that the beneficial effects of targeting systolic blood pressure <120 mm Hg were accompanied by more adverse events. De‐identified SPRINT database was used for this analysis. All subjects in each group that achieved their respective target blood pressure (<120, intensive; <140, standard) were included. Only readings after reaching target blood pressure for the first time were included. Subjects that never reached target or had <2 readings upon reaching target were excluded. Coefficient of Variation (CV) of systolic blood pressure was calculated for each subject to characterize variability. Cox proportional hazards regression was used in the overall cohort as well as the intensive and standard treatment subgroups separately, to identify the effect of CV of systolic blood pressure on occurrence of hyponatremia. P<.05 was considered statistically significant. A total of 8884 subjects met the inclusion criteria; 4323 in intensive and 4561 in standard group. Two hundred and sixty five hyponatremic events occurred in the overall cohort; 168 in intensive, and 127 in standard treatment group. CV of systolic blood pressure consistently and independently predicted a greater hazard of hyponatremia on overall (HR 1.08, P<.001), as well as separate regressions by treatment arms (each HR=1.08 and P<.05). In conclusion, visit‐to‐visit systolic blood pressure variability is independently associated with a small but significant risk of hyponatremia in the SPRINT trial .     

Ultracompact alignment-free single molecule fluorescence device with a foldable light path

Instruments with single-molecule level detection capabilities can potentially benefit a wide variety of fields, including medical diagnostics. However, the size, cost, and complexity of such devices have prevented their widespread use outside sophisticated research laboratories. Fiber-only devices have recently been suggested as smaller and simpler alternatives, but thus far, they have lacked the resolution and sensitivity of a full-fledged system, and accurate alignment remains a critical requirement. Here we show that through-space reciprocal optical coupling between a fiber and a microscope objective, combined with wavelength division multiplexing in optical fibers, allows a drastic reduction of the size and complexity of such an instrument while retaining its resolution. We demonstrate a 4 × 4 × 18 cm(3) sized fluorescence correlation spectrometer, which requires no alignment, can analyze kinetics at the single-molecule level, and has an optical resolution similar to that of much larger microscope based devices. The sensitivity can also be similar in principle, though in practice it is limited by the large background fluorescence of the commonly available optical fibers. We propose this as a portable and field deployable single molecule device with practical diagnostic applications.     

Cortical tubers, cognition, and epilepsy in tuberous sclerosis

Tuberous sclerosis complex is an autosomal-dominant genetic disorder characterized by hamartomatous growth in various organs. Patients who have this disorder exhibit a high rate of epilepsy and cognitive problems. We investigated number of tubers, location, seizure types, and cognitive outcome, and we analyzed the relationships among them in our tuberous sclerosis patients in the Comprehensive Epilepsy Program at the University of Alberta. We also examined the seizure outcome after tuber resection. Our study cohort included 24 patients with tuberous sclerosis complex. We obtained seizure history, electroencephalogram, and neuropsychologic parameters. Magnetic resonance imaging was used to examine tuber numbers and locations. Ten patients underwent surgical removal of tubers responsible for intractable epilepsy. A negative correlation was found between the number of tubers and intelligent quotient score. Epilepsy surgery led to freedom from seizures in this patient group. We demonstrated that the total number and location of cortical tubers play a significant role in the extent of mental retardation in patients with tuberous sclerosis complex. In addition, patients with intractable seizures and well-defined epileptic focus had excellent surgical outcome.     

Prevalence and predictors of osteoporosis in an urban Sri Lankan population

Aim: To determine the prevalence of osteoporosis in both women and men and to determine the association between osteoporosis and selected risk factors among a sample of urban Sri Lankan adults. Methods: The population aged 35–64 years residing in 22 Grama Niladhari divisions, the smallest administrative units in the country, of the Medical Officer of Health area Ragama, Sri Lanka, was identified using the electoral list and stratified into three age groups (n = 3012). A random sample was obtained from each stratum and selected individuals were invited to participate in the study (n = 1100). A structured, interviewer‐administered questionnaire was used to collect information on demographic data and details of risk factors. Bone mineral density (BMD) was measured using a peripheral dual‐energy X‐ray absorptiometry (DEXA) scan in 700 subjects (64%). A BMD < ?2.5 was considered as osteoporosis. Although peripheral DEXA is less sensitive and specific compared to central DEXA it was used in this study as it is less costly and easily transportable. Results: Of the 700 subjects who consented to participate in the study, 60% (n = 421) were females. In subjects < 50 years, 9% of women and 3% of men had osteoporosis. In subjects ≥ 50 years, 27% of women and 7% of men had osteoporosis. Female sex (odds ratio [OR] 12.0), smoking (OR 5.5), age > 50 years (OR 3.1), low BMI (OR 3.1) and low level of education (OR 1.7) were positively associated with osteoporosis. Conclusions: Female sex, age, BMI, smoking and level of education were significant predictors of osteoporosis. The prevalence of osteoporosis increased in both women and men after 50 years.