Jet nebulization of prostaglandin E1 during neonatal mechanical ventilation: Stability, emitted dose and aerosol particle size

BACKGROUND: We have previously reported the safety of aerosolized PGE1 in neonatal hypoxemic respiratory failure. The aim of this study is to characterize the physicochemical properties of PGE1 solution, stability, emitted dose and the aerodynamic particle size distribution (APSD) of PGE1 aerosol in a neonatal ventilator circuit. METHODS: PGE1 was diluted in normal saline and physicochemical properties of the solution characterized. Chemical stability and emitted dose were evaluated during jet nebulization in a neonatal conventional (CMV) or high frequency (HFV) ventilator circuit by a high performance liquid chromatography-mass spectrometry method. The APSD of the PGE1 aerosol was evaluated with a 6-stage cascade impactor during CMV. RESULTS: PGE1 solution in normal saline had a low viscosity (0.9818 cP) and surface tension (60.8 mN/m) making it suitable for aerosolization. Little or no degradation of PGE1 was observed in samples from aerosol condensates, the PGE1 solution infused over 24h, or the residual solution in the nebulizer. The emitted dose of PGE1 following jet nebulization was 32-40% during CMV and 0.1% during HFV. The PGE1 aerosol had a mass median aerodynamic diameter of 1.4 microm and geometric S.D. of 2.9 with 90% of particles being <4.0 microm in size. CONCLUSION: Nebulization of PGE1 during neonatal CMV or HFV is efficient and results in rapid nebulization without altering the chemical structure. On the basis of the physicochemical properties of PGE1 solution and the APSD of the PGE1 aerosol, one can predict predominantly alveolar deposition of aerosolized PGE1.     

Isolation technology for research and development applications: from concept to production

A prototype parenteral manufacturing facility based on isolation technology was designed, constructed, and commissioned at Warner-Lambert Co., Morris Plains, NJ, with emphasis on its application to research and development (R&D) settings. The facility contains closed isolators for holding, transferring, and manufacturing sterile products. Vaporized hydrogen peroxide (VHP) was used for sanitization of the isolators. Various factors were evaluated to ensure complete distribution of VHP inside the isolators. VHP sanitization validation of the isolators was performed using chemical and biological indicators, and by swab testing the inside surfaces of the isolators. On the basis of these studies, operating conditions for routine VHP sanitization of the various isolators were established. Performance qualification of the manufacturing facility was conducted via media fills, which demonstrated sterile integrity of the manufacturing process. The media fills revealed certain deficiencies in handling procedures of filled product, which were subsequently corrected. The Warner-Lambert isolation technology-based parenteral facility proved to be a reliable and cost-effective alternative to standard clean room technology. The facility is ideally suited for manufacturing small batches. Closed isolator technology has its limitations when used for production-size batches involving automated processing.     

Optometric education in the post-COVID-19 era: A time of forced change!

There is a massive disruption of the global economy and education due to the coronavirus disease-2019 (COVID-19) pandemic. This has posed significant challenges and threats to the academic community, especially in health care where the learning and assessment are patient centered. Though blended learning had its emphasis in the pre-COVID-19 era, innovations are required to meet up to the increased demands on learning and assessment. This article uses an inductive approach and outlines the existing challenges, impact of COVID-19 era, the need for a mindset reframe, and the potential opportunities for innovations that underlie during these challenging times.     

Towards patient-centered health services in India--a scale to measure patient perceptions of quality.

OBJECTIVE: . (i) To develop a reliable and valid scale to measure in-patient and outpatient perceptions of quality in India and (ii) to identify aspects of perceived quality which have large effects on patient satisfaction. DESIGN: Cross-sectional survey of health facilities and patients at clinics. SETTING: Primary health centers, community health centers, district hospitals, and female district hospitals in the state of Uttar Pradesh in north India. MAIN OUTCOME MEASURES: Internal consistency, validity, and factor structure of the scale are evaluated. The association between patient satisfaction and perceived quality dimensions is examined. RESULTS: A 16-item scale having good reliability and validity is developed. Five dimensions of perceived quality are identified-medicine availability, medical information, staff behavior, doctor behavior, and hospital infrastructure. Patient perceptions of quality at public health facilities are slightly better than neutral. Multivariate regression analysis results indicate that for outpatients, doctor behavior has the largest effect on general patient satisfaction followed by medicine availability, hospital infrastructure, staff behavior, and medical information. For in-patients, staff behavior has the largest effect followed by doctor behavior, medicine availability, medical information, and hospital infrastructure. CONCLUSIONS: The scale developed can be used to measure perceived quality at a range of facility types for outpatients and in-patients. Perceived quality at public facilities is only marginally favorable, leaving much scope for improvement. Better staff and physician interpersonal skills, facility infrastructure, and availability of drugs have the largest effect in improving patient satisfaction at public health facilities.     

Detection of mycobacterium tuberculosis by nested polymerase chain reaction in a case of subconjunctival tuberculosis.

PURPOSE: To highlight the importance of nested polymerase chain reaction (PCR) in the detection of Mycobacterium tuberculosis in a case of subconjunctival tuberculosis. METHODS: We report a case of a 60-year-old man with subconjunctival nodule in the right eye for duration of 6 weeks. Biopsy of the nodule showed a granuloma with extensive caseation necrosis. Ziehl Neelsen staining for acid-fast bacilli (AFB) was negative. However, because of a strong suspicion of Mycobacterium infection, PCR for M. tuberculosis genome was done, using the nested PCR technique. RESULTS: Polymerase chain reaction for M. tuberculosis showed amplification of Mycobacterium tuberculosis genome with the nested PCR technique. CONCLUSION: Our case indicates that PCR can be a valuable tool in the diagnosis of conjunctival tuberculosis from paraffin sections.     

Metabolic remodeling precedes mitochondrial outer membrane permeabilization in human glioma xenograft cells

Glioma cancer cells adapt to changing microenvironment and shift from mitochondrial oxidative phosphorylation to aerobic glycolysis for their metabolic needs irrespective of oxygen availability. In the present study, we show that silencing MMP-9 in combination with uPAR/cathepsin B switch the glycolytic metabolism of glioma cells to oxidative phosphorylation (OXPHOS) and generate reactive oxygen species (ROS) to predispose glioma cells to mitochondrial outer membrane permeabilization. shRNA for MMP-9 and uPAR (pMU) as well as shRNA for MMP-9 and cathepsin B (pMC) activated complexes of mitochondria involved in OXPHOS and inhibited glycolytic hexokinase expression. The decreased interaction of hexokinase 2 with mitochondria in the treated cells indicated the inhibition of glycolysis activation. Overexpression of Akt reversed the pMU- and pMC-mediated OXPHOS to glycolysis switch. The OXPHOS un-coupler oligomycin A altered the expression levels of the Bcl-2 family of proteins; treatment with pMU or pMC reversed this effect and induced mitochondrial outer membrane permeabilization. In addition, our results show changes in mitochondrial pore transition to release cytochrome?c due to changes in the VDAC-Bcl-XL and BAX-BAK interaction with pMU and pMC treatments. Taken together, our results suggest that pMU and pMC treatments switch glioma cells from the glycolytic to the OXPHOS pathway through an inhibitory effect on Akt, ROS induction and an increase of cytosolic cytochrome c accumulation. These results demonstrate the potential of pMU and pMC as therapeutic candidates for the treatment of glioma.     

Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle

Helicobacter pylori cag+ strains enhance gastric epithelial cell proliferation and attenuate apoptosis in vivo, which may partially explain the increased risk of gastric cancer associated with these strains. The goals of this study were to identify specific H. pylori genes that regulate epithelial cell cycle events and determine whether these effects were dependent upon p53-mediated pathways. AGS gastric epithelial cells were cultured alone or in the presence of 21 clinical H. pylori isolates, H. pylori reference strain 60190, or its isogenic cagA-, picB-, vacA-, or picB-/vacA- derivatives. Coculture of H. pylori with AGS cells significantly decreased cell viability, an effect most prominent with cag+ strains (P < 0.001 versus cag-strains). cag+ strains significantly increased progression of AGS cells from G1 into G2-M at 6 h and enhanced apoptosis by 72 h. Compared with the parental 60190 strain, the picB- mutant attenuated cell cycle progression at 6 h (P < or = 0.05), and decreased apoptosis with enhanced AGS cell viability at 24 h (P < or = 0.04). The vacA- mutant decreased apoptosis and enhanced viability at later (48-72 h) time points (P < or = 0.05). Compared with the wild-type strain, the picB-/vacA- double mutant markedly attenuated apoptosis and increased cell viability at all time points (P < or = 0.05). Furthermore, cocolonization with H. pylori had no significant effect on expression of p53, p21, and MDM2. The diminished AGS cell viability, progression to G2-M, and apoptosis associated with cag+ H. pylori strains were dependent upon expression of vacA and genes within the cag pathogenicity island. These results may explain heterogeneity in levels of gastric epithelial cell proliferation and apoptosis found within H. pyloricolonized mucosa.