Category Archives: AMM 2017, Volume 63, Number 1
CRISPR and precision medicine
The deceiving outcome of Jerry Gelsinger’s volunteer enrollment in a genetic study threatened to put the brakes on genetic research. Instead, despite the hidden risks, unanticipated and obviously unwanted, knowledge continued to evolve. The tragic death of a naïve volunteer on the altar of genetics ended in four lessons written by the leading personality and at that time, culprit for the obviously surprising collateral loss . These were perceived at the time as a lecture behind the firewall the Penn University managed to build between James M. Wilson (the geneticist in cause) and the prosecutors . Nine years have passed between J. Gelsinger’s lethal outcome and Wilson’s mea culpa. His death was preceded by seven years of intense research in genetics at the Penn University in the USA.
Today we are confronted with unacceptable mortality in sepsis and septic shock despite large and intense initiatives to oppose it. Antibiotics are either under optimally used, stewardship is reduced sometimes to a matter of perception. These tools are improperly used or inefficient at the end of the day. [More]
The Influence of Some Parameters on Chiral Separation of Ibuprofen by High-Performance Liquid Chromatography and Capillary Electrophoresis
Objective: The aim of the study was to compare the influence of mobile phase composition and temperature on chiral separation of racemic ibuprofen by capillary electrophoresis and high performance liquid chromatography with UV detection.
Materials and methods: Racemic ibuprofen was analysed on a chiral OVM column with an HPLC system 1100 Agilent Technologies, under isocratic elution, by using potassium dihydrogen phosphate 20 mM and ethanol in mobile phase. The flow rate was set at 1 mL/min, UV detector at 220 nm and different column temperatures were tested. For electrophoresis separation an Agilent CE G1600AX Capillary Electrophoresis System system, with UV detection, was used. The electrophoresis analysis was performed at different pH values and temperatures, with phosphate buffer 25 mM and methyl-β-cyclodextrin as chiral selector.
Results: The chromatograhic analysis reveals a high influence of mobile phase pH on ibuprofen enantiomers separation. An elution with a mixture of potassium dihydrogen phosphate 20 mM pH=3 and ethanol, at 25ºC, allowed enantiomers separation with good resolution in less than 8 min.
Conclusions: The proposed HPLC method proved suitable for the separation of ibuprofen enantiomers with a good resolution, but the capillary electrophoresis tested parameters did not allow chiral discrimination.
Relationship Between High Levels of Salivary Cotinine Test and Demographic Characteristics of Pregnant Smokers from Mures County
Objectives: To evaluate the relationship between the frequency of self-declared status regarding smoking in a group of pregnant women from Mures county, Romania and the high levels of Salivary Cotinine (SC) like biomarkers.
Material and methods: It was conducted a retrospective study among 230 pregnant women presented for prenatal care at 50 General Practitioners cabinets in Mures county, Romania, in 2015. Data were collected with a validated questionnaire which included age, level of education, socioeconomic status and ethnicity, also the self-reported smoking status. The Salivary Cotinine level was evaluated using NicAlert Saliva test kits.
Results: Using salivary test we identified a high prevalence of involuntary exposure to cigarette smoke among both non-smokers and those who quit smoking before pregnancy. Also we registered pregnant women that although declared smoking cessation before pregnancy their salivary Cotinine levels were high, almost like to an active smoker, probably because of second-hand exposure or because they didn’t say the truth about their habit.
Conclusions: We underline the importance of implementing more efficient community interventions among this vulnerable group in order to reduce the frequency of smoking and sustain quitting.
Development, Applications, Benefits, Challenges and Limitations of the New Genome Engineering Technique. An Update Study
We assume that the CRISPR Cas9 theory must be delimited by applicability because the consequences of long-term DNA manipulation remain unknown. Moreover, the irreversibility of this procedure should instigate researchers to reserved opinions. Usefulness as well as benefits of CRISPR Cas9 made it one of the most popular and used genome editing technique. But with its huge potential, ethical and safety concerns emerge. Therefore, before continuing research in this direction, we should have a well-organized system that is able to make that differentiation between research and reproduction. However, we truly believe in the future of genetic engineering and with the CRISPR-Cas9 system, we expect that the opportunity of treating now so called incurable diseases arises. Time is all we need.
Precursor Synthesis of Some New Macrocyclic Compounds
Objective: Development of new electronic devices with applications in computer science as well as new medical devices pushed the researcher to find new technologies. Based on those new techniques we have designed and synthesized compounds with possible application in the field of advanced materials.
Material and method: Compounds were analyzed by TLC and NMR. Routine 1H NMR (250 MHz) spectra were recorded at room temperature in deuterated acetone, unless stated otherwise. Thin-layer chromatography (TLC) was carried out on aluminum sheets coated with silicagel 60 F254 Merck TLC plates.
Results: Starting from commercial available compounds intermediates were obtained in a good yield. 4,4′-(2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-diyl)diphenol was obtained starting from pentaerythritol and p-hydroxy-benzaldehyde in the presence of catalytic amounts of APTS (p-toluensulfonic acid). The product was purified by recrystallization and characterized by NMR spectroscopy. The structure exhibit 2 different signals for equatorial and axial position. Furthermore di, tri and tetra ethylene glycol were obtained by microwave assisted synthesis in a matter of minutes. Compounds were separated by recrystallization.
Conclusions: In conclusion, several intermediates were synthesized and characterized from spectroscopic point of view. Further analyses should be carried out and the compounds should be tested as advanced materials.
Kinetics and Mechanism of Drug Release from Loratadine Orodispersible Tablets Developed without Lactose
Objective: The aim of this study is to develop lactose-free orodispersible tablets with loratadine for patients with lactose intolerance.
Materials and methods: Seven compositions (F1-F7) of 10 mg loratadine were prepared in form of orally disintegrating tablets, by direct compression, using croscarmellose sodium and pre-gelatinized starch in various concentrations as superdisintegrants, diluted with microcrystalline cellulose and combined with mannitol and maltodextrin as binder agents. The tablets had been studied in terms of their pharmacotechnical characteristics, by determining: the weight uniformity of the tablets, their friability, breaking strength and disintegration time, drug content and the dissolution profile of loratadine. The statistical analyses were performed with GraphPad Prism Software Inc. As dependent variables, both the hardness of the tablets and their disintegration ability differ between batches due to their compositional differences (as independent variables). DDSolver were used for modeling the kinetic of the dissolution processes by fitting the dissolution profiles with time-dependent equations (Zero-order, First-order, Higuchi, Korsmeyer-Peppas, Peppas-Sahlin).
Results: All proposed formulas shows rapid disintegration, in less than 15 seconds, and the dissolution loratadine spans a period of about 10 minutes. Akaike index as well as R2 adjusted parameter have demonstrated that the studied dissolution profiles are the best fitted by Zero-order kinetic.
Conclusion: In conclusion, association of croscarmellose sodium (7.5%) with pre-gelatinized starch (6%) as superdisintegrants and mannitol as the binder agent (35%), positively influences the dissolution properties of loratadine from orally fast dispersible tablets.
Practical Advantages of CBCT in the Surgical Treatment of Impacted Lower Third Molar
Introduction: The imaging method of cone beam is an improved, extremely accurate computed tomography applicable in the whole field of dentistry. Due to its ability to locate the exact position of the impacted teeth, CBCT software has an important role in the management of difficult cases of impacted third molar. In some situations, the lower third molar is quite near to the inferior alveolar nerve that the surgical extraction can present a high risk of post-operative sensitive impairs of the skin and mucosa of the lower lip and chin on the same side.
Presentation of case series: Our study tried to assess the contribution of CBCT in the pre-operative evaluation and further treatment of patients with impacted third molars in mandibular bone with high risk of inferior alveolar nerve injury. The paper presents three clinical cases showing positive signs on standard OPG, which exhibit indicators of a potential contact between the inferior alveolar nerve and the impacted lower third molars. For an improved exploration Dental CT Scan, DICOM image acquisition program, and 3D reconstruction with a special software were used. Conclusions: The study showed that compared with panoramic radiography, CBCT improve the evaluation of the surgical risk and allow a more accurate planning of surgery.
Characteristics of Sleep Apnea Assessed Before Discharge in Patients Hospitalized with Acute Heart Failure
Objectives. Evaluation of the characteristics of sleep apnea (SA) in patients hospitalized with acute heart failure, considering that undiagnosed SA could contribute to early rehospitalization.
Methods. 56 consecutive patients (13 women, 43 men, mean age 63.12 years) with acute heart failure, in stable condition, underwent nocturnal polygraphy before hospital discharge. The type and severity of SA was determined. Besides descriptive statistics, correlations between the severity of SA and clinical and paraclinical characteristics were also analyzed (t-test, chi-square test, significancy at alpha < 0.05).
Results. 12 (21.4%) subjects were free of SA (AHI – apnea-hipopnea index <5/h), 15 (26.7%) had mild SA (AHI=5-14/h), 17 (30.3%) had moderate SA (AHI 15-30/h), and 12 (21.4 %) had severe SA (AHI>30/h). The apnea was predominantly obstructive (32 cases vs. 12 with central SA). Comparing the patients with mild or no SA with those with severe SA, we did not find statistically significant correlations (p>0.05) between the severity of SA and the majority of main clinical and paraclinical characteristics – age, sex, BMI, cardiac substrates of heart failure, comorbidities. Paradoxically, arterial hypertension (p=0.028) and atrial fibrillation (p=0.041) were significantly more prevalent in the group with mild or no SA.
Conclusions. Before discharge, in the majority of patients hospitalized with acute heart failure moderate and severe SA is present, and is not related to the majority of patient related factors. Finding of significant SA in this setting is important, because its therapy could play an important role in preventing readmissions and improving prognosis.
The Prevalence of Dysphotopsia in Patients with Recent Cataract Surgery
Pseudophakic dysphotopsia are becoming increasingly important as unwanted side effect after cataract surgery. Objective: The purpose of this study is to compare the photic symptoms experienced by patients after cataract surgery.
Material and method: This is a prospective study that included 105 eyes from 99 patients, which underwent uncomplicated phacoemulsification and IOL implantation, between June 2015 and June 2016, performed at Ophthalmology Clinic Tg Mureș. Patients without visually consequential ocular co-morbidity completed a questionnaire, designed to assess subjectively perceived visual functioning and identify symptoms of dysphotopsia.
Results: From the total number of patient, hydrophobic lenses were implanted in 95 patients and 10 patients received hydrophilic lenses. Photic effects were reported in 18% of treated eyes. Although the percentage of dysphotopsia is higher in the hydrophobic lenses category, there was no significant statistical difference between the two categories.
Conclusion: The incidence and significance should not be overlooked, thus visual acuity is not enough for evaluating postoperative visual function.