Two decades of the synthesis of mono- and bis-aminomercapto[1,2,4]triazoles

4-Amino-5-mercapto[1,2,4]triazole and its 3-substituted derivatives have proven to be of biological interest and provide access to a new class of biologically active heterocyclic compounds for biomedical applications. This study will be helpful for scientific researchers interested in the chemistry of bifunctional versatile compounds as it provides a collection of all the methods for the preparation of 3-substituted-4-amino-5-mercapto[1,2,4]triazoles with aliphatic, aromatic, and heterocyclic moieties during the period from 2000 to mid-2020.

4-Amino-5-mercapto[1,2,4]triazole and its 3-substituted derivatives have proven to be of biological interest and provide access to a new class of biologically active heterocyclic compounds for biomedical applications.     

Combination of ventilator care bundle and regular oral care with chlorhexidine was associated with reduction in ventilator associated pneumonia

BackgroundVentilator associated pneumonia (VAP) is an important source of morbidity and mortality in patients receiving mechanical ventilation. VAP is associated with prolongation of mechanical ventilation, ICU and hospital stay and increases in costs.MethodsQuality improvement project. Mechanically ventilated patients received oral care every 8 h with chlorhexidine 2%. A formal process was developed to evaluate compliance with the following ventilator bundle initiatives: head of the bed elevation to 30–45°, daily sedation vacation and assess the readiness to extubate, providing peptic ulcer disease prophylaxis and providing deep vein thrombosis prophylaxis (unless contraindicated).ResultsThe rate of VAP before starting the project, in the first 6 months of year 1431H, was 16.2 cases/1000 ventilator days. Six month after inception of the quality improvement project, the VAP rates decreased to 5.6 cases/1000 ventilator days at the end of 1431H, and at the end of 1432H, it was 5.5 cases/1000 ventilator days. This leads to significant reduction in mortality (adjusted according to APACHE II) from 23.4% to 19.1% (p value 0.024) and the length of stay in ICU from 9.7 to 6.5 days (p value 0.00002).ConclusionThe combination of regular oral hygiene with chlorhexidine 2% and rigorous implementation of ventilator care bundle was associated with significant reduction in VAP rate in mechanically ventilated patients. This has led to reduction in length of stay in ICU from 9.7 to 6.5 days and reduction in mortality from 23.4% to 19.1%.     

Dendritic cells, antibodies reactive with oxLDL, and inflammation

Periodontitis appears to promote chronic inflammatory diseases, including atherosclerosis, but relevant mechanisms need clarification. Oral bacteria induce antibodies that bind not only bacteria, but also oxLDL. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans induce remarkable IgG responses that are dominated by IgG2, and IgG2 is IFN-γ-dependent and is promoted by dendritic cells (DCs). LDL-reactive antibodies induced by P. gingivalis and A. actinomycetemcomitans include anti-phosphorylcholine (α-PC) and β2-glycoprotein-1-dependent anticardiolipin (α-CL), and these antibodies may link chronic inflammatory diseases at a mechanistic level. Antibody-mediated uptake of oxLDL or bacteria dramatically enhances DC-IL-12, and DC-IL-12 induces NK-cell-IFN-γ responses that promote Th-1 responses and sustained inflammation. DCs may be derived from monocytes, and this is striking in cultures of aggressive periodontitis (AgP) monocytes, where DC numbers are about double control levels. Moreover, serum α-CL levels in individuals with AgP are frequently elevated, and these antibodies promote atherosclerosis in persons with antiphospholipid syndrome. Elevated serum levels of soluble-intercellular adhesion molecule, soluble-vascular cell adhesion molecule, and soluble-E-selectin are atherosclerosis-associated indicators of vascular inflammation, and these markers are elevated in the subset of AgP patients with high α-CL. We reason that periodontitis patients with elevated antibodies reactive with oxLDL could be a subgroup at high risk for cardiovascular sequelae.     

Portable solid-state sensor for therapeutic monitoring of an antineoplastic drug; vinblastine in human plasma

During cancer treatment, doses must be carefully administered and monitored to guarantee efficacy and minimize side-effects. A potentiometric sensor was developed for the direct real-time assay of a widely used antineoplastic drug (vinblastine (VB)) in plasma samples. Membrane cocktails were drop-casted over a glassy-carbon electrode coated with a lipophilic conducting polymer (polyaniline). The study investigated five cation exchangers, five plasticizers (of different polarities and dielectric constants), and four ionophores with different physicochemical characters on the sensor performance. The study substantiates a data-driven selection of the optimum membrane recipe. The latter included sodium tetraphenylborate as an ion exchanger, dioctylphthalate as a plasticizer, and hydroxypropyl-β-cyclodextrin as ionophore. The membrane proved a near-Nernstian slope of 37.5 mV per decade, a LOQ of 2.99 × 10⁻⁶ M, and a stable fast response. The selectivity study proved poor responses to common physiological ions. The developed sensor was used for the determination of VB in its pure powder form, marketed formulation, and plasma samples. The fast and direct sensor response enables a wide range of applications in quality control laboratories and clinical studies.

Potentiometric glassy carbon electrode for determination of vinblastine.     

Magnetic resonance imaging of the proximal tibial epiphysis: could it be helpful in forensic age estimation?

There is an increasing demand for age estimations of living persons who are involved in civil and criminal procedures but lack a valid birth certificate indicating their date of birth. Several studies have recommended the application of magnetic resonance imaging (MRI) and assessment of the stage of epiphyseal fusion in age estimation. This study involved retrospective MRI analysis of 335 cases (217 males and 118 females) whose ages ranged from 8 to 28 years (yrs). We assessed the degree of ossification of the proximal tibial epiphysis depending on the classifications of Schmeling and Kellinghaus used for the main stages (I, II, III, IV & V) and substages (IIa, b, c & IIIa, b, c). Significant differences between males and females at stages IIIc, IV and V (p < 0.001) were observed. Additionally, the ossification of the proximal tibial epiphyses occurred earlier in females than in males (2–4 yrs). The mean of ages in stage IV was approximately 18.6 yrs. in females and 22.5 yrs. in males, meaning that stage IV can be used as a valuable forensic marker to determine whether the person in question has reached the age of 18 yrs. We concluded that the application of MRI in the assessment of the ossification status of the proximal tibial epiphysis could be helpful in age estimation for various forensic purposes.