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.     

Iron dysregulation in Alzheimer's disease: multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents

Considering the multi-etiological character of Alzheimer's disease (AD), the current pharmacological approaches using drugs oriented towards a single molecular target possess limited ability to modify the course of the disease and thus, offer a partial benefit to the patient. In line with this concept, novel strategies include the use of a cocktail of several drugs and/or the development of a single molecule, possessing two or more active neuroprotective-neurorescue moieties that simultaneously manipulate multiple targets involved in AD pathology. A consistent observation in AD is a dysregulation of metal ions (Fe²⁺, Cu²⁺ and Zn²⁺) homeostasis and consequential induction of oxidative stress, associated with beta-amyloid aggregation and neurite plaque formation. In particular, iron has been demonstrated to modulate the Alzheimer's amyloid precursor holo-protein expression by a pathway similar to that of ferritin L-and H-mRNA translation through iron-responsive elements in their 5′UTRs. This review will discuss two separate scenarios concerning multiple therapy targets in AD, sharing in common the implementation of iron chelation activity: (i) novel multimodal brain-permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities; (ii) natural plant polyphenols (flavonoids), such as green tea epigallocatechin gallate (EGCG) and curcumin, reported to have access to the brain and to possess multifunctional activities, such as metal chelation-radical scavenging, anti-inflammation and neuroprotection.     

Demonstration of In Vitro Host-Guest Complex Formation and Safety of para-Sulfonatocalix[8]arene as a Delivery Vehicle for Two Antibiotic Drugs

The macrocycle para-sulfonatocalix[8]arene, sCX[8], was examined with 2 antibiotic drugs, ciprofloxacin (CIP) and isoniazid. The drugs were shown to form complexes with sCX[8] using proton nuclear magnetic resonance, thermogravimetric analysis, fluorescence spectroscopy, and molecular modeling. Both drugs form 1:1 hydrated (H₂O: 13%-14% w/w) host-guest complexes, with sCX[8] binding around the pyridine ring of isoniazid, and around the piperazine and cyclopropane rings of CIP. From proton nuclear magnetic resonance, the binding constant of isoniazid to sCX[8] was 6.8 (±0.3) × 10³ M^?1. Addition of 2 equivalents of sCX[8] to CIP resulted in a 58% decrease in fluorescence, and time-resolved fluorescence anisotropy of CIP doubles with sCX[8]. Each drug binds into the cavity of the macrocycle, with binding stabilized via combinations of hydrogen bonding, electrostatic interactions, π-π stacking, and hydrophobic effects. The safety of sCX[8] was examined in vitro with human embryonic kidney 293 cells. The IC₅₀ of sCX[8] was 559 μM, which is a minimum of 5-fold higher than the concentration that would be used in the clinic. The in vitro effect of sCX[8] on the action of CIP was examined on a panel of bacterial lines. The results showed that sCX[8] has no inherent antibiotic activity and had no negative effect on the action of CIP.     

In-Situ Molecular Vapor Composition Measurements During Lyophilization

Purpose

Monitoring process conditions during lyophilization is essential to ensuring product quality for lyophilized pharmaceutical products. Residual gas analysis has been applied previously in lyophilization applications for leak detection, determination of endpoint in primary and secondary drying, monitoring sterilization processes, and measuring complex solvents. The purpose of this study is to investigate the temporal evolution of the process gas for various formulations during lyophilization to better understand the relative extraction rates of various molecular compounds over the course of primary drying.

Methods

In this study, residual gas analysis is used to monitor molecular composition of gases in the product chamber during lyophilization of aqueous formulations typical for pharmaceuticals. Residual gas analysis is also used in the determination of the primary drying endpoint and compared to the results obtained using the comparative pressure measurement technique.

Results

The dynamics of solvent vapors, those species dissolved therein, and the ballast gas (the gas supplied to maintain a set-point pressure in the product chamber) are observed throughout the course of lyophilization. In addition to water vapor and nitrogen, the two most abundant gases for all considered aqueous formulations are oxygen and carbon dioxide. In particular, it is observed that the relative concentrations of carbon dioxide and oxygen vary depending on the formulation, an observation which stems from the varying solubility of these species. This result has implications on product shelf life and stability during the lyophilization process.

Conclusions

Chamber process gas composition during lyophilization is quantified for several representative formulations using residual gas analysis. The advantages of the technique lie in its ability to measure the relative concentration of various species during the lyophilization process. This feature gives residual gas analysis utility in a host of applications from endpoint determination to quality assurance. In contrast to other methods, residual gas analysis is able to determine oxygen and water vapor content in the process gas. These compounds have been shown to directly influence product shelf life. With these results, residual gas analysis technique presents a potential new method for real-time lyophilization process control and improved understanding of formulation and processing effects for lyophilized pharmaceutical products.

     

Seropositivity in animals and risk of occupational brucellosis among abattoirs personnel associated with poor work practices and absence of safety policy in Egypt

Background Occupational hazards are the leading cause of morbidity and mortality among abattoirs personnel and animal workers. These hazards result from direct or indirect exposure to potential infection and several distressing events during routine procedures.

Objectives To serologically investigate the potential occupational brucellosis hazard at Egyptian abattoirs. To provide an insight on the needed biosafety practices that should be implemented to mitigate the spread of occupational brucellosis among abattoir workers.

Methods Two hundred and thirty (n = 230) blood samples were collected from animals in two Egyptian abattoirs. The rose Bengal test was used to evaluate the seroprevalence of Brucella in abattoir animals. A questionnaire was distributed among abattoir personnel to address biosafety gaps and deficiencies as a cause of occupational brucellosis.

Results The overall seroprevalence of Brucella using the rose Bengal test was 75.2% in the two targeted abattoirs. It was obvious that there are gaps of malpractices and inconvenient behavior among individuals of the targeted community.

Conclusions The current findings reveal the missing role of concerned authorities and lack of written safety policy. The data highlights the need for further research, including isolation and characterization of the causative agents, and reliable epidemiological studies.     

Assessing Community-Based Injury Prevention Services in U.S. Children's Hospitals

ObjectiveNot-for-profit hospitals are required to meet federal reporting requirements detailing their community benefit activities, which support their tax-exempt status. Children''s hospitals have long provided community injury prevention (IP) programming and thus can inform public health outreach work in other areas. This work describes IP programming as a community service offered by children''s hospitals in the U.S.MethodsThe IP specialist at 232 US-based member institutions of the Children''s Hospital Association were invited to complete an assessment of their hospital''s IP outreach programming.Results47.7 percent of hospitals request financial data from IP programming for tax reporting purposes. Almost all offer injury prevention (IP) services; the majority are in the community (60.3%) and 34.5% are hospital-based. Most IP units are independent (60.3%) and 71.8% are responsible for their own budgets.ConclusionsBy integrating dissemination and implementation sciences and community health needs assessments, these findings can help advance community services provided by hospitals to impact public health.     

Origin and Spread of the Dengue Virus Type 1, Genotype V in Senegal, 2015–2019

Dengue virus (DENV) is the most widespread arthropod-borne virus, with the number and severity of outbreaks increasing worldwide in recent decades. Dengue is caused by genetically distinct serotypes, DENV-1–4. Here, we present data on DENV-1, isolated from patients with dengue fever during an outbreak in Senegal and Mali (Western Africa) in 2015–2019, that were analyzed by sequencing the envelope (E) gene. The emergence and the dynamics of DENV-1 in Western Africa were inferred by using maximum likelihood and Bayesian methods. The DENV-1 grouped into a monophyletic cluster that was closely related to those from Southeast Asia. The virus appears to have been introduced directly into Medina Gounass (Suburb of Dakar), Senegal (location probability = 0.301, posterior = 0.76). The introduction of the virus in Senegal occurred around 2014 (95% HPD = 2012.88–2014.84), and subsequently, the virus moved to regions within Senegal (e.g., Louga and Fatick), causing intense outbreaks in the subsequent years. The virus appears to have been introduced in Mali (a neighboring country) after its introduction in Senegal. In conclusion, we present evidence that the outbreak caused by DENV-1 in urban environments in Senegal and Mali after 2015 was caused by a single viral introduction from Asia.