Smartphone Applications for Use in Drug Overdose: A review

As smartphone use increases, the use of applications (apps) regarding healthcare expands. Using medical apps has become commonplace for both medical professionals and the general public. Before apps are used it is important that the information that they deliver is accurate and can be used with confidence. Overdose is a common problem presenting to emergency departments and apps provide an opportunity to provide information to both patients and healthcare professionals regarding initial management.

Smartphone use is increasing amongst healthcare professionals and as a result there are smartphone applications available for a variety of healthcare related tasks. As smartphone use becomes ubiquitous, the general public are likely to access medical information this way. Many healthcare apps have been developed for healthcare professionals and are available to download including dose calculators, reference guides and log books. The ability of an app to act as an interactive tool by making calculations or seeking information ‘on-the-go’ in the clinical environment means it can outperform a traditional computer. Similarly, patients can access information stored on their smartphone and this can be carried with them and accessed when traditional information technology (IT) facilities are not available. Although apps are unique in their ability to perform a specific task in a streamlined way, there is currently no regulation of their content and healthcare professional involvement can be variable.

Toxicology: The Basis for Development of Antidotes

Toxicology is the study of poison. Sources of poisons include animals, microorganisms, plants and chemicals. Although, Paracelsus who was a lecturer at the University of Basel, Switzerland in 1520s had hypothesized that the ability of an agent to cause poisoning is dependent on the dose of that agent. It was on this basis the median lethal dose (LD50) was introduced in 1920. LD50 is the dose which has proven to cause death to 50% of the test group of animals. It is an initial assessment of toxic manifestations and is one of the initial screening experiments usually performed with carcinogenic, anticarcinogenic, venomous, anti-venomous, toxicogenic, anti-toxicogenic, immunogenic and anti-immunogenic compounds. An antidote is any is any substance that counteracts a poison by, (a) chemically destroying the poison, (b) mechanically preventing absorption, or (c) physiologically opposing the effects of the poison in the body after absorption. The data from median lethal estimation serve as the basis for classification and labelling; provide initial information on the mode of toxic substance; help arrive at a dose of a new compound and help determine LD50 values that may indicate potential types of drug activity. The different methods used in determination of LD50 include Arithmetical method of Karber, Lorke method, arithmetical method of Reed and Muench, graphical method of Miller and Tainter, graphical method of Litchfield and Wilcoxon, revised up-and-down procedure, a modified arithmetical method of Reed and Muench and arithmetic-geometric-harmonic method. All the methods employ summation of the doses of toxicant that caused death in the test group of animals.

However, for Reed and Muench method, the sum of cumulative dead and cumulative survived of each dose is taken. The percent survival to two doses adjacent to LD50 is calculated and the LD50 determined. In another report, LD50 is calculated using the data on percent mortality instead of percent survival. Having noted the marked difference between the estimated LD50 from percent survival and percent mortality using Reed and Muench method, Saganuwan modified and validated the method using the average of median lethal dose (LD50) and median survival dose (MSD50) which gave a relatively ideal LD50. The method was also validated by other authors with precision and accuracy. Kue et al. used quick chick embryo chorioallantoic membrane (CAM) as an alternative predictive model in acute toxicological studies for cyclophosphamide, cisplatin, vincristine, carmustin, campothecin, aloin, mitomycin-C, actinomycin–D, melphalan and paclitaxel. The authors used the method of Reed and Muench modified by Saganuwan, and determined LD50 of all the anticancer agents and there was significant correlation between the ideal LD50 for the CAM and LD50 for mice. Signifying the versatility of the revised Reed and Muench method using CAM model as a replacement for toxicological studies inrodents.

Molar Concentration Welcomes Avogadro in Postgenomic Analytics

At the end of the 18^th century the physicist Amedeo Avogadro formulated the law, which subsequently allowed establishing one of the fundamental constants called Avogadro's number. The Avogadro’s number defined the number of molecules in one grammolecule. The Avogadro’s constant (N_A) is expressed in the unit mol⁻¹ and used in the International System of Units (SI), instead of the dimensionless Avogadro’s number, which counts for the number of molecules.

For a century the Avogadro’s number and molar concentration existed in parallel. These two terms were rarely used together to characterize the number of molecules of any substance in a solution. In the early 21st century the situation changed due to the emergence of genomics and its derivatives – transcriptomics and proteomics. Postgenomic science aroused a necessity to characterize the number of molecules of DNA (for genome), RNA (for transcriptome), and proteins (for proteome) in the copies of molecules in a biological sample. Combining the concepts of the Avogadro’s number and molecular concentration it was possible to revisit the notion of protein content in a solution (and cells) using number of molecules instead of chemistryimposed concentration units. The reverse Avogadro’s number was introduced for recalculating the concentration of substances in a solution to the copy numbers, i.e. the determination of the number of entities of a certain biomacromolecule in a cell volume or in a biofluid, for example, in blood plasma.

Intracranial Neurostimulation for Central Pain Relief

Central pain is an expression of a primary or secondary lesion or dysfunction of central nervous system and represents a very difficult condition to treat. Often pharmacotherapy allows a benefit clinically important only in a limited number of patients and clinical use of some drugs is rendered problematic by their poor handling and tolerability.

Intracranial neurostimulation represents a reversible method of functional neurosurgery, adaptable and free of major side effects, indicated in cases of intractable chronic pain when other conservative treatment modalities have been exhausted. Currently two types of intracranial neurostimulation are commonly used for control pain: deep brain stimulation (DBS) and motor cortex stimulation (MCS).

The relief of pain with chronic electrical stimulation of deep sensory thalamic nuclei (DBS) was first reported by Mazars et al. and Hosobuchi et al. Although Europe and the United States over the past 20 years have been several interventions of deep brain stimulation for the treatment of chronic pain syndromes, this method over the years has been gradually replaced by less invasive as spinal cord stimulation, intrathecal infusion pumps and epidural cortical stimulation. Despite this trend, some conditions of chronic pain refractory to drugs still represent a valid indication. DBS may be employed for a number of nociceptive and neuropathic pain states, including cluster headaches, chronic low back pain, failed back surgery syndrome, peripheral neuropathic pain and facial deafferentation pain. Patients are selected for DBS for pain if they experienced chronic pain unresponsive to medical or surgical therapies over many years and to treatment administered during an admission to a pain clinic.

Relationship of Il-5 with Th1 and Th2 Cytokines in Individuals with or without Type-2 Diabetes

Obesity is linked to metabolic syndrome including insulin resistance, type-2 diabetes (T2D), and cardiovascular disease. Persistent low-grade inflammation is associated with metabolic disorders. Changes in plasma cytokines have been reported in obesity and T2D. Functionally polarized CD4+ T cells are classified as Th1, Th2, Th17, and Treg subsets depending on the pattern of their cytokine production. Th1 cytokines, such as interleukin (IL)-2 and interferon (IFN)-γ activate macrophages and are involved in inflammatory immune responses whereas Th2 cytokines, such as IL-4, IL-5, IL-10, and IL-13 have antiinflammatory properties and are involved in antibody production, eosinophil activation, and suppression of macrophage functions. Th1/Th2 cytokine imbalance has been reported in chronic disease progression and in metabolic syndrome. IL-2 is a proinflammatory cytokine that promotes synthesis of tumor necrosis factor (TNF)-α and IFN-γ from natural killer cells (NK) cells and is associated with atherogenesis and T2D. IFN-γ is related with the production of macrophage mediators, chemokines, induction of leukocyte adhesion molecules and class II major histocompatibility antigens, and potentiates the antigen presenting cell functioning. IL-4 which is secreted by activated Th2 cells, basophils, and mast cells has pleiotropic functions including Th2 differentiation, B-cell proliferation and immunoglobulin class switching. IL-10 is an antiinflammatory cytokine which attenuates inflammation induced by IL-1, IL-6, and TNF-α while it also promotes the release of anti-inflammatory IL-1RA.

IL-5 is an important T cell-derived cytokine that regulates the expression of diverse genes involved in proliferation, cell survival, as well as maturation and effector functioning of B cells and eosinophils. IL-5 plays a pivotal role in both the innate and adaptive immune responses and the biologic effects of IL-5 are best characterized for eosinophils in humans. It is not clear whether plasma IL-5 levels are modulated and also relate with the Th1/Th2 cytokine profile in metabolic disorders such as obesity and T2D. The aim of the study was, therefore, to determine the circulatory IL-5 levels in diabetic and nondiabetic individuals and evaluate the relationship of IL-5 levels with Th1/Th2 cytokine profile in these two populations. Here, we show that plasma IL-5 levels were significantly lower in diabetic individuals and these changes correlated with Th1/Th2 cytokines and clinical metabolic markers differentially between diabetics and non-diabetics.