Of mitochondrion and COVID-19.

COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19.

Attitudes and practices of community pharmacists and barriers to their participation in public health activities in Yemen: mind the gap.

BACKGROUND: Patients in Yemen commonly visit community pharmacies to obtain consultation or treatment for common ailments. Community pharmacists have an opportunity to optimize medication use and improve patient outcomes. This study aimed to evaluate the attitudes and practices of community pharmacists regarding their participation in public health activities and barriers to their participation in these activities. METHODS: This cross-sectional study was carried out among community pharmacists working in pharmacies located in urban areas of the Aden governorate of Yemen from March to June 2017 using a self-administered questionnaire. We selected pharmacies from a line list using proportional sampling according to the number of pharmacies in the urban areas of each district. The questionnaire contained four sections: demographic characteristics, attitudes, practices, and barriers encountered. Data were analyzed descriptively, and the Chi-square test was used for analyzing the association of variables (alpha = 0.05). RESULTS: The questionnaire was distributed to 200 community pharmacists working in community pharmacies. Of the 200 respondents, 62% (n = 124) were male. Overall, the mean age (sd) was 30.0 years (8.6) with the number of years of work experience between 2 and 9.9 years (n = 158, 79%). On average, 62.3% of the pharmacists had a positive attitude toward participation in public health activities. Providing education to stop tobacco chewing, smoking, alcohol drinking and improve oral hygiene was an important activity of the community pharmacists. Blood pressure measurements (86%, n = 172) and glucose tests (45%, n = 90) were commonly conducted for clients. Lack of time (71%, n = 142) and lack of teamwork (70%, n = 140) were mentioned as common barriers to participation in public health activities. CONCLUSIONS: Community pharmacists had a positive attitude toward public health activities. Health education and routine health tests were important practices of the community pharmacists. Barriers need to be overcome to enable more active participation by community pharmacists in public health activities by consulting with all stakeholders, assessing the situation, considering alternatives and taking action.

Linking Aromatic Hydroxy Metabolic Functionalization of Drug Molecules to Structure and Pharmacologic Activity.

Drug functionalization through the formation of hydrophilic groups is the norm in the phase I metabolism of drugs for the modification of drug action. The reactions involved are mainly oxidative, catalyzed mostly by cytochrome P450 (CYP) isoenzymes. The benzene ring, whether phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand, the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e., the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e., the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retention, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues are presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design, and drug development.

Immunogenic characterization of AlPO4 adsorbed Td vaccine and liposome-mediated Td vaccine.

Purpose: The purpose of this study was to compare the antigenic potency and stability of tetanus and diphtheria (Td) vaccines when combined with aluminum phosphate (AlPO4) and liposome adjuvants. Materials and Methods: In vitro and in vivo analyses were conducted using the single radial immunodiffusion method and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The Td vaccines were prepared with AlPO4 adsorption and liposome-mediated delivery, and protein antigens were characterized using these methods. Results: The results revealed that the liposome-mediated Td vaccines exhibited higher immunogenicity compared to the AlPO4-adsorbed Td vaccines. Additionally, the liposome-mediated Td vaccines demonstrated higher stability as native antigens. Conclusion: This study highlights the importance of utilizing liposome adjuvants in vaccine development. The liposome-mediated Td vaccines showed enhanced immunogenicity and stability, making them a promising approach for improving vaccine efficacy. Understanding and optimizing adjuvant strategies can contribute to the development of effective vaccines against various diseases.

Pathogenesis and Management of COVID-19.

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.

Advances in Nanoparticles as Anticancer Drug Delivery Vector: Need of this Century.

BACKGROUND: Nanotechnology has contributed a great deal to the field of medical science. Smart drugdelivery vectors, combined with stimuli-based characteristics, are becoming increasingly important. The use of external and internal stimulating factors can have enormous benefits and increase the targeting efficiency of nanotechnology platforms. The pH values of tumor vascular tissues are acidic in nature, allowing the improved targeting of anticancer drug payloads using drug-delivery vectors. Nanopolymers are smart drug-delivery vectors that have recently been developed and recommended for use by scientists because of their potential targeting capabilities, non-toxicity and biocompatibility, and make them ideal nanocarriers for personalized drug delivery. METHOD: The present review article provides an overview of current advances in the use of nanoparticles (NPs) as anticancer drug-delivery vectors. RESULTS: This article reviews the molecular basis for the use of NPs in medicine, including personalized medicine, personalized therapy, emerging vistas in anticancer therapy, nanopolymer targeting, passive and active targeting transports, pH-responsive drug carriers, biological barriers, computer-aided drug design, future challenges and perspectives, biodegradability and safety. CONCLUSION: This article will benefit academia, researchers, clinicians, and government authorities by providing a basis for further research advancements.

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH.

The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the "Warburg Effect". However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer.

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer.

Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics driven by a combination of poor vascular perfusion, regional hypoxia, and increased the flux of carbons through fermentative glycolysis. This leads to extracellular acidosis and intracellular alkalinization. Dysregulated pH dynamics influence cancer cell biology, from cell transformation and tumorigenesis to proliferation, local growth, invasion, and metastasis. Moreover, this dysregulated intracellular pH (pHi) drives a metabolic shift to increased aerobic glycolysis and reduced mitochondrial oxidative phosphorylation, referred to as the Warburg effect, or Warburg metabolism, which is a selective feature of cancer. This metabolic reprogramming confers a thermodynamic advantage on cancer cells and tissues by protecting them against oxidative stress, enhancing their resistance to hypoxia, and allowing a rapid conversion of nutrients into biomass to enable cell proliferation. Indeed, most cancers have increased glucose uptake and lactic acid production. Furthermore, cancer cells have very dysregulated electrolyte balances, and in the interaction of the pH dynamics with electrolyte, dynamics is less well known. In this review, we highlight the interconnected roles of dysregulated pH dynamics and electrolytes imbalance in cancer initiation, progression, adaptation, and in determining the programming and reprogramming of tumor cell metabolism.

Gas chromatography-mass spectrometry designation and prediction of metabolic dealkylation and hydroxylation reactions in xenobiotics exemplified by tramadol.

Metabolic dealkylation and hydroxylation reactions in xenobiotics are common and may take place at different sites in the molecules. Sometimes confusion may arise as to the nature and site of the resulting metabolic change when there is more than one potential site. The use of GC-MS in resolving the problem has been demonstrated by using tramadol as example. Human urine samples containing tramadol and its metabolites were extracted under basic pH conditions and analyzed by GC-MS, in the electron impact and chemical ionization modes, before and after trimethylsilyl (TMS) derivatization. By recognizing the mass-to-charge ratios of molecular and base-peak ions in the mass spectra, it was possible to predict and designate sites of demethylation and hydroxylation in tramadol metabolites. In addition to the designation of the known tramadol metabolites, the practice has led to the tentative characterization of hydroxytramadol and norhydroxytramadol as new metabolites of tramadol in humans. Possible extension of the modus operandi to other xenobiotics was discussed.

Antioxidant Properties of Solenostemma argel Effervescent Tablets.

OBJECTIVE: In the present study, Solenostemma argel effervescent tablets were prepared from Argel methanolic extract. METHODS: The tablets were examined for their ability to impede carbon tetrachloride (CCl4)-induced lipid peroxidation in mice liver. The antioxidant activities of the enzymes; super-oxide dismutase (SOD), glutathione peroxidase (GS-PX) along with malondialdehyde level were tested in liver tissues. RESULTS: The obtained results indicated that the antioxidant enzyme activities were remarkably reduced while the level of Malondialdehyde (MDA), which shows lipid peroxidation, and the activity of alanine aminotransferase (a liver function test) were remarkably intensified following intra-peritoneal i.p injection with the single sub-lethal hepatotoxic dose of CCl4 compared to the control. A necrotic lesion in the liver of mice injected with CCl4 was observed by the histopathological examination. The damaging influence of CCl4 was improved by the retreatment with Argel or BHT, which could also be observed in the normal appearance of the liver tissue. CONCLUSION: In this study, it was concluded that S. Argel and butylated hydroxytoluene (BHT) could be effective by decreasing lipid peroxidation and increasing the activities of antioxidant enzymes. Therefore, Argel might be applied as a hepatoprotective agent without any side effects.

Preliminary investigation of novel tetra-tailed macrocycle amphiphile based nano-vesicles for amphotericin B improved oral pharmacokinetics.

Supramolecular macrocycles-based drug delivery systems are receiving wider recognition due to their self-assembly into nanostructures with unique characteristics. This study reports synthesis of resorcinarene-based novel and biocompatible amphiphilic supramolecular macrocycle that self-assembles into nano-vesicular system for Amphotericin B (Am-B) delivery, a model hydrophobic drug. The macrocycle was synthesized through a two-step reaction and was characterized with 1 H NMR and mass spectrometric techniques. Its biocompatibility was assessed in cancer cell lines, blood and animals. Its critical micelle concentration (CMC) was determined using UV spectrophotometer. Am-B loaded in novel macrocycle-based vesicles were examined according to their shape, size, surface charge, drug entrapment efficiency and excepients compatibility using atomic force microscope (AFM), Zetasizer, HPLC and FT-IR spectroscopy. Drug-loaded vesicles were also investigated for their in-vitro release, stability and in-vivo oral bioavailability in rabbits. The macrocycle was found to be nontoxic against cancer cells, haemo-compatible and safe in mice and revealed lower CMC. It formed mono-dispersed spherical shape vesicles of 174.4 ± 3.78 nm in mean size. Vesicles entrapped 92.05 ± 4.39% drug and were stable upon storage with gastric-simulated fluid and increased the drug oral bioavailability in rabbits. Results confirmed novel macrocycle as biocompatible vesicular nanocarrier for enhancing the oral bioavailability of lipophilic drugs.

Target urinary analytes for the gas chromatographic- mass spectrometric detection of procyclidine and benzhexol in drug abuse cases.

The two antiparkinsonian drugs procyclidine and benzhexol are presently finding considerable favor for their euphoric hallucinogenic effects among drug abusers in some countries. In anticipation of their possible scheduling in national drug laws, gas chromatography-mass spectrometry (GC-MS) methods for their detection in urine will be required. However, because of uncertainty of the metabolic fate of the two drugs in humans, the urinary target analytes for GC-MS detection were not well defined. The problem was addressed in the present study in which it was found that mono-hydroxy metabolites, where hydroxylation took place at the cyclohexane ring in both drugs, could be endorsed as the major target analytes. The metabolites could only be detected as the mono- and/or di-trimethylsilyl (TMS) derivatives. The predominance of either derivative depended on the temperature and time of heating with the derivatizing reagent. Because of the basic properties of the hydroxy metabolites, analytic method optimization was needed for their detection in urine included extraction under basic pH conditions. Urine hydrolysis with ß-glucuronidase did not have an effect on the recovery of the metabolites, but was usually performed in search for other drugs. Because of the relative abundance of ions, the electron impact mass spectra of the mono-TMS derivatives and the chemical ionization (CI) mass spectra of the mono- and di-TMS derivatives of the hydroxy metabolites of both drugs were found to be more structurally informative. The CI mass spectra of the di- TMS derivatives have the additive advantage of being potentially useful for quantitative analysis.

Professional practices and perception towards rational use of medicines according to WHO methodology in United Arab Emirates.

UNLABELLED: Inappropriate prescribing reduces the quality of medical care and leads to a waste of resources. No study has been reported concerning rational drug use in United Arab Emirates, UAE, recently. OBJECTIVES: assessing patterns of use and defining problems regarding the rational drug use.Setting baseline situational analysis study for practices in the health care system relevant to drug use. METHOD: A descriptive pilot study, consisting of pharmacists, physicians and patients (100 of each of category) from four private hospitals, (12) medical clinics, (80) community pharmacies in addition to 150 prescriptions. A questionnaire of three sections was designed to include WHO indicators regarding patients, facility and prescribing patterns that are relevant to rational drug use was carried out in four emirates of the UAE in the period December 2008-Febreuary 2009. RESULTS: Consultation and dispensing times were 10 (SD=2.75) min and 68 (SD=9.7) seconds, respectively. Average no. of drugs per prescription was (2.9 + 0.97), % of prescriptions using generic name (7.35%), % of antibiotic containing prescriptions (31.1%), % of injection containing prescriptions (2.9%), adherence to Standard Treatment Protocols (46%), adherence to the essential drug list (64%), patient's knowledge of correct dosage (55%), adequately labeled drugs (45%), patient's information (65%). CONCLUSIONS: Several areas of deficiency in rational drug use had been defined in the private sector through UAE that can be remedied through adopting several strategies such as adherence to national standard treatment guidelines and essential drug list based on treatments of choice, interaction between health care system and providing drugs information to consumers.