Estimation of urinary delta aminolevulinic acid levels in gasoline and petrol pump workers as an index of lead exposure

Lead poisoning is a phenomenon which with growing globalization is being a subject of worry.ALA i.e Amino levulinic acid is a precursor of hemoglobin, which is synthesized in mitochondria by two main components succinyl Co-A and glycine in presence of ALA-S i.e. amino levulinic acid-synthase. Urinary ALA (ALA-U) has been a recommended biomarker for lead exposure. Inhibition of Amino levulinic acid-dehydratase (ALA-D) results into activation of ALA-S which further synthesizes ALA, excess of ALA is accumulated in the blood, plasma, urine. Present manuscript is focused on the estimation of levels of ALA in the urine of gasoline and pertol pump workers, by acidifying the urine to extract out ALA and reading it colorimetrically as they are exposed to fumes released by gasoline, petrol, and petroleum products which contains lead. Awareness and safety measures such as protective masks and gears should be provided by the respective organisations to the workers.

Possible Antiviral Activity of 5-Aminolevulinic Acid in Feline Infectious Peritonitis Virus (Feline Coronavirus) Infection

Feline infectious peritonitis (FIP) is a life-threatening infectious disease of cats caused by virulent feline coronavirus (FIP virus: FIPV). For the treatment of FIP, several effective antivirals were recently reported, but many of these are not available for practical use. 5-amino levulinic acid (5-ALA) is a low-molecular-weight amino acid synthesized in plant and animal cells. 5-ALA can be synthesized in a large amount, and it is widely applied in the medical and agricultural fields. We hypothesized that 5-ALA inhibits FIPV infection. Therefore, we evaluated its antiviral activity against FIPV in felis catus whole fetus-4 cells and feline primary macrophages. FIPV infection was significantly inhibited by 250 μM 5-ALA. Our study suggested that 5-ALA is applicable for the treatment and prevention of FIPV infection.

Management of Anaemia of Chronic Disease: Beyond Iron-Only Supplementation

Chronic diseases are characterised by altered autophagy and protein metabolism disarrangement, resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia is linked to a worse prognosis independent of the target organ affected by the disease. Currently, the cornerstone of the therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of haematopoiesis. However, treatment strategies should incorporate the promotion of the synthesis of heme, the principal constituent of haemoglobin (Hb) and of many other fundamental enzymes for human metabolism. Heme synthesis is controlled by a complex biochemical pathway. The limiting step of heme synthesis is D-amino-levulinic acid (D-ALA), whose availability and synthesis require glycine and succinil-coenzyme A (CoA) as precursor substrates. Consequently, the treatment of anaemia should not be based only on the sufficiency of iron but, also, on the availability of all precursor molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate a standard iron infusion and a supply of essential amino acids and vitamins involved in heme synthesis. We reported preliminary data in a select population of aged anaemic patients affected by congestive heart failure (CHF) and catabolic disarrangement, who, in addition to the standard iron therapy, were treated by reinforced therapeutic schedules also providing essential animo acids (AAs) and vitamins involved in the maintenance of heme. Notably, such individualised therapy resulted in a significantly faster increase in the blood concentration of haemoglobin after 30 days of treatment when compared to the nonsupplemented standard iron therapy.

Heme biosynthesis depends on previously unrecognized acquisition of iron-sulfur cofactors in human amino-levulinic acid dehydratase

Heme biosynthesis and iron-sulfur cluster (ISC) biogenesis are two major mammalian metabolic pathways that require iron. It has long been known that these two pathways interconnect, but the previously described interactions do not fully explain why heme biosynthesis depends on intact ISC biogenesis. Herein we identify a previously unrecognized connection between these two pathways through our discovery that human aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme biosynthesis, is an Fe-S protein. We find that several highly conserved cysteines and an Ala306-Phe307-Arg308 motif of human ALAD are important for [Fe4S4] cluster acquisition and coordination. The enzymatic activity of human ALAD is greatly reduced upon loss of its Fe-S cluster, which results in reduced heme biosynthesis in human cells. As ALAD provides an early Fe-S-dependent checkpoint in the heme biosynthetic pathway, our findings help explain why heme biosynthesis depends on intact ISC biogenesis.

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

The current COVID-19 pandemic requires urgent development of effective therapeutics. 5-amino levulinic acid (5-ALA) is a naturally synthesized amino acid and has been used for multiple purposes including as an anticancer therapy and as a dietary supplement due to its high bioavailability. In this study, we demonstrated that 5-ALA treatment potently inhibited infection of SARS-CoV-2, a causative agent of COVID-19. The antiviral effects could be detected in both human and non-human cells, without significant cytotoxicity. Therefore, 5-ALA is a candidate as an oral antiviral drug for COVID-19.

Cubosome: A Potential Liquid Crystalline Carrier System

: Cubosome is a biocompatible, thermodynamically stable and bioadhesive drug carrier that is prepared from certain amphiphilic lipids and surfactants when mixed in a definite ratio. Structurally, they are selfassembled nano-constructed liquid crystalline particles comprising three-dimensionally arranged bicontinuous as well as nonintersecting lipid bilayers that give them a honeycomb-like appearance. Morphological characterization through SAXS (small-angle X-ray scattering) and cryo-TEM (cryo-transmission electron microscopy) revealed that they are square and round shaped particles in the nanometer range. These carriers have two separate aqueous regions and a large interfacial area that allow them to carry a variety of bioactive molecules having hydrophobic, hydrophilic or amphiphilic behavior. : One of either two strategies i.e., top-down or bottom-up methods can be adopted to prepare these cubic structures. A number of dispersion techniques like sonication, spray drying, high-pressure homogenization or spontaneous emulsification can be adopted to prepare cubosomes. Their characteristics and benefits like multicompartmental structure, high drug loading, simple and convenient method of preparation, use of biodegradable lipids such as glycerol monooleate, encapsulation of hydrophilic, hydrophobic and amphiphilic moieties, targeted and controlled release make them versatile bioactive carriers that can be administered through multiple biological routes like topical, transdermal, parenteral, and oral. Cubosomes have appreciable applications in various fields especially in the pharmaceutical industry where they are used as potential bioactive carriers. Molecules like paclitaxel, oligonucleotide, δ-amino-levulinic acid, bovine serum albumin, etc. can be easily delivered through this system. : This article provides a detailed note on the structure of cubosomes, ingredients and techniques used for their preparation, mechanism of drug release, applications and routes of drug administration, their formulations, patent review and market scenario.