Phosgene Toxicity Clinical Manifestations and Treatment: A Systematic Review

Exposure to phosgene, a colourless poisonous gas, can lead to various health issues including eye irritation, a dryand burning throat, vomiting, coughing, the production of foamy sputum, difficulty in breathing, and chest pain. Thissystematic review aims to provide a comprehensive overview of the clinical manifestations and treatment of phosgenetoxicity by systematically analyzing available literature. The search was carried out on various scientific online databasesto include related studies based on inclusion and exclusion criteria with the use of PRISMA guidelines. The quality ofthe studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Thirteen articles were included in thisstudy after the screening process. Inhalation was found to be the primary health problem of phosgene exposure withrespiratory symptoms such as coughing and dyspnea. Chest pain and pulmonary oedema were also observed in somecases. Furthermore, pulmonary crackle was the most common reported physical examination. Beyond respiratory tracthealth issues, other organs involvements such as cardiac, skin, eye, and renal were also reported in some studies. Thesymptoms can occur within minutes to hours after exposure, and the severity of symptoms depends on the amount ofinhaled phosgene. The findings showed that bronchodilators can alleviate symptoms of bronchoconstriction causedby phosgene. Oxygen therapy is essential for restoring oxygen levels and improving respiratory function in casesof hypoxemia. In severe cases, endotracheal intubation and invasive mechanical ventilation are used for artificialrespiration, along with the removal of tracheal secretions and pulmonary oedema fluid through suctioning as crucialcomponents of supportive therapy

An application of failure mode and effect analysis (FMEA) to assess risks in petrochemical industry in Iran

Petrochemical industries have a high rate of accidents. Failure mode and effect analysis (FMEA) is a systematic method and thus is capable of analyzing the risks of systems from concept phase to system disposal, detecting the failures in design stage, and determining the control measures and corrective actions for failures to reduce their impacts. The objectives of this research were to perform FMEA to identify risks in an Iranian petrochemical industry and determine the decrease of the risk priority number (RPN) after implementation of intervention programs. This interventional study was performed at one petrochemical plant in Tehran, Iran in 2014. Relevant information about job categories and plant process was gathered using brainstorming techniques, fishbone diagram, and group decision making. The data were collected through interviews, observation, and documents investigations and was recorded in FMEA worksheets. The necessary corrective measures were performed on the basis of the results of initial FMEA. Forty eight failures were identified in welding unit by application of FMEA to assess risks. Welding processes especially working at height got the highest RPN. Obtained RPN for working at height before performing the corrective actions was 120 and the score was reduced to 96 after performing corrective measures. Calculated RPN for all processes was significantly reduced (p≤0.001) by implementing the corrective actions. Scores of RPN in all studied processes effectively decreased after performing corrective actions in a petrochemical industry. FMEA method is a useful tool for identifying risk intervention priorities and effectiveness in a studied petrochemical industry

Selenium supplementation in the form of selenium nanoparticles and selenite sodium improves mature male mice reproductive performances

Objective(s): The current study was conducted to examine the possible protective and retentive effects of one-week intra-peritoneal (IP) administration of selenium nanoparticles (Se-NPs), compared to its bulk counterpart, selenite sodium (Ss), after one complete cycle of spermatogenesis in mature male mice. Materials and Methods: Thirty adult male mice were divided into 3 groups. Control group was administrated phosphate-buffered saline (IP) and the other groups received Ss (0.50 mg kg-1) and Se-NPs (0.50 mg kg-1) for seven successive days. Then, the animals were monitored for 28 days and finally sacrificed and tissue and blood samples were taken. Histopathological features, sperm quality, in vitro fertilization (IVF) capability and selenium (Se) content in testicular tissue were analyzed. Antioxidant enzyme activities including catalase, glutathione peroxidase, and superoxide dismutase as well as total antioxidant capacity and malondialdehyde levels were assessed in blood and the tissue samples. Results: Remarkable differences were found in sperm characteristics, histopathological features and oxidative stress biomarkers between control and treatment groups. Moreover, IVF evaluation and tissue Se concentration examination weren’t similar for Se-NPs and Ss. Conclusion: Conclusively, Se-treated groups had more antioxidant capacity than the control group, but sperm quality and histopathological features revealed that Se-NPs might possess more antioxidative and retentive potential compared to Ss in one spermatogenesis cycle

Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide

Structural and physiological changes in sperm and semen parameters reduce fertility in diabetic patients. Securigera Securidaca (S. Securidaca) seed is a herbal medicine with hypoglycemic, antioxidant, and anti-hypertensive effects. The question now is whether this herbal medicine improves fertility in diabetic males. The study aimed to evaluate the effects of hydroalcoholic extract of S. Securidaca seeds (HESS), glibenclamide and a combination of both on fertility in hyperglycemic rats by comparing histological and some biochemical changes in testicular tissue and sperm parameters. The treatment protocol included administration of three doses of HESS and one dose of glibenclamide, as well as treatment with both in diabetic Wistar diabetic rats and comparison of the results with untrated groups. The quality of the testicular tissue as well as histometric parameters and spermatogenesis indices were evaluated during histopathological examination. Epididymal sperm analysis including sperm motility, viability, abnormalities, maturity, and chromatin structure were studied. The effect of HESS on the expression of LDH and FGF21 genes and tissue levels of glycogen, lactate, and total antioxidant capacity in testicular tissue was investigated and compared with glibenclamide. HESS improved sperm parameters in diabetic rats but showed little restorative effect on damaged testicular tissue. In this regard, glibenclamide was more effective than the highest dose of HESS and its combination with HESS enhanced its effectiveness so that histological tissue characteristics and sperm parameters were were comparable to those of healthy rats. The expression level of testicular FGF21 gene increased in diabetic rats, which intensified after treatment with HESS as well as glibenclamide. The combination of HESS and glibenclamide restored the expression level of testicular LDH gene, as well as tissue storage of glycogen, lactate and LDH activity, and serum testosterone to the levels near healthy control. S. Securidaca seeds can be considered as an effective supplement in combination with hypoglycemic drugs to prevent infertility complications in diabetes

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Equine laminitis: ultrastructural changes, lamellar microcirculation and drug delivery

In order to investigate the early ultrastructural lesions at the first sign of lameness in the oligofructose (OF) model of laminitis, the disease was induced in four horses, while another four horses were sham-treated controls. Minor lesions were detected in lamellar samples examined by light microscopy. Examination by transmission electron microscopy (TEM) showed excessive waviness, breaks and separation of portions of lamellar basement membrane (BM) in the treated horses. There was also disintegration and disappearance of hemidesmosomes (HD) and epidermal basal cell (EBC) cytoskeleton, and an increase in the distance between the EBC plasmalemma and the centre of the BM. A link was thus established between the first clinical signs of lameness and ultrastructural changes in the lamellar dermo-epidermal interface. This implied that pathogenesis was underway well before clinical signs (24 h) and that successful therapy would need to be instituted earlier than previously considered. Earlier therapy may be facilitated if delivery of efficacious drugs to the foot was achievable. A treatment modality that delivered effective concentrations of anti laminitic drugs to the target organ (the epidermal lamellae) was thus an objective of this study. Hoof lamellar tissue from five ponies treated with prolonged euglycaemic hyperinsulinaemia and four control (sham-treated) ponies were harvested and processed for TEM. Lamellae from treated ponies showed attenuation and elongation of secondary epidermal lamellae (SEL), HD number reduction and infiltration of leukocytes. Unlike carbohydrate induced laminitis in horses, there was no global separation at the lamellar dermal/epidermal interface in ponies. Two unique lamellar lesions found in this induction model was mitosis among EBCs and thickening of the BM, not normally characteristic of acute laminitis. The pathophysiology of hyperinsulinaemic laminitis remains unresolved but if insulin, delivered directly to the foot, induced laminitis several pathophysiological questions would be answered. In particular, it would emphasise the laminitogenic potential of insulin alone in the pathogenesis of laminitis. It also allows the treatment foot to be compared with the remaining three that act as internal controls. A modality that delivered drugs like insulin to the target organ (the epidermal lamellae) was needed and was an objective of this study. A microdialysis (MD) method, based on continuous sampling of the lamellar extracellular fluid (ECF), was developed to monitor lamellar drug concentrations. MD probes were implanted in the hoof lamellar tissue of six normal Standardbred horses under local anaesthesia. A bolus intravenous (IV) dose (5 mg/kg BWT) of gentamicin sulfate was injected into the jugular vein. MD and blood samples were collected at different time points during 24 h, and calibrated and analyzed using an ELISA method for gentamicin. During the first 8 h, the concentration of gentamicin was significantly higher in blood than lamellar ECF, a result that is reversed when lamellar MD is repeated during IO infusion of gentamicin. The results showed that this modestly invasive method was a useful tool to monitor changes in the lamellar ECF during drug delivery or during laminitis development. Knowledge of the anatomy and dynamics of blood circulation in the equine foot is fundamental to understand laminitis pathophysiology. Using histology, decalcification, diaphanization, computed tomography (CT), micro CT and gelatin-India Ink vascular perfusion, the normal anatomy of the dorsal part of distal phalanx (DP) and its vascular relationship to hoof lamellae was characterised. The results showed a close relationship between the distal phalangeal and lamellar circulations and raised the possibility of accessing the lamellar circulation via the DP and the possibility that IO perfusion (IOP) of the DP could deliver drugs to the lamellae. IOP of the DP with methyl methacrylate (MMA) corrosion casting material resulted in filling of the lamellar and sublamellar vascular network and incomplete filling of lamellar capillaries. Perfusion of common digital artery with a suspension of barium sulfate resulted in filling of lamellar arteries but not capillaries. Perfusion of the common digital vein resulted in filling of lamellar veins but not capillaries. Perfusion with barium sulfate partitioned veins from arteries because particle size prevented entry into capillaries. IOP with barium sulfate filled only veins revealing that vascular egress from the DP was venous. This study showed that a retrograde venous connection exists between the DP and lamellar circulations with the potential for lamellar drug delivery. Intra-arterial (IA) and IO infusion results using gelatin-India Ink were markedly improved when cadaver limbs were subjected to cyclic loading within the physiological range. Without loading lamellar capillaries failed to fill no matter what the injection pressure. Cyclic loading cadaver limbs 6 times resulted in complete lamellar capillary filling and suggested that cyclic limb loading contributed to perfusion of lamellar capillaries normally in horses. To evaluate IO delivery of drugs to hoof lamellae in the standing, conscious horse, gentamicin solution (25 mg/mL) was slowly infused (20 µL/min) through an IO bone screw. Lamellar ECF was collected via a lamellar MD probe and blood was collected from the jugular vein. Gentamicin was 50-100 times more concentrated in lamellar ECF than in blood. This study introduces a potential method for delivery of drugs into the lamellar tissue in the standing, conscious horse. Laminitis pathology occurs before clinical signs and can be induced by insulin as well as enteric OF overload. Thus therapy delivered to the target of laminitis, the hoof lamellae, has an improved chance of success if delivered promptly, safely and at high concentrations. A validated drug delivery and lamellar analysis system that achieves these criteria, was the discovery of this project and is now available to combat laminitis

Biliary parascarosis in a foal

Migration of Ascaris lumbricoides through the papilla of Vater in humans, and entry into the biliary tree, is well-recognised. Ascaris suum and Toxocara vitulorum have been recovered from the liver of swine and buffalo. We necropsied a Persian Kurdish filly at age 6 months, weighing similar to 100 kg. Death evidently was caused by oleander (Nerium oleander) intoxication. An 8-cm adult male Parascaris was found at the lobar-left hepatic bile duct junction. We suggest that the nematode entered anteriorly into the hepatic tree, via the duodenum, major duodenal papilla, bile duct, left hepatic duct and finally the lobar duct. Considering the brief 4-h elapsed time between death and necropsy, and the 18-cm distance from the major duodenal papilla to the location of the parasite, we conclude that entry into the biliary tree likely occurred ante-mortem. We advise consideration of Parascaris infection in differential diagnosis of equine hepatic and pancreatic dysfunction