Optimization and Characterization of Quercetin Vitamin C Nano-Phytosome Formulation

Objective: To design an optimal formulation for quercetin and vitamin C nano-phytosome. Method(s): Nano-phytosomes are prepared by the thin layer hydration technique using a 2-level-5-factor design experimental. A total of 32 experimental formulas were used for data analysis. The ratio of quercetin: soy lecithin (X1), the ratio of quercetin: cholesterol (X2), stirring speed (X3), stirring temperature (X4), and stirring time (X5) were used as independent factors, while globule size as a dependent factor. Data analysis was carried out by Design Expert12 application. Characterization of the optimal formula included physicochemical evaluation, globule size analysis, zeta potential, polydispersity index, entrapment efficiency, Transition Electron Microscopy (TEM) analysis, and FTIR analysis. Result(s): The optimal formula consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, at temperature 51.73 degreeC which produced 59.26 nm average globule size, PDI value 0.66;zeta potential value-35.93+/-0.95 mV and average SPAN value 0.61. This formulation showed entrapment efficiency of quercetin 91.69+/-0.18 % and vitamin C 90.82+/-0.13 %. The TEM and FITR analysis showed the morphological of the globules and interactions between the drugs, soy lecithin, and cholesterol to form nano-phytosomes. Conclusion(s): The conditions to obtain the optimal formula for quercetin vitamin C nano-phytosome consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, and at temperature 51.73 degreeC.Copyright © 2023 The Authors.

Time course study of optical coherence tomography angiography in patients with methanol induced optic neuropathy.

INTRODUCTION: In countries where alcoholic beverages are legally prohibited, methanol toxicity usually occurs due to ingesting homemade alcoholic drinks. The initial ophthalmologic symptoms of methanol toxicity typically appear 6-48 h after ingestion, and the severity of symptoms varies widely from mild and painless decreased vision to no-light perception vision. METHODS: This prospective study examines 20 patients with acute methanol poisoning within 10 days of use. Patients underwent ocular examinations, BCVA (Best Corrected Visual Acuity) recording, and OCTA (Optical Coherence Tomography Angiography) of the macula and optic disc. BCVA measurement and imaging were repeated one month and three months after intoxication. RESULTS: There was a statistically significant reduction in superficial parafoveal vascular density (P-value = 0.026), inner retinal thickness (P-value = 0.022), RNFL (Retinal Nerve Fiber Layer) thickness (P-value = 0.031), and an increase in cup to disc ratio (P-value < 0.001), and central visual acuity (P-value = 0.002) in this time course. However, there was no statistically significant difference in FAZ (Foveal Avascular Zone) area (P-value = 0.309), FAZ perimeter (P-value = 0.504), FD-300 (Foveal density, vascular density within a 300 µm wide region of the FAZ) (P-value = 0.541), superficial vascular density (P-value = 0.187), deep foveal vascular density (P-value = 0.889), deep parafoveal vascular density (P-value = 0.830), choroidal flow area (P-value = 0.464), total retinal thickness (P-value = 0.597), outer retinal thickness (P-value = 0.067), optic disc whole image vascular density (P-value = 0.146), vascular density inside the disc (P-value = 0.864), or peripapillary vascular density (P-value = 0.680) at different times. CONCLUSION: Over time, methanol poisoning can cause changes in retinal layers thickness, vasculature, and optic nerve head. The most important changes include cupping of the optic nerve head, reduction in RNFL thickness, and inner retinal thickness.

Synthesis and evaluation of imidazole-bearing chalcones as a potential treatment for pulmonary aspergillosis

Pulmonary aspergillosis (PA) is a category of respiratory illnesses that significantly impacts the lives of immunocompromised individuals. However, new classifications of secondary infections like influenza associated aspergillosis (IAA) and COVID-19 associated pulmonary aspergillosis (CAPA) only exacerbate matters by expanding the demographic beyond the immunocompromised. Meanwhile anti-fungal resistant strains of Aspergillus are causing current treatments to act less effectively. Symptoms can range from mild (difficulty breathing, and expectoration of blood) to severe (multi organ failure, and neurological disease). Millions are affected yearly, and mortality rates range from 20-90% making it imperative to develop novel medicines to curtail this evolving group of diseases. Chalcones and imidazoles are current antifungal pharmacophores used to treat PA. Chalcones are a group of plant-derived flavonoids that have a variety of pharmacological effects, such as, antibacterial, anticancer, antimicrobial, and anti-inflammatory activities. Imidazoles are another class of drug that possess antibacterial, antiprotozoal, and anthelmintic activities. The increase in antifungal resistant Aspergillus and Candida species make it imperative for us to synthesize novel pharmacophores for therapeutic use. Our objective was to synthesize a chalcone and imidazole into a single pharmacophore and to evaluate its effectiveness against three different fungi from the Aspergillus or Candida species. The chalcones were synthesized via the Claisen-Schmidt aldol condensation of 4-(1H-Imizadol-1-yl) benzaldehyde with various substituted acetophenones using aqueous sodium hydroxide in methanol. The anti-fungal activity of the synthesized chalcones were evaluated via a welldiffusion assay against Aspergillus fumigatus, Aspergillus niger, and Candida albicans. The data obtained suggests that chalcone derivatives with electron-withdrawing substituents are moderately effective against Aspergillus and has the potential for further optimization as a treatment for pulmonary aspergillosis. This project was supported by grants from the National Institutes of Health (NIH), National Institute of General Medicine Sciences (NIGMS), IDeA Networks of Biomedical Research Excellence (INBRE), Award number: P20GM103466. The content is solely the responsibility of the authors and do not necessarily represent the official views of the NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Assessment of uncertainty estimation for measurement of ethanol concentration in COVID-19 hand sanitizer using FTIR spectroscopy

Analysis of uncertainty estimation for measurement of type and concentration of alcohol in hand sanitisers is a matter of urgency in the COVID-19 situation. FTIR spectroscopy was used to investigate hand sanitisers made in our laboratory and commercial products. An internal standard addition method was used to control the measurement quality. The absorption spectra of ethanol were found to be at 1086 and 1044 cm-1, corresponding to C-O stretching. The area under the C-O adsorptions is used to create a calibration curve, which is then used to calculate the ethanol percentage. Additional standard sample and quality control sample showed calibration curves with slopes of 0.1267 and 0.1285, respectively. The regression coefficients and residual variance of 0.0057 showed a 'best fit' with the predicted value. These parameters were used to estimate the uncertainty of six commercial products. The ethanol concentration of commercial products is measured between 71.38 and 81.54% v/v, with an estimated uncertainty of 1.14% v/v. The results showed that the ethanol content of all products differed from the label but could be used to kill bacteria and viruses. This entire process was established as a SOP for measuring alcohol concentration in hand sanitizer.

Apport de l'imagerie dans l'intoxication au methanol: a propos de 4 cas

Objectifs: - Analyser le profil clinico-radiologique des patients victimes d'intoxications methyliques - Souligner l'interet diagnostique de l'imagerie dans l'intoxication au methanol. Methodes: Il s'agit d'une etude retrospective qui a concerne quatre cas d'intoxications au methanol etudies sur dossiers medicaux, colliges au sein des services de reanimation, neurologie et ophtalmologie du CHU Mohammed VI d'Oujda, durant une periode de 2 ans s'etalant de septembre 2020 au mois de septembre 2022. L'analyse a concerne les caracteristiques liees a l'intoxication. Resultats: Nos 4 patients etaient de sexe masculin, dont l'age moyen etait de 57 ans avec des extremes de 36 et 71 ans. La duree entre consommation et apparition des symptomes etait de 1 jour. Le tableau clinique etait domine par les troubles de la conscience et la cecite. Le bilan biologique a objective une acidose metabolique. 3 de nos patients ont beneficie d'une IRM encephalique objectivant des anomalies de signal caracteristiques a savoir une necrose putaminale bilaterale, une atteinte de la substance blanche et des voies optiques. Tandis que le 4eme patient a beneficie d'une TDM cerebrale montrant une anomalie de densite de la substance blanche frontale bilaterale. 2 patients ont beneficie d'un traitement symptomatique. 3 patients ont garde une cecite bilaterale sequellaire, et l'autre est decede suite au Covid-19. Discussion(s): l'intoxication au methanol et rare et grave engageant le pronostic vital et fonctionnel. Le diagnostic est confirme par un taux sanguin eleve de methanol. L'imagerie joue un role primordial dans l'explication des atteintes, elle objective des anomalies de signal bilaterales et symetriques des noyaux gris centraux, une atteinte des voies optiques et de la substance blanche sous corticale, du cervelet et de l'hypothalamus. Elle impose une prise en charge rapide afin d'eviter les atteintes qui sont irreversibles.Copyright © 2023

The danger of the toxicity and inefficacy of alcohol-based hand rubs in Iran during COVID-19: a cross-sectional study.

BACKGROUND: The use of disinfectants and alcohol-based hand rubs (ABHR) to prevent COVID-19 transmission increased in the first wave of the infection. To meet the increased demand, the Iranian Ministry of Health issued an emergency use authorization allowing new manufacturers to enter the market, despite the limited capacity for surveillance of these products during COVID-19. Methanol poisoning outbreaks spread rapidly, and more people died from methanol poisoning than COVID-19 in some cities. The aim of this study was to analyze some ABHRs in the Iranian market to see if (a) ABHRs are standard and suitable for hand antisepsis and (b) contained potentially dangerous toxic alcohols. METHOD: Between February and March 2020, 64 brands of ABHR were conveniently collected from pharmacies, supermarkets, and shops selling hygienic products and analyzed using Gas Chromatography. World Health Organization and Food and Drug Administration guidelines were used to define minimum requirements for ABHR. For estimating the risk for acute methanol poisoning, we assumed a serum methanol concentration of 200 mg/L following ABHR ingestion was sufficient to cause intoxication. This threshold concentration would be achieved in an average 75-kg adult after consuming 8000 mg (or eight grams) methanol in 1-2 h. RESULTS: The median [IQR] (range) concentration of ethanol, isopropanol, and methanol were 59% v/v [32.2, 68] (0, 99), 0 mg/L [0, 0] (0, 197,961), and 0 mg/L [0, 0] (0, 680,100), respectively. There was a strong negative correlation between methanol and ethanol contents of hand rubbers (r= -0.617, p < 0.001). Almost 47% of ABHRs complied with minimum standards. In 12.5% of ABHRs, high concentrations of methanol were observed, which have no antiseptic properties but could cause acute methanol poisoning if ingested. CONCLUSION: COVID-19 initiated a policy for distribution and use of ABHR with little control. As ABHR and masks are still accepted preventive measures of the disease, non-standard ABHR compositions may increase the population's risk to both COVID-19 infection and methanol poisoning.

Awareness raising and dealing with methanol poisoning based on effective strategies.

Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are greater than 50 mg/dl should raise some concern. Ingested methanol is typically digested by alcohol dehydrogenase (ADH), and it is subsequently redistributed to the body's water to attain a volume distribution that is about equivalent to 0.77 L/kg. Moreover, it is removed from the body as its natural, unchanged parent molecules. Due to the fact that methanol poisoning is relatively uncommon but frequently involves a large number of victims at the same time, this type of incident occupies a special position in the field of clinical toxicology. The beginning of the COVID-19 pandemic has resulted in an increase in erroneous assumptions regarding the preventative capability of methanol in comparison to viral infection. More than 1000 Iranians fell ill, and more than 300 of them passed away in March of this year after they consumed methanol in the expectation that it would protect them from a new coronavirus. The Atlanta epidemic, which involved 323 individuals and resulted in the deaths of 41, is one example of mass poisoning. Another example is the Kristiansand outbreak, which involved 70 people and resulted in the deaths of three. In 2003, the AAPCC received reports of more than one thousand pediatric exposures. Since methanol poisoning is associated with high mortality rates, it is vital that the condition be addressed seriously and managed as quickly as feasible. The objective of this review was to raise awareness about the mechanism and metabolism of methanol toxicity, the introduction of therapeutic interventions such as gastrointestinal decontamination and methanol metabolism inhibition, the correction of metabolic disturbances, and the establishment of novel diagnostic/screening nanoparticle-based strategies for methanol poisoning such as the discovery of ADH inhibitors as well as the detection of the adulteration of alcoholic drinks by nanoparticles in order to prevent methanol poisoning. In conclusion, increasing warnings and knowledge about clinical manifestations, medical interventions, and novel strategies for methanol poisoning probably results in a decrease in the death load.

Scientometric analysis of methanol intoxication literature: Global publication output between 1980 and 2019

Aim: Scientometrics refers to the analysis of scientific literature related to a certain field. Even though the number of publications on methyl alcohol poisoning has recently increased, there has been no bibliometric or scientometric analysis conducted to date. In 2020 in particular, cases of methyl alcohol poisoning have increased due to the COVID-19 pandemic, which is expected to draw greater attention to this field. Material(s) and Method(s): All data used in this study were collected from four databases accessed via the Web of Science. All studies published between 1980 and 2019 identified by searching for the keywords "methanol" and "poisoning" were included in the study. The relationship between the number of publications and productivity and characteristics of countries was analyzed with Spearman's correlation test, while GunnMap and VOSviewer were used to create infographics and infomaps. This study was conducted in accordance with the Declaration of Helsinki Results: A total of 744 articles, most of which were original (79.70%), were identified from the four databases accessed via the Web of Science. An analysis of the number of publications by country ranked the United States in the first place, with 174 articles (23.387 %), while the Czech Republic was found to have the most productive researchers. The most popular area was toxicology (20.565%), and Charles University was the most productive institution. It was found that the number of publications and citations did not increase over the years Discussion: The developed countries dominated the literature on methyl alcohol poisoning. It was further observed that articles on methyl alcohol abuse started to appear in 2020 in developing countries, which can be attributed to the COVID-19 pandemic, and the mistaken belief that it has anti-viral properties. Since the diagnosis and treatment of methyl alcohol poisoning are gaining significance, we recommend that researchers be encouraged to make further studies in this area.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Identification of Adulteration in Hand Sanitizers of Jaipur City Using Raman Spectroscopy

Hand hygiene has been established as an important part of our lives leading to reduction of colonization and communicable diseases for all. Since the World Health Organization (WHO) declared COVID-19 a global pandemic, fake hand sanitizers have appeared on the market often, posing risk to the public due to the undeclared addition of methanol and Iso-propanol. This study examined the chemical components stated on the hand sanitizer component label and investigated how people used hand sanitizer and their level of chemical awareness. 30 distinct samples, both brand-name and locally produced, were gathered from Jaipur's local markets. In addition, the samples' iso-propanol and methanol contents were examined using Raman spectroscopy. The findings of this study demonstrate that almost 37% of the samples were adulterated which is still a minacious stats considering the consumption and effects these sanitizers are having on the consumers. The adsorption of such adulterated sanitizers through skin causes irritations on skin and hands which may lead to inflammation and can also have carcinogenic effects. So, the study concludes that the identification and quality assessment of such sanitizers should be done on a large scale to prevent the spread of toxicity.Copyright © 2022, Medico Legal Society. All rights reserved.

Evaluation of The Effect of Crude Extracts of Fenugreek on Resistant Isolates of Candida species (In vitro study)

Background: The recent emergence of fungal resistance strains has caused concern in medical settings. Medicinal plants continue to be viable sources of bioactive chemicals with therapeutic potential. These compounds can be extracted in different techniques using various solvents that give rise to a wide variety of extracted bioactive compounds that act as anti-fungal. The research aimed to evaluate the effect of fenugreek seed extracts on resistant isolates of Candida spp. isolated from sever COVID-19 patients. Methodology: The study was conducted from August 2021 to November 2022 at Al-Imam Al-Hussein Medical City and Al-Hayat Respiratory Diseases Units. Under a specialist's physician's supervision, severe COVID-19 cases were collected. The collected 455 sputum samples were examined directly and cultured on Sabouraud's Dextrose agar (SDA) media;growth colonies were distinguished and used Grams stain with the API system before the antifungal susceptibility test was performed in accordance with clinical and laboratory standards institute (CLSI 2020) by disc diffusion method to differentiate the resistance microorganism. The extraction process was conducted using the soxhlet technique (100 grams of seed powder and 800 milliliters of solvents (chloroform, methanol, and water) for eight hours. Electrical rotatory evaporators were used to evaporate the extract to get the concentrated crude extracts. FTIR and GC-MS instruments used to detection of bioactive compounds in crude fenugreek seed extracts(aqueous, methanol, and chloroform). Then, different concentrations of each extract (25, 50, 100, and 150 mg/ml) and their effect against the tested resistance study isolated were examined by well diffusion method and Minimum inhibitory concentration was measured. Result(s): A 455 were enrolled in this study. Patients' ages ranged from 20 to 91 years (mean 52.23, SD 15.009). This study indicated that more than half of the samples were males [(262) 57.6%] and [(193) 42.4%] were females. The FTIR and GC-MS showed the methanolic extract potent the most bioactive compounds, followed by the chloroform and water extracts. Evaluation of antimicrobial effects at 50 mg/ml, the methanolic extract showed the greatest effect, with a mean inhibition zone of 9.33 mm and a significant value of 0.01;at 100 mg/ml, the chloroform extract showed the next greatest effect, with a mean inhibition zone of 10.33 mm and a significant value of 0.005. At 150 mg/ml, the aqueous extracts showed the least effect, with a mean inhibition zone of 8.33 mm and a non-significant value of 0.024. Conclusion(s): Candida spp. were most frequent isolated yeast from sputum of patients with severe COVID-19. Methanol extract was the most effective anti-candida, followed by chloroform extract, and the aqueous extract was the least effective. The most effective anti-candida drug is ketoconazole.Copyright © 2022.

Environmental impact assessment of a newly developed solid oxide fuel cell-based system combined with propulsion engine using various fuel blends for cleaner operations

After the COVID-19 pandemic has spread throughout the world, many research institutions and industrial organizations are putting great efforts into producing environmentally friendly solutions for the transportation sector. This paper presents a newly developed combined solid oxide fuel cell system with a turbofan engine that can use five alternative fuels, such as dimethyl ether, methanol, hydrogen, methane, and ethanol, with different blending ratios to form five fuel blends. The proposed system is studied in this paper using exergoenvironmental analysis (which is known as environmental impact assessment by exergy) in order to quantify and evaluate the environmental impact. The combined turbofan has an exergetic efficiency of 82%, with total fuel and product exergy rates of 905 and 743 MW, respectively. The total environmental impact caused by emissions and exergy destructions has a range of 4000 to 9000 Pt/h for all the fuel blends. The specific exergoenvironmental impact values of electricity production vary from about 3 to 8 mPt/MJ for solid oxide fuel cells and 10 to 25 mPt/MJ for the three turbines. The exergoenvironmental impact of the thrust force is a minimum of 34 Pt/(h.kN) for the RF1 fuel and a maximum of 87 Pt/(h.kN) for the RF4 fuel. © 2022

Analytical Method Development And Validation Parameters Of Drug Ivermectin

An accurate, easy, detailed, selective and fast RP-HPLC stability representative technique was developed and validated for assessment of ivermectin in tablet dosage form. The Reverse Phase High Performance Liquid Chromatographic technique was developed for routine quantification of ivermectin in laboratory prepared mixtures as well as in combined dosage forms. The chromatographic separation was accomplished with INERTSIL C-18 ODS 250x4.6mm, 5 mu m particle size column along with acetonitrile and methanol as the mobile phase at a flow rate of 1 ml/min. Quantification was completed by using a UV detector at 245 nm and the run time was 10 minutes. The retention time was found to be 4.198 min for ivermectin. The linearity was observed in the range of 1-32 mu g/ml with correlation coefficient r= 0.9798. The % RSD for intraday and interday precision was 1.352 and 1.589 respectively. The LOD and LOQ values were found to be 2.93 and 8.79, respectively. The system suitability parameters for ivermectin such as theoretical plates and tailing factor were found to be 129.949 and 2.0, respectively. Robustness was also studied and there was no significant variation in the system suitability of the analytical method by incorporating small changes in experimental parameters. The technique has been validated for linearity, precision, accuracy and other parameters as approved by ICH guidelines. The results obtained by RP- HPLC methods are found to be fast, detailed, selective and accurate. Therefore, proposed analytical method can be used for regular analysis of ivermectin in injection, tablet and other formulations.

Determination of Methanol in Commercialized Alcohol-based Hand Sanitizing and Other Similar Products using Headspace GC-MS

Background: Demand for alcohol-based products, including gel- and aqueous-type hand sanitizers, room sprays, and mouthwashes, has rapidly increased during the ongoing COVID-19 pandemic because of their microbicidal properties. However, toxic methanol can be found from the intentional addition of methanol by manufacturers and invariable production during the manufacturing of alcohol (ethanol). Although the FDA has recommended that such products should contain less than 630 ppm of methanol, it is only a temporary measure established specifically to regulate such products during the current COVID-19 pandemic and hence is not strictly regulated. Objective: This study aims to detect and quantify the level of methanol in alcohol-based products. However, some manufacturers unethically add methanol to their products and promote them as methanol-free. Besides, they do not provide proficiency and toxicity test results. Therefore, these kinds of products need to be analyzed to determine if they are acceptable to use. Methods: This study qualitatively and quantitatively investigates the amount of methanol in commercial alcohol-based products using a newly developed headspace gas chromatography/mass spectrometry method. Moreover, alcoholic beverages which contain methanol are analyzed to be compared with the levels of methanol in alcohol-based products and determine if their methanol levels are acceptable. Results: Methanol concentrations in gel-type hand sanitizers (517 ppm) and mouthwashes (202 ppm) were similar to those in white wine (429 ppm) and beer (256 ppm), respectively, while that of aqueous-type hand sanitizers (1139 ppm) was 1.5 times more than that of red wine (751 ppm). Conclusion: Methanol levels in most of the alcohol-based products did not exceed the FDA-recommended limit.

QUICK SCREENING OF HAND SANITIZERS FOR ADULTERANTS AND QUANTIFICATION OF ETHANOL CONTENT USING ATTENUATED TOTAL REFLECTANCE SPECTROSCOPY

In the current study, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy has been utilized for the analysis of 24 different brands of hand sanitizers. Methanol was detected in few of the samples analyzed. Principal component analysis (PCA) was utilized on the obtained ATR-FTIR data to investigate and recognize the patterns of hand sanitizers on the PCA plot, and it further validated the presence of methanol in some samples. Finally, ethanol concentrations in hand sanitizers were determined by building a predictive model using different concentrations of standard ethanol. Three samples were found to have less than recommended ethanol concentration. The technique utilized in the present study has the ability to give results in quick time (within 5 minutes) and can be helpful for utilization in commercial regulations i.e., to quickly and reliably identify adulterants in hand sanitizers and also quantify ethanol content to see whether the concentration matches with that of the labeled concentration in the bottle.

LC-MS Identification and Effects of Diplotaxis acris Metabolites Against SARS-CoV-2 Main Protease Supported by In Silico Computational Studies

SUMMARY. Covid-19 was announced as a pandemic in March 2020, since then scientists are trying to find out effective therapeutics as treatment. Many medicinal herbs contain antiviral compounds, such as rutin, and flavonoid glycosides that are efficient against viruses. Diplotaxis acris is a famous plant traditionally used to prepare rocket salad. LC-MS of methanol extract revealed the presence of 12 compounds, quercetin 3-O-β-rhamnoside, isorhamnetin 7-O-β-glucoside, kaempferol 3,7-diglucoside, apigenin 7-rhamnoside, and apigenin 7-O-β-glucoside as major compounds. The computational studies showed that all flavonoids form strong interaction with SARS-CoV-2 main protease with good CDOCKER interaction energy (Kcal/mol) of-53.1,-51.7,-44.1,-48.0, and-49.7, respectively, which are apigenin 7-rhamnoside as a suitable contender for oral administration. Results suggest that Diplotaxis acris have potential against SARS-CoV-2 and could be a good source of lead compounds against the novel coronavirus.

A Cluster of Five Deaths Due to Methanol Toxicity After Apparent Hand Sanitizer Ingestion in the Setting of Chronic Alcoholism.

Methanol toxicity and its associated pathologies have been widely studied, however, at the beginning of the COVID-19 pandemic, there was an increase in methanol toxicity due to apparent consumption of contaminated hand sanitizer. We report a cluster of five deaths and one presumed death due to the apparent consumption of hand sanitizer, contaminated with methanol, in the setting of chronic alcoholism. The deaths occurred in Coconino County, Arizona, over a four-and-a-half-month period (June-October 2020), before and during a Food and Drug Administration recall of contaminated hand sanitizer. Methanol-related deaths are relatively uncommon in Coconino County, with only one methanol associated death (source of ingestion unknown) occurring over the previous five years.

Methanol intoxication outbreak during the COVID-19 pandemic in Cape Town, South Africa: a case series

Objective: Methanol poisoning may result in significant morbidity and mortality, particularly during poisoning outbreaks in lowand- middle-income countries (LMIC) [1]. Although not readily available to the public in South Africa, methanol may be used as a substitute for ethanol in alcoholic beverages or to fortify illicit spirits. Following the announcement of the global COVID-19 pandemic, the South African government declared a State of Emergency in March 2020 which amongst other things prohibited the consumption, sale and transportation of alcohol [2]. We aim to describe the clinical presentation, diagnosis, treatment and outcome of a series of cases presenting to a Cape Town hospital after reportedly drinking illicit alcohol. Case series: We performed a retrospective case record review using the available records for 19 of 24 patients presenting to False Bay Hospital during June 2020 with presumed methanol poisoning. Almost all the patients were male (n=18), with a mean age of 35.1 years (SD =7.3). At least half of the patients had central nervous system effects (n=12;headache, ataxia, confusion, weakness), as well as gastrointestinal symptoms (n=10;abdominal pain, nausea, vomiting), and 5 patients reported visual loss. Time from exposure to presentation varied from 12 hours to 8 days, with 47.4% (n=9) presenting within the first 24 hours. On admission, venous blood gas samples from the patients showed the following mean values: pH of 7.14 (SD =0.23);serum bicarbonate 17.4 (SD =8.5) mmol/L;base deficit of -7.8 (SD =11.6) mmol/L, and lactate concentration of 4.1 (SD =4.0) mmol/ L. Assays to measure methanol or formate concentrations were not performed as these are not routinely available. Ten patients (52.6%) received both ethanol via nasogastric tube and intravenous sodium bicarbonate. Haemodialysis was considered for one patient but never started due to intensive care unit (ICU) resource constraints with COVID-I9 admissions. The mortality rate was 26.3% (n=5) and one patient had ongoing visual loss. Conclusion: To the authors' knowledge, this is the first published data concerning a methanol poisoning outbreak in South Africa. As described in other LMICs, the mortality rate was high, diagnosis was difficult, and access to ethanol antidote and supportive care was challenging, particularly during the COVID-19 pandemic. (Table Presented).

Poison Center hand sanitizer exposure characterization peri- and during the COVID-19 pandemic

Objective: Poison centers frequently manage calls involving ethanol-containing hand sanitizers. During the 2020 COVID-19 pandemic, our Specialists in Poison Information sensed rising numbers of cases. The increased use was not surprising due to the desire to sanitize skin and reduce transmission of COVID-19. We sought to compare hand sanitizer trends pre-pandemic and during the pandemic including a sub-analysis for children 0-5 years. Methods: We queried the National Poison Data System for human exposures of all ages within our 4-state poison center from 1 January 2015 to 31 October 2021. Generic codes for all types of hand sanitizers were included plus 2 product codes for methanol-containing hand sanitizer. Data captured included age range, product type, reason, gender, route, clinical effect, medical outcome, month, management site, and therapies. The query was repeated for the same parameters in children 0-5 years old. Descriptive statistical analyses were utilized. Results: Our poison center managed 5,819 human hand sanitizer exposures during the study period;67% occurred in children 0-5 years old. From 2019 (n=723) to 2020 (n=1,272), hand sanitizer exposures increased by 76%, 38% [all ages, children 0-5 years];52% were male. Most [77%, 99%] of these exposures were unintentional and [89%, 96%] involved ingestion as the primary route and exposures in children 0-5 years represented 64% of the total number of ingestion cases. Exposures in 2020 occurred throughout the year with higher volumes in March and July through December. Most cases were managed on-site (non-hospital) [81%, 89%], with [18%, 11%] evaluated in or referred to a hospital. Most [87%, 89%] clinical outcomes were minor or no effect overall, with similar numbers in 2020 [82%, 87%]. The top clinical effect in children 0-5 years was vomiting. For all ages, the most common effects were vomiting, nausea, and drowsiness. There was one death involving an adult who intentionally consumed hand sanitizer as an alcohol substitute. The product was contaminated with methanol and he died from methanol intoxication. Non-ethanol or isopropanol hand sanitizers were involved in 10% of exposures during the study period and 19% of exposures in 2020. Conclusion: We confirmed our suspicion that hand sanitizer exposures rose significantly in 2020. Explanations include increased usage and availability in the home paired with more time spent at home overall due to coronavirus school restrictions, working from home, and quarantine. Fortunately, even during 2020, most medical outcomes resulted in none or minor effects. Additional sub-analyses are needed to characterize other aspects including non-ethanol hand sanitizer exposures.

COVID-19 and methanol poisoning in Azerbaijan

Objective: The global pandemic of coronavirus SARS-CoV-2 has been a serious stress test for healthcare systems in many countries, with a significant impact on the structure and number of acute chemical poisonings. The aim of this study was to examine the impact of the COVID-19 pandemic on the toxic-epidemiological situation in Azerbaijan. Methods: We conducted a comparative analysis of the database of the Poison Center in Baku during the 9 months of the pandemic period (20 March - 21 December 2020) with the data of the same period in 2019 and the previous decade (2009-2018). Results: The alarming dynamics of a significant increase in the number of alcohol surrogates, primarily methanol poisoning, was revealed. In the 10-year period 2009-2018, alcohol surrogates intoxication was only 0.09% (18 patients) of total poisoning cases (20,266), but during the study period of 2020 increased to 3.4% (32 patients of 946 poisoning cases). The mortality rate in the ethanol and alcohol surrogate intoxication group in 2019 was 7.5% (8/ 106) versus 28.3% (30/106) in March-December 2020. All fatal cases in the alcohol surrogate poisoning cohort were related to methanol, thus, the mortality rate of this pathology was 61.5% (16/26). At the same time, no case of methanol poisoning was recorded in March-December 2019, and in the previous decade (2010-2018), only 1 case of methanol intoxication was recorded. The source of methanol during the pandemic was ingestion of counterfeit medical alcohol and alcohol-containing disinfectant products purchased by the victims themselves in the pharmacy network. Conclusion: The COVID-19 pandemic and quarantine measures had a significant impact on the epidemiology of poisoning in Azerbaijan, with an increase in cases and mortality of methanol poisoning. The outbreak of methanol poisoning in Azerbaijan revealed many shortcomings and weaknesses in the country's public health system. Late or erroneous diagnosis, lack of knowledge and clinical experience in the diagnosis and management of poisoned patients, difficulties with laboratory and diagnostic confirmation of the diagnosis, restrictions in the treatment of patients, relating to the lack of an effective antidote (fomepizole) resulted in high mortality. Considering the almost complete absence of methanol poisoning in Azerbaijan over the previous decade, the question of the source of the methanol is raised. Until a few years ago, the only methanol plant in the Caucasus was opened in Azerbaijan with a production capacity of more than 400 thousand tons per year. The plant stores more than 48 thousand metric tons of finished product, and should be investigated for possible leakage to the illegal market.

Diabetic ketoacidosis as a complication of methanol poisoning; a case report.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a complication of diabetes presenting with high anion gap metabolic acidosis. Methanol poisoning, on the other hand, is a toxicology emergency which presents with the same feature. We present a case of methanol poisoning who presented with DKA. CASE PRESENTATION: A 28-year-old male was referred to us with blurred vision and loss of consciousness three days after ingestion of 1.5 L of an unknown mixture of bootleg alcoholic beverage. He had history of insulin-dependent diabetes and had neglected his insulin shots on the day prior to hospital admission due to progressive loss of consciousness. Vital signs were normal and venous blood gas analysis showed severe metabolic acidosis and a methanol level of 10.2 mg/dL. After eight hours of hemodialysis, he remained unresponsive. Diabetic ketoacidosis was suspected due to positive urine ketone and blood sugar of 411 mg/dL. Insulin infusion was initiated which was followed by full awakening and extubation. He was discharged completely symptom-free after 4 weeks. CONCLUSIONS: Diabetic ketoacidosis and methanol poisoning can happen simultaneously in a diabetic patient. Given the analogous high anion gap metabolic acidosis, physicians should pay particular attention to examination of the diabetic patients. Meticulous evaluation for both conditions is highly recommended.