Amination of naringinase to improve citrus juice debittering using a catalyst immobilized on glyoxyl-agarose.

A naringinase complex was chemically aminated prior to its immobilization on glyoxyl-agarose to develop a robust biocatalyst for juice debittering. The effects of amination on the optimal pH and temperature, thermal stability, and debittering performance were analyzed. Concentration of amino groups on catalysts surface increased in 36 %. Amination reduced the ß-glucosidase activity of naringinase complex; however, did not affect optimal pH and temperature of the enzyme and it favored immobilization, obtaining α-l-rhamnosidase and ß-d-glucosidase activities of 1.7 and 4.2 times the values obtained when the unmodified enzymes were immobilized. Amination favored the stability of the immobilized biocatalyst, retaining 100 % of both activities after 190 h at 30 °C and pH 3, while its non-aminated counterpart retained 80 and 52 % of α-rhamnosidase and ß-glucosidase activities, respectively. The immobilized catalyst showed a better performance in grapefruit juice debittering, obtaining a naringin conversion of 7 times the value obtained with the non-aminated catalyst.

Profile of incidental exposures to e-cigarette liquids in Europe, 2018-2019.

BACKGROUND: Following the implementation of the European Union Tobacco Product Directive (EU TPD) regulations on e-cigarette products in 2016, we assessed the current profile of e-cigarette liquid exposure incidents and their associated health outcomes. METHODS: De-identified data were received from poison centers in eight EU Member States (Sweden, the Netherlands, Italy, Hungary Austria, Finland, Spain and Croatia) reporting on e-cigarette liquid exposure incidents between August 2018 to December 2019. Descriptive analysis was conducted to present incident characteristics and health outcomes. Chi-square tests and multivariable logistic regression analysis were used to test associations. RESULTS: Of the 223 e-liquid exposure incidents recorded by poison centers in multiple EU MS, 64.7% of the cases were unintentional exposures, ranging from 48.4% among adults aged ≥19 years to 100.0% among children aged 0-5 years (p < 0.05). The most frequent route of exposure was ingestion (73.5%) while55.2% experienced any clinical symptoms, including nausea (16.6%), vomiting (11.1%), and dizziness (9.0%). 57.8% of the cases were treated at the residence or on-site. CONCLUSION: Further monitoring is warranted, using uniform reporting requirements, to ensure the continued compliance to the EU TPD and assess its long-term impact on related incident characteristics.

Ingestions of benzydamine-containing vaginal preparations.

OBJECTIVE: Benzydamine is a non-steroidal antiinflammatory drug used as vaginal lavage for non-specific vaginitis. Data on overdoses are scarce despite its wide availability. METHODS: Retrospective analyses of single ingestions of benzydamine vaginal irrigation products from January 1991 to December 2003 reported to the Spanish Poison Control Centre. RESULTS: 724 cases met the inclusion criteria; 86.2% of the patients were over age 14 years. Gender was not a factor in young children but 80.9% of patients older than 14 years were female. In 85.9% of cases, benzydamine was ingested when it was mistaken for an oral preparation or for an oral antiseptic. The rest were unintentional exposures in children (13.8%) or suicidal attempts (0.3%). Clinical signs or symptoms, when present, were mainly gastrointestinal (48% of symptomatic patients) followed by neurological (31%) or both (21%). The most common symptom was nausea (32.8% of symptomatic patients) followed by vomiting (27.9%), dizziness (20.1%), hallucinations (15.3%), abdominal pain (13.4%), and esophageal irritation and agitation (10.5%, each). Six of 68 children (mean age 6.2, range 3-11 years) had hallucinations. A severe case was that of a 4-year-old child who had convulsions caused by the unintentional ingestion of benzydamine. CONCLUSION: This is the largest report of benzydamine ingestions. The outstanding feature was the high percentage of neurological manifestations in children and adults, mainly hallucinations, following the ingestion of an over-the-counter product.

Oral tetridamine exposures.

OBJECTIVE: Tetridamine is a non-steroidal anti-inflammatory drug of the class indazols used topically as co-adjuvant for vaginitis. No previous data have been published about tetridamine overdoses. METHODS: Retrospective analysis of single ingestions of tetridamine vaginal douches reported to the Spanish Poison Control Centre from January 1991 to December 2003. RESULTS: Seventy-seven cases met the inclusion criteria; 89.6% of the patients were over age 14 years. Exposures primarily involved female patients (94.4%). In 87% of cases, the tetridamine was ingested when it was mistaken for an oral preparation or for an oral antiseptic. The rest were unintentional exposures in children (10.4%) or suicide attempts (2.6%). Clinical effects, present in 17 patients, were mainly gastrointestinal (11 patients) followed by neurological (3 patients) or both (3 patients). The most common symptom was vomiting, followed by nausea, abdominal pain, and headache. One woman who ingested 4 g in a suicidal attempt became comatose. CONCLUSION: This is the first report of tetridamine overdoses. An effort should be made by physicians and pharmacists to explain clearly the correct directions for the use of vaginal irrigation preparations.

Ten years of latrogenic intoxications from the Spanish poison control center.

Iatrogenic incidents involving drugs are the main type of nosocomial intoxications reported to the Spanish Poison Control Center. We examined 231 such incidences from January 1991 to December 2000; 46.1% were route errors, 42.4% overdoses and 7.3% administration to the wrong patient. The most important cause of error in hospitals and dentist consults was route confusions and overdoses in primary health care units. In 56.2% of the dose errors the patient was a child < 2y old in a pediatric inpatient setting, involving the iv route; the common administered drugs were anti-infectives, anticoagulants, analgesics and sedatives. Poison Control Centers have an important role in the prevention of iatrogenic intoxications.

Volatile substance and other drug abuse inhalation in Spain.

OBJECTIVE: Inhalant misuse is the intentional inhalation of volatile substances in order to obtain euphoric, disinhibiting, and exciting effects. Solvents, glues, adhesives, paints, varnishes, paint removers, dry cleaning agents, spray paints, nail polish removers, typewriter correction fluids, and aerosol propellants are common sources of volatile substance abuse. In recent years the abuse of inhalant substances, not only among those who abuse other drugs but also in teenagers and younger children, has been reported. We reviewed retrospectively the cases of inhalant misuse reported to the Spanish Poison Control Center. METHODS: Human intoxications from abuse of inhalant substances registered by our service from 1991 to 2000 were studied. Data analyzed were relative to age, gender, signs and symptoms, drug dependence antecedents, and severity of symptoms of the patients. The type of product and composition were also investigated. RESULTS: During the study period 109 cases of patients aged from 8 to 50 years were collected. A percentage of 36.6% was less or equal to 20 years old. Seventy percent corresponded to males. Of the patients, 11% presented dependence antecedents to other abuse drugs and 72.5% were symptomatic. In the symptomatic exposures clinical features affected the following systems: CNS (62.8%), gastrointestinal (8.1%), cardiovascular (8.1%), respiratory (2.9%), peripheral nervous system (1.1%), renal (1.1%), haematological (1.1%), hepatic (1.7%), and other (13.1%). The commercial products more frequently inhaled were solvents (34.9%) and glues/adhesives (22.9%). We noted the use of medicines with ethyl chloride-local anaesthetic (8.3%), three cases with aerosol bronchodilator (with fluorocarbons as propellants), and one case of xylazine inhalation. The composition most often involved was aromatic hydrocarbons (46.9%), halogenated hydrocarbons (16.5%), aliphatic hydrocarbons (11.4%), ketones (10.1%), local anaesthetic (ethyl chloride) (8.4%), ethers (2.5%), nitrous oxides (2.5%), and aliphatic nitrites (1.7%). The calls received were 59.6% from health care units and 22% from general public. Only 14% of cases were at home and 48% had moderate to severe clinical effects. Acute intoxications occurred in 82% of cases. CONCLUSIONS: Inhalation of volatile substance as abuse drugs has been detected in different age groups, including very young people. Although the principal source was industrial products, the use of drugs such as local anaesthetics and aerosol broncodilators was also detected. Based on epidemiological studies in the Spanish population (essentially adolescents and childhood) together with the ability of a Poison Center to detect sentinel-events, the community and authorities should develop strategies to prevent these exposures and the later use of other substances of abuse. In fact, recently a Law on Drug Dependences and Other Addictive Alterations has been approved in Madrid in order to take precautionary measures.

Optimization of yield in kinetically controlled synthesis of ampicillin with immobilized penicillin acylase in organic media.

Immobilized penicillin acylase is a moderately priced versatile enzyme, that is able to catalyze the synthesis of derived penicillins and cephalosporins from the corresponding beta-lactam nuclei and proper side-chain precursors. Kinetically controlled synthesis is a better strategy when product yield is a key issue. Yield should increase at reduced water activity by depressing the competing hydrolytic reactions in favor of synthesis; therefore, organic cosolvents can be a suitable reaction media for synthesis. Using response surface methodology and product yield as objective function, temperature and pH were optimized in the kinetically controlled synthesis of ampicillin using previously screened cosolvents and reaction conditions. Optimum pH was 6.0 for ethylene glycol (EG) and glycerol (GL) and 6.6 for 1-2 propanediol (PD); optimum temperature was 30 degrees C for GL and for EG and PD was in the lower extreme of the range studied, optimum lying below 26 degrees C. Maximum molar yields predicted by the model were 58,51, and 46% for EG, GL, and PD, respectively, which were experimentally validated. Highest yield in aqueous buffer was always <40%. Molar yields about 60% compare favorably with values reported for the kinetically and thermodynamically controlled synthesis of ampicillin and other derived penicillins.