A case of severe benzalkonium chloride intoxication in a cat.

BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC), that can be found in a wide variety of household products-from disinfectants to medicaments and home fragrances-but also professional products. In pets, cats have long been reported as more sensitive than dogs to QACs; in fact, signs of irritation such as oral ulcerations, stomatitis and pharyngitis can be observed after contact with concentrations of 2% or lower. In a review of 245 cases of BAC exposure in cats, reported by the Veterinary Poisons Information Service (United Kingdom) only 1.2% of the cases died or were euthanized. Nevertheless, BAC toxidromes in cats can result in transitory CNS and respiratory distress, as well as severe mucosal and cutaneous lesions. Currently, only a few reports are available concerning BAC poisoning in this species. CASE PRESENTATION: A 4 month-old kitten presented with severe glossitis, lameness in the hindlimbs and episodes of vomiting and diarrhoea. The cause was unknown until the owners reported use of a BAC-containing mould remover (5%) 4 days later. The patient developed severe oral burns requiring a pharyngeal tube for feeding and severe cutaneous chemical burns. The kitten was managed with supportive therapy and required hospitalization for 10 days. The symptoms disappeared completely 3 weeks after exposure. CONCLUSIONS: BAC is a very common compound contained in several household and professional products but, to the best of our knowledge, no previous case had been reported in Italy. We hope that this report will help raise awareness on the hazards of BAC products for cats in both domestic and work contexts.

First Report of Pinnatoxin-G (PnTX-G) in a Marine-Coastal Area of the Adriatic Sea Associated with the Presence of the Dinoflagellate Vulcanodinium rugosum.

This study reports the first detection of the marine neurotoxin pinnatoxin-G (PnTX-G) in clams collected in the northwestern Adriatic Sea (Italy). It also represents the first report of the potential toxin-producing dinoflagellate, Vulcanodinium rugosum, in Italian seas. This result, from the coasts of the Emilia-Romagna Region, indicates a successful colonization process, reflecting conditions in France where V. rugosum was initially documented. In this case, the concentration of PnTXs was very low, making further sampling necessary to fully understand the extent of the phenomenon. Discussions on the need to obtain more data to support a proper risk assessment and the need to implement a monitoring program that includes emerging marine biotoxins are also included.

Chemical Composition and Anti-Candida Activity of Mentha suaveolens Ehrh. Essential Oils Obtained by Different Distillation Processes.

A comparative study on essential oils extracted from Mentha suaveolens Ehrh. from Italy is reported. Two extraction procedures were investigated: hydrodistillation and steam distillation, carried out as a continuous and fractionated procedure. Fresh and dried plant material from two harvests was used. The hydrodistillation method yielded a higher amount of essential oil. The dried plant was significantly richer in essential oil per kg of starting plant material. Gas chromatography-mass spectrometry analysis of 112 samples showed that the essential oils belong to the piperitenone oxide-rich chemotype. In addition, piperitenone, p-cymen-8-ol, and limonene were among the most abundant compounds in the different samples. A higher amount of piperitenone oxide was obtained by hydrodistillation, while steam distillation gave a higher percentage of piperitenone and limonene. The essential oils were characterized for their anti-Candida albicans activity; higher potency was observed for the samples rich in piperitenone oxide, with MIC values ranging from 0.39 to 0.78 mg·mL-1 (0.039% and 0.078% p/v). The results of this work provide a deep insight into the methodology of essential oil extraction and the associated chemical variability of M. suaveolens Ehrh. Some of the essential oils are potent against C. albicans and could be considered for potential use in therapy.

Up-Cycling of Olea europaea L. Ancient Cultivars Side Products: Study of a Combined Cosmetic-Food Supplement Treatment Based on Leaves and Olive Mill Wastewater Extracts.

In recent years, a reversal of the global economic framework has been taking place: from the linear model, there has been a gradual transition to a circular model where by-products from the agri-food industry are taken and transformed into value products (upcycling) rather than being disposed of. Olive tree pruning represents an important biomass currently used for combustion; however, the leaf part of the olive tree is rich in phenolic substances, including hydroxytyrosol. Mill wastewater is also discarded, but it still contains high amounts of hydroxytyrosol. In this study, cosmetic and food supplement formulations were prepared using biophenols extracted from leaves and wastewater and were tested in a placebo-controlled study on healthy volunteers using a combined cosmetic and food supplement treatment. A significant improvement in skin health indicators (collagen density, elasticity, etc.) and a 17% improvement against Photo-induced Irritative Stimulus was observed.

A Safe-by-Design Approach for the Synthesis of a Novel Cross-Linked Hyaluronic Acid with Improved Biological and Physical Properties.

Hyaluronic acid (HA) is a polymer with unique biological properties that has gained in interest over the years, with applications in pharmaceutical, cosmetic, and biomedical fields; however, its widespread use has been limited by its short half-life. Therefore, a new cross-linked hyaluronic acid was designed and characterized using a natural and safe cross-linking agent, such as arginine methyl ester, which provided improved resistance to enzymatic action, as compared to the corresponding linear polymer. The antibacterial profile of the new derivative was shown to be effective against S. aureus and P. acnes, making it a promising candidate for use in cosmetic formulations and skin applications. Its effect on S. pneumoniae, combined with its excellent tolerability profile on lung cells, also makes this new product suitable for applications involving the respiratory tract.

Magnolia officinalis L. bark extract and respiratory diseases: From traditional Chinese medicine to western medicine via network target.

The understanding of the use of Magnolia officinalis L. (Magnoliaceae) as a possible dietary supplement for supporting the treatment of airway pathologies might be of clinical interest. Two commercially available bark extracts (M. officinalis extract [MOE]) were characterized by quantitation in honokiol and magnolol content by means of high-performance liquid chromatography with UV detection. MOE effects, as well as those of the reference compounds per se, on some targets connected to airway pathologies (antibacterial- and lung and trachea relaxing- activities) were investigated. Results showed that MOE possessed interesting antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae. This was accompanied by a spasmolytic and antispasmodic activity, possibly owing to its ability to concurrently modulate different targets such as H1 -, ß2 - and muscarinic receptors and l-type calcium channels involved in bronchodilation. All these effects were directly related to the MOE content in honokiol and magnolol. In conclusion, the properties of MOE highlighted here strongly encourage its application as dietary supplement in the treatment of airway diseases.

Multifunctional Profiling of Moringa oleifera Leaf Extracts for Topical Application: A Comparative Study of Different Collection Time.

This research investigated plant extracts as a source of potential new actives in the nutritional, cosmetic, and pharmaceutical fields. Moringa oleifera, which is extensively known for its nutritional properties, has been investigated in this work by preparation, characterization, and evaluation of the antioxidant (FRAP, DPPH, ORAC, and PCL test), antifungal, photoprotective, and cytotoxicity profile against human melanoma Colo38 cell line of two different extracts (hydroalcoholic and methanolic) and one infusion of dry leaves collected from Paraguay in four distinct harvest times (February, March, April, and May 2017). The outcomes of this study highlight Moringa oleifera as a potential ally to counteract skin aging and oxidative stress, as indicated by the favorable antioxidant profile of the extracts and infusions of Paraguay, which was, in all cases, superior to that provided by the same plant species when collected from Senegal. Moreover, some samples were more efficient in preventing the photodegradation of UVA filter butyl methoxydibenzoylmethane (Avobenzone) compared to commercial filters, thus suggesting an interesting future role as natural additives in sunscreens.

A Safe-by-Design Approach to "Reef Safe" Sunscreens Based on ZnO and Organic UV Filters.

In recent years, the issue of coral bleaching has led to restrictions in some tropical locations (i.e., Palau, Hawaii, etc.) on the use of some organic UV sunscreen filters, such as oxybenzone and ethyl hexyl methoxycinnamate. In contrast, ZnO is considered safe for marine environments and thus is often used without considering its photocatalytic and oxidative activities related to the generation of O2•- and HO•. Moreover, ZnO needs to be used in combination with other filters to reach higher protection factors. Thus, the study of its interaction with formulations and with organic filters is important in sunscreen technology for the development of safer by-design products. In this work, the photocatalytic activity of zinc oxides with different surface areas (30, 25 and 9 m2/g) and their interaction with selected organic sunscreen filters were investigated. In particular, the ZnO photocatalytic kinetics were studied following the photodegradation of Acid Blue 9 (AB9) observing a first-order reaction with a chemical regime. Our evaluations of the selective inhibitions by hvb+ and HO• demonstrated a substantial predominance of the hydroxide radicals in the expression of the photocatalysis, a trend that was also confirmed by the irradiation of ZnO in an ethanolic solution. Indeed, the formulations containing both ZnO and organic filters defined as "safe" for coral reefs (i.e., Diethylamino Hydroxybenzoyl Hexyl Benzoate, DHHB, and Ethylhexyl Triazone, EHT) showed a non-negligible photocatalytic oxidation and thus the combination was underlined as safe to use.

Expert Systems for Predicting the Bioavailability of Sun Filters in Cosmetic Products, Software vs. Expert Formulator: The Benzophenone-3 Case.

There are only a limited number of molecules in a cosmetic formulation, which can passively cross the stratum corneum and be absorbed into the skin layers. However, some actives should never cross the skin in large concentrations due to their potential for side effects, for example, sunscreens. Artificial intelligence is gaining an increasing role as a predictive tool, and in this regard, we selected the Formulating for Efficacy® Software to forecast the changes in bioavailability of selected topical cosmetic compounds. Using the Franz diffusion cell methodology, various oils were selected as those with low release capability, and these were compared to those suggested by the software in Benzophenone-3-containing formulations. The software was able to predict the lipophilic phases, which, if utilized in the emulsion, were stable and sometimes even more pleasant in appearance and consistency than the reference emulsions prepared by the formulator. To date, however, Formulating for Efficacy® Software still has limitations as far as predicting the hydrophilic phase, as well as not being able to choose the emulsifier or the preservative system.

Phylogenomic analysis of the genus Leuconostoc.

Leuconostoc is a genus of saccharolytic heterofermentative lactic acid bacteria that inhabit plant-derived matrices and a variety of fermented foods (dairy products, dough, milk, vegetables, and meats), contributing to desired fermentation processes or playing a role in food spoilage. At present, the genus encompasses 17 recognized species. In total, 216 deposited genome sequences of Leuconostoc were analyzed, to check the delineation of species and to infer their evolutive genealogy utilizing a minimum evolution tree of Average Nucleotide Identity (ANI) and the core genome alignment. Phylogenomic relationships were compared to those obtained from the analysis of 16S rRNA, pheS, and rpoA genes. All the phylograms were subjected to split decomposition analysis and their topologies were compared to check the ambiguities in the inferred phylogenesis. The minimum evolution ANI tree exhibited the most similar topology with the core genome tree, while single gene trees were less adherent and provided a weaker phylogenetic signal. In particular, the 16S rRNA gene failed to resolve several bifurcations and Leuconostoc species. Based on an ANI threshold of 95%, the organization of the genus Leuconostoc could be amended, redefining the boundaries of the species L. inhae, L. falkenbergense, L. gelidum, L. lactis, L. mesenteroides, and L. pseudomesenteroides. Two strains currently recognized as L. mesenteroides were split into a separate lineage representing a putative species (G16), phylogenetically related to both L. mesenteroides (G18) and L. suionicum (G17). Differences among the four subspecies of L. mesenteroides were not pinpointed by ANI or by the conserved genes. The strains of L. pseudomesenteroides were ascribed to two putative species, G13 and G14, the former including also all the strains presently belonging to L. falkenbergense. L. lactis was split into two phylogenetically related lineages, G9 and G10, putatively corresponding to separate species and both including subgroups that may correspond to subspecies. The species L. gelidum and L. gasicomitatum were closely related but separated into different species, the latter including also L. inhae strains. These results, integrating information of ANI, core genome, and housekeeping genes, complemented the taxonomic delineation with solid information on the phylogenetic lineages evolved within the genus Leuconostoc.

Acetylcholinesterase (AChE) Reversible Inhibitors: The Role of Oxamyl in the Production of Poisoned Baits.

Oxamyl is a highly toxic carbamate molecule with toxicological risk from contamination, used as an insecticide, nematicide, and acaricide on many field crops, vegetables, fruits, and ornamentals. Suspected poisoned animals and baits were collected between January 2018 and August 2021 from Lombardy and Emilia-Romagna regions and analyzed at the chemical toxicology laboratory of the Experimental Zooprophylactic Institute of Lombardy and Emilia-Romagna, located in Brescia. The analyses were carried out by an ion trap GC-MS system in 2467 suspected samples and showed the presence of oxamyl in 67 of these. In this study, we analyzed 47 (out of 67) positive baits: the provinces in which more cases have been recorded are Mantua, Ferrara, and Cremona, which overall had 72% of positivity. The nature of the analyzed samples was mostly corn (55.3%), followed by bird carcasses (19.1%), apples (14.8%), meatballs (2.1%), bread (2.1%), and other (8.5%). The use of oxamyl to produce poisoned baits is constantly increasing, proving that it must be considered as a public health risk for the possible consequences on target and non-target organisms, including humans.

Benzothiazole Derivatives as Multifunctional Antioxidant Agents for Skin Damage: Structure-Activity Relationship of a Scaffold Bearing a Five-Membered Ring System.

Skin diseases often give multifactorial damages; therefore, the development of multifunctional compounds represents a suitable approach especially against disorders that are induced by oxidative stress. Thus, taking into account the successful results we achieved on benzimidazoles, we have devised a new series of isosteric benzothiazoles and investigated their antioxidant, photoprotective, antifungal and antiproliferative activity. Particular attention has been paid to synergistic antioxidant and photoprotective properties. For compounds 9a and 10a, a multifunctional profile was outlined, supported by an excellent filtering capacity, mainly UVB, which has higher capacities than those of the reference PBSA which is currently in the market as a UV sunscreen filter. The two compounds were also the best in terms of growth inhibition of dermatophytes and Candida albicans, and 10a also showed good antioxidant activity. Furthermore, 9a was also effective on melanoma tumor cells (SK-Mel 5), making these compounds good candidates in the development of new skin protective and preventive agents.

Machine Learning Data Augmentation as a Tool to Enhance Quantitative Composition-Activity Relationships of Complex Mixtures. A New Application to Dissect the Role of Main Chemical Components in Bioactive Essential Oils.

Scientific investigation on essential oils composition and the related biological profile are continuously growing. Nevertheless, only a few studies have been performed on the relationships between chemical composition and biological data. Herein, the investigation of 61 assayed essential oils is reported focusing on their inhibition activity against Microsporum spp. including development of machine learning models with the aim of highlining the possible chemical components mainly related to the inhibitory potency. The application of machine learning and deep learning techniques for predictive and descriptive purposes have been applied successfully to many fields. Quantitative composition-activity relationships machine learning-based models were developed for the 61 essential oils tested as Microsporum spp. growth modulators. The models were built with in-house python scripts implementing data augmentation with the purpose of having a smoother flow between essential oils' chemical compositions and biological data. High statistical coefficient values (Accuracy, Matthews correlation coefficient and F1 score) were obtained and model inspection permitted to detect possible specific roles related to some components of essential oils' constituents. Robust machine learning models are far more useful tools to reveal data augmentation in comparison with raw data derived models. To the best of the authors knowledge this is the first report using data augmentation to highlight the role of complex mixture components, in particular a first application of these data will be for the development of ingredients in the dermo-cosmetic field investigating microbial species considering the urge for the use of natural preserving and acting antimicrobial agents.

Design, Synthesis, Characterization, and In Vitro Evaluation of a New Cross-Linked Hyaluronic Acid for Pharmaceutical and Cosmetic Applications.

Hyaluronic acid (HA), an excellent biomaterial with unique bio properties, is currently one of the most interesting polymers for many biomedical and cosmetic applications. However, several of its potential benefits are limited as it is rapidly degraded by hyaluronidase enzymes. To improve the half-life and consequently increase performance, native HA has been modified through cross-linking reactions with a natural and biocompatible amino acid, Ornithine, to overcome the potential toxicity commonly associated with traditional linkers. 2-chloro-dimethoxy-1,3,5-triazine/4-methylmorpholine (CDMT/NMM) was used as an activating agent. The new product (HA-Orn) was extensively characterized to confirm the chemical modification, and rheological analysis showed a gel-like profile. In vitro degradation experiments showed an improved resistance profile against enzymatic digestions. Furthermore, in vitro cytotoxicity studies were performed on lung cell lines (Calu-3 and H441), which showed no cytotoxicity.

New Trends in the Occurrence of Yessotoxins in the Northwestern Adriatic Sea.

Yessotoxins (YTXs) are polycyclic toxic ether compounds produced by phytoplanktonic dinoflagellates which accumulate in filter-feeding organisms. We know that the water temperature in our areas Northwestern Adriatic Sea is optimal for the growth of potentially toxic algae (around 20 °C). In recent years, these temperatures have remained at these levels for longer and longer periods, probably due to global warming, which has led to an excessive increase in toxin levels. The interruption of mussel harvesting caused by algae negatively affects farmers' revenues and the availability of local fish, causing a major economic loss in Italy's main shellfish sector. METHODS: In the nine years considered, 3359 samples were examined: 1715 marine waters, 73 common clams; 732 mussels; 66 oysters; and 773 veracious clams. Bivalve molluscs were examined for the presence of marine biotoxins, including YTXs, while potentially toxic algae, including those producing YTXs, were searched for and counted in marine waters. The method adopted for the quantification of lipophilic toxins involves the use of an LC-MS/MS system. The enumeration of phytoplankton cells was performed according to the Utermhöl method. RESULTS: Between 2012 and 2020, 706 molluscs were tested for YTXs. In total, 246 samples tested positive, i.e., 34.84%. Of the positive samples, 30 exceeded the legal limit. CONCLUSION: In this regard, it is essential to develop and activate, as soon as possible, an "early warning" system that allows a better control of the production areas of live bivalve molluscs, thus allowing an optimal management of the plants in these critical situations.

Biotransformation of Cortisone with Rhodococcus rhodnii: Synthesis of New Steroids.

Cortisone is a steroid widely used as an anti-inflammatory drug able to suppress the immune system, thus reducing inflammation and attendant pain and swelling at the site of an injury. Due to its numerous side effects, especially in prolonged and high-dose therapies, the development of the pharmaceutical industry is currently aimed at finding new compounds with similar activities but with minor or no side effects. Biotransformations are an important methodology towards more sustainable industrial processes, according to the principles of "green chemistry". In this work, the biotransformation of cortisone with Rhodococcus rhodnii DSM 43960 to give two new steroids, i.e., 1,9ß,17,21-tetrahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11,20-dione and 1,9ß,17,20ß,21-pentahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11-one, is reported. These new steroids have been fully characterized.

Heavy metals and potential risks in edible seaweed on the market in Italy.

The seaweed food has always been important in Asia, but recently increased in the Western diet. Superfood known for health benefits and rich in essential elements, can also accumulate high contents of heavy metals and iodine from the environment, becoming a health hazard. In particular for iodine, an appropriate labelling of seaweed is needed to warn the consumer of the potential risks. The aim of the study was to analyze the content of 20 heavy metals in seaweeds, distributed in Italy, by ICP-MS, also determining iodine and arsenic (total and inorganic fraction). A total of 72 samples of European and Asian seaweed of 8 genera were analyzed and the results correlated the content of heavy metals to genus, geographical origin and type of sample; 8.33% of the products lacked in the label of the indications of allergens, while 9.72% had irregularities in the label language. The highest concentration of elements was found in the Rhodophyta. The Aluminum level was the highest in the mixed seaweed (165.39 mg/kg) and for the Cadmium in the Asian seaweed (1.16 mg/kg). The amounts of Iron, Zinc and Magnesium, was highest in the Asian seaweed. The values of Arsenic (total and inorganic contents) were compared with the limits: 2.78% exceeds France and USA limits for inorganic, while higher content of total was found in Phaeophyta, which also showed the highest Iodine content (6770.80 mg/kg) that can be dangerous if not reported correctly in the label.

Skin Damages-Structure Activity Relationship of Benzimidazole Derivatives Bearing a 5-Membered Ring System.

In the search for scaffolds for multifunctional compounds we investigated the structure activity relationship of a class of benzimidazole derivatives bearing 5-membered ring. The newly synthesized and the already known compounds were divided into three classes that present different substituent at 5 position of the benzimidazole ring (-H, -COOH or -SO3H) and different heterocycle at position 2 (thiophene, furan or pyrrole). All the derivatives were synthesized and tested to determine their photoprotective profile against UV rays, in vitro antioxidant capacity against different radicals (DPPH and FRAP test), antifungal inhibitory activity (dermatophytes and Candida albicans), antiviral and antiproliferative activity. A Structure-Activity Relationship study indicated compound 10, bearing a pyrrole heterocycle on the benzimidazole ring, as the best multifunctional derivative of the series and as potential candidate for the development of drugs especially in case of melanoma.

Design, synthesis and evaluation of benzothiazole derivatives as multifunctional agents.

Oxidative stress is the product or aetiology of various multifactorial diseases; on the other hand, the development of multifunctional compounds is a recognized strategy for the control of complex diseases. To this end, a series of benzothiazole derivatives was synthesized and evaluated for their multifunctional effectiveness as antioxidant, sunscreen (filter), antifungal and antiproliferative agents. Compounds were easily synthesized via condensation reaction between 2-aminothiophenols and different benzaldehydes. SAR study, particularly in position 2 and 6 of benzothiazoles, led to the identification of 4g and 4k as very interesting potential compounds for the design of multifunctional drugs. In particular, compound 4g is the best blocker of hERG potassium channels expressed in HEK 293 cells exhibiting 60.32% inhibition with IC50 = 4.79 µM.

Comparative Study of SPA Mud from "Bacino Idrominerario Omogeneo dei Colli Euganei (B.I.O.C.E.)-Italy" and Industrially Optimized Mud for Skin Applications.

The term "Salus per aquam (SPA) therapies" refers to therapeutic pathways that includes mud therapy. The therapeutic efficacy of a peloid depends on its chemical and mineralogical composition, as well as its technological properties. Considering the increasing use of clay-based products, it becomes essential to characterize peloids from a qualitative and quantitative point of view. Therefore, this research project aimed to develop a protocol that allows characterization of the chemical-physical composition of sludges collected from different areas of the Homogeneous Euganean Hills Hydromineral Basin (B.I.O.C.E.). The study established a comparative study both between different matrices and between the same matrices at different maturation times, including also a comparison with an industrialized product, that can be used at home, which maintains the characteristics of a natural mud. This research was developed studying the pH, grain size distribution, and chemical and mineralogical composition. Peloids are characterized by a neutral/basic pH and are divided into two categories from a granulometric point of view: The chemical composition allowed observation of numerous correlations between oxides present in the samples and to quantify the presence of heavy metals. Mineralogical analysis made it possible to identify and compare the composition of each sample, also according to the maturation time. Thanks to the methods adopted, important correlations were achieved.