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Longer life expectancy has led to an increase in efforts directed to the discovery of new healing agents for disorders related to aging, such as bone diseases. Harboring an incredible variety of bioactive metabolites, marine organisms are standing out as fruitful sources also in this therapeutic field. On the other hand, the in vivo zebrafish model has proven to be an excellent low-cost screening platform for the fast identification of molecules able to regulate bone development. By using zebrafish larvae as a mineralization model, we have thus evaluated the effects of the crude acetonic extract from the marine sponge Aplysina aerophoba and its bromotyrosine components on bone development. Obtained results led to the selection of aerophobin-1 (1) as a promising candidate for applications in regenerative medicine, paving the way for the development of a novel therapeutic option in osteoporosis treatment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction: Moraxella nonliquefaciens (M. nonliquefaciens) is a low pathogenicity microorganism, which rarely causes ocular infections, unless there is a predisposing factor. The main clinical manifestation of M. nonliquefaciens ocular infections is endophthalmitis and only five cases of corneal infection have been reported. This work shows an update in M. nonliquefaciens corneal infections, and the first reported case of keratitis due to M. nonliquefaciens superinfecting herpes simplex infection. Case report: A 84-year old woman with worsening of her herpes simplex keratitis, diagnosed, and treated 2 days before. The slit lamp showed deep paracentral infiltrate and hypopyon. A corneal sample was collected for culture prior to initiation of empiric antibiotic therapy with vancomycin and ceftazidime fortified, oral acyclovir, and cyclopentolate. The strain was identified as M. nonliquefaciens and topical antibiotic therapy was adjusted to ciprofloxacin and ceftazidime. After 2 weeks, the epithelial defect and the infiltrate were resolved and prednisolone was added to the regimen. As the corneal oedema and neovascularization decreased, acyclovir, and prednisolone were slowly tapered. About 4 months later, the visual outcome was 20/50 and the ophthalmic examination showed a clear cornea with a paracentral leucoma. Conclusion: Keratitis due to M. nonliquefaciens is rare and should be suspected in patients with local predisposing factors such as corneal damage or previous corneal infection. Prompt and appropriate combined treatment for the predisposing lesions and the keratitis may improve the prognosis and avoid a more aggressive approach.

Biological invasions by non-indigenous species have been widely recognized among the most important threats to the integrity of Mediterranean ecosystems, often resulting in huge economic and societal impacts. The success of non-indigenous macrophytes in the new range may be due to a variety of factors such as their vegetative reproductive strategy and synthesis of toxic compounds. These toxic compounds may influence native consumers by reducing their performance with negative implications for their overall grazing activity and, ultimately, for their ability to control the spread of the invasive algae in the new area. In particular, the invasive algae Caulerpa taxifolia (Vahl) C. Agardh (Ct) and Caulerpa cylindracea (Sonder) (Cc) are known to contain two main bioactive metabolites, the toxic sequiterpene caulerpenyne (CYN) and the bisindolic pigment caulerpin (CAU), potentially acting as chemical stressors for several Mediterranean species. Novel and urgent questions have also been raised by the spread of Caulerpa taxifolia (Vahl) C. Agardh var. distichophylla (Sonder) Verlaque, Huisman e Procaccini along Italian and Turkish coasts. Although the levels of CYN in Ctvd collected in the Eastern Mediterranean were determined to be much lower than those determined for Ct in the Western Mediterranean, the possible presence of CAU in Ctvd still has to be ascertained. The present work confirms and quantify the presence of CYN in Ctvd from Sicilian coasts by means of liquid chromatography/mass spectrometry (LC-MS), while the same procedure did not allow detection of CAU in the algal extracts, thus supporting substantial differences in the chemical composition of the two C. taxifolia alien strains, and implying “different ecological effects on the resident biota”.

Importance Rare transforming growth factor beta-induced (TGFBI) gene variants are involved in autosomal dominant corneal dystrophies (CDs) with heterogeneous clinical features. Background The purpose of this study was to analyse TGFBI gene variants and genotype-phenotype correlations in a cohort affected by atypical stromal CD. Design Retrospective cohort study (from May 2014 to September 2017). Participants Thirty-five individuals from 10 unrelated South European families presenting atypical lattice CD (LCD) were included. Methods Corneal phenotypes were assessed by slit-lamp examination and optical coherence tomography (OCT). Contrast sensitivity was measured under mesopic conditions. Genomic DNA was obtained from blood samples, and all 17 TGFBI exons were screened for variants by Sanger sequencing. Main Outcome Measures p.(L558P) variant of TGFBI gene. Results The p.(L558P) variant was identified in 22 members of the 10 families diagnosed with atypical LCD, characterized by late-onset and absence of recurrent erosion syndrome. OCT revealed punctiform deposits in the deep-mid stroma and normal anterior stroma. This variant was demonstrated to be transmitted with the disease according to autosomal dominant inheritance in most families. Conclusions and Relevance To the best of our knowledge, we describe a detailed clinical characterization of the largest CD cohort carrying the TGFBI p.(L558P) variant. We propose that the atypical phenotype of this recently reported alteration can be classified as a form of LCD type IV. The results show that OCT and anterior-posterior analysis of the stromal location of the opacities, along with a genetic analysis of TGFBI, are required to ensure accurate diagnosis and management of CDs.

Orbital emphysema is an abnormal presence of air in the orbit. It usually arises after blunt trauma or periorbital surgery. When it occurs after dacryocystorhinostomy, usually it is reported as a benign condition. We present a case of a severe orbital emphysema secondary to transcanalicular diode laser-assisted dacryocystorhinostomy. The day after the surgery, the examination revealed crepitant periorbital swelling, general restriction of extraocular motility, visual loss and intraocular pressure of more than 70 mmHg. A computed tomography showed a massive orbital emphysema. An emergency decompression, using a 25-gauge needle attached to an empty syringe lacking a plunger was performed, achieving a quick decrease of intraocular pressure and pain and swelling improvement. Then, in this case, orbital decompression by passive airflow using a needle without a plunger was an effective treatment method to resolve a serious orbital emphysema after transcanalicular laser-assisted dacryocystorhinostomy.

The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk-derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen-containing compounds. The “promise” of a mollusk-derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk-derived anticancer agents and solutions to their procurement in quantity., SCOPUS: re.j, info:eu-repo/semantics/published

In the Mediterranean Sea, the biological invasion by the green algae Caulerpa racemosa var. cylindracea is maybe the most striking marine sea-bottom landscape change of the last decades. In this paper, we have synthesized the results of 5 years of studies about the C. cylindracea effects on fish of ecological and economic importance, such as the white sea bream Diplodus sargus. We found that secondary metabolite of C. cylindracea has the potential to enter in trophic chains and accumulate in fish tissues. Ecotoxicological analyses made on tissues of the D. sargus specimens showed alterations of some of main antioxidant systems, such as catalase, glutathione peroxidases and total glutathione, and a significant induction of P450 biotransformation system. We found also that the C. cylindracea based-diet can alter muscle fatty acids composition in the white sea bream by reducing the percentage of polyunsaturated fatty acids (PUFA) of the n-3 and n-6 series, such as eicosapentaenoic (EPA, C20:5), docosahexaenoic (DHA, C22:6) and arachidonic acids (AA, C20:4). On the whole, this work sheds light on an unexplored and critical aspect of biological invasions with implication on the health of both humans and the environment.

PURPOSE: To evaluate corneal endothelial changes after intracameral injection of vancomycin at the end of routine cataract surgery. SETTING: Department of Ophthalmology, Hospital Virgen de los Lirios, Alcoy, Alicante, Spain. DESIGN: Prospective comparative case series. METHODS: Eyes received an intracameral injection of vancomycin (1 mg/0.1 mL) or cefuroxime (1 mg/0.1 mL) at the end of surgery. The visual acuity, corneal clarity, pachymetry, anterior chamber reaction, endothelial cell density (EGO), coefficient of variation (CoV), and hexagonality were evaluated at baseline and 1 week, 1 month, and 3 months after surgery. RESULTS: Sixty eyes (42 patients), 30 in each group, were enrolled. In the vancomycin group, there was a significant decrease in EGO 1 week after surgery (P = .000), after which the EGO stabilized. There were no statistically significant changes in postoperative CoV values between preoperatively and postoperatively, although there was a transient decrease in hexagonality 1 week after surgery (P = .006). In the cefuroxime group, the ECD significantly decreased 1 week after surgery (P = .000) and then stabilized. There was a statistically significantly decrease in the CoV between preoperatively and 3 months postoperatively (P = .014). No changes were noted in hexagonality. The postoperative EGO, CoV, and hexagonality values were not significantly different between the vancomycin group and the cefuroxime group. CONCLUSIONS: Endothelial cell changes observed after intracameral vancomycin were similar to those observed after intracameral cefuroxime in cataract surgery. The results indicate that intracameral vancomycin is safe for use in cataract surgery.

The purpose of this study was to determine the effect of intracameral injection of vancomycin at the end of routine cataract surgery on macular thickness using spectral domain optical coherence tomography. This prospective comparative case series included sixty eyes of 42 patients undergoing cataract surgery. Eyes were divided into two groups: 30 eyes (Group 1) received an intracameral injection of vancomycin (1 mg/0.1 ml) at the end of surgery, and 30 eyes (Group 2) received an intracameral injection of cefuroxime (1 mg/0.1 ml). Visual acuity, average macular thickness, and retinal thickness in 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors were measured at baseline, and 1 week, 1 month, and 3 months after surgery. There were no differences in age, gender, visual acuity, and preoperative macular thickness between groups. In Group 1, average macular thickness significantly increased 1 month after surgery compared with baseline (P = 0.000) and then stabilized. Retinal thickness significantly increased in most of the ETDRS map sectors at 1-month follow-up. In Group 2, there was a significant increase in average macular thickness 1 month after surgery compared with baseline (P = 0.037). Likewise, retinal thickness increased in most of the ETDRS subfields at 1 month. Postoperative retinal thickness values and best-corrected visual acuity were similar in both groups 1 week, 1 month, and 3 months after surgery. Intracameral injection of vancomycin at the end of cataract surgery showed comparable effects to cefuroxime in terms of macular thickness changes and visual acuity.

The usual definition of smell and taste as distance and contact forms of chemoreception, respectively, has resulted in the belief that, during the shift from aquatic to terrestrial life, odorant receptors (ORs) were selected mainly to recognize airborne hydrophobic ligands, instead of the hydrophilic molecules involved in marine remote-sensing. This post-adaptive evolutionary scenario, however, neglects the fact that marine organisms 1) produce and detect a wide range of small hydrophobic and volatile molecules, especially terpenoids, and 2) contain genes coding for ORs that are able to bind those compounds. These apparent anomalies can be resolved by adopting an alternative, pre-adaptive scenario. Before becoming airborne on land, small molecules, almost insoluble in water, already played a key role in aquatic communication, but acting in "contact" forms of olfaction that did not require major molecular innovations to become effective at a distance in air. Rather, when air was "invaded" by volatile marine terpenoids, an expansion of the spatial range of olfaction was an incidental consequence rather than an adaptation. © 2014 Mollo, Fontana, Roussis, Polese, Amodeo and Ghiselin.

Three novel halogenated C15-acetogenins, compounds 1-3, have been isolated, together with known metabolites, from a South China Sea collection of the anspidean mollusc Aplysia dactylomela. The structures have been suggested by both NMR analysis and comparison with literature data. The structure 1 was confirmed by a single crystal X-ray study, which also allowed the establishment of its absolute stereochemistry.

The isolation and structure elucidation of 10 unreported polypropionate metabolites (compounds 6-15), structurally related to either ilikonapyrone (1) or onchidione (3), from two onchidiid pulmonate mollusk species are discussed. Structure elucidation was achieved by NMR spectroscopy and chemical correlation with model compounds. Evaluation of in vitro growth-inhibitory properties in human cancer cells was also carried out on some of the isolated polypropionates including previously reported onchidione metabolites.

Background:Storage of secondary metabolites with a putative defensive role occurs in the so-called mantle dermal formations (MDFs) that are located in the more exposed parts of the body of most and very likely all members of an entire family of marine mollusks, the chromodorid nudibranchs (Gastropoda: Opisthobranchia). Given that these structures usually lack a duct system, the mechanism for exudation of their contents remains unclear, as does their adaptive significance. One possible explanation could be that they are adapted so as to be preferentially attacked by predators. The nudibranchs might offer packages containing highly repugnant chemicals along with parts of their bodies to the predators, as a defensive variant of the strategic theme of the Trojan horse.Methodology and Principal Findings:We detected, by quantitative 1H-NMR, extremely high local concentrations of secondary metabolites in the MDFs of six species belonging to five chromodorid genera. The compounds were purified by chromatographic methods and subsequently evaluated for their feeding deterrent properties, obtaining dose-response curves. We found that only distasteful compounds are accumulated in the reservoirs at concentrations that far exceed the values corresponding to maximum deterrent activity in the feeding assays. Other basic evidence, both field and experimental, has been acquired to elucidate the kind of damage that the predators can produce on both the nudibranchs' mantles and the MDFs.Significance:As a result of a long evolutionary process that has progressively led to the accumulation of defensive chemical weapons in localized anatomical structures, the extant chromodorid nudibranchs remain in place when molested, retracting respiratory and chemosensory organs, but offering readily accessible parts of their body to predators. When these parts are masticated or wounded by predators, breakage of the MDFs results in the release of distasteful compounds at extremely high concentration in a way that maximizes their repugnant impact. © 2013 Carbone et al.

The striking color patterns of chromodorid (and other) nudibranchs appear to be indicative of aposematism. In Mu¨ llerian mimicry, all the mimic species have a defense mechanism. It has been proposed that a group of blue, white, and yellow Mediterranean and northeastern Atlantic species of the genus Hypselodoris form a Mu¨ llerian mimetic circle. One of these, H. fontandraui, lacks the mantle dermal formations (repugnatorial glands) that are typically found in other members of this circle and are reservoirs of feeding deterrent compounds. It therefore seemed possible that this animal lacks chemical defense and acts like a Batesian mimic. Within this study, we found that this nudibranch contains the furanosesquiterpenoid tavacpallescensin, most probably derived from sponges of the genus Dysidea, upon which it probably feeds. The metabolite concentrations were measured from samples of the mantle rim, other external parts, and internal organs. Concentrations were about 4 times higher in the mantle rim than in the other external parts, and more than 20 times higher in the mantle rim than in the internal organs, considerably exceeding the threshold value of concentration showing the maximum dose effect as feeding deterrent against the crustacean Palaemon elegans. In conclusion, the reported data clearly demonstrate that H. fontandraui is chemically defended in much the same way as its aposematic, co-occurring, and blue-colored congeners within the Mu¨ llerian mimetic circle and is not a Batesian mimic.

Objetivo: Valorar los resultados quirúrgicos a largo plazo de la trabeculotomía-trabeculectomía combinada (TTC) como tratamiento preferente del glaucoma congénito primario. Métodos: Se seleccionaron 22 ojos de 14 pacientes consecutivos con glaucoma congénito primario en los que se empleó la TTC como procedimiento inicial entre 1981 y 2005. Se introdujo en una base de datos la información relacionada con la historia familiar, edad de inicio del glaucoma, síntomas y signos, integridad corneal, presión intraocular (PIO), gonioscopia, cirugía, complicaciones postoperatorias, agudeza visual, defecto de refracción, microscopia endotelial, longitud axial, campos visuales y estado final de la papila. El resultado de la presión intraocular fue evaluado usando el análisis de supervivencia Kaplan-Meier. Resultados: Las probabilidades acumuladas de éxito después de realizar una TTC como procedimiento inicial fueron del 95,5% a los 12 meses y del 78,2% a los 24 meses, manteniéndose esta proporción durante 15 años de seguimiento. Cuatro ojos (18,1%) requirieron más de un procedimiento debido a una PIO elevada persistente. Las complicaciones postoperatorias fueron raras. Al final del seguimiento, de 12 ojos de 8 pacientes cooperadores, la mejor agudeza visual corregida fue igual o mayor de 0,5 en el 75% (9 ojos). Conclusiones: La TTC como cirugía primaria ofrece una alta eficacia a largo plazo en el control de la PIO sin tratamiento farmacológico, mostrando mínimas complicaciones quirúrgicas y una baja incidencia de reintervenciones. Purpose: To evaluate the long-term outcome of trabeculotomy-trabeculectomy as the primary surgical treatment for primary congenital glaucoma. Methods: Twenty-two eyes of 14 consecutive patients with primary congenital glaucoma who underwent combined trabeculotomy-trabeculectomy as the initial procedure between 1981 and 2005 were selected for review. Records of ocular family history, age at onset of glaucoma, symptoms and signs, corneal integrity, intraocular pressure (IOP), gonioscopy, surgery, postoperative complications, visual acuity, refractive error, endothelial microscopy, axial length, visual fields and final status of the optic nerve head were entered into a computer database. The outcome, in terms of IOP obtained, was evaluated using Kaplan-Meier survival analysis. Results: Cumulative probabilities of success, after performing combined trabeculotomy-trabeculectomy as the initial operative procedure, were 95.5% after 12 months and 78.2% after 24 months, with this rate being maintained during 15 years of follow-up. Four eyes (18.1%) required more than one operative procedure because of persistent raised IOP. Postoperative complications were rare. At the time of the last follow-up, of 12 eyes from 8 co-operative patients, the final best spectacle-corrected visual acuity was 0.5 (20/40) or better, in 75% (9 eyes). Conclusion: Combined trabeculotomy-trabeculectomy as the primary surgical procedure offers long-term high efficacy in the control of IOP without medical treatment, is rarely associated with surgical complications, and a low need for re-operations.

The Mediterranean Sea is losing its biological distinctiveness, and the same phenomenon is occurring in other seas. It gives urgency to a better understanding of the factors that affect marine biological invasions. A chemoecological approach is proposed here to define biotic conditions that promote biological invasions in terms of enemy escape and resource opportunities. Research has focused on the secondary metabolite composition of three exotic sea slugs found in Greece that have most probably entered the Mediterranean basin by Lessepsian migration, an exchange that contributes significantly to Mediterranean biodiversity. We have found toxic compounds with significant activity as feeding deterrents both in the cephalaspidean Haminoea cyanomarginata and in the nudibranch Melibe viridis. These findings led us to propose aposematism in the former and dietary autonomy in producing defensive metabolites in the latter case, as predisposing factors to the migration. In the third mollusk investigated, the anaspidean Syphonota geographica, the topic of marine invasions has been approached through a study of its feeding biology. The identification of the same compounds from both the viscera of each individual, separately analyzed, and their food, the seagrass Halophila stipulacea, implies a dietary dependency. The survival of S. geographica in the Mediterranean seems to be related to the presence of H. stipulacea. The initial invasion of this exotic pest would seem to have paved the way for the subsequent invasion of a trophic specialist that takes advantage of niche opportunities. © 2008 by The National Academy of Sciences of the USA.

The unusual structural features of syphonoside (1), recently reported from the marine mollusc Syphonota geographica and its prey Halophila stipulacea, stimulated further investigations on the minor secondary metabolites of both organisms. The three novel macrocyclic glycoterpenoids 2-4, structurally related to the main co-occurring metabolite 1, have been isolated and chemically characterized mainly by NMR spectroscopic techniques and degradation methods. Compounds 2 and 3 were found only in the mollusc whereas compound 4 was isolated in trace quantities exclusively from the sea-grass. © 2007 Elsevier Ltd. All rights reserved.

Introducción: Las heridas por asta de toro, comunes en países con afición al toreo y festejos relacionados, representan lesiones graves con un elevado grado de contaminación. Caso clínico: Varón de 19 años que sufrió traumatismo por asta de toro con herida penetrante en párpado superior izquierdo acompañada de fractura del techo de la órbita y hernia grasa. Se indicó profilaxis antibiótica y antitetánica y se reconstruyó quirúrgicamente la herida. Posteriormente, desarrolló una celulitis orbitaria, que evolucionó satisfactoriamente con tratamiento sistémico en unos pocos días. Discusión: El éxito del tratamiento en este tipo de heridas se fundamenta en una exploración meticulosa, diagnóstico temprano, manejo quirúrgico precoz y profilaxis antibiótica y antitetánica. Introduction: Bull horn injuries are severe lesions with a high risk of bacterial contamination, and are common in countries where people are fond of bullfighting and related spectacles. Case report: A 19-year-old man was referred with a penetrating wound in the superior left eyelid produced by a bull horn and resulting in a fracture of the orbital roof and a fat hernia. Prophylactic antibiotics and tetanus toxoid were administered and surgical reconstruction of the wound performed. Orbital cellulitis did develop, but this responded to systemic antibiotic therapy within a few days. Discussion: Successful treatment of this type of lesion requires early diagnosis, meticulous surgical exploration and appropriate use of prophylactic antibiotics and tetanus toxoid.

(Figure Presented) The glycoterpenoid syphonoside (1) is the main secondary metabolite of both the marine mollusk Syphonota geographica and the sea-grass Halophila stipulacea, two Indo-Pacific species migrated to the Mediterranean Sea through the Suez Canal. The structure and the absolute stereochemistry of 1, which displays unique structural features, has been accomplished by using a combination of spectroscopic techniques, degradation reactions, and conformational analysis methods. Compound 1 was able to inhibit high density induced apoptosis in a number of human and murine carcinoma cell lines. © 2007 American Chemical Society.

Two new polyhydroxylated steroids, (2 beta,3 beta,4 alpha,5 beta,8 beta,11 beta)-4-methylergost-24(28)-ene-2,3,8,11-tetrol-(1) and (3 beta,5 alpha,6 beta)-ergosta-22,24(28)-diene-3,5,6,19-tetrol (3), together with the six known related steroids 2 and 4-8, were isolated from the Hainan soft coral Sinularia sp. Their structures were elucidated on the basis of spectroscopic analysis and by comparison with previously reported data. The structure of the known compound 9 (hyrtiosterol) was revised as 2 by extensive analysis of the ROESY data and by the NOE difference experiment.

Two unprecedented degraded sterols, aplykurodinone-1 (1) and -2 (2), have been isolated from the skin of the marine anaspidean Syphonota geographica, collected along the coasts of Greece. The structures and the relative stereochemistry were established by spectroscopic analysis and confirmed by chemical correlation with related known compounds. Two novel degraded sterols, e.g. aplykurodinone-1 (1), have been isolated from the skin of sea hare S. geographica from Greek coasts. The structure and the absolute stereochemistry have been established by spectral methods and chemical correlation with related compounds. © 2004 Elsevier Ltd. All rights reserved.