Promising activities of marine natural products against hematopoietic malignancies

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially available marine-derived compounds for the treatment of various hematopoietic cancers (e.g., leukemia and lymphoma), two molecules in clinical trials, and series of compounds and/or extracts from marine micro-and macroorganisms which have shown promising properties. In addition, the mechanisms of action of several active compounds and extracts are still unknown and require further study. The continuous upgrading of omics technologies has also allowed identifying enzymes with possible bioactivity (e.g., L-asparaginase is currently used for the treatment of leukemia) or the enzymes involved in the synthesis of bioactive secondary metabolites which can be the target of heterologous expression and genetic engineering

Evidencia del síndrome neuropático en un estudio neurofisiológico e inmunohistoquímico de las fibras nerviosas en pacientes con síndrome de boca ardiente

espanolIntroduccion: El sindrome de la boca ardiente (SBA) es una enfermedad de frecuente aparicion, caracterizada para un dolor quemante y ardiente en la lengua y en la cavidad oral, en ausencia de alteraciones estructurales macroscopicas de las mucosas. La etiopatogenesis del SBA no es todavia conocida y por lo tanto no presenta un esquema diagnostico claro y bien definido. Material y metodos: Para evaluar la hipotesis que contempla una alteracion de las fibras nerviosas perifericas de pequeno calibre, asociada o no con una alteracion trofica de las mucosas, hemos seleccionados 25 pacientes (7 varones y 18 mujeres, con una edad comprendida entre 36 y 75 anos, una media de 54 anos) afectados por SBA, que llegaron a nuestra clinica para una serie de examenes que suelen realizarse de forma rutinaria en las sindromes de dolor neurologico. En todos los pacientes se ha realizado un cuidadoso examen objetivo y una ortopantomografia, con la finalidad de excluir alteraciones de las mucosas y enfermedades odontologicas. En todos los pacientes se han realizado: examenes hematoquimicos, examenes objetivos neurologicos, teletermografia de la lengua y de la cara, examen cuantitativo de la sensibilidad termica de la lengua, de las manos y de la parte dorsal del pie. Los resultados del examen cuantitativo de la sensibilidad termica de la lengua y de la muneca se confrontaban con una poblacion control homogenea. En una poblacion de 10 pacientes (3 varones y 7 mujeres; de una edad comprendida entre 34 y 53 anos, una media de 49 anos) se ha realizado un biopsia de la parte dorsal de la lengua, la biopsias se han analizado con microscopia optica e inmunofluresencia tras un tratamiento con anticuerpos activos para proteinas neuronales citoplasmaticas (protein gene product 9.5). Resultados: Los datos obtenidos evidenciaban la presencia de una polineuropatia subclinica en el 50% de los pacientes. Especialmente se apreciaban signos de baja funcionalidad de las fibras nerviosas de pequeno calibre de la lengua en casi la mitad de los pacientes examinados. El examen histologico de la mucosa lingual evidenciaba una atrofia discreta en el 70% de los pacientes, mientras que la observacion de las fibras nerviosas de pequeno calibre por medio de la inmunofluoresencia hacia suponer la presencia de alteraciones relacionadas con una polineuropatia de tipo periferico. EnglishAims. Burning pain is considered characteristic of chronic neuropathic pain condition in general, and so me recent data seem to suggest peripheral or central nervous system involvement as possible underlying factor in BMS. This study was designed to determinate if burning mouth symptoms could be originated from a peripheal neuropathy of small diameter nerve fibres. Material and methods. The material of the study consisted of 25 patients (18 female, 7 male, 30-75 years; means 54 years). In all patients there were not: oral muco membranes lesions, oral muco membranes diseases, oral correlated diseases, oral dysfunctions, dental and periodontal diseases. Besides there were: no evidence of central nervous system pathology, no evidence of peripheral nervous system pathology, no presence of organic body disfunctions. AIIpatients didn't show significant alterations of blood investigations. AII patients were undermitted to our protocol including: oral and facial clinical examinations, neurological exam, blood investigations, Mc Gill Pain Questionnaire, VAS (visual analogical scale), biopsy of tongue mucosa with hystological and immunofluorescence exams, quantitative somatosensory thermotest and teletermography examination of tongue mucosa. ResuIts. These examinations have showed subclinical polineurophaty in 50% of patients. In particular were observed a loss of function in small diameter nervous fibres in about 50% of patients. Hystological exam of mucosal tongue revealed a moderate atrophy and alterations of structures. Conclusion. Etiology, pathogenetic processes, clinical and diagnostic approaches, therapeutical resolutions and researches of burning mouth syndrome are not clear yet. The local alterations of small diameter sensitive nerve fibres could cause an increase of oral burning, without muco membranes pathologies. These locallesions could justify the bms clinical symptomatology. The hystological alteration of small diameter sensitive nerve fibres could involve meaningful alterations of thermal reactivity of oral and body surfaces. These clinical reactivities are evident in chronic peripheal neuropathy (diabetes). These conclusions and our study results are still provisory. It will be necessary to estend and to increase our results, comparing our research with other bms etio-pathogenetic hypotesis

Aging and oral care: An observational study of characteristics and prevalence of oral diseases in an Italian cohort

Background: Poor oral health is a common condition in patients suffering from dementia. Several aspects of this systemic pathology contribute to causing oral problems: cognitive impairment, behavior disorders, communication and, motor skills deterioration, low levels of cooperation and medical-nursing staff incompetency in the dental field. Objectives: The objectives of this study were to evaluate the prevalence and the characteristics of oral pathology in a demented elderly population, as well as to check the association between the different degree of dementia and the oral health condition of each patient. Materials and Methods: In this observational study (with cross-sectional design) two groups of elderly patients suffering from dementia, living in two different residential care institutions were recruited. The diagnosis of dementia of each included patient was performed using the Clinical Dementia Rating Scale. In order to evaluate the oral health condition of the included subjects, each patient underwent a physical examination of the oral cavity, during which different clinical parameters were analyzed (number of remaining teeth, oral mucosa, periodontal tissues, bone crests). To each parameter, a score was assigned. Spearman’s Rho test was used. Results: Regarding the prevalence of oral pathology in elderly suffering from dementia, it emerged that 20.58% of the included patients had mucosal lesions and/or new mucosal formations (in most cases undiagnosed and therefore untreated). The prevalence of periodontal disease was equal to 82.35% and a marked clinically detectable reabsorption of bone crests was found in almost all patients (88.23%). 24.13% of patients, who underwent the oral examination, had totally edentulous maxillae and/or with retained roots, without prosthetic rehabilitations. The correlation index r showed the presence of a linear correlation (inverse relationship) between the degree of dementia and the state of health of the oral cavity of each patient. Conclusions: Several factors contribute to poor oral health in the elderly suffering from dementia: cognitive functions deterioration, behavioral disorders and inadequate medical-staff nursing training on oral hygiene. This study also demonstrated that the lower the dementia degree is, the lower tends to be the oral health status. In order to guarantee a complete assistance to these patients, residential care institutions should include in their healthcare program specific dental protocols

Conocimiento y actitud del odontólogo frente al manejo del tabaquismo: estudio comparativo entre España, Italia y Venezuela

espanolIntroduccion: El Odontologo es capaz de ejercer un gran impacto en el tabaquismo a traves de su contacto con los pacientes y la deteccion precoz de lesiones bucales. El objetivo de este estudio fue determinar el conocimiento y la actitud de los odontologos frente al tabaquismo en tres paises distintos. Materiales y metodos: Se realizo una encuesta a 293 odontologos, 93 de ellos localizados en Caracas (OV), 90 con practica odontologica en Madrid (OE) y 110 en Milan (OI). Resultados: 46 OE y 22 OI indicaron ser fumadores, mientras que tan solo 10 OV admitieron ser fumadores. 80 (86,02%) OV, 66 (73,33%) OE y todos los OI refirieron registrar en la historia datos relacionados con tabaquismo en la primera consulta del paciente. La mayoria motiva a sus pacientes a dejar de fumar, sin embargo, 72,04% (67) OV, 55,55% (50) OE y 100% OI no recomiendan ninguna terapia de apoyo. Solo 7 odontologos (2,38%) (2 OV y 5 OE) reconocieron el medicamento Bupropion pero ningun odontologo lo ha indicado. Finalmente, 137 odontologos han diagnosticado cancer bucal, de los cuales 108 eran OI. Conclusiones: Los odontologos, independientemente del pais, tienen actitudes positivas para participar en el control del tabaquismo, pero no manejan la informacion relacionada ni ejercen un rol activo en la cesacion. Probablemente esta situacion se deba a la falta de entrenamiento durante sus estudios de pre y/o postgrado lo cual amerita una revision de los planes curriculares de Odontologia a nivel mundial. EnglishIntroduction: Health care professionals have an important role in tobacco control. Dentists are capable of having a great impact in smoking cessation due to their regular contact with patients and the rapid detection of oral signs produced by smoking. Unfortunately, there are few dentists actively involved in smoking control. The aim of this study was to investigate various aspects of dentists' beliefs and practices with respect to smoking cessation. Materials & Methods: A questionnaire about smoking cessation was filled in person by 293 dentists. 93 dentists were from Caracas-Venezuela (VD), 90 were from Madrid-Spain (SD) and 110 from Milan-Italy (ID). Results: 46 SD and 22 ID were smokers. Only 10 VD admitted to smoke. 80 (86.02%) VD, 66 (73.33%) SD and 100% of ID said that they recorded smoking status during the first consultation. However, none routinely update their records on smoking status. The majority of respondents encourage their patients to stop smoking, though, 72.04% (67) VD, 55.55% (50) SD and 100% ID do not recommend or prescribe any cessation therapy. Just 7 (2.38%) of all dentists had heard about the use of Bupropion, however, they had never indicated. Finally, 137 dentists (108 ID) have diagnosed oral cancer in their patients. Conclusions: Dentists have positive attitudes to being involved in smoking cessation interventions, but they do not manage all the information related to it. It is probably due to a lack of training or education during their undergraduate and postgraduate studies. Further studies should evaluate inclusion of smoking cessation instruction in Venezuelan, Spanish and Italian dentistry curriculum

Drug-induced gingival hyperplasia : an in vitro study using amlodipine and human gingival fibroblasts

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast\u2019s function in gingival overgrowth. To determine whether amlodipine alters the inflammatory responses, we investigated its effects on gingival fibroblast gene expression as compared with untreated cells. Fragments of gingival tissue of healthy volunteers (11 years old boy, 68 years old woman, and 20 years old men) were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblast cell culture treated with amlodipine, compared with untreated cells. Among the studied genes, only 15 (CCL1, CCL2D, CCL5, CCL8, CXCL5, CXCL10, CCR1, CCR10, IL1A, IL1B, IL5, IL7, IL8, SPP1, and TNFSF10) were significantly deregulated. In particular, the most evident overexpressed genes in treated cells were CCR10 and IL1A. These results seem to indicate a possible role of amlodipine in the inflammatory response of treated human gingival fibroblasts

Phenytoin and gingival mucosa: A molecular investigation.

Several distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers, caused gingival overgrowth. One of the main drugs associated with the gingival overgrowth is the anti-epileptic such as phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. In our study, we evaluate the effect of phenytoin, a drug whose active substance is phenytoin, on gingival fibroblasts of healthy volunteers. Gene expression of 29 genes was investigated in gingival fibroblasts' cell culture treated with phenytoin compared with untreated cells. Among the studied genes, only 13 genes (CXCL5, CXCL10, CCR1, CCR3, CCR5, CCR6, IL-1A, IL-1B, IL-5, IL-7, IL-6R, BMP-2, and TNFSF-10) were statistically significant. All but one gene resulted downregulated after 24\u2009h of treatment with phenytoin. BPM2 was the only, although weakly, up-expressed gene. Probably, we have not highlighted overexpression of the other inflammatory molecules because the study was performed on healthy people. Many studies show that phenytoin induces the overexpression of these cytokines but, probably, in our study, the drug does not have the same effect because we used gingival fibroblasts of healthy people

A new strategy against peri-implantitis: Antibacterial internal coating

The bacterial biofilm formation in the oral cavity and the microbial activity around the implant tissue represent a potential factor on the interface between bone and implant fixture that could induce an inflammatory phenomenon and generate an increased risk for mucositis and peri-implantitis. The aim of the present clinical trial was to investigate the bacterial quality of a new antibacterial coating of the internal chamber of the implant in vivo at six months. The PIXIT implant (Edierre srl, Genova Italy) is prepared by coating the implant with an alcoholic solution containing polysiloxane oligomers and chlorhexidine gluconate at 1%. A total of 15 healthy patients (60 implants) with non-contributory past medical history (nine women and six men, all non-smokers, mean age of 53 years, ranging from 45–61 years) were scheduled to receive bilateral fixed prostheses or crown restorations supported by an implant fixture. No adverse effects and no implant failure were reported at four months. All experimental sites showed a good soft tissue healing at the experimental point times and no local evidence of inflammation was observed. Real-Time Polymerase Chain Reaction (PCR) analysis on coated and uncoated implants showed a decrease of the bacterial count in the internal part of the implant chamber. The mean of total bacteria loading (TBL) detected in each PCR reaction was lower in treated implants (81,038 units/reaction) compared to untreated implants (90,057 units/reaction) (p < 0.01). The polymeric chlorhexydine coating of the internal chamber of the implant showed the ability to control the bacterial loading at the level of the peri-implant tissue. Moreover, the investigation demonstrated that the coating is able to influence also the quality of the microbiota, in particular on the species involved in the pathogenesis of peri-implantitis that are involved with a higher risk of long-term failure of the dental implant restoration

De novo transcriptome assembly and gene expression profiling of the copepod Calanus helgolandicus feeding on the PUA-producing diatom Skeletonema marinoi

Diatoms are the dominant component of the marine phytoplankton. Several diatoms produce secondary metabolites, namely oxylipins, with teratogenic effects on their main predators, crustacean copepods. Our study reports the de novo assembled transcriptome of the calanoid copepod Calanus helgolandicus feeding on the oxylipin-producing diatom Skeletonema marinoi. Differential expression analysis was also performed between copepod females exposed to the diatom and the control flagellate Prorocentrum minimum, which does not produce oxylipins. Our results showed that transcripts involved in carbohydrate, amino acid, folate and methionine metabolism, embryogenesis, and response to stimulus were differentially expressed in the two conditions. Expression of 27 selected genes belonging to these functional categories was also analyzed by RT-qPCR in C. helgolandicus females exposed to a mixed solution of the oxylipins heptadienal and octadienal at the concentration of 10 \ub5M, 15 \ub5M, and 20 \ub5M. The results confirmed differential expression analysis, with up-regulation of genes involved in stress response and down-regulation of genes associated with folate and methionine metabolism, embryogenesis, and signaling. Overall, we offer new insights on the mechanism of action of oxylipins on maternally-induced embryo abnormality. Our results may also help identify biomarker genes associated with diatom-related reproductive failure in the natural copepod population at sea

Prevalence of Enterococci and Vancomycin Resistance in the Throat of Non-Hospitalized Individuals Randomly Selected in Central Italy

Enterococci are commonly found in the environment and humans as a part of the normal microbiota. Among these, Enterococcus faecalis and Enterococcus faecium can convert into opportunistic pathogens, making them a major cause of nosocomial infections. The rapid diffusion of vancomycin-resistant strains and their impact on nosocomial settings is of considerable concern. Approximately one-third of the E. faecium infections in Italy are caused by vancomycin-resistant strains. This study explored the hypothesis that the oral cavity could represent a silent reservoir of virulent enterococci. A sample of 862 oral flora specimens collected from healthy human volunteers in Central Italy was investigated by real-time PCR to detect E. faecalis and E. faecium, as well as the genetic elements that most frequently determine vancomycin resistance. The prevalence of E. faecalis was 19%, a value that was not associated with alcohol consumption, tobacco smoking, or age of the subjects. Less frequently detected, with an overall prevalence of 0.7%, E. faecium was more common among people older than 49 years of age. The genes conferring vancomycin resistance were detected in only one sample. The results indicate that the oral cavity can be considered a reservoir of clinically relevant enterococci; however, our data suggest that healthy individuals rarely carry vancomycin-resistant strains

Oral health status and need for oral care in an aging population: A systematic review

Background. The world population is aging. This phenomenon is accompanied by an increase in the number of elderly with dementia, whose oral hygiene care is a challenge. Objective. This paper presents a literature review of oral health status and the need for oral care in people with dementia, as compared to people without dementia and also of the relationship between periodontal disease and cognitive impairment. Methods. A systematic review was conducted in PubMed, CINAHL, and the Cochrane Library. Fifty-six articles met the inclusion criteria and were consequently included for quality assessment and data extraction. Results. No significant differences were found between both groups with regard to the number of present teeth, DMFT Index, edentulousness/use of denture, and orofacial pain. Coronal/root caries and retained roots were more common in people with dementia than in those without dementia. Most of the participants with dementia presented gingival bleeding or inflammation and they suffered from the periodontal disease more than people without dementia. Conclusions. Poor oral health is a common condition among the elderly with dementia. The education process of caregivers might improve the oral health status of people with dementia. Finally, periodontal disease might contribute to the onset or progression of dementia