Bisfosfonatos y Patología Oral I: aspectos generales y preventivos

Los bisfosfonatos constituyen un grupo de fármacos capaces de modular el recambio óseo y disminuir su remodelado cuando existe una reabsorción excesiva. Por ello están indicados en numerosas patologías óseas como la osteoporosis postmenopáusica o la osteolisis asociada al cáncer de mama o al mieloma múltiple. En los últimos años y a raíz de su utilización masiva se han ido publicando numerosos casos de complicaciones asociadas a su uso. Entre los posibles efectos adversos más importantes se encuentran los orales, con la aparición de ulceraciones y sobre todo los casos de osteonecrosis de los maxilares asociados a esta terapéutica. En esta revisión analizamos las características generales de estos medicamentos y su mecanismo de actuación, así como los efectos adversos descritos, especialmente los orales y maxilofaciales, haciendo una referencia especial sobre la prevención de la osteonecrosis de los maxilares, a la luz de los casos descritos en la literatura médica y odontológica. El protocolo preventivo refuerza el papel fundamental del odontólogo en la prevención efectiva de este proceso antes, durante y después del tratamiento.Bisphosphonates constitute a group of drugs capable of modulating bone turnover, and reduce its remodelling when an excessive resorption occurs. This is why they are indicated in a large group of bone diseases like postmenopausal osteoporosis or osteolisis associated with breast cancer or multiple myeloma. Over the last years and due to their extensive use, many cases of complications associated with their use have been published. Among the most important possible adeverse effects are the oral ones, with the appearance of ulcerations and, especially, osteonecrosis of the jaws associated with this therapy. In this paper, we have analyzed the general characteristics of these drugs and their mechanisms of action as well as the described adverse effects, especially oral and maxillofacial has been made special reference regarding the prevention of osteonecrosis of the jaws, hightened by cases described in medical and odontological literature. The preventive protocol backs up the fundamental role of the odontologist in the effective prevention of this process before, during and after the treatment

On malfunctioning software

Artefacts do not always do what they are supposed to, due to a variety of reasons, including manufacturing problems, poor maintenance, and normal wear-and-tear. Since software is an artefact, it should be subject to malfunctioning in the same sense in which other artefacts can malfunction. Yet, whether software is on a par with other artefacts when it comes to malfunctioning crucially depends on the abstraction used in the analysis. We distinguish between “negative” and “positive” notions of malfunction. A negative malfunction, or dysfunction, occurs when an artefact token either does not (sometimes) or cannot (ever) do what it is supposed to. A positive malfunction, or misfunction, occurs when an artefact token may do what is supposed to but, at least occasionally, it also yields some unintended and undesirable effects. We argue that software, understood as type, may misfunction in some limited sense, but cannot dysfunction. Accordingly, one should distinguish software from other technical artefacts, in view of their design that makes dysfunction impossible for the former, while possible for the latter

Algorithmic iteration for computational intelligence

Machine awareness is a disputed research topic, in some circles considered a crucial step in realising Artificial General Intelligence. Understanding what that is, under which conditions such feature could arise and how it can be controlled is still a matter of speculation. A more concrete object of theoretical analysis is algorithmic iteration for computational intelligence, intended as the theoretical and practical ability of algorithms to design other algorithms for actions aimed at solving well-specified tasks. We know this ability is already shown by current AIs, and understanding its limits is an essential step in qualifying claims about machine awareness and Super-AI. We propose a formal translation of algorithmic iteration in a fragment of modal logic, formulate principles of transparency and faithfulness across human and machine intelligence, and consider the relevance to theoretical research on (Super)-AI as well as the practical import of our results

The systematicity challenge to anti-representational dynamicism

After more than twenty years of representational debate in the cognitive sciences, anti-representational dynamicism may be seen as offering a rival and radically new kind of explanation of systematicity phenomena. In this paper, I argue that, on the contrary, anti-representational dynamicism must face a version of the old systematicity challenge: either it does not explain systematicity, or else, it is just an implementation of representational theories. To show this, I present a purely behavioral and representation-free account of systematicity. I then consider a case of insect sensorimotor systematic behavior: communicating behavior in honey bees. I conclude that anti-representational dynamicism fails to capture the fundamental trait of systematic behaviors qua systematic, i.e., their involving exercises of the same behavioral capacities. I suggest, finally, a collaborative strategy in pursuit of a rich and powerful account of this central phenomenon of high cognition at all levels of explanation, including the representational level

Amino acids in the development of Prodrugs

Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs.NV acknowledges support from Fundação para a Ciência e Tecnologia (FCT, Lisbon, Portugal) and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004. NV also thanks FCT for the IF position and Fundação Manuel António da Mota (FMAM, Porto, Portugal) and Pfizer (Portugal) for support for the Nuno Vale Research Group. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the FCT, FMAM and Pfizer

Bisphosphonates and Oral Pathology II. Osteonecrosis of the jaws : Review of the literature before 2005

Bisphosphonates are bone-turnover modulating drugs which are used in the management of a number of bone diseases ranging from osteoporosis to neoplasic pathology-associated osteolysis. In the last years a number of cases of osteonecrosis of the jaws associated with these drugs have been reported. In this review we analyze the cases published in the literature indexed from 2003 to December 2005. During this period 246 cases were reported, being more frequently associated with women in the sixth decade of life. More frequently associated bisphosphonates were the nitrogenated bisphosphonates (pamidronate, zolendronic acid) and the most common oral antecedent was a dental extraction. Nevertheless more than 25% of the cases were spontaneous. The most frequent site was the mandible and most of the cases presented clinical evidence of bone exposure and pain. Different treatments have been proposed with different antibiotic therapies with or without surgery, showing in general terms an uncertain prognosis with low healing rates

Bisphosphonates and Oral Pathology I : general and preventive aspects

Los bisfosfonatos constituyen un grupo de fármacos capaces de modular el recambio óseo y disminuir su remodelado cuando existe una reabsorción excesiva. Por ello están indicados en numerosas patologías óseas como la osteoporosis postmenopáusica o la osteolisis asociada al cáncer de mama o al mieloma múltiple. En los últimos años y a raíz de su utilización masiva se han ido publicando numerosos casos de complicaciones asociadas a su uso. Entre los posibles efectos adversos más importantes se encuentran los orales, con la aparición de ulceraciones y sobre todo los casos de osteonecrosis de los maxilares asociados a esta terapéutica. En esta revisión analizamos las características generales de estos medicamentos y su mecanismo de actuación, así como los efectos adversos descritos, especialmente los orales y maxilofaciales, haciendo una referencia especial sobre la prevención de la osteonecrosis de los maxilares, a la luz de los casos descritos en la literatura médica y odontológica. El protocolo preventivo refuerza el papel fundamental del odontólogo en la prevención efectiva de este proceso antes, durante y después del tratamiento

On malfunctioning software

Artefacts do not always do what they are supposed to, due to a variety of reasons, including manufacturing problems, poor maintenance, and normal wear-and-tear. Since software is an artefact, it should be subject to malfunctioning in the same sense in which other artefacts can malfunction. Yet, whether software is on a par with other artefacts when it comes to malfunctioning crucially depends on the abstraction used in the analysis. We distinguish between “negative” and “positive” notions of malfunction. A negative malfunction, or dysfunction, occurs when an artefact token either does not (sometimes) or cannot (ever) do what it is supposed to. A positive malfunction, or misfunction, occurs when an artefact token may do what is supposed to but, at least occasionally, it also yields some unintended and undesirable effects. We argue that software, understood as type, may misfunction in some limited sense, but cannot dysfunction. Accordingly, one should distinguish software from other technical artefacts, in view of their design that makes dysfunction impossible for the former, while possible for the latter

Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite

Carbidopa is used for the treatment of Parkinson's disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT, in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).” NV thanks FCT for IF position, Fundação Manuel António da Mota (FMAM, Portugal) for support. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the FCT and FMAMinfo:eu-repo/semantics/publishedVersio