Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders.

Obesity is considered a major health problem. However, mechanisms involved and its comorbidities are not elucidated. Recent theories concerning the causes of obesity have focused on a limit to the functional capacity of adipose tissue, comparing it with other vital organs. This assumption has been the central point of interest in our laboratory. We proposed that the failure of adipose tissue is initiated by the difficulty of this tissue to increase its cellularity due to excess in fat contribution, owing to genetic or environmental factors. Nevertheless, why the adipose tissue reduces its capacity to make new adipocytes via mesenchymal cells of the stroma has not yet been elucidated. Thus, we suggest that this tissue ceases fulfilling its main function, the storage of excess fat, thereby affecting some of the key factors involved in lipogenesis, some of which are reviewed in this paper (PPARγ, ROR1, FASN, SCD1, Rab18, BrCa1, ZAG, and FABP4). On the other hand, mechanisms involved in adipose tissue expandability are also impaired, predominating hypertrophy via an increase in apoptosis and a decrease in adipogenesis and angiogenesis. However, adipose tissue failure is only part of this great orchestra, only a chapter of this nightmare.

Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration.

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that "treat and extend" and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.

An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

Role of Age and Sex in the Diagnosis of Early-stage Malignant Melanoma: A Cross-Sectional study.

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). This aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2430 patients with MM were recruited. Cases of in situ-T1 MM were more frequent than T2-T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r   = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0-29 years (1.18), and 30-59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis-T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM.

Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.

Le suicidant, sa famille et son médecin

Résumé : Le suicidant, sa famille et son médecin. - Dans une lignée systémique, nous avons à nous demander quelle représentation du suicide ont les suicidants par rapport à l'acte lui-même et par rapport à l'impact que ces mêmes actes ont sur leur famille. D'autre part, il convient de nous interroger sur les représentations que chaque membre de la famille peut construire de l'acte suicidaire lui-même, du sens qu'il revêt pour le jeune et les proches. Notre expérience de psychiatres dans un hôpital général nous amène à nous questionner aussi sur les représentations de cet acte chez les professionnels qui offrent des soins aigus somatiques et qui luttent pour la vie lorsque les patients eux ont opté pour la mort. Ce geste nous envoie un signal fort de perte d'espoir et d'absence de perspectives futures chez les suicidants. Il nous renvoie aussi à la question de la mort chez les médecins formés à lutter pour la vie. L'acte suicidaire est un geste violent qui renvoie aux soignants un sentiment d'impuissance et pour lequel ils se sentent démunis. Nous aborderons dans une première partie l'attitude adoptée dans le service de psychiatrie de liaison à Lausanne. Nous exposerons ensuite quelques pistes de réflexion sur la prise en charge des suicidants dans un effort de compréhension systémique. Une responsabilité majeure éthique et humaine nous incombe.Summary : The suicidal person, his family and his doctor. - In a systemic lineage, we have to ask ourselves what representation of suicide do people with suicidal tendencies have, and what is the impact of suicide on their families and their doctor. On the other hand, it is advisable to ask ourselves what does suicide mean to their relatives. Our practice as psychiatrists in a general hospital leads us also to try and understand the image and impact of suicide on the medical staff who constantly aims at saving lives, while patients opted for death. This act sends us a strong signal of loss of hope and the absence of prospects for suicidal people. It has also a strong emotional impact on health practitioners and frequently makes them feel helpless. It also sends back to us to the question of the image of death among doctors. We will discuss, in a first part, the adopted attitude in the service of liaison psychiatry in Lausanne. We will try and develop then a way of taking care of suicidal patients, their families and the medical staff, attending them in a systemic approach. This is a great ethical and human responsibility to all health practitioners.

Phytobezoar by aloe vera as long term complication after oesophagectomy resolved using cellulase.

Bezoars are uncommon diseases caused by the presence of indigestible mass of strange material in the gastrointestinal tract. Gold-standard treatment remains unclear and there are not clinical guidelines to follow. We present a very rare case of 53-year-old man suffering phytobezoar in a gastroplasty after oesophagectomy due to aloe vera ingestion as natural medicine. Finally it was solved with cellulase. Therefore, this is a scarcely complication after esophagectomy. Cellulase is a very good option to treat phytobezoar avoiding reintervention in this kind of patient.

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.

Manejo perioperatorio de medicación crónica : documento de apoyo al PAI atención al paciente quirúrgico

Documento de Apoyo al Proceso Asistencial Integrado Atención al Paciente Quirúrgico (http://hdl.handle.net/10668/1713). Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

Adjuvant treatment of melanoma.

Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50-80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon- α 2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas.

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol.

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.

Cuestiones controvertidas en evaluación económica (III). Intervenciones sanitarias en tres situaciones especiales: enfermedades raras, tratamientos al final de la vida y externalidades en las evaluaciones.

The development of the economic evaluation of health care interventions has become a support tool in making decisions on pricing and reimbursement of new health interventions. The increasingly extensive application of these techniques has led to the identification of particular situations in which, for various reasons, it may be reasonable to take into account special considerations when applying the general principles of economic evaluation. In this article, which closes a series of three, we will discuss, using the Metaplan technique, about the economic evaluation of health interventions in special situations such as rare diseases and end of life treatments, as well as consideration of externalities in assessments, finally pointing out some research areas to solve the main problems identified in these fields.

Phytobezoar by aloe vera as long term complication after oesophagectomy resolved using cellulase.

Bezoars are uncommon diseases caused by the presence of indigestible mass of strange material in the gastrointestinal tract. Gold-standard treatment remains unclear and there are not clinical guidelines to follow. We present a very rare case of 53-year-old man suffering phytobezoar in a gastroplasty after oesophagectomy due to aloe vera ingestion as natural medicine. Finally it was solved with cellulase. Therefore, this is a scarcely complication after esophagectomy. Cellulase is a very good option to treat phytobezoar avoiding reintervention in this kind of patient.