Modulating Expression of Endogenous Interleukin 1 Beta in the Acute Phase of the Pilocarpine Model of Epilepsy May Change Animal Survival.

The pilocarpine-induced (PILO) model has helped elucidate the electrophysiological and molecular aspects related to mesial temporal lobe epilepsy. It has been suggested that the extensive cell death and edema observed in the brains of these animals could be induced by increased inflammatory responses, such as the rapid release of the inflammatory cytokine interleukin 1 beta (Il1b). In this study, we investigate the role of endogenous Il1b in the acute phase of the PILO model. Our aim is twofold. First, we want to determine whether it is feasible to silence Il1b in the central nervous system using a non-invasive procedure. Second, we aim to investigate the effect of silencing endogenous Il1b and its antagonist, Il1rn.We used RNA interference applied non-invasively to knockdown Il1b and its endogenous antagonist Il1rn. We found that knocking down Il1b prior to pilocarpine injection increased the mortality rate of treated animals. Furthermore, we observed that, when exposing the animals to more Il1b by silencing its endogenous antagonist Il1rn, there was a better response to status epilepticus with decreased animal mortality in the acute phase of the PILO model. Thus, we show the feasibility of using a novel, less invasive approach to study genes involved in the inflammatory response in the central nervous system. Furthermore, our results provide suggestive evidence that modulating endogenous Il1b improves animal survival in the acute phase of the PILO model and may have effects that extend into the chronic phase.

Pharmacist assessment of drug-gene interactions and drug-induced phenoconversion in major depressive disorder: a case report.

BACKGROUND: Response to antidepressant therapy is highly variable among individuals. Pharmacogenomic (PGx) testing presents an opportunity to guide drug selection while optimizing therapy outcomes and/or decreasing the risk for toxicity. CASE PRESENTATION: A patient with multiple comorbidities, including severe major depressive disorder (MDD), experienced adverse drug events and undesirable response to multiple antidepressant medications (i.e., bupropion, escitalopram, and venlafaxine). A clinical pharmacist assessed significant drug-gene, drug-drug, and drug-drug-gene interactions as well as other clinical factors to provide recommendations for antidepressant therapy optimization. CONCLUSION: This case highlights the importance of PGx testing and the key role of pharmacists in identifying and mitigating drug-related problems and optimizing drug therapy in patients with MDD.

Efficacy of the laser at low intensity on primary burning oral syndrome: a systematic review.

BACKGROUND: Primary burning mouth syndrome (BMS) is a chronic clinical condition of idiopathic mainly characterized by pain and a burning sensation in the oral cavity. The application of laser at low intensity therapy is a treatment option. This systematic review evaluated the efficacy of laser therapy in treating symptoms of burning mouth syndrome. MATERIAL AND METHODS: The study was formulated according to the PRISMA and Cochrane guidelines. Seven databases were used as primary sources of research. Only randomized controlled clinical trials were included. The efficacy of the therapy was estimated comparing the values of the visual and numerical scales of pain before and after laser treatment, through qualitative analysis. RESULTS: The search resulted in 348 records and only eight filled the eligibility criteria and were included. All studies evaluated pain and / or a burning sensation considering a time interval of two to ten weeks. The total sample consisted of 314 patients submitted to treatment: 123 from the control group, who participated with laser off or with the tip blocked, and 191 from the intervention group, treated with low-level laser therapy. The female gender stood out and the average age of the participants was 60.89 years. The main symptoms reported were pain and a burning sensation in the oral mucosa and tongue. The parameters adopted by the authors for laser treatment were diverse and the variables were not fully described in the published studies. Visual analog and numerical scales were used to assess symptoms and only three studies showed statistical significance. CONCLUSIONS: It is suggested that laser therapy may be an effective alternative in the treatment of BMS. New randomized clinical trials should consider well-established protocols to better understand the efficacy of laser therapy without confounding the effects.

Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36-month prospective cohort study of 334 patients.

OBJECTIVE: The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. METHODS: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ΔPGA ≥ 0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operating characteristic (ROC) analysis. RESULTS: Adjusted mean PGA and SLEDAI-2K scores presented a high correlation (rho = 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628-0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K ≥ 4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822-0.932), p < 0.0005), with a sensitivity of 35.3%. CONCLUSIONS: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research.

Using modified fish scale waste from Sardinella brasiliensis as a low-cost adsorbent to remove dyes from textile effluents.

Textile industry wastewater has become a cause of concern to environmentalists due to its toxic composition and the difficulty of breaking down certain dyes. In this study, modified fish scales of Sardinella brasiliensis (SSb) were used as an alternative for a low-cost adsorbent to remove dyes from textile wastewaters. Adsorption efficiency was assessed by measuring the general, kinetic, and thermodynamic physico-chemical parameters of adsorption isotherms, using Reactive Turquoise Blue 15 (RTB15) and Reactive Red 120 (RR120) dyes as adsorbate models, as local textile industries commonly use these dyes. The isothermal data from the batch experiments were inserted in the Langmuir, Freundlich, and Langmuir-Freundlich (SIPS) equations; the Langmuir isotherm equation showed the most appropriate. The thermodynamic parameters showed that adsorption of dyes by the modified SSb adsorbent was an endothermic yet spontaneous process in the case of RR120. Sorbent-based on SSb material was concluded as adsorbing both of the tested dyes. Because of its abundant availability, and the small amount of activation needed to turn it into an adsorbent, this biowaste can be employed as a low-cost alternative for removal of dyes in the treatment of textile wastewater.

A morphoanatomical approach to the adaptive features of the epidermis and proboscis of a marine Polychaeta: Eulalia viridis (Phyllodocida: Phyllodocidae).

Eulalia viridis is a marine Polychaeta of the rocky intertidal that, despite its simple anatomy, is an active predator of much larger invertebrates, from which it extracts pieces of soft tissue through suction. This uncanny feeding strategy triggered the pursuit for the morphological mechanisms that enable adaptation to its environment. The evaluation of the worm anatomy and microanatomy, combining electron and optical microscopy, revealed a series of particular adaptations in the epidermis and in the proboscis (the heavily muscled eversible pharynx). Besides its function in feeding, the proboscis is the main sensory organ, being equipped with numerous sensorial papillae holding chemoreceptors. Additionally, the proboscis possesses tentacles that become exposed when the organ is everted. These provide fast release of mucus and toxins, from mucocytes and special serous cells, respectively (the latter involving both merocrine and apocrine processes), whenever contact with a prey occurs. In its turn, the epidermis provides protection by cuticle and mucus secretion and has a sensorial function that may be associated to the worm's uncommon green pigment cells. Eulalia viridis presents a series of elegant adaptive tools to cope with its environment that are evolutionarily designed to counterbalance its relatively simple body plan.

Assessing epidemiology of leprosy and socio-economic distribution of cases.

Leprosy still represents a serious health problem in a number of countries, including Brazil. Although leprosy has been associated with poverty for a long time, it is still difficult to accurately define this relationship. Here, we evaluated in an endemic municipality the progress from 1995 to 2015 of epidemiological indicators to establish if there were any strong associations between social indicators and the occurrence of leprosy. An ecological study was conducted using the SINAN database (Brazilian leprosy-national notifiable diseases information system) in combination with georeferencing of leprosy cases. The georeferencing used the ArcGis programme and occurrence of cases was evaluated in relation to the Health Vulnerability Index (HVI), an indicator that categorises socio-economic and sanitation factors. The data identified a marked decrease in the overall prevalence of leprosy, a reduction in the new case-detection rate and a reduction in the number of cases with grade 2 disabilities (albeit with transient peaks in 2007 and 2015). Logistic regression analysis showed association of detection rates with elevated HVI. Thus, while the epidemiological indicators point to the elimination of leprosy, there is evidence of hidden cases and an association between higher rates of leprosy detection and greater social vulnerability remain.

Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis.

OBJECTIVE: To investigate whether the Cdc2-like kinase 2 (CLK2) is expressed in hypothalamic neurons and if it is, whether the hypothalamic CLK2 has a role in the regulation of energy balance. SUBJECTS: Swiss mice on chow or high-fat diet (HFD) and db/db mice on chow diet were used to address the role of CLK2 in the hypothalamus. RESULTS: Hypothalamic CLK2Thr343 phosphorylation, which induces CLK2 activity, is regulated in vivo by refeeding, insulin and leptin, in a PI3K (phosphoinositide 3-kinase)-dependent manner. The reduction of CLK2 expression in the hypothalamus, by chronic pharmacological inhibition with TG003 or by chronic knockdown with small interfering RNA was sufficient to abolish the anorexigenic effect of insulin and leptin, to increase body weight, fat mass, food intake and to decrease energy expenditure in mice on chow. In contrast, CLK2Thr343 phosphorylation in the hypothalamus in response to insulin, leptin or refeeding was impaired in mice on HFD or in db/db mice. Chronic CLK2 inhibition in the hypothalamus was associated with a slight increase in the fasting blood glucose levels, reduction in PEPCK (phosphoenolpyruvate carboxykinase) expression in the liver and enhanced glucose production from pyruvate, suggesting a regulation of hepatic glucose production. Further, overexpressing CLK2 in the mediobasal hypothalami of mice on HFD or in db/db mice by adenovirus partially reversed the obese phenotype. CONCLUSIONS: Thus, our results suggest that protein CLK2 integrates some important hypothalamic pathways, and may be a promising molecule for new therapeutic approaches for obesity and diabetes.

Comparison of simple sucrose and percoll based methodologies for synaptosome enrichment.

Synaptosomes are isolated nerve terminals. They represent an extremely attractive in vitro model system to study synaptic physiology since they preserve morphological and functional characteristics of the synapse. As such they have been used to investigate synaptic dysfunctions associated with neuropathologies like Alzheimer's disease. In the present work two simple methodologies for isolating synaptosomal-enriched fractions were compared for the first time. The starting points of both protocols were rat cortical or hippocampal homogenized tissues that underwent several differential centrifugation steps followed by a final purification of synaptosomal-enriched fractions using either a Percoll gradient or a Sucrose gradient. Comparison of the fractions obtained was carried out, using both biochemical and electron microscopy approaches. In the biochemical analysis the protein levels of pre-synaptic, post-synaptic, nuclear and mitochondrial markers were evaluated. Additional characterization of the synaptosomal-enriched fractions was performed using transmission electron microscopy. In summary, the results indicate that under the conditions tested the Sucrose based protocol is more efficient for the isolation of synaptosomal-enriched fractions from both neuronal tissues, being particularly efficient for hippocampus that is a less abundant brain tissue. Further, the sucrose protocol apparently results in a higher yield of viable synaptosomes suitable for further assays, including structural and functional studies of synapses; making this an attractive procedure to study processes associated with neuropathologies.

Rubisco mutants of Chlamydomonas reinhardtii display divergent photosynthetic parameters and lipid allocation.

Photosynthesis and lipid allocation were investigated in Rubisco small subunit mutants of the microalga Chlamydomonas reinhardtii. Comparative analyses were undertaken with cells grown photoheterotrophically under sulphur-replete or sulphur-depleted conditions. The Y67A Rubisco mutant, which has previously demonstrated a pronounced reduction in Rubisco levels and higher hydrogen production rates than the wild type, also shows the following divergences in photosynthetic phenotype and lipid allocation: (i) low Fv/Fm (maximum photochemical efficiency), (ii) low effective quantum yield of photosystem II (ΦPSII), (iii) low effectiveness at protection against high light intensities, (iv) a higher level of total lipids per pigment and (v) changes in the relative proportions of different fatty acids, with a marked decrease in unsaturated fatty acids (FAs). The most abundant thylakoid membrane lipid, monogalactosyldiacylglycerol, decreased in amount, while the neutral lipid/polar lipid ratio increased in the mutant. The low amount and activity of the mutated Rubisco Y67A enzyme seems to have an adverse effect on photosynthesis and causes changes in carbon allocation in terms of membrane fatty acid composition and storage lipid accumulation. Our results suggest that Rubisco mutants of Chlamydomonas might be useful in biodiesel production.