Several studies show that chronic marijuana use opens doors to several disorders, especially neuropsychiatric disorders. Others consider cannabinoids to be promising in therapeutic practice. Here, we present a literature review, based on selected publications on the Medline and Scielo databases, on health and cannabis use. This review aims to assist health professionals and students in understanding the growing number of marijuana users who look for help in outpatient clinics and offices. Therefore, there is an increase in the frequency of hospital admissions for psychotic disorders in clinics and specific treatment institutions. Research over the past 35 years has shown that marijuana use promotes only momentary anxiolysis. This drug alone or in combination with cigarette, when consumed for a long term, can deteriorate the user’s intellectual capacity, academic performance, and professional achievements and finally results in social isolation. The current situation demonstrates that cannabis usage is a public health issue that needs to be addressed in health policy because the majority of users get sick and lose their ability to work.

The interaction of HSA with hydrochlorothiazide in absence and presence of glucose was studied through UV-Vis absorption and fluorescence spectroscopy at 37 ºC.The interaction of a drug with human serum albumin influences its bioavailability and the high blood glucose level can promote the formation of glycation end products, and affect protein ability to transport drugs.To assess the glucose effect on the ability of hydrochlorothiazide to bind HSA, normoglycemic (80 mg glucose/dl) and hyperglycemic (320 mg glucose/dl) solutions were used.Competitive binding studies were performed using markers for Sudlow I (warfarin) and Sudlow III (digitoxin).Results showed good correlation of the observations made through the UV-Vis spectroscopy and the spectrofluorimetric measurements, concerning the association of ground state and the disturbance in the microenvironment around the aromatic amino acid residues.The fluorescence quenching of HSA by hydrochlorothiazide in the GLU absence and presence occurred by formation of complex drug-HSA.High glucose concentrations may decrease the number of available binding sites for drug in the IIA subdomain, probably due to albumin conformational change, making the binding of drug in the vicinity of residue Triptophan-214 difficult.Results suggest that a glycemic control is required to obtain an appropriate treatment with hydrochlorothiazide.

The aim of the present study is to contribute to the knowledge about the functioning of the neuronal circuits.We built a mathematical-computational model using graph theory for a complex neurophysiological circuit consisting of a reverberating neuronal circuit and a parallel neuronal circuit, which could be coupled.Implementing our model in C++ and applying neurophysiological values found in the literature, we studied the discharge pattern of the reverberant circuit and the parallel circuit separately for the same input signal pattern, examining the influence of the refractory period and the synaptic delay on the respective output signal patterns.Then, the same study was performed for the complete circuit, in which the two circuits were coupled, and the parallel circuit could then influence the functioning of the reverberant.The results showed that the refractory period played an important role in forming the pattern of the output spectrum of a reverberating circuit.The inhibitory action of the parallel circuit was able to regulate the reverberation frequency, suggesting that parallel circuits may be involved in the control of reverberation circuits related to motive activities underlying precision tasks and perhaps underlying neural work processes and immediate memories.

Characteristics of the interaction of haloperidol with HSA and BSA at 25°C and 37°C were studied by applying a computational model based on spectrofluorimetry data. The relative positions of primary binding sites for this drug in albumins were estimated. Haloperidol is a typical or first-generation antipsychotic medication and a neuroleptic drug from the butyrophenone group. Results suggested that the primary binding site for haloperidol in HSA and BSA is located inside the subdomain IB. At 37°C, HPD quenched 12.2(± 0.6)% of HSA fluorescence and 22.7(± 0.9)% of BSA fluorescence when [HPD]/[albumin] ratio was 1/1000. For [HPD]/[albumin] ratio equal 2/300, HPD was able to quench 58-65% of fluorescence of the two albumins at 37°C. The association constant of the HSA fluorescence by HPD was found in the order of 107 M-1, approximately two orders of magnitude larger than that found for risperidone, and about three orders of magnitude than those estimated for clorpromazine and sulpiride.

Comparative study of haloperidol (HPD), biperiden (BPD) and clonazepam (CNZ) interactions with human and bovine serum albumin was performed based on fluorescence quenching analysis. We used mathematical modeling comparing spectrofluorimetric data to obtain information on the possibility of competition among three drugs by sites binding. Results showed that the three drugs studied have high affinity for albumin and suggest the existence of two site classes in HSA for HPD and only one class for BPD and CNZ, in the range of concentrations tested for each drug. Among them, only HPD forms complex with HSA. Comparing normalized quenching plots suggested that the primary sites in HSA and BSA for HPD and CNZ are located at subdomain IB, whereas BPD would bind in the subdomain IIA. Considering the competition for binding sites in HSA, titrations of HPD-HSA complex by BPD and CNZ, as well as the titration of HSA solution containing CNZ titrated by BPD, show that although the three drugs do not compete with each other for binding sites, their interaction with HSA can cause conformational change in the protein, and to increase or decrease the accessibility to binding sites for other drug. This may mean alteration in the free plasma drug concentrations.

•A mathematical model to estimate the relative position of binding sites for ligands in HSA and BSA is presented.•The structural and spectroscopic similarities/differences between HSA and BSA are considered in the model.•The model also considers the Stern-Volmer Theory and the Förster's model.•The model was suitable to estimate the positions of binding sites in HSA and BSA, and the binding dynamics as ligand concentration increased.

Arbovirus infections represent a global public health problem, and recent epidemics of yellow fever, dengue, and Zika have shown their critical importance in Brazil and worldwide. Whilst a major effort for vaccination programs has been in the spotlight, a number of aptamer approaches have been proposed in a complementary manner, offering the possibility of differential diagnosis between these arboviruses, which often present similar clinical symptoms, as well as the potential for a treatment option when no other alternative is available. In this review, we aim to provide a background on arbovirus, with a basic description of the main viral classes and the disease they cause, using the Brazilian context to build a comprehensive understanding of their role on a global scale. Subsequently, we offer an exhaustive revision of the diagnostic and therapeutic approaches offered by aptamers against arboviruses. We demonstrate how these promising reagents could help in the clinical diagnosis of this group of viruses, their use in a range of diagnostic formats, from biosensors to serological testing, and we give a short review on the potential approaches for novel aptamer-based antiviral treatment options against different arboviral diseases.

This review paper attempts to approximate the concept of biological stress to the stress concept in Physics using the phenomenological view of physics to discuss the source of generator forces of biological stress state.Based on the literature, parallels are drawn between the two concepts and a discussion on the steady state in open systems and homeostatic state in biological systems is developed.Using the concepts of thermodynamic entropy and informational entropy, and comparing stress in living systems and nonliving, we attempt to build a basis for a view of stress as a principle of nature linked to the adaptability property of matter, opposing entropy.It is known that the increasing number of microstates possible in a complex system increases the entropy.In that way, entropy is related to the amount of additional information needed to specify the exact physical state of a system, given its macroscopic specification.By controlling the metabolic processes (catabolism-anabolism) to decrease the entropy, stress reduces the number of possible states for which the living system could evolve, avoiding the loss of "life information", preserving its characteristics and preventing its extinction.The loss of function of a species within an ecosystem or of cells within an organ can be showing that the limits of the stress principle were "transgressed".That is, the intensity and/or duration of stress exceeded the capacity of living organism to process of information extracted from stressor and reprogram its physiological mechanisms, activating its adaptability process, while its internal balance is preserved.

Computational mathematical models have shown promise in the biological mechanism's reproduction. This work presents a computational mathematical model of the hormonal storage control applied to an endocrine cell. The model is based on a system of differential equations representing the internal cell dynamics and governed by the Lyapunov control function. Among the stages of these dynamics, we analyze the storage and degradation, which occur within some endocrine cells. The model’s evaluation considers, as an example, the synthesis–storage-release regulation of catecholamine in the adrenal medulla. Seven experiments, varying the input parameters, were performed to validate and evaluate the model. Different behaviors could be observed according to the numerical data used for future research and scientific contributions, besides confirming that Lyapunov control function is feasible to govern the cell dynamics.

This work presents a mathematical-computational model designed to assess the position of binding sites for ligands in human and bovine serum albumins. The model associates geometric resources to the phenomenon of fluorescence quenching in albumin. The results showed that the mean distance between the binding site for risperidone and tryptophan residue 212 of bovine serum albumin would be 2.59 (+/- 0.92) nm, and the mean distance between this binding site and the tryptophan residue 134 would be 2.25 (+/- 0.80) nm. Thus, the binding site would be slightly closer to tryptophan residue 134 than the residue 212.

Zika virus (ZIKV) belongs to the Flaviviridae family and its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns. The viral NS5 protein is the most conserved ZIKV protein, and is comprised of two domains, an N-terminal methyltransferase domain and an RNA-dependent RNA polymerase (RdRP) domain at the C-terminal end. The fact that viral NS5 is essential for viral replication but lacks a human counterpart makes NS5 an important target to be studied. Single-stranded DNA oligonucleotides aptamers can fold into unique three-dimensional conformations that recognize targets with high-specific and affinity. This work aims to study single-stranded DNA aptamers displaying high -affinity and specificity generated against ZIKV NS5 protein to be used in diagnostic platforms.

Introduction: The infection caused by the flavivirus Zika (ZIKV) remained as a tropical neglected disease until November 2015, when cases of microcephaly in infants born after a ZIKV epidemic, together with an increase in cases of Guillain-Barré syndrome and other neurological disorders were associated with the ZIKV infection. Nonstructural protein 5 (NS5) is essential for replication of the genome, whose RdRp domain synthesizes viral RNA through a de novo synthetic mechanism. Aptamers are single stranded DNA (or RNA) molecules, which bind to a wide range of ligands with high specificity and affinity, and can be used as relevant molecular tools.

Hantavirus is a zoonotic, viral respiratory disease and is recent associated with human diseases that need a qualitative diagnosis method to promote a rational treatment as well as controlling the spread ability of the virus. Thus a early rational treatment is necessary in the outcome of the disease that on a identification etiological agent is essential. This paper shows results obtained from hantavirus aptamers interaction with the hantavirus protein, ANDES solution, throw fluorometric methods, that will assist in the determination of a secure path to aim an identification mechanism to identify the virus. The investigation revels that aptamer C2526 shows a high affinity binding with hantavirus protein, ANDES, being a promise reactive for recognizing assays.

Along these last six years, we have been organizing the above titled symposium, focused in general, on biological targets, and more specifically on computational methods and tools applied to health and environmental themes. We have brought then a meaningful number of good talks and presentations broadcasting research results as well as a sort of correlated models. The use of computational methods and mathematical tools in biological and medicine targets has been successfully supporting scientists to understand physical and biological phenomena. As we recently discussed in our previous symposium, current technological advances allow the simulation of larger systems, with greater accuracy. Our expectation is that scientists take advantage of the increasing computational power now available to model and simulate more complex structures. In this sense each edition of the symposium registers the path we have been grooving along the time since we joined the ICCMSE to overtake this challenge.

Both aptamers and siRNA technologies have now reached maturity, and both have been validated with a product in the market. However, although pegaptanib reached the market some time ago, there has been a slow process for new aptamers to follow. Today, some 40 aptamers are in the market, but many in combination with siRNAs, in the form of specific delivery agents. This combination offers the potential to explore the high affinity and specificity of aptamers, the silencing power of siRNA, and, at times, the cytotoxicity of chemotherapy molecules in powerful combinations that promise to delivery new and potent therapies. In this review, we report new developments in the field, following up from our previous work, more specifically on the use of aptamers as delivery agents of siRNA in nanoparticle formulations, alone or in combination with chemotherapy, for the treatment of cancer.

Zika virus (ZIKV) belongs to the Flaviviridae family and its recent outbreak and association with human diseases (e.g. neurological disorders and microcephaly in babies) have raised global health concerns. Its differentiation from Dengue in accurate diagnostic assays are of great importance. The viral NS1 protein is a secreted protein and can be an ideal target for diagnostic assay development. We have thus selected NS1 as target for aptamer selection and study. Single-stranded DNA oligonucleotides aptamers have been previously selected for this target, and here we present the study of such aptamers by fluorescent spectroscopy, CD and ELISA in order to characterize their interaction and select the best candidate for further future assay development.

The Zika virus (ZIKV) is an Arbovirus belonging to the family Flaviviridae, genus Flavivirus, whose transmission occurs mainly by bites of mosquitoes of the genus Aedes. Although clinical manifestations of the disease are usually mild, increasing evidence is associated with ZIKV infection with increased congenital neurological abnormalities and neuropathic disorders. The laboratory diagnosis of the infection is based on molecular tests and viral isolation since serological tests usually present cross - reaction with other Flaviviruses. A promising solution for rapid and early diagnosis of infection is the development of nucleic acid aptamers capable of specifically interacting, recognizing infectious agents or detecting antibodies. Following this premise, this study aims to identify specific aptamers for NS5 protein of ZIKV, in order to use them in serological tests.

The Zika virus (ZIKV) is an Arbovirus belonging to the family Flaviviridae, genus Flavivirus, whose transmission occurs mainly by bites of of Aedes aegypti mosquitoes. Although clinical manifestations of the disease are usually mild, increasing evidence is associated with ZIKV infection with increased congenital neurological abnormalities and neuropathic disorders. The laboratory diagnosis of the infection is based on molecular tests and viral isolation since serological tests usually present cross-reaction with other Flaviviruses. A promising solution for rapid and early diagnosis of infection is the development of nucleic acid aptamers capable of specifically interacting, recognizing infectious agents or detecting antibodies. Following this premise, this study aims to identify specific aptamers for NS1 protein of ZIKV, in order to use them in serological tests.