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The overexpression of ATP-binding cassette (ABC) transporters contributes to the failure of chemotherapies and symbolizes a great challenge in oncology, associated with the adaptation of tumor cells to anticancer drugs such that these transporters become less effective, a mechanism known as multidrug resistance (MDR). The aim of this review is to present the most widely used methodologies for induction and comprehension of in vitro models for detection of multidrug-resistant (MDR) modulators or inhibitors, including biochemical and morphological techniques for chemosensitivity studies. The overexpression of MDR proteins, predominantly, the subfamily glycoprotein-1 (P-gp or ABCB1) multidrug resistance, multidrug resistance-associated protein 1 (MRP1 or ABCCC1), multidrug resistance-associated protein 2 (MRP2 or ABCC2) and cancer resistance protein (ABCG2), in chemotherapy-exposed cancer lines have been established/investigated by several techniques. Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase assays to distinguish types of interaction with ABC transporters, (vi) morphology to detail phenotypic characteristics in transformed cells, (vii) molecular testing of resistance-related proteins (RT-qPCR) and (viii) 2D and 3D models, (ix) organoids, and (x) microfluidic technology. Then, in vitro models for detecting chemotherapy MDR cells to assess innovative therapies to modulate or inhibit tumor cell growth and overcome clinical resistance. It is noteworthy that different therapies including anti-miRNAs, antibody-drug conjugates (to natural products), and epigenetic modifications were also considered as promising alternatives, since currently no anti-MDR therapies are able to improve patient quality of life. Therefore, there is also urgency for new clinical markers of resistance to more reliably reflect in vivo effectiveness of novel antitumor drugs.

Background: Migraine is a recurrent headache disorder characterized by moderate to severe, throbbing pain, typically unilateral. It can be classified as migraine with or without aura, depending on the presence or absence of visual or sensory disturbances known as auras, respectively., Aim: The objective of this study was to determine the prevalence of ecchymosis in patients with migraine and its accuracy parameters in the differential diagnosis between migraine and tension-type headache (TTH)., Method: Patients with migraine or tension-type headache, diagnosed according to the International Classification of Headache Disorders (ICHD-3) criteria, were assessed regarding the prevalence of skin ecchymosis, both during headache attacks and in the pain-free period., Results: Four hundred patients were investigated. The subjects were equally divided in two groups presenting the diagnosis of migraine and TTH. Ages were, respectively, 37.3 ± 9.0 years for migraineurs and 40.0 ± 10.0 years for sufferers of TTH. Ecchymosis was present in 76% of patients with migraine and in 11% of patients with TTH ( p  < 0.0001). In both patients with migraine and TTH, ecchymosis predominated in women, respectively in 92.1% and 63.6% ( p  < 0.0001). Among the 152 patients with migraine who reported ecchymosis, they were present in most of headache attacks (69.7%), occurred within the first 24 hours after the headache onset (68.4%) and were unilateral in location (65.1%), mainly on the arms (34.9%) and thigh (24.3%). The ecchymosis were larger than 2 cm in diameter (60.5%), lasting longer than four days (89.5%). During the presence of ecchymosis, the headache was unilateral (91.5%), pulsatile (80.3%), severe to very severe (67.8%) and worsening with physical activity (75%)., Conclusions: Intermittent skin ecchymosis may be a differentiating factor between migraine and tension-type headache and a specific marker of migraine to be considered as a criterion for its diagnosis.

During the COVID-19 pandemic, several drugs were repositioned and combined to quickly find a way to mitigate the effects of the infection. However, the adverse effects of these combinations on the gastrointestinal tract are unknown. We aimed investigate whether Hydroxychloroquine (HD), Azithromycin (AZ), and Ivermectin (IV) used in combination for the treatment of COVID-19, can lead to the development of gastrointestinal disorders. This is a systematic review and network meta-analysis conducted using Stata and Revman software, respectively. The protocol was registered with PROSPERO (CRD42023372802). A search of clinical trials in Cochrane Library databases, Embase, Web of Science, Lilacs, PubMed, Scopus and Clinicaltrials.gov conducted on November 26, 2023. The eligibility of the studies was assessed based on PICO criteria, including trials that compared different treatments and control group. The analysis of the quality of the evidence was carried out according to the GRADE. Six trials involving 1,686 COVID-19 patients were included. No trials on the association of HD or AZ with IV met the inclusion criteria, only studies on the association between HD and AZ were included. Nausea, vomiting, diarrhea, abdominal pain and increased transaminases were related. The symptoms of vomiting and nausea were evaluated through a network meta-analysis, while the symptom of abdominal pain was evaluated through a meta-analysis. No significant associations with these symptoms were observed for HD, AZ, or their combination, compared to control. Low heterogeneity and absence of inconsistency in indirect and direct comparisons were noted. Limitations included small sample sizes, varied drug dosages, and potential publication bias during the pandemic peak. This review unveils that there are no associations between gastrointestinal adverse effects and the combined treatment of HD with AZ in the management of COVID-19, as compared to either the use of a control group or the administration of the drugs individually, on the other hand, highlighting the very low or low certainty of evidence for the evaluated outcomes. To accurately conclude the absence of side effects, further high-quality randomized studies are needed.

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.

Buthionine sulfoximine (BSO) is a synthetic amino acid that blocks the biosynthesis of reduced glutathione (GSH), an endogenous antioxidant cellular component present in tumor cells. GSH levels have been associated with tumor cell resistance to chemotherapeutic drugs and platinum compounds. Consequently, by depleting GSH, BSO enhances the cytotoxicity of chemotherapeutic agents in drug-resistant tumors. Therefore, the aim of this study was to conduct a systematic review with meta-analysis of preclinical studies utilizing BSO in cancer treatments. The systematic search was carried out using the following databases: PubMed, Web of Science, Scopus, and EMBASE up until March 20, 2023, in order to collect preclinical studies that evaluated BSO, alone or in association, as a strategy for antineoplastic therapy. One hundred nine investigations were found to assess the cytotoxic potential of BSO alone or in combination with other compounds. Twenty-one of these met the criteria for performing the meta-analysis. The evidence gathered indicated that BSO alone exhibits cytotoxic activity. However, this compound is generally used in combination with other antineoplastic strategies, mainly chemotherapy ones, to improve cytotoxicity to carcinogenic cells and treatment efficacy. Finally, this review provides important considerations regarding BSO use in cancer treatment conditions, which might optimize future studies as a potential adjuvant antineoplastic therapeutic tool.

The aim of this review was to (i) acknowledge structural advantages of natural products (NPs) for designing therapeutic drugs; (ii) emphasize how wildlife conservation is socially and economically necessary for scientific and commercial progress in Brazilian regions; and (iii) show how decisions by governmental regulations exert damaging effects on safeguarding of biodiversity. Natural products (NPs) from animals (e.g.: bufadienolides as marinobufagin), plants (diterpenes: casearin X and paclitaxel; triterpenes: betulinic acid) and microorganisms (depsipeptides: geodiamolides; antraciclines: doxorubicin) are the main source of oral drugs and have innate advantages for enteral and parenteral drug design, synthesis and combinational chemistry using novel techniques, including green chemistry. NPs possess high chemical diversity, binding flexibility to biological targets, chiral centers, aliphatic systems, hydrogen-bond acceptors and donors, and/or heteroatoms, and broad-spectrum pharmacological properties, including against malign disorders. Nonetheless, all Brazilian biomes and connected ecosystems have been systemically threatened since 2019 by the following fire, deforestation, monocultures, cattle raising, mining and/or oil spills mainly as consequence of financial cuts in key institutions which oversee environmental stability for terrestrial and marine Brazilian fauna and flora. Nevertheless, natural chemical entities, broad traditional knowledge on agrobiodiversity, fishing, fire management, and pioneering processes of economic interest play a vital role for "Science of Biodiversity," which arises as business bioeconomy opportunities to convert Brazil into a self-sufficient country for production of pharmaceutical supplies, cosmeticsand foods. Hence, Brazil needs sustainable development projects supported by government and scientific input if one wishes to use the chemical and biological biodiversity to treat individuals and improve the quality of life.

To compare the prevalence and characteristics of hypertension in women experiencing incarceration (WEI) to the general population in Brazil: (1) a prison survey conducted from January 2014 to December 2015 in 15 states, with 1,327 WEI; and (2) a household survey in the 26 states and the Federal District of Brazil administered to women in the general population (WGP). Data analysis used SPSS® version 20.0. The point estimates and the prevalence ratio with their respective confidence intervals were calculated using Poisson regression. Ages in the two populations differed, 27.9% of WGP were over 50, while 7.3% of WEI were. The overall prevalence of arterial hypertension was 31.3% (95% CI: 28.6-34.0) in the WEI and 38.9% (95% CI: 37.8-39.9) for WGP. For individuals under 30, hypertension was found in 22.4% of WEI and 13.4% of WGP. WEI have a higher prevalence of hypertension at an earlier age than the GP. Less education, obesity, using illegal drugs, previous pregnancy, and not using contraceptives were more frequent in this group, revealing the need to implement policies aimed at treating both their hypertension and other health issues in prison.

Aim: The study investigated the cortical activity changes and time production task performance induced by changes in motion speed of a non-immersive 3D virtual stimulus., Material and Methods: Twenty-one individuals were participated in the crossover study with the visual-time reproduction task under three-speed conditions: original, slow and fast virtual stimulus. In addition, the electroencephalographic analysis of the theta band power in the dorsolateral prefrontal cortex was done simultaneously with time production task execution., Results: The results demonstrated that in the slow speed condition, there is an increase in the error in the time production task after virtual reality ( p  < 0.05). There is also increased EEG theta power in the right dorsolateral prefrontal cortex in all speed conditions ( p  < 0.05)., Conclusions: We propose that the modulations of speed of virtual stimulus may underlie the accumulation of temporal pulses, which could be responsible for changes in the performance of the production task of the time intervals and a substantial increase in right dorsolateral prefrontal cortex activity related to attention and memory, acting in cognitive domains of supraseconds.

There is robust evidence of using Curcuma longa L. in reducing metabolic levels in people with diabetes. This study analysed the effectiveness of Curcuma longa L. in the metabolic control of patients with type 2 diabetes in Brazil. A randomised double-blind placebo-controlled clinical trial was conducted with 71 participants divided into a Curcuma longa L. group (500 mg/day with piperine 5 mg) and a placebo group, for 120 days. Anthropometric, clinical and biochemical variables were evaluated at baseline, 60 and 120 days after the beginning of the intervention. Paired and independent Student's t -test and chi-square test were used for statistical analysis. The curcuma group presented a significantly decreased glycaemia ( p =.013), glycated haemoglobin ( p =.015), HOMA index ( p =.037) and triglycerides (TGs) ( p =.002). The use of piperine-added Curcuma longa L. was effective in the glycaemic and TG control of patients with type 2 diabetes.

Background : Food is already recognized as a trigger for migraine, but its mechanism of action has not been fully clarified. There is evidence that they act on the pathogenesis of migraine, interfering with meningeal inflammation, vasodilation and cerebral glucose metabolism. Aim : The aim of this study was to know which plant foods are triggers for migraine and the latency time for the onset of pain. Method : We interviewed patients with migraine and tension-type headache about plant foods that trigger headache and onset time of the headache. We studied 3,935 migraine patients and 1,163 with tension-type headache. Results : There were headaches triggered by plant foods after 90.5 ± 7.9 minutes of ingestion in 40.3% (1,584/3,935) of migraine patients and none with tension-type headache. Headaches triggered by plant foods intake are distributed in the following order of frequency: watermelon (29.5%), passion fruit (3.73%), orange (2.01%), pineapple (1.52%), grape (0.51%), banana (0.46%), cucumber (0.43%), acerola (0.25%) and papaya (0.25%). Conclusions : Many plant foods, especially watermelon, may trigger headache attacks in migraine patients within a few minutes.

Objective: To analyse the virtual reality applications in the subjects' neuro-psychomotor functions rehabilitation with motor and/or neuropsychiatric impairment., Methods: The search was carried out in nine databases (Scopus, PubMed, Web of Science, ScienceDirect, Cochrane Library, CINAHL, PsycINFO, LILACS, and SciELO), from December 2017 to March 2019. An additional manual search was performed, taking into consideration references of the included papers, through the same eligibility criteria. The methodological quality of the included papers was evaluated using the Physiotherapy Evidence Database (PEDro)., Results: One hundred and twenty-two papers were selected by the initial screening, but only 33 studies participated in the final inclusion in the study (11 clinical trials and 14 experimental studies). The data extracted were: the proposed objective, the sample population, the neurological condition treated, the VR modality used in the procedures and the study intervention period., Conclusions: Virtual reality supports the rehabilitation process of neuro-psychomotor functions, allowing potential gains in the patients' recovery. Therefore, its development facilitates its availability and access in the future.Implications for rehabilitationIt has minimal adverse effects during the virtual therapies performance, such as the presence of vertigo related to cybersickness conditions, suggesting virtual reality as a safe rehabilitation tool, compared to other therapies.Virtual reality use is useful and effective in helping the rehabilitation process of motor, cognitive and psychosocial functions.It plays a role as an adjunctive and complementary therapy in the neuro-psychomotor rehabilitation process to obtain a clinically significant result.

Aim: This study investigated whether time-estimation task exposure influences the severity of Attention Deficit Hyperactivity Disorder (ADHD), as well as theta band activity in the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex., Material and Methods: Twenty-two patients with ADHD participated in a crossover experiment with a visual time-estimation task under control conditions (without exposure to time estimation tasks) and experimental (thirty days exposure to time-estimation tasks) in association with electroencephalographic analysis of theta band., Results: ADHD patients with thirty days of time-estimation task exposure presented a worse performance of the time-estimation task, as revealed by the measurements of the absolute error and relative error ( p  ≤ 0.05). However, our findings show the improvement of self-reported symptoms of attention, impulsivity, and emotional control in patients after the time-estimation task exposure ( p  = 0.0001). Moreover, the theta band oscillations in the right dorsolateral prefrontal cortex and in the ventrolateral prefrontal increased with thirty days of time-estimation task exposure ( p  ≤ 0.05)., Conclusion: We propose that the decrease in EEG theta power may indicate an efficient accumulation of temporal pulses, which could be responsible for the improvement in the patient cognitive aspects as demonstrated by the current study. Time-estimation task improves ADHD cognitive symptoms, with a substantial increase in cortical areas activity related to attention and memory, suggesting its use as a tool for cognitive timing function management and non-invasive therapeutic aid in ADHD.

Background: Transcranial direct current stimulation (tDCS) has emerged as a promising therapeutic tool to improve balance and optimize rehabilitation strategies. However, current literature shows the methodological heterogeneity of tDCS protocols and results, hindering any clear conclusions about the effects of tDCS on postural control. Objective: Evaluate the effectiveness of tDCS on postural control, and identify the most beneficial target brain areas and the effect on different populations. Methods: Two independent reviewers selected randomized tDCS clinical-trials studies from PubMed, Scopus, Web of Science, and reference lists of retrieved articles published between 1998 and 2017. Most frequently reported centre of pressure (COP) variables were selected for meta-analysis. Other postural control outcomes were discussed in the review. Results: Thirty studies were included in the systematic review, and 11 were submitted to a meta-analysis. A reduction of COP displacement area has been significantly achieved by tDCS, evidencing an improvement in balance control. Individuals with cerebral palsy (CP) and healthy young adults are mostly affected by stimulation. The analysis of the impact of tDCS over different brain areas revealed a significant effect after primary motor cortex (M1) stimulation, however, with no clear results after cerebellar stimulation due to divergent results among studies. Conclusions: tDCS appears to improve balance control, more evident in healthy and CP subjects. Effects are observed when primary MI is stimulated. Cerebellar stimulation should be better investigated.

Aim of the Study: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1 Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction., Materials and Methods: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1 Hz)., Results: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p < .05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p < .05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p < .05)., Conclusions: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.

Introduction: Primary dysmenorrhea (PD) is another term for idiopathic menstrual cramps. Treatments include the use of oral non-steroidal anti-inflammatory drugs (NSAIDs). These drugs have several side effects. The objective of this study was to perform a systematic review on the transdermal administration of drugs and the use of alternative therapies for the treatment of PD., Areas Covered: The article bases were Web of Science, PubMed and Sciencedirect and the patent bases were INPI, EPO and WIPO with publications on Primary Dysmenorrhea and associations with Transdermal Administration; Complementary Therapies and Medicinal Plants. 21 articles and 12 patents were analyzed. The results demonstrate the need for alternative therapies for the treatment of PD, with greater effectiveness and lower side effects, mainly in an attempt to reduce the intensity and duration of pain as well as reducing the continuous use of medications., Expert Opinion: The study of technological prospection highlighted the relevant importance in seeking new methods for the relief of the symptoms provoked by this condition. The perspectives coexist in the discovery of new natural and biotechnological pharmacological applications, mainly in the development of new devices capable of facilitating and optimizing this form of administration in an attempt to reduce side effects.

Introduction: Ethyl ferulate is a phenylpropanoid with anti-inflammatory, antioxidant and neuroprotective activities of natural and synthetic origin with potential uses in the nutraceutical and pharmaceutical industry. Therefore, the aim of this study was to investigate the current scenario regarding patents and scientific articles available involving the substance in question, regarding aspects such as quantity, areas of knowledge and depositor countries., Areas Covered: To do so, we conducted technological and scientific prospecting on the WIPO, EPO, USPTO and INPI and scientific databases in PubMed, Web of Science and Lilacs databases using the keywords 'ferulic acid ethyl ester' and 'ethyl ferulate' in English and Portuguese. A total of 16 articles and 17 patents of which 10 were Chinese and 11 claimed the use of ethyl ferulate or for the synthesis of other substances or synthetic methods of the same. Five of the patents selected claimed therapeutic applications related to the treatment of mycobacterial infections, use as a cosmetic and neuroprotective activity. The systematic review of the literature revealed antioxidant, neuroprotective, anti-inflammatory, antimutagenic, antiapoptotic, antimutagenic and antiproliferative activities., Expert Opinion: The technological and scientific prospection highlighted ethyl ferulate, despite its known pharmacological activities, is little explored by the pharmaceutical and nutraceutical industries.

Objective: This work aimed to develop and characterize a topical emulgel of amphotericin B (AmB) with bacuri butter (Platonia insignis Mart.) and evaluate its antileishmanial activity using in vitro assays., Significance: Leishmaniasis is considered an infectious disease, with high incidence and capacity to produce deformities. The first-line treatment recommended by WHO, with pentavalent antimonials, is aggressive and very toxic. Therefore, the development of topical treatments can emerge as a promising and less offensive alternative., Methods: The developed formulations were evaluated for organoleptic characteristics, centrifugation resistance, globule size, pH, electrical conductivity, viscosity, spreadability, drug content, preliminary stability, in vitro release profile, evaluation of antileishmanial activity using promastigotes forms of Leishmania major as infecting agents, macrophage cytotoxicity and selectivity index (IS)., Results: Formulated emulsions presented organoleptic characteristics compatible with its constituents; pH values were suitable for topical application, ranging from 4.73 to 5.02; introduced non-Newtonian shear thinning system; drug content was within the established standards, and the most suitable kinetic model of release was the first order. Regarding the in vitro assays, formulations containing both 1% and 3% of AmB presented similar outcomes, indicating a synergism between the bacuri butter and the drug, possibly showing a reduction on cytotoxicity to host cells., Conclusions: It was concluded that the formulations developed showed promising antileishmanial action and high potential for topical use.

Introduction: Microemulsions are thermodynamically stable translucent systems widely used for systemic delivery of drugs. The present study is the first to analyze the biotechnological potential of microemulsion systems for therapeutic purposes, through transdermal route, for pain treatment., Areas Covered: Patents were searched in the World Intellectual Property Organization (WIPO), European Patent Office (Espacenet), United States Patent and Trademark Office (USPTO) and National Institute of Intellectual Property (INPI). The inclusion criteria were published patents containing the keywords; 'microemulsion' and 'transdermal' in their title or abstract. 208 patents were found. However, only those patents which mentioned in their abstract or in their description the use of microemulsion system (object of invention) for pain treatment were selected. Were excluded duplicate patents and those that did not report pharmacological use of MEs specifically for pain treatment. Thus, sixteen patents were selected and described in the present study., Expert Opinion: Patents were found that focused specifically on the development process of microemulsion systems, the inclusion of essential oils in microemulsions, which place microemulsions as delivery systems for NSAIDs and other substances, as well as microemulsions for transdermal administration. These studies reinforce the therapeutic applicability of MEs in the treatment of acute and chronic pain.

Introduction: Rosmarinus officinalis L. is an aromatic plant with a number of biological properties. Recently, has been studied regarding its therapeutic potential. The objective of this study was to perform a systematic review on R. officinalis essential oil for its pharmacological properties and biotechnological applications., Areas Covered: The databases were searched for articles (Science Direct, Pub Med and Web of Science) and patents (INPI, WIPO and EPO) with publications on R. officinalis and associations with essential oil (EO-Ro), cardiovascular system, hypertension and cyclodextrin. We selected 305 articles on EO-Ro in the most diverse subjects and six articles with of R. officinalis associated with hypertension. 59 patents were analyzed. The results demonstrate how extensive the studies are on the biological activities with the extract and EO-Ro. These have shown effects antibacterial, antifungal, anti-inflammatory, antitumor and other. The properties exhibited by EO-Ro reinforce the use of this plant as a phytotherapeutic agent., Expert Opinion: Although there are several pharmacological properties, studies on the prevention or treatment of cardiovascular diseases with EO-Ro are scarce, especially to evaluate the antihypertensive activity of EO-Ro. It has also become clear that EO-Ro can be exploited in different commercial products as supplement, cosmetics and new formulations.

Dopaminergic system plays a key role in perception, which is an important executive function of the brain. Modulation in dopaminergic system forms an important biochemical underpinning of neural mechanisms of time perception in a very wide range, from milliseconds to seconds to longer daily rhythms. Distinct types of temporal experience are poorly understood, and the relationship between processing of different intervals by the brain has received little attention. A comprehensive understanding of interval timing functions should be sought within a wider context of temporal processing, involving genetic aspects, pharmacological models, cognitive aspects, motor control and the neurological diseases with impaired dopaminergic system. Particularly, an unexplored question is whether the role of dopamine in interval timing can be integrated with the role of dopamine in non-interval timing temporal components. In this review, we explore a wider perspective of dopaminergic system, involving genetic polymorphisms, pharmacological models, executive functions and neurological diseases on the time perception. We conclude that the dopaminergic system has great participation in impact on time perception and neurobiological basis of the executive functions and neurological diseases.

Introduction: Diabetes Mellitus has been considered an epidemic by the World Health Organization, with a high risk of morbidity and mortality. The treatment of this pathology consists in glycemic control, which can be done by oral hypoglycemic agents, insulin therapy, dietary guidance, regular physical activity, and psychosocial support. In addition, other adjuvant treatments are employed, such as phytotherapic, and one of the most used plants is Bauhinia forficata., Areas Covered: In the current review, patents using Bauhinia forficata for the Diabetes Mellitus treatment have been analyzed. There were 03 patents in WIPO, 01 in Espacenet, 01 in USPTO, and 02 in INPI., Expert Opinion: Patents on the adjuvant treatment of Diabetes Mellitus by Bauhinia forficata are discussed. Although there are some phytotherapy products containing this medicinal plant which has hypoglycemic effect here is still a need for the development of more products based on natural resources, for the treatment of this pathology, without side effects and with other benefits, to assist in the glycemia control in diabetic patients, and to improve their quality of life.

The physiotherapist's clinical practice includes proprioceptive neuromuscular facilitation (PNF), which is a treatment concept that accelerates the response of neuromuscular mechanisms through spiral and diagonal movements. The adaptations that occur in the nervous system following PNF are still poorly described in the literature. Thus, this study had a goal to investigate the electrophysiological changes in the fronto-parietal circuit during PNF and movement in sagittal and diagonal patterns. This study included 30 female participants, who were divided into three groups (control, PNF, and flexion groups). Electroencephalogram measurements were determined before and after tasks were performed by each group. For the statistical analysis, a two-way ANOVA was performed for the factors group and time. Interactions between the two factors were investigated using a one-way ANOVA. A value of p < 0.004 was considered significant. The results showed an increase in alpha absolute power in the left dorsolateral prefrontal cortex and upper left parietal cortex of the PNF group, suggesting these areas work together to execute a motor action. The PNF group showed a greater alpha absolute power compared with the other groups, indicating a specific cortical demand for planning and attention, reinforcing its use for the rehabilitation of individuals.

Objectives: To evaluate Ki-67 antigen expression in mammary epithelium of female rats in persistent estrus treated with anastrozole., Materials and Methods: Twenty-eight Wistar-Hanover female rats in persistent estrus induced by subcutaneous injection of 1.25 mg of testosterone propionate in the second day of life were randomly divided into two groups, control and experimental, with 14 animals each. The animals of control group received only the vehicle (propyleneglycol) and the animals of group experimental received 0.125 mg daily of anastrozole by gavage during 28 days. After 28 days of treatment, all animals were sacrificed and the first pair of abdominal-inguinal mammary glands was removed and fixed in 10% buffered formalin to investigate Ki-67 antigen expression by immunohistochemistry., Results: The mean percentage of Ki-67-stained nuclei per 500 cells in the mammary epithelium was 76.97 ± 0.76 and 14.44 ± 2.02 [mean ± standard error of the mean (SEM)] in the control and experimental groups, respectively (p < 0.0001)., Conclusions: Anastrozole treatment significantly reduced Ki-67 expression in the mammary epithelium of rats in persistent estrus.

Objective: The Pressure Biofeedback Unit (PBU) is used to assess the transversus abdominis muscle activity in order to determine the effectiveness of segmental stabilization, but not to verify its accuracy for measuring the pressure values of breathing from transversus abdominis activation. The objective of this study was to cross-validate the PBU pressure evaluated in transversus abdominis muscle activation with the respiratory pressure assessed through manovacuometry in order to verify the extent to which the PBU can be used to indirectly evaluate the strength of the respiratory muscle in both men and women and verify the reliability of the methods., Participants: A total of 39 healthy subjects., Methods: Manovacuometry and Pressure Biofeedback Unit tests were performed in three days each with three replications: 1) Maximal Inspiratory Pressure; 2) Maximal Expiratory Pressure; and 3) Pressure Biofeedback Unit., Results: Both tests showed good reliability and low correlation between the Pressure Biofeedback Unit and Maximal Inspiratory Pressure (r = 0.40; p = 0.01) and Maximal Expiratory Pressure (r = 0.33; p = 0.04). High differences were observed between pressures and wide limits of agreement in Bland-Altman analysis., Conclusion: It seems that the Pressure Biofeedback Unit is not able to effectively predict the respiratory muscles' strength as routinely evaluated through the use of the manovacuometry presenting a low cross-validation and good reliability.

Objective: The aim of this study was to evaluate the effects of raloxifene and tamoxifen on Ki-67 antigen expression in the vaginal epithelium of castrated rats., Material and Methods: Thirty-nine virgin, adult, castrated female Wistar-Hannover rats were randomly divided into three groups: Group I (control, n = 13), Group II (raloxifene, n  = 13) and Group III (tamoxifen, n = 13). After confirmation of their hypoestrogenic state, the rats were given 0.5 ml of propylene glycol (vehicle), 750 μg of raloxifene or 250 μg of tamoxifen, respectively, by gavage, for 30 days. On the 31st day, the rats were euthanized and their vaginas removed and fixed in 10% buffered formalin for of Ki-67 immunohistochemical evaluation. Data were analyzed using Levene's test and Tukey's method (p < 0.05)., Results: Mean Ki-67 expression in groups I, II and III was 27 ± 2.6, 32.3 ± 1.9 and 43.7 ± 3.5, respectively. In Group III (tamoxifen), there was a greater proportion of stained cells compared to Groups I and II (p < 0.0003), with no statistically significant difference between Groups I and II (p = 0.3626)., Conclusions: The present results show that tamoxifen significantly increased cell proliferation in the vaginal epithelium of the castrated rats and no difference between the raloxifene and control groups.

Objectives: To determine plasma concentrations of malondialdehyde (MDA) and of inflammatory markers in women with preeclampsia., Methods: A case-control study was conducted on 50 preeclamptic and 50 healthy pregnant women. The concentrations of MDA were determined by the method of thiobarbituric acid reactive substances. Markers of inflammation were determined by the multiplex method., Results: The concentrations of MDA did not differ between groups (p > 0.05) and the preeclampsia group had significantly higher IL-6, IL-10, TNF-α and IL-6/IL-10 ratio, compared to those with normal pregnancy., Conclusions: The MDA is a nonspecific marker for oxidative stress in preeclampsia, and the gestantes with preeclampsia have immune dysfunction.

Many algal species contain relatively high concentrations of polysaccharide substances, a number of which have been shown to have anti-inflammatory and/or immunomodulatory activity. In this study, we evaluated the anti-inflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction (PLS) extracted from the algae Gracilaria caudata. The antiinflammatory activity of PLS was evaluated using several inflammatory agents (carrageenan, dextran, bradykinin, and histamine) to induce paw edema and peritonitis in Swiss mice. Samples of the paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity or TNF-α and IL-1β levels, respectively. Mechanical hypernociception was induced by subcutaneous injection of carrageenan into the plantar surface of the paw. Pretreatment of mice by intraperitoneal administration of PLS (2.5, 5, and 10 mg/kg) significantly and dose-dependently reduced carrageenan-induced paw edema (p < 0.05) compared to vehicle-treated mice. Similarly, PLS 10 mg/kg effectively inhibited edema induced by dextran and histamine; however, edema induced by bradykinin was unaffected by PLS. PLS 10 mg/kg inhibited total and differential peritoneal leukocyte counts following carrageenan-induced peritonitis. Furthermore, PLS reduced carrageenan-increased MPO activity in paws and reduced cytokine levels in the peritoneal cavity. Finally PLS pretreatment also reduced hypernociception 3-4 h after carrageenan. We conclude that PLS reduces the inflammatory response and hypernociception in mice by reducing neutrophil migration and cytokines concentration.

Objective: The aim of this study was to evaluate the morphological and morphometric alterations produced by raloxifene in the mammary epithelium of female rats in persistent estrus., Materials and Methods: Twenty-one female Wistar-Hannover rats in persistent estrus induced by 1.25 mg of testosterone propionate were randomly divided into two groups: Group I (n = 10), receiving only water and used as control; Group II (experimental, n = 11), treated with 3 mg of raloxifene daily for 21 days. The first abdominoinguinal pair of mammary glands was extirpated and processed for morphological and morphometric evaluation. The data were statistically analysed using Student's t-test (p < 0.05)., Results: Morphology revealed signs of epithelial atrophy, and morphometry showed a significant reduction in the mean number of ducts and alveoli in the experimental group (12.82 +/- 0.42 and 2.91 +/- 0.53, respectively) when compared with the control group (28.70 +/- 1.15 and 7.20 +/- 0.57, respectively). This difference was statistically significant, both for the ducts and for the alveoli (p < 0.001)., Conclusion: The present results indicate that, at the dose and during the time of treatment used, raloxifene induced atrophy of the mammary epithelium of rats in persistent estrus.

Objective: The aim of this study was to evaluate the effects of tamoxifen on vascular endothelial growth factor (VEGF) expression in the urethral epithelium of castrated rats., Materials and Methods: Thirty-six adult, castrated, female Wistar-Hannover rats were randomly divided into two groups: group I (n = 16, control), receiving only propylene glycol, and group II (n = 20, tamoxifen), treated with 250 microg/day of tamoxifen for 30 consecutive days by gavage. On the 31st day, the animals were sacrificed and the urethras were immediately removed, separated into the proximal and distal segments and processed for VEGF immunohistochemistry. The data were analysed using Student's t-test (p < 0.05)., Results: The mean percentage of VEGF expression in the epithelium of the proximal urethra of the animals in groups I and II was 64.47+/-3.70 and 74.69+/-3.03, respectively (p < 0.03), whereas the mean percentage of VEGF expression in the distal urethral epithelium of the animals in groups I and II was 53.49+/-4.64 and 68.57+/-3.67, respectively (p < 0.01)., Conclusions: Our results indicate that, at the dose and during the time of treatment used, tamoxifen increased VEGF expression in the urethral epithelium of castrated rats.

Objective: The objective of this study was to evaluate the effects of raloxifene on the weight and epithelial thickness of the urethra of castrated female rats., Methods: Forty castrated female rats were randomly separated into two groups: group I (control, n = 20) received only the vehicle, and group II (raloxifene, n = 20) received 750 microg/day of raloxifene for 30 days. On the 31st day, the animals were sacrificed and the urethras were removed for the study. A model for categorical data using the weighted minimum mean square error method and Student's t test were used for the data analysis (p < 0.05)., Results: The mean weights of the urethras in groups I and II were 22 +/- 1.6 mg and 24 +/- 1.7 mg, respectively (p = 0.371). There was an increase in the mean epithelial thickness of the distal segments in group II compared to group I (50.7 +/- 1.9 microm vs. 45.3 +/- 1.6 microm, respectively) (p < 0.04). No statistically significant difference was found in the mean epithelial thickness of the proximal urethra between the two groups (p = 0.187)., Conclusion: Raloxifene administered to castrated female rats for 30 days increased the distal urethral epithelial thickness and did not alter the weight of the urethra.