Compatibility Assessment of Novel Orodispersible Film Vehicle for Personalized Medicine with Selected Active Pharmaceutical Ingredients.

Orodispersible films (ODFs) are solid pharmaceutical forms for rapid local or systemic release of active ingredients. They are formed by a water-soluble polymer film that hydrates rapidly, adhering and dissolving immediately when placed on the tongue or in the oral cavity. In this paper, we describe the compatibility and disintegration times of compounded ODFs using OrPhylloTM, a new ready-to-use-vehicle, and APIs from different pharmacological classes, such as 5-hydroxytryptophan (5-HTP) 50 mg, bromopride 5 mg, coenzyme Q10 20 mg, melatonin 3 mg, resveratrol 5 mg, tadalafil 10 mg, vitamin B12 1 mg, or vitamin D3 2000 UI. ODFs were compounded and, subsequently, the samples were assayed using HPLC at initial (t = 0), 7 days (t = 7), 14 days (t = 14), 30 days (t = 30), 60 days (t = 60), 90 days (t = 90), 120 days (t = 120), 150 days (t = 150), and 180 days (t = 180) after compounding. Given the percentage of recovery of the APIs within the films, the beyond-use date of the final products (API + vehicle) was at least 90 days for vitamin D3, 150 days for bromopride and 5-HTP, and 180 days for coenzyme Q10, tadalafil, vitamin B12, resveratrol, and melatonin, when stored at room temperature. The average disintegration time was 46.22 s. This suggests that the OrPhylloTM vehicle is suitable for compounding ODFs with APIs from different pharmacological classes, with good compatibility and fast disintegration.

Three-Dimensionally Printed Vaginal Rings: Perceptions of Women and Gynecologists in a Cross-Sectional Survey.

Three-dimensional printing technologies can be implemented for the fabrication of personalized vaginal rings (VRs) as an alternative approach to traditional manufacturing. Although several studies have demonstrated the potential of additive manufacturing, there is a lack of knowledge concerning the opinions of patients and clinicians. This study aimed to investigate the perception of women and gynecologists regarding VRs with personalized shapes. The devices were printed with different designs (traditional, "Y", "M", and flat circle) by Fused Deposition Modeling for a cross-sectional survey with 155 participants. Their anticipated opinion was assessed through a questionnaire after a visual/tactile analysis of the VRs. The findings revealed that most women would feel comfortable using some of the 3D-printed VR designs and demonstrated good acceptability for the traditional and two innovative designs. However, women presented multiple preferences when the actual geometry was assessed, which directly related to their age, previous use of the vaginal route, and perception of comfort. In turn, gynecologists favored prescribing traditional and flat circle designs. Overall, although there was a difference in the perception between women and gynecologists, they had a positive opinion of the 3D-printed VRs. Finally, the personalized VRs could lead to an increase in therapeutic adherence, by meeting women's preferences.

Interobserver Agreement and Satisfaction With the use of Telemedicine for Evaluating low Back Pain: A Primary, Observational, Cross-Sectional, Analytical Study.

STUDY DESIGN: A primary, observational, cross-sectional, analytical study. OBJECTIVE: The development of a framework for systematic telemedicine (TM) for orthopedic physicians in frequent clinical care may increase agreement in diagnosis and satisfaction among users of TM. Therefore, this study aimed to estimate the agreement in the diagnosis of low back pain (LBP) between TM, systematized by a self-completed digital questionnaire, and face-to-face (FF) care in patients with LBP. METHODS: This study included adults up to 75 years of age with LBP for more than 6 weeks. They were evaluated at 2 independent time points (TM and FF) by different orthopedists with 3 different levels of expertise. Professionals evaluated the sample without prior knowledge of the diagnosis, and each orthopedist provided a diagnosis. Diagnostic agreement was the primary outcome. Secondary outcomes were the duration of the visit and satisfaction among healthcare professionals. RESULTS: A total of 168 participants were eligible, of whom 126 sought care through TM and 122 sought FF care (mean age, 47 years [range, 18-75 years]; 66.4% women). The agreement among professionals regarding the diagnosis was moderate (kappa = .585, P = .001). TM was faster than FF (11.9 minutes (standard deviation = 4.1) vs 18.6 (SD = 6.9), P < .001). Professional satisfaction was higher among spine specialists than among orthopedic residents and orthopedists who were not specialists in spine surgery. CONCLUSION: Agreement in diagnosis was moderate for TM, with a 30% shorter visit duration than FF. Satisfaction varied by professional expertise and was higher among spine specialists than among professionals with other expertise.

25-Hydroxyvitamin D as a biomarker of vitamin D status in plaque psoriasis and other dermatological diseases: a cross-sectional study

ABSTRACT BACKGROUND: Hypovitaminosis D is a public health problem associated with several chronic inflammatory and immunological diseases, including psoriasis. OBJECTIVES: This study aimed to determine the prevalence of hypovitaminosis D in patients with plaque psoriasis. A comparison was made between vitamin D levels in patients with psoriasis and those with other non-inflammatory dermatoses without photosensitivity. In addition, it evaluated the effects of the patients' Fitzpatrick skin phototype and the season of the year on the serum levels of vitamin D. DESIGN AND SETTINGS: A retrospective cross-sectional study was conducted at an outpatient clinic in a university center in Juiz de Fora (MG), Brazil. METHODS: A review of dermatology patients' demographic data, including skin phototype and serum levels of 25-hydroxyvitamin D [25(OH)D], over 12 months in 2016. RESULTS: This study included 554 patients: 300 patients allocated to the plaque psoriasis group and 254 control patients with other dermatological diseases. Regarding the season of the year, 229, 132, 62, and 131 participants were evaluated in summer, autumn, winter, and spring, respectively. As for the skin phototype, 397, 139, and 18 patients had phototypes III, IV, and V, respectively. The serum levels of 25(OH)D were significantly lower in the psoriasis group (24.91 ± 7.16 ng/mL) than in the control group (30.37 ± 8.14 ng/mL). CONCLUSIONS: Hypovitaminosis D (< 30 ng/mL) was present in 76.66% of patients with psoriasis versus 53.94% of control patients. Vitamin D deficiency (< 20 ng/mL) was observed in 25% of the patients with psoriasis versus 8.66% in the control group (P < 0.001). The season and patient's skin phototype were independent predictors of serum vitamin D levels.

Protocol of HOTFy: randomised clinical trial to hyperbaric oxygen therapy in fibromyalgia.

INTRODUCTION: Fibromyalgia is a polysymptomatic syndrome with a prevalence between 0.2% and 13% of the population and causes work disabilities in approximately half of affected patients. Several treatments to fibromyalgia have been proposed with partial improvement. This study aims to evaluate the efficacy of hyperbaric oxygen therapy and when it should be introduced to fibromyalgia. METHODS AND ANALYSIS: This is a protocol for an open-label, crossover, randomised clinical trial comparing treatment with hyperbaric oxygen therapy and standardised treatment to fibromyalgia. In the proposed study, 56 individuals with fibromyalgia will be randomised in a 1:1 ratio into a single, fixed, random block, in which one group will receive hyperbaric oxygen therapy and another will receive standard treatment. Subsequently, the groups will be crossed. Participants will be evaluated at baseline, eight and 16 weeks based on functional impairment assessed with the Fibromyalgia Impact Questionnaire-Brazilian Portuguese version, psychopathological symptoms questionnaire and short-form quality of life questionnaire. The improvement of symptoms concerning the moment of therapy used will be compared between groups. For sample size calculation, a moderate effect size, 80% power and 95% CI will be estimated, in a total of 46 patients. Considering a dropout of 20%, 56 patients should be recruited. ETHICS AND DISSEMINATION: The study was approved by the Universidade Federal de Juiz de Fora Teaching Hospital ethics committee and assigned the number 53058421.9.0000.5133 (version 3). The results will be disseminated via publications in peer-reviewed journals and presentations in medical meetings. TRIAL REGISTRATION NUMBER: RBR-6prps8g)/UTN U1111-1278-3224.

Is vitamin D status relevant to psoriasis and psoriatic arthritis? A retrospective cross-sectional study

Abstract BACKGROUND: Psoriasis is a systemic, immune-mediated disease characterized by inflammatory manifestations in the skin and joints. Vitamin D deficiency is currently considered a pandemic and is associated with comorbidities including psoriasis and psoriatic arthritis (PsA). OBJECTIVES: To determine the prevalence of hypovitaminosis D [25(OH)D] in patients with plaque psoriasis, with and without PsA, and of independent predictors of serum 25(OH)D levels. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, Minas Gerais, Brazil. METHODS: Demographic and clinical data (psoriasis area and severity index [PASI], family history, age at onset, disease duration, and the presence of PsA according to Classification Criteria for Psoriatic Arthritis), skin phototype, and season of the year were reviewed. RESULTS: Hypovitaminosis D (< 30 ng/mL) was highly prevalent in patients with psoriasis with and without PsA (82.2% and 74.9%, respectively). An inverse correlation between PASI and vitamin D was found (without PsA r = -0.59 and, PsA r = -0.52, P < 0.001), and multivariate regression revealed that hypovitaminosis D was associated with disease severity, season, and phototype. It was confirmed by binary logistic regression between PASI and vitamin D deficiency (< 30 ng/mL), (odds ratio, OR 1.78 CI: -0.20-0.53, P < 0.001). CONCLUSION: Hypovitaminosis D (< 30 ng/mL) was highly prevalent in psoriatic patients with and without PsA. Season and skin phototype were associated with 25(OH)D levels. An inverse association between PASI and serum 25(OH)D levels was established.

Is vitamin D status relevant to psoriasis and psoriatic arthritis? A retrospective cross-sectional study.

BACKGROUND: Psoriasis is a systemic, immune-mediated disease characterized by inflammatory manifestations in the skin and joints. Vitamin D deficiency is currently considered a pandemic and is associated with comorbidities including psoriasis and psoriatic arthritis (PsA). OBJECTIVES: To determine the prevalence of hypovitaminosis D [25(OH)D] in patients with plaque psoriasis, with and without PsA, and of independent predictors of serum 25(OH)D levels. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, Minas Gerais, Brazil. METHODS: Demographic and clinical data (psoriasis area and severity index [PASI], family history, age at onset, disease duration, and the presence of PsA according to Classification Criteria for Psoriatic Arthritis), skin phototype, and season of the year were reviewed. RESULTS: Hypovitaminosis D (< 30 ng/mL) was highly prevalent in patients with psoriasis with and without PsA (82.2% and 74.9%, respectively). An inverse correlation between PASI and vitamin D was found (without PsA r = -0.59 and, PsA r = -0.52, P < 0.001), and multivariate regression revealed that hypovitaminosis D was associated with disease severity, season, and phototype. It was confirmed by binary logistic regression between PASI and vitamin D deficiency (< 30 ng/mL), (odds ratio, OR 1.78 CI: -0.20-0.53, P < 0.001). CONCLUSION: Hypovitaminosis D (< 30 ng/mL) was highly prevalent in psoriatic patients with and without PsA. Season and skin phototype were associated with 25(OH)D levels. An inverse association between PASI and serum 25(OH)D levels was established.

25-Hydroxyvitamin D as a biomarker of vitamin D status in plaque psoriasis and other dermatological diseases: a cross-sectional study.

BACKGROUND: Hypovitaminosis D is a public health problem associated with several chronic inflammatory and immunological diseases, including psoriasis. OBJECTIVES: This study aimed to determine the prevalence of hypovitaminosis D in patients with plaque psoriasis. A comparison was made between vitamin D levels in patients with psoriasis and those with other non-inflammatory dermatoses without photosensitivity. In addition, it evaluated the effects of the patients' Fitzpatrick skin phototype and the season of the year on the serum levels of vitamin D. DESIGN AND SETTINGS: A retrospective cross-sectional study was conducted at an outpatient clinic in a university center in Juiz de Fora (MG), Brazil. METHODS: A review of dermatology patients' demographic data, including skin phototype and serum levels of 25-hydroxyvitamin D [25(OH)D], over 12 months in 2016. RESULTS: This study included 554 patients: 300 patients allocated to the plaque psoriasis group and 254 control patients with other dermatological diseases. Regarding the season of the year, 229, 132, 62, and 131 participants were evaluated in summer, autumn, winter, and spring, respectively. As for the skin phototype, 397, 139, and 18 patients had phototypes III, IV, and V, respectively. The serum levels of 25(OH)D were significantly lower in the psoriasis group (24.91 ± 7.16 ng/mL) than in the control group (30.37 ± 8.14 ng/mL). CONCLUSIONS: Hypovitaminosis D (< 30 ng/mL) was present in 76.66% of patients with psoriasis versus 53.94% of control patients. Vitamin D deficiency (< 20 ng/mL) was observed in 25% of the patients with psoriasis versus 8.66% in the control group (P < 0.001). The season and patient's skin phototype were independent predictors of serum vitamin D levels.

Broad-spectrum cannabis oil ameliorates reserpine-induced fibromyalgia model in mice.

Fibromyalgia (FM) is an idiopathic disorder characterized by generalized pain and associated symptoms such as depression and anxiety. Cannabis sativa shows different pharmacological activities, such as analgesic, anti-inflammatory, neuroprotective, and immunomodulatory. Associated with this, the use of an oil with low concentrations of THC can reduce the psychomimetic adverse effects of the plant. Therefore, the present study aimed to evaluate the analgesic effect of broad-spectrum cannabis oil with low THC concentration in an experimental model of FM. Mechanical hyperalgesia, thermal allodynia, depressive- and anxious-related behavior, and locomotor activity were evaluated after reserpine (0.25 mg/kg; injected subcutaneously (s.c.) once daily for three consecutive days) administration. Our results showed that oral administration of broad-spectrum cannabis oil (0.1, 1, and 3 mg/kg, p.o.) in a single dose on the 4th day inhibited mechanical hyperalgesia and thermal allodynia induced by reserpine. Relevantly, treatment during four days with broad-spectrum cannabis oil (0.1 mg/kg, p.o.) reduced mechanical hyperalgesia 1 h after reserpine administration. Intraplantar treatment with cannabis oil significantly reversed mechanical and heat thermal nociception induced by reserpine injection. Interestingly, spinal and supraspinal administration of broad-spectrum cannabis oil completely inhibited mechanical hyperalgesia and thermal sensitivity induced by reserpine. The repeated cannabis oil administration, given daily for 14 days, markedly mitigated the mechanical and thermal sensitivity during the FM model, and its reduced depressive-like behavior induced by reserpine. In summary, broad-spectrum cannabis oil is an effective alternative to reverse the reserpine-induced fibromyalgia model.

Systemic, Intrathecal, and Intracerebroventricular Antihyperalgesic Effects of the Calcium Channel Blocker CTK 01512-2 Toxin in Persistent Pain Models.

CTK 01512-2 toxin is a recombinant peptide of the Phα1ß version derived from the venom of the Phoneutria nigriventer spider. It acts as an N-type voltage-gated calcium channel (VGCC) blocker and shows a prolonged effect on preventing and reducing nociception. Herein, CTK 01512-2 was tested on two models of persistent pain, the chronic post-ischemia pain (CPIP) and the paclitaxel-induced peripheral neuropathy, to evaluate its systemic, intrathecal, and intracerebroventricular effects on mechanical hypersensitivity and thermal allodynia. Glial cell viability was also investigated using the MTT test. The results showed that CTK 01512-2 intrathecal and systemic treatments reduced the mechanical hypersensitivity induced by CPIP, mainly between 1-4 h after its administration. Additionally, intrathecal treatment reduced the CPIP-induced thermal allodynia. In its turn, the intracerebroventricular treatment showed mechanical antihyperalgesic and thermal antiallodynic effects in the paclitaxel-induced peripheral neuropathy. These data reinforce the therapeutic potential of CTK 01512-2 to treat persistent pain conditions and offer a perspective to use the systemic route. Moreover, CTK 01512-2 increased the glial cell viability in the MTT reduction assay, and it may indicate a new approach to managing chronic pain. The results found in this study help to pave new perspectives of pain relief treatments to patients affected by chronic pain.

Coupling of Fused Deposition Modeling and Inkjet Printing to Produce Drug Loaded 3D Printed Tablets.

In the current study, we have coupled Fused Deposition Modelling (FDM) for the fabrication of plain polyvinyl alcohol (PVA) tablets followed by dispensing of minoxidil ethanolic solutions using inkjet printing. The use of a drop-on-solid printing approach facilitates an accurate and reproducible process while it controls the deposition of the drug amounts. For the purpose of the study, the effect of the solvent was investigated and minoxidil ink solutions of ethanol 70% v/v (P70) or absolute ethanol (P100) were applied on the plain PVA tablets. Physicochemical characterization showed that solvent miscibility with the polymer substrate plays a key role and can lead to the formation of drug crystals on the surface or drug absorption in the polymer matrix. The produced minoxidil tablets showed sustained release profiles or initial bursts strongly affected by the solvent grade used for dispensing the required dose on drug loaded 3D printed tablets. This paradigm demonstrates that the coupling of FDM and inkjet printing technologies could be used for rapid development of personalized dosage forms.

Microagulhamento e fator de crescimento epidérmico (EGF) como estratégias para o tratamento de cicatrizes de acne / Microneedling and epidermal growth factor (EGF) as strategies for the acne scars

Introdução: a técnica de microagulhamento e aplicação de drug delivery transdérmico é indicada para o tratamento das cicatrizes de acne. Objetivos: avaliar a técnica de microagulhamento associada à aplicação de fator de crescimento epidérmico (EGF) em drug delivery. Métodos: ensaio clínico duplo-cego randomizado, com seleção de 30 pacientes, divididos em dois grupos: (1) duas sessões de microagulhamento com intervalo de 30 dias e (2) duas sessões de microagulhamento com mesmo intervalo e associação de drug delivery de EGF. Os pacientes foram submetidos à avaliação clínica (escala global de cicatriz de acne - Goodman e Baron, 2006), a avaliação por imagem multiespectral e por questionários de autopercepção. A avaliação estatística (Teste T Student, Teste SNK, análise de variância) foi realizada com o software estatístico SisVar (UFLA, 1996). Resultados: os grupos foram homogêneos quanto à idade, sexo e fototipo. Na avaliação clínica, houve redução dos escores de gravidade para ambos os grupos. A análise multiespectral revelou redução das porfirinas (p=0,0296) e melhora da textura da pele, ambas para o grupo 2. Conclusão: a terapia com microagulhamento foi eficaz e segura para o tratamento de cicatrizes de acne, e o EGF demonstrou ser um ativo promissor.

Background: The microneedling technique and the transdermal drug delivery are indicated to treat acne scars. Objective: Evaluation of the microneedling technique associated with the drug delivery of the epidermal growth factor (EGF). Methods: Randomized double-blind clinical trial of 30 patients divided into two groups: (1) - two microneedling sessions with a 30-day interval, (2) - two microneedling sessions with the same interval but associated with EGF drug delivery. The patients were evaluated clinically (global acne scarring grading system - Goodman and Baron) global acne scarring grading system via multispectral image and through self-perception questionnaires. The statistical analysis (Student T-test, SNK test, analysis of variance) was performed with the SisVar software (UFLA, 1996). Results: The groups were homogeneous regarding age, gender, and phototype. Clinical assessments showed a reduction in severity scores for both groups. The multispectral analysis revealed a decrease in porphyrins (p = 0.0296) and an improvement in skin texture in group 2 subjects. Conclusion: Microneedling therapy was effective and safe for the acne scars treatment, and EGF demonstrated to be a promising strategy as well.

Assessment of a Novel Vitamin D3 Formulation with Nanostructured Lipid Carriers for Transdermal Delivery.

OBJECTIVE: Develop and assess a transdermal emulsion loaded with nanostructured lipid carriers for vitamin D3 supplementation. METHODS: Vitamin D3 loaded nanostructured lipid carriers, produced via high shear homogenization and ultrasonication, were assessed for their particle size, distribution, morphology, zeta potential, entrapment efficiency, and cytotoxicity. They were incorporated into a transdermal vehicle, and the stability and ex vivo permeation were evaluated. RESULTS: Spherical nanoparticles were developed with a particle size of 192.5 nm, a polydispersity index of 0.13, a zeta potential of -29.0 mV, and an entrapment efficiency of 99.75%. They were stable (particle size and distribution) for 15 days when stored in a refrigerator, and for 30 days at room temperature and 32°C. The nanoparticles decreased the drug cytotoxicity against fibroblasts, as shown by IC50 (nanoparticle: 32.48 µg mL-1 vitamin D3: 16.73 µg mL-1). The emulsion loaded with nanoparticles minimized the degradation of vitamin D3 when compared with the nanoparticle dispersion. Additionally, the emulsion provided the skin permeation of vitamin D3 following the recommended daily allowance. CONCLUSION: To the best of our knowledge, this is the first study to use nanostructured lipid carriers for transdermal delivery of vitamin D. The developed formulation is a promising strategy to overcome the vitamin D3 variable oral bioavailability. It also represents a comfortable route of administration; thus it could be beneficial for patients and clinicians. However, further studies are needed to allow the permeation of larger amounts of vitamin D3, and the combination of these nanoparticles with microneedles would be interesting.

Aplicações da manufatura aditiva em oftalmologia / Applications of additive manufacturing in ophthalmology

RESUMO A manufatura aditiva, mais popularmente conhecida como impressão tridimensional, baseia-se no desenvolvimento de um objeto com a ajuda de um software de desenho assistido por computador seguido de sua impressão por meio da deposição de uma matéria-prima, camada por camada, para a construção do produto desejado. Existem vários tipos de técnicas de impressão tridimensional, e o tipo de processo de impressão escolhido depende da aplicação específica do objeto a ser desenvolvido, dos materiais a serem utilizados e da resolução necessária à impressão do produto final. A impressão tridimensional abriu perspectivas na pesquisa e revolucionou o campo das ciências da saúde, com a possibilidade de criação e de desenvolvimento de produtos personalizados de maneira rápida, econômica e de forma mais centralizada do que no processo de manufatura tradicional. As tecnologias de manufatura aditiva remodelaram os diagnósticos médicos; as medidas preventivas e pré-operatórias; o tratamento e a reabilitação, assim como os processos de engenharia de tecidos nos últimos anos. Na oftalmologia, as aplicações da impressão tridimensional são extensas. Modelos anatômicos para aplicação na área da educação e planejamentos cirúrgicos, desenvolvimento de implantes, lentes, equipamentos para diagnósticos, novas aplicações terapêuticas e desenvolvimento de tecidos oculares já estão em desenvolvimento. Por possuir um campo amplo e ser alvo de pesquisa constante, a área oftalmológica permite que a manufatura aditiva ainda seja amplamente utilizada a favor dos médicos e dos pacientes.

ABSTRACT Additive manufacturing, more popularly known as three-dimensional (3D) printing, is based on the development of an object with the help of computer-aided design software followed by its printing through the deposition of a material, layer by layer, to create the desired product. There are several types of 3D printing techniques and the type of printing process chosen depends on the specific application of the object to be developed, the materials to be used, and the resolution required to print the final product. 3D printing has brought new perspectives to research and revolutionized the field of health sciences, with the possibility of creating and developing customized products in a faster, more economical, and more centralized way than in the traditional manufacturing process. Additive manufacturing technologies have reformulated medical diagnostics, preventive, preoperative, treatment, and rehabilitation, as well as tissue engineering processes in recent years. In ophthalmology, the applications of 3D printing are extensive. Anatomical models for application in education and surgical planning, development of implants, lenses, diagnostic equipment, new therapeutic applications, and development of ocular tissues (3D bioprinting) are already under development. As it has a wide field and is the subject of constant research, the ophthalmic area allows additive manufacturing to still be widely used in favor of doctors and patients.

Antidepressant-like effect of rosmarinic acid during LPS-induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR-γ signaling pathway.

Rosmarinic acid (RA), an ester of caffeic acid and 3, 4-dihydroxyphenyllactic acid, has anti-inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug-likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant-like potential of RA in the lipopolysaccharide (LPS)-induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters. Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator-activated receptor (PPAR) and the cannabinoid receptors CB1 and CB2 . In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant-like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB1 , CB2 , and PPAR-γ receptors significantly blocked the antidepressant-like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR-γ signaling pathways are involved with the antidepressant-like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.

Chia oil prevents chemical and immune-mediated inflammatory responses in mice: Evidence for the underlying mechanisms.

Chia (Salvia hispanica L.) is an herbaceous plant used as omega-3 polyunsaturated fatty acid (ω-3 PUFA) source that presents a range of beneficial effects on human health. Herein, it was used a chia oil containing over than 62% of α-linolenic acid (ALA), a compound widely related to anti-inflammatory actions. Chia oil effect was tested using paw edema and mechanical hyperalgesia induced by carrageenan, and ear edema induced by croton oil, histamine, and capsaicin. Croton oil was used in both preventive and therapeutic treatment schedules of chia oil while histamine and capsaicin were used only in preventive treatment schedule. Chia oil mechanism of action was investigated using nociception and paw edema response induced by intraplantar injection of acidified saline (ASIC activator), PGE2 (prostaglandin pathway), cinnamaldehyde (TRPA1 activator), bradykinin (BK pathway), menthol (TRPM8 activator), and capsaicin (TRPV1 activator). Further, RT-PCR for inflammatory mediators (TRPA1, NF-κB, PPAR-γ, COX-2, IL-6, TNF, FPR2, FAAH, MAGL, and IL-12A) induced by carrageenan, NLRP3 inflammasome activation, and the cell viability were then accessed. Later, chia oil actions were evaluated in the experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Chia oil showed anti-edematogenic and anti-hyperalgesic effects when administered 1 h before pro-inflammatory stimulus - particularly carrageenan and croton oil. Moreover, chia oil upregulated the mRNA levels of COX-2 and formyl peptide receptor 2 (FPR2) while reduced IL-6 expression in the spinal cord of mice submitted to i.pl. injection of carrageenan. Interestingly, chia oil mediates antinociceptive effects in mice decreasing the nociceptive response induced by acidified saline, PGE2, and cinnamaldehyde, but not by bradykinin, menthol, and capsaicin. On the EAE model, chia oil preventively administered attenuated EAE-induced motor deficits and mechanical hyperalgesia in mice, suggesting a valuable effect of chia oil supplementation in regulating inflammatory responses and some immune functions during immune-mediated inflammatory disorders (IMID). Nonetheless, additional reports will need to assess the effect of chia oil in well-controlled clinical trials performed in MS patients.

Prevalence of psoriatic arthritis among patients with plaque psoriasis: a Brazilian retrospective study.

BACKGROUND: Psoriatic arthritis is the most frequent and impactful comorbidity among psoriatic patients and appears in most cases after skin disease. Dermatologists play a key role in its early diagnosis and treatment. OBJECTIVE: To determine the prevalence of psoriatic arthritis and associated variables among patients with plaque psoriasis seen at a reference center for treating psoriasis. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, MG, Brazil. METHODS: Standardized records of 300 patients with plaque psoriasis were examined. Demographic data and medical variables relating to psoriasis (Psoriasis Area and Severity Index (PASI), family history, age at onset and disease progression) and psoriasis arthritis (CASPAR criteria) were evaluated. Laboratory and radiographic tests in the medical records were reviewed. RESULTS: Seventy-three (24.3%) of these 300 patients with plaque psoriasis had psoriatic arthritis. Asymmetric oligoarthritis (58.9%) was the most common clinical form, followed by polyarthritis (20.5%), distal interphalangeal arthritis (15.2%) and spondyloarthritis (5.4%). Dactylitis was present in 21.9% and enthesitis in 35.6% of patients. Compared with patients without arthritis, patients with arthritis had higher average age, higher frequency of positive family history of psoriasis, longer duration of evolution and higher PASI rates. CONCLUSION: Psoriatic arthritis is often underdiagnosed. Since dermatologists perform the initial approach, these professionals need to be trained to diagnose this comorbidity and treat it, together with rheumatologists.

Licochalcone A-loaded solid lipid nanoparticles improve antischistosomal activity in vitro and in vivo.

Aim: To isolate licochalcone A (LicoA) from licorice, prepare LicoA-loaded solid lipid nanoparticles (L-SLNs) and evaluate the L-SLNs in vitro and in vivo against Schistosoma mansoni. Materials & methods: LicoA was obtained by chromatographic fractionation and encapsulated in SLNs by a modified high shear homogenization method. Results: L-SLNs showed high encapsulation efficiency, with satisfactory particle size, polydispersity index and Zeta potential. Transmission electron microscopy revealed that L-SLNs were rounded and homogenously distributed. Toxicity studies revealed that SLNs decreased the hemolytic and cytotoxic properties of LicoA. Treatment with L-SLNs showed in vivo efficacy against S. mansoni. Conclusion: L-SLNs are efficient in reducing worm burden and SLNs may be a promising delivery system for LicoA to treat S. mansoni infections.

Prevalence of psoriatic arthritis among patients with plaque psoriasis: a Brazilian retrospective study

ABSTRACT BACKGROUND: Psoriatic arthritis is the most frequent and impactful comorbidity among psoriatic patients and appears in most cases after skin disease. Dermatologists play a key role in its early diagnosis and treatment. OBJECTIVE: To determine the prevalence of psoriatic arthritis and associated variables among patients with plaque psoriasis seen at a reference center for treating psoriasis. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, MG, Brazil. METHODS: Standardized records of 300 patients with plaque psoriasis were examined. Demographic data and medical variables relating to psoriasis (Psoriasis Area and Severity Index (PASI), family history, age at onset and disease progression) and psoriasis arthritis (CASPAR criteria) were evaluated. Laboratory and radiographic tests in the medical records were reviewed. RESULTS: Seventy-three (24.3%) of these 300 patients with plaque psoriasis had psoriatic arthritis. Asymmetric oligoarthritis (58.9%) was the most common clinical form, followed by polyarthritis (20.5%), distal interphalangeal arthritis (15.2%) and spondyloarthritis (5.4%). Dactylitis was present in 21.9% and enthesitis in 35.6% of patients. Compared with patients without arthritis, patients with arthritis had higher average age, higher frequency of positive family history of psoriasis, longer duration of evolution and higher PASI rates. CONCLUSION: Psoriatic arthritis is often underdiagnosed. Since dermatologists perform the initial approach, these professionals need to be trained to diagnose this comorbidity and treat it, together with rheumatologists.