Repeated cannabidiol treatment affects neuroplasticity and endocannabinoid signaling in the prefrontal cortex of the Flinders Sensitive Line (FSL) rat model of depression.

Delayed therapeutic responses and limited efficacy are the main challenges of existing antidepressant drugs, thereby incentivizing the search for new potential treatments. Cannabidiol (CBD), non-psychotomimetic component of cannabis, has shown promising antidepressant effects in different rodent models, but its mechanism of action remains unclear. Herein, we investigated the antidepressant-like effects of repeated CBD treatment on behavior, neuroplasticity markers and lipidomic profile in the prefrontal cortex (PFC) of Flinders Sensitive Line (FSL), a genetic animal model of depression, and their control counterparts Flinders Resistant Line (FRL) rats. Male FSL animals were treated with CBD (10 mg/kg; i.p.) or vehicle (7 days) followed by Open Field Test (OFT) and the Forced Swimming Test (FST). The PFC was analyzed by a) western blotting to assess markers of synaptic plasticity and cannabinoid signaling in synaptosome and cytosolic fractions; b) mass spectrometry-based lipidomics to investigate endocannabinoid levels (eCB). CBD attenuated the increased immobility observed in FSL, compared to FRL in FST, without changing the locomotor behavior in the OFT. In synaptosomes, CBD increased ERK1, mGluR5, and Synaptophysin, but failed to reverse the reduced CB1 and CB2 levels in FSL rats. In the cytosolic fraction, CBD increased ERK2 and decreased mGluR5 expression in FSL rats. Surprisingly, there were no significant changes in eCB levels in response to CBD treatment. These findings suggest that CBD effects in FSL animals are associated with changes in synaptic plasticity markers involving mGluR5, ERK1, ERK2, and synaptophysin signaling in the PFC, without increasing the levels of endocannabinoids in this brain region.

Scurvy and food selectivity in childhood: a case report.

Despite its rarity, symptomatic micronutrient deficiency remains a public health problem. Scurvy is the differential diagnosis for bleeding disorders and hematological and rheumatological diseases, especially in patients with eating disorders. However, it is unrelated to autism spectrum disorders or other neurodevelopmental disorders. A previously healthy 10-year-old boy living in São Paulo, Brazil, had a history of significant food selectivity unrelated to autism spectrum disorder, resulting in symptomatic ascorbic acid deficiency (scurvy). This resulted in pain and purpuric lesions on the lower limbs, gingival edema, bleeding during tooth brushing, asthenia, weakness, malaise, and sadness. Therefore, dietary anamnesis is important for routine monitoring of child growth and development. This process helps prevent nutritional deficiencies, facilitates early diagnosis of eating disorders, and enables multidisciplinary follow-up for these patients.

Neighborhood Collective Efficacy: A Longitudinal Social Determinant of Access to Medical Care Among Recently Immigrated Latina Young Adults.

The present longitudinal study examined changes in perceived access to health care among a recently immigrated cohort of Latina young adults who were assessed annually during their first 3 years in the United States. A parallel process growth model of perceived access to health care and neighborhood collective efficacy was examined, accounting for socioeconomic indicators and immigration status. Five hundred thirty Latina young adults (ages 18-23) participated at baseline assessment, and approximately 95% were retained over three annual assessment time points. Participants' mean level of perceived access to health care increased during their initial 3 years in the United States. Women who reported more of an increase in perceived access to health care tended to also indicate increased neighborhood collective efficacy relative to their peers during their first 3 years in the United States. Findings offer important information about the individual- and community-level factors that influence recently immigrated Latinas' health care access.

Monoolein-based nanodispersions for cutaneous co-delivery of methylene blue and metformin: Thermal and structural characterization and effects on the cutaneous barrier, skin penetration and cytotoxicity.

This study evaluated the potential of monoolein (MO)-based nanodispersions to promote the cutaneous co-delivery of metformin (MET) and methylene blue (MB) for the treatment of non-melanoma skin cancer. MO-based nanodispersions were obtained using Kolliphor® P407 (KP) and/or sodium cholate (CH), and characterized concerning the structure, thermal stability, ability to disrupt the skin barrier, cutaneous permeation and retention of MB and MET. Additionally, the cytotoxic effect of MO nanodispersions-mediated combination therapy using MET and MB in A431 cells was evaluated. The nanodispersions exhibited nanometric size (<200 nm) and thermal and physical stability. Small angle X-ray scattering studies revealed multiple structures depending on composition. They were able to interact with stratum corneum lipid structure, increasing its fluidity. The effect of MO-nanodispersions on topical/transdermal delivery of MB and MET was composition-dependent. Nanodispersions with low MO content (5 %) and stabilized with KP and CH (0.05-0.10 %) were the most promising, enhancing the cutaneous delivery of MB and MET by 1.9 to 2.2-fold and 1.4 to 1.7-fold, respectively, compared to control. Cytotoxic studies revealed that the most promising MO nanodispersion-mediated combination therapy using MET and MB (1:1) reduced the IC50 by 24-fold, compared to MB solution, and a further reduction (1.5-fold) was observed by MB photoactivation.

Scurvy and food selectivity in childhood: a case report

ABSTRACT Despite its rarity, symptomatic micronutrient deficiency remains a public health problem. Scurvy is the differential diagnosis for bleeding disorders and hematological and rheumatological diseases, especially in patients with eating disorders. However, it is unrelated to autism spectrum disorders or other neurodevelopmental disorders. A previously healthy 10-year-old boy living in São Paulo, Brazil, had a history of significant food selectivity unrelated to autism spectrum disorder, resulting in symptomatic ascorbic acid deficiency (scurvy). This resulted in pain and purpuric lesions on the lower limbs, gingival edema, bleeding during tooth brushing, asthenia, weakness, malaise, and sadness. Therefore, dietary anamnesis is important for routine monitoring of child growth and development. This process helps prevent nutritional deficiencies, facilitates early diagnosis of eating disorders, and enables multidisciplinary follow-up for these patients.

Are home-based exercises effective to reduce blood pressure in hypertensive adults? A systematic review.

Sedentarism and chronic non-communicable diseases have been a worldwide health problem that is drastically exacerbated by the COVID-19 pandemic social impacts. Home-based exercises are widely encouraged during social isolation to counterbalance the physical inactive impacts. Although, in the context of hypertension, are home-based exercises effective in blood pressure controlling? Our objective is to conduct a systematic review of high-quality controlled trials comparing the possible effects of different types of home-based exercises in hypertensive patients. The literature search was carried out in three scientific databases: Medline, Europe PMC, and Lilacs. Articles were included following three criteria: analyzing the effect of home-based exercise programs on blood pressure in treated and untreated hypertensive patients; exercises must perform at home and on the frequency, intensity, time, and type (FITT) principle, and the articles were published in English. From the qualitative analysis of 27 original trials screened through 451 identified studies, the main results are the following: 1) both endurance, isometric strength, and respiratory home-based exercise programs were efficient to decrease blood pressure in hypertensive patients; 2) differences in methodological approaches regarding FITT components, distinct blood pressure values at baseline and specific underlying mechanisms must be considered as a potential bias of each home-based interventions. In conclusion, endurance, isometric strength, and breathing home-based programs seems to be effective to reduce blood pressure in hypertensive patients. However, further randomized controlled trials and mechanistic studies must be performing to guide evidence-based recommendations of home-based exercises as antihypertensive therapy.

Marianismo Beliefs, Intimate Partner Violence, and Psychological Distress Among Recently Immigrated, Young Adult Latinas.

Marianismo is a Latino cultural value that describes both positive and negative aspects of traditional Latina femininity. Marianismo emphasizes culturally valued qualities such as interpersonal harmony, inner strength, self-sacrifice, and morality. Endorsement of marianismo is hypothesized to correlate with individual economic, educational, and personal variables. Marianismo also is theorized to potentially influence attitudes about, experiences of, and responses to intimate partner violence (IPV) among Latina women. The present study examined whether endorsement of marianismo beliefs mitigated or exacerbated psychological distress after experiences of IPV in a sample of 205 recently immigrated Latina women, aged 18 to 23 years. Latina women experiencing higher levels of IPV and endorsing greater marianismo beliefs were hypothesized to indicate greater psychological distress. Unexpectedly, women who endorsed more Subordinate to Others/Self-Silencing to Maintain Harmony marianismo beliefs indicated more psychological distress (p = .05), greater symptoms of psychological distress (p = .01), and greater average distress (p = .03) when they also reported less IPV than peers. Implications for understanding Latinas' responses to and reporting of IPV, as well as for culturally tailored counseling interventions for this underserved and understudied population, are discussed.

Blockade of bradykinin receptors or angiotensin II type 2 receptor prevents paclitaxel-associated acute pain syndrome in mice.

BACKGROUND: Paclitaxel (PCX) is the first-line choice for the treatment of several types of cancer, including breast, ovarian, and lung cancers. However, patients who receive even a single dose with PCX commonly develop mechanical and cold allodynia, a symptom known as PCX-associated acute pain syndrome (P-APS). Here, we assessed possible involvement of kinin-kallikrein and renin-angiotensin systems in P-APS in mice. METHODS: Male mice C57Bl/6 wild type (WT) and knockouts for bradykinin receptors, B1 (B1-/- ) and B2 (B2-/- ), were used. Mechanical and cold allodynia were evaluated by using von Frey filaments and acetone test, respectively. P-APS was induced by administration of PCX 4 mg/kg, i.v.. ACE inhibitors (captopril and enalapril), antagonists for angiotensin II type 1 (losartan) and type 2 ([AT2R]; PD123319 and EMA 401) receptors were administrated prior the treatment with PCX. RT-PCR was used to analyse the expression of mRNA for B1, B2 and AT2R receptors. RESULTS: Administration of PCX in B1-/- and B2-/- mice induced lower mechanical and cold allodynia compared to the WT. However, the pre-treatment with ACE inhibitors reduced the development of mechanical and cold allodynia in P-APS. Surprisingly, we found that mice pre-treatment with the PD123319 or EMA401, but not losartan, prevented the development of mechanical and cold allodynia induced by PCX. CONCLUSION: Our results demonstrated the involvement of bradykinin receptors B1 and B2 as well as AT2R in the induction of P-APS in mice, and suggest the use of AT2R antagonists as a potential therapy for the prevention of P-APS in humans. SIGNIFICANCE: Kinin-kallikrein and renin-angiotensin systems, through B1, B2 and AT2 receptors, potentiates paclitaxel-associated acute pain syndrome (P-APS) in mice. Antagonists for AT2R are potential alternatives to prevent P-APS.

Acculturative Stress, Psychological Distress, and Religious Coping Among Latina Young Adult Immigrants.

Religion is a source of strength in Latina/o culture during challenging life transitions, such as the immigration process. Guided by a sociological stress-process model, this study examines relations between dimensions of religious coping, acculturative stress, and psychological distress among 530 young Latina women (ages 18-23 years) who recently immigrated to the United States (i.e., approximately 12 months prior to assessment). Higher levels of acculturative stress were associated with higher levels of psychological distress. Negative religious coping (i.e., the tendency to struggle with faith) moderated the relation between acculturative stress and psychological distress. Participants experiencing higher levels of acculturative stress reported greater psychological distress when they indicated more negative religious coping. Positive religious coping (i.e., the tendency to relate to faith with comfort and certainty) was not linked with acculturative stress or psychological distress. Implications for culturally tailored counseling interventions for this underserved and understudied population are discussed.

Recruiting and Assessing Recent Young Adult Latina Immigrants in Health Disparities Research.

The authors interviewed 4 researchers to identify facilitators in recruiting and assessing Latina immigrants. The 4 researchers recruited 530 recent Latina immigrants (ages 18-23 years) for a study of social and cultural determinants of health. Consensual qualitative research methods revealed that respondent-driven sampling was an effective recruitment method. Fear of deportation was a barrier. Stigma about sensitive topics (e.g., sex, drug use) did not affect participation. Findings can help counselors conduct health disparities research.

Seguridad de los pacientes con tratamiento medicamentoso para el trastorno de humor / Patient safety in drug therapy for mood disorders

Introducción: las reacciones adversas a los medicamentos son indicadores de seguridad del paciente, que pueden causar impactos clínicos y económicos. Objetivo: describir las reacciones adversas a los medicamentos en pacientes con trastorno de humor. Métodos: estudio observacional, descriptivo, transversal y prospectivo con un método de búsqueda activa en farmacovigilancia, en pacientes con trastornos de humor atendidos por el Centro de Atención Psicosocial y Ambulatorio de salud en Alfenas, Brasil, durante el periodo de enero a julio de 2011. Los pacientes fueron invitados a participar y respondieron preguntas realizadas en su domicilio a fin de detectar las reacciones adversas a los medicamentos, las que fueron analizadas en cuanto a la causalidad y a la gravedad. Resultados: del total de 31 pacientes, 23 presentaron 60 reacciones adversas a los medicamentos, de ellas el 41,6 por ciento clasifican como probables y 48,3 por ciento como posibles. Todas fueron consideradas no graves, que varían de una a cinco reacciones adversas por paciente. De los 16 medicamentos diferentes utilizados, solo clorhidrato de bupropión no presentó reacciones adversas. Fueron detectadas al menos dos reacciones adversas medicamentos para el resto de los medicamentos. Conclusión: la búsqueda activa identificó que de cada diez pacientes tratados con medicamentos para el control de los trastornos de humor, siete sufrieron una reacción no grave(AU)

Introduction: adverse drug reactions are indicators of patient safety, which can cause clinical and economic impacts. Objective: to describe the adverse drug reactions in patients with mood disorders. Methods: observational, descriptive, cross-sectional and prospective study, with active search method in pharmacovigilance in patients with mood disorders attended by the Center for Psychosocial Ambulatory Health Care in Brazil from January to July 2011. Patients were invited to participate and answer questions posed in their residences in order to detect the adverse drug reactions and to analyze them in terms of causality and severity. Results: of 31 patients, 23 presented with 60 adverse drug reactions, being 41.6% probable and 48.3 percent possible. All the adverse drug reactions were not considered serious, ranging one to five adverse reaction per patient. Of the 16 different medicines used, only bupropion hydrochloride did not present ADR. At least two adverse drug reactions were detected for each medicine. Conclusion: The active search identified that seven patients out of 10 treated with medicines to control mood disorders, had no serious adverse reaction(AU)

Contributions from extracellular sources of adenosine to the ethanol toxicity in zebrafish larvae.

The effects of ethanol exposure on extracellular adenosine sources in zebrafish were evaluated. In the acute treatment, the embryos were exposed to 2% ethanol on day 1 post-fertilization (dpf). In the chronic treatment, the exposure was continued for 2h/day up to 6 dpf. Ecto-5'-nucleotidase activity was assessed by colorimetric method and gene expression determined by RT-qPCR in 7 dpf zebrafish. Body length, ocular distance and surface area of the eyes were registered in animals acutely exposed to ethanol and pretreated with AOPCP (5-500 nM), an ecto-5'-nucleotidase inhibitor, or dipyridamole (10-100 µM), a blocker of nucleoside transport. Both ethanol exposures promoted increased ecto-5'-nucleotidase activity, impaired locomotion and morphology. Ecto-5'-nucleotidase expression was not affected. AOPCP promoted mild prevention of morphological defects caused by acute treatment, while dipyridamole worsened these defects. Early ethanol exposure altered adenosinergic tonus, especially through nucleoside transporters, contributing to morphological defects produced by ethanol in zebrafish.

Post-transplantation encapsulating peritoneal sclerosis in a pediatric patient.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis (PD), but only a few cases have been described in the pediatric patient population. There is no established medical treatment, and surgery has been reported with variable success. The number of reports of EPS being successfully treated with tamoxifen, based on its anti-fibrotic effects, are increasing. The role of sirolimus, an mTOR inhibitor with immunomodulatory and anti-proliferative properties, has been less well-defined. CASE-DIAGNOSIS/TREATMENT: A 17-year-old kidney transplant recipient, with a previous cumulative time on PD of 8 years and 3 months, developed severe bowel obstruction 8 months after undergoing a second kidney graft. Her immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisolone. The patient underwent laparotomy, which revealed multiple thick leathery adhesions with an encapsulated small bowel. Enterolysis was performed, and total parenteral nutrition was commenced after surgery to provide an adequate food intake. Treatment with tamoxifen was initiated, but the patient developed significant liver toxicity 2 weeks later, and the drug was withdrawn. The immunosuppressive regimen was changed to an increased dose of prednisolone, and tacrolimus was replaced with sirolimos. At 20 months of follow-up, the patient remains symptom-free, with a functioning kidney transplant. CONCLUSION: Although EPS is a very rare condition in the pediatric population, it should be considered when a child or adolescent with a long-term history of PD presents with nonspecific gastrointestinal symptoms or with signs of bowel obstruction. There is an urgent need for alternative immunosuppressive protocols. The use of sirolimus in this group of patients remains controversial.