Perspectivas epidemiológicas, clínicas e terapêuticas do transtorno bipolar em comorbidade com o uso de drogas: revisão de sistemática: Epidemiological, clinical and therapeutic perspectives of bipolar disorder in comorbidity with drug use: a systematic review

Conhecida como transtorno maníaco-depressivo, atualmente possui um novo nome: Transtorno Afetivo Bipolar, visto que com o passar do tempo foi se percebendo que esse transtorno não se tratava de uma alteração psicótica, e mais de um prejuízo afetivo. O transtorno bipolar possui alguns tipos, não se caracterizando em apenas uma forma, sua manifestação varia conforme o indivíduo e suas tendências, disforia e/ou euforia porém independente da forma expressa o paciente bipolar pode ter sua vida social comprometida, se não tratada, visto a irregularidade no estado de humor; bem como pode fazer uso de substâncias psicoativas, o que prejudica a sua condição clínica. Objetivo central da pesquisa é de apresentar a correlação do transtorno bipolar com o uso de drogas, mediante uma revisão de literatura integrativa realizada entre os meses de março de 2022 a julho de 2022, através da busca de artigos científicos nos bancos de dados online PubMed, Scielo e Google Acadêmico, utilizando como critério de refinamento de pesquisa artigos de todas as línguas publicados entre os anos 2000 e 2022

Changes in glutamatergic neurotransmission in the nucleus tractus solitarius of rats submitted to sustained hypoxia are related to the inflammatory process

A hipóxia mantida de curta duração (HM) está associada a alterações cardiorrespiratórias e ao desencadeamento de processo inflamatório em humanos e modelos experimentais. Ademais, há evidências de que a HM pode alterar a transmissão sináptica na região do Núcleo do Trato Solitários (NTS). No presente estudo, utilizamos a minociclina, um inibidor da ativação microglial e antiinflamatório, para avaliar a influência da inflamação desencadeada pela HM sobre a neurotransmissão glutamatérgica nos neurônios do NTS que enviam projeções para a região ventrolateral da medula (NTS-VLM). A hipótese geral do nosso estudo foi a seguinte: a HM induz processo inflamatório no tronco encefálico, o qual contribui para o aumento da neurotransmissão glutamatérgica em neurônios NTS-VLM, colaborando para a elevação da pressão arterial média (PAM) observada nestes ratos. Embora tenhamos observado aumento da pressão arterial média em ambos os grupos de ratos tratados com veículo (solução salina + água destilada, ip) ou minociclina [(30mg/Kg ip por 3 dias) submetidos a 24h de HM (FiO2 0.1) em relação aos seus respectivos grupos controle (FiO2 0,28), o aumento da MAP foi menor nos ratos previamente tratados com minociclina. Os registros eletrofisiológicos utilizando a técnica de whole cell patch-clamp mostraram que a HM não produziu alterações nas propriedades ativas e passivas dos neurônios NTS-VLM. No entanto, os neurônios de ratos submetidos a HM apresentaram aumento nas correntes glutamatérgicas espontâneas e evocadas pelo estímulo do trato solitário. Esse grupo de animais também apresentou aumento no número de microgliais na região do NTS. As alterações mencionadas foram atenuadas pelo tratamento prévio com minociclina. Concluímos que a inflamação induzida pela HM contribui para o aumento da neurotransmissão glutamatérgica nos neurônios NTS-VLM o qual poderia estar relacionado com a hipertensão arterial observada nestes ratos.Short-term Sustained hypoxia (SH) is associated with cardiorespiratory changes and inflammatory process in humans and experimental models. There is also evidence that SH can change the synaptic transmission in the nucleus tractus solitarius (NTS) region. Here we use the minocycline, an anti-inflammatory and microglial inhibitor, to evaluate the role of inflammation triggered by SH on the excitatory neurotransmission in the NTS neurons sending projections to the ventrolateral medulla (NTS-VLM). We hypothesized that SH induces brainstem inflammatory process, which may contribute to increase in excitatory neurotransmission and excitability of the NTS-VLM neurons, collaborating to the high blood pressure observed on these rats. Although we have observed increased MAP in both groups of rats treated with vehicle (saline + distilled water, i.p) or minociclina [(30mg/Kg i.p for 3 days) submitted to 24h of SH (FiO2 0.1) in relation to their respective control groups (FiO2 0.28), the MAP increase was lower in rats treated with minociclina. The whole cell patch-clamp recordings showed that SH produced no changes in active properties of NTS neurons. However, neurons of rats submitted SH presented an increase in the glutamatergic neurotransmission and the number of microglial at the NTS region. These increases were prevented in the groups previously treated with minociclina. We conclude that inflammation induced by SH contributes to the increased excitatory neurotransmission in NTS-VLM neurons that could be associated to high blood pressure observed in these rats

Correction: Apical periodontitis healing and postoperative pain following endodontic treatment with a reciprocating single-file, single-cone approach: A randomized controlled pragmatic clinical trial.

[This corrects the article DOI: 10.1371/journal.pone.0227347.]

Apical periodontitis healing and postoperative pain following endodontic treatment with a reciprocating single-file, single-cone approach: A randomized controlled pragmatic clinical trial.

This trial assessed post-operative pain and healing of apical periodontitis following endodontic therapy with a reciprocating system compared to a crown-down technique with hand files and lateral compaction filling. One-hundred and twenty nonvital anterior teeth with apical periodontitis were randomly treated using either a reciprocating single file followed by matching-taper single-cone filling or a hand file and lateral compaction filling. Postoperative pain was assessed during the 7 days after the treatment, using a visual analogue scale and a verbal rating scale. Apical healing was assessed using the periapical index score after a 12-month follow-up. The hypothesis tested was that both protocols were equivalent and present similar effectiveness in healing periapical lesions. Data were analyzed through two one-sided tests, t-tests, as well as Mann-Whitney and Chi-squared tests (α = 0.05). Logistic regression was used to investigate the association of clinical and demographic factors with the success of treatment. Regardless of the assessment time, no difference in incidence (38%-43% at first 24h), intensity of postoperative pain, and incidence of flare-up (≈ 3%) was observed between the two endodontic protocols. Both protocols resulted in a similar healing rate of apical periodontitis. After 12 months, the success rate ranged from 73% to 78% and the difference between the treatments fell within the pre-established equivalence margin (-0.1; -0.41 to 0.2). Endodontic treatment combining a reciprocating single file with matching-taper single cone showed similar clinical effectiveness to the treatment using hand-file instrumentation and the lateral compaction filling

Involvement of the median preoptic nucleus in blood pressure control

Studies have demonstrated that median preoptic nucleus (MnPO) neurons play a role in organizing the cardiovascular responses induced by changes in the circulating blood volume. The present study examined whether the MnPO controls cardiovascular function. Male Wistar normotensive (NT) rats and spontaneously hypertensive rats (SHRs; 250-300 g) were anesthetized with urethane (1.2 g kg(-1), i.v.) and instrumented for recordings of mean arterial blood pressure (MAP) and renal blood flow (RBF). The renal vascular conductance (RVC) was calculated as the RBF:MAP ratio and was expressed as a percentage of the baseline value. In the NT rats (n = 6), MnPO inhibition produced a MAP reduction (-8.1 +/- 1.1 mmHg, p<0.05). In the SHRs (n = 6), the MAP response to MnPO inhibition was significantly greater (-22.3 +/- 4 mmHg, p<0.05) than in the NT rats. Furthermore, the increase in the RVC was higher in the SHRs (10.9 +/- 3.3%, p<0.05). Histological analyses confirmed that the injection sites were confined to the MnPO. We conclude that the MnPO is involved in the tonic regulation of blood pressure in NT rats. Moreover, the greater cardiovascular response to MnPO inhibition observed in the SHRs strongly suggests that the MnPO may contribute to the pathophysiology of essential hypertension. (C) 2013 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

THE ROLE OF PET/CT IN DETECTING OCCULT DISEASE IN SYNCHRONOUS TUMORS: A CASE REPORT OF MERKEL CELL CARCINOMA AND NON-HODGKIN LYMPHOMA

Introduction/Justification: Merkel Cell Carcinoma (MCC) is a rare and aggressive cutaneous neoplasm characterized by a high tendency for recurrence and metastasis, primarily affecting older adults with fair skin. The introduction of PET/CT with 18F-FDG has significantly enhanced the diagnosis and management of MCC, providing superior sensitivity in detecting occult disease compared to computed tomography. This advancement profoundly impacts patient staging and therapeutic decisions. Similarly, non-Hodgkin lymphomas, a heterogeneous group of neoplasms originating from B cells, T cells, or natural killer cells, also benefit from PET/CT for diagnosis and follow-up, underscoring the significance of this modality in oncological practice. Herein, we present a rare case of synchronous Merkel cell carcinoma and non-Hodgkin lymphoma. Report: A 61-year-old male patient with a history of treated diffuse large B-cell lymphoma and multiple comorbidities presented with symptoms of progressive asthenia, night sweats without fever, weight loss, and a nodular reddish lesion on the left thigh; no palpable lymph nodes were found. Initial blood work showed pancytopenia; bone marrow biopsy did not reveal infiltration by high-grade histological non-Hodgkin lymphoma, but could not rule out focal infiltration by a low-grade histological lymphoma of immunophenotype B. Further investigation included a skin nodule biopsy, histopathologically consistent with Merkel cell carcinoma. PET/CT revealed extensive neoplastic involvement, including a retroperitoneal mass, neoplastic involvement of multiple bilateral lymph node chains, diffuse hyperdensities throughout the body, and a pulmonary nodule. Biopsy of the retroperitoneal mass confirmed low-grade non-Hodgkin lymphoma, suggesting a follicular subtype. The patient underwent resection of the Merkel cell carcinoma lesion in his thigh. A compromised deep margin was detected, warranting adjuvant radiotherapy and adjuvant chemotherapy with cisplatin + etoposide, administered concurrently with rituximab for lymphoma treatment. Conclusion: This case underscores the complexity of diagnosing and treating synchronous neoplasms, emphasizing the need for a multidisciplinary and individualized approach. 18F-FDG-PET/CT plays a pivotal role in detecting occult disease and assessing the extent of the conditions in this setting

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats

Epigenetic studies suggest that diseases that develop in adulthood are related to certain conditions to which the individual is exposed during the initial stages of life. Experimental evidence has demonstrated that offspring born to mothers maintained on high-Na diets during pregnancy have higher mean arterial pressure (MAP) in adulthood. Although these studies have demonstrated the importance of prenatal phases to hypertension development, no evidence regarding the role of high Na intake during postnatal phases in the development of this pathology has been reported. Therefore, in the present study, the effects of Na overload during childhood on induced water and Na intakes and on cardiovascular parameters in adulthood were evaluated. Experiments were carried out in two groups of 21-d-old rats: experimental group, maintained on hypertonic saline (0·3 M-NaCl) solution and food for 60 d, and control group, maintained on tap water and food. Later, both groups were given water and food for 15 d (recovery period). After the recovery period, chronic cannulation of the right femoral artery was performed in unanaesthetised rats to record baseline MAP and heart rate (HR). The experimental group was found to have increased basal MAP (98·6 (SEM 2·6) v. 118·3 (SEM 2·7) mmHg, P,0·05) and HR (365·4 (SEM 12·2) v. 398·2 (SEM 7·5) beats per min, P,0·05). There was a decrease in the baroreflex index in the experimental group when compared with that in the control group. A water and Na intake test was performed using furosemide. Na depletion was found to induce an increase in Na intake in both the control and experimental groups (12·1 (SEM 0·6) ml and 7·8 (SEM 1·1), respectively, P , 0·05); however, this increase was of lower magnitude in the experimental group. These results demonstrate that postnatal Na overload alters behavioural and cardiovascular regulation in adulthood.Coordenadoria de Aperfeiçoamento em Pesquisa (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity

Recent studies suggest that the association of antigens in microparticles increases the anti-Leishmania vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(D,L-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP1, containing poly(D,L-lactide) (PLA) 1% wt/v and chitosan 1% wt/v; and SMP2, containing PLA 5% wt/v and chitosan 5% wt/v. After a single dose of the unloaded SMP1 or SMP2 in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-β-D-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the Leishmania braziliensis antigen was encapsulated in SMPs (SMP1Ag and SMP2Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3−CD49+) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3+CD4+) and CD3+CD8+) and B cells (CD19+) of the SMP2 group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered Leishmania antigens