Clínicas de ketamina: usos actuales según la evidencia / Ketamine clinics: current uses based on evidence

Resumen: La ketamina es un medicamento conocido por sus bondades como inductor anestésico y para disminuir la posibilidad de complicaciones, por ejemplo, exacerbación del dolor neuropático e hiperalgesia asociada a opioides. En esta revisión nos enfocaremos en otras indicaciones en las que también ha demostrado ser útil y que, bajo observación e instrucción adecuadas en una infraestructura diseñada para ello (clínicas de ketamina), mejora la calidad en el comportamiento y disminuye el estrés, ansiedad y dolor. Entre las indicaciones para su uso se encuentran los trastornos depresivos, el trastorno de ansiedad, el trastorno obsesivo compulsivo y los relacionados con traumas emocionales; el trastorno bipolar, anormalidades en conducta e ingesta alimentaria, al igual que los trastornos adictivos.

Abstract: Ketamine is a drug known for its benefits as an anesthetic inducer and to reduce the possibility of complications such as exacerbation of neuropathic pain and hyperalgesia associated with opioids. In this review we will focus on other indications in which it has also proven to be useful and that, under adequate observation and instruction in an infrastructure designed for it (ketamine clinics), improves the quality of behavior and decreases stress, anxiety and pain. Among the indications for its use are depressive disorders, anxiety disorder, obsessive-compulsive disorder and those related to emotional trauma; bipolar disorder, abnormalities in behavior and eating intake as well as addictive disorders.

A bullous variant of central serous chorioretinopathy treated with oral spironolactone / Uma variante bolhosa da coriorretinopatia serosa central tratada com espironolactona oral

ABSTRACT We report the case of a 39-year-old male patient who presented with visual loss in the right eye for 6 weeks. The best-corrected visual acuity was counting fingers in the right eye and 20/30 in the left eye. The fundus examination demonstrated a right retinal detachment inferiorly extending to the fovea and a left macular serous detachment. After multimodal imaging study, the patient was diagnosed as having a bullous variant of central serous chorioretinopathy and treated with oral spironolactone associated with adjuvant laser photocoagulation. The retinal changes resolved after 6 months. The final visual acuity was 20/20 in both eyes.

RESUMO Relatamos o caso de um homem de 39 anos apresentando perda visual no olho direito há seis semanas. A melhor acuidade visual corrigida foi conta-dedos no olho direito e 20/30 no esquerdo. A fundoscopia demonstrou descolamento de retina direito inferiormente com extensão à fóvea e descolamento macular seroso à esquerda. Após estudos de imagem multimodal, o paciente foi diagnosticado com uma variante bolhosa de coriorretinopatia serosa central e tratado com espironolactona oral associada à fotocoagulação a laser adjuvante. As alterações retinianas resolveram após seis meses. A acuidade visual final foi 20/20 em ambos os olhos.

The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial

Abstract Objective: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. Methods: Between July 2018- February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. Results: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p<0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p>0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p< 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p>0.05). Conclusion: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. Level of evidence: 1B.

Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: A randomized controlled pilot study

Background & objectives: Studies have shown that insulin resistance and hyperinsulinaemia play a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, the use of insulin sensitizing drugs in the treatment of PCOS has attracted the attention of medicine and researchers. The aim of this study was to investigate the effects of sitaformin (sitagliptin/metformin) and metformin on the quality of oocyte and embryo in classic PCOS patients undergoing intracytoplasmic sperm injection (ICSI). Methods: Sixty patients of PCOS (25-35 yr) were randomly allocated into three groups (n=20, each group): a metformin-treated group (administered metformin 500 mg twice daily), a sitaformin-treated group (administered sitaformin 50/500 mg twice daily) and a placebo group. Participants in all the groups received the drug two months prior to the start of the ovulation cycle and treatment continued until the day of the oocyte aspiration. Results: Serum insulin and total testosterone levels decreaseed significantly after treatment in both the treatment groups as compared to the placebo (P<0.05). A significant decrease in the number of immature oocytes [MI + germinal vesicle (GV) stage] was observed in metformin and sitaformin groups as compared to the placebo. In addition, sitaformin group when compared to the metformin group showed a significant decrease in the number of immature oocytes (P<0.05). The number of mature and normal MII oocytes increased significantly in both the treatment groups compared to the placebo group (P<0.05). The number of mature and normal oocytes increased in sitaformin group in comparison to the metformin group, but the difference was not significant. There was a significant increase in the number of grade I embryos, fertilization and cleavage rates in the sitaformin group compared to the other groups (P<0.05). Interpretation & conclusions: This is the first study to compare the impact of sitaformin with metformin on oocyte and embryo quality in women with PCOS undergoing a gonadotropin-releasing hormone (GnRH) antagonist cycle. In conclusion, sitaformin can be more effective in decreasing immature oocytes and increasing the quality of embryos than the use of metformin.

Corifollitropin Alfa for Controlled Ovarian Stimulation in Assisted Reproductive Technologies: State of the Art / Alfacorifolitropina para estimulação ovariana controlada em tecnologias de reprodução assistida: Estado da arte

Abstract Physical and emotional burdens during the journey of infertile people through assisted reproductive technologies are sufficient to justify the efforts in developing patient-friendly treatment strategies. Thus, shorter duration of ovarian stimulation protocols and the need for less injections may improve adherence, prevent mistakes, and reduce financial costs. Therefore, the sustained follicle-stimulating action of corifollitropin alfa may be the most differentiating pharmacokinetic characteristic among available gonadotropins. In this paper, we gather the evidence on its use, aiming to provide the information needed for considering it as a first choice when a patient-friendly strategy is desired.

Resumo O desgaste físico e emocional durante a jornada de pessoas inférteis pelas tecnologias de reprodução assistida é suficiente para justificar esforços no desenvolvimento de estratégias de tratamento compassivas. Desta forma, a menor duração dos protocolos de estimulação ovariana e a necessidade de menos injeções podem melhorar a adesão, prevenir erros e reduzir custos financeiros. Portanto, a estimulação folicular sustentada da alfacorifolitropina parece ser a característica farmacocinética que melhor a diferencia das gonadotrofinas atualmente disponíveis no mercado. No presente artigo, reunimos evidências sobre seu uso, com o objetivo de fornecer as informações necessárias para considerá-la como primeira escolha quando se deseja uma estratégia amigável ao paciente.

Research Progress in Androgen Receptor and Triple Negative Breast Cancer / 中国医学科学院学报

The research on androgen receptor (AR) in breast cancer is advancing.Although the prognostic value of AR in triple negative breast cancer (TNBC) is controversial,a variety of studies have demonstrated that the lack of AR expression exacerbates disease progression.Moreover,the TNBC subtype of AR(-) is more aggressive than that of AR(+) due to the lack of prognostic biomarkers and therapeutic targets.With the discovery and deepening research of novel therapeutic targets such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin and S-phase kinase-associated protein 2 signaling pathways,as well as the emerging of immunotherapies,the treatment options for TNBC are increasing.Regarding the role of AR in TNBC,the studies about the tumor biology of AR(-)TNBC and novel biomarkers for improved management of the disease remain insufficient.In this review,we summarize the research progress of AR in TNBC,put forward avenues for future research on TNBC,and propose potential biomarkers and therapeutic strategies that warrant investigation.

Changes of RAGE/p38MAPK/NF-κB signaling pathway in brain tissue of subchronic fluorosis rats and protective effects of Ginkgo biloba extract and RAGE antagonist / 环境与职业医学

Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L−1), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L−1 fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg−1·d−1 EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg−1·d−1 FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.

Rational use of acid suppressant for stress ulcer in PICU / 中国小儿急救医学

Stress-related digestive tract mucosal disease is a common complication in pediatric intensive care unit(PICU). It may progress to stress ulcer and severe ulcer bleeding, which may lead to death.Currently, stress ulcer prophylaxis is recommended for critically ill children with high risk factors for stress ulcer, and the most commonly used acid suppression drugs are proton pump inhibitor and histamine-2 receptor antagonist.However, excessive prophylactic acid suppression is common and can increase the risk of hospital-acquired pneumonia and clostridium difficile infection in PICU.This review aimed to analyze the advantages and disadvantages of preventive acid suppressant therapy and promote the rational use of acid suppressant in PICU.

Corticotropin releasing factor type 1 receptor antagonist: a promising therapy for 21-hydroxylase deficiency / 中华实用儿科临床杂志

21-hydroxylase deficiency(21-OHD) is mainly characterized by cortisol deficiency with or without aldosterone deficiency and hyperandrogenemia.The disease requires lifelong exogenous glucocorticoid/salt supplementation.Excessive doses of exogenous glucocorticoids are often needed to control hyperandrogenemia, but the effect is not satisfactory.Corticotropin releasing factor (CRF) type 1 receptor antagonist can directly block the production of adrenocorticotropin, inhibit the generation of adrenogenic androgen, reduce the dose of glucocorticoid therapy, and thus lower the incidence of adverse reactions.In this article, the current research progress on 21-OHD therapy and CRF1 receptor antagonist was reviewed.

Laboratory Monitoring of Non-Vitamin K Antagonist Oral Anticoagulants and Their Use in Special Populations / 中山大学学报(医学科学版)

In the past few decades， heparin and warfarin have been the main anticoagulants used to treat and prevent venous thromboembolism. Recent studies at home and abroad have shown that non-vitamin K antagonist oral anticoagulants （NOACs） have similar or better efficacy and safety in the prevention and treatment of venous thromboembolism and non-valvular atrial fibrillation. NOACs do not require routine coagulation monitoring when used at a fixed dose. However， in special populations or specific scenarios such as emergency surgery， etc.， an overdose or underdose and abnormal metabolism of NOACs may reduce the drug efficacy and safety， so monitoring and evaluating the anticoagulant effect of NOACs is more conducive to the prognosis of patients.This paper briefly reviewed the common laboratory monitoring methods of NOACs and their use in special populations， aiming to explain different monitoring methods for different NOACs and the applicability of NOACs in special populations， and hoping to provide reference for clinical standard monitoring and use of NOACS.

Research progress on AMPARs involved in regulating orofacial pain / 口腔疾病防治

@#The incidence of orofacial pain is high, and its pathological mechanism is complex. Currently, there is a lack of long-lasting and effective clinical treatment drugs, resulting in a major economic burden to patients and society. Therefore, it is important to develop more durable and effective drugs for treatment. In recent years, substantial evidence has shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) play a vital role in somatic and orofacial pain. Among them, subunit phosphorylation regulated by protein kinases and interactions with partner proteins promote the activation and trafficking of AMPARs and signal transduction to regulate the expression of AMPARs. The increase of GluA1-containing AMPARs promotes calcium ion influx, further activating protein kinases and auxiliary proteins, which forms a self-feedback loop. This is an important mechanism that promotes chronic pain. The expression of AMPARs in the trigeminal nervous system and the spinal cord nervous system overlaps, and the above mechanism may also participate in regulating orofacial pain. However, research on AMPARs in orofacial neuropathic pain or cancer-related pain is relatively insufficient, and more in-depth research is needed in the future. Furthermore, there is a lack of clinical evidence for AMPAR antagonists to treat pain. Understanding the regulatory mechanisms of the activation and trafficking of AMPARs and precisely intervening in the activation and trafficking of AMPARs may provide effective strategies for the development of new analgesics and offer new insights for treating orofacial pain.

The screening model for dopamine receptor agonists by a dopamine sensor / 药学学报

Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×104, and the effective concentration of the positive drug was 1-100 µmol·L-1. In addition, pretreated with 10 µmol·L-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.

Establishment and application of path-based management mode of 5-HT3 receptor antagonists in chemotherapy patients / 中国药房

OBJECTIVE To establish the path-based management mode of 5-hydroxytryptamine-3 receptor antagonist （5- HT3RA） in chemotherapy patients， and to improve the rationality of medication in chemotherapy patients. METHODS 5-HT3RA standardized drug use control rules were formulated， with the help of medical intelligence and decision support （MINDS） system， path-based management was carried out for chemotherapy patients using 5-HT3RA in the form of whole-process information capture and prescription pre-review， and whole-process intervention was implemented on medication indications， usage and dosage， course of treatment， etc. The intervention effect was analyzed by comparing the changes in the use of 5-HT3RA without indication， unreasonable usage and dosage， repeated medication， unreasonable course of treatment， and per capita drug cost before and after the implementation of path-based management. RESULTS A total of 9 181 patients were included. After the implementation of path- based management， the proportion of unindicated drugs decreased by 0.48%， and the rate of unreasonable single dosage， unreasonable frequency， repeated medication， unreasonable treatment course （5-HT3RA still used 3 days after chemotherapy） decreased by 10.48%， 0.65%， 1.33% and 0.34%； per capita cost of 5-HT3RA decreased by 13.72 yuan； there were statistical significance （P＜0.05）. CONCLUSIONS 5-HT3RA path-based management mode effectively improves the rationality of medication and provides a new idea for rational clinical drug use.

Effect of Elevated Basal LH on IVF-ET Outcomes in Patients with Polycystic Ovary Syndrome / 中山大学学报(医学科学版)

ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.

C5aR antagonist inhibits LPS-induced inflammation in human gingival fibroblasts via NF-κB and MAPK signaling pathways

Abstract Objective Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). Methodology HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. Results Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1β, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. Conclusion These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways.

A-80426 suppresses CFA-induced inflammatory pain by suppressing TRPV1 activity via NFκB and PI3K pathways in mice

Abstract Objectives Pain is associated with many circumstances, including inflammatory reactions, which arise from modification of the features of signaling pathways. α2-adrenergic receptor antagonists are widely utilized in narcosis. Here, the authors focused on the narcotic effect of A-80426 (A8) on Complete Freund's Adjuvant (CFA) injections-triggered chronic inflammation pain in WT and TRPV1-/- mice and explored whether its antinociceptive impact was modulated via Transient Receptor Potential Vanilloid 1 (TRPV1). Method CFA with or without A8 was co-administered to the mice, which were categorized randomly into four groups: CFA, A8, control, and vehicle. Pain behaviors underwent evaluation through mechanical withdrawal threshold, abdominal withdrawal reflex, and thermal withdrawal latency of WT animals. Results Quantitative polymerase chain reaction revealed that inflammation-promoting cytokines (IL-1β, IL-6, and TNF-α) were upregulated in Dorsal Root Ganglion (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT animals. A8 administration reduced the pain behaviors and production of pro-inflammatory cytokines; however, this effect was significantly reduced in TRPV1-/- mice. Further analysis showed that CFA treatment reduced the TRPV1 expression in WT mice and A8 administration increased its expression and activity. The co-administration of SB-705498, a TRPV1 blocker, did not influence the pain behaviors and inflammation cytokines in CFA WT mice; however, SB-705498 the effect of A8 in WT mice. In addition, the TRPV1 block decreased the NFκB and PI3K activation in the Dorsal Root Ganglia (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT mice. Conclusions Together, A8 exerted a narcotic impact on CFA-supplemented mice via the TRPV1-modulated NFκB and PI3K pathway.

Nueva evidencia en el tratamiento de la enfermedad renal diabética: ¿qué aporta la finerenona?

Contexto: la enfermedad renal diabética (ERD) es la primera causa a nivel mundial de enfermedad renal crónica (ERC) e impacta directamente en el riesgo cardiovascular y mortalidad de los pacientes con diabetes mellitus (DM). La finerenona, un antagonista selectivo del receptor mineralocorticoide (ARM), ha sido descrito en diversos estudios recientes como un fármaco que contribuye a la reducción de la progresión de la ERD y la disminución del riesgo cardiovascular, con un adecuado perfil de seguridad. Objetivo: realizar una revisión de la literatura sobre el impacto de la finerenona en la progresión del daño renal y el riesgo cardiovascular en los pacientes con ERD. Metodología: se realizó una búsqueda sistemática en diversas fuentes: PubMed (Medline, Biblioteca del Congreso de los Estados Unidos), Science Direct, Scopus, Embase y Lilacs; la búsqueda fue restringida a referencias en idioma español e inglés, sin límites en la fecha de publicación. Se utilizaron las siguientes palabras clave en el idioma inglés: diabetic renal disease, chronic kidney disease, diabetes mellitus, spironolactone, eplerenone, finerenone, mineralocorticoid receptor antagonist y sus correspondientes versiones en español. Resultados: Las referencias encontradas en la búsqueda fueron revisadas entre los diferentes autores para, posteriormente, proceder a realizar la elaboración del documento. Conclusiones: la finerenona es un medicamento que brinda cardio y nefroprotección en pacientes con ERD de fenotipo albuminúrico.

Background: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide and has a direct impact on cardiovascular risk and mortality in patients with diabetes mellitus (DM). Finerenone, a selective mineralocorticoid receptor (MRA) antagonist, has been described in several recent studies as a drug that contributes to slowing the progression of CKD and reducing cardiovascular risk, with an adequate safety profile. Purpose: To carry out a review of the literature on the impact of finerenone on the progression of renal damage and cardiovascular risk in patients with DKD. Methodology: A systematic search were carried out in various sources: PubMed (Medline, United States Library of Congress), Science Direct, Scopus, Embase and Lilacs; the search was restricted to references in Spanish and English, with no limits on publication date. The following keywords in the English language were used: diabetic renal disease, chronic kidney disease, diabetes mellitus, spironolactone, eplerenone, finerenone, mineralocorticoid receptor antagonist and their corresponding Spanish versions. Results: The references found in the search were reviewed among the different authors to subsequently proceed to prepare the document. Conclusions: Finerenone is a drug that provides cardio and nephroprotection in patients with DKD albuminuric phenotype.

Perioperative Management of Patients with Prosthetic Heart Valves?A Narrative Review

Worldwide, about 13% of the 200,000 annual recipients of prosthetic heart valves (PHV) present for various surgical procedures. Also, more and more females are opting for pregnancies after having PHV. All patients with PHV present unique challenges for the anesthesiologists, surgeons and obstetricians (in case of deliveries). They have to deal with the perioperative management of anticoagulation and a host of other issues involved. We reviewed the English language medical literature relevant to the different aspects of perioperative management of patients with PHV, particularly the guidelines of reputed societies that appeared in the last 20 years. Regression of cardiac pathophysiology following valve replacement is variable both in extent and timeline. The extent to which reverse remodeling occurs depends on the perioperative status of the heart. We discussed the perioperative assessment of patients with PHV, including focused history and relevant investigations with the inferences drawn. We examined the need for prophylaxis against infective endocarditis and management of anticoagulation in such patients in the perioperative period and the guidelines of reputed societies. We also reviewed the conduct of anesthesia, including general and regional anesthesia (neuraxial and peripheral nerve/plexus blocks) in such patients. Finally, we discussed the management of delivery in this group of high?risk patients. From the discussion of different aspects of perioperative management of patients with PHV, we hope to guide in formulating the comprehensive plan of management of safe anesthesia in such patients.

Prevention of Premature Ovulation by Administration of Gonadotropin Releasing Hormone Antagonist the day After Ovulation Triggering in Diminished Ovarian Reserve Patients / Prevenção da ovulação prematura por meio da administração de antagonismo de liberação de gonadotropismo no dia seguinte à ovulação

Abstract Objective The aim of the present retrospective study was to investigate the effectiveness of single-dose gonadotropin releasing hormone (GnRH) antagonist administration, the day after human chorionic gonadotropin (hCG) triggering for final oocyte maturation, on the prevention of premature luteinization in patients with diminished ovarian reserve in in-vitro fertilization (IVF) cycles. The secondary objective of the study was to search the effect of this protocol on pregnancy outcomes. Methods This is a retrospective study including 267 infertile patients who have single antral follicle seen with ultrasonography on the 2nd or 3rd day of the menstrual cycle before starting IVF treatment. We randomized patients into two groups. The case group comprised patients who had single-dose GnRH antagonist injection the day after hCG triggering formed, and the patients who had the standard treatment regime formed the control group. In both groups, the oocytes were collected 36 hours after hCG injection. Results The premature ovulation rate was significantly low in the case group compared with the control group (6.86 versus 20.6% per scheduled cycle) (p=0.022). Also, the oocyte retrieval rate (93.14 versus 67.87% per scheduled cycle) (p=0.013), the oocyte maturity rate (79.42 versus 47.87%) (p=0.041), the fertilization rate (65.68 versus 34.54%) (p=0.018), and the embryo transfer rate per scheduled cycle (44.11 versus 18.78%) (p=0.003) were higher in the GnRH antagonist group than in the control group. Conclusion The administration of GnRH antagonist the day after hCG trigger in IVF treatments of patients with diminished ovarian reserve enabled a significant decrease in the rate of premature ovulation but had no effect on live birth rate.

Resumo Objetivo O objetivo do presente estudo retrospectivo foi investigar a eficácia da administração do antagonista do hormônio liberador da gonadotrofina (GnRH) em dose única no dia seguinte ao desencadeamento da gonadotrofina coriônica humana (hCG) para a maturação final do oócito, na prevenção da luteinização prematura em pacientes com diminuição do ovário reserva em ciclos de fertilização in vitro (FIV). O objetivo secundário do estudo foi pesquisar o efeito deste protocolo nos resultados da gravidez. Métodos Trata-se de um estudo retrospectivo incluindo 267 pacientes inférteis que apresentam um único folículo antral visto por ultrassonografia no 2° ou 3° dia do ciclo menstrual antes de iniciar o tratamento de FIV. Nós randomizamos os pacientes em dois grupos. Os pacientes que receberam injeção de antagonista de GnRH em dose única no dia seguinte ao desencadeamento do hCG formaram o grupo caso, e os pacientes que receberam o regime de tratamento padrão formaram o grupo controle. Em ambos os grupos, os oócitos foram coletados 36 horas após a injeção de hCG. Resultados A taxa de ovulação prematura foi significativamente baixa no grupo caso em comparação com o grupo controle (6,86 versus 20,6% por ciclo programado) (p=0,022). Além disso, a taxa de recuperação de oócitos (93,14 versus 67,87% por ciclo programado) (p=0,013), a taxa de maturidade do oócito (79,42 versus 47,87%) (p=0,041), a taxa de fertilização (65,68 versus 34,54%) (p=0,018) e a taxa de transferência de embriões por ciclo programado (44,11 versus 18,78%) (p=0,003) foram maiores no grupo antagonista de GnRH do que no grupo controle. Conclusão A administração de antagonista de GnRH, no dia seguinte ao desencadeamento de hCG em tratamentos de FIV de pacientes com reserva ovariana diminuída permitiu uma redução significativa na taxa de ovulação precoce,mas não teve efeito na taxa de nascidos vivos.

Tirofiban interferes with antibody-mediated transfusion-related acute lung injury by inhibiting platelet-neutrophil binding / 中国输血杂志

【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.