Vaginosis citolítica: actualización diagnóstica y terapéutica / Cytolytic vaginosis: diagnostic and therapeutic update

El objetivo es conocer el abordaje diagnóstico y terapéutico de la vaginosis citolítica. Para ello se hizo una búsqueda sistemática de la literatura médica mediante las bases de datos: PubMed, Central, etc. Se limitó a ensayos clínicos aleatorizados, metaanálisis y revisiones bibliográficas, con disponibilidad del texto completo para evaluarlos en su totalidad e incluirlos en la revisión; publicados entre 1980 y 2021. Se incluyeron 27 publicaciones. La vaginosis citolítica es un trastorno infradiagnosticado. En mujeres con síntomas y signos de candidiasis vulvovaginal, que no responden a la terapia, se debe considerar la probabilidad de estar en presencia de una vaginosis citolítica. El tratamiento obliga a elevar el pH vaginal a valores básicos y a disminuir el número excesivo de Lactobacillus, resultando de utilidad las duchas vaginales con bicarbonato de sodio y/o un tratamiento con antibióticos derivados de la penicilina junto a un inhibidor de ß-lactamasas o doxiciclina en las pacientes alérgicas a la penicilina. Finalmente, se concluye que la vaginosis citolítica es una afección común, frecuentemente se diagnostica de forma errónea porque se confunde con la candidiasis vulvovaginal; se caracteriza por producir un cuadro clínico similar. El tratamiento se enfoca en disminuir el número de Lactobacillus y la elevación del pH vaginal.

The objective is to know the diagnostic and therapeutic approach of cytolytic vaginosis. A systematic search of the medical literature was carried out using the following databases: Medline via PubMed, Central, and Cochrane Database of Systematic Reviews, among others. The search was limited to randomized clinical trials, meta-analyses, and literature reviews that had the full text available for full evaluation and inclusion in the review; published between 1980 and 2021. Twenty-seven publications were included. Cytolytic vaginosis is a frequently underdiagnosed disorder, which mimics Candida vaginitis. In women with symptoms and signs of vulvovaginal candidiasis who do not respond to antifungal therapy, the possibility of cytolytic vaginosis should be considered. The treatment of this condition requires raising the vaginal pH to basic values and reducing the excessive number of Lactobacillus, resulting in useful vaginal douches with sodium bicarbonate and/or treatment with antibiotics derived from penicillin together with a ß-lactamases inhibitor or doxycycline in patients allergic to penicillin. Finally, we conclude that cytolytic vaginosis is a common condition, frequently misdiagnosed because it is confused with vulvovaginal candidiasis, since it is characterized by producing a similar clinical picture. Treatment focuses on reducing the number of Lactobacillus and raising vaginal pH.

Despigmentação precoce em caso de ceratopigmentação / Early depigmentation in case of keratopigmentation

RESUMO A ceratopigmentação teve seu primeiro registro pelo filósofo Galeno há muitos séculos como uma estratégia utilizada para o tratamento estético de pacientes com leucomas. As córneas com leucoma são patológicas e, muitas vezes, intolerantes a lentes de contato cosméticas ou próteses oculares, sendo comum a queixa de desconforto excessivo, proporcionado pela superfície corneana irregular. Assim, a ceratopigmentação é uma alternativa para a melhora estética de pacientes com opacidades corneanas. Descrevemos o caso de um paciente do sexo masculino, 39 anos, que apresentou despigmentação precoce em caso de ceratopigmentação associado a quadro de ceratite herpética necrotizante. O paciente foi submetido ao tratamento com aciclovir 2g ao dia e doxiciclina 200mg ao dia, evoluindo com melhora do quadro clínico, apesar da má adesão medicamentosa.

ABSTRACT Keratopigmentation was first recorded many centuries ago by the philosopher Galeno, as a strategy used for the aesthetic treatment of patients with leukomas. Corneas with leucoma are pathological and often intolerant of cosmetic contact lenses or ocular prostheses, with complaints of excessive discomfort provided by the irregular corneal surface being common. Therefore, keratopigmentation is an alternative for the aesthetic improvement of patients with corneal opacities. We describe the case of a 39-year old male patient, who presented early depigmentation in a case of keratopigmentation associated with necrotizing herpetic keratitis. The patient was treated with Acyclovir 2g/day and Doxycycline 200mg/day, evolving with clinical improvement, despite poor medication adherence.

Doxycycline hyclate may damage testicular germinal epithelium in Wistar rats

Broad-spectrum antimicrobial doxycycline acts as an inhibitor of protein synthesis and it is widely used in the clinical treatment of various infections by microorganisms that are sensitive to the drug, as well as in animal feed. Its liposolubility guarantees its high tissue bioavailability, being associated with several biochemical changes in the organism and potentially adverse effects on reproduction. This study aims to evaluate the effects of the action of doxycycline on spermatogenesis to provide a complete analysis of the tubular and interstitial compartments and to identify possible changes in the testicular parenchyma. Adult male Wistar rats were divided into three groups: one control (water), and two treated with doxycycline at the doses of 10mg/kg and 30mg/kg, for 30 days. After euthanasia and sample processing, the following parameters were evaluated: a) tubular diameter and height of the seminiferous epithelium; b) volumetric proportions (%) and volumes (mL) of the components of the testicular parenchyma; c) counting testicular germ cell populations; d) evaluation of cell viability. The results of the comparative evaluation between the experimental groups demonstrated a significant increase in the diameter and area of the tubular lumen and a reduction in the count of spermatogonia in the experimental group that received doxycycline hyclate at a dose of 30mg/kg. In the same experimental group, an increase in the overall yield of spermatogenesis was found as a consequence of the increase in the mitotic index.

Atrofodermia de Pasini-Pierini, presentación de dos casos clínicos / Atrophoderma of Pasini and Pierini. Presentation of two clinical cases / Atrofodermia de Pasini-Pierini, apresentação de dois casos clínicos

La atrofodermia de Pasini-Pierini es una enfermedad rara con menos de 100 reportes de casos en la literatura, más frecuente en mujeres, predominando en la segunda o tercera década de la vida. Genera una atrofia a nivel dérmico, presentándose como una placa única o múltiple, de bordes bien definidos con un desnivel en profundidad. La causa es desconocida, se ha relacionado con infecciones por Borrelia Burgdorferi. En cuanto a los tratamientos disponibles, no existe un tratamiento comprobado de primera línea, se indica en algunos casos doxiciclina por periodos prolongados. Se presentan dos casos clínicos de la atrofodermia de Pasini-Pierini y se revisan las características de dicha entidad.

Summary: Atrophoderma of Pasini and Pierini is a rare disease, there being under 100 cases reported in literature. It is more frequent in women, and mainly occurs in their twenties or thirties. This condition results in dermal atrophy, and it may present as single or multiple plaques, with well-defined borders by differences in depth. The cause is unknown, although it has been related to Borrelia Burgdorferi infections. As to available therapies, there is no first line clinically proven treatment, although in some cases doxycycline is indicated for long periods. The study presents two clinical cases of atrophoderma of Pasini and Pierini and reviews the main characteristics of this condition.

A atrofodermia de Pasini-Pierini é uma doença rara com menos de 100 casos relatados na literatura; é mais frequente em mulheres, predominando na segunda ou terceira década de vida. Gera atrofia em nível dérmico, apresentando-se como placa única ou múltipla, com bordas bem definidas e depressão em relação à pele adjacente. A causa é desconhecida e tem sido associada a infecções por Borrelia burgdorferi. Em relação aos tratamentos disponíveis, não há tratamento comprovado de primeira linha, sendo a doxiciclina indicada por longos períodos em alguns casos. Apresentam-se dois casos clínicos de atrofodermia de Pasini-Pierini e faz-se uma revisão das características desta entidade.

La mutación N15Y en la proteína E del coronavirus 2 del síndrome respiratorio agudo severo afecta la unión de doxiciclina y rutina / The N15Y mutation in the E protein of severe acute respiratory syndrome coronavirus 2 affects the binding of doxycycline and rutin

The severe acute respiratory syndrome coronavirus 2 genetic variation must be closely monitored. Viral transmission can inevitably result from mutations in the viral genome and functional proteins that aid in the virus's adaptation to the host. This study aimed to look for mutations in the E protein and see how they affected the ligands' molecular docking. Mathematical saturation mutagenesis and other informatics techniques were used. Fourteen severe acute respiratory syndrome coronavirus 2 isolates from Iraq were selected. Doxycycline and rutin were chosen as ligands. In four strains of severe acute respiratory syndrome coronavirus 2, the N15Y mutation was detected in the envelope protein. Depending on the calculation of the amount of energy of the atoms, this mutation is critical in modifying the shape of the protein as well as increasing protein stability. In the single-chain mutation, one pocket was determined, while all pentamer chains had two pockets. The N15Y mutation altered the degree of doxycycline binding by affecting the residue of attachment of the ligands. It also altered the position of the rutin's attachment to the E protein, which has a clear impact on the virion particle(AU)

La variación genética del coronavirus 2 del síndrome respiratorio agudo severo debe ser monitoreada de cerca. La transmisión viral puede resultar inevitablemente de mutaciones en el genoma viral y proteínas funcionales que ayudan en la adaptación del virus al hospedero. Este estudio tuvo como objetivo buscar mutaciones en la proteína E y ver cómo afectaban el acoplamiento molecular de los ligandos. Se utilizó la mutagénesis de saturación matemática y otras técnicas informáticas. Se seleccionaron 14 aislamientos del coronavirus 2 del síndrome respiratorio agudo severo en Irak. Se eligieron doxiciclina y rutina como ligandos. En cuatro cepas del coronavirus 2 del síndrome respiratorio agudo severo, se detectó la mutación N15Y en la proteína de la envoltura. Dependiendo del cálculo de la cantidad de energía de los átomos, esta mutación es fundamental para modificar la forma de la proteína y aumentar la estabilidad de la proteína. En la mutación de cadena única, se determinó un bolsillo, mientras que todas las cadenas de pentámero tenían dos bolsillos. La mutación N15Y alteró el grado de unión de doxiciclina al afectar el residuo de unión de los ligandos. También alteró la posición de unión de la rutina a la proteína E, lo que tiene un claro impacto en la partícula del virión(AU)

Linfogranuloma venéreo genital en un hombre que tiene sexo con hombre: reporte de caso no importado en Chile / Lymphogranuloma venerous genital in men who have sex with men: a non-imported case report in Chile

Resumen El linfogranuloma venéreo (LGV) es una infección de transmisión sexual (ITS) causada por Chlamydia trachomatis. En los últimos años, ha emergido principalmente en hombres que tienen sexo con hombres (HSH). Es frecuente su asociación con otras ITS como el virus de inmunodeficiencia humana (VIH) y la sífilis. Si bien el compromiso genital es la forma de presentación clásica, el síndrome anorrectal constituye el principal cuadro clínico en la actualidad. Presentamos el caso de un HSH con infección por VIH en terapia anti-retroviral, herpes genital recurrente y sífilis latente tratada, sin viajes recientes al extranjero, con adenopatías inguinales fistulizadas a piel, asociada a una úlcera genital dolorosa, sin síntomas anorrectales ni sistémicos, refractario a múltiples tratamientos antibacterianos y antivirales. El estudio con RPC de secreción de la fístula fue positiva a C. trachomatis. Se trató con doxiciclina por seis semanas, con buena respuesta clínica, sin complicaciones.

Abstract Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis bacteria. In the past years, it has emerged as a relevant infectious agent, mainly affecting men who have sex with men (MSM), frequently associated with other sexually transmitted infections as human immunodeficiency virus (HIV) and syphilis. Even though genital lesions correspond to the classical presentation of LGV, nowadays anorectal syndrome is more frequently reported. We present a MSM patient, HIV infected, being treated with antiretroviral drugs, with a history of recurrent genital herpes, also recently treated for a syphilis in a latent stage. He had no recent trips. He referred inguinal fistulized enlarged lymph nodes, associated with a painful genital ulcer, he denied anorectal or systemic symptoms. He had been treated with multiple antibiotic and antiviral drugs, with no clinical response. Molecular studies from the content of the fistulized lymph node identified C. trachomatis. The patient received doxycycline for 6 weeks, showing good clinical response.

Terapêutica adjuvante na modulação da resposta imune no tratamento da doença periodontal: uma revisão de literatura / Adjuvant therapeutic in the modulation of the immune response in the treatment of periodontal disease: a literature review

Introdução: A Doença Periodontal tem caráter multifatorial, já que depende de condições microbiológicas, imunogenéticas e sistêmicas do hospedeiro. Representa inflamação crônica das estruturas de suporte e proteção dental. Desencadeia uma complexa estimulação imunológica, bem como a produção de citocinas inflamatórias, que mediam a destruição óssea e de tecido conjuntivo, provocando perda dental e complicações à distância. A compreensão da etiopatogênese, permitiu os conceitos de modulação, que referem-se às modificações dos aspectos danosos da resposta inflamatória. Objetivo: O presente artigo tem como objetivo realizar uma revisão dos estudos sobre as principais terapêuticas adjuvantes na modulação da resposta imune frente à doença periodontal. Revisão de Literatura: Foi realizada uma revisão da literatura, onde foram selecionados artigos científicos em inglês, publicados entre os anos 2005 a 2020, por meio das bases de dados PubMed e ScienceDirect. No decorrer das buscas, foram utilizadas as palavraschaves "Inflamation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Resultados e Conclusão: A literatura é bem promissora em relação à terapia de controle complementar da doença periodontal. Dessa forma, novas pesquisas nessa área podem trazer inúmeros beneficos aos pacientes, sendo, assim, um novo caminho para o contorno da resistência bacteriana(AU)

Introduction: Periodontal disease has a multifactorial character, depending on the host's microbiological, immunogenetic and systemic conditions. It represents chronic inflammation of dental support and protection structures. It triggers a complex immune stimulation, as well as the production of inflammatory cytokines, which mediate bone and connective tissue destruction, causing tooth loss and complications at a distance. The understanding of etiopathogenesis allowed the concepts of modulation, which refers to the modifications of the harmful aspects of the inflammatory response. This article has the escape of conducting a review of studies on the main mechanisms of modulation against periodontal disease. Objective: This article aims to rev iew the studies on the main modulation mechanisms in the face of periodontal disease. Literature Review: A literature review was carried out in which scientific articles were selected in English, published between 2005 and 2020, through the PubMed and ScienceDirect databases. During the searches, the keywords "Inflammation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Results and Conclusion: The literature is very promising with complementary control therapy for periodontal disease. Thus, new research in this area can bring countless benefits to patients, thus being a new way to bypass bacterial resistance(AU)

An uncommon case of brucellosis with ocular presentation / Um caso incomum de brucelose com apresentação ocular

ABSTRACT We report an unusual case of brucellosis presented with headache, diminished vision, papillitis and multiple peripapillary hemorrhages accompanied by subretinal fluid extending up to macula. Diagnosis of brucellosis was made based on positive polymerase chain reaction of cerebrospinal fluid sample for Brucella species DNA, accompanied by a raised titer of anti-brucella antibodies. Patient showed remarkable improvement on triple drug therapy in form of doxycycline, rifampicin and ceftriaxone.

RESUMO Relatamos um caso incomum de brucelose apresentada com cefaleia, visão diminuída, papilite e múltiplas hemorragias peripapilares acompanhadas por fluido sub-retinal, estendendo-se até a mácula. O diagnóstico de brucelose foi feito com base na reação em cadeia da polimerase positiva de amostra de líquido cefalorraquidiano para DNA de espécies de Brucella, acompanhada por um título elevado de anticorpos antibrucela. O paciente apresentou melhora notável com a terapia tripla com drogas na forma de doxiciclina, rifampicina e ceftriaxona.

Manejo farmacológico del sangrado irregular no menstrual asociado al uso de implantes anticonceptivos subdérmicos / Pharmacological management of irregular non-menstrual bleeding associated with the use of subdermal contraceptive implants

El spottingo sangrado irregular no menstrual es uno de los principales efectos secundarios de los implantes anticonceptivos, situación que se recomienda discutir con la usuaria previo a la colocación, para evitar falsas expectativas o temores que lleven a la extracción temprana del dispositivo. A propósito de una paciente sin antecedentes relevantes que consultó al centro de salud por spotting desde la colocación del implante cuatro meses antes, decidimos revisar la evidencia sobre la efectividad de los distintos esquemas farmacológicos disponibles para el manejo de este evento adverso. Luego de realizar una búsqueda bibliográfica concluimos que, si bien existe sustento para indicar algunos de los esquemas farmacológicos, este es aún débil y son necesarios estudios clínicos adicionales que brinden evidencia sólida sobre qué esquema en particular utilizar, evaluando sus riesgos y beneficios. (AU)

Spotting or irregular non-menstrual bleeding is one of the main side effects of contraceptive implants, a situation that health professionals must discuss with the user prior to its placement in order to avoid false expectations or fears that lead to early removal of the implant. Regarding a patient with no relevant history who consulted the health center due to spotting four months after implant placement, we decided to review the evidence onthe effectiveness on different pharmacological schemes available for the management of this adverse event. After performing a literature search, we concluded that, although there is support for indicating some of the pharmacological schemes, this is still weak, and further clinical studies are needed to provide solid evidence on which particular scheme touse, assessing its risks and benefits. (AU)

The Effect of Doxycycline on the Expression of MMP-2 and MMP-9 in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in multiple myeloma (MM) patients, and analyze the effect of doxycycline (DOX) on the expression of MMP-2 and MMP-9 in MM cells.@*METHODS@#The peripheral blood and bone marrow samples of MM patients were collected, and the patients were divided into three groups: newly diagnosed group, remission group and relapsed/refractory group, while the peripheral blood samples of 34 health people and the bone marrow samples of 17 IDA patients were selected as normal control and control group. The levels of MMP-2 and MMP-9 were detected by ELISA. The protein levels of MMP-2 and MMP-9 in H929 cells treated by different concentrations of DOX were analyzed by Western blot. After H929 cells was treated by Akt inhibitor MK-2206 2HCl in combination with DOX, Western blot was used to detect the levels of MMP-2 and MMP-9.@*RESULTS@#The levels of MMP-2 and MMP-9 in newly diagnosed MM patients were higher than those in control (P<0.05), while for the patients in the remission group were decreased, but still higher than those in control. The levels of MMP-2 and MMP-9 were increased again for the patients in relapsed/refractory group, and showed no significant difference as compared with those in newly diagnosed group. The levels of MMP-2 and MMP-9 could be inhibited by 10 mg/L and 15 mg/L DOX treated by H929 cell. The protein levels of MMP-2 and MMP-9 showed no altered in H929 cells treated by 5 nmol/L MK-2206 2HCl alone. DOX exerted more profound inhibitory effect to MMP-2 and MMP-9 expression in H929 cells when Akt inhibitor MK-2206 2HCl was combined with DOX.@*CONCLUSION@#The levels of MMP-2 and MMP-9 are increased in MM patients and related to the disease status of MM. DOX can inhibit the expression of MMP-2 and MMP-9 in MM cells, and antagonizing its activation of Akt signaling pathway can further enhance the inhibitory effect.

Effect of Doxycycline on Intrinsic Apoptosis of Myeloma Cell Line H929 and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity.@*METHODS@#Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively.@*RESULTS@#DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05).@*CONCLUSION@#DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.

Hipomelanosis macular progresiva: comunicación de un caso y revisión de la literatura científica / Progressive macular Hypomelanosis: case report andr review of scientic literature

La hipomelanosis macular progresiva es un trastorno adquirido de la pigmentación que aparece con más frecuencia en mujeres, adolescentes y adultas jóvenes. Se caracteriza por máculas hipopigmentadas asintomáticas, mal delimitadas, no descamativas, simétricas y de predominio en región lumbar. El estudio histopatológico evidencia disminución del contenido de melanina en la epidermis afectada, con número y distribución de los melanocitos conservados. En su etiopatogenia interviene el Cutibacterium acnes tipo III, bacteria responsable de la característica fluorescencia rojiza de distribución folicular que se observa con la lámpara de Wood. Por este motivo, los tratamientos propuestos incluyen el uso de tetraciclinas por vía oral y tratamientos tópicos como el peróxido de benzoílo, asociados a fototerapia UVA o UVB de banda angosta. Se presenta una paciente con hipomelanosis macular progresiva del tronco que respondió satisfactoriamente al tratamiento con doxiciclina vía oral

Progressive macular hypomelanosis is an acquired pigmentation disorder that occurs mostly in adolescent and young women. It is characterized by asymptomatic, poorly defined, non-scaly, symmetrical hypopigmented macules localized predominantly in the lumbar area. Histopathology shows a decrease in melanin content with preserved number and distribution of melanocytes in the affected epidermis. Cutibacterium acnes type III appears to be the responsible for the dermatosis and for the characteristic reddish fluorescence of follicular distribution observed with Wood´s lamp. Treatment include oral tetracyclines and topical benzoyl peroxide associated with UVA or narrow band UVB phototherapy. We present a patient with progressive macular hypomelanosis of the trunk with excellent response to treatment with oral doxycycline

Ulceración esofágica por ingestión de doxiciclina / Doxycycline induced esophageal ulceration

La ulceración esofágica por ingestión de doxiciclina es una de las causas más frecuentes de lesión esofágica. Ha sido subdiagnosticada y escasamente reconocida en dermatología. El dolor retroesternal, la odinofagia de aparición brusca y el antecedente de ingesta de doxiciclina u otros fármacos son características que facilitan su diagnóstico. Puede presentar complicaciones serias, como hemorragias, estenosis y mediastinitis.

Esophageal ulceration due to ingestion of doxycycline is one of the most frequent causes of esophageal injury. It has been underdiagnosed and scarcely recognized in dermatology. Retrosternal pain, sudden odynophagia and a history of doxycycline or other drugs intake are some of the characteristics that lead to diagnosis. It may cause severe complications such as bleeding, stenosis and mediastinitis.

Síndrome Dress relacionada ao uso de Alopurinol: relato de caso / Dress Syndrome related to the use of allopurinol: case report

A síndrome DRESS é uma reação adversa a medicamentos pouco conhecida dentro da prática clínica, porém com grande potencial de letalidade devido a combinação de manifestações cutâneas e envolvimento de múltiplos órgãos. Objetivo: identificar possíveis reações adversas graves e incomuns secundárias ao uso de medicações usadas frequentemente na prática clínica. Métodos: Trata-se de um relato de caso construído com base em levantamento de dados do prontuário do paciente e análise a partir de um referencial teórico para comprovação de sua relevância na prática clínica. Resultado: Enfatizou-se a importância de um reconhecimento precoce dessa condição, a fim de evitar desfechos graves

The DRESS syndrome is an adverse drug reaction that is unsual in clinical practice, but with a high potential for lethality, due to the combination of cutaneous manifestations and involvement of multiple organs. Objective: identify possible serious and unusual adverse reactions secondary to the use of medications frequently used in clinical practice. Methods: This is a case report built on the basis of data collection from the patient's medical record and analysis from a theoretical framework to prove its source in clinical practice. Outcome: The importance of early recognition of this condition was emphasized, in order to avoid serious outcomes

Endometrite crônica e infertilidade / Chronic endometritis and infertility

A endometrite crônica (EC) é uma doença que, apesar de ainda pouco investigada, tem sido associada a resultados reprodutivos desfavoráveis. Estudos têm mostrado que a EC pode prejudicar a receptividade endometrial, levando a falhas de implantação e perdas gestacionais recorrentes. Os métodos padronizados para diagnóstico incluem histeroscopia, histologia para pesquisa de plasmócitos e cultura endometrial para identificação de agentes bacterianos. O tratamento com antibióticos para EC parece melhorar as taxas de gestação e nascidos vivos em pacientes com falhas de implantação e perdas gestacionais recorrentes sem causa conhecida. Esta publicação tem por objetivo fazer uma revisão da etiologia, fisiopatologia, diagnóstico e tratamento da EC, seu impacto no microambiente endometrial e sua associação com infertilidade. Esta revisão narrativa da literatura atualizada sintetiza os achados encontrados em bases de dados computadorizadas.(AU)

Chronic endometritis (CE) is a poorly investigated disease, which has been related to adverse reproductive outcomes. Published studies have shown that CE can impair endometrial receptivity, which is associated with implantation failure and recurrent pregnancy loss. The standard tools for diagnosis include hysteroscopy, histology to identification of plasma cells and endometrial culture for identification of bacterial pathogens. Effective antibiotic treatment for CE seems to improve the pregnancy and live birth rates in patients with implantation failure and unexplained recurrent pregnancy loss. This paper intends to provide an overview of etiology, pathophysiology, diagnosis and treatment of CE, its impact on endometrial microenvironment and its association with infertility. This narrative review of the current literature synthesizes the findings retrieved from searches in computerized databases.(AU)

A Randomised Study Comparing the Efficacy of Low-Dose Oral Azithromycin versus Doxycycline in Combination with Topical Benzoyl Peroxide in the Treatment of Moderate to Severe Acne Vulgaris

Background@#Acne vulgaris is a common chronic inflammatory skin disease. Long term therapy involving antibiotics warrants for drug with a long half-life to increase compliance of patients. @*Methods@#A twelve-week prospective randomized study was performed on 40 subjects with moderate to severe facial acne to compare the efficacy of oral azithromycin with oral doxycycline. Thirty-six subjects completed the study. Subjects in azithromycin group received azithromycin 250mg three times a week plus topical benzoyl peroxide 5% (BPO), whereas subjects in doxycycline group received doxycycline 100mg daily plus topical BPO 5%. Efficacy evaluation included treatment success rate (Comprehensive Acne Severity Score /CASS of 0 or 1 or improvement of two grades from baseline) and lesion counts.@*Results@#Treatment was successful in 94.4% of subjects in azithromycin group, compared to 88.9% in doxycycline group (p=1.000) at week 12.However, percentage of clear or almost clear by CASS was higher in the doxycycline group ( 83.3% vs 66.7%; p= 0.443).Percentage reduction of inflammatory lesion counts in azithromycin and doxycycline group following treatment for 12 weeks were 78.3% and 85.3% (p=0.133) respectively, whereas for non-inflammatory lesion counts were 77.7% and 78.8% (p=0.852) respectively. Nausea was reported in 77.8% at week 6 and 66.7% at week 12 in doxycycline group, but none in azithromycin group. There were no significant differences in incidence of diarrhoea and abdominal pain.@*Conclusion@#Azithromycin 250mg three times a week plus topical BPO 5% is as effective as doxycycline 100mg daily plus topical BPO 5%.

Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline / Alterações da superfície ocular no tratamento da Rosácea: comparação entre isotretinoína oral em baixa dosagem e doxiciclina

ABSTRACT Purpose: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea. Methods: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment. Results: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance. Conclusion: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.

RESUMO Objetivos: Comparar o impacto das alterações oculares entre o tratamento sistêmico de doxiciclina e isotretinoína em baixa dosagem em pacientes com rosácea papulopustulosa moderada a grave. Métodos: Os pacientes form randomizados para receber isotretinoína 0,3 a 0,4 mg/kg (grupo A) ou doxiciclina 100mg/dia (grupo B) por 16 semanas. Os sintomas oculares foram pesquisados e avaliados, incluindo melhor acuidade visual corrigida, teste de Schirmer, tempo de ruptura do filme lacrimal, coloração de rosa bengala e graduação da disfunção de glândula de Meibomius. Os pacientes foram novamente testados no final do tratamento. Resultados: O presente estudo incluiu 39 pacientes (30 mulheres e 9 homens). A melhor acuidade visual corrigida foi >20/30 em >90% dos pacientes em ambos os grupos e não se alterou após o tratamento. A melhora dos sintomas oculares e da disfunção de glândula de Meibomius foi mais pronunciada no grupo B (p<0,05) após o tratamento; as demais variáveis não atingiram significância estatística. Conclusão: A doxiciclina melhorou a disfunção de glândula de Meibomius, os sintomas oculares e a superfície ocular de pa cientes com rosácea. Mesmo que alguns pacientes tenham piorado a disfunção e os sintomas da glândula de Meibomius, nenhum indivíduo apresentou complicações graves após a admi nistração de baixas doses de isotretinoína.

A case of Bartonella neuroretinitis with macular star diagnosed by clinical, epidemiological, serological, and molecular data: resolution after initiation of antimicrobial therapy

Abstract The differential diagnosis of optic neuritis is broad and varied. We report the case of a 24-year-old Brazilian man who presented with five-week history of fever, malaise, myalgia, severe fatigue, tender right preauricular lymphadenopathy, and acute vision blurring associated with right optic disc swelling and exudates in a macular star pattern. His illness developed soon after an infestation of fleas broke out among his cats. Diagnosis of ocular bartonellosis was confirmed by serological and molecular analyses targeting amplification of Bartonella spp. htrA gene. Signs and symptoms only improved after initiation of antimicrobial therapy.

Caracterização físico-química e atividade biológica de um cimento dentário à base de quitosana, nanohidroxiapatita, nanopartículas de óxido de zinco para estimulação de células nervosas de Schwann (HS-SCH-2) / Physical-chemical characterization and biological activity of a dental cement based on chitosan, nano-hydroxyapatite, and zinc oxide nanoparticles for Schwann nervous cell stimulation (hs-sch-2)

Os cimentos dentários e ortopédicos são utilizados amplamente em diversas aplicações clínicas. Novos cimentos vêm sendo propostos visando à preservação ou regeneração tecidual. Contudo, pouco se conhece sobre o papel desses biomateriais na regeneração nervosa. As células mais comumente envolvidas na regeneração nervosa são as células de Schwann (SCs) sendo sua principal função o suporte aos axônios através da liberação de fatores de crescimento e isolamento axonal através da formação da bainha de mielina. Como estratégia da presente pesquisa, foi estudado um cimento à base da quitosana com adição de substâncias que podem atuar sinergicamente na resposta celular nervosa, tais como, as nanopartículas (NPs) de hidroxiapatita e o óxido de zinco, visto que têm propriedades bioativas e biocondutoras, além de promoverem a condução de prolongamento axonal. A doxiciclina (Dox) foi acrescida como antimicrobiano, potente inibidora de metaloproteinases (MMPs) e estimuladora da diferenciação celular no processo de regeneração tecidual. Assim, as propriedades físico-químicas e biológicas do cimento de nano-hidroxiapatita, quitosana, óxido de zinco e doxiciclina foram avaliadas, bem como a capacidade de promover um ambiente favorável para as células nervosas periféricas. Os cimentos foram caracterizados físico-químicamente mediante a determinação do pH, tempo de presa e solubilidade, lixiviação de íons cálcio, liberação controlada de doxiciclina, difração de Raios X, Termogravimetria (TG), espectroscopia Raman, molhabibidade, e testes de atividade biológica, para assim também serem avaliados em contato com células nervosas de Schwann (HS-Sch-2). O cimento apresentou pH neutro (7,0), tempo de presa de 5,7 ± 0,22 minutos, solubilidade menor que 3%, lixiviação de cálcio de 8,14 ± 0,71 mg L-1 após 14 dias, estabilidade térmica e a análise espectroscópica ratificou a presença e diferenciação das estruturas químicas dos componentes do cimento coerentemente com as imagens das análises microscópicas. Além disso, o cimento se mostrou hidrofílico, teve efeito hemolítico baixo (17%), obteve alta citocompabilidade celular em fibroblastos ATCC 3T3 (72%) e ação antimicrobiana. O cimento aumentou significativamente o crescimento das células de Schwann, 48,6% a mais do que o grupo controle (p≤0.05), e maior capacidade metabólica na análise mitótica quando em contato com este material (33%). Pode-se concluir que o cimento proposto à base de quitosana contendo hidroxiapatita e óxido de zinco nanoparticulados com adição de doxiciclina obteve efeito bioativo em células de Schwann promovendo, assim, o crescimento e a atividade mitótica celular, sendo então um biomaterial promissor para estudos de remielinização de nervos periféricos e regeneração nervosa in vivo.

Dental and orthopedic cements are used widely in several clinical applications. New cements have been proposed aimed the tissue preservation or regeneration. Nevertheless, nerve regeneration is not well known. The cells most commonly used in nerve regeneration are Schwann cells (SCs) which represent glial cells in the peripheral nervous system, their main function being supporting axons by releasing growth factors and axonal isolation through the formation of the myelin sheath. As a strategy of this research, chitosan-based cement was studied with the addition of substances that can act synergistically in the nervous cell response, such as the hydroxyapatite and zinc oxide nanoparticles (NPs), since they have bioactive and bioconductive properties; in addition to furthermore, they promote the conduction of axonal prolongation. Doxycycline (Dox) was added as an antimicrobial, a potent inhibitor of MMPs, a stimulator of cell differentiation in the tissue regeneration process. Thus, the physical-chemical and biological properties of nanohydroxyapatite, chitosan, zinc oxide and doxycycline cements were evaluated, as well as the ability to promote a favorable environment for peripheral nerve cells. Blocks of cements were characterized physically and chemically by determining pH, setting time and solubility, calcium ions leaching, controlled release of doxycycline, X-ray diffraction, Thermogravimetry (TG), Raman spectroscopy, wetness, and biological activity tests, so they can also be evaluated in contact with Schwann nerve cells (HS-Sch-2). The cement showed neutral pH (7.0), setting time of 5.7 ± 0.22 minutes, solubility less than 3%, calcium leaching of 8.14 ± 0.71 mg L-1 after 14 days, stability thermal and spectroscopic analysis confirmed the presence and differentiation of the chemical structures of the cement components coherently with the images of the microscopic analysis. In addition, the cement was shown to be hydrophilic, had a low hemolytic effect (17%), and obtained high cell cytocompatibility in ATCC 3T3 fibroblasts (72%) and antimicrobial action. The cement significantly increased the growth of Schwann cells, 48.6% more than the control group (p≤0.05), and greater metabolic capacity in the mitotic analysis when in contact with this material (33%). It can be concluded that the proposed chitosan-based cement containing hydroxyapatite and zinc oxide nanoparticulated with the addition of doxycycline has a bioactive effect in Schwann cells, thus promoting cell growth and mitotic activity, thus being a promising biomaterial for studies of remyelinization of peripheral nerves and nerve regeneration in vivo.