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.

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.

O uso do Twitter como minerador de eventos adversos de medicamentos de combate à malária: o caso da doxiciclina / El uso de Twitter como localizador de eventos adversos con medicamentos de combate a la malaria: el caso de la doxiciclina / Mining in Twitter for adverse events from malaria drugs: the case of doxycycline

Durante o período de pós-comercialização, quando medicamentos são usados por grandes populações e por períodos de tempo maiores, eventos adversos (EA) inesperados podem ocorrer, o que pode alterar a relação risco-benefício dos medicamentos o suficiente para exigir uma ação regulatória. Eventos adversos são agravos à saúde que podem surgir durante o tratamento com um produto farmacêutico, os quais, no período de pós-comercialização do medicamento, podem requerer um aumento significativo de cuidados de saúde e resultar em danos desnecessários aos pacientes, muitas vezes fatais. Portanto, o quanto antes, a descoberta de EA no período de pós-comercialização é um objetivo principal do sistema de saúde. Alguns países possuem sistemas de vigilância farmacológica responsáveis pela coleta de relatórios voluntários de EA na pós-comercialização, mas estudos já demonstraram que, com a utilização de redes sociais, pode-se conseguir um número maior e mais rápido de relatórios. O objetivo principal deste projeto é construir um sistema totalmente automatizado que utilize o Twitter como fonte para encontrar EA novos e já conhecidos e fazer a análise estatística dos dados obtidos. Para isso, foi construído um sistema que coleta, processa, analisa e avalia tweets em busca de EA, comparando-os com dados da Agência Americana de Controle de Alimentos e Medicamentos (FDA) e do padrão de referência construído. Nos resultados obtidos, conseguimos encontrar EA novos e já existentes relacionados ao medicamento doxiciclina, o que demonstra que o Twitter, quando utilizado em conjunto com outras fontes de dados, pode ser útil para a farmacovigilância.

Durante el período de poscomercialización, cuando grandes poblaciones consumen medicamentos durante períodos más prolongados de tiempo, se pueden producir eventos adversos (EA) inesperados, lo que puede alterar la relación riesgo-beneficio de los medicamentos. Esta situación es suficiente para exigir una acción regulatoria. Los EA son agravios a la salud que pueden surgir durante el tratamiento con un producto farmacéutico, los cuales, durante el período de poscomercialización del medicamento, pueden requerir un aumento significativo de cuidados de salud y resultar en lesiones innecesarias para los pacientes, muchas veces fatales. Por lo tanto, el hallazgo anticipado de EA durante el período de poscomercialización es un objetivo primordial del sistema de salud. Algunos países cuentan con sistemas de vigilancia farmacológica, responsables de la recogida de informes voluntarios de EA durante la poscomercialización, pero algunos estudios ya demostraron que, con la utilización de las redes sociales, se puede conseguir un número de informes mayor y más rápido. El objetivo principal de este proyecto es construir un sistema totalmente automatizado que utilice Twitter como fuente para encontrar nuevos EA y ya conocidos, además de realizar un análisis estadístico de los datos obtenidos. Para tal fin, se construyó un sistema que recoge, procesa, analiza y evalúa tweets en búsqueda de eventos adversos, comparándolos con datos de la Agencia Americana de Control de Alimentos y Medicamentos (FDA) y del estándar de referencia construido. En los resultados obtenidos, conseguimos encontrar nuevos eventos adversos y ya existentes, relacionados con el medicamento doxiciclina, lo que demuestra que Twitter, cuando es utilizado junto a otras fuentes de datos, puede ser útil para la farmacovigilancia.

During the post-marketing period, when medicines are used by large population contingents and for longer periods, unexpected adverse events (AE) can occur, potentially altering the drug's risk-benefit ratio enough to demand regulatory action. AE are health problems that can occur during treatment with a pharmaceutical product, which in the drug's post-marketing period can require a significant increase in health care and result in unnecessary and often fatal harm to patients. Therefore, a key objective for the health system is to identify AE as soon as possible in the post-marketing period. Some countries have pharmacovigilance systems responsible for collecting voluntary reports of post-marketing AE, but studies have shown that social networks can be used to obtain more and faster reports. The current project's main objective is to build a totally automated system using Twitter as a source to detect both new and previously known AE and conduct the statistical analysis of the resulting data. A system was thus built to collect, process, analyze, and assess tweets in search of AE, comparing them to U.S. Food and Drug Administration (FDA) data and the reference standard. The results allowed detecting new and existing AE related to the drug doxycycline, showing that Twitter can be useful in pharmacovigilance when employed jointly with other data sources.

Reacciones adversas causadas por quimioprofilaxis con doxiciclina / Adverse reactions caused by chemoprophylaxis with doxicicline

Se realizó un estudio descriptivo y prospectivo de 86 trabajadores del Puerto Guillermón Moncada de Santiago de Cuba, quienes recibieron tratamiento quimioprofiláctico con doxiciclina y presentaron reacciones adversas asociadas a dicho tratamiento, en noviembre del 2015, con vistas a caracterizarles y determinar la relación de causalidad existente entre la administración del medicamento, la aparición de efectos indeseables y las posibles interacciones farmacológicas. En esta serie, las reacciones adversas resultaron leves y no graves; las relaciones de causalidad, definitivas en la mayoría de los afectados (65,1 por ciento), aunque se determinaron algunas como probables y posibles, en tanto, las reacciones más frecuentes se presentaron en la esfera gastrointestinal

A descriptive and prospective study of 86 workers from Guillermón Moncada Port was carried out in Santiago de Cuba. They received chemoprophylactic treatment with doxicicline and presented adverse reactions associated with this treatment, in November, 2015, aimed at characterizing them and determining the relationship of causation existing between the administration of medication, emergence of undesirable effects and possible pharmacological interactions. In this series, the adverse reactions were light and no severe; the causation relationships, were definitive in most of the affected patients (65.1 percent), although some were determined as probable and possible, while, the most frequent reactions were presented in the gastrointestinal sphere

Doxiciclina em pacientes com linfangioleiomiomatose: biomarcadores e resposta funcional pulmonar / Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response

OBJETIVO: Avaliar o bloqueio da metaloproteinase da matriz (MMP)-2 e da MMP-9 e a variação do VEF1 em pacientes com linfangioleiomiomatose (LAM) após o uso de doxiciclina, um conhecido inibidor de MMP, durante 12 meses. MÉTODOS: Ensaio clínico aberto de braço único no qual as pacientes com diagnóstico de LAM receberam doxiciclina (100 mg/dia) durante 12 meses. Elas foram submetidas a prova de função pulmonar completa, teste de caminhada de seis minutos, avaliação da qualidade de vida e coleta de amostras séricas e urinárias para dosagem de MMP-2, MMP-9 e VEGF-D antes do início do tratamento com doxiciclina e após 6 e 12 meses de tratamento. RESULTADOS: Trinta e uma pacientes com LAM receberam doxiciclina durante 12 meses. Embora tenha havido um bloqueio efetivo da MMP-9 urinária e da MMP-2 sérica após o tratamento, os níveis séricos de MMP-9 e VEGF-D permaneceram estáveis. Com base na resposta à doxiciclina (determinada pela variação do VEF1), as pacientes foram divididas em dois grupos: respondedoras (doxi-R; n = 13) e não respondedoras (doxi-NR; n = 18). As pacientes com alterações espirométricas leves apresentaram melhor resposta à doxiciclina. Os efeitos colaterais mais comuns foram epigastralgia, náusea e diarreia, todos de leve intensidade. CONCLUSÕES: Em pacientes com LAM, o tratamento com doxiciclina resulta em um bloqueio eficaz das MMP, além de melhorar a função pulmonar e a qualidade de vida daqueles com doença menos grave. No entanto, esses benefícios não parecem estar relacionados ao bloqueio das MMP, o que sugere um mecanismo de ação diferente. (Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]).

OBJECTIVE: To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months. METHODS: An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline. RESULTS: Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre- and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV1), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea. CONCLUSIONS: In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action. (Brazilian Registry of Clinical Trials - ReBEC; identification number RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]).

Esofagitis inducida por doxiciclina: reporte de un caso clínico / Doxycycline-induced esophagitis: a case report

La esofagitis asociada a ingesta de medicamentos es una complicación poco frecuente. Su real incidencia es subestimada debido a que es una patología autolimitada y no siempre diagnosticada. Presentamos el caso de una mujer de 17 años que consulta por dolor a nivel de tercio medio del tórax que aparece después de una semana de consumo de doxiciclina. El diagnóstico se certificó mediante endoscopia, se indicó la suspensión del antibiótico y la administración de ranitidina por 7días. La paciente se hizo asintomática al tercer día de suspensión del fármaco y la endoscopia de control realizada 45 días después fue normal.

Esophagitis due to pill ingestion is an uncommon condition. The real incidence is underestimated because it is usually a self limited disorder and the diagnosis is not always established. We report a case of a 17 years old female presenting with an acute onset of pain in the middle chest one week after consumption of doxycycline. Endoscopy confirmed the diagnosis. The antibiotic was withdrawned and ranitidine was administered for seven days. The patient was asymptomatic at the third day of treatment and a control endoscopy at day 45 was normal.

Uso de antimicrobianos locais em periodontia: uma abordagem crítica / Use of local antimicrobials in periodontics: A critical approach

A presença da placa bacteriana representa o principal fator etiológico envolvido na iniciação e progressão da doença periodontal inflamatória. O tratamento instituído para esta patologia baseia-se essencialmente na eliminação dos patógenos periodontais, através do debridamento mecânico. Entretanto, nem sempre a raspagem e alisamento radicular promovem resultados clínicos satisfatórios, guiando o profissional a buscar meios alternativos para este tratamento. Neste sentido surgiram os antimicrobianos de ação local, sendo atualmente empregados: gel de metronidazol, chip de clorexidina, fibra de tetraciclina, esferas de minociclina e gel de doxiciclina Diversos relatos na literatura sustentam o emprego desses dispositivos e comprovam a sua eficácia clínica.No entanto, aspectos como custo e acessibilidade vêm sendo discutidos a fim de avaliar a real aplicabilidade.O objetivo desta revisão de literatura é fazer uma abordagem crítica a respeito da utilização de antimicrobianos locais no tratamento da doença periodontal enfatizando as suas indicações, vantagens, desvantagens, custo, viabilidade clínica e eficácia terapêutica.

Doxycycline-induced esophagitis

Esophageal ulceration occasionally occurs in patients taking doxycycline capsules or tablets. We report two patients who develop acute esophageal ulceration after ingestion of doxycycline capsules for Acne vulgaris. Despite extensive investigation, no evidence of other causes was found. The ulcers are postulated to result from close contact between the capsules and the esophageal mucosa. We show the endoscopic image of the lesion, symptomatology, diagnosis, treatment, and prevention of doxycycline-induced esophageal lesions

A Sporadic Outbreak of Human Brucellosis in Korea

Eleven cases of human brucellosis occurred among livestock workers and a veterinarian who lived and worked in a rural area around Jeongeup City, Jeollabuk-Do, Korea from February 2003 to August 2003. Eight of the patients had taken care of Korean native cattle that were infected with bovine brucellosis and had already been slaughtered. Two of the patients had taken care of dairy cattle, and one case was a veterinarian who acquired the disease through an accidental contact with infected cattle while assisting in calf delivery. Eleven cases were identified by serologic work ups and four cases were identified via positive blood cultures. This study shows that the Republic of Korea is no longer free of human brucellosis, Brucella abortus biotype 1. We reviewed the patients' characteristics and serologic data during the oneyear follow up period, and we also discuss on the efficacy and side effects of the rifampin and doxycyline regimen used for the treatment of human brucellosis.

Doxycycline in the treatment of rheumatoid arthritis--a pilot study.

OBJECTIVE: To assess the efficacy and safety of doxycycline as a disease modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA) and compare it with methotrexate, a standard DMARD. MATERIAL AND METHODS: A single (assessor) blind prospective study with 15 patients of RA randomized to doxycycline and 14 to methotrexate. Baseline disease characteristics were similar in both groups. RESULTS: All disease activity measures studied viz. tender and swollen joint counts, physician and patient global assessment, visual analogue pain scale, health assessment questionnaire and ESR improved in both the treatment groups after six months of treatment. The difference between doxycycline and methotrexate was not statistically significant. No major side effects necessitating drug withdrawal were reported from either group. The side effects were few and mostly gastrointestinal. CONCLUSION: Doxycycline is a safe disease modifying drug in RA whose effect is sustained at six months. It compared favourably with methotrexate over a six month follow up.

Prospective evaluation of medication-induced esophageal injury and its relation to esophageal function.

BACKGROUND: Few prospective studies are available on the incidence of medication-induced esophageal injury (MIEI). AIMS: To prospectively study the occurrence of MIEI with indomethacin and doxycycline and the predictive factors for its development. METHODS: In an operator-blinded study, 51 patients (age 16-65 y) requiring indomethacin (n = 24) or doxycycline (27) underwent symptom evaluation, endoscopy and scintigraphy before and after 7 days of therapy. MIEI was defined as de novo occurrence or worsening of pre-existing esophagitis or development of esophageal ulcer. RESULTS: Pre-therapy endoscopy was normal in 32 patients and revealed esophagitis in 19 (grade I--11, grade II--8). Post-therapy, 16 patients developed esophageal symptoms, which appeared earlier with doxycycline (2.0 [0.8] vs 4.1 [1.7] days, p = 0.016). MIEI developed in 23 patients--de novo esophagitis in 16, worsening of esophagitis in 6; 5 patients developed ulcer. Seven of 12 patients with hiatus hernia developed MIEI. Presence of pre-therapy gastroesophageal reflux disease did not predict MIEI. There was no difference in pre- or post-therapy transit values between patients with and without MIEI; patients who developed ulcers had significantly slower esophageal transit (p < 0.05). There was no difference in esophageal transit or occurrence of MIEI between patients who received indomethacin or doxycycline; however, 5 of 8 patients with hiatus hernia who received doxycycline developed MIEI (p = 0.02; relative risk 3.96 [CI 1.2-12.7]). CONCLUSIONS: 40% of patients receiving doxycycline or indomethacin developed MIEI; 10% developed ulcers. Hiatus hernia increased the risk for MIEI.

Ulceras esofágicas inducidas por doxiciclina / Doxycycline induced esophageal ulcers

Las tetraciclinas están descritas como antibióticos que suelen producir úlceras esofágicas. Objetivo. Ver el comportamiento de este tipo de úlceras, así como la respuesta al manejo con sucralfato. Método. Es un estudio retrospectivo de los últimos dos años donde se revisaron los casos de odinofagia y disfagia sometidos a endoscopia con antecedentes de ingesta reciente de doxiciclina. Todos fueron tratados suspendiendo la droga, mientras la gran mayoría recibieron tratamiento adicional con sucralfato 1 g cada ocho horas. Resultados. Once pacientes tuvieron como indicación: enfermedad pélvica inflamatoria, acné, infecciones urinarias y respiratorias. El síntoma más común fue odinofagia, presentándose aproximadamente 6 días después de iniciado el tratamiento con varios factores contribuyentes bien comprobados como ingesta antes de acostarse y con poco líquido. Las úlceras se caracterizaron por ser múltiples y localizadas principalmente en el tercio medio. La sintomatología en general cedió 3.7 días después de suspender los medicamentos, mientras aquellos con sucrafalto no mostraron menor duración de los síntomas. Conclusiones. Debemos ser conscientes de la inducción de úlceras por estos medicamentos, basando su tratamiento en la suspensión del antibiótico, recordando que el sucralfato puede ser parte del tratamiento ya que ha demostrado su adherencia a úlceras y lesiones esofágicas, aunque su uso no ha demostrado significancia clínica. Por ende debemos explicar las medidas prevención, como tomarlas con suficiente volumen de agua, en posición, como tomarlas con suficiente volumen de agua, en posición supina y tener precaución especial en ancianos y pacientes con patología anatómica y/o de motilidad esofágica

Doxycline-induced esophageal ulcerations

Over a period of six years 16 patients presented to Dr. Al Mofarreh's polyclinic with drug-induced esophageal ulcerations. One patient had esophagitis without ulcerations and two patients, who declined endoscopy were not included in this analyzis. The mean age of the remaining 13 patients was 28.92 +/- 10.39 years. The mean ulcers number was 3.69 +/- 2.76. The ulcers were located at the mid-esophagus, 29.23 +/- 3.94 cm from the incisors teeth. Odynophagea, retrosternal pain and dysphagea in 13 [100%], 12[92%] and 9[69%] patients, respectively, were the most frequent presenting symptoms. All patients took a doxycycline preparation at bed time with little water. The mean elapse between the drug intake and endoscopy was 7.85 +/- 9.96 days. The symptoms resolved within a maximum of one week of antireflux treatment despite the continuation of doxycycline therapy in three patients with brucellosis. The current data confirmed the role of oral doxycycline intake, the timing and the amount of concurrent fluid in the etiology of esophageal ulcerations

Liquen plano en un niño: reporte de un caso / Lichen planus in a child: report of a case

Este es el reporte de un caso clínico de liquen plano en cara dorsal de lengua de un niño de 5 años de edad. Es interesante señalar que existen pocos reportes sobre estas enfermedades en niños, la mayor referencia es de lesiones en piel. En este caso, la aparición de esta lesión es posible que esté relacionada con la administración de doxicilina.

Tetracycline-induced esophageal ulcer: a condition that probably more common than it appears to be.

Ten cases of tetracycline derivatives related drug induced esophageal ulceration were described. Five cases were due to minocycline and another five were due to doxycycline. Recumbent posture after drug ingestion was one of the predisposing factors. Odynophagia was the main symptom but may not be the presenting symptom. The diagnosis was easily confirmed by endoscopy. Single-contrast barium study was not sensitive for the demonstration of the esophageal ulcers. The recommended treatment includes cessation of the offending drug and symptomatic treatment. All recovered without any sequela within 3 to 11 days. The most important measure to prevent this condition is to instruct patients to take drugs in the upright position with at least 100 ml of water.

Medication induced esophageal injury.

Five patients of medication-induced esophageal injury are reported. A history of ingestion of medications preceding the onset of dysphagia was obtained in all patients. Endoscopy revealed localised mucosal ulceration with surrounding edematous mucosa at the level of the aortic arch in four, and in the retro-cardiac esophagus in one patient. The medications involved were sustained release potassium chloride, doxycycline, ibuprofen, and an unidentified antibiotic and antihypertensive (one each). Healing of the esophageal ulcers was confirmed in all the patients by endoscopy.

Lesión esofágica por drogas / Esophageal lesion by drugs

Se presentan dos casos de daño esofágico producido por drogas de prescripción habitual en la práctica médica. Se realiza una revisión de las diversas drogas asociadas a lesiones esofágicas describiendo los factores predisponentes, la sintomatología, los hallazgos semiológicos, la fisiopatogenia, los exámenes complementarios, las complicaciones, la evolución y las medidas que deben adoptarse para prevenir esta patología