Uterine rescue in high-risk gestational trophoblastic neoplasia treated with ema-co by uterine arteries embolization due to arteriovenous malformations / Resgate uterino em neoplasia trofoblástica gestacional de alto risco tratada com EMA-CO por embolização de artérias uterinas devido a malformações arteriovenosas

Abstract Complete hydatidiform mole (CHM) is a rare type of pregnancy, in which 15 to 20% of the cases may develop into gestational trophoblastic neoplasia (GTN). The diagnostic of GTN must be done as early as possible through weekly surveillance of serum hCG after uterine evacuation.We report the case of 23-year-old primigravida, with CHM but without surveillance of hCG after uterine evacuation. Two months later, the patient presented to the emergency with vaginal bleeding and was referred to the Centro de Doenças Trofoblásticas do Hospital São Paulo. She was diagnosed with high risk GTN stage/score III:7 as per The International Federation of Gynecology and Obstetrics/World Health Organization (FIGO/WHO). The sonographic examination revealed enlarged uterus with a heterogeneous mass constituted of multiple large vessels invading and causing disarrangement of the myometrium. The patient evolved with progressive worsening of vaginal bleeding after chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) regimen. She underwent blood transfusion and embolization of uterine arteries due to severe vaginal hemorrhage episodes, with complete control of bleeding. The hCG reached a negative value after the third cycle, and there was a complete regression of the anomalous vascularization of the uterus as well as full recovery of the uterine anatomy. The treatment in a reference center was essential for the appropriate management, especially regarding the uterine arteries embolization trough percutaneous femoral

Resumo Mola hidatiforme completa (MHC) é um tipo raro de gravidez, na qual 15 a 20% dos casos podem desenvolver neoplasia trofoblástica gestacional (NTG). O diagnóstico de NTG deve ser feito o mais cedo possível, pelo monitoramento semanal do hCG sérico após esvaziamento uterino. Relatamos o caso de uma paciente primigesta, de 23 anos de idade, com MHC, sem vigilância de hCG após esvaziamento uterino. Dois meses depois, a paciente compareceu na emergência com sangramento vaginal, sendo encaminhada ao Centro de Doenças Trofoblásticas do Hospital São Paulo, onde foi diagnosticada com NTG de alto risco, estádio e score de risco III:7 de acordo com a The International Federation of Gynecology and Obstetrics/Organização Mundial de Saúde (FIGO/OMS). O exame ultrassonográfico revelou útero aumentado com uma massa heterogênea constituída pormúltiplos vasos volumosos invadindo e desestruturando o miométrio. A paciente evoluiu com piora progressiva do sangramento vaginal após quimioterapia com o regime etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO). Ela foi submetida a transfusão de sangue e embolização das artérias uterinas devido aos episódios graves de hemorragia vaginal, com completo controle do sangramento. O hCG atingiu valor negativo após o terceiro ciclo, havendo regressão completa da vascularização uterina anômala, assim como recuperação da anatomia uterina. O tratamento em um centro de referência permitiu o manejo adequado, principalmente no que se refere à embolização das artérias uterinas através da punção percutânea da artéria femoral, que foi crucial para evitar a histerectomia, permitindo a cura da NTG e a manutenção da vida reprodutiva.

Antimicrobial activity of actinomycetes and characterization of actinomycin-producing strain KRG-1 isolated from Karoo, South Africa

In the present study we reported the antimicrobial activity of actinomycetes isolated from aridic soil sample collected in Karoo, South Africa. Eighty-six actinomycete strains were isolated and purified, out of them thirty-four morphologically different strains were tested for antimicrobial activity. Among 35 isolates, 10 (28.57%) showed both antibacterial and antifungal activity. The ethyl acetate extract of strain KRG-1 showed the strongest antimicrobial activity and therefore was selected for further investigation. The almost complete nucleotide sequence of the 16S rRNA gene as well as distinctive matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry (MALDI-TOF/MS) profile of whole-cell proteins acquired for strain KRG-1 led to the identification of Streptomyces antibioticus KRG-1 (GenBank accession number: KX827270). The ethyl acetate extract of KRG-1 was fractionated by HPLC method against the most suppressed bacterium Staphylococcus aureus (Newman). LC//MS analysis led to the identification of the active peak that exhibited UV-VIS maxima at 442 nm and the ESI-HRMS spectrum showing the prominent ion clusters for [M-H2O+H]+ at m/z 635.3109 and for [M+Na]+ at m/z 1269.6148. This information could be assigned to chromopeptide lactone antibiotic - actinomycin. Our results suggest that unexplored soils could be an interesting source for exploring antibacterial secondary metabolites.

Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women / Tratamento da neoplasia trofoblástica gestacional de baixo-risco, comparando aplicação quinzenal de oito dias de Metotrexato com ácido folínico versus Actinomicina D em bolo, em mulheres brasileiras

PURPOSE: To compare two single-agent chemotherapy (ChT) regimens evaluating, in first-line treatment, response and side effects and, in final single-agent treatment, the outcomes, among Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN), according to International Federation of Gynecology and Obstetrics (FIGO) 2002. METHODS: Retrospective analysis of two concurrent cohorts with 194 low-risk GTN patients: from 1992 to 2012, as first-line treatment, 115 patients received 4 intramuscular doses of methotrexate alternated with 4 oral doses of folinic acid (MTX/FA) repetead every 14 days and, since 1996, 79 patients received an endovenous bolus-dose of actinomycin D (Act-D), biweekly. At GTN diagnosis, patient opinion was taken into consideration when defining the initial single-agent ChT regimen, and when there was resistance or toxicity to one regimen, the other drug was used preferentially. This study was approved by the Irmandade da Santa Casa de Misericórdia de Porto Alegre Ethical Committee. RESULTS: Both groups were clinically similar (p>0.05). In first-line treatments, frequency of complete response was similar (75.7% with MTX/FA and 67.1% with bolus Act-D); the number of ChT courses -median 3 (range: 1-10) with MTX/FA and 2 (range: 1-6) with bolus Act-D - and the time to remission -median 9 weeks (range: 2-16) with MTX/FA and 10 weeks (range: 2-16) with bolus Act-D) - were not different between the groups. In both groups, first-line side effects frequency were high but intensity was low; stomatitis was higher with MTX/FA (p<0.01) and nausea and vomit with Act-D (p<0.01). Final single-agent ChT responses were high in both groups (94.8% with MTX/FA and 83.5% with bolus Act-D; p<0.01) and 13% higher in the group initially treated with MTX/FA. Rates of hysterectomy and of GTN recurrence were low and similar. No patient died due to GTN. CONCLUSION: The two regimens had similar first-line ChT response. ...

OBJETIVO: Em mulheres brasileiras com neoplasia trofoblástica gestacional (NTG) de baixo-risco, de acordo com a Federação Internacional de Ginecologia e Obstetrícia (FIGO) 2002, comparar dois regimes de quimioterapia (Qt) por agente único avaliando resposta e efeitos colaterais no tratamento de primeira linha, e a eficácia no tratamento final por agente único de Qt. MÉTODOS: Análise retrospectiva de duas coortes concorrentes com 194 pacientes com NTG de baixo risco: de 1992 a 2012; como primeira linha, 115 pacientes receberam 4 doses intramusculares de metotrexato alternado com 4 doses orais de ácido folínico (MTX/FA) repetidos a cada 14 dias e, desde 1996, 79 pacientes receberam quinzenalmente dose em bolo de actinomicina D (Act-D) por via endovenosa. No momento do diagnóstico da NTG, a opinião da paciente foi levada em consideração para definir o regime de Qt por agente único inicial e, quando havia resistência ou toxicidade a um regime, o outro fármaco era usado preferentemente. Este estudo foi aprovado pelo Comitê de Ética da Irmandade da Santa Casa de Misericórdia de Porto Alegre. RESULTADOS: Ambos os grupos eram clinicamente semelhantes (p>0,05). Nos tratamentos de primeira linha, a frequência de resposta completa foi semelhante (75,7% com MTX/FA e 67,1% com Act-D em bolo); não houve diferença entre os grupos quanto ao número de séries de Qt - mediana 3 (intervalo: 1-10) com MTX/FA e 2 (intervalo: 1-6) com Act-D em bolo - e ao tempo para remissão - mediana 9 semanas (intervalo: 2-16) com MTX/FA e 10 semanas (intervalo: 2-16) com Act-D em bolo. Em ambos os grupos, foi elevada a frequência de efeitos colaterais no tratamento de primeira linha, mas com intensidade baixa; estomatite foi mais frequente com MTX/FA (p<0.01) e náuseas e vômitos com Act-D (p<0.01). A resposta final à Qt por agente único foi alta nos dois grupos (94,8% com MTX/FA e 83,5% com Act-D em bolo; p<0,01) e 13% maior no grupo inicialmente tratado com ...

Production of actinomycin-D by the mutant of a new isolate of Streptomyces sindenensis / Produção de actinomicina-D por um mutante de uma nova cepa de Streptomyces sindenensis

An actinomycin-D producing strain was isolated from soil and characterized as Streptomyces sindenensis. The culture was subjected to UV irradiation and a mutant with 400 percent higher actinomycin-D production was isolated (400 mg/l-1 as compared to 80 mg/l-1 produced by the parent). Production medium was optimized and antibiotic yield with the mutant was enhanced to 850 mg/l-1 which is 963 percent higher as compared with the parent.

Uma cepa produtora de actinomicina-D foi isolada de solo e caracterizada como Streptomyces sindenensis. A cultura foi submetida à radiação UV, e um mutante capaz de produzir 400 por cento mais actinomicina-D foi isolado (400mg/L comparado a 80mg/L produzido pela cepa parental). O meio de produção do antibiótico foi otimizado e o rendimento aumentou para 850 mg/L, ou seja, 963 por cento mais alto que a cepa parental.

Intracaval and intracardiac extension of Wilms' tumor: the influence of preoperative chemotherapy on surgical morbidity

OBJECTIVES: The aim of this retrospective study is to compare surgical complications and long-term survival in children with Wilms' tumor (WT) and tumor thrombus receiving or not preoperative chemotherapy MATERIALS AND METHODS: Review of the charts of 155 children with WT treated between 1983 and 2005, and analysis of 16/155 (10.3 percent) children with WT who presented cavoatrial tumor extension, being 8/16 IVC and 8/16 atrial thrombus RESULTS: Median age was 54 months. 2/16 had cardiac failure as the first symptom. 11/16(7 IVC and 4 atrial extension) (67 percent) were submitted to preoperative chemotherapy with vincristine plus actinomycin D, and 5/16(1 IVC and 4 atrial) (33 percent) underwent initial nephrectomy and thrombus resection. So, 11 patients were submitted to preoperative VCR/ACTD and 2/11 (18.1 percent) had complete regression of the thrombus, 6/11(54.5 percent) partial regression and 3/11 (27 percent) had no response. Among the partial responders, nephrectomy with thrombus removal was performed in all, including one patient with previous intracardiac involvement, without extracorporeal circulation procedures. In two of the three non-responders, cardiopulmonary bypass was necessary for thrombus removal. There were no surgical related deaths. Long-term survival is 91 percent in the group submitted to preoperative chemotherapy and 100 percent in the group who had surgery as first approach CONCLUSION: Preoperative chemotherapy was able to reduce thrombus extension in 8/11 (73 percent) treated patients and cardiopulmonary bypass was avoided in 2 patients with atrial thrombus. Surgical resection of tumor and thrombus was successful in all cases, receiving or not preoperative chemotherapy and overall survival was similar in both groups.

Tratamento da neoplasia trofoblástica gestacional resistente ao metotrexate / Treatment of gestational trophoblastic neoplasia resistant to methotrexate

O presente estudo tem como objetivo revisar o tratamento da neoplasia trofoblástica gestacional resistente à quimioterapia primária de acordo com as proposições dos centros de referência relatadas na literatura, e também o consenso da FIGO (2003). Neoplasia trofoblástica gestacional é extremamente responsiva à quimioterapia apropriada, no entanto o fenômeno da quimiorresistência é observado em 10 a 30 porcento dos casos. Constatada a resistência ao metotrexate, deve ser feito o reestadiamento da paciente segundo padronização da FIGO 2000, e sendo de baixo risco, o tratamento recomendado é agente único alternativo, actinomicina-D. Se houver resistência à segunda linha de agente único de quimioterapia, indica-se tratamento com quimioterapia combinada, de acordo com o protocolo de cada serviço. A histerectomia é opção oferecida à paciente com neoplasia trofoblástica e quimiorresistência, entretanto é necessária cuidadosa investigação de metástases antes da cirurgia. O encaminhamento antecipado para centros de referência otimiza o tratamento das pacientes, possibilitando abordagem multidisciplinar, identificação precoce de resistência e mudança rápida para novo protocolo de quimioterapia.

Genital Sensory Stimulation Shifts Estradiol Intraoviductal Signaling from Nongenomic to Genomic Pathways, Independently from Prolactin Surges

Estradiol (E2) accelerates oviductal egg transport through nongenomic pathways involving oviductal protein phosphorylation in non-mated rats, and through genomic pathways in mated rats. Here we investigated the ability of cervico-vaginal stimulation (CVS) to switch the mode of action of E2 in the absence of other male-associated components. Pro-estrous rats were subjected to CVS with a glass rod and 12 hours later were injected subcutaneously with E2 and intrabursally with the RNA synthesis inhibitor Actinomycin D or the protein phosphorylation inhibitor H-89. The number of eggs in the oviduct, assessed 24 h later, showed that Actinomycin D, but not H-89 blocked the E2-induced egg transport acceleration. This clearly indicates that CVS alone, without other mating-associated signals, is able to shift E2 signaling from nongenomic to genomic pathways. Since mating and CVS activate a neuroendocrine reflex that causes iterative prolactin (PRL) surges, the involvement of PRL pathway in this phenomenon was evaluated. Prolactin receptor mRNA and protein expression in the rat oviduct was demonstrated by RT-PCR and Western blot, but their levels were not different on day 2 of the cycle (C2) or pregnancy (P2). Activated ST AT 5a/b (phosphorylated) was detected by Western blot on P2 in the ovary, but not in the oviduct, showing that mating does not stimulate this PRL signalling pathway in the oviduct. Other rats subjected to CVS in the evening of pro-estrus were treated with bromoergocriptine to suppress PRL surges. In these rats, H-89 did not block the E2-induced acceleration of egg transport suggesting that PRL surges are not essential to shift E2 signaling pathways in the oviduct. We conclude that CVS is one of the components of mating that shifts E2 signaling in the oviduct from nongenomic to genomic pathways, and this effect is independent of PRL surges elicited by mating.

Comparative quantification of umbilical cord blood CD34+ and CD34+ bright cells using the ProCount™-BD and ISHAGE protocols

The total number of CD34+ cells is the most relevant clinical parameter when selecting human umbilical cord blood (HUCB) for transplantation. The objective of the present study was to compare the two most commonly used CD34+ cell quantification methods (ISHAGE protocol and ProCount™ - BD) and analyze the CD34+ bright cells whose 7-amino actinomycin D (7AAD) analysis suggests are apoptotic or dead cells. Twenty-six HUCB samples obtained at the Placental Blood Program of New York Blood Center were evaluated. The absolute numbers of CD34+ cells evaluated by the ISHAGE (with exclusion of 7AAD+ cells) and ProCount™ (with exclusion of CD34+ bright cells) were determined. Using the ISHAGE protocol we found 35.6 ± 19.4 CD34+ cells/æL and with the ProCount™ method we found 36.6 ± 23.2 CD34+ cells/æL. With the ProCount™ method, CD34+ bright cell counts were 9.3 ± 8.2 cells/æL. CD34+ bright and regular cells were individually analyzed by the ISHAGE protocol. Only about 1.8 percent of the bright CD34+ cells are alive, whereas a small part (19.0 percent) is undergoing apoptosis and most of them (79.2 percent) are dead cells. Our study showed that the two methods produced similar results and that 7AAD is important to exclude CD34 bright cells. These results will be of value to assist in the correct counting of CD34+ cells and to choose the best HUCB unit for transplantation, i.e., the unit with the greatest number of potentially viable stem cells for the reconstitution of bone marrow. This increases the likelihood of success of the transplant and, therefore, the survival of the patient.

Obstrução urinária aguda por rabdomiossarcoma pélvico / Acute urinary obstruction due to pelvic rhabdomyosarcoma

Os autores relatam um caso raro de obstrução urinária aguda por rabdomiossarcoma pélvico envolvendo a próstata em uma criança de quatro anos e seis meses de idade. São comentados as características desses tumores, as formas de apresentação clínica, os aspectos diagnósticos por imagem — ultra-som, cistografia e tomografia computadorizada —, o tratamento com poliquimioterapia e o prognóstico.

The authors report a rare case of acute urinary obstruction caused by pelvic rhabdomyosarcoma in a 4-year-old children. The diagnosis aspects for imaging e some therapeutic considerations are related.

Tumores germinativos do ovário: conduta / Germ cell ovary tumors: conduct

O artigo apresenta uma revisão sobre o manejo de tumores malignos de células germinativas do ovário, com especial atenção para o tratamento cirúrgico e adjuvante. Adicionalmente, discute a repercussão desta conduta no futuro reprodutivo e endocrinológico das pacientes.

This article reviews ovary germ cells malignant tumors management with special attention to surgical and adjuvant treatments. In addition, the consequence of these procedures on patient's reproduction and endocrinology are discussed.

Cáncer de testículo / Testicular cancer

Introducción: El cáncer de testículo es en la actualidad un cáncer de gente joven, si se detecta tempranamente es factible su curación con distintas alternativas. Material y métodos. Se revisaron los expedientes clínicos de 42 pacientes que presentaron cáncer de testículo durante un período de 5 años. Resultados. La edad más afectada fue la comprendida entre 21-35 años. La manifestación clínica más frecuente fue el crecimiento testicular en 42 pacientes (100/100), seguido de dolor testicular en 10 casos (24/100). El tipo histológico más frecuente fue la variedad mixta (seminoma/carcinoma embrionario y seminoma/teratocarcinoma). El estadío I fue el más frecuente 13 casos (30/100). Se efectuó orquiectomía en todos los pacientes. Se realizaron 4 linfadenectomías retroperitoneales en pacientes que después de la administración de quimioterapia aún presentaban masa retroperitoneal residual comprobada por tomografía axial computarizada de abdomen. La respuesta al tratamiento fue favorable, con un número de 33 (78/100) pacientes vivos a la fecha. Se documentaron 9 (21.4) pacientes que fallecieron por complicaciones del cáncer los cuales estaban en estadío IV. Conclusiones. El cáncer de testículo es una patología frecuente en la consulta externa de Urología del Instituto Guatemalteco de Seguridad Social. El cuadro clínico es generalmente asintomático, pero su diseminación es rápida. La orquiectomía es el tratamiento de elección, y en los casos avanzados es de utilidad la quimioterapia y la radioterapia. La sobrevida fue del 92.8/100.

Absence of peripheral blood mononuclear cells priming in hemodialysis patients

As a consequence of the proinflammatory environment occurring in dialytic patients, cytokine overproduction has been implicated in hemodialysis co-morbidity. However, there are discrepancies among the various studies that have analyzed TNF-alpha synthesis and the presence of peripheral blood mononuclear cell (PBMC) priming in this clinical setting. We measured bioactive cytokine by the L929 cell bioassay, and evaluated PBMC TNF-alpha production by 32 hemodialysis patients (HP) and 51 controls. No difference in TNF-alpha secretion was observed between controls and HP (859 ± 141 vs 697 ± 130 U/10(6) cells). Lipopolysaccharide (5 æg/ml) did not induce any further TNF-alpha release, showing no PBMC priming. Paraformaldehyde-fixed HP PBMC were not cytotoxic to L929 cells, suggesting the absence of membrane-anchored TNF-alpha. Cycloheximide inhibited PBMC cytotoxicity in HP and controls, indicating lack of a PBMC TNF-alpha pool, and dependence on de novo cytokine synthesis. Actinomycin D reduced TNF-alpha production in HP, but had no effect on controls. Therefore, our data imply that TNF-alpha production is an intrinsic activity of normal PBMC and is not altered in HP. Moreover, TNF-alpha is a product of de novo synthesis by PBMC and is not constitutively expressed on HP cell membranes. The effect of actinomycin D suggests a putative tighter control of TNF-alpha mRNA turnover in HP. This increased dependence on TNF-alpha RNA transcription in HP may reflect an adaptive response to hemodialysis stimuli

Effect of actinomycin D on simian rotavirus (SA11) replication in cell culture

Rotaviruses are the major cause of viral diarrhea in humans and animals. Actinomycin D (Act D) is an antibiotic that intercalates DNA and therefore inhibits DNA-dependent transcription. The current study was carried out to assess the influence of Act D on the replication of simian rotavirus (SA11) in cell culture. Virus-infected MA-104 cell cultures were studied in the presence of Act D at concentrations of 1.25 and 2.5 æg/ml. Treatment of rotavirus-infected cells with 2.5 æg/ml Act D 48 h post-infection reduced the cytoplasmic metachromasia after staining with acridine orange by 25 percent. Viral RNA labeled with ³H-uridine in the presence of the drug was separated by polyacrylamide gel electrophoresis. Viral RNA replication was not affected by Act D, but increased ³H-uridine uptake was demonstrable by infected cells in the presence of the drug. This possibly was due to the inhibition of cellular RNA synthesis by Act D, which thus enhances incorporation of the radionuclide into the viral RNA. Act D reduced the number of infected cells presenting virus-specific fluorescence 48 h post-infection by more than 50 percent. These data suggest that Act D may have complexed with viral RNA and prevented newly synthesized mRNA from being translated, but may not have prevented early replication

Prevención de reestenosis post implante de stents coronarios / The restenosis prevention post coronary stent implantation

Los stent coronarios fueron grandes optimizadores de la angioplastia coronaria con balón. Los estudios stress, benestent 1 y 2 evidenciaron reducciones importantes en las tasas de reestenosis coronaria. El proceso de reestenosis fue afectado por los stents en el sentido de reducir el retroceso elástico precoz y el remodelamiento negativo, pero el proceso de hiperplasia neoíntimal sólo no fue modificado sino que exagerado. En el sentido de minimizar la hiperplasia debemos establecer formas de reducir la injuria durante el implante del stent, reducir el proceso inflamatorio, inhibir la migración y proliferación celular y favorecer el proceso de endotelización del stent. Varias opciones farmacológicas han sido discutidas y presentaremos los resultados con dichas drogas tales como: actinomocina, tacrolimus, taxol y sirolimus

A chemically defined medium for production of actinomycin D by Streptomyces parvulus / A chemically defined medium for production of actinomycin D by Streptomyces parvulus

Um meio quimicamente definido composto de D (+) FRUTOSE, L (-) treonina, K2HPO4, MgSO4.7H2O, ZnSO47H2O, CaCl2.2H2o, FeSO4.7H2O e água deionizada, foi desenvolvido para maximizar a síntese de actinomicina D pelo Streptomyces parvulus DAUFPE3124. o meio proposto resultou numa concentraçäo antibiótica máxima de 133mg/L enquanto que no meio inicial a produçäo antibiótica foi baixa, näo ultrapassando 43mg/L

Enfermedad trofoblástica gestacional (ETG) / Gestational trophoblastic disorders

La enfermedad trofoblástica gestacional es un espectro de neoplasias que se inician en el tejido trofoblástico placentario, luego de un proceso de fertilización anormal, e incluye al embarazo molar, la mola invasiva o corioadenoma destruens, el tumor trofoblástico de sitio placentario y el coriocarcinoma. Estas constituyen menos del 1 por ciento de las malignidades ginecológicas, pero es importante su reconocimiento dado su potencial de mortalidad y su alta curación si son tratadas tempranamente por centros especializados. El tratamiento del embarazo molar es la evacuación completa del útero. En el caso de los tumores malignos derivados del trofoblasto la decisión terapéutica es planeada en base al puntaje de riesgo desarrollado por el Charing Cross Hospital, adoptado por la OMS y modificado por la FIGO, clasificación que permite distinguir a los pacientes que requerirán un régimen de tratamiento más intensivo con múltiples medicamentos

Cara inchada of cattle, an infectious, apparently soil antibiotics-dependant periodontitis in Brazil: Review

The objective of this review on the investigation of "cara inchada" in cattle (CI), pursued over the last 30 years, was to elucidate the pathogenicity of the disease and come to proper conclusions on its etiology. CI has been widely considered to be of nutritional origin, caused primarily by mineral deficiency or imbalance. However, the disease consists of a rapidly progressive periodontitis, affecting the periodontal tissues at the level of the premolars and molars during the period of tooth eruption generally starting in young calves. The disease led to great economic losses for farmers in central-western Brazil, after the occupation of new land for cattle raising in the 1960s and 1970s. The lateral enlargement of the maxillary bones of affected calves gave the disease the popular name of "cara inchada", i.e., swollen or enlarged face. The enlargement was found to be due to a chronic ossifying periostitis resulting from the purulent alveolitis of CI. Black-pigmented non-saccharolytic Bacteroides melaninogenicus, always together with Actinomyces (Corynebacterium) pyogenes, were isolated in large numbers from the periodontal lesions. B. melaninogenicus could be isolated in small numbers also from the marginal gingiva of a few healthy calves maintained on CI-free farms. "In vitro"-assays showed that streptomycin and actinomycin, as well as the supernatants of cultivates of actinomycetes from soils of CI-prone farms, applied in subinhibitory concentrations to the bacteria tested, enhanced significantly (up to 10 times) the adherence of the black-pigmented B.melaninogenicus to epithelial cells of the bovine gingiva. The antibiotics are apparently produced in large quantities by the increased number of soil actinomycetes, including the genus Streptomyces, that develop when soil microflora are modified by cultivating virgin forest or "Cerrado" (tree-savanna) for the first time for cattle grazing. The epidemiology of CI now provides strong evidence that the ingestion with the forage of such antibiotics could possibly be an important determinant factor for the onset and development of this infectious periodontitis. The antibiotic enhanced adherence of B.melaninogenicus to the sulcus-epithelium of the marginal gingiva, is thought to allow it to colonize, form a plaque and become pathogenic...(au)