RESUMO
Ewing sarcoma is a rare aggressive malignant round cell tumor, primarily presenting in bone and soft tissues. This study presents two cases of this tumor in unusual locations, one in right colon which presented with intussusception and other in ovary which presented clinically as carcinoma ovary. Both the cases showed histomorphology of primitive round cell tumor with characteristic immunohistochemical profile and was confirmed on molecular analysis. We aim to highlight the importance of considering Ewing sarcoma in the differential diagnoses in these locations as they have dismal prognosis with no standard treatment modality.
Assuntos
Tumores Neuroectodérmicos Primitivos Periféricos , Sarcoma de Ewing , Colo/patologia , Feminino , Humanos , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Ovário/patologia , Prognóstico , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/patologiaRESUMO
Anti-M antibodies are usually of IgM, appear as cold agglutinins and are clinically insignificant. We are reporting two cases of anti-M in cases of solid tumors where the anti-M caused discrepancy in blood grouping, reacted in coombs phase of crossmatching. Anti-M in first case showed dosage effect. These antibodies can be clinical significant when detected in coombs phase, making M antigen negative coombs compatible unit transfusion imperative.
RESUMO
PURPOSE: We determined the effects of low androgens in the neonatal period on biomarkers of smooth muscle cell differentiation, Myh11 and Acta2, and on Pde5A expression in the penis. MATERIALS AND METHODS: One-day-old pups were treated daily with the gonadotropin-releasing hormone antagonist antide with or without dihydrotestosterone for 1 to 6 days. Tissues were collected at age day 7 and at adulthood at age 120 days. Penes were examined by quantitative reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry. Testes were assayed for the intratesticular testosterone and steroidogenic enzymes Cyp17α1 and StAR. RESULTS: Gonadotropin-releasing hormone antagonist exposure suppressed the neonatal testicular testosterone surge 70% to 80%. Quantitative reverse transcriptase-polymerase chain reaction revealed 80% to 90% reductions in Cyp17α1 and StAR protein, and 40% to 60% reductions in Myh11 and ACTA2 as a result of gonadotropin-releasing hormone antagonist compared to controls. Dihydrotestosterone co-administration mitigated these decreases. Western blot confirmed the Myh11 decrease at the protein level. Immunohistochemistry of Acta2 confirmed cavernous smooth muscle cell loss at the tissue level. Also, gonadotropin-releasing hormone antagonist exposure decreased Pde5a expression and dihydrotestosterone co-administration mitigated the decrease. Comparison of data between 2 parts of the penis body (corpora cavernosa and corpus spongiosum) showed that antagonist induced decreases in Myh11, Acta2 and Pde5a expression occurred only in the corpora cavernosa, implying that the latter is the target site of low androgen action. CONCLUSIONS: As evidenced by gonadotropin-releasing hormone antagonist induced suppression of the neonatal testosterone surge and reduced steroidogenesis, low androgens in the neonatal period altered gene expression of biomarkers of smooth muscle cell differentiation. This led to loss of cavernous smooth muscle cells and consequently to penile maldevelopment.
Assuntos
Androgênios/deficiência , Diferenciação Celular , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/biossíntese , Músculo Liso/citologia , Músculo Liso/fisiologia , Cadeias Pesadas de Miosina/biossíntese , Pênis/anormalidades , Pênis/crescimento & desenvolvimento , Actinas/biossíntese , Animais , Animais Recém-Nascidos , Biomarcadores , Regulação da Expressão Gênica , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
In the current study, ferritic stainless grades AISI 439 and AISI 444 were investigated as possible construction materials for machinery and equipment in the cane-sugar industry. Their performance in corrosive cane-sugar juice environment was compared with the presently used low carbon steel AISI 1010 and austenitic stainless steel AISI 304. The Tafel plot electrochemical technique was used to evaluate general corrosion performance. Microbiologically influenced corrosion (MIC) behaviour in sugarcane juice environment was studied. Four microbial colonies were isolated from the biofilms on the metal coupon surfaces on the basis of their different morphology. These were characterized as Brevibacillus parabrevis, Bacillus azotoformans, Paenibacillus lautus and Micrococcus sp. The results of SEM micrographs showed that AISI 439 and AISI 304 grades had suffered maximum localized corrosion. MIC investigations revealed that AISI 444 steel had the best corrosion resistance among the tested materials. However from the Tafel plots it was evident that AISI 1010 had the least corrosion resistance and AISI 439 the best corrosion resistance.
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Bactérias/classificação , Bactérias/isolamento & purificação , Saccharum/microbiologia , Aço Inoxidável/química , Bacillus/isolamento & purificação , Biofilmes , Brevibacillus/isolamento & purificação , Corrosão , Técnicas Eletroquímicas , Teste de Materiais , Micrococcus/isolamento & purificação , Paenibacillus/isolamento & purificação , Preparações de PlantasAssuntos
Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Exantema/induzido quimicamente , Antineoplásicos/uso terapêutico , Criança , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , GencitabinaRESUMO
Cavernous smooth muscle cells are essential components in penile erection. In this study, we investigated effects of estrogen exposure on biomarkers for smooth muscle cell differentiation in the penis. Neonatal rats received diethylstilbestrol (DES), with or without the estrogen receptor (ESR) antagonist ICI 182,780 (ICI) or the androgen receptor (AR) agonist dihydrotestosterone (DHT), from Postnatal Days 1 to 6. Tissues were collected at 7, 10, or 21 days of age. The smooth muscle cell biomarker MYH11 was studied in depth because microarray data showed it was significantly down-regulated, along with other biomarkers, in DES treatment. Quantitative real time-PCR and Western blot analyses showed 50%-80% reduction (P ≤ 0.05) in Myh11 expression in DES-treated rats compared to that in controls; and ICI and DHT coadministration mitigated the decrease. Temporally, from 7 to 21 days of age, Myh11 expression was onefold increased (P ≥ 0.05) in DES-treated rats versus threefold increased (P ≤ 0.001) in controls, implying the long-lasting inhibitory effect of DES on smooth muscle cell differentiation. Immunohistochemical localization of smooth muscle alpha actin, another biomarker for smooth muscle cell differentiation, showed fewer cavernous smooth muscle cells in DES-treated animals than in controls. Additionally, DES treatment significantly up-regulated Esr1 mRNA expression and suppressed the neonatal testosterone surge by 90%, which was mitigated by ICI coadministration but not by DHT coadministration. Collectively, results provided evidence that DES treatment in neonatal rats inhibited cavernous smooth muscle cell differentiation, as shown by down-regulation of MYH11 expression at the mRNA and protein levels and by reduced immunohistochemical staining of smooth muscle alpha actin. Both the ESR and the AR pathways probably mediate this effect.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Dietilestilbestrol/farmacologia , Miócitos de Músculo Liso/fisiologia , Cadeias Pesadas de Miosina/genética , Pênis/crescimento & desenvolvimento , Actinas/análise , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Biomarcadores , Di-Hidrotestosterona/farmacologia , Regulação para Baixo/efeitos dos fármacos , Estradiol/análogos & derivados , Estradiol/farmacologia , Fulvestranto , Imuno-Histoquímica , Masculino , Miócitos de Músculo Liso/química , Cadeias Pesadas de Miosina/análise , Pênis/química , Pênis/metabolismo , RNA Mensageiro/análise , Ratos , Receptores Androgênicos/efeitos dos fármacos , Receptores de Estrogênio/antagonistas & inibidores , Testículo/química , Testículo/efeitos dos fármacos , Testosterona/análiseRESUMO
Although male infertility is well researched, the effects of inorganic mercury on male reproduction and fertility are less well known. Studies pertaining to mercury and male fertility identified reduced concentration of testosterone in the serum of male workers, a toxic influence on fertility of organic mercury compounds within concentrations at the workplace, and increased days to pregnancy. We evaluated the effect of chronic mercuric chloride (HgCl(2)) exposure in male rats on reproductive endpoints. Thirty-day old male Sprague Dawley rats (n = 31) were exposed to 0.0, 1.0, or 2.0 mg/kg/day of HgCl(2) via gavage. After 60 days exposure, they were housed with nonexposed females for 21 days. A survivor analysis revealed the exposed animals took longer to impregnate the females and had a lower rate of impregnation. Further statistical analysis revealed a lower correlation between testicular testosterone levels and days to impregnate, and also lower sperm counts in the epididymis head and body of the exposed males. The results indicate that HgCl(2) exposure had significant adverse effects on male rat reproduction endpoints including fertility at a dose that was not clinically toxic.
Assuntos
Fertilidade/efeitos dos fármacos , Cloreto de Mercúrio/administração & dosagem , Cloreto de Mercúrio/toxicidade , Testosterona/sangue , Animais , Peso Corporal/efeitos dos fármacos , Epididimo/citologia , Epididimo/efeitos dos fármacos , Feminino , Estimativa de Kaplan-Meier , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Contagem de EspermatozoidesRESUMO
Previously, we reported that estrogen receptor α mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and maldeveloped penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < .05) lower as compared with controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, genetically induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except for limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles.
Assuntos
Receptor alfa de Estrogênio/genética , Fertilidade/genética , Pênis/embriologia , RNA Mensageiro/genética , Animais , Sequência de Bases , Western Blotting , Peso Corporal , Primers do DNA , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Tamanho do Órgão , Reação em Cadeia da Polimerase , Ratos , Testosterona/sangue , Testosterona/metabolismoRESUMO
The objectives of this study were to find a minimal dose of 17alpha-ethinyl estradiol (EE) that is detrimental to the developing penis and fertility and to compare estrogenic effects between EE and diethylstilbestrol (DES). Neonatal rats received EE at 10 ng (1 microg/kg), 100 ng, 1 microg, or 10 microg per pup on alternate days from postnatal days 1 to 11 (dose-response study) or received EE or DES at 100 ng per pup daily from postnatal days 1 to 6 (comparative study). Effects of EE were dose dependent, with > or = 100-ng dose inducing significant (p < 0.05) reductions in penile length, weight, and diameter. Additionally, the penis was malformed, characterized by underdeveloped os penis and accumulation of fat cells. Fertility was 0% in the > or = 1-microg groups, in contrast to 60% in the 100-ng group and 100% in the 10-ng and control groups. Animals treated with > or = 10 ng had significant reductions in the weight of bulbospongious muscle, testis, seminal vesicle, epididymal fat pad, and in epididymal sperm numbers. A comparison of EE and DES effects showed similar reductions in penile weight and length and the weight of bulbospongiosus muscle, testis, seminal vesicle, epididymis, and epididymal fat pad in both adolescent and adult rats. While 5/6 control males sired, only 1/6 in the EE group and 0/6 in the DES group sired. Hence, neonatal exposure to EE at 10 ng (environmentally relevant dose) adversely affects male reproductive organs. A dose ten times higher than this leads to permanently mal-developed penis and infertility. Furthermore, EE and DES exposures show similar level of toxicity to male reproductive organs.
Assuntos
Animais Recém-Nascidos , Dietilestilbestrol/toxicidade , Etinilestradiol/toxicidade , Infertilidade Masculina/induzido quimicamente , Pênis/efeitos dos fármacos , Teratogênicos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , Pênis/anormalidades , Ratos , Testosterona/sangueRESUMO
Exposure to the estrogen receptor alpha (ERalpha) ligand diethylstilbesterol (DES) between neonatal days 2 to 12 induces penile adipogenesis and adult infertility in rats. The objective of this study was to investigate the in vivo interaction between DES-activated ERalpha and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma). Transcripts for PPARs alpha, beta, and gamma and gamma1a splice variant were detected in Sprague-Dawley normal rat penis with PPARgamma predominating. In addition, PPARgamma1b and PPARgamma2 were newly induced by DES. The PPARgamma transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPARgamma protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ERalpha and induced adipocyte differentiation in corpus cavernosum penis. Those adipocytes exhibited strong nuclear PPARgamma expression. These results suggest a biological overlap between PPARgamma and ERalpha and highlight a mechanism for endocrine disruption.
RESUMO
Uterine choriocarcinoma developing in patients beyond reproductive age is a rare occurrence. We report a case of choriocarcinoma of uterine corpus in a 54-yr-old woman after 7 yr of menopause and 25 yr after last child birth. She presented with pain in the abdomen, and on radiological investigation a left uterine adnexal mass of 3.4 x 2.8 cm size was detected. Her serum CA125 level was 40 mIU/mL (normal up to 35 mIU/mL). Hysterectomy revealed an intramural growth in left uterine cornu measuring 3.5 x 3.0 x 2.5 cm. Histological features of the tumor were consistent with choriocarcinoma, and immunohistochemistry detected strong reactivity for beta-hCG in the tumor cells. Serum beta-hCG level 4 wk after surgery was 1345 mIU/mL. The patient was put on combination chemotherapy (EMACO). She achieved serological remission but showed a rise in serum beta-hCG level 4 wk after completion of chemotherapy. We conclude that a high level of suspicion may help in preoperative diagnosis of uterine choriocarcinoma in the postmenopausal age group. However, the response to chemotherapy in these cases may not be as encouraging as in choriocarcinoma of reproductive age.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Coriocarcinoma , Pós-Menopausa , Neoplasias Uterinas , Antígeno Ca-125/sangue , Coriocarcinoma/sangue , Coriocarcinoma/diagnóstico , Coriocarcinoma/patologia , Coriocarcinoma/terapia , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Terapia Combinada/métodos , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Leucovorina/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa/metabolismo , Neoplasias Uterinas/sangue , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Vincristina/administração & dosagemAssuntos
Interferons/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/patologia , Adulto , Humanos , Interferons/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Nefrite Lúpica/tratamento farmacológico , MasculinoRESUMO
This study evaluated the effects of neonatal exposure to different doses of diethylstilbestrol (DES) or estradiol valerate (EV) on penile morphology, penile skeletal muscles, and fertility. Male pups received DES or EV at a dose of 10 microg, 1 microg, 100 ng, 10 ng, or 1 ng per rat on alternate days from postnatal days 2-12. Fertility was tested at 120 days, and tissues were examined at 150 days. Generally, DES and EV induced similar effects within the 10- and 1-microg groups. Fertility was reduced to 0; the weight, length, and diameter of the penis and the weight of penile skeletal muscles, especially bulbocavernosus muscle, were decreased (P <.05) in a dose-dependent manner; the preputial sheath was partially released or its release was delayed; testicular descent was delayed; and the cavernous spaces and smooth muscle cells in the corpora cavernosa penis were replaced by fat cells. Conversely, all of the above parameters were similar in controls and the lower dose groups, except in the 100-ng DES group, in which 4 of 7 males did not sire pups (compared with 1 of 7 in controls and 2 of 6 in the 100-ng EV group). The loss of fertility in these 4 males of the DES group and 1 male of the EV group was associated with partial release of the preputial sheath and abnormal penile morphology. Plasma testosterone was reduced (P <.05) in the 100-ng and higher dose groups for DES and EV. Hence, neonatal exposure to DES or EV at a cumulative dose of 600 ng per rat or more lowers fertility, which is associated with permanent alterations in penile morphology and penile skeletal muscles and decreased testosterone.