The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis

ABSTRACT Purpose: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. Materials and Methods: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Results: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Conclusion: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations.

Histological study of experimental hyperprolactinemia on the prostate lateral lobe of adult albino rats

Prolactin, besides androgens, plays an important role in the regulation of prostatic function. This study aimed to demonstrate the influence of experimental hyperprolactinemia on the structure of the prostate lateral lobe in adult albino rats. Twenty healthy adult albino rats were equally divided into two groups: a control group and an experimental group. Rats of the experimental group were intraperitoneally injected with metoclopramide at a dose of 2.2mg/kg for 14 successive days to induce hyperprolactinemia. The control group was injected with saline in the same manner. Hormonal assays for serum prolactin and testosterone levels were carried out. Prostate was extirpated and the lateral lobes were processed for examination by light and electron microscopy. Epithelial height of the prostatic lateral lobes acini was determined morphometrically and analyzed statistically. In the experimental hyperprolactinemic group, numerous prostatic acini were lined by multiple layers of epithelial cells [hyperplasia]. Acinar epithelium had different ultrastructural features. Some acini had pleomorphic nuclei, cytoplasmic vacuoles, and residual bodies. Others were packed with extensive cisternae of rough endoplasmic reticulum and secretory vesicles. Others had few secretory vesicles and the majority of them had centrally located flocculent material surrounded by electron-lucent zones. Some epithelial cells contained lipofuscin pigments. The prostatic epithelial lining was infiltrated by inflammatory cells. Stromal thickening was found in between some acini that was surrounded by prominent smooth muscle cells and may connective tissue cells. Hormonal assays showed increased serum prolactin and decreased testosterone as compared with the control group. The estimated and analyzed epithelial height of the prostatic acini showed a highly significant increase compared with the control group. Hyperprolactinemia altered the morphology of epithelium and stroma of the prostate lateral lobe. It played a significant role in inducing a prostatic hyperplasia and an inflammatory response that triggered the abnormal growth of prostate

Effect of experimentally induced diabetes on adult albino rats' ventral prostate gland and role of selenium: histological and biochemical study

The relationship between the occurrence of benign hyperplasia and prostatic cancer with diabetes is a controversial issue. Selenium has been found to alleviate diabetic complications in many organs. To clarify the impact of diabetes on the histological structure of the albino rats' ventral prostate gland and the possible role of selenium supplementation. Thirty adult male albino rats were divided equally into three groups. Group 1 served as control. Group 2 was given a single intraperitoneal injection of 65 mg/kg body weight streptozotocin. Group 3 in which the rats, 1 week after diabetes induction, received 2 mg/kg body weight/day sodium selenite orally. Thirty days after diabetes induction, all rats were weighed, anesthetized, and sacrificed. The ventral prostatic lobes were dissected out, weighed, and processed for light and electron microscope examinations. The area percentage of collagen fibers, epithelial height, and acinar diameter were morphometrically measured. Statistical analysis was carried out using SPSS program. Examination of the ventral prostate gland of rats from group 2 revealed that the diameter of most acini was highly significantly increased when comparing it with group 1. The epithelial height of their acini was highly significantly decreased when comparing with group 1. Acini were lined by flat-to-low cuboidal cells with few papillary projections. The acinar lining showed focal areas of stratification. Few acini had columnar epithelium. Most cells had irregular-shaped nuclei, a dilated rough endoplasmic reticulum, numerous electron-lucent vacuoles, and few secretory granules. Areas of irregular basement membrane were seen. Thick bundles of collagen fibers and cellular infiltration were seen. Examination of group 3 revealed that it nearly regained its normal architecture. Most acini had many papillary projections and were lined by columnar cells. Acinar cells had euchromatic basal nuclei, rough endoplasmic reticulum, and secretory granules of different sizes and densities, which might seem almost vacuolated with minimum secretory content. The body and prostatic weights were highly significantly lowered in group 2 in comparison with groups 1 and 3. Diabetes mellitus had a deleterious effect on the histological structure of the ventral prostate gland, and selenium could ameliorate diabetic effects on the prostate

Estudio morfológico de la próstata y glándulas vesiculares de cobayo (Cavia porcellus) / Morphologic study of the prostate and vesicular glands of the guinea pig (Cavia porcellus)

El objetivo de esta investigación fue conocer la morfología de la próstata y glándula vesicular del cobayo (Cavia porcellus), describiéndose aspectos mesoscópicos, histológicos e histoquímicos. Se utilizaron 5 cobayos machos adultos (Cavia porcellus) sanos y alimentados con pellets, zanahorias y frutas ad libitum, en el Bioterio de la Universidad de La Frontera. Una vez sacrificados los animales, fueron aisladas las estructuras cuyos conductos terminaban en la uretra (conductos deferentes, glándulas vesiculares, glándulas coaguladoras, próstata y glándulas bulbouretrales). La próstata y las glándulas vesiculares fueron fijadas en formalina tamponada durante 24 horas y procesadas para su inclusión en paraplast. Se realizaron cortes seriados de 4 µm de grosor, los cuales fueron teñidos para los estudios histológico e histoquímicos. El análisis se realizó a través de un microscopio Carl Zeiss, Axiolab, con cámara Cannon, G6. La próstata se encuentra dorsal a la uretra y está constituída por una masa de tejido glandular cubierto por una delgada cápsula de tejido fibroso y células musculares lisas. Presenta dos lóbulos, derecho e izquierdo, unidos por un istmo dorsal a la uretra, por la cara ventral de cada lóbulo emergen de 8 a 10 pequeños conductos excretores. Histológicamente, está compuesta por unidades túbulo-alveolares recubiertos por epitelio secretor simple cúbico. Las glándulas vesiculares son dos estructuras túbulo-lobulares. Se ubican dorsal a la uretra, relacionándose ventralmente con los conductos deferentes y la cara dorsal de la vejiga. Histológicamente, presentan una capa mucosa con un epitelio cilíndrico de tipo secretor; una capa media constituida principalmente por tejido muscular liso y una capa externa serosa. La histoquímica, en ambas glándulas fue negativa para glucógeno, mucinas neutras y ácidas, sulfatadas y no sulfatadas, tanto en el tejido glandular como en su producto de secreción. La próstata y glándulas vesiculares del cobayo, guardan...

The objective of this investigation was to study the morphology of the prostate and vesicular gland of the guinea pig (Cavia porcellus), describing the mesoscopic, histological and histochemical aspects. Five healthy adult male guinea pigs (Cavia porcellus) were used. The animals received pellets, carrots and fruit ad libitum in the Biotherium of the Universidad de La Frontera. Once the animals were sacrificed the structures which ducts ended in the urethra, (vas deferens, vesicular glands, coagulator glands, prostate and bulbourethral glands) were isolated. The prostate and vesicular gland were fixed in buffered formalin during 24 hours and processed for their inclusion in paraplast. Serial cuts 4 µm thick were realized and stained for histological and histochemical studies, using a Carl Zeiss, Axiolab microscope with a Cannon G6 camera. The prostate is located dorsal to the urethra and is constituted by a mass of glandular tissue covered by a thin capsule of fibrous tissue and smooth muscular cells presenting two lobes, right and left joined to the urethra by a dorsal isthmus. Emerging through the ventral surface of each lobe are 8 to 10 small excretory ducts. Histologically it is composed by alveolar tubular units covered by a simple cubical secretor epithelium. The vesicular glands are two tubular lobular structures located dorsal to the urethra and are connected ventrally with the vas deferens and the dorsal surface of the bladder. Histologically presenting a mucous layer with a secretor type cylindrical epithelium, a medium layer namely constituted by smooth muscular tissue and a serous external layer. Histochemical reaction in both glands was negative for glycogen, for neutral and acid mucins, both sulfate and non sulfate, in the glandular tissue as well as the secretor product. The prostate and vesicular glands of the guinea pig are related to morphological aspects of other mammals. However, the differences found in the histochemical results suggest t...

Relato de caso: carcinoma basaloide da próstata, um achado incomum / Case report: basaloid carcinoma of the prostate, an uncommon finding

Relata-se caso de paciente com 56 anos de idade, com disúria, estrangúria, um episódio de hematúria macroscópica e dosagem de antígeno prostático específico (PSA) total de 1,35 ng/mL. A propedêutica para doença oncológica da próstata diagnosticou carcinoma basaloide, um tumor com rara histologia e poucas vezes descrito na literatura.

Repod of a 56 years old patient with dysuria, stranguria, an episode of gross hematuria and serum prostate specific antigen (PSA) total of 1.35 ng / mL. Workup for prostate cancer disease diagnosed basaloid carcinoma, a tumor with rare histology and scarcely described in the literature.

Age-related ultrasonography, cytology, and microbiologic exam of canine prostate / Ultrassonografia, citologia e exame microbiológico da próstata de cães em diferentes idades

The physiological parameters that could be reference for trustful diagnosis and prognosis of prostate disorders in dogs were obtained. Thirty six intact male dogs without clinical signs of neither prostatic nor reproductive disorders were allocated according the age in three groups. These animals were submitted to semen manual collection for microbiological exams; transabdominal ultrasonography to evaluate dimensions, ecogenicity, and texture of prostatic parenchyma and aspirative puncture with fine needle for cytological and microbiological analyses. Ultrasonography revealed that the predominant prostatic shape was round with regular surface. Dimensions varied according to age, being small in young animals and large in old ones. There was a positive correlation between prostatic dimensions and body weight. Microbiological exams detected microorganisms on seminal plasma from 11 dogs and prostate tissue aspirated from 10 animals, although they were healthy. Cytology did not reveal any inflammatory, proliferative, or neoplasic alteration in young and middle age dogs, but in three older dogs signs of hyperplasia/hypertrophy was found. It was observed positive correlation between age and cellular area but a negative correlation was observed between nucleus:cytoplasm ratio and craniocaudal dimension.

Obtiveram-se parâmetros fisiológicos que pudessem ser utilizados como referência para diagnóstico e prognóstico confiáveis de doença prostática em cães. Trinta e seis cães, sem sinais clínicos de doença prostática ou distúrbios reprodutivos, foram distribuídos em três grupos de acordo com a idade.Os animais foram submetidos à colheita manual de sêmen para exames microbiológicos, à ultrassonografia transabdominal, para avaliar as dimensões, a ecogenicidade e a ecotextura prostática, e à punção aspirativa com agulha fina, para análise citológica e microbiológica. A ultrassonografia revelou que a forma predominante da próstata foi globosa, com superfície de contorno regular. As dimensões variaram de acordo com a idade, sendo pequena em animais jovens e grande nos animais idosos. Houve correlação positiva entre as dimensões prostáticas e o peso corporal. Os exames microbiológicos detectaram microrganismos no plasma seminal de 11 cães e no tecido prostático aspirado de 10 animais, embora eles fossem saudáveis. A citologia não revelou nenhuma alteração inflamatória, proliferativa ou neoplásica nos cães jovens e de meia idade, mas, em três cães idosos foram encontrados sinais de hiperplasia/hipertrofia. Foi observada correlação positiva entre a idade e a área celular e correlação negativa entre a relação núcleo:citoplasma e a dimensão craniocaudal.

Estereología comparativa entre las glándulas del complejo prostático del conejo Oryctolagus cunniculus / Comparative stereology between the glands of the prostatic complex in the rabbit Oryctolagus cunniculus

El objetivo del estudio fue determinar algunos parámetros estereológicos de las glándulas que conforman el complejo prostático en el conejo y así, sentar las bases para estudios morfofuncionales. Se utilizaron 5 conejos (Oryctolagus cuniculus), machos, adultos y clínicamente sanos, mantenidos en el Bioterio de la Facultad de Medicina de la Universidad de La Frontera, Temuco, Chile. Fue disecada la región pélvica y se aisló el complejo prostático de las otras glándulas anexas. Las muestras fueron fijadas en Bouin, durante 24 horas y procesadas para su inclusión en paraplast. Se realizaron cortes seriados de 5 Jm de espesor, los cuales fueron teñidos con hematoxilina eosina, para su análisis estéreo lógico. Los resultados mostraron que el complejo prostático del conejo está formado por 4 glándulas: próstata (craneal a la glándula vesicular), propróstata (caudal a la glándula vesicular y craneal a la próstata) y dos parapróstata (inferiores y lateralmente situadas a la propróstata). El promedio de células glandulares en la próstata fue de 7,3 x 10(6)/ mm³ (D. E. 1,8 x 10(6)); en la propróstata fue de 10,33 x 10(6)/ mm³ (D. E. 2,45 x 10(6)); en la parapróstata derecha fue de 13,57 x 10(6)/ mm³ (D. E. 2,84 x 10(6)) y en la parapróstata izquierda fue de 11,91 x 10(6)/mm³ (D. E. 2,97 x 10(6)).E1 porcentaje promedio de células glandulares en la próstata fue de 14,12 por ciento (D. E. 3,01); en la propróstata fue de 13,56 por ciento (D. E. 3,13); en la parapróstata derecha fue de 18,80 por ciento (D. E. 3,04) y en la parapróstata izquierda de 18,59 por ciento (D. E. 3,43). Las glándulas del complejo prostático presentan diferencias morfológicas entre sí y, en especial, en sus aspectos estereológicos, siendo las parapróstatas las que presentaron un mayor número de células glandulares y mayor porcentaje de tejido glandular (semejante a la glándula bulbouretral), lo que podría indicar que cada una de las glándulas de este complejo cumple roles funcionales...

The aim of this study was to determine some stereological parameters of the glands of the prostatic complex in the rabbit and thereby setting the basis for future morphofunctional studies. Five rabbits (Oryctolagus cuniculus), males, adults, clinically healthy and mantained in the Biotery of the Faculty of Medicine of the Universidad de La Frontera, Temuco, Chile, were used. The pelvic region was dissected and the prostatic complex of the other glands was isolated. The samples were fixed in Bouin solution for 24 hours and processed for inclusion in paraplast. Serial cuts of 5mm which were stained with hematoxilin eosin for stereological analysis. The results showed that the prostatic complex of the rabbit was composed of four glands: prostate (cranial to vesicular gland), proprostate (caudal to vesicular gland and cranial to the prostate) and two paraprostates (inferior and lateral to the prostate). The average of the glandular cells in the prostate was 7,3 x 107 mm³ (S. D. 1,8 x 10s); in the proprostate was 10,33 x 107 mm³ (S. D. 2,45 x 10s); in the right paraprostate was 13,57 x 107 mm³ (S. D. 2,84 x 10s) and in the left paraprostate was 11,91 x 107 mm³ (S. D. 2,97 x 10s). The percentage average of the glandular cells in the prostate was 14,12 percent (S. D. 3,01); in the proprostate was 13,56 percent (S. D. 3,13); in the right paraprostate was 18,80 percent (S. D. 3,04) and in the left paraprostate was 18,59 percent (S. D. 3,43). The gland of the prostatic complex show morphological differences among themselves and in particular, its stereological aspects, with paraprostates which showed an increased number of glandular cells and higher percentage of glandular tissue ( similar to the bulbourethral gland), which could indicate that each of the glands of this complex plays specific functional roles in the reproductives processes.

Câncer de próstata com PSA normal / Prostate cancer with normal PSA

Relata-se o caso de paciente de 64 anos de idade no qual, apesar do exame de PSA normal para câncer de próstata (CaP), foi diagnosticado o tumor. O exame de toque retal da próstata (TR), com identificação de nódulo, foi indicação absoluta para realização da biópsia comprobatória. Apesar de ser um dos melhores marcadores tumorais conhecidos, o exame de PSA normal não é suficiente para descartar a presença de câncer de próstata. A associação do toque retal com o PSA é defendida para melhoria diagnóstica.

Tissue alterations in the Guinea pig lateral prostate following antiandrogen flutamide therapy

The flutamide antiandrogenic effects on the Guinea pig male prostate morphology in puberal, post-puberal and adult ages were evaluated in the present study. Daily-treated group animals received flutamide subcutaneous injection at a dose of 10 mg/Kg body weight for 10 days. The control group animals received a pharmacological vehicle under the same conditions. The lateral prostate was removed, fixed and processed for light and transmission electron microscopy. The results revealed an increase of the acinus diameter in the treated puberal animals and straitness in the stromal compartment around the acini. The epithelial cells exhibited cubic phenotype. In the post-puberal and adult animals, a decrease of the acinus diameter was observed, as well as an increase of the smooth muscle layer and presence of the folds at epithelium. The ultrastructural evaluation of the secretory cells in the treated group demonstrated endomembrane enlargement, mainly in the rough endoplasmic reticulum and Golgi apparatus. In addition, a decrease of the microvilli and alterations in the distribution patterns and density of the stromal fibrillar components were observed. In conclusion, the flutamide treatment exerts tissue effects on the lateral prostate, promoting stroma/epithelium alterations.

Histological and morphometric study of testosterone effects on the ventral prostate in the adult albino rat

This study was carried out to throw light on the histological and morphometric changes induced in the ventral prostate of the adult albino rat, when injected with testosterone-enanthate for 6 months. Twenty adult male rats were used, which were divided into two groups [control and experimental]. The control group consisted of five rats two of which were not injected [normal control], but the remaining three rats [sham control] were injected once weekly for 6 months with I.M.0.2m1 olive oil vehicle. The experimental group consisted of fifteen animals; each animal was injected once weekly for 6 months with I.M. testosterone-enanthate in a dose of 4.5mg/200g b.w. dissolved in 0.2m1 olive oil. Specimens from the ventral lobe of the prostate gland were taken and processed for light and electron microscopic examination. Morphometric measurements were done using image analyzer computer system and the data obtained were statistically analyzed. The present work revealed that injection of testosterone for 6 months induced marked histological and morphometric changes as follows; Light microscopic examination revealed enlargement of the prostatic acini with marked infolding of the lining epithelium, which showed blebs and extrusion of secretory globules. The cytoplasm showed numerous apical secretory vacuoles. The interacinar fibromuscular stroma showed marked increase of its thickness with congestion and dilatation of the blood vessels. On the contrary, the basal cells appeared normal as compared with control. Electron microscopic examination showed that, the nuclei of the epithelial cells appeared either indented with prominent nucleoli and dispersed chromatin or irregular with condensed chromatin. The cytoplasm contained many secretory granules and different sized vacuoles, numerous mitochondria and secondary lysosomes with dilatation of the rER and Golgi apparatus. Morphometric and statistical study revealed a very highly significant increase in the mean height and number of the epithelial cells with a mild significant increase in the mean value of the area% of the secretory vacuoles in comparison to the control group. So, it could be concluded that testosterone therapy for 6 months induces histological and morphometric changes in the ventral prostate of the adult albino rat, which, should be taken into consideration during testosterone therapy

Ultrastructure of the dorsal prostate gland in zinc and cadmium treated rats

Changes in the ultrastructure of the dorsal lobe of the prostate gland from cadmium and zinc treated rats were studied using transmission electron microscopy. Two groups of rats [10 in each group] were injected subcutaneously [s.c.] with 2mg/kg cadmium chloride [Cdc12] and 10mg/kg zinc sulfate[ZnSO4], respectively. A third group was injected s.c. withnormal saline and served as a control. Tissues from the dorsal lobe of the prostate gland from the three groups were processed for transmission electron microscopy. Epithelial cells of the dorsal lobe of prostate gland from the cadmium and zinc treated groups showed a considerable variation in the morphology of the rough endoplasmic reticulum, Golgi comlex, secretory vesicles, mitochondria, and microvilli as compared with the control group. These variations may be due the direct effect of zinc and cadmium, and/or due to meta llothionein [MT] synthesis induced by zinc and cadmium. Further studies will be required to identify the active factor[s]

Anatomia, histologia e ultra-estrutura do lobo ventral da próstata de ratos (Rattus norvegicus) vasectomizados / Anatomy, histology and ultrastructure of prostate ventral lobe of vasectomized (Rattus norvegicus)

A vasectomia é um método de contracepçäo amplamente utilizado, que tem sido associado ao carcinoma da próstata em estudos epidemiológicos. Contudo, poucos estudos morfológicos foram realizados sobre a possibilidade da vasectomia alterar a estrutura da próstata. Este trabalho apresenta uma revisäo de literatura que associa a vasectomia ao câncer da próstata, bem como resultados de estudo experimental em ratos. Dividiu-se um total de 48 ratos machos albinos (Rattus norvegicus), com 6 a 8 semanas de idade, em dois grupos : simulado e vasectomizado. Perfundiu-se, com glutaraldeído a 2,5 por cento, seis ratos de cada grupo após 60, 120, 180 e 360 dias pós-vasectomia. Coletou-se o lobo ventral da próstata para análise microscópica. No estudo ao microscópio de luz, näo se observaram diferenças estruturais entre os grupos estudados. Em ambos grupos näo se encontraram evidências de carcinoma da próstata. A análise morfométrica da altura do epitélio prostático näo demonstrou diferença significativa entre vasectomizados e simulados. Ultra-estruturalmente, as células epiteliais do grupo simulado apresentaram núcleo basal com contorno irregular, retículo endoplasmático rugoso amplamente distribuído, complexo de Golgi bem desenvolvidos, grânulos de secreçäo em diferentes graus de maturidade no citoplasma apical, e microvilos na superfície luminal. Detectou-se características similares nas células prostáticas dos animais vasectomizados, porém, nos períodos iniciais pós-cirurgia, o citoplasma apical continha menor quantidade de grânulos de secreçäo. Os resultados permitem sugerir que a secreçäo prostática diminui logo após a vasectomia, voltando à normalidade posteriormente. Nos ratos vasectomizados, as células epiteliais do lobo ventral da próstata näo demonstraram quaisquer sinais de degeneraçäo ou de carcinoma como efeito da vasectomia.

Autoinmunidad experimental contra glandulas sexuales accesorias masculinas de rata: correlación entre lesion tisular especifica y reactividad de linfocitos de timo, medula osea, bazo, ganglios y sangre / Experimental autoimmunity against male accessory glands of rats: correlation between specific tissular lesion and lymphocyte reactivity of thymus, bone marrospleen, ganglia and blood

En el modelo experimental de vesículoprostatitis autoimune logrado por isoinmunización de ratas con homogenato de glándulas sexualess accesorias masculinas (GAM-R) y coadyuvante de Freund completo (CFC) se estudió la respuesta de anticuerpos hemaglutinantes, precipitantes y fijadores de complemento. Tambíen se analizó la respuesta imune mediada por células (IMC) en órganos inmunnocompetentes (OIC) primarios (médula ósea timo), OIC secundarios (bazo, ganglios linfáticos) y en circulación mediante cultivo de linfocitos, inhibición de la migración de macrófagos (MIF) indirecta y factor reactivo de piel (SRF), incluyéndose también la detección de reacciones de hipersensibilidad cutánea demorada (HCD) en ratas inmunes a GAM-R y en controles tratados con CFC o con glándulas sexuales accesorias de conejo (GAM-C) y CFC. Asimismo, estudios histológicos y demicroscopía electrónica permitieron establecer las características de las alteraciones hísticas inducidas en las glándulas objetivo. En 16 de 22 ratas inmunizadas con GAM-R se observó infiltrado de células mononucleares principalmente en intersticio de próstata y vesícula seminal. A nivel ultraestructural se observaron alteraciones en células epiteliais y linfocitos infiltrado el tejido epitelial. El análisis de la correlación entre alteraciones tisulares específicas y presencia de anticuerpos circulantes, demostró que en 13 de 16 animales con daño tisular evidente, la búsqueda de respuesta inmune humoral resultó negativa. Por el contrario, la respuesta IMC fue demostrada en todos ellos con alto grado de activación, ya que varios factores que median la inmunidad celular fueron detectados. Estos resultados y las características histopatológicas de las glándulas objetivo sugiere que un mecanismo efector mediado por células conduce al daño tisular. El número de factores mediadores detectados en los diferentes sectores (central y periférico) se consideró índice de expansión y activación de la respuesta IMC. Su correlación con los estudios histológicos demostró que en el grupos con histología negativa las células inmunococmpetentes de OIC primarios no revelan respuesta IMC o responden débilmente en el 67% de los casos, mientras que la respuesta en OIC secundarias y en circulación presenta un buen nivel de activación, ya que en el 100% de los casos 2 o más factores fueron detectados...