The karyometric signature is altered in fallopian tubes with serous tubal intraepithelial carcinoma.

OBJECTIVE: Recent evidence suggests that the fimbriated end of the fallopian tube harbors the precursor cells for many high-grade ovarian cancers, opening the door for development of better screening methods that directly assess the fallopian tube in women at risk for malignancy. Previously we have shown that the karyometric signature is abnormal in the fallopian tube epithelium in women at hereditary risk of ovarian cancer. In this study, we sought to determine whether the karyometric signature in serous tubal intraepithelial carcinoma (STIC) is significantly different from normal, and whether an abnormal karyometric signature can be detected in histologically normal tubal epithelial cells adjacent to STIC lesions. METHODS: The karyometric signature was measured in epithelial cells from the proximal and fimbriated portion of the fallopian tube in fallopian tube specimens removed from women at: 1) average risk for ovarian cancer undergoing surgery for benign gynecologic indications (n = 37), 2) hereditary risk of ovarian cancer (germline BRCA alterations) undergoing risk-reducing surgery (n = 44), and 3) diagnosed with fimbrial STICs (n = 17). RESULTS: The karyometric signature in tubes with fimbrial STICs differed from that of tubes with benign histology. The degree of karyometric alteration increased with increasing proximity to fimbrial STICs, ranging from moderate in the proximal portion of the tube, to greatest in both normal appearing fimbrial cells near STICs as well as in fimbrial STIC lesions. CONCLUSION: These data demonstrate an abnormal karyometric signature in STICs that may extend beyond the STIC, potentially providing an opportunity for early detection of fallopian tube neoplasia.

Automated detection of cancer cells in effusion specimens by DNA karyometry.

BACKGROUND: The average sensitivity of conventional cytology for the identification of cancer cells in effusion specimens is only approximately 58%. DNA image cytometry (DNA-ICM), which exploits the DNA content of morphologically suspicious nuclei measured on digital images, has a sensitivity of up to 91% for the detection of cancer cells. However, when performed manually, to our knowledge to date, an expert needs approximately 60 minutes for the analysis of a single slide. METHODS: In the current study, the authors present a novel method of supervised machine learning for the automated identification of morphologically suspicious mesothelial and epithelial nuclei in Feulgen-stained effusion specimens. The authors compared this with manual DNA-ICM and a gold standard cytological diagnosis for 121 cases. Furthermore, the authors retrospectively analyzed whether the amount of morphometrically abnormal mesothelial or epithelial nuclei detected by the digital classifier could be used as an additional diagnostic marker. RESULTS: The presented semiautomated DNA karyometric solution identified more diagnostically relevant abnormal nuclei compared with manual DNA-ICM, which led to a higher sensitivity (76.4% vs 68.5%) at a specificity of 100%. The ratio between digitally abnormal and all mesothelial nuclei was found to identify cancer cell-positive slides at 100% sensitivity and 70% specificity. The time effort for an expert therefore is reduced to the verification of a few nuclei with exceeding DNA content, which to our knowledge can be accomplished within 5 minutes. CONCLUSIONS: The authors have created and validated a computer-assisted bimodal karyometric approach for which both nuclear morphology and DNA are quantified from a Feulgen-stained slide. DNA karyometry thus increases the diagnostic accuracy and reduces the workload of an expert when compared with manual DNA-ICM.

Evaluating IPMN and pancreatic carcinoma utilizing quantitative histopathology.

Intraductal papillary mucinous neoplasms (IPMN) are pancreatic lesions with uncertain biologic behavior. This study sought objective, accurate prediction tools, through the use of quantitative histopathological signatures of nuclear images, for classifying lesions as chronic pancreatitis (CP), IPMN, or pancreatic carcinoma (PC). Forty-four pancreatic resection patients were retrospectively identified for this study (12 CP; 16 IPMN; 16 PC). Regularized multinomial regression quantitatively classified each specimen as CP, IPMN, or PC in an automated, blinded fashion. Classification certainty was determined by subtracting the smallest classification probability from the largest probability (of the three groups). The certainty function varied from 1.0 (perfectly classified) to 0.0 (random). From each lesion, 180 ± 22 nuclei were imaged. Overall classification accuracy was 89.6% with six unique nuclear features. No CP cases were misclassified, 1/16 IPMN cases were misclassified, and 4/16 PC cases were misclassified. Certainty function was 0.75 ± 0.16 for correctly classified lesions and 0.47 ± 0.10 for incorrectly classified lesions (P = 0.0005). Uncertainty was identified in four of the five misclassified lesions. Quantitative histopathology provides a robust, novel method to distinguish among CP, IPMN, and PC with a quantitative measure of uncertainty. This may be useful when there is uncertainty in diagnosis.

[Karyometry of BBN-induced precancerosis of the urothelium : An experimental analysis]. / Karyometrie BBN-induzierter Präkanzerosen des Urothels : Eine experimentelle Analyse.

BACKGROUND: The morphology of experimental precancerous lesions of the urinary bladder has been interpreted quite differently by various authors. OBJECTIVES: The aim of this investigation was to quantify these lesions by karyometry and, thus, to gain a more reliable understanding of the process. MATERIALS AND METHODS: A total of 60 Wistar rats were fed with N­butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at a concentration of 0.05 % in their drinking water to induce preneoplastic changes of the urothelium. After the second week of BBN exposition, 6 animals were killed every 2 weeks up to week 20. Smears of the scraped off urothelium of 3 urinary bladders of each group were analyzed cytologically and karyometrically. RESULTS: BBN exposition led to statistically significant changes of the karyometric values using the χ2 test to differentiate the control animals from the ones that had ingested BBN and the 2­week groups from each other. These changes consisted mainly in significant deviations of the size of the nuclear area within the different groups. CONCLUSION: Morphological and karyometrical analysis showed that biologically relevant stages in the development of chemically induced urothelial precancerous lesions could be realized much earlier than had been assumed in recent publications. Karyometric analysis offered a valid basis to describe the early morphologic alterations of carcinogenesis.

Nuclear morphometry and chromatin textural characteristics of basal cell carcinoma

Abstract: Histological subtypes of basal cell carcinoma have biological, evolutionary and distinct prognostic behavior. The analysis of characteristics of the nucleus can provide data on their cellular physiology and behavior. The authors of this study evaluated nuclear morphological parameters and textural patterns of chromatin from different subtypes of basal cell carcinoma: nodular (n=37), superficial (n=28) and sclerodermiform (n=28). The parameters were compared between neoplasms' subtypes and with unaffected adjacent basal epithelium. Nuclear area and diameter of sclerodermiform neoplasms were superior to the other subtypes. Chromatin's color intensity and fractal dimension were less intense in superficial subtypes. Nuclear roundness and chromatin's entropy presented lower values in tumors than in normal epithelium. There was significant correlation between morphological and textural variables of normal skin and tumors. Morphometric elements and textural chromatin's homogeneity of basal cell carcinomas may be related to evolutionary, biological and behavior particularities related to each histotype.

The pineal complex in the cichlid Cichlasoma dimerus: effect of different photoperiods on its cell morphology.

This research describes the pineal complex histology in juvenile and adult Cichlasoma dimerus, and the effect of different photoperiods on its cell morphology. In both juveniles and adults, the pineal complex of C. dimerus has three components: the pineal organ, consisting of a pineal vesicle (PV) and a pineal stalk, the parapineal organ and the dorsal sac. Although a strong morphological resemblance exists between the two stages, different synthesis patterns of cone and rod opsins were detected in the two life stages. An effect of the photoperiod length was observed on putative pinealocytes' activity from the PV, measured indirectly through nuclear area morphometry. Individuals exposed to a natural photoperiod (14L:10D) had smaller nuclear areas (mean ± s.e. = 13·82 ± 1·52 µm(2) ) than those exposed to a short photoperiod (8:16) (21·45 ± 2·67 µm(2) ; P < 0·001). Eventually, the nuclear area of pinealocytes could be used as a putative indicator of melatonin synthesis in fishes where it is difficult to obtain plasma samples, e.g. due to its small size or age. This work constitutes one of the few comparative descriptions of the pineal complex of juvenile and adult teleost and suggests potential approaches for the study of melatonin synthesis in fish larvae or small adult fishes.

Phenotypic and metabolic aspects of prostatic epithelial cells in aged gerbils after antisteroidal therapy: turnover in the state of chromatin condensation and androgen-independent cell replacement.

The gerbil is a rodent considered a good model for studies of prostatic morphophysiology under different experimental conditions. Studies involving castration and steroidal blockers of aged gerbils showed that the glandular epithelium persists after long-term therapy, preventing the organ atrophy. Thus, the objective of this study was to evaluate the phenotypic characteristics and behavior of prostatic epithelial cells that remained after different periods of hormone ablation in aged gerbils. The identification of elements that influenced the survival of this cell type was performed by morphometric, nuclear phenotypes, ultrastructural and immune histochemical analysis. The most significant responses to treatment, by analyzing morphometric features, were observed during the first three time points (day 1, day 3, and day 7), after which there appeared to be an adjustment of the gland to the hormone ablation. All treatments led to changes in the state of chromatin condensation, DNA methylation pattern and phenotypic changes indicated cell senescence. Additionally, an increase in the basal cells seemed to guarantee self-renewal properties to the epithelium. These data indicate that changes occur at many levels, including gene expression and nuclear architecture in the epithelial cells, when aging and steroidal blockade are associated. These aspects are important when considering castration-resistant prostate cancer, a malignant tumor posing difficult therapeutic intervention.

Estresse pós-privação de sono: análises morfométricas do fígado / Stress caused by sleep deprival: liver morphometric analysis

OBJETIVO: Avaliar o efeito da exposição ao estresse pós-privação de sono em características celulares e nucleares do fígado de ratos. MÉTODOS: 16 ratos (Wistar) machos adultos (200-260 g) foram mantidos em ciclo de luz controlado recebendo dieta com quantidades usuais de sal e livre acesso à água e alimento. Os animais foram divididos em dois grupos de oito animais (grupo experimental e grupo controle). Os animais permaneceram na mesma gaiola (dois de cada vez) durante sete dias e, após esse período, foram pesados e separados. O animal do grupo controle continuou na mesma gaiola e o animal do grupo experimental foi colocado em aparato de privação de sono. Após as 96 horas, os dois ratos foram pesados,anestesiados, sacrificados com dose excessiva de anestésico e os fígados foram retirados. RESULTADOS: Não há diferença significante entre o grupo experimental e grupo controle em relação ao peso, embora haja diminuição de peso no grupo experimental. Nas análises cariométricas, houve diferença significante em relação ao diâmetro menor (p=0,03) e volume (p=0,04) do núcleo dos hepatócitos do grupo experimental. Nas análises esteriológicas, houve diferença significante do grupo experimental no núcleo (maior, p=0,036), do citoplasma (menor p=0,009) e outras estruturas (maior p=0,008). CONCLUSÃO: O estresse parece contribuir para alteração na estrutura celular hepática.

OBJECTIVE: To evaluate the effect of stress induced by sleep deprivation on nuclear and cellular features of rat liver. METHODS: 16 adult male Wistar rats (200-260 g) in controlled light cycle received diet with customary salt quantity and free access to water and food. The animals were divided into two groups with 8 animals each (experimental group and control group). Animals stayed in the same box (two at a time) during seven days andafter that period they were weighted e separated. The control group animal continued in the same box and the experimental group animal were transferred to a sleep deprivation apparatus. After the 96 hours the animals were sacrificed by an excessive anesthetic dose; animals were weighted and their liver extracted. RESULTS: There was no significant difference between experimental and control group regarding weight, although therewas a decrease of weight on the experiment group. Karyotipical analysis showed significant smaller diameter (p=0.03) and volume (p=0.044) of hepatocyte nuclei in experimental group. Stereological analyses showed significant differences in experimental group for nucleus (larger, p=0.036), cytoplasm (smaller, p=0.009) and other structures (larger, p=0.008). CONCLUSION: Stress seems to contribute to alteration of hepatic cell structure.

Effect of sodium cyclamate on the rat fetal exocrine pancreas: a karyometric and stereological study / Efectos del ciclamato de sodio en el pancreas exocrino fetal de ratas: estudio cariométrico y estereológico

The cyclamate, a sweetner substance derived from N-cyclo-hexyl-sulfamic acid, is largely utilized as a non-caloric artificial edulcorant in foods and beverages as well as in the pharmaceutical industry. The objective of this study was to evaluate karyometric and stereological alterations in the rat fetal pancreas resulting from the intraperitoneal administration of sodium cyclamate. The exocrine pancreas of ten fetuses of rats were evaluated, five treated and five controls chosen at random, in which five rats that received from the 10th to 14th days of pregnancy an intraperitoneal daily injection of sodium cyclamate at 60 mg/Kg of body weight during 5 days. At the 20th day of gestation, the animals were removed and weighed, as were their placentas; the length of the umbilical cords also were measured. After the laboratory processing, semi-seriated 6mm cuts stained with haematoxyline and eosine were performed. In seven karyometric parameters (major, minor, and medium diameters, volume, area, perimeter, and volume-area ratio), the increase was statistically significant in the treated group when compared with control group. Stereological parameters showed in the treated group a significant increase in the cellular volume and a significant reduction in the numerical cellular density. These results showed that the sodium cyclamate in pregnant rats led to retardation of fetal development and hypertrophy in the exocrine pancreas of the rat fetuses.

El ciclamato, es una substancia derivada del ácido N-ciclo-hexil-sulfámico, bastante usada como edulcorante no calórico en los alimentos y bebidas, así como en la industria farmacéutica. El objetivo de este estudio fue evaluar las alteraciones cariométricas y estereológicos en páncreas fetal de rata tras la administración intraperitoneal de ciclamato de sodio. El páncreas exocrino de diez de los fetos de rata fueron evaluados, cinco tratados y cinco controles seleccionados al azar, en el que cinco ratas recibieron del día 10 al día 14 de preñez una inyección intraperitoneal diaria de ciclamato de sodio a 60 mg/Kg de peso corporal durante 5 días. En el día 20 de gestación, los animales fueron retirados y pesados, al igual que sus placentas. Asimismo, se midió la longitud de los cordones umbilicales. Después del procesamiento de laboratorio, cortes semi-seriados de 6µm, se tiñeron con hematoxilina-eosina. En siete parámetros cariométricos (diámetros mayor, menor y medio, volumen, área, perímetro y relación área/volumen). El aumento fue estadísticamente significativo en el grupo tratado comparado con el grupo control. Los parámetros estereológicos mostraron en el grupo tratado un aumento significativo del volumen celular y una reducción significativa en la densidad numérica celular. Estos resultados mostraron que el uso del ciclamato de sodio en las ratas preñadas causa retardo en el desarrollo fetal e hipertrofia en el páncreas exocrino de los fetos de rata.

Estudio cariométrico de placentas de ratones con infección aguda por diferentes cepas de Trypanosoma cruzi / Karyometric study of placentas from mice with acute infection by different strains of Trypanosoma cruzi

El objetivo de este trabajo fue evaluar cariometricamente las alteraciones causadas por diferentes cepas de T. cruzi en la placenta del ratón. Ratones hembras de 60 días, grávidas, fueron inoculadas, intraperitonealmente, con 2 x 10(5) tripomastigotes sanguíneos de las cepas colombiana, Y, Solivia o RC del T. cruzi. Fueron observadas claras diferencias en las alteraciones cariométricas de las células trofoblásticas gigantes y de las células trofoblásticas de la zona esponjosa. Los resultados demostraron que las cepas colombiana y RC causan alteraciones tanto en las células trofoblásticas gigantes como en las células del trofoblasto esponjoso, mientras que las cepas Y y Bolivia provocan alteraciones solamente en las células trofoblásticas gigantes. Es posible concluir que cada cepa posee características propias y que, a pesar del tipo similar de transmisión, presenta matices diferenciales en el proceso de la patogénesis placentaria.

The objective of this work was to evaluate karyometrically the alterations caused by different strains of Trypanosoma cruzi in the mouse placenta. Pregnant mice, 60-day old, were intraperitoneally inoculated with 2 x 10(5) bloodstream trypomastigotes of the Colombian, Y, Bolivia or RC strain of T cruzi. There were observed clear differences in the karyometric alterations of the trophoblast giant cells and in the spongiotrophoblast cells. The results demonstrate that the Colombian and RC strains cause alterations both in the trophoblast giant cells and in the spongiotrophoblast cells, whereas the Y and Bolivia strains provoke alterations only in the trophoblast giant cells. It is possible concluding that each strain has its own characteristics and that, in spite of the similar type of transmission, it show differential nuances in the placental pathogenic process.

Evaluation of epithelial cell proliferating activity and fibroblast nuclear kariometry in recurrent pterygium treated with mitomycin C / Avaliação da atividade proliferativa das células epiteliais e da cariometria do núcleo dos fibroblastos em pterígios recidivados previamente tratados com a mitomicina C

PURPOSE: To evaluate the effectiveness of mitomycin C (MMC) in preventing recurrence of pterygium following conjunctival autograft transplantation (CAT). Ki-67 antigen to evaluate epithelial cell proliferation and fibroblast nuclear kariometry were used to assist treatment evaluation. METHODS: Twenty-nine patients with recurrent pterygium were divided into three groups: Group (G) 1 - CAT and placebo eyedrops (PED); G2 - CAT, 0.015 percent MMC subconjunctivally, and PED; G3 - CAT and 0.02 percent MMC eyedrops. Immunohistochemistry for the Ki-67 antigen and fibroblast nuclei kariometry were performed on the excised tissue, divided into nasal and temporal sides. Kariometry was evaluated in terms of volume (Vl) and area (Ar) using at least 50 cells/patient. RESULTS: The percentage of positive epithelial cells for the Ki-67 antigen on the nasal and temporal side after treatment of the three groups were: nasal (5.39 percent G1, 4.49 percent G2, and 3.88 percent G3); temporal (3.30 percent G1, 4.46 percent G2, 4.14 percent G3), did not show significant differences. Fibroblast nucleus kariometry was: nasal Vl (792.1 µ3 G1, 605.1 µ3 G2, and 549.9 µ3 G3) and Ar (100.58 µ2 G1, 83.13 µ2 G2, and 78.41 µ2 G3). The three groups showed significant differences: p=0.039 and p=0.035, for respectively Vl and Ar, on the nasal side. After a six month of treatment, the three groups presented the following recurrence rates: G1, 22.22 percent, G2, 18.18 percent and G3, 33.33 percent, respectively. CONCLUSION: MMC did not reduce the number of positive epithelial cells for the Ki-67 antigen in recurrent pterygium, but decreased fibroblast nucleus volume and area on the nasal side of the pterygia. The number of positive epithelial cells for the Ki-67 antigen seemed not to be related to pterygium recurrence observed over a six-month post-surgery period. The role of epithelial cell proliferation in pterygium recurrence should be evaluated by further studies.

OBJETIVO: Avaliar a eficácia da mitomicina C (MMC) na prevenção da recorrência quando previamente utilizada no transplante autólogo de conjuntiva (TAC). A avaliação da proliferação celular epitelial pelo antígeno Ki-67 e a cariometria do núcleo dos fibroblastos foram usados como auxiliares na avaliação do tratamento. MÉTODOS: Vinte e nove pacientes com pterígio recidivado foram divididos em três grupos: Grupo (G) 1-TAC e colírio placebo (PLA); G2-TAC, MMC 0,015 por cento subconjuntival e PLA; G3-TAC e colírio de MMC 0,02 por cento. A imuno-histoquímica foi realizada no tecido excisado para o antígeno Ki-67, como a cariometria dos núcleos dos fibroblastos (divididos em lado nasal e temporal). A cariometria dos núcleos dos fibroblastos foi avaliada de acordo com os seguintes parâmetros: volume (Vl) e área (Ar) em pelos menos 50 células por paciente. RESULTADOS: A porcentagem das células epiteliais positivas para o antígeno Ki-67 no lado nasal e temporal após o tratamento dos três grupos estudados foi: nasal (3,30 por cento G1, 4,49 por cento G2 e 3,38 por cento G3) e temporal (3,30 por cento G1, 4,46 por cento G2 e 4,14 por cento G3) não mostrando diferença significativa. A cariometria do núcleo dos fibroblastos foi: Vl nasal (792,1 µ3 G1, 605,1 µ3 G2, e 549,9 µ3 G3) e a Ar (100,58 µ2 G1, 83,13 µ2 G2, e 78,41 µ2 G3). Os três grupos mostraram uma diferença significativa p=0,039 e p=0,035, respectivamente do Vl e da Ar no lado nasal. Após seis meses de tratamento, os três grupos apresentaram a seguinte taxa de recidiva: 22,22 por cento G1, 18,18 por cento, G2 e 33,33 por cento G3 respectivamente. CONCLUSÃO: O uso da MMC não interferiu nas células epiteliais positivas para o antígeno Ki-67 no pterígio recidivado, mas acarretou diminuição do volume e área dos núcleos dos fibroblastos no lado nasal do pterígio. As células epiteliais positivas para o antígeno Ki-67 parecem não ter relação com a recidiva do pterígio após seis meses...

Study of the Nuclear Volume of Testicular Cells of Rats Receiving Ofloxacin Through Lactation / Estudio del Volumen Nuclear de Células Testiculares de Ratas que Recibieron Ofloxacin Durante la Lactancia

Ofloxacin presents an ample spectrum of antimicrobial action, including combating Mycobacterium leprae, and is currently employed as a substitute when the use of rifampicin is impossible. The objective of this work was to study alterations in testicular cell nuclei of suckling rats, whose dams were submitted to oral application of ofloxacin, and respective control groups. The method utilized was morphometry by the karyometric technique. The main structures observed in histological preparations of the testicles were interstitial cells, spermatogonias, and sustentacular cells. 10 Wistar rats were utilized, four treated and five controls, in the period of the first 25 days of life, whose dams received ofloxacin 12 mg/ Kg of body weight / day orally, before being killed on the 25th day after birth. The karyometric study of interstitial cells and spermatogonias revealed that there were no changes in the form of their nuclei (p > 0.05). Since sustentacular cell nuclei presented increased major diameter, minor diameter, mean geometric diameter, volume, area, volume/area ratio and perimeter, as well as an augmented and statistically different eccentricity (p < 0.05) in suckling pups whose dams were administered ofloxacin, the nuclei presented larger size and more elongated form. It was concluded that the sustentacular cells were more sensitive to the ofloxacin effect at the administered dose.

El ofloxacin presenta un amplio espectro de acción antimicrobiana, incluyendo el combate a.Mycobacterium leprae, y es frecuentemente empleado como un sustituto cuando el uso de la rifampicina es imposible. El objetivo del trabajo fue estudiar las alteraciones en el núcleo de las células testiculares en ratas que se encontraban amamantando y que fueron sometidas a la aplicación oral de ofloxacin. El método utilizado fue la técnica morfométrica de la cariometría. Las principales estructuras observadas en las preparaciones histológicas fueron las células intersticiales, espermatogenias y células sustentaculares. Se utilizaron 10 ratas Wistar, cinco fueron el grupo control y cinco sometidas al tratamiento, cuyas madres recibieron ofloxacin en dosis oral diaria de 12 mg/Kg de peso corporal los primeros 25 días de vida, para luego ser sacrificadas al día 25 después del nacimiento. El estudio cariométrico de las células intersticiales y de la espermatogénesis revelaron que no hubo cambios en la forma de sus núcleos (p > 0,05). Las células sustentaculares presentaron un incremento en su diámetro mayor, diámetro menor, diámetro geométrico promedio, volumen, área, razón volumen/área y perímetro, también hubo aumento con una diferencia de la excentricidad estadísticamente significativa (p < 0,05) en las crías amamantadas, a las cuales se les administró ofloxacin. Los núcleos presentaron un gran tamaño y una forma más alargada. Esto concluye que las células sustentaculares son más sensibles al efecto de la administración de ofloxacin.

Effect of Sodium Cyclamate on the Rat Fetal Liver: A Karyometric and Stereological Study / Efectos del Ciclamato de Sodio en el Hígado Fetal de Ratas: Estudios Cariométrico y Estereológico

The cyclamate, a sweetner substance derived from N-cyclo-hexyl-sulfamic acid, is largely utilized as a non-caloric artificial edulcorant in foods and beverages as well as in the pharmaceutical industry. The objective of this study was to evaluate fetal hepatic karyometric and stereological alterations in the rat fetal liver resulting from the intraperitoneal administration of sodium cyclamate. The livers of ten rats were evaluated, five treated and five controls chosen at random, in which five rats that received from the 10th to 14th days of pregnancy an intraperitoneal daily injection of sodium cyclamate at 60 mg/Kg of body weight during 5 days. At the 20th day of gestation, the animals were removed and weighed, as were their placentas, on a precision balance; the length of the umbilical cords also were measured. After the laboratory processing, semi-seriated 6mm cuts stained with haematoxyline and eosine were performed. In seven karyometric parameters (major, minor, and medium diameters, volume, area, perimeter, and volume-area ratio), the increase was statistically significant in the treated group when compared with control group. Stereological parameters showed in the treated group a significant increase in the cytoplasmatic and cellular volume, and a significant reduction in the nucleus-cytoplasm ratio as well as in the numerical cellular density. These results showed that the sodium cyclamate in pregnant rats led to retardation of fetal development and hepatic-cellular hypertrophy in the offspring, suggesting toxicity in liver of rat fetuses.

El ciclamato, es una substancia derivada del ácido N-ciclo-hexil-sulfámico, bastante usada como edulcorante no calórica en alimentos y bebidas, así como en la industria farmacéutica. El objetivo del trabajo fue evaluar los efectos del ciclamato de sodio en hígados de fetos de ratas, considerándose las alteraciones cariométricas y estereológicas. Fueron utilizadas 10 ratas adultas (Rattus norvegicus) variedad Wistar, con peso medio de 240 g, siendo 5 el grupo control y 5 tratadas con ciclamato de sodio. Entre el 10 y 14 día de la preñez, 5 ratas recibieron una inyección diaria intraperitoneal de 60mg/Kg/día de ciclamato de sodio durante 5 días. En el 20 día, los animales fueron sacrificados y los fetos fijados en solución de Alfac, incluidos en parafina, cortados a 6 µm y teñidos com H-E. Hubo aumento estadísticamente significativo en siete parámetros cariométricos (diámetros mayor, menor y medio, volumen, área, perímetro y relación área/volumen) en el grupo tratado con ciclamato de sodio comparado con el grupo control. Parámetros estereológicos mostraron aumento significativo en los volúmenes citoplasmático y celular y disminución significativa en la relación núcleo/citoplasma y densidad numérica celular. Los resultados mostraron que el uso del ciclamato de sodio en las ratas preñadas causó retardo en el desarrollo fetal e hipertrofia celular hepática en los fetos, sugerente de toxicidad en el hígado fetal de las ratas.

Acción del Etanol sobre el Epitelio Nasal y Glándulas Septales de Ratas, Durante la Lactancia / Action of Ethanol on Rat Pups Nasal Epithelium and Septal Glands, During Lactation

El consumo materno de etanol durante la lactancia altera la composición de la leche, provoca la aparición de etanol y acetaldehído en la leche y agrava los efectos del etanol en las crías de ratas. De este modo, fueron estudiados los efectos del etanol, administrado a las ratas madres durante la lactancia, sobre el epitelio respiratorio y en las glándulas septales anterior y posterior de las crías lactantes con 21 días de vida postnatal. Las ratas recibieron etanol al 20% en el bebedero, ad libitum durante los 21 días que amamantaron. Los controles recibieron un volumen similar de agua sin alcohol. Las crías fueron sacrificadas en el 21 día. Las cabezas fueran cortadas frontalmente. Los cortes seriados de 6 µm de grosor fueron teñidos con hematoxilina y eosina. Fueron determinados los parámetros nucleares de los epitelios respiratorio y glandular, así como los volúmenes citoplasmático y celular, relación núcleo-citoplasma, densidades numérica y superficial y espesor del epitelio. El peso corporal medio de las crías control fue 34,9 g y en las tratadas 20,2 g. Histologicamente, el epitelio respiratorio se mostró adelgazado en el grupo tratado, constituido por células abundantes y menores, con núcleos menores. La glándula septal posterior presentó ácinos menores. En este trabajo, el etanol indujo un cuadro de hipotrofia epitelial (respiratorio y glandular), indicando una acción directa sobre las células de la mucosa nasal, además de retardar el desarrollo de las crías intoxicadas.

Maternal ingestion of ethanol during lactation alters the chemical composition of milk, results in the appearance of ethanol and acetaldehyde in milk, and exacerbates the effects of ethanol on the rat pups. So that, the effect on respiratory epithelium and anterior and posterior septal glands in 21-day-old suckling pups of ethanol treated mothers was studied. Female rats received dinking water ad libitum containing ethanol (20%) throughout the whole lactation. Control animals received a similar volume of water without ethanol. Lactent rats (21 day-old) were killed by lethal dose of anesthetic. The heads were serially sectioned (6µm thick) in a frontal plain, and stained with haematoxylin and eosin. Cell nuclear parameters were estimated, as well as cytoplasm and cell volume, nucleus-cytoplasm ratio, number and surface densities, and epithelial thickness. Mean body weight of the pups was 34.9 g for the controls and 20.2 g for the treated group. Histologically, the respiratory epithelium was thinner, with more numerous and smaller cells and small nuclei. The posterior septal glands showed smaller acini. In this paper, ethanol induced epithelial (respiratory and glandular) hypotrophy, indicating a direct action in nasal mucous cells, besides retarded development in pups.

Karyometry of malignant melanoma cells present in skin strippings.

BACKGROUND/AIMS: Skin strippings harvest the malignant melanoma cells eliminated through the stratum corneum. In this study, morphometry was applied to such non-invasive samplings in order to derive objective information about nuclear atypia. METHOD: Cyanoacrylate skin surface strippings were collected from 140 malignant melanomas. Karyometry was performed to quantify the size and shape of malignant cell nuclei. RESULTS: Anisokaryosis was prominent although the outline of nuclei were rather smooth. CONCLUSION: Image analysis of skin strippings harvested from malignant melanomas shows that anisokaryosis is the major cytologic feature of malignant melanoma cells in transit in the stratum corneum.