Numerical Density Of Cells Research Articles

Structural and Functional Peculiarities of Mast Cells in Undifferentiated Connective Tissue Dysplasia

We performed an immunomorphological study of mast cells from undamaged skin in women with phenotypical evidence of undifferentiated connective tissue dysplasia syndrome, patients of cosmetological clinics. It was found that the numerical density of mast cells containing chymase granules in this condition 1.7-fold surpassed the corresponding parameter in patients without signs of connective tissue dysplasia syndrome, which probably was a result of compensatory and adaptive reaction aimed at activation of the synthesis of the connective tissue extracellular matrix components. It was hypothesized that increased content of chymase-positive mast cells in the skin of patients with connective tissue dysplasia syndrome contributed to the formation of associated arterial hypertension.

Alterations in hippocampal calcium-binding neurons induced by stress models of depression: a preliminary assessment

In this study, the neuropathological changes induced by chronic unpredictable stress (CUS) and chronic mild stress (CMS) in calbindin D-28K (CB) and parvalbumin (PV) immunoreactive neurons in the rat hippocampus were demonstrated. We used immunohistochemical techniques to quantify the numerical density and morphological changes of PV immunoreactive and CB immunoreactive neurons in the dentate gyrus (DG) and the CA1 and CA3 regions of the hippocampus. We also assessed cell proliferation (Ki-67) and apoptotic processes (active caspase-3) in the DG. We found a significant decrease (16.6% for CUS and 13.3% for CMS) in the numerical density of granule cells (GC), alterations in the CB immunoreactive cells of the GC in the DG and an impairment of mossy fiber CB immunolabelling in the CA3. These changes were not accompanied by a decrease in Ki-67 labeling or the level of capsase-3in the DG. These data indicate a stress-induced reduction of calcium binding neuron parameters, which may be related to the behavioral paradigms exhibited in these models.

MORPHOLOGICAL STUDIES OF HEPATIC TISSUE OF MICE REINFECTED WITH DENGUE VIRUS SEROTYPES 1 OR 2

Histopathological and ultrastructural aspects of liver of non-neuroadapted BALB/c mice reinfected by the intravenous route with dengue virus serotypes 1 and 2 were presented. The hepatic tissue was processed following the standard techniques for photonic and transmission electron microscopy. Morphological studies showed vacuolization of hepatocytes, inflammatory cells inside sinusoidal capillaries, enlargement of sinusoidal capillaries, foci of hemorrhage inside the interstitium, increase of surface density of reticular fibres, increase of numerical density of sinusoidal cells, decrease of surface density of hepatocytes, edema in the peri centrolobular vein space and presence of phyllopods and pseudopod-like extensions in endothelial cells. DENV particles, virus antigens and DENV RNA were observed in mosquito cells (C6/36) inoculated with sera of the animals 72 hours post-reinfection. The hepatic alterations observed in our experimental model were similar to those observed in human cases of dengue hemorrhagic fever. The present study shows that BALB/c mice reinfected with a heterologous serotype of DENV develop more severe lesions than those observed in mice in primary infection. DOI: http://dx.doi.org/10.17525/vrr.v15i2.68

Histological and histomorphometrical evaluation of furcation perforations filled with MTA, CPM and ZOE

To evaluate the biological response of the periodontium adjacent to furcation perforations in rat molars filled with Endo-CPM-Sealer (CPM), MTA-Angelus (MTA) or zinc oxide-eugenol cement (ZOE). The pulp chamber floors of maxillary right first molar teeth were perforated and sealed with CPM, mineral trioxide aggregate (MTA) or ZOE; the left first molars, without any treatment, were used as controls (CG). After 7, 15, 30 and 60 days, fragments of maxilla were fixed, decalcified and embedded in paraffin. Sections were stained with H&E, Masson's trichrome and submitted to tartrate-resistant acid phosphatase (TRAP) reaction, used as an osteoclast marker. The width of the periodontal space, the numerical density of inflammatory cells and the number of TRAP-positive osteoclasts in the bone surface were measured, and statistical analyses were performed using analysis of variance and Tukey test (P ≤ 0.05). In all experimental groups, the greatest number of inflammatory cells was observed at 7 days, especially in the ZOE group. In this group, the intense inflammatory process was related to a significant increase (P ≤ 0.05) in the number of osteoclasts and, thereby, in an increase in the width of the periodontal space. At 60 days, no significant differences in osteoclast numbers amongst CPM, MTA and CG groups occurred; the periodontal space was also significantly reduced in the experimental groups in comparison with the initial periods. However, in the ZOE group, the periodontal space was significantly larger (P ≤ 0.05) in comparison with MTA-based materials. The periodontium adjacent to perforations filled with MTA and CPM exhibited clear evidence of re-establishment and thus better biocompatibility than ZOE.

Tunel and Growth Factor Expression in the Prefrontal Cortex of Alzheimer Patients over 80 Years Old

To elucidate factors underlying the increased risk of developing Alzheimers disease (AD) in older individuals, the prefrontal cortices of younger (58-79 years) and of older (over 80 years) AD patients were examined by silver impregnation, TUNEL assay and immunohistochemistry for hyperphosphorylated tau, LDH and two growth factors (BDNF, NGF). Quantitative data were compared with those of age-matched controls. TUNEL-positive cells were mainly located in superficial cortical layers of younger and in deeper layers of older AD patients. Their density was more than 5 times higher in older AD than in younger AD (p < or = 0.05), but apoptotic cell morphology was rarely seen. Significantly more neuronal somas were contacted by degenerating fibers both in younger and older AD cortices. Density of tau-immunoreactive cells, which were virtually absent in controls, was twice as high in older AD patients as in younger AD individuals (p < or = 0.05). In younger AD, TUNEL positive cells generally lacked tau immunoreaction, whereas in older AD, most cells were double-labeled for hyperphosphorylated tau and TUNEL (p < or = 0.05). Numerical density of BDNF-immunoreactive cells was significantly reduced by 20 percent in older AD patients, compared to both control individuals and younger AD patients, whereas density of NGF-positive cells was the same in all patient groups examined. The distinct differences between younger and older AD patients suggest a faster progression of AD in older patients.

Structural Peculiarities of Epidermal Barrier in Individuals with Syndrome of Undifferentiated Connective Tissue Dysplasia

Histological, morphometric, and immunohistochemical analysis showed that the specific features of epidermal barrier structure in patients with undifferentiated connective tissue dysplasia syndrome are increases number of keratinocyte rows in the basal and prickly layer as a result of their higher mitotic activity, increased numerical density of Langerhans cells, and suppression of terminal keratinocyte differentiation.

Effects of folic acid and homocysteine on spinal cord morphology of the chicken embryo

Maternal ingestion of folic acid (FA) reduces neural tube defects, which are associated with high homocysteine levels. Present study evaluated the effects of FA and homocysteine on cell proliferation and cell adhesion, as well as on apoptosis, throughout the development of the spinal cord and mesenchyme of chicken embryos. Normal closure of the neural tube and a regular distribution of the mesenchymal cells were observed in control and FA-treated embryos. All homocysteine-treated embryos and also 6 of 10 embryos treated with FA+homocysteine showed failure of closure of the neural tube. Homocysteine decreased the thickness of the mantle and marginal layers of the spinal cord, and FA did not prevent this effect. FA treatment reversed the decrease of proliferating cells in the spinal cord induced by homocysteine. FA-treated embryos showed the highest numerical density of apoptotic cells. Homocysteine treatment reduced NCAM expression in both spinal cord and mesenchymal tissue, and FA prevents this effect. These results are important because they demonstrate in situ that the imbalance between FA and homocysteine levels can lead to disruptions in spinal cord development, changing proliferation, apoptosis, and cell adhesion and consequently changing the arrangement of the spinal cord layers.

Structural Transformations of Myocytes during Gestation and Early Postpartum Involution of the Uterus

Myocytes with large homogeneous vacuoles and numerous protrusions of the cytoplasm into extracellular space (manifestations of clasmatosis) were detected in rat myometrium during normal gestation and early postpartum period. The percentage of vacuolated smooth-muscle cells and numerical density of inflammatory cells in the myometrium were evaluated. The data indicate the absence of typical inflammatory reaction in the myometrium during elimination of smooth-muscle cells in the course of postpartum involution. Clasmatosis and apoptosis are hypothesized to be the main mechanisms providing reduction of the uterine weight after delivery.

Mast Cells and Angiogenesis in Oral Malignant and Premalignant Lesions

Mast cell contribution to neoangiogenesis during tumorigenesis in oral squamous cell carcinoma is not determined yet. Objectives: To associate numerical mast cell density (MCD) to numerical microvessel density (MVD) during the progression of oral leukoplakia without dysplasia and leukoplakia with dysplasia to squamous cell carcinoma (OSCC). Materials and methods: MVD was analysed immunohistochemically (mouse monoclonal anti-human CD34) in 49 paraffin-embedded specimens, 35 OSCCs, 9 leukoplakias and 5 normal oral tissues. Toluidine blue counterstaining revealed mast cells. MCD and MVD were assessed at the same optical field. Results: MVD increased between: normal oral mucosa, dysplasia (p=0.004), OSCC (p=0.001), leukoplakia and OSCC (p=0.041). MCD increased between: normal oral mucosa, dysplasia (p=0.003), OSCC (p=0.000), leukoplakia and OSCC (p=0.007). MVD was found to depend on MCD (p=0.000) in a percent 28.3% (power curve fit model). Conclusions: Mast cells are attracted at the lesion site and may turn on an angiogenic switch during tumorigenesis in OSCC.

Cannabis and psychiatric disorders: it is not only addiction

Since the discovery of the endocannabinoid system, a growing body of psychiatric research has emerged focusing on the role of this system in major psychiatric disorders like schizophrenia (SCZ), bipolar disorder (BD), major depression and anxiety disorder. Continuing in the line of earlier epidemiological studies, recent replication studies indicate that frequent cannabis use doubles the risk for psychotic symptoms and SCZ. Further points of clinical research interest are alterations of endocannabinoids and their relation to symptoms as well as postmortem analyses of cannabinoid CB(1) receptor densities in SCZ. A possible neurobiological mechanism for the deleterious influence of cannabis use in SCZ has been suggested, involving the disruption of endogenous cannabinoid signaling and functioning. Even though the number of studies is still limited for affective and anxiety disorders, previous results suggest these diseases to be exciting objectives of cannabinoid-associated research. Therefore, it became apparent that cannabis use is not only frequent in patients suffering from BD, but that it also induces manic symptoms in this group. In addition, prior antipsychotic treatment decreased the numerical density of CB(1) immunoreactive glial cells in bipolar patients. Although the data on the influence of cannabis use on the development of major depression is controversial, cannabinoid compounds could display a new class of medication, as suggested by the antidepressive effects of the fatty acid amino hydrolase inhibitor URB597 in animal models. With numerous open questions and controversial results, further research is required to specify and extend the findings in this area, which provides a promising target for novel pharmacotherapeutic interventions.

A stereological study of copper toxicity in gills of Oreochromis niloticus

Stereological methods were used to estimate the volumetric density (VV) of the filamentar epithelium (FE, 39%), lamellae (L, 28%), central venous sinus (CVS, 14%), central axis (16%), mucous cells (MC, 2%) and chloride cells (CC, 1%) in the gill filament of control Nile Tilapia. The relative volumes of FE and L, and the relative volumes of CVS and central axis, varied inversely under exposure to copper, with high copper toxic levels declanching a chronic defence mechanism that was, nevertheless, overcome, and low copper toxic levels causing adaptation within a moderate acute phase type of response. Copper also induced a decrease of the VV (MC, gill filament) due to reduction of surface MC, despite the marked increase of stem MC at chronic exposure to high copper toxic levels. Diminution of the numerical density of filamentar CC was responsible for the decreased VV (CC, gill filament), although lamellar CC significantly increased at chronic exposure to low copper toxic levels. The present results demonstrate that cell relative volumes, mean volumes and numerical densities are dependent on the variations of the FE and L, which without a quantitative approach may be misinterpreted, thus stressing the importance of using stereological tools for analyzing histopathological patterns.

Surgical suturing of articular cartilage induces osteoarthritis-like changes

In clinical tissue-engineering-based approaches to articular cartilage repair, various types of flap are frequently used to retain an implanted construct within the defect, and they are usually affixed by suturing. We hypothesize that the suturing of articular cartilage is associated with a loss of chondrocytes from, and osteoarthritis-like changes within, the perisutural area. We established a large, partial-thickness defect model in the femoral groove of adult goats. The defects were filled with bovine fibrinogen to support a devitalized flap of autologous synovial tissue, which was sutured to the surrounding articular cartilage with single, interrupted stitches. The perisutural and control regions were analyzed histologically, histochemically and histomorphometrically shortly after surgery and 3 weeks later. Compared to control regions, chondrocytes were lost from the perisutural area even during the first few hours of surgery. During the ensuing 3 weeks, the numerical density of cells in the perisutural area decreased significantly. The cell losses were associated with a loss of proteoglycans from the extracellular matrix. Shortly after surgery, fissures were observed within the walls of the suture channels. By the third week, their surface density had increased significantly and they were filled with avascular mesenchymal tissue. The suturing of articular cartilage induces severe local damage, which is progressive and reminiscent of that associated with the early stages of osteoarthritis. This damage could be most readily circumvented by adopting an alternative mode of flap affixation, such as gluing with a biological adhesive.

The effect of prenatal X-irradiation on the developing cerebral cortex of rats. II: A quantitative assessment of glial cells in the somatosensory cortex

The developing central nervous system is known to be highly vulnerable to X-irradiation. Although glial cells are involved in various brain functions, knowledge on the effects of X-irradiation on glial cells is limited. Therefore, the purpose of the present study was to evaluate the effects of prenatal X-irradiation on glial cells. Pregnant Wistar rats were exposed to X-irradiation at a dose of 1.0Gy on day 15 of gestation. Their offspring were examined at 7 weeks of age. The forebrain weight of X-irradiated rats was significantly lower than that of the age-matched controls. Histological quantification with stereology of the somatosensory cortex (SC) revealed no significant difference in the numerical density of glial cells between the X-irradiated and control rats. However, the glial cells in the X-irradiated animals had significantly larger nuclear size. We had previously reported that a similar X-irradiation paradigm resulted in no significant change in the numerical density of neurons in the SC. According to the results of the present study, there were no significant differences in the glial cell-to-neuron ratios between the X-irradiated and control animals. Taken together, it is speculated that prenatal X-irradiation has an equal effects on the numerical densities of glial cells and neurons.

Insulin-like growth factor-I (IGF-I) inhibits neuronal apoptosis in the developing cerebral cortex in vivo

Increased expression of insulin-like growth factor-I (IGF-I) in embryonic neural progenitors in vivo has been shown to accelerate neuron proliferation in the neocortex. In the present study, the in vivo actions of (IGF-I) on naturally occurring neuron death in the cerebral cortex were investigated during embryonic and early postnatal development in a line of transgenic (Tg) mice that overexpress IGF-I in the brain, directed by nestin genomic regulatory elements, beginning at least as early as embryonic day (E) 13. The areal density of apoptotic cells (NA, cells/mm2) at E16 in the telencephalic wall of Tg and littermate control embryos was determined by immunostaining with an antibody specific for activated caspase-3. Stereological analyses were conducted to measure the numerical density (NV, cells/mm3) and total number of immunoreactive apoptotic cells in the cerebral cortex of nestin/IGF-I Tg and control mice at postnatal days (P) 0 and 5. The volume of cerebral cortex and both the NV and total number of all cortical neurons also were determined in both cerebral hemispheres at P0, P5 and P270. Apoptotic cells were rare in the embryonic telencephalic wall at E16. However, the overall NA of apoptotic cells was found to be significantly less by 46% in Tg embryos. The volume of the cerebral cortex was significantly greater in Tg mice at P0 (30%), P5 (13%) and P270 (26%). The total number of cortical neurons in Tg mice was significantly increased at P0 (29%), P5 (29%) and P270 (31%), although the NV of cortical neurons did not differ significantly between Tg and control mice at any age. Transgenic mice at P0 and P5 exhibited significant decreases in the NV of apoptotic cells in the cerebral cortex (31% and 39%, respectively). The vast majority of these apoptotic cells (>90%) were judged to be neurons by their morphological appearance. Increased expression of IGF-I inhibits naturally occurring (i.e. apoptotic) neuron death during early postnatal development of the cerebral cortex to a degree that sustains a persistent increase in total neuron number even in the adult animal.

Qualitative and quantitative differences between taste buds of the rat and mouse

BackgroundNumerous electrophysiological, ultrastructural, and immunocytochemical studies on rodent taste buds have been carried out on rat taste buds. In recent years, however, the mouse has become the species of choice for molecular and other studies on sensory transduction in taste buds. Do rat and mouse taste buds have the same cell types, sensory transduction markers and synaptic proteins? In the present study we have used antisera directed against PLCβ2, α-gustducin, serotonin (5-HT), PGP 9.5 and synaptobrevin-2 to determine the percentages of taste cells expressing these markers in taste buds in both rodent species. We also determined the numbers of taste cells in the taste buds as well as taste bud volume.ResultsThere are significant differences (p < 0.05) between mouse and rat taste buds in the percentages of taste cells displaying immunoreactivity for all five markers. Rat taste buds display significantly more immunoreactivity than mice for PLCβ2 (31.8% vs 19.6%), α-gustducin (18% vs 14.6%), and synaptobrevin-2 (31.2% vs 26.3%). Mice, however, have more cells that display immunoreactivity to 5-HT (15.9% vs 13.7%) and PGP 9.5 (14.3% vs 9.4%). Mouse taste buds contain an average of 85.8 taste cells vs 68.4 taste cells in rat taste buds. The average volume of a mouse taste bud (42,000 μm3) is smaller than a rat taste bud (64,200 μm3). The numerical density of taste cells in mouse circumvallate taste buds (2.1 cells/1000 μm3) is significantly higher than that in the rat (1.2 cells/1000 μm3).ConclusionThese results suggest that rats and mice differ significantly in the percentages of taste cells expressing signaling molecules. We speculate that these observed dissimilarities may reflect differences in their gustatory processing.

COMBINED PARS PLANA PHACOFRAGMENTATION, VITRECTOMY, AND ARTISAN LENS IMPLANTATION FOR TRAUMATIC SUBLUXATED CATARACTS

To report on the outcome of combined pars plana phacofragmentation, vitrectomy, and Artisan lens implantation in the management of subluxated cataracts. This prospective, interventional, nonrandomized case series included nine eyes of seven consecutive adult patients with traumatic lens subluxation. Pre- and postoperative data (complete manifest refraction, best spectacle-corrected visual acuity, slit-lamp examination findings, intraocular pressure, fundus status, numerical density of endothelial cells, corneal thickness, and complications) were collected prospectively for all patients. After a median postoperative follow-up of 12 months (range, 8-18 months), a mean spherical equivalent of -0.50 +/- 0.87 diopter (range, +1 to -1.50 diopter) was achieved. The mean logarithm of the minimum angle of resolution visual acuity improved from 1 (preoperatively) to 0.1 (postoperatively) (P = 0.007, Wilcoxon test). Median endothelial cell losses of 15 +/- 8% (P = 0.008) and 14 +/- 16% (P = 0.011) were registered at follow-ups of 1 month and 12 months, respectively. Postoperative complications included chronic intraocular inflammation and superior corectopia. Our procedure appears to be a safe, accurate, stable, and efficacious option for the management of traumatic subluxated cataracts in adults. However, longer-term data are needed to evaluate the corneal endothelium.

Lack of Annexin 1 Results in an Increase in Corticotroph Number in Male but not Female Mice

Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the pituitary. We have examined corticotrophs in wild-type and ANXA1 knockout mice to determine the effects of lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1 wild-type, heterozygote and null mice was fixed and examined (i) by confocal immunocytochemistry to determine the number of corticotrophs and (ii) by electron microscopy to examine the size, secretory granule population and secretory machinery of corticotrophs. No differences in these parameters were detected in female mice. In male ANXA1 null mice, there were approximately four-fold more corticotrophs than in wild-type animals. However, the corticotrophs in ANXA1 null mice were smaller and had reduced numbers of secretory granules (the reduction in granules paralleled the reduction in cell size). No differences in the numerical density of folliculo-stellate, gonadotroph, lactotroph or somatotroph cells were detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic hormone (ACTH) and pituitary pro-opiomelanocortin mRNA were unchanged but pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)-6 pituitary content was significantly elevated in male and reduced in female ANXA1 null mice compared to wild-type. In conclusion, these data indicate that ANXA1 deficiency is associated with gender-specific changes in corticotroph number and structure, via direct actions of ANXA1 and/or indirect changes in factors such as IL-6.

Pattern differentiation of excitatory and inhibitory synaptic inputs on distinct neuronal types in the rat caudal nucleus of the tractus solitarius

Region- and size-specific neuronal organizations of the caudal nucleus of the tractus solitarius (cNTS) were investigated, followed by analyses of excitatory and inhibitory synaptic input patterns onto specific cell types by patch clamp recordings and immunoelectron microscopy. Cell size distribution and numerical density of cNTS neurons were examined in subregions at levels of the area postrema. In the subpostremal and dorsomedial subnuclei, characterized by the presence of dense glutamatergic and sparse GABAergic somata, small calbindin neurons constituted 42% of the total cells. The medial subnucleus contained large numbers of glutamatergic, GABAergic, and catecholaminergic somata and large tyrosine hydroxylase-containing cells constituted 13% in this region. In total, small neurons (<150 μm 2) represented about 80% of the cell population in the cNTS. Predominant excitatory postsynaptic currents were observed in the adult small neurons, while inhibitory postsynaptic currents were more evident in larger neurons, irrespective of subnuclear location. This distinct differentiation of postsynaptic current patterns was not evident in neonates. GABAergic synapses were more frequently associated with dendrites of large catecholaminergic cells (73%) than with those of small calbindin-containing cells (10%) in adults. These results indicate that differential synaptic input patterns were developmentally established in distinct small and large neurons.

Quantitative analysis of influence of sevoflurane on the reactivity of microglial cells in the course of the experimental model of intracerebral haemorrhage

Microglial cells play an important role in the pathophysiology of intracerebral haemorrhage. We have examined the possible influence of sevoflurane on the reactivity of microglial cells during intracranial haemorrhage. Forty adult male rats were divided into two groups. All animals were anaesthetized with fentanyl, dehydrobenzperidol and midazolam. In the experimental group animals additionally received sevoflurane 2.2 vol% end-tidal concentration. Intracranial haemorrhage was produced through infusion of blood into the striatum. The microglial cell population (numerical density of immunoreactive cells and their distribution) was assessed on days 1, 3, 7, 14 and 21 after producing a haematoma using antibodies OX42 and OX6. In the control group significant differences in the density of OX42-ir cells between 3rd and 7th (81.86 vs. 129.99) (95% CI: -77.99 to -18.25, P = 0.0035) and between 14th and 21st (105.36 vs. 63.81) (95% CI: 13.21 to 69.89, P = 0.006) survival days were observed. However, significant increase of percentage of amoeboid OX42-ir cells between 3rd and 7th (0.98 vs. 48.71) (95% CI: -52.17 to -43.30, P = 0.0001) and between 7th and 14th (48.71 vs. 58.47) (95% CI: -13.96 to -5.55, P = 0.0002) and then their decrease - between 14th and 21st (58.47 vs. 31.74) (95% CI: 22.52 to 30.93, P = 0.0001) days of observation were noted. In the sevoflurane groups OX42-ir cells were not found. On the 3rd day the density of OX6-ir cells in the sevoflurane group was significantly lower than that in the control group (12.39 vs. 34.57) (95% CI: -49.78 to -2.96, P = 0.02). The percentage of an amoeboid form of OX6-ir cells was significantly lower in the sevoflurane group than that in the control group (27.31 vs. 82.03) (95% CI: -72.52 to -36.92, P = 0.0001) (58.76 vs. 82.37) (95% CI: -38.81 to -8.41, P = 0.003) (42.87 vs. 81.55) (95% CI: -53.23 to -24.10, P = 0.0001) respectively for 3rd, 7th and 14th days of survival. Administration of sevoflurane during anaesthesia in animals with intracerebral haemorrhage evoked a decrease of activation of the microglial cells.

Immunohistochemical Study of Cell Proliferation, Bcl-2, p53, and Caspase-3 Expression on Preneoplastic Changes Induced by Cadmium and Zinc Chloride in the Ventral Rat Prostate

This work was directed to evaluate immunoexpression of markers for apoptosis, resistance to apoptosis, and cell proliferation, as well as estimates of nuclear size in ventral prostate of rats treated with cadmium chloride and cadmium+zinc chloride because a possible protective effect of zinc has been postulated. The following variables were studied: volume fraction (VF) of Bcl-2 immunostaining, percentage of cells immunoreactive to proliferating cell nuclear antigen (LIPCNA) and p53 (LIp53), numerical density of caspase-3 immunoreactive cells (NV caspase-3), and estimates of volume-weighted mean nuclear volume (upsilonV). The LIPCNA and VF of Bcl-2 were significantly increased in the treated animals. The dysplasias (independent of their origin) showed a significant increase of the LIp53, NV caspase-3, and upsilonV in comparison with normal acini from treated and control animals. It can be concluded that cell proliferation is enhanced in long-term cadmium-exposed rats, and exposure to zinc combined with cadmium had no effect on any of the variables studied when comparing with normal acini. The increase of nuclear upsilonV could indicate a more aggressive behavior for pretumoral lesions.