Early changes induced by short-term low-dose cadmium exposure in rat ventral and dorsolateral prostates

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The etiology of PCa in humans is multifactorial and includes age, ethnicity, environmental factors, and other unknown causes. Epidemiological and experimental evidence has shown that cadmium is associated with PCa both in humans and rodents. This metal can act as an endocrine disruptor during prostate development, and it induces prostate lesions late in life. In this study, we investigated the effects of low-dose cadmium on rat prostate morphology during puberty. Two-month-old male Wistar rats were randomized into two experimental groups: cadmium-treated and control. The ventral and dorsolateral prostates were dissected, weighed, and immunohistochemically stained with specific antibodies against Ki-67 and the androgen receptor (AR). The concentration of cadmium was measured in the blood and prostate, and testosterone concentration was measured from the plasma. Our results show that cadmium concentration was increased in both the blood and the prostate of cadmium-treated rats, but there were no changes in the prostatic weight, epithelial cell height, or testosterone levels. However, AR immunostaining and epithelial cell proliferation (Ki-67 index) were increased in both prostates with an increase in apoptosis only in the dorsal lobe. Furthermore, atypical hyperplasic proliferative lesions were found in the dorsolateral lobe after cadmium exposure. Cadmium treatment reduced collagen fiber absolute volume in both prostates. Thus, low-doses of cadmium, even for a short period of time, can interfere with prostate epithelium-stroma homeostasis, and this disruption might be an important factor in the onset of prostate lesions late in life.     

Doxazosin treatment alters stromal cell behavior and increases elastic system fibers deposition in rat prostate

Doxazosin (DOX), an α‐adrenoceptor antagonist, induces the relaxation of smooth muscle cell tonus and reduces the clinical symptoms of benign prostatic hyperplasia (BPH). However, the effects of DOX in the prostate stromal microenvironment are not fully known. In a previous study, we showed that DOX treatment for 30 days increased deposition of collagen fibers in the three rat prostatic lobes. Herein, we investigated the effects of DOX on stromal cell ultrastructure and elastic fiber deposition. Adult Wistar rats were treated with DOX (25 mg/kg/day); and the ventral, dorsal, and anterior prostates were excised at 30 days of treatment. The prostatic lobes were submitted to histochemical and stereological‐morphometric analyze and transmission electron microscopy (TEM). Histochemical staining plus stereological analysis of the elastic fiber system showed that DOX‐treated prostatic lobes presented more elaunin and elastic fibers than controls, mainly in the ventral lobe. Ultrastructural analysis showed that fibroblasts and smooth muscle cells from DOX‐treated prostates presented active synthetic phenotypes, evidenced by enlarged rough endoplasmic reticulum and Golgi apparatus cisterns, and confirmed the observation of thickened elaunin fibers. Our findings suggest that, under α‐adrenergic blockade by DOX, the fibroblasts become more active and smooth muscle cells shift from a predominantly contractile to a more synthetic phenotype. The deposition of collagen and elastic system fibers in the prostatic stroma may counterbalance the absence of smooth muscle tone during α‐blockers treatment. Microsc. Res. Tech. 73:1036–1044, 2010. © 2010 Wiley‐Liss, Inc.     

Quantitative analysis of pore patterns on rat prostate nuclei using spatial statistics methods

Spatial statistics methods have been used to analyse the nuclear pore pattern in rat ventral prostate nuclei isolated from adult animals. The observed results show that: (1) pores on prostate nuclear membranes are not randomly distributed; (2) the data sets obtained from different micrographs are consistent with the same statistical model thus suggesting the existence of a typical pore distribution.     

Modulation of IL-10/IL-10R expression by mafosfamide,a derivative of 4-hydroxycyclophosphamide,in a rat B-cell lymphoma

We have already shown that IL-10 plays an important role in immunosuppression and metastatic dissemination in the rat B-cell lymphoma L-TACB model. It was suggested that the up-regulation of IL10 production and IL-10 receptor (IL-10R) expression would be part of the transition from primary tumor to metastatic phenotype and that IL-10, besides its immunosuppressive activity, may act as a growth factor for metastatic L-TACB cells. The treatment of L-TACB-bearing rats with a single low-dose cyclophosphamide decreased IL-10 production, reverted immunosuppression and induced the immunologic rejection of tumor metastasis without any effect on primary tumor growth. Our current aim was to investigate the effects of cyclophosphamide on the expression of IL-10 and IL-10R on primary and metastatic L-TACB cells. Considering that cyclophosphamide is a prodrug, we used mafosfamide, a compound that yields in vivo the same active metabolites as cyclophosphamide does in vivo. Mafosfamide induced down-regulation of IL-10 production and IL-10R expression on metastatic cells and, concomitantly, inhibited metastatic cell proliferation. We suggest that mafosfamide would inhibit the regulatory loop mediated by the IL-10/IL-10R system and, as a consequence, metastatic cell proliferation. These results may have a considerable impact on the design of new therapies for metastatic lymphomas.     

Postnatal development of Mongolian gerbil female prostate: An immunohistochemical and 3D modeling study

The development of the prostate in male rodents, which involves complex epithelial–mesenchymal interactions between the urogenital sinus epithelium (UGE) and the urogenital sinus mesenchyme (UGM), has been deeply studied. In females, however, this process is not very clear. In this study, the postnatal development of the prostate in female Mongolian gerbils employing three‐dimensional (3D) reconstructions, histochemical, and immunohistochemical techniques was characterized. It was observed that prostatic branching and differentiation in females was induced by a single mesenchyme localized at a ventrolateral position, which was named as ventrolateral mesenchyme (VLM); furthermore, the canalization of solid buds began on the third postnatal day (P3) and the branching morphogenesis on P5. We observed secretions in the acini at the end of the first month, and, on P45, the acini were completely differentiated. The strong cell proliferation phase in the first week coincided with the mesenchymal expression of estrogen receptor 1 (ESR1). The expression of androgen receptor (AR) paralleled cell differentiation, and, on P30, immunolabelling with p63 was restricted to basal cells. This study serves as a baseline parameter for future research on disruptions that could affect the development of the female prostate. Microsc. Res. Tech. 79:438–446, 2016. © 2016 Wiley Periodicals, Inc.     

前列腺高精度穿刺机理及策略研究

针介入前列腺中,前列腺会产生漂移、变形以及针尖会产生偏转等问题。为了改善机器人操控穿刺针的定位精度,研究了振动、旋转穿刺软组织机理,建立针-前列腺相互作用力模型。利用制备的实验平台分别完成了振动穿刺和旋转穿刺效果评估实验;通过对上述实验结果的分析,提出了一种基于振动和旋转的高精度进针策略,并设计了相应的进针策略控制软件;最后,采用高精度进针策略完成了穿刺力评估实验,实验结果验证本文进针策略的有效性。     

Post-treatment with plant extracts used in Brazilian folk medicine caused a partial reversal of the antiproliferative effect of glyphosate in the<i> Allium cepa </i> test

Species of the genus Psychotria are used for multiple purposes in Brazilian folk medicine, either as water infusions, baths or poultices. This study was aimed to evaluate the genotoxic and antiproliferative effects of infusions of Psychotria brachypoda and P. birotula on the Allium cepa test. Exposure to distilled water was used as a negative control, while exposure to glyphosate was used as a positive control. The interaction of extracts (as a post-treatment) with the effects of glyphosate was also studied. Results showed that glyphosate and the extracts of both P. brachypoda and P. birotula reduced the mitotic index as compared with the negative control (distilled water). Surprisingly, however, both extracts from P. brachypoda and P. birotula caused a partial reversal of the antiproliferative effect of glyphosate when used as a post-treatment. Glyphosate also induced the highest number of cells with chromosomal alterations, which was followed by that of P. birotula extracts. However, the extracts from P. brachypoda did not show any signifi cant genotoxic effect. Post-treatment of glyphosate-treated samples with distilled water allowed a partial recovery of the genotoxic effect of glyphosate, and some of the Psychotria extracts also did so. Notably, post-treatment of glyphosatetreated samples with P. brachypoda extracts induced a statistically signifi cant apoptotic effect. It is concluded that P. brachypoda extracts show antiproliferative effects and are not genotoxic, while extracts of P. birotula show a less potent antiproliferative effect and may induce chromosomal abnormalities. The finding of a partial reversion of the effects of glyphosate by a post-treatment with extracts from both plants should be followed up.     

Morphology of the intralobular duct of the submandibular gland in rats in case of experimental diabetes mellitus

The objective of study is to study the peculiarities of morphological changes in different subdivisions of the intralobular duct of the submandibular gland (SMG) in rats in case of experimental diabetes mellitus (DM). The study included sexually mature male Wistar rats. Experimental DM was induced by streptozotocin. Electron microscopic study of subdivisions of the intralobular duct of the SMG was carried out on the 14th, 28th, 42nd, 56th, and 70th days of the experiment. In early stages of experimental DM the intercalated ducts are characterized by a relatively unchanged structure, and in late stages vacuolization of the cytoplasm of their epithelial cells is observed. Since the 14th day vacuolization of mitochondria is observed in epithelial cells of the granular ducts being the most pronounced on the 28th day and not apparent over the subsequent periods. The degree of filling with granules reduces till 56th day, however, it increases sligthly on the last day of the experiment. On the 28th–70th days vacuolization of the cytoplasm is observed in epithelial cells of the striated ducts. In addition, on the 14th day the mitochondrial matrix of these cells condenses; over the next periods it becomes enlightened and mitochondrial cristae are clearly visualized and disorganized. Conclusion: In the intralobular duct of the SMG in experimental DM dystrophic changes of different intensity occur in the granular and striated ducts on the 14th day and in the intercalated ducts only since the 42nd day of the experiment.     

辛伐他汀和罗格列酮对糖尿病患者动脉粥样硬化的影响

目的研究辛伐他汀和罗格列酮对2型糖尿病患者动脉粥样硬化的作用。方法 78例2型糖尿病伴颈动脉粥样斑块患者随机分为辛伐他汀组、罗格列酮组和联合组,分别口服辛伐他汀20mg/次、罗格列酮4mg/次及辛伐他汀20mg+罗格列酮4mg/次,每日1次,疗程3个月。在基线水平和疗程结束时经颈动脉超声检测CIMT,同时检测患者脂肪因子和炎症因子水平。观察治疗前后颈动脉内膜中层厚度及斑块变化。结果各组用药治疗3月后血脂、脂肪因子和炎性因子降低,CIMT厚度减低、斑块面积缩小,但斑块数量无减少,且联合用药比单一用药效果更显著。结论 2型糖尿病患者联合使用辛伐他汀和罗格列酮可改善胰岛素抵抗、改善脂类代谢、抑制大血管炎症反应、稳定和缩小动脉粥样斑块。     

Extraglandular and intraglandular vascularization of canine prostate

The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism.     

Theoretical analysis on effects of grain size variation

Grinding wheels consist of abrasive grains, bonding materials and porous, which are specified by five factors; type of grain, size of grain, bonding material, bonding strength and grain concentration or volume fraction of grain. The grain size is represented by the mean diameter/radius of grains. However, the abrasives in a grinding wheel are randomly scraggly in size and shape. There is no particular aspect to regulate the variation in grain size. This paper addresses, via a theoretical analysis on the distribution of grain size, the average volume of a grain, the number of grains contained in a specific volume of the wheel, the number and protrusion distribution of grains exposed in a wheel working surface and the fraction of effective grain, when the grain size varies. The effect on the resultant finished surface roughness is also discussed.     

Microscopic comparative study of the exposure effects of testosterone cypionate and ethinylestradiol during prenatal life on the prostatic tissue of adult gerbils

There is an increasing variety of endocrine disrupting chemicals (EDCs) either with (anti)estrogenic or (anti)androgenic potential widely present in the environment. These xenosteroids may mimic endogenous steroid hormones disrupting the homeostasis of physiological pathways and leading to several disturbances, especially in tissues highly dependent on steroid hormones such as the prostate. Taking this into account, this comparative study aimed to verify the potential of ethinylestradiol (EE) and testosterone acting as ECDs on the prostate of both male and female adult gerbils exposed to these agents during the embryonic phase. Consequently, pregnant gerbils were treated either with 10 μg/kg/day of EE or with a single dose of 1 mg of testosterone cypionate. The pups that were born 6-8 days after testosterone exposure and the pups that were born after 3 days of EE exposure were allowed to grow but were sacrificed within 4 months. Serological, morphological, stereological, and immunohistochemical analyses were used. Overall, the results showed that both sexes exposed to testosterone and EE during gestation had a prostatic gland with an increased stromal and epithelial and a reduced luminal compartment. Moreover, we observed that glands affected with prostatic intraepithelial neoplasia showed intense stromal reshuffling. In conclusion, although these alterations were observed in both sexes, more relevant to this study was the differential responsiveness of males and females exposed to these different drugs. Whereas the EE affected males more, the testosterone was more harmful to the females.     

Inhibitory effects of Broccolini leaf flavonoids on human cancer cells

Broccolini (Brassica oleracea Italica × Alboglabra) is a hybrid between broccoli and Gai Lan, also known as Chinese broccoli and Chinese kale. The aim of this study was to assess the antitumor activity of Broccolini leaf flavonoids (BLF). Cell growth inhibition was evaluated using a standard colorimetric MTT assay, cellular morphology was observed using phase contrast microscopy and flow cytometry was introduced to further investigate cells apoptosis effect. The results showed that BLF possess a dose-dependent antiproliferative effects on four human cancer cell lines (SW480, HepG2, Hela, and A549) and apoptosis induction activity on SW480 cell line. Thus, the hybrid species Broccolini could be considered as a functional vegetable with potential in assisting for the treatment of four human cancers examined here.     

基于水平集的前列腺磁共振图像分割方法研究

基于前列腺磁共振图像(MRI)特征信息及其病变好发特定区域等先验知识,针对前列腺内外轮廓全分割问题,提出基于边缘距离调整水平集演化(DRLSE)的前列腺MRI两步分割方法。在构建统一水平集能量函数的基础上,第1步基于前列腺MR的T1(纵向弛豫时间)图像实现其外轮廓分割,第2步在外轮廓约束限定条件下,基于前列腺MR的T2(横向弛豫时间)图像实现前列腺的内部轮廓分割,进而完成前列腺内外轮廓的全面有效分割。设计了前列腺分割的人机交互界面,对10个前列腺病例MR图像(含正常、增生和癌变共30幅)进行了分割实验研究,并采用Dice相似性系数(DSC)对分割结果进行评价分析,DSC值达到90%以上。实验结果表明,所提出的基于边缘DRLSE的前列腺MRI两步分割方法能够有效地实现前列腺内外轮廓的全面分割,非常接近于临床专家手动分割的理想结果,对前列腺疾病的临床诊断和治疗有较好的参考价值。     

Systematic variation of polymer jacketed fibres and the effects on tip etching dynamics

Using a chemically etched fibre probe through a plastic jacket provides a simple way to smooth a tip's surface. Convection flow in the plastic tube and lateral diffusion with fixed meniscus height has been proposed to explain such improvement. Fibres with additive thin polymer layers and bare fibres with thick untapered/tapered plastic layers have been prepared to verify the dominant mechanism. The additive layers greatly change the tip's geometry and bare‐fibres with untapered plastics cannot form tips. This confirmed that lateral diffusion dominates the etching process. Based on our investigation, we propose a new non‐meniscus end‐etching method by using tapered plastics. Unlike etching methods with meniscus, the end‐etching method can regularly form very smooth tips. It is insensitive to vibrations and temperature drifts and also suitable for most fibres.     

Effect of streptozotocin on the ultrastructure of rat pancreatic islets

Our objective was to study the effects of three (30, 40, and 50 mg/kg) doses of Streptozotocin (STZ) on fasting plasma glucose level (FPG) and observe its effects at the cellular level in rat pancreas by electron microscopy. FPG was measured in rats before induction of diabetes and then on 3, 7, and 14 days after induction of diabetes with STZ. Keto diastix urine strips were used to check urine glucose and ketone bodies. Two weeks after the induction of diabetes, the rat pancreas was removed and fixed for light and electron microscopic studies. Three days after induction, the mean FPG level was 112 mg/dl in Group I (30 mg/kg STZ), 217 mg/dl in Group II (40 mg/kg STZ), and 376 mg/dl in Group III (50 mg/kg STZ). Histology was normal in Group I but revealed altered islet structure in Groups II and III. Ultrastructure revealed intact D cells in all three groups. The focal mitochondria and Golgi complex swelling found in A and B cells was occasional in Group I and frequent in Groups II and III. Swelling of other organelles and reduction in the size and number of granules was further observed in Group III. It is our conclusion that the 30-mg/kg body weight STZ produces mild changes while 50 mg/kg proves to be fatal. STZ at 40 mg/kg has a moderate effect on plasma glucose as well as on the islets of Langerhans at a cellular level.