Stromal Volume Research Articles

Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common urologic disease in older men. Prostatic inflammation research has focused on the magnitude of inflammation; its location has received little attention. We investigated whether the anatomic location of prostatic inflammation is related to the severity of lower urinary tract symptoms (LUTS), measured subjectively and objectively. We retrospectively analyzed hematoxylin+eosin-stained tissue specimens from 179 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Each inflammation-finding type was evaluated in relation to these clinical parameters: age, prostate volume, prostate-specific antigen (PSA) value, body mass index (BMI), the frequency of acute urinary retention (AUR) episodes, the international prostatic symptom score (IPSS), and urodynamic study results. The magnitude and extent of inflammation were not associated with any clinical parameters. We classified the BPH patients into stromal (n = 72) versus non-stromal (n = 105) groups based on their inflammation's dominant location. The stromal group's prostatic volume was significantly larger than the non-stromal group's (63.8 vs 53.8 mL; P = 0.032). AUR episodes were more significantly frequent in the stromal group (36.1% vs 11.4%; P = 0.006). Between-group differences in storage parameters (ie, maximum cystometric capacity) in the urodynamic study were not significantly different. Voiding parameters differed significantly between the stromal and non-stromal groups: maximum detrusor pressure (maxPdet) (116.8 vs 94.5 cmH2 O, P = 0.014), Pdet at the maximum flow rate (Qmax) (95.8 vs 75.4 cmH2 O, P = 0.014), and the bladder outlet obstruction index (BOOI) (78.5 vs 56.3, P = 0.014). The stromal group's Qmax was significantly lower than the non-stromal group's (7.3 vs 9.8 mL/s, P = 0.004). The location of inflammation in the prostate might be an important factor affecting the severity of LUTS, especially voiding dysfunction.

1128 - Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia

Background Benign prostatic hyperplasia (BPH) is a common urologic disease in older men. Prostatic inflammation research has focused on the magnitude of inflammation; its location has received little attention. We investigated whether the anatomic location of prostatic inflammation is related to the severity of lower urinary tract symptoms (LUTS), measured subjectively and objectively. Methods We retrospectively analyzed hematoxylin+eosin-stained tissue specimens from 179 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Each inflammation-finding type was evaluated in relation to these clinical parameters: age, prostate volume, prostate-specific antigen (PSA) value, body mass index (BMI), the frequency of acute urinary retention (AUR) episodes, the international prostatic symptom score (IPSS), and urodynamic study results. Results The magnitude and extent of inflammation were not associated with any clinical parameters. We classified the BPH patients into stromal (n = 72) versus non-stromal (n = 105) groups based on their inflammation's dominant location. The stromal group's prostatic volume was significantly larger than the non-stromal group's (63.8 vs 53.8 mL; P = 0.032). AUR episodes were more significantly frequent in the stromal group (36.1% vs 11.4%; P = 0.006). Between-group differences in storage parameters (ie, maximum cystometric capacity) in the urodynamic study were not significantly different. Voiding parameters differed significantly between the stromal and non-stromal groups: maximum detrusor pressure (maxPdet) (116.8 vs 94.5 cmH2 O, P = 0.014), Pdet at the maximum flow rate (Qmax) (95.8 vs 75.4 cmH2 O, P = 0.014), and the bladder outlet obstruction index (BOOI) (78.5 vs 56.3, P = 0.014). The stromal group's Qmax was significantly lower than the non-stromal group's (7.3 vs 9.8 mL/s, P = 0.004). Conclusions The location of inflammation in the prostate might be an important factor affecting the severity of LUTS, especially voiding dysfunction.

Diagnosis of Prostate Cancer with Noninvasive Estimation of Prostate Tissue Composition by Using Hybrid Multidimensional MR Imaging: A Feasibility Study.

Purpose To evaluate whether compartmental analysis by using hybrid multidimensional magnetic resonance (MR) imaging can be used to diagnose prostate cancer and determine its aggressiveness. Materials and Methods Twenty-two patients with prostate cancer underwent preoperative 3.0-T MR imaging. Axial images were obtained with hybrid multidimensional MR imaging by using all combinations of echo times (47, 75, 100 msec) and b values of 0, 750, 1500 sec/mm2, resulting in a 3 × 3 array of data associated with each voxel. Volumes of the tissue components stroma, epithelium, and lumen were calculated by fitting the hybrid data to a three-compartment signal model, with distinct, paired apparent diffusion coefficient (ADC) and T2 values associated with each compartment. Volume fractions and conventional ADC and T2 were measured for regions of interest in sites of prostatectomy-verified malignancy (n = 28) and normal tissue (n = 71). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of various parameters in differentiating prostate cancer from benign tissue. Results Compared with normal tissue, prostate cancer showed significantly increased fractional volumes of epithelium (23.2% ± 7.1 vs 48.8% ± 9.2, respectively) and reduced fractional volumes of lumen (26.4% ± 14.1 vs 14.0% ± 5.2) and stroma (50.5% ± 15.7 vs 37.2% ± 9.1) by using hybrid multidimensional MR imaging. The fractional volumes of tissue components show a significantly higher Spearman correlation coefficient with Gleason score (epithelium: ρ = 0.652, P = .0001; stroma: ρ = -0.439, P = .020; lumen: ρ = -0.390, P = .040) compared with traditional T2 values (ρ = -0.292, P = .132) and ADCs (ρ = -0.315, P = .102). The area under the ROC curve for differentiation of cancer from normal prostate was highest for fractional volume of epithelium (0.991), followed by fractional volumes of lumen (0.800) and stroma (0.789). Conclusion Fractional volumes of prostatic lumen, stroma, and epithelium change significantly when cancer is present. These parameters can be measured noninvasively by using hybrid multidimensional MR imaging and have the potential to improve the diagnosis of prostate cancer and determine its aggressiveness. © RSNA, 2018 Online supplemental material is available for this article.

Phenotypic subtypes and risk of local recurrence after radical resection for rectal cancer.

637 Background: Phenotypic subtypes for CRC are reported to stratify outcomes. The four subtypes are based on features within the consensus molecular subtypes (CMS): immune, canonical, latent and stromal. In 81 pts, we recently reported concordance between CMS and phenotypic subtypes. Of note, the stromal subtype matched the CMS4 subtype in 84%. Local recurrence (LR) after rectal cancer surgery remains a problem. Identifying those at risk determines who should receive neoadjuvant therapy (NT) and guides surgery. We evaluated whether phenotypic subtypes are associated with LR after radical treatment of rectal cancer. Methods: From a CRC database, pts with rectal cancer and phenotypic subtyping available were identified. Subtyping was performed based on immune cell infiltrate, stromal volume and tumor proliferation. LR was considered pelvic or peritoneal. Results: Between 1997-2007, 260 pts had surgery for rectal cancer. Most were > 65yrs (63%), male (58%) and TNM stage II (39%) or III (37%). 32 (13%) received NT. For phenotypic subtypes, 88 (35%) were Immune, 47 (19%) Canonical, 48 (19%) Latent and 67 (27%) Stromal. Median FU was 138 months (min 88). 70 pts (27%) developed recurrence: LR in 23 (8.8%) and systemic in 44 (16.9%). LR was associated with higher T stage (pT1-3 7% vs pT4 17%, p = 0.024), presence of vascular invasion (15% vs 6%, p = 0.018), serosal involvement (21% vs 6%, p = 0.001), margin involvement (22% vs 7%, p = 0.010), > 50% tumor stroma (18% vs 3%, p = 0.002) and phenotypic subtype (immune 5%, canonical 6%, latent 4% and stromal = 21%, p = 0.002). Similar LR rates were obtained after excluding pts who had NT: Immune (4%), canonical (4%), latent (5%) and stromal (23%). Of the 23 LRs, most were Stromal subtype (n = 14) vs Immune (n = 4), Canonical (n = 3) and Latent (n = 2). Apart from increased node positivity (50% vs 30-44% p < 0.05), there were no differences in rates of pT4 disease, tumor grade, vascular invasion, serosal involvement and margin positivity between stromal subtype and other groups. Conclusions: LR after rectal cancer surgery was associated with the stromal subtype. Validation is needed but pre-treatment tumor subtyping may identify subsets at risk of LR and have implications for patient selection for neoadjuvant therapy.

Risk Stratification of Equivocal Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate

We systematically analyzed the records of patients with PI-RADS™ (Prostate Imaging Reporting and Data System) 3 lesions, which are called equivocal according to PI-RADS version 2, using prostate multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsies. Systematic transrectal ultrasound guided biopsies served as the reference standard. A total of 120 consecutive patients were retrospectively included in the study. In these patients the overall PI-RADS score was 3 after 3 Tesla T2-weighted imaging, diffusion weighted imaging and dynamic contrast enhanced multiparametric magnetic resonance imaging as well as subsequent targeted magnetic resonance imaging/ultrasound fusion guided biopsies plus systematic 12-core transrectal ultrasound guided biopsies. The study end points were the prostate cancer detection rate, the Gleason score distribution, the prostate cancer location and risk stratification by subgroup analyses. Prostate cancer was detected in 13 of 118 patients for a detection rate of 11%, including 5 patients (4.2%) with a Gleason score of 3 + 4 = 7 or greater. Three of the 212 lesions (1.4%) in the transition zone and 6 of the 64 (9.4%) in the peripheral zone were positive for prostate cancer. Multiparametric magnetic resonance imaging revealed patterns of peripheral prostatitis combined with diffuse stromal hyperplasia in 54% of the patients with prostate cancer. Prostate volume was significantly lower in patients with prostate cancer (p = 0.015) but differences in prostate specific antigen levels were not statistically significant (p= 0.87). Prostate specific antigen density was higher in patients with prostate cancer (0.19 vs 0.12 ng/ml/ml). Low grade prostate cancer (Gleason score 3 + 3 = 6) can develop in patients with an overall PI-RADS score of 3. Prostate cancer with a Gleason score of 3 + 4 = 7 or greater can be detected by multiparametric magnetic resonance imaging with a high degree of certainty. Gleason score 4 + 3 = 7 or greater prostate cancer is unlikely in PI-RADS 3 lesions. Therefore, these patients should primarily undergo followup multiparametric magnetic resonance imaging. In patients with a combination of multiparametric magnetic resonance imaging aspects of extensive prostatitis and diffuse stromal hyperplasia low prostate volume and/or high prostate specific antigen density biopsy might be considered.

Гистоархитектоника паренхимы лимфатических узлов млекопитающих с различными типами строения внутриузлового лимфатического русла

<p>The article analyzes the features of the histoarchitectonics of the lymph nodes of the bull (Bos taurus) and the pig (Sus scrofa domestica), depending on the type of structure and localization of the intranodal lymphatic channel. We studied somatic (Limphonodi (L.) cervicales superficiales) and visceral (L. jejunales) lymph nodes of clinically healthy mature male bulls and swine (16 and 6 months old, respectively). A complex of classical histological techniques was used, as well as the method of impregnating sections of lymph nodes with silver nitrate, modified by the authors. The main accumulative-distribution link in the lymph nodes of the bull is the subcapsular sinus (type I lymphatic collector), and in the lymph nodes of the pig - the capsular (intratrabecular) lymphatic tanks (type II lymphatic colector). In nodes with collectors of type I, the cortex has a simple layered structure, its outer layer is formed by a compact cortical plateau (interfollicular zone), and the inner layer is formed by a complex of spherical units of the deep cortex. In nodes with collectors of type II, the cortex is layered-folded, uneven in width. Cortical folds are formed along the capsular trabeculae with intratrabecular lymphatic tanks. The cortex plateau in the layered-folded cortex is more developed at the base of the folds, and the units of the deep cortex are at their apexes, where they form clusters in the form of specific nest-shaped structures. In nodes, regardless of the type of intranodal lymphatic channel, the surface cortex (cortical plateau) is located directly under the underlying lymphatic collectors, repeating their shape, the zones of clonal proliferation of B-lymphocytes are formed along the main collector on the basis of cortical plateau and its derivative structures (on the basis of paracortical and medullary cords). The zones of proliferation of T-lymphocytes are maximally close to the main collector, separated from it by a strip of cortical plateau, form a complex of spherical thickenings, which together form a deep cortex. The stroma and parenchyma are more developed in the nodes with collectors of type II (cumulative relative volume of stroma – 9-14% and 6-10%, parenchyma – 80-87% and 70-81%, respectively), and lymphatic sinuses - in nodes with collectors of I type (13-20% and 4-6% respectively). In the parenchyma of the lymph nodes of both groups, the zones of proliferation of T-lymphocytes predominate (the centers of deep cortex units are 27-42%), as well as the zones of accumulation of plasma cells and antibody formation (medullary cords – 17-29%), the first of which are more developed in the pig, and the latter at the nodes of the bull. The cumulative relative volume of the interfollicular zone (cortical plateau) in the studied nodes does not exceed 6-11%, and the zone of clonal proliferation of B lymphocytes (lymph nodulus) is 5-14%. These zones are more developed in the lymph nodes of the pig. Paracortical cords have the minimum and practically equivalent relative volume in the nodes of both groups (3-5%). The study shows that the principles of localization of the main specialized cellular zones in the lymph nodes of the domestic bull and the pig are universal, and the histoarchitectonics of the parenchyma has a clearly expressed specificity. Features of the histoarchitectonics of the parenchyma and its quantitative characteristics are determined by the type of structure of the intranodal lymphatic channel (the character of the localization and spatial configuration of the main accumulative-distributive unit of the nodes). </p>

The chloroplast RNA helicase ISE2 is required for multiple chloroplast RNA processing steps in Arabidopsis thaliana.

INCREASED SIZE EXCLUSION LIMIT2 (ISE2) is a chloroplast-localized RNA helicase that is indispensable for proper plant development. Chloroplasts in leaves with reduced ISE2 expression have previously been shown to exhibit reduced thylakoid contents and increased stromal volume, indicative of defective development. It has recently been reported that ISE2 is required for the splicing of group II introns from chloroplast transcripts. The current study extends these findings, and presents evidence for ISE2's role in multiple aspects of chloroplast RNA processing beyond group II intron splicing. Loss of ISE2 from Arabidopsis thaliana leaves resulted in defects in C-to-U RNA editing, altered accumulation of chloroplast transcripts and chloroplast-encoded proteins, and defective processing of chloroplast ribosomal RNAs. Potential ISE2 substrates were identified by RNA immunoprecipitation followed by next-generation sequencing (RIP-seq), and the diversity of RNA species identified supports ISE2's involvement in multiple aspects of chloroplast RNA metabolism. Comprehensive phylogenetic analyses revealed that ISE2 is a non-canonical Ski2-like RNA helicase that represents a separate sub-clade unique to green photosynthetic organisms, consistent with its function as an essential protein. Thus ISE2's evolutionary conservation may be explained by its numerous roles in regulating chloroplast gene expression.

Histomorphometric Comparison of Induction of Polycystic Ovary Syndrome by Exposure to Constant Light in Primiparous and Nulliparous Rats

Different animal models of polycystic ovary syndrome (PCOS) are introduced but most of them are induced by exogenous chemical or hormonal manipulation. The aim of the present study was to evaluate histomorphometric characteristics of ovaries in primiparous and nulliparous PCOS rats which were exposed to 90 days constant fluorescent light. Twenty-four adult female primiparous and nulliparous rats were divided into two subgroups of light exposure and control (n = 6). Both light exposure groups were exposed to 90 days constant 24 h per day light with the intensity of 350 Lx to 1 m2 on floor. Ovaries of all rats were histomorphometrically evaluated after 90 days. The following indices were calculated and compared between groups: ovary volume, stroma volume, total follicular volume, number of secondary follicle, number of tertiary follicle, mean of tertiary follicle volume, corpus luteum volume, number of corpus luteum, and mean of corpus luteum volume. Serum testosterone concentrations were measured. In both primiparous and nulliparous rats, ovary volume and number and volume of corpora lutea of control groups were more than of light exposure groups (P < 0.05). While, total follicular volume and volume of single tertiary follicle of light exposure rats were more than control ones (P < 0.05). Concerning serum testosterone concentrations both light exposure groups showed hyperandrogenemia. In conclusion, induction of PCOS with the same characteristics of PCOS ovary of women was observed after 90 days exposure to constant light in both primiparous and nulliparous rats.

Citrus flavanones mildly interfere with pituitary-thyroid axis in old-aged male rats

Citrus flavanones naringenin (NAR) and hesperetin (HES) are potent antioxidants that may contribute to maintenance of health at old age by improving cardiovascular and metabolic status. However, they may also affect thyroid hormone economy. Keeping in mind impaired thyroid function at older age, in this study we tested wheather NAR or HES administration potentiate this decline. NAR or HES were administrated orally (15mg/kg) to male 24-month-old Wistar rats during 4 weeks. Control groups received vehicle, sunflower oil. Qualitative and quantitative immunohistochemical and immunofluorescent expression of specific proteins and stereological analyses of thyroid tissue were performed. Thyroid stimulating hormone (TSH) and total thyroxine (T4) concentrations were measured in serum. Thyroid parenchyma of both flavanone-treated groups was characterized by lower (p<0.05) absolute and relative volume of luminal colloid, accompanied by elevated (p<0.05) relative volume of stroma in comparison with the controls. No hypertrophy or absolute thyroid volume change was detected. Intensity of immunopositive signal for thyroglobulin (Tg) and T4 bound to Tg (T4-Tg) increased (p<0.05) in the colloid of thyroid follicles after both flavanone treatments. Serum TSH increased (p<0.05) after NAR, while T4 remained unchanged after both treatments. In conclusion, NAR elevated serum TSH in old-aged males, thus being more potent than HES in altering pituitary-thyroid axis. However, changes in thyroid structure, namely moderate colloid depletion and higher Tg and T4-Tg protein expressions after both treatments, indicate preserved capacity of the gland to compensate flavanone interfering, and maintain T4 production in old-aged males.

Multicompartmental Pharmacokinetic Model of Tenofovir Delivery to the Rectal Mucosa by an Enema.

Rectal enemas that contain prophylactic levels of anti-HIV microbicides such as tenofovir have emerged as a promising dosage form to prevent sexually transmitted HIV infections. The enema vehicle is promising due to its likely ability to deliver a large amount of drug along the length of the rectal canal. Computational models of microbicide drug delivery by enemas can help their design process by determining key factors governing drug transport and, more specifically, the time history and degree of protection. They can also inform interpretations of experimental pharmacokinetic measures such as drug concentrations in biopsies. The present work begins rectal microbicide PK modeling, for enema vehicles. Results here show that a paramount factor in drug transport is the time of enema retention; direct connectivity between enema fluid and the fluid within rectal crypts is also important. Computations of the percentage of stromal volume protected by a single enema dose indicate that even with only a minute of enema retention, protection of 100% can be achieved after around 14 minutes post dose. Concentrations in biopsies are dependent on biopsy thickness; and control and/or knowledge of thickness could improve accuracy and decrease variability in biopsy measurements. Results here provide evidence that enemas are a promising dosage form for rectal microbicide delivery, and offer insights into their rational design.

Two-photon optical microscopy imaging of endothelial keratoplasty grafts.

To investigate the microstructure of endothelial keratoplasty grafts using two-photon optical microscopy. Six endothelial keratoplasty grafts obtained from human donor corneoscleral tissues and prepared by submerged hydrodissection technique were imaged by two-photon optical microscopy. In each graft, two liquid bubbles were created in order to investigate the presence of a conserved cleavage plane regardless of the volume of posterior stroma that remained attached to Descemet's membrane (DM); the first bubble (bubble A) was generated under DM and the second bubble (bubble B) injection was done in order to obtain a layer of deep stroma that kept the two bubbles separated. Six human donor corneoscleral tissues were used as controls. Second harmonic generation and two-photon emitted fluorescence signals were collected from each specimen. Dissection of stroma occurred along the posterior collagen lamellae at variable distance from DM, which ranged between 3 and 16 μm in bubble A and between 23 and 41 μm in bubble B. The residual stroma included, anteriorly, bands of collagen lamellae, and thin bundles of stromal collagen fibrils, posteriorly, which were tightly intertwining with the underlying DM. There was no anatomically distinct plane of separation between these pre-Descemetic stromal collagen bundles and the overlying collagen lamellae with this hydrodissection technique. Two-photon optical microscopy provided label-free high-resolution imaging of endothelial keratoplasty grafts, showing that the most posterior stroma changes organization at approximately 10 μm above the DM. The pre-Descemetic stromal collagen fibrils form an intertwined complex with DM, which cannot be separated using hydrodissection.

Highlights of This Issue

Multigene assays have been incorporated into the management of patients with node-negative hormone receptor-positive breast cancer for determining adjuvant treatment strategies. To compare prognostic accuracy of two multigene assays, Sestak and colleagues examined cross-stratification between Breast Cancer Index (BCI) and the 21-gene recurrence score (RS) in the TransATAC study. The findings show that BCI demonstrates increased prognostic accuracy versus RS. BCI restratified women with low and intermediate risk by RS into clinically relevant risk groups with significantly different risks of distant recurrence. These findings indicate that BCI may have potential impact to improve individualized risk stratification for patients with early-stage breast cancer.Dennison and colleagues evaluated the associative effects of breast cancer with the tumor microenvironment and its influence on tumor behavior. The reactive subtype of breast cancer, identified by reverse-phase protein arrays to have high expression of ECM proteins, was demonstrated to indicate a favorable outcome. The lowest risk tumors, typically ER+ER2− breast cancer, were more likely to have high expression of stromal proteins, high intratumoral stromal volume, and increased cell density within the stromal compartment.Antibody–drug conjugates (ADC) have become a promising anticancer agent. Ogitani and colleagues generated and evaluated a novel HER2-targeting ADC called DS-8201a, with a DNA topoisomerase I inhibitor. It showed potent antitumor activity against T-DM1-insensitive tumors and HER2 low-expressing tumors due to the different mechanism payload from T-DM1 and higher a drug-to-antibody ratio than T-DM1. Moreover, favorable pharmacokinetic and safety profiles in monkeys were observed. These data suggest that DS-8201a is an attractive and promising HER2-targeting ADC, which provides an additional treatment option for current HER2-targeting therapy.Antibody–drug conjugates directed at specific antigens preferentially expressed on cancer cells are gaining traction in the clinic. Here, Almhanna and colleagues perform the first-in-human phase 1 study investigating TAK-264 targeting guanylyl cyclase, a transmembrane cell-surface receptor expressed in many gastrointestinal cancers. The results demonstrate a manageable safety profile at the maximum tolerated dose, preliminary evidence of antitumor activity, and early signs of clinical benefit in patients with pancreatic, esophageal, and gastric carcinoma.

Pharmaceutical evaluation of naftopidil enantiomers: Rat functional assays in vitro and estrogen/androgen induced rat benign prostatic hyperplasia model in vivo

Naftopidil (NAF) is a α1D/1A adrenoceptor selective drug used for the treatment of both benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS). However, NAF is used as a racemate in clinic. To compare the differences and similarities among two enantiomers and racemate, pharmacological activities were evaluated through rat functional assays in vitro and estrogen/androgen (E/T) induced rat BPH model in vivo. NAF and the two enantiomers showed similar blocking activity on α1 receptor. S-NAF exhibited more α1D/1A adrenoceptor subtype selectivity than R-NAF and the racemate. The selectivity ratios pA2 (α1D)/pA2 (α1B) and pA2 (α1A)/pA2 (α1B) were 40.7- and 16.2-fold, respectively. NAF and its enantiomers effectively prevented the development of rat prostatic hyperplasia via suppressing the increase of the prostatic wet weight, visually. The quantitative analysis of the relative acinus volume, relative stroma volume, relative epithelial volume, epithelial height and expression of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were carried out. S-NAF showed an advantage on the effect of inhibiting prostate wet weight and stroma volume over R-NAF and racemate NAF (P<0.05). Nevertheless, no other significant difference was observed between these two enantiomers. In conclusion, both R-NAF and S-NAF not only relax prostate muscle but also inhibit the prostate growth, thus relieve BPH.

Variations in Concentration and Distribution of Several Androgen-Dependent and Independent Trace Elements in Nonhyperplastic Prostate Gland Tissue throughout Adulthood

The variation with age of the Br, Fe, Rb, Sr, and Zn concentration in prostatic tissue and the relationship of these trace elements with basic histological structures of nonhyperplastic prostate glands of 65 subjects aged 21-87 years was investigated by an energy-dispersive X-ray fluorescence (EDXRF) and a quantitative morphometric analysis. Mean values ± standard error of the mean (M±SEM) for the concentrations (mg/L) of these trace elements were: Br 7.89±0.93, Fe 22.2±1.2, Rb 3.49±0.18, Sr 0.43±0.08, and Zn 191±16. The significant trend for increase with age in Fe and Zn concentration as well as for increase with age in relative volume of stroma and decrease in relative volume of epithelium was found. Using the Pearson correlation between trace element concentration and morphometric parameters, it was demonstrated that the glandular lumen is a main pool of Sr and Zn accumulation in the normal human prostate, for the age range 21 to 87 years. It was concluded that the Sr and Zn bind tightly within the prostatic fluid, because the volume of glandular lumen reflects the volume of prostatic fluid. For ages above 40 years conclusive evidence of a disturbance in prostatic intracellular homeostasis of Fe was also shown. PCa development. The etiology of both BPH and PCa is believed to be multifactorial. Both diseases may occur due to subtle changes in male hormones with age as well as other factors including levels of Ca, Zn, and other chemical elements in prostate tissue (8-14). In our previous studies higher levels of Zn, Ca, and Mg as well as some other chemical elements were observed in prostate tissue of adult males when compared with nonprostatic soft tissues of the human body (15-19). High accumulation of these elements suggests that they may play an important role in prostate function and health. Moreover, levels of some chemical elements were found to increase in the prostate tissue after puberty and throughout adulthood, and in some cases this increase was shown to be androgen-dependent (20-27). The reason for this increase in chemical element content in the normal prostate gland is not completely understood. In addition, longstanding questions about the main pool and the local distribution of chemical elements in adult and geriatric prostate still remain open (28-37). Prostatic tissue contains three main components: glandular tissue, prostatic fluid, and fibromuscular tissue or stroma. Glandular tissue includes acini and ducts. Epithelial cells (E) surround the periphery of the acini and luminal surfaces (L) in acini (glandular lumina). Prostatic fluid fills the lumina in the acini. Stromal tissue (S) is composed of smooth muscle, connective tissue, fibroblasts, nerves, lymphatic and blood vessels. Thus, the volume of the prostate gland may be represented as a sum of volumes (E+L+S). This makes it possible to quantitative morphological data using a stereological approach (20). Cellular alterations that include changes in the epithelium and stroma are implicated in the development and growth of the prostate gland, as well as in BPH and PCa pathogenesis (38,39). However, the data on age-dependence of main histological components of normal prostates is extremely limited (40,41). Moreover, some contradictory results were obtained in these studies.

Morphology of exorbital lacrimal glands of not purebred white rats at high-intensity light influence

Purpose: this study morphological changes the exorbital lacrimal glands at experimental impact on an organ of vision of high-intensity light. Material and methods. White not purebred rats males (n = 40) were subjected to continuous influence of light intensity by 3500 lx within 1, 7, 14 and 30 days, the control group (n = 10) contained in conditions of natural lighting (20 lx). Exorbital lacrimal glands fixed in formalin, embedded in paraffin wax, stained hematoxylin-eosine. By means of an oculary insert of Avtandilov counted specific volumes of output channels, an epithelium, stroma and vessels of exorbital lacrimal glands, defined an epitelio/stroma ratio. The analysis of data was carried out by methods of descriptive statistics with calculation of a median (Ме) and interquartile range (Q1 –Q3). For an assessment of distinctions used nonparametric criterion of Mann – Whitney. Results. In 1 days in response to high-intensity light influence there is a reflex strengthening of synthetic function of exorbital lacrimal glands. For the 7th days the first signs of violation of functioning with development of hydropic dystrophy in the lacrimacytes appear. By 14th days fibrous changes develop, in a glandular parenchyma harderization sites appear. For the 30th days the nuclear pycnosis of separate lacrimacit, accumulation of a lipofuscin in cytoplasm is observed. Conclusion. The obtained data allow to estimate in dynamics compensatory and adaptive reactions of lacrimal gland in response to high-intensity light influence from the moment of the beginning of their development before emergence of the first signs of a decompensation.

Differential Associations of MMP-2 and MMP-14 with Stromal Amounts and T lymphocyte Presence in Ovarian Cancer

Aim: Ovarian cancer prognosis is influenced by factors such as intratumoral T-lymphocyte presence and the amount of stroma formation relative to the epithelial tumor compartment. The regulation of these factors is unknown. Matrix metalloproteinases are involved in stromal remodeling and may be involved in T-cell trafficking as well. This study investigates the quantitative relationships between the matrix metalloproteinases MMP-2 and MMP-14 and both relative stroma amounts (‘stroma percentage’) and the presence of T lymphocytes in the stromal and epithelial compartments of ovarian cancer. Patients and methods: In 86 patients with ovarian cancer, MMP-2 and MMP-14 expression and T-lymphocyte presence was determined using semi quantitative immunohistochemistry. Stroma percentage was determined by area calculation in haematoxylin eosin slides. Per slide, 3 random images at the tumor-stroma interface were investigated. Results: Epithelial MMP-14 scoring correlated negatively with T-lymphocytes in tumor epithelium: correlation coefficient rho −0.36 (p < 0.01) for CD3, −0.30 (p < 0.01) for CD8 and −0.24 (p < 0.05) for CD45Ro. Stromal MMP-2 was positively related to stroma percentage (rho 0.29; p < 0.01). No significant correlations were found for MMP-14 with stromal amounts, or MMP-2 with T-cell presence in stroma or tumor epithelium. Conclusion: Opposite to our hypothesis that MMPs reduce stromal amounts and permit T cell trafficking into both stromal and epithelial tumor parts, MMP expression was associated with higher relative stromal amounts and lower presence of T lymphocytes. In particular, we found that epithelial MMP-14 expression was negatively associated with T-lymphocyte presence in the tumor suggesting a role for MMP-14 in negatively regulating T-cell trafficking by other means. Stromal MMP-2 expression was associated with an increase in stromal amounts suggesting an ineffective feedback on tumor stroma volume growth of the expression of this gelatinase. More research is necessary to determine the specific actions of MMPs in ovarian cancer.

Changes in Epithelium, Stroma, and Lumen Space Correlate More Strongly with Gleason Pattern and Are Stronger Predictors of Prostate ADC Changes than Cellularity Metrics.

To investigate the hypothesis that the clinically observed decrease in apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance imaging with increasing prostate cancer Gleason grade can be attributed to an increasing volume of low-diffusivity epithelial cells and corresponding decreasing volumes of higher-diffusivity stroma and lumen space rather than to increased cell density. Tissue samples were acquired after institutional ethics review committee approval and informed consent from patients were obtained. Nuclear count, nuclear area, and gland component volumes (epithelium, stroma, lumen space) were measured in tissue from 14 patients. Gland component volumes and cellularity metrics were correlated with Gleason pattern (Spearman rank correlation coefficient) and measured ADC (Pearson correlation coefficient) in six prostates ex vivo. Differences between metrics for cancerous tissue and those for normal tissue were assessed by using a two-tailed two-sample t test. Linear mixed models with a post hoc Fisher least significant difference test were used to assess differences between gland component volumes and cellularity metrics for multiple groups. To adjust for a clustering effect due to repeated measures, the organ mean value of the measured metric for each tissue type was used in the analysis. There were significant differences between Gleason patterns for gland component volumes (P < .05) but not nuclear count (P = .100) or area (P = .141). There was a stronger correlation of Gleason pattern with gland component volumes (n = 553) of epithelium (Spearman ρ = 0.898, P < .001), stroma (ρ = -0.651, P < .001), and lumen space (ρ = -0.912, P = .007) than with the cellularity metrics (n = 288) nuclear area (ρ = 0.422, P = .133) or nuclear count (ρ = 0.082, P = .780). There was a stronger correlation between measured ADC and lumen volume (r = 0.688, P < .001) and epithelium volume (r = -0.647, P < .001) than between ADC and nuclear count (r = -0.598, P < .001) or nuclear area (r = -0.569, P < .001) (n = 57). Differences in the gland compartment volumes of prostate tissue having distinct diffusivities, rather than changes in the conventionally cited "cellularity" metrics, are likely to be the major contributor to clinically observed variations of ADC in prostate tissue.

Histomorphometric Evaluation of Superovulation Effect on Follicular Development after Autologous Ovarian Transplantation in Mice.

The effect of superovulation by pregnant mare serum gonadotropin (PMSG) on autologous transplanted ovaries in the lumbar muscles of mice was histomorphometrically evaluated using the indices of number and volume of different kind of follicles and volume of corpora lutea, ovary, and stroma. Angiogenesis was observed after mouse ovarian transplantation on days 14 and 21 after ovarian grafting. After transplantation, the total number and volume of primary and secondary follicles reduced, while PMSG superovulation increased the total number and total volume of tertiary follicles and also the ovarian volume after transplantation. Transplantation increased the average size of primary, secondary, and tertiary follicles. Therefore, primary and secondary follicles can survive after autologous transplantation but their reservations diminished by increasing the time of transplantation. However, number of tertiary follicles and their response to superovulation increased over time after transplantation.

Effect of Urtica dioica extract on stereological structure of ventral prostate in streptozotocin induced diabetic rats

Diabetes mellitus is a common and important metabolic disorder that can be associated with many functional and structural complications in male sex organs and infertility. Many studies showed that Urtica dioica caused hypoglycemia and prevented diabetes undesirable side effects on the different organs. This study was done to investigate the effects of ethanol extract of Urtica dioica on ventral prostate in streptozotocin induced diabetic rats. In this study, 15 adult male wistar rats were divided into control, diabetic and treatment groups. Hyperglycemia was induced by 50 mg/kg Streptozotocin (STZ) in diabetic and treatment groups. One week after STZ injection, treatment group received 30 mg/kg/day Urtica dioica extract by oral gavage for 30 consecutive days. Finally animals were euthanized and ventral prostate were removed and fixed in 10% neutral buffered formalin. Samples of the ventral prostate were obtained according to the orientator to produce an isotropic uniform random sample. The volumes of the lumen, glandular epithelium and fibromuscular stroma were estimated by multiplying each respective volume density. This study showed that diabetes could lead to structural changes in ventral prostate. Stereological results indicated that volume of lumen and fibromuscular stroma of ventral prostate was significantly increased in diabetic rats but Urtica dioica could in hibit these changes partially. It was also revealed that volume of glandular epithelium was significantly reduced in ventral prostate of diabetic rats but it was significantly increased in treated animals compared to diabetic animals (p<0.05). It can be concluded that ad ministration of ethanolic extract of Urtica dioica a can inhibit side effect of diabetes on structure of ventral prostate and has protective effects on its histoarchitecture.

A Postmortem Histological Study on Percentage Volume of Parenchyma and Stroma of the Human Parathyroid Glands

A cross-sectional descriptive study was performed in the Department of Anatomy, Dhaka Medical College, Dhaka, from January to December 2008, on post mortem parathyroid glands of 60 Bangladeshi people in different age groups. A total of 207 parathyroid glands were identified in relation to posterior border of thyroid lobes and collected from those 60 cadavers. The samples were collected from the unclaimed dead bodies within 24 hours after death that were under examination in the Department of Forensic Medicine of Dhaka Medical College, Dhaka. The samples were divided into three different age groups ranging from 15 to 75 years. The three groups are group A (10-30 years), group B (31-60 years) and group C (61-90 years). From each group, 20 best prepared slides were taken for examination. The percentage volume of parenchyma (glandular portion) and stroma (fibrous part with blood vessels and fat) were estimated by the point counting technique with Zeiss-I integrating eyepiece under the light microscope at low magnification. The mean SD percentage volume of parenchyma varies 64.88 2.75 to 65.90 2.33 in group A, 56.40 12.57 to 59.10 3.87 in group B and 38.80 2.77 to 41.50 2.38 in group C. In contrast, the mean SD percentage volume of stroma varies 33.50 2.27 to 34.88 2.95 in group A, 40.30 3.83 to 41.56 4.16 in group B and 58.50 2.38 to 61.20 2.77 in group C. The percentage volume of connective tissue stroma was found to increase with increasing age with simultaneous decrease in glandular parenchyma. DOI: http://dx.doi.org/10.3329/akmmcj.v5i1.18765 Anwer Khan Modern Medical College Journal Vol. 5, No. 1: January 2014, Pages 10-13