Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction

Intraurethral inoculation of mice with uropathogenic E. coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and in CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells using a combination of mast cell stabilizer (MCS), cromolyn sodium, and the histamine 1 receptor antagonist (H1RA), cetirizine di-hydrochloride, in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain (MLC)-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.

Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction

ABSTRACTIntraurethral inoculation of mice with uropathogenic E. coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and in CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells and the histamine 1 receptor in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain (MLC)-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.NEW AND NOTEWORTHYLUTS-associated BPH is derived from a combination of immune activation, extracellular matrix remodeling, hyperplasia, and smooth muscle cell contraction in prostates of men. Using a mouse model, we describe the importance of mast cells in regulating these multiple facets involved in the pathophysiology of LUTS. Mast cell inhibition alleviates both pathology and urinary dysfunction in this model suggesting the potential for mast cell inhibition as a therapeutic that prevents and reverses pathology and associated symptomology.

A Study on Prostate Inflammation in SD Rats After Castration Under the Effect of Estrogen/androgen at Different Concentrations

Background: To clarify the expression of histological inflammation and major inflammatory factors in prostate of castrated rats induced by different concentrations estrogen/ androgen. Methods: Male Sprague-Dawley (SD) rats aged 3-4 months were randomly divided into the blank group (sham operation group, bilateral testicular specimens were retained), and the castration group (surgical removal of bilateral testes) and different concentrations of estrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and estradiol (E) were administered daily by subcutaneous injection for one month, and the rats in each group were sacrificed by neck-broken method after one month. Obtained prostate specimens by surgery, and performed routine paraffin embedding and sectioning of prostate tissue. Observed the changes of prostate tissue structure and prostate inflammation under light microscope after Hematoxylin-eosin (HE) staining. Immunohistochemical method was used to detect the expression of TGF-β1, IL-6 and IL-8 in the rats prostate tissues. Results: After castration, when the exogenous E concentration was constant, the exogenous DHT(0-0.15mg/kg) concentration of SD rats in each group increased gradually, and the anatomical position score of inflammatory cell infiltration in each group of rats gradually increased. Further, even if the DHT concentration increased again after the exogenous DHT concentration reached at 0.5mg/kg, the score did not increase but decreased insteadly. From the area of tissues involved in inflammatory cell infiltration and the density of typical inflammatory cells, the inflammation score of each group of rats increased gradually with the increase of DHT concentration. When the exogenous DHT concentration was constant, from the anatomical location and the area of tissues involved in inflammatory cell infiltration in each group of SD rats, the inflammation score of each group of rats increased gradually with the increase of exogenous E concentration. The results of the immunohistochemical reaction showed that the positive rates of TGF-β1, IL-6 and IL-8 in SD rats after castration were higher than those in the blank group, and the positive rate of TGF-β1 was statistically significant compared with the blank group (P<0.05). When the concentration of exogenous E was constant, the positive rates of TGF-β1 and IL-8 in each group of DHT0.015-0.5mg/kg increased with the increase of the concentration of exogenous DHT. However, even if the exogenous DHT concentration increased again after the exogenous DHT concentration exceeded 0.5mg/kg, the positive rates of TGF-β1 and IL-8 in the E0.05+DHT1.5 group did not increase with the further increase of exogenous DHT, but decreased to a certain extent. In addition, when the exogenous DHT concentration was constant, the exogenous E concentration was gradually increased, and the positive rates of TGF-β1, IL-6 and IL-8 in SD rats in each group increased to some extent with the increase of exogenous E concentration. Conclusions: Sex hormone levels are involved in the regulation of prostate inflammation in SD rats. Different levels of estrogen and androgen have different levels of inflammatory response to prostate inflammation and the expression of TGF-β1, IL-6, IL-8 in castrated SD rats, and the positive expression of TGF-β1, IL-6, IL-8 can reflect the inflammation of prostate tissue in SD rats to a certain extent. In addition, there may be an inflection point between the ratio of estrogen/ androgen and prostate inflammation. After crossing this inflection point, the inflammation of the prostate did not further deepen even if the concentration of exogenous androgens increased again. Of course, it needs to be confirmed by more systematic and comprehensive experiments in vivo and vitro.

The wild raspberry in Serbia: An ethnobotanical study

An ethnobotanical survey of the traditional use of the wild raspberry (Rubus ideaus) was conducted on nine sites in the regions of southwest (SWS) and southeast (SES) Serbia. The regions studied belong to mountainous rural areas in Serbia, mainly populated by Serbian people of the Orthodox faith. In total, 93 respondents were interviewed about the medicinal, food and cosmetic uses of the wild raspberry. In terms of plant parts in traditional use, the leaf and fruit are known to be used frequently. The dry leaf is more commonly used in the SES (78%) than in the SWS (25%) region. In the SWS region, the most frequent use of the wild raspberry leaf is linked to gastrointestinal disorders and prostate inflammation. In the SES region, the leaves are mostly used for the prevention and healing of gynecological disorders during both pregnancy and lactation. The local population of the SWS region uses the fruits mainly for the preparation of syrup juice (92%), fruit preserves (42%) and in desserts (62%), while in the SES area the fruits are most frequently used for the preparation of nonalcoholic (97.4%) and alcoholic beverages (35.9%). Our results provide some novel information on the use of the wild raspberry in Serbia and in the Balkans, such as for the treatment of prostate inflammation, use during breastfeeding and to alleviate inflammation of the eyes.

Beneficial Effects of Inflammatory Cytokine-Targeting Aptamers in an Animal Model of Chronic Prostatitis

Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 µg) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.

A rare case of sarcoidosis affecting the nasopharynx

Sarcoidosis is a rare condition, presenting with granulomatous lesions typically located in the lungs, spleen and lymph nodes. We present an atypical case of sarcoidosis, with an initial lesion located in the nasopharynx. The patient is a 38-year-old male, with the complaints of cephalalgia, nasal obstruction and hyposmia, detected during further examination with degenerative spinal modifications, prostate inflammation and lung-based sarcoidosis. A biopsy of the lesion located in the postnasal cavity revealed granulomatous origin. The patient underwent total endoscopic adenoid removal and radiofrequency-assisted bilateral turbinate reduction, with favourable post operatory evolution. Atypical localizations of sarcoidosis lesions must be considered in the case of unusual lesions, regardless of localisation.