The Immunitary role in chronic prostatitis and growth factors as promoter of BPH

In the actual medical therapy of BPH, we can see: antibiotics, alpha blockers, 5-ARI, fi totherapeutics/natural products (Serenoa repens) with different which display clinical activities and other molecules such as FANS (local or systemic dosage forms) cortisones and others. Relationship between immune systems and chronic prostatitis are strictly involved in BPH progression. A vicious cycle that involve chronic fl ogosis, tissue remodeling, grow factors, inhibition of apoptosis, and other phenomena. Observing BPH pathogenesis under an immunologic point of view make possible to search new pharmacological strategies, to improve actual therapy. The aim of this work is to observe some relevant literature in our opinion related the management of BHP and its progression under a pharmaceutical and immunological point of view. A deep knowledge in the pharmaceutical properties of some molecules (antimicrobials, antiphlogosis agents, Anti-androgenic agents, alpha blockers, 5-ARI and other treatments, techniques, interventions or instruments) can help the physicians to pick the right choice. Research Article The Immunitary role in chronic prostatitis and growth factors as promoter of BPH Mauro luisetto1*, Behzad Nili-Ahmadabadi2, Ghulam Rasool Mashori3, Ram Kumar Sahu4, Farhan Ahmad Khan5, Cabianca luca6 and Heba Nasser7 1Applied Pharmacologist, Independent Researcher, Italy 2Pharm D/PhD innovative Pharmaceutical Product Development Specialist, USA 3Professor & Director, Department of Medical & Health Sciences for Woman, Peoples University of Medical and Health Sciences for Women, Pakistan 4Assitant Professor Columbia Institute of Pharmacy, Tekari, Raipur (CG)-493111, India 5Professor & Head, Department of Pharmacology, AIMSRC, Udaipur, Rajasthan, India 6Biomedical Laboratory, Turin, Italy 7Pharm D/PhD in Microbiology & Immunology, Faculty Member at Heliopolis University, Italy *Address for Correspondence: Mauro luisetto, Applied Pharmacologist, Independent Researcher, Italy, Tel: +393402479620; Email: maurolu65@gmail.com Submitted: 10 April 2018 Approved: 24 April 2018 Published: 25 April 2018 Copyright: 2018 luisetto M, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited


Introduction
BPH Benign prostate hyperplasia is currently consider a common progressive enlargement of the prostate gland caused by a benign overgrowth of chie ly glandular tissue that occurs especially in some men over 50 years old and that tends to obstruct urination by constricting the urethra with heavy symptomatology and related consequences in quality of life.
The current medical therapy (based on 5-ARI, alfa blokers, antimicrobials, itotherapics, anti logosys Antiedemigen and other) can and must be improved to delay or avoid surgery. In order to introduce new pharmacological strategy is crucial to observe the immune implications in BPH. Reports in biomedical litrerature indicate that in BPH progression some of the following factors are heavily involved: All these events contribute to an increased production of phlogosis mediators, growth factors (stromal and epithelial) in a vicious cycle and as a result, we would have an increase and complication of the pathogenic conditions. The presence of immune system in prostate prostate gland is very well alive and manifest itself in different forms, from in iltration of lymphocytes T and macrophages caused by phlogosis to cytokines that cause hypertrophy. These reactions along with cellular damage produce ROS reactive oxygen species, increase in production of growth factors (VGEF, IL 8 FGF 7, TGFB, FGF 2 and others), inhibition of apoptosis and tissue remodelling with hyperproduction of extracellular matrix and stromal parts.
Other factor that can be responsible in the relapse in chronic prostatitis in BPH are microcalci ications and obstruction of the ducts. But it is not all over, there are still other conditions that can be involved, such as metabolic syndrome, diabetes and the related biochemical and hormonal factors that can modify methabolisms that can worsen the pathogenesis. Many other factors still play in. Example are factors, such as the command-and-control of the nervous systems over the bladder, uretral restrictions and other Urological disease can cause important complications. Also the creation of a bio ilm over the prostate capsule makes the penetration of several antimicrobial agents look like resistant which reduces their prostatic in lux. Be patient it's not over yet, we can still mention complications caused by such as IPB, urinary re lux (chemical cystitis and prostatitis), prostate cancer and other factors. But those are not the only factors, there are also often Intestinal functional abnormalities and pathologies, anorectal, sexually transmitted infectious comma as well as complications due to bacterical sanctuaries and intraprostatic calci ications.
We have seen that a bacterial infection can be primary or secondary (bacteria that causes infections or superinfectious in a tissue affected by phlogosis or to other conditions), for example in hypertonic pelvic sphincter muscle. (Bacteria can come across also lymphatic way (from rectum), by emetic way, rising uretral infectious). Adrenergic ipertonus of prostate capsule contribute to BPH physiopathology. Involved often Intestinal functional abnormalities and pathologies like ano-rectal disease, sexual transmission infectious and also due to the bacterial prostate sanctuaries properties and role played by the intraprostatic calci ications.
In The actual medical therapy of BPH we can see: antibiotics, alfa blokers, 5-ARI, and itothearapic (Serenoa repens) with different clinic functions and activities and other molecule as fans (local or systemic), cortisons et. Other.
The aim of this work is to observe some relevant literature in our opinion related the management of BPHS and progression under a pharmaceutical-Eendocrinologicmetabolic disease and immunologic point of view. A deep knowledge in the pharmaceutical properties of some molecule (antimiciobials, anti logosis Antiedemigen, alfa blochers, 5-ARI and other intruments) can help the physicians in the right choice. The same pharmaceutical industries can introduce in therapy new drugs improving molecular formula or delivery systems to achieve improvement in kinetics and dynamics. Also little improvement in pharmaceutical or pharmacological molecular properties can produce relevant clinical effect.

Material and Methods
Using a review method and observing some literature in biomedical database can be produced a new approach in pharmacological strategies in some relevant urologic disease or to prevent it. Observing some works related to pathology like BPH we to try ind NEW strategies that could be translated in order to achieve better clinical results adding new drug delivery system or other improvement in molecular structure in order to achieve more ef icacy and reduced relapses or surgical needs (treating, controlling or even curing the root causes or to manage to lessen the security or prevent some of those role playing factors).

Results
From literature we can ind: • According V. Ficarra "In this issue of BJU International, Gandaglia et al., summarize the evidence supporting the role of chronic prostatic in lammation in the pathogenesis and progression of BPH. Brie ly, one or more concomitant factors (bacterial infections, viruses, sexually transmitted organisms, dietary factors, hormones, autoimmune response and urine re lux) can stimulate an in lammatory reaction in prostatic tissue characterized by in iltration of T-lymphocytes, activation and up-regulation of pro-in lammatory cytokines, increased expression of potent stromal and epithelial growth factors (e.g. ibroblast growth factor, FGF-2) and consequently abnormal proliferation of prostatic cells. Moreover, local hypoxia plays an important role stimulating reactive oxygen species (ROS) release, Continuous repair gives tissue remodeling. Neo-vascularization processes and the production of other additional growth factors (vascular endothelial growth factor, interleukin 8, FGF-7, TGF-b and FGF-2). Interestingly, this mechanism is self-perpetuating, creating a local vicious cycle. Available clinical data seems to emphasise the prevalence of chronic prostatic in lammation in BPH. Indeed, a sub-analysis of the REDUCE (Reduction by DUtasteride of prostate Cancer Events) trial shows that in patients with BPH a chronic prostatic in lammation can be detected in 77% of patients who underwent prostate biopsies. Moreover, this study also showed a statistically and clinically signi icant correlation between chronic prostatic in lammation and LUTS severity, especially when the storage subscale was considered. As extensively described by Gandaglia et al.,., other studies have shown a signi icant correlation between chronic prostatic in lammation and prostate volume and an increased risk of acute urinary retention. Obviously, chronic prostatic in lammation can be histologically detected only in patients who undergo prostate biopsies for suspicion of prostate cancer. However, most patients with LUTS/BPH do not undergo a prostate biopsy. For this last category, the use of speci ic biomarkers correlated with chronic prostatic in lammation has been proposed as a potential alternative. Although interleukin 8 seems to be the most reliable and predictive surrogate marker to identify patients with chronic prostatic in lammation, its use is not yet popular, it is expansive and probably requires further clinical evaluation before introduction into daily clinical practice. In this context, the detection of prostatic calci ications can represent a simple ultrasound sign to suspect the presence of chronic prostatic in lammation. In patients aged >50 years, prostatic calci ications represent an age-related alteration of the prostatic luid. Prostatic calci ications can produce an obstruction of the intraprostatic ducts stimulating an in lammatory response in prostatic tissue characterised by lymphocyte in iltration, cytokine activation and ROS release. This results in damage of epithelial and stromal prostatic cells and a subsequent process of wound healing consisting of stromal proliferation and excessive extracellular matrix production; summarises these mechanisms following prostatic duct obstruction.
I think that in patients with prostatic calci ications and severe LUTS (with predominant storage symptoms) the presence of chronic prostatic in lammation should be strongly considered. Patients with high-grade prostatic in lammation seem to have a worse response to traditional medical therapy for LUTS/BPH (a -adrenergic blockers and 5 a -reductase inhibitors) compared with patients without or with lowgrade prostatic in lammation [1]. Indeed, neither a-adrenergic blockers nor 5. A -reductase inhibitors have an anti-in lammatory effect. Therefore, drugs commonly used for the treatment of non-neurogenic LUTS cannot in luence the described chronic in lammatory status. An anti-in lammatory effect on human prostate has been ascribed to the hexanic lipidosterolic extract of Serenoa repens. Speci ically, in 2003 Vela Navarrete et al.,. [2] reported a signi icant reduction of interleukin 1 and TNFa levels 3 months after Serenoa repens treatment compared with the placebo arm. Recently, Latil et al. [3], showed that Serenoa repensinhibits the expression of two" [4].
• Hoon Choi et al., writed that "Dutasteride showed greater ef icacy in reduction of TPV and PSA and in symptomatic improvementby IPSS score than inasteride [5]." See the different chemistry formula and related pharmacolgocial pfro ile of action (reversible or irreversible activity in 5-HT INIBITION) but also related to other factors as tissue penetration. Related chemical groups ad lipo ilic balances.
• Luisetto et al., "It is clearly known that the prostatic gland is frequently involved in Different pathologies in adults and elderly patients. Benignant or malignant: anatomic of functionally disease. Frequently other condition as bladder dysfunctions can be associated or added to this pathologies or causated by it. Some of these pathologies give low level in patient quality life and reducing in life expectance (malignant). Malignant pathologies start as local disease but can diffused as metastatic interesting other apparatus of the patient (patient frequently show resistance to irst line therapy in example hormonal blocks, or different chemiotherapic). But In all of this pathology we can see a not complete resolution with current medical therapy in all patients and this can be related with the dif iculties of some drugs to penetrate adequately in the tissue. In example we can see that I many benignant cases as IPERTROPHIA also itotherapic produces or dietetic integrator are frequently added by the specialist to the classic drugs politherapy. This shows that the classic drug therapy can be improved. In example Relapses in bacterial chronic prostatitis are commonly in great number of patient even under the best pharmacological therapies available today. It means that something goes wrong in this kind of therapy [6].
(Remember that fl ogosis can results in partial ineffi cacy of 5-AR1) FINASTERIDE DUTASTERIDE. Vela Navarrete R et al., write that "The role of in iltrating cells (I.C.), commonly observed in the adenoma interstitial tissue, is unknown. We tested the hypothesis that I.C. are related with BPH progression by: phenotypically characterizing these cells; quantifying the expression of lymphokines and growth factors; investigating the response to Permixon (P) in a clinical study. Permixon is a lipido sterolic extract of Serenoa repens possessing pharmacological activities and widely used in the treatment of men with BPH.

Histological
A difference was observed in the number of lymphocytes B between C (91.4+/-44.1) and P treated (58.2+/-53.7) groups (p=0.097). BIOLOGICAL MARKERS: TNFalpha and IL-1beta were dramatically lower in the Permixon treated group. Other parameters did not show signi icant changes. CLINICAL: IPSS in the Permixon treated group was signi icantly reduced (p<0.006) from 20.0+5.9 to 14.9+3.8 after three months of treatment.
The BPH in lammatory hypothesis was tested in humans. Our pilot study shows a signi icant reduction of some in lammatory parameters in prostatic tissues of patients treated with Permixon. These biological indings justify a pharmacological effect of this drug on the in lammatory status of the adenoma. A correlation with clinical improvement was observed [5].
Latil A et al., "What's known on the subject? And what does the study add? Pervasive in lammatory in iltrates, mainly composed of chronically activated T cells and monocytes/macrophages, have been observed in benign prostatic hyperplasia (BPH). Permixon®, a hexanic lipidosterolic extract of Serenoa repens (hexanic LSESr) used to treat urinary dysfunction in BPH patients, has anti-in lammatory activities. This paper provides new insights into the anti-in lammatory properties of Permixon®. We report that hexanic LSESr inhibits early steps of leukocyte in iltration in vitro by downregulating MCP-1/CCL2 and VCAM-1 expression.
To investigate the mechanisms by which hexanic lipidosterolic extract of Serenoa repens (hexanic LSESr) may prevent leukocyte in iltration in benign prostatic hyperplasia by studying its impact on monocyte chemoattractant protein 1/ chemokine (C-C motif) ligand 2 (MCP-1/CCL2) and vascular cell adhesion molecule 1 (VCAM-1) expression in vitro. After pretreatment with hexanic LSESr, human prostate (epithelial and myo ibroblastic) cells and vascular endothelial cells were stimulated with proin lammatory cytokines. MCP-1/CCL2 and VCAM-1 mRNA expression was quanti ied by real-time PCR. ELISA kits were used to determine MCP-1/CCL2 levels in culture supernatants and VCAM-1 expression in living cells.
• Skeldon SC et al., "We investigated the risk of cardiovascular events among patients receiving dutasteride relative to inasteride. We performed a population based cohort study of Ontario men 66 years old or older who commenced treatment with dutasteride or inasteride between October 1, 2005 and March 31, 2015. For each individual treated with dutasteride, we identi ied 1 treated with inasteride, matching on a propensity score and calendar quarter of treatment initiation to account for temporal changes in prescribing. The primary outcome was hospitalization for heart failure. Secondary analyses were done to examine acute myocardial infarction and stroke. Cox proportional hazards regression was used to adjust for differences between groups.
We studied 36,311 men who commenced dutasteride and 36,311 treated with inasteride. In the primary analysis, we found no difference in the risk of heart failure among patients receiving dutasteride relative to those receiving inasteride (adjusted HR 0.98, 95% CI 0.88-1.08). Similarly, we found no difference in the risk of acute myocardial infarction (HR 0.94, 95% CI 0.82-1.08) or stroke (HR 1.03, 95% CI 0.88-1.20). In this population based cohort study of more than 72,000 older men, dutasteride was not associated with an increased risk of cardiovascular events relative to inasteride [7].
• According Loke YK et al., "A recently published large, long-term randomized controlled trial (RCT) brought into question the safety of dutasteride after a signi icantly increased risk of 'cardiac failure' was noted in the dutasteride arm of the trial compared with placebo. Our objective was to perform a meta-analysis to assess the risk of cardiovascular adverse events with the use of dutasteride for the prevention or treatment of prostatic disease. We searched MEDLINE and EMBASE, unpublished articles identi ied through FDA/EMEA websites, study registers of pharmaceutical companies and reference lists of articles. Parallelgroup, randomized controlled trials where men received dutasteride for the prevention of prostate cancer or treatment of prostatic hyperplasia against any comparator intervention were included. Heart failure was the primary outcome of interest but we also looked at myocardial infarction and stroke. Fixed-effect meta-analysis of pooled relative risk (RR) ratios of adverse effect outcomes was conducted.
• I. R. Ravish et al., "Dutasteride signi icantly improved Qmax, reduced IPSS score, and improved Quality of Life as compared to Finasteride at the end of the 12-week period. Dutasteride with its inhibitory effects on type 1 and 2 5 alfa reductase, produces signi icantly better results than Finasterid [9].
• Liptay S1 et al., writed that "1. Chronic in lammatory diseases have been shown to be associated with NF-kappaB activation and impaired apoptosis of immune cells. The aim of the present study was to investigate if sulfasalazine and its colonic metabolites 5-aminosalicylic acid (5ASA) and sulfapyridine affect NF-kappaB/Rel activation and viability of T-lymphocytes. 2. Sulfasalazine inhibits NF-kappaB/Rel activation in the murine T-lymphocyte cell line RBL5 using electrophoretic mobility shift assays. In transfection assays sulfasalazine treatment for 4 h inhibits kappaB-dependent transcription with an IC50 value of approximately 0.625 mM. 3. Higher doses or prolonged treatment result in cell death of T-lymphocytes in a dose-and time-dependent manner. Cell death is caused by apoptosis as judged by DNA fragmentation, annexin V and Apo 2.7 staining. Induction of apoptosis is a fast event with 50% apoptotic cells after a 4 h incubation with 2.5 mM sulfasalazine. The ED50 value for apoptosis induction after 24 h treatment was approximately 0.625 mM. 4. In contrast, 5ASA and sulfapyridine neither inhibit NF-kappaB/Rel activation nor induce apoptosis in T-lymphocytes at doses up to 5.0 mM. 5. These results demonstrate that sulfasalazine, but not 5ASA or sulfapyridine, strongly inhibits NF-kappaB activation and potently induces apoptosis in T-lymphocytes. Inhibition of NF-kappaB/Rel activation and subsequent clearance of activated T-lymphocytes by apoptosis might thus explain the bene icial effects of sulfasalazine in the treatment of chronic in lammatory disorders [11]. Perletti G et al., "Chronic bacterial prostatitis (CBP) is a persistent infection of the prostate characterized by poor quality of life mainly due to frequent relapse episodes caused by incomplete eradication of causative pathogens. Aggressive antibacterial therapy is required to attenuate the severe symptoms of CBP and to achieve a permanent cure. Although luoroquinolones are currently recommended as irst-choice agents, macrolide antibiotics are emerging as a noteworthy option for the treatment of CBP. Macrolide antibiotics are characterized by an impressive array of distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties. These properties include high intracellular accumulation in phagocytes and at sites of infection, including the prostate; broad antibiotic but also bio ilm-inhibiting properties; immunomodulating and in lammation-resolving activities. These features offer particular advantages for the treatment of chronic infections of the prostate gland, which are not easily amenable to drug therapy. Macrolides may be exploited to counteract the unsatisfactory rates of clinical symptom improvement and pathogen eradication. The results of a number of clinical trials support this proposal [12].
Ikeuchi T et al., "We analyzed the incidence of anal disease in patients with nonbacterial prostatitis (NBP) or with prostatitis-like syndrome (PLS), and evaluated the clinical ef icacy. The complicated rate of anal disease in these patients was 29.7% (31.8% for NBP and 28.1% for PLS), and the overall incidence of active anal disease was 15.4% (16.2% for NBP and 14.8% for PLS), it yielded a signi icantly higher complicated rate than other urological disease (p less than 0.01). The most common type of anal disease was hemorrhoids, especially piles. The clinical cure rate for anal disease in NBP patients was 71.4%, and in PLS patients was 58.2%. The high incidence of hemorrhoids (especially piles) was in these patients by clinico-statistical observation suggests that the development of anal disease may be etiologically correlated with NBP and PLS. Furthermore, we noted that Kampo treatment (Keisibukuryogan) was useful in the treatment of prostatitis complicated by anal disease, especially when combined with anti-hemorrhoidal suppositories against active anal disease in PLS patients (p less than 0.05) [13].
And according Takechi S et al., "The pathogenesis of nonbacterial prostatitis (NBP) is not understood mainly due to the lack of appropriate experimental models. We developed a new experimental model of NBP by inducing a partial obstruction of the urethra (PUO) in the rat. Male Wistar rats aged 12 weeks were used. PUO was produced by a nylon ligature on the urethra over a rubber tube. The tube was slipped out after the ligature had been tied. Two rats were examined histologically 6 h, 1 day, 3 days and 7 days after PUO. In another group, two rats were killed at 1, 3 and 7 days after the release of the PUO that had been left in place for 3 days. On day 3, another eight rats with PUO and eight control rats had 2 ml of urine in the bladder replaced by the same volume of lucifer yellow (LY; 10 microg/ml, MW 500), microperoxidase (MP; 20 microg/ml, MW 1900), horseradish peroxidase (HRP; 10 microg/ml, MW 40 000), or saline as control, respectively. Lymphocytic in iltration and interstitial edema were noted in the prostate following PUO, being most prominent on day 3. After the release of the PUO, these in lammatory changes gradually disappeared. Only LY was noted within the prostatic stroma of the rats 2 h after bladder instillation. Intraprostatic urinary re lux may be an etiologic factor in NBP. The present study showed that lower urinary tract obstruction caused NBP in the rat. Penetration of prostatic tissue by lowmolecular-weight substances in the urine may trigger NBP [14].

Discussion
In BHP we can observe a great damage to the patient quality of life and cost for public institutions and insurance. We must consider that BHP disease under an infective, endocrine and immune phenomena deeply interconnected. Non pharmacological strategies can be Kegel exercise to reduce pelvic ipertonus, lifestyle, dietary, physical activity and other factor can reduce relapsis in chronic and acute prostatitis related in BPH, reduction of pelvic congestion. No sedentariety, no stinging species, no etilic alcohol drinks, no cured meats et other. The Intestinal lora situation is relevant to prevent exchange of bacteria form rectum, proctological disease, hemorrhoids.
In relapses of BHP as chronic or acute prostatitis factors like different kind of bacteria population in the infectious and related activity pro ile of antimicrobial used ( gram+, gram -, mycoplasma and calmidya, herpes virus), pro ile of resistance, bio ilm presence, tissue iperplasia, chronic logosis, autoimmunity, kinetics of tissue penetration etc. must be high considered to achieve the best results. Also the receptor local situation in bladder and trigon (adrenergic, cholinergic) are relevant factors useful in therapy strategy to improve urinary low (as wee as anatomic obstruction of prostate uretra) and other.
Under the light o reported literature Prostate gland must be considered an immunology's subject in some disease at BHP and chronic prostatitis and this aspect must not to be overlooked especially in therapy. In resistances pro ile other antimicrobials as, ampicillin, carbenicillin, doxicillin, gentamicin, imipenem, piperacillina tazob, Fosfomicin parenteral and other. In this paper we have see only some molecule currently in use to show the relationship between dynamics, kinetics, drug delivery strategy and medicinal chemistry properties. Prostate gland is considered a pharmacological sanctuaries and for this reason using the best strategies it can result in more % of global clinical ef icacy. Rigth spectrum anti-microbial covering, right time of the cure, the right anti logosis and anti edemigen therapy associated to 5-ARI to induce apoptosis and alfa blockers can be the golden endpoint to prevent the progression of BHP. Also a good blood glucose control prevent recurrent urinary infectious (glucose is normally used by microbs growth) and uric acid blood monitoring and control and therapy can be useful to reduce global stinging Situation (crystals).
Observing some of these works related to some pathological conditions like BPHP in attempt to ind NEW treatment strategies that could be translated in new ef icient treatments in order to achieve much better enhanced clinical results, such as: New therapeutical combinatorial cocktail regimen.
Drug delivery systems, achieving more ef icacy and reduced both side effects and relapses or surgical needs: to for instance the penetration of antibacterial antiviral drugs or bypassing the bio ilm capsule or when we have already less in lammation, obviously we would have less hypertrophy, and consequently and obviously we will logically need less dosage and drug levels in each case.

4.
Moreover once the drug is released locoregionally, more safe type of molecules for example 4a. antibacterial 4b. antiviral or 4c. even anti in lammatory responses can be used or even improvements in by manipulating or modifying the molecular structure in order to render the molecule more potent do an increased hydrophobicity or even speci ic receptor af inity while avoiding less toxic structures such as the presence of extremely molecular moieties with in some cases very strong electrophilic nature and a tendency to create covalent bonds with DNA [15], achieving much less toxic and more potent drugs which is translated in more ef icacy and reduced both side effects and relapses or the need surgical interventions.

Conclusion
From literature we can see some relevant implication in pharmacological therapy related to medicinal chemistry, pharmacological or delivery system properties of some molecule currently in use. In medical approach the right pro ile of action (dynamics, antibacterial spectrum, dosage, duration of therapy, pharmacokinetics, tissue penetration and other characteristics) are to take in great consideration in this kind of situation. Even little modify in kinetics, dynamics or delivery system and sequential approach (for antimicrobials) can produce improve in clinical outcomes in BPH medical therapy and control. Drugs strategies that must consider antimicrobial power, antimicrobial concentration, alfa bloccants effect, 5 HT inhibitions, anti logosis but also new drug delivery systems. Andi edemigen, antioxidant et other as well as preventive non pharmacological strategies like right water intake, physical activity, no traumatic sports, not sexual abuse but regular (spermatozoa degradation products), and other From literature we have see the preminent role played in BPH by chronic logosis,as well as hormonal umbalancec that produce tissue remodeling, preproduction of growth factors and reduced apoptosis.

All factors involved in BHP progression
So a deep knowledge in medicinal chemistry of molecule currently used make possible a more rational therapy of chronic prostatitis as well as BHP as well as to introduce by pharmaceutical industries improved or new molecule with a better pro ile of action. What is relevant is that all chronic prostatitis must be treated in the right way since irst time to prevent chronic progression and the vicious circle. Can we think new delivery system to achieve better improvement in local tissue penetration of Therapeutics principles?
We know that it clear that the drugs vehicle is important as the same drugs and that modifying the molecule we can improve the activity in relevant way also due by different tissue diffusion (In example see the chinolons and luoro chinolons different pattern of tissue penetration) and in duration of action time As request to prevent relapses in acute and chronic prostatitis.
Lipophilic hydrophilic balances, acid-bases properties, molecular weight and other pharmaceutical characteristics great in luence the pk. Kinetics as VD or T1/2 but also the pro ile of linked chemical groups can give new delivery of classic drugs (Other can be acid or basic molecular properties or velocity in metabolism). We know that for example in the same drug classes in examples chinolons little chemistry modify can results in improvement of ef icacy so we can think that little chemical modify o new delivery system can produce better clinical results by a better pharmacokinetics in this sanctuaries.
We can consider innovative drug delivery systems to improve clinical ef icacy reducing global toxicity. Novel loco-regional drug delivery systems or more targeted to prostatic tissue, more time extended drug. Presence in prostatic tissue, using of innovative technologies as colloidal micro-Nano systems and other, better bio ilm discgregation properties, modifying lipo ilic-idro ilic molecular balances, acid bases properties of molecule, add of more useful chemical groups to classic formula to improve kinetics and prostatic intake, implants, and other medicinal chemistry new technologies that can add advantages vs the actual therapy models.
All this strategies must be added to adeguate logosys control and towards preventing linphocite T and macrophages prostate in iltration and an ef icacy grow factors control.

Clarifi cations
This paper was not written for any diagnostic or therapeutic intent, only to produce new research hypotesys.