Endoscopic treatment of bleeding gastric varices with histoacryl (N-butyl-2-cyanoacrylate): a South European single center experience

BACKGROUND: Endoscopic injection of N-butyl-2-cyanoacrylate is the current recommended treatment for gastric variceal bleeding. Despite the extensive worldwide use, there are still differences related to the technique, safety, and long term-results. We retrospectively evaluated the efficacy and safety of cyanoacrylate in patients with gastric variceal bleeding. PATIENTS AND METHODS: Between January 1998 and January 2010, 97 patients with gastric variceal bleeding underwent endoscopic treatment with a mixture of N-butyl-2-cyanoacrylate and Lipiodol(TM). Ninety-one patients had cirrhosis and 6 had non-cirrhotic portal hypertension. Child-Pugh score at presentation for cirrhotic patients was A-12.1 %; B-53.8 %; C-34.1 % and median MELD score at admission was 13 (3-26). Successful hemostasis, rebleeding rate and complications were reviewed. Median time of follow up was 19 months (0.5-126). RESULTS: A median mixture volume of 1.5 mL (0.6 to 5 mL), in 1 to 8 injections, was used, with immediate hemostasis rate of 95.9 % and early rebleeding rate of 14.4 %. One or more complications occurred in 17.5 % and were associated with the use of Sengstaken-Blakemore tube before cyanoacrylate and very early rebleeding (p < 0.05). Hospital mortality rate during initial bleeding episode was 9.3 %. Very early rebleeding was a strong and independent predictor for in-hospital mortality (p < 0.001). Long-term mortality rate was 58.8 %, in most of the cases secondary to hepatic failure. CONCLUSION: N-butyl-2-cyanoacrylate is a rapid, easy and highly effective modality for immediate hemostasis of gastric variceal bleeding with an acceptable rebleeding rate. Patients with very early rebleeding are at higher risk of death.

Effect of portal hypertension in the small bowel: an endoscopic approach

BACKGROUND AND AIM: The effects of portal hypertension in the small bowel are largely unknown. The aim of the study was to prospectively assess portal hypertension manifestations in the small bowel. METHODS: We compared, by performing enteroscopy with capsule endoscopy, the endoscopic findings of 36 patients with portal hypertension, 25 cirrhotic and 11 non-cirrhotic, with 30 controls. RESULTS: Varices, defined as distended, tortuous, or saccular veins, and areas of mucosa with a reticulate pattern were significantly more frequent in patients with PTH. These two findings were detected in 26 of the 66 patients (39%), 25 from the group with PTH (69%) and one from the control group (3%) (P < 0.0001). Among the 25 patients with PTH exhibiting these patterns, 17 were cirrhotic and 8 were non-cirrhotic (P = 0.551). The presence of these endoscopic changes was not related to age, gender, presence of cirrhosis, esophageal or gastric varices, portal hypertensive gastropathy, portal hypertensive colopathy, prior esophageal endoscopic treatment, current administration of beta-blockers, or Child-Pugh Class C. More patients with these endoscopic patterns had a previous history of acute digestive bleeding (72% vs. 36%) (P = 0.05). Active bleeding was found in two patients (5.5%). CONCLUSIONS: The presence of varices or areas of mucosa with a reticulate pattern are manifestations of portal hypertension in the small bowel, found in both cirrhotic and non-cirrhotic patients. The clinical implications of these findings, as regards digestive bleeding, are uncertain, although we documented acute bleeding from the small bowel in two patients (5.5%).

Cardiac magnetic resonance imaging in the diagnosis and determination of outcome of pulmonary hypertension

Pulmonary hypertension (PH) is a rare but serious condition that causes progressive right ventricular (RV) failure and death. PH may be idiopathic, associated with underlying connective-tissue disease or hypoxic lung disease, and is also increasingly being observed in the setting of heart failure with preserved ejection fraction (HFpEF). The management of PH has been revolutionised by the recent development of new disease-targeted therapies which are beneficial in pulmonary arterial hypertension (PAH), but can be potentially harmful in PH due to left heart disease, so accurate diagnosis and classification of patients is essential. These PAH therapies improve exercise capacity and pulmonary haemodynamics, but their overall effect on the right ventricle remains unclear. Current practice in the UK is to assess treatment response with 6-minute walk test and NYHA functional class, neither of which truly reflects RV function. Cardiac magnetic resonance (CMR) imaging has been established as the gold standard for the evaluation of right ventricular structure and function, but it also allows a non-invasive and accurate study of the left heart. The aims of this thesis were to investigate the use of CMR in the diagnosis of PH, in the assessment of treatment response, and in predicting survival in idiopathic and connective-tissue disease associated PAH. In Chapter 3, a left atrial volume (LAV) threshold of 43 ml/m2 measured with CMR was able to distinguish idiopathic PAH from PH due to HFpEF (sensitivity 97%, specificity 100%). In Chapter 4, disease-targeted PAH therapy resulted in significant improvements in RV and left ventricular ejection fraction (p<0.001 and p=0.0007, respectively), RV stroke volume index (p<0.0001), and left ventricular end-diastolic volume index (p=0.0015). These corresponded to observed improvements in functional class and exercise capacity, although correlation coefficients between Δ 6MWD and Δ RVEF or Δ LVEDV were low. Finally, in Chapter 5, one-year and three-year survival was worse in CTD-PAH (75% and 53%) than in IPAH (83% and 74%), despite similar baseline clinical characteristics, lung function, pulmonary haemodynamics and treatment. Baseline right ventricular stroke volume index was an independent predictor of survival in both conditions. The presence of LV systolic dysfunction was of prognostic significance in CTD-PAH but not IPAH, and a higher LAV was observed in CTD-PAH suggesting a potential contribution from LV diastolic dysfunction in this group.

Medication adherence and direct treatment cost among diabetes patients attending a tertiary healthcare facility in Ogbomosho, Nigeria

Background Diabetes mellitus (DM) is now prevalent in many countries in sub- Saharan Africa, with associated health and socioeconomic consequences. Adherence to antidiabetic medications has been shown to improve glycaemic control, which subsequently improves both the short- and longterm prognosis of the disease. The main objective of this study was to assess the level of adherence to antidiabetic drugs among outpatients in a teaching hospital in southwestern Nigeria. Methods A cross-sectional study was carried out using the eight-item Morisky Medication Adherence Scale (MMAS-8) among diabetic patients attending the medical outpatients’ diabetes clinic of Ladoke Akintola University Teaching Hospital, in Ogbomosho, Oyo State in southwestern Nigeria, during a three-month period (October to December 2013). Results A total of 129 patients participated in the study with a male-to-female ratio of 1:1.5. Seventy-eight (60.5%) patients had systemic hypertension as a comorbid condition while the remaining were being managed for diabetes mellitus alone. Only 6 (4.7%) of the patients had type 1 DM while the remaining 123 (95.3%) were diagnosed with type 2 DM. Metformin was the most prescribed oral hypoglycaemic agent (n = 111, 58.7%) followed by glibenclamide (n = 49, 25.9%). Medication adherence was classified as good, medium, and poor for 52 (40.6%), 42 (32.8%), and 34 (26.6%) patients, respectively. Medication costs accounted for 72.3% of the total direct cost of DM in this study, followed by the cost of laboratory investigations (17.6%). Conclusion Adherence of diabetes patients in the study sample to their medications was satisfactory. There is a need for the integration of generic medicines into routine care as a way of further reducing the burden of healthcare expenditure on the patients.

Hypertension in the National University of Distance Education’s personnel

The prevalence of Arterial Hypertension (AHT) has increased worldwide and preventive measures areinsufficient since only one third of the population is being treated. AHT is the primary cause of morbidity andmortality in the world. In this article is presented the first study on hypertension levels of personnel of aDistance Education university based on the analysis of all medical consultations in the Costa Rican StateUniversity for Distance Education (Universidad Estatal a Distancia-UNED) as of December 15, 2007 (1,526medical files). The population studied ranges from 20 to 70 years of age and is comprised of residents of theGreater Metropolitan Area (Costa Rica) with varied socioeconomic and academic levels. The StatgraphicsCenturion XV software and the chi-square test were used to analyze variables such as treatment administered,sex, age, and type of work. Only 45 patients knew that they suffered from hypertension prior to theirconsultation with the university medical service and 136 were treated with Enalapril and Hydrochlorothiazide.The number of hypertensive patients is higher among those who have worked at the institution for more than 20years, especially in those holding higher positions. No marked differences were found between men andwomen. It is concluded that the existence of a university medical service has permitted faculty and staff tosatisfactorily control their blood pressure.

The role of non-coding RNA in the development of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease of the small pulmonary arteries, characterised by pulmonary vascular remodelling due to excessive proliferation and resistance to apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). The increased pulmonary vascular resistance and elevated pulmonary artery pressures result in right heart failure and premature death. Germline mutations of the bone morphogenetic protein receptor-2 (bmpr2) gene, a receptor of the transforming growth factor beta (TGF-β) superfamily, account for approximately 75%-80% of the cases of heritable form of PAH (HPAH) and 20% of sporadic cases or idiopathic PAH (IPAH). IPAH patients without known bmpr2 mutations show reduced expression of BMPR2. However only ~ 20% of bmpr2-mutation carriers will develop the disease, due to an incomplete penetrance, thus the need for a ‘second hit’ including other genetic and/or environmental factors is accepted. Diagnosis of PAH occurs most frequently when patients have reached an advanced stage of disease. Although modern PAH therapies can markedly improve a patient’s symptoms and slow the rate of clinical deterioration, the mortality rate from PAH remains unacceptably high. Therefore, the development of novel therapeutic approaches is required for the treatment of this multifaceted disease. Noncoding RNAs (ncRNAs) include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs are ~ 22 nucleotide long and act as negative regulators of gene ex-pression via degradation or translational inhibition of their target mRNAs. Previous studies showed extensive evidence for the role of miRNAs in the development of PAH. LncRNAs are transcribed RNA molecules greater than 200 nucleotides in length. Similar to classical mRNA, lncRNAs are translated by RNA polymerase II and are generally alternatively spliced and polyadenylated. LncRNAs are highly versatile and function to regulate gene expression by diverse mechanisms. Unlike miRNAs, which exhibit well-defined actions in negatively regulating gene expression via the 3’-UTR of mRNAs, lncRNAs play more diverse and unpredictable regulatory roles. Although a number of lncRNAs have been intensively investigated in the cancer field, studies of the role of lncRNAs in vascular diseases such as PAH are still at a very early stage. The aim of this study was to investigate the involvement of specific ncRNAs in the development of PAH using experimental animal models and cell culture. The first ncRNA we focused on was miR-143, which is up-regulated in the lung and right ventricle tissues of various animal models of PH, as well as in the lungs and PASMCs of PAH patients. We show that genetic ablation of miR-143 is protective against the development of chronic hypoxia induced PH in mice, assessed via measurement of right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodelling. We further report that knockdown of miR-143-3p in WT mice via anti-miR-143-3p administration prior to exposure of mice to chronic hypoxia significantly decreases certain indices of PH (RVSP) although no significant changes in RVH and pulmo-nary vascular remodelling were observed. However, a reversal study using antimiR-143-3p treatment to modulate miR-143-3p demonstrated a protective effect on RVSP, RVH, and muscularisation of pulmonary arteries in the mouse chronic hypoxia induced PH model. In vitro experiments showed that miR-143-3p overexpression promotes PASMC migration and inhibits PASMC apoptosis, while knockdown miR-143-3p elicits the opposite effect, with no effects observed on cellular proliferation. Interestingly, miR-143-3p-enriched exosomes derived from PASMCs mediated cell-to-cell communication between PASMCs and PAECs, contributing to the pro-migratory and pro-angiogenic phenotype of PAECs that underlies the pathogenesis of PAH. Previous work has shown that miR-145-5p expression is upregulated in the chronic hypoxia induced mouse model of PH, as well as in PAH patients. Genetic ablation and pharmacological inhibition (subcutaneous injection) of miR-145-5p exert a protective against the de-velopment of PAH. In order to explore the potential for alternative, more lung targeted delivery strategies, miR-145-5p expression was inhibited in WT mice using intranasal-delivered antimiR-145-5p both prior to and post exposure to chronic hypoxia. The decreased expression of miR-145-5p in lung showed no beneficial effect on the development of PH compared with control antimiRNA treated mice exposed to chronic hypoxia. Thus, miR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while the inhibition of miR-143-3p prevented the development of experimental pulmonary hypertension. We focused on two lncRNAs in this project: Myocardin-induced Smooth Muscle Long noncoding RNA, Inducer of Differentiation (MYOSLID) and non-annotated Myolnc16, which were identified from RNA sequencing studies in human coronary artery smooth muscle cells (HCASMCs) that overexpress myocardin. MYOSLID was significantly in-creased in PASMCs from patients with IPAH compared to healthy controls and increased in circulating endothelial progenitor cells (EPCs) from bmpr2 mutant PAH patients. Exposure of PASMCs to hypoxia in vitro led to a significant upregulation in MYOSLID expres-sion. MYOSLID expression was also induced by treatment of PASMC with BMP4, TGF-β and PDGF, which are known to be triggers of PAH in vitro. Small interfering RNA (siR-NA)-mediated knockdown MYOSLID inhibited migration and induced cell apoptosis without affecting cell proliferation and upregulated several genes in the BMP pathway in-cluding bmpr1α, bmpr2, id1, and id3. Modulation of MYOSLID also affected expression of BMPR2 at the protein level. In addition, MYOSLID knockdown affected the BMP-Smad and BMP-non-Smad signalling pathways in PASMCs assessed by phosphorylation of Smad1/5/9 and ERK1/2, respectively. In PAECs, MYOSLID expression was also induced by hypoxia exposure, VEGF and FGF2 treatment. In addition, MYOSLID knockdown sig-nificantly decreased the proliferation of PAECs. Thus, MYOSLID may be a novel modulator in pulmonary vascular cell functions, likely through the BMP-Smad and –non-Smad pathways. Treatment of PASMCs with inflammatory cytokines (IL-1 and TNF-α) significantly in-duced the expression of Myolnc16 at a very early time point. Knockdown of Myolnc16 in vitro decreased the expression of il-6, and upregulated the expression of il-1 and il-8 in PASMCs. Moreover, the expression levels of chemokines (cxcl1, cxcl6 and cxcl8) were sig-nificantly decreased with Myolnc16 knockdown. In addition, Myolnc16 knockdown decreased the MAP kinase signalling pathway assessed by phosphorylation of ERK1/2 and p38 MAPK and inhibited cell migration and proliferation in PASMCs. Thus, Myolnc16 may a novel modulator of PASMCs functions through anti-inflammatory signalling pathways. In summary, in this thesis we have demonstrated how miR-143-3p plays a protective role in the development of PH both in vivo animal models and patients, as well as in vitro cell cul-ture. Moreover, we have showed the role of two novel lncRNAs in pulmonary vascular cells. These ncRNAs represent potential novel therapeutic targets for the treatment of PAH with further work addressing to investigate the target genes, and the pathways modulated by these ncRNAs during the development of PAH.

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: experience of four years in a single centre

Background: Balloon pulmonary angioplasty (BPA) has recently been developed as an alternative and less- invasive treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH), but therapeutic efficacy and technical safety of the technique have to be established. Aim: effects of BPA on patients with inoperable disease or residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Methods: From June 2015 to September 2019 we enrolled symptomatic (NYHA ≥ II) inoperable CTEPH patients and patients with residual PH after PEA. At baseline, immediately before the first BPA session and 3-6 months after last BPA session all patients underwent clinical evaluation, six-minute walking distance and right heart catheterization. For comparisons Friedman test (with Bonferroni post-hoc pairwise analysis) was used. Survival curves were done with Kaplan Meier method. Results: Forty-seven patients [male 45%, median age 68 (51-74) years, 40 inoperable and 7 with residual PH after PEA] were treated for a total of 136 sessions (median number of sessions for each patient: 2); during each session we treated 2 (2-3) vessels; BPA significantly improved symptoms (NYHA III-IV from 85 to 42%), exercise capacity (from 425 to 446 m) and hemodynamic profile (reduction of mean pulmonary arterial pressure from 41 to 35 mmHg and of pulmonary vascular resistance from 7.1 to 4.7 WU). Five pulmonary artery dissection and 2 hemoptysis with clinical impairment were documented; 33 patients had lung injury (radiographic opacity with/without hemoptysis and/or hypoxemia), 7 patients had access site complications. Five patients died during follow-up (none within 30 days from the procedure) because of sepsis (1), heart failure (1), cancer (1), arrhythmic storm (1) and sudden death in a patient with severe coronary atherosclerosis (1). Conclusions: BPA is a safe and effective treatment able to improve symptoms and hemodynamic profile in inoperable CTEPH patients and in patients with residual PH after PEA.

Design and Synthesis of Novel Kinase Inhibitors for the Treatment of Chronic Respiratory Diseases

In 2017, Chronic Respiratory Diseases accounted for almost four million deaths worldwide. Unfortunately, current treatments are not definitive for such diseases. This unmet medical need forces the scientific community to increase efforts in the identification of new therapeutic solutions. PI3K delta plays a key role in mechanisms that promote airway chronic inflammation underlying Asthma and COPD. The first part of this project was dedicated to the identification of novel PI3K delta inhibitors. A first SAR expansion of a Hit, previously identified by a HTS campaign, was carried out. A library of 43 analogues was synthesised taking advantage of an efficient synthetic approach. This allowed the identification of an improved Hit of nanomolar enzymatic potency and moderate selectivity for PI3K delta over other PI3K isoforms. However, this compound exhibited low potency in cell-based assays. Low cellular potency was related to sub optimal phys-chem and ADME properties. The analysis of the X-ray crystal structure of this compound in human PI3K delta guided a second tailored SAR expansion that led to improved cellular potency and solubility. The second part of the thesis was focused on the rational design and synthesis of new macrocyclic Rho-associated protein kinases (ROCKs) inhibitors. Inhibition of these kinases has been associated with vasodilating effects. Therefore, ROCKs could represent attractive targets for the treatment of pulmonary arterial hypertension (PAH). Known ROCK inhibitors suffer from low selectivity across the kinome. The design of macrocyclic inhibitors was considered a promising strategy to obtain improved selectivity. Known inhibitors from literature were evaluated for opportunities of macrocyclization using a knowledge-based approach supported by Computer Aided Drug Design (CADD). The identification of a macrocyclic ROCK inhibitor with enzymatic activity in the low micro molar range against ROCK II represented a promising result that validated this innovative approach in the design of new ROCKs inhibitors.

Psychological characterization of hypertensive patients: associations with adherence to pharmacological treatment and self-management

Introduction: The role of psychosocial factors in the onset and progression of essential hypertension has been object of a large body of literature, yet findings appear to be controversial. Aims: We assessed the predictive role of psychosomatic syndromes, affective symptomatology, psychological reactance, psychological distress, well-being and quality of life on adherence to antihypertensive medications, lifestyle behaviors, hypertension severity and absolute cardiovascular risk grading, as well as their temporal stability at 1-year follow-up, in a sample of hypertensive patients. In addition, we aimed to validate the Italian version of the Hong Psychological Reactance Scale (HPRS). Methods: Eighty consecutive hypertensive outpatients treated with antihypertensive medications were compared to 80 controls. Psychosocial variables were assessed using clinical interviews and self-rating questionnaires at baseline and at 1-year follow-up. Cardiac parameters were also collected. One-hundred and fifty individuals from general population provided data for the HPRS validation. Results: Hypertensive patients reported significantly higher levels of psychological distress and lower levels of psychological well-being at baseline compared to controls. Among hypertensive patients, allostatic overload (AO) was the most frequently reported psychosomatic syndrome at baseline. Patients with AO displayed significantly greater levels of psychological distress and lower levels of well-being and quality of life than those without. Further, patients with illness denial were significantly more likely to report poor adherence to pharmacological treatment and, as well as those with higher levels of affective symptomatology, were less likely to follow a balanced diet. At follow-up, patients displayed significantly higher levels of well-being and lower levels of stress, mental pain and quality of life. Conclusions: Findings suggest the clinical relevance of psychosocial factors and psychosomatic syndromes in the progression of hypertension, with important implications for its management. As to the Italian validation of the HPRS, results support previous findings, even though a confirmatory factor analysis should be carried out.

Triple combination therapy in pulmonary arterial hypertension

Pulmonary arterial hypertension is a severe disease characterized by increasing in pulmonary vascular resistance leading to right ventricular failure and death. Currently available drugs for treatment of PAH act on three different pathways responsible of the pathogenesis of this disease: the endothelin pathway, the nitric oxide pathway and the prostacyclin pathway. The purpose of our study was to reassess our experience on the use of drugs that interact on the pathobiological line of prostacyclin so we retrospectively included all patients, referred to our center from February 1995 to December 2021, who received therapy with i.v. Epoprostenol, s.c. Treprostinil or oral Selexipag. Firstly, we observed that patients treated with Epoprostenol were significantly more compromised at baseline when compared to the two other groups and evaluating the effects of the three different drugs, it emerged that patients treated with Epoprostenol had significantly greater improvements in respect to those treated with Treprostinil and Selexipag. In the second part of our analysis we assessed the effects of these drugs when used as third line strategy in order to limit many confounding factors that could influence demographic, clinical and hemodynamic characteristics of patient populations. The differences emerged in exercise capacity and baseline hemodynamics reflect the fact that in our clinical practice, we add Epoprostenol as third line therapy in more compromised patients, Treprostinil in intermediate situations and Selexipag in less impaired conditions. Comparing the effects of treatments between baseline and first follow-up we noticed smaller benefits with Selexipag when compared with intravenous and subcutaneous strategies but it’s important to weight baseline patient’s differences. Our analysis confirmed clinical and functional benefits for the use of both prostacyclin analogues and prostacyclin receptor agonists in terms of improved functional class, six-minute walking distance and cardiopulmonary hemodynamics.

Minimal Invasive Ostheosintesis For Treatment Of Diaphiseal Transverse Humeral Shaft Fractures.

To evaluate patients with transverse fractures of the shaft of the humerus treated with indirect reduction and internal fixation with plate and screws through minimally invasive technique. Inclusion criteria were adult patients with transverse diaphyseal fractures of the humerus closed, isolated or not occurring within 15 days of the initial trauma. Exclusion criteria were patients with compound fractures. In two patients, proximal screw loosening occurred, however, the fractures consolidated in the same mean time as the rest of the series. Consolidation with up to 5 degrees of varus occurred in five cases and extension deficit was observed in the patient with olecranon fracture treated with tension band, which was not considered as a complication. There was no recurrence of infection or iatrogenic radial nerve injury. It can be concluded that minimally invasive osteosynthesis with bridge plate can be considered a safe and effective option for the treatment of transverse fractures of the humeral shaft. Level of Evidence III, Therapeutic Study.

The Effect Of Pelvic Floor Muscle Training Alone Or In Combination With Electrostimulation In The Treatment Of Sexual Dysfunction In Women With Multiple Sclerosis.

Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients. The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS. Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire. After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire. This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD.

Impact Of Benign Prostatic Hyperplasia Pharmacological Treatment On Transrectal Prostate Biopsy Adverse Effects.

Background. Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Among 242 consecutive unselected patients who underwent prostate biopsy, after excluding those with history of prostate biopsy/surgery or using medications not for BPH, we studied 190 patients. On the 15th day after procedure patients were questioned about symptoms lasting over a week and classified according to pharmacological BPH treatment. Results. Thirty-three patients (17%) were using alpha-blocker exclusively, five (3%) 5-alpha-reductase inhibitor exclusively, twelve (6%) patients used both medications, and 140 (74%) patients used none. There was no difference in regard to age among groups (P = 0.5). Postbiopsy adverse effects occurred as follows: hematuria 96 (50%), hematospermia 53 (28%), hematochezia 22 (12%), urethrorrhagia 19 (10%), fever 5 (3%), and pain 20 (10%). There was a significant negative correlation between postbiopsy hematuria and BPH pharmacological treatment with stronger correlation for combined use of 5-alpha-reductase inhibitor and alpha-blocker over 6 months (P = 0.0027). Conclusion. BPH pharmacological treatment, mainly combined for at least 6 months seems to protect against prostate biopsy adverse effects. Future studies are necessary to confirm our novel results.

Blockade Of Renin-angiotensin System Prevents Micturition Dysfunction In Renovascular Hypertensive Rats.

Association between hypertension and bladder symptoms has been described. We hypothesized that micturition dysfunction may be associated with renin-angiotensin system (RAS) acting in urethra. The effects of the anti-hypertensive drugs losartan (AT1 antagonist) and captopril (angiotensin-converting enzyme inhibitor) in comparison with atenolol (β1-adrenoceptor antagonist independently of RAS blockade) have been investigated in bladder and urethral dysfunctions during renovascular hypertension in rats. Two kidney-1 clip (2K-1C) rats were treated with losartan (30 mg/kg/day), captopril (50mg/kg/day) or atenolol (90 mg/kg/day) for eight weeks. Cystometric study, bladder and urethra smooth muscle reactivities, measurement of cAMP levels and p38 MAPK phosphorylation in urinary tract were determined. Losartan and captopril markedly reduced blood pressure in 2K-1C rats. The increases in non-voiding contractions, voiding frequency and bladder capacity in 2K-1C rats were prevented by treatments with both drugs. Likewise, losartan and captopril prevented the enhanced bladder contractions to electrical-field stimulation (EFS) and carbachol, along with the impaired relaxations to β-adrenergic-cAMP stimulation. Enhanced neurogenic contractions and impaired nitrergic relaxations were observed in urethra from 2K-1C rats. Angiotensin II also produced greater urethral contractions that were accompanied by higher phosphorylation of p38 MAPK in urethral tissues of 2K-1C rats. Losartan and captopril normalized the urethral dysfunctions in 2K-1C rats. In contrast, atenolol treatment largely reduced the blood pressure in 2K-1C rats but failed to affect the urinary tract smooth muscle dysfunction. The urinary tract smooth muscle dysfunction in 2K-1C rats takes place by local RAS activation irrespective of levels of arterial blood pressure.

Evaluation Of Different Treatment Methods Against Denture Stomatitis: A Randomized Clinical Study.

The aim of this clinical study was to determine the efficacy of Uncaria tomentosa (cat's claw) against denture stomatitis (DS). Fifty patients with DS were randomly assigned into 3 groups to receive 2% miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately, after 1 week of treatment, and 1 week after treatment. The clinical effectiveness of each treatment was measured using Newton's criteria. Mycologic samples from palatal mucosa and prosthesis were obtained to determinate colony forming units per milliliter (CFU/mL) and fungal identification at each evaluation period. Candida species were identified with HiCrome Candida and API 20C AUX biochemical test. DS severity decreased in all groups (P < .05). A significant reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups and remained after 14 days (P > .05). C albicans was the most prevalent microorganism before treatment, followed by C tropicalis, C glabrata, and C krusei, regardless of the group and time evaluated. U tomentosa gel had the same effect as 2% miconazole gel. U tomentosa gel is an effective topical adjuvant treatment for denture stomatitis.