Novel in vitro evidence on the beneficial effect of quercetin treatment in vascular calcification.

Vascular calcification is a pathological chronic condition characterized by calcium crystal deposition in the vessel wall and is a recurring event in atherosclerosis, chronic kidney disease, and diabetes. The lack of effective therapeutic treatments opened the research to natural products, which have shown promising potential in inhibiting the pathological process in different experimental models. This study investigated the anti-calcifying effects of Quercetin and Berberine extracts on vascular smooth muscle cells (VSMCs) treated with an inorganic phosphate solution for 7 days. Quercetin has shown the highest anti-calcifying activity, as revealed by the intracellular quantitative assay and morphological analysis. Confocal microscopy revealed downregulation of RUNX2, a key marker for calcified phenotype, which was otherwise upregulated in calcified VSMCs. To investigate the anti-inflammatory activity of Quercetin, culture media were subjected to immunometric assays to quantify the levels of IL-6 and TNF-α, and the caspase-1 activity. As expected, calcified VSMCs released a large quantity of inflammatory mediators, significantly decreasing in the presence of Quercetin. In summary, our findings suggest that Quercetin counteracted calcification by attenuating the VSMC pathological phenotypic switch and reducing the inflammatory response. In our opinion, these preliminary in vitro findings could be the starting point for further investigations into the beneficial effects of Quercetin dietary supplementation against vascular calcification.

Self-efficacy in non-concussed youth: a normative study.

OBJECTIVE: In pediatric concussion, there has been a shift to consider how pre-injury profiles, such as self-efficacy, affect the recovery trajectory. The aim of this study was to investigate normal ranges of self-efficacy (overall, academic, social, emotional) in youth and to explore its relationship with the effects of daily stressors, operationalized as concussion-like symptoms, demographic factors, pre-injury/learning related factors, and concussion history. METHODS: A cross-sectional study of 1300 uninjured youth 13-18 years old (1111 males, 189 females) was conducted by secondary analysis of clinical pre-injury/baseline concussion data. Demographic information, concussion-like symptoms (Post-concussion Symptom Inventory), and self-efficacy (Self-efficacy Questionnaire for Children) were self-reported. RESULTS: The most reported concussion-like symptoms were common stress symptoms and there was a strong negative relationship with self-efficacy. Males reported higher self-efficacy than females, but no age effects were observed. Pre-injury factors including learning disability, ADHD, special education, IEP, mental health challenges, history of headaches/migraines, and concussion history were associated with significantly lower overall self-efficacy. CONCLUSIONS: These normative ranges and predictive model can be used to provide a benchmark of self-efficacy to indicate how youth may respond to a concussion, and to inform clinical care during recovery.

Health-Related Quality of Life in Non-Concussed Children: A Normative Study to Inform Concussion Management.

Purpose: There has been a shift to consider pediatric concussion recovery beyond symptom management by considering how health-related quality of life (HRQoL) affects recovery. This study investigated normative ranges of HRQoL in children and explored its relationship with common pediatric concussion variables. Methods: A cross-sectional study of 1,722 non-concussed children 8-12 years old (M = 10.52 ± 1.23 years; 1,335 males, 387 females) was conducted by secondary analysis of clinical baseline concussion data. Demographic information, concussion-like symptoms (PCSI-C), and HRQoL (KIDSCREEN-10 Index) were self-reported. Results: The most reported concussion-like symptoms were common stress symptoms and were significantly negatively correlated with HRQoL. Premorbid histories of attention deficit hyperactivity disorder, mental health challenges, headaches/migraines, and concussion significantly lowered HRQoL. The number of diagnosed concussions and PCSI-C scores were significantly negatively correlated with HRQoL. Conclusions: The normative ranges and model can indicate HRQoL levels to inform clinicians how children may respond to concussion and streamline care beyond traditional assessment models.

Immunohistochemical localization of histidine-rich glycoprotein in human skeletal muscle: preferential distribution of the protein at the sarcomeric I-band.

Histidine-rich glycoprotein (HRG) is a relatively abundant plasma protein that is synthesized by parenchymal liver cells. Using Western blot analysis and immunoperoxidase techniques, we have previously shown the presence of HRG in human skeletal muscle. This paper reports the results of immunofluorescence experiments carried out on sections of human normal skeletal muscle biopsies to investigate the subcellular localization of HRG. The HRG localization was also compared with that of skeletal muscle AMP deaminase (AMPD1), since we have previously described an association of the enzyme with the protein. The obtained results give evidence for a preferential localization of HRG at the I-band level, where it shows the same distribution of actin and where AMPD1 is present in major concentration.

Effects of L-DOPA/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration.

INTRODUCTION: The mainstay therapy for Parkinson's disease (PD) relies on L-3,4-dihydroxyphenylalanine (L-DOPA) plus a DOPA-decarboxylase inhibitor. However, their effects on colonic dysmotility and inflammation observed in PD are undetermined. This study examined the effects of L-DOPA plus benserazide (BE) on colonic motility and inflammation in rats with central nigrostriatal dopaminergic denervation. METHODS: Neurodegeneration was induced by 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). 6-OHDA animals were treated orally with L-DOPA/BE for 28 days, starting 28 days after 6-OHDA injection. At the end of treatment, in vivo colonic transit was evaluated by a radiologic assay. Electrically stimulated (ES) cholinergic contractions were recorded in vitro from colonic preparations, while acetylcholine release was measured in the incubation medium. Choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) expression as well as eosinophil and mast cell density were examined in the colonic wall by immunohistochemistry. Colonic TNF and IL-1ß levels were also assayed. RESULTS: 6-OHDA animals displayed: 1) decrease in in vivo colonic transit; 2) impairment of ES-stimulated cholinergic contractions; 3) decreased acetylcholine release from myenteric nerves; 4) decrease in ChAT and increase in GFAP myenteric immunopositivity; 5) increase in eosinophil and mast cell density; 6) increase in TNF and IL-1ß levels. Treatment with L-DOPA/BE elicited an improvement of in vivo and in vitro colonic motor activity, a normalization of acetylcholine release, ChAT immunopositivity, as well as pro-inflammatory cytokine patterns, ganglionic GFAP levels, eosinophil and mast cell density. CONCLUSION: Under dopaminergic nigrostriatal denervation, treatment with L-DOPA/BE ameliorated colonic motility through a normalization of myenteric cholinergic neurotransmission, along with an improvement of colonic inflammation.

A randomized single-center study to compare the efficacy and tolerability of tadalafil once daily plus lidocaine anesthetic spray on premature ejaculation.

OBJECTIVE: The use of topical local anesthetics in the form of creams, gel or spray is the oldest method of retarding ejaculation. However, several studies have suggested that phosphodiesterase type 5 inhibitors (5-PDEiS) show a potential therapeutic use in the treatment of premature ejaculation (PE). The aim of this study was to compare the efficacy and tolerability of tadalafil-only, tadalafil plus local anesthetic spray (lidocaine), and topical lidocaine spray-only before intercourse on the intravaginal ejaculatory latency time (IELT) of patients with lifelong PE. PATIENTS AND METHODS: The study included 78 men in stable heterosexual, monogamous relationships (of ≥3 months) who were diagnosed with lifelong PE. The patients were divided into three groups: G1: 25 patients who received lidocaine spray 10 g/100 ml at 5 min before intercourse; G2: 27 patients who received tadalafil 5 mg once daily; G3: 26 patients who treated with tadalafil once daily plus lidocaine spray before planned sexual activity. The treatments were continued for up to three months in all groups. Moreover, the quality of their sexual attempts was rated on a 5-point scale. Follow-up was made at 1-month and 3-month. RESULTS: Not statistically significant differences emerged between the three groups at baseline. Mean ejaculatory latency time at the 3-month follow-up in G1, G2 and G3 was 3.7±1.3, 3.4±1.5, 5.6±1.7 (p<0.001). Mean satisfaction score was at the 3-month follow-up in G1: 2.8±1.4, in G2: 2.9±1.8, and G3: 3.7±1.5 (p<0.002). None of the patients withdrew from the study because of these adverse events. CONCLUSIONS: This study demonstrates that tadalafil used daily has a role on treatment in lifelong PE. This action is valid when combined strategically to the synergistic action of lidocaine spray applied before intercourse increasing significantly the mean IELT.

Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease.

BACKGROUND AND PURPOSE: The COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD). EXPERIMENTAL APPROACH: Longitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis. KEY RESULTS: In control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle. CONCLUSIONS AND IMPLICATIONS: In control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity.

Stem cell transplantation for primary immunodeficiencies.

BMT is curative in almost 75% of children affected by severe primary immunodeficiencies (PIDs). Recently, the chance of cure has increased thanks to the availability of matched unrelated donors (MUDs). Nevertheless, besides the conventional indications to BMT (profound or absent T-cell function, profound or absent natural killer function, known syndromes with T-cell deficiencies), indications to BMT for PIDs affecting the quality of life or having an expectation of life that does not exceed the third-fourth decade remain unclear. Infact, if it is evident that the survival rate in an infant grafted for a PID with a MUD is expected to be more than 80%, alternative treatments such as gene therapy are now available.

CEACAM1/VEGF cross-talk during neuroblastic tumour differentiation.

The role of angiogenesis in tumour progression is a major subject in modern oncology and a correlation between angiogenesis and poor outcome has been demonstrated for human neuroblastomas. However, the role of angiogenesis in the maturation phase of neuroblastic tumours has never been considered. Human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a potent pro-angiogenic factor and mediator of vascular endothelial growth factor (VEGF)-induced angiogenesis, plays a crucial role during the activation phase of angiogenesis and it has been shown to be expressed in the microvessels of the developing central nervous system as well as in newly formed immature blood vessels in many different tumours and under physiological conditions. The present study has investigated the role of CEACAM1/VEGF-mediated angiogenesis across the whole spectrum of neuroblastic tumours, from undifferentiated to fully differentiated mature ganglioneuromas. CEACAM1 is peculiarly expressed in the microvessels of areas of active tumour maturation among differentiating neuroblastic/ganglion cells, whereas it is completely absent in the vessels of poorly differentiated/undifferentiated as well as in entirely mature Schwannian-rich areas. Interestingly, VEGF expression has been found in differentiating neuroblastic/ganglion cells adjacent to CEACAM1-positive microvessels. In keeping with these observations, VEGF expression was found in human neuroblastoma SH-SY5Y cells during differentiation after retinoic acid treatment. Moreover, conditioned medium from SH-SY5Y cells collected at different stages of differentiation induced progressive in vitro up-regulation of CEACAM1 expression in human umbilical vein endothelial cells (HUVECs) that was abrogated by the specific VEGF receptor-2/KDR inhibitor SU5416. Taken together, these data point to a role for CEACAM1/VEGF cross-talk during the maturation phase of neuroblastic tumours. This may mimic physiological events leading to maturation of the vasculature in the developing normal central nervous system. On the other hand, in poorly differentiated/undifferentiated lesions, VEGF-sustained angiogenesis does not reproduce physiological steps, but rather is associated with tumour aggressiveness and may involve other molecular pathways.

[Adenoid cystic carcinoma of the prostate. Clinical case]. / Carcinoma adenoido-cistico della prostata. Caso clinico.

The authors report an extremely rare case of adenoid cystic carcinoma of the prostate. No satisfactory clinical and pathological classification exists for this tumour, creating particular difficulties for therapeutic decisions and prognosis. Descriptions of cases with excellent survival rates are reported in the literature, to the extent that this is sometimes regarded as a low-malignancy tumour, but other reports also exist of massive diffusion of the pathology with fatal consequences. Advances in the knowledge of this tumour have enabled a number of earlier pathogenetic hypotheses to be ruled out, namely its possible derivation from ectopic salivary cells, ectopic periurethral glands or metaplastic urethral mucosa, but the origin of this carcinoma is still not certain. It is also difficult to differentiate this form from the typical adenocarcinoma and to make a prognosis for survival. In the case reported here, the final diagnosis was made on the lymph node biopsy obtained during surgery, given that a preoperative biopsy was not feasible owing to the scarcity of material available. The patient received standard hormonal therapy for prostate carcinoma.

[Fibrous pseudotumors of the tunica vaginalis testis. A clinical case]. / Pseudotumore fibroso della tunica vaginale del testicolo. Caso clinico.

A case of multiple fibrous pseudotumors of the tunica vaginalis is reported. Ultrasonography led to diagnosis 10 years previously and the patient underwent surgical exploration when the lesions were up to 6 cm in diameter.

[Prostatic endoprosthesis in the treatment of prostatic obstruction: preliminary experience with the new Trestle model]. / Le protesi endoprostatiche nel trattamento dell'ostruzione prostatica: esperienza preliminare con il nuovo modello Trestle.

The urethral stent is a relatively new treatment modality for benign prostatic hypertrophy ostruction. Although the ultimate prostatic endoprosthesis has yet to be developed, various stents have been produced and investigated with good results. We review the several currently available stents and we report the preliminary clinical experience with a new device (Trestle).

Correlation between Gleason score of needle biopsy and radical prostatectomy tissue.

Gleason score has been identified as an important variable to predict disease extent and biologic behaviour of prostate cancer. However, the correlation between Gleason score of needle biopsy and surgical specimen is often poor. We studied 72 patients who underwent needle biopsy and radical prostatectomy to correlate Gleason score with PSA, clinical and pathological tumour stage. Only 47.2% of Gleason scores were identical in the biopsy and specimens, 37.5% were undergraded and 15.2% were overgraded. Correlations between clinical and pathological stage were identical in 30.5% of patients, 61.1% of patients were understaged and 8.3% overstaged. In conclusion, accuracy of clinical staging and grading of prostate cancer is low. Although the Gleason score on needle biopsy might be useful to predict the final stage and grade, correlation with surgical specimen is poor.

[Fracture of the penis: description of a case]. / Frattura del pene: descrizione di due casi.

Fracture of the penis is not a frequent event and it consists of a rupture of the tunica albuginea of the corpora cavernosa and sometimes of the urethra; the lesion occurs when the penis is erect because during erection the tunica albuginea is very thin and not flexible and it can be easily damaged by a trauma; most lesions occur during intercourse for impact of the erect penis against the female perineum or the pubic synphisis, but lesions during masturbation, fightings or falling off the bed are also described [1-2-3]. Clinically there are pain, detumescence, hematoma and recurvatum of the penis toward the opposite side of the lesion and hematuria if also the urethra is damaged. Usually diagnosis is quite easy with a good anamnesis, clinical examination and echotomography which can reveal presence of hematoma and hypoechogenic areas along the tunica albuginea or the urethra that appears irregular. Nowadays, fractures of the penis need a surgical approach to obtain good results avoiding consequences such as recurvatum or fibrotic areas [3-4-7-8]. We describe two cases of fracture of the penis occurred in two young men during masturbation and treated surgically with excellent results: twelve and eighteen months respectively after surgery patients are well and can enjoy a normal sexual activity with no problems at all.

Urinary tract endometriosis: report of 2 cases and a review of the literature.

Endometriosis of the urinary tract is a relatively rare condition. Since clinical signs are not specific the diagnosis is difficult and the therapy is not well defined. Two cases and a review of the literature are presented.

Painless treatment of hydrocele: EMLA cream anaesthesia and fibrin adhesive sclerotherapy.

Sclerotherapy for hydroceles was performed in 18 patients. Cutaneous anaesthesia was induced with an anaesthetic cream (lidocaine and prilocaine, EMLA cream) and a fibrin sealant (Tissucol) was injected into the sac after fluid aspiration. Patients experienced no pain during needle insertion and sclerosant procedure; 2 recurrences were observed during follow-up. EMLA cream anaesthesia and fibrin adhesive sclerotherapy represent a useful alternative to surgical treatment of hydroceles.

[Unusual development of urothelioma of the upper urinary tract]. / Insolita evoluzione di urotelioma delle vie urinarie superiori.

A case of extrarenal spreading of transitional cell carcinoma caused by rupture of ureterohydronephrosis by ureteral transitional cell carcinoma is reported. Ultrasonography and CT revealed the presence of a severe right ureterohydronephrosis with large septa and a 2 cm diameter exophytic neoplasia of the middle ureter. Nephroureterectomy was performed with excision of a perirenal mass. Histologic examination revealed the presence of transitional cell carcinoma in the perirenal mass, caused by dissemination after renal rupture. CT and ultrasonography were not able to differentiate hydronephrosis from pericapsular spreading because of the extreme disruption of the renal parenchyma.

[Electrovaporization of the prostate]. / Elettrovaporizzazione della prostata.

Electrovaporization is a new and potentially useful modification of transurethral resection of the prostate which is rapidly becoming a treatment of choice for symptomatic benign prostatic hyperplasia. We report our experience with 22 patients treated using the Circon Acmi Grooved Vaportrode vaporization electrode. Procedures were carried out using the standard technique of electrovaporization with general or regional anaesthesia. Mean operative time was 40 minutes (range 25-65 minutes) and all patients were discharged without catheter after 1 or 2 days. Symptom score, peak uroflow and postvoid residual urine showed statistically significant improvement at 3 months (p < 0.01). There were no significant complications. Transurethral electrovaporization of the prostate seems to be a easy and safe procedure with significantly lower costs and excellent results. However, long-term efficacy and complications need to be evaluated in multicentre clinical trials.