Protective effects induced by the food supplement Fluxonorm® in the lower urinary tract.

OBJECTIVE: Fluxonorm® is a dietary supplement that includes water-soluble extracts of Solidago virga-aurea, Phyllantus niruri, Epilobium angustifolium, Peumus boldus and Ononis spinosa. The aim of the present study was to evaluate the tolerability and efficacy of Fluxonorm® in improving lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH) in combination with standard of care. PATIENTS AND METHODS: Lower urinary tract symptoms can be improved by a marked anti-inflammatory action on the lower urinary tract (irritative symptoms) and/or by an anti-proliferative action (obstructive symptoms) on the prostate. Thirty patients were enrolled to evaluate the effect of Fluxonorm® on improving lower urinary tract symptoms. All patients complained of lower urinary tract symptoms (LUTS), such as hesitancy, poor flow, intermittent flow, incomplete voiding (obstructive symptoms), as well as increased frequency, nocturia and urgency (storage symptoms). All patients were treated with one tablet of Fluxonorm® (1200 mg) daily for 30 days to corroborate the results of our observation in which the food supplement (800 µg/mL) was also studied on the human prostate cancer PC3 cell line (antiproliferative activity) and on prostaglandin (PG)E2 production (anti-inflammatory activity). In addition, the effect of this compound on cyclooxygenase-2 (COX-2) gene expression was investigated. Finally, a bioinformatic analysis was conducted with the aim of unravelling the mechanism of action underlying the observed bio-pharmacological effects. RESULTS: As hypothesized in our preclinical research, adding Fluxonorm® to the therapy of enrolled patients improved all studied clinical parameters, including maximum flow (Qmax), after one month of treatment. In the preclinical evaluation, this formulation reduced PC3 cell viability and PGE2 production. The effects were also paralleled by reduced COX-2 gene expression and Fluxonorm®'s partly related content of catechin. While docking studies pointed out to the putative inhibition of matrix metalloproteinse-2 by gallic acid, as a further mechanism underlying the observed anti-proliferative effects, in PC3 cells exposed to Fluxonorm®. CONCLUSIONS: Fluxonorm® improved the efficacy of standard therapy, in terms of antioxidant/anti-inflammatory effects, for the management of lower urinary tract symptoms (LUTS). This could be related, albeit partially, to the blunting effect of this compound on PGE2 production.

Crocus sativus, Serenoa repens and Pinus massoniana extracts modulate inflammatory response in isolated rat prostate challenged with LPS.

Prostatitis is a common prostate disease that could be promoted by bacterial or non-bacterial infectious agents. In addition, inflammatory pathways involved in prostatitis have been increasingly studied, and herbal extracts endowed with anti-inflammatory effects are under investigation, individually or in combination, for their efficacy in alleviating the burden of inflammation, with possible improvements in symptoms. Serenoa repens (Serenoa), in combination with Crocus sativus (Crocus) and Pinus massoniana (Pinus), has previously shown to improve sexual function and limit urinary symptoms in patients suffering from concomitant erectile dysfunction and lower urinary tract symptoms. In this context, the aim of the present study is to evaluate the efficacy of Serenoa, Crocus and Pinus extracts, either alone or in combination, on immortalized prostate cells (PC3) and in an experimental model of bacterial prostatitis constituted by ex vivo prostate specimens challenged with lipopolysaccharide (LPS). We found that the tested extracts were able to reduce ROS production by PC3 cells and NFkB and PGE2 activity in prostate specimens challenged with LPS. In addition, the pharmacological association of the extracts displayed synergistic effects indicating a rational use of the mixture of the tested extracts as a novel anti-oxidant and anti-inflammatory formulation in bacterial prostatitis. Finally, we performed analytical and in vitro evaluation to better characterize the phytochemical profile and the mechanism of action of selected secondary metabolites.

Central apelin-13 administration modulates hypothalamic control of feeding.

The 77 amino prepropeptide apelin has been isolated from bovine stomach tissue and several smaller fragments, including apelin-13, showed high affinity for the orphan APJ receptor. The distribution of apelinergic fibers and receptors in the hypothalamus may suggest a role of apelin-13 on energy balance regulation, albeit the studies reporting the acute effects of apelin on feeding control are inconsistent. Considering the possible involvement of apelinergic system on hypothalamic appetite controlling network, in the present study we evaluated in the rat the effects of intrahypothalamic apelin-13 injection on food intake and the involvement of orexigenic and anorexigenic hypothalamic peptides and neurotransmitters. Eighteen rats (6 for each group of treatment) were injected into the ARC with either vehicle or apelin-13 (1-2 µg/rat). Food intake and hypothalamic peptide and neurotransmitter levels were evaluated 2 and 24 h after injection. Compared to vehicle, apelin-13 administration increased food intake both 2 and 24 h following treatment. This effect could be related to inhibited cocaine- and amphetamine-regulated transcript (CART) gene expression and serotonin (5-hydroxytryptamine, 5-HT) synthesis and release, and increased orexin A gene expression in the hypothalamus.

A natural formula containing lactoferrin, Equisetum arvensis, soy isoflavones and vitamin D3 modulates bone remodeling and inflammatory markers in young and aged rats.

A pivotal role in osteoporosis development is played by radical oxygen species (ROS), the increased production of which is related to inhibited osteoblastic activity and bone formation. A new field of research could involve medicinal plants with antioxidant and protective effects in osteoporosis. Furthermore, considering the multifactorial metabolic aspects of osteoporosis, the pharmacological association of multiple medicinal plants could improve patient response. The aim of the present study is to evaluate in vitro and in vivo the protective effects of a natural formula containing lactoferrin 12%, Equisetum arvensis ES 54%, soy isoflavones 34% and vitamin D3 0.002%, in PBMC and C2C12 cells and in the bone matrix of young (3-month-old) and aged (12-month-old) female Sprague-Dawley rats, following chronic (21 days) administration. In this context, we assayed the activities of several inflammation and bone homeostasis mediators, such as IL-6, TNFα, PGE2, osteoprotegerin, RANK, RANKL and NFkB. In vitro studies showed that natural formula (5-1000µg/ml) was able to significantly inhibit ROS and PGE2 production. In the same concentration range, the natural formula inhibited both TNFα and IL-6 gene expression. In the in vivo studies, we administered to young and aged female rats the natural formula at 5mg/rat for 21 days, finding a significant reduction in inflammatory PGE2 and NFkB activity. Nevertheless, we observed a significant increase in osteoprotegerin/RANKL ratio only in aged rats, compared to the respective control group. In conclusion, our findings corroborate the rational use of natural formula in the prevention and management of osteoporotic disease.

Human colostrum oligosaccharides modulate major immunologic pathways of immature human intestine.

The immature neonatal intestinal immune system hyperreacts to newly colonizing unfamiliar bacteria. The hypothesis that human milk oligosaccharides from colostrum (cHMOSs) can directly modulate the signaling pathways of the immature mucosa was tested. Modulation of cytokine immune signaling by HMOSs was measured ex vivo in intact immature (fetal) human intestinal mucosa. From the genes whose transcription was modulated by cHMOSs, Ingenuity Pathway Analysis identified networks controlling immune cell communication, intestinal mucosal immune system differentiation, and homeostasis. cHMOSs attenuate pathogen-associated molecular pattern-stimulated acute phase inflammatory cytokine protein levels (interleukin-8 (IL-8), IL-6, monocyte chemoattractant protein-1/2 and IL-1ß), while elevating cytokines involved in tissue repair and homeostasis. In all, 3'-, 4-, and 6'-galactosyllactoses of cHMOSs account for specific immunomodulation of polyinosinic:polycytodylic acid-induced IL-8 levels. cHMOSs attenuate mucosal responses to surface inflammatory stimuli during early development, while enhancing signals that support maturation of the intestinal mucosal immune system.

Silymarin and S-adenosyl-L-methionine (SAMe): two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view.

The alcoholic liver disease (ALD) is the leading cause of death from liver failure in Italy and worldwide. Ethanol abstention, a healthy diet, and a significant improvement of life-style are the mainstay of treatment for this disease. Currently, we do not have effective therapeutic options are at our disposal to restore and maintain an improved clinical status. Silymarin is a complementary and alternative medicine often prescribed and self-prescribed; it has anti-oxidant, anti-inflammatory, anti-fibrotic, and metabolic properties. It improves the laboratoristic values and the ultrasonographic grading of liver disease in case of steatosis/steatohepatitis. S-adenosyl-L-methionine (SAMe) is the principal biological methyl donor, and it is also a precursor of glutathione (GSH), essential for the anti-oxidant pathways. SAMe is particularly important for opposing the toxicity of free radicals generated by various toxins, including alcohol. An association between Silymarin and SAMe (labelled as a dietary supplement) has been recently brought to market, and seems to be promising. It could be beneficial in such cases of alcoholic hepathopathies. New therapeutic options are needed by hepatologists to successfully overcome a constantly growing disease.

Effects of visfatin/PBEF/NAMPT on feeding behaviour and hypothalamic neuromodulators in the rat.

Visfatin, also known as pre-B cell colony enhancing factor (PBEF) or nicotinamide phosphoribosyltransferase (NAMPT), is a cytokine that is produced by adipose tissue, skeletal muscle, liver and immune cells. We studied the effects of visfatin/PBEF/NAMPT on feeding behavior, hypothalamic steady state concentrations of aminergic neurotransmitters and hypothalamic mRNA levels of anorexigenic peptides, such as cocaine- and amphetamine-regulated transcript (CART) peptide, corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and orexigenic peptides, such as agouti-related peptide (AgRP) and neuropeptide Y (NPY). Forty-eight rats were injected in the arcuate nucleus (ARC) of the hypothalamus with either saline or visfatin/PBEF/NAMPT (3 microg). Food intake was recorded 1, 2 and 24 h following injection, and either dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT) or peptide gene expression were evaluated 2 and 24 h after visfatin/PBEF/NAMPT administration. Compared to vehicle, visfatin/PBEF/NAMPT significantly increased food intake, as evaluated 1, 2 and 24 h post-injection. Visfatin/PBEF/NAMPT treatment led to a significant decrease of DA steady state concentration, CART and CRH mRNA levels. Consequently, visfatin/PBEF/NAMPT could play an orexigenic role in the ARC, and the effect could be mediated by modulation of DA, CART and CRH activity in the hypothalamus.

Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia.

Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes. Only patients treated with aminoglycosides, fluoroquinolones, and beta-lactams were evaluated. MICs were determined using standard National Committee for Clinical Laboratory Standards procedures. Antibiotics were assayed using validated high-performance liquid chromatographic methods. Pharmacokinetic/pharmacodynamic markers adopted were: aminoglycoside peak/MIC ratio >or=8 mg L(-1); fluoroquinolone peak/MIC >or=10 mg L(-1); beta-lactam peak/MIC >or=4 mg L(-1) and time that plasma levels remain above the MIC >or=70%. 638 patients with NP were included in the study. In 205 patients, both drug concentration and isolate MIC were available, while in other patients, used as controls, one or both parameters were lacking. For clinical outcome, the Acute Physiology and Chronic Health Evaluation II score (p<0.0001), the presence of combination therapy (p = 0.0014) and whether both MIC and drug concentration(s) were measured (p = 0.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the beta-lactams (

A pilot study on prevention of catheter-related urinary tract infections with fluoroquinolones.

The objective of this multicenter, randomized, controlled, parallel group trial was to evaluate the efficacy of levofloxacin 250 mg oral, once daily (LVFX), placebo one tablet oral once daily (Placebo [P] group) and ciprofloxacin (CPFX) 500 mg oral, twice daily (single blind), prophylaxis in preventing bacteriuria (> or = 10(3) CFU/ml) in post-surgical catheterized patients. In the modified intention-to-treat (M-ITT) population of the 82 enrolled patients, negative bacteriuria was observed in 92% of LVFX group, in 80% of P group and in 100% of CPFX group while in the per-protocol (PP) population figures were: 100%, 86.4% and 100% respectively. Only one symptomatic urinary tract infection and one surgical wound infection were observed in the P group. Both drugs were well tolerated, showing a safety profile comparable to placebo. The high frequency of negative bacteriuria in the placebo group sounds encouraging as it underlines that the adoption of closed urinary drainage system catheters in hospital setting may reduce the frequency of hospital-acquired infections.

[Management of serious bacterial infections: general considerations]. / La gestione delle infezioni batteriche gravi: considerazione generali.

Many efforts have been made in the recent years to improve the prognosis of severe bacterial infections by reducing the risk of treating the patients inadequately. The reasons responsible for inadequate treatment have been intensively studied and antibiotic resistance has been identified as one of the main risks. Currently different strategies are considered to optimize antibiotic therapy, such as the adoption of local guidelines, de-escalation, rotation and association therapies. Each appears to prove efficacy in the containment of resistance and improvement of outcome; however, further studies, continuous monitoring of the epidemiology of severe infections and antibiotic resistance, and finally, availability of new drugs are needed. It is the authors' opinion that, despite the importance of guidelines for the optimal treatment and most appropriate management of severe infections, closer collaboration should be established between the medical staff in the wards and IDS, who can bridge the gap between the guidelines and the individual needs of the patient, thereby improving the decision-making process. The IDS, as consultant in different medical and surgical wards and as a member of the Infectious Diseases Control local Committees, can interact at different levels and can improve the management of severe bacterial infections.