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.

Hyperhomocysteinaemia and poor vitamin B status in chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Patients with chronic obstructive pulmonary disease (COPD) are at increased atherothrombotic risk. Preliminary findings have suggested that COPD patients may have increased plasma total homocysteine (tHcy), a cardiovascular risk factor often caused by a poor B vitamin status, but plasma levels of such vitamins were not measured. The aim of this study was to investigate hyperhomocysteinaemia in COPD and to determine whether it may be secondary to poor plasma concentrations of B vitamins. METHODS AND RESULTS: We performed a case-control, cross-sectional study of 42 patients with COPD and 29 control subjects. Folate, vitamin B12, vitamin B6, tHcy, renal function, C-reactive protein, blood gases and lipids were measured in patients and controls. COPD patients had higher plasma tHcy (median: 13.9mumol/l, interquantile range [IQR]: 12.1-18.5 versus 11.5, IQR: 10.1-14, p=0.002) and lower circulating folate (median: 2.5ng/ml, IQR: 1.2-3.3 versus 2.8, IQR: 2.1-4 of controls, p=0.03) than controls had. Compared to the control group, COPD was associated with higher tHcy concentrations also after adjusting for smoking, heart failure, renal function and C-reactive protein with logistic regression analysis (OR 1.36, 95% CI 1.06-1.72, p=0.01). In the COPD group, low levels of folate (beta=-0.27, p=0.02) and vitamin B12 (beta=-0.24, p=0.04), and hypertriglyceridaemia (beta=0.580, p<0.0001) were independent predictors of the presence of high tHcy concentrations in a multiple linear regression model (adjusted R(2)=0.522). CONCLUSION: COPD patients have a poor B vitamin status and, as a consequence, increased tHcy. These abnormalities may contribute to the COPD-related atherothrombotic risk.

Therapeutic management of hematological malignancies in elderly patients. Biological and clinical considerations. Part IV: Multiple myeloma and Waldenström's macroglobulinemia.

Following recent data on multiple myeloma (MM) in the literature, a possible model of myeloma development, involving different cytokine signals, is advanced, and the prognostic significance of two principle staging systems is evaluated. Different therapeutic approaches to MM have been employed, consisting of either treatment with only melphalan and prednisone, or combination chemotherapy, especially in patients with a poor prognosis. However, for the initial therapy, melphalan plus prednisone in doses that compensate for individual variation in drug absorption still appears the best choice in the vast majority of MM patients. The main clinical and hematological features which distinguish Waldenström's macroglobulinemia from MM are described, as are the criteria which should be used in choosing the most appropriate treatment based, when necessary, on chemotherapy with standard alkylating agents, as well as on the new nucleoside analogues, and repeated courses of plasmapheresis.

Association between chronic lymphocytic leukaemia and secondary tumours: unusual occurrence of a neuroendocrine (Merkell cell) carcinoma.

The authors describe a case of cutaneous neuroendocrine (Merkell cell) carcinoma in a patient previously treated for Chronic Lymphocytic Leukaemia (CLL). The authors discuss some of the mechanisms concerning the increased frequency of a second tumour in patients with CLL and focus attention on the high incidence in CLL of secondary tumours, especially skin tumours, of which Merkell cell carcinoma is a rare example. The authors consider the possible therapeutic approaches, reported in the literature, for the treatment of this particular skin carcinoma, which on account of its aggressiveness and the preexistence of a leukaemic process requires a particularly careful therapeutic approach.

Circadian rhythm of cardiac output, peripheral vascular resistance, and related variables by a beat-to-beat monitoring.

This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomanometric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus.

[The disappearance of the circadian rhythm of the heart rate in heart transplantation in the presence of acute rejection]. / Scomparsa del ritmo circadiano della frequenza cardiaca nel trapianto di cuore in presenza di rigetto acuto.

The present study is aimed to investigate the circadian rhythm (CR) of heart rate (HR) in acute rejecting and non-rejecting heart transplanted patients (HTP). The purpose is to provide evidence that an impairment in the HR CR may have a role in predicting episodes of acute rejection in HTP. The study was carried out on 32 Holter monitorings of 13 patients: 9 Holter monitorings were carried out during an episode of acute rejection documented by endomyocardial biopsy. Time data series were analyzed by Cosinor method in order to validate the occurrence of HR CR. The Cosinor analysis found a highly statistically significant HR CR in non-rejecting HTP. The occurrence of the HR CR was not statistically validated in acute rejecting HTP. These findings suggest that the lack of a periodic variability in the 24-hour HR pattern may be useful to diagnose acute heart rejection.

Bartter's syndrome associated with indirect hyperbilirubinemia: a possible clinical variety.

This report deals with three cases of Bartter's syndrome whose symptomatology was associated with indirect hyperbilirubinemia. The bilirubin disorder was suggestive of Gilbert's syndrome, with no pathological findings being detected as far as the liver function was concerned. Furthermore, the unconjugated fraction of bilirubin increased after fasting. The therapy with indomethacin exerted beneficial effects on both electrolytes and bilirubin disorders, and the patients recovered a good healthy state. These findings suggest the possibility that Bartter's syndrome may coexist in a variety associated with indirect hyperbilirubinemia.