Inhibition of human breast cancer cell growth and enzymatic activity by a fermented nutraceutical: an in vitro and in vivo study .

Human breast cancer cell lines MCF-7 (ER-positive) and Hs578T (ER-negative) were cultured and one lot incubated for 48 h with 5-50 mug/ml of a fermented phytocompound (MK: Manda-Koso, Innoshima, Japan). In vitro, it appeared a dose-dependent decrease of cell viability (5-57%) in MK group in both cell lines (P < 0.001, plateau: 30 microg/ml), decreased beta-galactosidase activity, enhanced apoptosis, and inversely increased Bax/Bcl2 ratio (P < 0.01) with an upregulation of p53 (P < 0.05). In the in vivo model, Balb-c mice were inoculated with tumor cells and the treatment group was fed with 20 mg of MK. Tumor weight in MK-fed group was time-course reduced by 22% to 51% at 2 and 4 weeks, respectively (P < 0.05) with increased survival (P < 0.05). Tumour tissue of MK-fed mice showed a downregulated Bcl-2 with increased Bax/Bcl-2 ratio, reduced PCNA, and activated caspase 3. Although more studies are ongoing to foster the clinical applicability of MK integrated within a rational chemopreventive and therapeutic strategy, a p53-mediated mechanism is likely to play a relevant role, besides its reported antioxidant capacity, NK cell activity enhancement, cancer-cytostatic activity properties.

[Work integration of impaired workers in a type-B social cooperative]. / L'inserimento professionale di lavoratori disabili in una cooperativa sociale di tipo B.

This research aims to evaluate job occupation results of impaired workers in a type-B social cooperative, taking into consideration not only specific occupational risks' analysis and assessment, but also organisational, relational and psycho-social matters essential for their stable job occupation. The impaired workers involved were all those hired by a type-B social cooperative from Jan 1999 until Dec 2007, ie. 16 workers (M 8, F 8), equal to 40% of employees' total number. Every impaired worker has been submitted to preventive health surveillance in order to evaluate the degree of disability and residual job ability in relation to the job tasks suitable for him/her. In order to find available tasks which can be performed by disadvantaged workers, the personnel chart has been analyzed, and 10 of the 16 workers (equal to 62.5%) have been considered fit for the specific task without limitations. The other 6 (37.5%) have been considered capable of the specific task with limitations and/or prescriptions, and for 2 of them (12.5%) a tutorial supervision prescription was also necessary. Among those 6 workers with limitations and/or prescriptions, 4 were psychologically impaired (67%) and 2 were physically impaired (37%). The situation of these 16 impaired workers has been periodically verified and followed up for 8 years. Not only have the fifteen workers continued to perform the task initially considered suitable for their health status, but for some of them (5 workers), an increase in job performance, in both complexity and shift duration, has been observed. Moreover, with the only exception of a psychologically impaired worker who did alternate between good comfort times and occasional disease acute phases, all other workers have shown good and stable gains in psychological and physical health conditions, performing requested tasks not only with efficiency, but also with commitment and motivation. All workers have shown a remarkable improvement in their ability to form relationships, mainly within the work environment amongst colleagues and supervisors, but also in a social and family environment. A special mention is deserved in the case of the only worker hired in our research who left the cooperative after many years of work activity where, after having attended specific professional courses, steadily and successfully joined a company still in the social field but not exclusively dedicated to impaired workers. It may be observed that when one faces the work integration of impaired workers, the usual risk evaluation processes cannot be enough for the reason that these workers, due to their 'disability', find themselves in hypersusceptible conditions in respect to occupational risk factors which are generally acceptable for the other workers. In risk assessment it is therefore necessary to perform an accurate and all-round study in every aspect of the job duty, even around those considered irrelevant which, as a result, may show to be unsuitable to the worker's health status or might alter his/her often precarious psychological-physical condition. In conclusion, in the risk assessment process used prior to the work integration of impaired workers considered by our research, the organisational, relational and psycho-social aspects of work activity have often played a primary role in respect to traditional risk factors usually monitored and evaluated.

Nutraceutical strategy in aging: targeting heat shock protein and inflammatory profile through understanding interleukin-6 polymorphism.

The aging process is paralleled by two- to fourfold increases in plasma/serum levels of inflammatory mediators, such as cytokines and acute-phase proteins. In this study we assessed the inflammatory profile and polymorphism of healthy elderly subjects and the influence of a nutraceutical supplement. Forty elderly, generally healthy subjects were recruited, divided into two matched groups, and given either a fermented papaya preparation 9 g/day by mouth or the same amount of placebo. Treatments were carried out in a cross-over manner with a 3-month supplementation period followed by a 6-week washout period between treatments. Ten healthy young subjects served as controls. Interleukin-6 (IL-6) promoter -174 G/C polymorphism genotype was determined together with blood levels for redox status, proinflammatory cytokines, high sensitivity C-reactive protein, and serum 70 kDa heat shock protein (Hsp70) concentrations. Tumor necrosis factor-alpha and IL-6 were higher in elderly subjects (P < 0.05 versus young controls). The concentration of Hsp70 inversely correlated with markers of inflammation in -174 G/C-negative subjects (r = 0.62, P < 0.05). Nutraceutical intervention normalized the inflammatory parameters (P < 0.05) with a rise of Hsp70 (P < 0.05). This suggests that healthy elderly individuals may have a proinflammatory profile playing as a downregulating factor for inducible Hsp70, particularly if -174 G/C-negative. A nutraceutical intervention seems able to beneficially modulate such a phenomenon.

[Reactive anxiety crisis: a unique case of work injury]. / Crisi d'ansia reattiva: un caso particolare di infortunio sul lavoro.

The present study aims to describe a unique case in view of the disease diagnosed, the conditions of onset and the management by INAIL (Italian National Institute of Insurance for Injuries at Work and Occupational Diseases). A worker, after a verbal, animated dispute with some collegues, had an acute psychiatric agitation attack and went to the nearest emergency room, where he was investigated. No neuropsychiatric alteration was diagnosed, but based on anamnestic data, the physicians diagnosed an anxiety crisis reactive to work environment. A medical certificate for injury at work was produced and sent to the Insurance Board (INAIL). The worker was off work for 105 days diagnosed with a persistent anxious depressive syndrome, secondary to the traumatic event. INAIL reassessed the case later and confirmed only the first 30 days as due to work accident, while the following period was judged as related to affectivity disturbance due to common disease, not to work environment. Our case opens new perspective for the occupational physician in the assessment of ASD as work injury and of PTSD as professional disease, suggesting to give more attention to psychiatric health of workers.

Redox status impairment in liver and kidney of prematurely senescent mice: effectiveness of DTS phytotherapeutic compound.

T-maze test-selected prematurely senescent mice (PSM) were allocated into two groups: (A) those given DTS (150 mg/kg) orally for 30 days and (B) untreated PSM with age-matched fast T-maze performers as control. After sacrifice, the liver and kidney were analyzed for catalase (CAT) activity, glutathione peroxidase (GPx), superoxide dismutase (SOD), malondyaldehyde (MDA), and plasma thiols. Untreated PSM showed decreased plasma thiols and tissue level of CAT, SOD, GPx, with higher MDA (P < 0.01 vs. fast performers), while DTS (Denshichi-Tochiu-Sen) significantly improved glutathione and cysteine (P < 0.05) and tissue concentration of the above parameters (P < 0.05). Such preliminary data suggest that DTS mitigated oxidative damage in PSM, with likely action on the cytoplasm and mitochondrial matrix.

A dietary supplement improves outcome in an experimental influenza model in old mice.

Twenty-month-old Swiss mice were allocated into three groups: (A) control; (B) infected group; and (C) infected but treated with 5 mg of the phytocompound MMT. Mice were infected intranasally with 30 microL of 75 HA viral units. MMT markedly blunted the nasal signs of virus infection and the febrile response. Formazan-positive cells, lung and plasma lipoperoxides, and TNF-alpha in lung tissue increased during viral infection, but improvement was seen in the MMT-treated group (P < 0.05). MMT also normalized SOD, catalase activities, and ascorbic acid and determined a significant decrease of lung but not nasal viral titer, although nasal inflammatory infiltrate dropped significantly. MMT has potential clinical applications with and has an excellent safety profile even in old animals.

Relationship between aging and susceptibility of erythrocytes to oxidative damage: in view of nutraceutical interventions.

Twelve (12) healthy elderly subjects were divided into two groups: (a) those given an antioxidant/NO-modulating fermented papaya preparation (FPP) 9 g/day for 4 weeks, and (b) a placebo group. No protein/lipid distribution in erythrocytes (RBC) membranes was noted among different ages and treatments. Higher RBC concentration of malondialdehyde and nitric oxide synthase were found in the elderly (p < 0.05 versus "young" controls), whereas superoxide dismutase was unaltered. Such abnormalities were prevented by FPP supplementation (p < 0.01). RBC and RBC ghosts showed an enhanced susceptibility to lipid peroxidation by using cumene hydroperoxide (p < 0.01 versus young) but FPP supplementation significantly protected intact RBC (p < 0.05). These preliminary data suggest that nutraceuticals with antioxidant/NO-regulating properties significantly protect from RBC oxidative damage, and are potential weapons for the aging process and chronic and degenerative diseases.

Liver exposure to xenobiotics: the aging factor and potentials for functional foods.

Hepatocytes isolated from 20- and 4-month Wistar rats and cultured with or without alpha-linolenic acid (LNA) were then added with nutraceutical YHK or sylibin before the test with iron or copper. Overall, YHK proved to be more effective than sylibin in Fe/Cu-induced peroxidative damage on normal and LNA-loaded hepatocytes (p < 0.05). YHK exerted a significant protection against DPPH radical-scavenging activity in the "old" group (p versus sylibin) and against lipophilic generators in both age groups (p < 0.05 versus sylibin). Both compounds were ineffective on age-related increase of surface-charge density. These preliminary data suggest that age per se enhances the vulnerability of hepatocytes to xenobiotics, whereas some safe nutraceuticals seem to exert significant protective effects.

Anti-inflammatory and neuroprotective effect of a phytoestrogen compound on rat microglia.

Ovariectomized Wistar rats received orally 15 mg/kg of a phytoestrogen compound (genistein, daidzein, glycitein, black cohosh, angelica sin., licorice, vitex agnus) for 2 weeks to test its ability to modulate inflammatory microglia response. Microglial proliferation was tested by trypan blue and by absorbance. Serial supernatant sampling was performed for 24 h to check TNF-alpha, IL-beta, IL-6, and TGF-beta. LPS caused a time course increase of all cytokines, with IL-beta and TNF-alpha peaking at the 12th hour, whereas IL-6 and TGF-beta peaked at the 24 h observation. Rats fed with the phytoestrogen displayed a significantly lower level of proinflammatory cytokines and a higher level of TGF-beta, as shown also by Western blot analysis. This finding may offer promise in the field of nutraceutical intervention.

Molecular biology and the staging of prostate cancer.

Cancer of the prostate is still controlled or cured by surgery, radiotherapy, and hormone therapy. The present criteria of complication and prediction are criticized more and more for not being sufficiently reliable, due to the high heterogeneity of prostatic cells. The continuing discoveries of intra- and extracellular mechanisms of the molecular informational network, which allow the continuity or discontinuity of the cell's life, are also related to prostate cancer. The role of androgen receptors is now under close scrutiny, in the light of the knowledge of regulatory genes and their molecular expression. In the near future, a complete study of prostate cancer's DNA is certainly envisaged. Looking forward to the extraordinary applications of molecular biology in this field, this article is aimed at establishing a clear link between the conventional ways of interpreting the clinical expression of prostate cancer and the oncoming applications of genomics and proteomics.

Correction of complete urogenital prolapse with infibulation.

OBJECTIVE: The clinical case presented herein is part of a study intended to demonstrate the validity of infibulation, either alone or combined with bladder neck suspension, for correction of genital prolapse associated with urinary disturbances (incontinence, urine retention) in elderly patients whose general condition does not permit the use of prolonged anesthesia or major destructive surgery. METHODS: Urodynamic and echographic tests are carried out before and after the operation to evaluate changes in mictional kinetics and postmictional residues. RESULTS: To date, four other cases have benefited from the treatment described. CONCLUSION: While no definitive conclusions can be drawn from such a limited number of cases, they do however encourage continued experimentation given the frequency of the problem and its social importance.

Case report: uneventful treatment of a giant prostate.

OBJECTIVE: Redefine the meaning of the old term "giant adenoma" and evaluate the diagnosis and safest method of treatment of such cases. METHOD: The world literature was reviewed, particularly concerning diagnostic approaches and therapeutic techniques. RESULTS: The open surgery technique appears to be the safest in the treatment of giant adenoma. CONCLUSIONS: We recommend further study of the factors affecting growth of giant prostatic adenoma.

Quantitative and qualitative AgNORs rates of prostate cancer on needle core biopsies: a multicentric study.

From 1992 to 1993, the Scarpa Foundation Center of Pavia (SFCP) with 12 associated Italian Urological Units selected 40 cases of prostate diseases discovered on needle core biopsies, 5 of which were benign hyperplasias (BPH) in patients without clinical and morphological evidence of cancer and 35 prostate cancers (PRC) classified according to Gleason's histological grades (GLG) of PRC malignancy. Serum prostatic specific antigen (PSA) values were tested before clinical urological examination or biopsy or surgery. In all groups, AgNORs scores/nucleus were obtained by semi- and -automatic computerized image analysis and also by qualitative subjective counts of three observers on light microscopy. Our results pointed out a good correlation between PSA levels, GLG of PRC malignancy and AgNORs scores. The quantitative method showed an average number of AgNORS dots per nucleus between 2 and 3 in well differentiated PRC and higher than 3 in moderately differentiated and undifferentiated PRC, and exhibited more sensitivity over GLG3 than the qualitative investigation. The qualitative subjective count of AgNORs dots/nucleus seemed to be more reliable in differentiating the AgNORs scores of BPH (average of 1.81 dots/nucleus) from very well differentiated PRC with GLG1 + 2(average of 2.25 dots/nucleus) than quantitative analysis, which showed the same average value in both groups (2.11 dots/nucleus). For these reasons, also on needle biopsies of benign and malignant prostate diseases the subjective AgNORs count may aid the histological diagnostic judgement of malignancy, by avoiding misleading diagnoses of microscopic pictures of BPH cancer look likes and a predictive histologic malignant factor, in identifying PRC with low or high progression.

The Aristotelian kidney.

Aristotle incorrectly observed the absence of the kidney in fish and birds and deduced that it was not essential for the existence of a living organism. This underlies his observations on structure and function of the kidney. From examination of rhesus monkeys he generalized that the right kidney is higher than the left. Aristotle did not consider that the renal pelvis is divided by a filter membrane into 2 chambers, and wrote that no blood reaches the renal pelvis. The theory of the 'filter kidney' cannot thus be attributed to Aristotle. The function of the kidney was described as being to separate the surplus liquid from the blood inside the renal meat (not in the renal pelvis) and to transform this liquid into what Aristotle called residuum, i.e. the urine. Aristotle also considered that the kidneys acted to anchor the blood vessels to the body. He only briefly considered renal pathology.

The Medical School at Ravenna.

The existence of the Ravenna School of Medicine can be deduced from a codex in the Ambrosian Library of Milan, which contains Latin translations of 3 Hippocratic works and commentaries on 4 works by Galen. Although it was written in the 9th century, the codex appears to be a copy of an earlier work, probably 7th century. The Ambrosian commentaries follow other commentators on Aristotle, rather than the original Aristotelian works, and contain a number of misinterpretations. Nevertheless, the commentaries make it clear that the earliest literature in Salerno had its roots in the studies of classical medicine at the Ravenna School of Medicine, where the teaching was essentially Galenic in structure.

[The anterior approach after Chute, Baron and Olsson in renal pathology: the authors' own experience]. / Abordaje anterior según Chute, Baron y Olsson en patología renal: experiencia personal.

The authors describe their experience of 79 operations using the Chevron anterior transperitoneal approach in the treatment of 71 renal tumors and 8 cases of renal trauma. This approach respects the physiology of the respiratory system, has a low morbidity and mortality, in the post-operative period the need for anesthesia is moderate and hospitalization is shorter. The authors underscore the following advantages of the Chute-Baron-Olsson technique: it is easy to perform and can be easily extended, dehiscence and laparoceles are uncommon (only 2 of 79 patients). Furthermore, the Chevron partial or total approach in tumors and renal trauma permits exposure of an excellent inframesocolic and supramesocolic field and perfect control of the important elements of the renal vasculature.

Nucleolar organizer regions: preliminary results of the clinical use of a new marker for prostatic carcinoma (40 cases).

It is a widely diffused opinion that moving backwards in time the moment of the diagnosis of cancer of prostate, so that the tumor is detected earlier than normal, means that the treatment would be more effective than the one adopted in the usual times of diagnosis. For this reason the earlier diagnosis of prostate cancer has become more and more a compulsory target of the modern urologist, at a time of booming of the third age, of increased lifetime expectancy, of significant elevation of prostate cancer rate and of the persistent uncertainty of the efficacy of available treatments. Theoretically the mortality rate of prostate cancer can be reduced by the prevention programs and by the improvements of treatment methods, but the 'earlier' diagnosis is certainly an easier and less expensive strategy to achieve the same objective. The authors have evaluated the argyrophilic-nucleolar organizer region (Ag-NOR) proteins on 40 cases of adenocarcinoma of prostate collected through a multicentric program in France and in Italy. The Ag-NOR have been stained with silver technique set up by Ploton and Derenzini while the quantitative index has been evaluated by a semiautomatic system partially commercially available, partially modified by the authors. The conclusions: (a) the Ag-NOR index is a simple and reproducible method; (b) the Ag-NOR staging system corresponds to Gleason's grading; (c) the Ag-NOR elevation is a reliable marker of increased cell proliferation and is detectable much earlier than the morphologic changes of Gleason's classification.

A new marker for early detection and indicator of progression of cancer of the bladder. Preliminary results with Ag-NOR index in 38 cases of superficial bladder cancer.

The multiform biology of superficial bladder tumors, both morphologically and evolutively, and the lack of reliable predictors of progression have led the authors to study the Ag-NOR proteins as a new marker of these tumors. It is well known that particularly the low-grade superficial tumors frequently relapse on the same histologic and proliferative module. Their potential of progression is probably present at the time of the first manifestation of the disease or it can show itself along the relapsing evolution with classic modifications translating the cellular dedifferentiation. The NOR index, set up by the authors, has several advantages: firstly, it corresponds to a functional value of normal and neoplastic cells; secondly, it can be used also with paraffin blocks. Another advantage is the semiautomatic lecture, reproducible also in the urinary cytology, mainly of low-grade tumors, reducing the number of false-negatives. The conclusion of the study of 38 cases of superficial bladder cancer has induced the authors to believe that an increased NOR index is a reliable 'marker' of their progression. Therefore, the authors suggest the use of the NOR activity for the surveillance of the urothelial disease and for a more logical therapeutic strategy.

[Ectopic adrenal cortex tissue in the spermatic cord: clinico-surgical implications]. / Tejido córticosuprarrenal ectópico en el cordón espermático: implicaciones clínico-quirúrgicas.

Ectopic corticoadrenal tissue is not a very uncommon finding during orchiopexy in children. The causes can be found in the period of organ development and gonadal migration (spermatic cord). From 1986 to 1990, we have performed 88 orchiopexy procedures in the Urology Service of "San Antonio Abad de Gallarate" Hospital. Only one case (1.13%) of juxta-funicular corticoadrenal ectopia has been observed. The aim of the present study is to determine the correct surgical approach to this incidental finding during surgery of the inguinal canal in pediatric patients.