Immunomodulation mediated by a herbal syrup containing a standardized Echinacea root extract: a pilot study in healthy human subjects on cytokine gene expression.

In this study, the immunomodulatory effect of a triply standardized Echinacea angustifolia root extract (Polinacea(®)) was evaluated in 10 healthy subjects. Ten ml of syrup containing one hundred mg of extract (corresponding to 4.7 mg of Echinacoside and 8.0mg of a high molecular weight-20,000 Da- polysaccharide) were administered as a herbal syrup once a day for one month. The immunomodulatory effect was evaluated before and after herbal syrup administration evaluating the expression levels of the cytokines IL-2, IL-8, IL-6 and TNF-α. Cytokine expression was studied in lympho-monocytes and in plasma samples measuring the mRNA and protein levels, respectively. The results were analysed by ANOVA and non-parametric Friedman rank sum tests; when possible it was adopted a pair-wise comparisons at different post-treatment times, using the paired t-tests with Holm correction. The correlation between the variations of cytokine plasma levels and the respective mRNA was carried out using a linear regression model. In lympho-monocytes our data indicate the up-regulation of the mRNA levels of IL-2 and IL-8 and the down regulation of the mRNA levels of the pro-inflammatory cytokines TNF-α and IL6. The differential regulation was maximal after 14 days of treatment. IL-2 up-regulation and IL-6 down-regulation were also confirmed at the protein level in plasma. Finally, the up-regulation of the mRNA of IL-2/IL-8 and the down-regulation of IL-6 positively correlated with the protein levels detected in the plasma. In conclusion, this pilot study suggests a relevant role for the standardized Echinacea angustifolia root extract in the control of cytokine expression. This first demonstration of the immuno-modulating activity of Echinacea angustifolia root extract in the healthy subject, supports at least in part the common use of such products as health promoting supplement.

Pharmacokinetics and immunomodulatory effects of phytotherapeutic lozenges (bonbons) with Echinacea purpurea extract.

The relative bioavailability of the major alkamides, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, from Echinacea purpurea phytotherapeutic lozenges at three different dose levels (0.07, 0.21 and 0.9 mg) was evaluated in a pharmacokinetic study in humans and the possible effects on the immunological system were measured. Alkamides were found to be rapidly absorbed and measurable in plasma 10 min after administration of 0.21 and 0.9 mg lozenges and remained detectable for 3h for the 0.21 mg lozenges and for more then 3h for the 0.9 mg lozenges; 0.07 mg lozenges were measurable 20 min after administration and remained detectable for only 2h after the administration. A significant dose-independent down-regulation of the pro-inflammatory cytokines IL-12p70, IL-8, IL-6, IL-10 and TNF was observed 24h after oral administration. The results of non-compartmental pharmacokinetic analysis revealed that a C(max) of (0.65+/-0.41 ng/ml) was reached at 32 min with the 0.07 mg lozenges, (1.00+/-0.21ng/ml) at 25 min with the 0.21 mg lozenges and (8.88+/-5.89 ng/ml) at 19 with the 0.9mg lozenges. As evidenced by the dose-exposure relationship, no significant departure from dose proportionality was observed, indicating linearity in pharmacokinetics. To get a further insight in pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides a compartmental population pharmacokinetic model was developed applying mixed effect modelling procedure. The results demonstrate that within the dose range studied pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides are linear and that absorption is very rapid (t(1/2)=6 min) with apparently no lag time, thus indicating the possibility that a fraction of the drug is absorbed through the oral mucosa.

[Bladder hernia: a clinical case]. / A proposito di ernia vescicale: caso clinico.

The Authors report a case of inguinal bladder hernia and briefly refer about the different kinds of this rare pathology which is often associated to the commonest inguinal hernia. They, moreover, point out the surgical treatment which has to aim to the repositioning of the bladder and to solve the cervicovesical obstruction.

[A new biological irradiator for the laboratory]. / Un nuovo irradiatore biologico da laboratorio.

The use of high doses (15-20 Gy) of X- or gamma-rays to irradiate blood-derived materials is a common practice by now. It is usual especially when materials must be transfused into non-immunocompetent patients. This is done to avoid the so-called GVH disease. Nowadays, for this purpose, units containing radioactive gamma-emitting sources with high activity and long half-life (usually 137Cs) are on the market. The characteristics of these "irradiators" allow their implementation in any laboratory with no need of structural shieldings. In spite of it, serious accidents (e.g., fire, fallings, etc.) which could imply hazards for the operating staff and even the general population, cannot be excluded. At the same time, the problem of long-term disposal of exhausted sources cannot be neglected. For these reasons, a new type of self-shielded irradiator was designed. It is equipped with an X-ray tube, operating at nearly 200-kV voltage, with 12-mA anodic current. The system is water- and oil-cooled and can work for a long time without thermal overloads. In this paper, the environmental and dosimetric measurements for beam characterization are reported. The system can produce beams with satisfactory characteristics for this specific problem. Moreover, its use may greatly reduce administrative radioprotection problems.

Quantitative analysis of the Hopf bifurcation in the Goodwin n-dimensional metabolic control system.

We study, from a quantitative point of view, the Hopf bifurcation in an ODE model of feedback control type introduced by Goodwin (1963) to describe the dynamics of end-product inhibition of gene activity. We formally prove that the exchange of linear stability of the positive equilibrium in the n-dimensional Goodwin system with equal reaction constants coexists with a Hopf bifurcation of nontrivial periodic solutions emanating from this equilibrium, without any further restriction on the dimension n greater than or equal to 3 or on the Hill coefficient. The direction of the bifurcation and the stability and the period of the bifurcating orbits are estimated by means of the algorithm proposed by Hassard et al. (1981).

[Limitations and complications of the use of the basket]. / Limiti e complicanze nell'uso del basket.

During the last 15 years the Dormia stone dislodger has been used in 352 cases (80%) out of 435 of ureteral stones: 318 were at ileo pelvic, 34 at lumbar level. 303 ileo pelvic and 21 lumbar stones have been successfully removed (92%). Considering that the probability of stone removal is directly proportional to the ureteral expansibility and indirectly proportional to the volume of the stone, the Basket technique isn't indicated: When the stone is more than 1 cm.; When the ureter is widely stiff (as in Ormond d. or post-radiotherapy stiffness); When stenosis is present. The impossibility of bypassing the stone, the insufficient expansion of the Basket, the stone irremovability and the difficult extraction through the meatus, my limit the successes of this technique while iperating. The immediate complications have been: 4 sectoral rips of the mucosa surrounding the ureteral end, cured by catheterisation without aftereffects (1.2%); 1 sliding of the ureter through the trigone up to urethral meatus (in a woman), which has been repaired, without aftereffects, by direct catheterisation of the ureter, out of the urethra, after removal of the Basket and stone from the ureteral extremity. (0.3%) Strictures occurred in 5 cases (1.5%) and vescicoureteral reflux in 6 (1.8%). These results of the sole Basket technique (performed according to the well-known directions) seem to be much better than those (which have been illustrated) obtained with the endoscopic lithotripsy.