In vivo stimulation of IL-12 secretion by subcutaneous low-dose IL-2 in metastatic cancer patients

Despite the well-demonstrated involvement of both interleukin 2 (IL-2) and interleukin 12 (IL-12) in the activation of host anti-cancer response, the knowledge of IL-2-IL-12 interactions has still to be better investigated. This study was performed to evaluate the effects of subcutaneous (s.c.) low-dose IL-2 on IL-12 secretion in metastatic cancer patients. The study included 19 evaluable metastatic renal cell cancer patients, who received s.c. low-dose IL-2 (6 MIU day(-1) for 6 days per week for 4 weeks) as a first-line immunotherapy of their metastatic disease. Serum levels of IL-12 were measured using an enzyme immunoassay on venous blood samples collected before the immunotherapy and at 1-week intervals. The clinical response consisted of partial response (PR) in four and stable disease (SD) in eight patients, whereas the other seven patients progressed. Mean serum levels of IL-12 observed in the overall patients significantly increased in response to IL-2 injection. Moreover, by evaluating IL-12 variations in relation to the clinical response, a marked significant increase in IL-12 mean values occurred in patients with response or SD, whereas the progressing patients showed a significant decline in IL-12 levels during IL-2 administration. Finally, IL-12 mean pretreatment values observed in patients who progressed were significantly higher than those seen in non-progressing patients. This study shows that low-dose IL-2 immunotherapy of cancer may stimulate the in vivo release of IL-12, and it would suggest that IL-2-induced IL-12 enhancement is associated with a favourable prognosis.     

Studies on brain sterols in normal and pathological conditions

Desmosterol (24-dehydrocholesterol), a normal constituent of developing brain, rapidly disappears during the prenatal and postnatal development, according to the degree of maturation, in all species considered (chicken, mouse, rat, guinea pig, man). During brain maturation, desmosterol concentrations are sensitive to treatments with drugs interfering with sterol synthesis (Triparanol) or with nervous tissue differentiation (thyroxine and propylthiouracil). Desmosterol has been also detected in some experimental and human glial tumors, and the concentra. in the tumor may be specifically increased in the tumoral tissue by the administration of Triparanol.     

Inhibitors of cholesterol synthesis and myelin formation

Inhibitors of cholesterol biosynthesis AY 9944 and 20,25 diazacholesterol were administered by stomach tube to suckling rats in varying doses during the time of rapid myelination (15–22 days of age). Purified myelin was prepared from the brains and spinal cords, and the sterol content analyzed. Up to 50% of the myelin sterol consisted of desmosterol in rats treated with 20,25 diazacholesterol, while 7-dehydrocholesterol comprised at least one third of the myelin sterol in rats administered AY 9944. Myelin from rats treated with both compounds contained desmosterol, 7-dehydrocholesterol, Δ^5,7,24 cholestatriene-3-β-ol and an unknown sterol, the four comprising about 45% of the total sterol. The proportion of phospholipid: galactolipid-total sterol in myelin from the drug-treated rats was not significantly different from the normal, although much less myelin was recovered. Brain and spinal cord slices from 22 to 25-day rats pretreated with inhibitors showed decreased uptake of U-¹⁴C-glucose into all myelin components. The decreased uptake was approximately proportional in all lipids and the protein was also affected. It is proposed that myelin composition is fixed, and that a deficiency of one of the lipid components will limit the assembly of the whole lipid portion of the membrane. Presented at the AOCS Meeting, San Francisco, April 1969.     

Fetal growth restriction: adaptations and consequences

A range of pathophysiological factors can result in a perturbation or restriction of fetal growth, and the cardiovascular, neuroendocrine and metabolic adaptations of the fetus to these stimuli will depend on their nature, timing and intensity. The critical importance of these physiological adaptations for both immediate survival and long-term health outcomes has provided an impetus for experimental studies of the nature and consequences of specific fetal adaptations to a poor intrauterine environment. This review summarizes data from recent studies that have focused on the responses of the fetal cardiovascular, sympathoadrenal, hypothalamo-pituitary-adrenal and renin-angiotensin systems to experimental restriction of placental function in the sheep and discusses the consequences of these adaptations for fetal, neonatal and adult health.     

Photonic slot routing: a cost effective approach to designingall-optical access and metro networks

In the backbone network, the high level of traffic aggregation achieved by numerous users is efficiently served by means of optical circuit switched solutions-the so-called wavelength routing approach. In the access and metro networks, on the contrary, the reduced level of traffic aggregation makes wavelength routing solutions inadequate. The finer and more dynamic bandwidth allocation provided by packet-interleaved optical time-division multiplexing is thus advocated in these network areas. This article presents a survey of an OTDM approach, known as photonic slot routing, or PSR. It is illustrated how this approach may provide a cost-effective solution to deploying all-optical access and metro networks with today's technology     

Bryophytes as indicators of trace metals pollution in the River Brenta (NE Italy)

The performance of aquatic bryophytes for detecting metal pollution was tested along the River Brenta, in NE Italy. Nine sampling sites were selected, three of them along short tributaries with no anthropic influence upstream, the others along the main bed of the river. Two sites were deliberately placed downstream from a previously known pollution focus. The multivariate analysis (classification and ordination) of the matrix of 10 metals and 38 samples revealed: (i) a good discrimination between 'clean' and potentially polluted sites; (ii) two contamination syndromes, one by As and, to a lesser degree, Pb, and the other by Cr, due to agricultural and industrial activities, respectively; and (iii) the previously known pollution focus was clearly detected. The magnitude of contamination was estimated by means of a comparison between local backgrounds and concentrations of metals measured. The distance of aquatic bryophytes from the center of the river was negatively correlated with metal concentrations, which suggests that this factor should be taken into account in the implementation of sampling protocols.     

Predictive value of the shunt-to-infarct size ratio as a surgical risk factor in patients with decompensated post-ischemic interventricular septal rupture

Postischemic septal rupture has always been evaluated, in respect of surgical indication, as regards the time lapse between infarct and rupture, interval between rupture and operation, extension of myocardial damage and general risk factors such as age, sex and associated pathologies. But in fact the surgeon is dealing with a two sided problem, the MI and the rupture, and thus surgical results depend upon both the residual ventricular function after MI and the consequences of volume overload on a damaged muscle. Surgical indication could not be based on a single criterion only. Extension of the MI alone is not fully predictive of operative mortality because, aside the reperfusion injury, the repair further jeopardizes viable myocardium and alters ventricular geometry; although the shunt appears unrelated to mortality it certainly interferes with operative outcome at least because of the time elapsed between rupture and repair. So far an index which could correlate the extension of myocardial damage and the entity of the shunt with each other was not available. Patients with septal rupture follow an emergency protocol and are often insufficiently investigated but every patients has a least one echo-Doppler evaluation or even a ventriculography while one or more ECGs are always available. With the presumption that the Qp/Qs is roughly indicative of the right ventricular volume overload and that ecg signs of myocardial infarct are always reliable, we have reviewed among our 24 patients with septal rupture those where a full ecg tracing and a quantitative Echo or angiographic evaluation of the shunt were available.(ABSTRACT TRUNCATED AT 250 WORDS)