An anti-IL-2 antibody increases serum half-life and improves anti-tumor efficacy of human recombinant interleukin-2

We examined the ability of anti-human recombinant interleukin-2 (hu rIL-2) monoclonal antibody DMS-1.10 to increase serum half-life of hu rIL-2, and the effect of this complex on inhibition of tumor progression in a B16-F10 murine melanoma model. In C57B1/6 mice, intravenous (i.v.) injection of DMS-1.10 premixed with 1 x 10(4) units (U) of hu rIL-2 at a 1:1 molar ratio extended serum half-life greater than 10-fold (222 min) when compared to the same dose of hu rIL-2 alone (20 min). In a murine tumor model, multiple intraperitoneal (i.p.) injections of non-neutralizing DMS-1.10 premixed with hu rIL-2 at a 5:1 molar ratio reduced the growth rate of subcutaneous (s.c.) B16-F10 tumor in C57B1/6 mice by 64% when compared to PBS and irrelevant antibody treated controls. Although similar treatment with hu rIL-2 alone reduced tumor growth rate by 46%, it was significantly less effective than the premixed treatment. Results from a flow cytometry assay confirm B16-F10 does not have IL-2 receptors, precluding direct inhibition of tumor growth by hu rIL-2 treatments. We propose that therapeutic efficacy of hu rIL-2 is improved by prolonging the in vivo half-life with an anti-IL-2 antibody, thus augmenting hu rIL-2 bioactivity and enhancing the hosts immune response against tumor.     

THE EFFECT OF CATHODIC PROTECTION POTENTIAL ON CORROSION FATIGUE CRACK GROWTH RATE OF AN OFFSHORE STRUCTURAL STEEL

Abstract— Duplicate tests have been performed to determine the effect of cathodic protection potential on corrosion fatigue crack growth rate of a modern offshore structural steel, produced by thermo-mechanically controlled processes. The experiments were carried out using compact tension specimens exposed to artificial seawater at 10°C and subjected to constant amplitude loading at 0.35 Hz. Reproducible results showed that the merits of cathodic protection potentials are strongly dependent on stress intensity ratio R and stress intensity range Δ K . It appears that a specific value of cathodic potential may not give comprehensive protection against corrosion fatigue within the spectrum of variable amplitude loading experienced in service. Fractography showed the initiation of secondary cracks on the fracture surface to be associated with the dissolution of calcium sulphide inclusions, regardless of imposed cathodic potential.     

Bone replacement in head and neck surgery: a biocompatible alternative

BACKGROUND: Defects in the skull have presented difficult reconstructive problems. Recently glass-ionomer cement and preformed. implants have been used to repair bony defects in the skull base and in cranio-facial surgery. Three patients are reported to illustrate possible applications for this new material. METHODS: Ionocap cement and Ionoroc-skull standardized implants have been used. The cement is available as a two component blister pack. When mixed and blended a gel is produced which can be worked for approximately 5 min before hardening. It can then be contoured and drilled to the required shape. The resultant material is biocompatible and biostable, is non-toxic and permanently bonds to bone with no increase in temperature or shrinkage. RESULTS: The material has been used to fill the temporal defect left by transplantation of the temporalis muscle for oral reconstruction, the anterior and lateral walls of the maxilla and following craniofacial resection, the posterior wall of the frontal sinus and anterior skull base. CONCLUSIONS: Three patients with different reconstructive problems have been presented to illustrate the use of an alloplastic material that has a tensile strength similar to bone and firmly adheres to it. The material was found to be safe and easy to use. All three patients have now been followed for 12 months with no adverse affects.     

Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites

OBJECTIVE: Large volume paracentesis is an effective treatment for refractory ascites, but the need for routine infusion of albumin or other volume expanders remains controversial. The aim of this study was to assess the short term effects of a single 5-L paracentesis without albumin replacement on total central blood volume, systemic and renal hemodynamics, sodium homeostasis, and neurohumoral factors. PATIENTS AND METHODS: Twelve patients with biopsy-proven cirrhosis and tense, diuretic-resistant ascites were studied before and 48 h after a single 5-L paracentesis without albumin infusion. Systemic hemodynamics and total central blood volume were assessed using radionuclide angiography. Glomerular filtration rate and effective renal plasma flow were measured by inulin and para-aminohippurate clearances, respectively. Lithium clearance was used as an index of proximal tubular reabsorption of sodium. In addition, plasma concentrations of neurohumoral factors were determined. RESULTS: Total central blood volume was 2.41 +/- 0.33 L/m2 (mean +/- SEM) before and 2.34 +/- 0.18 L/m2 48 h after large volume paracentesis (p = 0.76). Similarly, no differences were detected in the cardiac index, glomerular filtration rate, effective renal plasma flow, urinary sodium excretion, hematocrit, plasma renin activity, or concentrations of plasma aldosterone, norepinephrine, or atrial natriuretic factor. CONCLUSIONS: A single large volume paracentesis without albumin replacement causes no disturbances in systemic and renal hemodynamics 48 h after the procedure. These results suggest that a single 5-L paracentesis without albumin infusion is a safe and satisfactory short term option for the management of patients with cirrhosis and tense, diuretic-resistant ascites.     

"Even", integral indicators in systemic mathematical analysis of fatigue

The article considers 3 different points of view on systemic mathematical analysis of human fatigue process. In this case, the same physiologic information is processed according to various algorithms for integral and digital estimates of lowered performance and energy expenditure, as well as indirect characteristics of inhibition and excitation processes in the brain cortex. The mathematical results are applied in computer forecasting of individual occupational risk at the specific workplace.     

Posterodorsal amygdaloid lesions in rats: long-term effects on body weight

Bilateral lesions in the most posterodorsal aspects of the amygdala in female rats resulted in immediate and dramatic weight gains on a standard lab chow diet. The rate of weight gain returned to normal by Day 20, but the difference in body weight between animals with amygdaloid lesions and those with sham lesions was maintained for the duration of the study (60 days). Because rats with posterodorsal amygdaloid lesions have also been found to be hyperinsulinemic, it is hypothesized that the lesions result in a similar, though smaller, version of the syndrome that follows lesions of the ventromedial hypothalamus.