Influence of the peptide chain length of new elongated tuftsin analogs on phagocytosis process

In this paper the synthesis of the following elongated tuftsin analogs: Arg-Thr-Lys-Pro-Arg (1), Pro-Arg-Thr-Lys-Pro-Arg(II), Lys-Pro-Arg-Thr-Lys-Pro-Arg(III) and Thr-Lys-Pro-Arg-Thr-Lys-Pro-Arg(IV) by classical and solid-phase methods are described. The obtained peptides were tested for their biological activity: restoration of the phagocytosis of defected granulocytes from blood of children with acute lymphoblastic leukemia (ALL).     

Standard and intermediate risk acute lymphoblastic leukemia in Poland: A report of the Polish Children's Leukemia/Lymphoma Study Group

A total of 527 children with acute lymphoblastic leukaemia (ALL) from the most frequent risk groups: standard risk group (SRG) and intermediate risk group (IRG) were treated between 1987 and 1991 according to an intensified treatment program (based on the BFM protocol) including the use of an intermediate dose of methotrexate in the IRG. A comparison of the treatment results in this group from 513 children treated between 1981 and 1987 indicates that the chance for a 6 year event-free survival has increased to 73% (previously 55%).     

Conformational investigation of α,β-dehydropeptides Part VI. Molecular and crystal structure of benzyloxycarbonylglycyl-(Z)-dehydrophenylalanine

The structure of a peptide containing C-terminal dehydrophenylalanine, Z-Gly-(Z)-δPhe (C₁₉H₁₈N₂O₅, MW = 354) was determined from single-crystal X-ray diffraction data. Needle-shaped crystals were grown from a 1:1 mixture of methanol-acetone in the monoclinic space group P2₁ with a= 14.717(4), b= 4.941(2), c= 12.073(4) Å, β= 103.72(4)?; V= 852.86(8) ų, Z= 2 and D_c= 1.32 g cm ^?3. The structure was solved by direct methods using SHELXS-86 and refined to a final R-index of 0.032 for 1714 observed reflections. The peptide adopts a conformation folded at the glycine residue, and principal torsion angles are ω₀= 167.6(2)?, pHGR;₁= -71.8(3)?, ψ₁= -31.6(4)?, ω_l= - 165.7(3)?, pHGR;₂= 65.6(4)?, ψ1/2 = -174.4(3)? and ψ2/2 = 5.2(4)?. Two intermolecular hydrogen bonds, N₁—H…O_o and O₂—H…O′₁, join the folded molecules into columns and link columns to each other, respectively. FTIR spectroscopy shows the presence of three hydrogen bonds. This third one has been interpreted as an intramolecular hydrogen bond of the N₂—H…N₁ type. © Munksgaard 1994.     

Relapses after termination of therapy of acute lymphoblastic leukemia in children

In the past 16 years, 2004 children with acute lymphoblastic leukemia (ALL) have been treated in the Polish Pediatric Group centers. Eight hundred and eighty-seven (44.3%) of these patients discontinued treatment after the first remission. Acute lymphoblastic leukemia relapse occurred in 180 patients (20.3%). This group was analyzed for the method of treatment and its influence on long-term survival, the time between cessation of treatment and relapse, the character and localization of relapse and later follow-up. It was shown that the patients with the best chance of a second remission are those with late testicular relapse. The most frequent and prognostically poor are bone marrow (BM) relapses which warrant intensive chemotherapy with BM transplantation. Patients with ALL relapse still have the possibility of a second remission and long-term survival.     

TUMOR LOCALIZATION AND SYSTEMIC ABSORPTION OF INTRAVESICAL INSTILLATION OF RADIO-IODINATED IODODEOXYURIDINE IN PATIENTS WITH BLADDER CANCER

PURPOSE: We evaluated tumor uptake and systemic distribution of intravesically instilled iododeoxyuridine (IUdR) in patients with superficial bladder cancer. MATERIALS AND METHODS: We performed 24 intravesical instillation studies in 11 patients with a mean age of 71 years. Radio-iodinated IUdR was administered through a Foley catheter. Gamma camera imaging was done after instillation and after 5 to 7 bladder irrigations. Tumor uptake was estimated by region of interest analysis. Bladder biopsy samples and surgical tumor specimens were tested for acid insoluble (deoxyribonucleic acid incorporated) radioactivity. Blood samples were obtained and analyzed for systemic absorption. RESULTS: Imaging was positive in all patients with bladder cancer. Average tumor uptake plus or minus standard deviation was 0.185+/-0.120% of the instilled dose. Preferential uptake of IUdR in the tumor was observed in all 6 patients undergoing tissue analysis. The tumor-to-normal bladder ratio ranged from 3.2 to 74,000 (median 202). Systemic absorption of IUdR was minimal. Blood sample analysis performed after intravesical instillation in all 11 cases revealed an average uptake of 3.2x10(-5)% instilled dose per ml. (range 0.69x10(-5) to 6.7x10(-5)) in the systemic circulation. Instillation within 24 hours after transurethral bladder tumor resection in 5 cases resulted in a higher but not dangerous average systemic uptake of 7.3x10(-4)% instilled dose per ml. (range 1.3x10(-5) to 2.6x10(-3)). Instillation 1 to 4 weeks after transurethral surgery in 8 cases resulted in no increased systemic absorption with an average blood level of 3.4+/-1.8x10(-5)% instilled dose per ml. There was no detectable distribution of radioactivity into other organs, including the thyroid. We noted no evidence of systemic toxicity in the study. CONCLUSIONS: Intravesical instillation of radio-iodinated IUdR achieves selective localization in the bladder tumor with minimal uptake by the normal bladder and minimal systemic absorption. The use of intravesical IUdR therapy for bladder cancer appears to be promising and requires further study.     

The Effect of a Drug-delivery System Consisting of Soybean Phosphatidyl Choline and Medium-chain Monoacylglycerol on the Intestinal Permeability of Hexarelin in the Rat

The aim of this study was to investigate if the effective in-situ permeability (P_eff) of a new growth hormone-releasing peptide, hexarelin, along rat intestine was enhanced by a lipid matrix drug-delivery system comprising a mixture of soybean phosphatidyl choline and medium-chain monoacylglycerol (PC-MG). The study was performed with and without a protease inhibitor, Pefabloc SC. To enable better understanding of the mechanism of action of this delivery system we also studied the uptake of a small hydrophilic molecule, atenolol. PC-MG at a concentration of 15 mmol L^?1 increased the jejunal P_eff of hexarelin approximately 20-fold, both in the presence and absence of Pefabloc SC, whereas P_eff was not increased in the ileum and colon. PC-MG had no effect on the jejunal, ileal and colonic P_eff of atenolol. Complete recovery of the non-absorbable molecule PEG 4000 showed that functional intestinal viability was maintained in all experiments. Although the results obtained in this study are promising, pharmacokinetic and toxicological studies are required to investigate if this delivery system is a suitable and safe candidate for improving the oral bioavailability of hexarelin.