Studies on the sterilization of pharmaceutical base materials with ionizing radiation and ethylene oxide.

The use of ionizing radiation and ethylene oxide for the sterilization of pharmaceutical base materials of animal origin, used to produce organopreparations, was studied. The materials included liver extract, pancreas extract, dried thyroid and intrinsic factor. The effective sterilizing doses for the examined materials and dependence between effective ionizing radiation dose and primary contamination were determined.     

An exploration of the effects of L- and D-tetrahydroisoquinoline-3-carboxylic acid substitutions at positions 2,3 and 7 in cyclic and linear antagonists of vasopressin and oxytocin and at position 3 in arginine vasopressin

We have investigated the effects of mono-substitutions with the conformationally restricted amino acid, 1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid (Tic) at position 3 in arginine vasopressin (AVP), at positions 2, 3 and 7 in potent non-selective cyclic AVP V₂/V_1a antagonists, in potent and selective cyclic and linear AVP V_1a antagonists, in a potent and selective oxytocin antagonist and in a new potent linear oxytocin antagonist Phaa-D -Tyr(Me)-Ile-Val-Asn-Orn-Pro-Orn-NH₂ (10). We report here the solid-phase synthesis of peptide 10 together with the following Tic-substituted peptides: 1, [Tic³]AVP; 2, d(CH₂)₅[D -Tic²]VAVP; 3, d(CH₂)₅[D -Tyr(Et)²Tic³]VAVP; 4, d(CH₂)₅[Tic²Ala-NH₂⁹]AVP; 5, d(CH₂)₅[Tyr(Me)², Tic³, Ala-NH₂⁹]AVP; 6, d(CH₂)₅ [Tyr(Me)², Tic⁷]AVP; 7, Phaa-D -Tyr(Me)-Phe-Gln-Asn-Lys-Tic-Arg-NH₂; 8, desGly-NH₂,d(CH₂)₅[Tic²,Thr⁴]OVT; 9, desGly-NH₂d(CH₂)₅[Tyr(Me)²Thr⁴, Tic⁷]OVT; 11, Phaa-D-Tic-Ile-Val-Asn-Orn-Pro-Orn-NH₂, using previously described methods. The protected precursors were synthesized by the solid-phase method, cleaved, purified and deblocked with sodium in liquid ammonia to give the free peptides 1–11 which were purified by methods previously described. Peptides 1–11 were examined for agonistic and antagonistic potency in oxytocic (in vitro, without Mg²⁺) and AVP antidiuretic (V₂-receptor) and vasopressor (V_1a-receptor) assays. Tic³ substitution in AVP led to drastic losses of V₂, V_1a and oxytocic agonistc activities in peptide 1.L - and D -Tic² substitutions led to drastic losses of anti-V₂/anti-V_1a and anti-oxytocic potencies in peptides 2, 4, 8 and 11 (peptide 2 retained substantial anti-oxytocic potency; pA₂ = 7.25 ± 0.25). Whereas Tic³ substitution in the selective V_1a antagonist d(CH₂)₅[Tyr(Me)², Ala-NH₂⁹]APV(C) led to a drastic reduction in anti-V_1a potency (from anti-V_1a pA₂) 8.75 to 6.37 for peptide 5, remarkably, Tic³ substitution in the V₂/V_1a antagonist d(CH₂)₅[D -Tyr(Et)²]VAVP(B) led to full retention of anti-V₂ potency and a 95% reduction in anti-V_1a potency. With an anti-V₂ pA₂ = 7.69 ± 0.05 and anti-V_1a pA₂ = 6.95 ± 0.03, d(CH₂)₅[D -Tyr(Et)²,Tic³]VAVP exhibits a 13-fold gain in anti-V₂/anti-V_1a selectivity compared to (B). Tic⁷ substitutions are very well tolerated in peptides 6, 7 and 9 with excellent retention of the characteristic potencies of the parent peptides. The findings on the effects of Tic³ substitutions reported here may provide promising leads to the design of more selective and possibly orally active V₂ antagonists for use as pharmacological tools and as therapeutic clinical agents for the treatment of the syndrome of the inappropriate secretion of antidiuretic hormone (SIADH).     

Cytologic appearance of esthesioneuroblastoma in a fine needle aspirate

Esthesioneuroblastoma (olfactory neuroblastoma) is a rare malignant neoplasm derived from the olfactory epithelium. It was diagnosed by cytologic study of fine needle aspiration biopsy smears of a tumor situated in the nasopharynx in a 57-year-old man.     

Lead uptake,localization and changes in cell ultrastructure ofFunaria hygrometrica protonemata

The main sites of lead entering the protonemata were spores with broken cell walls and apical cells of protonemata. The lead ions could enter the symplast probably by endocytosis but we can not exclude diffusion as the way of entering. Lead deposits inside a protoplast were observed after 2 h of lead application. After 12 h, Pb deposits were commonly present in all cell structures surrounded by a membrane. Some disturbances in ultrastructure of organelles were found after 8 h. The most frequent were: change of endoplasmatic reticulum configuration from linear to concentric one in many cases surrounding other organelles (e.g. mitochondria) and large and numerous plastoglobuli in chloroplasts. Longer treatment of protonemata with lead (24 h or 48 h) caused degeneration of organelles and even death of the cell. The present work was supported by a grant from the State Commitee for Scientific Research no. 1575 9101 for E.A.G.     

Value of intermittent pneumatic massage in the treatment of upper extremity lymphedema]

Technique and results of the conservative treatment of 116 female patients with secondary lymphedema of the upper extremity following total mastectomy are discussed. It was found, that intermittent pneumatic massage combined with exercises decreased mild edema by more that 50%, moderate edema by nearly 40%, and marked edema by more that 25%. Complete disappearance of edema was achieved in nearly 50% of patients with mild swelling. Improvement was seen in 20% of the treated patient independently of the extension of edema.     

Neoplastic diseases of the hematopoietic system and ischemia of the lower limbs]

The possible interaction between hematopoietic neoplasms and ischemia of the lower limbs in patients with both pathologies was subjected to analysis. Anaemia, polycythemia, thrombocythemia, increased leucocytosis in the peripheral blood, and hyperuricemia exerted unfavourable effect on the blood flow through the arteries of the lower limbs. In some cases effective cytostatic treatment diminished the ischemia of the lower limbs. Interactions between various drugs used in the chronic treatment of both pathologies in the same patient was also examined.     

Regions of lead uptake inLemna minor plants and localization of this metal within selected parts of the root

Investigations were carried out to determine the sites of lead uptake within the frond and the root ofLemna minor. With the sodium rhodizonate four regions favoured in lead uptake were distinguished: the frond region between the base and the node, the basal part of the root, and the regions at the proximal and distal ends of the root cap. For analysis in electron microscope only the root regions were chosen. The highest rate of lead uptake was found in the basal part of the root. Lead was present in the apoplast of this region after 5 min of exposure and was observed in the stelar cells after 30 min of incubation. Lead deposits were detected mostly in the cell walls adjacent to the plasma membrane and in the lumen of several endomembrane compartments - the endoplasmic reticulum (ER), dictyosomal vesicles, nuclear envelope and the vacuoles. Lead induced changes of cell ultrastructure; an increase in the number of membraneous structures, swelling of ER cisternae and distortion of the dictyosomal cisternae were observed after 2 to 6 h of exposure. We wish to thank Mrs. G. Winiecka for her technical assistance in preparing the photographs.