Omeprazole-induced interstitial nephritis.

Acute renal impairment secondary to interstitial nephritis is a rare complication of omeprazole. We describe a 50-year-old woman who took 20 mg omeprazole twice daily for endoscopically proved ulcerative esophagitis. At the same time, Duke's C colonic cancer was diagnosed and completely resected.

Synthesis of gonadotropin-releasing hormone III analogs. Structure-antitumor activity relationships.

Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor activity. Compounds synthesized include analogs with changes in the central sequence in which GnRH-III differs from GnRH and in the C- and N-terminal regions. The results indicate that a salt bridge between Asp6 and Lys8 stabilizes the active conformation of GnRH-III and show the importance of the Trp7.

A single in vivo administration of bombesin antagonist RC-3095 reduces the levels and mRNA expression of epidermal growth factor receptors in MXT mouse mammary cancers.

Epidermal growth factor (EGF) and its receptors (EGFR) play important roles in tumorigenesis. In various experimental cancers, treatment with antagonists of bombesin/gastrin-releasing peptide (BN/GRP) produces a reduction in EGFRs, concomitant to inhibition of tumor growth. To investigate the mechanisms involved, we monitored concentrations of BN/GRP antagonist RC-3095 in serum of mice, rats, and hamsters given a single subcutaneous or intravenous injection of this analog.

[Leukocyte migration during erythrocyte sedimentation].

Sedimentation properties of leukocytes was measured with a new, simple and reproducible method. The increment of leukocyte concentration was determined in the upper 100 mm section of the sedimentation blood column after one hour gravity sedimentation of the whole blood. The result (leukocyte antisedimentation rate, LAR) was expressed in percentage of the original, presedimentation leukocyte concentration.

Synthesis and in vitro evaluation of new potent antagonists of growth hormone-releasing hormone (GH-RH).

In the search for more potent antagonists of hGH-RH, 20 new analogs were synthesized, purified and tested in vitro. All the analogs were based on the N-terminal sequence of 28 or 29 amino acid residues of hGH-RH, but contained D-Arg2 and Nle27 modifications. Most analogs had Phe (pCl)6 and Agm29 substituents.

[In vivo effect of etoposide on the pharmacokinetics of methotrexate].

High dose (5 g/m2/24 h) methotrexate therapy was combined two times with etoposide (100 mg/m2/1h) infusions as a part of the Medulloblastoma protocol developed in our Department Vepesid therapy was administered in two different schedules. The first group of the patients have received etoposide immediately before and at the end (24th h) of methotrexate treatment. The second group was treated with etoposide at 24 h and at 48 hour after starting methotrexate infusion.

Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques.

Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes.

A unique design for ease of access and movement of captive Papio hamadryas.

Baboons are widely used in biomedical research but their size and behaviour present potential problems with accessibility. A unique system has been developed that ensures ease of access to all animals in a colony of Papio hamadryas. Two distinct caging complexes were linked by a network of overhead races, that are connected to a physical restraint area where individual animals could be separated, restrained and weighed without being handled.

Rabies virus binding to the nicotinic acetylcholine receptor alpha subunit demonstrated by virus overlay protein binding assay.

A virus overlay protein binding assay was used to study binding of 125I-labelled rabies virus to the acetylcholine receptor (AChR) from Torpedo californica electric organ membranes. After gel electrophoresis of electric organ membranes and transfer of proteins to nitrocellulose, 125I-labelled alpha-bungarotoxin, a curaremimetic neurotoxin, bound to a 40 kDa band and 125I-labelled rabies virus bound to 51 kDa and 40 kDa bands. Binding of rabies virus to the 40 kDa band was inhibited by unlabelled alpha-bungarotoxin.

Reproductive and neonatal outcomes in captive bred baboons (Papio hamadryas).

Baboons are widely used in biomedical research. Although it is widely held that Papio hamadryas breed well in captivity, each established colony has a different reproductive success often hypothesised to be due to husbandry practices. The National Baboon Colony in Australia is a unique colony that houses Papio hamadryas to mimic that structure seen in the wild.

Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxorubicin, a derivative 500-1000 times more potent.

Doxorubicin (DOX) and its daunosamine-modified derivative, 2-pyrrolino-DOX, which is 500-1000 times more active than DOX, were incorporated into agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH). The conjugation of DOX with LH-RH analogs was performed by using N-(9-fluorenylmethoxycarbonyl)-DOX-14-O-hemiglutarate, a dicarboxylic acid ester derivative of DOX. Coupling this derivative covalently to the epsilon-amino group of the D-Lys side chain of agonist [D-Lys6]LH-RH or antagonistic analog AC-D-Nal(2)-D-Phe(4Cl)-D-Pal(3)-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-Ala-NH 2 [where Nal(2) = 3-(2-naphthyl)alanine, Pal(3) = 3-(3-pyridyl)alanine, and Phe(4CI) = 4-chlorophenylalanine] was followed by the removal of the 9-fluorenylmethoxycarbonyl protective group to yield cytotoxic derivatives of LH-RH analogs containing DOX.

The use of respiratory-tract cultures in the diagnosis of invasive pulmonary aspergillosis.

Purpose: To define the role of lower-respiratory-tract cultures in the diagnosis of invasive pulmonary aspergillosis (IPA) in immunocompromised hosts.

Methods: Immunocompromised patients with a positive, nonbiopsy, lower-respiratory-tract culture for Aspergillus species were classified as having definite, probable, indeterminate, or no IPA. Culture data, positive predictive values (PPVs), correlation with clinical and radiographic findings, and the relationship between the number of specimens submitted and the likelihood of recovering Aspergillus were assessed.

[Analysis of costs of drug therapy in patients with acute respiratory insufficiency].

In a retrospective study, the authors analysed the clinical data of 38 patients who were admitted to a surgical intensive care unit (SICU) for mechanical ventilation lasted for at least 72 hours. The APACHE III score was calculated on the basis of clinical data documented during the first 24 hour of the treatment and the cost of drug administrations per patients per day was also determined by analysing all the drugs prescribed on the first 5 days of intensive care. The patients admitted to SICU with polytrauma or with abdominal septic focus required significantly higher cost of drug treatment than the patients after cardiopulmonary resuscitation or with bronchial asthma or pneumonia.

Synthesis of GnRH analogs having direct antitumor and low LH-releasing activity.

New chicken I GnRH agonists and antagonists have been synthesized and tested for their biological activities. The common feature of these analogs was that the molecules had a beta-L-aspartyl residue inserted in position 6. The agonist bound to the pituitary still had low endocrinological activity.

Gonadectomy modifies the gender specific pattern of desensitization of pituitary cells by gonadotropin-releasing hormone in the superfusion system.

The effect of a 6-h infusion of 1 nM gonadotropin-releasing hormone (GnRH) on LH release from dispersed anterior pituitary cells from rats in metoestrus ("metoestrus cells"), intact male rats ("male cells"), ovariectomized rats ("ovx cells"), and from orchidectomized rats ("orchidex cells") was investigated. Using metoestrus cells the initial amplitude of the response was high but desensitization was strong: the amount of LH secreted in the last 90-min period of the 6-h incubation was less than 20% of the initial value. In male cells, the immediate response was weaker; however, in the second 90-min of the 6-h incubation a 20% to 30% increase was observed and even in the fourth 90-min period the amount of LH secreted was more than 70% of the initial levels.

Palladium-catalyzed homogeneous coupling reactions of steroids with organostannanes.

Direct and carbonylative coupling reactions of various steroid derivatives possessing iodo- and bromo-alkenyl moiety (17-iodo-androst-16-ene, 1, 17-bromoandrost-2,16-diene, 2, 17-iodo-4-aza-4-methylandrost-16-en-3-one, 3, 17-iodo-4-azaandrost-16-en-3-one, 4) with vinyltributylstannane and ethynyltributylstannane were carried out in the presence of various palladium catalysts. While carbonylation took place only with vinyltributylstannane, 17-vinyl-, and 17-ethynyl-delta 16 steroids were produced via direct coupling with vinyltributylstannane and ethynyltributylstannane, respectively. Activities of some catalysts based on Pd(0) and Pd(II) precursors were compared, and Pd(PPh3)4 was found to be superior to other complexes in most cases.

Steroidal alkenylphosphonates via palladium-catalyzed coupling reactions.

The palladium-catalyzed coupling of various 17-iodo-delta 16 steroids (17-iodo-androst-16-ene, 17-iodo-4-methyl-4-aza-androst-16-en-3-one, and 17-iodo-4-aza-androst-16-en-3-one) with dialkyl phosphites (dimethyl phosphite, diethyl phosphite, and diisopropyl phosphite) was examined in detail. The only successful condition for homogeneous coupling involved carrying out the reaction in the absence of any solvents. A large excess of dialkyl phosphite was used, which means that the phosphite itself acted as a solvent.

Homogeneous catalytic dehalodimerization of 17-iodo-delta 16 steroids.

17-Iodo-delta 16 steroids undergo selective dimerization and carbonylative dimerization in the presence of palladium catalysts in dimethylformamide which result in 16-17'-coupled dienes and 17-carboxylic anhydrides, respectively. Moderate to good yields have been obtained for both types of dimers.

Antagonists of bombesin/gastrin-releasing peptide inhibit growth of SW-1990 human pancreatic adenocarcinoma and production of cyclic AMP.

We investigated the effects of bombesin/GRP antagonists RC-3095 and RC-3940-II on the growth of SW-1990 human pancreatic adenocarcinoma cells xenografted into nude mice or cultured in vitro. Nude mice implanted with SW-1990 tumors received s.c.

Effect of long-acting antagonists of growth hormone (GH)-releasing hormone on GH and cyclic adenosine 3',5'-monophosphate release in superfused rat pituitary cells.

In a recent study, investigating the time course of both GH and cAMP secretion induced by GH-releasing hormone (GHRH) in the superfusion system, we found that the amount of cAMP liberated from the cells was not proportional to GH release and that cAMP discharged after a GHRH pulse alone cannot maintain the release of GH. In the present study, two potent antagonists of GHRH, MZ-4-71 ([Ibu0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27]human GHRH-(1-28)Agm) and MZ-4-243 ([Nac0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27]human GHRH-(1-28)Agm) were evaluated for their long term effect in the superfusion system and for their ability to influence the release of GH and cAMP. Our present findings showed that after a 9-min preincubation, antagonist MZ-4-71 and MZ-4-243 at 3 and 1 nM, respectively, caused an inhibition of GH release, stimulated by 1 nM GHRH, similar to that caused by the 100-nM dose of the standard antagonist ([Ac-Tyr1,D-Arg2]human GHRH-(1-29)NH2).

[Soy formula in the feeding of infants with milk allergy].

Authors administered soy formula to 16 infants and toddlers with clinically diagnosed cow's milk allergy. During 3 months of soy feeding it was not observed signs indicating soy allergy. The patients showed normal length and weight development.

Development of a radioimmunoassay for a pseudononapeptide bombesin/GRP antagonist with antitumor activity.

Bombesin-like and GRP-like peptides may act as autocrine growth factors in the proliferation of some cancers. A pseudononapeptide bombesin antagonist, [D-Tpi6,Leu13 psi(CH2NH)-Leu14]bombesin(6-14), and related analogs synthesized in our laboratory significantly inhibit tumor growth in various cancer models. A radio-immunoassay (RIA), suitable for determination of RC-3095 and its congeners in unextracted serum, was developed in order to facilitate further experimental and clinical evaluation of this bombesin/GRP receptor antagonist for the treatment of various tumors.

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system.