Antibacterial activity of the derivatives of cholic acid (author''s transl)

Serum and urinary myo-inositol and urinary glucose were estimated by means of gas-liquid chromatography in 54 patients with glomerulonephritis with and without renal failure. myo-Inositol clearance was calculated and an index was formulated which reflected changes in glomerular filtration, tubular reabsorption and catabolism of myo-inositol by the kidney. Serum and urinary myo-inositol levels were increased in glomerulonephritis with a close correlation to the degree of renal failure. In advanced forms of glomerulonephritis, glomerular filtration, tubular reabsorption and catabolism of myo-inositol were shown to be markedly deranged. Evidence obtained showed further that a derangement of tubular reabsorption and catabolism of myo-inositol also accompany milder forms of glomerulonephritis without decreased glomerular filtration. The myo-inositol index value, especially, was increased in patients with signs of disease activity as indicated by a histological examination of the kidney tissue. The index can also be regarded as a highly sensitive test of renal failure. Low grade glucosuria was shown to be frequently associated with glomerulonephritis with renal failure. Evidence was produced which suggested that the tubular reabsorption of myo-inositol was deranged earlier than glucose reabsorption in glomerulonephritis, although they may share a common step in the reabsorption process. The data suggest that the estimation of serum and urinary myo-inositol has advantages in the evaluation of kidney function.     

Study of the antiviral activity of some new classes of AS-triazine derivatives (preliminary note)

Monoclonal antibodies were raised to a synthetic peptide corresponding to amino acids 1-29 of the human gonadotropin-releasing hormone (GnRH) receptor. One of the two antibodies was found to recognise GnRH receptors on human pituitary gonadotrophs as determined by immunohistochemistry and supported by Western blotting. The antibody also bound to T47D human breast carcinoma cell line as determined by flow cytometric analysis.     

Potential anxiolytic-like activity of some amino acid derivatives

This report describes a case of uterine didelphys, lipomeningocele, meatal stenosis, and inguinal hernia presenting in a single individual. This unusual group of birth defects suggests a common mechanism of malformation in tailbud maturation which involves both the müllerian duct and the distal spinal cord.     

Synthesis and antiallergic activity of dimethyl-2-(phenylcarbamoyl)ethylsulfonium p-toluenesulfonate derivatives

The derivatives of dimethyl-2-(phenylcarbamoyl)ethylsulfonium p-toluenesulfonates were synthesized and evaluated for antiallergic activity. The 2,3-dihydroxyethoxy group was introduced to the phenyl ring from the standpoint of lipophilicity and electronic effects of substituent. The IgE-induced rat passive cutaneous anaphylaxis (PCA) was inhibited by oral administration of several substituted 2-[(4-propoxyphenyl)carbamoyl]ethyldimethylsulfonium p-toluenesulfonate derivatives. Among them (+/-)-2-[N-[4-(3-ethoxy-2-hydroxypropoxy)phenyl]carbamoyl]ethyldimeth ylsulfonium p-toluenesulfonate (1a, IPD-1151T) was found to possess considerable activity in the PCA test, and it was launched as Suplatast tosilate in Japan.     

Regioselective ring opening of steroidal epoxide with hydrides: formation of C(2)- and C(3)-deoxyasiatic acid derivatives

In their 4 short years in medical school, members of the Class of '98 have witnessed massive changes within the health care system. These are going to have a direct, and often negative, impact on the way they practise. Despite this, members of this group can't wait to become full-fledged members of the medical profession.     

Antimicrobial activity of carbapenem antibiotics against gram-negative bacilli

Antimicrobial activities of meropenem (MEPM), imipenem (IPM), panipenem (PAPM), ceftazidime (CAZ), cefozopran (CZOP), aztreonam (AZT), norfloxacin (NFLX) and tetracycline (TC) against clinically isolated Gram-negative bacilli [271 strains of Enterobacteriaceae and 242 strains non-fermentative Gram-negative bacteria (NFB)] were investigated. Among carbapenem antibiotics, MEPM showed the lowest MIC90, which activity was about four-hold higher than those of IPM and PAPM. The activity of IPM was equal or slightly superior to that of PAPM. Resistance to IPM (> 16 micrograms/ml) was observed in 3 strains of Enterobacteriaceae (1.1%) and 14 strains of NFB (5.8%). It is conceivable that these strains produce metallo-beta-lactamase. Referring to the correlation among MICs of MEPM, IPM and PAPM, 3 strains in 3 species of Enterobacteriaceae showed cross resistance to carbapenems; while 14 strains of NFB showed cross resistance to MEPM and IPM, 15 strains to MEPM and PAPM, and 29 strains to IPM and PAPM, and all of these strains were Pseudomonas aeruginosa. Fifteen of 29 strains of IPM-resistant and 77 of 92 strains of PAPM-resistant P. aeruginosa were susceptible to MEPM. Thirty-three strains (12%) of the Enterobacteriaceae were resistant to CAZ and AZT (> or = 32 micrograms/ml) and these were considered as ESBL-producing strains.     

Stereoselective synthesis and thromboxane A2 (TXA2) receptor antagonistic activity of optically active phenol derivatives

At the present time monotherapy is preferable to polytherapy if the epilepsy can be controlled with a single drug. However, persons with intractable epilepsy may need more than one antiepileptic drug to attain the best seizure control with the fewest side-effects. Although clinical studies have not been performed to identify the best combinations, rational polytherapy would imply combining antiepileptic drugs with different mechanisms of action.     

Synthesis, structure elucidation and antimicrobial activity of some 3-hydroxy-2-naphthoic acid hydrazide derivatives

In this study, some 1,4-disubstituted thiosemicarbazide, 1,2,4-triazole and 1,3,4-thiadiazole type novel compounds derived from 3-hydroxy-2-naphthoic acid hydrazide were synthesized to screen for their antimicrobial activity. The structures of these substances were elucidated using elemental analysis and UV, 1H NMR, and mass spectral methods. All of these compounds were tested in vitro for their antibacterial and antifungal activity.     

Bilayer packing characteristics of mixed chain phospholipid derivatives: Raman spectroscopic and differential scanning calorimetric studies of 1-stearoyl-2-capryl-sn-glycero-3-phosphocholine (C(18):C(10)PC) and 1-stearoyl-2-capryl-sn-glycero-3-phospho-N-trimethylpropanolamine (C(18):C(10)TMPC)

Raman spectroscopy and high-sensitivity differential scanning calorimetry (DSC) were used to compare the effects of headgroup conformation on the acyl chain packing arrangements in two highly asymmetric phosphatidylcholine (PC) analogues, 1-stearoyl-2-capryl-sn-glycero-3-phosphocholine (C(18):C(10)PC) and a polar headgroup derivative of C(18):C(10)PC, 1-stearoyl-2-capryl-sn-glycero-3-phospho-N-trimethylpropanolami ne (C(18):C(10)TMPC), which contains an additional methylene group within the choline moiety; namely, -P-O-(CH2)3-N(CH3)3. The C(18):C(10)TMPC headgroup exhibits an extended trans conformation which is independent of bilayer phase. A comparison of gel phase spectral order parameters of the two lipid species indicates a mixed interdigitated state characteristic of three chains per headgroup for C(18): C(10)TMPC. A more intermolecularly ordered liquid crystalline phase is observed, however, for the C(18):C(10)TMPC bilayers. The phase transition cooperative unit size estimated for the C(18):C(10)PC bilayers (approximately 140 molecules per unit) is about 7-fold greater than that for the C(18):C(10)TMPC dispersions (approximately 20 molecules per unit). We suggest that the extended headgroup for C(18):C(10)TMPC induces a slight tilt in the gel phase packing arrangements for the acyl chains, which may persist in the partially interdigitated liquid crystalline phase bilayer. Macroscopically, tighter packed multilamellar dispersions of C(18):C(10)TMPC occur for systems prepared first in the presence of a higher ionic strength medium. The stacked bilayers may then be transferred to a lower ionic strength environment without loss of their more closely packed adjacent lamellae.     

Fungitoxic activity of some cytochalasins and their derivatives on Phytophthora species

The activity of cytochalasin B was tested on 8 Phytophthora species, while the same toxin, some of its derivatives and natural analogues, namely cytochalasin F and deoxaphomin, were assayed at 2 x 10(-5) - 2 x 10(-4) M on the most sensitive species, P. cactorum. A significant inhibitory activity on P. cactorum was shown by cytochalasin B, its 7-monoacetyl derivative, and deoxaphomin. The hydroxy group at C-20 and the conformational freedom of the macrocyclic ring proved to be important structural features for this activity. The 7-hydroxy group at C-7 appeared to have no influence on this toxicity, while a size reduction associated with the carbocyclic nature of the macrocycle seems to lightly increase the activity. The 7-O-acetylcytochalasin B showed selective toxic activity on P. cactorum at the tested concentration, thus suggesting a possible use as a fungicide for this compound.     

Synthesis and local anaesthetic activity of some 7-amino-2-dialkylaminoalkylpyrrolo[3,4-c]pyridine derivatives

A number of 7-amino-2-dialkylaminoalkylpyrrolo[3,4-c] pyridin-1,3(2H)-dione derivatives were synthesized and their local anaesthetic activity was evaluated in vivo by corneal anaesthesia in rabbits. Only compounds 3,9 and 14 showed any activity, albeit lower than that of the reference drug lidocaine.     

Antibacterial activity of efrotomycin

Efrotomycin is a narrow spectrum antibiotic. Among the genera tested for susceptibility in vitro it is most active against isolates of Moraxella, Pasteurella, Yersinia, Haemophilus, Streptococcus and Corynebacterium. The drug is as active by oral administration as by the subcutaneous route. Blood levels rise rapidly to high concentrations, after oral dosing, and are prolonged. Two peaks occur which may indicate biliary excretion and reabsorption. Urinary excretion is minimal. The high blood concentrations explain, in part, the in vivo activity against pathogens such as Bordetella bronchiseptica which are relatively insensitive in vitro. Oral activity of efrotomycin is an advantage over the related antibiotics. X-5108 and mocimycin.     

Synthesis of some chroman derivatives and preliminary investigation on their vasodilatory activity

In this study, some N'-(chroman-4-yliden)-4-aryl-2-thiazolylhidrazide derivatives were synthesized. Their structures were elucidated by IR, NMR and microanalyses. The vasodilatory activities of the compounds obtained were examined in vitro.     

Synthesis and anti-inflammatory activity of some indazole derivatives. 36. Azoles

The synthesis of water soluble hydrochlorides of indazole derivatives 1b, 8 and 9 is described. By treating of 2,5-dinitroindazole with thiomorpholine 3-thiomorpholino-5-nitroindazole (10) and 3,5-dinitroindazole (11) in the form of the molecular compound 11a are obtained. The known indazole derivatives 1 and 7 as well as the newly synthesized hydrochlorides of 1b, 8 and 9 are, except of 8.HCl, less toxic than benzydamine hydrochloric (BZD). The same compounds show with some excepts a comparable or greater antiinflammatory effect than BZD in the carrageenin induced oedema test.     

1,6-anhydro-1(6)-thio-L-iditol and -D-mannitol, and some derivatives thereof

Starting from 1,2:5,6-dianhydro-3,4-O-isopropylidene-L-iditol (1) and -D-mannitol (6), respectively, the corresponding 1,6-anhydro-1,(6)-thio derivatives (2a and 7a) were synthesized. The discrepancy in the yields obtained, as well as the different behavior of their methylated derivatives (2e and 7c) towards acid hydrolysis, could be explained by steric factors. The di-O-mesyl derivatives 3d and 12c were unstable compounds, and showed no ulcerostatic activity, unlike the D-glucitol analog.