Extractable sulphate and organic sulphur in soils and their availability to plants

Ten soils collected from the major arable areas in Britain were used to assess the availability of soil sulphur (S) to spring wheat in a pot experiment. Soils were extracted with various reagents and the extractable inorganic SO₄-S and total soluble S(SO₄-S plus a fraction of organic S) were determined using ion chromatography (IC) or inductively-coupled plasma atomic emission spectrometry (ICP-AES), respectively. Water, 0.016 M KH₂PO₄, 0.01 M CaCl₂ and 0.01 M Ca(H₂PO₄)₂ extracted similar amounts of SO₄-S, as measured by IC, which were consistently smaller than the total extractable S as measured by ICP-AES. The amounts of organic S extracted varied widely between different extractants, with 0.5 M NaHCO₃ (pH 8.5) giving the largest amounts and 0.01 M CaCl₂ the least. Organic S accounted for approximately 30–60% of total S extracted with 0.016 M KH₂PO₄ and the organic C:S ratios in this extract varied typically between 50 and 70. The concentrations of this S fraction decreased in all soils without added S after two months growth of spring wheat, indicating a release of organic S through mineralisation. All methods tested except 0.5 M NaHCO₃-ICP-AES produced satisfactory results in the regression with plant dry matter response and S uptake in the pot experiment. In general, 0.016 M KH₂PO₄ appeared to be the best extractant and this extraction followed by ICP-AES determination was considered to be a good method to standardise on.     

Antimicrobial susceptibility of non-O1 Vibrio cholerae isolated from wastewater stabilization ponds in Marrakesh,Morocco

The 365 strains of Vibrio cholerae, isolated in Marrakesh from raw sewage and stabilization pond effluent, were all identified as non-O1 Vibrio cholerae. When tested for their susceptibilities to ampicillin, amoxicillin, cephalothin, streptomycin, novobiocin, chloramphenicol, nalidixic acid and trimethoprim-sulphamethoxazole, 13% of the strains from raw sewage and 20% of those from stabilization pond effluent were found to be resistant to one or more of the antibiotics. There were no significant differences, in terms of drug resistance, between isolates from the new sewage and those from the ponds' effluent.The authors are with the Université Cadi Ayyad, Faculté des Sciences Semialia, Département de Biologie, Laboratoire de Microbiologie, BP S/15, Marrakesh, Morocco     

Enantioselective inhibitory effect of nicardipine on the hepatic clearance of propranolol in man

The influence of a single oral dose of 30 mg nicardipine on the pharmacokinetics of (R)- and (S)-propranolol, given orally as rac-propranolol 80 mg, was studied in 12 healthy volunteers. The plasma concentrations were higher for the (S)-enantiomer than for the (R)-enantiomer. The Cl_o and the Cl′_intr of (S)-propranolol were significantly lower than the Cl_o and Cl′_intr of (R)-propranolol. The unbound fraction of (R)-propranolol was significantly higher than that of (S)-propranolol. Coadministration of nicardipine significantly increased the AUC and C_max and significantly decreased the Cl_o and Cl′_intr for unbound drug of (R)- and (S)-propranolol. These changes were more important for (R)- than for (S)-propranolol. The protein binding was not altered by nicardipine. The enantioselective effect of nicardipine on the metabolic clearance of propranolol appears to be due to an interaction at the level of the metabolizing enzymes. The effect on blood pressure of rac-propranolol was little affected when nicardipine was coadministered with rac-propranolol, and its bradycardic effect was reduced. © 1994 Wiley-Liss, Inc.     

药敏药片对临床235株细菌实验观察报告

药敏药片经临床对金黄色葡萄球菌、大肠埃希氏菌、铜绿假单胞菌等２３５株考核．表明药片工艺研究先进,药片与培养基结合牢固,无断裂、崩解,不渗出颗粒,抑菌圈呈同心园扩散．边缘清楚。药物含量均匀,释放度好。药片抑菌差仅１～３ｍｍ;而纸片抑菌差为２～１２ｍｍ。药片变黑系数ＣＶ为２．７１～４．２１;而纸片ＣＶ为３．８２～１４．３６。表明纸片片间差大,药片精密度明显好于纸片。     

Comparative efficacy of amphotericin B,clotrimazole and itraconazole againstAspergillus spp.

The susceptibilities of two isolates ofAspergillus flavus, one from a human case of recalcitrant mycotic keratitis, and an environmental isolate ofA. fumigatus, to itraconazole, clotrimazole and amphotericin B were measured. Observations of macroscopic growth and microscopic evaluations of conidia germination both indicated that the two isolates ofA. flavus were markedly more resistant to amphotericin B than to itraconazole and clotrimazole. Itraconazole was more effective than clotrimazole for all isolates. Ourin vitro susceptibility results suggest the use of itraconazole should be a primary consideration in the treatment ofAspergillus keratitis.     

Synthesis and characterization of two potential impurities (des-ethyl-Ganirelix) generated in the Ganirelix manufacturing process

Controlling certain diseases using peptide drugs has remarkably increased in the past two decades. In this regard, a generic formulation is an upfront solution to fulfill market demands. Ganirelix, a leading peptide active pharmaceutical ingredient (API) primarily used as a gonadotropin-releasing hormone antagonist (GnRH), has established a potential market value worldwide. But its generic formulation mandates detailed impurity profiles from a synthetic source and contemplates the sameness of a reference-listed drug (RLD). Post-chemical synthesis and processing of Ganirelix, some commercial sources have revealed two new potential impurities among many known, which show the deletion of an ethyl group from the hArg(Et)₂ residue at the sixth and eighth positions, named des-ethyl-Ganirelix. These impurities are unprecedented in traditional peptide chemistry, and such monoethylated-hArg building blocks are not easily accessible commercially to synthesize these two impurities. Here, we have outlined the synthesis, purification, and enantiomeric purity characterization of the amino acids and their incorporation in the Ganirelix peptide sequence to synthesize these potential peptide impurities. This methodology will enable the convenient synthesis of side-chain substituted Arg and hArg derivatives in peptide drug discovery platforms.     

Methods to identify protein targets of metal-based drugs

Metal-based anticancer agents occupy a distinct chemical space due to their particular coordination geometry and reactivity. Despite the initial DNA-targeting paradigm for this class of compounds, it is now clear that they can also be tuned to target proteins in cells, depending on the metal and ligand scaffold. Since metallodrug discovery is dominated by phenotypic screenings, tailored proteomics strategies were crucial to identify and validate protein targets of several investigative and clinically advanced metal-based drugs. Here, such experimental approaches are discussed, which showed that metallodrugs based on ruthenium, gold, rhenium and even platinum, can selectively and specifically target proteins with clear-cut down-stream effects. Target identification strategies are expected to support significantly the mechanism-driven clinical translation of metal-based drugs.     

Framework for validation and implementation of in vitro toxicity tests

Summary The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technologic developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial, and regulatory communities, is recommended. Test validation acceptance is contingent on broad buy-in by disparate groups in the scientific community—academics, industry, and government. This is best achieved by early and frequent communication among parties and agreement on common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction, and refinement alternatives in toxicity testing.