Laxative-induced Diarrhoea: A Continuing Clinical Problem

Seven women spent an average of 127 days in hospital and were extensively investigated, including a laparotomy, before their complaints of abdominal pain, diarrhoea, and weight loss were shown to be due to excessive taking of laxatives. All denied taking laxatives and in none were the characteristic features of the effects of cathartics on the colon seen on sigmoidoscopy or radiological examination.Hypokalaemia and other electrolyte abnormalities were common and were thought to be due to a combination of severe diarrhoea and vomiting. The rectal mucosa was seen to be abnormal on biopsy only in the three patients who had taken senna preparations. The diagnosis was not easy and was finally established either by analysis of the urine and stools or by searching the patient''s ward locker.     

Host plant selection of Chrysolina clathrata (Coleoptera: Chrysomelidae) from Mpumalanga, South Africa

Hyperaccumulated elements such as Ni may defend plants against some natural enemies whereas other enemies may circumvent this defense. The Ni hyperaccumulator Berkheya coddii Roessler (Asteraceae) is a host plant species for Chrysolina clathrata (Clark), which suffers no apparent harm by consuming its leaf tissue. Beetle specimens collected from B. coddii had a whole body Ni concentration of 260 μg/g dry weight, despite consuming leaf material containing 15 100 μg Ni/g. Two experiments were conducted with adults of this beetle species: a no-choice experiment and a choice experiment. In the no-choice experiment we offered beetles foliage of one of four species of Berkheya: B. coddii, B. rehmannii Thell. var. rogersiana Thell., B. echinacea (Harv.) O. Hoffm. ex Burtt Davey, and B. insignis (Harv.) Thell. The two former species are Ni hyperaccumulators (defined as having leaf Ni concentration > 1 000 μg/g) whereas the latter have low Ni levels (< 200 μg/g) in their leaves. Masses of beetles were monitored for 6 days. Choice experiments used growing stem tips from the same Berkheya species, placed into Petri dishes with five Chrysolina beetles in each, and the amount of feeding damage caused on each of the four species was recorded. Beetles in the no-choice experiment gained mass when offered B. coddii , maintained mass on leaves of the other Ni hyperaccumulator ( B. rehmannii var. rogersiana ), and lost mass when offered non-hyperaccumulator leaves. In the choice test, beetles strongly preferred B. coddii to other Berkheya species. We conclude that C. clathrata may be host-specific on B. coddii.     

Clinical picture of secondary pneumonia in our observations

Hundred sixty four patients with the secondary pneumonia were analysed. The secondary pneumonia amounted to 65.8% of all cases of pneumonia treated within several years. Patients' sex, age, clinical symptoms, X-ray findings, coexisting diseases, sequence of the symptoms and the rate of their disappearance were analysed. It was found that the secondary pneumonia is prevailing in males over 40 years of age and most frequently accompany cardiac failure and chronic unspecific respiratory diseases. It is characterized by slow onset and the lack of typical symptoms in the high percentage of patients. Radiological and clinical symptoms disappear more slowly. However, various ausculatory symptoms of pulmonary involvement often accompany the secondary pneumonia and are not directly related to the inflammatory lesion to the lungs.     

Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE), Part II: Development of inhibitors with broad spectrum,Gram-negative antibacterial activity

The structurally related bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as prime candidates for the development of broad spectrum antibacterial agents. However, GyrB/ParE targeting antibacterials with spectrum that encompasses robust Gram-negative pathogens have not yet been reported. Using structure-based inhibitor design, we optimized a novel pyrrolopyrimidine inhibitor series with potent, dual targeting activity against GyrB and ParE. Compounds were discovered with broad antibacterial spectrum, including activity against Pseudomonas aeruginosa, Acinetobacter baumannii and Escherichia coli. Herein we describe the SAR of the pyrrolopyrimidine series as it relates to key structural and electronic features necessary for Gram-negative antibacterial activity.     

A novel method for the study of fluorescent probes in biological material during exposure to microwave radiation

Instrumentation has been developed which allows the monitoring of fluorescnece in erythrocyte ghost membranes before, during, and after exposure to microwave radiation. Using non-fluorescent, UV-transmitting transmitting fiber optic cables, excitation light of specific wavelengths was delivered to a stirred sample undergoing irradiation (2450 MHz, CW) within a fluid-filled, temperature-controlled waveguide. Fluorescence was collected using an identical cable and transferred through appropriate filters to standard detecting, amplification and recording devices. We have used the fluorescent probe, 1-anilino-8-naphthalene sulfonate (ANS)_to monitor the effect of mirowave radiation on the binding of calcium to erthrocyte ghosts. Microwave radiation at specific absorption rates of 10 and 200 mW/g had no effect on the binding of ANS to the membranes. Dose-responses curves also showed no influence of microwaves on calcium binding between 2.0 and 10.0 · 10^?4 M. In addition, experiments studying fluorescence energy transfer between intrinsic tryptophan residues and membrane bound ANS showed that intermolecular distance between donor and acceptor are also unaffected by microwave radiation. We have thus shown that 2450 MHz microwve radition at the specific absorption rates studies rates used does not interfere with the binding of calcium to erythrocyte ghosts or alter intermolecular distances intrinsic molecules and bound ANS.     

Significant natural product biosynthetic potential of actinorhizal symbionts of the genus frankia, as revealed by comparative genomic and proteomic analyses

Bacteria of the genus Frankia are mycelium-forming actinomycetes that are found as nitrogen-fixing facultative symbionts of actinorhizal plants. Although soil-dwelling actinomycetes are well-known producers of bioactive compounds, the genus Frankia has largely gone uninvestigated for this potential. Bioinformatic analysis of the genome sequences of Frankia strains ACN14a, CcI3, and EAN1pec revealed an unexpected number of secondary metabolic biosynthesis gene clusters. Our analysis led to the identification of at least 65 biosynthetic gene clusters, the vast majority of which appear to be unique and for which products have not been observed or characterized. More than 25 secondary metabolite structures or structure fragments were predicted, and these are expected to include cyclic peptides, siderophores, pigments, signaling molecules, and specialized lipids. Outside the hopanoid gene locus, no cluster could be convincingly demonstrated to be responsible for the few secondary metabolites previously isolated from other Frankia strains. Few clusters were shared among the three species, demonstrating species-specific biosynthetic diversity. Proteomic analysis of Frankia sp. strains CcI3 and EAN1pec showed that significant and diverse secondary metabolic activity was expressed in laboratory cultures. In addition, several prominent signals in the mass range of peptide natural products were observed in Frankia sp. CcI3 by intact-cell matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). This work supports the value of bioinformatic investigation in natural products biosynthesis using genomic information and presents a clear roadmap for natural products discovery in the Frankia genus.     

Capsular perstraction as a novel methodology for the recovery and purification of geldanamycin

The molecular complex “Heat shock protein 90” has become a novel target for anticancer drugs in recent times on account of its ability to perform as a chaperone toward proteins involved in cancer progression. The geldanamycin binds to this complex with high affinity and prevents it from performing correctly, which results in tumor destruction. The aim of this study was to investigate the feasibility of applying liquid‐core microcapsules as a novel technique (termed “capsular perstraction”), for the recovery and purification of geldanamycin from culture media. Results demonstrated how this procedure was capable of rapidly extracting >70% of geldanamycin from culture media using a liquid‐core volume to medium ratio of only 1%. Optimum conditions for removal, including agitation speed, microcapsule size, and membrane thickness were examined, and it was shown how the stagnant aqueous film around the microcapsules was the main resistance to mass transfer. A volumetric mass transfer coefficient of 5.66 × 10^?6 m/s was obtained for the highest agitation speed (400 rpm), which was considerable greater compared to the value of 0.88 × 10^?6 m/s achieved for the lowest speed of 100 rpm. Removal of geldanamycin from microcapsules was also examined to fully investigate the potential of such particles for in situ product recovery, and it was demonstrated how the methodology can be used as a simple mechanism for purifying the compound (>99%) through solvent extraction and crystallization. The results of this work demonstrate the novel use of capsular perstraction as a methodology for the recovery and purification of geldanamycin from culture environments. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011