Current perspectives on glycopeptide resistance.

In the last 5 years, clinical isolates of gram-positive bacteria with intrinsic or acquired resistance to glycopeptide antibiotics have been encountered increasingly. In many of these isolates, resistance arises from an alteration of the antibiotic target site, with the terminal D-alanyl-D-alanine moiety of peptidoglycan precursors being replaced by groups that do not bind glycopeptides. Although the criteria for defining resistance have been revised frequently, the reliable detection of low-level glycopeptide resistance remains problematic and is influenced by the method chosen. Glycopeptide-resistant enterococci have emerged as a particular problem in hospitals, where in addition to sporadic cases, clusters of infections with evidence of interpatient spread have occurred. Studies using molecular typing methods have implicated colonization of patients, staff carriage, and environmental contamination in the dissemination of these bacteria. Choice of antimicrobial therapy for infections caused by glycopeptide-resistant bacteria may be complicated by resistance to other antibiotics. Severe therapeutic difficulties are being encountered among patients infected with enterococci, with some infections being untreatable with currently available antibiotics.     

紫外分光光度法测定复方酮康唑软膏中酮康唑和氧氟沙星的含量

目的：建立复方酮康唑软膏的含量测定方法。方法：用双波长分光光度法测定酮康唑的含量，用单波长法测定氧氟沙星的含量。结果：两被测组分的平均回收率和相对标准偏差分别为酮康唑１００．３３％和０．３２％；氧氟沙星１００．８５％和０．２７％。结论：方法简便、准确，可用于复方酮康唑软膏的质量控制。     

High thermal stability and cold-denaturation of an artificial polypeptide

An amphipathic polypeptide, P_n, with a tandemly repeated LKELPEKL sequence including a proline every eight residues, as well as a series of shorter peptides having the same sequence, P₂, P₃, P₄, P₅ and P₆, were synthesized. Their conformation in aqueous solution was mainly studied by CD. At low temperature, these peptides and polypeptide are completely unordered and undergo a reversible transition leading to a partly α-helical structure upon heating. Such behavior has been demonstrated for a few proteins by other authors and has been called cold-denaturation. The transition temperature of the polypeptide is close to 20 ° C. The conformational change does not depend on concentration, indicating a monomolecular process. The high-temperature structure seems to be compact as for globular proteins. A model of folded structure is proposed from experimental data and from molecular modelling studies. © Munksgaard 1996.     

Salt-dependent conformational diversity of alternating poly (Glu-Leu)

Alternating poly(Glu-Leu) was synthesized by the condensation of the corresponding dipeptide p-nitrophenyl ester at high concentration. It exhibits a random coil structure in pure water at neutral pH. Addition of monovalent cations, such as NH⁺₄ to a final 0.1 M solution, induces a transition to a water soluble β-structure. The salt effect is quite selective since no transition was observed with Li⁺, Na⁺ or Cs⁺ ions. Addition of 0.5 equiv. of calcium, cobalt or manganese chlorides per glutamyl residue induces similar coil to β-sheet transitions. No polymer precipitation was observed at these very low salt concentrations. Addition of 0.5 equiv. of Cu²⁺ or 0.15 equiv. of Fe³⁺ induces a coil to α-helix transition. Molecular modeling has been used to understand tentatively the main factors controlling the different conformations observed with the various metal ions. © Munksgaard 1997.     

6-取代苯基哒嗪的3位γ-氨基丁酸衍生物的合成及抗惊活性

GABA的合成类似物是开发新型抗惊剂和抗癫痫药物的新领域。由芳香醛与吗啉、氰化钾反应形成的α-芳基-α-(4-吗啉)乙腈,可对α,β-不饱和腈或酯进行1,4-加成,生成1,4-酮酸型化合物。此物与肼缩合,再经芳构化即得6-芳基-3(2H)哒嗪酮。后者再经氯化后。与GABA缩合,制备3-(N-GABA)-6-芳基哒嗪类及其分子内脱水产物3-(N-丁内酰胺)-6-芳基哒嗪类化合物。本文应用此法合成了17个上述苯代哒嗪的GABA衍生物,并初步测验了它们的抗惊(MES)活性。活性最强的是3-(N-GABA)-6-(2′,4′-二氯苯基)哒嗪(ED₅₀=21.05mg/kg)。     

Emergency hospital admissions in idiopathic Parkinson's disease.

Little is known about the hospital inpatient care of patients with idiopathic Parkinson's disease (PD). Here, we describe the features of the emergency hospital admissions of a geographically defined population of PD patients over a 4-year period. Patients with PD were identified from a database for a Parkinson's disease service in a district general hospital with a drainage population of approximately 180,000. All admissions of this patient subgroup to local hospitals were found from the computer administration system. Two clinicians experienced in both general medicine and PD then reviewed the notes to identify reasons for admission. Admission sources and discharge destinations were recorded. Data regarding non-PD patients was compared to PD patients on the same elderly care ward over the same time period. The total number of patients exposed to analysis was 367. There was a total exposure of 775.8 years and a mean duration of 2.11 years per patient. There were 246 emergency admissions to the hospital with a total duration of stay of 4,257 days (mean, 17.3 days). These days were accounted for by 129 patients (mean age, 78 years; 48% male). PD was first diagnosed during 12 (4.9%) of the admissions. The most common reasons for admission were as follows: falls (n=44, 14%), pneumonia (n=37, 11%), urinary tract infection (n=28, 9%), reduced mobility (n=27, 8%), psychiatric (n=26, 8%), angina (n=21, 6%), heart failure (n=20, 6%), fracture (n=14, 4%), orthostatic hypotension (n=13, 4%), surgical (n=13, 4%), upper gastrointestinal bleed (n=10, 3%), stroke/transient ischemic attack (n=8, 2%), and myocardial infarction (n=7, 2%). The mean length of stay for the PD patients on the care of elderly ward specializing in PD care was 21.3 days compared to 17.8 days for non-PD patients. After hospital admission, there was a reduction in those who returned to their own home from 179 to 163 and there was an increase in those requiring nursing home care from 37 to 52. Infections, cardiovascular diseases, falls, reduced mobility, and psychiatric complications accounted for the majority of admissions. By better understanding the way people with PD use hospital services, we may improve quality of care and perhaps prevent some inpatient stays and care-home placements.     

Magnetite biomineralization in the human brain.

Although the mineral magnetite (Fe3O4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron microscopy, electron diffraction, and elemental analyses identify minerals in the magnetite-maghemite family, with many of the crystal morphologies and structures resembling strongly those precipitated by magnetotactic bacteria and fish. These magnetic and high-resolution transmission electron microscopy measurements imply the presence of a minimum of 5 million single-domain crystals per gram for most tissues in the brain and greater than 100 million crystals per gram for pia and dura. Magnetic property data indicate the crystals are in clumps of between 50 and 100 particles. Biogenic magnetite in the human brain may account for high-field saturation effects observed in the T1 and T2 values of magnetic resonance imaging and, perhaps, for a variety of biological effects of low-frequency magnetic fields.     

伊贝碱甙B的分离和结构测定

本文报道自吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)中分得一种新的C-去甲-D-异甾体生物碱甙,命名为伊贝碱甙B(yibeinoside B)。根据红外、质谱、氢谱和碳谱确定了结构。     

Optic disc oval ness,refractive error and axial length of Hong Kong Chinese

Myopic crescent, refractive error and axial length were previously investigated in Hong Kong Chinese subjects. The myopic crescent was found to correlate with axial length and myopic refraction. In this study, three groups of Hong Kong Chinese with different degrees of myopia were assessed for optic disc ovalness, refractive error and axial length. The axial length was significantly correlated with the degree of myopia, indicating that the myopia was axial in nature. The regression line shows that 0.44 mm of axial elongation would give about one dioptre of increase in myopia. The elliptical ratio of the optic disc was defined as the maximal disc diameter divided by the minimal disc diameter. All three groups showed an oval disc with vertical axis greater and an increased ovalness for the high myopic group with an elliptical ratio from 1.11 in low myopia to 1.29 in high myopia. There is a small amount (about four degrees) of temporal rotation of this vertical oval orientation, which is independent of the amount of myopia. This result shows an association between axial elongation of the globe and optic disc ovalness, in addition to the previously described temporal myopic crescent. Therefore, in myopic subjects, a vertically oval disc may be associated with a myopic refraction rather than glaucoma.