Unraveling the mechanism of octenidine and chlorhexidine on membranes: Does electrostatics matter?

The increasing problem of antibiotic resistance in bacteria requires the development of new antimicrobial candidates. There are several well-known substances with commercial use, but their molecular mode of action is not fully understood. In this work, we focus on two commonly used antimicrobial agents from the detergent family—octenidine dichloride (OCT) and chlorhexidine digluconate (CHX). Both of them are reported to be agents selectively attacking the cell membrane through interaction inducing membrane disruption by emulsification. They are believed to present electrostatic selectivity toward charged lipids. In this study, we tested this hypothesis and revised previously proposed molecular mechanisms of action. Employing a variety of techniques such as molecular dynamics, ζ potential with dynamic light scattering, vesicle fluctuation spectroscopy, carboxyfluorescein leakage measurement, and fluorescence trimethylammonium-diphenylhexatriene- and diphenylhexatriene-based studies for determination of OCT and CHX membrane location, we performed experimental studies using two model membrane systems—zwitterionic PC and negatively charged PG (18:1/18:1):PC (16:0/18:1) 3:7, respectively. These studies were extended by molecular dynamics simulations performed on a three-component bacterial membrane model system to further test interactions with another negatively charged lipid, cardiolipin. In summary, our study demonstrated that detergent selectivity is far more complicated than supposed simple electrostatic interactions. Although OCT does disrupt the membrane, our results suggest that its primary selectivity was more linked to mechanical properties of the membrane. On the other hand, CHX did not disrupt membranes as a primary activity, nor did it show any sign of electrostatic selectivity toward negatively charged membranes at any stage of interactions, which suggests membrane disruption by influencing more discrete membrane properties.     

¿Carcinoma de mama o carcinoma de glándula sudorípara? Presentación de dos casos y análisis de la literatura

Primary apocrine carcinoma of the sweat gland is a neoplasm with a very low incidence that may represent a clinical and histological diagnostic challenge, as well as for adequate local, adjuvant, and advanced disease management. The average age of patients is around 67 years with no gender preference. This cancer develops primarily at the axillary and scalp levels and is clinically characterized by slow growth, but can progress aggressively with local, nodal, and metastatic involvement (primarily lung, liver, and bone). The recommended management, once the histology is established, consists of a wide local resection with a clear margin of 1 to 2 cm and regional lymphadenectomy if clinically positive nodes are detected. The adjuvant treatment (radiotherapy or chemotherapy) and for the advanced disease is not established.We report here the cases of two female patients initially diagnosed with breast cancer who were finally diagnosed with apocrine carcinoma of the sweat gland.     

A 14 000-year record of paleoenvironmental change in the western basin of China's third largest lake,Lake Taihu

Effect of leaf extract of Ocimum sanctum on (i) the specific and non-specific immune responses and (ii) disease resistance against Aeromonas hydrophila was investigated in Oreochromis mossambicus. Sheep red blood cells (SRBC) and Heat aggregated bovine serum albumin (HA-BSA) were used as antigens for specific and non-specific immune response studies, respectively. Antigens were administered through intraperitoneal route. Anti-SRBC antibody titres were determined by direct haemagglutination and anti-bacterial antibodies were determined by bacterial agglutination. Nitroblue tetrazolium (NBT) assay was used to determine neutrophil activity. Disease resistance was measured in terms of relative percent survival (RPS). The immunostimulatory effect of the leaf extract of O. sanctum, when administered through intraperitoneal and oral routes was obvious. Leaf extract of O. sanctum, when administered intraperitoneally, stimulated both antibody response and neutrophil activity. Dietary intake of O. sanctum also enhanced the antibody response and disease resistance against A. hydrophila. Possibility of using O. sanctum as immunostimulant in the maintenance of finfish health in intensive freshwater aquaculture is suggested.     

Hombre de 18 años con síndrome verrugoso tropical: ¿leishmaniasis o esporotricosis?

The tropical verrucous syndrome includes infectious, chronic, and granulomatous skin conditions appearing with plaques, nodules, or ulcers with a warty surface which gives name to the syndrome. It includes forms of chromoblastomycosis, sporotrichosis, paracoccidioidomycosis, lobomycosis, leishmaniasis, and tuberculosis verrucosa cutis with ample distribution in tropical and subtropical areas. The diagnoses may be difficult and confused among them, especially between sporotrichosis and leishmaniasis.Clinical, epidemiologic, intradermal reactions, direct smears, skin biopsies, cultures, immunofluorescence, and PCR are used to differentiate them, although several of these methods are not commonly used.We present an 18-year-old man with extensive verrucous plaques in one knee interpreted by clinic, epidemiology, and biopsy as verrucous cutaneous leishmaniasis. He was treated with Glucantime® for 20 days without improvement. A new biopsy was made that was also interpreted as cutaneous leishmaniasis. The revision of both biopsies showed inflammation with abscessed granulomas and asteroid sporotrichotic bodies at the center of the granulomas that led to the diagnosis of sporotrichosis later confirmed by the fungus culture. The patient responded to the treatment with itraconazole. As clinical and epidemiological findings of leishmaniasis and sporotrichosis can be similar, skin biopsy and other paraclinical studies are necessary to establish a proper diagnosis. The asteroid sporotrichotic body is pathognomonic of this mycosis. We review here the essential concepts of leishmaniasis and sporotrichosis and the criteria to differentiate them.     

Paleoenvironmental history of the Popayán area since 27 000 yr BP at Timbio, Southern Colombia

A pollen record from Timbio, located at an elevation of 1750m on the high plain of Popayán (2 degrees 24'N, 76 degrees 36'W) is presented. This forms the basis for reconstructing the vegetation and climate history for the periods from 27000 to 9200 radiocarbon years before the present (14Cyr BP) and 2100 14Cyr BP to sub-recent. The 5m sediment core has time control based on seven AMS radiocarbon dates. Four pollen assemblage zones (TIM-1 to TIM-4) are recognized. During the period of 27200 to 26000 14Cyr BP, an Andean forest was near the site. The vegetation consisted of forest and open herb-rich vegetation, climatic conditions were moist and temperatures some 6 degrees C lower than compared to those of today. During the period of 26000 to 16000 14Cyr BP forest was less open. The observed succession from a Podocarpus-Weinmannia dominated forest to a Hedyosmum dominated forest, and finally to a forest with Ilex, Myrica and ferns indicates a progressive decrease of temperature during this period, with a maximum temperature depression of ca. 5-7.5 degrees C compared to present-day conditions. During the period of 16000 to 9200 14Cyr BP, temperature decrease is estimated at ca. 7.5 degrees C and the climate was the driest. During the period of 2100 to 600 14C2600m altitude (ca. 8 degrees C) and those at sea-level (2.5-6 degrees C) and supports the observation that glacial lapse rates were higher than in modern times.     

cDNA and protein sequence of a major pea seed albumin (PA 2 : Mr≈26 000)

Summary Pea albumin 2 (PA2:M_r26000) is a major component of the albumin fraction derived from aqueous salt extracts of pea seed. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and chromatography on DEAE-Sephacel resolve PA2 into two closely related components (PA2a and PA2b). A cDNA clone coding for one of these components has been sequenced and the deduced amino acid sequence compared with partial, chemically-determined sequences for cyanogen bromide peptides from both PA2 components. Complete amino acid sequences were obtained for the C-terminal peptides. The PA2 molecule of 230 amino acids contains four imperfect repeat sequences each of approximately 57 amino acids in length.The combined sequence data, together with a comparison of PA2-related polypeptides produced in vitro and in vivo, indicate that PA2 is synthesized without a signal sequence and does not undergo significant post-translational modification. Although both forms of PA2 contain Asn-X-Thr consensus sequences, neither form is glycosylated. Accumulation of PA2 contributes approximately 11% of the sulfur-amino acids in pea seeds (cysteine plus methionine equals 2.6 residues percent). Suppression of levels of PA2 polypeptides and their mRNAs in developing seeds of sulfur-deficient plants is less marked than that for legumin, in spite of the lower content of sulfur-amino acids in legumin.     

Purification of an elicitor-induced glucan synthase (callose synthase) from suspension cultures of French bean (Phaseolus vulgaris L.): purification and immunolocation of a probable Mr-65 000 subunit of the enzyme

Membrane preparations from suspension-cultured cells of French bean (Phaseolus vulgaris L.) contained callose synthase (EC 2.4.1.34) activity which was preserved upon solubilisation. Following elicitor treatment of cell cultures, increased activity could be extracted and this increase was maintained during purification. The enzyme was purified by high-pressure liquid chromatography and active fractions showed a variable association of two polypeptides of relative molecular masses (M_r) 55 000 and 65 000, the latter being in excess. The M_r-65 000 polypeptide was purified to homogeneity and an antibody raised to it. This antibody showed complex effects on callose synthase activity when incubated with membrane and soluble extracts. In comparison with other systems, the M_r-55 000 subunit is likely to represent the catalytic subunit while the M_r-65 000 polypeptide is a possible regulatory subunit. The M_r-65 000 polypeptide was immunolocated in membranes at sites of callose synthesis in the plant, in cell plates, in sieve plates, at the plasma membrane-wall interface of wounded cells and in papillae in infected cells. Received: 18 January 1997 / Accepted: 8 May 1997     

最近12 000年来青藏高原植被的时空分布

青藏高原30个点湖泊的孢粉记录综合研究显示: 在进入全新世之前(12 ka BP以前),除最东南部外,高原从东到西均发育为荒漠草原植被.全新世早期(12.0-9.0 ka BP)高原东南部(104°-98° E)为落叶阔叶林/针阔叶混交林; 中部(98°-92° E)为草甸或灌丛草甸,再向西至80° E左右为草原植被; 全新世中期(9.0-3.2 ka BP)高原由东向西古植被依次发育为针阔混交林和硬叶阔叶林(104°-98° E)→针阔混交林(98°-94° E)→灌丛草甸(94°-92° E)→草原(92°-80° E);全新世晚期(3.2 ka BP以后)由东向西古植被依次为硬叶阔叶林→针阔混交林→草甸→草原→荒漠.     

High frequency palaeoceanographic changes during the past 140?000 yr recorded by the organic matter in sediments of the Iberian Margin

Biogenic records of the marine palaeoproductivity (carbonates, organic carbon, and C₃₇ alkenones) and the molecular stratigraphy of past sea surface temperatures (SSTs; U₃₇^K′) were studied at high resolution in two cores of the Iberian Margin. The comparison of these records indicates that the oceanographic conditions switched abruptly during the past 160 kyr between three kinds of regimes. A first regime with high (17-22°C) SST and low productivity typifies the interglacial periods, marine isotopic stages (MIS) 5 and 1. Several periods during MIS 6, 2, and the terminations II and I are characterised by about 4-5°C colder SST and a higher organic matter accumulation, both of which define the second regime. This anticorrelation between SST and marine productivity suggests that these variations are related to the intensity of the coastal upwelling. By contrast with this upwelling behaviour, extremely low biological productivity and very cold SST (6-12°C) occurred during short phases of glacial MIS 6, 4, and 2, and as abrupt events (≈1 kyr or less) during MIS 3. The three oceanographic regimes are consistent with micropalaeontological changes in the same cores based on foraminifera and diatoms.The general trend of these hydrologic changes follows the long-term glacial/interglacial cycle, but the millennium scale variability is clearly related to Heinrich events and Dansgaard-Oeschger cycles. Strengthening of the upwelling corresponds probably to an intensification of the subtropical atmospheric circulation over the North Atlantic which was influenced by the presence of continental ice sheets. However, extreme glacial conditions due to massive discharges of icebergs interrupted the upwelling. Interestingly, both terminations II and I coincided with strong but transient intensification of the upwelling.     

先天性尿道下裂的矫治(附1 000例报告)

目的:总结先天性尿道下裂的矫治经验.方法:尿道下裂患者1000例,年龄1～26岁,平均4岁.冠状沟型118例,阴茎体型593例.阴茎阴囊型189例,会阴型100例.791例采用尿道板切开卷管成形法(TIP),117例采用Duckett+Duplay术,92例采用二期手术,一期行阴茎伸直及皮辩转移,二期行尿道成形术(TIP).术中遵循微创原则,使用显微器械,尽量保留原有的正常组织结构.结果:随访6月至2年,TIP术741例手术一次成功,Duckett+Duplay术99例一次成功,分期手术二期成功86例.并发尿道皮肤瘘51例,尿道狭窄17例,尿道憩室6例,均经再次手术治愈.结论:尿道下裂矫治手术中,首先保留尿道板手术,并发症少,成功率高,值得推广,阴茎严重弯曲者或重度尿道下裂患者可选Duckett+Duplay术或者分期手术.     

成都平原4 000aBP以来的孢粉记录与环境变化

成都平原晚全新世以来沉积的泥质层发现丰富的孢粉。根据孢粉成分组合特征和生态类型可划分出5个孢粉组合带,结合剖面上6个14^C测年数据,提出在过去的4000a研究区植被类型及气候环境经历了5个阶段的变化：3800-3600aBP为亚热带常绿阔叶林,气候暖偏湿;3600-3400aBP为含常绿树种的落叶阔叶林,气候温暖湿润;3400-2600aBP为草／湿地,气温下降,环境更潮湿;2600-900aBP为落叶阔叶林,温度又开始逐渐回升,气候温和偏湿;900-300aBP再次变为草／湿地,偏干冷的气候环境。     

Effect of 50?000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality.Design Randomised placebo controlled trial.Setting Bandim Health Project’s demographic surveillance system in Guinea-Bissau, covering approximately 90 000 inhabitants. Participants 4345 infants due to receive BCG.Intervention Infants were randomised to 50 000 IU vitamin A or placebo and followed until age 12 months.Main outcome measure Mortality rate ratios.Results 174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration.Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival.Trial registration Clinical trials {"type":"clinical-trial","attrs":{"text":"NCT00168597","term_id":"NCT00168597"}}NCT00168597.     

大鼠在模拟5 000米低氧下心力储备的动态变化

目的和方法：采用电刺激大鼠坐骨神经引起心阴抗图相应参数变化来测算心力储备的方法,测定了大鼠在模拟５０００ｍ氏氧下不同时间心力储备的动态变化。结果：心力储备在低氧３ｄ已开始增加,７ｄ增加显著（Ｐ〈０．０５）,低氧１０ｄ及１４ｄ又降至接近正常组水平,低氧３０ｄ略低于正常水平;每搏储备的变化规律和变化量均与心力领略相近,低氧７ｄ增加显著（Ｐ〈０．０１）,人低氧１４ｄ仍显著地对照组（Ｐ〈０．０５）;心率储