Genomic localization of a T serotype locus to a recombinatorial zone encoding extracellular matrix-binding proteins in Streptococcus pyogenes

Streptococcus pyogenes is an important bacterial pathogen afflicting humans. A striking feature is its extraordinary biological diversity, evident in the wide range of diseases it can cause and the antigenic heterogeneity present on its surface. The T antigens form the basis of a major serological typing scheme that is often used as an alternative or supplement to M typing. Unlike M typing, the genetic basis for T typing is poorly understood. In this report, the tee6 gene is localized to a position approximately equal to 3.3 kb downstream from prtF1 (or sfbI), which encodes the Fn-binding protein, protein F, a key virulence factor. Comparison of this portion of the genome with those of four additional strains reveals the presence of genes encoding a collagen-binding protein (Cpa) and a second Fn-binding protein (PrtF2 or PfbpI). This chromosomal region--here designated the FCT region--is approximately 11 to 16 kb in length and is flanked at both ends by long stretches of highly conserved sequence. For each of the five strains, the FCT region contains a unique combination of semiconserved loci, indicative of extensive intergenomic recombination. The data provide evidence that the highly recombinatorial FCT region of the S. pyogenes genome is under strong selection for change in response to the host environment.     

Interdisciplinary approaches to adult orthodontic care

The orthodontic treatment of adult patients is most frequently just one component of a more complex treatment involving several dental disciplines. This report discusses the potential problems related to the establishment of a treatment plan and the necessity for the patient's full acceptance, and understanding of the pros and cons related to different treatment approaches. In addition, the case report underlines the importance of a well-defined treatment goal. We have illustrated the team approach and the treatment principles in this combined perio-, ortho-, and prosthodontic patient.     

Permeation enhancement of a highly lipophilic drug using supersaturated systems

The potential of supersaturation as a method for enhancing the membrane permeation of highly lipophilic compounds has been investigated using, as a model system, the transport of a lavendustin derivative (LAP, log K(o/w) = 5) through silicone membrane. Propylene glycol-water mixtures, which permitted the formulation of LAP at different levels of saturation, were prepared and tested for stability prior to conducting membrane permeation studies. The transport of LAP across silicone membrane from donor solutions containing the drug at different degrees of saturation (DS = 1-5) was evaluated by two independent experimental methods: (i) using attenuated total-reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and (ii) using standard vertical diffusion cells followed by quantification with high-performance liquid chromatography (HPLC). Both methods demonstrated a linear relationship between the DS of the applied solution and the flux through the membrane, yielding similar values for the diffusion coefficients of LAP [diffusion cells, D = 1.75 ( +/- 0.16) x 10(-7) cm(2) s(-1) and ATR-FTIR, D = 1.42 ( +/- 0.26) x 10(-7) cm(2) s(-1)). In addition to the characterization of LAP permeation, ATR-FTIR spectroscopy enabled an examination of solvent transport across the membrane.     

Contributions of Electromigration and Electroosmosis to Iontophoretic Drug Delivery

Purpose. To determine the electromigration and electroosmotic contributions to the iontophoretic delivery of lidocaine hydrochloride, in addition to the more-lipophilic quinine and propranolol hydrochlorides, in the presence and absence of background electrolyte.Methods: In vitro experiments, using excised pig ear skin and both vertical and side-by-side diffusion cells, were performed as a function of drug concentration and with and without background electrolytes in the anodal formulation. Concomitantly, the contribution of electroosmosis in each experimental configuration was monitored by following the transport of the neutral, polar marker molecule, mannitol. Results. Electromigration was the dominant mechanism of drug iontophoresis (typically representing 90% of the total flux). In the presence of background electrolyte, lidocaine delivery increased linearly with concentration as it competed more and more effectively with Na⁺ to carry the charge across the skin. However, iontophoretic delivery of quinine and propranolol increased non-linearly with concentration. Without electrolytes, on the other hand, electrotransport of the three drugs was essentially independent of concentration over the range 1-100 mM. Transport efficiency of lidocaine was 10%, whereas that of the more lipophilic compounds was significanly less, with the major charge carrier being Cl^– moving from beneath the skin into the anodal chamber. Both quinine and propranolol induced a concentration-dependent attenuation of electroosmotic flow in the normal anode-to-cathode direction. Conclusion. Dissecting apart the mechanistic contributions to iontophoretic drug delivery is key to the optimization of the formulation, and to the efficient use of the drug substance.     

Iontophoretic transport across the skin

There have been many attempts to define the key relationships between passive drug diffusion across the skin and the molecular and physicochemical properties of the permeant. At the present time, the importance of lipophilicity (or hydrogen bond donor and acceptor properties) and of molecular volume are well established, and useful predictive relationships for passive percutaneous permeability exist. With respect to iontophoresis, on the other hand, the situation is far less clear and the mechanisms involved have not been completely defined. The roles of electromigration and electroosmosis (current-induced convective solvent flow) are now beginning to be understood and experimentally separated. In turn, this allows the manner in which certain physicochemical parameters influence the efficiency of drug electrotransport to be deduced. An initial examination of a database drawn from the literature and from our own work (for which the experimental conditions employed were reasonably constant) suggests a rather sharp dependence of cationic drug delivery via electromigration upon molecular size. We suggest that the analysis reveals useful paths for further investigation.     

医用聚乳酸类高分子材料的应用

目的:阐述医用聚乳酸类高分子材料的需求,综述聚乳酸类高分子材料在生物医学领域的应用,并对其在医学领域的应用前景进行展望。资料来源:应用计算机检索ACS美国化学学会数据库2000-01/2006-12关于医用聚乳酸类高分子材料的文章,检索词“polylactide”;利用Elsevier Science全文电子期刊数据库2000-01/2006-12进行检索,检索词“polylactide”和全文检索“Medical polymeric material”。同时利用计算机检索中国期刊全文数据库1994-01/2005-12的相关文章,限定文章语言种类为中文,检索词“聚乳酸类医用高分子材料”。资料选择:对资料进行初审,纳入标准:①关于聚乳酸类医用高分子材料的需求。②医用聚乳酸类高分子材料的合成及应用。排除标准:重复性研究。资料提炼:共收集到符合上述要求的文献100篇,排除70篇重复性研究。30篇符合纳入标准:其中6篇关于聚乳酸类医用高分子材料的需求,24篇关于医用聚乳酸类高分子材料的合成及应用。资料综合:聚乳酸是一种具有良好的生物相容性和可生物降解的聚合物,最终的降解产物是二氧化碳和水,对人体无毒、无刺激。目前,聚乳酸类材料产品在医学领域广泛用于药物控制释放载体、组织工程、骨内固定、修复、手术缝合线、人造皮肤以及三维多孔支架等。结论:医用聚乳酸类高分子材料有非常广阔的应用前景,今后研究的重点是研发高效低成本的聚乳酸制备方法,合成适应于不同医疗或其他用途的、具有优良生物相容性的聚乳酸共聚物高分子材料。     

耐力训练过程中大鼠体内糖储备及胰岛激素变化与黄芪、生脉穴位注射的干预效应

目的:穴位注射疗法在临床应用较多,但在运动医学领域研究不多。观察穴位注射黄芪、生脉对耐力训练大鼠糖储备和运动能力的影响。方法:实验于2004-07在陕西师范大学完成。①实验分组:健康雄性SD大鼠32只,体质量180～220g,随机抽签法分为安静对照组、训练对照组、生理盐水组、药物注射组,每组8只。②实验方法:建立穴位注射黄芪、生脉大鼠的耐力跑台训练实验模型,安静对照组安静笼饲养。训练对照组、生理盐水组、药物注射组先于动物跑台上进行5周适应性训练,之后跑速每周递增,5d/周,共5周;然后进行2周的大强度耐力训练,30min/d,7d/周,共2周。训练对照组、生理盐水组、药物注射组第8周第1天以速度为35m/min运动至力竭。③实验评估:7周后取材测定肝糖原、肌糖原、血清胰岛素、胰高血糖素的变化。实验中对动物处置符合动物伦理学标准。结果:纳入大鼠32只,均进入结果分析。①通过大强度耐力训练,药物注射组与其他3组相比,肝糖原含量均升高(P<0.05);训练对照组肌糖原比安静对照组降低(P<0.05),生理盐水组与训练对照组相比则显著性升高(P<0.01)。②训练对照组胰岛素比安静对照组明显降低(P<0.01);生理盐水组及药物注射组都能抑制这种降低的趋势(P<0.01);药物注射组胰高血糖素较安静对照组、训练对照组要高,且有显著性差异(P<0.01)。结论:穴位注射黄芪、生脉使大强度耐力训练大鼠体内糖储备显著增加,同时可以提高胰岛激素水平,从而提高了大鼠的运动能力。     

Antiepileptic potential of flavonoids fraction from the leaves of Anisomeles malabarica

Ethnopharmacological relevance

The plant Chodara (Anisomeles malabarica R.Br. Family: Lamiaceae) has numerous therapeutic utilities in folk medicine.

Aim of the study

To isolate and evaluate the anti-epileptic potential of fractions from the ethyl acetate extract (EAE) of Anisomeles malabarica leaves.

Materials and methods

The EA extract (2.12% w/w) of the leaves of Anisomeles malabarica was prepared and fractionated into total flavonoids fraction (AMFF) and tannins fraction (AMTF), which subsequently evaluated for the antiepileptic activity against PTZ- and MES model in wistar rats. Diazepam and phenytoin (2 mg/kg and 25 mg/kg, i.p., respectively), were used as a reference drugs. Further, the presence of flavonoid was confirmed by chemical test, TLC and HPTLC were done for the identification of the number of flavonoids with reference to standard.

Results

Single dose pretreatment with AMFF (25 and 50 mg/kg, i.p.) has found to be effective against both MES and PTZ-convulsions, but associated with a marked decrease in locomotor activity and motor activity performance (i.e., neurotoxic effects), similar to that of diazepam treatment. Interestingly, chronic treatment with AMFF at lower doses (6.25 and 12.5 mg/kg, i.p., 1 week) has also produced significant antiepileptic activity, but without causing neurotoxic effects.

Conclusion

Thus, it may be concluded that the flavonoids fraction of the EA extract of Anisomeles malabarica leaves has antiepileptic potential against both MES and PTZ convulsion models. Acute treatment (25 and 50 mg/kg, i.p.) is associated with neurotoxic activity. Whereas, chronic treatment (6.25 and 12.5 mg/kg, i.p., 1 week) also shown significant antiepileptic effect without causing neurotoxic side effects. However, further research is in progress to determine the component(s) of the flavonoids fraction of Anisomeles malabarica involved and their mechanism of action in bringing about the desirable anti-epileptic effect.     

NMDA receptors in clinical neurology: excitatory times ahead

Since the N-methyl-D-aspartate receptor (NMDAR) subunits were cloned less than two decades ago, a substantial amount of research has been invested into understanding their physiological function in the healthy CNS. Research has also been directed at their pathological roles in various neurological diseases, including disorders resulting from acute excitotoxic insults (eg, ischaemic stroke, traumatic brain injury), diseases due to chronic neurodegeneration (eg, Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis), disorders arising from sensitisation of neurons (eg, epilepsy, neuropathic pain), and neurodevelopmental disorders associated with NMDAR hypofunction (eg, schizophrenia). Selective NMDAR antagonists have not produced positive results in clinical trials. However, there are other NMDAR-targeted therapies used in current practice that are effective for treating some neurological disorders. In this Review, we describe the evidence for the use of these therapies and provide an overview of drugs being investigated in clinical trials. We also discuss new NMDAR-targeted strategies in clinical neurology.