Molecular approach for development of new medicaments for chronic infections treatment

Owing to the progress in cellular microbiology it has been evidently proved that inflammation induced by infectious agents forms the basis of many chronic conditions. Therefore a microbial infection can be considered as a triggering factor of such widespread and significant diseases as infertility, arthritis, atherosclerosis, asthma, gastritis, stomach ulcer and cancer, neurological syndromes and some oncological formations. Practically all pathogenic and conditionally pathogenic bacteria can induce chronic infections of different organs and tissues. It has been revealed that in spite of differences of clinical syndromes and participation of different bacteria in their induction the several general mechanisms of chronic infections are detected. Failure in chronic infections therapy is due to the absence of medicaments to eradicate persistent forms of pathogens. The development of new medicaments for chronic infections treatment should be based on the selection of new specific targets, influence on which would to inhibit the mechanism of chronic infections induction.     

Molecular engineering as an approach to design new functional properties of alginate

Through enzymatic modification, we are now able to manipulate the composition and sequential nanostructures of alginate, one of the most versatile gelling polymers found in nature. Here we report the application of a set of processive polymer-modifying epimerases for the preparation of novel alginates with highly improved functional properties essential for numerous applications as gel matrices. Gels of enzymatically engineered alginate were found to be more elastic and compact, less permeable, and extremely stable under physiological conditions, offering significant advantages over native alginates. As a result, this study shows that, by controlling alginate nanostructure, its macroscopic properties can be highly controlled. The ability to tailor alginate has a great impact on the wide use of this biomaterial in industry and medicine. More importantly, this adds more knowledge to the link between polymer nanostructure and macroscopic properties and may serve as a model system for other polymer-based materials.     

Relaxation training as a treatment for irritable bowel syndrome

Although there have been many successful, controlled demonstrations of the clinical efficacy of multicomponent treatments for irritable bowel syndrome (IBS), in the present study we sought to evaluate a single component of many of these regimens, relaxation training. Eight IBS patients received a 10-session (over 8 weeks) regimen of abbreviated progressive muscle relaxation with regular home practice while 8 comparable patients merely monitored GI symptoms. Based on daily GI symptom diaries collected for 4 weeks before and 4 weeks after treatment (or continued symptom monitoring), the Relaxation condition showed significantly (p=.05) more improvement on a composite measure of primary GI symptom reduction than the Symptom Monitoring condition. Fifty percent of the Relaxation group were clinically improved at the end of treatment.     

Inflammatory bowel disease serologies in ankylosing spondylitis patients: a pilot study

Introduction  

Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) share similarities and are classified as spondyloarthropathies. In IBD, anti-Saccharomyces cerevisiae antibody (ASCA), anti-I2 (associated with anti-Pseudomonas activity), anti-Escherichia coli outer membrane porin C (anti-OmpC), anti-flagellin (anti-CBir1), and antineutrophil cytoplasmic antibodies (ANCA) possess clinical significance. Because of the overlap between the two conditions, a pilot study was designed to compare the frequency of these antibodies in AS patients compared to normal controls.     

Phospholipid-mediated signaling systems as novel targets for treatment of heart disease

The phospholipases associated with the cardiac sarcolemmal (SL) membrane hydrolyze specific membrane phospholipids to generate important lipid signaling molecules, which are known to influence normal cardiac function. However, impairment of the phospholipases and their related signaling events may be contributory factors in altering cardiac function of the diseased myocardium. The identification of the changes in such signaling systems as well as understanding the contribution of phospholipid-signaling pathways to the pathophysiology of heart disease are rapidly emerging areas of research in this field. In this paper, I provide an overview of the role of phospholipid-mediated signal transduction processes in cardiac hypertrophy and congestive heart failure, diabetic cardiomyopathy, as well as in ischemia-reperfusion. From the cumulative evidence presented, it is suggested that phospholipid-mediated signal transduction processes could serve as novel targets for the treatment of the different types of heart disease.     

Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents

Background

Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels.

Methods and Findings

We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studies revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)-induced ostoeporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density.

Conclusion

Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts.     

Molecular interactions between light and hormone signaling to control plant growth

As sessile organisms, plants modulate their growth rate and development according to the continuous variation in the conditions of their surrounding environment, an ability referred to as plasticity. This ability relies on a web of interactions between signaling pathways triggered by endogenous and environmental cues. How changes in environmental factors are interpreted by the plant in terms of developmental or growth cues or, in other words, how they contribute to plant plasticity is a current, major question in plant biology. Light stands out among the environmental factors that shape plant development. Plants have evolved systems that allow them to monitor both quantitative and qualitative differences in the light that they perceive, that render important changes in their growth habit. In this review we focus on recent findings about how information from this environmental cue is integrated during de-etiolation and in the shade-avoidance syndrome, and modulated by several hormone pathways—the endogenous cues. In some cases the interaction between a hormone and the light signaling pathways is reciprocal, as is the case of the gibberellin pathway, whereas in other cases hormone pathways act downstream of the environmental cue to regulate growth. Moreover, the circadian clock adds an additional layer of regulation, which has been proposed to integrate the information provided by light with that provided by hormone pathways, to regulate daily growth.     

Medical treatment of inflammatory bowel disease: new therapies,new drugs.

Ulcerative colitis, ulcerative proctitis and Crohn''s disease are chronic inflammatory conditions that affect the gastrointestinal tract. Conventional treatment has stressed the role of anti-inflammatory agents to suppress the inflammatory response. New compounds that can deliver 5-aminosalicylic acid to the colon have recently been released in Canada. Metronidazole and azathioprine may also be of benefit in Crohn''s disease. Therapy with cyclosporine and clonidine should be based on the results of further clinical trials. The use of nutritional support as primary therapy in Crohn''s disease appears promising. At present, both pharmacologic and nutritional therapies should be considered in the treatment of inflammatory bowel disease.     

Antivirulence as a new antibacterial approach for chemotherapy

Bacterial resistance to antibiotics is an issue that has led to the search for new antibacterial approaches. Drugs targeting virulence is an alternative approach to treat infections due to resistant bacteria. There is extensive literature and knowledge in the field of bacterial pathogenesis and genomic determinant of virulence. As therapeutic targets, virulence factors have been primarily addressed in the vaccine field to prevent infection by specific pathogens. Recently novel strategies to identify virulence inhibitors have been numerous and several new compounds were recently reported. This review emphasizes the new virulence inhibitors that have shown a biological activity and have made a proof of concept that disarming bacteria lead to the inhibition of bacterial infection in experimental models in vivo. Moreover, some of these new antivirulence compounds are able to inhibit the virulence of different related pathogenic species, indicating that it is possible to target common virulence mechanisms. The progress reported recently with proof of concept for antivirulence molecules at the preclinical stages should allow the antivirulence concept to become a reality as a new antibacterial approach.     

Bowel sound biofeedback as a treatment for irritable bowel syndrome

Using an electronic stethoscope placed on subjects' abdomens, bowel sound biofeedback was administered to five subjects suffering from irritable bowel syndrome (functional diarrhea). They were instructed to alternately increase and decrease colonic sounds in an attempt to gain control over bowel activity. Using daily ratings of diarrhea as the primary dependent measure, three of five subjects reduced mean ratings enough at posttreatment to meet our 50% criterion for success (100%, 94%, and 54%). At 1-year follow-up, two of the three short-term successes had maintained their level of improvement — each had ratings 75% below those of pretreatment.     

白头翁汤治疗炎症性肠病的分子机制研究

目的：探讨白头翁汤治疗炎症性肠病的分子机制。方法：40只Wistar雄性大鼠随机分为5组（n=8）：正常对照组、模型组、模型＋阳性对照组（美沙拉嗪）、模型＋中药治疗组,中药治疗组又分为中、高剂量组。阳性对照组、中药治疗组分别灌胃给药。疗程结束后取大鼠结肠组织利用免疫组织化学、Western blot等方法检测Smad7及p-Smad3在各组中的表达变化。结果：模型与组相比较,阳性药物及中药组尤其是高剂量组可有效抑制Smad7的表达,同时增强p-Smad3的表达。结论：白头翁汤可能通过激活TGF-β1/Smad3信号通路从而发挥了对炎症性肠病中的抗炎作用。     

Buspirone, a new approach to the treatment of anxiety

Anxiety has historically been treated by agents with a sedative component to their action. In the last decade or so it has been determined that gamma-aminobutyric acid (GABA) receptors may mediate the anxiolytic actions of the benzodiazepines, propanediol carbamates, barbiturates, and ethanol. However, inasmuch as these drugs have additional pharmacological properties (sedation, muscle relaxation, seizure control), the search for an anxioselective drug was continued. Buspirone appears to be such a drug. Clinical studies have clearly demonstrated the efficacy of buspirone in the treatment of generalized anxiety disorder without the ancillary pharmacology of earlier anxiolytics. Buspirone does not act on the GABA receptor. Rather, its most salient interaction with neurotransmitter receptors occurs at the 5-HT1A serotonin receptor. This action is supported by studies focused on receptor binding, anatomical localization, biochemistry, neurophysiology, and animal behavior. The recognition that action at 5-HT1A receptors may be a viable approach to the pharmacotherapy of anxiety is evidenced by the number of other agents of this class under development by a number of pharmaceutical companies.     

Prepartum nausea and vomiting; a new approach to treatment

A controlled study of 101 patients indicated that a combination of amphetamine and Rauwolfia was effective in the treatment of prepartum nausea and vomiting. Good to excellent results were obtained in 53 (83 per cent) of 64 patients who received the combination. Five patients reported fair results; six were not benefited by the treatment. Only five of a control group of 37 patients who received placebos reported good results. In addition to relief of the symptoms of nausea and vomiting, concomitant emotional disturbances, notably anxiety and depression, were alleviated by the drug combination.