Self-instructed relaxation: a therapeutic alternative

A self-instructed relaxation program was compared with therapist-instructed relaxation and waiting list controls. Self-report anxiety measures ( IPAT and STAI ) and a psychophysiological stress profile (frontal EMG, GSR, heart rate, finger temperature monitored under relaxation and stressor conditions) were utilized pre- and posttreatment to determine efficacy. Self-monitored heart rate, respiration rate, and finger temperature were used to monitor home practice sessions. Subjects reported increased ability to relax and control stress; however, frontal EMG measured under stressor conditions was the only dependent measure to confirm this perception. No between-group differences on any other dependent measures were observed. Reliable changes on all self-monitored home practice measures were observed, suggesting that this procedure is a useful gauge of home practice.     

Arjunolic acid: A new multifunctional therapeutic promise of alternative medicine

Importance of the field

In recent years, a number of studies describing the effective therapeutic strategies of medicinal plants and their active constituents in traditional medicine have been reported. Indeed, tremendous demand for the development and implementation of these plant derived biomolecules in complementary and alternative medicine is increasing and appear to be promising candidates for pharmaceutical industrial research. These new molecules, especially those from natural resources, are considered as potential therapeutic targets, because they are derived from commonly consumed foodstuff and are considered to be safe for humans.

Areas covered in this review

This review highlights the beneficial role of arjunolic acid, a naturally occurring chiral triterpenoid saponin, in various organ pathophysiology and the underlying mechanism of its protective action. Studies on the biochemistry and pharmacology suggest the potential use of arjunolic acid as a novel promising therapeutic strategy.

What the readers will gain

The multifunctional therapeutic application of arjunolic acid has already been documented by its various biological functions including antioxidant, anti-fungal, anti-bacterial, anticholinesterase, antitumor, antiasthmatic, wound healing and insect growth inhibitor activities. The scientific basis behind its therapeutic application as a cardioprotective agent in traditional medicine is justified by its ability to prevent myocardial necrosis and apoptosis, platelet aggregation, coagulation and lowering of blood pressure, heart rate, as well as cholesterol levels. Its antioxidant property coupled with metal chelating property (by its two hydroxyl groups) protects different organs from metal and drug-induced organ pathophysiology. Arjunolic acid also plays a beneficial role in the pathogenesis of diabetes and its associated complications. The mechanism of cytoprotection of arjunolic acid, at least in part, results from the detoxification of reactive oxygen species (ROS) produced in the respective pathophysiology. In addition to its other biological functions, it also possesses vibrant insecticidal properties and it has the potential to be used as a structural molecular framework for the design of molecular receptors in the general area of supramolecular chemistry and nanochemistry. Esters of arjunolic acid function as organogelators which has wide application in designing thermochromic switches and sensor devices. Arjunolic acid derived crown ether is an attractive candidate for the design of molecular receptors, biomimetics and supramolecular systems capable of performing some biological functions.

Home message

This review would provide useful information about the recent progress of natural product research in the domain of clinical science. This review also aims to untie the multifunctional therapeutic application of arjunolic acid, a nanometer-long naturally occurring chiral triterpenoid biomolecule.     

Tolerating diabetes: an alternative therapeutic approach for diabetic neuropathy

It is becoming apparent that a number of pathogenic mechanisms contribute to diabetic neuropathy, so that therapeutic interventions that target one particular mechanism may have limited success. A recently published preclinical study has adopted an alternative approach by using a novel small molecule to induce heat-shock protein 70. This confers upon neurons, and perhaps other cells of the nervous system, the ability to better tolerate the diverse stresses associated with diabetes rather than intervening in their production.     

Resveratrol in cardioprotection: a therapeutic promise of alternative medicine

Resveratrol, a polyphenol phytoalexin, possesses diverse biochemical and physiological actions, including estrogenic, antiplatelet, and anti-inflammatory properties. Several recent studies determined the cardioprotective abilities of resveratrol. Both in experiments (acute) and in chronic models, resveratrol attenuates myocardial ischemic reperfusion injury, atherosclerosis, and reduces ventricular arrhythmias. It appears that resveratrol-mediated cardioprotection is achieved through the preconditioning effect (the best yet devised method of cardioprotection), rather than direct protection. Thus, resveratrol likely fulfills the definition of a pharmacological preconditioning compound and gives hope to the therapeutic promise of alternative medicine.     

A therapeutic alternative for tension headache in children: Treatment and 1-year follow-up results

Ten young subjects, ranging in age from 12 to 15 years, suffering from tension headache were treated by electromyographic biofeedback (EMG-BFB) twice a week for 12 sessions. The Pain Total Index (PTI) was recorded every month from the beginning to the end of the treatment. At the end of the treatment the PTI decreased significantly in all our patients and, at the same time, the muscular tension values also decreased. This result supports the hypothesis of a correlation between clinical symptom and muscular tension level. We saw our patients for follow-up sessions, and the clinical improvement was confirmed to 1 year from the completion of the treatment; however, the muscular tension values were increased with respect to the last-session values.     

Muscle relaxation techniques: a therapeutic tool for family physicians.

Muscle relaxation techniques are important adjunctive therapy for anxiety-related conditions. Family physicians can learn to teach the techniques so as to try helping anxious patients themselves rather than automatically referring them to a psychiatrist. The exercises are generally acceptable to patients, are easy to learn and do not require expensive equipment. They are beneficial in insomnia and tension headache, of some value in chronic anxiety states and a useful adjunct in hypertension. In this paper the evidence supporting the value of muscle relaxation therapy is briefly reviewed, methods of teaching and of practising the techniques are described in detail, and answers to some of the questions and problems that may arise are presented.     

Effects of alternative control procedures for electromyographic biofeedback relaxation training

Twenty-four college students participated in a single session of electromyographic (EMG) biofeedback in a comparison of three experimental control procedures commonly employed in biofeedback relaxation training research. One group received contingent EMG biofeedback from the forehead area, and each subject in this group served as his or her own control. Subjects in a second group received noncontingent EMG feedback from a tape recorder but were instructed to use the feedback signal to relax their forehead muscles (single blind). Subjects in a third group received the same auditory feedback as those in the second group but were not told the purpose or source of the feedback stimulus (yoked control). The contingent feedback group showed significantly less EMG activity when compared to the other two groups. However, this group did not exhibit significant EMG level decrements from the beginning to end of the session. This seemingly contradictory finding may have been due to statistically capitalizing on the artifactually high EMG level of the experimental and control groups, although the single-blind and yoked-control groups showed nonsignificant increases across the session. The single-blind group's data had a variance several times larger than the other two groups' variance. Findings are discussed with respect to a probing hypothesis as opposed to the previously offered frustration hypothesis. Of the three control procedures, the data suggest the yoked control as the procedure of choice for EMG biofeedback relaxation research.The authors would like to thank David Kazar and Claudia Coleman for their technical assistance with this article.     

Human African trypanosomiasis: potential therapeutic benefits of an alternative suramin and melarsoprol regimen

Treatment of late-stage human African trypanosomiasis is complicated by the presence of trypanosomes within the central nervous system (CNS). The regimen commonly prescribed to treat CNS-stage disease involves the use of the trypanocidal drugs suramin and melarsoprol. Suramin does not cross the blood–brain barrier efficiently and therefore, at normal dosages, will not cure CNS-stage infections. An initial treatment with suramin is given to eliminate the parasites from the peripheral tissues. This is followed by a course of intravenous melarsoprol, which can enter the CNS. However, melarsoprol not only produces severe adverse reactions but also is extremely painful to administer. One possible method to help alleviate these problems is to reduce the total amount of melarsoprol in the treatment regimen. This study indicates a synergism between suramin and melarsoprol and demonstrates that experimental murine CNS-trypanosomiasis can be cured with a single intraperitoneal dose of 20 mg/kg suramin followed almost immediately by 0.05 ml (4.5 μmol) topical melarsoprol. These dosages will not cure the infection when administered as monotherapies. Moreover, the timing of the drug administration appears to be crucial to the successful outcome of the regimen. If the interval between injection of suramin and application of topical melarsoprol is extended from 15 min to 3 or 7 days, the infections are not cured. Although extended relapse times occur following these regimens when compared with monotherapy approaches. Thus, there is strong evidence that injected suramin and topical melarsoprol should be given almost simultaneously to achieve the most effective combination of the two drugs.     

An alternative model for the selection of therapeutic chelating agents

An alternative model is presented for the selection of therapeutic chelating agents to enhance the mobilization and excretion of a toxic metal. The model is based on the in vivo patterns of absorption, distribution, reaction and excretion of the chelating agent, a typical toxic metal ion and complexes of the two. The model emphasizes the kinetic aspects of the processes involved and indicates how other processes may be incorporated such as redox reactions involving the chelating agent or metal. The identification of rate determining steps and methods for their manipulation are assumed to be of importance. The application of this model to specific metals is outlined.     

Biofeedback-induced relaxation training as an alternative for the elementary school learning-disabled child

This study examined the effects of biofeedback-induced relaxation training on attention to task, impulsivity, and locus of control among 32 learning-disabled children between the ages of 8 and 11 years. Attention to task and impulsivity were measured by the Matching Familiar Figures Test and locus of control was measured by the Nowicki-Strickland Scale. Participants were randomly assigned to experimental (N = 16) and control (N = 16) groups. The study spanned a total of 8 weeks, with the experimental treatment consisting of three sessions spaced approximately 2 weeks apart. The treatment included EMG biofeedback training used with relaxation tapes. Univariate F values and discriminant analysis procedures revealed that the attention to task and impulsivity measures proved to be valid discriminators, respectively beyond the .01 and .05 levels of significance. Experimental group subjects had significantly fewer number of errors on the attention to task measure and significantly lower impulsivity scores. It was concluded that the biofeedback-induced relaxation training affords promise in assisting learning-disabled children in reaching their education potentials. It was recommended that future research examine the long-term efficacy and the transfer to school-related tasks of this intervention.     

Biofeedback-induced relaxation training as an alternative for the elementary school learning-disabled child

This study examined the effects of biofeedback-induced relaxation training on attention to task, impulsivity, and locus of control among 32 learning-disabled children between the ages of 8 and 11 years. Attention to task and impulsivity were measured by the Matching Familiar Figures Test and locus of control was measured by the Nowicki-Strickland Scale. Participants were randomly assigned to experimental (N=16) and control (N=16) groups. The study spanned a total of 8 weeks, with the experimental treatment consisting of three sessions spaced approximately 2 weeks apart. The treatment included EMG biofeedback training used with relaxation tapes. Univariate F values and discriminant analysis procedures revealed that the attention to task and impulsivity measures proved to be valid discriminators, respectively beyond the .01 and .05 levels of significance. Experimental group subjects had significantly fewer number of errors on the attention to task measure and significantly lower impulsivity scores. It was concluded that the biofeedback-induced relaxation training affords promise in assisting learning-disabled children in reaching their education potentials. It was recommended that future research examine the long-term efficacy and the transfer to school-related tasks of this intervention.     

Peptibodies: A flexible alternative format to antibodies

Peptibodies or peptide-Fc fusions are an attractive alternative therapeutic format to monoclonal antibodies. They consist of biologically active peptides grafted onto an Fc domain. This approach retains certain desirable features of antibodies, notably an increased apparent affinity through the avidity conferred by the dimerization of two Fcs and a long plasma residency time. Peptibodies can be made in E. coli using recombinant technology. The manufacturing process involves fermentation and downstream processing, including refolding and multiple column chromatographic steps, that result in overall yields and quality suitable for commercial development. Romiplostim, marketed under the brand name Nplate®, is the first peptibody to be approved by the United States Food and Drug Administration and the European Medicines Agency and is indicated for the treatment of immune thrombocytopenic purpura. AMG 386, a peptibody antagonist to angiopoietins 1 and 2, is being evaluated in Phase 3 clinical testing in combination with chemotherapy in women with ovarian cancer. AMG 819, a peptibody targeting nerve growth factor for pain has also progressed to clinical trials. These peptibodies illustrate the versatility of the modality.     

Peptibodies: A flexible alternative format to antibodies

Peptibodies or peptide-Fc fusions are an attractive alternative therapeutic format to monoclonal antibodies. They consist of biologically active peptides grafted onto an Fc domain. This approach retains certain desirable features of antibodies, notably an increased apparent affinity through the avidity conferred by the dimerization of two Fcs and a long plasma residency time. Peptibodies can be made in E. coli using recombinant technology. The manufacturing process involves fermentation and downstream processing, including refolding and multiple column chromatographic steps, that result in overall yields and quality suitable for commercial development. Romiplostim, marketed under the brand name Nplate®, is the first peptibody to be approved by the United States Food and Drug Administration and the European Medicines Agency and is indicated for the treatment of immune thrombocytopenic purpura. AMG 386, a peptibody antagonist to angiopoietins 1 and 2, is being evaluated in Phase 3 clinical testing in combination with chemotherapy in women with ovarian cancer. AMG 819, a peptibody targeting nerve growth factor for pain has also progressed to clinical trials. These peptibodies illustrate the versatility of the modality.     

Mitochondria: A therapeutic target in neurodegeneration

Mitochondrial dysfunction has long been associated with neurodegenerative disease. Therefore, mitochondrial protective agents represent a unique direction for the development of drug candidates that can modify the pathogenesis of neurodegeneration. This review discusses evidence showing that mitochondrial dysfunction has a central role in the pathogenesis of Alzheimer's, Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. We also debate the potential therapeutic efficacy of metabolic antioxidants, mitochondria-directed antioxidants and Szeto–Schiller (SS) peptides. Since these compounds preferentially target mitochondria, a major source of oxidative damage, they are promising therapeutic candidates for neurodegenerative diseases. Furthermore, we will briefly discuss the novel action of the antihistamine drug Dimebon on mitochondria.     

Mesenchymal stem cells: A therapeutic update

Mesenchymal stem cells/multipotent marrow stromal cells (MSC) have the ability to participate in there construction of tissues both directly by providing repair cells (essentially those originating from mesoderm)and indirectly by modulating inflammatory and immune responses. This wide range of properties makes these cells very appealing to treat various pathological conditions. They have been first used in 1995 as supportive cells to facilitate hematopoietic stem cells engraftment, and then to minimize the deleterious consequences of graft versus host disease by their immunosuppressive function. Their robust osteogenic differentiation capacity has also been evaluated in numerous preclinical settings of healing/repair but more rarely in human clinical trials. During the past 10-15 years, the potential benefit of their paracrine actions has been tested in various situations such as to facilitate repair after cutaneous defects after burns or lower consequences of ischemic strokes. The purpose of this series of short texts is not to give an exhaustive panorama, but to discuss some well-identified indications in four different fields : auto-immune diseases,bone repair, vascular regeneration and eye lesions such as corneal and retinal defects.     

A plant alternative to animal caspases: subtilisin-like proteases

Activities displaying caspase cleavage specificity have been well documented in various plant programmed cell death (PCD) models. However, plant genome analyses have not revealed clear orthologues of caspase genes, indicating that enzyme(s) structurally unrelated yet possessing caspase specificity have functions in plant PCD. Here, we review recent data showing that some caspase-like activities are attributable to the plant subtilisin-like proteases, saspases and phytaspases. These proteases hydrolyze a range of tetrapeptide caspase substrates following the aspartate residue. Data obtained with saspases implicate them in the proteolytic degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) during biotic and abiotic PCD, whereas phytaspase overproducing and silenced transgenics provide evidence that phytaspase regulates PCD during both abiotic (oxidative and osmotic stresses) and biotic (virus infection) insults. Like caspases, phytaspases and saspases are synthesized as proenzymes, which are autocatalytically processed to generate a mature enzyme. However, unlike caspases, phytaspases and saspases appear to be constitutively processed and secreted from healthy plant cells into the intercellular space. Apoplastic localization presumably prevents enzyme-mediated protein fragmentation in the absence of PCD. In response to death-inducing stimuli, phytaspase has been shown to re-localize to the cell interior. Thus, plant PCD-related proteases display both common (D-specific protein fragmentation during PCD) and distinct (enzyme structure and activity regulation) features with animal PCD-related proteases.