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1.  PA01.17. A clinical study to evaluate the effect of extract based herbal formulation on hypertension- a single blinded standard controlled randomized study 
Ancient Science of Life  2012;32(Suppl 1):S66-S67.
Purpose:
In Ayurveda although there is no such terminology like hypertension but still this work is an approach to establish relationship between Hypertension & vitiated functioning of three governing forces of our body i.e. Tridosha and to treat Hypertension on Ayurvedic principles. The logic behind such correlation is based on the fact that, like other physiological processes, B.P. too is normal phenomenon of our body which is governed by Tridosha. After going through modern pathogenesis of primary hypertension and its symptomology, in present study it has been correlated with Vata Kaphaja Vikara with Rasavaha, Raktavaha and Manovahi Srotas as the seat of disease. Looking at its pathogenesis, the term Uccha Vyan Bala (exaggerated physiological functioning of Vyan Vayu leading to increase contractility of heart & blood vessels) can be coined for hypertension.
Method:
Subjective criteria Headache, Palpitation, Vertigo, Dyspnoea on walks and Fatigue. Objective criteria BP value recorded by sphygmomanometer in supine position. Final assessment of results; Subjective assessment 75 to 100% disappearance of symptoms effectively cured. 50 to 74% disappearance of symptoms well cured. 25 to 49% disappearance of symptoms fairly cured. 0 to 24% disappearance of symptoms poorly cured. Objective assessment Patient showing reduction in BP by 10mmHg Poorly cured; Patient showing reduction in BP between 11 to 20mmHg Fairly cured; Patient showing reduction in BP between 21 to 30 mmHg Well cured; Patient showing reduction in BP by more than 30 mmHg Effectively cured. Research methodology Type of study-Single blinded comparative study. Study site IPD and OPD department of Shubhdeep ayurved medical college, Indore (MP). Sample size 50 patients divided randomly into two equal groups. Group A given trial drug whereas Group B given control drug. Drug dosage and vehicle 1 capsule twice daily with lukewarm water after meals. Duration of treatment one month (examined at weekly intervals.) Dietary advice to strictly restrict the daily intake of Amla, Lavana, Guru & Vidahi diet.
Result:
70% Patients found to be hypertensive were above 40 years of age. 60% Patients were fond of salty & spicy diet. Out of 50 patients 30 patients (60%) belongs to service class. Out of 50 patients 35 patients (70%) were male. Regarding prevalence of symptoms, Dyspnoea on routine work was found in 82%, Headache & palpitation in 80%, Vertigo in 78% & Fatigue in 66% patients.
Conclusion:
As per classical texts, Vata predominant diseases are caused due to vitiation of Vata due to emaciation (Dhatu Kshaya) & obstruction (Marg avarodha). Hypertension seems to be Vata predominant disease due to obstruction. Reason being that, Lavana is Vata Shamak, & should therefore decrease Blood pressure but on contrary it increases B.P. Similarly increase in weight leads to greater chances of High Blood pressure. Above discussion favours that Hypertension can be considered Vata predominant disease due to Marg avarodha by Kapha Dosha and Pitta Dosha in Anubandh. Finally it can be concluded that the drug under study has shown enthusiastic results in reducing the overall value of blood pressure. 64% patients got effectively cured, 24% got well cured and 12% got fairly cured. Regarding symptomatic relief, out of 25 patients 8 showed more than 75% relief, 9 showed more than 50% relief, 7 showed more than 25% relief and only 1 patient showed less than 25% relief in overall symptoms. No significant side effects have been reported in any subject.
PMCID: PMC3800947
2.  Critical appraisal of Doshavaha Srotas 
Ayu  2012;33(3):337-342.
Tridoshas viz Vata, Pitta, and Kapha are responsible for health and disease depending on their normalcy and disequilibrium state. Improper usage of foods and drinks along with abnormal activities manifests diseases of respective Doshik predominance. Sira (vein) is the synonym of Srotas, keeping this in mind, Vatavaha Sira is correlated with Vatavaha Srotas, Pittavaha Sira with Pittavaha Srotas, Kaphavaha Sira with Kaphavaha Srotas, and Sarvavaha Sira with Sarvavaha Srotas. The purpose of detail understanding of Doshavaha Srotas is essential to understand the role of Doshas in the manifestation of diseases. One can easily predict by observing the color changes in particular area to be able to predict the predominance of Doshas in that area. Manifestation of a disease occurs in the body as a result of the defective Srotas favoring the Dosha–Dushya conglomeration. Hence, any defect in the Srotas must be corrected quickly for the restoration of normal health. Present article emphasis on the proper understanding of Doshavaha Srotas in a systematic manner to understand its root, causative factors, signs and symptoms, and diseases produced due to their vitiation.
doi:10.4103/0974-8520.108819
PMCID: PMC3665105  PMID: 23723638
Kapha; nanatmaja vikara; pitta; Sarvavaha Srotas; sira; vata
3.  Infertility caused by tubal blockage: An ayurvedic appraisal 
Ayu  2010;31(2):159-166.
Tubal blockage is one of the most important factors for female infertility. This condition is not described in Ayurvedic classics, as the fallopian tube itself is not mentioned directly there. The present study is an effort to understand the disease according to Ayurvedic principles. Correlating fallopian tubes with the Artavavaha (Artava-bija-vaha) Srotas, its block is compared with the Sanga Srotodushti of this Srotas. Charak's opinion that the diseases are innumerable and newly discovered ones should be understood in terms of Prakriti, Adhishthana, Linga, and Aayatana, is followed, to describe this disease. An effort has been made to evaluate the role of all the three Doshas in producing blockage, with classification of the disease done as per the Dasha Roganika.
doi:10.4103/0974-8520.72378
PMCID: PMC3215358  PMID: 22131704
Artavadiushti; Asrigdara; Bandhyatva; Rati-janya Vikara; Tubal blockage; Yonivyapada; Infertility
4.  A comparative study of Shvasahara Leha and Vasa Haritaki Avaleha in the management of Tamaka Shvasa (Bronchial Asthma) 
Ayu  2011;32(4):500-506.
Tamaka Shvasa is a type of Shvasa Roga associated with difficulty in breathing as a result of which the patient prefers to sit in bed to get relief from his discomfort. Movement of air through Pranavaha Srotas is hampered in this disease resulting in the cry of organ heading toward complete failure for want of air. Tamaka Shvasa is well known for its episodic and chronic course which comes under the life-threatening disease. It is analogous to bronchial asthma due to similarity in symptoms, pathogenesis, onset, causes, and precipitating factors. In this study, 40 patients of Tamaka Shvasa were registered and randomly divided into two groups, out of which 31 patients completed the treatment. In Group A, Shvasahara Leha (5 g twice a day) was given for 2 months, while in Group B Vasa Haritaki Avaleha (5 g twice a day) was given for 2 months and follow-up was done for one month in both groups. The effects of therapy in both groups were assessed by a specially prepared proforma. Diagnosis was done by adult asthma diagnosis questionnaire and differential diagnosis with COPD (Chronic obstructive pulmonary disease) was done by differential diagnosis questionnaire as both these conditions are overlapping. The results of the study indicate that the Vasa Haritaki Avaleha provided better relief than Shvasahara Leha in Tamaka Shvasa.
doi:10.4103/0974-8520.96123
PMCID: PMC3361925  PMID: 22661844
Bronchial asthma; Shvasahara Leha; Tamaka Shvasa; Vasa Haritaki Avaleha
5.  Critical analysis of herbs acting on Mutravaha srotas 
Ayu  2010;31(2):167-169.
Ayurveda has given prime importance to Mutravaha srotas (urinary system) and Srotogata Vikaras (urinary disorders). Being a system responsible for homeostasis of fluids in the body it also detoxifies the body by eliminating certain waste products through urine. When diseased, people produce symptoms such as, increased or decreased urine production, painful maturition, formation of stones, and thereby obstructed micturition, increased frequency of micturition, and so on. There are many herbs with varied actions specifically aimed at mitigating urinary system disorders. Drugs such as Jambu, Amrasthi, and the like, reduce the increased flow of urine, and hence, are considered as Mutrasangrahaneeya, whereas, drugs like Ikshu, Kustha, and so on, increase the flow of urine, and hence, are considered as Mutravirechaneeya. There are drugs like Padma, Utpala, and so on, which impart normal color to the urine and are known as Mutravirajaneeya dravyas. Asmarighna dravyas break down the calculi and remove them through the urine. These dravyas, when used under proper direction, help in relieving the pain and apathy caused by the disease.
doi:10.4103/0974-8520.72379
PMCID: PMC3215359  PMID: 22131705
Ashmarighna dravya; Mutrasangrahaneeya dravya; Mutravirajaneeya dravya; Mutravirechaneeya dravya; urinary system; herbs
6.  OA03.07. A comparative clinical study to evaluate the therapeutic effect of shivagutika in patients with H.I.V infection 
Ancient Science of Life  2013;32(Suppl 2):S30.
Purpose:
HIVAIDS is the most dreaded challenge that the today's medical world is facing! As patients do not have many options, they tend to look at ayurveda to help improve their condition clinical presentation of HIV is akin to the description of Rajayakshma characterized by involvement of multiple srotas and presenting with diarrhea, cough, fever and similar other symptoms. Shiva guttika is used here as a rasayana to improve the immunity.
Method:
A Single blind comparative clinical study with Pretest & Post test design. The patients were randomly categorized into two groups as shivagutika group and ART group consisting of 20 patients each Shivagutika group In this group the 20 patients were treated orally with shivagutika in a dose of 12 grams od, for 6 months ART group In this the patients were treated with ART for six months.
Result:
The criteria's selected for the evaluation like Cough, Dyspnoea, fever,body weight, HB%, ESR, CD4 count etc all were statistically analyzed. Following medication with shivagutika the value of cd4 count was 567 in comparison to initial value of 391. in the ART group the initial value of 417.6 increased to 447.6 following treatment.
Conclusion:
CD4 count affirms the therapeutic benefit of shivagutika in HIV infection /AIDS beyond doubt Various other vyadhi hara rasayanas can be used in the management of immuno compromised conditions and in reoccurant diseases.
doi:10.4103/0257-7941.123844
PMCID: PMC4147500
7.  Experimental evaluation of Hingusauvarchaladi Ghrita and Saptavartita Hingusauvarchaladi Ghrita with special reference to their anticonvulsant activity 
Ayu  2010;31(4):500-503.
Incidence of epilepsy is 0.3 to 0.5% in different populations throughout the world, and the prevalence of epilepsy has been estimated at 5 to 10 persons per 1000. Scanning of the Ayurvedic classics reveals that 90% of the formulations mentioned to have action on sajnavaha srotas are ghrita-based formulations. Ghrita because of its yogavahi guna, incorporates the qualities of the drugs added to it without losing its own qualities. In the present study Hingusauvarchaladi ghrita and saptavartita Hingusauvarchaladi ghrita have been selected, to prove their anticonvulsant activity experimentally on albino mice, by the chemoshock method. The observations recorded have been analyzed by one-way ANOVA followed by Scheffe's test, statistically. Saptavartita Hingusauvarchaladi ghrita has shown better anticonvulsant activity in comparison to Hingusauvarchaladi ghrita.
doi:10.4103/0974-8520.82037
PMCID: PMC3202270  PMID: 22048547
Hingusauvarchaladi ghrita; Clonus; Seizures; Convulsion; Pentylenetetrazol; Sneha Kalpana
8.  Modifiable Etiological Factors and the Burden of Stroke from the Rotterdam Study: A Population-Based Cohort Study 
PLoS Medicine  2014;11(4):e1001634.
Using data from the Rotterdam study, Michiel Bos and colleagues estimate the proportion of strokes that are attributable to established modifiable etiological factors for stroke.
Please see later in the article for the Editors' Summary
Background
Stroke prevention requires effective treatment of its causes. Many etiological factors for stroke have been identified, but the potential gain of effective intervention on these factors in terms of numbers of actually prevented strokes remains unclear because of the lack of data from cohort studies. We assessed the impact of currently known potentially modifiable etiological factors on the occurrence of stroke.
Methods and Findings
This population-based cohort study was based on 6,844 participants of the Rotterdam Study who were aged ≥55 y and free from stroke at baseline (1990–1993). We computed population attributable risks (PARs) for individual risk factors and for risk factors in combination to estimate the proportion of strokes that could theoretically be prevented by the elimination of etiological factors from the population.
The mean age at baseline was 69.4 y (standard deviation 6.3 y). During follow-up (mean follow-up 12.9 y, standard deviation 6.3 y), 1,020 strokes occurred. The age- and sex-adjusted combined PAR of prehypertension/hypertension, smoking, diabetes mellitus, atrial fibrillation, coronary disease, and overweight/obesity was 0.51 (95% CI 0.41–0.62) for any stroke; hypertension and smoking were the most important etiological factors. C-reactive protein, fruit and vegetable consumption, and carotid intima-media thickness in combination raised the total PAR by 0.06. The PAR was 0.55 (95% CI 0.41–0.68) for ischemic stroke and 0.70 (95% CI 0.45–0.87) for hemorrhagic stroke.
The main limitations of our study are that our study population comprises almost exclusively Caucasians who live in a middle and high income area, and that risk factor awareness is higher in a study cohort than in the general population.
Conclusions
About half of all strokes are attributable to established causal and modifiable factors. This finding encourages not only intervention on established etiological factors, but also further study of less well established factors.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, 15 million people worldwide have a stroke. About 6 million of these people die within hours, and another 5 million are left disabled. Stroke occurs when the brain's blood supply is suddenly interrupted by a blood vessel in the brain being blocked by a blood clot (ischemic stroke) or bursting (hemorrhagic stroke). Deprived of the oxygen normally carried to them by the blood, the brain cells near the blockage die. The symptoms of stroke depend on which part of the brain is damaged but include sudden weakness or paralysis along one side of the body, vision loss in one or both eyes, and trouble speaking or understanding speech. Anyone experiencing these symptoms should seek immediate medical attention because prompt treatment can limit the damage to the brain. In the longer term, post-stroke rehabilitation can help overcome the disabilities caused by stroke, and various drugs alongside behavioral counselling can reduce the risk of a second stroke.
Why Was This Study Done?
Fifty years ago, it was discovered that treatment of high blood pressure (hypertension) reduces the risk of stroke among people with severe hypertension. This discovery led researchers to search for other potentially modifiable etiological factors for stroke (risk factors that cause stroke). The list of established etiological factors now includes smoking, diabetes, atrial fibrillation (an irregular heartbeat), heart disease, and overweight/obesity, in addition to hypertension. But how many strokes would modification of these causal risk factors prevent? In this population-based cohort study, the researchers calculate the individual and combined population attributable risks (PARs) for these established etiological factors to provide an estimate of what proportion of strokes could theoretically be prevented by optimal treatment of known etiological factors. A population-based cohort study enrolls a group of people, determines their characteristics at baseline, and follows them to see whether specific characteristics are associated with specific outcomes. A PAR of an etiological factor for a disease indicates the proportion of that disease in the population that would not occur in the absence of the risk factor.
What Did the Researchers Do and Find?
The researchers used data from 6,844 participants in the Rotterdam Study, which was designed to investigate the causes and consequences of long-term and disabling diseases in the elderly. At baseline, all of the participants were over 55 years old and free from stroke. During follow-up, 1,020 strokes occurred among the participants. Using data on exposure at baseline to various etiological factors for stroke, the researchers calculated PARs for individual factors and used a special statistical technique to calculate PARs for the factors in combination. The combined PAR of prehypertension/hypertension, smoking, diabetes, atrial fibrillation, heart disease, and overweight/obesity was 0.51 for any stroke. That is, about half of the strokes in the study population were attributable to this combination of etiological factors. Hypertension and smoking were the most important individual factors (PARs of 0.36 and 0.16, respectively). Notably, the inclusion of several less well established etiological factors (increased blood levels of C-reactive protein, low fruit and vegetable consumption, and thickening of the lining of arteries) only raised the total PAR for any stroke by 0.06.
What Do These Findings Mean?
These findings indicate that about half of the strokes in the study cohort were attributable to established modifiable etiological factors and could theoretically be prevented by eliminating these risk factors from the population. Previous studies have estimated that a larger proportion of strokes could be prevented by eliminating known etiological factors. The researchers acknowledge that some aspects of their study may have led to an underestimation of the proportion of stroke attributable to established etiological factors and note that their findings may not be generalizable to underprivileged or racially diverse populations. Nevertheless, they argue that previous studies are likely to have overestimated the PARs for stroke because they were based on case–control studies (in which exposure to etiological factors was assessed after a stroke had occurred in cases and control individuals, rather than before a stroke as in a population-based cohort study) and often did not use optimal statistical techniques to calculate the total PAR. Importantly, these new findings underscore the importance of interventions targeted at reducing smoking and hypertension and support the search for additional etiological factors for stroke.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001634.
The US National Institute of Neurological Disorders and Stroke provides information about all aspects of stroke (in English and Spanish); its Know Stroke site provides educational materials about stroke prevention, treatment, and rehabilitation including personal stories (in English and Spanish); the US National Institutes of Health SeniorHealth website has additional information about stroke
The Internet Stroke Center provides detailed information about stroke for patients, families, and health professionals (in English and Spanish)
The UK National Health Service Choices website also provides information about stroke for patients and their families, including personal stories
MedlinePlus has links to additional resources about stroke (in English and Spanish)
Information about the Rotterdam Study is available
The UK not-for-profit website Healthtalkonline provides personal stories about stroke
doi:10.1371/journal.pmed.1001634
PMCID: PMC4004543  PMID: 24781247
9.  Ancient-modern concordance in Ayurvedic plants: some examples. 
Environmental Health Perspectives  1999;107(10):783-789.
Ayurveda is the ancient (before 2500 b.c.) Indian system of health care and longevity. It involves a holistic view of man, his health, and illness. Ayurvedic treatment of a disease consists of salubrious use of drugs, diets, and certain practices. Medicinal preparations are invariably complex mixtures, based mostly on plant products. Around 1,250 plants are currently used in various Ayurvedic preparations. Many Indian medicinal plants have come under scientific scrutiny since the middle of the nineteenth century, although in a sporadic fashion. The first significant contribution from Ayurvedic materia medica came with the isolation of the hypertensive alkaloid from the sarpagandha plant (Rouwolfia serpentina), valued in Ayurveda for the treatment of hypertension, insomnia, and insanity. This was the first important ancient-modern concordance in Ayurvedic plants. With the gradual coming of age of chemistry and biology, disciplines central to the study of biologic activities of natural products, many Ayurvedic plants have been reinvestigated. Our work on Commiphora wightti gum-resin, valued in Ayurveda for correcting lipid disorders, has been described in some detail; based on these investigations, a modern antihyperlipoproteinemic drug is on the market in India and some other countries. There has also been concordance for a few other Ayurvedic crude drugs such as Asparagus racemosus, Cedrus deodara, and Psoralea corylifolia.
Images
PMCID: PMC1566595  PMID: 10504143
10.  Postprandial transduodenal bolus transport is regulated by complex peristaltic sequence 
AIM: To study the relationship between the patterns of postprandial peristalsis and transduodenal bolus transport in healthy subjects.
METHODS: Synchronous recording of chyme transport and peristaltic activity was performed during the fasting state and after administration of a test meal using a special catheter device with cascade configuration of impedance electrodes and solid-state pressure transducers. The catheter was placed into the duodenum, where the first channel was located in the first part of the duodenum and the last channel at the duodenojejunal junction. After identification of previously defined chyme transport patterns the associated peristaltic patterns were analyzed.
RESULTS: The interdigestive phase 3 complex was reliably recorded with both techniques. Of 497 analyzed impedance bolus transport events, 110 (22%) were short-spanned propulsive, 307 (62%) long-spanned propulsive, 70 (14%) complex propulsive, and 10 (2%) retrograde transport. Short-spanned chyme transports were predominantly associated with stationary or propagated contractions propagated over short distance. Long-spanned and complex chyme transports were predominantly associated with propulsive peristaltic patterns, which were frequently complex and comprised multiple contractions. Propagated double wave contraction, propagated contraction with a clustered contraction, and propagated cluster of contractions have been identified to be an integralted part of a peristaltic sequence in human duodenum.
CONCLUSION: Combined impedancometry and manometry improves the analysis of the peristaltic patterns that are associated with postprandial transduodenal chyme transport. Postprandial transduodenal bolus transport is regulated by propulsive peristaltic patterns, which are frequently complex but well organized. This finding should be taken into consideration in the analysis of intestinal motility studies.
doi:10.3748/wjg.v12.i37.6008
PMCID: PMC4124409  PMID: 17009400
Transduodenal bolus transport; Organization of duodenal peristalsis; Combined impedance manometry
11.  Abnormal postprandial duodenal chyme transport in patients with long standing insulin dependent diabetes mellitus 
Gut  1997;41(5):624-631.
Abstract 
Background—Patients with long standing diabetes mellitus frequently have upper gut dysmotility. Gastroparesis has been well studied, whereas detailed data on duodenal motor function are limited. 
Aims—To characterise postprandial duodenal chyme transport in such patients. 
Methods—Intraluminal multiple impedance measurement, recently introduced as a novel technique for investigation of chyme transport, was used to study postprandial duodenal chyme flow in 10 patients with long standing insulin dependent diabetes mellitus with gastroparesis, and 10 healthy volunteers. 
Results—Four distinct transport patterns of chyme, termed bolus transport events (BTEs), were found in both groups and could be characterised as: short distance propulsive; simple long distance propulsive; retrograde; and complex long distance propulsive. Diabetic patients had significantly lower numbers of propulsive BTEs (p<0.01), and higher proportions of retrograde BTEs and complex long distance BTEs (p<0.05) than control subjects, whereas the proportion of simple long distance BTEs was significantly lower (p<0.05). The mean propagation velocities of the BTEs were similar in both groups. 
Conclusion—Abnormal postprandial duodenal chyme transport was found in patients with long standing insulin dependent diabetes mellitus. This is characterised by transport disorganisation and may result in disturbed chyme clearance. 


Keywords: diabetic gastroparesis syndrome; postprandial chyme transport; intraluminal impedance measurement
PMCID: PMC1891578  PMID: 9414968
12.  OA02.17. Medicinal plant tissue culture and its ayurvedic perspective. 
Ancient Science of Life  2013;32(Suppl 2):S23.
Purpose:
Introduction of Plant tissue culture (PTC) concept to the Ayurveda realm.
Method:
1. Analysis of principles the plant tissue culture based on the literature review and real wet lab images of tissue culture 2. Analysis of ayurvedic principles which are relevant in the context 3. Logical concept development.
Result:
Plant tissue culture is based on the natural ability of plant cells to grow in to fullfledged organism, called as totipotency. Plant cell can exhibit totipotency only when it is placed in a suitable micro condition where it is supplied with all essential nutrients such as minerals, water, light source, carbon source and air. Two branches of tissue culture a. micropropagation b. in vitro adventitious root development (Sivakumar 2006), are relevant for ayurvedic industry in purview of increasing demand for good quality raw materials and decreasing wild sources of medicinal plants. Ayurvedic concept of Anukta dravya grahana (Reddy 2008; Kusuma and Joshi 2010) describes the need for understanding the properties of an undocumented drug or medicinal plant experimentally before considering it as an ayurvedic drug. Ayurvedic system dravya guna vijnana is for understanding and classification of medicinal plants based on their seven fold properties (Valiathan 2003). The concept of ‘Abhava prathinidhi dravya’ (Padma et al. 2010) explains the situations where original drugs are substituted with substances of similar qualities, which were prescribed in case of several unavailable or rare drugs. The efficacy of medicinal plants or plant part produced through tissue culture has to be determined even though those are botanically and genetically the same. Rasanirdharana method (Dhyani 2008) can be combined efficiently with phytochemical screening for this purpose.
Conclusion:
Plant materials produced through PTC can be ideologically acceptable for ayurvedic industry when principles of plant tissue culture is analysed in detail in the light of certain ayurvedic principles.
doi:10.4103/0257-7941.123837
PMCID: PMC4147492
13.  Incorporating Information of microRNAs into Pathway Analysis in a Genome-Wide Association Study of Bipolar Disorder 
Frontiers in Genetics  2012;3:293.
MicroRNAs (miRNAs) are known to be important post-transcriptional regulators that are involved in the etiology of complex psychiatric traits. The present study aimed to incorporate miRNAs information into pathway analysis using a genome-wide association dataset to identify relevant biological pathways for bipolar disorder (BPD). We selected psychiatric- and neurological-associated miRNAs (N = 157) from PhenomiR database. The miRNA target genes (miTG) predictions were obtained from microRNA.org. Canonical pathways (N = 4,051) were downloaded from the Molecule Signature Database. We employed a novel weighting scheme for miTGs in pathway analysis using methods of gene set enrichment analysis and sum-statistic. Under four statistical scenarios, 38 significantly enriched pathways (P-value < 0.01 after multiple testing correction) were identified for the risk of developing BPD, including pathways of ion channels associated (e.g., gated channel activity, ion transmembrane transporter activity, and ion channel activity) and nervous related biological processes (e.g., nervous system development, cytoskeleton, and neuroactive ligand receptor interaction). Among them, 19 were identified only when the weighting scheme was applied. Many miRNA-targeted genes were functionally related to ion channels, collagen, and axonal growth and guidance that have been suggested to be associated with BPD previously. Some of these genes are linked to the regulation of miRNA machinery in the literature. Our findings provide support for the potential involvement of miRNAs in the psychopathology of BPD. Further investigations to elucidate the functions and mechanisms of identified candidate pathways are needed.
doi:10.3389/fgene.2012.00293
PMCID: PMC3524550  PMID: 23264780
microRNA; bipolar disorder; pathway analysis; genome-wide association; ion channel
14.  Trinitrophenyl-ATP blocks colonic Cl- channels in planar phospholipid bilayers. Evidence for two nucleotide binding sites 
The Journal of General Physiology  1993;101(4):545-569.
Outwardly rectifying 30-50-pS Cl- channels mediate cell volume regulation and transepithelial transport. Several recent reports indicate that rectifying Cl- channels are blocked after addition of ATP to the extracellular bath (Alton, E. W. F. W., S. D. Manning, P. J. Schlatter, D. M. Geddes, and A. J. Williams. 1991. Journal of Physiology. 443:137-159; Paulmichl, M., Y. Li, K. Wickman, M. Ackerman, E. Peralta, and D. Clapham. 1992. Nature. 356:238-241). Therefore, we decided to conduct a more detailed study of the ATP binding site using a higher affinity probe. We tested the ATP derivative, 2',3',O-(2,4,6- trinitrocyclohexadienylidene) adenosine 5'-triphosphate (TNP-ATP), which has a high affinity for certain nucleotide binding sites. Here we report that TNP-ATP blocked colonic Cl- channels when added to either bath and that blockade was consistent with the closed-open-blocked kinetic model. The TNP-ATP concentration required for a 50% decrease in open probability was 0.27 microM from the extracellular (cis) side and 20 microM from the cytoplasmic (trans) side. Comparison of the off rate constants revealed that TNP-ATP remained bound 28 times longer when added to the extracellular side compared with the cytoplasmic side. We performed competition studies to determine if TNP-ATP binds to the same sites as ATP. Addition of ATP to the same bath containing TNP-ATP reduced channel amplitude and increased the time the channel spent in the open and fast-blocked states (i.e., burst duration). This is the result expected if TNP-ATP and ATP compete for block, presumably by binding to common sites. In contrast, addition of ATP to the bath opposite to the side containing TNP-ATP reduced amplitude but did not alter burst duration. This is the result expected if opposite-sided TNP- ATP and ATP bind to different sites. In summary, we have identified an ATP derivative that has a nearly 10-fold higher affinity for reconstituted rectifying colonic Cl- channels than any previously reported blocker (Singh, A. K., G. B. Afink, C. J. Venglarik, R. Wang, and R. J. Bridges. 1991. American Journal of Physiology. 260 [Cell Physiology. 30]:C51-C63). Thus, TNP-ATP should be useful in future studies of ion channel nucleotide binding sites and possibly in preliminary steps of ion channel protein purification. In addition, we have obtained good evidence that there are at least two nucleotide binding sites located on opposite sides of the colonic Cl- channel and that occupancy of either site produces a blocked state.
PMCID: PMC2216774  PMID: 8389396
15.  PA01.13. Hemiplegia - An ayurvedic perspective 
Ancient Science of Life  2012;32(Suppl 1):S62.
Purpose:
Hemiplegia is a prevalent and disabling neurological disorder, which arises from multiple etiologies like Systemic Hypertension, Injuries, Tumors, Embolism and other vascular occlusions of the brain. It is well explained in Ayurveda as Pakshaghata one of the kevala vata vyadhis, resulting when Vatakopa affects the Siras (vascular structures) and Snayus (Tendons and Ligaments) of any one half of the body characterized by paralysis of the affected half of the body, face and impaired movements of joints and extremities. In modern science, the lesion and clinical symptoms stands classified in accordance with the site of infarction of the brain. Hemiplegia Pakshaghata however today, currently challenges the clinicians warranting a comprehensive and effective medication. Ayurvedic polyherbal formulations have been found to have therapeutic efficacy for Hemiplegia. This study aims to determine the clinical efficacy of Danadanayanadi Kasayam, Ksheerabala Avarthi and Ekangavir Ras towards restoring the normalcy in Pakshaghata.
Method:
15 patients in the age group of 30 70 with Pakshaghata were randomly selected and administered Danadanayanadi Kasayam, Ksheerabala Avarthi and Ekangavir Ras for a period of 6 - 8 weeks. The clinical progress of the patients was observed daily. The gradual recovery from the clinical symptoms was observed and documented.
Result:
The patients administered with the trial drugs portrayed a marked recovery from the inability to move the arms and legs, stiffness, incoherent speech, deviation of mouth, hyperreflexia, poor concentration, confusions and impaired functions of the sensory organs.
Conclusion:
It is extrapolated and fortified from the observations that Ayurvedic polyherbal formulations viz. Danadanayanadi Kasayam, Ksheerabala Avarthi and Ekangavir Ras undoubtedly has the efficacy of treating Hemiplegia and helps in the recovery from ailment.
PMCID: PMC3800943
16.  Prostaglandin E2 activates clusters of apical Cl- channels in principal cells via a cyclic adenosine monophosphate-dependent pathway. 
Journal of Clinical Investigation  1994;93(2):829-837.
We examined cell-attached patches on principal cells of primary cultured, rabbit cortical collecting tubules. Under basal conditions, apical 9-pS Cl(-)-selective channels were observed in 9% of patches (11/126), and number of channels times open probability (NP0) was 0.56 +/- 0.21. The channel had a linear current-voltage relationship, reversal potential (Erev) near resting membrane potential, a P0 (0.30-0.70) that was independent of voltage, and complicated kinetics (i.e., bursting) at hyperpolarized potentials. NP0 and channel frequency were increased after 30 min of basolateral exposure to 0.5 microM PGE2 (18/56), 10 microM forskolin (23/36), or 0.5 mM dibutyryl cyclic adenosine monophosphate (cAMP) (25/41). Increases in NP0 appeared to be mediated primarily through an increase in the number of observed channels per patch (N), not changes in P0. After these cAMP-increasing maneuvers, N was inconsistent with a uniform distribution of channels in the apical membrane (P < 0.001), but rather the channels appeared to be clustered in pairs. Apical 0.5 microM PGE2 (12/91), apical or basolateral 0.5 microM PGF2 alpha (8/110), or 0.25 microM thapsigargin (releaser of intracellular Ca2+ stores) (7/73) did not increase NP0 or channel frequency. Conclusions: (a) 9-pS Cl- channels provide a conductive pathway for apical membrane Cl- transport across principal cells. (b) Channel activation by basolateral PGE2 is mediated via a cAMP-, but not a Ca(2+)-dependent mechanism. (c) Apical channels are clustered in pairs. (d) With its low baseline frequency and Erev near resting membrane potential, this channel would not contribute significantly to transcellular Cl- flux under basal conditions. (e) However, cAMP-producing agonists (i.e., PGE2, arginine vasopressin) would increase apical Cl- transport with the direction determined by the apical membrane potential.
PMCID: PMC293942  PMID: 8113415
17.  Provocative dietary factors in geriatric hypertension: A surveillance study 
Ayu  2012;33(4):530-536.
Hypertension is the most common psychosomatic disorder affecting 972 million people worldwide being more prevalent in old age. The present survey of hypertensive patients fulfilling the standard diagnostic criteria of WHO/ISH (2004) is carried out in geriatric age group from the Saurashtra region of Gujarat in India to observe the dietary pattern and provocative factors. Total 120 patients of 50 to 80 years of age having systolic blood pressure >140 mm Hg and ≤180 mm Hg and diastolic blood pressure >90 mm Hg and ≤110 mm Hg irrespective of gender and religion were selected for the present study. They were interviewed for list of provocative factors enlisted in Ayurveda. As observed, the study supported the facts described in Ayurveda that dietary etiological factors, such as excess intake of Lavana (salty), Amla (sour), Katu (pungent), Tikshna, Ushna (hot), Vidahi (producing burning sensation), Viruddha (incompatible), Snigdha (unctuous), Abhishyandi (leading to obstruction), Madhura (sweet), Guru (heavy to digest) dietary articles, Ajirnashana (taking diet before complete digestion of previous meal), Adhyashana (repeated eating at short intervals), will vitiate Rakta dhatu as well as Pitta dosha in the body leading to disorders like hypertension. Hypertension in old age is found to be a disease of Vata-Pitta dominant vitiation with the involvement of Rasa, Rakta, Meda as main Dushya (vitiated factors) and dietary factors can contribute to worsening of the disease. The etiological factors having role in the pathogenesis can also be applied for preventive guidelines for the management of hypertension.
doi:10.4103/0974-8520.110537
PMCID: PMC3665196  PMID: 23723671
Ayurveda; dietary factors; geriatric age group; hypertension
18.  Inhibition of apical Na+ channels in rabbit cortical collecting tubules by basolateral prostaglandin E2 is modulated by protein kinase C. 
Journal of Clinical Investigation  1992;90(4):1328-1334.
We used the cell-attached patch clamp technique to investigate the interaction of exogenous prostaglandins (PG), intracellular [Ca2+]i, and protein kinase C (PKC) on the high selectivity, 4 pS Na+ channel found in the principal cell apical membrane of rabbit cortical collecting tubule (CCT) cultures grown on collagen supports with 1.5 microM aldosterone. Application of 0.5 microM PGE2 to the basolateral membrane decreased mean NP0 (number of channels times the open probability) for apical Na+ channels by 46.5% (n = 9). There was no consistent change in NP0 after apical 0.5 microM PGE2 (n = 12) or after apical or basolateral 0.5 microM PGF2 alpha (n = 8). Release of [Ca2+]i stores with 0.25 microM thapsigargin (n = 7), or activation of apical membrane PKC with apical 0.1 microM 4 beta-phorbol-12-myristate-13-acetate (n = 5) or 10 microM 1-oleyl-2-acetylglycerol (n = 4) also decreased NP0. Depletion of [Ca2+]i stores (0.25 microM thapsigargin pretreatment) (n = 7) or inhibition of apical PKC (100 microM D-sphingosine pretreatment) (n = 8) abolished the inhibitory effects of basolateral PGE2. Conclusions: (a) apical Na+ transport in rabbit CCT principal cells is modulated by basolateral PGE2; (b) the mechanism involves release of IP3-sensitive, [Ca2+]i stores; and (c) Ca(2+)-dependent activation of apical membrane PKC, which then inhibits apical Na+ channels.
Images
PMCID: PMC443177  PMID: 1328297
19.  Compartment Syndrome: Diagnosis, Management, and Unique Concerns in the Twenty-First Century 
HSS Journal  2014;10(2):143-152.
Background
Compartment syndrome is an elevation of intracompartmental pressure to a level that impairs circulation. While the most common etiology is trauma, other less common etiologies such as burns, emboli, and iatrogenic injuries can be equally troublesome and challenging to diagnose. The sequelae of a delayed diagnosis of compartment syndrome may be devastating. All care providers must understand the etiologies, high-risk situation, and the urgency of intervention.
Questions/Purposes
This study was conducted to perform a comprehensive review of compartment syndrome discussing etiologies, risk stratification, clinical progression, noninvasive and invasive monitoring, documentation, medical-legal implication, and our step-by-step approach to compartment syndrome prevention, detection, and early intervention.
Methods
A literature search was performed using the PubMed Database and the following search terms: “Compartment syndrome AND Extremity,” “Compartment syndrome AND Gluteal,” and Compartment syndrome AND Paraspinal.” A total of 2,068 articles were identified. Filters allowed for the exclusion of studies not printed in English (359) and those focusing on exertional compartment syndrome (84), leaving a total of 1,625 articles available for review.
Results
The literature provides details regarding the etiologies, risk stratification, clinical progression, noninvasive and invasive monitoring, documentation, medical-legal implication, and our step-by-step approach to compartment syndrome prevention, detection, and early intervention. The development and progression of compartment syndrome is multifactorial, and as complexity of care increases, the opportunity for the syndrome to be missed is increased. Recent changes in the structure of in-hospital medical care including resident work hour restrictions and the incorporation of midlevel providers have increased the frequency of “signouts” or “patient handoffs” which present opportunities for the syndrome to be mismanaged.
Conclusion
The changing dynamics of the health care team have prompted the need for a more explicit algorithm for managing patients at risk for compartment syndrome to ensure appropriate conveyance of information among team members.
Electronic supplementary material
The online version of this article (doi:10.1007/s11420-014-9386-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s11420-014-9386-8
PMCID: PMC4071472  PMID: 25050098
compartment syndrome; intracompartmental pressure; ischemia
20.  Ayurvedic concepts related to psychotherapy 
Indian Journal of Psychiatry  2013;55(Suppl 2):S310-S314.
The perfect balance of mind, body and soul is considered as complete health in Ayurveda. Ayurveda has its own identity as most ancient and traditional System of Medicine in India. Even Ayurveda emphasizes its treatment modalities into three parts viz. Satwawajay Chikitsa, Yuktivyapashray and Daivyapashray Chikitsa. Sattvavajaya therapy mentioned in Charakasamhita and it used as new concept of psychotherapy in Ayurveda. The effectiveness of “traditional mental health promoting practices” was identified as health regimens (swasthvrtt), correct behavior (sadvrtt), and yoga. Sattvavajaya as psychotherapy, is the mental restraint, or a “mind control” as referred by Caraka, is achieved through “spiritual knowledge, philosophy, fortitude, remembrance and concentration. Ayurvedic psychotherapy would play a dual role: First, as a revival of authentic medical culture, the exercise of a practice with an assumed primordial dimension, and second as a discovery of authentic subjectivity, the revelation of a self with an assumed interior depth. When we integrate the contemporary art of psychotherapy with the ancient science of Ayurveda, it becomes a powerful combination that is called Psycho Veda. The integration of Psycho and Veda is motivated by the complete integration of the immense but fairly contemporary view of the mind, emotions and psyche and how this performs in our lives. Integrating Psychotherapy and Vedic principles teaches us how to rediscover critical knowledge and awareness of the natural forces and rhythms that compliment and strengthen our human experience, through the understanding of the psyche and what our inner experiences are and also involving practical daily activities with thorough attention to our total environment to bring about radical changes in our mental outlook and in physical health.
doi:10.4103/0019-5545.105556
PMCID: PMC3705701  PMID: 23858273
Achar rasayana; Ayurveda; psychotherapy; psychoveda; sattvavajaya
21.  A Role for Benzamil-Sensitive Proteins of the Central Nervous System in the Pathogenesis of Salt-Dependent Hypertension 
SUMMARY
While increasing evidence suggests that salt-sensitive hypertension is a disorder of the central nervous system, little is known about the critical proteins (e.g., ion channels or exchangers) that play a role in the pathogenesis of the disease.Central pathways involved in the regulation of arterial pressure have been investigated. In addition, systems such as the renin-angiotensin-aldosterone axis, initially characterized in the periphery, are present in the central nervous system, and seem to play a role in the regulation of arterial pressure.Central administration of amiloride, or its analogue benzamil hydrochloride, has been shown to attenuate several forms of salt-sensitive hypertension. In addition, intracerebroventricular (ICV) benzamil effectively blocks pressor responses to acute osmotic stimuli, such as ICV hypertonic saline. Amiloride or its analogues have been shown to interact with the brain renin-angiotensin-aldosterone system (RAAS) and to effect the expression of endogenous ouabain-like compounds; both could play a role in the interaction between amiloride compounds and arterial pressure. Peripheral treatments with benzamil, even at higher doses than those given centrally, have little or no effect on arterial pressure. These data provide strong evidence that benzamil-sensitive proteins (BSPs) of the central nervous system play a role in cardiovascular responsiveness to sodium.Mineralocorticoids have been linked to human hypertension; many patients with essential hypertension respond well to pharmacological agents antagonizing the mineralocorticoid receptor (MR), and certain genetic forms of hypertension are due to chronically elevated levels of aldosterone. The deoxycorticosterone acetate (DOCA) -salt model of hypertension is a benzamil-sensitive model that incorporates several factors implicated in the etiology of human disease, including mineralocorticoid action and increased dietary sodium. The DOCA-salt model is ideal for investigating the role of BSPs in the pathogenesis of hypertension, because mineralocorticoid action has been shown to modulate the activity of at least one benzamil-sensitive protein, the epithelial sodium channel (ENaC).Characterizing the BSPs involved in the pathogenesis of hypertension may provide a novel clinical target. Further studies are necessary to determine which BSPs are involved, and where in the nervous system they are located.
doi:10.1111/j.1440-1681.2008.04929.x
PMCID: PMC2693203  PMID: 18387084
Sympathetic Nervous System; Epithelial Sodium Channel (ENaC); Acid Sensitive Ion Channel (ASIC); Aldosterone; DOCA; Benzamil; Salt-sensitive Hypertension
22.  Heart Failure Etiology Is Usually Pluricausal Whether or Not There is Associated Coronary Disease 
The Permanente Journal  2007;11(1):13-18.
The heart failure syndrome (HF) has diverse etiologies. In a 22-year study of predictors of HF in 126,235 persons, we attempted to identify etiologic factors independent of associated coronary heart disease (CAD) in 2594 persons hospitalized for the condition. For this purpose, subjects were stratified according to whether CAD was present. Of the subjects, 60% had evidence for CAD (CAD-HF). Because we also wished to study HF predictors in subjects without associated CAD according to specific HF etiology, the paper records of the other 40% of subjects (non-CAD-HF) underwent a detailed review so that we could determine the apparent primary etiology and contributory factors. A random sample of all subjects with CAD-HF underwent a similar paper record review so that we could ascertain contributory factors. The primary etiology among the subjects with non-CAD-HF was categorized as systemic hypertension (HTN) in 354, valve disease in 110, cardiomyopathies (including alcoholic and idiopathic) in 93, other specific miscellaneous in 55, and primary etiology not evident (unclear) in 423. The unclear-group subjects generally had multiple probable contributing factors. In addition to the preponderant etiology in subjects with non-CAD-HF, the mean number of contributory factors was 1.5; among subjects with CAD-HF, the mean number of contributory factors was 1.9. Frequent additional factors, in both CAD-HF and non-CAD-HF, were HTN, diabetes mellitus, atrial fibrillation, and heavy alcohol consumption. These data show that primary HF etiology is often uncertain and that HF etiology is usually multifactorial, whether or not CAD is present.
PMCID: PMC3061373  PMID: 21472049
23.  Alpha1 Na,K-ATPase and Na,K,2Cl-cotransporte/D3mit3 loci interact to increase susceptibility to salt-sensitive hypertension in Dahl S(HSD) rats. 
Molecular Medicine  2001;7(2):125-134.
BACKGROUND: Essential (multigenic) hypertension is a complex multifactorial disease whose genetic etiology has not been unraveled on a major locus-effect investigative paradigm. As with other complex genetic diseases, applying an interacting loci paradigm could be critical in the elucidation of genetic determinants. Having defined the alpha1 Na,K-ATPase (alpha1NK) as a hypertension susceptibility gene in Dahl salt-sensitive (Dahl S) rats, we determined whether alphaINK interacts with another renal epithelial Na transporter to increase susceptibility to salt-sensitive hypertension. We focused on alpha1NK and Na,K,2Cl-cotransporter (NKC) as an a priori candidate interacting gene pair because they comprise a functionally linked Na transport system in renal thick ascending limb of Henle (TALH) epithelial cells and exhibit altered function in prehypertensive Dahl S rats in contrast to Dahl salt-resistant normotensive (Dahl R) rats. MATERIAL AND METHOD: Cosegregation analysis of alphaNK and NKC loci was done in a (Dahl S x Dahl R) F2 cohort characterized for blood pressure by radiotelemetry using the D2mghII microsatellite marker in the alpha1NK gene and the D3mit3 microsatellite marker close to the NKC gene (NKC/D3mit3 locus). Single locus and digenic analyses were performed to establish the individual and interactive genetic contribution to salt-sensitive hypertension. Molecular analysis was then done to support the NKC gene as the likely candidate gene interacting with alpha1NK in Dahl salt-sensitive hypertension pathogenesis. RESULTS: Compared with respective single locus analysis, digenic analysis of 96 F2 (Dahl S x Dahl R) hybrid male rats revealed cosegregation of alpha1NK and NKC/D3mit3 loci as interacting pair with salt-sensitive hypertension with markedly increased significance for systolic (one-way ANOVA p = 10(-6)), diastolic (p = 10(-5)), and mean arterial (p = 10(-6)) blood pressures. Concordantly, two-way ANOVA detected interaction between alpha1NK and NKC loci in determining the levels of systolic (p = 0.004), diastolic (p = 0.008), and mean arterial (p = 0.006) pressures. To unravel potential NKC molecular dysfunction(s) involved in hypertension pathogenesis, we investigated putative differences between Dahl S and Dahl R rats in nucleotide sequence and isoform gene expression of the renal-specific Na,K,2Cl-cotransporter. Molecular analysis revealed an inversion of alternatively spliced NKC-isoform ratios (4B:4A:4F) between Dahl S and Dahl R prehypertensive kidneys supported by four mutations in intron-3 immediately upstream to alternatively spliced exons 4B, 4A, and 4F. No nucleotide changes were detected within the aminoacid encoding exons of NKC. CONCLUSIONS: Altogether, these current data and previous characterization of the role of the Q276L alpha1NK molecular variant in Dahl S hypertension provide cumulative compelling evidence that alpha1NK and NKC/D3mit3 loci interact to increase susceptibility to hypertension in Dahl S rats and that NKC is the likely candidate gene that interacts with alpha 1NK. More importantly, the data substantiate gene interaction as an operative mechanism in multigenic hypertension.
PMCID: PMC1950017  PMID: 11471547
24.  Potential Therapeutic Benefits of Strategies Directed to Mitochondria 
Antioxidants & Redox Signaling  2010;13(3):279-347.
Abstract
The mitochondrion is the most important organelle in determining continued cell survival and cell death. Mitochondrial dysfunction leads to many human maladies, including cardiovascular diseases, neurodegenerative disease, and cancer. These mitochondria-related pathologies range from early infancy to senescence. The central premise of this review is that if mitochondrial abnormalities contribute to the pathological state, alleviating the mitochondrial dysfunction would contribute to attenuating the severity or progression of the disease. Therefore, this review will examine the role of mitochondria in the etiology and progression of several diseases and explore potential therapeutic benefits of targeting mitochondria in mitigating the disease processes. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate and manipulate mitochondrial function and genomics for therapeutic benefit. These approaches to treat mitochondrial dysfunction rationally could lead to selective protection of cells in different tissues and various disease states. However, most of these approaches are in their infancy. Antioxid. Redox Signal. 13, 279–347.
Introduction and Topics Reviewed
Anatomy and Function of Mitochondrial Membranes
Outer mitochondrial membrane and its potential role as therapeutic target
Inner mitochondrial membrane and its potential role as therapeutic target
Mitochondrial permeability transition pore
Electron Transport Chain and Oxidative Phosphorylation: Modulation by Mitochondrial Ion Channels and Exchangers
Mitochondrial ROS and RNS
Mitochondria and reactive oxygen species
Mitochondria and reactive nitrogen species
Mitochondrial ROS Scavenging and Its Potential Therapeutic Value
Manganese superoxide dismutase
Glutathione thioredoxin, and peroxiredoxin systems
Catalase and glutathione peroxidase
Cytochrome c
Mitochondria as scavengers of cytosolic O2•−
Uncoupling Proteins in Modulation of Mitochondrial Function: Physiological and Pharmacologic Relevance
Mitochondrial DNA-Related Pathologies and a Potential Therapeutic Target
Mitochondrial Interaction with other Organelles: Therapeutic Implications
Mitochondrion—mitochondrion interaction
Mitochondrion—nucleus interaction
Mitochondria—endoplasmic/sarcoplasmic reticulum interaction
Mitochondria-Related Diseases and Cell Injury
Mitochondria and cardiac ischemia and reperfusion injury
Mitochondria and the failing heart
Mitochondria and diabetes
Mitochondria and hypertension
Mitochondria and neurodegenerative diseases
Alzheimer's disease
Parkinson's disease
Amyotrophic lateral sclerosis
Friedreich's ataxia
Neoplastic diseases
Other mitochondria-related diseases
Mitochondria and psychiatric disorders
Mitochondria and migraine headache
Mitochondrial Pharmacology and Therapeutic Potential
Strategies for drug delivery to mitochondria
Mitochondria-targeted drugs
Approaches to improve mitochondrial function during ischemia and reperfusion
Preconditioning
Postconditioning
Other Mitochondrial Therapeutic Approaches
Lipid replacement therapy
Transactivator of transcription proteins and mitochondrial therapy
Molecular genetics approaches
Mitochondria and caloric restriction
Mitochondria and dietary supplements
Mitochondria Age and Lifespan
Mitochondria and age-associated diseases
Mitochondrial p66shc and lifespan
Caveats and Potential Limitations in Mitochondrial Drug Targeting
Conclusion and Perspectives
doi:10.1089/ars.2009.2788
PMCID: PMC2936955  PMID: 20001744
25.  Theoretical Study of the Transpore Velocity Control of Single-Stranded DNA 
The electrokinetic transport dynamics of deoxyribonucleic acid (DNA) molecules have recently attracted significant attention in various fields of research. Our group is interested in the detailed examination of the behavior of DNA when confined in micro/nanofluidic channels. In the present study, the translocation mechanism of a DNA-like polymer chain in a nanofluidic channel was investigated using Langevin dynamics simulations. A coarse-grained bead-spring model was developed to simulate the dynamics of a long polymer chain passing through a rectangular cross-section nanopore embedded in a nanochannel, under the influence of a nonuniform electric field. Varying the cross-sectional area of the nanopore was found to allow optimization of the translocation process through modification of the electric field in the flow channel, since a drastic drop in the electric potential at the nanopore was induced by changing the cross-section. Furthermore, the configuration of the polymer chain in the nanopore was observed to determine its translocation velocity. The competition between the strength of the electric field and confinement in the small pore produces various transport mechanisms and the results of this study thus represent a means of optimizing the design of nanofluidic devices for single molecule detection.
doi:10.3390/ijms150813817
PMCID: PMC4159826  PMID: 25116683
ssDNA; micro/nanofluidics; langevin dynamics simulation; transpore dynamics; coarse-graining

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