Early phase research in complementary and alternative medicine (CAM) is especially important because of the large influence it has on the subsequent expenditure of money and effort in particular areas of CAM therapies. The culture of biomedical research has, however, blurred the distinction between early and late-phase research, and this has distorted the very distinct aims of these two activities. The purpose of this paper is to reaffirm the critical role of early phase CAM research and to encourage CAM researchers to value and conduct early phase studies for their proper purposes.
To determine the potential toxicity and safety of the Chinese herbal medicine NPI-028 in rats following subchronic (3-month) exposure via daily oral consumption.
Subchronic toxicity was evaluated in four groups of rats (n = 10 per group) receiving NPI-028 orally at a dose of either 0.0 (normal diet control), 0.5, 1.0, or 2.0 g/kg, ingested as part of their daily diet for 3 months. NPI-028 was incorporated into powdered rat chow diet as a specific percent of the total diet provided each day. The primary active isoflavone content of NPI-028 (puerarin) used in the rat diet was also determined.
Subchronic toxicity was assessed over a 3-month period by biweekly measurement of water and food intake, weight gain, and visual inspection for maintenance of grooming and normal behavior. At the end of the study period rats were euthanized and blood was obtained for hematologic and chemical analysis. Organs were removed for histopathologic examination.
Rats in all three NPI-028 dose groups were similar to the control group in weight gain, food intake, and water intake over the study period. Hematology, blood chemistries, and organ histology in rats at all three NPI-028 doses did not significantly differ from control rats. Minor exceptions were elevated urea nitrogen values at all NPI-028 doses, and increased triglyceride and thyroid-stimulating hormone values in the lowest NPI-028 dose-treated group. Puerarin (used as a dietary isoflavone marker) content of NPI-028 was 26 mg/g dry weight.
NPI-028 ingested orally at doses up to 2.0 g/kg per day in the rat diet for up to 3 months resulted in normal growth with no changes in hematologic or hepatic parameters, and only minor alterations in renal and blood chemistry parameters. There was no evidence of abnormal histology. These data suggest the long-term daily oral consumption of NPI-028 as a part of the daily diet for 3 months, at the doses studied, is safe in rats. Thus, NPI-028 may potentially be safe for clinical use as an antidipsotropic agent.
This study was proposed to evaluate the reliability by 2005 Sasangin Diagnosis Questionnaire for Mongolian (05' SDQ-M).
Questions from the 05'SDQ were translated into Mongolian, and the 05'SDQ-M was constructed. The questionnaire was administered to 193 Mongolians and they were asked to complete the questionnaire again 2 weeks after the first administration. To evaluate the internal consistency, Cronbach's alpha coefficient was calculated. A reliability analysis for each individual question was conducted using the test-retest method to verify the independence and agreement between the questions. To verify independence, a chi(2) test with crosstabs analysis and p-values was used. The agreement verification was conducted by using the Cohen kappa coefficient. In addition, the constitutional variable was defined as the constitutional attribute of each question, and Pearson's correlation coefficient was confirmed after testing the scale.
After testing the internal consistency of the scale, the consistency was shown to range from 0.59 to 0.67, suggesting that the questions on the questionnaire were reliable. The test-retest method showed that Pearson's correlation coefficients for the results of the two tests ranged from 0.65 to 0.80. The x(2) test results indicated that one independent item demanded close attention. Among the other 123 questions, the agreement test revealed that 80 questions (64.5%) showed common agreement.
The aim of this study was to investigate the potential role of vitamin D in autism through serum level assessment.
This was a case-controlled cross-sectional study.
The study was conducted at the Out-patient Clinic for "Children with Special Needs" at the Medical Services Unit of the National Research Centre in Cairo, Egypt.
Seventy (70) children with autism diagnosed according to the DSM-IV criteria of the American Psychiatric Association were recruited for this study. The mean age +/- standard deviation (SD) of the patients was 5.3 +/- 2.8 years. Controls included 42 age-matched randomly selected healthy children of the same socioeconomic status (mean age +/- SD, 6.1 +/- 1.8 years).
Circulating levels of both forms of vitamin D (25(OH)D and 1,25(OH)(2)D) and serum calcium were measured for all subjects. Associations between vitamin D status, birth season, and clinical characteristics of autism were examined.
Children with autism had significantly lower 25(OH)D (p < 0.00001) and 1,25(OH)(2)D (p < 0.005) as well as lower calcium (p < 0.0001) serum values than the controls. A significant positive correlation was obtained between 25(OH)D and calcium (correlation coefficient r = 0.309, p < 0.01) within the children with autism. No significant difference was found on comparison of birth month and season of birth between children with autism and healthy controls. Furthermore, associations linking parental consanguinity or convulsions with vitamin D could not be established.
Serum values of 25(OH)D in the children with autism of this study could classify them as being "vitamin D inadequate," which lends support to the hypothesis that autism is a vitamin D deficiency disorder.
This study examines involvement with a range of complementary and alternative medicine (CAM) during pregnancy on the use of pharmacologic (PPMT) and nonpharmacologic (NPMT) pain management techniques for labor and birth.
Longitudinal analysis of survey data.
A substudy (n=2445) of the "young" cohort of the nationally representative Australian Longitudinal Study on Women's Health was conducted.
Use of PPMT and NPMT during labor and birth.
The survey was completed by 1835 women (response rate, 79.2%). Most respondents used either intrapartum PPMT (81.9%) or NPMT (74.4%). Many (60.7%) used some form of CAM during pregnancy and also used PPMT during birth. More than two thirds of women (66.7%) who used NPMT used CAM during pregnancy. There was a general trend of increased likelihood of NPMT use by women who applied CAM during pregnancy. There was an inverse effect on use of epidural analgesia for women who consumed herbal teas during pregnancy (odds ratio, 0.60).
Because of the study design, this paper does not confirm a causative relationship between the use of CAM during pregnancy and intrapartum pain management choices. It does, however, indicate that the use of CAM during pregnancy may not significantly affect the uptake of intrapartum PPMT, despite possible attempts to reduce PPMT by using NPMT. It also highlights the possibility of potential interactions between CAM and PPMT, given the high prevalence of concomitant use.
This study was performed to investigate the effect of immune-related acupuncture points on serum tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hsCRP) levels.
Ninety (90) healthy volunteers (aged 20-30 years) were randomly assigned into five equal groups. Acupuncture needles were placed into single acupoints bilaterally in each group. The points were Da Zhui (Du-14), Qu Chi (Li-11), Zu San Li (St-36), San Yin Jiao (Sp-6) and a sham point, which is not an acupoint. Manual acupuncture treatment was performed in 6 sessions of 30 minutes each, 3 times per week for 2 weeks. Serum samples were obtained before and after the acupuncture treatments and the serum TNF-α and hsCRP levels were measured.
The TNF-α values (mean ± standard deviation) in the Du-14, Li-11, St-36, Sp-6, and sham acupuncture groups at baseline were 37.63 ± 10.58, 37.36 ± 10.24, 33.83 ± 7.36, 35.73 ± 6.75, and 32.05 ± 5.66 pg/mL, respectively. After treatment, the mean TNF-α values were 35.89 ± 11.61, 34.80 ± 6.98, 35.89 ± 9.22, 33.30 ± 5.45, and 33.78 ± 5.98 pg/mL, respectively. In the serum TNF-α levels, no significant change was seen in any of the groups (p > 0.05). The mean hsCRP values in the Du-14, Li-11, St-36, Sp-6, and sham acupuncture groups at baseline were 0.90 ± 0.77, 1.07 ± 1.35, 0.77 ± 0.54, 0.75 ± 0.54, and 0.94 ± 0.68 mg/L, respectively. After treatment, they were 1.09 ± 1.17, 0.84 ± 0.43, 0.74 ± 0.49, 0.80 ± 0.53, and 0.62 ± 0.44 mg/L, respectively. In the statistical analysis, it was found that hsCRP levels were significantly reduced in the sham acupuncture group (p < 0.01). There was not any significant difference between acupuncture and sham groups in terms of serum TNF-α and hsCRP values (p > 0.05).
Acupoints, which are considered to have effects on the immune system, may not mediate the immune system via TNF-α, a known inflammatory cytokine, directly in healthy young individuals. However, the changes related to hsCRP values in the sham group need future confirmation studies.
Aqueous, methanolic, and dichloromethane extracts from 27 Lebanese plants were investigated for their in vitro immunomodulatory and antileishmanial activities as compared to their toxicity against human cells. Extracts from yellow chamomile (Anthemis tinctoria), white larkspur (Consolida rigida), Syrian broom (Cytisus syriacus), coast spurge (Euphorbia paralias), shield fibigia (Fibigia clypeata), Auchers golden-drop (Onosma aucheriana), shell-flower sage (Salvia multicaulis), snowy woundwort (Stachys nivea), Palestine woundwort (Stachys palaestina), and polium-leaved speedwell (Veronica polifolia) exhibited interesting antileishmanial activities on the intracellular amastigote form of the parasite, while several extracts from A. tinctoria, F. clypeata, and O. aucheriana were shown to induce nitrous oxide (NO) production by human macrophages. Further experiments should be performed in order to purify and characterize the chemical compounds responsible for these activities.
Although numerous trials have demonstrated the clinical effects of acupuncture, the mechanism of its therapeutic effect still remains uncertain. Recent neuroimaging studies using functional magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) have revealed that acupuncture therapy may alter brain activity. This study was performed to evaluate changes in regional cerebral blood flow and glucose metabolism following electroacupuncture (EA) in normal volunteers.
Twenty (20) normal volunteers were enrolled for brain SPECT and 13 normal volunteers were enrolled for (18)F-fluorodeoxyglucose PET. A few days after the baseline measurements, EA was performed at two acupoints (LI 4 and LI 11) for 15 minutes and a second brain image was acquired for each subject. We used statistical parametric mapping 2 to analyze the changes in brain perfusion and glucose metabolism.
Significant increases in perfusion were observed in the left middle frontal gyrus, the superior parietal gyrus, the right superior frontal gyrus, and the middle parietal gyrus. Following EA, glucose metabolism significantly increased in the left superior medial frontal gyrus, the middle frontal gyrus, and the right superior medial frontal gyrus (paired t-test, uncorrected p < 0.005).
There were specific increases in both regional cerebral blood flow and glucose metabolism following EA in both frontal regions. This common brain response in localized regions was induced from stimulation of specific acupoints (LI 4 and LI 11).
Japanese style, superficial acupuncture (SA) has been clinically evaluated for its therapeutic benefit, yet the neurophysiologic responses associated with SA remain unclear. This study was performed to measure changes in regional cerebral blood flow (rCBF) following SA at LI-4 and LI-11 in healthy volunteers using single photon emission computed tomography (SPECT). Changes in SPECT activity following Japanese style SA were compared to previous reports of SPECT changes following electroacupuncture (EA) at the same acupoints.
Ten (10) healthy volunteers were enrolled for this study. A few days after the baseline brain SPECT, SA was performed at LI-4 and LI-11 for 15 minutes and a second brain perfusion image was acquired for each subject. We used SPM2 to analyze the changes in rCBF after SA through a paired t test. In addition, the differences of rCBF changes between SA and EA were compared using a two-sample t test.
Cerebral blood perfusion significantly increased after SA in the left superior frontal gyrus, left middle cingulum, left insular, right medial orbital frontal gyrus, and right middle cingulum (paired t test, uncorrected p < 0.005), while no regions showed a significant decrease. The results comparing poststimulation images between SA and EA demonstrated that the perfusion in the right lingual, both thalamus, left middle temporal gyrus, left insula, and both cerebellum were significantly increased in SA compared with EA (false discovery rate [FDR] corrected p < 0.05).
There were specific increase patterns of rCBF following SA at LI-4 and LI-11, which were similar to those following EA. However, there were significant differences in the decrease pattern of rCBF between SA and EA, which might be due to the difference of the strength of acupuncture stimulation between the two methods. These results may contribute to developing a better strategy to a select stimulation method in acupuncture therapy.
The objectives of this study were to chart the patterns and determine the factors associated with acupuncture consultations among a large cohort of mid-aged women in Australia over a 6-year period.
A longitudinal analysis of questionnaires completed in 2001, 2004, and 2007 as part of the Australian Longitudinal Study on Women's Health. Statistical analyses included Generalized Estimating Equations.
Mid-aged women (n=11,200) were randomly selected from the Australian Medicare database, with oversampling of women from rural and remote areas.
The outcome measure was consultation with an acupuncturist in the 12 months prior to each survey.
The percentage of women who consulted an acupuncturist in the years 2001, 2004, and 2007 were 4.2%, 4.3%, and 5.9%, respectively. Only 0.5% of women consulted with an acupuncturist at all survey periods, 2.0% at two survey periods, and 7.4% at only one survey period. Acupuncture consultations significantly increased if the women had back problems (odds ratio [OR]=1.5), arthritis (OR=1.3), had higher levels of education (OR=1.9), were high users of general practitioners/family practitioners (OR=2.6), and high users of biomedical specialists (OR=1.4).
Use of acupuncturists among mid-age women appears to be strongly influenced by poor physical health. The percentage of women in the community who use acupuncture remained relatively consistent over the study period. Women do not tend to consistently use acupuncture over time, but instead appear to use acupuncture as a one-off treatment or at selected time points.
We aim to identify the genetic loci responsible for Sasang constitution type, which is important for effective personalized treatments in traditional Korean medicine.
Forty (40) individuals in a Korean family were recruited for linkage analysis and 310 unrelated individuals for association analysis to confirm the linkage result. Outcome measures: Genome-wide linkage analysis was performed for the Korean family using the Affymetrix 500K arrays. MERLIN software was used for multipoint nonparametric linkage (NPL) analysis. The significant candidate regions in linkage analysis were also investigated with association analysis of independent 310 individuals.
Linkage analysis showed four significant peaks, 3q27.3, 8p11.21, 8q11.22-23, and 11q22.1-3, whose NPL Z scores are greater than 5.0. Among the significant loci, the 8q11.22-23 and 11q22.1-3 regions were supported by independent association analysis at the level of p < 0.05.
The 8q11.22-23 and 11q22.1-3 regions were suggested as the candidate region for significant linkage to Sasang constitution.
To investigate the change of skin impedance of acupoints along the Lung meridian in response to transcutaneous electrical nervous stimulation over an acupoint (Acu-TENS) over BL13 (Feishu).
This was a double-blinded, randomized, controlled crossover study.
The study was conducted in a laboratory.
Eighteen (18) healthy individuals comprised the study subjects.
The intervention was a session of 45-minute Acu-TENS (application of TENS on BL13, Feishu) or placebo-TENS (similar to Acu-TENS but without electrical output).
Skin impedance at 10 acupoints on the Lung meridian was recorded before and after the 45-minute intervention period. Heart rate variability during the intervention was analyzed from continuous heart rate monitoring.
Skin impedance at all acupoints along the lung meridian decreased significantly after Acu-TENS, when compared to placebo-TENS (p<0.05). A significant reduction in sympathetic activity was also observed after Acu-TENS (p=0.012).
Acu-TENS appears to modify skin impedance of acupoints along a related meridian and possibly modulates sympathovagal balance.
In order to facilitate the conduct and dissemination of high-quality systematic reviews in CAM further, three key issues were discussed at the Melbourne Cochrane Colloquium: (a) How to improve the overall methodological quality of CAM reviews in general, (b) how to improve the quality of Traditional Chinese Medicine reviews and trials; and (c) how to make the CAM reviews more accessible to the lay public throughout the world. A summary of each of these is presented.
This paper reports on the results of a literature survey involving 166 different species of plants used in the Ayurvedic pharmacopoeia, based on a sampling of the literature available to us. We found a wide range of clinical and other in vivo studies for many of the plant-based therapies utilized in the Ayurvedic system. Of the 166 plants investigated, 72 (43%) had at least one or more human studies and 103 (62%) had one or more animal studies. These results appear to contradict the generally held notion that herbal remedies used in non-Western systems of botanical medicine have not been evaluated in human or in vivo trials. Some of these studies are not always as large or methodologically rigorous as clinical studies reported in major medical journals. Indeed, a critical assessment of the research according to the standards of evidence-based medicine would eliminate many of these studies for lack of rigor according to criteria of randomization, sample size, adequacy of controls, etc. However, the studies do suggest which species might be appropriate for larger and better-controlled trials in the future. Accordingly, a synopsis of the plants, their therapeutic applications, and their clinical or experimental evaluations is presented.
The "Neurobiological Correlates of Acupuncture" Conference was convened November 17-18, 2005 in Bethesda, Maryland. The conference was sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS). Its goals were to encourage exchange of ideas regarding the direction of neuroimaging in acupuncture research as well as to discuss some of the challenges in this field. The use of neuroimaging, a relatively recent advance in the study of acupuncture, holds the promise of localizing and characterizing brain activity associated with acupuncture interventions in real time and in a minimally invasive way. Among the main challenges to research into the biological mechanisms of acupuncture are the multiple treatment variables and the difficulties of selecting appropriate experimental controls. Despite these challenges, numerous findings from acupuncture neuroimaging experiments were presented and discussed at the conference on topics related to possible signaling networks, sham acupuncture controls, acupoint specificity, acupuncture analgesia, acupuncture-associated brain response, and the potential for using neuroimaging in conjunction with translational and clinical acupuncture research. Future directions in acupuncture neuroimaging research, as recommended by conference participants, should focus on (1) continuing exploration of acupuncture signaling networks; (2) establishing standards and recommendations for performing and reporting acupuncture neuroimaging results; (3) enabling data sharing in the acupuncture neuroimaging community; (4) gaining a better understanding of placebo and control groups in acupuncture neuroimaging experiments; and (5) developing biomarkers that relate to physiologically and/or clinically relevant acupuncture responses to neuroimaging results.
Hwang-Yeon-Hae-Dok-San (TJ-15) and Ou-Ryung-San (TJ-17) are two common herbal formulas that have been used to treat atopic dermatitis (AD), especially the Dampness-Heat pattern of AD. The aim of this study was to determine the safety and efficacy of TJ-15 plus TJ-17 for patients with the Dampness-Heat pattern of AD based on pattern identification.
This study was a parallel, randomized, active-controlled, double-blind trial. A total of 24 patients were enrolled. Either a combination of TJ-15 plus TJ-17, or TJ-15 alone was orally administered 3 times daily for 4 weeks. Of the patients enrolled, 19 patients completed the 4-week treatment course (TJ-15 plus TJ-17: n=8, TJ-15: n=11). Efficacy was assessed using the scoring atopic dermatitis (SCORAD) index; area of eczema and severity index (EASI); as well as the symptoms related to the Dampness-Heat by pattern identification. Efficacy measures were evaluated at the baseline and at 4 weeks. Safety was assessed throughout the study using ongoing laboratory tests.
Both the SCORAD and EASI showed more improvement in the TJ-15 plus TJ-17 group than in the TJ-15 group; however, the differences were not statistically significant. The symptoms related to the Dampness-Heat pattern were reduced in both groups, and the changes were similar. There were no reported adverse events during this study, or abnormalities observed on aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine testing.
The results of this study suggest that both the TJ-15 plus TJ-17 and the TJ-15 provided safe and effective treatment for patients with the Dampness-Heat pattern type of AD.
Background: Recent evidence shows that acupuncture is effective for chronic pain. However we do not know whether there are characteristics of acupuncture or acupuncturists that are associated with better or worse outcomes.
It has been reported that postherpetic neuralgia (PHN) in patients over 60 years of age is aggravated under cold stimulation and is often difficult to treat. Keishikajutsubuto (TJ-18) and Bushi-matsu (TJ-3022) are traditional Japanese herbal medicines and have long been used to treat neuralgia and arthralgia, which are aggravated following cold stimulation. This study was designed to evaluate the effectiveness of combined TJ-18 and TJ-3022 therapy in cases of PHN aggravated by self-reported cold stimulation.
Fifteen (15) PHN patients aged 60 years and over were examined. Patients were aware of the persistent pain despite other treatments; pain was generally aggravated following exposure to cold stimulation. First, TJ-18 (7.5 g/day) was administered to patients, and then TJ-3022 (1.0 g/day) was also administered and progressively increased by 0.5-1.0 g increments every 2-4 weeks, until stable improvement was achieved, which was rated using the visual analogue scale (VAS). Analgesic effects were evaluated using the VAS during each patient visit.
Background variables, responses to treatment (time course of VAS rating, VAS improvement rate), the amount of additional TJ-3022 administered, and adverse reactions were analyzed.
Twelve (12) of the 15 patients completed the entire trial. Patient ages were 61-85 years, the male-to-female ratio was 4:8, and length of time after onset of herpes zoster was 2-92 months. In 3 patients, oral TJ-18 treatment was not possible due to hot flash or gastric discomfort. The VAS improvement rate for patients being orally administered both TJ-18 and TJ-3022 was 76.5±27.7% (mean±standard deviation). The additional TJ-3022 dose was 1.0-5.0 g/day. Twelve (12) patients have been treated without serious adverse reactions.
TJ-18 and TJ-3022 combination treatment is a promising means of treating intractable PHN, which has a self-reported tendency to aggravate pain under cold stimulation.