CONTEXT: The incidence of tendon injuries and tendinopathy has risen substantially in the past decades. OBJECTIVE: To assess the noninferiority of therapy based on the homeopathic preparation Traumeel S ointment (Heel GmbH, Baden-Baden, Germany) compared with treatment based on diclofenac 1% gel in patients with tendinopathies of varying etiology. DESIGN: Nonrandomized, observational study. SETTING: Ninety-five homeopathy and conventional medical practices in Germany. PATIENTS: Three hundred fifty-seven patients aged 18 to 93 years with tendinopathy of varying etiology based on excessive tendon load rather than inflammation. INTERVENTIONS: Traumeel S ointment or diclofenac 1% gel for a maximum of 28 days. MAIN OUTCOME MEASURES: Efficacy was measured on a four-degree scale on pain-related variables, on variables related to motility, and on overall treatment outcome. Tolerability was monitored as adverse events. Compliance was assessed by practitioner and patient on a four-degree scale. RESULTS: The patients groups were comparable at baseline. The changes in summary score of all pain-related variables were -5.3 +/- 2.7 (all values means +/- SD) in the Traumeel group and -5.0 +/- 2.7 in the control group. Changes for all motility-related variables were -4.2 +/- 3.8 with Traumeel and -3.7 +/- 3.4 with control therapy. The summary scores for all clinical variables were reduced by -9.5 +/- 5.7 with Traumeel therapy and by -8.7 +/- 5.4 with diclofenac-based treatment. Homeopathic therapy was noninferior to diclofenac therapy on all variables. For motility-related variables, there was a trend toward superiority of Traumeel. Treatments were well tolerated with no treatment-related adverse events. CONCLUSIONS: The results suggest that Traumeel ointment is an effective alternative to nonsteroidal antiinflammatory drugs therapy for the acute symptomatic treatment of patients with tendinopathy.

OBJECTIVE:To synthesize evidence on the effectiveness of acupuncture and related therapies for primary carpal tunnel syndrome (CTS) by conducting a systematic review of randomized controlled trials (RCTs).

DATA SOURCES:Nine databases were searched for potential RCTs from their inception till July 2019.

REVIEW METHODS:RCTs which reported at least one of the three outcomes were included: symptom severity, functional status and pain. Included RCTs were appraised using the Cochrane Risk of Bias Tool.

RESULTS:A total of 10 RCTs (728 participants) were included. Majority were at high risk of bias for blinding of participants, personnel and outcome assessors. When compared to conventional medications, manual acupuncture showed significant superior effect in reducing symptom than ibuprofen (mean difference (MD) on Symptom Severity Scale (SSS)) = -5.80, 95% confidence interval (CI): -7.95 to -3.65) and prednisolone (MD = -6.50, 95% CI: -10.1, -2.86). Electroacupuncture plus splinting was more effective in reducing symptom severity than splinting alone (SSS score: MD = -0.20, 95% CI: -0.36 to -0.03). Manual acupuncture showed significantly superior effect than ibuprofen in improving functional status (Functional Status Scale (FSS): MD = -1.84, 95% CI: -2.66 to -1.02). The combination of electroacupuncture and splinting showed more improvement in functional status compared to splinting alone (FSS: MD = -6.22, 95%CI: -10.7 to -1.71). Triple treatment of acupuncture, magnetic spectrum heat lamp and splinting showed stronger pain relief than splinting alone.

CONCLUSION:For both symptom relief and function improvement, manual acupuncture is superior to ibuprofen while electroacupuncture plus splinting outperforms splinting alone. Limited evidence showed electroacupuncture's potential role in pain reduction.

OBJECTIVES: To investigate the efficacy of acupuncture compared with steroid treatment in patients with mild-to-moderate carpal tunnel syndrome (CTS) as measured by objective changes in nerve conduction studies (NCS) and subjective symptoms assessment in a randomized, controlled study. METHODS: A total of 77 consecutive and prospective CTS patients confirmed by NCS were enrolled in the study. Those who had fixed sensory complaint over the median nerve and thenar muscle atrophy were excluded. The CTS patients were randomly divided into 2 treatment arms: (1) 2 weeks of prednisolone 20 mg daily followed by 2 weeks of prednisolone 10 mg daily (n = 39), and (2) acupuncture administered in 8 sessions over 4 weeks (n = 38). A validated standard questionnaire as a subjective measurement was used to rate the 5 major symptoms (pain, numbness, paresthesia, weakness/clumsiness, and nocturnal awakening) on a scale from 0 (no symptoms) to 10 (very severe). The total score in each of the 5 categories was termed the global symptom score (GSS). Patients completed standard questionnaires at baseline and 2 and 4 weeks later. The changes in GSS were analyzed to evaluate the statistical significance. NCS were performed at baseline and repeated at the end of the study to assess improvement. All main analyses used intent-to-treat. RESULTS: A total of 77 patients who fulfilled the criteria for mild-to-moderate CTS were recruited in the study. There were 38 in the acupuncture group and 39 in the steroid group. The evaluation of GSS showed that there was a high percentage of improvement in both groups at weeks 2 and 4 (P < 0.01), though statistical significance was not demonstrated between the 2 groups (P = 0.15). Of the 5 main symptoms scores (pain, numbness, paresthesia, weakness/clumsiness, nocturnal awakening), only 1, nocturnal awakening, showed a significant decrease in acupuncture compared with the steroid group at week 4 (P = 0.03). Patients with acupuncture treatment had a significant decrease in distal motor latency compared with the steroid group at week 4 (P = 0.012). Acupuncture was well tolerated with minimal adverse effects. CONCLUSIONS: Short-term acupuncture treatment is as effective as short-term low-dose prednisolone for mild-to-moderate CTS. For those who do have an intolerance or contraindication for oral steroid or for those who do not opt for early surgery, acupuncture treatment provides an alternative choice.

OBJECTIVES:Evidence from clinical trials questions the benefit-risk ratio of first-line antibiotic treatment for uncomplicated acute otitis media in childhood. Alternative treatment strategies are very popular but have not been the subject of larger controlled clinical trials. This trial compares an alternative with a conventional treatment strategy for acute otitis media.

METHODS AND PATIENTS:390 children aged 1-10 years presenting with uncomplicated acute otitis media participated in a prospective, open, non-randomized, controlled, parallel-group study. According to self-assignment of investigators, children were treated either conventionally (free combinations of decongestant nose drops, mucolytics, analgesics and antibiotics) or alternatively with Otovowen (fixed combination of plant-based tinctures and homeopathic potencies), supplemented by conventional medications when considered necessary.

RESULTS:Alternatively treated patients (n = 192) had significantly less severe otoscopic findings and clinical symptom ratings at baseline than children treated in conventional centers (n = 193). Patients cared for by conventional therapists took more antibiotics (80.5% vs. 14.4%; chi2-test, p<0.001) and analgesics (66.8% vs. 53.2%; chi2-test, p = 0.007). Times to recovery were 5.3 +/- 2.4 and 5.1 +/- 2.2 days for alternative and conventional treatment, respectively. Odds ratios (OR) with a lower limit of 1-sided 97.5% confidence interval (CI) were 0.98 (0.76), 0.95 (0.73) and 0.88 (0.69) for results adjusted to baseline otoscopy, pain and symptom score, respectively (Cox-Mantel test). Absence from school or preschool nursery was 1.7 days in both groups; ORs (CI) were 1.00 (0.76), 0.96 (0.73) and 1.04 (0.80). Noninferiority of alternative treatment (CI limit of OR above 0.696) was not proven for pain resolution (-5.2 vs. -5.8 score points); OR (CI) were 0.87 (0.68), 1.15 (0.87) and 0.74 (0.58). Alternative treatment was judged both by doctors (Mann-Whitney estimator with 2-sided 95% CI 0.41 (0.35-0.47)) and parents (0.42 (0.36-0.48)), to be significantly better tolerated than conventional treatment.

CONCLUSIONS:In primary care management of uncomplicated acute otitis media in childhood, an alternative treatment strategy based on the natural medicine, Otovowen may substantially reduce the use of antibiotics without disadvantage to the clinical outcome.

Because five-year survival rates for patients with metastatic melanoma remain below 25%, there is continued need for new therapeutic approaches. For some tumors, pharmacologic ascorbate treatment may have a beneficial antitumor effect and may work synergistically with standard chemotherapeutics. To investigate this possibility in melanoma, we examined the effect of pharmacologic ascorbate on B16-F10 cells. Murine models were employed to compare tumor size following treatment with ascorbate, and the chemotherapeutic agents dacarbazine or valproic acid, alone or in combination with ascorbate. Results indicated that nearly all melanoma cell lines were susceptible to ascorbate-mediated cytotoxicity. Compared to saline controls, pharmacologic ascorbate decreased tumor size in both C57BL/6 (p<.0001) and NOD-scid tumor bearing mice (p<.0001). Pharmacologic ascorbate was superior or equivalent to dacarbazine as an antitumor agent. Synergy was not apparent when ascorbate was combined with either dacarbazine or valproic acid; the latter combination may have additional toxicities. Pharmacologic ascorbate induced DNA damage in melanoma cells, as evidenced by increased phosphorylation of the histone variant, H2A.X. Differences were not evident in tumor samples from C57BL/6 mice treated with pharmacologic ascorbate compared to tumors from saline-treated controls. Together, these results suggest that pharmacologic ascorbate has a cytotoxic effect against melanoma that is largely independent of lymphocytic immune functions and that continued investigation of pharmacologic ascorbate in cancer treatment is warranted.

This study investigated the alleviating effects of aromatherapy massage and acetaminophen on menstrual pain in Korean high school girls. Subjects were divided into two groups: the aromatherapy massage (treatment) group (n = 32) and the acetaminophen (control) group (n = 23). Aromatherapy massage was performed on subjects in the treatment group. The abdomen was massaged once using clary sage, marjoram, cinnamon, ginger, and geranium in a base of almond oil. The level of menstrual pain was assessed using a visual analogue scale at baseline and twenty-four hours afterward. The reduction of menstrual pain was significantly higher in the aromatherapy group than in the acetaminophen group. Using multiple regression, aromatherapy massage was found to be more highly associated with reduction in the level of menstrual pain than acetaminophen. These finding suggest that aromatherapy massage may be an effective treatment for menstrual pain in high school girls. However, it could not be verified whether the positive effects derived from the aromatherapy, the massage, or both. Further rigorous studies should be conducted using more objective measures.

BACKGROUND:Studies on alternative medicines for generalized anxiety disorder (GAD) are few. Manasamitra Vataka (an Ayurveda preparation) is explored for its efficacy in patients with GAD with comorbid generalized social phobia.

MATERIALS AND METHODS:Seventy-two (72) patients with GAD with comorbid social phobia meeting DSM IV TR criteria, and who were between the ages of 20 and 55 of either sex, participated in the study. They were randomly divided into three treatment groups: Group 1 (n=24) and Group II (n=24) received Manasamitra Vataka tablets (100 mg twice daily for 30 days). Group II, in addition to Manasamitra Vataka, underwent Shirodhara (therapy involving dripping of medicated oil [Brahmi tail] over the forehead) treatment for the first 7 days. Group III (n=24) received clonazepam 0.75 mg daily in divided dose for 30 days. The assessment of the study was done using the Hamilton Anxiety Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, Epworth Sleepiness Scale (ESS), World Health Organization Quality of Life BREF, and Clinical Global Impression scales (Improvement and Efficacy).

RESULTS:Patients from all the groups showed significant reduction in clinical parameters evaluated. However, improvement in ESS was observed only in Group II. The treatment outcome was comparable between the three groups.

CONCLUSIONS:This is the first study conducted on the efficacy of Manasamitra Vataka in anxiety disorders. The results suggest that Manasamitra Vataka is effective in the management GAD with comorbid generalized social phobia. Add-on effect of Shirodhara reduced the daytime sleepiness. Further studies on Manasamitra Vataka need to be carried out to judge its potential as a first-line treatment modality.

OBJECTIVE: To probe a better method for treatment of trigeminal neuralgia. Methods One hundred and four cases of trigeminal neuralgia were randomly divided into a treatment group (n=57) and a control group (n=47). The treatment group were treated witb acupoint injection of 2000 microg of VitB12, with Xiaguan (ST 7) selected as main point, and the control group witb oral administration of Carbamazepine. The therapeutic effect were analyzed after 3 tberapeutic courses. RESULTS: Tbe cured and markedly effective rate and the effective rate were 82.5% and 98.2% in the treatment group, and 57.4% and 8O.9% in the control group, with a very significant difference between the two groups (P<0.01). After treatment, there was a very significant difference in the cumulative score of pain between the two groups (P<0.01). CONCLUSION: Acupoint injection of VitB12 has a better therapeutic effect than that of oral administration of Carbamazepine.

The comparison of chamomile and corticosteroids for treating ulcers was done in vitro and in vivo. The experimental groups were: control; chamomile recutita; triamcinolone acetonide and clobetasol propionate. For the in vitro study the cell viability of fibroblasts cultured for 24 h in media conditioned by the substances was obtained by the MTT reduction analysis. For the in vivo study, 125 male rats were submitted to experimental ulcers treated or not (control) by the substances tested. At 1, 3, 5, 7 and 14 days later 5 animals of each group were sacrificed. The lesions were analyzed by means of clinical observation and histological wound-healing grading. Data were compared by ANOVA (p </= 0.05). All experimental groups presented positive cell viability in 24 h. The cultures treated with chamomile presented the smallest cell viability. All animals of the chamomile group exhibited complete wound healing 9 days before the other groups. Complete repaired lesions were observed after 5 days of treatment only in the chamomile group. Animals treated with chamomile presented significantly faster wound healing in comparison to those treated with corticosteroids. Based on the conditions of this study, we concluded that chamomile in comparison to corticosteroids promotes faster wound healing process. Copyright (c) 2008 John Wiley & Sons, Ltd.

OBJECTIVE: To assess effect of acupuncture combined with massage of sole on sleeping quality of the patient with insomnia. METHODS: Fifty-eight cases of insomnia were randomly divided into an observation group (n = 32) and a control group (n = 26). The observation group were treated with oral administration of Alprazolam, massage of sole, and acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), etc. on the abdomen as main points; the control group were treated with Alprazolam. Clinical therapeutic effects, and scores for Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were assessed before and after treatment in the two groups. RESULTS: The effective rate was 93.75 in the observation group and 88.46% in the control group with no significant difference between the two groups; after treatment, there were significant or very significant differences in scores for various factors in the PSQI, SAS and SDS (P < 0.01, P < 0.05). CONCLUSION: Abdominal acupuncture as main combined with massage of sole can obviously improve sleeping quality of the patient with insomnia.

OBJECTIVE: To assess effect of acupuncture combined with massage of sole on sleeping quality of the patient with insomnia. METHODS: Fifty-eight cases of insomnia were randomly divided into an observation group (n = 32) and a control group (n = 26). The observation group were treated with oral administration of Alprazolam, massage of sole, and acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), etc. on the abdomen as main points; the control group were treated with Alprazolam. Clinical therapeutic effects, and scores for Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were assessed before and after treatment in the two groups. RESULTS: The effective rate was 93.75 in the observation group and 88.46% in the control group with no significant difference between the two groups; after treatment, there were significant or very significant differences in scores for various factors in the PSQI, SAS and SDS (P < 0.01, P < 0.05). CONCLUSION: Abdominal acupuncture as main combined with massage of sole can obviously improve sleeping quality of the patient with insomnia.

BACKGROUND:The current study was performed to determine the effects of cumin cyminum L. intake on weight loss and metabolic profiles among overweight subjects.

METHODS:This randomized double-blind placebo-controlled clinical trial was conducted among 78 overweight subjects (male, n = 18; female, n = 60) aged 18-60 years old. Participants were randomly assigned into three groups to receive: (1) cumin cyminum L. capsule (n = 26); (2) orlistat120 capsule (n = 26) and (3) placebo (n = 26) three times a day for 8 weeks. Anthropometric measures and fasting blood samples were taken at baseline and after 8 weeks of intervention.

RESULTS:Consumption of the Cuminum cyminum L. and orlistat120 resulted in a similar significant decrease in weight (-1.1± 1.2 and -0.9 ± 1.5 vs. 0.2 ± 1.5 kg, respectively, p = 0.002) and BMI (-0.4 ± 0.5 and -0.4 ± 0.6 vs. 0.1 ± 0.6 kg/m(2), respectively, p = 0.003) compared with placebo. In addition, taking Cuminum cyminum L., compared with orlistat and placebo, led to a significant reduction in serum insulinlevels (-1.4 ± 4.5 vs. 1.3 ± 3.3 and 0.3 ± 2.2 µIU/ml, respectively, p = 0.02), HOMA-B (-5.4 ± 18.9 vs. 5.8 ± 13.3 and 1.0 ± 11.0, respectively, p = 0.02) and a significant rise in QUICKI (0.01 ± 0.01 vs. -0.005 ± 0.01 and -0.004 ± 0.01, respectively, p = 0.02).

CONCLUSION:Taking cumin cyminum L. for eight weeks among overweight subjects had the same effects of orlistat120 on weight and BMI and beneficial effects on insulin metabolism compared with orlistat120 and placebo.© 2015 S. Karger AG, Basel.

Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), urea, and creatinine increased significantly in the DPN and diabetic rats without peripheral neuropathy (PN) compared with control group. The treatment of DNP with gabapentin induced significant increases in ALAT and ASAT activities but LLLT treatment induced significant decreases in ALAT and ASAT activities as compared with DNP group. Neither gabapentin nor LLLT could improve the elevated levels of serum urea and creatinine in the DNP. It could be concluded that LLLT is more safe and effective than gabapentin in the management of neuropathy in diabetic rats.

The outbreak of SARS warrants the search for antiviral compounds to treat the disease. At present, no specific treatment has been identified for SARS-associated coronavirus infection. We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS admitted to the clinical centre of Frankfurt University, Germany. Of all the compounds, glycyrrhizin was the most active in inhibiting replication of the SARS-associated virus. Our findings suggest that glycyrrhizin should be assessed for treatment of SARS.

The outbreak of SARS warrants the search for antiviral compounds to treat the disease. At present, no specific treatment has been identified for SARS-associated coronavirus infection. We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS admitted to the clinical centre of Frankfurt University, Germany. Of all the compounds, glycyrrhizin was the most active in inhibiting replication of the SARS-associated virus. Our findings suggest that glycyrrhizin should be assessed for treatment of SARS.

AIM AND METHOD: The objective of this research was to study the effect of homeopathic treatment with Plumbum metallicum (Plumbum met.) on mandibular bone repair in rats. MATERIALS AND METHODS: We analyzed the mandibles of 60 male rats, approximately 3-month-old, randomly divided into three groups of 20 animals each: control, treated with calcitonin, and treated with a homeopathic medicine. A circumscribed bone defect measuring 4mm in diameter was made in the mandible and covered with a polytetrafluorethylene (PTFE) barrier. The group treated with calcitonin received 2IU/kg intramuscularly three times a week; the group treated with Plumbum met. 30c received three drops in water every day. The animals were sacrificed after 7, 14, 21 and 28 days. The mandibles were removed and submitted to histologic and histomorphometric analyses. RESULTS: Data were analyzed statistically by two-way ANOVA and by the Tukey test. The interaction effect (ANOVA, F df(6; 48)=4.64; p=0.001<0.05) indicated that the relationship between treatments was not the same at each time of sacrifice. Although statistical analysis of the histomorphometric data showed a similar results for the treated and control groups. But histological analysis showed complete filling of the surgical defect throughout its extent was only for the group treated with Plumbum met. CONCLUSION: The study demonstrated that for repair of surgical defects in rat mandibles Plumbum met. 30c and control did not differ significantly in histomorphometric terms.

Hypericum extract (HE) might be favourably active in depressed patients with reversed vegetative signs (RVS). Therefore, we performed an exploratory subgroup analysis of a three-armed study to compare HE, fluoxetine, and placebo in patients with major depressive disorder (MDD) in a 12 wk trial. A total of 135 patients were randomized to 12 wk treatment with HE LI 160 (900 mg/d), fluoxetine (20 mg/d), or placebo. Patients with RVS were defined in two steps, according to DSM-IV. First, patients with melancholy-related vegetative signs were excluded. Secondly, patients had to have at least one score of 2 for the items 22-26 of the HAMD-28 scale, which are related to hypersomnia and hyperphagia. Twenty-seven patients remained in the group. Analysis of covariance (ANCOVA) was applied using the HAMD-17 score. Secondly a chi2 test for response was performed, using the same and further an adapted criterium as in recently published studies. ANCOVA revealed a trend to a global difference. Post-hoc analysis showed a trend to superiority of HE compared to placebo and to fluoxetine, but a very large effect size for both differences. Fluoxetine was not different from placebo. The adapted response criterium showed a significant global difference as well as a significant superiority of HE over placebo and over fluoxetine. These data are based on a small sample size and must be considered tentative. A characterization of vegetative features of patients with depression could lead to an overall increased effect size in the treatment with HE.

Hyperlipidemia is an associated complication of diabetes mellitus. Many spices and herbs are known to be hypoglycaemic. Cuminum cyminum belonging to the family Apiaceae is widely used in Ayurvedic medicine for the treatment of dyspepsia, diarrhoea and jaundice. The present work was done to study the role of C. cyminum supplementation on the plasma and tissue lipids in alloxan diabetic rats. Oral administration of 0.25 g kg(-1) body weight of C. cyminum for 6 weeks to diabetic rats resulted in significant reduction in blood glucose and an increase in total haemoglobin and glycosylated haemoglobin. It also prevented a decrease in body weight. C. cyminum treatment also resulted in a significant reduction in plasma and tissue cholesterol, phospholipids, free fatty acids and triglycerides. Histological observations demonstrated significant fatty changes and inflammatory cell infiltrates in diabetic rat pancreas. But supplementation with C. cyminum to diabetic rats significantly reduced the fatty changes and inflammatory cell infiltrates. Moreover, C. cyminum supplementation was found to be more effective than glibenclamide in the treatment of diabetes mellitus. Copyright 2002 Elsevier Science Ltd.

BACKGROUND: An increase in inflammatory response and an imbalance between T-helper (Th) 1 and 2 functions have been implicated in major depression. The aims of the present study were to 1) study the relationship between pro- and anti-inflammatory cytokines and between Th1 and Th2 produced cytokines in depressed patients and 2) evaluate and compare the effect of treatments with electroacupuncture (EA) and fluoxetine on these cytokines. METHODS: 95 outpatients with major depressive disorder were treated for 6 weeks with EA, fluoxetine or placebo. Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression (CGI) were used to assess severity and therapeutic effects. 30 volunteers served as controls. Serum cytokine concentrations were measured by ELISA. RESULTS: Increased proinflammatory cytokine interleukin (IL)-1beta and decreased anti-inflammatory cytokine IL-10 were found in the depressed patients. By contract, Th1 produced proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were decreased, and Th2 produced cytokine IL-4 was significantly increased in depressed patients. The ratio of IFN/IL-4 was also increased. Both acupuncture and fluoxetine treatments, but not the placebo, reduced IL-1beta concentrations in responders. However, only acupuncture attenuated TNF-alpha concentration and INF-gamma/IL-4 ratio towards the control level. DISCUSSION: These results suggest that an imbalance between the pro- and anti-inflammatory cytokines (IL-1 and IL-10), and between Th1 and Th2 cytokines (INF-gamma or TNF-alpha and IL-4) occurred in untreated depressed patients. Both EA and fluoxetine had an anti-inflammatory effect by reducing IL-1beta. EA treatment also restored the balance between Th1 and Th2 systems by increasing TNF-alpha and decreasing IL-4. Georg Thieme Verlag KG Stuttgart - New York.

Stem bromelain (EC 3.4.22.32) is a major cysteine proteinase, isolated from pineapple ( Ananas comosus) stem. Its main medicinal use is recognized as digestive, in vaccine formulation, antitumoral and skin debrider for the treatment of burns. To verify the identity of the principle in stem fractions responsible for the antitumoral effect, we isolated bromelain to probe its pharmacological effects. The isolated bromelain was obtained from stems of adult pineapple plants by buffered aqueous extraction and cationic chromatography. The homogeneity of bromelain was confirmed by reverse phase HPLC, SDS-PAGE and N-terminal sequencing. The in vivo antitumoral/antileukemic activity was evaluated using the following panel of tumor lines: P-388 leukemia, sarcoma (S-37), Ehrlich ascitic tumor (EAT), Lewis lung carcinoma (LLC), MB-F10 melanoma and ADC-755 mammary adenocarcinoma. Intraperitoneal administration of bromelain (1, 12.5, 25 mg/kg), began 24 h after tumor cell inoculation in experiments in which 5-fluorouracil (5-FU, 20 mg/kg) was used as positive control. The antitumoral activity was assessed by the survival increase (% survival index) following various treatments. With the exception of MB-F10 melanoma, all other tumor-bearing animals had a significantly increased survival index after bromelain treatment. The largest increase ( approximately 318 %) was attained in mice bearing EAT ascites and receiving 12.5 mg/kg of bromelain. This antitumoral effect was superior to that of 5-FU, whose survival index was approximately 263 %, relative to the untreated control. Bromelain significantly reduced the number of lung metastasis induced by LLC transplantation, as observed with 5-FU. The antitumoral activity of bromelain against S-37 and EAT, which are tumor models sensitive to immune system mediators, and the unchanged tumor progression in the metastatic model suggests that the antimetastatic action results from a mechanism independent of the primary antitumoral effect.