Spicing up” of the immune system by curcumin

“Spicing up” of the immune system by curcumin”.

Jagetia GC, Aggarwal BB.

Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract

Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. Traditionally known for its an antiinflammatory effects, curcumin has been shown in the last two decades to be a potent immunomodulatory agent that can modulate the activation of T cells, B cells, macrophages, neutrophils, natural killer cells, and dendritic cells. Curcumin can also downregulate the expression of various proinflammatory cytokines including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, most likely through inactivation of the transcription factor NF-kappaB. Interestingly, however, curcumin at low doses can also enhance antibody responses. This suggests that curcumin’s reported beneficial effects in arthritis, allergy, asthma, atherosclerosis, heart disease, Alzheimer’s disease, diabetes, and cancer might be due in part to its ability to modulate the immune system. Together, these findings warrant further consideration of curcumin as a therapy for immune disorders.

Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro

Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro.

Gao X, Kuo J, Jiang H, Deeb D, Liu Y, Divine G, Chapman RA, Dulchavsky SA, Gautam SC.

Division of Surgical Research, Department of Surgery, Henry Ford Health System, One Ford Place-4D, Detroit, MI 48202, USA.

Abstract

Curcumin (diferuloylmethane), a major curcumanoid found in the spice turmeric, exhibits anti-inflammatory, anti-oxidant, and chemopreventive activities. However, the effect of curcumin on the development of T cell-mediated immunological responses largely remains unknown. In this study we have investigated the effect of curcumin on mitogen/antigen induced proliferation of splenic lymphocytes, induction of cytotoxic T lymphocytes (CTLs), lymphokine activated killer (LAK) cells, and the production of cytokines by T lymphocytes and macrophages. We found that mitogen, interleukin-2 (IL-2) or alloantigen induced proliferation of splenic lymphocytes, and development of cytotoxic T lymphocytes is significantly suppressed at 12.5-30 micromol/L curcumin. The generation of LAK cells at similar concentrations was less sensitive to the suppressive effect of curcumin compared to the generation of antigen specific CTLs. Curcumin irreversibly impaired the production of these immune functions, since lymphoid cells failed to respond to the activation signals following 8h pretreatment with curcumin. Curcumin also inhibited the expression/production of IL-2 and interferon-gamma (IFN-gamma) by splenic T lymphocytes and IL-12 and tumor necrosis factor-alpha (TNF-alpha) by peritoneal macrophages irreversibly. Curcumin inhibited the activation of the transcription factor nuclear factor kappaB (NF-kappaB) without affecting the levels of constitutively expressed NF-kappaB. The latter result suggests that curcumin most likely inhibits cell proliferation, cell-mediated cytotoxicity (CMC), and cytokine production by inhibiting NF-kappaB target genes involved in induction of these immune responses.

Critically attained threshold of cerebral hypoperfusion: can it cause Alzheimer’s disease?

Critically attained threshold of cerebral hypoperfusion: can it cause Alzheimer’s disease?

de la Torre JC.

Source

Department of Neurosciences, University of California, San Diego, La Jolla 92093, USA. jdelator@ucsd.edu

Abstract

After nearly a century of inquiry, the cause of sporadic Alzheimer’s disease (AD) remains to be found. On the subject of AD pathogenesis, recent basic and clinical evidence strongly argues in favor of the concept that AD is linked to brain circulatory pathology. This concept, when viewed from many different medical disciplines and from close pre-morbid similarities to vascular dementia, assembles and hypothetically explains most of the key pathologic events associated with the development of AD. These pathologic events are triggered in AD by impaired cerebral perfusion originating in the microvasculature which affects the optimal delivery of glucose and oxygen and results in an energy metabolic breakdown of brain cell biosynthetic and synaptic pathways. We propose that two factors converge to initiate cognitive dysfunction and neurodegeneration as expressed in AD brain: (1) advanced aging, and (2) the presence of a condition that lowers cerebral perfusion. The first factor introduces a normal but potentially deconstructing process that lowers cerebral blood flow in proportion to increased aging, whereas the second factor adds a crucial burden that further lowers brain perfusion to a critical threshold that triggers neuronal metabolic compromise. When age and a condition that lowers cerebral perfusion converge, critically attained threshold of cerebral hypoperfusion (CATCH) results. CATCH is a cyclical and progressive cerebrovascular insufficiency that will destabilize neurons, synapses, neurotransmission, and cognitive ability, eventually evolving into a neurodegenerative process characterized by the formation of senile plaques, neurofibrillary tangles, and amyloid angiopathy. The concept of impaired cerebral perfusion as the cause of this dementia also explains the heterogeneic profile observed in AD patients, because an extensive list of risk factors for AD are also reported to significantly diminish blood flow to the aging brain.

Treatment of medial and lateral epicondylitis–tennis and golfer’s elbow–with low level laser therapy: a multicenter double blind, placebo-controlled clinical study on 324 patients

Treatment of medial and lateral epicondylitis–tennis and golfer’s elbow–with low level laser therapy: a multicenter double blind, placebo-controlled clinical study on 324 patients.

Simunovic Z, Trobonjaca T, Trobonjaca Z.

Laser Center, Locarno, Switzerland. tzlatko@mamed.medri.hr

Abstract

BACKGROUND AND OBJECTIVE:

Among the other treatment modalities of medial and lateral epicondylitis, low level laser therapy (LLLT) has been promoted as a highly successful method. The aim of this clinical study was to assess the efficacy of LLLT using trigger points (TPs) and scanner application techniques under placebo-controlled conditions.

STUDY DESIGN/MATERIAL AND METHODS:

The current clinical study was completed at two Laser Centers (Locarno, Switzerland and Opatija, Croatia) as a double-blind, placebo controlled, crossover clinical study. The patient population (n = 324), with either medial epicondylitis (Golfer’s elbow; n = 50) or lateral epicondylitis (Tennis elbow; n = 274), was recruited. Unilateral cases of either type of epicondylitis (n = 283) were randomly allocated to one of three treatment groups according to the LLLT technique applied: (1) Trigger points; (2) Scanner; (3) Combination Treatment (i.e., TPs and scanner technique). Bilateral cases of either type of epicondylitis (n = 41) were subject to crossover, placebo-controlled conditions. Laser devices used to perform these treatments were infrared (IR) diode laser (GaAlAs) 830 nm continuous wave for treatment of TPs and HeNe 632.8 nm combined with IR diode laser 904 nm, pulsed wave for scanner technique. Energy doses were equally controlled and measured in Joules/cm2 either during TPs or scanner technique sessions in all groups of patients. The treatment outcome (pain relief and functional ability) was observed and measured according to the following methods: (1) short form of McGill’s Pain Questionnaire (SF-MPQ); (2) visual analogue scales (VAS); (3) verbal rating scales (VRS); (4) patient’s pain diary; and (5) hand dynamometer.

RESULTS:

Total relief of the pain with consequently improved functional ability was achieved in 82% of acute and 66% of chronic cases, all of which were treated by combination of TPs and scanner technique.

CONCLUSIONS:

This clinical study has demonstrated that the best results are obtained using combination treatment (i.e., TPs and scanner technique). Good results are obtained from adequate treatment technique correctly applied, individual energy doses, adequate medical education, clinical experience, and correct approach of laser therapists. We observed that under- and overirradiation dosage can result in the absence of positive therapy effects or even opposite, negative (e.g., inhibitory) effects. The current clinical study provides further evidence of the efficacy of LLLT in the management of lateral and medial epicondylitis.

Superpulsed laser irradiation increases osteoblast activity via modulation of bone morphogenetic factors

Superpulsed laser irradiation increases osteoblast activity via modulation of bone morphogenetic factors.

Saracino S, Mozzati M, Martinasso G, Pol R, Canuto RA, Muzio G.

Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.

Abstract

BACKGROUND AND OBJECTIVE:

Laser therapy is a new approach applicable in different medical fields when bone loss occurs, including orthopedics and dentistry. It has also been used to induce soft-tissue healing, for pain relief, bone, and nerve regeneration. With regard to bone synthesis, laser exposure has been shown to increase osteoblast activity and decrease osteoclast number, by inducing alkaline phosphatase (ALP), osteopontin, and bone sialoprotein expression. Studies have investigated the effects of continuous or pulsed laser irradiation, but no data are yet available on the properties of superpulsed laser irradiation. This study thus aimed to investigate the effect of superpulsed laser irradiation on osteogenic activity of human osteoblast-like cells, paying particular attention to investigating the molecular mechanisms underlying the effects of this type of laser radiation.

STUDY DESIGN/MATERIALS AND METHODS:

Human osteoblast-like MG-63 cells were exposed to 3, 7, or 10 superpulsed laser irradiation (pulse width 200 nanoseconds, minimum peak power 45 W, frequency 30 kHz, total energy 60 J, exposure time 5 minutes). The following parameters were evaluated: cell growth and viability (light microscopy, lactate dehydrogenase release), calcium deposits (Alizarin Red S staining), expression of bone morphogenetic factors (real-time PCR).

RESULTS:

Superpulsed laser irradiation decreases cell growth, induces expression of TGF-beta2, BMP-4, and BMP-7, type I collagen, ALP, and osteocalcin, and increases the size and the number of calcium deposits. The stimulatory effect is maximum on day 10, that is, after seven applications.

CONCLUSIONS:

Reported results show that superpulsed laser irradiation, like the continuous and pulsed counterparts, possesses osteogenic properties, inducing the expression of molecules known to be important mediators of bone formation and, as a consequence, increasing calcium deposits in human MG-63 cells. Moreover, the data suggest a new potential role for PPARgamma as a regulator of osteoblast proliferation.

Low-level laser irradiation enhances BMP-induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway

Low-level laser irradiation enhances BMP-induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway.

Hirata S, Kitamura C, Fukushima H, Nakamichi I, Abiko Y, Terashita M, Jimi E.

Division of Molecular Signaling and Biochemistry, Department of Biosciences, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.

Abstract

Low-level laser irradiation (LLLI) has been shown to induce bone formation and osteoblast differentiation both in vivo and in vitro. However, the molecular mechanism by which LLLI stimulates osteoblast differentiation is still unclear. The aim of the present study was to examine whether Ga-Al-As laser irradiation could enhance BMP2-induced alkaline phosphatase (ALP) activity in C2C12 cells. Laser irradiation at 0.5 W for 20 min enhanced BMP2-induced ALP activity. Laser treatment alone did not affect ALP activity. To exclude the effect of pH or temperature changes during irradiation, we shortened the exposure time to 2 min, with various levels of laser power. At 2.5 W, irradiation stimulated BMP2-induced ALP activity but not cell proliferation, whereas 1 or 5 W laser power did not induce any significant effects. Irradiation stimulated BMP2-induced phosphorylation of Smad1/5/8 and BMP2 expression, but had no effect on the expression of inhibitory Smads 6 and 7, BMP4, or insulin-like growth factor 1. Laser irradiation enhanced Smad-induced Id1 reporter activity as well as expression of bone morphogenetic protein (BMP)-induced transcription factors such as Id1, Osterix, and Runx2. Laser irradiation also stimulated BMP-induced expressions of type I collagen, osteonectin, and osteocalcin mRNA, markers of osteoblasts. This enhancement of BMP2-induced ALP activity and Smad phosphorylation by laser irradiation was also observed in primary osteoblasts. These results suggest that LLLI accelerates the differentiation of BMP-induced osteoblasts by stimulating the BMP/Smad signaling pathway.

Effect of multiple exposures of low-level laser therapy on the cellular responses of wounded human skin fibroblasts

Photomed Laser Surg. 2006 Dec;24(6):705-14.

Effect of multiple exposures of low-level laser therapy on the cellular responses of wounded human skin fibroblasts.

Hawkins D, Abrahamse H.

Laser Research Unit, Group of Health Sciences, University of Johannesburg, Doornfontein, Johannesburg, South Africa.

Abstract

OBJECTIVE:

This study aimed to establish the behavior of wounded human skin fibroblasts (HSF) after heliumneon (HeNe) (632.8 nm) laser irradiation using one, two, or three exposures of different doses, namely, 2.5, 5.0, or 16.0 J/cm(2) on each day for 2 consecutive days.

BACKGROUND DATA:

Low-level laser therapy (LLLT) is a form of phototherapy used to promote wound healing in different clinical conditions. LLLT at than adequate wavelength, intensity, and dose can accelerate tissue repair. However, there is still conflicting information about the effect of multiple irradiations on the cellular responses of wounded cells.

METHODS:

Cellular responses to HeNe laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, and damage caused by multiple irradiations.

RESULTS:

A single dose of 5.0 J/cm(2), and two or three doses of 2.5 J/cm(2) had a stimulatory or positive effect on wounded fibroblasts with an increase in cell migration and cell proliferation while maintaining cell viability, but without causing additional stress or damage to the cells. Multiple exposures at higher doses (16 J/cm(2)) caused additional stress, which reduces cell migration, cell viability, and ATP activity, and inhibits cell proliferation.

CONCLUSION:

The results show that the correct energy density or fluence (J/cm(2)) and number of exposures can stimulate cellular responses of wounded fibroblasts and promote cell migration and cell proliferation by stimulating mitochondrial activity and maintaining viability without causing additional stress or damage to the wounded cells. Results indicate that the cumulative effect of lower doses (2.5 or 5 J/cm(2)) determines the stimulatory effect, while multiple exposures at higher doses (16 J/cm(2)) result in an inhibitory effect with more damage.

PMID: 17199470 [PubMed – indexed for MEDLINE]

Photobiomodulation of pain in carpal tunnel syndrome: review of seven laser therapy studies

Photobiomodulation of pain in carpal tunnel syndrome: review of seven laser therapy studies.

Naeser MA.

Department of Neurology, Boston University School of Medicine, MA 02130, USA. mnaeser@bu.edu

Abstract

In this review, seven studies using photoradiation to treat carpal tunnel syndrome (CTS) are discussed: two controlled studies that observed real laser to have a better effect than sham laser, to treat CTS; three openprotocol studies that observed real laser to have a beneficial effect to treat CTS; and two studies that did not observe real laser to have a better effect than a control condition, to treat CTS. In the five studies that observed beneficial effect from real laser, higher laser dosages (9 Joules, 12-30 Joules, 32 J/cm(2), 225 J/cm(2)) were used at the primary treatment sites (median nerve at the wrist, or cervical neck area), than dosages in the two studies where real laser was not observed to have a better effect than a control condition (1.8 Joules or 6 J/cm(2)). The average success rate across the first five studies was 84% (SD, 8.9; total hands = 171). The average pain duration prior to successful photoradiation was 2 years. Photoradiation is a promising new, conservative treatment for mild/moderate CTS cases (motor latency < 7 msec; needle EMG, normal). It is cost-effective compared to current treatments.

Frozen shoulder: the effectiveness of conservative and surgical interventions–systematic review

Br J Sports Med. 2011 Jan;45(1):49-56. doi: 10.1136/bjsm.2010.071431. Epub 2010 Jul 20.

Frozen shoulder: the effectiveness of conservative and surgical interventions–systematic review.

Favejee MM, Huisstede BM, Koes BW.

Department of Rehabilitation Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Abstract

BACKGROUND:

A variety of therapeutic interventions is available for restoring motion and diminishing pain in patients with frozen shoulder. An overview article concerning the evidence for the effectiveness of these interventions is lacking.

OBJECTIVE:

To provide an evidence-based overview regarding the effectiveness of conservative and surgical interventions to treat the frozen shoulder.

METHODS:

The Cochrane Library, PubMed, Embase, Cinahl and Pedro were searched for relevant systematic reviews and randomised clinical trials (RCTs). Two reviewers independently selected relevant studies, assessed the methodological quality and extracted data. A best-evidence synthesis was used to summarise the results.

RESULTS:

Five Cochrane reviews and 18 RCTs were included studying the effectiveness of oral medication, injection therapy, physiotherapy, acupuncture, arthrographic distension and suprascapular nerve block (SSNB).

CONCLUSIONS:

We found strong evidence for the effectiveness of steroid injections and laser therapy in short-term and moderate evidence for steroid injections in mid-term follow-up. Moderate evidence was found in favour of mobilisation techniques in the short and long term, for the effectiveness of arthrographic distension alone and as an addition to active physiotherapy in the short term, for the effectiveness of oral steroids compared with no treatment or placebo in the short term, and for the effectiveness of SSNB compared with acupuncture, placebo or steroid injections. For other commonly used interventions no or only limited evidence of effectiveness was found. Most of the included studies reported short-term results, whereas symptoms of frozen shoulder may last up to 4 years. High quality RCTs studying long-term results are clearly needed in this field.

Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials

Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials

Dr Roberta T Chow MBBS a , Prof Mark I Johnson PhD b, Prof Rodrigo AB Lopes-Martins PhD c, Prof Jan M Bjordal PT d e

Summary

Background

Neck pain is a common and costly condition for which pharmacological management has limited evidence of efficacy and side-effects. Low-level laser therapy (LLLT) is a relatively uncommon, non-invasive treatment for neck pain, in which non-thermal laser irradiation is applied to sites of pain. We did a systematic review and meta-analysis of randomised controlled trials to assess the efficacy of LLLT in neck pain.

Methods

We searched computerised databases comparing efficacy of LLLT using any wavelength with placebo or with active control in acute or chronic neck pain. Effect size for the primary outcome, pain intensity, was defined as a pooled estimate of mean difference in change in mm on 100 mm visual analogue scale.

Findings

We identified 16 randomised controlled trials including a total of 820 patients. In acute neck pain, results of two trials showed a relative risk (RR) of 1·69 (95% CI 1·22—2·33) for pain improvement of LLLT versus placebo. Five trials of chronic neck pain reporting categorical data showed an RR for pain improvement of 4·05 (2·74—5·98) of LLLT. Patients in 11 trials reporting changes in visual analogue scale had pain intensity reduced by 19·86 mm (10·04—29·68). Seven trials provided follow-up data for 1—22 weeks after completion of treatment, with short-term pain relief persisting in the medium term with a reduction of 22·07 mm (17·42—26·72). Side-effects from LLLT were mild and not different from those of placebo.

Interpretation

We show that LLLT reduces pain immediately after treatment in acute neck pain and up to 22 weeks after completion of treatment in patients with chronic neck pain.