Anwar Suhaimi

CAFFEIC ACID PHENETHYL ESTER (CAPE): SCAVENGER OF PEROXYNITRITE IN VITRO AND IN SEPSIS MODELS

ABSTRACT Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-&ggr; that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-&ggr;–treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.

Gelam Honey Scavenges Peroxynitrite During the Immune Response

Monocytes and macrophages are part of the first-line defense against bacterial, fungal, and viral infections during host immune responses; they express high levels of proinflammatory cytokines and cytotoxic molecules, including nitric oxide, reactive oxygen species, and their reaction product peroxynitrite. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death. Honey, in addition to its well-known sweetening properties, is a natural antioxidant that has been used since ancient times in traditional medicine. We examined the ability of Gelam honey, derived from the Gelam tree (Melaleuca spp.), to scavenge peroxynitrite during immune responses mounted in the murine macrophage cell line RAW 264.7 when stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ) and in LPS-treated rats. Gelam honey significantly improved the viability of LPS/IFN-γ-treated RAW 264.7 cells and inhibited nitric oxide production—similar to the effects observed with an inhibitor of inducible nitric oxide synthase (1400W). Furthermore, honey, but not 1400W, inhibited peroxynitrite production from the synthetic substrate 3-morpholinosydnonimine (SIN-1) and prevented the peroxynitrite-mediated conversion of dihydrorhodamine 123 to its fluorescent oxidation product rhodamine 123. Honey inhibited peroxynitrite synthesis in LPS-treated rats. Thus, honey may attenuate inflammatory responses that lead to cell damage and death, suggesting its therapeutic uses for several inflammatory disorders.

Recent advances on the use of biochemical extracts as filaricidal agents.

Lymphatic filariasis is a parasitic infection that causes a devastating public health and socioeconomic burden with an estimated infection of over 120 million individuals worldwide. The infection is caused by three closely related nematode parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera. The species have many ecological variants and are diversified in terms of their genetic fingerprint. The rapid spread of the disease and the genetic diversification cause the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. This in turn prompts the current challenge encountered in its management. Furthermore, most of the chemical medications used are characterized by adverse side effects. These complications urgently warrant intense prospecting on bio-chemicals that have potent efficacy against either the filarial worms or thier vector. In lieu of this, we presented a review on recent literature that reported the efficacy of filaricidal biochemicals and those employed as vector control agents. In addition, methods used for biochemical extraction, screening procedures, and structure of the bioactive compounds were also presented.

Optimising the Bariatric Patients’ Outcome through Cardiac Rehabilitation Approach

Bariatric surgery offers a therapeutic alternative with favourable weight management, cardiovascular, metabolic and functional outcomes. Bariatric individuals often have functional impairments pre-operatively that can be addressed to improve post-operative results and eventual functional independence. Multidisciplinary team offers the best approach to address peri-operative needs and sustainable weight loss thereafter. We exemplified the application of cardiac rehabilitation therapeutic model in managing two bariatric clients with specific bariatric-related challenges. Our approach focuses on adaptive physical activity, sustainable lifestyle changes to promote post-operative weight loss through education and problem solving as well as secondary prevention of cardiovascular disease. Putting emphasis on addressing physical and psychosocial barriers towards physical activity alongside nutritional aspects potentially confers sustained if not better outcomes on weight reduction and functional improvement.

Treatment of chronic back pain using indirect vibroacoustic therapy: A pilot study

BACKGROUND Low frequency sound wave stimulation therapy has become increasingly popular in the rehabilitation fields, due to its ease, less fatiguing and time efficient application. OBJECTIVE This 12-week pilot study examines the efficacy of applying low frequency sound wave stimulation (between 16-160 Hz) through both hands and feet on relieving pain and improving functional ability in patients with chronic back pain. METHODS Twenty-three participants with chronic shoulder (eleven participants) or low back pain (twelve participants) underwent a 12-week vibration therapy program of three sessions per week. A low frequency sound wave device comprising four piezoelectric vibration-type tactile tranducers enclosed in separate 5-cm diameter circular plates, which generate sinusoidal vibratory stimuli at a frequency of 16-160 Hz, was used in this study. Primary outcome measure was pain sensation measured using the Visual Analogue Scale (P-VAS). The secondary outcome measures were pain-related disability measured using the pain disability index (PDI) and quality of life measured using the SF-12. RESULTS At week 12, significant reductions in pain sensation and pain-related disability were observed, with mean reductions of 3.5 points in P-VAS and 13.5 points in the PDI scores. Sixty-five percent of the participants had a reduction of at least 3 points on the P-VAS score, while 52% participants showed a decrease of at least 10 points in the PDI score. Significant improvement was observed in the SF-12 physical composite score but not the mental composite score. CONCLUSIONS The preliminary findings showed that passive application of low frequency sound wave stimulation therapy through both hands and feet was effective in alleviating pain and improving functional ability in patients with chronic back pain.

Recovery of H-Reflex with Transforaminal Epidural Steroid Injection in S1 Radiculopathy

Transforaminal epidural steroid injection (TFESI) is a recognized nonsurgical management of radicular back pain through its effects on neural inflammation and edema [1]. Electrodiagnostic changes of the compressed nerve root such as Hoffmann reflex (H-reflex) are apparent within days following injury and persist throughout nerve compression [2], with sensitivity and specificity of 50% and 91%, respectively, making the detection of H-reflex abnormality an option to identify early radiculopathy [3]. Despite its prevalent diagnostic use, to our knowledge there is limited information in the current literature regarding changes of an abnormal H-reflex following treatment of radiculopathy. We have investigated the changes of the H-reflex profile following fluoroscopyguided epidural steroid injections in three patients with S1 radiculopathy secondary to disc herniation.

Perineural Injection Therapy in the Management of Complex Regional Pain Syndrome: A Sweet Solution to Pain

Perineural injection therapy (PIT) is one of the latest advancements in regenerative medicine. It targets cutaneous nerves as a potential pain generator. First described by Dr. Paul Pybus and Dr. Roger WyburnMason, PIT targets neurogenic inflammation in subcutaneous nerves that potentially generates pain [1,2]. PIT was further refined by Dr. John Lyftgoft using dextrose injection, which provided substantial pain control in a series of 300 Achilles tendinopathy [3]. However, this treatment approach remains largely unknown; thus we sought to document the effect of PIT in the management of complex regional pain syndrome (CRPS) and its outcome on pain and functional restoration.

Electrical stimulation-evoked contractions blunt orthostatic hypotension in sub-acute spinal cord-injured individuals: two clinical case studies

Study design:Prospective study of two cases.Objectives:To describe the effects of electrical stimulation (ES) therapy in the 4-week management of two sub-acute spinal cord-injured (SCI) individuals (C7 American Spinal Injury Association Impairment Scale (AIS) B and T9 AIS (B)).Setting:University Malaya Medical Centre, Kuala Lumpur, Malaysia.Methods:A diagnostic tilt-table test was conducted to confirm the presence of orthostatic hypotension (OH) based on the current clinical definitions. Following initial assessment, subjects underwent 4 weeks of ES therapy 4 times weekly for 1 h per day. Post-tests tilt table challenge, both with and without ES on their rectus abdominis, quadriceps, hamstrings and gastrocnemius muscles, was conducted at the end of the study (week 5). Subjects’ blood pressures (BP) and heart rates (HR) were recorded every minute during pre-test and post-tests. Orthostatic symptoms, as well as the maximum tolerance time that the subjects could withstand head up tilt at 60°, were recorded.Results:Subject A improved his orthostatic symptoms, but did not recover from clinically defined OH based on the 20-min duration requirement. With concurrent ES therapy, 60° head up tilt BP was 89/62 mm Hg compared with baseline BP of 115/71 mm Hg. Subject B fully recovered from OH demonstrated by BP of 105/71 mm Hg during the 60° head up tilt compared with baseline BP of 124/77 mm Hg. Both patients demonstrated longer tolerance time during head up tilt with concomitant ES (subject A: pre-test 4 min, post-test without ES 6 min, post-test with ES 12 min; subject B: pre-test 4 min, post-test without ES 28 min, post-test with ES 60 min).Conclusions:Weekly ES therapy had positive effect on OH management in sub-acute SCI individuals.

How long does the prevention effect last? A comparison of two case studies of different FES stimulation frequencies in stroke shoulder subluxation follow up period

There is strong evidence on the positive effect of functional electrical stimulation (FES) in preventing shoulder subluxation (SS) following stroke. However, the extent of such intervention has not been weekly documented with regards to different stimulation frequencies. It is unknown whether high or low frequency (35 Hz or 20 Hz) has better potential in maintaining the FES effect in preventing SS during the follow-up period. Two participants underwent standard prescribed physiotherapy sessions in a rehabilitation centre during their hospitalisation period. Electrical stimulation was administered to their supraspinatus and posterior deltoid muscles for up to 2 hours a day for 4 weeks. All stimulation parameters were set constant except the stimulation current, which depended on the subject tolerance, and stimulation frequency, which was set to high (35Hz: Subject A) and low (20 Hz: Subject B). No SS among the intervened subjects during the 4 weeks FES therapy period. The high (35 Hz) stimulation frequency prevented subluxation until the end of 4 weeks follow up period in Subject A while low stimulation (20 Hz) frequency stimulation maintained the effect for up to 2 weeks in Subject B. The effect of FES on SS could be maintained up to 4 weeks upon withdrawal without undergoing subsequent FES therapy. Given all parameters fixed and the stimulation current dependent on the subjects tolerance, high frequency stimulation (35Hz) may be recommended in a subluxation prevention programs to further maintain the stability of the shoulder joint.