PURPOSE OF REVIEW: Although many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review.
RECENT FINDINGS: Although complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value.
SUMMARY: The adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals' patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.
METHODOLOGY/PRINCIPAL FINDINGS: Ten SAGs, belonging to two previously defined multigene families (A and B), were expressed as soluble recombinant (r) fusion proteins in E. coli. Chicken macrophages were treated with purified rSAGs and changes in macrophage nitrite production, and in mRNA expression profiles of inducible nitric oxide synthase (iNOS) and of a panel of cytokines were measured. Treatment with rSAGs 4, 5, and 12 induced high levels of macrophage nitric oxide production and IL-1β mRNA transcription that may contribute to the inflammatory response observed during E. tenella infection. Concomitantly, treatment with rSAGs 4, 5 and 12 suppressed the expression of IL-12 and IFN-γ and elevated that of IL-10, suggesting that during infection these molecules may specifically impair the development of cellular mediated immunity.
CONCLUSIONS/SIGNIFICANCE: In summary, some E. tenella SAGs appear to differentially modulate chicken innate and humoral immune responses and those derived from multigene family A (especially rSAG 12) may be more strongly linked with E. tenella pathogenicity associated with the endogenous second generation stages.
METHODS: A non-blinded, randomised controlled trial will be conducted. A total of sixty-six patients who fulfil the inclusion criteria will be recruited. The participants will be randomly allocated into intervention (traditional Malay massage) and control (relaxation position) groups. Blood and saliva samples will be collected before and immediately after intervention. All collected samples will be analysed. The primary outcomes are the changes in the level of substance P in both saliva and blood samples between both groups. The secondary outcomes include the levels of inflammatory mediators [i.e. TNF-α, IL-1β, IL-8, monocyte chemotactic protein-1, IL-6 and IL-10, and the soluble form of the intercellular adhesion molecule], the pain intensity as measured by a visual analogous scale and functional outcomes using the Roland-Morris Disability Questionnaire.
DISCUSSION: Massage is a type of physical therapy that has been proven to be potentially capable of reducing unpleasant pain sensations by a complex sensory response and chemical mediators such as substance P and various inflammatory mediators. Previous studies conducted using Thai, Swedish, or other forms of massage therapies, have showed inconsistent findings on substance P levels pre and post the interventions. Each massage genre varies in terms of massage and joint mobilization points, as well as the lumbar spinous process. Traditional Malay massage, known locally as "Urut Melayu", involves soft-tissue manipulation of the whole body applied using the hands and fingers. This massage technique combines both deep muscular tissue massage and spiritual rituals. This trial is expected to give rise to new knowledge underlying the mechanisms for pain and inflammation relief that are activated by traditional Malay massage.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials ACTRN12615000537550 .