Stereological and gene expression examinations on the combined effects of photobiomodulation and curcumin on wound healing in type one diabetic rats.

We examined the effects of photobiomodulation (PBM) independently and combined with curcumin on stereological parameters and basic fibroblast growth factor (bFGF), hypoxia-inducible factor-1α (HIF-1α), and stromal cell-derived factor-1α (SDF-1α) gene expressions in an excisional wound model of rats with type one diabetes mellitus (T1DM). T1DM was induced by an injection of streptozotocin (STZ) in each of the 90 male Wistar rats. One round excision was generated in the skin on the back of each of the 108 rats. The rats were divided into six groups (n = 18 per group): control (diabetic), untreated group; vehicle (diabetic) group, which received sesame oil; PBM (diabetic) group; curcumin (diabetic) group; PBM + curcumin (diabetic) group; and a healthy control group. On days 4, 7, and 15, we conducted both stereological and quantitative real-time PCR (qRT-PCR) analyses. The PBM and PBM + curcumin groups had significantly better inflammatory response modulation in terms of macrophages (P < .01), neutrophils (P < .001), and increased fibroblast values compared with the other groups at day 4 (P < .001), day 7 (P < .01), and day 15 (P < .001). PBM treatment resulted in increased bFGF gene expression on days 4 (P < .001) and 7 (P < .001), and SDF-1α gene expression on day 4 (P < .001). The curcumin group had increased bFGF (P < .001) expression on day 4. Both the PBM and PBM + curcumin groups significantly increased wound healing by modulation of the inflammatory response, and increased fibroblast values and angiogenesis. The PBM group increased bFGF and SDF-1α according to stereological and gene expression analyses compared with the other groups. The PBM and PBM + curcumin groups significantly increased the skin injury repair process to more rapidly reach the proliferation phase of the wound healing in T1DM rats.

Improvement in infected wound healing in type 1 diabetic rat by the synergistic effect of photobiomodulation therapy and conditioned medium.

We investigated the effects of photobiomodulation therapy (PBMT) and conditioned medium (CM) of human bone marrow mesenchymal stem cells (hBM-MSC) individually and/or in combination on the stereological parameters and the expression of basic fibroblast growth factor (bFGF), hypoxia-inducible factor (HIF-1α), and stromal cell-derived factor-1α (SDF-1α) in a wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) in diabetic rats. CM was provided by culturing hBM-MSCs. Type 1 diabetes mellitus (T1DM) was induced in 72 rats, divided into four groups, harboring 18 rats each: group 1 served as a control group, group 2 received PBMT, group 3 received CM, and group 4 received CM + PBMT. On days 4, 7, and 15, six animals from each group were euthanized and the skin samples were separated for stereology examination and gene expression analysis by real-time polymerase chain reaction. In the CM + PBMT, CM, and PBMT groups, significant decreases were induced in the number of neutrophils (1460 ± 93, 1854 ± 138, 1719 ± 248) and macrophages (539 ± 69, 804 ± 63, 912 ± 41), and significant increases in the number of fibroblasts (1073 ± 116, 836 ± 75, 912 ± 41) and angiogenesis (15 230 ± 516, 13 318 ± 1116, 14 041 ± 867), compared with those of the control group (2690 ± 371, 1139 ± 145, 566 ± 90, 12 585 ± 1219). Interestingly, the findings of the stereological examination in the CM + PBMT group were statistically more significant than those in the other groups. In the PBMT group, in most cases, the expression of bFGF, HIF-1α, and SDF-1α, on day 4 (27.7 ± 0.14, 28.8 ± 0.52, 27.5 ± 0.54) and day 7 (26.8 ± 1.4, 29.6 ± 1.4, 28.3 ± 1.2) were more significant than those in the control (day 4, 19.3 ± 0.42, 25.5 ± 0.08, 22.6 ± 0.04; day 7, 22.3 ± 0.22, 28.3 ± 0.59, 24.3 ± 0.19) and other treatment groups. The application of PBMT + CM induced anti-inflammatory and angiogenic activities, and hastened wound healing process in a T1 DM model of MRSA infected wound.

Correlation between Total Solar Irradiance and Glycated Hemoglobin 2 to 3 Months Later in Patients with Diabetes: A Big-Data Analysis.

OBJECTIVES: Much attention has been paid recently to a relationship between glucose metabolism and weather. This study investigated the temporal correlation between total solar irradiance (TSI) and glycated hemoglobin (A1C) values in patients with diabetes. METHODS: In 1531 patients with diabetes who received follow-up care between 2009 and 2013 (type 1 diabetes, 123 patients; type 2 diabetes, 1408 patients; male 53.6%; mean age, 61.2 years), A1C levels were measured a total of 58,830 times. The correlation between mean monthly TSI and mean A1C values from 1 to 4 months later was then examined. RESULTS: The mean values for TSI and A1C throughout the entire study period were 13.7 MJ/m2 and 7.7%, respectively. The correlation coefficient between TSI and mean monthly A1C values at 1 to 4 months was -0.516, -0.734, -0.726 and -0.475, respectively (all p<0.001). CONCLUSIONS: There was a highly negative correlation between TSI and mean A1C values 2 to 3 months later in this population; thus, this fact may need to be considered when using A1C levels as a glycemic control index in patients with diabetes. Further studies are warranted.

Histological and gene expression analysis of the effects of pulsed low-level laser therapy on wound healing of streptozotocin-induced diabetic rats.

Diabetes mellitus (DM) is associated with poor wound healing. Studies have shown accelerated wound healing following pulsed low-level laser therapy (LLLT) in non-diabetic animals. The present study aims to evaluate the effect of pulsed LLLT on wound healing in streptozotocin-induced diabetic (STZ-D) rats. We divided 48 rats into two groups of non-diabetic and diabetic. Type 1 DM was induced in the diabetic rat group by injections of STZ. Two, full-thickness skin incisions were made on the dorsal region of each rat. One month after the STZ injection, wounds of the non-diabetic and diabetic rats were submitted to a pulsed, infrared 890-nm laser with an 80-Hz frequency and 0.2 J/cm(2) for each wound point. Control wounds did not receive LLLT. Animals were sacrificed on days 4, 7, and 15 post-injury for histomorphometry and reverse transcription polymerase chain reaction (RT-PCR) analyses of basic fibroblast growth factor (bFGF) gene expression. Pulsed LLLT significantly increased the numbers of macrophages, fibroblasts, and blood vessel sections compared to the corresponding control groups. Semi-quantitative analysis of bFGF gene expression at 48 h post-injury revealed a significant increase in gene expression in both non-diabetic and diabetic rats following LLLT (the ANOVA test). Pulsed LLLT at 0.2 J/cm(2) accelerated the wound healing process in both non-diabetic and diabetic rats as measured by histological characteristics and semi-quantitative bFGF gene expression.

Attenuation of diabetes-induced renal dysfunction by multiple exposures to low-dose radiation is associated with the suppression of systemic and renal inflammation.

Renal protection against diabetes-induced pathogenic injuries by multiple exposures to low-dose radiation (LDR) was investigated to develop a novel approach to the prevention of renal disease for diabetic subjects. C57BL/6J mice were given multiple low-dose streptozotocin (STZ; 6 x 60 [corrected] mg/kg) to produce a type 1 diabetes. Two weeks after diabetes onset, some of diabetic mice and age-matched nondiabetic mice were exposed whole body to 25 mGy X-rays every other day for 2, 4, 8, 12, and 16 wk. Diabetes caused a significant renal dysfunction, shown by time-dependent increase in urinary microalbumin (Malb) and decrease in urinary creatinine (Cre), and pathological changes, shown by significant increases in renal structural changes and PAS-positive staining. However, diabetes-induced renal dysfunction and pathological changes were significantly, albeit partially, attenuated by multiple exposures to LDR. Furthermore, LDR protection against diabetes-induced renal dysfunction and pathological changes was associated with a significant suppression of diabetes-increased systemic and renal inflammation, shown by significant increases in serum and renal TNFalpha, ICAM-1, IL-18, MCP-1, and PAI-1 contents. To further explore the mechanism by which LDR prevents diabetes-induced renal pathological changes, renal oxidative damage was examined by Western blotting and immunohistochemical staining for 3-nitrotyrosine and 4-hydroxynonenal. Significant increase in oxidative damage was observed in diabetic mice, but not diabetic mice, with LDR. Renal fibrosis, examined by Western blotting of connective tissue growth factor and Masson's trichrome staining, was also evident in the kidneys of diabetic mice but not diabetic mice with LDR. These results suggest that multiple exposures to LDR significantly suppress diabetes-induced systemic and renal inflammatory response and renal oxidative damage, resulting in a prevention of the renal dysfunction and fibrosis.

Exogenous insulin treatment after hypofractionated radiotherapy in cats with diabetes mellitus and acromegaly.

BACKGROUND: The optimal treatment for feline acromegaly has yet to be established. Surgical and medical therapies are minimally effective although radiotherapy might have greater efficacy. The purpose of this study was to review the response and outcome of cats with acromegaly and insulin-resistant diabetes mellitus (DM) to radiotherapy. HYPOTHESES: That radiotherapy improves glycemic control in cats with acromegaly and that improved glycemic control is due to remission of clinical acromegaly; demonstrated by a fall in serum insulin-like growth factor-1 (IGF-1) concentrations. ANIMALS: Fourteen cats with naturally occurring acromegaly. METHODS: Retrospective case review; records of all cats treated for acromegaly with radiotherapy were reviewed from 1997 to 2008. Cats were selected on the basis of compatible clinical signs, laboratory features, and diagnostic imaging findings. Fourteen cats received radiotherapy, delivered in 10 fractions, 3 times a week to a total dose of 3,700 cGy. RESULTS: Thirteen of 14 cats had improved diabetic control after radiotherapy. These improvements were sustained for up to 60 months. DM progressed in 2 cats and 1 did not respond. Seven cats responded before the final treatment. Ten cats were euthanized, 1 as a consequence of radiotherapy. In 8 cats in which IGF-1 was measured after treatment, changes in its concentration did not reflect the clinical improvement in glycemic control. CONCLUSIONS AND CLINICAL IMPORTANCE: Radiotherapy represents an effective treatment for cats with insulin-resistant DM resulting from acromegaly. IGF-1 concentration after treatment does not provide a suitable method by which remission from either acromegaly or insulin-resistant DM may be assessed.

High-dose total body irradiation and bone marrow cells may improve efficiency of bone marrow transplantation therapy in treating type 1 diabetes.

Bone marrow transplantation (BMT) has been used to treat autoimmune diseases for many years. Insulin-dependent diabetes mellitus (IDDM), also called type 1 diabetes mellitus (T1DM), is a T cell-mediated autoimmune disease resulting from a selective destruction of pancreatic islet beta cells. Recently, T1D has been a common significant cause of morbidity and mortality. However, whether BMT can be used to treat T1DM is still controversial. During BMT procedure, recipients underwent total body irradiation (TBI) and subsequent bone marrow cells (BMCs) infusion, in which TBI kills off the most T lymphocytes and BMCs stimulates hematopoiesis and immune reconstitution. We suggest that high-dose TBI and BMCs may improve efficiency of BMT therapy in T1DM treatment.

The restorative effects of pulsed infrared light therapy on significant loss of peripheral protective sensation in patients with long-term type 1 and type 2 diabetes mellitus.

Pulsed infrared light therapy (PILT) has been shown to increase peripheral sensation in diabetic patients with diabetic peripheral neuropathy (DPN). However, most studies last for very short periods, with the subjects receiving only 6-20 treatments. The purpose of this study was to evaluate the effectiveness of an eight-week course of PILT in reversing long-standing, profound DPN in patients with type 1 and type 2 diabetes. Twenty-two subjects with a diagnosis of type 1 (n=2) or type 2 (n=20) diabetes participated in the study. PILT was administered to one foot chosen at random with the other foot serving as a within-subject control (no treatment). Patients underwent 24 treatments (3 times/week, for eight weeks) for 30 min per treatment. Changes in peripheral protective sensation (PPS) were measured using Semmes-Weinstein monofilaments (SWM) ranging from 3.7 to 6.48. PILT improved PPS even in patients with long-standing chronic neuropathies whose initial pre-study sensation was not measurable with a 200-g SWM. PILT significantly improves PPS. While the exact mechanism of action is not understood, infrared light may improve peripheral neuropathies by improving foot perfusion by stimulating nitric oxide production.

Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome.

Immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX, OMIM 304790) is a rare, recessive disorder resulting in aggressive autoimmunity and early death. Mutations in FOXP3 have been identified in 13 of 14 patients tested. Research in the mouse model, scurfy, suggests that autoimmunity may stem from a lack of working regulatory T cells. We review published reports regarding the genetics, clinical features, immunology, pathology, and treatment of IPEX. We also report three new patients who were treated with long term immunosuppression, followed by bone marrow transplantation in two. IPEX can be differentiated from other genetic immune disorders by its genetics, clinical presentation, characteristic pattern of pathology, and, except for high IgE, absence of substantial laboratory evidence of immunodeficiency. While chronic treatment with immunosuppressive drugs may provide temporary benefit for some patients, it does not cause complete remission. Remission has been observed with bone marrow transplantation despite incomplete engraftment, but the long term outcome is uncertain.

[Laser therapy in diabetes mellitus]. / Lazeroterapiia pry tsukrovomu diabeti.

Diabetic patients have been shown to derive great benefit from treatment with laser therapy as evidenced by experience gained with its use over many years. Laser therapy promotes compensation, has an antiatherogenic, antioxidant, immunomodulating effects, improves microcirculation, myocardial contractility and performance capability.

[Laser puncture in the treatment of diabetic angiopathies of the lower extremities]. / Lazeropunktura pri lechenii diabeticheskikh angiopatii nizhnikh konechnostei.

Laseropuncture in patients with diabetes mellitus associated with angiopathies of the lower extremities (grade II and III) produced a pronounced clinical effect which was manifested by removing the pain syndrome, improvement of the peripheral circulation and extremity function and function of the lower extremities, improvement of thermographic values. But this positive dynamics was more pronounced in angiopathies of the lower extremities of the stage of functional disorders than obliterating atherosclerosis of the legs. Sterility of the laser beam, possibility of local effect on biologically active points, non-painful procedure, absence of age limits and side effects allow to widely recommend this method for the treatment of Diabetes mellitus associated with angiopathies of the lower extremities.

[The effect of microwave resonance therapy on the clinical and metabolic indices of diabetic patients]. / Vliianie mikrovolnovoi rezonansnoi terapii na nekotorye klinicheskie i metabolicheskie pokazateli u bol'nykh sakharnym diabetom.

It has been established during studies carried out in 195 diabetes mellitus patients that the action of microwave resonance therapy on the points used in traditional acupuncture accelerates carbohydrate metabolism compensation, improves peripheral circulation. The beneficial effect of microwave resonance therapy on the clinical and metabolic characteristics in diabetes mellitus patients is likely to be determined by the lowering of the content of certain contrainsular hormones (cortisol, adrenaline) and by the improvement of the parameters of the T-cell immunity system.

Remission of the newly diagnosed type 1 diabetes by radiation of the pancreas.

The process of autoaggression of the IDDM causes an "insulitis" leading to the destruction of the beta-cells. By photons (9 MV) in a total dose of 10 Gy, divided into 5 single doses at an interval of 2 days in each case we could get a total remission in 3 out of 4 diabetics, a partly remission in the fourth patient. The therapeutic effect lasts till now (1-6 months) without any further treatment. The combination of a radiation of 5 x 1 Gy with 1 mg methylprednisolon/kg body weight at the beginning of the treatment leads to a partly remission in 5 out of 7 patients lasting 3-7 months hitherto. Beside the antiinflammatory effect of the radiation on the "insulitis" an effect on the activated lymphocytes can be supposed. Side effects were not observed. They need not to be expected in a local therapy in a relatively small field size with a low radiation dose. Further research is necessary to confirm the results.