The Beneficial Effects of Actinomycetales Immune Modulators in the Pancreas of Diabetic Rats.

Purpose: Type 1 diabetes mellitus (T1DM) has dramatically increased in recent years, especially in young people, and limits the life quality of the patients involved. Thus, many researchers are performing extensive studies to find alternative treatments for DM. Methods: Here, we evaluated the improvement effects of the heat-killed Actinomycetales species, including Gordonia bronchialis, and Tsukamurella inchonensis in streptozotocin (STZ)- diabetic rats by biochemical, immunological, and histopathological examinations. Results: The present findings exhibited a dramatic and progressive alteration in the serum levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) in the diabetic group, which were related to the blood glucose and insulin levels, oxidative stress defense (evaluated by TAC and MDA activities), and the pancreas biochemical indicators (such as amylase and lipase). More importantly, the present results were consistent with the histopathological findings, which included cellular degeneration, vascular congestion, hemorrhage, focal necrosis associated with mononuclear cell infiltration. Interestingly, all of the diabetic changes in the blood serum and tissues improved remarkably in the treated groups by Actinomycetales species. Conclusion: Surprisingly, most of the current diabetic complications effectively attenuated after oral administration of both Actinomycetales species, particularly with a high dose of T. inchonensis. Thus, it is concluded that the heat-killed Actinomycetales species can prevent and improve the progression of T1DM and its various complications profoundly.

Transmission of a novel sonotubometry acoustic click stimulus in healthy and patulous eustachian tube subjects: a retrospective case -control study.

BACKGROUND: Eustachian tube (ET) dysfunction can be very difficult to diagnose accurately. Our aim is to determine whether a newly developed sonotubometric test using clicks can reliably detect ET opening during swallowing in normal ET subjects, and patulous ET (PET) in subjects with ET dysfunction. METHODS: Sixteen subjects (19 normal ET ears and 6 PET ears) were individually placed in a sound-isolated audiometry booth and subjected to a 1000Hz click train stimulus, played through the nose. PET subjects were identified through the ET clinic at our institution, while healthy subjects were recruited. Transmission through the ET was recorded by a microphone in the ear ipsilateral to the presenting nostril, during no swallow and swallow states, and this was used to compute a power ratio (power in the frequency range of interest to the whole frequency range). The power transmission ratio both before and after the swallow was averaged, and represented the baseline (BaseR). The power transmission ratio during swallow represented the peak (PeakR). The same process was repeated in the absence of a stimulus to account for swallowing noise. Wilcoxon rank rum tests were performed to determine statistical significance. RESULTS: It was found that for healthy ET patients, the median difference between the PeakR and BaseR was 0.51 (p = 0.004). For the PET patients in this study, the median difference between the PeakR and the BaseR was 3.30 (p = 0.041). Comparing the baseline between groups revealed that PET patients had a median BaseR 1.05 higher than healthy ET patients. PET patients had a median PeakR of 3.84 higher than healthy ET patients. Both were deemed to be statistically significant (p = 0.003, p = 0.003 respectively). A significant difference was found between median PeakR for the stimulus and no-stimulus condition for the healthy ET group (0.59, p < 0.001) and for the PET group (4.39, p = 0.031), indicating that it was unlikely that swallowing noise caused false positive results. CONCLUSION: The results of this study suggest that a novel click stimulus is capable of detecting ET opening during swallowing in healthy patients as well as highlighting PET in diseased subjects.

Beneficial effects of immunotherapy with extracts derived from Actinomycetales on rats with spontaneous obesity and diabetes.

AIMS: To determine whether immunotherapy with heat-killed, selected Actinomycetales species could influence the progression of spontaneous Type 2 diabetes mellitus and obesity in a rat model. MATERIALS & METHODS: Preparations of either Gordonia bronchialis, Tsukamurella inchonensis or a saline placebo were given by three subcutaneous injections, 30 days apart, starting when rats were aged 120 days, just before development of Type 2 diabetes mellitus, and at day 440, when the disease was well established. Bodyweight, blood sugar, cholesterol, triglycerides and insulin levels were measured to determine the effects and at the end of the experiments, animals were subjected to necropsy. RESULTS: The development of Type 2 diabetes mellitus was prevented by both reagents, most effectively by T. inchonensis. In the treatment experiment, the effects of the disease were reduced by both treatments, markedly so by T. inchonensis. In both experiments obesity was reduced in treated animals. The possible mechanisms of action are discussed. CONCLUSION: Our findings suggest that Type 2 diabetes mellitus in the studied rats is associated with obesity, and that both diabetes and obesity can be prevented or improved by treatment with Actinomycetales immune modulators.

Successful immunotherapy of canine flea allergy with injected Actinomycetales preparations.

AIMS: Can heat-killed, borate-buffered suspensions of Gordonia bronchialis, Rhodococcus coprophilus or Tsukamurella inchonensis be used to treat canine flea allergy? MATERIALS & METHODS: Organisms cultured on Sauton's medium into stationary phase were autoclaved in borate-buffered saline and stored at 10 mg wet weight/ml. Intradermal injections of 0.1 ml containing 1 mg of bacilli were administered on the first and 20th days of the study. G. bronchialis and R. coprophilus were most effective in a pilot study of a small number of dogs with flea allergy. A larger number of affected dogs were then randomized to receive placebo or either of the two selected reagents. The extent and severity of allergic signs and symptoms were scored and blood samples were collected just before the first injection and 28 days after the second. RESULTS: Both selected reagents reduced the extent and severity of lesions (p < 0.001) and reduced scratching. Eosinophil numbers were reduced (p < 0.0001) between the first and second assessment. CONCLUSIONS: Injections of G. bronchialis or R. coprophilus effectively reduce the signs and symptoms of flea allergy in dogs.

Immunotherapy for the prevention of myointimal hyperplasia after experimental balloon injury of the rat carotid artery.

We assessed the effect of novel immunotherapeutic heat-killed bacterial (Actinomycetales) preparations on the development of myointimal hyperplasia (MIH) in a rat carotid balloon trauma model and the effect on the immune response by measuring the expression of interferon gamma (IFN-gamma; (Th1) and interleukin 4 (IL-4; Th2). There was a significant reduction (P < .001) in intima/media ratios (mean +/- SEM) in the rats treated by immunomodulation (0.52 +/- 0.03 Gordonia bronchialis, 0.60 +/- 0.03 Rhodococcus coprophilus, 0.43 +/- 0.03 Tsukamurella inchonensis, 0.37 +/- 0.03 Mycobacterium vaccae), in comparison with untreated controls (0.91 +/- 0.05). Postballoon trauma G bronchialis increased messenger RNA (mRNA) IFN-gamma (P < .02) and reduced mRNA IL-4 (P < .05). R coprophilus, T inchonensis, and M vaccae significantly increased production of mRNA IFN-gamma (P < .001). R coprophilus and M vaccae also decreased production of mRNA IL-4 (P < .05, P < .01). Treatment with heat-killed Actinomycetales inhibits MIH through a combination of enhanced Th1 and attenuated Th2 response. Immunomodulation may provide a novel therapeutic option to prevent restenosis.