| Background and Objectives:Interstitial cystitis (IC) is chronic suprapubic/bladder disorders (such as urgency, frequency, and pain with filling or emptying of the bladder)of unknown etiology, and exhibits inflammation and interstitial fibrosis in bladder tissues. The final diagnosis rate of IC in China was increased in recent years. It is a challenging and frustrating problem that affects 10% of middle-aged women. Knowledge of the basic mechanisms causing IC is fragmentary. In the diagnosis of IC, most patients had to undergo two cystoscopies or more, which caused greatly misery and currency waste to the patients. To this day, there are still no conclusive answers to many vital issues (e.g. etiology, diagnostic standardization and therapy), which has become a challenging problem for all urinologist. Although the presumption of some undiscovered infectious agents as the etiology of IC is controversial, some evidence suggests that IC may be caused by some infectious organisms, and some studies have shown that some IC patients reported significant reduction in the severity of IC symptoms after tetracycline treatment. Therefore, it is needed to explore a new agent to be related with IC, which may provide a potential target for the diagnosis and treatment of IC.Nanobacteria (NB) are a newly-discovered infectious agent linked with some inflammatory diseases. They are fastidious and difficult to be cultured and detectd with standard microbiologic methods. In our preliminary experiment, NB were successfully cultured from IC bladder biopsies and identified to be NB. Therefore, we infered that NB may participate in the clinical pathological process of IC. In this study, our study will show a preliminary association between NB and IC. Our results suggest that nanobacterial infection might be an important etiologic factor for IC/PBS, which may provide a potential rationale and experimental basis for the further study of the association between between NB and IC. Methods:1) IC patients were enrolled in this study according to the criteria of the National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK). All enrolled patients received a cystoscopy under anesthesia and bladder biopsies were obtained by cold cup technique. The NB were detected with indirect immunofluorescent staining (IIFS) and and transmission electron microscope (TEM).2) Bladder biopsies and urine samples after treatment were cultured for NB, which were identified by indirect immunofluorescent staining, transmission electron microscope and 16s rRNA gene expression.3) The patients with positive NB were received a combination of intravesical (500 mg mixed with 30 ml sterile normal buffered saline, bladder instillation) and oral tetracycline (500 mg/day, 3 months). OSPI and PUT were used at the beginning and the end of the trial to assess any changes in symptoms.4) Adult female SD rats were randomly divided into control group, physiological saline group, NB group and anti-NB group respectively. Bladder injection was used to build the model. Targets including urination, ethology observation, correlated inflammation, mast cells and correlated pain were all observed and detected to compare them among all groups. NB were also re-cultured and detected from the bladder tissues.Main results and conclusions:1?Twenty-seven IC patients were successfully enrolled in this study. NB were detected in bladder tissues from IC/PBS patients by IIFS and TEM, which were found tiny, existing in cytoplasm or bladder interstitium and clustered with different sizes. These results demonstrated that NB do exist in the bladder wall of IC/PBS patients.2?13 out of 27 (48.1%) bladder biopsies showed growth of white granular sediments which firmly were identified to be NB. However, the negative controls showed no microbe growth except one analogue of NB. These findings suggest that nanobacterial infection may participate clinical pathological process of IC and further study is needed.3?Anti-NB therapy could significantly relieve IC disorders and effectively improve the quality of life of IC patients.4?NB could cause bladder chronic inflammation of rat and anti-NB could significantly relieve bladder inflammation. 5?Bladder chronic inflammation caused by NB has in some aspects to IC, including: increased proinflammatory cytokines, mast cell proliferation and activation, and increased SP expression in the spine.6?These findings suggest that NB might be a potential etiologic factor of IC, which may provide a potential target for the diagnosis and treatment of IC. |
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