Long-term aspirin administration suppresses inflammation in diabetic cystopathy.

Diabetic cystopathy (DCP) is one of the most common and troublesome urologic complications of diabetes mellitus, characterized by chronic low-grade inflammatory response. However, the correlation between inflammation and disease progression remains ambiguous and effective drugs interventions remain deficient. Herein, during 12-week study, 48 male Sprague-Dawley rats were randomly assigned to four groups: negative control (NC), NC treated with aspirin (NC+Aspirin), DCP, and DCP treated with aspirin (DCP+Aspirin). Type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin (65 mg/kg). After 2 weeks modeling, the rats in treatment groups received daily oral aspirin (100 mg/kg/d). After 10 weeks of treatment, aspirin ameliorated pathological weight loss and bladder weight increase in diabetic rats, accompanied by a 16.5% decrease in blood glucose concentrations. H&E, Masson, immunohistochemistry and transmission electron microscopy revealed that a dilated bladder with thickened detrusor smooth muscle (DSM) layer, inflammatory infiltration, fibrosis and ultrastructural damage were observed in diabetic rats, which were obviously ameliorated by aspirin. The dynamic investigations at 4, 7 and 10 weeks revealed inflammation gradually increased as the disease progresses. After 10 weeks of treatment, the expression of TNF-α, IL-1ß, IL-6, and NF-κB has been decreased to 78%, 39.7%, 44.1%, 33.3% at mRNA level and 67.6%, 76.7%, 71.4%, 67.1% at protein level, respectively (DCP+Aspirin vs. DCP, p < 0.01). Aspirin partially restored the increased expression of inflammatory mediators in bladder DSM of diabetic rats. The study provided insight into long-term medication therapies, indicating that aspirin might serve as a potential strategy for DCP treatment.

A Spectrum of Age- and Gender-Dependent Lower Urinary Tract Phenotypes in Three Mouse Models of Type 2 Diabetes.

Lower urinary tract symptoms are extremely common in people with diabetes and obesity, but the causes are unclear. Furthermore, it has proven difficult to reliably demonstrate bladder dysfunction in diabetic mouse models, thus limiting the ability to gain mechanistic insights. Therefore, the main objective of this experimental study was to characterize diabetic bladder dysfunction in three promising polygenic mouse models of type 2 diabetes. We performed periodic assessments of glucose tolerance and micturition (void spot assay) for eight to twelve months. Males and females and high-fat diets were tested. NONcNZO10/LtJ mice did not develop bladder dysfunction over twelve months. TALLYHO/JngJ males were severely hyperglycemic from two months of age (fasted blood glucose ~550 mg/dL), while females were moderately so. Although males exhibited polyuria, neither they nor the females exhibited bladder dysfunction over nine months. KK.Cg-Ay/J males and females were extremely glucose intolerant. Males exhibited polyuria, a significant increase in voiding frequency at four months (compensation), followed by a rapid drop in voiding frequency by six months (decompensation) which was accompanied by a dramatic increase in urine leakage, indicating loss of outlet control. At eight months, male bladders were dilated. Females also developed polyuria but compensated with larger voids. We conclude KK.Cg-Ay/J male mice recapitulate key symptoms noted in patients and are the best model of the three to study diabetic bladder dysfunction.

Diabetes mellitus urological complication.

Diabetes mellitus is a disease characterized by chronic hyperglycaemia due to an absolute or relative lack of insulin. The disease mainly affects the nervous system, and the urological complications themselves develop on the basis of these disorders. Urological patients with diabetes present in ambulance with manifestations of common urological diseases, but also suffer from complications of the urinary system or genital organs that are specific for diabetic patient. Usually, these complications go unrecognized for a long time or manifest only non-specifically. But they are often life-threatening for patients. Treatment does not consist only in urological stabilization, but stabilization of the diabetes itself is also necessary. It can be said that diabetes increases the risk of urological problems, and on the contrary, urological problems (especially inflammation) can lead to decompensation of the patient's diabetes.

Anti-inflammation properties of resveratrol in the detrusor smooth muscle of the diabetic rat.

PURPOSE: In this paper, we aimed to prove that resveratrol can inhibit inflammation in the detrusor smooth muscle of diabetic rats, which may provide a new direction for diabetic cystopathy (DCP) treatment. METHODS: We induced a Sprague-Dawley (SD) rat model of type 1 diabetes by intraperitoneal injections of streptozotocin (STZ). Then, we separated the SD rats into four groups: (1) an excipient-treated control group; (2) a resveratrol-treated control group; (3) an excipient-treated streptozotocin (STZ)-injected group; and (4) a resveratrol-treated STZ-injected group. We administered the resveratrol or excipient by intragastric administration. After 12 weeks of diabetes induction, we measured the blood-sugar concentrations and bladder weights, and we took the bladder tissues of each group of rats for hematoxylin-eosin staining to observe the histological changes. We used real-time quantitative polymerase chain reaction (qPCR) and Western blotting to analyze the expression levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin (IL)-6, and IL-1ß. RESULTS: The bodyweights of the diabetic rats were appreciably reduced, while the bladder weights and blood-glucose concentrations were substantially increased. Oral resveratrol could not improve the changes in the bodyweights and blood-glucose concentrations, but it had a certain effect on the bladder weights. In a macroscopic evaluation, the bladder walls of the STZ-induced diabetes rats were thickened, and, from the H&E staining, we could see that the bladder tissues of the diabetic rats had inflammatory cell infiltration, edema, and the capillary congestion of the mucosa and lamina propria. After resveratrol treatment, the bladder-wall thickening was reduced, and the tissue damage and inflammation were significantly ameliorated. We could associate all these changes with markedly heightened expressions of TNF-α, IL-1ß, IL-6, and NF-κB in the detrusor smooth muscle (DSM) tissues of the diabetic rats. Oral treatment with resveratrol alleviated the expressivity of the inflammatory cytokines in the DSM tissues. CONCLUSIONS: Resveratrol treatment ameliorated the histological changes in the bladder and inhibited the expressions of DSM-tissue inflammatory factors in diabetes rats. Resveratrol may provide a new direction of research for the treatment of diabetic cystopathy.

Myogenic Underactive Bladder and Heart Failure Resemblance: A Novel Role for SGLT2 Inhibition?

The heart and bladder share physiological biomechanical determinants of contraction. Heart failure (HF) and myogenic underactive bladder (mUAB) also share similarities in their pathophysiology. In both cases there is muscle injury that is directly linked to disease stage. In the final stage, both myocardium and detrusor show marked fibrosis and lower contractility. While HF has an established pharmacological treatment, there are still no effective drugs for mUAB. This mini-review explores the similarities between HF and mUAB and suggests that, as in HF, SGLT2 inhibitors may also have a beneficial role in mUAB. PATIENT SUMMARY: To date, there is no treatment for underactive bladder caused by problems with the bladder muscle (mUAB). We review similarities between this condition and heart failure and hypothesize that a recent drug class with striking results in heart failure might also have a beneficial role in mUAB.

Daidzein attenuates urinary bladder dysfunction in streptozotocin-induced diabetes in rats by NOX-4 and RAC-1 inhibition.

Reactive oxygen species via NADPH oxidase (NOX) activation are involved in the pathogenesis of many disease conditions such as diabetes and its complications. In the present study, we have examined the effect of daidzein in the management of diabetic cystopathy. Diabetes was induced in male Sprague Dawley rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg. After 6 weeks of diabetes induction, animals were treated with daidzein orally at a dose of 25, 50, and 100 mg/kg for 4 weeks. Diabetic animals showed increase (p < 0.001) in bladder capacity (4.32 ± 0.43 mL) and residual volume (2.53 ± 0.19 mL) when compared with normal control animals (2.10 ± 0.40 mL and 0.51 ± 0.12 mL res). Treatment with daidzein at dose of 50 and 100 mg/kg significantly reduced the elevated bladder capacity (2.91 ± 0.11 mL, p < 0.01 and 2.65 ± 1.13 mL, p < 0.001) and residual volume (1.40 ± 0.15 mL, p < 0.001 and 1.15 ± 0.05 mL, p < 0.001). Daidzein-treated animals also showed improvement in voiding efficiency. Elevated threshold and baseline pressure were also found to be reduced in diabetic animals after 4 weeks of daidzein treatment. Daidzein treatment also prevented the loss of antioxidant enzymes in the urinary bladder and also reduced the expression of NOX-4 and RAC-1 in the bladder. From the results, it can be concluded that daidzein showed a beneficial effect on urinary bladder dysfunction in diabetic animals.

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model.

BACKGROUND: Diabetic cystopathy (DCP) is a chronic complication of diabetes mainly within the submucosal and muscular layers of the bladder due to the hyperglycemia-induced ischemia. As no effective therapies are currently available, the administration of optimized mesenchymal stem cells (MSCs) provides a potential treatment of DCP. Thus far, new strategy, such as genetic modification of MSCs, has been developed and has shown promising outcomes of various disorders. METHODS: This study was conducted using integrin-linked kinase (ILK) gene-modified bone marrow-derived stem cells (BMSCs) for streptozotocin (STZ)-induced diabetic cystopathy in a rat model. In total, 68 male Sprague-Dawley rats were randomized into five groups: sham control (control group, n = 10); DCP model alone (DM group, n = 10); DCP rats intravenously treated with BMSCs (BMSC group, n = 16); DCP rats accepted adenoviral vector-infected BMSCs (Ad-null-BMSC group, n = 16) and DCP rats accepted ILK adenoviral vector-infected BMSCs (Ad-ILK-BMSC group, n = 16). Diabetic rats accepted cell transplantation in the experimental group (2 rats per group) were sacrificed for the bladder tissue on the third day, 7th day, and 14th day of treatment respectively ahead of schedule. At 4 weeks after treatment, all rats in five groups accepted urodynamic studies to evaluate bladder function and were sacrificed for bladder tissue. RESULTS: Our data showed that the underactive bladder function was significantly improved in DCP rats intravenously treated with ILK gene-modified BMSCs compared to those in the DM, BMSCs, and Ad-null-BMSC group. Meanwhile, we found that gene-modified BMSC treatment significantly promoted the activation of the AKT/GSK-3ß pathway by increasing phosphorylation and led to the enhancement of survival. In addition, the expression levels of angiogenesis-related protein vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1 (SDF-1) were significantly higher in the Ad-ILK-BMSC group than that in the DM, BMSCs, and Ad-null-BMSC group as assessed by enzyme-linked immunosorbent assay and western blot. As two indicators of vascular endothelial cell markers, the expression of von Willebrand factor (vWF) and CD31 by western blot and immunofluorescent staining revealed that the percentage of the vascular area of the bladder tissue significantly increased in Ad-ILK-BMSC group compared with the BMSCs and Ad-null-BMSC group on the 14th day of treatment. Histological and immunohistochemical staining (hematoxylin and eosin (HE), vWF, Ki67, and TUNNEL) on the bladder tissue revealed statistically different results between groups. CONCLUSION: ILK gene-modified BMSCs restored the bladder function and histological construction via promoting the process of angiogenesis and protecting cells from high glucose-associated apoptosis in STZ-induced DCP rat model, which provides a potential for the treatment of patients with DCP.

Detrusor contractility to parasympathetic mediators is differentially altered in the compensated and decompensated states of diabetic bladder dysfunction.

Diabetic bladder dysfunction (DBD) affects up to 50% of all patients with diabetes, characterized by symptoms of both overactive and underactive bladder. Although most diabetic bladder dysfunction studies have been performed using models with type 1 diabetes, few have been performed in models of type 2 diabetes, which accounts for ~90% of all diabetic cases. In a type 2 rat model using a high-fat diet (HFD) and two low doses of streptozotocin (STZ), we examined voiding measurements and functional experiments in urothelium-denuded bladder strips to establish a timeline of disease progression. We hypothesized that overactive bladder symptoms (compensated state) would develop and progress into symptoms characterized by underactive bladder (decompensated state). Our results indicated that this model developed the compensated state at 1 wk after STZ and the decompensated state at 4 mo after STZ administration. Diabetic bladders were hypertrophied compared with control bladders. Increased volume per void and detrusor muscle contractility to exogenous addition of carbachol and ATP confirmed the development of the compensated state. This enhanced contractility to carbachol was not due to increased levels of M3 receptor expression. Decompensation was characterized by increased volume per void, number of voids, and contractility to ATP but not carbachol. Thus, progression from the compensated to decompensated state may involve decreased contractility to muscarinic stimulation. These data suggest that the compensated state of DBD progresses temporally into the decompensated state in the male HFD/STZ model of diabetes; therefore, this male HFD/STZ model can be used to study the progression of DBD.

Urodynamic analysis of the impact of diabetes mellitus on bladder function.

OBJECTIVES: To analyze sequential changes of diabetic cystopathy based on urodynamic data in patients with diabetes mellitus. METHODS: Participants included male diabetes patients who underwent a pressure flow study at Nagoya University Graduate School of Medicine, Nagoya, Japan, from April 2005 to October 2016. Patients with a previous history of lower urinary tract dysfunction were excluded. Bladder dysfunction was categorized into four urodynamic patterns: (i) normal; (ii) detrusor overactivity with normal detrusor contractility; (iii) detrusor hyperreflexia/impaired contractility; and (iv) detrusor underactivity. The urodynamic patterns were evaluated according to the presence of diabetic retinopathy and nephropathy, which was correlated to diabetes mellitus duration. Furthermore, the association of clinical factors with voiding function, as well as sensory function, was investigated. RESULTS: A total of 57 patients were enrolled. Detrusor overactivity with normal detrusor contractility patterns was seen only in cases with neither diabetic retinopathy nor diabetic nephropathy, whereas the prevalence of detrusor hyperreflexia/impaired contractility pattern was highest in cases with diabetic retinopathy. Detrusor underactivity pattern was found with the highest frequency in cases with both diabetic retinopathy and diabetic nephropathy. On multivariate analysis, the existence of diabetic retinopathy was only significantly correlated with bladder contractility index. Furthermore, multivariate analysis showed that first desire volume and maximum cystometric capacity were significantly positively correlated with post-void residual urine volume, and also negatively correlated with voiding efficiency independent of bladder contractility index. CONCLUSIONS: Diabetes patients have diverse progressive bladder dysfunction according to the diabetes stage. An optimal screening program is necessary to detect and manage diabetic cystopathy at an early stage.

[Urinary disturbances in patients with diabetes].

The significance of diabetes is not only due to its high prevalence, but also to its serious complications. Urinary disturbances, which are referred as diabetic cystopathy, are among the most common complications of diabetes. The current data on the prevalence, manifestations, and possible pathogenesis of diabetic cystopathy are presented in the review of literature.

Urothelial Senescence in the Pathophysiology of Diabetic Bladder Dysfunction-A Novel Hypothesis.

Diabetic bladder dysfunction (DBD) is a well-recognized and common symptom affecting up to 50% of all diabetic patients. DBD has a broad range of clinical presentations ranging from overactive to underactive bladder symptoms that develops in middle-aged to elderly patients with long standing and poorly controlled diabetes. Low efficacy of current therapeutics and lifestyle interventions combined with high national healthcare costs highlight the need for more research into bladder dysfunction pathophysiology and novel treatment options. Cellular senescence is an age-related physiologic process in which cells undergo irreversible growth arrest induced by replicative exhaustion and damaging insults. While controlled senescence negatively regulates cell proliferation and promotes tissue regeneration, uncontrolled senescence is known to result in tissue dysfunction through enhanced secretion of inflammatory factors. This review presents previous scientific findings and current hypotheses that characterize diabetic bladder dysfunction. Further, we propose the novel hypothesis that cellular senescence within the urothelial layer of the bladder contributes to the pro-inflammatory/pro-oxidant environment and symptoms of diabetic bladder dysfunction. Our results show increased cellular senescence in the urothelial layer of the bladder; however, whether this phenomenon is the cause or effect of DBD is unknown. The urothelial layer of the bladder is made up of transitional epithelia specialized to contract and expand with demand and plays an active role in transmission by modulating afferent activity. Transition from normal functioning urothelial cells to secretory senescence cells would not only disrupt the barrier function of this layer but may result in altered signaling and sensation of bladder fullness; dysfunction of this layer is known to result in symptoms of frequency and urgency. Future DBD therapeutics may benefit from targeting and preventing early transition of urothelial cells to senescent cells.

Store operated calcium channels are associated with diabetic cystopathy in streptozotocin­induced diabetic rats.

Store operated calcium channels (SOCCs) have been suggested to play a critical role in many diabetic complications. Diabetic cystopathy (DCP) is common in patients with diabetes, but the role of SOCCs in DCP is still unclear. The aim of the present study was to investigate the role of SOCCs in DCP with streptozocin (STZ)­induced diabetic rats. Specifically, the authors investigated whether SOCCs were altered in streptozocin (STZ)­induced diabetic rats and, if so, how this may contribute to the contraction of bladder detrusor strips and the intracellular Ca2+ concentration of bladder smooth muscle cells in diabetic rats. Cyclopiazonic acid (CPA, 10 µM) and SKF­96365 (10 µM) were used to activate and inhibit SOCCs respectively, to research the effects of SOCCs on the contraction of the bladder detrusor strips in normal and STZ­induced diabetic rats at the 4th, 8th and 12th week after the diabetic rat model was established. The changes of intracellular Ca2+ were also evaluated under confocal microscopy with pretreated Fluo­4AM. In addition, the expressions of Orai1 and STIM1 were detected by reverse transcription­quantitative polymerase chain reaction and western blotting at different time points. According to the results, the contractive frequency of diabetic bladder muscle strips was higher than that of controls in the 4th and 8th week. The increased fluorescence intensity was detected after using CPA and SKF­96365 in diabetic groups. The expressions of Orai1 and STIM1 changed in a time­dependent manner.

Inosine protects bladder structure and function in rats with diabetic cystopathy / 医学研究生学报

Objective At present,there is still a lack of effective means for the treatment of diabetic cystopathy,and to find natural antioxidants for this purpose has become a hot spot in research. This study is to investigate the protective effect of inosine on the bladder of diabetic rats and its antioxidative stress mechanisms. Methods A total of 60 adult male Sprague-Dawley rats were ran-domly divided into three groups of equal number:normal control,diabetes mellitus(DM) model control,and inosine intervention. The DM model was made by intraperitoneal injection of streptozotocin at 60 mg/kg. The DM model controls were injected with saline while the model rats in the intervention group with inosine, all at 75 mg/kg, ip,bid. After 4 and 8 weeks of treatment, the bladder tissues were collected from the rats for examination of the structural changes by HE staining,determination of the expressions of c-kit and nerve growth factor (NGF) by immunofluorescence assay, and observation of the ultrastructure of the bladder tissue under the electron microscope,de-tection of the cell apoptosis by TUNEL,and measurement of the con-tents of malondialdehyde (MDA),superoxide dismutase (SOD),and glutathione (GSH). Results HE staining indicated signifi-cant mucosal hyperplasia, disordered arrangement, loose structure, fracture, expanded intervals and collagen fiber filling of muscle bundles,muscular atrophy,lymphocytes infiltration,vascular hyperplasia and congestion,and few muscle bundles,while electron mi-croscopy manifested disordered arrangement, interrupted connection, mitochondrial vacuolation in muscular and interstitial cells, shrinkage of nuclear membrane,disappearance of nucleoli,and irregular chromatin margination and condensation in the bladder tissues of the DM rat models. Immunofluorescence assay showed that the signals of c-kit and NGF were reduced in the DM models as compared with those in the normal controls. After 4 and 8 weeks of intervention,the cell apoptosis rate was significantly higher in the DM model control ([1.68±3.04]% and [10.51±0.90]%) and inosine-treated rats ([7.00±1.72]% and [7.24±1.66]%) than in the normal controls ([4.65±3.04]% and[5.48±2.00]%),but remarkably lower in the inosine-treated than in the DM model controls(P<0.01). The contents of SOD and GSH were increased(P<0.05) while that of MDA decreased markedly in the DM models(P<0.05),but the former decreased (P<0.05) while the latter increased significantly in the inosine intervention group as compared with the DM model control group (P<0.05). At 8 weeks,the contents of SOD and GSH were remarkably lower in the DM model than in the normal con-trols (P<0.01),while that of MDA markedly higher than in both the normal control and inosine intervention groups (P<0.01). The wet weight of the bladder was significantly increased in the DM model and inosine intervention groups in comparison with that of the nor-mal controls(P<0.01). Conclusion Oxidative stress plays an important role in the development and progression of diabetic cystopa-thy. Inosine can protect the bladder structure and function of the DM rat by reducing oxidative stress and injury to the bladder tissue.

Human Umbilical Cord Mesenchymal Stem Cells Overexpressing Nerve Growth Factor Ameliorate Diabetic Cystopathy in Rats.

Diabetic cystopathy is a common complication of voiding disorders in diabetes mellitus. Neuropathy and bladder remodeling underlie the lack of efficacy of pharmacological and surgical treatments. Previous studies have shown that decreased levels of nerve growth factor (NGF) are closely associated with disease progression. Besides, application of human umbilical cord mesenchymal stem cells (hUC-MSCs) is also considered a promising therapeutic strategy for treatment of diabetic neuropathy. In our study, we determine the therapeutic efficacy and mechanisms of hUC-MSCs which transfected with NGF geen in ameliorating diabetic cystopathy for the first time. We transducted hUC-MSCs with NGF-expressing lentivirus so that the hUC-MSCs can express NGF efficiently, then the NGF-expressing hUC-MSCs were intrathecally administrated in L6-S1 spinal cord of diabetic rats 3 days after induced by streptozotocin. Nine weeks later, the level of neurotrophins and voiding function of bladder were detected. Results show that improvements in voiding function were related to the neurotrophins and cytokines released by the intrathecally transplanted hUC-MSCs. In addition, the hUC-MSCs also differentiated into neurons and astrocytes within the spinal cord in rats. These two mechanisms play a combined role in neural regeneration and the amelioration of the symptoms of diabetic cystopathy.

Integrin-Linked Kinase Improves Functional Recovery of Diabetic Cystopathy and Mesenchymal Stem Cell Survival and Engraftment in Rats.

OBJECTIVES: Diabetic cystopathy (DCP), characterized by peripheral neuropathy-associated bladder dysfunction, is a common urinary complication in patients with diabetes (~80%). Bone marrow mesenchymal stem cell (BMMSC) transplantation, a new and emerging regenerative therapy, provides a curative option for DCP. However, the application of this therapy is limited by the low survival rate and engraftment of transplanted stem cells. This study was undertaken to determine whether integrin-linked kinase (ILK) overexpression would improve stem cell survival and engraftment after BMMSC transplantation. METHODS: Diabetes was induced in rats by injection of streptozotocin. ILK expression was detected by qRT-PCR and Western blot. Bladder function was measured by urodynamic analyses. Smooth-muscle regeneration and vascularization were evaluated by immunohistochemistry staining. RESULTS: ILK overexpression by adenovirus promotes proliferation of BMMSCs in vitro. ILK overexpression enhanced the ability of BMMSCs to decrease the volume threshold for micturition and residual urine in the rats with diabetes. The contractile response of bladder strips, tissue structure of bladder and smooth-muscle regeneration/vascularization were also improved in the rats receiving ILK-modified BMMSCs. CONCLUSIONS: Our data highlight the clinical potential of transplantation of gene-modified BMMSCs in the treatment of DCP, thereby serving as a rapid and effective first-line strategy to cure the bladder dysfunction resulting from long-term diabetes.

Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats.

AIMS: Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS-associated detrusor muscle apoptosis in streptozocin (STZ)-induced diabetic rats. METHODS: At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub-cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS-associated apoptosis, including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time-dependent fashion were detected. CONCLUSIONS: The occurrence of ERS-associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65-72, 2017. © 2015 Wiley Periodicals, Inc.

Genitourinary Complications of Diabetes Mellitus: An Overview of Pathogenesis, Evaluation, and Management.

BACKGROUND: Diabetes mellitus is a vastly prevalent metabolic disorder with escalating global health concerns. Particularly when mismanaged, chronic micro- and macrovascular complications may highly impair physiological systems while immunodeficiency disposes us to infection. OBJECTIVE: We investigate infections, localized complications, and neoplasms of the genitourinary system secondary to the chronic complications of diabetes mellitus in males and females. METHOD: A comprehensive MEDLINE® search was guided using key words relevant to diabetes mellitus and the genitourinary system. RESULTS: Pathogen-friendly environments may implicate the sequelae of urinary tract and genital mycotic infections, potentially generating necrosis, abscess, and other inflammatory complications, which may present concomitantly with neurogenic and/or vasculogenic dysfunction to further exacerbate an existing genitourinary condition. Manifestations of the adrenal, renal, and genital organs and tissues are discussed as they relate to vascular, immunodeficient, and other hyperglycemic complications of the diabetic state. Among those, chronic kidney disease and cystopathy are the most prevailing and detrimental. Though studies have connected diabetes to either an increased risk of developing or poor prognosis of bladder, renal, prostate, endometrial, and cervical cancers, the explicit biological relationships are as of yet inconclusive. CONCLUSION: Despite the availability of precise treatments to ameliorate most presently reviewed conditions, particularly urinary tract and genital mycotic infection-related sequelae, reversing permanent vascular damage remains a great challenge. Leading a healthier lifestyle and managing diabetes mellitus with a patient-centric approach from the outset are the most putative methods for preventing critical long-term genitourinary manifestations of diabetes mellitus.

Research progress about the cause of diabetic cystopathy and the treatment of it by caffeine / 医学研究生学报

Diabetic cystopathy is one of the most common complications caused by diabetes in urinary system.There were no obvious clinical manifestations in the early stage of the disease.With the progress of the disease, various complicated lower urinary tract symptoms appeared gradually.All these clinical manifestations cause grate trouble in the health and the quality of life of patients.However, its pathogenesis is not clear, myogenic and neurogenic is the main theory of its pathogenesis.Some studies indicate that long-term consumption of caffeine can reduce the incidence of it, and this article will discuss the cause of this disease and the treatment of caffeine in order to guide clinical practice.

Pathogenic Significance and Treatment of Qi Deficiency and Blood Stasis in Diabetic Cystopathy / 中国中医药信息杂志

The etiology and pathogen of diabetic cystopathy is mainly due to qi deficiency of spleen and kidney, which leads to bladder and Sanjiao hypo-function of vital energy, losing opening and closing. In addition to blood stasis injury essence, it blocks the urinary tract. The main pathogen is qi deficiency and blood stasis. The qi deficiency of spleen and kidney is the fundamental aspect, while the blood stasis is the surface aspect. Excess resulted from deficiency, intermingled deficiency and excess, belong to asthenia in origin and asthenia in superficiality. Clinical application of method of invigorating qi, removing blood stasis and eliminating stagnation for diabetic cystopathy has a good clinical efficacy.