scholarly journals Non-invasive investigation of early kidney damage in streptozotocin-induced diabetic rats by intravoxel incoherent motion diffusion-weighted (IVIM) MRI

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
You-Zhen Feng ◽  
Xiao-Qiao Chen ◽  
Zhong-Yuan Cheng ◽  
Qi-Ting Lin ◽  
Ping-Kang Chen ◽  
...  

Abstract Background The current study investigated the performance of intravoxel incoherent motion diffusion (IVIM) technology in monitoring early renal injury in streptozotocin rats. Methods Forty-eight Sprague-Dawley (SD) rats were divided into a control group and a diabetic mellitus (DM) group. Six rats in each group were randomly selected for MR scans at four different time points (0, 4, 8, and 12 weeks). The IVIM-derived parameters (D, D*, f and ADC values) of the renal cortex (CO), outer and inner stripe of the outer medulla (OS, IS), and internal medulla (IM) were acquired. Changes in each IVIM-derived parameter over time were analyzed, and differences between the two groups at each point were assessed. The associations between the IVIM parameters and IV collagen expression, urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) were investigated. Results The D and D* values of CO and the ADC values of CO, OS, IS and IM displayed significantly different trends between the two groups over time (P<0.05). In addition, significant correlations were discovered between the D* value of CO and UV and BUN (r=0.527, P=0.033; r=0.617, P=0.005), between the ADC value of IM and BUN (r=0.557, P=0.019) and between the f value of IM and BUN (r=0.527, P=0.033). No correlation was found between IVIM parameters and IV collagen expression and Scr. Conclusions IVIM is a potential sensitive and noninvasive technology for the simultaneous assessment of early renal cortical and medullary injuries induced by diabetes.

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqin Zhang ◽  
Jiarui Li ◽  
Xiaolin Nong ◽  
Yuxiang Zhan ◽  
Jiazhi Xu ◽  
...  

Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren’s syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague–Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.


Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu

The purpose of this study was to investigate the effects of electroacupuncture at Zusanli acupoint on the enteric neuropathy in diabetic rats. Sprague–Dawley rats were divided into different groups depending on the total electroacupuncture span and frequency. The expression of nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5 (PGP9.5), and doublecortin was significantly decreased in the diabetic group compared with the control group. Long-term electroacupuncture at Zusanli with either high frequency or low frequency could increase the expression levels of nNOS, CHAT, PGP9.5, and doublecortin, and the increase was greater in the high-frequency group. But no obvious changes were seen in the short-term electroacupuncture groups. These results suggest that electroacupuncture at Zusanli can restore the deficiency of enteric neurons in diabetes partly but a comparative long duration of stimuli (6 weeks) is required. The increase of doublecortin may be involved in this positive process.


2019 ◽  
Vol 17 ◽  
pp. 205873921985855
Author(s):  
Kaijian Hou ◽  
Wansheng Ke ◽  
Jianping Xiong

This study was designed to investigate the effect of metformin on the improvement of prostate cancer in diabetic rats. A total of 20 Sprague Dawley (SD) rats were equally divided into control and intervention groups. The intervention group received intragastric metformin 200 mg/kg, while the control group was given intragastric drinking water for 4 weeks. Tumor volumes were compared, all tumor specimens underwent routine pathological examination, immunohistochemical detection of E-cadherin and N-cadherin, and western blot assay. The tumor volume of control and intervention group was 462.15 ± 45.67 and 23.46 ± 5.32 mm3, respectively. Hematoxylin and eosin (HE) staining showed partial visible glandular structure with deepened nuclear staining in the intervention group. Immunohistochemistry showed high expression (6.5 ± 0.28 vs 3.8 ± 0.26, P < 0.05) of E-cadherin and low expression (3.4 ± 0.12 vs 7.8 ± 0.34, P < 0.05) of N-cadherin in the intervention group. Western blot assay showed higher expression of E-cadherin, while low N-cadherin in the intervention group. Metformin can effectively alleviate lesion extent of prostate cancer and mechanism may be related to upregulation of E-cadherin and downregulation of N-cadherin expression.


Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Fouad Al-Bayaty ◽  
Mahmood Ameen Abdulla

Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full-thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular proliferation, the number of blood vessels, and the level of collagen synthesis. Aftamed induced an increase in the free radical-scavenging enzyme activity and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in the MDA level. Conclusions. This study showed that Aftamed gel is able to significantly accelerate the process of wound healing in diabetic rats.


2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Liu ◽  
Jinggang Zhang ◽  
Man Jiang ◽  
Yue Zhang ◽  
Tongbing Chen ◽  
...  

ObjectivesTo explore the differences between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion-weighted imaging (DWI) in evaluating the histopathological characters of pancreatic ductal adenocarcinoma (PDAC).MethodsThis retrospective study enrolled 50 patients with PDAC confirmed by pathology from December 2018 to May 2020. All patients underwent DWI and IVIM-DWI before surgeries. Patients were classified into low- and high-fibrosis groups. Apparent diffusion coefficient (ADC), diffusion coefficient (D), false diffusion coefficient (D*), and perfusion fraction (f) were measured by two radiologists, respectively in GE AW 4.7 post-processing station, wherein ADC values were derived by mono-exponential fits and f, D, D* values were derived by biexponential fits. The tumor tissue was stained with Sirius red, CD34, and CK19 to evaluate fibrosis, microvascular density (MVD), and tumor cell density. Furthermore, the correlation between ADC, D, D*, and f values and histopathological results was analyzed.ResultsThe D values were lower in the high-fibrosis group than in the low-fibrosis group, while the f values were opposite. Further, no statistically significant differences were detected in ADC and D* values between the high- and low-fibrosis groups. The AUC of D and f values had higher evaluation efficacy in the high- and low-fibrosis groups than ADC values. A significant negative correlation was established between D values, and fibrosis and a significant positive correlation were observed between f values and fibrosis. No statistical difference was detected between DWI/IVIM parameters values and MVD or tumor cell density except for the positive correlation between D* values and tumor cell density.ConclusionsD and f values derived from the IVIM model had higher sensitivity and diagnostic performance for grading fibrosis in PDAC compared to the conventional DWI model. IVIM-DWI may have the potential as an imaging biomarker for predicting the fibrosis grade of PDAC.


2017 ◽  
Vol 59 (6) ◽  
pp. 694-699 ◽  
Author(s):  
Hans-Jonas Meyer ◽  
Oliver Ziemann ◽  
Malte Kornhuber ◽  
Alexander Emmer ◽  
Ulf Quäschling ◽  
...  

Background Magnetic resonance imaging (MRI) is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an imaging modality, which can reflect microstructural tissue composition. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules in tissue. Purpose To investigate ADC values in patients with myositis and non-inflammatory myopathy and to analyze possible associations between ADC and laboratory parameters in these patients. Material and Methods Overall, 17 patients with several myositis entities, eight patients with non-inflammatory myopathies, and nine patients without muscle disorder as a control group were included in the study (mean age = 55.3 ± 14.3 years). The diagnosis was confirmed by histopathology in every case. DWI was obtained in a 1.5-T scanner using two b-values: 0 and 1000 s/mm2. In all patients, the blood sample was acquired within three days to the MRI. The following serological parameters were estimated: C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, and myoglobine. Results The estimated mean ADC value for the myositis group was 1.89 ± 0.37 × 10–3 mm2/s and for the non-inflammatory myopathy group was 1.79 ± 0.33 × 10–3 mm2/s, respectively. The mean ADC values (1.15 ± 0.37 × 10–3 mm2/s) were significantly higher to unaffected muscles (vs. myositis P = 0.0002 and vs. myopathy P = 0.0021). There were no significant correlations between serological parameters and ADC values. Conclusion Affected muscles showed statistically significantly higher ADC values than normal muscles. No linear correlations between ADC and serological parameters were identified.


2004 ◽  
Vol 286 (4) ◽  
pp. R751-R755 ◽  
Author(s):  
Daiyi Tang ◽  
Tianzheng Yu ◽  
Ali A. Khraibi

Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague-Dawley rats were studied: normal control group (C), untreated diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with insulin for 2 wk was initiated immediately when diabetes was confirmed, which was 2 days after STZ injection), and delayed insulin-treated diabetic group (DDI; treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FENa), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (ΔRIHP), and FENa and V responses to VE (ΔFENa and ΔV) were significantly lower in the D group compared with the C group of rats. ΔRIHP was significantly higher in both DI and DDI groups compared with D group but was similar to that of the C group of rats. While in the DI group the ΔFENa response to VE was restored, ΔFENa was significantly increased in DDI compared with D group, but it remained lower than that of the C group. In conclusion, insulin treatment initiated immediately after the onset of diabetes restores basal RIHP and RIHP, natriuretic, and diuretic responses to VE; however, delayed insulin treatment restores the basal RIHP and RIHP response to VE but does not fully restore the natriuretic response to VE.


2005 ◽  
Vol 83 (8-9) ◽  
pp. 775-783 ◽  
Author(s):  
Jiping Tang ◽  
Sharyn M Fitzgerald ◽  
Brandi N Boughtman ◽  
Samuel W Cole ◽  
Michael W Brands ◽  
...  

Diabetic cardiomyopathy is 1 of the major causes of death in diabetic patients, but the pathogenesis is unclear. There is evidence that RhoA, a small GTPase, might be involved in cardiac function. This study, therefore, analyzed RhoA expression and activation in hearts of diabetic rats. Male Sprague–Dawley rats were divided into control and diabetic groups of 18 each. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). Rats were studied 3 weeks after induction of diabetes. Heart rate, which was measured 24 h/day, decreased by 93 ± 7 beats/min in diabetic rats. There was a 62% decrease (p < 0.01) in RhoA mRNA expression in heart tissues (left ventricle) of diabetic rats (38.5 ± 6.7 × 106 molecules/µg total RNA) compared with controls (101 ± 10.3 × 106 molecules/µg total RNA). Western blot showed a 33% decrease in total RhoA protein expression in heart tissues of diabetic rats compared with controls (p < 0.05). A reduced RhoA translocation in heart tissues of diabetic rats was determined by a 64% decrease in membrane-bound RhoA (p < 0.01 vs. control group), indicating that the activation of RhoA is markedly reduced in diabetic myocardium. Our data suggest that down-regulated RhoA may be involved in cardiomyopathy in diabetic rats.Key words: RhoA, diabetes, heart.


2019 ◽  
Vol 28 (Sup10) ◽  
pp. S26-S36
Author(s):  
Mohammad Hashemnia ◽  
Zahra Nikousefat ◽  
Adel Mohammadalipour ◽  
Mohammad-Mahdi Zangeneh ◽  
Akram Zangeneh

Objective: To assess the wound healing potential of Pimpinella anisum on cutaneous wounds in diabetic rats. Method: Full-thickness excisional wounds were made on the back of male, Sprague-Dawley rats with diabetes. The rats were randomly allocated into four treatment groups: 1ml basal cream; tetracycline (3%); Pimpinella anisum 10% for 14 days; and a control group. At days seven, 14 and 21 post-injury, five animals of each group were euthanised, and wounds were assessed through gross, histopathological and oxidant/antioxidant evaluations. Additionally, the dry matter and hydroxyproline contents of the skin samples were measured. Results: A total of 60 rats were used in the study. A significant decrease in the wound size was observed in treated animals with Pimpinella anisum compared with other groups during the experiment. Additionally, treatment with Pimpinella anisum decreased the number of lymphocytes and improved the number of fibroblasts at the earlier stages and increased a number of fibrocytes at the later stages of wound healing. Other parameters such as re-epithelialisation, tissue alignment, greater maturity of collagen fibres and large capillary-sized blood vessels revealed significant changes when compared with the control. Pimpinella anisum significantly reverted oxidative changes of total antioxidant capacity, malondialdehyde and glutathione peroxidase induced by diabetic wounds (p<0.05). Furthermore, it significantly increased the dry matter and hydroxyproline contents at various stages of wound healing (p<0.05). Conclusion: The present study showed that application of Pimpinella anisum extract promotes wound healing activity in diabetic rats. The wound-healing property of Pimpinella anisum can be attributed to the phytoconstituents present in the plant.


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