Laparoscopic adenomyomectomy combined with levonorgestrel-releasing intrauterine system is effective for long-term management of adenomyosis.

BACKGROUD: Laparoscopic adenomyomectomy combined with intraoperative placement of levonorgestrel-releasing intrauterine device (LNG-IUS) is a novel conservative surgical procedure for adenomyosis. Our study aimed to compare the efficacy of surgery with or without intraoperative placement of LNG-IUS treatment in adenomyosis. METHODS: We retrospectively reviewed the medical records of adenomyosis patients who received laparoscopic adenomyomectomy from January 2014 to April 2020, finally including 70 patients undergoing surgery-LNG-IUS as group A and 69 patients undegoing surgery only as group B. Risk factors for three-year relapse were analyzed using Cox's multivariate proportional hazard analysis. RESULTS: Visual analog scale and Mansfield-Voda-Jorgensen Menstrual Bleeding Scale scores of group A at 3, 6, 12, 24, and 36 months were significantly lower than those of group B at the corresponding points (P < .001 for both scales). Individuals in both groups showed statistically significant symptom relief. The recurrence rate in group A was significantly lower than that in group B at 36 months after the surgery (2.94% vs. 32.84%, P < .001). A cox proportional hazard model showed that relapse was significantly associated with coexisting ovarian endometriosis (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 1.33-7.02, P = .015). Patients who received surgery-LNG-IUS had a lower risk of recurrence than those with surgery-alone (aHR, 0.07; 95% CI, 0.016-0.31, P < .001). CONCLUSIONS: Conservative surgery with intraoperative placement of LNG-IUS is effective and well-accepted for long-term therapy with a lower recurrence rate for adenomyosis. Coexistent ovarian endometriosis is a major factor for adenomyosis relapse.

Risk Factors for Symptomatic Recurrence after Laparoscopic Adenomyomectomy: A 3-Year Follow-up.

STUDY OBJECTIVE: To identify the clinical risk factors for symptomatic recurrence of adenomyosis after laparoscopic adenomyomectomy with a three-year follow-up. DESIGN: Retrospective study. SETTING: University-affiliated hospital. PATIENTS: A total of 149 patients were included in this study, including 52 patients with symptomatic recurrence and 97 without recurrence. INTERVENTION: Laparoscopic adenomyomectomy was performed first. MEASUREMENTS AND MAIN RESULTS: General clinical data, including preoperative, intraoperative, and postoperative indices, symptomatic recurrence, and follow-up information, were collected. Comparison of women with and without symptomatic recurrence revealed significant differences for age at surgery (p = .026), presence of concomitant ovarian endometrioma (p <.001), and prescription of postoperative hormonal suppression (yes/no) (p <.0001). A Cox proportional hazard model indicated that concomitant ovarian endometrioma was a significant risk factor for recurrence (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.10-3.85, p = .001). Patients who received postoperative hormonal suppression had a lower risk of recurrence than those without hormonal suppression (HR, 0.30; 95% CI, 0.16-0.55, p <.0001). Those aged ≥40 years also had a lower risk of symptomatic recurrence than those <40 years (HR, 0.46; 95% CI, 0.24-0.88, p = .03). CONCLUSIONS: Concomitant ovarian endometrioma is a risk factor for symptomatic recurrence of adenomyosis after laparoscopic adenomyomectomy. Postoperative hormonal suppression and older age at surgery (≥40 years) are protective factors.

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

Objective: To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. Methods: This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. Results: The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine ß2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Conclusion: Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Observation of pregnancy outcomes in patients with hysteroscopic resection on submucous myomas.

OBJECTIVE: The aim of this study was to assess postoperative pregnancy outcomes in patients with different types of submucous myomas after hysteroscopic resection. MATERIALS AND METHODS: This retrospective unicentric study used data from the electronic medical records system of the hospital. All patients (n = 77) who underwent hysteroscopy for submucous myomas between November 2010 and December 2018 were included. Patients were divided into three groups according to the myoma classification (G0, G1, and G2). Medical files were reviewed and phone questionnaires were conducted to evaluate demographic characteristics, clinical features, surgical treatment, and pregnancy outcomes. RESULTS: The median age of the patients was 32 (30.0, 34.0) years. The myoma diameter was 2.9 (2.0, 3.8) cm. The operation duration was 50.0 (30.0, 75.0) min. There were 15 patients in Group G0, 20 patients in Group G1, and 37 patients in Group G2. Follow-up data were available for 65 of the 77 patients. The total pregnancy rate was 58 (89.2%) of 65. The live birth rate was 41 (70.7%) of 58. There was no significant difference in pregnancy rate (G0 100% vs. G1 76.5% vs. G2 91.2%; p = 0.097) or in live birth rates among the three groups (G0 78.6% vs. G1 53.8% vs. G2 74.2%; p = 0.325). CONCLUSION: There was no difference in pregnancy outcome among the three types of submucosal myomas. Our results support the idea that hysteroscopic myomectomy is an effective option for submucous myomas with good long-term pregnancy outcomes.

Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice.

BACKGROUND: /Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and effective treatments are lacking. Bariatric surgery, including sleeve gastrectomy (SG), is a potential therapeutic strategy for NAFLD, but the molecular mechanisms underlying its effects are not fully understood. In this study, the effects of SG and the underlying mechanisms were evaluated in a mouse model of high-fat diet (HFD)-induced NAFLD. METHODS: C57BL/6 mice were randomly divided into three groups: normal diet with sham operation (NC-Sham group), HFD with sham operation (HFD-Sham group), and HFD with sleeve gastrectomy (HFD-SG group). Glucose metabolism and fat accumulation in the body and liver were analyzed before and after SG. Lipid metabolism and inflammation in the liver were evaluated. Nicotinamide adenine dinucleotide (NAD+) levels as well as nicotinamide riboside kinase (NRK1) and Sirtuin-1 (SIRT1) expression levels were evaluated. RESULTS: SG attenuated the HFD-induced increases in glucose and insulin levels, fat accumulation, and lipid droplet accumulation. Fatty acid biosynthesis, the expression of the metabolism-related genes ACC1, FASN, SCD1, and DGAT1, and the levels of inflammatory factors were higher in HFD mice than in NC mice and decreased after SG. NAD + concentrations were 54.9 ± 13.4 µmol/mg in NC-Sham mice, 37.6 ± 8.1 µmol/mg in HFD-Sham mice, and 79.9 ± 13.0 µmol/mg in HFD-SG mice (p < 0.05). NRK1 and SIRT1 expression increased dramatically after SG at both the RNA and protein levels. CONCLUSION: SG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway.

Laparoscopic adenomyomectomy combined with levonorgestrel-releasing intrauterine system in the treatment of adenomyosis: Feasibility and effectiveness.

AIM: To evaluate the clinical efficacy and safety of laparoscopic adenomyomectomy combined with intraoperative replacement of levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of symptomatic adenomyosis. METHODS: This is a case-series study in a university medical center. A total of 52 patients with symptomatic adenomyosis were treated by laparoscopic adenomyomectomy combined with intraoperative replacement of LNG-IUS from January 2015 to July 2018. Visual analog scale, menstrual flow and uterine volume were compared before and after the surgery (3, 12 and 24 months). Meanwhile, LNG-IUS-induced adverse reactions (e.g. irregular vaginal bleeding, amenorrhea, expulsion, and perforation) were also recorded. RESULTS: All operations were successfully completed via laparoscopy without conversion to laparotomy. No severe complications were noted during the surgical procedure or follow-up period. The mean postoperative visual analog scale and menstrual flow scores and the volume of the uterus were significantly decreased (all P < 0.001) at 3, 12, and 24 months postoperatively, compared with preoperative scores. The clinical effective rates among the patients with dysmenorrhea were 98%, 96% and 96% at 3, 12 and 24 months after the operation, respectively. And the clinical effectiveness rate of menorrhagia was 97.6%, 95.2% and 95.2% at 3, 12 and 24 months after treatment, respectively. Among all related adverse reactions, amenorrhea was the most common (n = 12, 23.1%). There was one case of LNG-IUS perforation (1.9%) and two cases of expulsion (3.8%). CONCLUSION: Laparoscopic adenomyomectomy combined with intraoperative replacement of LNG-IUS is a novel and effective conservative surgical procedure for symptomatic adenomyosis treatment.

Efficacy and predictors of short-term first-generation somatostatin analog presurgical treatment in acromegaly: A hospital-based study of 237 cases.

OBJECTIVE: To investigate the effectiveness and predictors of short-term somatostatin analog (SSA) presurgical therapy in a large cohort and to assess the correlation between clinical and pathological variables. DESIGN: 237 newly diagnosed patients with acromegaly received presurgical SSA treatment for three months were recruited. Clinical characteristics were collected, and response to SSA in hormone and tumor size was evaluated. The correlation between clinical information and pathological variables were analyzed. RESULTS: After 3 months presurgical SSA therapy, 51 (21.5%) patients were biochemically responsive with ≥50% decrease in IGF-1 while 126 (53.2%) patients showed at least 20% tumor size decrease. Biochemical responders were associated with a smaller maximum tumor diameter (MTD) and an older age (OR, 0.448; P = 0.003; OR, 1.050; P = 0.001). Tumor size responders were associated with a smaller MTD (OR, 0.435; P < 0.001). A combination of MTD < 2 cm and age ≥49 years predicted biochemical responders (PPV, 54.5%; NPV, 86.0%; P < 0.001), while MTD ≤2.2 cm (PPV, 67.1%; NPV, 67.0%; P < 0.001) predicted tumor size responders. Compared to patients with MTD < 2 cm, patients with MTD ≥ 2 cm showed higher percentage of sparsely granulated (SG) adenoma (62.1% vs. 31.3%, P = 0.005). In addition, the percentage of SG adenoma tended to be higher in patients < 49 years than ≥49 years (48.1% and 31.0% P = 0.089). CONCLUSIONS: The baseline MTD and age correlate with granulation patterns and may be used as easily acquired predictors of presurgical SSA treatment in acromegaly. Patients over their 50s with a tumor less than 2 cm in diameter are more likely to have a response to the short-term presurgical SSA therapy.

Laparoscopic Management of 42 Cases of Tubal Stump Pregnancy and Postoperative Reproductive Outcomes.

STUDY OBJECTIVE: Tubal stump pregnancy is a rare variant of ectopic pregnancy. The aim of this study was to evaluate laparoscopic surgery for tubal stump pregnancy and to investigate postoperative pregnancy outcomes. DESIGN: Retrospective study. SETTING: University-affiliated hospital. PATIENTS: Patients (n = 42) diagnosed with tubal stump pregnancy. INTERVENTIONS: Data were extracted from the electronic medical records system of the hospital. MEASUREMENTS AND MAIN RESULTS: Patients diagnosed with tubal stump pregnancy between June 2010 and July 2018 were included. Data included demographic characteristics, gravidity and parity, history of pelvic surgery, clinical features, and treatment. All procedures were laparoscopic. Postoperative pregnancy outcomes were identified from electronic medical records or by telephone. Patients' mean age was 30 (range, 21-39) years. Twelve of 42 tubal stump pregnancies (28.6%) had ruptured ectopic pregnancy at the time of operation. The remaining 30 cases had intact stump pregnancy during surgery. Patients were followed for a mean of 31 (range, 10-60) months. Follow-up data were available for 33 of 39 patients (3 with heterotopic tubal stump pregnancy were not included in follow-up data because all resulted in a live births and had no desire for future pregnancy). Eighteen of 28 patients (64.3%) who attempted conception had intrauterine pregnancies (IUPs) during the follow-up period; of these 18 IUPs, 14 (77.8%) resulted in live births. There was 1 case of uterine rupture in a singleton pregnancy at 20+5 weeks that resulted in fetal death. Three of 18 IUPs (16.7%) ended in the first trimester with spontaneous abortions. CONCLUSION: Laparoscopic surgery is a feasible option for tubal stump pregnancy and is associated with favorable pregnancy outcomes.

Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology.

The eutopic endometrium has been suggested to play a crucial role in the pathogenesis of adenomyosis. However, the specific genes in eutopic endometrium responsible for the pathogenesis of adenomyosis still remain to be elucidated. We aim to identify differentially expressed genes (DEGs) and molecular pathways/networks in eutopic endometrium from adenomyosis patients and provide a new insight into disease mechanisms at transcriptome level. RNA sequencing (RNA-Seq) was performed with 12 eutopic endometrium from adenomyosis and control groups. Differentially expressed genes in adenomyosis were validated by quantitative real-time PCR (qPCR) and immunochemistry. Functional annotations of the DEGs were analysed with Ingenuity Pathway Analysis (IPA). Quantitative DNA methylation analysis of CEBPB was performed with MassArray system. A total of 373 differentially expressed genes were identified in the adenomyosis eutopic endometrium compared to matched controls. Bioinformatic analysis predicted that IL-6 signalling and ERK/MAPK signalling were activated in adenomyosis endometrium. We also found that the increased expression and DNA hypomethylation of CEBPB were associated with adenomyosis. Our results revealed key pathways and networks in eutopic endometrium of adenomyosis. The study is the first to propose the association between C/EBPß and adenomyosis and can improve the understanding of the pathogenesis of adenomyosis.

High glucose-induced ubiquitination of G6PD leads to the injury of podocytes.

Oxidative stress contributes substantially to podocyte injury, which plays an important role in the development of diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase (G6PD) is critical in maintaining NADPH, which is an important cofactor for the antioxidant system. Here, we hypothesized that high glucose induced ubiquitination and degradation of G6PD, which injured podocytes by reactive oxygen species (ROS) accumulation. We found that G6PD protein expression was decreased in kidneys of both diabetic patients and diabetic rodents. G6PD activity was also reduced in diabetic mice. Overexpressing G6PD reversed redox imbalance and podocyte apoptosis induced by high glucose and palmitate. Inhibition of G6PD with small interfering RNA induced podocyte apoptosis. In kidneys of G6PD-deficient mice, podocyte apoptosis was significantly increased. Interestingly, high glucose had no effect on G6PD mRNA expression. Decreased G6PD protein expression was mediated by the ubiquitin proteasome pathway. We found that the von Hippel-Lindau (VHL) protein, an E3 ubiquitin ligase subunit, directly bound to G6PD and degraded G6PD through ubiquitylating G6PD on K366 and K403. In summary, our data suggest that high glucose induces ubiquitination of G6PD by VHL E3 ubiquitin ligase, which leads to ROS accumulation and podocyte injury.-Wang, M., Hu, J., Yan, L., Yang, Y., He, M., Wu, M., Li, Q., Gong, W., Yang, Y., Wang, Y., Handy, D. E., Lu, B., Hao, C., Wang, Q., Li, Y., Hu, R., Stanton, R. C., Zhang, Z. High glucose-induced ubiquitination of G6PD leads to the injury of podocytes.

Cesarean scar endometriosis: presentation of 198 cases and literature review.

BACKGROUND: Cesarean scar endometriosis (CSE) is the most common type of abdominal wall endometriosis (AWE). The aim of this study was to systematically identify the clinical features of CSE and recommend precautionary measures. METHODS: A large, retrospective study was undertaken with CSE patients treated surgically at our hospital between January 2005 and December 2017. RESULTS: A total of 198 CSE patients were enrolled, with a mean age of 32.0 ± 4.0 years. The main complaint of the patients was abdominal mass (98.5%), followed by cyclic pain (86.9%). The latency period of CSE was 31.6 ± 23.9 months, and the duration between the onset of symptoms and this surgery was 28.3 ± 25.0 months. A majority (80.8%, n = 160) of the patients had undergone a Pfannenstiel incision, and a minority (19.2%, n = 38) a vertical midline incision. The latency period of CSE in the case of a Pfannenstiel incision was significantly shorter than that in the case of a vertical midline incision (24.0 vs 33.0 months, P = 0.006). A total of 187 (94.4%) patients had a single endometrioma, 11 (5.6%) patients had multiple endometriomas, and the 11 multiple-endometrioma patients had all undergone a Pfannenstiel incision. Lesions of endometrioma were common in corner sites, after either incision: 142/171 (83.0%) in Pfannenstiel incision scars and 32/38 (84.2%) in vertical incision scars. CONCLUSIONS: The findings of this study indicate that the Pfannenstiel incision carries a higher risk of CSE than the vertical midline incision. Thorough cleaning at the conclusion of CS, particularly of both corner sites of the adipose layer and the fascia layer, is strongly recommended for CSE prevention. Further studies might provide additional recommendations.

The comprehensive impact on human body induced by resolution of growth hormone excess.

CONTEXT: Chronic excess of growth hormone (GH) often leads to systemic complications. The reversibility of these complications after GH resolution is not fully understood. OBJECTIVE: To investigate when and to what extent will the comorbidities be ameliorated. DESIGN: We conducted a prospective study comprising 24 patients with acromegaly, who achieved remission after transsphenoidal surgery. The dynamic changes of endocrine, cardiovascular, respiratory, sleep, bone and morphology parameters were evaluated at enrollment and 1 week, 1 month, 3 months, 6 months and 12 months after surgery. RESULTS: Random GH dropped by 98.4% at the first day postoperatively. IGF-I index dropped by 50% and 64% at 1 week and 1 month respectively and remained unchanged onwards. Glucose metabolism improved significantly at 1 week and stabilized at 1 month. Testosterone in male patients recovered to normal range since 1 month. Systolic blood pressures dropped markedly at 3 months while diastolic blood pressures fell mildly at later visits. Abnormal lung function showed no improvement. The decrease of bone formation and resorption markers occurred at 1 week and 3 months, respectively. At 1 month, the tongue area declined while the airway volume increased significantly, accompanied with improved obstructive sleep apnea syndrome. Extremities, lips and nasal ala became smaller since 1 week. Liver, kidney and spleen volumes declined by 6.4, 15.9, 9.2%, respectively at 1 month. The volumes of pancreas and adrenal showed no change. CONCLUSIONS: The rapid resolution of excessive GH led to the reversible changes of systemic comorbidities in a time-dependent and organ-specific manner.

Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues.

The expression of somatostatin receptor subtypes (SSTRs) in pituitary growth hormone- (GH-) secreting adenomas may predict the response to somatostatin analogues (SSA). Our aim was to evaluate the value of the immunohistochemical (IHC) scores of 2 subtypes, SSTR2 and SSTR5, in predicting the short-term efficacy of SSA therapy in patients with active acromegaly. Ninety-three newly diagnosed acromegalic patients were included in our study. These patients were categorized into either a SSA-pretreated group (SA, n = 63) or a direct-surgery group (DS, n = 30), depending on whether or not presurgical SSA treatment was received. IHC analysis, using a 12-grade scoring system, with rabbit monoclonal antibodies against SSTR2 and SSTR5, was performed on all adenoma tissues. The reduction of GH, IGF-1, and tumor size after treatment with SSA for 3 months was measured. Compared with that in the DS group, SSTR2 expression was lower in the SA group. Additionally, in the SA group, SSTR2 expression was positively correlated with the reduction of IGF-1 and tumor volume. However, there was no correlation between the SSTR5 score and the efficacy of SSA. In conclusion, the protein expression of SSTR2, but not of SSTR5, is a valuable indicator in predicting biochemical and tumor size response to short-term SSA treatment in acromegalic patients.

Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly.

INTRODUCTION: The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR). METHODS: This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient. RESULTS: T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5. CONCLUSION: T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly.

Exogenous kallikrein protects against diabetic nephropathy.

The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.

The value of an acute octreotide suppression test in predicting short-term efficacy of somatostatin analogues in acromegaly.

Predicting the efficacy of long-acting somatostatin analogues (SSA) remains a challenge. We aim to quantitatively evaluate the predictive value of the octreotide suppression test (OST) in short-term efficacy of SSA in active acromegaly. Sixty-seven newly diagnosed acromegaly patients were assessed with OST. Subsequently, all patients were treated with long-acting SSA for 3 months, followed by reassessment. Nine parameters were tested, including GHn (the nadir GH during OST), ΔGH1 (= [GH0h-GHn]/GH0h, GH0h was the baseline GH during OST), ΔGH2 (= [GHm-GHn]/GHm, GHm was the mean GH on day curve), AUC(0-6h) (the GH area under the curve during OST) , ΔAUC1 (= [GH0h-AUC(0-6h)]/GH0h), ΔAUC2 (=[GHm-AUC(0-6h)]/GHm), AUC(m-6h) (the GH AUC during OST where GHm was used instead of GH0h), ΔAUC1' (=[GH0h-AUC(m-6h)]/GH0h) and ΔAUC2' (=[GHm-AUC(m-6h)]/GHm). The Youden indices were calculated to determine the optimal cutoffs to predict the short-term efficacy of SSA. ΔGH2 more than 86.83%, ΔAUC2 more than -57.48% and ΔAUC2' more than -57.98% provided the best predictors of a good GH response (sensitivity 93.8%, specificity 85.7%). ΔGH2 more than 90.51% provided the best predictor of a good tumor size response (sensitivity 84.8%, specificity 87.5%). The percentage fall of GHn (ΔGH) was a better predictive parameter than GHn. OST showed higher efficiency in predicting the efficacy of octreotide LAR than lanreotide SR. In conclusion, OST is a valid tool to predict both GH and tumor size response to short-term efficacy of SSA in acromegaly, especially for octreotide LAR. GHm is better to be used as basal GH than GH0 during OST.