Grim-19 plays a key role in mitochondrial steroidogenic acute regulatory protein stability and ligand-binding properties in Leydig cells.

Grim-19 (gene associated with retinoid-IFN-induced mortality 19), the essential component of complex I of mitochondrial respiratory chain, functions as a noncanonical tumor suppressor by controlling apoptosis and energy metabolism. However, additional biological actions of Grim-19 have been recently suggested in male reproduction. We investigated here the expression and functional role of Grim-19 in murine testis. Testicular Grim-19 expression was detected from mouse puberty and increased progressively thereafter, and GRIM-19 protein was observed to be expressed exclusively in interstitial Leydig cells (LCs), with a prominent mitochondrial localization. In vivo lentiviral vector-mediated knockdown of Grim-19 resulted in a significant decrease in testosterone production and triggered aberrant oxidative stress in testis, thus impairing male fertility by inducing germ cell apoptosis and oligozoospermia. The control of testicular steroidogenesis by GRIM-19 was validated using the in vivo knockdown model with isolated primary LCs and in vitro experiments with MA-10 mouse Leydig tumor cells. Mechanistically, we suggest that the negative regulation exerted by GRIM-19 deficiency-induced oxidative stress on steroidogenesis may be the result of two phenomena: a direct effect through inhibition of phosphorylation of steroidogenic acute regulatory protein (StAR) and subsequent impediment to StAR localization in mitochondria and an indirect pathway that is to facilitate the inhibiting role exerted by the extracellular matrix on the steroidogenic capacity of LCs via promotion of integrin activation. Altogether, our observations suggest that Grim-19 plays a potent role in testicular steroidogenesis and that its alterations may contribute to testosterone deficiency-related disorders linked to metabolic stress and male infertility.

Sesquiterpenoids from the twigs and leaves of Fokienia hodginsii.

A rare carotane-type sesquiterpenoid, forkienin A (1), a new eudesmane-type sesquiterpenoid, forkienin B (2), and a new natural eudesmane-type sesquiterpenoid, forkienin C (3), were isolated from the twigs and leaves of Fokienia hodginsii, along with eight known sesquiterpenoids. The structures of the new compounds were elucidated on the basis of their spectroscopic analysis, including 1D and 2D NMR methods. All compounds were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines.

Targeted Next-Generation Sequencing for the Diagnosis of Gene Variants in Patients with 46,XY Disorder of Sex Development.

INTRODUCTION: Disorders of sex development (DSDs) are congenital abnormalities in which chromosomal, gonadal, and anatomical sex development are atypical. One of these disorders, 46,XY DSD, is particularly difficult to diagnose and manage because its etiology and clinical phenotypes are highly heterogeneous. METHODS: We used a gene panel containing 141 genes implicated in DSDs to perform targeted next-generation sequencing (NGS) in 50 patients with 46,XY DSD. RESULTS: Gene variants were detected in 23 patients (46%). Among them, 13 patients had previously reported pathogenic or likely pathogenic variants, 9 patients had novel variants, and 1 patient had a previously reported variant of uncertain significance. Three of the novel variants were pathogenic, and the remaining were variants of uncertain significance; therefore, 16 patients had pathogenic or likely pathogenic variants according to ACMG guidelines, and the overall diagnostic rate of 46,XY DSD was 32%. The most common gene variants were SRD5A2 variants, followed by the AR variant. In addition, we analyzed the association between gene variants and clinical phenotypes. Most patients presented with multiple DSD phenotypes (i.e., two or more DSD phenotypes were observed, such as micropenis, hypospadias, and cryptorchidism), but the phenotype with the highest diagnostic rate was micropenis. CONCLUSION: Our results indicate that targeted NGS can effectively detect pathogenic gene variants in patients with 46,XY DSD.

Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma.

Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.

[Different prevalence of impaired glucose tolerance between hyperinsulinemic and normoinsulinemic subjects].

OBJECTIVE: To study the impact of different insulin levels on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM), through analysis of different glycometabolism condition among quinquagenarian population. METHODS: Subjects enrolled were Beijing habitants who received annual physical examination [including oral glucose tolerance test (OGTT)] in the Chinese PLA General Hospital from 2005 - 2007. According to the OGTT results, the subjects were divided into three groups, including normal glucose tolerance-non-hyperinsulinemia group (NGT-NHIns), IGT-hyperinsulinemia group (IGT-HIns) and IGT-non-hyperinsulinemia group (IGT-NHINS). The prognosis between the year 2009 and 2010 of the three groups was observed. Hyperinsulinemia was diagnosed with fasting serum insulin ≥ 15 mU/L and/or 2-hour serum insulin ≥ 80 mU/L after glucose loading. RESULTS: The rate of case number of conversion to T2DM in IGT-NHIns group (42/133) was higher than that in IGT-HIns group (24/154) or NGT-NHIns group (12/126). The HOMA insulin resistance index (HOMA-IR) of individuals with IGT-NHIns was lower than that of IGT-HIns [0.96 (0.40, 3.53) vs 2.04 (0.59, 23.20), P < 0.05], while whole body insulin sensitivity index (WBISI) was higher than that of IGT-HIns [7.48 (3.20, 31.35) vs 3.28 (0.86, 7.67), P < 0.05]. Modified ß-cell function index (MBCI) and insulin secretion index (ISI) in IGT-NHIns was poorer than that of IGT-HIns respectively [2.57 (0.58, 10.98) vs 5.17 (1.04, 65.09); 7.66 (0.99, 28.40) vs 17.56 (4.18, 96.46), all P values < 0.01]. CONCLUSIONS: The risk of IGT-NHIns progressing into T2DM is higher than that of IGT-HIns. For the prevention of T2DM, individuals with IGT-NHIns should be paid more attention than keeping an eye on IGT-HIns patients. Early control of risk factors could protect ß cell function and prevent the progression to T2DM.

Medullar thyroid carcinoma in mediastinum initially presenting as Ectopic ACTH syndrome. A case report.

A rare case with ectopic adrenocorticotrophic hormone syndrome (EAS) caused by medullar thyroid carcinoma (MTC) in mediastinum was reported. This 49 year-old male patient initially presented with serious and intractable hypokalemia. Endocrine evaluations showed increased levels of adrenocorticotrophic hormone (ACTH) and urinary free cortisol, which could not be suppressed more than 50% by high-dose dexamethasone suppression test. Computed tomography (CT) scan detected a 5×5×5 cm mass at the bottom of thyroid in anterior mediastinum. The patient underwent total thyroidectomy with central compartment and ipsilateral modified radical neck dissection. Pathological examination showed an infiltrating thyroid medullary carcinoma with abundant amyloid deposition, meanwhile immunohistochemical positive for ACTH. After surgery, serum levels of kalium, as well as cortisol and ACTH returned to normal range. During follow-up, the patient's clinical manifestation of Cushing syndrome relieved.

[The clinical characteristics and trend of conversion to type 2 diabetes mellitus of individuals with normal glucose tolerance-hyperinsulinemia].

OBJECTIVE: To study the outcomes and influencing factors of the conversion from normal glucose tolerance-hyperinsulinemia (NGT-HINS) to diabetes in the population of a community in Beijing. METHODS: All the subjects investigated received 75 g oral glucose tolerance test (OGTT) for diabetes screening carried out in May, 2006 and May, 2008. Data were calculated to analyze the outcomes and influencing factors of the conversion. HINS was diagnosed if fasting serum insulin≥15 mIU/L and/or 2-hour serum insulin after glucose loading≥80 mIU/L. RESULTS: The prevalence of NGT-HINS in the community in 2006 and 2008 was 5.28% and 8.67% (P<0.01) respectively and that of diabetes mellitus (DM) and impaired glucose regulation (IGR) was 3.52%, 6.56% in 2006 and 4.42%, 6.47% in 2008. The probability of the conversion from NGT-HINS to IGR and DM was 18.6% and 2.3%, being much higher than that from normal glucose tolerance-normoinsulinemia (NGT-NINS) (5.4% and 0.7%, P<0.01). However, the probability of the conversion from NGT-HINS to DM was 2.3%, which was much lower than that from IGR (26.3%, P<0.01). The reason might be that individuals with NGT-HINS had a higher waist circumference, BMI, fasting plasma glucose, 2 h plasma glucose and TG but a lower HDL-C than individuals with NGT-NINS in 2006. The HOMA ß-cell function index/HOMA insulin resistance index (HBCI/IR) of individuals with NGT-HINS was much lower than that of individuals with NGT-NINS, but much higher than that of individuals with IGR. Logistic regression analysis showed that age, TG and HBCI/IR were the major influencing factors of the conversion from NGT to glucose metabolic disorders. CONCLUSIONS: The probability of conversion from NGT to DM was increased remarkably when HINS was diagnosed. The reason might be that individuals with NGT-HINS suffered more metabolic risk factors and had a decreased ß-cell function. Therefore, individuals with NGT-HINS should be paid attention to in diabetes prevention study.

Intravenous injections of the oncolytic virus M1 as a novel therapy for muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells. Knocking down ZC3HAV1 (ZAP), an antiviral factor in ISGs, restores M1 virus reactivity in resistant cells, and overexpressing ZAP partially reverses M1 virus-induced decreases in cell viability in sensitive cells. In orthotopic MIBC mice, tail vein injections of M1 significant inhibit tumor growth and prolong survival period, antitumor effects of M1 are stronger than those of the first-line chemotherapy agent cisplatin (CDDP). Treated tumors display enhanced cleaved-caspase-3 signals, which are representative of cell apoptosis, and decreased Ki-67 signals, which are representative of cell proliferation. Moreover, tissue microarray (TMA) analyses of clinical tumor specimens revealed that up to 45.6% of cases of MIBC presented with low ZAP expression, a finding that is prevalent in advanced MIBC. Our results indicate that the oncolytic virus M1 is a novel agent capable of functioning as a precise and effective therapy for MIBC.

[A preliminary survey of primary hyperparathyroidism in middle-aged and elderly Beijing Chinese].

OBJECTIVE: To study the prevalence of hypercalcemia and primary hyperparathyroidism in middle-aged and elderly Chinese people who live in Beijing. METHODS: This research was performed in a large elderly population group who came to our hospital for health checkup. The medical histories and relevant data of all the subjects were collected. Serum parathyroid hormone (PTH) concentration was determined in the 83 subjects whose blood calcium level was >or= 2.6 mmol/L. Meanwhile, another 83 of the subjects whose calcium level was < 2.6 mmol/L were chosen randomly as controls. RESULTS: 2451 subjects underwent the investigation. 83 (3.39%) out of the total 2451 subjects were found to have calcium level >or= 2.6 mmol/L, and 5 of them had PTH > 65 ng/L but no causative factors for the elevation. These subjects were thought to have primary hyperparathyroidism and its prevalence was 0.204%. CONCLUSION: The prevalence of primary hyperparathyroidism was 0.204% in the investigated elderly subjects.

Gold-chrysophanol nanoparticles suppress human prostate cancer progression through inactivating AKT expression and inducing apoptosis and ROS generation in vitro and in vivo.

Controlled releasing of regulations remains the most convenient method to deliver various drugs. In the present study, we precipitated gold nanoparticles with chrysophanol. The gold-chrysophanol into poly (DL-lactide-co-glycolide) nanoparticles was loaded and the biological activity of chrysophanol nanoparticles on human LNCap prostate cancer cells, was tested to acquire the sustained releasing property. The circular dichroism spectroscopy indicated that chrysophanol nanoparticles effectively resulted in conformational alterations in DNA and regulated different proteins associated with cell cycle arrest. The reactive oxygen species (ROS), apoptosis, cell cycle, DNA damage, Cyto-c and caspase-3 activity were analyzed, and the expression levels of different anti- and pro-apoptotic were studied using immunoblotting analysis. The cytotoxicity assay suggested that chrysophanol nanoparticles preferentially killed prostate cancer cells in comparison to the normal cells. Chrysophanol nanoparticles reduced histone deacetylases (HDACs) to suppress cell proliferation and induce apoptosis by arresting the cell cycle in sub-G phase. In addition, the cell cycle-related proteins, including p27, CHK1, cyclin D1, CDK1, p-AMP-activated protein kinase (AMPK) and p-protein kinase B (AKT), were regulated by chrysophanol nanoparticles to prevent human prostate cancer cell progression. Chrysophanol nanoparticles induced apoptosis in LNCap cells by promoting p53/ROS crosstalk to prevent proliferation. Pharmacokinetic study in mice indicated that chrysophanol nanoparticle injection showed high bioavailability compared to the free chrysophanol. Also, in vivo study revealed that chrysophanol nanoparticles obviously reduced tumor volume and weight. In conclusion, the data above suggested that chrysophanol nanoparticles might be effective to prevent human prostate cancer progression.

[Efficacy and safety analysis of interferon combined with imatinib in treating chronic myeloid leukemia].

Imatinib has been recognized as the frontline therapy drug in chronic myeloid leukemia (CML), however, only limited patients could achieve complete molecular remission (CMR). Recent clinical and basic proofs indicated an improved treatment outcome by the combination of interferon and Imatinib. This study was purposed to evaluated systematically the efficacy and safety of interferon plus Imatinib in patients with CML. Data from relative clinical trials were from clinical trial of gov and Cochrane Collaboration. A comprehensive literature search was performed from data bases such as pubMed and EM. The results indicated that 7 clinical trials and 12 research papers met the criteria enrolled in study, included 697 cases in total. The combination group had higher complete cytogenetic remission (CCgR) rate than imatinib alone at 6 months (58% vs 42%; P = 0.0001) and 12 months (74% vs 68%; P = 0.004). The major molecular remission (MMR) rate was also higher in the combination group at 6 months (58% vs 34%; P = 0.0001) and 12 months (66% vs 47%; P < 0.0001). Furthermore, compared with single drug, the combination group had superior CMR rate at 6 months (13% vs 2%; P = 0.0002) and 12 months (14% vs 5%; P = 0.0009). The major adverse effects of combination therapy were rash, asthenia, edema and musculoskeletal events, and combination therapy was more prone to inducing neutropenia, thrombocytopenia and mild anemia. It is concluded that compared with Imatinib alone, the combination of interferon and Imatinib has better clinical efficacy in treating CML with earlier cytogenetic and molecular remission. It is also a safe therapy in spite of slightly weaker tolerance than single drug therapy.

[Clinical significance of ID4 methylation detection by quantitative methylation-specific PCR in acute leukemia].

The advances of treatment improved the prognosis of the patients with acute leukemia (AL) in the last decade, but the lack of general biomarker for predicting relapse in AL, which is one of the most important factors influencing the survival and prognosis. DNA methylation of ID4 gene promoter occurred frequently in patients with AL and was found to be highly related to the tumor progression. Based on the previous work of the setup of methylation-specific quantitative PCR system for ID4 gene, this study was designed to investigate the relation between the quantitative indicator of methylation density, percentage of methylation reference(PMR) value, and different disease status of AL. PMR of ID4 was detected by MS-PCR in bone marrow (BM) samples of 17 healthy persons and 54 AL patients in the status of newly diagnosis, complete remission and disease relapse. The results showed that at different disease status, PMR value in newly diagnosed group was significantly lower than that in complete remission group (P = 0.031). Among serial samples, PMR value remained very low at the status of patients with continuous complete remission (<1.5‰), and increased along with the accumulation of tumor cells at relapse. In 1 relapse case, the abnormal rise of PMR value occurred prior to morphological relapse. PMR value seemed to be related to body tumor cell load. It is concluded that the quantitative indicator of methylation density and PMR value may reflect the change of tumor cell load in acute leukemia patients. Dynamic monitoring of PMR maybe predict leukemia relapse.

Insulin resistance correlates with the arterial stiffness before glucose intolerance.

OBJECTIVE: The elevated plasma glucose level and/or insulin resistance in diabetes or impaired glucose tolerance play important roles in the pathogenesis of arterial stiffness. The present study investigated whether insulin resistance correlated with arterial stiffness before the development of glucose intolerance. METHODS: We conducted a cross-sectional analysis in 872 young to middle-age individuals with normal glucose tolerance (aged 36.2±8.5 years, BMI 24.6±3.1 kg/m2 [mean±SD]). The homeostasis model assessment (HOMA) index was used as a quantitative assessment of the fasting insulin resistance (FIR), and the plasma insulin level after glucose loading was adopted as an index of the post-challenge insulin resistance (PIR). The Matsuda index [ISI (composite)] was used as a measurement of the insulin sensitivity. The arterial stiffness assessed by the brachial-ankle pulse wave velocity (baPWV) was adopted to quantify its independent associations with insulin resistance. RESULTS: The univariate linear regression analysis indicated that the fasting plasma glucose level (FPG, ß = 68.2; 95% CI 40.9, 95.6; p<0.001), post-challenge plasma glucose level (PPG, ß = 25.3; 95% CI 15.6, 35.0; p<0.001), FIR (ß = 24.5; 95% CI 14.1, 35.0; p<0.001), PIR (ß=1.30; 95% CI 0.87, 1.73; p<0.001) and ISI (composite) (ß = -3.55; 95% CI -5.02, -2.07; p<0.001) were all significantly correlated with the baPWV. After adjustment for sex, age, BMI, heart rate, smoking, systolic blood pressure, total cholesterol, LDL-cholesterol and family history of diabetes, the multivariate linear regression analysis demonstrated that the PIR (model 1, ß = 0.39, p=0.038; model 2, ß = 0.39, p=0.035; model 3, ß = 0.39, p=0.035) was an independent contributor to the baPWV, while the FIR, FPG, PPG and ISI (composite) failed to show any significant contribution. CONCLUSION: The insulin resistance correlated with the arterial stiffness before glucose intolerance.

Photosynthetic production of wheat under precision planting patterns in northern china / Produção fotossintética de trigo através de padrões de plantação de precisão no norte da china

Winter wheat (Triticum aestivum) is cultivated across a wide region; however, water is scarce during the growing season of wheat in the Northern Plain of China. Therefore, winter wheat should be irrigated to maintain a stable and high grain yield. The aim of this field study was to develop a water-conserving precision planting pattern for winter wheat that is grown in the Northern China Plain with the purpose of exploring the benefits in maintaining water and effects on wheat productivity. To accomplish this, several production variables and photosynthetic indexes were measured, including the number of stems, the leaf area index (LAI), photosynthetically available radiation (PAR), net photosynthetic rate, and grain yield. The study was carried out during the 2011­2012 and 2012­2013 winter wheat growing seasons. The experiment included a double-row planting pattern (DRPP) and a single-row planting pattern (SRPP), both of which were either irrigated or rainfed. The area of each plot was 9 m2, and the experimental design was a randomized blocks design with three replicates. All results were analyzed with an ANOVA, the F test, and the LSD (p 0.05) for means comparison. PAR capture ratios in the DRPP were higher than those in the SRPP at 50­120 cm above the ground. The photosynthetic traits of flag leaves under irrigated conditions were not significantly influenced by the respective planting pattern. However, at a growth stage of 80 under the rainfed conditions, the mean photosynthetic rate within flag leaves in the DRPP was higher than that in the SRPP. Furthermore, the DRPP under rainfed conditions was more likely to increase the apparent quantum yield (AQY) of flag leaves than the yield obtained under irrigation. These results suggest that DRPP optimizes the canopy PAR distribution in winter wheat and contributes to the maintenance of a higher photosynthetic capacity in the flag leaves under water stress (the rainfed condition). This relationship may be applied in demonstration trials to encourage winter wheat farmers to incorporate the use of DRPP in the drought-prone areas, which are subjected to insufficient precipitation during the growing stage of wheat in Northern China.

O trigo de inverno (Triticum aestivum) é cultivado em uma vasta região; no entanto, a água é escassa durante a estação de crescimento do trigo na Planície do Norte da China. Assim, o trigo de inverno deve ser irrigado para manter um rendimento de grãos estável e elevado. O objetivo deste trabalho de campo foi o de desenvolver um padrão de plantação de precisão que conserve a água para o trigo de inverno que é cultivado na Planície do Norte da China com o propósito de explorar os benefícios da retenção de água e os efeitos na produtividade do trigo. Para isso, diversas variáveis de produção e índices fotossintéticos foram medidos, incluindo o número de hastes, o índice de área da folha (do inglês, LAI - leaf area index), a radiação fotossinteticamente disponível (do inglês, PAR - photosynthetically available radiation), taxa fotossintética líquida e o rendimento de grãos. O estudo foi conduzido durante as estações de crescimento do trigo de inverno em 2011-2012 e 2012-2013. O experimento incluiu um padrão de plantação em fila dupla (do inglês, DRPP - double-row planting pattern) e um padrão de plantação em fila única (do inglês, SRPP - single-row planting pattern), em ambos os casos ou foram irrigados artificialmente ou através da chuva (regadio e sequeiro). A área de cada lote de terra foi de 9 m2, e o delineamento experimental foi um de blocos aleatórios com três repetições. Todos os resultados foram analisados com uma ANOVA, um teste F, e um LSD (p 0.05) para a comparação das médias. As taxas de captura de PAR no DRPP foram maiores do que aquelas no SRPP a 50-120 cm acima do solo. As características fotossintéticas das folhas-bandeira (do inglês, flag leaves) sob condições de irrigação artificial não foram significativamente influenciadas pelo respectivo padrão de plantação. No entanto, num estágio de crescimento de 80% abaixo das condições de irrigação pela chuva, a taxa fotossintética média dentre as folhas-bandeira no DRPP foi maior que aquela observada no SRPP. Além disso, o DRPP sob condições de irrigação pela chuva foi mais suscetível ao aumento do rendimento quântico aparente (do inglês, AQY - apparent quantum yield) das folhas-bandeira do que o rendimento obtido através da irrigação artificial. Estes resultados sugerem que o DRPP otimiza a distribuição PAR do dossel no trigo de inverno e contribui para a manutenção de uma maior capacidade fotossintética nas folhas bandeira sob estresse hídrico (a condição de sequeiro). Esta relação pode ser aplicada em ensaios de demonstração para encorajar os agricultores de trigo de inverno a incorporar o uso do DRPP em áreas propensas à seca, que estão submetidas a precipitação insuficiente durante a fase de crescimento do trigo no Norte da China.

Chronic inflammatory demyelinating polyneuropathy mimicking diabetic neuropathy in a young female with type 2 diabetes mellitus.

The presentations of chronic inflammatory demyelinating polyneuropathy (CIDP) overlap with those of diabetic peripheral neuropathy (DPN). We described a young girl with CIDP underlying type 2 diabetes mellitus, presenting with progressive numbness and limb weakness, who was initially misdiagnosed to have DPN. Finally immunosuppressive therapy got good response.

Mechanisms of genistein protection on pancreas cell damage in high glucose condition.

AIM: An adequate ß cell number is important to prevent the onset and development of type 2 diabetes. The aim of this study was to determine if phytoestrogen gesintein has protective effects against high glucose-induced cell apoptosis in human pancreas cells, and to try to determine the possible mechanism for this protection. METHODS: Human pancreatic ß cells were subjected to normal (5 mM) or high glucose (25 mM) with and without the presence of 100 nM genistein, and also in the presence and absence of the pure anti-estrogen ICI-182780 (100 nM). Bcl-2 siRNA transfection was performed to investigate if the effect of genistein was also Bcl-2 dependent. Cell proliferation and apoptosis were determined by Tritiated Thymidine Incorporation Assay and Cell Apoptosis Detection ELISA. Estrogen receptor and Bcl-2 mRNA expression was measured by Real-time Quantitative PCR. RESULTS: High glucose concentration caused cell proliferation inhibition and apoptosis in cultured human pancreatic ß cells, and these effects were significantly reversed by genistein (P<0.01). Estrogen receptor beta was expressed in the cultured cells, and genistein protection was blocked by ICI-182780 administration as well as Bcl-2 siRNA transfection. CONCLUSION: Phytoestrogen gave protection against high glucose-induced pancreatic cell damage through estrogen receptor beta and Bcl-2 dependent pathways.

Spontaneous remission of acromegaly or gigantism due to subclinical apoplexy of pituitary growth hormone adenoma.

BACKGROUND: Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. METHODS: Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. RESULTS: In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still > 1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. CONCLUSIONS: When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.