The progression from obesity to type 2 diabetes in Alström syndrome

Bettini V, Maffei P, Pagano C, Romano S, Milan G, Favaretto F, Marshall JD, Paisey R, Scolari F, Greggio NA, Tosetto I, Naggert JK, Sicolo N, Vettor R. The progression from obesity to type 2 diabetes in Alström syndrome. Background: Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease associated with obesity, hyperinsulinemia, and alterations of glucose metabolism that often lead to the development of type 2 diabetes at a young age. Objective: To study the relationship between weight and metabolism in a group of ALMS patients and matched controls. Research design and methods: Fifteen ALMS patients (eight males, seven females; aged 3–51) were compared in a cross‐sectional study with an age‐ and weight‐matched control population. Anthropometric parameters, fat mass, glucose and insulin secretion in basal and dynamic oral glucose tolerance test (OGTT) conditions were measured. Furthermore, anthropometric and body composition data were obtained from an international group of 27 ALMS patients (13 males, 14 females, age range: 4–29 yr). Results: In ALMS we observed an inverse correlation between age and standard deviation scores for height, weight, and body mass index. The OGTT glycemic curves of ALMS subjects were similar to those of age‐matched controls, whereas insulin response was clearly greater. In ALMS individuals the insulin response showed a reduction with age. We documented pathologic values of the derived indices homeostasis model assessment of insulin resistance (HOMA‐IR), insulin sensitivity index, HOMA%β‐cell and insulinogenic index in ALMS, but unlike the insulin‐resistance indices, the β‐cell function indices showed a significant reduction with age. Conclusions: In ALMS the progression from the early onset obesity toward the impaired fasting glucose or impaired glucose tolerance and overt diabetes is mostly because of a progressive failure of β‐cell insulin secretion without any further worsening of insulin resistance with age, even in the presence of weight reduction.     

Effects of chronic lead intoxication on rat serotoninergic system and anxiety behavior

Chronic lead exposure has been shown to produce behavioral disturbances in human and animal models. These disturbances are associated with alterations in monoaminergic neurotransmission in the central nervous system (CNS), some of which have been attributed to serotonin (5-HT). This study was undertaken to investigate the chronic effects of lead exposure on the serotoninergic system in the dorsal raphe nucleus (DRN) and the consequences of its toxicity on rat behavior. Adult male Wistar rats were chronically exposed for 3 months to 0.5% lead acetate in drinking water. The serotoninergic system was evaluated using immunohistochemistry and the anxiety behavior was assessed by the light/dark box test. The results show that chronic lead exposure induces a significant increase of blood and brain lead levels in treated rats compared with controls. The density of the immunoreactive serotoninergic cell bodies was significantly higher in treated rats in all parts of the DRN. Assessment of animal behavior using the light/dark box test showed that lead-treated rats spent significantly more time in the light chamber compared with controls (P = 0.001). These findings suggest that lead exposure may possibly induce increased anxiety as a consequence of changes in neuronal 5-HT content in the DRN.     

新型葡萄糖类似物~（99）Tc~mN-DGDTC的药代动力学和显像研究

目的探讨[99TcmN]2＋间接标记二硫代氨基甲酸脱氧葡萄糖（deoxyglucose dithiocarbamate,DGDTC）药代动力学特点以及在荷瘤模型小鼠和兔的显像效果。方法药代动力学研究：标记后的[99TcmN]-DGDTC化合物经耳缘静脉注射入健康成年新西兰大白兔体内,于特定时间点采血测定放射计数,以专业软件进行药代动力学计算。动物肿瘤模型显像：分别以荷瘤Balb/C小鼠和新西兰大白兔进行。分别移植H22鼠肝癌细胞系和VX2兔肝癌细胞系于10只小鼠和5只兔子皮下,待肿瘤成型后静脉注射99TcmN-DGDTC复合物行显像观察,并均以99Tcm-高锝酸盐显像作为对照研究。扫描方法：采集血流相、血池相和连续静态图像直至注射后2-4 h（小时）。结果药代动力学结果证明99TcmN-DGDTC复合物体内分布为二室模型,有效半衰期为34.05 min。显像结果证明99TcmN-DGDTC复合物能充分显示小鼠和兔肿瘤模型的病变所在,注射后2 h肿瘤区/周围组织放射计数比值大于2。结论药代动力学和显像研究结果充分证实了99TcmN-DGDTC作为新的肿瘤代谢显像剂的可行性。     

核素骨显像在骨纤维结构不良诊断中的价值

目的 总结骨纤维结构不良(FD)的核素骨显像特征,并与原发性骨肿瘤、肿瘤骨转移以及Paget's病等鉴别.方法 回顾性分析2003--2010年在上海交通大学附属第六人民医院骨质疏松和骨病专科门诊或者病房收治的27例FD患者的临床资料,所有FD患者均接受常规<'99>Tcm-MDP全身骨显像并经手术病理证实.对<'99...     

Neural structures and mechanisms involved in scene recognition: a review and interpretation

Since the discovery in 1996 that a region within caudal parahippocampal cortex subserves learning and recall of topographical information, numerous studies aimed at elucidating the structures and pathways involved in scene recognition have been published. Neuroimaging studies, in particular, have revealed the locations and identities of some of the principal cortical structures that mediate these faculties. In the present study the detailed organization of the system is examined, based on a meta-analysis of neuroimaging studies of scene processing in human subjects, combined with reviews of the results of lesions on this type of processing, single neuron studies, and available hodological data in non-human primates. A cortical hierarchy of structures that mediate scene recognition is established based on these data, and an attempt is made to determine the function of the individual components of the system.     

The role of IL-6, IL-8 and MCP-1 and their promoter polymorphisms IL-6 -174GC, IL-8 -251AT and MCP-1 -2518AG in the risk of venous thromboembolism: a case-control study

Introduction

Cytokines increased the risk of venous thromboembolism (VTE) in some case-control studies, but not in a prospective study. Data concerning the role of cytokines in the risk of VTE are limited. We examined in a case-control study the association of VTE and levels of interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) and assessed whether promoter polymorphisms (IL-6 -174GC, IL-8 -251AT, MCP-1 -2518AG) would affect the thrombotic risk and cytokine levels.

Materials and methods

The study included 119 patients (94 women) with a first event of VTE aged between 18-60 years, and 126 healthy controls (100 women) matched for age (± 5 years). Blood was collected > 7 months after the thrombotic event. Odds ratios (ORs) were calculated per increase of cytokines levels by 1 pg/mL.

Results

ORs adjusted for age and sex were 1.520 [95% Confidence Interval (CI) 1.177 - 1.962] for IL-6, 1.095 (95% CI 1.002 - 1.196) for IL-8 and 1.000 (0.988 - 1.012) for MCP-1. With additional adjustment for ethnic composition, body mass index (BMI) and high sensitive C-reactive protein (hs-CRP), risk estimates remained significant for IL-6 and became of borderline statistical significance for IL-8. Polymorphisms did not influence the thrombotic risk and the cytokine levels in study participants.

Conclusion

VTE was associated with IL-6 and IL-8 levels, and for IL-6 this association was independent of BMI and hs-CRP. Thus far, a causal relationship between inflammation and VTE remains to be clarified and more prospective data are warranted.     

Calcineurin inhibitor sparing regimens using m‐target of rapamycin inhibitors: an opportunity to improve cardiovascular risk following kidney transplantation?

Maintenance therapy with calcineurin inhibitors (CNIs) increases cardiovascular risk. Use of the m‐TOR inhibitors everolimus or sirolimus to minimize CNI exposure is usually undertaken to preserve renal function following kidney transplantation, but may also improve cardiovascular risk status. Recent studies of early conversion from CNI to m‐TOR inhibitors have shown a numerical improvement in the incidence of hypertension, but results are not clear‐cut. Dyslipidaemia, in contrast, is more frequent under m‐TORs than with CNI‐based immunosuppression. New‐onset diabetes is rare (≤5%) using modern m‐TOR regimens, for example, everolimus and reduced‐exposure CNI. Renal function improvement with m‐TOR inhibitor regimens versus CNIs would also be expected to improve cardiovascular risk. Moreover, m‐TOR‐based CNI‐minimization regimens are not associated with proteinuria, a known cardiovascular risk factor, with the possible exception of late conversion in patients with poor renal function. Interestingly, m‐TOR inhibitors may also exert cardioprotective effects. Animal data suggest that m‐TORs may restrict the pathogenesis of atherosclerosis, consistent with preliminary clinical data that conversion from CNIs to everolimus can stabilize markers for arterial stiffness. In conclusion, use of m‐TORs has the potential to lessen the toll of cardiovascular disease following kidney transplantation – an opportunity that merits further exploration.     

Waldenström’s macroglobulinemia masquerading as ovarian cancer with peritoneal carcinomatosis,ascites, and elevated CA-125

Waldenström’s macroglobulinemia is a rare hematology malignancy which often presents with “B symptoms,” anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM. Omental and bone marrow biopsy confirmed the diagnosis of Waldenström’s macroglobulinemia, with elevation in CA-125 thought to be secondary to peritoneal irritation. This patient has since been successfully treated with six cycles of bendamusine and rituximab with no evidence of disease on staging scans and normalization of both CA-125 and IgM. To our knowledge, this is the first documented case of Waldenström’s macroglobulinemia presenting with symptoms classically associated with ovarian cancer and demonstrates the importance of maintaining a broad differential when evaluating patients with abdominal carcinomatosis.     

99Tcm-DTPA肾动态显像测定肾小球滤过率的影响因素分析

肾小球滤过率(GFR)是反映肾功能的重要指标,利用99Tcm-二亚乙基三胺五乙酸(99Tcm-DTPA)进行肾动态显像检测GFR是目前临床最常用的方法,但测量过程中的一些可变因素和操作细节,如血浆蛋白结合、肾脏和本底感兴趣区勾画、肾脏深度、患者年龄及自身肾功能、患者准备情况和操作技术等,都可能对GFR的检测产生影响。该...     

The Assessment of Regional Skeletal Metabolism: Studies of Osteoporosis Treatments Using Quantitative Radionuclide Imaging

Studies of bone remodeling using bone biopsy and biochemical markers of bone turnover play an important role in research studies to investigate the effect of new osteoporosis treatments on bone quality. Quantitative radionuclide imaging using either positron emission tomography with fluorine-18 sodium fluoride or gamma camera studies with technetium-99m methylene diphosphonate provides a novel tool for studying bone metabolism that complements conventional methods, such as bone turnover markers (BTMs). Unlike BTMs, which measure the integrated response to treatment across the whole skeleton, radionuclide imaging can distinguish the changes occurring at sites of particular clinical interest, such as the spine or proximal femur. Radionuclide imaging can be used to measure either bone uptake or (if done in conjunction with blood sampling) bone plasma clearance. Although the latter is more complicated to perform, unlike bone uptake, it provides a measurement that is specific to the bone metabolic activity at the measurement site. Treatment with risedronate was found to cause a decrease in bone plasma clearance, whereas treatment with the bone anabolic agent teriparatide caused an increase. Studies of teriparatide are of particular interest because the treatment has different effects at different sites in the skeleton, with a substantially greater response in the flat bone of the skull and cortical bone in the femur compared with the lumbar spine. Future studies should include investigations of osteonecrosis of the jaw and atypical fractures of the femur to examine the associated regional changes in bone metabolism and to throw light on the underlying pathologies.