Fosinopril improves left ventricular diastolic function in young mildly hypertensive patients without hypertrophy

To clarify whether fosinopril monotherapy can improve left ventricular diastolic function (LVDF) in young mildly hypertensives without hypertrophy, we studied 66 patients (pts) with diastolic blood pressure 90–100 mmHg, aged <45 years, with normal 2-dimensional echocardiography (2-D echo), and impaired DF. Impaired DF was defined as a Doppler transmitral early (E) to atrial (A) filling velocity ratio (E/A ratio) <1. Thirty-eight pts were selected for fosinopril monotherapy. Mean age was 36 years. Duration of documented hypertension was 5.4 years. Mean daily dose of fosinopril was 20 mg. Twenty-eight controls were treated with hydrochlorothiazide and hydralazine combination. Sixty-six age- and sex-matched healthy subjects served to establish normal reference values of 2-D and Doppler echo measurements. All hypertensives were treated for 30 months and re-examined 4 weeks after cessation of treatment. The fosinopril-treated group showed improvements in transmitral E (52 ± 8 cm/s, vs. 61 ± 9 cm/s, p < 0.01), A (56 ± 9 cm/s, vs. 47 ± 6 cm/s, p < 0.05), and E/A ratio (0.93 ± 0.16, vs. 1.29 ± 0.18, p < 0.01). Moreover, the early to atrial velocity-time integral ratio (1.31 ± 0.10, vs. 2.24 ± 0.10, p < 0.001) improved. The pulmonary venous flow pattern normalized after fosinopril therapy. LV mass index, relative wall thickness, LV dimension, left atrial dimension, fractional shortening, heart rate, and body mass index did not change. The hydrochlorothiazide-hydralazine combination-treated group did not show an improved diastolic function. It is concluded that long-term fosinopril monotherapy leads to an improvement of impaired LVDF in young mildly hypertensives without hypertrophy.     

Modular patterning of structure and function of the striatum by retinoid receptor signaling

Retinoid signaling plays a crucial role in patterning rhombomeres in the hindbrain and motor neurons in the spinal cord during development. A fundamentally interesting question is whether retinoids can pattern functional organization in the forebrain that generates a high order of cognitive behavior. The striatum contains a compartmental structure of striosome (or "patch") and intervening matrix. How this highly complex mosaic design is patterned by the genetic programs during development remains elusive. We report a developmental mechanism by which retinoid receptor signaling controls compartmental formation in the striatum. We analyzed RARbeta(-/-) mutant mice and found a selective loss of striosomal compartmentalization in the rostral mutant striatum. The loss of RARbeta signaling in the mutant mice resulted in reduction of cyclin E2, a cell cycle protein regulating transition from G(1) to S phase, and also reduction of the proneural gene Mash1, which led to defective neurogenesis of late-born striosomal cells. Importantly, during striatal neurogenesis, endogenous levels of retinoic acid were spatiotemporally regulated such that transduction of high levels of retinoic acid through RARbeta selectively expanded the population of late-born striosomal progenitors, which evolved into a highly elaborate compartment in the rostral striatum. RARbeta(-/-) mutant mice, which lacked such enlarged compartment, displayed complex alternations of dopamine agonist-induced stereotypic motor behavior, including exaggeration of head bobbing movement and reduction of rearing activity. RARbeta signaling thus plays a crucial role in setting up striatal compartments that may engage in neural circuits of psychomotor control.     

Encephalopathy and acute axonal sensorimotor polyneuropathy following acute pancreatitis: a case report and review of the literature

A case of a 22-year-old woman with rare neurologic complications including encephalopathy and acute axonal sensorimotor polyneuropathy in the course of acute pancreatitis is reported. The encephalopathy emerged 3 weeks after the onset of the illness with complete remission being noted 1 week later. The polyneuropathy presented as quadriplegia and respiratory failure that required intubation and partially remitted gradually. There was no pancreatic lesion, no major pancreatic surgery, no sepsis, and no multiple organ failure, all of which had been proposed as the predisposing factors. Severe inflammatory response syndrome (SIRS) that developed during the clinical course of this patient might have induced these neurologic complications.     

Reappraisal of the characteristics of glucose abnormalities in patients with chronic hepatitis C infection

OBJECTIVES: There is growing evidence suggesting the mutual link between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the impact of HCV infection on the suite of glucose abnormalities has rarely been investigated. The study aimed to determine the difference regarding the prevalence and the characteristics of glucose abnormalities between chronic hepatitis C (CHC) patients and community-based controls. It also aimed to investigate the related clinical, virological, and histological features of glucose abnormalities in HCV infection.
METHODS: Six hundred eighty-three CHC patients and 515 sex-/age-matched controls were included. Oral glucose tolerance test (OGTT) was performed in 522 CHC patients and 447 controls without known T2DM. Clinical data were assessed upon the different stages of glucose abnormalities based on OGTT results.
RESULTS: The prevalence of normoglycemia, IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively. There was a significant linear trend from normoglycemia to T2DM in terms of age, family history of T2DM, and advanced liver fibrosis in CHC patients. For those CHC patients without fibrosis, the prevalence of glucose abnormalities reached 67.9% high. All CHC patients carried a significantly higher prevalence than controls regarding those aged <65 yr. For those without known DM, there was a 3.5-fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70–4.56, P < 0.001).
CONCLUSIONS: CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested.     

Apoptosis pathway of liver cells in chronic hepatitis

AIM: To study the pathway of apoptosis in chronic liver disease and the role of mitochondria in programmed cell death.METHODS: Liver biopsy specimens from 72 cases of chronic hepatitis and 29 cases of post hepatitis cirrhosis were studied. The pro-apoptotic protein Fas, FasL, Bax and the anti-apoptotic protein Bcl-2, Bcl-xL, Bcl-2α were studied immunohistochemically by SP method. Specimens from 15 cases of chronic hepatitis and post hepatitis cirrhosis were examined for their ultramicrostructures with special attention to their mitochondrial changes. Specimens from 3 normal adults (demised in traffic accidents) were used as control.RESULTS: The expression of proapoptotic proteins (Fas, FasL, Bax) in hepatocytes was significantly higher in the chronic hepatitis group than in the cirrhosis group (P&lt;0.001). In the study of ultramicrostructure 364 hepatocytes were examined, from 12 cases of chronic hepatitis (including 10 mild cases, 1 moderate case and 1 severe case). Out of 364 hepatocytes 40 (11.0%) hepatocytes were found with various kinds of destruction in their mitochondria. Rupture of the outer membrane of mitochondria and the leakage of matrix from the intermembrane space were definitely demonstrated. The ultramicrostructural changes of mitochondria in the chronic hepatitis group were statistically higher than that in normal adults control group(X^2=4.32, P&lt;0.05). CONCLUSION: The result of the study was in support of the current view that the apoptotic process in chronic hepatitis patients were largely along the intrinsic pathway (mitochondrial pathway), given that the intrinsic and extrinsic pathways could interlinked (converged) at some point on their progression, also it is impossible at present to exclude the possibility that the two pathways could be chosen by hepatocytes in parallel simultaneously.     

内嗅皮质萎缩评价糖尿病患者认知功能

目的 探讨2型糖尿病（T2DM）伴轻度认知功能损害（MCI）患者与单纯T2DM患者、健康对照者间各脑区皮质体积的差异,并分析其与认知下降的关联程度。方法 收集30例单纯T2DM患者、30例T2DM伴MCI患者和30名健康对照者,通过高分辨率MR T1WI采集大脑结构像数据,应用FreeSurfer软件处理获得各脑区体积参数。3组间各脑区体积的比较采用方差分析,对差异有统计学意义的脑区与心理学量表进行相关分析。结果 T2DM与T2DM伴MCI患者的听觉词语学习测验、复杂图形20 min回忆测验、数字符号编码测验、连线测验A、连线测验B、蒙特利尔认知评估量表分数差异有统计学意义（P均<0.05）。与T2DM患者比较,T2DM伴MCI患者的左侧内嗅皮质、左侧外侧眶额皮层、左侧后扣带回皮质、右侧外侧眶额皮质、右侧眶部皮质、右侧岛叶皮质体积均降低（P均<0.05）;T2DM伴MCI患者的左侧内嗅皮质体积与听觉词语学习测验评分（即刻）呈正相关（r=0.452,P=0.018）。结论 T2DM伴MCI患者出现多个脑区皮质体积降低,其中左侧内嗅皮质体积可作为诊断和衡量T2DM伴MCI的潜在生物学指标。