盐酸多奈哌齐干预血管性痴呆患者后的磁共振波谱分析

目的 利用氢质子磁共振波谱分析(1 H-magnetic resonance spectroscopy,1 H-MRS)技术研究脑卒中后血管性痴呆(vascular dementia,VD)患者颞叶海马区细胞代谢水平及给予盐酸多奈哌齐后,细胞代谢水平的改变及其与临床症状的关系.方法 脑卒中VD组18例,男性16例,女性2例,平均年龄(76.9±2.7)岁,符合痴呆的《神经病诊断和统计手册》第4版(DSM-Ⅳ)诊断标准;脑卒中非VD组13例,男性11例,女性2例,平均年龄(76.2±3.6)岁;正常对照组来源于门诊就诊者,共14例,男性12例,女性2例,平均年龄(75.1±2.4)岁.所有入组者均行简易精神状态量表(MMSE)、日常生活活动能力量表(ADL)、汉密尔顿抑郁量表(HAMD)评分以及1H-MRS检测患者双侧颞叶海马区细胞代谢水平.脑卒中VD组在盐酸多奈哌齐治疗6个月后复查MMSE评分及1H-MRS检查.结果 脑卒中VD组患者双侧颞叶海马区N-乙酰天门冬氨酸盐(NAA)/肌酸(Cr)比值较正常对照组及脑卒中非VD组均有显著下降(F=4.23、4.98,均P＜0.05);而双侧胆碱复合物(Cho)/Cr比值较正常对照组显著升高(P=0.005、0.010),较脑卒中非VD组左侧有显著升高(P=0.038),但右侧差异无统计学意义(P=0.066).脑卒中非VD组NAA/Cr比值及Cho/Cr比值较正常对照组虽有变化,但差异无统计学意义.脑卒中VD组MMSE评分与双侧颞叶海马区NAA/Cr及Cho/Cr比值有相关性,且MMSE分数越低,NAA/Cr比值越低,而Cho/Cr比值则越高.应用盐酸多奈哌齐干预治疗脑卒中VD组患者6个月后,患者MMSE及ADL评分均有显著提高(均P＜0.05);双侧颞叶海马区NAA/Cr比值无明显改善(t=-2.02、-2.04,均P＞0.05),而双侧颞叶海马区Cho/Cr比值有显著下降(t=2.86、2.23,均P＜0.05).结论 1 H-MRS技术可能有助于早发现脑卒中后血管性痴呆;盐酸多奈哌齐可通过调整脑内胆碱能系统,改善血管性痴呆患者的认知功能.     

Reversal of hepatic steatosis by omega-3 fatty acids measured non-invasively by (1) H-magnetic resonance spectroscopy in a rat model

Background and Aim: Living donors with marked (> 33%) macrovesicular steatosis (MaS) are excluded from living donor liver transplantation procedures. Experimental studies have shown that the development of steatosis can be prevented by supplementation with omega‐3 fatty acids (FA), but no studies have investigated the reduction of steatosis using omega‐3 FA. The aim of the present study was to investigate whether administration of omega‐3 FA is effective in reducing steatosis. Methods: After fatty liver (FL) induction by a 3‐week methionine/choline‐deficient (MCD) diet, male Wistar rats were daily administered per gavage omega‐3 FA (FL+Omega‐3), omega‐3‐poor lipid solution (FL+Lipid), or NaCl (FL+NaCl) during 2 weeks. Control animals received standard chow without treatment. Determination of steatosis degree was performed before, during, and after treatment by clinical 3.0T ¹H‐magnetic resonance spectroscopy (¹H‐MRS) and by histology and gas chromatography at the end of the 2‐week treatment period. Results: Hepatic fat content (¹H‐MRS) was significantly reduced after 1 and 2 weeks of omega‐3 FA treatment. Histological analysis revealed a mild (5–33%) MaS degree in omega‐3‐treated animals vs severe (> 66%) MaS in the FL+Lipid and FL+NaCl groups. Hepatic omega‐6 : 3 FA ratio and total FA content were reduced in the FL+Omega‐3 group. Furthermore, de novo lipogenesis (C16, C16 : 1ω7, C18 : 1ω9) was also lowered. The reduction in hepatic fat content was associated with decreased lobular inflammation and hepatic tumor necrosis factor‐ α and interleukin levels as well as an increased antioxidative capacity. Conclusion: Omega‐3 FA are capable of reversing severe hepatic MaS and ameliorating pathophysiological features of non‐alcoholic steatohepatitis such as hepatocellular damage, lobular inflammation, and a reduced antioxidative capacity.     

Intramyocellular lipid changes in men and women during aerobic exercise: a (1)H-magnetic resonance spectroscopy study

This study was designed to compare intramyocellular lipid (IMCL) changes during 60 min of submaximal exercise in men and women. Eighteen moderately active (18-38 yr) men (n = 9) and women (n = 9) were recruited. Maximum oxygen consumption (O(2)max) and body composition were used to match subjects for aerobic fitness and body composition. Subjects performed cycle ergometry for 1 h at 65% of O(2)max. Expired gases were collected throughout exercise to determine caloric expenditure and substrate use. Blood samples were collected before and after exercise to evaluate markers of lipid metabolism. Pre- and postexercise proton spectra were acquired from the vastus lateralis using a 3-T whole-body imaging system. Spectra were acquired from an 18-mm(3) region of interest (echo time = 45 msec; repetition time = 2000 msec) for IMCL evaluation. IMCL decreased significantly with exercise (11.5-28.5% for men and 17.1-21.7% for women) (P < 0.05); however, there were no significant differences between men and women. Although changes were found for many plasma variables [free fatty acids, glycerol, and norepinephrine (P < 0.05)], group differences were only evident for norepinephrine. In conclusion, a significant decrease in IMCL was observed during 60 min of cycling in matched men and women.     

Cardiac magnetic resonance spectroscopy

This review describes recent advances in cardiac magnetic resonance spectroscopy (MRS). MRS allows noninvasive characterization of the metabolic state of cardiac muscle, in both animal and human models. Recent experimental MRS studies have allowed new insights into the essential role of energetics in heart failure. Various new studies suggest a rapidly growing role of MRS for phenotyping new genetically modified mouse models, and recent methodologic advances include development of absolute quantification of high-energy phosphates, measurement of ATP turnover rates and thermodynamic parameters (such as free ADP and free energy change of ATP hydrolysis), and improved acquisition sequences. New patient studies demonstrate the potential value of MRS as a clinical diagnostic tool in patients with ischemic heart disease, heart failure, cardiac transplantation, valve disease, and genetic cardiomyopathy.     

Hepatic steatosis and type 2 diabetes mellitus

Type 2 diabetes is strongly associated with nonalcoholic fatty liver disease (NAFLD), a spectrum of liver damage that ranges from relatively benign hepatic steatosis to potentially fatal cirrhosis. The severities of insulin resistance and liver damage parallel each other, with the greatest prevalence of cirrhosis occurring in cirrhotics. However, it is unknown whether one of these conditions causes the other, or if both are consequences of another process. Experimental evidence suggests that both insulin resistance and NAFLD result from a chronic inflammatory state. The mechanisms driving this chronic inflammation are unknown but might include the egress of products from intestinal bacteria into the portal blood, liver, and systemic circulation to trigger a sustained inflammatory cytokine response in genetically susceptible individuals. More research is needed to evaluate this hypothesis and to determine the benefits of treatments that interrupt this pathogenic cascade.     

In vitro 1H-magnetic resonance spectroscopy of Barrett's esophageal mucosa using magic angle spinning techniques

OBJECTIVES: In vitro proton magnetic resonance spectroscopy (MRS) allows changes in cell membrane lipid structure associated with dysplasia and malignant transformation to be investigated. Magic angle spinning (MAS) MRS allows small esophageal tissue specimens to be studied directly without the need to extract the tissue, but it is not known how intact the tissue architecture remains after MAS. We report the first prospective MAS MRS study of Barrett's esophagus using endoscopic biopsies with direct histological correlation. METHODS: Biopsies were obtained during surveillance esophagoscopy from Barrett's epithelium and adjacent normal squamous epithelium in 16 patients (34 samples). High-resolution MAS MRS was performed at 500 MHz. Following MRS, the histology was evaluated. A further, separate group of 14 biopsies were examined histologically to assess architectural damage caused by tissue preservation alone. RESULTS: For squamous and Barrett's epithelium, respectively, metabolite ratios of choline-containing compounds to creatine plus phosphocreatine (Cho/Cr) were 1.99 and 5.65 (P < 10) and methyl lipid to creatine plus phosphocreatine ratios (lipid-CH3/Cr) were 4.07 and 7.4 (P < 10). There was no significant difference in histological preservation between the squamous and Barrett's mucosa without MRS (z = 0.67, P = 0.61), but significant differences were found post-MAS MRS (z = 4.06, P < 0.0001). CONCLUSIONS: Squamous and Barrett's epithelium can be distinguished metabolically, based on Cho/Cr and lipid-CH3/Cr ratios. Although MAS does affect the histological architecture in Barrett's epithelium, compared with squamous epithelium, direct histological assessment was possible in the majority of samples.     

Cardiac consequences of diabetes mellitus

A variety of disciplines including noninvasive and invasive cardiac methodologies, as well as epidemiologic studies, have provided information that has altered our view on the relation of diabetes to cardiac disease. Instead of an exclusive focus on coronary artery disease, it is now recognized that heart muscle can be independently involved in diabetic patients. In diabetics without known cardiac disease, abnormalities of left ventricular mechanical function have been demonstrated in 40 to 50% of subjects, and it is primarily a diastolic phenomenon. Left ventricular hypertrophy may eventually appear in the absence of hypertension. The diastolic dysfunction appears related to interstitial collagen deposition, largely attributable to diminished degradation. The presence of even moderate obesity intensifies the abnormality. Reversibility of this process is not readily achieved with chronic insulin therapy. Experimental studies have indicated normalization of the collagen alteration by endurance training, begun relatively early in the disease process. General measures of management include the control of other cardiac risk factors and a reasonable program of physical activity. The high mortality during an initial acute myocardial infarction has been attributed to heart failure, which is managed as in nondiabetic patients. Recently, the early introduction of aspirin, thrombolysis, and beta-adrenergic blockade has reduced mortality during the initial infarction. Chronic use of the latter agent over the subsequent years has also proven to be more beneficial in diabetic patients with acute myocardial infarction compared with nondiabetic patients.     

Cardiac mucormycosis complicating diabetes mellitus

Fewer than 25 cases of myocardial involvement with the Mucoraceae have been reported. We present a diabetic patient with recurrent ketoacidosis and staphylococcal septicemia whose demise was accelerated by unsuspected left atrial mural endocardial mucormycosis.     

Ophthalmoplegia in diabetes mellitus: a retrospective study

Ophthalmoplegia, despite being a rare entity in diabetes mellitus, is associated with great anxiety for the patients and often appears to be a serious problem from a diagnostic and therapeutic point of view. There have been few studies primarily concerned with the relative frequencies and clinical characteristics of oculomotor neuropathies in diabetic subjects. Those published have emanated largely from neurological and/or ophthalmological referral centres rather than metabolic departments. Objective of this study was to determine the incidence, the clinical characteristics and risk factors for developing ophthalmoplegia among persons with diabetes mellitus. We have performed a retrospective study of all diabetic patients with ophthalmoplegia who were seen in the Metabolic Division at “S. Biagio” Hospital, Marsala, over the 10 year period from 1998 to 2007. A detailed history and blood laboratory profile were obtained for each patient. During the period of the survey a total of 6,765 diabetic subjects were hospitalised and ophthalmoplegia was identified in 27 patients (0.40%). Isolated III nerve palsies accounted for the majority of patients (59.3%), with VI nerve palsies (29.6%) occurring more frequently than multiple palsies (11.1%). These patients had a marked comorbidity and were found to have a poorly controlled diabetes. The patients with VI nerve palsies showed a tendency toward a higher coexistence of diabetic retinopathy and cardiovascular risk factors than those with III cranial nerve palsies. Ophthalmoplegia is a serious and not common problem among patients with diabetes mellitus; the oculomotor nerve was most frequently affected in our case-report. The fact that the coexistence of diabetic complications and cardiovascular risk factors was slightly higher in patients with VI nerve palsy is compatible with the hypothesis that this ischemic event might be more closely related to diabetes and metabolic syndrome in its pathogenesis.     

Factors associated with microalbuminuria in type 1 diabetes mellitus: a cross-sectional study

In order to determine the prevalence of microalbuminuria in people with Type 1 diabetes mellitus (Type 1 DM) and identify factors associated with microalbuminuria, we studied 312 Type 1 DM patients attending in three hospitals in two Spanish regions over 6 months. Clinical characteristics, micro- and macro-vascular complications, blood pressure, 24-h urine albumin excretion, lipid profile, HbA1(c) levels, smoking habits, and family history of hypertension and diabetic nephropathy were recorded. Univariate analysis and multiple logistic regression were used to examine associations between these variables and the prevalence of microalbuminuria. We detected microalbuminuria in 29% of the patients. The prevalence of microalbuminuria was high during the second decade of diabetes and declined thereafter. Univariate analysis showed dyslipidaemia (P<0. 002), previously diagnosed hypertension (P<0.001), family history of hypertension (sibling alone P<0.006; mother alone P<0.05), family history of diabetic nephropathy (P<0.001), and laser-treated retinopathy (P<0.03) to be factors associated with the presence of microalbuminuria. Multiple logistic regression revealed an association between microalbuminuria and family history of nephropathy (OR 7.6, 3.6-16). In conclusion, in our sample the frequency of microalbuminuria seems to be related to the presence of dyslipidaemia, hypertension, and to a family history of hypertension or nephropathy.     

Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study

Aims/hypothesis We compared in vivo changes in liver glycogen concentration during exercise between patients with type 1 diabetes and healthy volunteers. Methods We studied seven men with type 1 diabetes (mean ± SEM diabetes duration 10 ± 2 years, age 33 ± 3 years, BMI 24 ± 1 kg/m², HbA_1c 8.1 ± 0.2% and VO₂ peak 43 ± 2 ml [kg lean body mass]⁻¹ min⁻¹) and five non-diabetic controls (mean ± SEM age 30 ± 3 years, BMI 22 ± 1 kg/m², HbA_1c 5.4 ± 0.1% and VO₂ peak 52 ± 4 ml [kg lean body mass]⁻¹ min⁻¹, before and after a standardised breakfast and after three bouts (EX1, EX2, EX3) of 40 min of cycling at 60% VO₂ peak. ¹³C Magnetic resonance spectroscopy of liver glycogen was acquired in a 3.0 T magnet using a surface coil. Whole-body substrate oxidation was determined using indirect calorimetry. Results Blood glucose and serum insulin concentrations were significantly higher (p < 0.05) in the fasting state, during the postprandial period and during EX1 and EX2 in subjects with type 1 diabetes compared with controls. Serum insulin concentration was still different between groups during EX3 (p < 0.05), but blood glucose concentration was similar. There was no difference between groups in liver glycogen concentration before or after the three bouts of exercise, despite the relative hyperinsulinaemia in type 1 diabetes. There were also no differences in substrate oxidation rates between groups. Conclusions/interpretation In patients with type 1 diabetes, hyperinsulinaemic and hyperglycaemic conditions during moderate exercise did not suppress hepatic glycogen concentrations. These findings do not support the hypothesis that exercise-induced hypoglycaemia in patients with type 1 diabetes is due to suppression of hepatic glycogen mobilisation. K. Chokkalingam and K. Tsintzas contributed equally to this study.     

Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy

Hyperglycemia and diabetes alter the function and metabolism of many tissues. The effect on the brain remains poorly defined, but some animal data suggest that chronic hyperglycemia reduces rates of brain glucose transport and/or metabolism. To address this question in human beings, we measured glucose in the occipital cortex of patients with poorly controlled diabetes and healthy volunteers at the same levels of plasma glucose using proton magnetic resonance spectroscopy. Fourteen patients with poorly controlled diabetes (hemoglobin A 1c = 9.8% +/- 1.7%, mean +/- SD) and 14 healthy volunteers similar with respect to age, sex, and body mass index were studied at a plasma glucose of 300 mg/dL. Brain glucose concentrations of patients with poorly controlled diabetes were lower but not statistically different from those of control subjects (4.7 +/- 0.9 vs 5.3 +/- 1.1 micromol/g wet wt; P = .1). Our sample size gave 80% power to detect a difference as small as 1.1 micromol/g wet wt. We conclude that chronic hyperglycemia in diabetes does not alter brain glucose concentrations in human subjects.     

Gestational diabetes mellitus in teenage pregnancy: a case-control study

In a retrospective study, teenage Asian pregnancies with gestational diabetes managed over a 4-year period were compared with a group of age and parity matched controls (2 for each study case) to determine the incidence of gestational diabetes and its impact on the pregnancy outcome. The incidence of gestational diabetes in teenage pregnancy was 5.4 % (33/611), and accounted for 1.4 % of all the cases of gestational diabetes. There was no difference in the maternal anthropometric parameters or antenatal complications, but the study group had a higher incidence of postpartum haemorrhage (p = 0.010), greater amount of estimated blood loss at delivery (p = 0.016), a trend towards a higher incidence of large-for-gestational age infants, a higher incidence of admission to the neonatal unit (p = 0.024), mostly due to meconium-stained liquor for observation (p = 0.014), and a lower first minute Apgar score (p = 0.012). Our findings support the recommendation that in ethnic groups with a high prevalence of diabetes, universal as opposed to age-limited screening for gestational diabetes should be undertaken. Copyright © 1998 John Wiley & Sons, Ltd.     

Cardiac health and diabetes mellitus in women: problems and prospects

Cardiovascular disease is the leading cause of morbidity and mortality in both genders. Although premenopausal women display a lower prevalence in cardiovascular diseases compared with age-matched men, they lose this 'female advantage' following menopause. There are significant gender differences in a wide spectrum of cardiovascular incidence, ranging from delayed disease onset to higher prevalence of comorbid diseases for females. Several factors have been suggested to contribute to such difference in cardiovascular incidence including sex hormones, gender-specific intrinsic organ function, difference in body size and cardiovascular risk factor profiles (e.g., use of tobacco and alcohol, hypertension, diabetes mellitus, dyslipidemia, obesity, sedentary lifestyle and atherogenic diet). A gender difference also exists for diabetes and diabetic complications. Heart diseases exhibits a 2-fold and a 5-fold increase in men and women with diabetes, respectively. Although female hearts are usually more tolerable to stress insults than their male counterparts, female sex hormone such as estrogen interacts with diabetic risk factors to precipitate cardiomyopathy. This review aims at recaping our knowledge on gender difference in diabetic heart disease with an emphasis on disease pathogenesis. Deficits and obstacles to optimal risk factor management in diabetic women are also discussed in an effort to improve the overall cardiovascular health of diabetic women.