Interaction of glucagon with artificial lipid bilayer membranes

The enhancement of fluorescence emission from the tryptophan residue of glucagon, the quenching of that emission with acrylamide and with 5-doxyl and 16-doxyl stearic acid, circular dichroism spectra, the release of 6-carboxytluorescein, and polarized infrared attenuated total reflection (IR-ATR) spectra were used to study the interaction of glucagon with intact lipid vesicles and flat bilayers. Dimyristoylphosphatidylcholine bound the peptide only below the main transition temperature, thus confirming earlier results of Epand et al. (1977). However, the peptide is also bound by vesicles of unsaturated lipids above their transition temperature, suggesting an influence of lipid area on the binding process. Circular dichroism showed that binding to such vesicles also increases the helix content of glucagon. The IR-ATR study and a comparison with dynorphin-A-(I-13)-tridecapeptide revealed profound differences in orientation of the two peptides. The dichroic ratios and the derived order parameters indicated an isotropic orientation of the helical segments of glucagon, but did not exclude a principal orientation of the molecules lying flat on the nienibrane surface. In contrast, the axis of the dynorphin helix is clearly oriented normal to the interface. The two peptides also differ in their rates of 6-carboxyfluorescein release, suggesting a deeper penetration of the primary amphiphilic helix of dynorphin A-(I-13) than of the secondary amphiphilic helix of glucagon.     

Complete structure of eclosion hormone of Manduca sexta

The locations of the three disulfide bonds of eclosion hormone (EH) isolated from Manduca sexta were assigned by sequence analysis of thermolysin fragments and by comparison of a key heterodimeric fragment to regiospecifically synthesized parallel and antiparallel isomers. We elucidated the complete structure of Manduca EH as a 62-residue peptide which has three disulfide bonds between Cys¹⁴-Cys³⁸, Cys¹⁸-Cys³⁴, and Cys²¹-Cys⁴⁹.     

Disinhibition of somatosensory evoked potential recovery in alcoholics

The pathogenesis of cognitive impairment in alcoholics remains unclear. Previous studies suggested that diffuse white matter atrophy is associated with cognitive impairment in alcoholics. To elucidate this issue, the present study evaluated alcoholics with cognitive impairment using the somatosensory evoked potential (SEP) recovery method, which is suitable for detecting subtle dysfunction at the cortical level. Subjects comprised 12 alcoholics with mild cognitive impairment [Mild group: Mini Mental State Examination Score (MMSE), ≥24; mean, 27.9 ± 1.6], 12 alcoholics with moderate to severe cognitive impairment (Moderate group: MMSE score, < 24; mean, 21.0 ± 2.5) and 12 normal subjects (Control group). SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Single-pulse or paired-pulse stimuli at various interstimulus intervals (10–300 ms) were administered. Recovery functions of N9 (a peripheral nerve component), N20, N20-P25 and P25-N33 (cortical components) were studied. N20 recovery curves of both alcoholic groups were less suppressive than those of Controls, and P25-N33 recovery curves of the Moderate group were more excitatory than those of the Mild or Control groups. A disinhibited recovery pattern of N20 indicates subcortical dysfunction, and a disinhibited pattern of P25-N33 would be induced by cortical dysfunction. Therefore, subcortical dysfunction indicated by an abnormal N20 recovery pattern may contribute to the early cognitive impairment of alcoholics, whilst the cortical dysfunction indicated by an abnormal P25-N33 recovery pattern may contribute to the later cognitive impairment of alcoholics.     

Fibrate for treatment of primary biliary cirrhosis

Recent studies of the effectiveness of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC) reported that UDCA therapy did not necessarily stop the progression of liver fibrosis in all patients, even those with early stage PBC. Thus, there is a need for more effective treatments that could prevent asymptomatic PBC from progressing to the icteric stage. Bezafibrate is effective in approximately two-thirds of non-icteric patients who have not shown a complete response to UDCA. Serum bilirubin, aspartate aminotransferase and γ-guanosine 5'-triphosphate levelswere significantly lower in patients who responded to additional bezafibrate on univariate analysis. The putative mechanism by which bezafibrate acts in cholestasis is by increasing phospholipid output into bile, which forms micelles with the hydrophobic bile acid that reduces its toxicity.     

Association of diabetes-related emotional distress with diabetes treatment in primary care patients with Type 2 diabetes.

AIMS: To characterize the determinants of diabetes-related emotional distress by treatment modality (diet only, oral medication only, or insulin). METHODS: A total of 815 primary care patients with Type 2 diabetes completed the Problem Areas in Diabetes (PAID) Scale and other questions. We linked survey data to a diabetes clinical research database and used linear regression models to assess the associations of treatment with PAID score. RESULTS: PAID scores were significantly higher among insulin-treated (24.6) compared with oral-treated (17.8, P < 0.001) or diet-treated patients (14.7, P < 0.001), but not different between oral- vs. diet-treated patients (P = 0.2). Group scores remained similar, but the statistical significance of their differences was reduced and ultimately eliminated after sequential adjustment for diabetes severity, HbA(1c), body mass index, regimen adherence, and self-blood-glucose monitoring. Insulin-treated patients reported significantly higher distress than oral- or diet-treated patients on 16 of 20 PAID items. 'Worrying about the future' and 'guilt/anxiety when ... off track with diabetes' were the top two serious problems (PAID >or= 5) in all treatment groups. Not accepting diabetes diagnosis was a top concern for oral- and diet-treated patients, and unclear management goals distressed diet-treated patients. CONCLUSIONS: Primary care patients treated with insulin reported higher diabetes-related emotional distress compared with oral- or diet-treated patients. Greater distress was largely explained by greater disease severity and self-care burdens. To improve diabetes-specific quality of life, clinicians should address patients' sense of worry and guilt, uncertain acceptance of diabetes diagnosis, and unclear treatment goals.     

肾癌多中心病灶发生机理的探讨

目的　探讨肾癌多中心病灶的发生机理。　方法　肾癌根治术标本 10 2例 ,间隔 3mm切开检查切面 ,原发灶外可疑处取材证实肾癌者为多中心灶阳性。免疫组化法检查肾癌原发灶及多中心灶p5 3、PCNA、c erbB2 、CD44 v6、bcl 2、nm2 3 H1 蛋白表达情况。　结果　多中心灶发生率为 15 .7%( 16 10 2 ) ,16例多中心性肾癌中 ,原发灶与多中心灶p5 3、PCNA、c erbB2 、CD44 v6、bcl 2、nm2 3 H1 蛋白表达情况均相近 ,统计学处理差异无显著性意义 (P均 >0 .4)。　结论　肾癌多中心灶具有与原发灶相似的生物学特征 ,其发生以原发灶肾内转移可能性大。     

原发性肝癌非规则性肝切除的疗效观察

目的探讨非规则性肝切除术治疗原发性肝癌的临床疗效。方法1995年1月～2003年5月采用非规则性肝切除治疗原发性肝癌106例，随访1～5年，对其临床资料进行分析。结果8例在术后3个月内死于肝肾功能衰竭，98例恢复良好。术后1、3、5年的生存率分别为84．9％、34．7％、27．8％。结论非规则性肝切除是治疗原发性肝癌的有效方法，特别对于合并肝硬化的患者更有临床应用价值。     

Clinical and demographical characteristics of primary progressive multiple sclerosis in Isfahan, Iran

Primary progressive multiple sclerosis (PPMS) is an uncommon form of multiple sclerosis (MS) in which the course of disease is progressive from onset. In a retrospective study amongst 1606 MS patients registered in Isfahan MS Society (IMSS) from April 2003 to 31 December 2005, 92 PPMS cases were identified. That means, the frequency of PPMS amongst all included MS patients would be 5.7% (95% CI: 6.7% and 4.7%). The mean expanded disability status scale (EDSS) for the group was 5.09 ± 1.3. The commonest mode of presentation was motor disturbance in 55 (59.8%), other modes of presentation were, vertigo in 15 (16.3%), visual problems in 12 (13%), sensory disturbances in six (6.5%), and diplopia in four (4.3%). The current existing symptoms were motor problems in all 92 (100%), cerebellar symptoms in 46 (50%), and cognitive impairment in only six (6.5%). Interestingly, two (2%) were affected by poliomyelitis during childhood and presenting symptom in both was limb weakness. Primary progressive form of MS is less common in Persian population and some of the rates observed in PPMS patients differ from those in other regions, these differences may be due to different ethnicity of Persian patients or to geographical differences.     

对原发性骨质疏松诊断的一些看法

原发性骨质疏松的诊断首先要除外继发性骨质疏松。后者包括的范围很广，内容也很多，需要广博的内科学基础和辨证的逻辑思维才能予以正确鉴别。骨密度检查只能作为一种参考，而不能作为诊断原发性骨质疏松的唯一依据。     

原发性高尿酸血症肾病的中西医治疗探讨

既往认为高尿酸血症肾病是西方国家的一种常见病,在中国少见。近年来,由于经济情况好转,饮食结构的变化,蛋白质及富含嘌呤成分的食物摄入量增加,中国发病率有增高的趋势。因此文章旨在通过探讨原发性高尿酸血症肾病的诊断及其中西医治疗方法,希望能够对临床及时正确的诊断和恰当周全的治疗该病提供一定的指导。