Hearing impairment and hypoxia ischaemic encephalopathy: Incidence and associated factors

Objective

To establish the local incidence of hearing loss in newborns with Hypoxic Ischaemic Encephalopathy (HIE) and to identify associated risk factors.

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

New options for the treatment of obesity and type 2 diabetes mellitus (narrative review)

Moderate weight loss (> 5%), which has been associated with improvements in glycemic parameters in patients with dysglycemia, also reduces the presence of other comorbidities, including dyslipidemia and hypertension, culminating in a reduced risk of cardiovascular disease. Lifestyle changes are the recommended preliminary approach to weight loss, with an initial weight-loss goal of 10% of body weight achieved over 6 months at a rate of 1–2 pounds per week selected as an appropriate target to decrease the severity of obesity-related risk factors. Implementing and maintaining the lifestyle changes associated with weight loss can, however, be challenging for many patients. Therefore, additional interventions sometimes may be necessary. Bariatric surgery can also be a highly effective option for weight loss and comorbidity reduction, but surgery carries considerable risks and is still applicable only to selected patients with type 2 diabetes. Thus, attention is turning to the use of weight-loss medications, including 2 recently approved compounds: twice-daily lorcaserin and a once-daily combination of phentermine and topiramate extended-release, both shown to be safe and effective therapies in the management of obesity in patients with type 2 diabetes.     

Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

Limited proteolysis of the bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica.

The structure and activity of the bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) from the protozoan parasite Leishmania tropica were examined by limited proteolysis with five different endopeptidases. Each reaction resulted in a rapid, time-dependent loss of TS activity and no effect on DHFR activity. The proteolytic products were examined by NaDodSO4/PAGE; each digestion produced a fragment of apparent Mr approximately 35,000, and three of the five digestions generated a fragment of Mr approximately 20,000. Attempts to separate the fragments under nondenaturing conditions failed, suggesting that the proteolyzed protein remains a dimer with the gross structure of the subunits more or less undisturbed. In contrast, kinetic data indicate that some aspects of higher-order structure in the native protein are affected by proteolysis. The fragments (Mr 36,600 and 20,000) generated by Staphylococcus aureus V8 protease were subjected to sequence analysis. Whereas neither the native protein nor the Mr 36,600 fragment yielded an NH2-terminal amino acid, we obtained the sequence of the first 28 amino acids of the Mr 20,000 fragment. This sequence bore strong homology with sequences situated within TS of human, Lactobacillus casei, Escherichia coli, and bacteriophage T4. These and other data indicate that the TS-DHFR polypeptide consists of a DHFR sequence at the blocked NH2-terminal and a TS sequence at the COOH-terminal end of the protein. The region that is the target of the five proteases corresponds to a highly variable region within the sequences of the other four TSs. We suggest that an insertion occurs within the TS-DHFR sequence, positioned on the surface of the protein and quite vulnerable to the action of endopeptidases.     

Operative compared with nonoperative treatment of a thoracolumbar burst fracture without neurological deficit. A prospective,randomized study

BACKGROUND: To our knowledge, a prospective, randomized study comparing operative and nonoperative treatment of a thoracolumbar burst fracture in patients without a neurological deficit has never been performed. Our hypothesis was that operative treatment would lead to superior long-term clinical outcomes. METHODS: From 1994 to 1998, forty-seven consecutive patients (thirty-two men and fifteen women) with a stable thoracolumbar burst fracture and no neurological deficit were randomized to one of two treatment groups: operative (posterior or anterior arthrodesis and instrumentation) or nonoperative treatment (application of a body cast or orthosis). Radiographs and computed tomography scans were analyzed for sagittal alignment and canal compromise. All patients completed a questionnaire to assess any disability they may have had before the injury, and they indicated the degree of pain at the time of presentation with use of a visual analog scale. The average duration of follow-up was forty-four months (minimum, twenty-four months). After treatment, patients indicated the degree of pain with use of the visual analog scale and they completed the Roland and Morris disability questionnaire, the Oswestry back-pain questionnaire, and the Short Form-36 (SF-36) health survey. RESULTS: In the operative group (twenty-four patients), the average fracture kyphosis was 10.1 degrees at the time of admission and 13 degrees at the final follow-up evaluation. The average canal compromise was 39% on admission, and it improved to 22% at the final follow-up examination. In the nonoperative group (twenty-three patients), the average kyphosis was 11.3 degrees at the time of admission and 13.8 degrees at the final follow-up examination after treatment. The average canal compromise was 34% at the time of admission and improved to 19% at the final follow-up examination. On the basis of the numbers available, no significant difference was found between the two groups with respect to return to work. The average pain scores at the time of the latest follow-up were similar for both groups. The preinjury scores were similar for both groups; however, at the time of the final follow-up, those who were treated nonoperatively reported less disability. Final scores on the SF-36 and Oswestry questionnaires were similar for the two groups, although certain trends favored those treated without surgery. Complications were more frequent in the operative group. CONCLUSION: We found that operative treatment of patients with a stable thoracolumbar burst fracture and normal findings on the neurological examination provided no major long-term advantage compared with nonoperative treatment.     

Lipoproteins in the DCCT/EDIC cohort: associations with diabetic nephropathy

BACKGROUND: Lipoproteins may contribute to diabetic nephropathy. Nuclear magnetic resonance (NMR) can quantify subclasses and mean particle size of very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL), and LDL particle concentration. The relationship between detailed lipoprotein analyses and diabetic nephropathy is of interest. METHODS: In a cross-sectional study, lipoproteins from 428 women and 540 men from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort were characterized by conventional lipid enzymology, NMR, apolipoprotein levels, and LDL oxidizibility. Linear regression was performed for each lipoprotein parameter versus log albumin excretion rate (AER), with and without covariates for age, diabetes duration, HbA1c, hypertension, body mass index, waist-hip ratio, and DCCT treatment group. Significance was taken at P < 0.05. RESULTS: By multivariate analysis, conventional profile, total triglycerides, total- and LDL cholesterol, but not HDL cholesterol, were associated with AER. NMR-determined large, medium, and small VLDL were associated with AER in both genders (except large VLDL in women), and intermediate density lipoprotein (IDL) was associated with AER (men only). LDL particle concentration and ApoB were positively associated with AER (in men and in the total cohort), and there was a borderline inverse association between LDL diameter and AER in men. Small HDL was positively associated with AER and a borderline negative association was found for large HDL. No associations were found with ApoA1, Lp(a), or LDL oxidizibility. CONCLUSION: Potentially atherogenic lipoprotein profiles are associated with renal dysfunction in type 1 diabetes and further details are gained from NMR analysis. Longitudinal studies are needed to determine if dyslipoproteinemia can predict patients at risk of nephropathy, or if lipoprotein-related interventions retard nephropathy.