利心丸对小鼠缺氧耐受的影响及机理

目的研究利心丸对小鼠缺氧耐受的影响并初步探讨其机理。方法小鼠随机分生理盐水(每天20g/kg)组、心得安(每天0.16g/kg)组、利心丸高剂量(每天5g/kg)和低剂量(每天1g/kg)组,连续给药5天并于末次给药1h后测定小鼠缺氧耐受能力以及血清乙酰胆碱酯酶(T-ChE)和总抗氧化能力(T-AOC)。结果利心丸低剂量组耗氧率和心得安组均较生理盐水组显著降低(P<0.05或0.01);心得安组T-ChE活性较生理盐水组显著增高(P<0.01);心得安组和利心丸高剂量组T-AOC均较生理盐水组显著增高(P均<0.01)。结论利心丸低剂量能提高小鼠抗常压的缺氧耐受能力,可能与提高机体总抗氧化能力有关。     

Intranasal Tat Alters Gene Expression in the Mouse Brain

Intranasal (IN) delivery of HIV-1 Tat in aging mice was investigated as a possible model for HIV-1 infection in the brain. After IN administration, the distribution of [¹²⁵I]-labeled Tat in the brains of Swiss Webster mice was evaluated by autoradiography and gamma counting. [¹²⁵I]-labeled Tat was detected at the highest concentrations in the olfactory bulb, cervical nodes, and trigeminal nerve tract. In another experiment, APPSw transgenic mice were used to model chronic Tat exposure. The mice were treated intranasally with 6 μg Tat (n = 4) or vehicle (n = 4) three times per week for 4 weeks. Total RNA was isolated from the frontal cortex, and differential gene expression analysis was performed using gene microarrays. Gene ontology profiles indicated innate immunity, inflammatory and apoptotic responses. Five genes of interest in the Tat-treated mice that were significantly elevated in the microarrays were validated by RT-PCR. One gene, the Toll-like receptor 9 (Tlr9), has previously been shown to activate signaling cascades leading to innate immunity and enhanced HIV-1 gene expression. A second gene, Fas, plays a key role in neuroinflammation. Two cysteine-rich cytokines associated with chemotaxis were elevated: MCP-1 (Ccl2), which is chemotactic for monocytes, and Ccl17 (TARC), which is chemotactic for lymphocytes. Finally, the gene sestrin was significantly elevated and has been associated with oxidative stress, in particular amyloid beta-induced oxidative stress. This IN Tat model of neuroinflammation may be useful to study HIV-1-induced neurodegeneration. This paper was presented at an NIMH workshop “HIV Preclinical–Clinical Therapeutics Research Meeting”, May 5–16, 2006.     

Meniere's disease: An immune complex-mediated illness?

The cause of Menière's disease is unknown. Recent clinical research suggests that one etiology is immune-mediated damage to the inner ear. The diagnosis of autoimmune Menière's syndrome is largely based on history, response to steroids, or results of nonspecific laboratory tests such as serological studies. Polyethylene glycol (PEG) assay was used to determine levels of circulating immune complexes (CIC) in 30 patients with Menière's disease and 20 control subjects. Patients with Menière's disease had a statistically significant elevation of serum circulating immune complexes when compared to the control group. This suggests that CICs may be involved in the pathogenesis of Menière's disease, either as a direct cause of damage, or as a by-product of an underlying autoimmune abnormality. Therapeutic implications include use of plasmapheresis to remove the complexes or CIC monitoring to serve as a marker for treatment efficacy.     

Indian preschool children--a profile of stunting and wasting

Anthropometric data collected on 18,938 preschool children (1-5 years) by the National Nutrition Monitoring Bureau (NNMB) in 10 states of the country were analysed for assessing growth status in terms of 'stunting' and 'wasting'. The results showed that the prevalence of stunting, reflective of chronic malnutrition, is of higher magnitude compared to wasting (considered to be an outcome of current acute malnutrition), as well as wasting and stunting. The stunting increased with increasing age of children. The data also suggested that over the period, the prevalence of stunting declined from 58 per cent in 1974 to 45 per cent in 1980. A corresponding increase in normals from 35 to 50 per cent has also been noticed during the same period.     

Importance of steroid receptors and aromatase activity in the prognosis of ovarian cancer: high tumor progesterone receptor levels correlate with longer survival

The presence of steroid receptors (82 tumors) and aromatase activity (39 tumors) in ovarian carcinomas was correlated with patient survival. No statistically significant correlation was found between the presence or absence of estrogen receptors (ER, 56.1%), progesterone receptors (PR, 57.3%), androgen receptors (AR, 91.5%), or aromatase activity (33.3%) and survival. However, high levels of PR were associated with better survival (P less than 0.05). Furthermore, there was a tendency for patients with advanced disease and PR-positive tumors to have better survival than those with advanced disease and PR-negative tumors (P = 0.13). Patients with tumors that did not contain any of the receptors and those in which ER and AR were absent, or in which PR and AR were absent, had poor survival. It is concluded that receptor status, especially of PR, may be of prognostic importance and that status of receptors and aromatase activity may become useful in selecting ovarian cancer patients for endocrine therapy.     

Evidence of pleiotropic loci for fasting insulin, total fat mass, and abdominal visceral fat in a sedentary population: the HERITAGE family study

OBJECTIVE: To examine whether there is a major gene effect on fasting insulin and pleiotropic loci for fasting insulin, total fat mass (FM), and abdominal visceral fat (AVF). RESEARCH METHODS AND PROCEDURES: A major gene hypothesis for fasting plasma insulin levels was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of white descent who participated in the HERITAGE Family Study. RESULTS: Segregation analyses were performed on insulin adjusted for age, on insulin adjusted for age and FM, and on insulin adjusted for age and AVF. Before adjustment for AVF and FM, a major gene effect on fasting insulin levels was indicated. The putative locus accounted for 54% of the variance under a recessive inheritance pattern, affecting 11% of the sample (i.e., allele frequency = 0.33). However, after adjusting for the effects of AVF or FM, neither a major effect alone nor a multifactorial component alone could be rejected, and support for a major gene was equivocal, i.e., neither the hypothesis of Mendelian tau values or that of the equal tau(s) were rejected and the equal tau model fit the data better than the Mendelian tau model. This pattern (i.e., major gene evidence for insulin before but not after adjustment for AVF or FM) suggests that there is a putative locus with pleiotropic effects on both insulin and FM and another pleiotropic locus for both insulin and AVF. DISCUSSION: Although these data do not directly support an additional major gene for insulin independent of AVF and FM, such support cannot be ruled out because there is still a significant major effect on FM- or AVF-adjusted insulin (albeit the Mendelian nature of this effect is ambiguous).     

Personality disorders among subjects recovered from eating disorders

OBJECTIVE: Personality disorders are common in symptomatic eating disorders subjects. Because personality symptoms could be exaggerated by malnutrition or Axis I disorders, we studied women who had recovered from eating disorders for at least 1 year to see if personality disorder symptoms persisted in the well state. METHOD: Personality disorders were evaluated in 10 women recovered from anorexia nervosa (AN), 28 women recovered from bulimia nervosa (BN), and 16 women recovered from AN and BN, using the Structured Clinical Interview for DSM-III-R personality disorders. RESULTS: Fourteen of 54 subjects (26%) met the criteria for at least one personality disorder, such as self-defeating, obsessive-compulsive, or borderline personality disorder. Cluster B personality disorders were closely associated with bulimic subtypes. CONCLUSIONS: While a recovery from eating disorders may have an attenuating influence on the symptoms of personality disorders, such personality disorder diagnoses persist after recovery in some recovered subjects.     

Modulation of fibrinolysis by ionizing radiation

Summary Radiation-induced damage to the central nervous system is believed to be targeted to glial or endothelial cells or both, although the pathophysiology of this process is still poorly understood. A series of experiments were, therefore, conducted, including irradiation to primary rat astrocytes (in vitro) and rat spinal cords (in vivo). The levels of plasminogen activators (uPA and tPA) and their inhibitors (PNI and PAI-1) were determined by fibrin zymography, ELISA, amidolytic activity assay, complex formation, and Western blot analysis. Fibrin zymography revealed the presence of M_r 48,000 (uPA) and M_r 68,000 (tPA) lytic bands that were increased in irradiated samples. Three- to four-fold higher levels of tPA and 8- to 10-fold higher levels of uPA were detected in irradiated samples. Western blot analysis confirmed the presence of a 51-kDa band (PAI-1) in irradiated samples. PAI-1 is undetectable in nonirradiated spinal cord. Serum-free medium and cell and spinal cord extracts of nonirradiated samples showed a 43-kDa band (PNI), the intensity of which is decreased in irradiated samples. Four- to five-fold decreased levels of PNI were detected in irradiated serum-free media and cell extracts, but no levels of PNI were detected in irradiated spinal cord extracts. This study provides additional information regarding the proposed roles of plasminogen activators and their inhibitors in the development of CNS damage after irradiation.