沙苑子化学成分的研究Ⅱ

A new flavonoid glucosidc-rhamnocitrin-3,4′-O-β-D-diglucoside named complanatuside was isolated from the seeds Astragalus complanatus R. Brown. The elucidation of its structure was based on chemical and spectroscopic data.     

Down‐regulation of receptors for semaphorins and VEGF in a transgenic model of CMT1A

Oxcarbazepine (OXC) is a keto‐10‐analogue of carbamazepine (CBZ) with linear pharmacokinetics and a better tolerability profile compared to CBZ. For this reason, OXC has been used in some studies in the treatment of neuropathic pain of various genesis, with administration doses ranging from 300 to 2400 mg/day. In this study we have assessed the efficacy and tolerability of OXC 600 mg/day, a dose considered, based on previous data, the minimal therapeutic dose in the treatment of neuropathic pain in some neuropathies, such as diabetic neuropathy. We have studied 11 patients affected by predominant sensitive painful neuropathy, of metabolic, compressive, inflammatory or dysimmune genesis, clinically characterized by paresthesias, dysesthesias and neuralgic pain not responding to other pharmacologic therapies. At the follow‐up analysis, 7 patients have referred an improvement of painful symptoms, as evidenced by Visual Analogue Scale score, the reduction of which ranged from 20 to 60% compared to baseline values. One patient interrupted the trial for incompliance, two patients for collateral events (excessive sleepiness) and another one for a worsening of clinical picture. In conclusion, our study suggests that OXC can be considered as a valid alternative in the treatment of painful neuropathies owing to its characteristics of tolerability and efficacy in such conditions.     

Risk status at discharge and cause of death for postneonatal infant deaths: a total population study

OBJECTIVES: To obtain population-based, clinical information regarding potentially modifiable factors contributing to death during the postneonatal period (28 to 364 days), we examined all postneonatal infant deaths in four areas of the United States to determine: (1) the cause of death from clinical and autopsy data rather than vital statistics, (2) whether death occurred during initial hospitalization or after discharge, and (3) the portion of postneonatal mortality attributable to infants who left the hospital with identified high-risk medical conditions. DESIGN AND SETTING: Retrospective medical record review of all postneonatal infant deaths with birth weights greater than 500 g (total N = 386) born to mothers residing in: (1) the city of Boston (1984 and 1985, N = 55), (2) the city of St Louis and contiguous areas (1985 and 1986, N = 123), (3) San Diego County (1985, N = 112), and (4) the state of Maine (1984 and 1985, N = 96). Deaths were identified using linked birth and death vital statistics, and medical record audits of infants' and mothers' charts were performed. Causes of death were obtained from medical record review in conjunction with autopsy if performed (72%, N = 278), medical record alone (17%, N = 67), or vital statistics if no other source was available (11%, N = 41). The medical conditions at the time of discharge for each infant were reviewed and, if judged to confer an increased risk of morbidity or mortality, were classified as high risk. RESULTS: The causes of death were sudden infant death syndrome (47%, N = 181), congenital conditions (20%, N = 77), prematurity-related conditions (11%, N = 43), infections (9%, N = 34), external causes (including injuries, drownings, ingestions, and burns) (7%, N = 25), and other (6%, N = 23). In 24% of congenital and 25% to 44% of prematurity-related deaths, infection was the acute or associated cause of death. Infants born to black mothers were more likely than those born to white mothers to die during the postneonatal period of all major causes of death (7.3 per 1000 vs 3.0 per 1000). Overall, 18% (N = 68) of deaths occurred to infants who never left the hospital; 79% (N = 305) of the infants were discharged before death; and discharge status was unknown in 3% (N = 13). Eighty-one percent of all infants with prematurity-related postneonatal deaths were never discharged, and of the total infants who were initially discharged, only 1% (N = 4) subsequently died of prematurity-related causes. Of all postneonatal deaths, only 16% (N = 62) left the hospital with identified high-risk medical conditions. CONCLUSIONS: These findings suggest that the etiology of postneonatal mortality is heterogeneous, with significant complexity in attributing specific causes of death and making designations of "preventability." The vast majority of infants who died of prematurity-related postneonatal causes never left the hospital, and only a small percentage of all infants that left the hospital before death were identified as being at high medical risk. Therefore, strategies for further decreasing postneonatal mortality must link high-risk follow-up programs to more comprehensive strategies that address risk throughout pregnancy and early childhood.     

Thyroid-pituitary function in eight anencephalic infants

The function of the thyroid pituitary axis was investigated in 8 anencephalic infants with no hypothalamus. Thyrotrophin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyrone (reverse T3 and rT3) were measured in the cord blood in 5 cases and during the first 4 h of life in 3 cases. TSH response to synthetic thyrotrophin-releasing hormone (TRH) (200 microgram iv) was carried out in two cases and thyroid hormone response to bovine TSH (5 IU iv) was evaluated in 3 cases. The following results wre obtained: 1) The pituitary gland was found in all infants and the thyroid was normal both grossly and by microscopic sections. 2) TSH levels at birth were normal but there was no spontaneous post-delivery surge. 3) T4 and T3 values at delivery were within normal range, but no T3 increase was present after birth. rT3 levels at birth were higher than normal in 3 cases. 4) Administration of TRH caused a marked and rapid TSH release. 5) Thyroid hormone response to TSH was normal. The present findings suggest that in the anencephalic foetus both pituitary TSH-secreting cells and the thyroid gland do develop despite the absence of the hypothalamus and are able to function if adequately stimulated.     

Dried blood spot sampling as an alternative for the improvement of hepatitis B and C diagnosis in key populations

BACKGROUNDTo achieve the elimination of hepatitis B and C, there is an urgent need to develop alternative strategies to increase the access of diagnosis, particularly among key populations such as people living with human immunodeficiency virus (HIV), individuals with coagulopathies and chronic kidney disease (CKD) patients. AIMTo evaluate the use of dried blood spot (DBS) in the detection of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers. METHODSA total of 430 individuals comprised of people living with HIV, coagulopathies and CKD provided paired serum and DBS samples. HBsAg, anti-HBc and anti-HCV were tested in those samples using a commercial electrochemiluminescence. Demographic and selected behavioral variables were evaluated to assess possible association with HBV and HCV positivity. RESULTSUsing DBS, HBsAg prevalence varied from 3.9% to 22.1%, anti-HBc rates varied from 25.5% to 45.6% and anti-HCV positivity ranged from 15.9% to 41.2% in key populations. Specificities of HBV and HCV tests using DBS varied from 88.9% to 100%. The HBsAg assay demonstrated the best performance in CKD and coagulopathy individuals and the anti-HCV test had a sensitivity and specificity of 100% in people living with HIV. Accuracy of HBV and HCV detection in DBS varied from 90.2% to 100%. In the CKD group, HBsAg positivity was associated with infrequent use of condoms, and anti-HBc positivity was associated with sharing nail cutters/razors/toothbrushes. Anti-HCV reactivity was positively associated with a history of transplantation and length of time using hemodialysis in both specimens. In people living with HIV, only the male gender was associated with anti-HBc positivity in serum and DBS.CONCLUSIONDBS with electrochemiluminescence are useful tools for the diagnosis and prevalence studies of hepatitis B and C among key populations and may increase the opportunity to foster prevention and treatment.     

Concordance of a point mutation 5' to the G gamma globin gene with G gamma beta +. Hereditary persistence of fetal hemoglobin in the black population

Hereditary persistence of fetal hemoglobin (HPFH) is a genetically heterogeneous and clinically benign condition characterized by persistent expression of fetal hemoglobin (Hb F) into adulthood. In the G gamma beta + type, no major deletions in the globin gene cluster occur; adult heterozygotes produce approximately 20% Hb F, which results from overproduction of G gamma chains, with no apparent increase in production from the adjacent A gamma gene. We have recently described a point mutation 202 base pairs 5' to the cap site of the G gamma gene in an individual with G gamma beta + HPFH. This mutation abolishes a normal ApaI restriction endonuclease site, and thus can be detected by blotting of genomic DNA. We present here further data on the ApaI mutation: (1) It occurs in six of seven families with G gamma beta + HPFH. (2) In three families, detailed haplotype analysis using 11 polymorphic restriction sites in the beta globin cluster has been done. The two that carry the missing ApaI site are identical but the third, which has a normal ApaI pattern, differs from the other two in at least two sites, one of which is a new polymorphic Nco I site between the delta and beta globin genes. This suggests the possibility of a different HPFH mutation in the third family. (3) The haplotype of the G gamma beta + HPFH chromosome carrying the ApaI mutation is different from that of 108 beta A chromosomes of black individuals that have been tested. (4) The G gamma ApaI site is normal in 61 beta A and 109 beta S alleles from non-HPFH black individuals, including 22 who share the same haplotype for the intragenic G gamma, A gamma HindIII polymorphisms. These data add support to the possibility that the -202 mutation is actually causative of the G gamma beta + HPFH phenotype.     

Neuromedin s as novel putative regulator of luteinizing hormone secretion

Neuromedin S (NMS), a 36 amino acid peptide structurally related to neuromedin U, was recently identified in rat brain as ligand for the G protein-coupled receptor FM4/TGR-1, also termed neuromedin U receptor type-2 (NMU2R). Central expression of NMS appears restricted to the suprachiasmatic nucleus, and NMS has been involved in the regulation of dark-light rhythms and suppression of food intake. Reproduction is known to be tightly regulated by metabolic and photoperiodic cues. Yet the potential contribution of NMS to the control of reproductive axis remains unexplored. We report herein analyses of hypothalamic expression of NMS and NMU2R genes, as well as LH responses to NMS, in different developmental and functional states of the female rat. Expression of NMS and NMU2R genes was detected at the hypothalamus along postnatal development, with significant fluctuations of their relative levels (maximum at prepubertal stage and adulthood). In adult females, hypothalamic expression of NMS (which was confined to suprachiasmatic nucleus) and NMU2R significantly varied during the estrous cycle (maximum at proestrus) and was lowered after ovariectomy and enhanced after progesterone supplementation. Central administration of NMS evoked modest LH secretory responses in pubertal and cyclic females at diestrus, whereas exaggerated LH secretory bursts were elicited by NMS at estrus and after short-term fasting. Conversely, NMS significantly decreased elevated LH concentrations of ovariectomized rats. In summary, we provide herein novel evidence for the ability of NMS to modulate LH secretion in the female rat. Moreover, hypothalamic expression of NMS and NMU2R genes appeared dependent on the functional state of the female reproductive axis. Our data are the first to disclose the potential implication of NMS in the regulation of gonadotropic axis, a function that may contribute to the integration of circadian rhythms, energy balance, and reproduction.     

Using psychological theory to understand the clinical management of type 2 diabetes in Primary Care: a comparison across two European countries

Background  

Long term management of patients with Type 2 diabetes is well established within Primary Care. However, despite extensive efforts to implement high quality care both service provision and patient health outcomes remain sub-optimal. Several recent studies suggest that psychological theories about individuals' behaviour can provide a valuable framework for understanding generalisable factors underlying health professionals' clinical behaviour. In the context of the team management of chronic disease such as diabetes, however, the application of such models is less well established. The aim of this study was to identify motivational factors underlying health professional teams' clinical management of diabetes using a psychological model of human behaviour.     

C2orf37 mutational spectrum in Woodhouse–Sakati syndrome patients

Alazami AM, Schneider SA, Bonneau D, Pasquier L, Carecchio M, Kojovic M, Steindl K, de Kerdanet M, Nezarati MM, Bhatia KP, Degos B, Goh E, Alkuraya FS. C2orf37 mutational spectrum in Woodhouse–Sakati syndrome patients. Woodhouse–Sakati syndrome (WSS) is a rare autosomal recessive disorder that encompasses hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus and progressive extrapyramidal defects. The syndrome is caused by mutation of the C2orf37 gene. Here we studied a cohort of seven new cases from three ethnic backgrounds, presenting with the hallmarks of WSS, in an effort to extend the mutational spectrum of this disorder. Genetic analysis revealed a novel mutation in each of the four families investigated, of which three were nonsense mutations and the fourth was a splice site ablation. We also examined a separate collection of 11 cases presenting with deafness and dystonia, two constituents of WSS, but found no pathogenic changes. This study doubles the number of known mutations for this disorder, confirms that truncating mutations in C2orf37 are the only known cause of WSS, and suggests that mutations in this gene do not contribute significantly to cases presenting with isolated elements of WSS such as deafness and dystonia. The lack of correlation between clinically expressivity of WSS and the site of the eight truncating mutations strongly supports that they are equally null, while the intrafamilial variability argues for an important role of modifiers in this disease.