绝经后女性骨折的预防

本文概述了绝经后妇女预防骨折的方法。骨折是指骨或软骨的断裂,伴随或不伴随临床症状。临床症状包括：制动、疼痛、压痛、麻木、创伤、关节变形、关节肿胀、四肢畸形和四肢缩短。骨折通常是依据典型的临床症状和合适的影像学技术作出诊断的。通常,在骨质疏松症的评价试验中,绝经确诊时间为距最后一次行经12个月后。     

Influence of food intake on the bioavailability and efficacy of oral calcitonin

AIMS

To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT).

METHODS

A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62–74 years. The influence of food intake on oral dosing with 0.8 mg of sCT at 22.00 h was evaluated for a (i) predose meal at 18.00 h, (ii) predose meal at 20.00 h, (iii) predose meal at 21.00 h, (iv) postdose meal at 22.10 h, (v) no meal, and (vi) meal at 20.00 h and placebo at 22.00 h. Study biomarkers were plasma sCT levels and changes in the bone resorption marker CTX-I (C-terminal telopeptide of collagen type I).

RESULTS

The predose meal at 18.00 and 21.00 h significantly decreased relative oral bioavailability of sCT to 26% [95% confidence interval (CI) 0.09, 0.73 and 0.09, 0.75, P= 0.009 and P= 0.01]. The meal consumed 10 min after dosing decreased the oral bioavailability of sCT to 59% (95% CI 0.21, 1.68), although nonsignificant (P= 0.48). This decreased bioavailability led to lower relative suppression of serum CTX-I, with an AUC of the 4-h efficacy response of −91%–×–hours for those receiving a meal at 18.00 h, compared with −238%–×–hours for fasting subjects. The Dunnett-adjusted difference between these two treatment sequences was 147%–×–hours (95% CI 68, 225) (P= 0.0003). The AUC was comparable among fasting subjects and those consuming a meal 10 min after dosing.

CONCLUSIONS

Postprandial dosing may limit the bioavailability of orally administered sCT. Maximal benefit can be achieved by dosing at least 10 min prior to meal time.     

Variations in 5-HTTLPR: Relation to familiar risk of affective disorder,life events,neuroticism and cortisol

Background

Variations in the serotonin transporter gene (5-HTTLPR) and stressful life events are associated with affective disorders.

Aim

To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether these variations interact with life events in relation to depressive symptoms, neuroticism and salivary cortisol.

Method

In a high-risk population study, healthy monozygotic and dizygotic twins with (high-risk twins) and without (low-risk twins) a co-twin history of affective disorder were identified through nationwide registers.

Results

When comparing the 81 individuals homozygote for the long allele with the 125 individuals hetero- and homozygote for the short allele no associations between the allele distribution and a genetic predisposition were found. The presence of the short allele of the 5-HTTLPR and the experience of SLE was associated with a higher neuroticism score, but not with depressive symptoms nor awakening or evening salivary cortisol.

Conclusion

A combination of variants in 5-HTTLPR and environmental stress seems to increase neuroticism in healthy individuals.     

The postnatal development of cerebellar Purkinje cells in the Göttingen minipig estimated with a new stereological sampling technique--the vertical bar fractionator

The postnatal development of total number and perikaryon volume of cerebellar Purkinje cells was estimated in the Göttingen minipig cerebellar cortex using a new stereological approach, the vertical bar fractionator. Data were obtained from the brains of five neonate and five adult female Göttingen minipigs. The total number of Purkinje cells ranged from 1.83 × 10⁶ in the neonate to 2.82 × 10⁶ in the adult Göttingen minipig. The number-weighted mean perikaryon volume of Purkinje cells increased concurrently from around 6800 µm³ in the neonate to 17 600 µm³ in the adult. The study demonstrates that a pronounced postnatal neurogenesis in Purkinje cell number and perikaryon volume is part of the growth and development of the cerebellum in the Göttingen minipig. The Purkinje cells of the Göttingen minipig were found to be substantially large compared with human and represents the largest cells described hitherto from mammalian cerebella. The vertical fractionator is a new sampling technique, which allows the combination of a fractionator design on vertical bar sections excluding exhaustive sampling and bias from artificial edges. By design, the sections are perfect stereological vertical sections and provide the basis for unbiased estimates of total number of structural entities in the brain, including surface area, fibre length and particle volume.     

Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope

Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2-restricted CTL epitope and found two principal, diametrically opposed evolutionary pathways that exclusively affect T cell-receptor contact residues. One pathway was characterized by acquisition of CTL escape mutations and the other by selection for wild-type amino acids. The pattern of CTL responses to epitope variants shaped which variant(s) prevailed in the virus population. The pathways notably influenced the amount of plasma virus, as patients with efficient CTL selection had lower plasma viral loads than did patients without efficient selection. Thus, viral escape from CTL responses does not necessarily correlate with disease progression.     

Lethal synchronization of multivessel instability in acute coronary syndrome

Patients with acute coronary syndromes can display widespread coronary instability. We report a case presenting with ST segment elevation myocardial infarction and rapid progression to thrombosis of all major epicardial coronary arteries documented by angiography and at autopsy.     

Activation of Platelets by Aspergillus fumigatus and Potential Role of Platelets in the Immunopathogenesis of Aspergillosis

Aspergillus fumigatus is the most frequent cause of invasive mold infections worldwide. Platelets contribute to inflammation and promote thrombosis, characteristically seen in aspergillosis, and might be involved both in antifungal defense and in the histopathological process. In the experiments reported here, in vitro activation of platelets by conidia, swollen conidia, and hyphae from A. fumigatus was assessed by flow cytometry and enzyme immunoassays. THP-1 monocytes and human monocytes with and without platelets were cultured with hyphae from A. fumigatus, and the release of interleukin-8 (IL-8) was measured by enzyme immunoassays. A. fumigatus potently induced the expression of CD62-p and CD63 and the release of CD40 ligand, RANTES, and Dickkopf homolog 1 in platelets, with particularly enhancing effects of hyphae compared with conidia. The hypha-mediated activation of platelets further enhanced the release of IL-8 both in THP-1 monocytes and in human adherent monocytes. In conclusion, we have found that A. fumigatus is a potent inducer of platelet-mediated inflammation, potentially promoting protective as well as harmful responses during aspergillosis.Aspergillosis is the most common mold infection worldwide, and Aspergillus fumigatus accounts for more than 90% of the cases (6). In contrast to most human pathogens, which are encountered infrequently, A. fumigatus spores are inhaled on a daily basis, and occasionally, exposure to large numbers of conidia can occur. The first-line host defense against Aspergillus infection is based on innate immunity mediated by monocytes/macrophages and neutrophils (11, 12, 17, 18). The adaptive immune system responds to a pathogen only after it has been recognized by the innate immune system (11). While inadequate immune responses may predispose to invasive disease, overly robust responses can result in immune-mediated inflammatory tissue damage. Thus, imbalanced immune responses to A. fumigatus may result in a spectrum of human disease states ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis in the immunocompromised host (9). Despite better diagnostic tools and therapeutic advances, the infection is difficult to diagnose and treat, and the outcome of invasive aspergillosis is often fatal.Several lines of evidence support a role for platelets in inflammation (10). Platelet-mediated inflammation has been demonstrated during various acute and chronic infections, and it has been suggested that platelets contribute to antimicrobial defenses (5, 8). Very little is known about the role of platelets in defense against Aspergillus infection. In this connection, it is interesting that important risk groups for invasive aspergillosis, e.g., patients with chemotherapy-induced neutropenia and recipients of hematopoietic stem cell transplants (6, 13), very often have concurrent thrombocytopenia in addition to neutropenia. Furthermore, it has been reported that liver transplant recipients with thrombocytopenia have a considerably higher incidence of fungal infection than nonthrombocytopenic patients (3). There are some reports on the interaction between A. fumigatus and platelets, showing inhibition of fungal growth potentially involving the release of known platelet-derived microbial peptides, as well as direct physical interaction between platelets and conidia or hyphae (4, 16).Aspergillus fumigatus is angioinvasive, leading to intravascular thrombosis and dissemination of the fungus through the bloodstream (1, 2, 21). In view of the well-known role of thrombocytes in vascular thrombosis in general, it is also possible that thrombocytes contribute to the vascular damage and thrombosis which are a hallmark of invasive aspergillosis.To further study the possible role of platelets in the immune response and pathogenesis of Aspergillus fumigatus, we have examined the effect of conidia and hyphae on relevant platelet-related inflammatory mediators. We have also examined the ability of Aspergillus-exposed platelets to modulate inflammatory responses in monocytes.