Structure elucidation of new compounds from acidic treatment of the progestins gestodene and drospirenone

Gestodene acidic treatment afforded a single rearrangement product, namely 13-beta-ethyl-18,19-dinorpregna-4,14,16-trien-3,20-dione 3, which was originated through HCl-catalyzed Rupe rearrangement. Drospirenone acidic treatment yielded two epimeric lactones by addition of HCl to the 6beta,7beta-cyclopropane ring, namely 7beta-(chloromethyl)-15beta,16beta-methylene-3-oxo-17beta-pregn-4-ene-21,17-carbolactone 4 and 7beta-(chloromethyl)-15beta,16beta-methylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactone 5. The structure of the compounds was assessed by spectroscopic and crystallographic methods.     

Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease

Background

It is hypothesized that decreased capillarization of limb skeletal muscle is implicated in the decreased exercise tolerance in COPD patients. We have recently demonstrated decreased number of capillaries per muscle fibre (CAF) but no changes in CAF in relation to fibre area (CAFA), which is based on the diffusion distance between the capillary and muscle fibre. The aim of the current study is to investigate the muscle-to-capillary interface which is an important factor involved in oxygen supply to the muscle that has previously been suggested to be a more sensitive marker for changes in the capillary bed compared to CAF and CAFA.

Methods

23 COPD patients and 12 age-matched healthy subjects participated in the study. Muscle-to-capillary interface was assessed in muscle biopsies from the tibialis anterior muscle using the following parameters:1) The capillary-to-fibre ratio (C:F_i) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre2) The ratio between C:F_i and the fibre perimeter (CFPE-index)3) The ratio between length of capillary and fibre perimeter (LC/PF) which is also referred to as the index of tortuosity.Exercise capacity was determined using the 6-min walking test.

Results

A positive correlation was found between CFPE-index and ascending disease severity with CFPE-index for type I fibres being significantly lower in patients with moderate and severe COPD. Furthermore, a positive correlation was observed between exercise capacity and CFPE-index for both type I and type IIa fibres.

Conclusion

It can be concluded that the muscle-to-capillary interface is disturbed in the tibialis anterior muscle in patients with COPD and that interface is strongly correlated to increased disease severity and to decreased exercise capacity in this patient group.     

Sic1 is phosphorylated by CK2 on Ser201 in budding yeast cells

We have previously identified Ser201 of Sic1, a yeast cyclin-dependent kinase inhibitor, as an in vitro target of protein kinase CK2. Here we present new evidence, by using specific anti-P-Ser201 antibodies and 2-D gel electrophoresis coupled to MALDI mass spectrometry analysis, that Sic1 is phosphorylated in vivo on Ser201 shortly after its de novo synthesis, during late anaphase in glucose-grown cells. This phosphorylation is also detected in Sic1 immunopurified from G1 cells. In agreement with these data we also show that the catalytic alpha' subunit of CK2, whose function is required for cell cycle progression, is detected in Sic1 immunopurified complexes, and that phosphorylation on Ser201 is reduced after CK2 inactivation at the non-permissive temperature in a cka1delta cka2(ts) yeast strain. These data strongly support the notion that CK2 phosphorylates Sic1 in vivo.     

Growth Monitoring: A Survey of Current Practices of Primary Care Paediatricians in Europe

Objective

We aimed to study current practices in growth monitoring by European primary care paediatricians and to explore their perceived needs in this field.

Methods

We developed a cross-sectional, anonymous on-line survey and contacted primary care paediatricians listed in national directories in the 18 European countries with a confederation of primary care paediatricians. Paediatricians participated in the survey between April and September 2011.

Results

Of the 1,198 paediatricians from 11 European countries (response rate 13%) who participated, 29% used the 2006 World Health Organization Multicentre Growth Reference Study growth charts, 69% used national growth charts; 61% used software to draw growth charts and 79% did not use a formal algorithm to detect abnormal growth on growth charts. Among the 21% of paediatricians who used algorithms, many used non-algorithmic simple thresholds for height and weight and none used the algorithms published in the international literature. In all, 69% of paediatricians declared that a validated algorithm to monitor growth would be useful in daily practice. We found important between-country variations.

Conclusion

The varied growth-monitoring practices declared by primary care paediatricians reveals the need for standardization and evidence-based algorithms to define abnormal growth and the development of software that would use such algorithms.     

Nitric Oxide Mediates the Glutamate-dependent Pathway for Neurotransmission in Sepia officinalis Chromatophore Organs

Chromatophore organs are complex and unique structures responsible for the variety of body coloration patterns used by cephalopods to communicate and camouflage. They are formed by a pigment-containing cytoelastic sacculus, surrounded by muscle fibers directly innervated from the brain. Muscle contraction and relaxation are responsible for expansion and retraction of the pigment-containing cell. Their functioning depends on glutamate and Phe-Met-Arg-Phe-NH₂-related peptides, which induce fast and slow cell expansion, respectively, and 5-hydroxytryptamine, which induces retraction. Apart from these three substances and acetylcholine, which acts presynaptically, no other neuroactive compounds have so far been found to be involved in the neuroregulation of chromatophore physiology, and the detailed signaling mechanisms are still little understood. Herein, we disclose the role of nitric oxide (NO) as mediator in one of the signaling pathways by which glutamate activates body patterning. NO and nitric-oxide synthase have been detected in pigment and muscle fibers of embryo, juvenile, and adult chromatophore organs from Sepia officinalis. NO-mediated Sepia chromatophore expansion operates at slower rate than glutamate and involves cGMP, cyclic ADP-ribose, and ryanodine receptor activation. These results demonstrate for the first time that NO is an important messenger in the long term maintenance of the body coloration patterns in Sepia.     

Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection

We found that the proteome of apoptotic T cells includes prominent fragments of cellular proteins generated by caspases and that a high proportion of distinct T cell epitopes in these fragments is recognized by CD8+ T cells during HIV infection. The frequencies of effector CD8+ T cells that are specific for apoptosis-dependent epitopes correlate with the frequency of circulating apoptotic CD4+ T cells in HIV-1-infected individuals. We propose that these self-reactive effector CD8+ T cells may contribute to the systemic immune activation during chronic HIV infection. The caspase-dependent cleavage of proteins associated with apoptotic cells has a key role in the induction of self-reactive CD8+ T cell responses, as the caspase-cleaved fragments are efficiently targeted to the processing machinery and are cross-presented by dendritic cells. These findings demonstrate a previously undescribed role for caspases in immunopathology.