Nitric oxide production in the ventilatory muscles in response to acute resistive loading

The effect of muscle activation on muscle nitric oxide (NO) production remains controversial. Whereas NO release increases in in vitro activated muscles and in vivo limb muscles, diaphragmatic NO synthase (NOS) activity declines after 3 h of inspiratory resistive loading (IRL). We tested in this study the hypotheses that acute IRL decreases diaphragmatic NO derivatives levels and reduces protein expression of neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) NO synthases, as well as 3-nitrotyrosine formation. Anesthetized, tracheostomized, spontaneously breathing adult rats were subjected to IRL (50% of the maximum inspiratory pressure) for 1, 3, or 6 h. Quietly breathing rats served as controls. After 3 h of IRL, muscle eNOS and nNOS protein levels rose by 80 and 60% of control values, respectively. Whereas eNOS expression did not change any further, nNOS expression reached 550% of control values after 6 h of IRL. Strong iNOS protein expression was detected in the diaphragms after 6 h of IRL. Total NO derivatives levels in the diaphragm declined during IRL as a result of reduction in nitrate, nitrite, and nitrosothiols. Diaphragmatic protein tyrosine nitration decreased in response to IRL, and this reduction was mainly due to reduced tyrosine nitration of enolase and aldolase. We conclude that diaphragmatic NO derivatives levels decline in response to IRL and that the rise in diaphragmatic NOS protein expression may be a compensatory response designed to counterbalance the decline in NOS activity.     

Inhibition of PrPSc formation in scrapie infected N2a cells by 5,7,8-trimethyl-3,4-dihydro-2H-1,4-benzoxazine derivatives

Prion diseases are fatal, neurodegenerative diseases characterized by the structural conversion of the normal, cellular prion protein, PrP^C into an abnormally structured, aggregated and partially protease-resistant isoform, termed PrP^Sc. Although substantial research has been directed toward development of therapeutics targeting prions, there is still no curative treatment for the disease. Benzoxazines are bicyclic heterocyclic compounds possessing several pharmaceutically important properties, including neuroprotection and reactive oxygen species scavenging. In an effort to identify novel inhibitors of prion formation, several 5,7,8-trimethyl-1,4-benzoxazine derivatives were evaluated in vitro for their effectiveness on the expression levels of normal PrP^C and its conversion to the abnormal isoforms of PrP^Sc in a scrapie-infected cell culture model. The most potent compound was 2-(4-methoxyphenyl)-5,7,8-trimethyl-3,4-dihydro-2H-1,4-benzoxazine, with a diminishing effect on the formation of PrP^Sc, thus establishing a class of compounds with a promising therapeutic use against prion diseases.     

Butterfly and grasshopper diversity patterns in humid Mediterranean grasslands: the roles of disturbance and environmental factors

The present paper studies butterfly, grasshopper and vascular plant communities in ten seasonally flooded grasslands with different anthropogenic disturbance regimes (NW Greece). Disturbance intensity was assessed on the basis of disturbance frequency and type (grazing, mowing, trampling, constructions). The distribution patterns of butterflies are regulated by humidity and elevation (Redundancy Analysis). Elevation, flower-heads abundance, low disturbance intensity and plant species richness predict grasshopper species richness well, while the latter together with humidity predict plant species richness (Generalized Linear Models). Chorthippus lacustris, a critically endangered endemic grasshopper species, is positively associated with humid microhabitats with high flower-heads abundance. An indicator value procedure reveals four butterfly species as being typical species for habitats with a pronounced character of hedgerows and tree lines. Conservation management of grassland butterflies should focus on the maintenance of the humid character of the humid grasslands as well as on the maintenance of hedgerows and tree lines. The reduction of human-induced disturbance towards occasional grazing and mowing seems to benefit both butterfly and grasshopper communities. Finally, we suggest the use of grasshoppers as surrogates for vascular plants and vice versa, given their congruent species richness patterns.     

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and cervical cancer risk: a meta-analysis

This meta-analysis aims to examine whether the genotype status of MspI and Ile462Val polymorphisms in Cytochrome-P450 1A1 (CYP1A1) is associated with cervical cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random effects models. Concerning MspI polymorphism, six studies were eligible (722 cases and 770 controls); four studies were eligible (350 cases and 519 controls) for Ile462Val. MspI polymorphism was associated with elevated cervical cancer risk (for heterozygous TC vs. TT carriers OR = 1.50, 95% CI: 0.93–2.42, random effects; for homozygous CC vs. TT carriers OR = 2.66, 95% CI: 1.14–6.19, random effects). Similarly, Ile462Val polymorphism was associated with elevated cervical cancer risk (for heterozygous Ile/Val vs. Ile/Ile carriers OR = 2.36, 95% CI: 1.10–5.08, random effects; for homozygous Val/Val vs. Ile/Ile carriers OR = 2.73, 95% CI: 1.21–6.15, fixed effects). The results were replicated upon Caucasian subjects, who represented the majority of existing data. The two examined CYP1A1 genotype polymorphisms seem to confer additional risk for cervical cancer. Accumulation of further data seems mandatory for future race-specific analyses and for the demonstration of CYP1A1-smoking interactions.     

HSP90, HSPA8, HIF-1 alpha and HSP70-2 polymorphisms in breast cancer: a case–control study

This case control study aims to investigate the role of HSP90 Gln488His (C?>?G), HSP70-2 P1/P2, HIF-1 alpha C1772T and HSPA8 intronic 1541–1542delGT polymorphisms as potential risk factors and/or prognostic markers for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy cases were recruited. The above mentioned polymorphisms were genotyped; multivariate logistic regression was performed. HSP90 GG (His/His) genotype was associated with elevated breast cancer risk. Similarly, the allele dose–response model pointed to increase in breast cancer risk per G allele. HSP70-2 P1/P2, HSPA8 intronic 1541–1542delGT and HIF-1 alpha polymorphisms were not associated with breast cancer risk, as evidenced by the dose–response allele models. The positive association between HSP90 G allele and breast cancer risk seemed to pertain to both premenopausal and postmenopausal women. With respect to survival analysis, none of the aforementioned polymorphisms was associated with either disease-free survival or overall survival. HSP90α Gln488His polymorphism seems to be a risk factor for breast cancer. On the other hand, our study did not point to excess risk conferred by HSPA8 1541–1542delGT, Hsp70-2 P1/P2 and HIF-1α C1772T.     

Spotted Fever Group <Emphasis Type="Italic">Rickettsiae</Emphasis> in Ticks in Cyprus

In two surveys conducted from March 1999 to March 2001 and from January 2004 to December 2006, a total of 3,950 ticks (belonging to ten different species) were collected from seven domestic and wild animals (goat, sheep, cattle, dog, fox, hare, and mouflon) from different localities throughout Cyprus. In order to establish their infection rate with Spotted Fever Rickettsiae (SFG), ticks were pooled and tested by polymerase chain reaction targeting gltA and ompA genes, followed by sequencing analysis. When tick pools tested positive, individual ticks were then tested one by one, and of the 3,950 ticks screened, rickettsial DNA was identified in 315 ticks (infection rate, 8%). Five SFG Rickettsiae were identified: Rickettsia aeschlimannii in Hyalomma marginatum marginatum, Rickettsia massiliae in Rhipicephalus turanicus and Rhipicephalus sanguineus, Rickettsia sibirica mongolotimonae in Hyalomma anatolicum excavatum, and a Rickettsia endosymbiont of Haemaphysalis sulcata (later described as Rickettsia hoogstraalii) in Haemaphysalis punctata. Two additional genes, 17 kDa and ompB, were targeted to characterize a new genotype of “Candidatus Rickettsia barbariae” genotype in R. turanicus, designated here as “Candidatus Rickettsia barbariae” Cretocypriensis. These results confirm the presence of a spectrum of SFG Rickettsiae on the island. Further studies are necessary to gain better knowledge on the epidemiology of SFG Rickettsiae in Cyprus.     

Pulmonary function in children with idiopathic scoliosis

ABSTRACT: Idiopathic scoliosis, a common disorder of lateral displacement and rotation of vertebral bodies during periods of rapid somatic growth, has many effects on respiratory function. Scoliosis results in a restrictive lung disease with a multifactorial decrease in lung volumes, displaces the intrathoracic organs, impedes on the movement of ribs and affects the mechanics of the respiratory muscles. Scoliosis decreases the chest wall as well as the lung compliance and results in increased work of breathing at rest, during exercise and sleep. Pulmonary hypertension and respiratory failure may develop in severe disease. In this review the epidemiological and anatomical aspects of idiopathic scoliosis are noted, the pathophysiology and effects of idiopathic scoliosis on respiratory function are described, the pulmonary function testing including lung volumes, respiratory flow rates and airway resistance, chest wall movements, regional ventilation and perfusion, blood gases, response to exercise and sleep studies are presented. Preoperative pulmonary function testing required, as well as the effects of various surgical approaches on respiratory function are also discussed.     

2011 SOSORT guidelines: Orthopaedic and Rehabilitation treatment of idiopathic scoliosis during growth

Background

The International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT), that produced its first Guidelines in 2005, felt the need to revise them and increase their scientific quality. The aim is to offer to all professionals and their patients an evidence-based updated review of the actual evidence on conservative treatment of idiopathic scoliosis (CTIS).

Methods

All types of professionals (specialty physicians, and allied health professionals) engaged in CTIS have been involved together with a methodologist and a patient representative. A review of all the relevant literature and of the existing Guidelines have been performed. Documents, recommendations, and practical approach flow charts have been developed according to a Delphi procedure. A methodological and practical review has been made, and a final Consensus Session was held during the 2011 Barcelona SOSORT Meeting.

Results

The contents of the document are: methodology; generalities on idiopathic scoliosis; approach to CTIS in different patients, with practical flow-charts; literature review and recommendations on assessment, bracing, physiotherapy, Physiotherapeutic Specific Exercises (PSE) and other CTIS. Sixty-five recommendations have been given, divided in the following topics: Bracing (20 recommendations), PSE to prevent scoliosis progression during growth (8), PSE during brace treatment and surgical therapy (5), Other conservative treatments (3), Respiratory function and exercises (3), Sports activities (6), Assessment (20). No recommendations reached a Strength of Evidence level I; 2 were level II; 7 level III; and 20 level IV; through the Consensus procedure 26 reached level V and 10 level VI. The Strength of Recommendations was Grade A for 13, B for 49 and C for 3; none had grade D.

Conclusion

These Guidelines have been a big effort of SOSORT to paint the actual situation of CTIS, starting from the evidence, and filling all the gray areas using a scientific method. According to results, it is possible to understand the lack of research in general on CTIS. SOSORT invites researchers to join, and clinicians to develop good research strategies to allow in the future to support or refute these recommendations according to new and stronger evidence.