Diabetes prevention--from physiology to implementation.

One of the major challenges today is the development of prevention programs for the clinical practice. Our aim was to develop a concept for a primary diabetes prevention program to be implemented in general health care. Lifestyle intervention addressing diet and exercise has reduced the diabetes risk by up to 58%. Early preventive pharmacological strategies have yielded a diabetes risk reduction of 25-30%. These findings offer a compelling evidence base, but delivery of intervention and care is essential. The challenge therefore is the management of prevention and intervention programs considering scientific aspects and practical requirements during implementation. The Diabetes Prevention Workgroup at the German Diabetes Association has developed a concept for a decentralized prevention program. Based on the results of the prevention studies, the intervention concept consists of a three-step program including identification of the individuals at high risk to develop type 2 diabetes (1), followed by general intervention based on individual choice (2) and maintained continuous intervention for motivation maintenance (3). Structured prevention programs will enable nationwide prevention of diabetes mellitus without consuming large resources. This process will be challenging and time consuming, requiring many partners but resulting in a profitable "health" investment.     

Calluses of Cynara cardunculus Var. Cardunculus cardoon (Asteraceae): determination of cynarine and chlorogenic acid by automated high-performance capillary electrophoresis

Summary Cynara cardunculus var. cardunculus L., also known as cardoon, is a perennial weed naturalized in the Pampas region of Argentina. A quantification of cynarine and chlorogenic acid of callus and leaves from cardoon was performed by means of micellar electrokinetic capillary chromatography, showing that the content of cynarine is higher in calluses than in vivo leaves. The scavenging effect of the callus extract, determined by the thiobarbituric acid method, demonstrated its significant antioxidant capacity. The obtained results revealed that in vitro tissue culture is an excellent tool for producing cynarine for therapeutical purposes.     

CD38 and CD157 as receptors of the immune system: a bridge between innate and adaptive immunity

This paper reviews some of the results and the speculations presented at the Torino CD38 Meeting in June, 2006 and focused on CD38 and CD157 seen as a family of molecules acting as surface receptors of immune cells. This partisan view was adopted in the attempt to combine the enzymatic functions with what the immunologists consider key functions in different cell models. At the moment, it is unclear whether the two functions are correlated, indifferent, or independent. Here we present conclusions inferred exclusively on human cell models, namely T and B lymphocytes, dendritic cells, and granulocytes. As an extra analytical tool, we try to follow in the history of life when the enzymatic and receptorial functions were generated, mixing ontogeny, membrane localization, and cell anchorage.     

Bacteriophages immunomodulate the response of monocytes

Bacteriophages are present in fluids from cirrhosis patients. However, their effect on the immune response is unknown. In this work, we explore the role of phages in the phenotype, function, and cytokine production of monocytes. We stimulated healthy monocytes with five different butanol-purified phage suspensions infective for Gram-negative and Gram-positive bacteria. We studied the expression of the monocyte markers involved in lipopolysaccharide recognition (LPS; CD14), antigen presentation (HLA-DR) and co-stimulation (CD86), and the concentration of induced cytokines (TNF-α, IFN-α, and IL-10) by phages. To confirm the direct role of phages without the interference of contaminating soluble LPS in phage suspensions, polymyxin B was added to the cell cultures. Phagocytosis experiments were assessed by flow cytometry using labeled phage suspensions. We observed that butanol-purified phages reduced the surface levels of CD14 and CD86 in monocytes and increased the secreted levels of TNF-α and IL-10 compared with the control sample containing only butanol buffer. All phage suspensions showed downregulation of HLA-DR expression but only Staphylococcus aureus phage contaminated with Escherichia coli reached statistical significance. The addition of polymyxin B did not restore the monocytic response induced by phages, suggesting that the effect was not caused by the presence of LPS. Monocytes were able to phagocyte phages in a dose- and time-dependent manner. To conclude, the phagocytosis of butanol-purified phages altered the phenotype and cytokine production of monocytes suggesting they become tolerogenic.     

In vivo motion of the rectus femoris muscle after tendon transfer surgery

Rectus femoris transfer surgery is performed to convert the rectus femoris muscle from a knee extensor to a knee flexor. In this surgery, the distal tendon of the rectus femoris is detached from the patella and reattached to one of the knee flexor tendons. The outcomes of this procedure are variable, and it is not known if the surgery successfully converts the muscle to a knee flexor. We measured the motion of muscle tissue within the rectus femoris and vastus intermedius during knee extension in 10 unimpaired control subjects (10 limbs) and 6 subjects (10 limbs) after rectus femoris transfer using cine phase-contrast magnetic resonance imaging. Displacements of the vastus intermedius during knee extension were similar between control and tendon transfer subjects. In the control subjects, the rectus femoris muscle consistently moved in the direction of the knee extensors and displaced more than the vastus intermedius. The rectus femoris also moved in the direction of the knee extensors in the tendon transfer subjects; however, the transferred rectus femoris displaced less than the vastus intermedius. These results suggest that the rectus femoris is not converted to a knee flexor after its distal tendon is transferred to the posterior side of the knee, but its capacity for knee extension is diminished by the surgery.     

Environmental control of crassulacean acid metabolism in Welwitschia mirabilis Hook. Fil. in its range of natural distribution in the Namib desert

Summary Within the area of its natural distribution in South West Africa, Welwitschia mirabilis has a less negative ¹³C value than C₃ plants and a more negative ¹³C value than C₄ species. This indicates that Welwitschia m. assimilates CO₂ partially via CAM when growing in its natural habitat. The difference between the ¹³C values of Welwitschia m. and of the C₃ species is significant in the savanna, whereas it is only small and statistically not significant in the grassland zone. The proportion of CO₂ fixed via CAM is largest in the coastal desert zone. There was no correlation between the ¹³C values and the Cl^- or ash content of the tissue. Thus, CAM in Welwitschia m. seems not to be induced by salt stress. There is no change in the ¹³C values along the persistent Welwitschia m. leaf. The present data indicate that on a broad geographical scale in the area of distribution temperature regime, and water stress as a modifying factor, determine CAM in Welwitschia m. The ecological implications are discussed by comparing the behaviour of Welwitschia m. with other CAM, C₃ and C₄ species of the accompanying flora.     

Evolution of ragweed pollen concentrations, sensitization and related allergic clinical symptoms in Parma (northern Italy)

The pollen released in the atmosphere by the ragweed represents a question of public health in several European countries. In Italy, the ragweed is mostly distributed in the North. In our region (Emilia Romagna), the presence of ragweed was not described yet if not occasionally, but this plant is thriving well in the North of the Po river. The aim of our study was to estimate the concentration trends of ragweed pollens in the air of Parma starting from 1992 until 2008 and to describe the clinical related situation. The aerobiological surveillance was made with the methods standardized by the Italian Association of Aerobiology. We analyzed 19,468 outpatients affected by respiratory disease. The patients studied address our clinical Center, mainly with pathologies respiratory, most of them with allergic origin. To detect the existence of significant trends and correlations since, we used the non-parametric tests with SPSS software. Our observations showed that since 1995, the year until when pollens of ragweed were only sporadically observed in the air of Parma, there has been a significant increase in ragweed pollens. Among the patients addressed at our clinical Center, 876 patients had positive SPT (skin prick test) for ragweed pollen with respiratory illnesses, all polysensitized. Besides, we found a significant increase in patients with positive SPT for the ragweed, and among these, the increase in the asthma has been significant. On the basis of our results, we expect, in the absence of intervention from public authorities, a more significant increase in the positive subjects and an aggravation of the symptoms related to the presence of ragweed pollen in the air of Parma.     

New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: a comparative study

Zoledronic acid (ZOL) is a drug whose potent anti-cancer activity is limited by its short plasma half-life and rapid uptake and accumulation within bone. We have recently proposed new delivery systems to avoid ZOL accumulation into the bone, thus improving extra-skeletal bioavailability. In this work, we have compared the technological and anti-cancer features of either ZOL-containing self-assembly PEGylated nanoparticles (NPs) or ZOL-encapsulating PEGylated liposomes (LIPO-ZOL). ZOL-containing NPs showed superior technological characteristics in terms of mean diameter, size distribution, and ZOL encapsulation efficiency, compared to LIPO-ZOL. Moreover, the anti-cancer activity of NPs in nude mice xenografted with prostate cancer PC3 cells was higher than that one induced by LIPO-ZOL. In addition, NPs induced the complete remission of tumour xenografts and an increase of survival time higher than that one observed with LIPO-ZOL. It has also to be considered that PC3 tumour xenografts were almost completely resistant to the anti-cancer effects induced by free ZOL. Both nanotechnological products did not induce toxic effects not affecting the mice weight nor inducing deaths. Moreover, the histological examination of some vital organs such as liver, kidney and spleen did not find any changes in terms of necrotic effects or modifications in the inflammatory infiltrate. On the other hand, NPs but not LIPO-ZOL caused a statistically significant reduction of the tumour associated macrophages (TAM) in tumour xenografts. This effect was paralleled by a significant increase of both necrotic and apoptotic indexes. The effects of the NPs were also higher in terms of neo-angiogenesis inhibition. These results suggest the future preclinical development of ZOL-encapsulating NPs in the treatment of human cancer.     

Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration

Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB. In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration). Further studies revealed that CS induced internalization of CFTR. Surprisingly, CS-internalized CFTR did not colocalize with lysosomal proteins. Instead, the bulk of CFTR shifted to a detergent-resistant fraction within the cell and colocalized with the intermediate filament vimentin, suggesting that CS induced CFTR movement into an aggresome-like, perinuclear compartment. To test whether airway dehydration could be reversed, we used hypertonic saline (HS) as an osmolyte to rehydrate ASL. HS restored ASL height in CS-exposed, dehydrated airway cultures. Similarly, inhaled HS restored mucus transport and increased clearance in patients with CB. Thus, we propose that CS exposure rapidly impairs CFTR function by internalizing CFTR, leading to ASL dehydration, which promotes mucus stasis and a failure of mucus clearance, leaving smokers at risk for developing CB. Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB.