Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma

¹⁷⁷Lu-DOTA-HH1 (¹⁷⁷Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of ¹⁷⁷Lu-HH1, ¹⁷⁷Lu-DOTA-rituximab (¹⁷⁷Lu-rituximab) and non-specific ¹⁷⁷Lu-DOTA-IgG₁ (¹⁷⁷Lu-IgG₁) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg ¹⁷⁷Lu-HH1 as compared with mice treated with similar activities of ¹⁷⁷Lu-rituximab or non-specific ¹⁷⁷Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of ¹⁷⁷Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg ¹⁷⁷Lu-rituximab experienced severe radiation toxicity. The retention of ¹⁷⁷Lu-rituximab in organs of the mononuclear phagocyte system was longer than for ¹⁷⁷Lu-HH1, which explains the higher toxicity observed in mice treated with ¹⁷⁷Lu-rituximab. In vitro internalization studies showed that ¹⁷⁷Lu-HH1 internalizes faster and to a higher extent than ¹⁷⁷Lu-rituximab which might be the reason for the better therapeutic effect of ¹⁷⁷Lu-HH1.     

Effect of chitosan chain architecture on gene delivery: comparison of self-branched and linear chitosans

Chitosan possesses many characteristics of an ideal gene delivery system. However, the transfection efficiency of conventional chitosans is generally found to be low. In this study, we investigated the self-branching of chitosans as a strategy to improve its gene transfer properties without compromising its safety profile. Self-branched (SB) and self-branched trisaccharide-substituted (SBTCO) chitosans with molecular weights of 11-71 kDa were synthesized, characterized, and compared with their linear counterparts with respect to transfection efficiency, cellular uptake, formulation stability, and cytotoxicity. Our studies show that in contrast with unmodified linear chitosans that were unable to transfect HeLa cells, self-branched chitosans mediated high transfection efficiencies. The most efficient chitosan, SBTCO30, yielded gene expression levels two and five times higher than those of Lipofectamine and Exgen, respectively, and was nontoxic to cells. Nanoparticles formed with SBTCO chitosans exhibited a higher colloidal stability of formulation, efficient internalization without excessive cell surface binding, and low cytotoxicity.     

Perspectives on providing good access to dental services for elderly people: patient selection,dentists’ responsibility and budget management

doi: 10.1111/j.1741‐2358.2012.00646.x Perspectives on providing good access to dental services for elderly people: patient selection, dentists’ responsibility and budget management Objectives: To suggest a model for organizing and financing dental services for elderly people so that they have good access to services. Background: There are few studies on how dental services for elderly people should be organized and financed. This is surprising if we take into consideration the fact that the proportion of elderly people is growing faster than any other group in the population, and that elderly people have more dental diseases and poorer access to dental services than the rest of the adult population. In several countries, dental services are characterized by private providers who often operate in a market with competition and free price‐setting. Private dentists have no community responsibility, and they are free to choose which patients they treat. Material and methods: Literature review and critical reasoning. Results: In order to avoid patient selection, a patient list system for elderly people is recommended, with per capita remuneration for the patients that the dentist is given responsibility for. The patient list system means that the dentist assumes responsibility for a well‐defined list of elderly people. Conclusion: Our model will lead to greater security in the dentist/patient relationship, and patients with great treatment needs will be ensured access to dental services.     

On the Relationship between Intramolecular Dynamics and the Density of States

The relationship between the intramolecular dynamics and the spectra has been analyzed by means of the molecular dynamics technique. Time autocorrelation functions of bond lengths, bending angles and torsional angles have been evaluated in a crystalline trans-polyacetylene system. The Fourier transforms of such functions have been compared with the densities of states obtained both for carbon and hydrogen atoms. This comparison is aimed at investigating the microscopic origin of the peaks which appear in the densities of states. This approach can be used in the analysis of the spectroscopic data of any molecular or polymeric system.     

Spermine and Citrate as Metabolic Biomarkers for Assessing Prostate Cancer Aggressiveness

Separating indolent from aggressive prostate cancer is an important clinical challenge for identifying patients eligible for active surveillance, thereby reducing the risk of overtreatment. The purpose of this study was to assess prostate cancer aggressiveness by metabolic profiling of prostatectomy tissue and to identify specific metabolites as biomarkers for aggressiveness. Prostate tissue samples (n = 158, 48 patients) with a high cancer content (mean: 61.8%) were obtained using a new harvesting method, and metabolic profiles of samples representing different Gleason scores (GS) were acquired by high resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS). Multivariate analysis (PLS, PLS-DA) and absolute quantification (LCModel) were used to examine the ability to predict cancer aggressiveness by comparing low grade (GS = 6, n = 30) and high grade (GS≥7, n = 81) cancer with normal adjacent tissue (n = 47). High grade cancer tissue was distinguished from low grade cancer tissue by decreased concentrations of spermine (p = 0.0044) and citrate (p = 7.73·10⁻⁴), and an increase in the clinically applied (total choline+creatine+polyamines)/citrate (CCP/C) ratio (p = 2.17·10⁻⁴). The metabolic profiles were significantly correlated to the GS obtained from each tissue sample (r = 0.71), and cancer tissue could be distinguished from normal tissue with sensitivity 86.9% and specificity 85.2%. Overall, our findings show that metabolic profiling can separate aggressive from indolent prostate cancer. This holds promise for the benefit of applying in vivo magnetic resonance spectroscopy (MRS) within clinical MR imaging investigations, and HR-MAS analysis of transrectal ultrasound-guided biopsies has a potential as an additional diagnostic tool.     

A revision of the Afrotropical genus Dhatrichia (Trichoptera, Hydroptilidae)

Five previously described species of Dhatrichia Mosely, 1948 are recognized: D. inasa Mosely, 1948 from Yemen; D. bipunctata Statzner, 1977 from Zaire; D. lerabae (Gibon, Guenda & Coulibaly, 1994) comb. n. from Burkina Faso and Ghana; and D. cinyra Wells & Andersen, 1995 and D. divergenta Wells & Andersen, 1995 from Tanzania. A sixth species D. feredougoubae Gibon, 1987 from the Ivory Coast and Ghana is transferred to Microptila Ris, 1897 comb. n. In addition, nine new species are described and illustrated as males: D. ankasaensis sp. n., D. botiensis sp. n., D. hunukani sp. n., D. minuta sp. n., D. paraminuta sp. n. and D. wliensis sp. n. from Ghana, D. anderseni sp. n. from Tanzania, and D. madagascarensis sp. n. and D. giboni sp. n. from Madagascar. Females are associated, described and illustrated for all species, except D. inasa and D. giboni. The larvae and pupae of D. ankasaensis, D. hunukani, D. lerabae, D. minuta and D. wliensis are described and illustrated as the first known immatures of the genus. Keys to known larvae, pupae, males and females are provided. A phylogenetic analysis of the genus revealed four species groups. The most plesiomorphous taxa are West African, followed by East African and Malagasian taxa. A sister group relationship between the Eburneo–Ghanean and the Sudanian biogeographical regions is encountered twice. Among several possible sister taxa, the sister group turned out to be Kumanskiella Harris & Flint, 1992 and Microptila Ris, 1897 in part, combined. Implications for generic classification and biogeography are outlined. A morphometric principal component analysis revealed good separation of the sexes by the number and shape of antennal segments, and by eye size. Other measures are strongly dependent on overall size, and show best separation of females between species and species groups. A functional fit between male inferior appendages and secondary sexual characters in female sternite VIII is demonstrated for all species with associated females.     

Home-based aerobic interval training improves peak oxygen uptake equal to residential cardiac rehabilitation: a randomized, controlled trial

Aerobic capacity, measured as the peak oxygen uptake, is a strong predictor of survival in cardiac patients. Aerobic interval training (AIT), walking/running four times four minutes at 85-95% of peak heart rate, has proven to be effective in increasing peak oxygen uptake in coronary heart disease patients. As some patients do not attend organized rehabilitation programs, home-based exercise should be an alternative. We investigated whether AIT could be performed effectively at home, and compared the effects on peak oxygen uptake with that observed after a standard care, four-week residential rehabilitation. Thirty patients undergoing coronary artery bypass surgery were randomized to residential rehabilitation or home-based AIT. At six months follow-up, peak oxygen uptake increased 4.6 (±2.7) and 3.9 (±3.6) mL·kg(-1) min(-1) (both p<0.005, non-significant between-group difference) after residential rehabilitation and AIT, respectively. Quality of life increased significantly in both groups, with no statistical significant difference between groups. We found no evidence for a different treatment effect between patients randomized to home-based AIT compared to patients attending organized rehabilitation (95% confidence interval -1.8, 3.5). AIT patients reported good adherence to exercise training. Even though these first data indicate positive effects of home-based AIT in patients undergoing coronary artery bypass surgery, more studies are needed to provide supporting evidence for the application of this rehabilitation strategy. Trial registration: ClinicalTrials.gov NCT00363922.     

Extreme precipitation variability,forage quality and large herbivore diet selection in arid environments

Nutritional ecology forms the interface between environmental variability and large herbivore behaviour, life history characteristics, and population dynamics. Forage conditions in arid and semi‐arid regions are driven by unpredictable spatial and temporal patterns in rainfall. Diet selection by herbivores should be directed towards overcoming the most pressing nutritional limitation (i.e. energy, protein [nitrogen, N], moisture) within the constraints imposed by temporal and spatial variability in forage conditions. We investigated the influence of precipitation‐induced shifts in forage nutritional quality and subsequent large herbivore responses across widely varying precipitation conditions in an arid environment. Specifically, we assessed seasonal changes in diet breadth and forage selection of adult female desert bighorn sheep Ovis canadensis mexicana in relation to potential nutritional limitations in forage N, moisture and energy content (as proxied by dry matter digestibility, DMD). Succulents were consistently high in moisture but low in N and grasses were low in N and moisture until the wet period. Nitrogen and moisture content of shrubs and forbs varied among seasons and climatic periods, whereas trees had consistently high N and moderate moisture levels. Shrubs, trees and succulents composed most of the seasonal sheep diets but had little variation in DMD. Across all seasons during drought and during summer with average precipitation, forages selected by sheep were higher in N and moisture than that of available forage. Differences in DMD between sheep diets and available forage were minor. Diet breadth was lowest during drought and increased with precipitation, reflecting a reliance on few key forage species during drought. Overall, forage selection was more strongly associated with N and moisture content than energy content. Our study demonstrates that unlike north‐temperate ungulates which are generally reported to be energy‐limited, N and moisture may be more nutritionally limiting for desert ungulates than digestible energy.     

Indicative value of mercury concentration in adipose fin of brown trout, Salmo trutta L.

Investigation of adipose fin and axial muscle mercury concentration in brown trout, Salmo trutta , from Lake Tyrifjorden, south-east Norway showed that these were highly correlated ( r = 0.93, P<0.001), but adipose fin mercury concentrations were approximately 80% lower. Analysis of adipose fin mercury concentration may prove helpful in documenting mercury contamination in aquatic environments. Conflicts regarding the highly-priced salmonids are reduced when sampling from living individuals.