Spermiogenesis and spermatozoon ultrastructure of the diphyllidean cestode Echinobothrium euterpes (Neifar, Tyler and Euzet 2001) Tyler 2006, a parasite of the common guitarfish Rhinobatos rhinobatos

Spermiogenesis and the ultrastructural characters of the spermatozoon of Echinobothrium euterpes are described by means of transmission electron microscopy, including cytochemical analysis for glycogen. Materials were obtained from a common guitarfish Rhinobatos rhinobatos caught in the Gulf of Gabès (Tunisia). Spermiogenesis in E. euterpes is characterized by the orthogonal development of two unequal flagella followed by the flagellar rotation and the proximodistal fusion of these flagella with the median cytoplasmic process. The most interesting pattern characterizing the diphyllidean cestodes is the presence of a triangular body constituted by fines and dense granules without visible striation and assimilated at the striated rootlets. This pattern, only related in the Diphyllidea cestodes may be a synapomorphy of this order. Spermiogenesis is also characterized by the presence of a very short flagellum (around 1 μm long), observed in all the stages of spermiogenesis. This type of flagellum has never been commented in the diphyllidean cestodes and should be considered as an evolved character in this group. In the latest stage of spermiogenesis, this short axoneme probably degenerates. Thus, the mature spermatozoon of E. euterpes possesses only one axoneme of 9 + “1” trepaxonematan pattern. It also exhibits a single helical electron-dense crested body, a spiraled nucleus, few parallel cortical microtubules, and α-glycogen granules. Similitudes and differences between spermatozoa of diphyllideans are discussed.     

Spermatological characters of <Emphasis Type="Italic">Acanthobothrium crassicolle</Emphasis> Wedl, 1855 (Tetraphyllidea,Onchobothriidae), a parasite of the common stingray <Emphasis Type="Italic">Dasyatis pastinaca</Emphasis>

We describe the spermiogenesis process and the ultrastructural characters of the spermatozoon of Acanthobothrium crassicolle by means of transmission electron microscopy, including cytochemical analysis for glycogen. Spermiogenesis in A. crassicolle begins with the formation of the differentiation zone that contains two centrioles associated with striated rootlets and an intercentriolar body. The latter is formed by one electron-dense layer. The centrioles develop into two free flagella that first grow orthogonally to a median cytoplasmic process and then undergo flagellar rotation becoming parallel to that median cytoplasmic process. After flagellar rotation only one of the flagella completes its growth and both short and long flagella undergo proximodistal fusion with the median cytoplasmic process. In the final stages of spermiogenesis, the nucleus becomes filiform and migrates into the spermatid body. Later, the ring of arched membranes constricts and the spermatozoon is liberated from the residual cytoplasm. The ultrastructural organization of the spermatozoon of A. crassicolle follows the general pattern of spermatozoa of the other Tetraphyllidea-Onchobothriidae species, but exhibits some differences. It is filiform, tapered at both extremities and lacks mitochondrion. It contains two axonemes of unequal length showing the 9 + “1“ pattern of Trepaxonemata, a nucleus, parallel cortical microtubules and electron-dense granules of glycogen. The anterior extremity of the male gamete contains a single crested body surrounding a thin and long apical cone. This type of apical cone has never been described in a tetraphyllidean spermatozoon. Another particularity is the presence of a single electron-dense microtubule at the vertex of the crested body.     

Utility‐based outcomes made easy: The number needed per quality‐adjusted life year gained. An observational cohort study of tumor necrosis factor blockade in inflammatory arthritis from Southern Sweden

Objective

To introduce a novel, simple, utility‐based outcome measure, the number needed per quality‐adjusted life year (QALY) gained (NNQ), and to apply it in clinical practice in anti–tumor necrosis factor (anti‐TNF)–treated patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondylarthritis (SpA).

Methods

The NNQ is the number of patients one has to treat in order to gain 1 QALY. It is calculated as the inverted value of the utility gain (area under the curve) over 1 year in a cohort subjected to an intervention. EuroQol Index utility data from the South Swedish Arthritis Treatment register were used.

Results

Patients with RA (n = 1,001), PsA (n = 241), and SpA (n = 255) were eligible for the study. First, second, and third treatment courses were studied. For RA, NNQ was 4.5, 6.4, and 5.2 for first, second, and third courses, respectively. For PsA and SpA, NNQ was 4.2–4.5, irrespective of treatment order. Treatment groups with <50 patients were not analyzed. During the study period 2002–2007, there were no secular trends of utility gains.

Conclusion

The NNQ is an easily derived and understandable utility‐based outcome measure that may be useful for stakeholders and decision makers as well as for clinicians. It was readily applied in this study of TNF blockade across 3 arthritis diagnoses. NNQ varied little over diagnoses and treatment course order, with a possible exception in second treatment course in RA.     

Comprehensive genetic and functional characterization of IPH‐926: a novel CDH1‐null tumour cell line from human lobular breast cancer

Infiltrating lobular breast cancer (ILBC) is a clinically and biologically distinct tumour entity defined by a characteristic linear cord invasion pattern and inactivation of the CDH1 tumour suppressor gene encoding for E‐cadherin. ILBCs also lack β‐catenin expression and show aberrant cytoplasmic localization of the E‐cadherin binding protein p120‐catenin. The lack of a well‐characterized ILBC cell line has hampered the functional characterization of ILBC cells in vitro. We report the establishment of a permanent ILBC cell line, named IPH‐926, which was derived from a patient with metastatic ILBC. The DNA fingerprint of IPH‐926 verified genetic identity with the patient and had no match among the human cell line collections of several international biological resource banks. IPH‐926 expressed various epithelial cell markers but lacked expression of E‐cadherin due to a previously unreported, homozygous CDH1 241ins4 frameshift mutation. Detection of the same CDH1 241ins4 mutation in archival tumour tissue of the corresponding primary ILBC proved the clonal origin of IPH‐926 from this particular tumour. IPH‐926 also lacked β‐catenin expression and showed aberrant cytoplasmic localization of p120‐catenin. Array‐CGH analysis of IPH‐926 revealed a profile of genomic imbalances that included many distinct alterations previously observed in primary ILBCs. Spectral karyotyping of IPH‐926 showed a hyperdiploid chromosome complement and numerous clonal, structural aberrations. IPH‐926 cells were anti‐cancer drug‐resistant, clonogenic in soft agar, and tumourigenic in SCID mice. In xenograft tumours, IPH‐926 cells recapitulated the linear cord invasion pattern that defines ILBCs. In summary, IPH‐926 significantly extends the biological spectrum of the established breast cancer cell lines and will facilitate functional analyses of genuine human ILBC cells in vitro and in vivo. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Differential effects of cancer rehabilitation depending on diagnosis and patients' cognitive coping style

OBJECTIVE: The major aim was to explore the extent to which the Miller Behavioral Style Scale (MBSS) can be used to differentiate cancer patients who are likely to benefit from rehabilitation efforts with a strong information component from those who are not. METHODS: Newly diagnosed patients with breast, gastrointestinal, or prostate cancer (N = 442) were included in a randomized, prospective study of the effects (on anxiety, depression, intrusion, avoidance) of rehabilitation approximately 4 months after diagnosis as compared with control patients. Patients were classified as "monitors" or "blunters" on the basis of the MBSS (368 patients, 83%, completed the MBSS). RESULTS: The expected interaction at postintervention between coping style and experimental condition (ie, rehabilitation or control) was found only for avoidance among breast and prostate cancer patients. Assignment to the rehabilitation or control condition was of no importance for outcome among blunters. Among monitors, the response pattern differed between breast and prostate cancer patients. Prostate cancer monitors seemed to benefit from rehabilitation on all outcome measures, whereas intrusion and avoidance were reduced among breast cancer patients in the control condition. This interaction of diagnosis with condition (rehabilitation or control) among monitors is suggested to be due to demands for diagnosis-specific information during diagnostic work, in the period just after diagnosis, and before treatment decision. CONCLUSIONS: Only the monitor concept seems useful for predicting response to cancer rehabilitation with a strong information component. However, whether rehabilitation is of benefit depends also on other factors.     

Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T‐cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL‐7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C–C motif) receptor‐like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1^hi) develop normally in immunocompetent and Rag2^?/?thymi, their differentiation is partially blocked in Rag2^?/?Il2rg^?/? counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross‐talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)⁺ mTEC subtypes expressing intermediate CCRL1 levels (CCRL1^int) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2^?/? thymi, CCRL1^int mTECs are restored in Rag2^?/?Marilyn TCR‐Tg mice, indicating that the appearance of postnatal‐restricted mTECs is closely linked with T‐cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.     

Semi-conducting properties of titanium dioxide surfaces on titanium implants

The properties of the TiO₂ layer on titanium implant surfaces are decisive for good contact with the surrounding tissue. The oxide properties can be deliberately changed by for example chemical etching, ion incorporation or anodisation. In the present study impedance spectroscopy was used to study the semi-conducting properties of the naturally formed oxide for different pre-treatment of the surface. A turned surface was used as a reference and both physical (blasting) and chemical (hydrofluoric acid etching) treatments were investigated. Blasting of a titanium sample introduces defects in the metal surface and the study clearly shows that also the oxide layer contains defects leading to a higher number of charge carriers (increased conductivity) compared with the oxide on the turned surface. The hydrofluoric acid etching of the blasted surface results in an oxide film with even higher conductivity. Indication of the defect oxide structure for fluoride treated samples was also seen when analysing the TiO⁺/Ti⁺ ratio from ToF-SIMS data. The lowest value of this ratio was obtained for the HF etched sample, indicating a less stoichiometric oxide compared to the other surfaces. This is a result of incorporation of fluoride ions in the oxide, as proven by adsorption studies on a TiO₂ suspension. The results were treated in the context of surface complexation and two surface complexes were identified. Our results are discussed in relation to pull-out data on rabbit. The pull-out forces depend primarily on surface roughness but the contribution from the hydrofluoric acid etching might be explained by fluoride ion incorporation and the resulting increase in oxide conductivity.     

Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR−/−)

BackgroundAtherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors.MethodsAnimals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses.ResultsNo changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly.ConclusionsThe results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis.     

Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation

Aim: The relationship between depression in adolescents and vitamin D was studied in a case‐series that included effects of vitamin D supplementation. Methods: Serum 25OH vitamin D (25OHD) levels in 54 Swedish depressed adolescents were investigated. Subjects with vitamin D deficiency were given vitamin D₃ over 3 months (n = 48). To evaluate well‐being and symptoms related to depression and vitamin D status, the WHO‐5 well‐being scale, the Mood and Feelings Questionnaire (MFQ‐S) and a vitamin D deficiency scale were used. Results: Mean serum 25OHD in the depressed adolescents was 41 at baseline and 91 nmol/L (p < 0.001) after supplementation. Basal 25OHD levels correlated positively with well‐being (p < 0.05). After vitamin D supplementation, well‐being increased (p < 0.001) and there was a significant improvement in eight of the nine items in the vitamin D deficiency scale: depressed feeling (p < 0.001), irritability (p < 0.05), tiredness (p < 0.001), mood swings (p < 0.01), sleep difficulties (p < 0.01), weakness (p < 0.01), ability to concentrate (p < 0.05) and pain (p < 0.05). There was a significant amelioration of depression according to the MFQ‐S (p < 0.05). Conclusion: This study showed low levels of vitamin D in 54 depressed adolescents, positive correlation between vitamin D and well‐being, and improved symptoms related to depression and vitamin D deficiency after vitamin D supplementation.