Spermicidal activity of chelated complexes of bis(cyclopentadienyl)vanadium(IV)

Transition metal complexes containing vanadium IV have been shown to modulate the cellular redox potential and catalyse the generation of reactive oxygen intermediates (ROI). Since sperm function is exquisitely susceptible to ROI, we examined the effects of stable chelate complexes of vanadocenes on human sperm motility. We synthesized seven structurally distinct chelate complexes of bis(cyclopentadienyl)vanadium(IV) with bidentate ligands [i.e. vanadocene acetylacetonato monotriflate (VDacac), vanadocene hexafluoro acetylacetonato monotriflate (VDHfacac), vanadocene N-phenyl benzohydroxamato monotriflate (VDPH), vanadocene acethydroxamato monotriflate (VDH), vanadocene catecholate (VDCAT), vanadocene bipyridino ditriflate (VDBPY), and vanadocene dithiocarbamate monotriflate (VDDTC)], and evaluated their spermicidal activity using computer-assisted sperm analysis (CASA; Hamilton-Thorne). All seven chelate complexes of vanadocene elicited potent spermicidal activity at micromolar concentrations (EC50 values: 3.9-106 microM) without affecting the sperm acrosome integrity. The catecholate and acetylacetonate complexes of vanadocene were the most active and the bipyridyl complex the least active with an order of efficacy VDCAT > VDacac > VDDTC > VDPH > VDH > VDHfacac > VDBPY. The spermicidal activity of chelate complexes of vanadocenes was rapid and irreversible since the treated spermatozoa underwent apoptosis, as determined by the flow cytometric analysis of mitochondrial membrane potential, surface annexin V binding assay, in-situ nick-end labelling of sperm nuclei, and confocal laser scanning microscopy. These results provide unprecedented evidence that chelate complexes of vanadocene with bidentate ligands have spermicidal and apoptosis inducing properties. These vanadocene complexes, especially VDacac, may be useful as contraceptive agents.      

神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice [see comments]

We report the successful long-term engraftment of normal male donor bone marrow (BM) transfused into noncytoablated female mice, challenging the assumption that "niches" need to be created for marrow to engraft. We have used chromosomal banding and Southern blot analysis to identify transplanted male marrow cells, and shown the long-term stability of the chimeric marrows. Balb/C, BDF1, or CBA-J female hosts (no irradiation) received for 5 consecutive days 40 x 10(6) male cells (per day) of the same strain, and repopulation patterns were observed. Parallel studies were performed using tibia/femur equivalents of normal marrow or marrow from Balb/C mice pretreated 6 days previously with 150 mg/kg 5-fluorouracil (5-FU). Chromosome banding techniques showed that 5% to 46% of marrow cells were male 3 to 9 months posttransplant with normal donor marrow. Southern blot analysis, using the pY2 probe, showed continued engraftment at 21 to 25 months posttransplant, ranging from 15% to 42% male engrafted cells in marrow. Normal donor male marrow engrafted significantly better than 5-FU-pretreated male marrow as shown 1 to 12 months posttransplant in non-cytoablated female recipients. Percentages of male engrafted cells in BM ranged from 23% to 78% for recipients of normal donor marrow and from 0.1% to 39% for recipients of 5-FU marrow. Mean engraftment for 6 mice receiving normal marrow was 38%, whereas that for 6 mice receiving post-5-FU marrow was 8%, as assayed 1 to 3 months posttransplant. At 10 to 12 months, mean engraftment for the normal donor group was 46%, compared with 16% for the 5-FU group. The patterns of engraftment with normal and 5-FU marrow were similar for spleen and thymus. These results show that long-term chimerism can be established after transplantation of normal donor marrow to normal nonirradiated host mice and indicate that marrow spaces do not have to be created for successful engraftment. They suggest that transplanted marrow competes equally with host marrow for marrow space. Finally, these data show that post-5-FU Balb/C male marrow is markedly inferior in the repopulation of Balb/C female host marrow, spleen, and thymus, and suggest that this population of cells may not be the ideal population for gene transfer studies.     

Possible mechanisms of valproate in migraine prophylaxis

Valproate has been shown to be an effective prophylactic treatment in migraine. Investigation of the mechanism of its antimigraine action is difficult due to the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valproate increases brain GABA levels and, in doing so, may suppress migraine-related events in the cortex, perivascular parasympathetics or trigeminal nucleus caudalis. There is experimental evidence that it suppresses neurogenic inflammation and directly attenuates nociceptive neurotransmission. In addition, valproate reportedly alters levels of excitatory and inhibitory neurotransmitters and exerts direct effects on neuronal membranes in vitro. Valproate's observed effect may ultimately result from a combination of actions at different loci.     

Improved survival of children with sepsis and purpura: effects of age,gender, and era

Background  

To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands).     

Doctor-patient communication with people with intellectual disability - a qualitative study

Background

Patients' priorities and views on quality care are well-documented in Western countries but there is a dearth of research in this area in the East. The aim of the present study was to explore Chinese patients' views on quality of primary care consultations in Hong Kong and to compare these with the items in the CARE measure (a process measure of consultation quality widely used in the UK) in order to assess the potential utility of the CARE measure in a Chinese population.

Methods

Individual semi-structured interviews were conducted on 21 adult patients from 3 different primary care clinics (a public primary healthcare clinic, a University health centre, and a private family physician's clinic). Topics discussed included expectations, experiences, and views about quality of medical consultations. Interviews were typed verbatim, and a thematic approach was taken to identify key issues. These identified issues were then compared with the ten CARE measure items, using a CARE framework: Connecting (Care Measure items 1–3), Assessing (item 4), Responding (items 5,6), and Empowering (items 7–10).

Results

Patients judged doctors in terms of both the process of the consultation and the perceived outcomes. Themes identified that related to the interpersonal process of the consultation fitted well under the CARE framework; Connecting and communicating (18/21 patients), Assessing holistically (10/21 patients), Responding (18/21 patients) and Empowering (19/21 patients). Patients from the public clinic, who were generally of lower socio-economic status, were least likely to expect holistic care or empowerment. Two-thirds of patients also judged doctors on whether they performed an adequate physical examination, and three-quarters on the later outcomes of consultation (in terms of relief or cure and/or side-effects of prescribed drugs).

Conclusion

These findings suggest that Chinese patients in Hong Kong value engaged, empathic primary care doctors and judge the quality of consultations largely on these human skills and the attitudes and values that underpin them, as well as on the perceived outcomes of treatment. The match between themes relating to consultation process and the CARE Measure items suggests utility of this measure in this population, but further quantitative validation is required.     

Ultrasound evaluation of the abductor hallucis muscle: Reliability study

Background

The Abductor hallucis muscle (AbdH) plays an integral role during gait and is often affected in pathological foot conditions. The aim of this study was to evaluate the within and between-session intra-tester reliability using diagnostic ultrasound of the dorso-plantar thickness, medio-lateral width and cross-sectional area, of the AbdH in asymptomatic adults.

Methods

The AbdH muscles of thirty asymptomatic subjects were imaged and then measured using a Philips HD11 Ultrasound machine. Interclass correlation coefficients (ICC) with 95% confidence intervals (CI) were used to calculate both within and between session intra-tester reliability.

Results

The within-session reliability results demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.99–0.99); medio-lateral width an ICC: of 0.97 (95% CI: 0.92–0.97) and cross-sectional area an ICC of 0.98 (95% CI: 0.98–0.99). Between-session reliability results demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.95 to 0.98); medio-lateral width an ICC of 0.94 (95% CI 0.90 to 0.96) and for cross-sectional area an ICC of 0.79 (95% CI 0.65 to 0.88).

Conclusion

Diagnostic ultrasound has the potential to be a reliable tool for evaluating the AbdH muscle in asymptomatic subjects. Subsequent studies may be conducted to provide a better understanding of the AbdH function in foot and ankle pathologies.