Drug-metabolizing enzyme activities in the liver and intestine of rats exposed to DDT: effects of vitamin A status

One-half of a group (deficient group) of male Wistar rats which received a daily intake of 50 IU of vitamin A/kg of body weight, and one-half of a second group (normal group), which received 500 IU of the same substance, were treated by intragastric intubation with 40 mg of DDT/day/kg body weight. Rats were killed after 5 or 12 days of exposure to DDT. The liver vitamin A contents indicated a different rate of storage depending on the amount of vitamin A. DDT increased the relative liver weight and decreased hepatic vitamin A storage in both groups; it induced benzo(a)pyrene hydroxylase (AHH) and glutathione-S-transferase (GST) activities in both organs and cytochrome P 450 only in the liver. At both ages, no change was noted in the cytochrome P450 content in the liver and intestine, whereas enzymatic activities, unchanged in the liver, were significantly modified in the intestine and included a reduction in AHH activity, an increase in UDP-glucuronosyl transferase (UDPGT) and GST activities. Vitamin A deficiency had no effect on AHH and UDPGT activities nor on the cytochrome P 450 content in the liver or intestine. However, it significantly increased the GST activity in the intestine, but not in the liver.     

Altered interpretation of neck proprioceptive signals in persons with subclinical recurrent neck pain.

OBJECTIVE: To evaluate whether subjects with subclinical recurrent neck pain have an altered interpretation of neck proprioceptive signals. DESIGN: A comparative group design. SUBJECTS: Twelve subjects with recurrent neck pain and 12 control subjects. METHODS: The shoulder, head, trunk and whole-body position were measured under the following conditions: active and passive elevation and depression of the right shoulder and vibration of the trapezius muscle. RESULTS: During passive shoulder movements both groups moved their head in the opposite direction (p<0.05). During passive elevation subjects with recurrent neck pain showed a significant over-appraisal of shoulder position. Both groups responded similarly to active movements. Subjects with recurrent neck pain and control subjects showed similar trunk and head-to-trunk movements during shoulder movements. Subjects with recurrent neck pain, however, made larger movements compared with healthy subjects (p<0.05). During trapezius muscle vibration similar whole-body movements were found in both groups. CONCLUSION: These results show a modified interpretation of neck proprioceptive signals in subjects with recurrent neck pain and may reflect an offset in the egocentric reference frame or a decreased capacity to switch between reference frames. Better insight into these mechanisms might lead to better evaluation and treatment of subjects with recurrent neck pain and to a reduction in recurrent episodes.     

Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement

This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of ⁸⁹Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed.     

[I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors

Dosimetry and therapeutic application of [¹³¹I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [¹³¹I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy·MBq⁻¹. No intolerance or adverse effects were observed after the therapeutic doses (3.3–6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.     

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes—including DYRK1A, which encodes a serine threonine kinase involved in cell cycle control—has been shown to present an increase in brain weight. We analyzed this new phenotype by measuring total and regional brain volumes at different ages, using a 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed a total volume increase of 13.6% in adult mice. Changes in brain morphogenesis were already visible at a very early postnatal stage (postnatal days 2–7). Region‐specific changes were characterized from postnatal day 15 to 5 months. These results, made it possible to define region‐specific effects of DYRK1A overexpression, with the strongest increase seen in the thalamus–hypothalamus area (24%). Anat Rec, 291:254–262, 2008. © 2008 Wiley‐Liss, Inc.     

Somatic markers and explicit knowledge are both involved in decision-making

In 1994, it was proposed that decision-making requires emotion-related signals, known as somatic markers. In contrast, some authors argued that conscious knowledge of contingencies is sufficient for advantageous decision-making. We aimed to investigate the respective roles of somatic markers and explicit knowledge in decision-making. Thirty healthy volunteers performed the Iowa Gambling Task (IGT). Conscious knowledge was assessed using a sensitive questionnaire and skin conductance responses (SCRs) were recorded. Most participants acquired a preference for advantageous choices during the task and generated larger anticipatory SCRs before disadvantageous relative to advantageous choices. Performance on the IGT and the autonomic response were positively correlated (r = 0.38, p = 0.045). Moreover, there was a statistically significant difference in performance according to conscious awareness (p = 0.009). There was no significant association between level of explicit knowledge and SCR (p = 0.1). Finally, we did not find any interaction between explicit knowledge and performance although a lack of statistical power is not to be excluded. Advantageous decision-making therefore seems to be associated with two distinct, namely implicit and explicit, systems.