Diphenyl diselenide ameliorates cognitive deficits induced by a model of menopause in rats

Ovarian hormone loss contributes to cognitive decline in postmenopausal women. Studies have demonstrated a positive role of the level of the element selenium in cognitive performance. The present study investigated the effects of the synthetic organoselenium compound diphenyl diselenide (PhSe)? on cognitive functions in ovariectomized rats. Ninety-day-old female Wistar rats were subjected to ovariectomy (OVX) or Sham operation. One week after surgery, rats were orally treated with (PhSe)? (5 mg/kg, per oral route) or vehicle once a day for 30 days. Next, the rats were evaluated in behavioral tests [Morris water maze (MWM) and open-field tests] and biochemical [cerebral acetylcholinesterase (AChE)] analyses were carried out. In MWM probe trial, (PhSe)? decreased the latency to reach the platform location and increased the number of crossings over the platform location, protecting against cognitive impairment induced by OVX. Furthermore, (PhSe)? prevented the stimulation of AChE activity caused by OVX. In conclusion, the present study showed a cognition-enhancing effect of (PhSe)? treatment for 30 days in ovariectomized rats in the MWM test, which could be related to its ability to prevent the stimulation of AChE activity caused by OVX in rats. These findings suggest that (PhSe)? might have a promising role in preventing the cognitive decline related to menopause.     

Colorectal Cancer in the Family: Psychosocial Distress and Social Issues in the Years Following Genetic Counselling

Background

This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequences of genetic counselling.

Methods

In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986–1998 completed a self-report questionnaire by mail.

Results

116 individuals (81% response rate) completed the questionnaire, on average 4 years after the last counselling session. Of all respondents, 6% had clinically significant levels of cancer-specific distress (Impact of Event Scale, IES). Having had contact with a professional psychosocial worker for cancer risk in the past 10 years was significantly associated with higher levels of current cancer specific distress. Only a minority of the counselees reported any adverse effects of genetic counselling on: communication about genetic counselling with their children (9%), family relationships (5%), obtaining life insurance (8%), choice or change of jobs (2%), and obtaining a mortgage (2%).

Conclusion

On average, four years after genetic counselling for HNPCC, only a small minority of counselled individuals reports clinically significant levels of distress, or significant family or social problems.

     

METHYLATION STATUS OF BCL6 DISTINGUISHES DNA SAMPLES FROM BENIGN AND MALIGNANT LYMPHOPROLIFERATIVE DISORDERS

INTRODUCTION: Core biopsy of the breast has become the method of choice for tissue diagnosis of screen detected microcalcifications and some mass lesions in many breast assessment centres. Biopsy results are not available until the following day. Imprint cytology of fresh breast core samples allows same-day reporting and patient counselling.
AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting.
METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report.
RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB.
CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB.     

The trouble with family medicine

BACKGROUND: The trouble with family medicine is that the perceptual framework it uses to view the phenomena of health and illness is at variance with the frameworks traditionally used by medicine generally. This creates difficulties in communication between those in family medicine and those in other disciplines, and sometimes leads to misunderstanding of the nature of the discipline of family medicine and its place in the health care system. Those who practise family medicine need to be 'multilingual', able to understand and speak the language and use the metaphors of family medicine, yet equally able to use the language and metaphors of other disciplines. OBJECTIVES: This paper, which begins with a clinical scenario, reviews the contemporary biomedical paradigm, proposes an alternative, and examines the conceptual frameworks which underpin the discipline of family medicine.      

Natural killer cell precursors in the CD44neg/dim T-cell receptor population of mouse bone marrow

Natural killer (NK) cells develop from the nonadherent cell component of NK long-term bone marrow (BM) cultures (NK-LTBMC). Because these nonadherent cells are depleted of mature NK cells and T cells, but appear to enriched for NK precursors, they were used as a starting population to begin to define the NK precursors that function in NK- LTBMC. As the stromal cell component of NK-LTBMC has been shown to support interleukin (IL)-2-induced, CD44 dependent, NK cell development from nonadherent NK precursors, NK-LTBMC stroma was used in a limiting dilution assay (LDA) to quantitate the precursors. NK-LTBMC in 96-well plates were irradiated (20 Gy) to kill hematopoietic cells (including the NK precursors), seeded with limiting dilutions of the cells to be quantitated, cultured with 500 U/mL IL-2 for 13 days and assayed for development of NK activity by adding 51Cr-labeled YAC-1 cells to the wells and evaluating the release of 51Cr after 4 hours. Flow cytometric analysis, sorting, and quantitation of the nonadherent cell component of NK-LTBMC showed that NK precursors were concentrated in the CD44neg/dim subset that comprised 10% of the "lymphoid" gated cells. When the CD44neg/dim subset was sorted from BM of mice treated with 5- fluorouracil (5-FU) day before (-1FUBM), there were about 30% T cells, but no NK-1.1+ cells. When the T cells were removed by sorting and the CD44neg/dim, alphabeta, gammadelta T-cell receptorneg (TCR-) subpopulation was seeded onto irradiated stroma with IL-2, they proliferated, developed NK activity, became NK-1.1+ and CD44bright and remained alphabeta, gammadelta TCR-. The frequency of NK precursors in this population as estimated from the LDA was about 1/500.     

A PIL for every ill? Patient information leaflets (PILs): a review of past, present and future use

This article reviews the usefulness and importance of written information, specifically leaflets, being given to patients. Evidence suggesting how both patient and doctor may benefit from the giving of written information is reviewed. Identification of good practice relating to the content and readability of leaflets is discussed. An argument is put forward that the giving of written information is an under-utilized resource in contributing to improving patient outcomes but that this may be changing with the increasing use of patient leaflet databases. The advantages and disadvantages of computer- generated patient leaflets are discussed and desirable further areas of research on computer-generated leaflets are proposed.      

TREK-1 channels do not mediate nitrergic neurotransmission in circular smooth muscle from the lower oesophageal sphincter

Background and purpose:

The ionic mechanisms underlying nitrergic inhibitory junction potentials (IJPs) in gut smooth muscle remain a matter of debate. Recently, it has been reported that opening of TWIK-related K⁺ channel 1 (TREK-1) K⁺ channels contributes to the nitrergic IJP in colonic smooth muscle. We investigated the effects of TREK-1 channel blockers on nitrergic neurotransmission in mouse and opossum lower oesophageal sphincter (LOS) circular smooth muscle (CSM).

Experimental approach:

The effects of TREK-1 channel blockers were characterized pharmacologically in murine and opossum gut smooth muscle using conventional intracellular and tension recordings.

Key results:

In LOS, L-methionine depolarized the resting membrane potential (RMP) but did not inhibit the nitrergic IJP. Cumulative application of theophylline hyperpolarized the RMP and inhibited the nitrergic IJP concentration dependently. The induced membrane hyperpolarization was prevented by pre-application of caffeine, but not by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. 8-Br-cAMP significantly hyperpolarized membrane potential and increased the amplitude of the nitrergic IJP. In opossum LOS muscle strips, L-methionine increased resting tone but had no effect on nerve-mediated LOS relaxation. On the other hand, theophylline markedly inhibited tone. In CSM from mouse proximal colon, L-methionine caused modest inhibition of nitrergic IJPs.

Conclusions and implications:

TREK-1 channels were not involved in the nitrergic IJP in LOS CSM. Not only does L-methionine have no effect on the nitrergic IJP or LOS relaxation, but the effect of theophylline appears to be due to interruption of Ca²⁺-releasing pathways (i.e. caffeine-like effect) rather than via blockade of TREK-1 channels.     

Effects of diphenyl diselenide on lipid profile and hepatic oxidative stress parameters in ovariectomized female rats

Objectives Ovarian hormone decline after menopause is linked to many pathophysiological reactions. Female rats submitted to ovariectomy are employed as a model of post‐menopausal condition. This study investigated the effects of diphenyl diselenide (PhSe)₂ on body weight gain, intra‐abdominal fat deposition, plasma lipid profile and hepatic oxidative stress in ovariectomized rats. Methods Female adult Wistar rats were ovariectomized (OVX rats) or sham‐operated and divided into four groups: (i) sham‐operated, (ii) (PhSe)₂, (iii) OVX and (iv) OVX + (PhSe)₂. (PhSe)₂ (5 mg/kg; 5 ml/kg, p.o.) was administered once a day for 30 days to groups (ii) and (iv). After that, rats were anaesthetized for blood sample gathering and submitted to euthanasia. Key findings (PhSe)₂ (5 mg/kg) was effective in preventing the rise in body weight gain and intra‐abdominal fat deposition induced in OVX rats. Although (PhSe)₂ was not effective in avoiding the increase in plasma total cholesterol and non‐HDL levels induced in OVX rats, (PhSe)₂ reduced plasma triglycerides and augmented HDL levels in OVX rats. (PhSe)₂ also increased hepatic ascorbic acid levels, reduced glutathione content, glutathione S‐transferase activity and restored catalase activity in liver of OVX rats. Conclusions These findings suggest that (PhSe)₂ could be a promising alternative to minimize menopause related symptoms.