Loading deproteinized bovine bone with strontium enhances bone regeneration in rat calvarial critical size defects

Clinical Oral Investigations - To evaluate the effect of grafting with strontium (Sr)-loaded deproteinized bovine bone (DBB) on bone healing in calvarial critical size defects (CSD) in rats. Two...     

Effects of high fat diet,ovariectomy, and physical activity on leptin receptor expression in rat brain and white fat tissue

Aim

To evaluate in a rat animal model whether ovariectomy, high fat diet (HFD), and physical activity in the form of running affect leptin receptor (Ob-R) distribution in the brain and white fat tissue compared to sham (Sh) surgery, standard diet (StD), and sedentary conditions.

Methods

The study included 48 female laboratory Wistar rats (4 weeks old). Following eight weeks of feeding with standard or HFD, rats were subjected to either OVX or Sh surgery. After surgery, all animals continued StD or HFD for the next 10 weeks. During these 10 weeks, ovariectomy and Sh groups were subjected to physical activity or sedentary conditions. Free-floating immunohistochemistry and Western blot methods were carried out to detect Ob-R in the brain and adipose tissue.

Results

StD-ovariectomy-sedentary group had a greater number of Ob-R positive neurons in lateral hypothalamic nuclei than StD-Sh-sedentary group. There was no difference in Ob-R positive neurons in arcuatus nuclei between all groups. Ob-R distribution in the barrel cortex was higher in HFD group than in StD group. Ob-R presence in perirenal and subcutaneous fat was decreased in StD-ovariectomy group.

Conclusion

HFD and ovariectomy increased Ob-R distribution in lateral hypothalamic nuclei, but there was no effect on arcuatus nuclei. Our results are first to suggest that HFD, ovariectomy, and physical activity affect Ob-R distribution in the barrel cortex, which might be correlated with the role of Ob-R in election of food in rats.Obesity is one of the leading health issues worldwide, associated with an increased risk of morbidity and mortality (1). In 1997, the World Health Organization (WHO) formally recognized obesity as a global epidemic (2). Increase in body fat stores and obesity is caused by an imbalance between energy intake and energy expenditure (3,4). Since childhood obesity is a predictor of an increased death rate, the “obesity epidemic” may reverse the current declining rate of death from cardiovascular diseases (5). Factors that contribute to obesity can be environmental (6), social (7), behavioral (8), psychological (9), and genetic (10,11).Women generally have more body fat than men (12). Nevertheless similar odds ratios were recorded in women and men for the association of abdominal obesity with acute myocardial infarction (13). Weight gain is common after menopause, indicating an association between hormones and fat stores (14). A large scale observational study found that both the body mass index and the level of physical activity were independent predictors of mortality and that a higher level of physical activity did not eliminate the risk associated with adiposity. At the same time, women who were both lean and physically active had the lowest mortality (15). In animal studies menopause can be induced by ovariectomy (OVX) (16).Obesity can also be called a disorder of appetite and it is controlled by complex homeostatic mechanisms involving the hypothalamus and brainstem (17). Many gut peptides like cholecystokinin, ghrelin, glucagon-like peptide-1 (GLP-1), and -2 and peptide YY (PYY) act on the brain to control eating behavior (18). There are two different system for controlling feeding behavior: short-term and long-term (19). Short-term regulation involves neural signals from the GI tract and its hormones, like insulin, glucagon, and ghrelin (20). A hormone that functions mainly within long-term regulation is leptin (16 kD), a hormonal product of the obesity (ob) gen, primarily secreted by adipocytes (21) and released in the brain. It generates a feeling of satisfaction and acts like an appetite-suppressing agent. Circulating leptin levels are lower in ovariectomized rats (22).Food intake is regulated via neural circuits located in the hypothalamus (23). Leptin acts via its leptin or Ob receptors (Ob-R) and is primarily expressed in hypothalamic neurons (19) especially in arcuate, ventromedial, and dorsomedial nuclei (24). Leptin is transported across the blood-brain barrier (BBB) by a saturable transporter (25). Ob-R is also detected in nonhypothalamic areas in the mice and in human brain neocortex, cerebellum, entorinal cortex, amygdale, and rostral medulla (26). Adipocytes, endothelial cells, and macrophages also have leptin receptor at its surface, which suggests autocrine and paracrine action for leptin in human adipose tissue (27). Association between the expression of Ob-R in target tissues and physiological and hormonal controlled processes is still unclear. Leptin receptors mRNA is found in each of the major components of the CNS “feeding” circuitry – the brainstem, hypothalamus, and is distributed reward centers (Allan brain) (28). Therefore, the aim of the current study was to evaluate whether HFD affects Ob-R distribution compared with StD specifically in the barrel field and piriform cortex compared to standard feeding centers in the hypothalamus. We supposed that the combination of OVX and HFD is interesting for further research on selected brain regions, which might be alleviated by physical activity. We also supposed that changes in Ob-R level in white fat tissue would correlate with the changes in brain regions.     

Job strain and psychological distress among employed pregnant Thai women: role of social support and coping strategies

Most Thai women continue to work throughout their pregnancy; however, little is known about job strain and its relation to psychological distress. This study aimed to examine: (1) the direct effects of job strain, perceived workplace support, perceived family support, and coping strategies on psychological distress and (2) the moderating effect of perceived workplace support, perceived family support, and coping strategies on the relationship between job strain and psychological distress. Lazarus and Folkman’s transactional model of stress and coping guided this cross-sectional study. Full-time employed pregnant women (N?=?300) were recruited from three antenatal clinics in Thailand. Thai versions of the following instruments were used: the State-Anxiety Inventory and Center for Epidemiological Studies—Depression Scale (psychological distress), the Job Content Questionnaire (job strain and perceived workplace support), the Medical Outcome Study Social Support Survey (perceived family support), and the Ways of Coping Checklist—Revised (coping strategies). Job strain with other predictors explained 54 % of the variance in psychological distress. In the separate hierarchical multiple linear regression models, two types of coping strategies, seeking social support and wishful thinking, moderated the effects of job strain on psychological distress. Perceived family support had a direct effect in reducing psychological distress. Job strain is a significant contributor to psychological distress. The average levels of seeking social support and wishful thinking were most beneficial in moderating the negative impact of job strain on psychological distress. Since perceived workplace and family support did not have moderating effects, stress management programs for decreasing the levels of job strain should be developed.     

Cyclin D1 and prognosis in human breast cancer

We have used immunohistochemical staining to assess the expression of cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating back 20 years. Clinical follow-up data were available on all patients. Approximately 50% of the tumours showed excessive nuclear staining for cyclin D1 as compared with normal epithelium. Some tumours showed strong cytoplasmic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D1. Contrary to expectations, moderate/strong staining for cyclin D1 was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin D1 staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D1 levels are abnormally low may have sustained mutations in other genes, such as RB1 and that it is this abnormality that has the more significant impact on survival from breast cancer. © 1996 Wiley-Liss, Inc.     

The influence of drug-exposure conditions on the development of resistance to methotrexate or ZD1694 in cultured human leukaemia cells

The influence of drug-exposure conditions on the development of resistance to methotrexate (MTX) or ZD1694 was studied by treating MOLT-3 human lymphoblastic-leukaemia cells in a continuous or a pulsatile (high-dose, short-term) drug-exposure schedule. Continuous exposure of the cells to MTX with stepwise escalation of the drug concentrations resulted in a MTX-resistant sub-line (MOLT-3/MTX_10,000) with impaired reduced-folate carrier (RFC) and increased dihydrofolate-reductase (DHFR) activity. Conversely, a MTX-resistant clone (MOLT-3/MTX·P-9) with unaltered RFC and DHFR activity, but with decreased cellular accumulation of antifolates, was selected by high-dose short-term treatment of the cells with MTX. MTX resistance in the latter cells was pronounced after short-term rather than continuous-exposure incubation with MTX, suggesting defective polyglutamation of the drug. On the other hand, 2 ZD1694-resistant sub-lines which were established by continuous (MOLT-3/ZD1694·C) or by pulsatile drug-exposure schedule (MOLT-3/ZD1694·P-9) demonstrated extremely low accumulation and poor retention of [³H]ZD1694, with no change of initial drug uptake and little or no increase of thymidylate-synthase (TS) activity, irrespective of drug-exposure conditions for their establishment. HPLC analysis displayed a virtual absence of ZD1694 polyglutamates in both ZD1694-resistant sub-lines and low accumulation in MOLT-3/MTX·P-9 as compared with the parent line. However, folylpolyglutamate-synthetase (FPGS) mRNA was only moderately decreased in the 2 ZD1694-resistant sub-lines and to an even lesser extent in MOLT-3/MTX·P-9. In addition, γ-glutamyl-hydrolase (GGH) activity was not increased, but was slightly down-regulated in the polyglutamation-defective sublines. These results indicate that the mechanism(s) of the resistance developed may depend not only on drug-exposure conditions while raising resistance but also on the biochemical properties of the drug. © 1996 Wiley-Liss, Inc.     

Behavioural problems in Sydney nursing homes

The prevalence of significant behavioural disturbance in 46 Sydney nursing homes was examined. All 2445 residents were rated on a brief screening questionnaire by senior nurses, who decided that 704 (29%) displayed at least one problem behaviour for much of the time. Primary care nurses (PCNs) then rated these ‘screen-positive’ residents using the Cohen-Mansfield Agitation Inventory (CMAI). In one nursing home the PCNs rated all 100 residents on the CMAI and found that 24 of 58 ‘screen-negative’ residents displayed CMAI behaviours once daily or more. Of CMAI behaviours rated as occurring daily or more often, 30% were manifested by ‘screen-negative’ residents. Prevalence figures based on ‘screen-positive’ residents are underestimates. Interrater reliability between PCNs was good. We report that at least 3.3% of residnets paced and 0.45% screamed several times an hour. Each of the following behaviours was manifested daily or more often by 10– 15% of the residents: restlessness, pacing, repetitive sentences, constant calls for help, cursing/verbal aggression and complaining. Aggressive behaviours (eg hitting, kicking, biting) were less common, and a relationship to cognitive impairment was demonstrated. Increased research on assessment and management of these behaviours is needed.     

Use of antidepressants,and the prevalence of depression and cognitive impairment in Sydney nursing homes

In 1993, a survey was conducted in 46 of the 47 nursing homes in a health district of Sydney. Medication cards and notes of all residents (N = 2414) were studied. Subjects who were willing and able to answer questions were interviewed by research assistants (senior nurses). Using the Mini-Mental State Examination and Mental Status Questionnaire, about 80% were found to be cognitively impaired. Of 874 subjects assessed with the Geriatric Depression Scale (GDS), 30.4% scored in the clearly depressed range (14 or more) of whom 27.4% were taking antidepressants. From a subsample of 26 with GDS scores of 14+, the psychiatrist concluded that only one-third would fulfil DSM-III-R criteria for major depression, with or without dementia. The dosages of antidepressants used in these nursing homes were relatively low. Of residents taking a tricyclic or mianserin, 48% were taking less than 30 mg daily, even though in 72% of cases their doctors stated the primary reason they were having this medication was to treat or prevent recurrence of depression. Opinions and evidence concerning the efficacy of such low dosage are conflicting. There is a need for further research, including correlation of efficacy with blood levels of antidepressants.