Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.     

The effect of bacterial melanin on electrical activity of neurons of the substantia nigra under conditions of GABA generation

The changes in spike activity of single neurons of the compact part of the substantia nigra, evoked by nucleus caudatus stimulation under conditions of long-term registration of the single and multiple, isolated and combined actions of GABA, GABA-amide, glutamine, and ethanolamine-O-sulfate (EOS) were studied in albino rats. Inhibition of poststimulus activity under GABA action was recorded and the inhibitory effect of GABA-amide was revealed. Primary excitatory and subsequent inhibitory effects of glutamine in combination with EOS were shown. The subsequent administration of bacterial melanin, synthesized by a mutant culture of Bacillus thuringiensis (BT-M) evoked a clear-cut and prolonged excitatory reaction during all the combined actions of GABA, GABA-amide, glutamine, and EOS. Preliminary administration of BT-M abolished the inhibitory poststimulus effects of GABA, GABA-amide, and EOS, as well as glutamine-induced excitation.     

Physical activity consultation for people with Type 2 diabetes: evidence and guidelines.

Physical activity is an important, but often underused, therapeutic strategy within diabetes care. To date, little is known about the best way to promote physical activity in diabetes care. Physical activity consultation is an intervention designed to promote physical activity behaviour change. This article provides guidelines on how to conduct a physical activity consultation with people who have Type 2 diabetes, and reviews the evidence surrounding the effectiveness of this intervention in this population. The trans-theoretical model is the underlying theory of behaviour change for the physical activity consultation intervention. The review identifies research which supports the use of this model for understanding physical activity behaviour in people with Type 2 diabetes. The review outlines a number of modifiable variables associated with physical activity behaviour change in this population. How each of these variables is addressed within the guidelines for conducting a physical activity consultation is identified. Finally, limited but consistent research highlights the effectiveness of physical activity consultation for promoting physical activity in people with Type 2 diabetes.     

Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis

OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti-irritative effect of PoCo was evaluated with a visual score and quantified by non-invasive bioengineering methods, namely chromametry and transepidermal water loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient; German pharmacopoeia) were tested in a 4-day repetitive irritation test using SLS. RESULTS: A statistically significant anti-inflammatory activity was observed for PoCo by all three methods when applied in parallel to the induction period of ICD. Application of PoCo after induction of ICD once a day for 5 days, starting just at the end of 4 days, was without any effect. CONCLUSION: An anti-inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by repeated SLS test could be observed and quantified by three independent, non-invasive biophysical assessment parameters. This effect can be explained by its influence on pro-inflammatory enzymes, namely phospholipase A2.     

蝙蝠葛碱对奎尼丁诱发的豚鼠乳头肌早后去极化及触发活动的作用

用标准微电极技术观察了中药蝙蝠葛的有效成分蝙蝠葛碱对奎尼丁诱发的豚鼠乳头肌早后去极化及触发活动的影响. 结果表明，奎尼丁2 μmol·L^-1能诱发豚鼠乳头肌早后去极化及触发活动,早后去极化的发生率为8/20, 幅值为13.4±2.6 mV, 起始电位为-42±5 mV, 触发活动的发生率为2/20. 蝙蝠葛碱20 μmol·L^-1能明显抑制奎尼丁诱发的早后去极化及触发活动，早后去极化的发生率为4/20，幅值为7.3±1.1 mV，无触发活动. 结果提示蝙蝠葛碱具有抗早后去极化所致心律失常.     

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity,reproductive factors,and venereal infections

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.Drs Kjaer, Engholm, and Lynge are with the Danish Cancer Registry. Dr Dahl is with the Department of Surgery, Slagelse Hospital, Denmark. Dr Bock is with the Department of Gynecology, Rigshospitalet, Copenhagen, Denmark. Dr Jensen, formerly with the Danish Cancer Registry, is deceased. Address correspondence to Dr Kjaer, Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvengets Hovedvej 35, Box 839, Copenhagen. Denmark. The Danish Cancer Society supported this study through grants.     

Cardiovascular autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome

Cardiovascular autonomic function in normotensive awake patients with obstructive sleep apnoea syndrome was studied in 21 normotensive (mean age 48 ± 14 years), drug-free men with obstructive sleep apnoea syndrome. Cardiovascular reflex tests with continuous blood pressure monitoring and biochemical indices were performed the morning after a standard polygraphic sleep recording. A group of 20 agematched (mean age 49 ± 19 years) normal subjects was used as controls. The obstructive sleep apnoea syndrome patients showed higher heart rate and noradrenaline plasma levels (p < 0.05) at rest and a higher blood pressure response to head-up tilt (p < 0.01), suggesting sympathetic overactivity. Respiratory arrhythmia, baroreflex sensitivity index and Valsalva ratio were significantly lower in the obstructive sleep apnoea syndrome group (p < 0.01) whereas the decrease in heart rate induced by the cold face test was significantly higher (p < 0.05) showing a blunting of reflexes dependent on baroreceptor or pulmonary afferents with normal or increased cardiac vagal efferent activity. These abnormalities in autonomic regulation may predispose obstructive sleep apnoea syndrome patients to cardiovascular complications like hypertension and cardiac arrhythmias.     

Physiological Effects of Mental Stress and Orthostasis in Young Insulin-Dependent Diabetic Patients

ABSTRACT. The effects of procedures which stimulate sympathetic activity, viz. mental stress induced by a colour-word conflict test (CWT) for 20 min, and orthostasis (ORT) for 8 min were studied in 8 young (16-20 yr) insulin-dependent diabetes mellitus (IDDM) patients and 9 age and sex-matched healthy controls. The IDDM patients showed no signs of neuropathy or retinopathy and their mean HbA_1c value was 8.4 ±0.6% (normal value < 5.0 %). Blood pressure and heart rate increased significantly during CWT and ORT in both groups. The changes in systolic blood pressure and heart rate were comparable in both groups during CWT; the IDDM group showed a higher ( p < 0.05) heart rate after 8 min of orthostasis, however. CWT and ORT elicited equivalent increases in noradrenaline in venous plasma in both groups ( p < 0.05), but the IDDM patients had 50% lower values ( p < 0.01) at rest, during CWT and at rest after CWT than controls. CWT and ORT evoked equivalent plasma adrenaline increases in both groups. The lipolysis marker, plasma glycerol, was about 40 % lower ( p < 0.05) in the IDDM group before and after CWT. Yet, mental stress evoked equivalent increases in glycerol levels ( p < 0.01) in both groups. These findings indicate that sympathetic activity in the young diabetic patients without signs of neuropathy may be blunted.     

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.