The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide

Background and purpose:

It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear.

Experimental approach:

The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique.

Key results:

The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 µM–10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 µM MK-801 or 60 µM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1–10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione.

Conclusions and implications:

These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds.     

Migration and lymphatic spread of calcified paraffinomas after breast augmentation

A 62 year old Chinese woman presented 25 years after having both breasts augmented with paraffin injections. Development of paraffinomas and multiple episodes of paraffin-related mastitis eventually resulted in bilateral mastectomies. The unusual distribution of migrated calcified paraffinomas in the thoracic wall and its lymphatic system is documented on computed tomography.     

Immunodeficiency and infantile bone and joint infection

Fifteen patients with infantile bone and joint infections were studied immunologically and clinically, 3 at the time of illness and 12 later. Abnormality of immunoglobulins, or complement, or phagocytes was found in 9 patients; 6 were within normal limits for the tests undertaken. Immunodeficiency is probably responsible for the subdued clinical signs of infection and for delayed diagnosis in some patients. It was also related to the extent of femoral head damage in infective arthritis of the hip and to the incidence of wound infection in late elective surgery.     

Use of tocolytics: what is the benefit of gaining 48 hours for the fetus?

Preterm birth remains one of the serious problems in perinatal medicine and is associated with an increased risk of neonatal complications and long-term morbidity. Although each day that delivery is delayed between 22 and 28 weeks of gestation increases survival by 3%, since most spontaneous preterm labour occurs between 28 and 34 weeks of gestation, this is of secondary concern; the primary goal of delay is to improve the function of certain systems in the fetus and to balance the risks of a hostile intrauterine environment with the complications of extrauterine preterm life. Although there is a lack of definitive evidence that tocolytic drugs improve outcome following spontaneous preterm labour and preterm birth, there is ample evidence that tocolysis delays delivery for long enough to permit administration of a complete course of antepartum glucocorticoids and to facilitate in utero transfer to a tertiary care unit where neonatal care will be optimal. Both these measures have been associated with improved outcomes; antepartum glucocorticoids reduce the incidence of respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia and necrotising enterocolitis, and in utero transfer is associated with decreased morbidity and mortality and less hospital-based intervention compared with postnatal transportation. Consequently, women who are more likely to benefit from tocolysis are those at early gestational ages, those needing transfer to a hospital that can provide neonatal intensive care and those who have not yet received a full course of antepartum glucocorticosteroids. In these cases, delaying labour for at least 48 hours with drugs such as atosiban should be considered, since it offers clear advantages for the fetus.     

Parental and primary care physicians'views on the management of chronic diseases: a study in Italy

A survey on the burden and quality of care and the parental and primary care physicians'views on management of eight chronic illnesses and disabilities was conducted from 1990 to 1993. Data were collected on 993 children and adolescents from family interviews and physicians'postal questionnaires. Approximately 70% of patients used two or more services for care management and 149 children were treated outside their region. Only 36% of the physicians were case managers and half of these agreed that better communication with other care providers could facilitate their role. A wide difference in parental satisfaction was found between medical and disabling conditions. Approximately 90% of the parents expressed satisfaction with care for children with coeliac disease (112/120), asthma (80/89) and diabetes (98/111), whereas approximately one-third of parents of children with cerebral palsy and Down's syndrome were dissatisfied (88/242 and 72/189, respectively). Primary care physicians expressed similar satisfaction with case management. Distance from hospital, the need for more information on disease management and financial aid were the sources of greatest dissatisfaction. Children with disabling diseases had more problems integrating at school than children with other chronic disorders. Closer interaction between health services, providers and families is necessary to manage the needs of disabled (Italian) children better. Chronic illness, disability, family, primary care, quality of care, special needs     

Comparison of a quantitative treadmill exercise score with standard electrocardiographic criteria in screening asymptomatic young men for coronary artery disease

A computer-derived treadmill exercise score that quantifies the electrocardiographic response to exercise has been reported to have a high sensitivity (87 per cent) and specificity (92 per cent) in patients with a high prevalence of coronary artery disease. To test its accuracy in young, asymptomatic men with a low prevalence of coronary artery disease, we evaluated the responses of 377 military officers (mean age, 36.6 years) by two independent methods. According to standard electrocardiographic criteria, 45 of the subjects (12 per cent) had positive tests, whereas the treadmill exercise score indicated that only 3 (less than 1 per cent) had positive tests. Since two of these three had left ventricular hypertrophy and met only the criteria for the latter without associated coronary artery disease, the treadmill exercise score predicted that only 1 of 377 subjects would have clinically important coronary artery disease. Coronary arteriography, performed in 10 persons with the most positive scores on standard treadmill tests and the highest scores for risk factors, showed that nine subjects did not have coronary artery disease and that one had single-vessel disease (the same subject who the treadmill score predicted would have mild disease). The treadmill exercise score appears to improve the diagnostic specificity of exercise electrocardiography and may be more useful than values on standard stress tests in screening asymptomatic populations for coronary artery disease.     

Reference ranges for bone densitometers adopted Australia‐wide: Geelong osteoporosis study

Bone densitometry reports a measure of fracture risk in comparison with young adults (T‐scores) and age‐matched peers (Z‐scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia‐wide. The GOS recruited a random, population‐based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX‐L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.     

Detection of monosomy 7 and trisomy 8 in myeloid neoplasia: a comparison of banding and fluorescence in situ hybridization

Fluorescence in situ hybridization (FISH) is a powerful tool for detection of numerical and structural chromosomal aberrations. We have compared conventional banding techniques and FISH for the detection of monosomy 7 (-7) and trisomy 8 (+8) in 89 patients with myeloid malignancies. Of these patients, 21 had -7, 30 had +8, four had both, and 34 had no aberrations or aberrations other than -7 or +8 as assessed by banding techniques. Sequential samples were available in 23 patients. Alphoid DNA probes specific for chromosomes no. 7 and 8 were used for FISH. As controls, 10 normal bone marrow (BM) samples were hybridized with the chromosomes no. 7 and 8 probes, and in addition all tumor samples were hybridized with a chromosome no. 1 specific probe. The cut-off value for -7 was 18% one-spot cells, and for +8 was 3% three-spot cells. FISH analysis of 44 samples with -7 or +8, and at least 10 metaphases evaluated, showed that the proportions of aberrant metaphase cells mirrored the interphase clone sizes. Most samples with nonclonal metaphase aberrations, including those with only a few metaphases, had increased numbers of aberrant interphase cells: 20% to 80% for -7, and 3% to 43% for +8. Interphase cytogenetics of the 34 samples without -7 or +8 did not show significant cell populations with -7 or +8. In four patients, -7 or +8 could not be confirmed by FISH due to additional structural aberrations, marker chromosomes, or wrongly interpreted banding results. As FISH will be used more and more in cytogenetic diagnosis, clinical follow-up, and therapy monitoring, it will be necessary to standardize FISH procedures and supplement the Standing Committee on Human Cytogenetic Nomenclature (ISCN) definitions of a clone with criteria specifically for in situ hybridization.     

酪氨酸相关肽的合成及抗孕酮生成活性

利用固相法合成了二十个含羟基氨基酸的小肽。其中,以0.5mol·L^-1二甲二氯硅烷/1.5mol·L^-1苯酚/DCM*为脱除Boc试剂,以TFMSA为切除树脂试剂。经C-18反相柱纯化后,全部产物均通过氨基酸分析要求。体外黄体细胞分泌孕酮实验表明有八个肽化物GlyTyrAlaLys,(SarSer)₂Lys及其申酯,TyrLys,HisTyr-NH₂,ThrProTyrLys-NH₂,TyrThrProArgLys,AspHisProThr-PheLys显示较强的抑制hCG致孕酮分泌的活性,而且前三个肽还能显著抑制基础孕酮的分泌,相反,GlySerTyr能刺激基础孕酮的分泌。目前尚未建立合理的结构一活性关系。