Free radicals and brain damage due to transient middle cerebral artery occlusion: the effect of dimethylthiourea

The objective of this study was to assess whether dimethylthiourea (DMTU), an established free radical scavenger, ameliorates ischaemic damage due to 2–3 h of transient middle cerebral artery (MCA) occlusion, induced by an intraluminal filament. A major point adressed was whether DMTU given before MCA occlusion only delayed the maturation of the damage, or if it had a lasting effect on infarct size. The end point was morphological, and either encompassed triphenyltetrazolium chloride (TTC) staining of tissue slices after 24 h or 48 h of recovery, or histopathological assessment of infarct size after 7 days of recovery. In a preliminary series of experiments, rats were subjected to 3 h of MCA occlusion, and infarct volume was assessed by TTC staining after 24 h of recovery. DMTU in a dose of 750 mg/kg reduced infarct volume by more than 50%. However, due to a high mortality rate, that protocol was not subsequently pursued. When the ischaemia duration was reduced to 2 h and the DMTU dose to 400 mg/kg, a similar amelioration of the tissue damage was observed. However, since DMTU reduced a spontaneous rise in body temperature to 39.0–39.5°C, DMTU-treated animals in the main series of experiments with 24 and 48 h of recovery were treated so that they had the same temperature rise as the saline controls. Under such constant temperature conditions, the effect of DMTU at 24 h of recovery was borderline (P= 0.052) and at 48 h it was nil. The lack of a lasting effect of DMTU was supported by the findings on evaluation of infarct area after 7 days of recovery. The results raise the important question whether DMTU, and perhaps other free radical scavengers, delay rather than ameliorate the ischaemic lesion developing after transient MCA occlusion.     

Invasive lobular breast cancer. Prognostic significance of histological malignancy grading

Invasive lobular carcinoma (ILC) is the second most reported type of breast cancer in the Danish Breast Cancer Cooperative Group (DBCG). Several histological subtypes exist, with reports of different prognosis. The aim was to present the incidence of ILC in DBCG from 1977-2004, and evaluate tumours regarding diagnosis, histological subtype and grade, and relate to prognosis. Eight hundred and sixty tumours from patients with a diagnosis of ILC or ILC/non-ILC, who underwent breast cancer surgery in the period of 1990-1998, were evaluated. The impact of histological malignancy grade on disease-free survival and overall survival was analysed using a multivariate analysis adjusting for tumour size, hormone receptor status, axillary lymph node status and patient age. The incidence of pure ILC has risen from 5 to 12%, the ILC/non-ILC is constant at 2% of all reported breast cancers in DBCG. Most of the tumours were classical ILC grade II. The majority of the grade III tumours were among the non-classical subtypes, showing a statistically significant worse disease-free and overall survival compared to grade II, regardless of type. The prognosis was the same for grade I and grade II tumours. The number of positive axillary lymph nodes and hormone receptor negative tumours increased among grade III tumours. We conclude that histological malignancy grade has an independent significant impact on the prognosis of ILC, and it should be taken into consideration when planning the postoperative treatment in this group of patients.     

Nursing students' attitudes towards HIV/AIDS patients in Finland, Estonia and Lithuania

This paper presents baseline data on attitudes towards HIV/AIDS patients and homophobic levels among nursing students in three Baltic Sea countries: Finland, Estonia and Lithuania. The aim is to describe and compare nursing students' attitudes in these three countries and to explore how attitudes towards HIV/AIDS correlate with background variables. The total sample comprised 471 nursing students. The respondents demonstrated average attitude scores towards patients with HIV/AIDS and rather positive attitudes towards homosexually oriented patients. Significant country differences were found, with Finnish nursing students showing the most positive attitudes towards HIV/AIDS patients and homosexually oriented patients. Previous experience of HIV/AIDS patients was the single factor with the greatest positive impact on nursing students' attitudes. Nursing students' willingness to provide care for an HIV/AIDS patient was associated with a positive attitude towards these patients. Length of employment experience correlated negatively with general attitude, and older nursing students with more work experience showed a more negative attitude towards homosexual patients. Proper education to achieve a sound knowledge base and good nursing skills promotes a more positive attitude to HIV/AIDS. It is important that nursing students are sensitive and show respect for the patient's human dignity. There is need for greater harmonization of education in the three countries.     

Brain damage in a mouse model of global cerebral ischemia. Effect of NMDA receptor blockade

The importance of particular genes in neuronal death following global cerebral ischemia can readily be studied in genetically modified mice provided a reliable model of ischemia is available. For that purpose, we developed a mouse model of global cerebral ischemia that induces consistent damage to different regions of the brain and with a low mortality rate. Twelve minutes of ischemia was induced in C57BL/6 mice by bilateral common carotid artery occlusion under halothane anesthesia and artificial ventilation. Body and brain temperature were monitored and cortical cerebral blood flow in each hemisphere was measured by laser Doppler flowmeter before, during, and for 5 min after ischemia. Extensive damage was found in the striatum and marked cell damage was observed in the CA1 and CA2 regions of hippocampus and in thalamus. Mild damage was seen in the CA3 region, dentate gyrus and cortex. Hippocampal damage in the CA1 region is delayed and developed over 48 h. Intraischemic hypothermia of 33 degrees C provided a robust neuroprotection. The non-competitive N-methyl-D-aspartate receptor blocker, MK-801, did not provide protection in the hippocampus, cortex, striatum or thalamus when administered 30 min prior to ischemia or 2 h after the end of ischemia, but selectively mitigated damage in the hippocampus, when administered immediately following ischemia. This model of global cerebral ischemia may be useful in pharmacological and genomic studies of ischemic brain damage.     

Hyperglycemia-exaggerated ischemic brain damage following 30 min of middle cerebral artery occlusion is not due to capillary obstruction

Transient focal ischemia of brief duration (15–30 min) gives rise to brain damage. In normoglycemic animals this damage usually consists of selective neuronal necrosis (SNN), and is largely confined to the lateral caudoputamen. In hyperglycemic subjects damage occurs more rapidly, involves also neocortical areas, and is often of the pan-necrotic type (`infarction'). Since experiments on forebrain ischemia of 30 min duration suggest that microcirculatory compromise develops during recirculation, we studied whether focal ischemia of the same duration, followed by reperfusion for 1, 2 or 4 h, leads to microcirculatory dysfunction. To test this possibility, we fixed the tissue by perfusion and counted the number of formed elements (leukocytes, macrophages and erythrocytes) in capillaries and postcapillary venules. Furthermore, capillary patency was evaluated following in vivo injection of Evan's blue. Histopathological examination of tissue fixed by perfusion after 1, 2 and 4 h of recirculation showed an increasing density of SNN in the caudoputamen of normoglycemic animals. Hyperglycemic, but not normoglycemic, animals showed pan-necrotic lesions (`infarction') after 4 h of recirculation. As a result, the total volume of tissue damage (SNN plus infarction) was larger in hyper- than in normoglycemic animals at 2 and 4 h of recirculation. In addition, hyperglycemic animals showed involvement of neocortex which increased with the time of reperfusion. In the ischemic hemisphere, between 5 and 10% of counted capillaries contained formed elements. However, since hyperglycemic animals contained an equal (or smaller) amount of cells the results did not suggest that capillary `plugging' could explain the aggravated damage. Moreover, both normo- and hyperglycemic animals showed close to 100% capillary patency. The results thus fail to support the notion that the aggravation of focal ischemic damage by hyperglycemia is due to obstruction of microvessel by swelling or leukocyte adherence.     

Hyperthermia aggravates and hypothermia ameliorates epileptic brain damage

The influence of hyperthermia and hypothermia on epileptic brain damage was studied in rats, in which status epilepticus was induced by flurothyl. Histopathological changes were examined by light microscopy after 1 or 7 days of recovery. Two series of animals were studied. In the first, short periods of seizures (20 and 25 min) were employed to examine whether moderate hyperthermia (39.5° C) would aggravate epileptic brain damage, and a longer period (45 min) was used to investigate whether moderate hypothermia (32.5° C) would ameliorate the damage. The second series investigated whether brief periods of status epilepticus (10 min) would cause brain damage if hyperthermia were high or excessive. For this series, animals with body temperatures of 37.0, 39.0, and 41.0° C were studied. Data from normothermic animals (37.5° C) confirmed previously described neuronal damage. Although hyperthermic animals failed to showe increased damage in the CA1 sector, or in the hilar region of the dentate gyrus, they showed enhanced damage in the neocortex and globus pallidus (GP). In substantia nigra pars reticulata (SNPR) four out of five hyperthermic animals had bilateral infarcts after 20 min of status epilepticus, whereas no normothermic animal showed such damage. Hypothermia seemed to ameliorate epileptic brain damage in the neocortex (n.s.) and GP (P < 0.05) following status epilepticus for 45 min. Three out of seven hypothermic animals had mild SNPR involvement compared to severe infarction of the nucleus in five out of six normothermic animals (P < 0.05). Thus, hyperthermia aggravated and hypothermia ameliorated epileptic brain damage both in regions showing selective neuronal necrosis (neocortex) and in regions developing pan-necrosis (GP and SNPR). The second series displayed an unexpected result of excessive hyperthermia. Animals subjected to only 10 min of status epilepticus at a temperature of 41° C showed not only neocortical lesions, but also moderate to extensive damage to the hippocampus (CA1, subiculum, and dentate gyrus). It is concluded that at high body and brain temperature, brief periods of status epilepticus can yield extensive brain damage, primarily affecting the hippocampus.     

Hyperthermia complicates middle cerebral artery occlusion induced by an intraluminal filament

The present experiments were designed to study under what circumstances middle cerebral artery (MCA) occlusion by an intraluminal filament technique leads to hyperthermia and what the mechanisms are. We found that permanent MCA occlusion by this technique lead to a rise in body (core) temperature to 39.0–39.5°C during the first 2–4 h, and to sustained hyperthermia thereafter (38.5–39.0°C). After2 h of transient MCA occlusion hyperthermia could only be avoided if anesthesia (with control of temperature) was maintained for 2 h of ischemia and 1 h of recirculation or, in unanesthetized animals, if external cooling was maintained for 2 h of ischemia and 2 h of recirculation. Control of temperature only during ischemia did not prevent a postischemic rise in temperature. One hour of MCA occlusion had less effect on body temperature. Results are presented which suggest that the hyperthermia observed is due to an interference, by the intraluminal filament, of circulation to hypothalamic centers regulating body temperature. It is speculated that the hyperthermia induced may blunt or obliterate the effect of drugs, normally considered to ameliorate brain damage due to focal ischemia.     

Nurses' and nursing students' perceptions of sexual risk behavior: a study in Finland, Estonia, and Lithuania

The continuing escalation of the global HIV/AIDS epidemic has changed our perceptions of sexual health. This article reports on a study of nurses' and nursing students' perceptions of sexual risk behaviour in Finland, Estonia and Lithuania and of how these perceptions are associated with background variables. Questionnaire data were collected in year 2006 with a modified version of Chng and Moore's Safer Sex Scale (1993), which consists of 12 background questions and 10 items exploring nurses' and nursing students' perceptions of sexual risk behaviour. Responses were obtained from 1152 nurses and nursing students. Their perceptions of sexual risk behaviour appeared to be quite cautious. The results revealed statistically significant country differences, with Finnish and Estonian respondents showing more cautious perceptions of sexual risk behavior than Lithuanian respondents. Some background variables were found to be associated with perceptions of sexual risk behavior. Nurses' perceptions differed from those of nursing students: the latter were less cautious in their perceptions. The most important background factor was previous experience of nursing an HIV/AIDS patient: nurses and students who had such experience reported more cautious perceptions than those who did not. In addition, age was found to correlate with perceptions of sexual risk behavior. Nurses and nursing students need to be more aware of their own perceptions of sexual risk behavior and the impact of those perceptions on their clinical practice. Interventions need to be developed in order to promote safer sex practices. Health care personnel should have the opportunity in their training to work with HIV/AIDS patients.     

No prediction of recurrence of meningiomas by PCNA and Ki-67 immunohistochemistry

Immunohistochemistry for the expression of the proliferation markersproliferating cell nuclear antigen (PCNA) and Ki-67 wasstudied in 16 non recurring meningiomas, 11 meningiomasrecurring as benign tumors, 6 recurring as atypicalmeningiomas and in 9 recurring as malignant meningiomas.Non recurring meningiomas were defined in this studyas tumors without recurrence at least 8 yearsafter surgery. In addition 16 benign recurrences, 14atypical- and 12 malignant meningiomas were studied. Ineach group great variation of labeling indices (LI)= per cent of tumor cells labeled wasobserved, especially of PCNA LIs. The non recurringmeningiomas displayed lower mean LI for PCNA andKi-67 than did the recurring meningiomas of allgroups but the differences were not statistically significant.The same pattern was seen when totally resectedtumors were studied alone. Benign-, atypical-, and malignantmeningiomas had labeling indices that were related tothe grade of malignancy. Only PCNA LIs ofatypical- and malignant meningiomas were statistically significantly higherthan PCNA LIs of non recurring meningiomas. Thestudy indicates that PCNA and Ki-67 are ofminor value as predictors of recurrence of benignmeningiomas.     

Lack of neuroprotection by heat shock protein 70 overexpression in a mouse model of global cerebral ischemia

Heat shock protein 70 (Hsp70) is induced in cells by a variety of stress conditions, is known to be cytoprotective, and has been proposed to be neuroprotective during brain ischemia. A recently developed mouse model of 12-min global cerebral ischemia by bilateral common carotid artery occlusion with artificial ventilation and bilateral monitoring of regional cerebral blood flow by laser Doppler was applied. We examined the expression and possible neuroprotective role of the inducible form of Hsp70 in the mouse brain following global cerebral ischemia. Ischemia induced a marked expression of Hsp70 in the ischemia vulnerable CA1-CA3 region of the hippocampus. Intraischemic hypothermia (33°C) prevented cell damage without noticeable expression of Hsp70. A transgenic mouse overexpressing Hsp70 was subjected to 12 min of global cerebral ischemia, and the brain damage was evaluated after 4 days. No neuroprotection of ischemia-induced brain damage in hippocampus, striatum, cortex or thalamus was found in Hsp70 transgenic animals compared with wild-type littermate mice. We suggest that overexpression of Hsp70 following cerebral ischemia is an indicator of cell stress. Also, constitutively overexpression of Hsp70 is insufficient to effectively influence cell death after global cerebral ischemia in the mouse.