[Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer].

Objective: To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods: In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results: In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions: In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

Application of ultrasound-based radiomics technology in fetal-lung-texture analysis in pregnancies complicated by gestational diabetes and/or pre-eclampsia.

OBJECTIVES: To analyze and compare, using ultrasound-based radiomics technology, fetal-lung texture in pregnancies affected by gestational diabetes mellitus (GDM) and/or pre-eclampsia (PE) and in normal pregnancies, overall and at different gestational ages. METHODS: In this retrospective study, 430 high-throughput features per fetal-lung image were extracted from 548 fetal-lung ultrasound images (obtained at the level of the four-chamber view of the heart) in 548 pregnant women who delivered between July 2018 and August 2019 at the Obstetrics and Gynecology Hospital of Fudan University. Images had been obtained during ultrasound examinations between 28 and 41 weeks of gestation. The data were divided randomly into training set (80% of fetal-lung images) and independent test set (20% of images), and 20% of the images in the training set were then selected as the validation set. A standard machine-learning model based on ultrasound-based radiomics technology was created using features of fetal-lung texture extracted from the images, and a regression model was used to evaluate the relationship between lung-texture features, GDM and/or PE and gestational age. RESULTS: Of the 548 pregnancies included, 108 were affected by GDM alone, 71 by PE alone and 25 by both GDM and PE, and 344 were normal. The overall performance of the GDM and PE prediction model was superior to that of the gestational-age prediction model, with an area under the receiver-operating-characteristics curve of 0.95-0.99, sensitivity of 78.8-97.1% in the validation set and 74.5-91.3% in the independent test set, specificity of 79.8-94.3% in the validation set and 75.7-88.4% in the independent test set and accuracy of 81.0-95.3% in the validation set and 80.6-86.4% in the independent test set. CONCLUSIONS: Using ultrasound-based radiomics technology, fetal lungs from pregnancies grouped according to whether they were affected by GDM and/or PE could be distinguished from each other and from fetal lungs of normal pregnancies, and lungs from pregnancies at different gestational ages could be distinguished. These findings support further research to explore the use of this non-invasive technology to predict neonatal respiratory complications in women with PE, GDM or their combination. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[Effects of 18ß-sodium glycyrrhetinic acid on TNF-α expression in rats with allergic rhinitis].

Objective:To observe the effect of 18ß-sodium glycyrrhetinic acid(18ß-SGA) on the expression of TNF-α in nasal mucosa of rats with allergic rhinitis（AR）, and explore the intervention mechanism of 18ß-SGA on AR. Method:One hundred and six SPF-level Wistar rats were randomly divided into control group, AR group, budesonide group, 18ß-SGA low dose group and high dose group. After the AR rat model was constructed by ovalbumin, the rats were given drug intervention and sacrificed after 2 and 4 weeks of intervention. The nasal mucosa of the rats was taken for immunohistochemical staining, RT-qPCR and Western-blotting to localize and quantify the expression of TNF-α. Result:By immunohistochemistry, Western-blotting and RT-PCR, TNF-α was mainly found in the columnar epithelium, vascular endothelium, glandular and some inflammatory cytoplasm of nasal mucosa. And the expression of TNF-α in the nasal mucosa of AR rats was significantly increased than the normal group at the protein and mRNA levels (P<0.01). After intervention with different doses of 18ß-SGA, the expression of TNF-α was significantly decreased (P<0.01), especially after 4 weeks of 18ß-SGA low dose group(P<0.01). Conclusion:Different doses of 18ß-SGA have therapeutic effects on AR, and its mechanism of action may be related to the inhibition of TNF-α expression.

An anti-αVß3 antibody inhibits coronary artery atherosclerosis in diabetic pigs.

BACKGROUND AND AIMS: Diabetes is a major risk factor for the development of atherosclerosis. Hyperglycemia stimulates vascular smooth muscle cells (VSMC) to secrete ligands that bind to the αVß3 integrin, a receptor that regulates VSMC proliferation and migration. This study determined whether an antibody that had previously been shown to block αVß3 activation and to inhibit VSMC proliferation and migration in vitro, inhibited the development of atherosclerosis in diabetic pigs. METHODS: Twenty diabetic pigs were maintained on a high fat diet for 22 weeks. Ten received injections of anti-ß3 F(ab)2 and ten received control F(ab)2 for 18 weeks. RESULTS: The active antibody group showed reduction of atherosclerosis of 91 ± 9% in the left main, 71 ± 11%, in left anterior descending, 80 ± 10.2% in circumflex, and 76 ± 25% in right coronary artery, (p < 0.01 compared to lesions areas from corresponding control treated arteries). There were significant reductions in both cell number and extracellular matrix. Histologic analysis showed neointimal hyperplasia with macrophage infiltration, calcifications and cholesterol clefts. Antibody treatment significantly reduced number of macrophages contained within lesions, suggesting that this change contributed to the decrease in lesion cellularity. Analysis of the biochemical changes within the femoral arteries that received the active antibody showed a 46 ± 12% (p < 0.05) reduction in the tyrosine phosphorylation of the ß3 subunit of αVß3 and a 40 ± 14% (p < 0.05) reduction in MAP kinase activation. CONCLUSIONS: Blocking ligand binding to the αVß3 integrin inhibits its activation and attenuates increased VSMC proliferation that is induced by chronic hyperglycemia. These changes result in significant decreases in atherosclerotic lesion size in the coronary arteries. The results suggest that this approach may have efficacy in treating the proliferative phase of atherosclerosis in patients with diabetes.

CD133 and DNA-PK regulate MDR1 via the PI3K- or Akt-NF-κB pathway in multidrug-resistant glioblastoma cells in vitro.

Chemotherapy is an adjuvant treatment for glioblastomas, however, chemotherapy remains palliative because of the development of multidrug resistance (MDR). Following prolonged chemotherapy, MDR protein 1 (MDR1) and CD133 increase in recurrent glioblastomas. CD133 positive (CD133+) glioma cancer stem-like cells (GCSCs) markedly promote drug resistance and exhibit increased DNA damage repair capability; thus they have a key role in determining tumor chemosensitivity. Although CD133, DNA-dependent protein kinase (DNA-PK), and MDR1 are elevated in CD133+ GCSCs, the relationship among these molecules has not been elucidated. In this study, MDR glioblastoma cell lines were created in response to prolonged doxorubicin chemotherapy. CD133, DNA-PK and MDR1 were markedly elevated in these cells. CD133 and DNA-PK may increase MDR1 via the phosphatidylinositol-3-kinase (PI3K)-Akt signal pathway. PI3K downstream targets Akt and nuclear factor (NF)-κB, which interacts with the MDR1 promoter, were also elevated in these cells. Downregulation of CD133 and DNA-PK by small interfering RNA, or inhibition of PI3K or Akt, decreased Akt, NF-κB and MDR1 expression. The results indicate that CD133 and DNA-PK regulate MDR1 through the PI3K- or Akt-NF-κB signal pathway. Consequently, a novel chemotherapeutic regimen targeting CD133 and DNA-PK in combination with traditional protocols may increase chemotherapeutic efficacy and improve prognosis for individuals who present with glioblastoma.

The epidemiology of human T-cell lymphotropic virus types I and II in Canadian blood donors.

OBJECTIVES: Blood donors in Canada have been tested for Human T-Cell Lymphotropic Virus (HTLV) since 1990. We report the epidemiology, risk factors and lookback/traceback of HTLV-positive donors/recipients. METHODS: The annual HTLV rate was calculated from 1990 to 2010. Residual risk was estimated as the product of incidence and window period. Twenty-nine HTLV-positive donors and 116 matched controls (ratio 1 : 4) were interviewed about risk factors. For HTLV-positive donations, lookback investigations involved identification of all previous donations, and attempting to locate and test recipients. Traceback was initiated when transfusion transmission was queried for HTLV-positive blood recipients. All donors of products that the recipient received were identified, with an attempt to locate and test them. RESULTS: The HTLV rate decreased from 9.35 per 100,000 donations in 1990 to 1.11 in 2010. The residual risk of infection was 1 in 7.6 million donations. In logistic regression birth overseas (OR 18.7), history of sexually transmitted diseases (OR 32.9), sex with unknown background (OR 5.4) and blood transfusion (OR 8.9) were significant predictors. In the lookback study, of 109 HTLV-positive donors, 508 components were transfused, of whom 147 recipients were tested and 18 (12%) were positive. All were transfused prior to the implementation of donor testing. Twenty-three traceback investigations were requested involving 324 transfused untested products,of whom 219 (67.6%) of donors were tested and 13 (6%) were positive for HTLV. CONCLUSIONS: With testing of the blood supply, the risk from HTLV is very low and while most HTLV-positive donors have risk factors, deferrable risk is rare.

The impact of increasing the upper age limit of donation on the eligible blood donor population in Canada.

OBJECTIVES: Using population prevalence data for deferrable diseases/conditions we estimated the Canadian population eligible to donate according to three upper-age limit scenarios. BACKGROUND: The donor selection criteria limit the number of potential blood donors but relaxing the upper age criteria could mitigate this. METHODS AND MATERIALS: Forty deferral criteria were identified and their corresponding prevalence data obtained to estimate the number of people excluded by the criteria. The eligible blood donor population was estimated from national census data taking the age limits, deferral criteria and deferral time-period into account. As more than one disease/condition may co-exist, the estimate was adjusted to avoid over-representation. RESULTS: Of about 33 million Canadians aged 17 (18 in Québec) to 65, 15·1 million (45·8%) are eligible to donate blood. This number increases to 15·7 million when including people up to 71 years and to 17·1 million in the absence of an upper age limit. CONCLUSION: As about 1·2 million units are collected from 600,000 donors annually, there are more than enough eligible people to meet the need. However, recruitment of donors is challenging and the absence of an upper age limit allows an additional 2 million people to donate. Other countries may wish to consider modification of the upper age criterion to address the effect of an aging population on the blood supply.

Clot formation, vascular repair and hematoma resolution after ICH, a coordinating role for thrombin?

Following intracerebral hemorrhage (ICH) there is a sequential response involving activation of the coagulation cascade/platelet plug formation, vascular repair, upregulation of endogenous defense mechanisms and clot resolution. How these responses are coordinated and modified by different hematoma sizes has received little attention. This paper reviews evidence that thrombin can modulate and may coordinate the components of the endogenous response. This has potential consequences for treatment of ICH with a number of modalities.

Minocycline attenuates brain edema, brain atrophy and neurological deficits after intracerebral hemorrhage.

Evidence suggests that microglia activation contributes to brain injury after intracerebral hemorrhage (ICH). The present study aimed to determine if minocycline, an inhibitor of microglia activation, can reduce brain edema, brain atrophy and neurological deficits after ICH.Male Sprague-Dawley rats received an infusion of 100-microL autologous whole blood into the right basal ganglia. Rats received minocycline or vehicle treatment. There were two sets of experiments in this study. In the first set of experiments, the effects of minocycline on ICH-induced brain edema were examined at day 3. In the second set, behavioral tests were performed at days 1, 3, 7, 14 and 28. Rats were killed at day 28 for brain atrophy measurement (caudate and lateral ventricle size).Minocycline reduced perihematomal brain edema in the ipsilateral basal ganglia (78.8 +/- 0.4 vs. 80.9 +/- 1.1% in the vehicle-treated group, p < 0.01). Minocycline also improved functional outcome. In addition, minocycline reduced brain tissue loss in the ipsilateral caudate (p < 0.01) and ventricular enlargement (p < 0.05).In conclusion, minocycline attenuates ICH-induced brain edema formation, neurological deficits and brain atrophy in rats suggesting an important role of microglia in ICH-related brain injury.

Estrogen reduces iron-mediated brain edema and neuronal death.

Our previous studies found that 17-beta estradiol attenuates edema formation after intracerebral hemorrhage (ICH). As brain iron overload occurs after ICH and contributes to ICH-induced brain injury, the present study examined the effects of estrogen on iron-induced brain injury in vivo and in vitro.There were two sets of experiments in this study. In the first set, male Sprague-Dawley rats were pretreated with 17-beta estradiol or vehicle prior to an intracerebral injection of ferrous iron. Ferrous iron was injected into the right caudate and the rats were killed 24 h later for brain edema measurement. In the second set, primary cultured neurons were pretreated with different doses of 17-beta estradiol or vehicle for 24 h. The cells were then exposed to ferrous iron for 48 h when culture medium was collected for lactate dehydrogenase measurement. Neuronal death was also assessed by live/dead cell assay.Estrogen pretreatment reduced brain water content (p < 0.01) 24 h after iron injection. Estrogen also protected against iron-induced cell death in cultured neurons. Estrogen reduces iron-induced brain edema in vivo and neuronal death in vitro suggesting estrogen could be a potential therapeutic agent for ICH.

Evaluation of the confidential unit exclusion form: the Canadian Blood Services experience.

BACKGROUND: In the mid-1980s, confidential unit exclusion (CUE) was implemented to permit donors unwilling to admit risk factors in screening to exclude their donation from transfusion. With changes in donor behaviour, epidemiology of disease and improvements in testing, many blood establishments have stopped using it. We evaluated its benefit in Canada, and reported its utility in predicting transmissible-disease (TD) and high-risk behaviour. STUDY DESIGN AND METHODS: TD-positive donations and incident cases between 2004 and 2008 were analyzed in CUE-safe and CUE-unsafe designated donations. An anonymous survey of 40,000 donors asked about CUE use and risk factors. RESULTS: There were 7104 (0.15%) donations designated CUE-unsafe of 4,775,044 donations. Most TD-positive donations were designated CUE-safe (1023/1030, 99.32%) with only seven (0.68%) designated CUE-unsafe. Of 95 incident cases, all were designated CUE-safe including three NAT-yield cases (1 HIV and 2 HCV). In the survey, some donors found the CUE difficult to understand [10.5% (first-time), 3.2% (repeat)], only half thought that the blood would still be tested [48.9% (first-time), 45.9% (repeat)], and about a fifth believed that collection site staff could see their designation. No survey respondents who used the CUE admitted to risk behaviour, but about 1% of donors who designated CUE-safe had high-risk behaviours. CONCLUSION: The data do not provide any indication of a safety benefit from CUE, but CUE use results in a small but constant loss of apparently safe donations.

Understanding non-disclosure of deferrable risk: a study of blood donors with a history of intravenous drug use.

Non-disclosure of deferrable risk has received little attention in the literature. We examined deferrable risk (history of intravenous drug use [IVDU]) and donor attitudes towards truthfulness, the screening process and interpretation of the screening question as well as risk profile. Donors negative for all markers with a self-reported history of IVDU (N = 30) and matched controls were identified from an anonymous mail-out survey. In a separate survey, hepatitis C virus (HCV)-positive donors participated in a telephone interview, from which all those with IVDU history (N = 29) were selected plus matched controls (combined total 59 IVDU, 236 controls). IVDU donors, when compared with matched controls, tended to believe that it is OK not to answer truthfully if one believes that her/his blood is safe (18.6% vs. 4.7%) and that some questions are a little too personal (35.6% vs. 21.7%). IVDU donors were more likely than controls to say they failed to acknowledge screening questions appropriately (23% vs. 2.2%) or to agree that IVDU questions are mainly about recent drug taking or sharing needles (29% vs. 11%) even though the screening question asked about IVDU ever without any such qualifiers. IVDU donors were also more likely to have other lifestyle/risk factors such as history of sex with IVDU (45.5% vs. 1.7%). Donors with deferrable IVDU history may rationalise that revealing their status is not necessary and may misinterpret the question. Failure to acknowledge risk behaviour is complex, and some degree of non-disclosure may be an inherent part of pre-donation screening.

Biomechanical study of hepatic portal vein in humans and pigs and its value in liver transplantation.

OBJECTIVE: Our aim was to explore the biomechanical properties of hepatic portal vein (HPV) in humans and pigs to provide evidence for liver xenotransplantation. MATERIALS AND METHODS: The pressure-diameter relationships of HPV from 6 deceased donors and 36 pigs were measured on a biomechanical experimental stand to calculate the elastic modulus and compliance. Each sample sliced into 5-mm frozen sections was stained with hematoxylin-eosin (H&E). Geometric morphological indices were measured with a computer image analysis system. RESULTS: The length, wall thickness, and diameters of HPV in pigs increased from 1 to 6 months (P < .05). There were no significant differences between 6-month-old pigs and adult humans (P > .05). The incremental elastic modulus of the pig HPV increased with age, whereas the compliance decreased. There was no difference in the elastic modulus of HPV between 5- to 6-month-old pigs and humans (P > .05). Also, there was no difference in HPV compliance between 6-month-old pigs and humans (P > .05). CONCLUSIONS: Our results suggested that the biomechanical properties of HPV in 6-month-old pigs were similar to those of humans. From a biomechanical perspective, anastomosis of corresponding HPV from 6-month-old pigs to humans may be feasible in the process of pig-to-human liver xenotransplantation.

Telmisartan versus angiotension-converting enzyme inhibitors in the treatment of hypertension: a meta-analysis of randomized controlled trials.

Telmisartan and angiotensin-converting enzyme inhibitors (ACEIs) are both effective and widely used antihypertensive drugs targeting renin-angiotensin-aldosterone system. The study aimed to estimate the efficacy and tolerability of telmisartan in comparison with different ACEIs as monotherapy in the treatment of hypertension. Cochrane Central Register of Controlled Trials, PubMed and Embase were searched for relevant studies. A meta-analysis of all randomized controlled trials fulfilling the predefined criteria was performed. A random-effect model was used to account for heterogeneity among trials. Twenty-eight randomized controlled trials involving 5157 patients were ultimately identified out of 721 studies. Telmisartan had a greater diastolic blood pressure (DBP) reduction than enalapril (weighted mean difference (WMD) 1.82, 95% confidence interval (CI) 0.66-2.99), ramipril (WMD 3.09, 95% CI 1.94-4.25) and perindopril (WMD 1.48, 95% CI 0.33-2.62). Telmisartan also showed a greater DBP response rate than enalapril (relative risk (RR) 1.15, 95% CI 1.05-1.26), ramipril (RR 1.34, 95% CI 1.11-1.61) and perindopril (RR 1.22, 95% CI 1.05-1.41). There was no statistical difference in DBP reduction or therapeutic response rate between telmisartan and lisinopril (WMD -0.30, 95% CI -0.65 to 0.05; RR 0.99, 95% CI 0.80-1.23, respectively). Telmisartan had fewer drug-related adverse events than enalapril (RR 0.57, 95% CI 0.44-0.74), ramipril (RR 0.44, 95% CI 0.26-0.75), lisinopril (RR 0.70, 95% CI 0.56-0.89) and perindopril (RR 0.52, 95% CI 0.28-0.98). The meta-analysis indicates that telmisartan provides a superior BP control to ACEIs (enalapril, ramipril and perindopril) and has fewer drug-related adverse events and better tolerability in hypertensive patients.

Deferoxamine therapy for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke with very high mortality. Experiments have indicated that clot lysis and iron play an important role in ICH-induced brain injury. Iron overload occurs in the brain after ICH in rats. Intracerebral infusion of iron causes brain edema and neuronal death. Deferoxamine, an iron chelator, is an FDA-approved drug for the treatment of acute iron intoxication and chronic iron overload due to transfusion-dependent anemia. Deferoxamine can rapidly penetrate the blood-brain barrier and accumulate in the brain tissue in significant concentration after systemic administration. We have demonstrated that deferoxamine reduces ICH-induced brain edema, neuronal death, brain atrophy, and neurological deficits. Iron chelation with deferoxamine could be a new therapy for ICH.

Deferoxamine reduces brain swelling in a rat model of hippocampal intracerebral hemorrhage.

In this study, we examine the effects of deferoxamine on hemoglobin-induced brain swelling in a newly developed hippocampal model of intracerebral hemorrhage (ICH). There were 2 parts to the experiments in this study. In the first part, male Sprague-Dawley rats received a 10-microL infusion of either packed red blood cells (RBC), lysed RBC, hemoglobin, ferrous iron, or saline, into the hippocampus. In the second part, rats received a 10-microL infusion of hemoglobin and then were treated with either deferoxamine (100 mg/kg, intraperitoneally, given immediately after hemoglobin injection, then every 12h for 24h) or vehicle. Rats were then killed to obtain hippocampus size and DNA damage measurements. We found that lysed RBC induced marked brain swelling in the hippocampus. Compared to saline, hemoglobin or iron injection caused swelling. Systemic use of deferoxamine reduced hemoglobin-induced brain swelling (6.14 +/- 0.45 vs. 7.11 +/- 0.58 mm2 in the vehicle group, p < 0.05). In addition, deferoxamine reduced hemoglobin-induced DNA damage. These results indicate that iron has a key role in hemoglobin-induced brain swelling. Deferoxamine may be a useful treatment for ICH patients.

Induction of autophagy in rat hippocampus and cultured neurons by iron.

Autophagy occurs in the brain after intracerebral hemorrhage (ICH). Iron is an important factor causing neuronal death and brain atrophy after ICH. In this study, we examined whether iron can induce autophagy in the hippocampus and in cultured neurons. For in vivo studies, rats received an infusion of either saline or ferrous iron into the right hippocampus and were killed 1, 3, or 7 days later for Western blot analysis of microtubule-associated protein light chain-3 (LC3). For in vitro studies, primary cultured cortex neurons from rat embryos were exposed to ferrous iron. Cells were used for Western blot analysis of LC3 and monodansylcadaverine (MDC) staining 24h later. Intrahippocampal injection of ferrous iron resulted in an increased conversion of LC3-I to LC3-II. Exposure of primary cultured neurons to ferrous iron also induced an enhanced conversion of LC3-I to LC3-II. MDC labeling showed an accumulation of MDC in cultured neurons exposed to ferrous iron. These results indicate that autophagy is induced by iron in neurons and that iron-induced autophagy may contribute to brain injury after ICH.

Metallothionein and brain injury after intracerebral hemorrhage.

Metallothioneins (MTs) are metal-binding proteins that can be upregulated in the brain after injury and are associated with neuroprotection. A recent genomics study has shown that brain MT-1 and MT-2 mRNA levels are upregulated following intracerebral hemorrhage (ICH) in rats. Our study examines whether brain MT-1 and MT-2 protein levels are increased after ICH. We also investigated the effect of exogenous MT-1 in perihematomal edema formation in vivo and iron-induced cell death in vitro. We found that MT-1/-2 immunoreactivity in ipsilateral basal ganglia was significantly increased after ICH and exogenous MT-1 attenuated perihematomal edema formation. In addition, MT-1 also reduced cell death induced by iron in cultured astrocytes. These results suggest a role for MT in ICH-induced brain injury, and MT could be a therapeutic target for ICH.

Increase in brain thrombin activity after experimental intracerebral hemorrhage.

Thrombin has been shown to play a major role in brain injury after intracerebral hemorrhage (ICH). In this study, we measured thrombin activity in the perihematomal zone and examined the role of thrombin in ICH-induced brain tissue loss. There were 2 experiments in this study. In the first part, adult male Sprague-Dawley rats received 100 microL of either autologous whole blood or saline. The rats were killed at 1 h or 24 h later for thrombin activity measurement. Thrombin activity was measured using the thrombin-specific chromogenic substrate, S2238. In the second part, rats received a 50-microL intracaudate injection of either thrombin or saline, and the rats were killed at days 1, 3, or 28 for determination of neuronal death and brain tissue loss. We found that brain thrombin activity was elevated in ipsilateral basal ganglia 1 h after ICH. Intracerebral injection of thrombin rather than saline caused significant neuronal death at days 1 and 3, and resulted in significant brain tissue loss at day 28. These results suggest that thrombin inhibition in the acute phase may reduce ICH-induced brain damage.