Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age

Background: Taking an advantage of the high sensitivity of 3D T2*‐weighted gradient‐recalled‐echo (GRE) imaging to cerebral microbleeds, we investigated the relationship between cerebral microbleeds and leukoaraiosis. Methods: Participants aged 40 years or more have been evaluated for the presence of cerebral microbleeds using 3D T2*‐GRE sequence since 2006. The severity of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on fluid attenuated inversion recovery images was assessed using Fazekas rating scales. Multivariate logistic regression analyses were conducted after adjustment for stroke subtype, age, PVH, DWMH, hypertension, dementia, and use of platelet aggregation inhibitors. Additionally, we examined the association between cerebral microbleeds and other covariates using a Pearson’s correlation analysis. Results: Amongst 389 patients, 67 patients had a single microbleed and 93 had multiple microbleeds. The prevalence of microbleeds was 83% amongst 53 patients with intracerebral hemorrhage (ICH), 49% amongst 173 with infarction, and 20% amongst 163 without any type of stroke. In the multivariate analyses, the odds ratio (95% CIs) of microbleed detection was 10.1, (4.12–24.8) for ICH, 2.33 (1.12–4.85) for atherosclerotic infarction, 1.66 (1.10–2.48) for PVH, and 1.49 (1.02–2.19) for DWMH. In the Pearson’s correlation analysis, cerebral microbleeds were closely related to PVH (Pearson’s correlation coefficient; 0.48) and DWMH (0.37), compared with age (0.16). Conclusions: High‐grade PVH, high‐grade DWMH, ICH, and atherosclerotic infarction were significantly independent predictors for cerebral microbleeds. In addition, we found that the grades of PVH and DWMH have a closer association with the number of cerebral microbleeds than age.     

Acetaminophen-induced hepatotoxicity in a liver tissue model consisting of primary hepatocytes assembling around an endothelial cell network

Primary hepatocytes have been used in drug development for the evaluation of hepatotoxicity of candidate compounds. However, the rapid depression of their hepatic characters in vitro must be improved to predict toxicity with higher accuracy. We have hypothesized that a well organized tissue construct that includes nonparenchymal cells and appropriate scaffold material(s) could overcome this difficulty by remediating the viability and physiological function of primary hepatocytes. In this study, we constructed an in vitro liver tissue model, consisting of mouse primary hepatocytes assembling around an endothelial cell network on Engelbreth-Holm-Swarm gel, and examined its response to acetaminophen treatment. The increase in lactate dehydrogenase release after the exposure to acetaminophen was induced earlier in the liver tissue model than in monolayer hepatocytes alone, suggesting that the tissue model was more sensitive to an acetaminophen-induced toxicity. On the basis of our results, we conclude that liver tissue models of this kind may enhance the responses of hepatocytes against xenobiotics via the maintenance of hepatic genes and functions such as cytochrome P450s. These findings will contribute to the development of more accurate systems for evaluating hepatotoxicity.     

Two patients with ovarian cancer refractory to cisplatin-based chemotherapy managed by a new combination chemotherapy with irinotecan hydrochloride and mitomycin-C

Two women with ovarian cancer refractory to cisplatin-based chemotherapy were managed by a new combination chemotherapy consisting of 2 courses of irinotecan hydrochloride and mitomycin-C (CPT-M therapy). One course of therapy consisted of irinotecan hydrochloride (100 mg/m²) and mitomycin-C (5 mg/m²) given 3 times at 2-week intervals. The second course was started 4 weeks after completion of the first course. Treatment effects, as well as disease conditions, were evaluated with imaging studies and by serially monitoring serum carcinoembryonic antigen or carbohydrate antigen-125 levels. The first patient was a 61-year-old woman who underwent surgery for stage IIIc mucinous cystadenocarcinoma, and whose residual tumor in the retroperitoneal lymph nodes after surgery did not respond to 2 types of cisplatin-based chemotherapy. The second patient was a 47-year-old woman treated for stage IIIc serous cystadenocarcinoma, whose multiple liver metastases failed to respond either to combination chemotherapy with irinotecan hydrochloride and cisplatin, or to transcatheter arterial chemoembolization, CPT-M therapy showed some usefulness for ovarian cancer refractory to cisplatin-based chemotherapy when used as third-line chemotherapy in these 2 patients who achieved partial responses with tolerable toxicities, although the duration of the response was short. Further studies on the effectiveness of the CPT-M therapy, including dose escalation, are needed.     

Effect of tritiated water on female germ cells: mouse oocyte killing and RBE

The relative biological effectiveness (RBE) of tritiated water (HTO) was investigated using mouse immature oocytes. Juvenile mice, having immature oocytes that are highly sensitive to radiation killing, were exposed to HTO, 137Cs gamma rays, 60Co gamma rays, or 252Cf fission neutrons. The 137Cs gamma rays were used to simulate the changing dose rate (but not the radiation quality) received from HTO (see section 2). On the 14th day after birth, female ICR strain mice were injected once in the abdominal cavity with HTO at levels of 1.70, 3.40, 6.81, or 10.21 MBq/10g body weight, and their ovaries were removed 2 weeks after the injection. (The cumulative doses are equivalent to 0.039, 0.077, 0.159 and 0.246 Gy, respectively.) The survival rate of oocytes was determined by light microscopy inspection of serial sections, and the results of the different exposures were compared. The number of surviving oocytes decreased exponentially with increasing dose of HTO or 137Cs, and RBEs of HTO compared to 137Cs gamma rays ranged from 1.1 to 3.5. The relative effectiveness of the different types of radiations was compared, and the results of the comparison, in order of increasing effectiveness, was 137Cs, 60Co, HTO, and 252Cf. The RBE of 252Cf compared to 60Co gamma rays ranged from 1.6 to 3.5.     

Low-frequency electric cortical stimulation has an inhibitory effect on epileptic focus in mesial temporal lobe epilepsy

PURPOSE: This study was conducted to investigate the effect of low-frequency electric cortical stimulation on epileptic focus in humans. METHODS: We stimulated the epileptic focus in a patient with medically intractable mesial temporal lobe epilepsy (MTLE) by means of subdural electrodes and evaluated the change in the number of interictal epileptiform discharges. We used biphasic electric current of 0.3-ms duration presented at 0.9-Hz frequency for 250 s, comparing stimulus intensity of 7.5, 2, and 0.5 mA. RESULTS: Interictal epileptiform discharges at the ictal focus occurred less frequently after the stimulation with the intensity of 0.5 mA. With the intensity of 7.5 mA and 2.0 mA, however, habitual auras were elicited by the stimulation, and afterdischarges were seen on the cortical EEG. CONCLUSIONS: Low-frequency, low-intensity electric cortical stimulation could produce inhibitory effects on epileptic activity. At the same time, however, a caution for possible induction of EEG seizures is needed, even when applying low-frequency electric stimulation.