Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective randomized controlled pilot study.

This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD). Thirty-two T2D patients with NAFLD diagnosed by computed tomography or abdominal sonography were recruited. Participants were randomly assigned to receive either luseogliflozin (2.5 mg, newly administered) or metformin (1500 mg, newly or additionally administrated). Data on the liver-to-spleen attenuation ratio (L/S), visceral fat area, body mass index, glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), fasting plasma glucose, C-peptide immunoreactivity (CPR), and CPR index were collected at baseline and after 6 months. The change in L/S was significantly greater in the luseogliflozin group than in the metformin group. Similarly, the changes in the visceral fat area, HbA1c, and body mass index were significantly greater in the luseogliflozin group than in the metformin group. The changes in ALT, fasting glucose, CPR, and CPR index were not significant in both groups. In conclusion, luseogliflozin significantly reduced liver fat deposition as compared to metformin, which may indicate clinical relevant benefits for NAFLD.

Topical cholesterol treatment ameliorates hapten-evoked cutaneous hypersensitivity by sustaining expression of 11ß-HSD1 in epidermis.

Changes in the stratum corneum extracellular matrix impair epidermal barrier function and may cause dermatoses. The aim of this study was to examine the effect of exogenous cholesterol application on skin barrier function and cutaneous inflammation. Skin barrier-disrupted or hapten-stimulated mice were treated with topical cholesterol. The effect of topical cholesterol application on an oxazolone (OXA)-induced hypersensitivity reaction was evaluated. Topical application of cholesterol efficiently decreased transepidermal water loss in areas of barrier-disrupted skin and ameliorated OXA-induced cutaneous hypersensitivity. These favourable effects may have resulted from sustained expression of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) in the cholesterol-treated skin. As 11ß-HSD1 is known to produce active cortisol, topical cholesterol may attenuate contact hypersensitivity by normalizing secretion of hormonally active cortisol from the skin.

Clinical and pathological improvement in stroke-prone spontaneous hypertensive rats related to the pleiotropic effect of cilostazol.

BACKGROUND AND PURPOSE: Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R). METHODS: Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1Rß expression in the hippocampus was assessed by Western blotting. RESULTS: The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (P<0.05) in the memory-related IGF-1R-positive ratio and IGF-1Rß expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels. CONCLUSIONS: The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and spatial cognitive functions. The increase of IGF-1R-positive cells in the hippocampal CA1 region could partly explain the preservation of spatial cognitive function in stroke-prone spontaneously hypertensive rats.

Aging of the Vascular System and Neural Diseases.

Vertebrates have acquired complex high-order functions facilitated by the dispersion of vascular and neural networks to every corner of the body. Blood vessels deliver oxygen and nutrients to all cells and provide essential transport systems for removing waste products. For these functions, tissue vascularization must be spatiotemporally appropriate. Recent studies revealed that blood vessels create a tissue-specific niche, thus attracting attention as biologically active sites for tissue development. Each capillary network is critical for maintaining proper brain function because age-related and disease-related impairment of cognitive function is associated with the loss or diminishment of brain capillaries. This review article highlights how structural and functional alterations in the brain vessels may change with age and neurogenerative diseases. Capillaries are also responsible for filtering toxic byproducts, providing an appropriate vascular environment for neuronal function. Accumulation of amyloid ß is a key event in Alzheimer's disease pathogenesis. Recent studies have focused on associations reported between Alzheimer's disease and vascular aging. Furthermore, the glymphatic system and meningeal lymphatic systems contribute to a functional unit for clearance of amyloid ß from the brain from the central nervous system into the cervical lymph nodes. This review article will also focus on recent advances in stem cell therapies that aim at repopulation or regeneration of a degenerating vascular system for neural diseases.

[A case of rectal cancer with lung metastases responding to cetuximab].

We report a 73-year-old male patient who underwent low anterior resection for rectal cancer (Stage IIIb). Nine months after the surgery, multiple metastases of liver, lung, brain and lymph node were detected. He was treated with FOLFOX4 and FOLFIRI though lung metastases progressed and caused dyspnea. Cetuximab plus irinotecan therapy was dramatically effective, which improved his quality of life for over 10 months.

Descriptive Sensory Traits of Cooked Eggs Laid from Hens Fed Rice Grain.

Descriptive sensory characteristics of eggs produced by conventional corn-based feeding and unhulled whole rice grain-feeding were compared in two cooking procedures using a trained panel. Rice-feeding significantly decreased brothy and roasted odor in eggs cooked into half-cooked egg yolks, and decreased the creamy odor, smoothness and moisture of eggs cooked into custard puddings. However, a statistical interaction between rice-feeding and production farm was not observed in every sensory attribute. These findings indicated that replacing corn with unhulled whole rice grain in diets for laying hens alters the sensory attributes of eggs.

Investigating the Relationship between Morning Glycemic Variability and Patient Characteristics Using Continuous Glucose Monitoring Data in Patients with Type 2 Diabetes.

Objective To investigate the relationship between patient characteristics and morning glycemic variability. Methods We retrospectively evaluated 106 patients with type 2 diabetes who underwent continuous glucose monitoring during admission. The highest postprandial glucose level (within 3 hours after breakfast; 'highest level'), the time from the start of breakfast to the highest postprandial glucose level ('highest time'), the difference between the pre-breakfast and highest postprandial breakfast glucose level ('increase'), the area under the curve (AUC; ≥180 mg/dL) for the glycemic variability within 3 hours after breakfast ('morning AUC'), and the post-breakfast glucose gradient ('gradient') were calculated. We analyzed the associations between these factors and nocturnal hypoglycemia and the patients' characteristics by using a regression analysis. Results After stepwise multivariate adjustment, significant independent associations were found between 'highest level' and high age, low BMI, and high HbA1c; 'highest time' and high HbA1c, low C-peptide immunoreactivity (CPR), and low fasting plasma glucose (FPG); the 'increase' and high age, low BMI, high HbA1c, low FPG and hypoglycemia; 'morning AUC' and high age, high HbA1c and hypoglycemia; and 'gradient' and long duration of diabetes and low BMI. Conclusion Higher age and lower BMI are associated with higher 'highest' and 'increase' levels. Higher HbA1c levels were linked to a longer 'highest time', and longer durations of the diabetes, while lower BMI values were related to a higher 'gradient'.

[The efficacy of continuous hepatic arterial infusion therapy in association with multidisciplinary treatment of two late stage cancer patients].

With continuous hepatic artery infusion (HAI), 2 cases including multiple hepatic lesions became lesion free, meaning a complete response (CR) to this treatment. Besides chemotherapy, we controlled the diet with a healthy food guidance plan containing low salt & fat, and a lot of juice. The 1st case is a 63-year-old female, suffered from simultaneous multisided metastatic liver tumor from advanced rectal cancer. Four months after the low anterior resection of the rectum, we recommended the diet 2 months later. The patient was treated by a 24-hour continuous HAI and the metastatic lesion disappeared (CR) within 8 weeks. The 2nd case is a 58-year-old male with hepatocellular carcinoma, suffered from 4 recurrent tumors in the retained liver. After 11 treatments of HAI, the tumors disappeared completely, and he has survived for 11.5 years. We believe it was due to the immunoactivation of functional foods such as unmilled-grain, fresh vegetables and fruits, seaweeds, honey, and mushrooms with the restriction of animal fat and meat intake. Dietary guidance in metabolic-nourishment therapy is very useful in the treatment of far advanced cancer patients.

Evaluation of safety of insulin degludec on undergoing total colonoscopy using continuous glucose monitoring.

AIMS/INTRODUCTION: There is little information regarding how to use insulin degludec (D) when diabetic patients are preparing for total colonoscopy (TCS). MATERIALS AND METHODS: A total of 12 patients with type 2 diabetes treated with insulin D and scheduled to undergo TCS were enrolled in the present study. A continuous glucose monitoring device was attached to each patient for 4 days, from two evenings before TCS to the morning after the procedure. The patients fasted for 24 h, starting after 18.00 h the day before TCS. Insulin D was only discontinued the morning of the day TCS was carried out. RESULTS: No patients experienced hypoglycemia during the daytime fasting period (08.00-18.00 h the day of TCS); the hypoglycemic index, mean glucose level, and standard deviation were 0, 141.3 ± 31.5 mg/dL and 15.6 ± 6.5 mg/dL. The mean glucose level and standard deviation during the daytime fasting period were significantly lower than during the daytime control period (08.00-18.00 h the day before TCS; P = 0.003, P = 0.001, respectively). The mean fasting glucose and fasting plasma glucose levels were significantly correlated (r = 0.78, P = 0.002), as were both the mean glucose level and standard deviation during the daytime control period, and the change in the mean glucose level (fasting period minus control period; r = -0.79, P = 0.002, and r = -0.69, P = 0.01, respectively). CONCLUSIONS: Patients can safely undergo TCS when insulin D is discontinued only once on the day of the procedure.

Hypoglycemia and glycemic variability are associated with mortality in non-intensive care unit hospitalized infectious disease patients with diabetes mellitus.

AIMS/INTRODUCTION: We aimed to identify factors - glycemic control, reactive inflammatory biomarkers or vital signs - associated with mortality in diabetic patients admitted to hospital for various infections (non-intensive care unit). MATERIALS AND METHODS: We retrospectively analyzed the cases of 620 diabetic patients admitted to hospital for various infections (non-intensive care unit) who underwent glucose monitoring >3 times per day. We extracted data regarding reactive inflammatory biomarkers and vital signs recorded on day 1 of hospital stay, and data on bacteremia and hypoglycemia status, glycemic variability (GV; coefficient of variation and standard deviation) and mean glucose concentrations during the entire hospital stay. Univariate and stepwise multivariate logistic regression analyses were carried out to determine the association between these factors and mortality. RESULTS: The mortality rate was 10.1%. Reactive inflammatory biomarkers, vital signs and bacteremia were not associated with mortality. According to the results of the adjusted analysis, hypoglycemia showed a significant positive association with mortality, increasing death risk by 266% (odds ratio [OR] 2.66, 95% confidence interval [95% CI] 1.22-5.83; P = 0.0006). High coefficient of variation and standard deviation values were significantly associated with increased mortality, increasing death risk by 18% (OR 1.18, 95% CI 1.01-1.38; P = 0.03) and 9% (OR 1.09, 95% CI 1.01-1.18; P = 0.03), respectively. Mean glucose concentrations were also significantly associated with mortality, increasing death risk by 5% (OR 1.05, 95% CI 1.02-1.08; P = 0.0008). CONCLUSIONS: Glycemic indices (especially hypoglycemia and GV), rather than reactive inflammatory biomarkers or vital signs, were associated with mortality in non-intensive care unit diabetes mellitus patients with infections.

Major Increases between Pre- and Post-breakfast Glucose Levels May Predict Nocturnal Hypoglycemia in Type 2 Diabetes.

Objective The aim of this study was to determine whether nocturnal hypoglycemia may be predicted according to morning glucose levels. Methods We retrospectively evaluated 106 patients with type 2 diabetes who underwent continuous glucose monitoring during admission. The pre-breakfast glucose level (Pre-breakfast level), highest postprandial glucose level within 3 hours after breakfast (Highest level), time from the start of breakfast to the highest postprandial glucose level (Highest time), difference between the pre-breakfast and highest postprandial breakfast glucose levels (Increase), area under the glucose curve (≥180 mg/dL) within 3 hours after breakfast (Morning AUC), post-breakfast glucose gradient (Gradient), and the increase-to-pre-breakfast ratio (Increase/Pre-breakfast) were calculated. The subjects were divided into hypoglycemic and non-hypoglycemic patients and compared for the above parameters using the t-test. A receiver operating characteristic analysis was used to determine the optimal cut-off values to predict nocturnal hypoglycemia (Hypoglycemia). Results Twenty-eight patients (26.4%) had hypoglycemia. The Pre-breakfast levels were significantly lower in patients with hypoglycemia than those without (p=0.03). The Increases were significantly higher in patients with hypoglycemia than those without (p=0.047). The Increase/Pre-breakfast ratio were significantly larger in patients with hypoglycemia than those without (p=0.0002). Their cut-off values were as follows (level, sensitivity, specificity, and area under the curve): 123 mg/dL, 0.89, 0.55, and 0.78 (p<0.0001); 90.5 mg/dL, 0.75, 0.64, and 0.76 (p<0.0001); and 90.2%, 0.75, 0.76, and 0.78 (p<0.0001), respectively. Conclusion Major increases between the pre- and post-breakfast glucose levels may predict nocturnal hypoglycemia in patients with type 2 diabetes.

Intraocular pressure lowering effect of brinzolamide 1.0% as adjunctive therapy to latanoprost 0.005% in patients with open angle glaucoma or ocular hypertension: an uncontrolled, open-label study.

PURPOSE: A prospective study was conducted to evaluate the intraocular pressure (IOP) lowering effect of brinzolamide 1.0% ophthalmic suspension as an adjunctive therapy with latanoprost 0.005% ophthalmic solution in patients with open angle glaucoma or ocular hypertension. PATIENTS AND METHODS: Fourteen patients with open angle glaucoma (OAG) or ocular hypertension (OH) who had been using latanoprost 0.005% for more than 6 months were initiated on adjunctive brinzolamide therapy. The IOP values at 1 month, 2 months, and 3 months were compared with those measured immediately before adding brinzolamide to the regimen (baseline). The incidence of adverse events such as conjunctival hyperemia and corneal epithelial defect were also examined. RESULTS: The baseline IOP was 21.1 +/- 4.8 mmHg (mean +/- standard deviation). After 1 month, 2 months, and 3 months of therapy IOP was 16.9 +/- 4.5 mmHg, 16.6 +/- 4.0 mmHg, and 15.9 +/- 3.1 mmHg, respectively, showing significant reductions in IOP at all the measuring time-points during the study compared with the baseline value (p < 0.01). Conjunctival hyperemia developed in one patient after 1 month and in another after 2 months; however, both were mild, and therapy was continued. Corneal epithelium defect was observed in 3 patients. One of them had mild defect before brinzolamide was added to the regimen. Increase of eye discharge was seen in one patient. No serious side effects were otherwise observed. CONCLUSION: The addition of brinzolamide to a latanoprost 0.005% regimen may further lower intraocular pressure in patients with open angle glaucoma or ocular hypertension.

[Comprehensive study on the prevention of food poisoning through the investigation of an affected hospital food service facility].

OBJECTIVES: In Japan, more than 20,000 people suffer from various types of food poisoning annually. In this paper, we discuss the prevention of food poisoning in hospital food service facilities from the perspective of hygiene management and organizational behavior. METHODS: We inspected the kitchen environment and the meal preparation process in a hospital food service facility in Japan that had been the site of a food poisoning incident. To clarify the present state of hygiene management, interviews were conducted with both the head of the nutrition and food service section and the administrative manager. In addition, questionnaires were distributed to the food service staff to assess their level of satisfaction with the working environment. RESULTS: The facility had been built about 10 years previously and was well maintained. Meal preparations were performed according to the operation manual, and education and training for the food service staff were carried out daily. No problems were evident regarding hygiene management. However, concerning organizational behavior, the satisfaction level of the staff was found to be relatively low, which may have led to a reduction in their organizational commitment and a decrease in their performance. CONCLUSIONS: To aid in the prevention of food poisoning incidents in hospital food service facilities, it is essential not only to conduct standard hygiene management and training, but also to consider the organizational behavior of the food service staff.

An integrated inpatient therapy for type 1 diabetic females with bulimia nervosa: a 3-year follow-up study.

OBJECTIVE: To describe an "integrated inpatient therapy" for type 1 diabetic patients with recurrent binge eating and to assess its effectiveness for females with bulimia nervosa (BN). METHODS: At the first visit to our outpatient clinic for treatment of an eating disorder and diabetes, type 1 diabetic females with BN underwent single session "outpatient counseling." All patients then returned to the referring physician for further treatment and observation. None of the BN patients had the minimum expected 1% fall in HbA1c and all were therefore encouraged to undergo our "integrated inpatient therapy." However, only patients accepting inpatient treatment on their own volition were admitted. An "INPATIENT" group (n=9) consisted of those who underwent inpatient therapy and had a 3-year follow-up period after discharge. The clinical course was assessed by the HbA1c and BMI course and by comparison of psychological/behavioral factors between baseline and follow-up. For reference, the clinical course of a "NON-INPATIENT" group (n=10), who did not have the inpatient therapy for at least 2 years after first visit, was also assessed. RESULTS: The "INPATIENTs" had significantly lower HbA1c; lower psychological test scores related to eating disorder psychopathology, depressiveness, and anxiety-proneness; a reduced frequency and amount of binge eating; and fewer patients exhibited purging behaviors at follow-up than at first visit. At follow-up, seven (78%) "INPATIENTs" no longer fulfilled any criterion for clinical or subclinical eating disorders. The "NON-INPATIENTs" had no significant improvement. CONCLUSION: The findings give interesting insights into the possibilities of "integrated inpatient therapy" as an effective treatment for type 1 diabetic females with BN.

[Transient dysfunction of the retinal ganglion cells after laser in situ keratomileusis].

PURPOSE: To evaluate the influence of high intraocular pressure(IOP) on the retinal ganglion cell function induced by suction during laser in situ keratomileusis(LASIK) using Frequency Doubling Technology(FDT). METHODS: Twenty-seven eyes of 15 patients were studied. Threshold values of 19 targeted areas, mean deviation(MD), and pattern standard deviation (PSD) were measured before LASIK, and 2 hours, 1 day, and 1 week after LASIK. These parameters obtained by N-30 program of FDT were compared between before and after LASIK. RESULTS: Significant decrease of MD and threshold value in all areas was recognized at 2 hours, but MD and threshold value in 6 of the 19 areas showed significant increase at 24 hours. Significant increase of PSD value at 2 hours was recognized. After 7 days, there were no significant differences in any parameters between before and after LASIK. CONCLUSION: These results indicated that a transient dysfunction of the magnocellular pathway might be induced by high IOP during LASIK procedure.

[The application of cross-linked hyaluronate hydrogel to trabeculectomy].

PURPOSE: We investigated the possibility of applying cross-linked hyaluronate hydrogel (HA gel) during trabeculectomy in rabbit eyes. SUBJECTS AND METHODS: 1. We injected 0.9% salt solution (n = 3), Opegan-HI (n = 3), or HA gel (n = 3) into the subconjunctiva to make a follicle, and investigated its size. 2. After making a limbal-based conjunctival flap and a scleral flap, we injected HA gel or 0.9% salt solution into the subconjunctiva of rabbit eyes and sutured each flap (n = 4 each). Three weeks after the operation, we incised the conjunctiva and investigated the case of peeling away the conjunctival flap or the scleral flap. 3. We performed trabeculectomy with and without subconjunctival HA gel (n = 7 and 6, respectively), and compared the reduction of intraocular pressure between the two groups. RESULTS: The results showed that the formation of the follicle was excellent and it was easy to peel away the adhesion. The reduction of intraocular pressure was statistically significant 4 weeks after the operation in which the HA gel was used. CONCLUSIONS: It could be useful to apply HA gel in trabeculectomy to prevent adhesion.

In vivo optical imaging correlates with improvement of cerebral ischemia treated by intravenous bone marrow stromal cells (BMSCs) and edaravone.

OBJECTIVE: Recent studies show that modern In vivo optical imaging can detect matrix metallopeptidase (MMP) activation in the ischemic brain. In this study, we analyze the protective effects of bone marrow stromal cells (BMSCs) and edaravone (EDA) against tissue plasminogen activator (tPA) risk in the ischemic brain with In vivo optical fluorescence MMP imaging. METHODS: At 48 hours after 60 minutes of transient middle cerebral artery occlusion (tMCAO) with tPA, C57BL/6J mice were subjected to motor function analysis, In vivo and ex vivo optical imaging for MMP activation, gelatin zymography, and double immunofluorescent analyses with or without intravenous BMSC transplantation and the intravenous free radical scavenger EDA. RESULTS: In vivo fluorescent signals for MMP were detected over the heads of living mice 48 hours after tMCAO; the strongest were in the tPA group, which were reduced by BMSC or EDA treatment. These In vivo data were confirmed by ex vivo fluorescence imaging. While massive intracerebral hemorrhages were observed in the ischemic hemispheres of the tPA group, only slight hemorrhages were found in the tPA/BMSC, tPA/EDA, and EDA groups. Gelatin zymography showed the strongest MMP-9 activation in the tPA group after tMCAO, which was reduced by BMSC or EDA treatment. CONCLUSION: The present study provides a correlation between In vivo optical imaging of MMP activation and the improvement of ischemic brain damage caused by tPA after tMCAO and treated by BMSC and EDA.

Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in Alzheimer's disease.

OBJECTIVES: To examine and compare the pleiotropic effects on oxidative stress and metabolic signaling pathways of atorvastatin and pitavastatin in mouse model of Alzheimer's disease (AD). METHODS: We gave the transgenic (Tg) mice either atorvastatin or pitavastatin from 5-20 months (M) of age, and performed immunohistological analysis [4-hydroxy-2-nonenal (4-HNE)-positive, advanced glycation end products (AGEs), low-density lipoprotein receptor (LDL-R)-positive neurons, apolipoprotein E (ApoE)-positive senile plaque (SP), and insulin receptor (IR)-positive endothelium], and biochemistry analysis (adiponectin and leptin). RESULTS: The numbers of 4-HNE- and AGE-positive neurons and the sum of ApoE-positive SP size progressively increased with age in amyloid precursor protein (APP)-Tg mice, while the amount of IR-positive endothelium and the number of LDL-R-positive neurons decreased. Adiponectin and leptin serum levels were lower in APP-Tg mice than in non-Tg mice. Treatment with statins reduced the number of AGE-positive neurons from as early as 10 M, preserved the numbers of 4-HNE- and LDL-R-positive neurons and the amount of IR-positive endothelium at 15 M, and reduced the sum of ApoE-positive SP size and adiponectin serum level at 20 M. DISCUSSION: Atorvastatin and pitavastatin reduced the level of oxidative stress, as revealed by the presence of 4-HNE and AGE, in AD mouse brains, and that treatment with statins improves insulin signaling and LDL-R/ApoE systems. The beneficial effects of these statins may be associated with direct pleiotropic effects on AD mouse brains, indirect effects through improving the serum adiponectin/leptin balance, or both.

Combination benefit of amlodipine plus atorvastatin treatment on carotid atherosclerosis in Zucker metabolic rats.

OBJECTIVES: Obesity is the major risk factor for metabolic syndrome and atherosclerotic cardiocerebrovascular diseases. METHODS: We studied effects of amlodipine, atorvastatin, and their combination on carotid arteriosclerotic processes in a metabolic syndrome model of Zucker fatty rats. Zucker fatty rats were treated with vehicle, amlodipine, atorvastatin, or combination amlodipine plus atorvastatin for 28 days. RESULTS: Compared with the single treatment with amlodipine or atorvastatin, the combination of amlodipine plus atorvastatin treatment prevented arteriosclerotic processes, and induced a strong recovery of Sirtuin1 (Sirt1) expression and a marked reduction in p53, p21, and monocyte chemoattractant protein-1 (MCP-1). DISCUSSION: As Sirt1 is a longevity gene that prevents endothelial atherosclerotic processes, and p53, p21, and MCP-1 play pivotal roles in the initiation and development of atherosclerosis, these data suggest a strong synergistic benefit of combination therapy with amlodipine and atorvastatin for preventing atherosclerotic processes, and potentially reducing the clinical risk of cerebrovascular events in metabolic obesity patients.

[iPS cell transplantation for ischemic brain].

Stroke is a major neurologic disorder. Induced pluripotent stem (iPS) cells can be produced from basically any part of patients, with high reproduction ability and pluripotency to differentiate into various types of cells, suggesting that iPS cells can provide a hopeful therapy for cell transplantation. However, transplantation of iPS cells into ischemic brain has not been reported. In this study, we showed that the iPS cells fate in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells (5×10(5)) were transplanted into ipsilateral striatum and cortex at 24 h after 30 mins of transient MCAO. Behavioral and histologic analyses were performed at 28 day after the cell transplantation. To our surprise, the transplanted iPS cells expanded and formed much larger tumors in mice postischemic brain than in sham-operated brain. The clinical recovery of the MCAO+iPS group was delayed as compared with the MCAO+PBS (phosphate-buffered saline) group. iPS cells formed tridermal teratoma, but could supply a great number of Dcx-positive neuroblasts and a few mature neurons in the ischemic lesion. iPS cells have a promising potential to provide neural cells after ischemic brain injury, if tumorigenesis is properly controlled.