Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue.

The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated ß-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.

Interconnection between Mixed-Handedness, Digit Ratios and Hand and Foot Minor Anomalies in Predicting Schizophrenia.

BACKGROUND: According to the neurodevelopmental theory, brain structuring early markers could be seen in different body parts as minor physical anomalies. Alongside minor physical anomalies, handedness and index to ring finger ratio are brain development indicators, specifically brain lateralization. Studies are consentient about the association of these findings with schizophrenia, though there is inconsistency about individual anatomical regions' contribution. We proposed that handedness in combination with morphological indicators of early brain development could be sensitive and specific in predicting schizophrenia status. SUBJECTS AND METHODS: Within the list for the assessment of schizophrenia patients and normal controls of the Caucasian race were seven categorical minor physical anomalies of hand and feet, handedness, and index to ring finger ratio. In this cross-sectional study the examinees were recruited from January 2012 to December 2015. RESULTS: Forced-entry binary logistic regression model correctly classified 86.5% of patients and 99.2% of the comparison subjects with a 92.8% overall accuracy. Mixed-handedness, hyperconvex fingernails, big gap between 1st and 2nd toe, and partial syndactyly of 2nd and 3rd toe made a significant independent contribution to the patient-control prediction group status. Furthermore, these items showed a significant correlation with the predictors of the head from the previous study. CONCLUSION: Briefly, the limb components, assessed independently of other body regions, proved to be worthy as schizophrenia predictors.

Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue-Relationship between AMPK and Glycolysis.

Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5'-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1-PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase-G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.

Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles.

INTRODUCTION: Metabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lipid storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT). MATERIAL AND METHODS: Gene and protein expression levels of leptin, adiponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and "at risk" groups. RESULTS: Compared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of "at risk" groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of "at risk" obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin. CONCLUSIONS: Low adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.

Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.

One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.

Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity.

Metabolic reprogramming that favors high glycolytic flux with lactate production in normoxia is among cancer hallmarks. Lactate is an essential oncometabolite regulating cellular redox homeostasis, energy substrate partitioning, and intracellular signaling. Moreover, malignant phenotype's chief characteristics are dependent on the interaction between cancer cells and their microenvironment. In breast cancer, mammary adipocytes represent an essential cellular component of the tumor milieu. We analyzed lactate concentration, lactate dehydrogenase (LDH) activity, and isozyme pattern, and LDHA/LDHB protein expression and tissue localization in paired biopsies of breast cancer tissue and cancer-associated adipose tissue in normal-weight and overweight/obese premenopausal women, compared to benign breast tumor tissue and adipose tissue in normal-weight and overweight/obese premenopausal women. We show that higher lactate concentration in cancer tissue is concomitant with a shift in isozyme pattern towards the "muscle-type" LDH and corresponding LDHA and LDHB protein expression changes. In contrast, significantly higher LDH activity in cancer-associated adipose tissue seems to be directed towards lactate oxidation. Moreover, localization patterns of LDH isoforms varied substantially across different areas of breast cancer tissue. Invasive front of the tumor showed cell-specific protein localization of LDHA in breast cancer cells and LDHB in cancer-associated adipocytes. The results suggest a specific, lactate-centric relationship between cancer tissue and cancer-associated adipose tissue and indicate how cancer-adipose tissue cross-talk may be influenced by obesity in premenopausal women.

Anthropometric and somatotype characteristics of women with breast cancer / Características antropométricas y somatotipos de mujeres con cáncer de mama

Inconsistent data are available on the relation between breast cancer, adiposity, body size and somatotype. The aim of our study was to compare anthropometric characteristics, body composition and somatotype between breast cancer patients and healthy controls. Study group consisted of 106 breast cancer patients while control group consisted of 100 healthy women who underwent 29 anthropometric measurements. Women with breast cancer expressed more male anthropometric features like higher stature (160.75±6.91 vs. 158.17±4.89 cm, p=0.020), shorter trunk (sitting height in premenopausal: 84.94±5.07 vs. 88.50±3.84 cm, p=0.001 and postmenopausal women: 81.96±6.08 vs. 85.19±3.36 cm, p=0.001), narrower hips (29.20±3.78 vs. 32.24±1.78 cm, p=0.000), higher biepicondylar diameter of humerus (premenopausal: 6.64±0.71 vs. 6.31±0.42 cm, p=0.012; postmenopausal: 6.95±0.63 vs. 6.54±0.49 cm, p=0.000), larger upper- and forearm as well as upper thigh circumferences followed by lower biceps and higher thigh skinfold thicknesses. They also had significantly lower endomorphy (premenopausal: 5.84±1.78 vs. 6.55±0.96, p=0.027; postmenopausal: 6.89±1.52 vs. 7.37±0.86, p=0.035) and significantly higher ectomorphy (premenopausal: 2.05±1.30 vs. 1.41±0.99, p=0.018; postmenopausal: 1.06±0.90 vs. 0.68±0.56, p=0.007), as well as higher mesomorphy only in postmenopausal women (6.10±2.04 vs. 5.37±1.34, p=0.022). Most represented somatotype among breast cancer patients was endomorph-mesomorph while the most healthy controls were mesomorphic endomorph. Android body type increases the risk of development of breast cancer. Indicators of skeletal dimensions, muscle volume and peripheral adiposity had better predictive value over markers of central and overall adiposity.

La información en la literatura es variable sobre la relación entre el cáncer de mama, la adiposidad, el tamaño corporal y somatotipo de las mujeres. El objetivo de este estudio fue comparar las características antropométricas, la composición corporal y el somatotipo entre pacientes con cáncer de mama y controles sanos. El grupo de estudio consistió en 106 pacientes con cáncer de mama y el grupo de control de 100 mujeres sanas que se sometieron a 29 mediciones antropométricas. Las mujeres con cáncer de mama tenían mayor cantidad características antropométricas masculinas, tal como una estatura más alta (160.75±6.91 vs. 158.17±4.89 cm, p = 0.020), tronco más corto (altura sentada en premenopáusica: 84.94±5.07 vs. 88.50±3.84 cm, p = 0.001 y mujeres posmenopáusicas: 81.96±6.08 vs. 85.19±3.36 cm, p = 0.001), caderas más estrechas (29.20±3.78 vs. 32.24±1.78 cm, p = 0.000), mayor diámetro biepicondilar del húmero (premenopáusico: 6.64±0.71 vs. 6.31 ±0.42 cm, p = 0.012; posmenopáusica: 6.95±0.63 vs. 6.54±0.49 cm, p = 0.000), mayor circunferencia del antebrazo y la parte superior del muslo, bíceps inferiores y mayor grosor del pliegue de la piel del muslo. Además se observó una endomorfia significativamente menor (premenopáusica: 5.84±1.78 vs. 6.55±0.96, p = 0.027; posmenopáusica: 6.89±1.52 vs. 7.37±0.86, p = 0.035) y una ectomorfia significativamente más alta (premenopáusica: 2.05±1.30 vs. 1.41 .990.99, p = 0.018; posmenopáusica: 1.06±0.90 vs. 0.68±0.56, p = 0.007), así como una mayor mesomorfia solo en mujeres posmenopáusicas (6.10±2.04 vs. 5.37±1.34, p = 0.022). El somatotipo más representado entre las pacientes con cáncer de mama fue el endomorfomesomorfo, mientras que los controles más sanos fueron el mesomórfico endomorfo. Las características del cuerpo tipo androide aumenta el riesgo de desarrollar cáncer de mama. Los indicadores de dimensiones esqueléticas, volumen muscular y adiposidad periférica tuvieron un mejor valor predictivo sobre los marcadores de adiposidad central y general.

Associations of visceral fat thickness and anthropometric measurements with non-alcoholic fatty liver disease development in male patients mono-infected with human immunodeficiency virus.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease in mono-infected (without concomitant hepatitis B and/or C virus infection) people living with human immunodeficiency virus (HIV). The proper and on time identification of at-risk HIV-positive individuals would be relevant in order to reduce the rate of progression from NAFLD into non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. OBJECTIVES: The aim of this study was to explore visceral fat thickness (VFT) and anthropometric measurements associated with the development of NAFLD in patients mono-infected with HIV and on long-standing combination antiretroviral therapy (cART). METHOD: Eighty-eight (n = 88) HIV-positive male patients, average age 39.94 ± 9.91 years, and stable on cART, were included in this prospective study. VFT was measured using ultrasonography. Anthropometric measurements included body mass index (BMI), waist-to-hip ratio (W/H), waist-to-height ratio (WHtR), waist and hip circumference (WC, HC). Differences between variables were determined using the chi-square test. The receiver operating characteristic (ROC) curve and the Youden index were used to determine optimal cut-off values of VFT and hepatic steatosis. The area under the curve (AUC), 95% confidence intervals, sensitivity and specificity are reported for the complete sample. Significance was set at p < 0.05. RESULTS: Patients with steatosis had significantly higher values of BMI, HC, WC, W/H and WHtR. The VFT was higher in patients with steatosis (p < 0.001). Specifically, VFT values above 31.98 mm and age > 38.5 years correlated with steatosis in HIV-positive patients, namely sensitivity 89%, specificity 72%, AUC 0.84 (95% CI, 0.76-0.93, p < 0.001), with the highest Youden index = 0.61. The sensitivity of the age determinant above this cut-off point was 84%, specificity 73% and AUC 0.83 (95% CI, 0.75-0.92, p < 0.001), with the highest Youden index of 0.57. CONCLUSION: In the absence of more advanced radiographic and histological tools, simple anthropometric measurements and VFT could assist in the early identification of persons at risk of hepatic steatosis in low- and middle-income regions.

AGING, HEART RATE VARIABILITY AND METABOLIC IMPACT OF OBESITY.

The relationship between aging and changes in heart rate variability (HRV) could depend on the metabolic profile of obese people, i.e. metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). We aimed to determine the age at which obesity related autonomic dysfunction becomes significant and whether it decreases differently according to metabolic profile. We analyzed HRV in 99 adults using Wildman's criteria for metabolic profile and 5-minute HRV for autonomic nervous system. In MHO, high frequency (HF) decreased in the 4th decade of life. In MUO, standard deviation of R-R intervals (SDNN), root mean square of successive differences of all R-R intervals (RMSSD), number of adjacent intervals differing by more than 50 ms expressed as percentage of all intervals in the collecting period (pNN50), HF, low frequency (LF), LF/HF (LF divided by HF) and total power (TP) decreased in the 4th decade of life (partial shared variance 28%-36%). In conclusion, an age dependent decrease of HRV occurs in MUO between the third and fifth decade of life. In MHO, HF significantly decreases around the age of 40 years. Cardiometabolic profile influences metabolic aging, altering the autonomic nervous system.

Secular trend of head and face shape in adult population of Vojvodina (Serbia).

BACKGROUND: Different populations show variation in the pattern of change in craniofacial dimensions over time. Earlier studies of craniofacial traits in the Republic of Serbia were carried out, without any particular reference to secular changes. AIM: The aim of the study is to determine possible changes in craniofacial dimensions among the adult population of Vojvodina (Serbia) during a 33 year period. SUBJECTS AND METHODS: The findings of the study are based on the comparison of data from two cross-sectional surveys. The earlier research was conducted in 1975 (n = 2600) and the second from 2001-2006 (n = 4504). Four craniofacial dimensions and body height were analysed. RESULTS: In terms of the head dimensions, head length in males has increased substantially, while head breadth has decreased in both sexes. The total change in the cephalic index is 0.58 (males) and 0.48 (females) units per decade. Morphological face height has substantially increased, while face breadth has decreased in both sexes over this period. The total change in the facial index per decade is 0.75 units in males and 0.98 in females. CONCLUSION: The results point to a trend of head and face shape remodelling toward a narrower head and more elongated face, consistent with ongoing dolichocephalisation.

Association between anthropometric measures of regional fat mass and heart rate variability in obese women.

AIM: Impaired autonomic function could be the mechanism for the development of cardiometabolic diseases in obesity. Hence, simple anthropometric measures of overall and central obesity could be screening markers for autonomic imbalance. We analysed the relationship between heart rate variability (HRV) parameters and obesity indicators. METHODS: Sixty-three obese women underwent blood pressure, lipids and anthropometric measurements, body composition assessment, HOMA (homeostasis model assessment) index calculation and short-term HRV analysis. RESULTS: The correlation between obesity indicators and HRV parameters was influenced by age. In the multiple regression model, sagittal abdominal diameter (SAD) was a significant negative predictor of lnLF/HF (logarithmically transformed ratio of low to high frequencies) and lnLFnorm, and positive predictor of HFnorm (normalized high frequencies); the significant relationship remained even after adjustment for age, HOMA, blood pressure, lipid profile, menopause, body mass index (BMI) and body fat percentage (FAT). Anterior forearm skinfold showed inverse association with HRV. Correlation between waist circumference and waist-to-height ratio (WHtR) with lnLF/HF, as well as between anterior thigh skinfold with lnLF/HF, LFnorm (normalised low frequencies) and HFnorm was lost after further adjustments. CONCLUSION: Among all anthropometric measures, SAD and anterior forearm skinfold thickness showed the highest predictive ability for HRV. Markers of lower sympathetic and higher cardiac parasympathetic activity corresponded with indicator of central obesity, while indicators of peripheral obesity showed completely opposite relationship with markers of cardiac autonomic activity.

Vitamin D and Dysfunctional Adipose Tissue in Obesity.

Vitamin D deficiency and dysfunctional adipose tissue are involved in the development of cardiometabolic disturbances (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated the relation between vitamin D and adipocytokines derived from adipose tissue. We studied 50 obese individuals who were classified into different subgroups according to medians of observed anthropometric parameters (body mass index, body fat percentage, waist circumference, and trunk fat mass). There was a negative correlation between vitamin D level and leptin and resistin (r = -.61, P < .01), while a positive association with adiponectin concentrations was found (r = .7, P < .001). Trend estimation showed that increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations (growth coefficient: 12.13). In conclusion, a positive trend was established between vitamin D and the protective adipocytokine adiponectin. The clinical relevance of this relationship needs to be investigated in larger studies.

Differences in the redox status of human visceral and subcutaneous adipose tissues--relationships to obesity and metabolic risk.

OBJECTIVE: Metabolic homeostasis depends on adipocyte metabolic responses/processes, most of which are redox-regulated. Besides, visceral and subcutaneous adipose tissues (VAT and SAT, respectively) differ metabolically and in their contribution to metabolic complications, but their redox characteristics in humans are still unknown. To understand the molecular mechanisms of metabolic syndrome development, we analysed the redox characteristics of VAT and SAT in groups with various body weights and metabolic risks. MATERIAL AND METHODS: Fifty premenopausal women were classified according to body mass index into normal-weight and obese groups, and these groups were further sub-classified into metabolically healthy and metabolically obese ("at risk") based on the homeostasis model assessment of insulin resistance (HOMA-IR) index and the triglyceride, total-, LDL- and HDL-cholesterol levels. Antioxidant components, NADPH oxidase protein and 4-hydroxynonenal (4-HNE) levels were analysed in VAT and SAT. RESULTS: Compared with the SAT, the VAT showed a higher basal level of glutathione (GSH) and GSH-dependent enzyme activities. Compared with the metabolically healthy normal-weight controls, the obese groups of women showed lower GSH levels in both depots. However, in these groups, additional prooxidative changes (increased NADPH oxidase and 4-HNE and decreased levels of SOD and/or CAT) were observed only in VAT. CONCLUSIONS: Because of the critical role of thiol-redox homeostasis in lipogenesis, interdepot-differences in the GSH-dependent antioxidant part may be connected to the higher metabolic activity found in VAT. Analogously, the lower GSH levels that occur during obesity and the corresponding additional redox imbalance may be signs of VAT metabolic dysfunction that underlie the subsequent metabolic impairment.

Anthropometric indicators of mass and distribution of adipose tissue in the assessment of cardiovascular and diabetes risk in women.

INTRODUCTION: From the clinical and epidemiological point of view it is very important to define easily measurable and simple anthropometric parameters of mass and distribution of adipose tissue that will also be good predictors of future complications of obesity. The aim of our study was to correlate anthropometric indicators of mass and distribution of adipose tissue with the risk of developing cardiovascular diseases and diabetes. MATERIAL AND METHODS: The study group consisted of 155 women aged 45.4 +/- 13.04y. The anthropometric measurements were performed in order to assess adipose tissue mass and its specific distribution. The 10-year risk of developing cardiovascular diseases was assessed by using two score-systems: Framingham and Prospective Cardiovascular Munster Study while the 10-year risk of development of diabetes was assessed by QDScore system. RESULTS: According to our results, the waist-to-stature ratio was the best predictor of cardiovascular and diabetes risk (r = 0.617-0.780; AUC = 0.872). The estimated cut-off value for the waist-to-stature ratio in cardiovascular and diabetes risk prediction was 0.486. Apart from the waist-to-stature ratio, the body mass index, body fat mass, waist circumference and indicators of upper extremity adiposity also correlated strongly with the assessed risk. The anthropometric indicators of lower body adiposity had no significant diagnostic values. CONCLUSION: The waist-to-stature ratio is the best anthropometric indicator of cardiovascular and diabetes risk.

[Expression of somatostatin in ischemia of rat brain]. / Ekspresija somatostatina pri ishemiji mozga pacova.

INTRODUCTION: This study used the immunohistochemical method to follow the expression of cytoplasmatic protein somatostanin in the course of ischemia of rat brain. The aim of the study was to define all the areas of expression of somatostain and to show the protein distribution on the map. MATERIAL AND METHODS: All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. RESULTS AND DISCUSSION: The results of this study show that there is a difference in the reaction between the resistant and transitory ischemia groups of rats, especially in the parietofrontal cortex, area amygdaloidea anterior, clastrum, nc. reuniens and nc. suprachiasmaticus. The mapping shows the reaction in the structures of motor, sensitive and sensory cortex, mostly in the laminae I/Ill and V/VI, hippocampus- gyrus dentatus and CA1, CA2, CA3, endopiriform nucleus, paraventricular and periventricular nucleus of hypothalamus, corpus amygdaloideum, claustrum and caudoputamen. The more primitive sections of the brain - rhinencephalon, also showed a reaction, which led us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data showed that small neurons are most commonly found while the second most common are big pyramidal cells of multipolar and bipolar type, with the different body shape. CONCLUSION: Our findings have confirmed the results of rare studies that dealt with these issues, and offered a precise and detailed map of cells expressing somatostanin in the rat brain following ischemic attack.