Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes

The influence of diabetes mellitus on brain pathology is increasingly recognized. Previous contributions of our laboratory demonstrated in models of type 1 diabetes (nonobese diabetic and streptozotocin (STZ)-treated mice), a marked astrogliosis and neurogenesis deficit in hippocampus and increased expression of hypothalamic neuropeptides. In the present investigation, we further analyzed alterations of astroglia and neurons in the hippocampus of mice 1 month after STZ-induced diabetes. Results showed that these STZ-diabetic mice presented: (a) increased number of astrocytes positive for apolipoprotein-E (Apo-E), a marker of ongoing neuronal dysfunction; (b) abnormal expression of early gene products associated with neuronal activation, including a high number of Jun + neurons in CA1 and CA3 layers and dentate gyrus, and of Fos-expressing neurons in CA3 layer; (c) augmented activity of NADPH-diaphorase, linked to oxidative stress, in CA3 region. These data support the concept that uncontrolled diabetes leads to hippocampal pathology, which adjoin to changes in other brain structures such as hypothalamus and cerebral cortex.     

Mineralocorticoid treatment upregulates the hypothalamic vasopressinergic system of spontaneously hypertensive rats

Mineralocorticoid effects in the brain include the control of cardiovascular functions, induction of salt appetite, interaction with the vasoactive neuropeptides arginine vasopressin (AVP) and angiotensin II and development or aggravation of hypertension. In this regard, mineralocorticoids may play a pathogenic role in rats with a genetic form of hypertension (spontaneously hypertensive rats, SHR). Our objective was to compare the response of the hypothalamic vasopressinergic system to mineralocorticoid administration in SHR and control Wistar-Kyoto (WKY) rats. Sixteen-week-old male SHR showing a systolic blood pressure of 190 +/- 5 mm Hg and normotensive WKY rats (130 +/- 5 mm Hg) were treated subcutaneously with oil vehicle or a single 10-mg dose of deoxycorticosterone acetate (DOCA). After 2 h, rats were sacrificed and brains prepared for immunocytochemistry of Fos and vasopressin V1a receptor (V1aR) and for non-isotopic in situ hybridization of AVP mRNA. In the basal state, SHR demonstrated a higher number of AVP mRNA- and V1aR-immunopositive cells in the magnocellular division of the paraventricular hypothalamic nucleus (PVN) than WKY rats. After DOCA injection, SHR responded with a significant increase in both parameters with respect to vehicle-injected SHR. In WKY rats, DOCA was without effect on AVP mRNA although it increased the number of V1aR-positive cells. Changes in the number of Fos-positive nuclei were measured in the PVN, median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT), a circumventricular region showing anatomical connections with the PVN. In vehicle-injected rats, the PVN of SHR showed a higher number of Fos-positive nuclei than in WKY rats, whereas after DOCA treatment, a significant increment occurred in the OVLT but not in the PVN or MnPO of the SHR group only. These data suggest that the enhanced response of the vasopressinergic system to mineralocorticoids may contribute to the abnormal blood pressure of SHR.     

Surgical Workload and Cost of Postoperative Adhesion-related Intestinal Obstruction: Importance of Previous Surgery

Postoperative intraabdominal adhesions cause morbidity of varying degree. Intestinal obstruction is the most severe complication of adhesions. This study examined the importance of previous surgery on clinical and economic workloads caused by intestinal obstruction due to postoperative intraabdominal adhesions. All emergency hospitalizations due to adhesion-related intestinal obstruction from January 1, 1999 to December 31, 1999 in a hospital district serving roughly 450,000 inhabitants was reviewed retrospectively. The patient population was divided into six groups according to the site of previous surgery, and the total as well as group-related surgical workload and direct costs of inpatient care were analyzed. There were 123 hospitalizations due to postoperative adhesion-related intestinal obstruction during the study period. A total of 101 patients had experienced 176 operations. The most prevalent operations were colorectal (with or without other operations), upper abdominal, and female reproductive system procedures. Colorectal surgery preceded 40% and 38% of inpatient episodes and inpatient days, respectively. Altogether, 40 operations were performed because of adhesion-related intestinal obstruction. No differences between groups were seen in terms of the mean operating or theater time. Total annual inpatient costs due to emergency hospitalizations for intestinal adhesion-related obstruction related to colorectal surgery in a hospital district serving roughly 450,000 inhabitants was $72,520.60 (U.S. dollars) which accounted for 35.3% of all annual costs caused by postoperative adhesion-related intestinal obstructions. There were no significant differences between groups regarding the total mean inpatient episode costs. Intestinal obstruction due to postoperative adhesions poses substantial costs for the society. Colorectal operations are the most important procedures preceding adhesion-related intestinal obstruction, accounting for 35.3% to 46.8% of the total clinical workload or costs attributable to postoperative adhesion-related obstruction.     

The predictive value of<Superscript>201</Superscript>Tl rest-redistribution and<Superscript>18</Superscript>F-fluorodeoxyglucose SPECT for wall motion recovery after recent reperfused myocardial infarction

201Tl and 18F-FDG are useful for acute myocardial infarction (MI) assessment. The goal of this study was to compare their predictive value for wall motion recovery in the culprit area after a recent reperfused MI using SPECT technique. METHODS: Forty-one patients (mean age: 56 +/- 12 years) were included, 81% of them male; all were studied within 1-24 days post MI. They underwent angioplasty in 27 cases (12 primary); bypass grafting in 10 cases and successful thrombolysis in 4. SPECT 201Tl injected at rest and redistribution (R-R) and also 18F-FDG, were performed on different days. Processed tomograms were interpreted blinded to clinical or angiographic data. Segmental wall motion assessed with echocardiography at baseline was compared with the 3 month follow up. RESULTS: Sensitivity [Confidence Interval] for 201Tl R-R was 74.6% [60.5-84.5], for FDG it was 82.1% [70.8-90.4]; specificities were 73% [64.3-80.5] and 54.8% [45.6-63.7], respectively. 18F-FDG tended to be more sensitive than 201Tl R-R, but the latter was more specific (p < 0.0004). Both 201Tl RR and 18F-FDG presented high negative predictive value (p: ns). CONCLUSION: In recent MI, SPECT 201Tl R-R is a valuable and widely available technique for viability detection, with similar sensitivity and significant better specificity than SPECT 18F-FDG.     

Motor vehicle deaths in Hong Kong: opportunities for improvement

OBJECTIVE: This study was undertaken to describe the epidemiology of motor vehicle mortality in Hong Kong, and to assess its impact on trauma service delivery. SETTING: Hong Kong has an area of 1,072 km2 and a population of 6,800,000. There were 500,000 registered vehicles in 2001. METHODS: All motor vehicle deaths must be reported to the coroner in Hong Kong. A manual retrospective review of all coroner case notes involving motor vehicles for 2001 was performed. RESULTS: The review identified 165 cases involving 111 male and 54 female patients. Elderly cases were predominant, with 37% of the cases involving individuals older than 60 years. Most of the cases involved pedestrians (59%), and half of these pedestrians had experienced collisions with public light buses and trucks. Alcohol was not commonly involved, and when it was, it was isolated to the group 20 to 40 years of age. Most individuals died of major head injury alone or multiple injuries. There were very few major vessel injuries, and these included 13 aortic transections. DISCUSSION: Hong Kong has a very low motor vehicle death rate relative to its population (2.4 per 100,000), but the rate is less impressive when it is related to motor vehicle registrations (33 per 100,000 vehicles). The low incidence of motor vehicle trauma has implications for trauma service delivery in terms of trauma expertise and specialization. Despite the low incidence of trauma, there still are opportunities for prevention, especially in relation to elderly pedestrians and public light buses.     

Evaluation of reliability for urine mucopolysaccharidosis screening by dimethylmethylene blue and Berry spot tests

BACKGROUND: The mucopolysaccharidosis (MPS) are a group of inherited metabolic disorders resulting from the deficiency of the enzyme responsible for intralysosomal catabolism of glycosaminoglycans (GAGs). GAGs are progressively accumulated in multiple tissues and released into the corporal fluids. The first laboratory approximation to MPS diagnosis is the identification of an increased urinary GAG excretion. For this, several semiquantitative and quantitative methods have been developed. The aim of this retrospective statistical study was to evaluate the reliability of MPS urine screening for the semiquantitative Berry spot test (BST) and the quantitative dimethylmethylene blue test (DMB). METHODS: The 24-h-urine samples (n = 246) were tested through BST, DMB, and for GAG excretion pattern by one-dimensional electrophoresis or thin layer chromatography. RESULTS: the 204 samples that demonstrated a normal GAG excretion pattern were considered as non-MPS samples. Forty-two samples presented an abnormal GAG excretion pattern. Enzyme analysis was available for 31 out of 42 patients (31/42), confirming that all were affected by MPS. Urinary GAG concentrations of MPS patients by DMB were increased 1.04- to 7.1-folds, compared to age-related normal levels. The sensitivity was 100% for DMB and 93.6% for BST. DMB demonstrated a specificity of 74.5%, while BST a specificity of 53.9%. The specificity of MPS screening increased to 84.3%, considering conjunctly DMB and BST. CONCLUSION: The DMB is a sensitive method, however, inclusion of BST could increase the specificity of MPS urine screening.     

Ambient, indoor and personal exposure relationships of volatile organic compounds in Mexico City Metropolitan Area

Air pollution standards and control strategies are based on ambient measurements. For many outdoor air pollutants, individuals are closer to their sources (especially traffic) and there are important indoor sources influencing the relationship between ambient and personal exposures. This paper examines the relationship between volatile organic compounds (VOCs) measured at central site monitoring stations and personal exposures in the Mexico City Metropolitan Area. Over a 1-year period, personal exposures to 34 VOCs were measured for 90 volunteers from 30 families living close to one of five central monitoring stations. Simultaneous 24-h indoor, outdoor and central site measurements were also taken. Dual packed thermal desorption tubes and C(18) DNPH-coated cartridges were used for sampling VOCs and these were analyzed by GC/MS and HPLC, respectively. A factor analysis of the personal exposure data aided in grouping compounds by the most likely source type: vehicular (BTEX, styrene and 1,3-butadiene), secondary formed or photochemical (most aldehydes), building materials and consumer products (formaldehyde and benzaldehyde), cleaning solvents (tetrachloroethene and 1,1,1-trichloroethane), volatilization from water (chloroform and trichloroethene) and deodorizers (1,4-dichlorobenzene). Mean ambient, indoor and personal concentrations were 7/7/14 microg/m(3) for benzene, 1/3/3 for 1,3-butadiene, 6/20/20 for formaldehyde and 3/9/50 for 1,4-dichlorobenzene. Geometric mean (GM) ambient concentrations of trichloroethene and carbon tetrachloride were similar to GM personal exposures. While outdoor and indoor home GM concentrations for most vehicular related compounds (benzene, MTBE, xylenes and styrene) were comparable, the GM personal exposures were twice as high. Indoor concentrations of 1,3-butadiene, 1,1,1-trichloroethane, tetrachloroethane, chloroform, formaldehyde, valeraldehyde, propionaldehyde and n-butyraldehyde were comparable to personal exposures. For certain compounds, such as chloroform, aldehydes, toluene, 1,3-butadiene and 1,4-dichlorobenzene, GM personal exposures were more than two times greater than GM ambient measurements.     

Small molecule mitochondrial F1F0 ATPase hydrolase inhibitors as cardioprotective agents. Identification of 4-(N-arylimidazole)-substituted benzopyran derivatives as selective hydrolase inhibitors

In this paper we show that 4-aryl-CH2-imidazole-substituted benzopyran compounds with 3S,4R-stereochemistry are cardioprotective by inhibiting the F1F0 mitochondrial ATP hydrolase. Compounds (e.g., 13) with 3R,4S-stereochemistry act as mitochondrial KATP openers. This resulted from an inversion of stereochemistry for the F1F0 mitochondrial ATP hydrolase vs mitochondrial KATP. Structure-activity relationships for the inhibition of mitochondrial ATP hydrolase are also delineated. It is not clear how 13 (3R,4S) can selectively inhibit the hydrolytic activity of the F1F0 mitochondrial enzyme without interfering with the synthase activity.     

Age-dependent effects of 5,7-dihydroxytryptamine on serotonin transporter in different brain areas in the rat

In the present study, we investigated the [(3)H]citalopram binding using a quantitative autoradiography following intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal and adult male Wistar rats. One group of animals was injected with 5,7-DHT at 3 days after birth while the second group received the neurotoxin at 3 months after birth. Control group was injected with saline. Afterwards, all rats were examined at 4(th) months after birth to determine the serotonin (5-HT) and catecholamines concentrations using the liquid chromatography with electrochemical detection HPLC system and distribution and density of [(3)H]citalopram binding sites in the brain using the quantitative autoradiography. A marked depletion of brain 5-HT was observed in rats lesioned either in postnatal or adult period of life. Rats lesioned in their adult period of life showed dramatic reduction of 5-HT transporter in all investigated brain areas (i.e.the frontal cortex, entorhinal cortex, hippocampus, caudate-putamen, nucleus accumbens and ventral tegmental area). On the other hand, administration of 5,7-DHT to newborn rats failed to reduce 5-HT transporter sites in the ventral tegmental area, and produced only slight or moderate reduction in the nucleus accumbens. Thus, it appears that the mesolimbic ventral tegmental area-nucleus accumbens systems are relatively more resistant to 5,7-DHT neurotoxicity in the early postnatal period.