Role of RanBP9 on amyloidogenic processing of APP and synaptic protein levels in the mouse brain.

We previously reported that RanBP9 binds low-density lipoprotein receptor-related protein (LRP), amyloid precursor protein (APP), and BACE1 and robustly increased Aß generation in a variety of cell lines and primary neuronal cultures. To confirm the physiological/ pathological significance of this phenotype in vivo, we successfully generated transgenic mice overexpressing RanBP9 as well as RanBP9-null mice. Here we show that RanBP9 overexpression resulted in >2-fold increase in Aß40 levels as early as 4 mo of age. A sustained increase in Aß40 levels was seen at 12 mo of age in both CHAPS-soluble and formic acid (FA)-soluble brain fractions. In addition, Aß42 levels were also significantly increased in FA-soluble fractions at 12 mo of age. More important, increased Aß levels were translated to increased deposition of amyloid plaques. In addition, RanBP9 overexpression significantly decreased the levels of synaptophysin and PSD-95 proteins. Conversely, RanBP9-null mice showed increased levels of synaptophysin, PSD-95, and drebrin A protein levels. Given that loss of synapses is the best pathological correlate of cognitive deficits in Alzheimer's disease (AD), increased Aß levels by RanBP9 observed in the present study provides compelling evidence that RanBP9 may indeed play a key role in the etiology of AD. If so, RanBP9 provides a great opportunity to develop novel therapy for AD.

Effect of carbon monoxide packaging and lactate enhancement on the color stability of beef steaks stored at 1°C for 9 days.

Our objective was to assess the effects of lactate enhancement in combination with different packaging systems on beef longissimus lumborum and psoas major steak color. Strip loins and tenderloins (n=16) were assigned to one of four injection treatments (non-injected control, water-injected control, 1.25%, and 2.5% lactate in the finished product). Steaks were individually packaged in either vacuum, high-oxygen (80% O(2)/20% CO(2)), or 0.4% CO (30% CO(2)/69.6% N(2)) and stored for either 0, 5, or 9 days at 1°C. The L(∗) and a(∗) values of both the longissimus and psoas responded similarly to lactate, which at 2.5% darkened steaks (P<0.05) packaged in all atmospheres and improved (P<0.05) the redness of steaks packaged in high-oxygen. Packaging steaks in CO did not counteract the darkening effects of lactate. Nevertheless, CO improved (P<0.05) color stability compared with high-oxygen packaging.

Effects of deep sedation under mechanical ventilation on cognitive outcome in patients undergoing surgery for oral and maxillofacial cancer and microvascular reconstruction.

OBJECTIVE: Cognitive impairment after intensive care unit (ICU) admission is becoming increasingly recognized. High-dose deep sedation has been suggested to play an important role in the development of cognitive impairment. However, the impact of heavy sedation as a single cause in the development of cognitive impairment in ICU patients remains unclear. In this study we investigated whether a three-day deep sedation protocol could reduce cognitive function in mechanically ventilated non-critical patients. DESIGN: A prospective observational study was carried out. PATIENTS: A total of 17 surgical patients were studied. INTERVENTION: None. VARIABLES OF INTEREST: Cognitive function before and after ICU admission. RESULTS: Thirty-one patients requiring three days of sedation after microvascular reconstruction were initially enrolled in the study. Sedation in the ICU was maintained with propofol and dexmedetomidine combined with fentanyl. Cognitive function was assessed using a battery of 6 neuropsychological tests two days before surgery and three weeks after surgery. Finally, a total of 17 patients were included in the analysis. Cognitive impairment (defined as a decline of >20% from the pre-admission cognitive evaluation scores in at least two of 6 tests) was observed in 5 of the 17 patients (29%). However, there were no significant differences between the pre- and post-admission cognitive evaluations in 6 tests. CONCLUSIONS: Middle-term cognitive function can be impaired in some patients subjected to deep sedation during several days following maxillary-mandibular oral surgery with microvascular reconstruction.

Effects of monthly feedback of VFA measured by dual BIA method in Japanese patients with obesity: a randomized controlled study.

Objective: To investigate the effects of monthly feedback of changes in visceral fat area (VFA) as measured by dual bioelectrical impedance analysis method and the importance of VFA in individuals with obesity. Methods: Thirty-eight Japanese patients with obesity underwent VFA measurements. The feedback group was given feedback on VFA measurements each month for 4 months. The control group underwent VFA measurements at the beginning and end of the study but was not informed of the results. All the study participants completed eating behaviour and weight efficacy lifestyle questionnaires. Results: Mean age was 53.9 (14.3) years; mean body mass index was 30.6 (4.3) kg m-2. At the 4-month follow-up, there was no significant difference in VFA reduction between the control and feedback groups (-4.4% vs. -3.0%; 95% CI, -3.8 to 5.5). In post-hoc analysis using the overall group irrespective of allocation, changes of eating style were significantly associated with a reduction in VFA at 4 months (p = 0.034). Conclusions: Monthly feedback on changes in VFA does not reduce VFA. More frequent feedback may be required. In post-hoc analysis, changes of eating style were associated with a reduction in VFA.

Hydrogenated benzo[f]quinolines and benz[e]indoles as analgetics. 1.

A series of octahydrobenzo[f]quinolines(IIIa) and hexahydro-1H-benz[e]indoles(IIIb), rigid structures related to 3-phenylpiperidine and pyrrolidine analgetics, has been synthesized. Structure-activity relationships were investigated by varying the structural parameters including a change in the stereochemistry of the ring junction. Several of the resulting compounds had analgetic activity on the order of meperidine.

Synthesis of halogen-substituted 1,5-benzothiazepine derivatives and their vasodilating and hypotensive activities.

In an attempt to improve the effectiveness and duration of the action of diltiazem (1), a 1,5-benzothiazepine calcium channel blocker, its derivatives (2) with halogen substituents on the fused benzene ring were synthesized. These compounds were evaluated for their effects on vertebral and coronary blood flows and antihypertensive activity. The structure-activity relationships are discussed. The 8-chloro derivative ((+)-2b), the most potent compound in this series, was selected for clinical evaluation as a cerebral vasodilating and antihypertensive agent.

[A study of cisterna magna on brain computerized tomography in children].

Although many publications on cranial computerized tomography have been reported in recent years, very little attention has been directed to the cisterna magna (CM) and its variations. The size of the cisterna magna is still debatable and the criterion of the mega cisterna magna is obscure. We studied age distribution, clinical manifestations, and other CT findings in the children with enlarged cisterna magna. A consecutive series of 367 computerized tomographic scans were reviewed. We classified four classes according to the degree of enlargement of the cisterna magna: CM is undetectable; CM (-), CM is detectable at the level of sella turcica and the fourth ventricle; CM(+), CM extends upward at the level of suprasellar cistern and colliculus inferior; CM (+ +), and CM extends extensively at the level of the third ventricle and colliculus superior; CM (+ + +). We judged 55 CT scans (15%) to belong to CM (+ + +) class and 100 scans (27%) to CM (+ +) class. The greater part of children with CM (+ + +) were younger in contrast with CM (+ +), which distributed uniformly in every ages. Also we differentiated the patients into three groups from clinical manifestations as follows: patients with developmental delayed; group D, patients with organic neurological diseases; group N, patients with other diseases; group O. The ratio of group D is significantly higher in CM (+ + +) than that of other groups. No children had posterior fossa symptoms of mass effect and required treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Longitudinal study of epileptic foci in childhood].

We performed the longitudinal study in patients with focal spikes about characteristic changes in epileptic foci for periods of between one year and 5 years 9 months. The 116 epileptic children were evaluated, ranging in onset age from 10 month to 12 year 9 month old (mean age: 6 year 11 month). They were subdivided into four groups according to their region of foci: group 1, 41 patients with the centro-temporal spikes (Rolandic discharges); group 2, 14 patients with the occipital spikes; group 3, 6 patients with frontal pole spikes; group 4, 55 patients with the other focal spikes. EEG examinations were followed 6 months interval in each patients, and total 412 EEG trancing were investigated. Migration of epileptic foci was recognized in thirty eight patients (32.8%): 17 (41%) in Rolandic discharges, 7 (50%) in occipital spikes, 4 (67%) in frontal pole spikes and 10 (18%) in other spikes. The mean time to the migration of next foci was 45.6 months in Rolandic discharges, 18.4 months in occipital spikes, 17.6 months in frontal pole spike and 61.4 months in other spikes. As to the regions of migrated foci, Rolandic discharges tended to move to the near and horizontal areas such as from central to temporal. Whereas, occipital spikes and frontal pole spikes tended to move to the distant and vertical areas such as from occipital to frontal pole and from frontal pole to occipital. But other spikes showed no tendency.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of some risk factors for diabetes across different social groups: a cross-sectional study.

BACKGROUND: In fast, developing economies such as India, the population is undergoing rapid social transition, which can increase the risk profile for diabetes. Market forces promoting lifestyles such as sedentary habits, alcohol and tobacco use, which earlier were more prevalent among affluent urban populations are now trickling into the urban poor and rural populations. AIM: The aim of the present research was to compare the prevalence of risk factors for diabetes among three distinct social groups-the urban affluent, the urban poor and the rural poor. SUBJECTS AND METHODS: A total of 775 adult population over 18 years and belonging to both genders were surveyed for prevalence of some of the risk factors for diabetes such as physical inactivity, obesity, alcohol, and tobacco use. The sample comprised of three distinct social groups as follows; 125 medical students representing the affluent, 400 subjects from urban slums, and 250 subjects from rural areas. Obesity was measured by body mass index (BMI) while central obesity was ascertained by waist hip ratio (WHR). Alcohol and tobacco use were elicited by interview. RESULTS: The overall response rate was 88.52% (686/775). Medical students were more sedentary with mean hours spent each day sitting or reclining at 10.47 (3.25) h, compared to corresponding figures of 6.34 (3.1) h and 7.49 (3.74) h for the rural and urban slum residents respectively (P < 0.001). However, all types of leisure time physical activities were significantly more among the medical students compared to the other groups (P < 0.001). BMI was significantly highest among the rural population with mean of 24.22 (4.17) kg/m(2) when compared to the other groups, (P < 0.001). Villagers also had higher WHR and had a higher proportion of persons above the WHR cut-off for gender (P < 0.001). Experimentation with alcohol was more prevalent among the medical students while the urban slum residents were more frequent and heavy drinkers. Smoking was most prevalent among the medical students, while smokeless tobacco use was more among the other groups. CONCLUSIONS: Physical inactivity, obesity, including central obesity, alcohol and tobacco use were found in various degrees in the study samples. An important finding was that both obesity and central obesity ascertained by BMI and WHR respectively were highest among the rural population implying the impact of social change on diabetic risk factors.

Chitosan inhibits premature browning in ground beef.

Our objective was to evaluate the effect of chitosan on premature browning in refrigerated ground beef patties stored in different packaging systems. Ground beef patties (15% fat) with chitosan (1% w/w) or without chitosan (control) were individually packaged either in vacuum (VP), aerobic packaging (AP), carbon monoxide modified atmosphere packaging (LO-OX; 0.4% CO+19.6% CO(2)+80% N(2)), or high-oxygen modified atmosphere packaging (HI-OX; 80% O(2)+20% CO(2)), and stored for 0, 1, or 3 days at 1°C. At the conclusion of storage, raw surface redness was evaluated, patties were cooked to internal end-point temperatures of either 66°C or 71°C, and internal cooked color was measured. The incorporation of chitosan increased (P<0.05) the interior redness of patties stored in AP, VP, and LO-OX, but not in HI-OX. The results of the present study suggest that the incorporation of 1% chitosan minimizes premature browning in ground beef patties stored under AP, VP, and LO-OX.

Effects of lactate-enhancement on surface reflectance and absorbance properties of beef longissimus steaks.

A completely randomized block design was used to assess the effects of lactate-enhancement on surface reflectance and absorbance properties of beef longissimus steaks. Loins were divided into sections, assigned to one of four treatments (non-enhanced day 0, non-enhanced day 5, water-enhanced, and 3% lactate), vacuum packaged, stored for 5 days at 4 degrees C, and then cut into steaks that were used to prepare 100% of deoxy-, oxy-, met-, and carboxymyoglobin according to AMSA (1991). Surface color was analyzed using a HunterLab Miniscan Plus Spectrocolorimeter. Lactate-enhanced steaks had the least overall surface reflectance and the darkest surface color (lower L*; P<0.05). For 100% of each myoglobin form, K/S values and ratios (isobestic wavelengths/525 nm) at 474, 525, 572, and 610 also were influenced by lactate-enhancement. Hence, when estimating surface myoglobin forms using K/S ratios, separate 100% myoglobin reference standards should be prepared from both non-enhanced and enhanced steaks.

Mass spectrometric investigations on lactate adduction to equine myoglobin.

Research focused on determining the fundamental mechanisms by which lactate influences color stability has not considered a direct effect of lactate on myoglobin. Thus, the objective of this study was to use Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry to examine lactate adduction to myoglobin. Equine oxymyoglobin and equine carboxymyoglobin (0.15mM) were incubated with sodium lactate (200mM) at 4 degrees C, pH 5.6 in 50mM sodium citrate buffer or at 37 degrees C, pH 7.4 in 50mM sodium phosphate buffer, simulating typical meat storage and physiological conditions, respectively. Controls consisted of myoglobin plus a volume of deionized water equivalent to that used to deliver the lactate treatments. No peaks corresponding to lactate-Mb adducts could be detected in the mass spectra of samples incubated up to 360min at pH 7.4, 37 degrees C or 8days at pH 5.6 and 4 degrees C. Our results suggest that lactate did not form covalent adducts with equine oxy- and carboxy-myoglobin.

Packaging-specific influence of chitosan on color stability and lipid oxidation in refrigerated ground beef.

We examined the influence of chitosan on lipid oxidation and color stability of ground beef stored in different modified atmosphere packaging (MAP) systems. Ground beef patties with chitosan (1%) or without chitosan (control) were packaged either in high-oxygen MAP (HIOX; 80% O(2)+20% CO(2)), carbon monoxide MAP (CO; 0.4% CO+19.6% CO(2)+80% N(2)), vacuum (VP), or aerobic packaging (PVC) and stored at 1 °C. Chitosan increased (P<0.05) redness of patties stored in PVC and CO, whereas it had no effect (P>0.05) in HIOX. Chitosan patties demonstrated lower (P<0.05) lipid oxidation than controls in all packaging. Control patties in PVC and HIOX exhibited greater (P<0.05) lipid oxidation than those in VP and CO, whereas chitosan patties in different packaging systems were not different (P>0.05) from each other. Our findings suggested that antioxidant effects of chitosan on ground beef are packaging-specific.

Color-stabilizing effect of lactate on ground beef is packaging-dependent.

Previous research on lactate-induced color stability in ground beef did not address the potential influence of packaging. The objective of the present study was to examine the effects of lactate on the color stability of ground beef patties stored in different modified atmosphere packaging (MAP) systems. Ground beef patties with either 2.5% potassium lactate or no lactate were packaged in vacuum (VP), high-oxygen MAP (HIOX; 80% O(2)+20% CO(2)), carbon monoxide MAP (CO; 0.4% CO+19.6% CO(2)+80% N(2)), or aerobic packaging (PVC) and stored for 0, 2, or 4 days at 2 degrees C. Lactate-treated patties were darker (P<0.05; lower L * values) than control patties. Surface redness (a * values) was greater (P<0.05) for lactate patties than the controls when stored in PVC, HIOX, and VP. However, lactate's effects on a * values were not evident when packaged in CO (P>0.05). The color-stabilizing effect of CO could have masked lactate's effect on surface redness. While lactate patties in PVC and VP demonstrated lower (P<0.05) discoloration than controls, no differences (P>0.05) existed between controls and lactate samples in CO and HIOX. Our results indicated that the effects of lactate on ground beef color are dependent on packaging.

Effects of lactate and modified atmospheric packaging on premature browning in cooked ground beef patties.

Our objectives were to determine the effects of lactate and modified atmosphere packaging on raw surface color, lipid oxidation, and internal cooked color of ground beef patties. Eight chubs (85% lean) were divided in half and each half was either assigned to the control (no lactate) or mixed with 2.5% lactate (w/w). Following treatment, patties were prepared and packaged in either vacuum, PVC (atmospheric oxygen level), high-oxygen (80% O(2)+20% CO(2)), or 0.4% CO (30% CO(2)+69.6% N(2)) and stored for 0, 2, or 4days at 2 degrees C. After storage, raw surface color and lipid oxidation were measured and patties were cooked to either 66 degrees C or 71 degrees C. Lactate improved (p<0.05) color stability of PVC, high-oxygen, and vacuum packaged raw patties, but had no effect (p>0.05) on the a * values and visual color scores of patties in 0.4% CO. Lactate decreased (p<0.05) lipid oxidation in all packaging atmospheres. Nevertheless, high-oxygen and PVC-packaged patties had more (p<0.05) lipid oxidation than patties in CO and vacuum. Lactate had no effect (p>0.05) on premature browning, whereas patties packaged in high-oxygen demonstrated premature browning. Conversely, cooked patties in 0.4% CO and vacuum were more red (p<0.05) than both high-oxygen and PVC-packaged patties. Although lactate improved raw color stability, it did not minimize premature browning in cooked ground beef patties.

Effect of lactate-enhancement, modified atmosphere packaging, and muscle source on the internal cooked colour of beef steaks.

Earlier studies on lactate-mediated colour stability in beef did not address the possible influence on cooked colour. Our objective was to examine the effect of lactate-enhancement, muscle source, and modified atmosphere packaging (MAP) on the internal cooked colour of beef steaks. Longissimus lumborum (LL) and Psoas major (PM) muscles from 16 (n=16) beef carcasses (USDA Select) were randomly assigned to 4 enhancement treatments (non-injected control, distilled water-enhanced control, 1.25% and 2.5% lactate), and fabricated into 2.54-cm steaks. Steaks were individually packaged in either vacuum (VP), high-oxygen MAP (HIOX; 80% O(2)+20% CO(2)), or carbon monoxide MAP (CO; 0.4% CO+19.6% CO(2)+80% N(2)), and stored for 0, 5, or 9 days at 1°C. At the end of storage, surface and internal colour (visual and instrumental) was measured on raw steaks. Steaks were cooked to an internal temperature of 71°C, and internal cooked colour (visual and instrumental) was evaluated. Lactate-enhancement at 2.5% level resulted in darker (P<0.05) cooked interiors than other treatments. Interior cooked redness decreased (P<0.05) during storage for steaks in VP and HIOX, whereas it was stable for steaks in CO. Our findings indicated that the beef industry could utilise a combination of lactate-enhancement and CO MAP to minimise premature browning in whole-muscle beef steaks.