Responses In Healthy Individuals Research Articles

FMRI Responses in Healthy Individuals and in Patients with Mild Depression to Presentation of Pleasant and Unpleasant Images.

Patients with mild depression and apparently healthy individuals were presented images and asked to sort them into "pleasant" and "unpleasant" subsets. In both groups, the main differences between brain activation patterns during presentation of pleasant and unpleasant images were localized in the motor regions (precentral and postcentral gyrus) and in the cerebellum (p<0.05 with FWE correction). Most likely, these clusters are associated with motion (pressing a button in accordance with the instruction). According to the data of intergroup contrasts, patients with depression had less pronounced activation of frontal structures (middle frontal gyrus and other areas, including the white matter) in response to both positive and negative images (p<0.001). In healthy subjects, the response of the temporo-occipital areas (lingual and fusiform gyrus) to unpleasant stimuli was more intensive than in patients (p<0.001). This can be due to differences in the semantic image processing. Thus, in case of mild depression, the response of the amygdaloid complex, the key structure in the development in affective disorder, was not always observed. At the same time, the response of frontal and temporo-occipital regions has a certain potential as a biomarker of mild depression, although the reliability of the obtained data requires additional confirmation.

The effects of added whey protein to a pre-operative carbohydrate drink on glucose and insulin response.

Pre-operative complex carbohydrate (CHO) drinks are recommended to attenuate post-operative insulin resistance. However, many institutions use simple CHO drinks, which while convenient, may have less metabolic effects. Whey protein may enhance insulin release when added to complex CHO. The aim of this study was to compare the insulin response to simple CHO vs. simple CHO supplemented with whey protein. Twelve healthy volunteers participated in this double-blinded, within subject, cross-over design study investigating insulin response to simple CHO drink vs. simple CHO+whey (CHO+W) drink. The primary outcome was the accumulated insulin response during 180min after ingestion of the drinks (Area under the curve, AUC). Secondary outcomes included plasma glucose and ghrelin levels, and gastric emptying rate estimated by acetaminophen absorption technique. Data presented as mean (SD). There was no differences in accumulated insulin response after the CHO or CHO+W drinks [AUC: 15 (8) vs. 20 (14)nmol/l, P=0.27]. Insulin and glucose levels peaked between 30 and 60min and reached 215 (95)pmol/l and 7 (1)mmol/l after the CHO drink and to 264 (232)pmol/l and 6.5 (1)mmol/l after the CHO+W drink. There were no differences in glucose or ghrelin levels or gastric emptying with the addition of whey. The addition of whey protein to a simple CHO drink did not change the insulin response in healthy individuals. The peak insulin responses to simple CHO with or without whey protein were lower than that previously reported with complex CHO drinks. The impact of simple carbohydrate drinks with lower insulin response on peri-operative insulin sensitivity requires further study.

Effect of a cod protein hydrolysate on postprandial glucose metabolism in healthy subjects: a double-blind cross-over trial.

The increased prevalence of lifestyle diseases, such as the metabolic syndrome and type 2 diabetes mellitus (T2DM), calls for more knowledge on dietary treatments targeting the specific metabolic pathways involved in these conditions. Several studies have shown a protein preload before a meal to be effective in lowering the postprandial glycaemic response in healthy individuals and patients with T2DM. The aim of the present study was to assess the effect of a marine protein hydrolysate (MPH) from Atlantic cod (Gadus morhua) on postprandial glucose metabolism in healthy, middle-aged to elderly subjects. This double-blind cross-over trial (n 41) included two study days with 4-7 d wash-out in between. The intervention consisted of 20 mg of MPH (or casein as control) per kg body weight given before a breakfast meal. The primary outcome was postprandial response in glucose metabolism, measured by samples of serum glucose, insulin and plasma glucagon-like peptide 1 (GLP-1) in 20 min intervals for 180 min. In a mixed-model regression analysis, no differences were observed between MPH and control for postprandial glucose concentration (mean difference: -0·04 (95 % CI -0·17, 0·09) mmol/l; P = 0·573) or GLP-1 concentration (mean difference between geometric means: 1·02 (95 % CI 0·99, 1·06) pmol/l; P = 0·250). The postprandial insulin concentration was significantly lower after MPH compared with control (mean difference between geometric means: 1·067 (95 % CI 1·01, 1·13) mIU/l; P = 0·032). Our findings demonstrate that a single dose of MPH before a breakfast meal reduces postprandial insulin secretion, without affecting blood glucose response or GLP-1 levels, in healthy individuals. Further studies with repeated dosing and in target groups with abnormal glucose control are warranted.

Follow-up of hepatitis b virus vaccine response in healthy individuals

Background The long-term protective effect of hepatitis B virus (HBV) vaccine and the need for booster dose vaccination remain unclear. Detection of nonresponders to HBV vaccine and search for factors that lead to nonresponse will help in prevention of HBV infection, hepatocellular carcinoma related to hepatitis B infection and hepatitis D virus infection. Aim The aim of this study was to assess the benefit of follow-up of hepatitis B vaccine response and evaluate the persistence of seroprotection after HBV vaccination to determine the necessity of a booster dose in healthy individuals after 5 and 10 years of vaccination. Patients and methods Serum samples were tested for quantitative detection of hepatitis B surface antibodies (HBsAb) using ELISA for 30 individuals who received HBV vaccine of less than or equal to 5 years (group I) and 30 individuals who received HBV vaccine for more than or equal to 10 years (group II), and if the results were negative or less than 10 IU/ml, evaluations of hepatitis B surface antigen and hepatitis B core antibodies (total) were done. Results HBsAb was positive among 66.7% of each group, and the median HBsAb level was 59.73 and 51.21 in groups I and II, respectively. Conclusion Approximately 33% of the studied groups were nonresponders of HBV vaccine regardless of postvaccination years (5–10). Hepatitis B infection and occult hepatitis B infection results were negative in all of nonresponders. Recommendations Follow-up of HBsAb levels in vaccinated individuals after having completed three doses of hepatitis B vaccination on a large scale is important to detect nonresponses and revaccinate them.

Impact of Aging on Nerve Conduction Velocities and Late Responses in Healthy Individuals.

Background:Nerve conduction studies are performed to diagnose the disorders of the peripheral nervous system. The reference values for nerve conduction velocity (NCV) and late responses for different nerves considerably vary in different group and type of population. Physiological factors such as age, temperature, height, and gender affect the NCV. However, there are very few studies which show the age group at which these changes become significant.Aim and Objectives:The aim of the study was to establish the electrophysiological data of the specific age group at which changes in NCV as well as late responses of median common peroneal nerve and also see the late response in the form of F-waves and H-reflex.Methodology:Study groups were divided into three categories based on the age: Group I (18–30 years) (n = 80), Group II (31–45 years) (n = 43), and Group III (46–60 years) (n = 27). Out of which, 93 patients were male and 57 were female. The NCVs were determined for median, common peroneal nerve (motor component and sensory component) along with late responses in the form of H-reflex and F-waves.Results:The mean and standard deviation of median, ulnar, peroneal, and tibial nerve was studied for latencies, amplitude, and velocities for both sensory and motor components. Patients with older age had longer latencies, smaller amplitudes, and slower conduction velocities compared with the younger age group. The change with age was greater in sensory nerve conduction and late responses in all the peripheral nerves.Conclusions:Aging has a definite correlation with the NCV and late responses of different peripheral nerves. There is a need to have reference values with relation to age.

Effects of AHCC® on Immune and Stress Responses in Healthy Individuals.

AHCC® is a functional food from the basidiomycete Lentinula edodes. We evaluated the effects of AHCC® on subjects under different kinds of stress and at rest. Physical stress was imposed using an active standing test, known as Schellong’s test. Sympathetic nervous activity in the standing position was significantly greater in AHCC®-treated subjects than in a placebo group. In contrast, AHCC® significantly increased parasympathetic nervous activity at rest. Under mental stress, AHCC® increased sympathetic nervous activity, with no difference in the parasympathetic nervous system. In subjects with chronic mental stress, self-reported “initiation and maintenance of sleep” was significantly greater in the AHCC®-intake period than in the placebo intake period, and natural killer cell activity also increased after AHCC® intake, suggesting a possible mechanism of action of AHCC®. Our findings indicate that AHCC® is potentially effective in stress management and may be useful in the treatment of depression.

Persons with secondary progressive and relapsing remitting multiple sclerosis reveal different responses of tryptophan metabolism to acute endurance exercise and training

Disturbances in Tryptophan metabolism play a crucial role in multiple sclerosis (MS). Exercise is suspected to counteract the progress of MS and its side effects. Current research suggests alterations of Tryptophan metabolism in healthy individuals in response to exercise. We investigated the influence of acute aerobic exercise and training on Tryptophan metabolism in 57 inpatients with relapsing remitting ((RRMS) n=33) and secondary progressive ((SPMS) n=24) MS. Serotonin increased after training, whereas the kynurenine pathway was only activated in persons with RRMS. Further research is warranted to investigate whether these changes are associated with clinical measures (e.g. depressions and immune function).

Regulation of circulating chromogranin B levels in heart failure

Background: Chromogranin B (CGB) regulates B-type natriuretic peptide (BNP) production. Circulating CGB levels are elevated in heart failure (HF) animal models and HF patients, but also increase in healthy individuals in response to physical activity. Therefore, CGB seems to integrate information from myocardial stress and systemic neuro-endocrine activation. Substantial gaps remain in our understanding of CGB regulation in HF.Methods and results: We conducted a retrospective registry study including 372 patients. CGB and N-terminal pro-BNP (NT-proBNP) plasma levels were assessed in acute HF and chronic valvular HF patients and controls. CGB levels were significantly increased in acute HF and chronic valvular HF, but significantly higher in the latter. Patients in chronic valvular HF with severe mitral regurgitation (cHF-MR) showed significantly higher CGB levels than patients in chronic valvular HF with severe aortic stenosis. CGB levels progressively increased with worsening NYHA functional status and were moderately correlated to NT-proBNP, but independent of left ventricular (LV) ejection fraction (LVEF), LV mass, age and body weight. Finally, cHF-MR patients showed significant reductions of CGB levels after interventional mitral valve repair.Conclusion: CGB is a promising emerging biomarker in HF patients with unique potential to integrate information from myocardial stress and neuro-endocrine activation.

In the mind's eye: The late positive potential to negative and neutral mental imagery and intolerance of uncertainty.

There are many advantages to human beings' ability to generate and sustain mental imagery in the absence of exteroceptive stimuli; however, this ability may also underlie emotional disorders characterized by worry, rumination, or excessive concern about the future. For instance, fear-based disorders may be characterized by heightened ERPs to negative imagery. On the other hand, distress disorders may be characterized by attempts to avoid engaging with negative mental imagery, and therefore reduced electrocortical response. Prior ERP work has used negative and neutral pictorial stimuli to establish the parameters of response in healthy individuals, before taking these paradigms to clinical samples to assess aberrant emotion processing. Yet despite its clinical relevance, no study to date has elicited a late positive potential (LPP), a robust measure of emotion processing, to standardized negative imagined scenes. Here, participants listened to audio descriptions of negative and neutral scenes, and were asked to imagine these scenes as vividly as possible. Results showed that negative imagined scenes elicited an increased LPP, lasting approximately 10 s after audio description offset, as well as heightened ratings of arousal and unpleasantness. Moreover, participants with greater self-reported cognitive concerns about uncertain future events (higher prospective intolerance of uncertainty) showed reduced emotional modulation of the LPP. These data provide the first evidence of sustained electrocortical processing of standardized negative imagery elicited in the absence of salient visual cues, and suggest that cognitive risk for anxiety in an unselected sample may be represented phenotypically by blunted LPPs to negative imagery.

Other race effect on amygdala response during affective facial processing in major depression.

The other race effect, also known as own race bias, refers to the enhanced ability to recognize faces belonging to one's own race relative to faces from another race. The other race effect is associated with increased amygdala response in healthy individuals. The amygdala is a key node in emotion processing which shows impaired functioning in depression and has been proposed to be a marker of depressive state. We investigated the impact of the other race effect on amygdala responses in depression. Participants were 30 individuals with major depression (mean age 39.4 years) and 23 healthy individuals (mean age: 38.8 years) recruited from the community. Participants were Asian, Black/African American and Caucasian. During a functional MRI scan, participants viewed Caucasian faces which displayed a range of sad expressions. A region of interest analysis of left and right amygdala responses was performed. Increased bilateral amygdala responses were observed in response to the Caucasian face stimuli in participants who were Asian or Black/African American as compared to Caucasian participants in both healthy individuals and individuals with major depression. There was no significant group by race interaction effect. Increased amygdala responses associated with the other race effect were evident in both individuals with major depression and in healthy participants. Increased amygdala responses with the other race effect is a potential confound of the neural correlates of facial processing in healthy participants and in mental health disorders. The implications of the other race effect on impairments in interpersonal functioning in depression require further investigation.

Cardiac Autonomic and Blood Pressure Responses to an Acute Bout of Kettlebell Exercise.

Wong, A, Nordvall, M, Walters-Edwards, M, Lastova, K, Francavillo, G, Tripken, J, Summerfield, L, and Sanchez-Gonzalez, M. Cardiac autonomic and blood pressure responses to an acute bout of kettlebell exercise. J Strength Cond Res 35(2S): S173-S179, 2021-Kettlebell (KB) training has become an extremely popular exercise program for improving both muscle strength and aerobic fitness. However, the cardiac autonomic modulation and blood pressure (BP) responses induced by an acute KB exercise session are currently unknown. Understanding the impact of this exercise modality on the postexercise autonomic modulation and BP would facilitate appropriate exercise prescription in susceptible populations. This study evaluated the effects of an acute session of KB exercise on heart rate variability and BP responses in healthy individuals. Seventeen (male = 10 and female = 7) healthy subjects completed either a KB or nonexercise control trial in randomized order. Heart rate variability and BP measurements were collected at baseline, 3, 10, and 30 minutes after each trial. There were significant increases (p < 0.01) in heart rate, markers of sympathetic activity (nLF), and sympathovagal balance (nLF/nHF) for 30 minutes after the KB trial, whereas no changes from baseline were observed after the control trial. There were also significant decreases (p < 0.01) in markers of vagal tone (RMMSD and nHF) for 30 minutes as well as (p < 0.01) systolic BP and diastolic BP at 10 and 30 minutes after the KB trial, whereas no changes from baseline were observed after the control trial. Our findings indicate that KB exercise increases sympathovagal balance for 30 minutes postintervention, which is concurrent with an important hypotensive effect. Further research is warranted to evaluate the potential clinical application of KB training in populations that might benefit from postexercise hypotension, such as hypertensives.

The Effect of Buffering High Acid Load Meal with Sodium Bicarbonate on Postprandial Glucose Metabolism in Humans-A Randomized Placebo-Controlled Study.

Background: High dietary acid load relates to increased risk of type 2 diabetes in epidemiological studies. We aimed to investigate whether buffering a high acid load meal with an alkalizing treatment changes glucose metabolism post meal. Methods: Non-diabetic participants (n = 32) were randomized to receive either 1680 mg NaHCO3 or placebo, followed by a high acid load meal in a double-blind placebo-controlled crossover (1–4 weeks apart) study. Thirty (20 men) participants completed the study. Venous blood pH, serum bicarbonate, blood glucose, serum insulin, C-peptide, non-esterified fatty acid (NEFA), and plasma glucagon-like peptide-1 (GLP-1) concentrations were measured at baseline (fasting) and at 15–30 min intervals for 3 h post meal. Results: The treatment was well tolerated. Venous blood pH declined in the first 15 min post meal with the placebo (p = 0.001), but not with NaHCO3 (p = 0.86) and remained decreased with the placebo for 3 h (pinteraction = 0.04). On average over the 3 h blood pH iAUC was greater with NaHCO3 compared with placebo (p = 0.02). However, postprandial glucose, insulin, C-peptide, NEFA and GLP-1 were not different between treatments (pinteraction ≥ 0.07). Conclusions: An alkalizing medication administered pre-meal has no acute effect on glycaemia and insulin response in healthy individuals. Long-term interventions in at-risk populations are necessary to investigate the effect of sustained alkalization on glucose metabolism.

Abstract LB-203: VXL100, a MUC1 signal peptide based immunotherapy, acts through a neoantigen-like mechanism, and shows promising effects in hematological cancers

Abstract VXL100 (ImMucin®), a 21mer peptide, pan-HLA vaccine derived from the MUC1 signal peptide (SP) domain, has been shown to be safe and to elicit a robust and specific T and B-cell responses in stable and progressive multiple myeloma patients in a phase I/II clinical trial. It is now becoming recognized that the advantages of using the signal peptide domain for immunization stem from its unique B and T cells epitope restriction density and TAP independent presentation. Additionally, the low avidity of signal peptides as antigens, is believed to result in escaping negative selection in the thymus during development, and preservation of active clones in the peripheral blood. This may allow signal peptides to be presented as true neoantigens during tumor development and generate a robust immune response. To prove the neoantigenic properties of MUC1 SP, we have recently tested endogenous levels of specific anti-VXL100 T-cells by staining for VXL100-specific or control multimers. We also performed proliferation assays for patient TIL and normal donors PBMCs using cells stimulated with VXL100 or other MUC1 antigenic control peptides. VXL100 specific T-cell were found in 100% of patients (1.3-6%), VS. 0% in normal donors. We have found a direct correlation between the MUC1 signal peptide expression levels on tumor cells and levels of endogenous VXL100 specific T-cells. Positive signals were observed for multimers of other MUC1 peptides as well, but these were also seen in normal donors, suggesting a non-specific binding. Moreover, we were able to show that VXL100 specific exhausted CD8 cells exist at a non-significant levels as compared to the total exhausted CD8. When stimulated in-vitro with VXL100, PBMCs from 70% of naive normal donors and 94% of cancer patients showed a strong proliferative response (average of 8.9% and 16.5% proliferating cells, respectively). When stimulated with control peptides 0.5% - 5.2% of patients and 0 - 13% of donors showed positive proliferation response. Conclusions: VXL100, a novel immunotherapy agent shows the capacity to elicit a specific and robust T-cell response in healthy individuals and hematological cancer patients. These features suggest that MUC1 SP is a native sequence functioning as a cancer neoantigen and preserved through normal and tumor development. It presents an attractive opportunity for the development of an effective cancer immunotherapy. Citation Format: Limor Chen, Riva Kovjazin, Michael Shapira. VXL100, a MUC1 signal peptide based immunotherapy, acts through a neoantigen-like mechanism, and shows promising effects in hematological cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-203. doi:10.1158/1538-7445.AM2017-LB-203

Effects of Viral Peptide Presentation on CD4+ T Cell Responses to MHC Class II-Restricted Tumor Peptides

Background: Designing a vaccine against a defined tumor is a promising but complicated process that can be used as tumor immunotherapy. The presence of human telomerase reverse transcriptase (hTERT) has been proved in about 85% of tumors; therefore, this enzyme is a promising vaccine target. Most studies in tumor immunotherapy have focused on induction and reinforcement of CD8+ T cell responses against tumor antigens, but some evidence indicates that CD4+ T cell responses are important for induction of CD8+ T cell response and memory. Therefore, in this in vitro study, we combined an hTERT peptide with HIV peptides restricted to HLA-DRB1*11:03/04, the most common MHC class II molecule in Iran, to induce CD4+ T cell responses in healthy individuals and lung cancer patients. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll gradient centrifugation from nine healthy individuals and six lung cancer patients who were HLA-DRB1*11:03/04 positive. PBMCs were incubated with the tumoral and viral peptides for five days and then exposed to A549 cells to evaluate specific proliferative responses. The proliferation of PBMCs was examined by the MTT assay. Then, levels of secreted interferon-γ in culture media were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: Proliferation of PBMCs was significantly greater in the presence of the tumoral peptide than in controls (P = 0.001). In addition, PBMC proliferation was greater when the viral peptides were added than with the tumoral peptide alone (P = 0.000). The IFN-γ secretion assay results supported the MTT assay (P = 0.000). Conclusions: In this study, we demonstrated that the hTERT-derived peptide induced CD4+ T cell proliferation in healthy individuals and patients with lung cancer. Both PBMC proliferation and IFN-γ secretion were further induced by the addition of tumor and viral peptides in combination.

Immunological effects of Lactobacillus johnsonii N6.2 in healthy adults: A double‐blind, randomized trial

The intestinal environment may play a central role in the development of Type 1 Diabetes (T1D). However, the use of bacteria to alleviate the onset of this disease has been restricted to studies in rodent models. To date, the ability of a Lactobacillus probiotic to prevent T1D onset in humans has not been evaluated. L. johnsonii N6.2 mitigated the onset of T1D when administered to Biobreeding diabetes‐prone rats by altering the activity of intestinal indoleamine 2,3‐dioxygenase‐1 (IDO), correlating with a Th17 bias in the mesenteric lymph nodes of animals protected from T1D onset. Translating this work toward the prevention of T1D in humans required a pilot study in healthy individuals. We performed a human trial to evaluate the immunological response in healthy individuals (n=42; F=30, M=12; 23.2±5.5 y). The 13‐week study was divided into three phases: 1‐week pre‐baseline, 8‐week intervention (1 capsule/d of L. johnsonii N6.2 at 108 CFU or placebo), and 4‐week wash‐out. Blood samples were collected and analyzed throughout the study. Leukocyte subpopulations were assessed at baseline, treatment, and washout by immunophenotyping using flow cytometry and serum blood markers were quantified by ELISAs. Consumption of the L. johnsonii N6.2 did not affect the B cells, dendritic cells or regulatory T cells subsets. However, significant changes were observed in Monocytes, Natural Killer cells, T cells, T effector and follicular helper T cells in the L. johnsonii group. Specifically, the administration of L. johnsonii N6.2 increased the population of activated effector T cells, Th1 (CD45RO+, CD183+, CD196−) after 8 weeks of treatment, an effect that was maintained after the wash‐out period (12 weeks). Based on these results, the concentrations of IL2, IL6, TNFa, INFa, IFNg, sCD25 (IL2Ra), C reactive protein, insulin and IgA were quantified in blood samples. It was found that the concentrations of IgA increased significantly over the time in the L. johnsonii group while no changes were observed for the others. In this study, we identified several biomarkers as a result of L. johnsonii N6.2 consumption in healthy subjects. The results of this pilot study provide a solid foundation for an investigation into prevention of T1D onset by L. johnsonii N6.2 in an at‐risk human population.Support or Funding InformationThese studies were funded by grants from the JDRF (1‐INO‐2014‐176‐A‐V to GLL and a Career Development Award 2‐2012‐280 to TMB) and grants from the National Institutes of Health P01 AI42288 (to MAA and TMB.).

Acute Effects of Dried Apple Consumption on Metabolic and Cognitive Responses in Healthy Individuals

The health‐protective effects of fruits and vegetables may be at least partly attributed to phytochemicals. Apples are known to be especially high in free phenolic compounds. Apples and apple products are associated with reduced risk of type II diabetes mellitus (T2DM), which is likely due to their rich content of fiber, nutrients and various phytochemicals. Insufficient evidence is available regarding the acute dietary effects apple intake on postprandial metabolic responses. We assessed the potential for dried apple to regulate blood glucose and insulin responses as well as satiety and total plasma antioxidant levels in an acute feeding study with healthy individuals and explored the acute effect of dried apple on cognitive responses using eight neurocognitive tests. A randomized crossover design with repeated measures and a minimum of one week washout period between tests was used. On each test day after a fast of 10 hours, a standardized serving size of either diced dried apple or two muffins, each providing 55 g carbohydrate, was consumed by the participants. Blood glucose, insulin and antioxidant concentrations were measured at 0, 15, 30, 45, 60, 90, and 120 minutes and satiety was assessed on 100 mm visual analog scales every 15 minutes for two hours. Cognitive tests were administered before and 2 hours after consumption of the test food. Twenty‐one healthy, normal weight subjects completed the study. Repeated‐measures analysis of variance evaluated the effects of dietary condition and time on blood glucose, insulin, satiety and total antioxidant levels. Paired t‐tests were used to compare the effects of diet at individual time points. Main effects for time (p ≤ 0.01) and dietary trial (p ≤ 0.01) were detected for plasma glucose responses. Dried apple produced lower (p ≤ 0.02) glucose concentrations at the 30, 45, 60 and 120‐minute time points than muffins. Main effects for time (p ≤ 0.01) were detected for insulin responses, and dried apple produced lower (p ≤ 0.03) insulin concentrations at the 30‐minute time point than muffins. No differences were detected for total plasma antioxidant capacity; however, the percent change from baseline for total plasma antioxidant levels was higher throughout the 120 minutes post food consumption for the dried apples versus muffins. Subjects reported that they could eat more food during the apple trial compared to the muffin trial; however, no differences in hunger, fullness or desire to eat were detected. Apple intake resulted in better post‐test performance (p ≤ 0.03) for psychomotor speed, and muffin intake resulted in better post‐test performance for executive function (p ≤ 0.01) and cognitive flexibility (p ≤ 0.02). These findings suggested that dried apple intake could reduce postprandial blood glucose and serum insulin responses in healthy individuals but little consistent difference antioxidant status, satiety and cognitive function.Support or Funding InformationNone

Ultrasound Detection of Regional Oxidative Stress in Deep Tissues Using Novel Enzyme Loaded Nanoparticles.

Oxidative stress is a powerful tool that is critical to immune mediated responses in healthy individuals, yet additionally plays a crucial role in development of cancer, inflammatory pathologies, and tissue ischemia. Despite this, there remain relatively few molecular tools to study oxidative stress, particularly in living mammals. To develop an intravenously injectable probe capable of labeling sites of oxidative stress in vivo, 200 nm catalase synthetic hollow enzyme loaded nanospheres (catSHELS) are designed and fabricated using a versatile enzyme nanoencapsulation method. catSHELS catalyze H2 O2 to water and oxygen producing microbubbles that can be detected and imaged using a clinical ultrasound system. catSHELS are optimized in vitro to maximize ultrasound signal and their functionality is demonstrated in rat ischemic renal injury model. Ischemic oxidative injury is induced in a single kidney of normal rats by clamping the renal artery for 1 h followed by 2 h of reperfusion. Imaging of both kidneys is performed following the intravenous bolus injection of 1012 catSHELS of the optimized formulation. There is significant increase in ultrasound signal of the injured kidney relative to controls. This method offers a novel intravenous approach to detect oxidative stress in deep tissues in living animals.

Mycobacterial Hsp65 antigen upregulates the cellular immune response of healthy individuals compared with tuberculosis patients

ABSTRACTPreviously we showed that 65-kDa Mycobacterium leprae heat shock protein (Hsp65) is a target for the development of a tuberculosis vaccine. Here we evaluated peripheral blood mononuclear cells (PBMC) from healthy individuals or tuberculosis patients stimulated with two forms of Hsp65 antigen, recombinant DNA that encodes Hsp65 (DNA-HSP65) or recombinant Hsp65 protein (rHsp65) in attempting to mimic a prophylactic or therapeutic study in vitro, respectively. Proliferation and cytokine-producing CD4+ or CD8+ cell were assessed by flow cytometry. The CD4+ cell proliferation from healthy individuals was stimulated by DNA-HSP65 and rHsp65, while CD8+ cell proliferation from healthy individuals or tuberculosis patients was stimulated by rHSP65. DNA-HSP65 did not improve the frequency of IFN-gamma+ cells from healthy individuals or tuberculosis patients. Furthermore, we found an increase in the frequency of IL-10-producing cells in both groups. These findings show that Hsp65 antigen activates human lymphocytes and plays an immune regulatory role that should be addressed as an additional antigen for the development of antigen-combined therapies.

Reaction of the hemocoagulation system to tissue hypoxia in patients with chronic obstructive pulmonary disease

Background. Nowadays little data related to the hemostatic system and fibrinolysis in patients with chronic obstructive pulmonary disease (COPD) are available. This is due to the lack of standardized methods for studying the hemostasis system, as well as to the lack of a single functional test that allows the evaluation of the complete fibrinogenesis cycle in whole blood. Aim. The aim of our study was to develop a functional test capable of analyzing the blood gas composition in the “point-of-care test” method for the evaluation of the hemostatic potential in patients with COPD, based on a standardized test stimulus, which is tissue hypoxia. The current level of clinical and laboratory diagnostics requires personification and research of the hemo-coagulation system in real time (point-of-care test), which allows low-frequency piezotromboelastography(NVTEG) to be performed. Materials and methods. NVTEG was chosen to estimate the state of the hemocoagulation system. Ten patients with COPD and 10 healthy volunteers were examined. Hypoxia was selected as a standardized test stimulus. Hypoxia conditions were caused by smoking one standard cigarette (composition: resin 10 mg/cig., nicotine 0,7 mg/cig., CO 10 mg/cig.). The degree of tissue hypoxia was assessed with the GASTAT-navi blood gas analyzer. Results. The study has shown that in response to the standard test stimulus, which is the tissue hypoxia caused by smoking of a standardized cigarette, two types of haemostatic potential reaction were detected both in patients with COPD and healthy volunteers. The first type of reaction – “hypercoagulation” – is characterized by the formation of chronometric and structural hypercoagulation at all stages of fibrinogenesis and increased coagulation activity by 25–30% compared with the response in healthy individuals. The second type of reaction – “hypocoagulation” – is characterized by the formation of chronometric and structural hypocoagulation, a decrease in coagulation activity by 25–30% compared with the response in healthy individuals. Conclusion. Test stimulus, which acts as tissue hypoxia, causes a uniform spectrum of changes in the blood gas composition and hemocoagulation system in both healthy volunteers and patients with COPD. The possibility of online assessment of all stages of fibrinogenesis makes it possible to stratify patients with COPD by type of reaction, which is certain to have an important diagnostic and prognostic value and in the future will allow a more personified approach for choosing the treatment tactics.

The relationship between dispositional empathy and prefrontal cortical functioning in patients with frontal lobe epilepsy.

Background & Objective:Rehabilitation focuses brain-behavior relationship which highlights interaction between psychological and neurobiological factors for better patient care. There is a missing link in the literature about socio-cognitive aspects of frontal lobe epilepsy. Our objective was to examine prefrontal cortical functioning (PCF) and empathic abilities in patients with frontal lobe epilepsy (FLE). Further, we analyzed whether any relationship between components of dispositional empathy and PCF exists in patients with FLE.Methods:The study was designed in an experimental paradigm. Sixty patients with FLE were recruited from Sheikh Zayed and Jinnah hospital, Pakistan. Sixty healthy individuals in response to an advertisement took part in the study as control subjects. Participants completed interpersonal reactivity index. Following they performed clock drawing test and word-color identification task switching experiment.Result:Patients with FLE demonstrated weaker PCF (i.e., cognitive flexibility and executive function) as compared to healthy control subjects. Patients with FLE scored lesser on cognitive empathy as compared to healthy control subjects. On contrary, there was no significant difference between patient and control group on affective empathy. Cognitive not affective empathy was potential predictor of PCF.Conclusion:Cognitive empathy is a significant marker of prefrontal cortical functioning (PCF) in FLE. Higher cognitive empathy would lead to efficient PCF.