Reactivity In Healthy Individuals Research Articles

Effect of glycosylation on the affinity of the MTB protein Ag85B for specific antibodies: towards the design of a dual-acting vaccine against tuberculosis

BackgroundTo create a dual-acting vaccine that can fight against tuberculosis, we combined antigenic arabino-mannan analogues with the Ag85B protein. To start the process, we studied the impact of modifying different parts of the Ag85B protein on its ability to be recognized by antibodies.ResultsThrough our research, we discovered that three modified versions of the protein, rAg85B-K30R, rAg85B-K282R, and rAg85B-K30R/K282R, retained their antibody reactivity in healthy individuals and those with tuberculosis. To further test the specificity of the sugar AraMan for AraMan antibodies, we used Human Serum Albumin glycosylated with AraMan-IME and Ara3Man-IME. Our findings showed that this specific sugar was fully and specifically modified. Bio-panning experiments revealed that patients with active tuberculosis exhibited a higher antibody response to Ara3Man, a sugar found in lipoarabinomannan (LAM), which is a major component of the mycobacterial cell wall. Bio-panning with anti-LAM plates could eliminate this increased response, suggesting that the enhanced Ara3Man response was primarily driven by antibodies targeting LAM. These findings highlight the importance of Ara3Man as an immunodominant epitope in LAM and support its role in eliciting protective immunity against tuberculosis. Further studies evaluated the effects of glycosylation on the antibody affinity of recombinant Ag85B and its variants. The results indicated that rAg85B-K30R/K282R, when conjugated with Ara3Man-IME, demonstrated enhanced antibody recognition compared to unconjugated or non-glycosylated versions.ConclusionsCoupling Ara3Man to rAg85B-K30R/K282R could lead to the development of effective dual-acting vaccines against tuberculosis, stimulating protective antibodies against both AraMan and Ag85B, two key tuberculosis antigens.

Untargeted Plasma Metabolomics and Gut Microbiome Profiling Provide Novel Insights into the Regulation of Platelet Reactivity in Healthy Individuals.

Considerable variation exists in platelet reactivity to stimulation among healthy individuals. Various metabolites and metabolic pathways influence platelet reactivity, but a comprehensive overview of these associations is missing. The gut microbiome has a strong influence on the plasma metabolome. Here, we investigated the association of platelet reactivity with results of untargeted plasma metabolomics and gut microbiome profiling. We used data from a cohort of 534 healthy adult Dutch volunteers (the 500 Functional Genomics study). Platelet activation and reactivity were measured by the expression of the alpha-granule protein P-selectin and the binding of fibrinogen to the activated integrin αIIbβ3, both in unstimulated blood and after ex vivo stimulation with platelet agonists. Plasma metabolome was measured using an untargeted metabolic profiling approach by quadrupole time-of-flight mass spectrometry. Gut microbiome data were measured by shotgun metagenomic sequencing from stool samples. Untargeted metabolomics yielded 1,979 metabolites, of which 422 were identified to play a role in a human metabolic pathway. Overall, 92/422 (21.8%) metabolites were significantly associated with at least one readout of platelet reactivity. The majority of associations involved lipids, especially members of eicosanoids, including prostaglandins and leukotrienes. Dietary-derived polyphenols were also found to inhibit platelet reactivity. Validation of metabolic pathways with functional microbial profiles revealed two overlapping metabolic pathways ("alanine, aspartate, and glutamate metabolism" and "arginine biosynthesis") that were associated with platelet reactivity. This comprehensive overview is an resource for understanding the regulation of platelet reactivity by the plasma metabolome and the possible contribution of the gut microbiota.

Возрастные изменения иммунной реактивности у жителей горной местности Кыргызстана

To study the immune reactivity in people of different ages living at different heights of the mountainous area. The following task was solved to achieve the aim of the research: to study of the age-related features of immune reactivity in healthy individuals living in low- and high-mountainous regions. Modern and classical methods of immunological analysis were used to determine the immune status and natural resistance in humans. The article presents the results of the study of immune reactivity in 116 people of both sexes aged from 16 to 63 years old that were divided into 3 age groups living at different altitude zones — in the low mountains (930 m above sea level) and in the highlands (2800 m above sea level). Results. Comparative evaluation of immune reactivity in low-mountain areas in two age groups (II–III) revealed significant changes, compared with the first age group. In the third age group, there is a distinctly pronounced decrease in all the basic indices of phagocytosis, as well as the level of lysozyme and complement. For all age groups in the highlands compared with the low-mountain range, there is a decrease in the number of all T-lymphocytes, their subpopulations and functional activity of all types of cells participating in phagocytosis. An increased concentration of circulating immune complexes (CIC) was detected. The revealed quantitative changes in the immunity indices in all age groups examined indicate a reduction in the reserve capacity of the body’s immune defenses with age, but more significantly in high-altitude inhabitants.

Does non-invasive brain stimulation modulate emotional stress reactivity?

Excessive emotional responses to stressful events can detrimentally affect psychological functioning and mental health. Recent studies have provided evidence that non-invasive brain stimulation (NBS) targeting the prefrontal cortex (PFC) can affect the regulation of stress-related emotional responses. However, the reliability and effect sizes have not been systematically analyzed. In the present study, we reviewed and meta-analyzed the effects of repetitive transcranial magnetic (rTMS) and transcranial direct current stimulation (tDCS) over the PFC on acute emotional stress reactivity in healthy individuals. Forty sham-controlled single-session rTMS and tDCS studies were included. Separate random effects models were performed to estimate the mean effect sizes of emotional reactivity. Twelve rTMS studies together showed no evidence that rTMS over the PFC influenced emotional reactivity. Twenty-six anodal tDCS studies yielded a weak beneficial effect on stress-related emotional reactivity (Hedges’ g = −0.16, CI95% = [−0.33, 0.00]). These findings suggest that a single session of NBS is insufficient to induce reliable, clinically significant effects but also provide preliminary evidence that specific NBS methods can affect emotional reactivity. This may motivate further research into augmenting the efficacy of NBS protocols on stress-related processes.

Dietary nitrate supplementation enhances cerebrovascular CO2 reactivity in a sex-specific manner.

Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction, and increased NO has the potential to enhance cerebral blood flow (CBF). Dietary supplementation with sodium nitrate, a precursor of NO, could improve cerebrovascular function, but this has not been investigated. In 17 individuals, we examined the effects of a 7-day supplementation of dietary nitrate (0.1 mmol·kg-1·day -1) on cerebrovascular function using a randomized, single-blinded placebo-controlled crossover design. We hypothesized that 7-day dietary nitrate supplementation increases CBF response to CO2 (cerebrovascular CO2 reactivity) and cerebral autoregulation (CA). We assessed middle cerebral artery blood velocity (MCAv) and blood pressure (BP) at rest and during CO2 breathing. Transfer function analysis was performed on resting beat-to-beat MCAv and BP to determine CA, from which phase, gain, and coherence of the BP-MCAv data were derived. Dietary nitrate elevated plasma nitrate concentration by ~420% (P < 0.001) and lowered gain (d = 1.2, P = 0.025) and phase of the BP-MCAv signal compared with placebo treatment (d = 0.7, P = 0.043), while coherence was unaffected (P = 0.122). Dietary nitrate increased the MCAv-CO2 slope in a sex-specific manner (interaction: P = 0.016). Dietary nitrate increased the MCAv-CO2 slope in men (d = 1.0, P = 0.014 vs. placebo), but had no effect in women (P = 0.919). Our data demonstrate that dietary nitrate greatly increased cerebrovascular CO2 reactivity in healthy individuals, while its effect on CA remains unclear. The selective increase in the MCAv-CO2 slope observed in men indicates a clear sexual dimorphic role of NO in cerebrovascular function.NEW & NOTEWORTHY We found dietary nitrate supplementation improved the brain blood vessels' response to CO2, cerebrovascular CO2 reactivity, without affecting blood pressure in a group of healthy individuals. Meanwhile, the effect of dietary nitrate on the relationship between blood pressure and brain blood flow, cerebral autoregulation, was inconclusive. The improvement in cerebrovascular CO2 reactivity was only observed in the male participants, alluding to a sex difference in the effect of dietary nitrate on brain blood flow control. Our findings indicate that dietary nitrate could be an effective strategy to enhance cerebrovascular CO2 reactivity.

(146) - Chronic perceived stress heightens laboratory pain in healthy young adults

Clinical observational studies report an association between chronic stress and heightened clinical pain, but the direction of causality remains unresolved because clinical pain can be a major cause of stress. To resolve this issue, the present study examined whether chronic psychological stress heightens laboratory induced pain, affect, and autonomic reactivity in healthy individuals reporting high and low levels of stress. Using a 2 (high vs. low stress) X 2 (pain vs. no pain) design, participants prescreened for high (n = 59) and low (n = 71) chronic perceived stress on the Perceived Stress Scale were randomized to either a pain or no pain condition. Participants immersed their dominant hand into a cold (0–2°C) or warm (35°C) water bath to induce a painful or neutral sensation and were told to keep their hand in the water for two minutes or until pain tolerance. After termination, participants rated both their pain and affect, then sat still during the recovery phase while recordings of heartrate and skin conductance were taken. After controlling for gender, pain intensity and unpleasantness reports were greater in the high stress pain group relative to those in the low stress pain group (p's < .05). Additionally, while both high and low stress groups demonstrated similar elevations in subjective arousal during laboratory pain, individuals in the high stress pain group maintained greater levels of arousal during the recovery period relative to their low stress counterparts (p = .032). Regarding autonomic reactivity, both high and low stress pain groups presented with comparable changes in heartrate and skin conductance during the pain and recovery phase. Together, these results suggest that chronic perceived stress contributes to heightened pain and psychological arousal to acute laboratory pain. These findings may provide insight into the effects of chronic stress on acute clinical pain experiences.

Beta-Glucans Supplementation Associates with Reduction in P-Cresyl Sulfate Levels and Improved Endothelial Vascular Reactivity in Healthy Individuals.

BackgroundOat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD).ObjectiveThe aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD.MethodsWe carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro “Cuore Mio” pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment.ResultsThe nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged.ConclusionsWe demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease.

Correlation of High Density Lipoproteins and Cerebral Vasomotor Reactivity in Healthy Individuals

Objective: Cerebral vasomotor reactivity (VMR) which reflects cerebrovascular autoregulation is impaired in stroke patients. Some risk factors for stroke such as hyperlipidemia affects endothelial layer of vessels and by disturbing of VMR make an important role in the occurrence of stroke. The aim of this study is the evaluation of high-density lipoproteins (HDL) effects in VMR of cerebral vessels. Methods and Materials: Sixty healthy male volunteers ( 40 mg/ml). The mean flow velocity of both middle cerebral arteries (MCA) continuously measured by transcranial Doppler (TCD) and VMR of MCA was calculated by breath-holding index (BHI). Results: Mean BHI of left MCA in persons with low, normal and high HDL levels were 1.32 ± 0.44 %/sec, 1.47 ± 0.65 %/sec and 1.18 ± 0.48 %/sec respectively. Mean BHI of right MCA in low, normal and high HDL groups were 1.13 ± 0.35 %/sec, 1.39 ± 0.62 %/sec and 1.36 ± 0.55 %/sec, respectively. There was no statistically significant difference among these groups (p>0.05). Conclusion: The current study showed that there is no statistically significant correlation between serum HDL level and BHI in left and right MCA of healthy persons.

Blunted autonomic reactivity to pharmacological panic challenge under long-term escitalopram treatment in healthy men.

Background:Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV).Methods:The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application.Results:Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; pη2 = 0.499), SDNN (p < 0.001; pη2 = 576), RMSSD (p = 0.015; pη2 = 194), NN50% (p = 0.008; pη2 = 0.224), and LF% (p = 0.014; pη2 = 0.196), and moderate effects with respect HF% (p = 0.099; pη2 = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response.Conclusions:Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.

Monocyte-derived dendritic cells can induce autoreactive CD4(+) T cells showing myeloid lineage directed reactivity in healthy individuals.

T cells against self-antigens can be detected in peripheral blood of healthy individuals, although intrathymic negative selection removes most high-avidity T cells specific for self-antigens from the peripheral repertoire. Moreover, spontaneous T-cell proliferation following stimulation with autologous monocyte-derived dendritic cells (autoDCs) has been observed in vitro. In this study, we characterized the nature and immunological basis of the autoDC reactivity in the T-cell repertoire of healthy donors. We show that a minority of naive and memory CD4(+) T cells within the healthy human T-cell repertoire mediates HLA-restricted reactivity against autoDCs, which behave like a normal antigen-specific immune response. This reactivity appeared to be primarily directed against myeloid lineage cells. Although cytokine production by the reactive T cells was observed, this did not coincide with overt cytotoxic activity against autoDCs. AutoDC reactivity was also observed in the CD8(+) T-cell compartment, but this appeared to be mainly cytokine-induced rather than antigen-driven. In conclusion, we show that the presence of autoreactive T cells harboring the potential to react against autologous and HLA-matched allogeneic myeloid cells is a common phenomenon in healthy individuals. These autoDC-reactive T cells may help the induction of primary T-cell responses at the DC priming site.

S.07.02 In vivo measurements of brain serotonergic markers and analysis of drug use profiles among recreational ecstasy and hallucinogen users

S.07. Young Scientists Award symposium 2 S.07. Young Scientists Award symposium 2 S.07.01 Frontal cortex serotonin transporter binding is positively associated with the cortisol awakening response in healthy volunteers V.G. Frokjaer 1 ° , D. Erritzoe 1 , P. Jensen 1 , P.M. Rasmussen 2 , K.K. Holst 3 , J. Madsen 4 , W. Baar´e 5 , C. Svarer 1 , G.M. Knudsen 1 . 1 Center for integrated molecular brain imaging and Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark; 2 The Danish National Research Foundation’s Center for Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark; 3 Department of Biostatistics, Copenhagen University Hospital, Copenhagen, Denmark; 4 PET and Cyclotron Unit, Copenhagen University Hospital, Copenhagen, Denmark; 5 Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark Stress vulnerability is linked to the serotonin transporter gene. Both stress and dysfunctional serotonergic neurotransmission are critical in the development and treatment of neuropsychiatric disorders. We studied associations between serotonergic markers and hypothalamic–pituitary–adrenal (HPA) axis activity in 32 healthy volunteers. Our results suggest that in mentally healthy individuals prefrontal serotonin transporter (SERT) binding is associated with basal HPA-axis reactivity. Thirty-two healthy vol- unteers (mean age 35 ±20, 7 women) underwent SERT imaging with 11C[DASB]-PET and performed saliva home-sampling of the cortisol awakening response. The cortisol awakening response (area under curve with respect to increase from baseline, AUCi) correlated positively with prefrontal SERT in a model adjusting for age and genotype (p = 0.01). The correlation was not accounted for by age, gender, BMI, personality, SERT promoter genotype, perceived stress, or seasonality (daylight minutes at scan). No significant correlation was demonstrated in midbrain (p = 0.48), pallidostriatum (p = 0.17), or occipital cortex (p = 0.88). However, a trend was observed in anterior cingulate (p = 0.07). Individuals carrying the s- or L G “stress-vulnerable” alleles of the SERT promoter gene did not show a stronger coupling between frontal SERT binding and the cortisol awakening response as tested by an interaction analysis. Our results are consistent with the hypothesis that prefrontal serotonergic neurotransmission is coupled with basal stress reactivity in healthy individuals. This coupling might be established through early neurodevelopment and seems not to be modified by SERT promoter genotype in the adult brain of mentally healthy individuals. S195 S.07.02 In vivo measurements of brain serotonergic markers and analysis of drug use profiles among recreational ecstasy and hallucinogen users D. Erritzoe 1 ° , V.F. Frokjaer 2 , C.L. Licht 2 , M. Christoffersen 2 , W. Baare 3 , T.Z. Ramshoy 3 , C. Svarer 2 , T.L. Jernigan 4 , 1 CIMBI Copenhagen and Imperial G.M. Knudsen 2 . College London, Neurobiology Research Unit in Copenhagen and Neuropsychopharmacology Unit in London, London, United Kingdom; 2 CIMBI Copenhagen and University Hospital Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark; 3 CIMBI Copenhagen and Hvidovre University Hospital, Danish Center for Magnetic Resonance Imaging, Copenhagen, Denmark; 4 CIMBI Copenhagen Hvidovre University Hospital and University of California San Diego, Danish Center for Magnetic Resonance Imaging in Copenhagen and Dept of Psychiatry in San Diego, San Diego, USA The aim of the current study was (1) to compare substance user profiles for MDMA (3,4-methylenedioxy-N-methamphetamine − ecstasy) preferring (MPU) and hallucinogen preferring users (HPU), and (2) in subgroup of these users to separate presynaptic (MDMA) from postsynaptic (MDMA and hallucinogens) drug ef- fect on in-vivo serotonergic markers using PET (positron emission tomography) [1]. Ninety-eight young recreational Danish drug users (26±5 y.o., 85 males) reporting minimum 15 illicit drug experiences and use of MDMA/hallucinogens within the last year were included and divided in MPUs (n = 50) and HPUs (n = 48) based on the relative number of lifetime exposures. A subgroup of 14 MPUs and 10 HPUs and a group of 21 non-using control subjects underwent [F-18]altanserin-(5-HT 2A )- and [11-C]DASB-(SERT)-PET. Compared to HPUs, more MPUs reported drug use at parties, in binges, administration of MDMA as tablets rather than powder, and co-use of stimulants. When compared to non-users, significant decreases in SERT binding were seen in MPUs (neocortex: −59%, pallidostriatum: −19%) but not in HPUs. The SERT binding was negatively correlated to the number of lifetime MDMA exposures, and the time of abstinence from MDMA was positively correlated to subcortical but not to cortical SERT binding. A small decrease in neocortical 5-HT 2A binding in the total drug user group was also detected. Since MDMA but not hallucinogen use was found to be asso- ciated with decreases in cerebral SERT binding, our data suggest that this effect is mediated through a direct presynaptic MDMA effect rather than by the 5-HT 2A agonistic effects of MDMA.

Subchronic duloxetine administration alters the extended amygdala circuitry in healthy individuals

Neuroimaging studies have consistently linked depression to hyperactivation of a (para)limbic affective processing network centered around the amygdala. Recent studies have started to investigate how antidepressant drugs affect amygdala reactivity in healthy individuals, but the influence of their subchronic administration on the functional integrity of the affective neurocircuitry as a whole remains unknown. Therefore, we used functional magnetic resonance imaging in nineteen healthy volunteers to assess the effect of two weeks of administration of the combined serotonin and norepinephrine reuptake inhibitor duloxetine (60mg) on reactivity and functional connectivity within the affective neurocircuitry in a double-blind, placebo-controlled, crossover design. Using an emotional face matching task we demonstrated that duloxetine reduced neural responses in affect processing regions including the amygdala, the anterior insula, the thalamus and the ventral aspect of the anterior cingulate cortex. Additionally, functional coupling between the amygdala and the anterior insula was enhanced by the drug. These results suggest that duloxetine attenuates the bottom-up processing of biologically salient information in an extended amygdala circuitry, while at the same time possibly potentiating the effective communication between its subparts. Since hyperactivation of the same affective neurocircuitry is thought to underlie emotional dysfunction in depression, these results suggest a putative neural mechanism through which duloxetine could normalize typical negativity biases in depression.

Differential Patterns of HPA Activity and Reactivity in Adult Posttraumatic Stress Disorder and Major Depressive Disorder

Despite a number of overlapping symptoms, individuals with posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) often display hypothalamic-pituitary-adrenal (HPA) profiles that appear quite different from one another. This review describes the patterns of HPA-axis activity and reactivity in healthy individuals compared to individuals with these two disorders. Measures of HPA-axis activity and reactivity include cortisol levels at rest, in response to the dexamethasone suppression test (DST), and in response to psychological stress. The research reviewed presents the possibility of diagnostic specificity with regard to HPA function. In particular, the differential response pattern to the DST suggests that, while it cannot be considered a pure diagnostic tool, it should be one measure taken into consideration during diagnosis.

Bronchial Reactivity in Healthy Individuals Undergoing Long-term Topical Treatment With β-Blockers

To assess the impact of long-term treatment with topical timolol on bronchial reactivity in healthy individuals. Twenty-one otherwise healthy individuals with high-pressure primary open-angle glaucoma were enrolled in a randomized controlled clinical trial. Eleven patients underwent 3 years of topical 0.5% timolol treatment followed by a 1-year washout period; 10 patients underwent primary argon laser trabeculoplasty. Functional variables and bronchial reactivity (forced expiratory volume in 1 second and metacholine challenge test results) were assessed in both groups at enrollment and after 3 and 4 years of follow-up. After 3 years, a measurable response to metacholine challenge was recorded in 6 of 11 otherwise symptom-free individuals treated with 0.5% timolol twice daily. A detectable response to metacholine challenge was still present in half of these individuals (3 of 6) when further washed out for 1 year from the topical beta-blocker. No significant variation in bronchial reactivity was measured in the laser-treated group during 4 years of follow-up. Healthy individuals who undergo long-term topical application of a nonselective beta-blocker (0.5% timolol) can develop a subclinical increase in bronchial reactivity. This phenomenon may not be completely reversible on withdrawal of the beta-blocker.

Mapping hypercapnia-induced cerebrovascular reactivity using BOLD MRI

Severe carotid artery stenosis or occlusion may put patients at risk for ischaemic stroke. Reduced cerebrovascular reserve capacity is a possible indicator of an imminent ischaemic event and can be determined by assessment of cerebrovascular reactivity to a vasodilative stimulus. However, little is known about the distribution of cerebrovascular reactivity in healthy individuals. In 13 healthy volunteers, dynamic T2* MR images, acquired at alternating inspiratory pCO2 levels, showed a high percentage of signal change in grey matter, with a strong linear correlation with end-tidal pCO2. The mean percentages of signal change for grey and white matter were 5.9 +/- 1.2% and 1.9 +/- 0.5%, respectively. The mean time lag between CO2 stimulus and haemodynamic response was 15 +/- 4 s for grey matter and 180 +/- 12 s for white matter. Parameter mapping revealed a hemispherically symmetrical and homogeneous distribution of cerebrovascular reactivity over the entire grey matter. These findings indicate that it may be feasible to detect exhausted cerebrovascular autoregulation in patients with a compromised cerebral vasculature.

Reduced cellular immune reactivity in healthy individuals during the malaria transmission season

Antigen-induced cellular immune responses are suppressed during acute malaria. The present study engages the possibility that malaria-induced alterations in cellular immune reactivity extend beyond the clinical disease. Thus, lymphoproliferative responses of healthy individuals were diminished during the malaria transmission period in individuals living in an area of highly seasonal, unstable malaria transmission. This finding may have important implications for the design of studies of stimulatory properties of antigens using lymphocytes of endemic origin.