Higher Set Point Research Articles

Counteraction of HLA-C-mediated immune control of HIV-1 by Nef.

A host genetic variant (-35C/T) correlates with increased human leukocyte antigen C (HLA-C) expression and improved control of HIV-1. HLA-C-mediated immunity may be particularly protective because HIV-1 is unable to remove HLA-C from the cell surface, whereas it can avoid HLA-A- and HLA-B-mediated immunity by Nef-mediated down-modulation. However, some individuals with the protective -35CC genotype exhibit high viral loads. Here, we investigated whether the ability of HIV-1 to replicate efficiently in the "protective" high-HLA-C-expression host environment correlates with specific functional properties of Nef. We found that high set point viral loads (sVLs) were not associated with the emergence of Nef variants that had acquired the ability to down-modulate HLA-C or were more effective in removing HLA-A and HLA-B from the cell surface. However, in individuals with the protective -35CC genotype we found a significant association between sVLs and the efficiency of Nef-mediated enhancement of virion infectivity and modulation of CD4, CD28, and the major histocompatibility complex class II (MHC-II)-associated invariant chain (Ii), while this was not observed in subjects with the -35TT genotype. Since the latter Nef functions all influence the stimulation of CD4(+) T helper cells by antigen-presenting cells, they may cooperate to affect both the activation status of infected T cells and the generation of an antiviral cytotoxic T-lymphocyte (CTL) response. In comparison, different levels of viremia in individuals with the common -35TT genotype were not associated with differences in Nef function but with differences in HLA-C mRNA expression levels. Thus, while high HLA-C expression may generally facilitate control of HIV-1, Nef may counteract HLA-C-mediated immune control in some individuals indirectly, by manipulating T-cell function and MHC-II antigen presentation.

Probing material properties of polymeric surface layers with tapping mode AFM: Which cantilever spring constant, tapping amplitude and amplitude set point gives good image contrast and minimal surface damage?

A phase shift between the oscillatory motion and drive motion of an AFM-cantilever used for tapping mode AFM imaging can be related to adhesive and elastic properties of surface layers. In this study it was studied how optimal contrast between hard and soft surface layers can be achieved while minimizing the surface damage. This was investigated by performing classical force-distance measurements while driving the cantilever as in tapping mode imaging. The amplitude and phase response as a function of the average tip-surface separation was recorded. Five different cantilevers with a wide range of spring constants and four different tapping amplitudes were investigated and compared. Based on these experiments it is concluded that too stiff cantilever, high free tapping amplitude and low amplitude set point value often lead to surface damage, while too low spring constant and low free tapping amplitude result in poor phase image contrast. Intermediate values where little surface damage and significant image contrast are obtained were identified. In all cases it was observed that the best image contrast was obtained when the amplitude set point was chosen such that the amplitude during imaging was reduced to approximately 50% of the free amplitude.

The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder

This review describes patients with schizophrenia and bipolar disorder. In such patients, a high inflammatory set point of circulating monocytes at the transcriptome level is observed, involving various inflammatory transcripts forming distinct fingerprints (the transcriptomic monocyte fingerprint in schizophrenia overlaps with that in bipolar disorder, but also differs with it at points). There are increased levels of compounds of the IL-1, IL-6 and TNF system in the serum (be it modest and inconsistent). There is also evidence that the IL-2 system is activated in patients with schizophrenia (and perhaps those with mania), although independently of the activation of the IL-1, IL-6 and TNF systems, suggesting separate inducing mechanisms for monocyte and T-cell activation. It is not yet known whether such T cell activation involves the Th1/Th2/Th17 or Treg systems.

Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals

Toll-like receptors (TLRs) are innate immune sensors that are integral to resisting chronic and opportunistic infections. Mounting evidence implicates TLR polymorphisms in susceptibilities to various infectious diseases, including HIV-1. We investigated the impact of TLR single nucleotide polymorphisms (SNPs) on clinical outcome in a seroincident cohort of HIV-1-infected volunteers. We analyzed TLR SNPs in 201 antiretroviral treatment-naive HIV-1-infected volunteers from a longitudinal seroincident cohort with regular follow-up intervals (median follow-up 4.2 years, interquartile range 4.4). Participants were stratified into two groups according to either disease progression, defined as peripheral blood CD4(+) T-cell decline over time, or peak and setpoint viral load. Haplotype tagging SNPs from TLR2, TLR3, TLR4, and TLR9 were detected by mass array genotyping, and CD4(+) T-cell counts and viral load measurements were determined prior to antiretroviral therapy initiation. The association of TLR haplotypes with viral load and rapid progression was assessed by multivariate regression models using age and sex as covariates. Two TLR4 SNPs in strong linkage disequilibrium [1063 A/G (D299G) and 1363 C/T (T399I)] were more frequent among individuals with high peak viral load compared with low/moderate peak viral load (odds ratio 6.65, 95% confidence interval 2.19-20.46, P < 0.001; adjusted P = 0.002 for 1063 A/G). In addition, a TLR9 SNP previously associated with slow progression was found less frequently among individuals with high viral setpoint compared with low/moderate setpoint (odds ratio 0.29, 95% confidence interval 0.13-0.65, P = 0.003, adjusted P = 0.04). This study suggests a potentially new role for TLR4 polymorphisms in HIV-1 peak viral load and confirms a role for TLR9 polymorphisms in disease progression.

Small intestine CD4+ cell reduction and enteropathy in simian/human immunodeficiency virus KS661-infected rhesus macaques in the presence of low viral load

Human immunodeficiency virus type 1, simian immunodeficiency virus and simian/human immunodeficiency virus (SHIV) infection generally lead to death of the host accompanied by high viraemia and profound CD4(+) T-cell depletion. SHIV clone KS661-infected rhesus macaques with a high viral load set point (HVL) ultimately experience diarrhoea and wasting at 6-12 months after infection. In contrast, infected macaques with a low viral load set point (LVL) usually live asymptomatically throughout the observation period, and are therefore referred to as asymptomatic LVL (Asym LVL) macaques. Interestingly, some LVL macaques exhibit diarrhoea and wasting similar to the symptoms of HVL macaques and are termed symptomatic LVL (Sym LVL) macaques. This study tested the hypothesis that Sym LVL macaques have the same degree of intestinal abnormalities as HVL macaques. The proviral DNA loads in lymphoid tissue and the intestines of Sym LVL and Asym LVL macaques were comparable and all infected monkeys showed villous atrophy. Notably, the CD4(+) cell frequencies of lymphoid tissues and intestines in Sym LVL macaques were remarkably lower than those in Asym LVL and uninfected macaques. Furthermore, Sym LVL and HVL macaques exhibited an increased number of activated macrophages. In conclusion, intestinal disorders including CD4(+) cell reduction and abnormal immune activation can be observed in SHIV-KS661-infected macaques independent of virus replication levels.

Potential use of model predictive control for optimizing the column flotation process

A constrained model predictive control (MPC) strategy is proposed to deal with the problem of optimizing flotation column operation using secondary variables. Froth depth, collection zone gas hold-up and bias rate are selected as secondary variables to be controlled whereas tailing, wash-water and gas flow rate are used as manipulated variables. The control problem was formulated in order to minimize the tracking error of the gas hold-up and bias rate by maintaining gas flow rate, wash-water flow rate and bias rate within their operational limits. In particular, a strategy was conceived to optimize the column flotation process based on establishing an unreachable high set point for the gas hold-up (which is equivalent to maximizing the bubble surface area available for particle collection at a given flotation reagent dosage and thus recovery), while simultaneously satisfying operational constraints (such as ensuring a positive bias rate to prevent gangue entrainment and therefore concentrate grade deterioration). Several other operational constraints on wash-water, gas rate, gas hold-up and bias rate were considered, their use being justified from a processing point of view. Since this study deals with the hydrodynamic characteristics of flotation columns, a pilot flotation column working with a two-phase system is sufficient to demonstrate the advantages of using predictive control for this process optimization.

Association of HIV-Specific and Total CD8+ T Memory Phenotypes in Subtype C HIV-1 Infection with Viral Set Point

Understanding early immunological events during HIV-1 infection that may set the course of disease progression is important for identifying correlates of viral control. This study explores the association of differentiation profiles of HIV-specific and total memory CD8(+) T cells with viral set point. A cohort of 47 HIV-1-infected individuals, with differing viral set points at 12 mo, were recruited during acute infection. We identified that the magnitude of IFN-gamma(+) T cell responses at 6 mo postinfection did not associate with viral set point at 12 mo. A subset of 16 individuals was further studied to characterize CD8(+) T cells for expression patterns of markers for memory differentiation, survival (CD127), senescence (CD57), and negative regulation (programmed death-1). We show that viral control and the predicted tempo of HIV disease progression in the first year of infection was associated with a synchronous differentiation of HIV-specific and total CD8(+) memory subpopulations. At 6-9 mo postinfection, those with low viral set points had a significantly higher proportion of early differentiated HIV-specific and total memory CD8(+) cells of a central memory (CD45RO(+)CD27(+)CCR7(+)) and intermediate memory (CD45RO(-)CD27(+)CCR7(-)) phenotype. Those with high viral set points possessed significantly larger frequencies of effector memory (CD45RO(+)CD27(-)CCR7(-)) cells. The proportions of memory subsets significantly correlated with CD38(+)CD8(+) T cells. Thus, it is likely that a high Ag burden resulting in generalized immune activation may drive differentiation of HIV-specific and total memory CD8(+) T cells.

The Effects of Acute Malaria on Epstein-Barr Virus (EBV) Load and EBV-Specific T Cell Immunity in Gambian Children

To investigate how intense Plasmodium falciparum infection predisposes to Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL), we analyzed the effect of acute malaria on existing EBV-host balance. EBV genome loads in peripheral blood mononuclear cells were assayed by quantitative polymerase chain reaction, and EBV-specific CD8(+) T cell responses were assayed by interferon-gamma enzyme-linked immunospot assay. Gambian children, from whom samples were obtained during an acute malaria attack and again up to 6 weeks later, had extremely high viral loads, reaching levels that in the United Kingdom are seen only in patients with infectious mononucleosis. Gambian control subjects (children and adults with no recent history of malaria) had lower median viral loads, although they were still >10-fold above the median for healthy UK adults. Limited experiments with EBV epitope peptides (restricted through the HLA-B 3501 and HLA-B 5301 alleles) also suggested an impairment of virus-specific CD8(+) T cell function in children with malaria, but only during acute disease. Acute malaria is associated with sustained increase in EBV load and, possibly, a transient decrease in EBV-specific T cell surveillance. We infer that the unusually high set point of virus carriage in P. falciparum-challenged populations, allied with the parasite's capacity to act as a chronic B cell stimulus, probably contributes to the pathogenesis of endemic BL.

Evolution of proviral gp120 over the first year of HIV-1 subtype C infection

The evolution of proviral gp120 during the first year after seroconversion in HIV-1 subtype C infection was addressed in a case series of eight subjects. Multiple viral variants were found in two out of eight cases. Slow rate of viral RNA decline and high early viral RNA set point were associated with a higher level of proviral diversity from 0 to 200 days after seroconversion. Proviral divergence from MRCA over the same period also differed between subjects with slow and fast decline of viral RNA, suggesting that evolution of proviral gp120 early in infection may be linked to the level of viral RNA replication. Changes in the length of variable loops were minimal, and length reduction was more common than length increase. Potential N-linked glycosylation sites ranged ±one site, showing common fluctuations in the V4 and V5 loops. These results highlight the role of proviral gp120 diversity and diversification in the pathogenesis of acute HIV-1 subtype C infection.

Rule extraction by fuzzy modeling algorithm for fuzzy logic control of cisatracurium as a neuromuscular block

This paper provides two rule bases to control administration of cisatracurium, a non-depolarizing neuromuscular blocking agent. One rule base is extracted from the objective approach of fuzzy modeling algorithm (FMA), and the other is from the subjective approach of experts' clinical experience. First, we established the data-acquisition system to record the manual neuromuscular block control during surgery. After collecting 15 patients data control by cisatracurium, we extracted six rules from these data via FMA. Another rule base also had six rules from experts with clinical anesthesia experience. Each rule-base was combined with three rules regarding the safety of the fuzzy controller. To compare their performance through simulations, we used the patient model established by our previous study which is a combination model consisting of a three-compartment mathematical model based on pharmacokinetics, and the Hill equation based on pharmacodynamics. In order to test the differences between these two rule-bases, the simulation used four disturbances: the different set points, the control interval strategy, the tolerance of noise effect, and the tolerance of delay time effect. The simulation shows that the FMA could successfully extract the fuzzy rules from the clinical data, and its control error is smaller than expert rules for different set point tests. However, the control error is increased and becomes worse when the set points are raised, which means that these two rule-bases are not appropriate to control the higher set points (i.e. T1% of 40 or higher). The t-test also shows that these two rule-bases performance of different set points have significant differences (p<0.05). Moreover, the results for control interval tests show that strategy has a significant influence, especially in reducing the standard deviation of control error. However, in simulations, these two rule-bases are not affected by noise disturbance, and the delay time affects only the overshoot for these two rule-bases.

Relationship between Human Immunodeficiency Type 1 Infection and Expression of Human APOBEC3G and APOBEC3F

Human immunodeficiency virus type 1 (HIV-1)-infected individuals with a high viral set point progress to acquired immunodeficiency syndrome (AIDS) more rapidly than those with a low viral set point. It is not entirely clear which host and viral factors are responsible for the viral set point. Host factors that affect virus replication are likely to influence the viral set point. Human APOBEC proteins have been shown to restrict HIV-1 replication. This prospective study was conducted to determine the relationship between human APOBEC3G (hA3G) and APOBEC3F (hA3F) levels and the viral set point. Fourteen subjects were classified as having a high viral set point, and 16 were classified as having a low viral set point. We quantified the levels of hA3G and hA3F mRNA in HIV-1-infected, antiretroviral drug-naive individuals before and after infection. We found a significant correlation between the hA3G mRNA level and the viral set point. The expression of hA3G and hA3F increased after infection, and the levels of hA3G and hA3F mRNA were significantly higher after infection in the low viral set point group, compared with the high viral set point group. The results suggest that the level of hA3G expression affects the establishment of the viral set point and may therefore function as a host determinant in the pathogenesis of HIV-1 infection.

A comparison of reactive oxygen species metabolism in the rat aorta and vena cava: focus on xanthine oxidase

Reactive oxygen species (ROS) are important mediators in vascular biology. Venous function, although relevant to cardiovascular disease, is still understudied. We compared aspects of ROS metabolism between a major artery (the aorta) and a major vein (the vena cava, VC) of the rat, with the hypothesis that venous ROS metabolism would be overall increased compared with its arterial counterpart. Superoxide and hydrogen peroxide (H2O2) release in basal conditions was higher in VC compared with aorta. The antioxidant capacity for H2O2 was also higher in VC than in aorta. Exogenous superoxide induced a higher contraction in VC compared with aorta. Protein expression of three major ROS metabolizing enzymes, xanthine oxidase (XO), CuZn-SOD, and catalase, was higher in VC compared with aorta. Because XO seemed a likely source of the higher VC ROS levels, we examined it further and found higher mRNA expression and activity of XO in VC compared with aorta. We also investigated the impact of XO inhibition by allopurinol on aorta and VC functional responses to norepinephrine, ANG II, ET-1, and ACh. Maximal ET-1-mediated contraction was decreased by allopurinol in VC but not in the aorta. Our results suggest that there are overall differences in ROS metabolism between aorta and VC, with the latter operating normally at a higher set point, releasing but also being able to handle, higher ROS levels. We propose XO to be an important source for these differences. The result of this particular comparison may be reflective of a general arteriovenous contrast.

Controlled Manipulation of Self-Organized Ni(II)−Octaethylporphyrin Molecules Deposited from Solution on HOPG with a Scanning Tunneling Microscope

The controlled manipulation of a physisorbed self-assembled monolayer is demonstrated at room temperature for the first time. Patterns are drawn in a NiOEP monolayer supported on freshly cleaved highly ordered pyrolytic graphite (HOPG) surface using a scanning tunneling microscope (STM) under ambient conditions. STM images acquired before and after pattern formation at low gap resistance reveal the creation of molecule-free regions. In these cleared regions, STM images display the two-dimensional HOPG lattice with atomic spacing of 2.5 Å and pattern depth of about 1.2 Å, typical of the STM apparent height for a monolayer NiOEP film on graphite. These molecule-free regions are created by removal of NiOEP molecules from the surface when the STM is operated at a very high current set point (tunneling resistance of about 120 MΩ or less) as confirmed by the absence of molecular buildup around the patterned areas in the STM images. We show that the removed molecules are not collecting at the boundaries of the scanned regions and discuss their fate. Once the molecular film is damaged, the size of the uncovered area keeps on growing with subsequent scans. We also observe that two different monolayer structures (triclinic and tetragonal) form under the same experimental conditions.

Focusing HIV Prevention on Those Most Likely to Transmit the Virus

Despite some success in reducing HIV incidence, the global epidemic continues to grow. For every person with AIDS in developing countries placed on treatment in 2005, many others were newly infected. We need more effective prevention programs that focus interventions on those most at risk for HIV transmission (MART), particularly those with 1) high behavioral risk and 2) high viral loads due to acute or recent infection, co-infections with other diseases, high viral set points, or untreated AIDS. This article provides examples of how prevention programs can incorporate emerging testing technologies and social/behavioral approaches to reach these individuals, their partners, and the social networks where active transmission is occurring.

Depressive Symptoms, Risk of Stroke and the Stress Response

HomeStrokeVol. 38, No. 6Depressive Symptoms, Risk of Stroke and the Stress Response Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBDepressive Symptoms, Risk of Stroke and the Stress Response Salvador Vale, MD, Psychiatrist Salvador ValeSalvador Vale Researcher from Departamento de Investigación, Laboratorios Trinidad, Roma Sur, Mexico DF Search for more papers by this author Originally published19 Apr 2007https://doi.org/10.1161/STROKEAHA.106.481655Stroke. 2007;38:e34Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: April 19, 2007: Previous Version 1 To the Editor:In their analysis of the association between depressive symptoms and an increased risk of stroke, Salaycik et al1 conclude that depressive symptoms are independent risk factors for incident stroke/TIA in individuals below the age of 65 years. They also mention a bibliographic search about possible causes for this relationship: genetic and biological markers that have been implicated include increased levels of fibrinogen, platelet activation, and catecholamines, or inflammatory markers such as C-reactive protein. The association between depression and the risk of stroke, they continue, may also be attributed to poor adherence to prescribed medical regimens, including medication, diet, and exercise.Depression is a silent killer, but how and why? Can a deregulated stress response be one of the culprits? Available evidence suggests that we can include depression among other chronic diseases with inflammatory components, as we do now with obesity or diabetes.2 Moreover, depression consistently shows a deregulated stress response.3 Intensity of immune-inflammatory responses to stress can be of different magnitude among different patients. (For example, early attacks to the immune system led to immune hyperreactivity thereafter).4 Thereby, there are subgroups of depressed patients reacting to mental stress with intense immune activation. These patients may have a high set-point for shutting down the stress response (or a deregulated stress response) forming an arteriosclerosis prone subgroup.2,5Nowadays, we do not know what percentage of patients can sustain, despite persistent depression, a low set-point for stopping their immune suppressive/immune activating response. These people will have few complications derived directly from their mental stress. Could it be the case for people above 65 years old? Further research is required to give an affirmative answer in this point. For the others, a proatherosclerotic deregulated response will result irrespectively of their predominant immunosuppression or their main response toward the inflammatory side. Finally, some patients may conserve the equilibrium between both arms of the stress response, but with an abnormally high set-point for stopping the response, a proatherosclerotic process also. Here, complications such as cardio- or cerebrovascular disease can be anticipated.2,5Pharmacological intervention to improve this pathological stress response could reduce patients’ comorbidities with profound positive effects on the quality of their lives. However, how do we know which patients with depression will benefit with those therapies? Standardized psychosocial stress significantly increases salivary α-amylase via adrenergic mechanisms6; consequently, if a deregulated stress response is the integrator of the many markers of vascular vulnerability in patients with depression, those depressed patients in high risk of experiencing a stroke incident may present elevations in the salivary amylase. Hence, I propose that further studies relating depression and stroke will be improved if they include measurements of salivary α-amylase.DisclosuresNone.1 Salaycik KJ, Kelly-Hayes M, Beiser A, Nguyen A-H, Brady SM, Kase CS, Wolf PA. Depressive symptoms and risk of stroke: The Framingham Study. Stroke. 2007; 38: 16–21.LinkGoogle Scholar2 Vale S. Psychosocial stress and cardiovascular diseases. Postgrad Med J. 2005; 81: 429–435.CrossrefMedlineGoogle Scholar3 Kennedy SE, Koeppe RA, Young EA, Zubieta JK. Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry. 2006; 63: 1199–208.CrossrefMedlineGoogle Scholar4 Maes M, Ombelet W, De Jongh R, Kenis G, Bosmans E. The inflammatory response following delivery is amplified in women who previously suffered from major depression, suggesting that major depression is accompanied by a sensitization of the inflammatory response system. J Affect Disord. 2001; 63: 85–92.CrossrefMedlineGoogle Scholar5 Kubzansky LD, Koenen KC, Spiro A III, Vokonas PS, Sparrow D. Prospective study of posttraumatic stress disorder symptoms and coronary heart disease in the Normative Aging Study. Arch Gen Psychiatry. 2007; 64: 109–116.CrossrefMedlineGoogle Scholar6 Ehlert U, Erni K, Hebisch G, Nater U. Salivary alpha-amylase levels after yohimbine challenge in healthy men. J Clin Endocrinol Metab. 2006; 91: 5130–5133.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails June 2007Vol 38, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.106.481655PMID: 17446418 Originally publishedApril 19, 2007 PDF download Advertisement

Baroreflex Control of Sympathetic Nerve Activity in Hypertensive Pregnant Rats with Reduced Uterine Perfusion

Objective: Baroreflex sensitivity is reduced in women with preeclampsia. The aim of this study was to determine whether baroreflex control of renal sympathetic nerve activity (RSNA) is altered in pregnant rats with reduced uterine perfusion (a model of human preeclampsia). Methods: Uterine perfusion was reduced in the third trimester by clipping the distal aorta and uterine branches of the ovarian arteries. RSNA baroreflex parameters were compared at term gestation in rats with reduced uterine perfusion (n = 12), in normal pregnant rats (n = 14) and in nonpregnant rats (n = 14). Results: Reduced perfusion rats were hypertensive (123.6 ± 2.3 mm Hg), and normal pregnant rats were hypotensive (97.7 ± 2.2 mm Hg), compared with controls. In rats with reduced perfusion, the baroreflex was shifted to a higher set-point, and maximum and minimum RSNA were increased compared with normal pregnant rats. Conclusion: The blunted baroreflex gain of normal pregnancy is maintained in rats with reduced uterine perfusion, but a hypertensive shift in baroreflex function exists in this rat model that is associated with a reversal of the reflex maximum and minimum RSNA observed in normal pregnancy.

Time Discrimination of Coulter Recount Artifact

The toning process has a strong size selectivity leading to filming of the carrier which can result in image fogging or high process control set points. Preparation of toners with minimal fines is needed to minimize these deleterious effects. The Coulter Counter technique has been the standard for characterizing toners because its ability to discriminate fines levels. It has been shown by using an internally purged aperture tube [1] that recounting of particles inside the aperture tube gives erroneously high fines measurements. The duration of the counting event is longer for particles inside the tube passing the aperture close enough to be recounted than it is for particles passing through the aperture. One can discriminate the recount artifacts from real counts using the pulse duration data available from measurements made the Multisizer 3.

WATER USE EFFICIENCY OF GREENHOUSE SUMMER SQUASH IN RELATION TO THE METHOD OF CULTURE: SOIL VS. SOILLESS

WATER USE EFFICIENCY OF GREENHOUSE SUMMER SQUASH IN RELATION TO THE METHOD OF CULTURE: SOIL VS. SOILLESS

A reassessment of the role of serotonergic system in the control of feeding behavior

The role of serotonergic system in the feeding behavior was appraised by electrolytic lesions in the dorsal raphe nucleus (DRN) and administration of para-chlorophenylalanine (PCPA, 3 mg/5 microl, icv). Chronic evaluations were accomplished through 120 and 360 days in PCPA-injected and DRN-lesioned rats, respectively. Acute food intake was evaluated in fasted rats and submitted to injection of PCPA and hydroxytryptophan (LHTP, 30 mg/kg, ip). DRN-lesioned rats exhibited 22-80% increase in food intake up to sixth month, whereas the obesity was evident and sustained by whole period. In PCPA-injected rats was observed an initial increase in the food intake followed by hypophagy from 25th to 30th day and a transitory increase of body weight from 5th to 60th day. In the acute study, the LHTP reverted partially the PCPA-induced increase in food intake of fasted rats suggesting a sustained capacity of decarboxylation of precursor by serotonergic neurons. Slow restoration of the levels of food intake in DRN-lesioned rats reveals a neuroplasticity in the systems that regulate feeding behavior. A plateau on the body weight curve in lesioned rats possibly represents the establishment of a new and higher set point of energetic balance.

Rearing environment and hypothalamic-pituitary-adrenal regulation in young rhesus monkeys (Macaca mulatta)

A mammal's early social environment has important regulatory effects on its behavior and physiology, and this is especially true for regulation of the hypothalamic-pituitary-adrenal (HPA) system. The present study was designed to test hypotheses that various aspects of the social environment are important influences on HPA regulation. Seven hundred seventy eight, 3- to 4-month-old rhesus monkeys were studied as part of a standardized, 24-hr biobehavioral assessment program, which included blood sampling to determine plasma cortisol concentrations. Results indicate that nursery-rearing results in a reduced cortisol set-point for the HPA system, and, for nursery-reared (NR) animals, more peer exposure during infancy is associated with a higher set-point. Age and sex differences during this period were evident but small in magnitude. These data demonstrate the important regulatory role of the social environment on nonhuman primate physiology and suggest caution in assuming that differences between individuals' cortisol levels reflect only differences in perceptions of the "stressfulness" of events.