Materials

and methods. Forty guinea pigs were assigned to one of four groups: HS+NOISE (i.p. injection hydrogen-rich saline), NS+NOISE (i.p. injection normal saline), NOISE ALONE (noise control), and NO TREATMENT (normal control) groups. The HS+NOISE, NS+NOISE, and NOISE ALONE groups were exposed to intensive noise JSH-23 (4 h at 115 dB SPL noise of 4000+/-100 Hz). The auditory brainstem response (ABR) was used to examine the hearing threshold in each group. Distortion product otoacoustic emission (DPOAE) was used to examine outer hair cell function. We also examined cochlear morphology to evaluate inner and outer hair cell trauma induced by noise exposure. Hydrogen-rich saline was administered twice daily for 6 days (2.5 ml/kg, i.p.) 24 h after noise exposure. Results.

Baseline ABR thresholds and DPOAE values were normal in all groups at the measured frequencies (2, 4, 8, and 16 kHz) before noise exposure. The ABR threshold shift was 50-55 dB across the frequencies tested, and average DPOAE declined in the NOISE ALONE, NS+NOISE, and HS+NOISE groups 24 h after noise exposure. However, the changes in cochlear parameters were different between groups. The HS+NOISE group showed a significantly find more decreased ABR threshold value as compared with the NS+NOISE or NOISE ALONE group (P<0.01) on day 7. The mean DPOAE recovered to some extent in the three noise exposure groups, but at most frequencies the HS+NOISE group showed significantly increased DPOAE on day 7 as compared with the NS+NOISE group or NOISE ALONE group (P<0.01). Surface Corti organ preparations stained with succinate dehydrogenase (SDH) showed that most outer hair cells (OHCs) were still dropsical and a few were missing 7 days after noise exposure in the NS+NOISE group. Only a few OHCs were slightly dropsical in the HS+NOISE group. The numbers of missing hair cells 7 days after noise exposure were significantly greater in the NOISE ONLY and NS+NOISE groups than the Plasma membrane Ca2+ ATPase HS+NOISE group (P<0.01). Conclusions. Hydrogen-rich saline can

alleviate experimental noise-induced hearing loss in guinea pigs, partially by preventing the death of cochlear hair cells after intensive noise exposure. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The reverse genetics technology for bluetongue virus (BTV) has been used in combination with complementing cell lines to recover defective BTV-1 mutants. To generate a potential disabled infectious single cycle (DISC) vaccine strain, we used a reverse genetics system to rescue defective virus strains with large deletions in an essential BTV gene that encodes the VP6 protein (segment S9) of the internal core. Four VP6-deficient BTV-1 mutants were generated by using a complementing cell line that provided the VP6 protein in trans.

Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from both peripheral and central terminals of C-fiber nociceptors. selleck screening library Neurogenic inflammatory responses were also observed in the affected skin via Evan’s Blue

extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-fiber polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive

field. Crown Copyright (C) 2011 Published by Elsevier Ltd on behalf of IBRO. All rights reserved.”
“Tiger frog virus (TFV), in the genus Ranavirus of the family Iridoviridae, causes high mortality of cultured tiger frog MI-503 tadpoles in China. To explore the cellular entry mechanism of TFV, HepG2 cells were treated with drugs that inhibit the main endocytic pathways. We observed that TFV entry was inhibited by NH(4)Cl, chloroquine, and bafilomycin, which can all elevate the pH of acidic organelles. In contrast, TFV entry

was not influenced by chlorpromazine or overexpression of a dominant-negative form of Esp15, which inhibit the assembly of clathrin-coated pits. These results suggested that TFV entry was not associated with clathrin-mediated endocytosis, but was related to the pH of acidic organelles. Subsequently, we found that many endocytosis of TFV was dependent on membrane cholesterol and was inhibited by the caveolin-1 scaffolding domain peptide. Dynamin and actin were also required for TFV entry. In addition, TFV virions colocalized with the cholera toxin subunit B, indicating that TFV enters as caveola-internalized cargo into the Golgi complex. Taken together, our results demonstrated that TFV entry occurs by caveola-mediated endocytosis with a pH-dependent step. This atypical caveola-mediated endocytosis is different from the clathrin-mediated endocytosis of frog virus 3 (FV3) by BHK cells, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection in lower vertebrates.”
“Purpose: Acute agitation is a common presentation in emergency departments and is often secondary to an underlying psychotic condition. The aim of this study was to compare the effectiveness of three second generation antipsychotics (risperidone, olanzapine, quetiapine) versus haloperidol in the treatment of psychotic agitation for up to 72 h.

(C) 2012 Elsevier Ltd. All rights reserved.”
“Fatty CBL0137 chemical structure acids and/or isoprenoids are covalently attached to a variety of disease-related proteins. The distinct chemical properties of each of these hydrophobic moieties allow lipid modification to serve as a mechanism to regulate protein structure, localization and function. This review highlights recent progress in identifying inhibitors of protein lipidation and their effects on human disease. Myristoylation inhibitors have shown promise in blocking the action of human pathogens. Although inhibitors

that block prenylation of Ras proteins have not yet been successful for cancer treatment, they may be efficacious in the rare premature

aging syndrome progeria. Agents that alter the palmitoylation status of Ras, Wnt and Hh proteins have recently been discovered, and represent the next generation of potential chemotherapeutics.”
“Secreted proteins play a pivotal role in cellular functions. To better understand malignant behavior, we adapted stable isotopic labeling with amino acids in cell culture technology to identify and quantify proteins differentially released into the extracellular media by a pair of normal and malignant breast-cancer cell lines. Approximately 380 non-redundant proteins were quantified in serum-free media. Of the assigned proteins, 62% are classified secreted learn more in protein databases and an additional 25%

are designated secreted in the literature. A number of growth factors were found differentially regulated. Tumor necrosis factor, pigment epithelial-differentiating factor and stem-cell growth factor precursor showed decreased expression in breast-cancer cell line, whereas Inhibin beta and macrophage migration inhibitory factor show increased expression. interestingly, protease inhibitors, including plasma protease (Cl) inhibitor, PZP precursor, and SerpinE2 were significantly down-regulated in cancer cell line as were angiostatic factors from extracellular matrix (ECM) such as endorepillin. Further, the C-terminal Amine dehydrogenase fragment of type XVIII collagen, endostatin, a potent angiostatic factor, was down-regulated as well whereas extracellular collagens and osteoblast-specific factor 2 (OSF-2), were up-regulated. Differential expression and secretion of SerpinE2 and OSF-2 were confirmed using Western blotting. These results corroborate models of invasive tumors sustained by elaborate coordination of stromal cells via chemokines and growth factors, while protease inhibitors remodel the ECM to stimulate angiogenesis.”
“We investigated the association between yes/no sentence comprehension and dysfunction in anterior and posterior left-hemisphere cortical regions in acute stroke patients.

Increased activation under bupropion may point to see more an opposite effect that may relate to the lack of impaired sexual functioning. Neuropsychopharmacology (2011) 36, 1837-1847; doi:10.1038/npp.2011.66; published online 4 May 2011″
“In this paper, with the method of adaptive dynamics and geometric technique, we investigate the adaptive evolution of foraging-related phenotypic traits in a predator-prey community with trade-off structure. Specialization on one prey type is assumed to go at the expense of specialization on another. First, we

identify the ecological and evolutionary conditions that allow for evolutionary branching in predator phenotype. Generally, if there is a small switching cost near the singular strategy, then this singular strategy is an evolutionary branching point, in which predator population will change from monomorphism to dimorphism. Second, we find that if the trade-off curve is globally convex, predator

population eventually Nirogacestat datasheet branches into two extreme specialists, each completely specializing on a particular prey species. However, if the trade-off curve is concave-convex-concave, after branching in predator phenotype, the two predator species will evolve to an evolutionarily stable dimorphism at which they can continue to coexist. The analysis reveals that an attractive dimorphism will always be evolutionarily stable and that no further branching is possible under this Sclareol model. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.”
“Epidemiological studies indicate that isolated persons have increased risk of developing Alzheimer’s disease (AD). This study investigated the cellular mechanisms of how social isolation influenced amyloid beta peptide (A beta) accumulation and affected the severity of AD-associated cognitive decline in a mouse model of AD. Amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice were placed either in isolation or in group from postnatal day 28 and tested for cognitive performance at the age of 3 months with

fear-conditioning paradigms. We found that social isolation accelerated impairment of contextual fear memory in the APP/PS1 mice. The magnitude of long-term potentiation in the hippocampal CA1 neurons was significantly lower in the isolated APP/PS1 mice compared with group APP/PS1 and wild-type mice. Hippocampal level of A beta was significantly elevated in the isolated APP/PS1 mice, which was accompanied by an increased calpain activity and p25/p35 ratio. In addition, surface expression of GluR1 subunit of AMPA receptor was decreased by social isolation. The association of p35, and alpha-CaMKII was significantly less in the isolated APP/PS1 mice indicating that their interaction was impaired.

On days 7, 14, 21, 35, and 52 after transplant, 5 mice per group were killed and evaluated by histologic assessment and scanning electronic microscopy for reepithelialization and fibrosis of tracheal grafts.

Results: Mean diameter of gelatin microspheres was 107 mu m. Microspheres could not be fully degraded until 35 days after transplant in vivo. On days 7, 14, and 21, epithelium score and ratio of lamina propria to tracheal cartilage were not statistically different between mice with epidermal growth

factor-loaded gelatin microspheres and other groups. On days 35 and 52, selleck chemical however, epithelium score was higher and ratio of lamina propria to tracheal cartilage was lower in epidermal growth factor-loaded gelatin microsphere recipients; these mice also had almost complete differentiation of regenerated epithelium into BTK inhibitor ciliated columnar epithelium on days 35 and 52, earlier than in other groups.

Conclusions: Gelatin microspheres act as a functional vector for

epidermal growth factor. Sustained local application of epidermal growth factor could accelerate reepithelialization of tracheal allografts. (J Thorac Cardiovasc Surg 2010; 140: 209-15)”
“The present paper reviews the enzymes catalyzing conversion of N alpha-benzyloxycarbony l-L lysine (N alpha-2-Llysine) to N alpha-benzyloxycarbonyl-L-aminoadipic acid (N alpha-Z-I-AAA) in fungal Parvulin and bacterial strains A spergillus niger AKU 3302 and Rhodococcus sp AIU Z-35-1 converted N alpha-Z-L lysine to N alpha-Z-L-AAA via Notbenzyloxycarbonyl-L-aminoadipate-delta-semialdehyde (N alpha-Z-L-AASA) However, different enzyme combinations were involved in the N alpha-Z-L-lysine metabolism of both strains A niger strain converted N alpha-Z-L-lysine to N alpha Z-L-AASA by amine oxidase, and the resulting N alpha-Z-L-AASA was converted to N alpha-Z-LAAA by an aldehyde oxidase In the Rhodococcus

strain, conversion of N alpha-Z-L-lysme to N alpha-Z-L-AASA was catalyzed by L-specific amino acid oxidase The resulting Na-Z-L-AASA was converted to N alpha-Z-L-AAA by an aldehyde dehydrogenase The present paper also describes characteristics of new enzymes obtained from those strains”
“Objective: In cardiac cell therapy almost every cell type tested experimentally has yielded some benefit. However, there is a lack of studies directly comparing the function of various stem/progenitor cell populations. This study describes the expansion of peripheral blood CD133(+) cells and compares their functional properties with those of other commonly used human progenitor cell populations.

Databases including PubMed, AlzGene, China National Knowledge Infrastructure (CNKI) and Wan Fang were searched to find relevant studies.

Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. All analyses were calculated using STATA Version 11.0 and RevMan (v.5.1) software. Ten total case-control studies were included. The statistical results showed that GAB2 SNP rs2373115 is significantly associated with an increased risk for SAD, and the subgroup analysis showed that SNP rs2373115 may only be associated with an increased risk for SAD risk in Caucasians but not in Asians. Furthermore, in APOE epsilon 4 carriers or noncarriers, those with rs2373115 genotype GG did not have a significantly higher Semaxanib concentration risk for SAD compared with those with genotype GT and IT (APOE epsilon 4 carriers: OR = 1.20,95% CI = 0.92-1.56, P = 0.178; APOE epsilon 4 noncarriers: OR = 1.08, 95% CI = 0.97-1.20, P = 0.157) in the present study. The current meta-analysis further supports previous findings that the GAB2 gene may be associated with SAD risk. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“The development of an effective prophylactic vaccine is still necessary to improve the safety of the conventional

although-discontinued smallpox vaccine, and to protect from the threat of deliberate release of variola virus. This need also arises from the number of new cases of animal orthopoxvirus infections each year, and to reduce the risk to animal handlers. Fowlpox (FP) IWR-1 recombinants only replicate in avian species and have been Suplatast tosilate developed against human infectious diseases, as they can elicit an effective immune response, are not cross-reactive immunologically with vaccinia, and represent safer and more promising immunogens for immunocompromised individuals. The aim of this study was the characterisation of two new fowlpox recombinants expressing the A33R vaccinia virus gene either alone (FRA33R) or with the green fluorescent protein (FPA33R-GFP) to verify whether GFP can affect the expression

of the transgene. The results show that both FPA33R and FPA33R-GFP can express A33R correctly, but A33R mRNA and protein synthesis are higher by FPA33R than by FPA33R-GFP. Therefore, GFP co-expression does not prevent, but can reduce the level of a vaccine protein, and may affect the protective efficacy of the immune response. (C) 2012 Elsevier B.V. All rights reserved.”
“Coactivator-associated arginine methyl transferase 1 (CARM1) is a protein arginine methyltransferase (PRMT) family member that functions as a coactivator in androgen and estrogen signaling pathways and plays a role in the progression of prostate and breast cancer. CARM1 catalyzes methylation of diverse protein substrates. Prior attempts to purify the full-length mouse CARM1 protein have proven unsatisfactory. The full-length protein expressed in Escherichia coli forms insoluble inclusion bodies that are difficult to denature and refold.

Male Fischer rats were injected i.p. with saline or cocaine three times daily at 1 h intervals in an escalating-dose paradigm for 14 days (from 3 x 15 mg/kg/injection on days 1-3 up to 3 x 30 mg/kg/injection on days 10-14). Identically treated separate groups were withdrawn from cocaine or saline for 24 h or 14 days. No significant change in KOPr agonist U-69593-stimulated [S-35]GTP gamma S was found in the seven regions studied 30

min or 14 days after chronic 14 days escalating-dose binge cocaine administration. However there was an increase in KOPr-stimulated [S-35]GTP gamma S binding https://www.selleckchem.com/products/prn1371.html in the VTA (P<0.01) of rats withdrawn for 24 h from chronic cocaine. Our results show a cocaine withdrawal induced increase of KOPr signaling in the VTA, and suggest that the KOPr may play a role in acute withdrawal from cocaine. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background Previous reviews have examined the existence of HIV prevention, treatment, and care services for injecting drug users (ID Us) worldwide, but they did not quantify the scale of coverage. We undertook a systematic review to

Dinaciclib order estimate national, regional, and global coverage of HIV services in IDUs.

Methods We did a systematic search of peer-reviewed (Medline, BioMed Central), internet, and grey-literature databases for data published in 2004 or later. A multistage process of data requests and verification was undertaken, involving UN agencies and national experts. National data were obtained for the extent of provision of the following core interventions for IDUs: needle and syringe programmes (NSPs), opioid substitution therapy (OST)

and other drug treatment, HIV testing and counselling, antiretroviral therapy (ART), and condom programmes. We calculated national, regional, and global coverage Nutlin 3 of NSPs, OST, and ART on the basis of available estimates of IDU population sizes.

Findings By 2009, NSPs had been implemented in 82 countries and OST in 70 countries; both interventions were available in 66 countries. Regional and national coverage varied substantially. Australasia (202 needle syringes per IDU per year) had by far the greatest rate of needle syringe distribution; Latin America and the Caribbean (0.3 needle syringes per IDU per year), Middle East and north Africa (0.5 needle syringes per IDU per year), and sub-Saharan Africa (0.1 needle syringes per IDU per year) had the lowest rates. OST coverage varied from less than or equal to one recipient per 100 IDUs in central Asia, Latin America, and sub-Saharan Africa, to very high levels in western Europe (61 recipients per 100 IDUs).

In our study, the frequency of the KIR2DL2 allele was significantly increased in NR (P < 0.001; odds ratio [OR] = 1.95), as was the frequency of the KIR2DL2/KIR2DL2 genotype (P < 0.005; OR = 2.52). In contrast, the frequencies of the KIR2DL3 genotype (P < 0.001) and KIR2DL3/KIR2DL3 genotype (P < 0.05; OR = 0.54) were significantly increased in the SVR. Different combinations of KIR2DL2 and KIR2DL3 alleles with their ligands were analyzed. The frequency of the KIR2DL2/KIR2DL2-HLA-C1C2 genotype was significantly increased in the NR (P < 0.01; OR = 3.15). Additionally, we found a higher frequency of the KIR2DL3/KIR2DL3-HLA-C1C1 genotype in the SVR

group (P < 0.05; OR = 0.33). These results were not affected by the HCV genotype. In conclusion, patients who carried the KIR2DL2/KIR2DL2-HLA-C1C2 genotype were less prone to respond to treatment. However, the KIR2DL3/KIR2DL3-HLA-C1C1 genotype clearly correlated with click here a satisfactory response to treatment, defined by the clearance of HCV RNA.”
“The

underlying neurobiology of major depression (MD) is likely to represent an interaction between genetic susceptibility and environmental factors such as stress. We investigated, in a multimodal high-resolution magnetic resonance Sirtuin activator inhibitor imaging (MRI) genetic study, whether reduced hippocampal volumes and other brain alterations are associated with the tri-allelic polymorphism of the serotonin transporter and childhood stress in patients with MD and healthy subjects. Patients with

MD and healthy participants were investigated using high-resolution MRI and genotyping for serotonin transporter polymorphism in the promoter region of the serotonin transporter STAT inhibitor gene (SLC6A4, 5-HTTLPR). Region of interest analysis of the hippocampus, whole-brain voxel-based morphometry (VBM), and assessment of childhood stress were carried out. Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic). In patients, childhood stress also predicted further hippocampal white matter alterations independently from the genotype. Moreover, the left prefrontal cortex was smaller in patients, whereby childhood stress resulted in larger prefrontal volumes in those subjects carrying the non-risk L-allele, suggesting preventive effects. The findings indicate that subjects with both environmental and genetic risk factors are susceptible to stress-related hippocampal changes. Structural brain changes due to stress represent part of the mechanism by which the illness risk and outcome might be genetically mediated. Neuropsychopharmacology (2010) 35, 1383-1390; doi: 10.1038/npp.2010.8; published online 10 February 2010″
“Using a cell-based replicon screen, we identified a class of compounds with a thiazolidinone core structure as inhibitors of hepatitis C virus (HCV) replication.

Here we investigated the distribution, phenotype, and function of rotavirus-specific CD8 T cells in multiple organs after rotavirus infection initiated via the intranasal, oral, or intramuscular route. The highest level of virus-specific CD8 T cells was observed in the Peyer’s patches of orally infected mice and in the lungs of intranasally infected animals. Very low levels of virus-specific CD8 T cells were detected in peripheral blood or spleen irrespective of the route of infection. Rotavirus-specific CD8 T cells from

Peyer’s patches of orally infected mice expressed high levels of CCR9, selleck products while CXCR6 and LFA-1 expression was associated with virus-specific CD8 T cells in lungs of intranasally infected mice. Oral infection induced the highest proportion of gamma interferon(-) CD107a/b(+) DAPT CD8 T cells in Peyer’s patches. When equal numbers of rotavirus-specific CD8 T cells were transferred into Rag-1 knockout mice chronically infected with rotavirus, the donor cells derived from Peyer’s patches of orally infected mice were more efficient than those derived from lungs of intranasally infected animals in clearing intestinal infection. These results suggest that different routes of infection induce virus-specific CD8 T cells with distinct homing phenotypes and effector

functions as well as variable abilities to clear infection.”
“For influenza viruses to become infectious, the proteolytic cleavage of hemagglutinin (HA) is essential. This usually is mediated by trypsin-like proteases in the respiratory tract. The binding of plasminogen to influenza virus A/WSN/33 leads to TCL the cleavage of HA, a feature determining its pathogenicity and neurotropism in mice. Here, we demonstrate that plasminogen also promotes the replication of other influenza virus strains. The inhibition of the conversion of plasminogen into plasmin blocked influenza virus replication. Evidence is provided that the activation of plasminogen is mediated by the host cellular protein annexin II, which is incorporated

into the virus particles. Indeed, the inhibition of plasminogen binding to annexin II by using a competitive inhibitor inhibits plasminogen activation into plasmin. Collectively, these results indicate that the annexin II-mediated activation of plasminogen supports the replication of influenza viruses, which may contribute to their pathogenicity.”
“The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity.

63). All other measured parameters were also unaffected in the AD brains: The mean fiber length density was 248 km/cm(3) in the AD group and 247 km/cm(3) in the control group; the volume of white

matter was 329 cm(3) (AD) and 321 cm(3) (control) and the volume density of myelinated fibers to white matter tissue volume was 0.30 in AD group and 0.31 in the control group. This is the first study of subcortical brain white matter fiber length using a stereological method on postmortem brains from AD patients and control subjects. (C) 2008 IBRO. Published P-gp inhibitor by Elsevier Ltd. All rights reserved.”
“The rapid and irreversible brain injury produced by anoxia when stroke occurs is well known. Cumulative evidence suggests that the activation of neuronal ATP-sensitive potassium (K(ATP)) channels may have inherent protective effects during cerebral hypoxia, yet little information regarding the therapeutic effects of K(ATP) channel openers is available. We hypothesized that pretreatment AG-014699 chemical structure with a K(ATP) channel opener might protect against brain injury induced by cerebral hypoxia. In this study, adult Wistar rats were treated with iptakalim, a new K(ATP) channel opener, which is selective for SUR2 type K(ATP) channels, by intragastric administration at doses of 2, 4, or 8 mg/kg/day for 7 days before being exposed to simulated high altitude equivalent to 8000 m in a decompression chamber

for 8 h leading to hypoxic brain injury. By light and electron microscopic images, we observed that hypobaric hypoxia-induced brain injury could be prevented by pretreatment secondly with iptakalim. It was also observed that the permeability of the blood-brain barrier, water content, Na(+) and Ca(2+) concentration, and activities of Na(+),K(+)-ATPase,

Ca(2+)-ATPase and Mg(2+)-ATPase in rat cerebral cortex were increased and the gene expression of the occludin or aquaporin-4 was down- or upregulated respectively, which could also be prevented by the pretreatment with iptakalim at doses of 2, 4, or 8 mg/kg in a dose-dependent manner. Furthermore, we found that in an oxygen-and-glucose-deprived model in ECV304 cells and rat cortical astrocytes, pretreatment with iptakalim significantly increased survived cell rates and decreased lactate dehydrogenate release, which were significantly antagonized by glibenclamide, a K(ATP) channel blocker. We conclude that iptakalim is a promising drug that may protect against brain injury induced by acute hypobaric hypoxia through multiple pathways associated with SUR2-type K(ATP) channels, suggesting a new therapeutic strategy for stroke treatment. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The CNS can be activated by both local and systemic inflammation, resulting in the manifestation of sickness symptoms. The pathways by which the CNS is activated under these two conditions, however, may differ. In this study, we injected casein into the peritoneal cavity (i.p.) or into an s.c.