Effect of lithium chloride-induced aversion on appetitive and consummatory behavior.

The effect of lithium chloride-induced conditioned taste aversions on appetitive and consummatory behavior was determined. Rats were given access to a 0.1% saccharin solution for 15 min either in bottles or by infusion through an intraoral cannula. Bottle-fed rats given postprandial injections of lithium chloride showed greater aversion to saccharin than cannula-fed rats. During extinction, cannula-fed rats gradually recovered to control levels of intake, whereas bottle-fed rats continued to avoid saccharin. These results suggest that lithium chloride affects appetitive behavior to a greater extent than it affects consummatory behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake.

Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a preferred substance such as sucrose or a drug of abuse. The reward comparison hypothesis suggests that rats avoid intake of a saccharin cue following pairings with a drug of abuse because the rats are anticipating the availability of the rewarding properties of the drug. The present study used bilateral ibotenic acid lesions to examine the role of the gustatory cortex in the suppression of CS intake induced by cocaine, morphine, and LiCl. The results show that bilateral lesions of the insular gustatory cortex (1) fully prevent the suppressive effects of both a 15 and a 30 mg/kg dose of morphine, (2) attenuate the suppressive effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose of the drug. Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prosaptide prevents hyperalgesia and reduces peripheral TNFR1 expression following TNF-alpha nerve injection

This study demonstrated that hyperalgesia resulting from an intraneural injection of the cytokine tumor necrosis factor-alpha (TNF) was prevented by preemptive administration of a single dose of the prosaptide TX14(A) (200 microg/kg). TX14(A) is a synthetic 14-mer peptide with neurotrophic and cytoprotective activities. Efforts to elucidate TX14(A) antagonism of hyperalgesia concentrated on determining the effect of TX14(A) on the up-regulation of the 55 kDa TNF receptor (TNFR1) at the nerve injury site. It has been previously shown that TNFR1 expression is upregulated following nerve injury and parallels the display of nociceptive behavior. In our experiments, TNFR1 was decreased at the TNF nerve injection site in TX14(A)-treated rats when compared to vehicle-treated or control peptide-treated rats. Light microscopic evaluation of nerve injury site tissue displayed qualitatively similar neuropathology in both treatment groups during the time of peak hyperalgesia (day 3), but appeared more normal than untreated nerves at day 7 (histological scoring, mean +/-s.d., 3.7+/-0.57 for TX14(A)-treated and 5.67+/-0.5 for control peptide-treated). These results suggest that TX14(A) decreased nociceptive behavior by attenuating both TNFR1 upregulation and Schwann cell activation in response to TNF injection. This prosaptide neurotrophin may also moderate nerve degeneration or promote regeneration. It is not known whether TX14(A) also acts rostral to the lesion site.     

Long-term glycemic control influences the onset of limited joint mobility in type 1 diabetes

BACKGROUND: Limited joint mobility (LJM) in childhood insulin-dependent (type 1) diabetes is associated with a substantially increased risk of microvascular complications. Cross-sectional studies have not demonstrated a relationship between LJM and metabolic control. This study was designed to determine whether glycemic control, as measured by glycohemoglobin (hgbA1C) levels from the onset of diabetes, is associated with the occurrence of LJM. METHOD: Probands (n = 18) had hgbA1C values and recorded observation of joint function from soon after onset of their diabetes. Controls (n = 40) were matched to probands for gender and age at diagnosis and had follow-up beyond the age at which the proband was found to have LJM. RESULTS: The odds ratio for occurrence of LJM for the mean hgbA1C from diabetes onset was 1.46, 95% confidence limits 1.07 to 2.00. Thus, for every unit increase in average hgbA1C, there was approximately a 46% increase in the risk of LJM. When hgbA1C was dichotomized, the OR for hgbA1C of more than 8% was 2.55, and the OR was 4.54 if the hgbA1C was greater than 12%. Age at diagnosis and duration of diabetes were not independent prognostic factors for LJM. CONCLUSION: Glycemic control from onset of diabetes is strongly associated with occurrence of LJM.     

Level of ICAM-1 surface expression on virus producer cells influences both the amount of virion-bound host ICAM-1 and human immunodeficiency virus type 1 infectivity

Using virions harvested from 293T cells stably expressing either low or high levels of surface ICAM-1, we determined that the number of virus-embedded host ICAM-1 proteins is positively influenced by the expression level of ICAM-1 on virus producer cells. Moreover, the increase in virion-bound host cell membrane ICAM-1 led to a concomitant enhancement of virus infectivity when a T-cell-tropic strain of human immunodeficiency virus type 1 (HIV-1) was used. The phenomenon was also seen when primary human cells were infected with virions pseudotyped with the envelope protein from a macrophage-tropic HIV-1 isolate, thus ruling out any envelope-specific effect. We also observed that target cells treated with NKI-L16, an anti-LFA-1 antibody known to increase the affinity of LFA-1 for ICAM-1, were markedly more susceptible to infection with HIV-1 particles bearing on their surfaces large numbers of host-derived ICAM-1 proteins. Given that cellular activation of leukocytes is known to modify the conformational state of LFA-1 and induce ICAM-1 surface expression, it is tempting to speculate that activation of virus-infected cells will lead to the production of HIV-1 particles bearing more host ICAM-1 on their surfaces and that such progeny virions will preferentially infect and replicate more efficiently in activated cells which are prevalent in lymphoid organs.     

Esophageal electrochemical burns due to button type lithium batteries in dogs

Microalbuminuria is a significant risk factor associated with nephropathy, retinopathy, and cardiovascular disease; however, there are no previous reports on the relationship of microalbuminuria with diabetic foot ulcers or stroke, despite the fact that microalbuminuria is a marker of vascular damage. The purpose of this study was to determine the relationship of microalbuminuria with diabetic foot ulcers in type II diabetes patients. In this, cross-sectional clinical study, outpatients of the offices at first level medical care in Durango, Mexico, were included in one of two groups; (a) patients with diabetic foot ulcers and (b) control of group patients without diabetic foot ulcers. Diabetic foot diagnosis was established on the basis of clinical criteria and pletismography. Patients diagnosed with renal disease, urinary tract infection, acute febrile illness, or heart failure and those receiving angiotensin-converting enzyme inhibitors were excluded from the study. Microalbuminuria was measured, on a 24-h urine collection, by precipitation with sulfasalicylic acid, and turbidity was determined by measuring absorbance with a spectrophotometer. The study included 670 diabetic patients. Using both odds ratio and logistic regression analyses, diabetes duration, cigarette smoking, aging, and microalbuminuria showed a strong relationship with diabetic foot ulcers. Microalbuminuria should be considered as an independent risk factor for diabetic foot ulcers.     

Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) receptor antagonist attenuates lithium chloride-induced c-Fos induction in rat brainstem

Studies of neuronal injury and death after cerebral ischemia and various neurodegenerative diseases have increasingly focused on the interactions between mitochondrial function, reactive oxygen species (ROS) production and glutamate neurotoxicity. Recent findings suggest that increased mitochondrial ROS production precedes neuronal death after glutamate treatment. It is hypothesized that under pathological conditions when mitochondrial function is compromised, extracellular glutamate may exacerbate neuronal injury. In the present study, we focus on the relationship between mitochondrial superoxide production and glutamate neurotoxicity in cultured cortical neurons with normal or reduced levels of manganese-superoxide dismutase (MnSOD) activity. Our results demonstrate that neurons with reduced MnSOD activity are significantly more sensitive to transient exposure to extracellular glutamate. The increased sensitivity of cultured cortical neurons with reduced MnSOD activity is characteristically subject only to treatment by glutamate but not to other glutamate receptor agonists, such as N-methyl-d-aspartate, kainate and quisqualate. We suggest that the reduced MnSOD activity in neurons may exacerbate glutamate neurotoxicity via a mechanism independent of receptor activation.     

Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells

A low concentration of bufalin, a component of bufadienoides in the traditional Chinese medicine chan'su, was shown previously to induce differentiation of a broad range of human leukemia cell lines. In the present study, we found that bufalin at concentrations of 10(-7) M and higher induced apoptosis in human leukemia cells, such as HL60, ML1, but not in mouse leukemia M1 cells. A mere 15 min pretreatment of HL60 cells with 10(-6) M bufalin, followed by incubation for 15 h without bufalin, caused fragmentation of DNA and a decrease in cell viability, indicating that the signal for induction of apoptosis is triggered rapidly upon treatment with bufalin. Bufalin-induced apoptosis in HL60 cells was inhibited by ZnCl2, an inhibitor of endonuclease, but not by cycloheximide, an inhibitor of protein synthesis. Northern blot analysis revealed that the levels of expression of the c-myc and bcl-2 genes in HL60 cells decreased with time after treatment with bufalin. These results suggest that bufalin induces apoptosis specifically in human leukemia cells by altering the expression of these genes involved in apoptosis.     

Bender-Gestalt Test performance in senile dementia of the Alzheimer type.

Bender-Gestalt Test performances of 144 persons with very mild, mild, or moderate senile dementia of the Alzheimer type (SDAT) and 96 healthy older adults ranging in age from 63 to 95 yrs were compared. Total scores and error types according to the modified Hutt-Briskin scoring system are reported. The Bender-Gestalt Test does not appear to be useful in differentiating very mild or mild SDAT from normal aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic lithium and electroconvulsive stimuli on cholecystokinin mRNA expression in the rat brain

This study compares the effect of lithium (Li+) and electroconvulsive stimuli (ECS), two treatments commonly used in the treatment of affective disorders, on CCK mRNA expression in the rat brain. Two groups of rats receiving either 4 week Li+ or vehicle food supplementation and two groups receiving 6 ECS or 6 sham ECS during 2 weeks were studied. A significant decrease in CCK mRNA levels was seen in the caudate putamen both after Li+ as compared to vehicle and ECS as compared to sham ECS, 27 and 25%, respectively. A small (10%), yet significant, decrease was also seen in the inner entorhinal cortex after Li+. The results indicate that both Li+ and ECS inhibit CCK synthesis in the caudate putamen and are consistent with other findings of presumed decreased dopaminergic action in this part of the brain following these treatments.     

Susceptibility to mercuric chloride-induced glomerulonephritis is age-dependent: study of the role of IFN-gamma

The repeated administration of low-dose HgCl2 to brown Norway (BN) rats induces an autoimmune syndrome which is characterized by polyclonal B cell activation, high-level synthesis of IgE and IgG1, and massive proteinuria. Data have been presented suggesting that during disease development there is a preferential expansion of CD4+ T cells belonging to the TH2 subset. In the present study it was found that aged BN rats are far less susceptible to the immunopathological effects of HgCl2 compared to their younger counterparts. Whereas rats at 10 weeks of age develop high-level proteinuria upon three repeated injections with HgCl2, animals at 18 to 24 months of age do not release urinary protein under these conditions and develop low-level proteinuria with a delayed onset after five repeated injections with HgCl2. FACScan analysis of splenocytes from old and young rats revealed a defined increase in the frequency of CD45RB(RC)+/CD4+ T cells in the splenocyte population of older rats, suggesting an age-related shift to a more TH1-like phenotype. Moreover, splenocytes of aged rats generated a threefold higher number of IFN-gamma-producing cells than those of young rats upon polyclonal activation in vitro. The administration of neutralizing anti-rat IFN-gamma mono- and/or polyclonal antibodies to aged BN rats just prior to HgCl2 exposure significantly augmented IgE and IgG1 serum levels and exerted a small but significant stimulatory effect on proteinuria in the initial stage but not in the more advanced stages of the renal disease. When antibodies were given 7 days after the beginning of HgCl2 exposure no stimulatory effect on both IgE/IgG1 levels and proteinuria was observed. The data indicate that splenic T cells of aged BN rats possess a higher capacity to release IFN-gamma than those of young rats and that this cytokine functions to downregulate IgG1 and IgE synthesis in HgCl2-exposed BN rats. The findings further suggest that IFN-gamma plays a regulatory role in the development of glomerulonephritis.     

Differential expression of methionine adenosyltransferase genes influences the rate of growth of human hepatocellular carcinoma cells

Methionine adenosyltransferase (MAT) catalyzes the formation of S-adenosylmethionine (SAM), the principal methyl donor, and is essential to normal cell function. The two forms of MAT, liver specific and non-liver specific, are products of two genes, MAT1A and MAT2A, respectively. We have reported a switch from MAT1A to MAT2A gene expression in human liver cancer cells. In the current work, we examined whether the type of MAT expressed by the cell influences cell growth. HuH-7 cells were stably transfected with MAT1A and were subsequently treated with antisense oligonucleotides directed against MAT2A. MAT2A antisense treatment reduced the amount of MAT2A mRNA by 99% but had no effect on MAT1A mRNA. Cell growth and DNA synthesis rates were reduced by approximately 20-25% after transfection with MAT1A and by an additional 30-40% after MAT2A antisense treatment. SAM level and SAM:S-adenosylhomocysteine (SAH) ratio increased by 50-75% after MAT1A transfection and by an additional 60-80% after MAT2A antisense treatment. DNA methylation changed in parallel to changes in SAM level and SAM:SAH ratio. Supplementing untransfected HuH-7 cells with SAM in the culture medium increased SAM level, SAM:SAH ratio, and DNA methylation and decreased cell growth and DNA synthesis. In conclusion, cell growth is influenced by the type of MAT expressed. The mechanism likely involves changes in SAM:SAH ratio and DNA methylation.     

Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats

The native TRH receptor (TRH-R), which is a G protein-coupled receptor that signals via the phosphoinositide transduction pathway, has been assumed to be inactive in the absence of agonist. In contrast, a mutant mouse TRH-R (C335Stop TRH-R) was shown previously to exhibit constitutive (or agonist-independent) signaling activity. In this report, we measured signaling activity of TRH-Rs using a protein kinase C-responsive reporter gene instead of formation of inositol phosphate second messenger molecules. Using this more sensitive system, we show that native mouse TRH-Rs exhibit agonist-independent signaling activity that is directly proportional to the number of receptors expressed in COS-1 cells and is inhibited by negative antagonist benzodiazepine drugs. As expected, the basal signaling activity of native TRH-Rs is lower than C335Stop TRH-Rs. Constitutive activity of native TRH-Rs is not peculiar to COS-1 cells in which receptor density is markedly elevated, because it can also be demonstrated in Madin Darby canine kidney cells stably expressing mouse TRH-Rs and GH4C1 cells endogenously expressing rat TRH-Rs. These findings support the thesis that native TRH-Rs oscillate between active and inactive states. We suggest that demonstration of constitutive activity of native receptors may depend on the sensitivity of the signaling assay employed.     

Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model

It has been suggested that neuroimmunologic mechanisms may be involved in the development and maintenance of neuropathic pain. To further address this concept, the immunoreactive spinal expression of the pro-inflammatory cytokine, interleukin-6 (IL-6), was determined in the mononeuropathy model in the rat, sciatic cryoneurolysis (SCN). This well-established animal model expresses behaviors suggestive of neuropathic pain in humans. Immunohistochemical localization in the spinal cord was determined at 3, 7, 14, 21, 35, and 120 days after SCN (n = 6 per time point). Immunoreactive IL-6 increased incrementally in the substantia gelatinosa and motoneurons over time following SCN as compared with normal rats. In an additional study, recombinant human IL-6 was administered intrathecally to normal and previously SCN-lesioned rats. Intrathecal IL-6 produced touch-evoked allodynia (increased sensitivity to a nonnoxious stimulus) in normal rats and thermal hyperalgesia (increased sensitivity to a noxious stimulus) in previously lesioned SCN rats. These results provide evidence that IL-6 may be involved in the cascade of events leading to the development and maintenance of behaviors suggestive of neuropathic pain following peripheral nerve injury.     

The role of nitric oxide in mercury chloride-induced vasculitis in the brown Norway rat

The molecular epidemiology of Pseudomonas aeruginosa infection in cystic fibrosis (CF) siblings was analysed by DNA fingerprinting using arbitrary primed polymerase chain reaction. A total of 306 strains collected from six pairs of siblings over a period of 20-126 months (median 64) was studied. Fifty-four different P. aeruginosa genotypes were recognized. Two out of six pairs of siblings were ultimately colonized by identical strains, and it was shown that a single P. aeruginosa clone can persist in an individual patient for over ten years. No overlap in P. aeruginosa genotypes was encountered between families, whereas in all families at least transient cross-colonization with the same genotype was observed. This finding demonstrates that P. aeruginosa cross-infection or acquisition of the same strain from an identical environmental source exists within the family situation, but does not always result in a long-term colonization by identical genotypes in all family members suffering from CF.     

Conditioned hyperalgesia depends on the pain sensitivity measure.

Conflicting reports about the acquisition of conditioned hyperalgesia during the development of conditioned morphine tolerance have led researchers to suggest that tolerance reflects a reduction of stimulus processing rather than a compensatory response interaction. I tested conditioned hyperalgesia on both the hot-plate and tail-flick tests in the same animals. In accordance with previous reports, the tail-flick responses in drug-free animals failed to reveal a conditioned compensatory hyperalgesia. Conditioning effects in the tail-flick test were found only when the animals were challenged with a low dose of morphine. However, the hot-plate response in drug-free animals replicated earlier demonstrations of conditioned hyperalgesia. The results suggests that the measurement of conditioned respones in drug-free animals depends on characteristics of the assessment procedure. These findings are consistent with accounts of morphine tolerance that depend on compensatory response interactions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)