Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice.

Background Cetuximab is a fully humanized IgG1 subclass monoclonal that binds specifically to the human epidermal growth factor receptor (EGFR). Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, such as colon, rectum and lung tumors. In this study, cetuximab with a combination of radiotherapy nuclear 188Re achieved better therapeutic effect on lung cancer. Methods188Re-cetuximab administered by the i.v. route in human NCI-H292 lung tumor-bearing mice was investigated. NanoSPECT/CT images were taken to evaluate the distribution and tumor targeting of 188Re-cetuximab in mice. The anti-tumor effect of 188Re-cetuximab was assessed by the tumor growth inhibition, survival ratio. Results For nanoSPECT/CT imaging, a significant uptake in tumor was observed at 24 and 48 h following the injection of 188Re-cetuximab. The anti-tumor effect of 188Re-cetuximab was assessed by tumor growth inhibition and the survival ratio. The tumor-bearing mice treated with 188Re-cetuximab showed a better mean tumor growth inhibition rate (MGI = 0.049) and longer median survival time and lifespan (62.50 d; 70.07%) than those treated with 188Re-perrhenate and cetuximab only by single injection. A synergistic effect of tumor growth inhibition was observed with the combination index exceeding one for 188Re-cetuximab (CI = 6.135 and 9.276). Conclusion The tumor targeting and localization of 188Re-cetuximab were confirmed in this study. Synergistic therapeutic efficacy was demonstrated for the radioimmunotherapy of 188Re-cetuximab. The results of this study reveal the potential advantage and benefit obtained from 188Re-cetuximab for diagnosis and therapy of oncology applications in the future.

Cultural issues in post-disaster reconstruction: the case of Typhoon Morakot in Taiwan.

Most members of Taiwan's indigenous communities live in areas that are prone to natural disasters. Yet, due to their marginalised cultural, economic and political status, each time such calamities strike, any assistance they receive is usually provided without considering their actual needs. The areas hardest hit by Typhoon Morakot in August 2009 were the indigenous villages in the southern and eastern parts of the island. After the initial emergency relief efforts had been completed, there remained the highly challenging task of reconstruction and the resettlement of those who lost their homes and livelihoods. This paper examines the cultural conflicts that arose during the reconstruction process, with special emphasis on the participation of Taiwan's indigenous communities and their capacity for resilience. It was found that community participation and identification are key issues in effective disaster governance.

Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes.

The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to Teff/TRM clusters in association with rejection. By integrating pre- and post-transplantation (Tx) mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in the human gut, providing novel insight into TRM biology.

[The aesthetic practice of care ethics].

Situated between the doctor and the patient, nurses play a central role in the doctor-patient relationship. Nurses attend to patients' exhaustion and take responsibility for the "Other," in Lévinas' sense of the word. In discussions of the doctor-patient relationship, the patient is often regarded as the "Other". This perspective seeks to challenge the traditional contention that the doctor plays the dominant role. In the structure of this relationship, the doctor, responsible for providing diagnoses, is the subject and the patient is the object. The latter constantly feels frustrated and helpless and requires the comfort of the nurse. In this sense, the nurse, having the direct contact with the patient, constantly sees the faces of the patients. In the care relationship, the patient's frustration and helplessness will sometimes be expressed to the nurse if the patient cannot be affectively affirmed. In this type of situation, the nurse bears not simply his / her routine work, but also affective devotion and endurance. On the one hand, the nurse must practice professional medical care in the face of patients' affective feelings and emotions and, on the other hand, he / she must treat the patient as a relative and suppress inner feelings and emotions. How does a nurse situate herself into the doctor-patient relationship? As the nurse is asked to treat the patient as a relative, how does he / she face inner emotions? This paper reflects on the possibility of the aesthetic practice of care ethics.

Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue.

Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, which can also generate human T cells, and demonstrated definitively the capacity of human T cells to develop in a grafted neonatal human thymus. Human T cells derived from the neonatal thymus tissue appeared in peripheral blood early post-transplantation and CB-derived T cells appeared later. Naïve T cells were demonstrated in peripheral blood but effector memory and T peripheral helper phenotypes predominated later, in association with development of autoimmunity in some animals. Treatment of thymus grafts with 2-deoxyglucose (2-DG) increased the proportion of stem cells derived from injected HSCs, delayed onset of autoimmune disease, reduced early T cell reconstitution, and reduced effector/memory T cell conversion. Younger neonatal human thymus tissue was associated with improved T cell reconstitution. While the NeoHu model bypasses the need for fetal tissue, it has yet to demonstrate equivalent reconstitution to fetal tissue, though 2-DG can improve results by removing native thymocytes prior to transplantation.

Psychometric Testing of the Newly Developed Competence Scale for Clinical Nurses.

BACKGROUND: Nursing competence is an essential element in ensuring high-quality nursing care and positive patient outcomes. Valid and reliable assessment tools for assessing nurse competence are needed to help nurse supervisors measure whether nurses are performing their job well and to provide a baseline for improving the competences of nurses. PURPOSE: This study was designed to develop and psychometrically validate the Competence Scale for Clinical Nurses (CSCN). METHODS: The CSCN was developed in three steps: (a) generalize assessment items from nursing competence-related scales and a review of the relevant literature, (b) determine the content validity of the developed scale, and (c) psychometrically test the developed scale. Five hundred nurses were recruited from a medical center in southern Taiwan. Exploratory and confirmatory factor analyses were executed to analyze construct validity and internal consistency reliability. RESULTS: The scale-content validity index was .87, as determined by five experts. Two thirds (63.29%) of the variance was explained by three factors: basic care skills (nine items), being dedicated to work (five items), and patient-centered and ethical considerations (four items). A second-order confirmatory factor analysis indicated that the data fit the model well. The Cronbach's alpha coefficients for each of the three factors and the total scale were .84-.91. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The 18-item CSCN is a feasible and time-efficient tool for assessing competence in clinical nurses. Nursing supervisors may use this tool to explore nurses' competency and routinely track the effect of continuing education on competence. Continuous evaluation of nurses' clinical-based competence using the CSCN is recommended.

Capture of metallic copper by high gradient magnetic separation system.

Valence copper was recovered from wastewater by chemical reduction and use of a high gradient magnetic separation (HGMS) system. Ammonia (NH3) and sodium dithionate (Na2S2O4) at a molar ratio of [Cu]:[NH3]:[Na2S2O4] = 1:4:3 at pH = 9.5 were used first to chemically reduce copper ion to metallic copper; the resultant metal solids were captured in an upflowing reactor space equipped with a permalloy matrix net under a high gradient magnetic field. The captured solids were predominantly 6-20 microm in diameter, with Cu2O and CuO present among the solids. Four treatment configurations with and without the use of magnetic field and metal alloy as the matrix net were tested and their effects evaluated: (1) no magnetic field or matrix, (2) no magnetic field but with matrix, (3) with magnetic field but no matrix, (4) with both magnetic field and matrix. At flow rates of 40, 60, 80 and 100 cm3/min, capture efficiencies for metallic copper in the absence of magnetic field were 87%, 86%, 63%, and 39%, respectively, and in the presence of magnetic field were 99%, 98%, 95%, and 93%, respectively. The HGMS was critical for a high capture efficiency, whereas a matrix net only marginally enhanced it. Additional tests with a larger reactor confirmed similarly high efficiencies of > 85%. The use of an alloy matrix appeared to be important when high flow rates are most likely to be employed in practical applications.

Recovery of metallic copper by integrated chemical reduction and high gradient magnetic separation.

The recovery of metals from waste effluents is necessary for pollution prevention and sustainable practice. High gradient magnetic separation (HGMS) is seen as a viable method. We investigated the capture of valence copper from aqueous copper ion by HGMS in combination with a chemical reduction process. When a copper solution (3.9 or 15.6 mM) was exposed to excess of dithionite (mole ratio of 1:3) in the presence of ammonia (mole ratio of 4) and amended with MnCl2 (2.5 g/L) and the mixture passed through a flow reactor under a strong magnetic field (10000 Gauss), valence copper was obtained and captured in the reactor with well over 95% yields. The chemical reduction reactions were unaffected by the presence of MnCl2 while the amount of MnCl2 (0, 20 and 32 mM) has significantly varied the copper recovery efficiency, especially in the case of high initial copper ion concentration (15.6 mM). Formation of MnO2 flocs was found to have a detrimental effect on copper removal efficiency. The HGMS method offers a tool of resource recovery for copper from waste effluents.

[Reducing patient pressure sore incidence in the surgical intensive care unit].

BACKGROUND: Pressure ulcers were an increasingly significant problem among patients in the authors' ward. The eight patients diagnosed with pressure ulcers (0.42% of all inpatients) during the first half of 2009 represented a 140% increase over the first half of 2008 (0.28% of all inpatients). PURPOSE: This project was designed to reduce pressure ulcer incidence in the surgical intensive care unit (ICU) to 0.05%. METHODS: Intervention measures included: 1) holding professional training on preventing pressure ulcers; 2) specifying appropriate patient turnover tools; 3) creating and distributing to nurses a proper turnover technique and positioning manual; 4) creating and distributing to nurses a comprehensive patient skin inspection checklist; and 5) organizing a permanent pressure ulcer care quality and audit committee. RESULTS: Pressure ulcer incidence fell from 0.42% to 0.04% following implementation of the methods. CONCLUSION: Results demonstrate the effectiveness of using the proposed methods to reduce pressure ulcer incidence and enhance nursing care quality.

Determinants Impacting User Behavior towards Emergency Use Intentions of m-Health Services in Taiwan.

Emergency usage intention and behavior are crucial to business service success for m-Health providers and patient healthcare service. This study aimed to identify the factors that influence m-Health acceptance and the effect of emergency use intentions on usage behavior among Taiwanese m-Health users by adopting and extending the Unified Theory of Acceptance and Use of Technology (UTAUT). This study also examines the moderating role of gender and age in the effects of the independent variables on satisfaction with m-Health services. An online questionnaire was used to collect data from 371 participants. The results revealed that performance expectancy, facilitating conditions, and trust had positive effects on user satisfaction. Additionally, m-Health knowledge and user satisfaction had positive effects on emergency use intentions. However, social influence and effort expectancy did not have a significant effect on satisfaction. Moreover, age and gender significantly moderated the effects of some predictors.

Effect of extraction parameters on curcumin yield from turmeric.

Effect of 4 independent variables - temperature (50-90°C), particle size (0.42-0.85 mm), mixing time (10-50 min) and solvent (ethanol) to meal ratio (10-50) on curcumin yield from turmeric (Curcuma longa L) was studied using central composite rotatable design. The experimental value of curcumin yield ranged between 4.49 and 12.89%. The second order model obtained for curcumin yield revealed a coefficient of determination (R(2)) of 0.78 and standard error of 0.72. The linear, square and interaction terms were significant at p <0.05 while lack of fit was non-significant at p >0.05. Surface graphs were plotted to optimize the curcumin extraction. The maximum curcumin yield was obtained when temperature, particle size, mixing time and solvent to meal ratio were 60°C, 0.42 mm, 30 min and 50, respectively.

p38 mitogen-activated protein kinase-dependent regulation of SRC-3 and involvement in retinoic acid receptor alpha signaling in embryonic cortical neurons.

Appropriate retinoic acid (RA) signaling is essential in the development of the central nervous system (CNS). Previous studies have shown that RA activates p38 mitogen-activated protein kinase (MAPK) and steroid receptor coactivator (SRC)-3 in tumor cells in vitro. It is unknown whether the activation of p38 MAPK and SRC-3 is involved in RA-mediated CNS development. The current study investigated a possible role for p38 MAPK in the regulation of (SRC)-3 phosphorylation/degradation and in retinoic acid receptor (RAR)alpha signaling in mouse fetal cortical neurons treated with all-trans retinoic acid (ATRA). Results showed that ATRA treatment rapidly activated p38 MAPK, which in turn resulted in phosphorylation with subsequent degradation of SRC-3. Inhibition of p38 MAPK by SB203580 blocked the phosphorylation and degradation of SRC-3. The binding of RARalpha to retinoic acid responsive element (RARE) was rapidly increased in neurons following ATRA treatment. Inhibition of p38 MAPK significantly enhanced the RARalpha-RARE binding activity, but had no effects on ATRA-induced decrease of RARalpha. Treatment of the fetal cortical neurons with ATRA significantly increased the expression of HOXd3, a retinoid-target gene. The increase of HOXd3 expression was augmented when p38 MAPK activity was inhibited by a specific inhibitor, SB203580. Results suggest that ATRA activates the p38 MAPK signal pathway with resultant degradation of SRC-3, and that p38 MAPK is involved in the regulation of RARalpha-mediated signaling in developing neurons.

All-trans-retinoic acid alters Smads expression in embryonic neural tissue of mice.

Retinoic acid can cause malformations of the developing nervous system. Smad signaling is involved in embryonic development. The current study investigated all-trans-retinoic acid (ATRA)-induced alteration of Smad expression in the developing neural tubes of mice. Pregnant mice were treated with a single dose of 50 mg/kg ATRA by oral gavage on embryonic day E7. Western immunoblotting was used to examine Smads proteins, particularly phosphorylated (p-) Smad1, total Smad1 and Smad6 in the neural tissue of the embryos on E8-E11 following treatment. Results showed that ATRA treatment significantly increased expression of both p-Smad1 and total Smad1, while Smad6 was decreased in neural tissues of ATRA-exposed embryos in utero from E8 to E11, a critical period for neural tube formation. Data suggest that disruption of Smad signaling may be involved in ATRA-induced neural tube defects.

Hepatocyte gene transfer mediated by stable polyplexes based on MPP-containing DNA complexes.

BACKGROUND: In the field of gene therapy, viral vectors as delivery tools have a number of disadvantages for medical application. This study aimed to explore a novel nonviral vector as a vehicle for gene therapy. METHODS: Transvector-rpE-MPP and EGFP (enhanced green fluorescent protein) were used as the gene transfer carrier and the reporter gene, respectively. Polyplexes which integrate transvector-rpE-MPP, the object gene, and EGFP were formed. The optimal charge ratio, stability, and transduction capacity of the polyplexes in mouse hepatocytes in vitro and in mouse liver in vivo were investigated. The polyplexes of transvector-rpE-MPP and pcDNA(3)-EGFP, with charge ratios of 0, 0.25, 0.5, 0.75, 1 and 1.5 were compared to determine the optimal charge ratio. RESULTS: Polyplexes with charge ratios of 1:1 were most stable; pcDNA(3)-EGFP in these complexes resisted digestion by DNase I and blood plasma. On the other hand, pcDNA(3)-EGFP alone was digested. Fluorescence analysis indicated that transvector-rpE-MPP successfully delivered the reporter gene EGFP into hepatocytes and that EGFP expression was detected in hepatocyte cultures and in liver tissue. CONCLUSION: These results have laid a foundation for further study of a novel nonviral gene delivery system.

Renal disease is a prodrome of multiple myeloma: an analysis of 50 patients from eastern India.

This study describes a spectrum of renal diseases that can precede the diagnosis of multiple myeloma (MM). Patients presenting manifestations of renal disease were recorded as individual patients of MM. Fifty patients (male 41; female 9) were included in this study. Diagnosis of MM was confirmed by two or more of the following four features: lytic bone lesions, serum or urine monoclonal peak, Bence Jones proteinuria, and greater than 20% plasma cells in bone marrow. Renal disease was present in 42 of 50 (84%) patients before MM was diagnosed. In only eight of 50 (16%) patients, diagnosis of MM preceded the detection of renal disease. Renal diseases consisted of acute renal failure in 26 patients (52%), chronic renal failure in 15 patients (30%) and nephrotic syndrome in 9 patients (18%). Some of the patients with acute or chronic renal failure also had heavy proteinuria. Percutaneous renal biopsy was done in 17 patients. Renal histopathology showed amyloidosis (n = 10), cast nephropathy (n = 5), nodular glomerulosclerosis (n = 1), and mesangioproliferative glomerulonephritis with plasma cell infiltration (n = 1). Hypercalcemia (calcium 11-13.8 mg/dL) was the most common precipitating factor for acute renal failure. All 50 patients received combination chemotherapy of melphalan and prednisolone or vincristine, Adriamycin, and dexamethasone. More than half of the total number of patients did not complete chemotherapy because of death or lost to follow-up. Nineteen patients with acute renal failure and eight patients with chronic renal failure were treated with hemodialysis. Fourteen patients (28%) with acute renal failure had recovery of renal function. Twenty-three patients (46%) were lost to follow-up. Seven patients (14%) died from sepsis, uremia, or hyperkalemia. Remission of MM was found in 9 of 21 (42.8%) patients who completed chemotherapy. Thus, acute renal failure is the most common renal disease preceding the diagnosis of MM. Reversal of renal function is achieved with chemotherapy and hemodialysis treatment.

Multiple myeloma--presenting as acute kidney injury.

BACKGROUND: Multiple myeloma (MM) is a commonly encountered hematological malignancy with significant renal involvement and often presents as renal failure. The aim of the present study is to analyze clinical spectrum of acute renal failure (ARF) in patients with MM. MATERIAL AND METHODS: We analyzed 26 (males 24; females 2) patients of multiple myeloma who were referred for evaluation of ARF between July 1994 - June 2007. The referral diagnosis did not include MM in majority 23 (88%) of the patients. Multiple myeloma was diagnosed by at least two of the four features; (1) lytic bone lesions, (2) serum or urine monoclonal peak, (3) Bence Jones proteinuria and (4) more than 20% plama cells in marrow aspirate. RESULTS: Multiple myeloma contributes 1.93% of total ARF cases (26/1342) over a period of thirteen years. Mean age of patients was 59.3 +/- 7.4 years. The clinical manifestations of myeloma included; anemia (100%), Bence Jones proteinuria (80%), "M" peak in serum electrophoresis (69%), lytic bone lesions (62%), "M" peak in urine electrophoresis (54%), body pain (58%), plasma cells more than 20% in bone marrow aspirate (38%). Oliguric ARF was seen in 73% patients. The precipitating factors of ARF identified were; hypercalcemia (31%); infection (23%); volume depletion (19%); and NSAIDs in (15%). Dialysis support was needed in 77% of the patients because of severe renal failure at presentation with mean serum creatinine of 9.05 +/- 2.84 mg%. Seventeen patients completed chemotherapy, seven last to follow up and two patients died. Ten (38.5%) patients had complete recovery of renal function; three patients had partial recovery and off dialysis and four patients remained dialysis dependent. Remission of myeloma was achieved in nine of seventeen patients treated with chemotherapy Renal biopsy finding in nine patients revealed-cast nephropathy in (4), amyloidosis in (3), proliferative glomerulonephritis in (1) and cast nephropathy with chronic interstitial nephritis and plasma cell infiltration in one patient. CONCLUSION: Acute reversible renal failure is a common complication in MM, multiple myeloma should be considered as cause a cause of unexplained ARF in middle aged and elderly patients.

Radiolabeling, Characteristics and NanoSPECT/CT Imaging of 188Re-cetuximab in NCI-H292 Human Lung Cancer Xenografts.

BACKGROUND/AIM: Cetuximab has exhibited high EGFR-targeting specificity and clinical promise in previous studies. In this study, we formulated unit dose kits for preparation of high specific activity 188Re-cetuximab for imaging and treatment of EGFR-positive cancer. MATERIALS AND METHODS: 188Re-cetuximab was prepared by adding 0.37-0.74 GBq/0.5 ml of 188Re-perrhenate for 4 h at 37°C. Cell surface expression of EGFR, cell binding and cytotoxic effects were evaluated in vitro using both EGFR-positive (NCI-H292, A431) and EGFR-negative (BT483) tumors. A nanoSPECT/CT imaging study was performed in mice bearing EGFR-expressing NCI-H292 tumors. RESULTS: 188Re-cetuximab bound specifically to EGFR-expressing cells and labeling of radionuclides to cetuximab preserved the binding ability of the antibody. Besides, the cytotoxic effect of 188Re-cetuximab was increased dose-dependently. NanoSPECT/CT imaging revealed that 188Re-cetuximab could continually target the tumor region for at least 48 h. CONCLUSION: The highly specific targeted property of 188Re-cetuximab suggested that it is suitable as a diagnostic tool and maybe a potent radioimmunotherapy agent in EGFR-positive cancers.

What grabs his attention but not hers? Estrogen correlates with neurophysiological measures of vocal change detection.

Prior research revealed sex differences in the processing of unattended changes in speaker prosody. The present study aimed at investigating the role of estrogen in mediating these effects. To this end, the electroencephalogram (EEG) was recorded while participants watched a silent movie with subtitles and passively listened to a syllable sequence that contained occasional changes in speaker prosody. In one block, these changes were neutral, whereas in another block they were emotional. Estrogen values were obtained for each participant and correlated with the mismatch negativity (MMN) amplitude elicited in the EEG. As predicted, female listeners had higher estrogen values than male listeners and showed reduced MMN amplitudes to neutral as compared to emotional change in speaker prosody. Moreover, in both, male and female listeners, MMN amplitudes were negatively correlated with estrogen when the change in speaker prosody was neutral, but not when it was emotional. This suggests that estrogen is associated with reduced distractibility by neutral, but not emotional, events. Emotional events are spared from this reduction in distractibility and more likely to penetrate voluntary attention directed elsewhere. Taken together, the present findings provide evidence for a role of estrogen in human cognition and emotion.

Correlation of polymorphism of MTHFRs and RFC-1 genes with neural tube defects in China.

BACKGROUND: Maternal periconceptional supplementation of folate reduces the incidence of neonatal Neural Tube Defects, indicating that changes in folate metabolism play a role in formation of NTDs. The mutations on two genes involved in folate metabolism, the C677 of the MTHFR gene and the RFC-1(A80G) gene are potential risk factors of NTDs. METHODS: In this study, we analyzed the genotypic distributions and allele frequencies of MTHFR C677T and RFC-1 A80G polymorphisms in DNA samples from mothers with at least one previous child with NTDs (the NTD group) and controls. RESULTS: Our results indicated that there was a significant difference in the genotype and allele frequencies of RFC-1 80A-->G between the NTD group and controls (p = .008 and p = .017, respectively). There was, however, no significant difference in the genotype and allele frequencies of the MTHFR 677C-->T polymorphism between the NTD group and controls. The NTD group was further separated into the upper and lower types by location of abnormalities. The frequency of RFC-1 80A/G and 80G/G was significantly higher in the upper group than the control (p = .009 and p = .005, respectively). The frequency of G-alleles was also significantly higher in the upper group than the control (OR 2.42; p = .006; 95% CI: 1.28-4.58). For the MTHFR C677 gene, the frequency of T-alleles was significantly lower in the lower defect type than the control group (OR 0.32; p = .027; 95% CI: 0.11-0.9). CONCLUSIONS: These results suggest that in the Shanxi population RFC-1 polymorphisms may play a role in NTD risk, whereas the impact of MTHFR C677T polymorphisms requires further clarification. Birth Defects Research (Part A) 2008.

Effect of Lactobacillus acidophilus supernatants on body weight and leptin expression in rats.

BACKGROUND: Lactobacillus extracts and supernatants have been used as probiotics in human and veterinary medicine for their ability to enhance wound healing and immunity. Previous data from our laboratory demonstrated that Lactobacillus supernatant (LS) stimulated wound healing, angiogenesis and proliferation of embryonic cells after topical application. This current study shows that LS after its administration into the cerebral ventricles of male rats exerts systemic effects. METHODS: The right lateral cerebral ventricle of young male rats was accessed through intracerebroventricular cannulation (ICV) under anesthesia and aseptic conditions. One group of control rats received saline solution, a second control group received 0.8 M lactic acid solution (to control for acidity of LS), and a third group received LS. The animals were sacrificed 12, 24, 48, 96 and 120 hours after the injection. Selected tissues were collected, fixed in 10% buffered formalin and used for immunohistochemistry and in situ hybridization. Other tissues were frozen and extracted for immunoblotting RESULTS: LS-injected animals had a slight decrease in body weight when compared to their initial weight and to both control groups. Using immunohistochemistry and in situ hybridization leptin expression was studied in multiple brain sections and peripheral adipose tissue of control and LS-injected rats. Strong cytoplasmic stain was observed by both techniques in neurons of the cerebral cortex, thalamus, hypothalamus, hippocampus and, to lesser degree, in the cells of the choroid plexus in the LS-injected rats. Control animals demonstrated much less intense staining in neurons located in the same regions using immunohistochemistry and almost no staining with in situ hybridization technique. Adipose tissue exhibited slight presence of leptin in LS-treated animals. In contrast no immunohistochemical staining for GM-CSF and TNFalpha was observed in brains from control and treated rats. Western blotting showed mild increase in leptin and leptin receptors in intestines and retroperitoneal adipose tissues of LS-injected rats. CONCLUSION: This study demonstrates that direct administration of LS into rat CNS leads to a decrease in body weight of rats and an increase in the expression of leptin in specific areas of the brain and retroperitoneal adipose tissue.