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Introduction: Invasive fungal infections are increasingly common in the nosocomial setting. Materials and Methods: The patients were divided into two groups immunocompetent and immunocompromised that is, patients with significant neutropenia

Background: The prevalence of multidrug-resistant-tuberculosis (MDR-TB) among new and previously treated cases is increasing worldwide as well as in India. Rapid detection of MDR-TB allows the establishment of an effective treatment regimen; minimizes the risk of further resistance, and limits the spread of drug-resistant strains. Early diagnosis of MDR-TB is the need of the hour in high-TB burden countries like India, and GenotypeMTBDRplus is quite sensitive and specific in determining the molecular resistance in drugs such as rifampicin and isoniazid. Methods: The present study was done for molecular detection of rifampicin and isoniazid resistance and resistance patterns among MDR-TB suspects and comparison of resistance patterns among new and previously treated cases by GenoType® MTBDRplus Line Probe Assay. A total of 1268 sputum samples of MDR-TB suspects were subjected to fluorescent microscopy. Fluorescent microscopy positive samples were subjected to GenoType® MTBDRplus (HAIN Lifescience) assay. Results: MDR-TB was detected 11.02%, 20.03% in new and previously treated cases. Among MDR-TB patients S531 L was the most common mutation detected in rpoB gene; 71.43% in new, and 72.17% in previously treated cases. S315T1 was the most common mutation noted in katG gene; 100% in new and 81.74% in previously treated. While in hA gene, it was C15T (7.8%) among previously treated cases. Conclusion: MDR-TB has high prevalence in the western part of Uttar Pradesh, India. Previously treated cases have even more high rate of MDR-TB than new TB cases. The most dominant gene mutations associated with resistance to INH and RIF were observed in codon 315 of the katG gene and codon 531 of the rpoB gene. While comparing the mutation patterns by Genotype MTBDRplus assay, previously treated cases showed more diversity of mutations and had greater number of unknown mutations.

The terminal step of ligation of single and/or double-strand breaks during physiological processes such as DNA replication, repair and recombination requires participation of DNA ligases in all mammals. DNA Ligase I has been well characterised to play vital roles during these processes. Considering the indispensable role of DNA Ligase I, a therapeutic strategy to impede proliferation of cancer cells is by using specific small molecule inhibitors against it. In the present study, we have designed and chemically synthesised putative DNA Ligase I inhibitors. Based on various biochemical and biophysical screening approaches, we identify two prospective DNA Ligase I inhibitors, SCR17 and SCR21. Both the inhibitors blocked ligation of nicks on DNA in a concentration-dependent manner, when catalysed by cell-free extracts or purified Ligase I. Docking studies in conjunction with biolayer interferometry and gel shift assays revealed that both SCR17 and SCR21 can bind to Ligase I, particularly to the DNA Binding Domain of Ligase I with KD values in nanomolar range. The inhibitors did not show significant affinity towards DNA Ligase III and DNA Ligase IV. Further, addition of Ligase I could restore the joining, when the inhibitors were treated with testicular cell-free extracts. Ex vivo studies using multiple assays showed that even though cell death was limited in the presence of inhibitors in cancer cells, their proliferation was compromised. Hence, we identify two promising DNA Ligase I inhibitors, which can be used in biochemical and cellular assays, and could be further modified and optimised to target cancer cells. © 2016 Wiley Periodicals, Inc.

A series of new dihydropyrimidinone–semicarbazone hybrids were successfully synthesised by integrating regioselective multicomponent reaction with the pharmacophore hybridization approach. All the synthesised compounds were evaluated for their hLig1 inhibition potency and most of them were found to be good to moderately active. Out of the tested derivatives, compound 6f showed selective anti-proliferative activity against HepG2 cells in a dose-dependent manner with an IC50 value of 10.07 ± 1.2. It also reduced cell survival at ≤20 μM concentration. Further, analysis of treated HepG2 cell lysates by western blot assay showed increased γ-H2AX levels and upregulation of p53, leading to apoptosis. In silico docking results explain the binding modes of compound 6f to the DNA-binding domain of hLig1 enzyme thereby preventing its nick sealing activity. In addition, the favourable pharmacokinetic properties suggest that this new class of hLig1 inhibitors could be promising leads for further drug development.

The processes of DNA replication and repair are accomplished by the concerted action of several proteins. Among them human DNA ligases play an important role during the last step of almost all DNA replication and repair processes, where they seal the nicks between DNA strands. In humans, three kinds of DNA ligases (human DNA ligase I, III, IV) are found. DNA ligase I (hLigI) is involved in both DNA replication as well as in DNA repair pathways and is reported to be over-expressed in rapidly dividing cells, including cancer cells. For this reason, in this study we have targeted hLigI for studying its response as a novel anticancer target. We have screened for ligase I inhibitors from our in-house small molecule library by a previously validated pharmacophore based virtual screening method and found a novel hLigI inhibitor. This compound (S-097/98) demonstrated antiproliferative activities specifically in DLD-1 (colon), MDA-MB-231 (triple negative breast) and HepG2 (liver) cancer cell lines at low micromolar concentrations of 6–7 μM. Mechanistic studies show that the compound can directly interacts with the hLigI protein and inhibits ligation of both the purified protein in vitro, as well as in cell lysate of DLD-1 cells treated with the inhibitor. The compound also arrests cell cycle progression at the G2/M phase and increases the nuclear size of DLD-1 cancer cells, thereby demonstrating its antiproliferative activity. Finally, the compound promotes cellular apoptosis in DLD-1 cells.

INTRODUCTION: Allergic rhinitis and bronchial asthma are thought to be sequela of the same allergic airway disease. The relationship between both diseases has been confirmed by various clinicopathological epidemiological and immunological studies. In this study, we tried to establish a different relationship between both diseases and strengthen the concept of “One-airway one disease.” MATERIALS AND METHODS: A total of 100 patients visiting ear, nose, and throat and respiratory medicine outpatient department were taken. They were divided into two groups of fifty each and were studied for various mediators of inflammation. Group 1 consisted of patients of allergic rhinitis and Group 2 consisted of patients of bronchial asthma. RESULTS: Most of the patients in Group 1 were in the age group of 21–30 years (40%) and in Group 2, in the age group of 11–20 years (38%) with a mean age 28.4 ± 1.3 years. The most common symptoms in Group 1 patients were sneezing (90%) and rhinorrhea (68%) and in Group 2 wheezing (86%), followed by shortness of breath (66%). The most common sign in Group 1 was B/L inferior turbinate hypertrophy (70%), while in Group 2, it was rhonchi (76%). Mean absolute eosinophil count was 575.35 in Group 1 and was 446.61 in Group 2. Nasal smear for eosinophil was positive for 86% of patients in Group 1 and bronchial lavage showed eosinophilia in 64% of Group 2 patients. Mean total serum immunoglobulin E was 777.23 IU/ml in Group 1 and 662.08 IU/ml in Group 2. The incidence of bronchial asthma in patients of allergic rhinitis was 36%, while the incidence of allergic rhinitis in patients in bronchial asthma was 74%. CONCLUSION: Thus, in our study, we found that both the diseases were closely linked clinicopathologically epidemiologically as well as immunologically pointing toward the concept one-airway one disease.

Introduction: Tuberculosis (TB) remains a significant public health problem with an estimated onethird of the world’s population being infected. Cytokines play a major role in protection against Mycobacterium tuberculosis infection and regulate the immune responses at cellular level. Most studies on cytokines during TB are from ‘in vitro’-stimulated lymphoid cells with few reports on in vivo plasma levels. This study was aimed to evaluate the levels of TNF-α & IL4 in new, underOriginal Research Article Fatima et al.; BMRJ, 7(4): 159-166, 2015; Article no.BMRJ.2015.107 160 treatment (UT) and multidrug resistant (MDR) pulmonary and extra-pulmonary cases. Methodology: The study was conducted at the Department Of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India. Levels of TNF-α and IL-4 were measured in 76 serum samples from TB patients by ELISA kit (Diaclone France) along with 10 BCG vaccinated control. A complete clinical, radiological & treatment data was collected on questionnaire forms of each patients. Results: TNF-α levels were elevated in new (P 0.05). TNF-α and IL-4 levels showed no significant variations according to site of involvement in pulmonary vs. extra-pulmonary TB cases. Conclusion: An understanding of the development of this response may lead to insight into pathogenesis and novel therapies for TB.

Existing cancer therapies are often associated with drug resistance and toxicity, which results in poor prognosis and recurrence of cancer. This necessitates the identification and development of novel therapeutics against existing as well as novel cellular targets. In this study, a novel class of Benzocoumarin-Stilbene hybrid molecules were synthesized and evaluated for their antiproliferative activity against various cancer cell lines followed by in vivo antitumor activity in a mouse model of cancer. The most promising molecule among the series, i.e. compound (E)-4-(3,5-dimethoxystyryl)-2H-benzo[h]chromen-2-one (19) showed maximum antiproliferative activity in breast cancer cell lines (MDA-MB-231 and 4T1) and decreased the tumor size in the in-vivo 4T1 cell-induced orthotopic syngeneic mouse breast cancer model. The mechanistic studies of compound 19 by various biochemical, cell biology and biophysical approaches suggest that the compound binds to and inhibits the human DNA ligase I enzyme activity that might be the cause for significant reduction in tumor growth and may constitute a promising next-generation therapy against breast cancers.

Living organisms belonging to all three domains of life, viz., eubacteria, archaeabacteria, and eukaryotes encode one or more DNA ligases. DNA ligases are indispensable in various DNA repair and replication processes and a deficiency or an inhibition of their activity can lead to accumulation of DNA damage and strand breaks. DNA damage, specially strand breaks at unsustainable levels can lead to replication block and/or cell death. DNA ligases as potential anticancer targets have been realized only recently. There is enough rationale to suggest that ligases have a tremendous potential for novel therapeutics including anticancer and antibacterial therapy, specially when the world is facing acute problems of drug resistance and chemotherapy failure, with an immediate need for new therapeutic targets. Here, we review the current state of the art in the development of human ligase inhibitors, their structures, molecular mechanisms, physiological effects, and their potential in future cancer therapy. Citing examples, we focus on strategies for improving the activity and specificity of existing and novel inhibitors by using structure-based rational approaches. In the end, we describe potential new sites on the ligase I protein that can be targeted for the development of novel inhibitors. This is the first comprehensive review to compile all known human ligase inhibitors and to provide a rationale for the further development of ligase inhibitors for cancer therapy.

Purpose: To study the factors influencing sputum smear conversion including Serum C-Reactive Protein (CRP) and its correlation with disease severity in tuberculosis patients. Method: Levels of Serum-CRP concentrations were deter-mined in 60 patients with pulmonary tuberculosis, 30 healthy volunteers and patients in follow-up after completion of antitubercular treatment (DOTS therapy). Results: Serum-CRP levels were found to be significantly higher in smear-positive group as compared with the follow-up patients and smear-negative control group. The values were 43.65 ± 23.68, 9.88 ± 5.23 and 4.04 ± 3.85 mg/L respectively (P Conclusion: Serum-CRP levels are significantly correlated with disease severity in patients with active pulmonary tuberculosis. Thus these findings from the present study would certainly add new criteria for early diagnosis of TB, which may lead to development of new strategies to treat TB.

Context: Asthma is a chronic airway disorder which is associated to the inflammatory cells. Inflammatory and immune cells generate more reactive oxygen species in patients suffering from asthma which leads to tissue injury. Aims: To investigate the role of oxidant-antioxidant imbalance in disease progression of asthmatic patients. Settings and Design: In this study, 130 asthmatic patients and 70 healthy controls were documented. Methods: For this malondialdehyde level, total protein carbonyls, sulfhydryls, activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), total blood glutathione, and total antioxidant capacity (FRAP) were measured. Statistical Analysis Used: Analysis of the data was done using unpaired student t test and one-way ANOVA analysis. P < 0.05 was considered significant. Results: The present work showed that the systemic levels of MDA (4.19 ± 0.10 nmol/ml, P < 0.001) and protein carbonyls (1.13 ± 0.02 nmol/mg, P < 0.001) were found to be remarkably higher in asthmatic patients while protein sulfhydryls (0.55 ± 0.01 mmol/l, P < 0.05) decreased as compared to controls (2.84 ± 0.12 nmol/ml, 0.79 ± 0.02 nmol/mg and 0.60 ± 0.02 mmol/l, respectively). We also observed decrease in activities of SOD (2047 ± 50.34 U/g Hb, P < 0.05), catalase (4374 ± 67.98 U/g Hb, P < 0.01), and GPx (40.97 ± 1.05 U/g Hb, P < 0.01) in erythrocytes compared to control (2217 ± 60.11 U/g Hb, 4746 ± 89.94 U/g Hb, and 48.37 ± 2.47 U/g Hb, respectively). FRAP level (750.90 ± 21.22 ΅mol/l, P < 0.05) in plasma was decreased, whereas total blood glutathione increased (0.94 ± 0.02 mmol/l, P < 0.05) as seen in control (840.40 ± 28.39 ΅mol/l and 0.84 ± 0.04 mmol/l). Conclusions: This work supports and describes the hypothesis that an imbalance between oxidant-antioxidant is associated to the oxidative stress which plays a significant role in severity of the disease.

Human DNA ligase1 (hLig1) is the major replicative enzyme in proliferating mammalian cells that join Okazaki fragments of the lagging strand during DNA replication. Interruptions in the process of ligation cause DNA damage to accumulate, resulting in cytotoxicity and cell death. In the present study we demonstrate that pyrrolo[1,4] benzodiazepine (PBD) derivatives exhibit anticancer properties by targeting the nick sealing activity of hLig1 as opposed to the DNA interaction activity known for such compounds. Our in silico and in vitro assays demonstrate the binding of these molecules with amino acid residues present in the DNA binding domain (DBD) of the hLig1 enzyme. Two of these hLig1 inhibitors S010–015 and S010–018 demonstrated selective cytotoxicity against DLD-1 (colon cancer) and HepG2 (hepatic cancer) cells in a dose dependant manner. The molecules also reduced cell viability and colony formation at concentrations of ⩽20 μM in DLD-1 and HepG2 cells and induced apoptotic cell death. In yet another significant finding, the molecules reduced the migration of cancer cells in wound healing experiments, indicating their anti-metastatic property. In summary, we report the anticancer activity of PBD derivatives against DLD-1 and HepG2 cells and propose a new molecular target for their activity.

Myelomatous pleural effusion is a very rare presentation of multiple myeloma. A 65-year-old male patient presented to us with complaints of dyspnea and left-sided chest pain. His contrast enhanced computed tomography of the thorax showed left-sided pleural effusion with multiple pleural nodules. His pleural fluid cytology shows malignant plasma cells with eccentric nuclei and cart wheel chromatin and a few cells showing binucleation and multinucleation suggestive of plasma cell myeloma. His pleural fluid and serum electrophoresis showed a distinct band in the gamma globulin region (M-spike). On immunofixation of pleural fluid and serum, immunoglobulin G lambda light chain band was detected. Bone marrow aspiration showed sheets of malignant plasma cells with large and binucleated cells suggestive of multiple myeloma. The patient was diagnosed with multiple myeloma presenting as myelomatous pleural effusion. Intercostal tube drainage and then pleurodesis with talc was performed.

Light chain multiple myeloma occurs in 20% of multiple myeloma cases. Extramedullary dissemination of multiple myeloma is rare and involvement of pleura by it is even more rare. A 40 years old female patient presented with complains of recurrent vomiting for last 2 months and cough with expectoration for last 1 week. Chest X-Ray (PA view) showed a rounded homogenous opacity in mid zone of left lung field. CECT (thorax) showed pleura based soft tissue density mass lesions overlying apicoposterior segment of left upper lobe and lingular lobe with lytic destruction of underlying 2nd rib. Ultrasound scan of abdomen was normal. CT guided FNAC from soft tissue mass lesion of left side revealed atypical plasma cells, some of them were binucleate and few appear pleomorphic. Bone marrow aspiration showed 20% atypical plasma cells. Serum protein electrophoresis revealed a thin discrete band in gamma globulin region, while serum immunofixation electrophoresis showed presence of lambda light chain band only, with absence of kappa band, IgG band, IgM band and IgA band. Patient was diagnosed as a case of lambda light chain multiple myeloma with extramedullary dissemination to pleura presenting as pleural mass.

The chloroform extract of the culture filtrate of a Streptomyces sp. yielded a new antibacterial substance, the structure of which was elucidated as dehydroaltenusinic acid {1} by extensive analyses of its spectral data as well as by comparison with those of related compounds, dehydroaltenusin {2} and altenusin {3}. Compound 1 was found to exhibit significant inhibitory activity against a number of both Gram-positive and Gram-negative bacteria.

BACKGROUND It is well known that oxidant-antioxidant imbalance plays a key role in the pathophysiology of chronic obstructive pulmonary disease (COPD). OBJECTIVES To examine the role of altered levels of oxidant-antioxidants in disease severity of COPD and correlate it with the degree of airflow obstruction. METHODS We assessed malondialdehyde (MDA), total protein carbonyl and sulfhydryl levels in blood plasma and examined the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in erythrocytes. We also evaluated the level of total blood glutathione in whole blood and ferric ion reducing antioxidant power (FRAP) in plasma. RESULTS Levels of MDA (P < 0.001) and total protein carbonyls (P < 0.01) were significantly increased, while total protein sulfhydryl (P < 0.01) was decreased in COPD patients. We also observed decreased SOD (P < 0.05), GPx (P < 0.01) and catalase (P < 0.05) activity. FRAP (P < 0.001) in plasma was also decreased, whereas total blood glutathione was increased (P < 0.01). Correlations between oxidative stress and antioxidant markers with forced expiratory volume in 1 second (FEV1%) in COPD were negative with plasma TBARS and total blood glutathione, whereas a positive correlation was noticed with erythrocyte GPx and FRAP. CONCLUSION These results support the hypothesis that an oxidant-antioxidant imbalance, associated with oxidative stress in COPD patients, plays an important role in the progression of disease severity.

One hundred and sixty symptomatic confirmed human immunodeficiency virus (HIV)-positive patients, of both sexes with lower respiratory tract infection were taken as a study population, and the clinicomycological profile was correlated with the immunological status of the patients with particular reference to CD4 counts. Relevant samples were collected and subjected to direct microscopy, fungal culture and antigen detection.

Introduction: Mycobacterium tuberculosis (Mtb) infects one third of the world population. Despite advance in therapy, tuberculosis (TB) remains responsible for 2-3 million deaths annually. During TB, cytokines play a role in host defense. Many cytokines are produced during TB with a predominance of Th1 cytokines during the early stage and Th2 cytokines in the later stages of the infection. The present study aims to screen tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-12p70, IL-4, IL-6, and IL-1β among TB patients and controls. Materials and Methods: The study was conducted at the Department Of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India. Different cytokine levels were measured in 65 samples of TB patients of whom 30 (46.1%) were new TB cases and 35 (53.8%) were suspected multidrug-resistant (MDR)-TB cases along with 15 bacille Calmette-Guerin (BCG) vaccinated healthy controls by enzyme-linked immunosorbent assay (ELISA) (Diaclone, France). Complete clinical, radiological, and treatment data were collected. Informed consent was taken from all subjects. Study was approved by the Institutional Bioethical Committee, Jawahar Lal Nehru Medical College. Statistical analysis had been performed by using Sigma plot (10.0). Results: The serum concentration of TNF-α, IFN-γ, IL-12p 70 , IL-1β, and IL-6 in patients with active TB and MDR-TB was elevated than in patients after anti-TB treatment (P < 0.001), in contacts (P < 0.001) and in controls (P < 0.001). It was found that IL-6 seems critical in resistance to TB. IL-4 concentration increased only in MDR-TB patients (P < 0.001) as compared to controls. All these cytokines showed no significant variations according to the site of involvement in pulmonary versus extrapulmonary TB cases. Conclusions: Measuring the serum levels of several cytokines may be useful for evaluating the activity of TB disease and monitoring the clinical effects of anti-tubercular treatment (ATT). The serum TNF-α, IFN-γ, IL-12p 70 , IL-1β and IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients.

Hydatid cyst is a disease caused by a parasitic tapeworm, Echinococcus granulosus, and most commonly involves liver and lung. Ruptured pulmonary hydatid cyst can present a diagnostic challenge, and radiograph can be inconclusive. Anaphylactic reaction is a rare complication of ruptured pulmonary hydatid cyst. A 22-year-old male came to our emergency department in shock with symptoms of shortness of breath and altered mental status from the previous day. Radiograph showed a thin-walled circular translucent area in the right upper lung field, which was misdiagnosed as pneumothorax, and an intercostal chest tube was inserted. After 5 days, repeat radiograph revealed a cavity with an air/fluid level. The chest tube was removed and contrast-enhanced computed tomogram showed a cavity with water-lily sign, which suggests ruptured hydatid cyst. Immunoglobin-G enzyme-linked immunosorbent assay for Echinococcus was positive. The patient responded well to treatment with crystalloid infusion, supplemental oxygen, and albendazole, and then underwent surgery. Anaphylactic reaction due to rupture of a hydatid cyst is rare, but hydatid disease should be suspected in patients from areas where Echinococcus is endemic.

Slowly sedimenting antigen (SE) and the rapidly sedimenting antigen (RE), associated with envelope glycoprotein E were prepared from the concentrated infected culture fluids of Japanese encephalitis (JE) virus. Mice were immunized by each antigen before and after inactivation of virus infectivity by ultraviolet (UV) irradiation. The immunogenicity of the antigens determined by the plaque reduction neutralization test (PRNT), indirect ELISA and hemagglutination-inhibition (HI) test, indicated that SE was almost equally immunogenic as RE, and that the PRNT epitopes on both antigens were more immunogenic before UV -inactivation than after the inactivation., 日本熱帯医学会雑誌, vol.19(4), pp.321-330; 1991

Introduction: Tuberculosis (TB) remains a significant public health problem, with an estimated one-third of the world's population being infected. Cytokines play a major role in protection against Mycobacterium tuberculosis ( M. tuberculosis ) infection and regulate the immune responses at a cellular level. Most studies on cytokines during TB are from in vitro -stimulated lymphoid cells with few reports on in vivo plasma levels. The aim of this study was to evaluate the levels of tumor necrosis factor-α (TNF-α) in new, undertreatment (UT), and multidrug-resistant (MDR) pulmonary and extrapulmonary cases. Materials and Methods: The study was conducted in the Department of Microbiology, Jawaharlal Nehru Medical College (J.N.M.C.), Aligarh Muslim University (A.M.U.), Aligarh, Uttar Pradesh, India. Results: The levels of TNF-α were measured in 76 serum samples from TB patients by an enzyme linked immunosorbent assay (ELISA) kit (Diaclone Sas, 1 BD, A Flemming Besancon Cedax, France), along with 10 healthy controls. Complete clinical, radiological and treatment data were collected. The TNF-α levels were elevated in new cases ( P P P > 0.05). Conclusions: An understanding of this response may lead to an insight into the pathogenesis and novel therapies for TB.

Mycobacterium tuberculosis (Mtb) infects approximately one third of world population. Many cytokines are produced during tuberculosis, with predominance of Th1 cytokines during the early stage and Th2 cytokines in the later stages of the infection. Most studies on cytokines during TB are from ‘in vitro’-stimulated lymphoid cells with few reports on in vivo plasma levels. The high expression of IL-4 has been implicated as a virulence factor. In the present study we examined the level of IL-4 in the serum of active tuberculosis in new cases, during anti-tubercular therapy and MDR cases. This Study was conducted at Department Of Microbiology, JNMC, AMU, Aligarh. A total 76 blood samples of Pulmonary & Extra-Pulmonary tuberculosis patients were tested by ELISA (Diaclone France) along with 10 healthy controls. The test was carried out according to the manufacturer instructions. O.D. was taken at 450 nm. There was no stastical difference in age and sex in our study. The level of IL-4 show significant changes in MDR TB cases (P 0.05). An understanding of the development of the cellular immune response may lead to insight into pathogenesis and novel therapies for TB. Further studies are needed to address the role of cytokines in immunity to TB under natural conditions.

BACKGROUND AND PURPOSE: The effects of nicotine on cerebral metabolism and its influence on smoking behavior is poorly understood. An understanding of the chronic effects of nicotine on excitatory and inhibitory metabolic demand, and corresponding neurotransmission may provide clues for designing strategies for the optimal smoking cessation intervention. The objective of the current study was to investigate neuronal and astroglial metabolism in mice exposed to nicotine (0.5 and 2.0 mg/kg, s.c.) three times in a day for 4 weeks. EXPERIMENTAL APPROACH/PRINCIPAL FINDINGS: Metabolic measurements were carried out by co-infusing [U-(13)C(6)]glucose and [2-(13)C]acetate, and monitoring (13)C labeling of amino acids in brain tissue extract using (1)H-[(13)C] and (13)C-[(1)H]-NMR spectroscopy. Concentration of (13)C-labeled glutamate-C4 was increased significantly from glucose and acetate with chronic nicotine treatment indicating an increase in glucose oxidation by glutamatergic neurons in all brain regions and glutamate-glutamine neurotransmitter cycle in cortical and subcortical regions. However, chronic nicotine treatment led to increased labeling of GABA-C2 from glucose only in the cortical region. Further, increased labeling of glutamine-C4 from [2-(13)C]acetate is suggestive of increased astroglial activity in subcortical and cerebellum regions of brain with chronic nicotine treatment. CONCLUSIONS AND SIGNIFICANCE: Chronic nicotine exposure enhanced excitatory activity in the majority of brain regions while inhibitory and astroglial functions were enhanced only in selected brain regions.