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Arvind Kumar

Publications and source records attributed to Arvind Kumar.

At least 19 recordsLinked to original sources
PubMed2026

In-Silico and Functional Characterization of EcdLp, an ABC Transporter of Aspergillus nidulans NRRL11440.

Echinocandin B (ECB) biosynthesis in Aspergillus nidulans is primarily governed by multiple genes located within the biosynthetic echinocandin (ecd) gene cluster. The contributory functions of many genes, including transcription factors and tailoring enzymes of the ecd gene cluster, have been previously studied. The present study focused on determining the role of transporter proteins, EcdLp, EcdCp, and EcdDp, in ECB efflux using in silico and biochemical approaches. The molecular docking analysis revealed that ECB relatively showed higher binding affinity for EcdLp than the other co-clustered MFS transporters EcdCp and EcdDp, suggesting a preferred substrate of EcdLp. These results were further confirmed by heterologous integration of the ecdL gene in the ABC transporters-deficient Saccharomyces cerevisiae AD1-8u⁻, confirming active efflux. However, the binding of ECB in EcdLp is distinct from the R6G binding, overlapping the promiscuous site of farnesol, resulting in inhibition of R6G efflux in a dose-dependent manner. In conclusion, these results decipher the ECB binding and efflux mechanism and unveil the evolutionarily specialized architecture of EcdLp that permits targeted metabolite export in addition to environmental responsiveness, and lay the groundwork for optimizing ECB production via transporter engineering.

Aspergillus nidulans↗
PubMed2006

IRS2-Akt pathway in midbrain dopamine neurons regulates behavioral and cellular responses to opiates.

Chronic morphine administration (via subcutaneous pellet) decreases the size of dopamine neurons in the ventral tegmental area (VTA), a key reward region in the brain, yet the molecular basis and functional consequences of this effect are unknown. In this study, we used viral-mediated gene transfer in rat to show that chronic morphine-induced downregulation of the insulin receptor substrate 2 (IRS2)-thymoma viral proto-oncogene (Akt) signaling pathway in the VTA mediates the decrease in dopamine cell size seen after morphine exposure and that this downregulation diminishes morphine reward, as measured by conditioned place preference. We further show that the reduction in size of VTA dopamine neurons persists up to 2 weeks after morphine withdrawal, which parallels the tolerance to morphine's rewarding effects caused by previous chronic morphine exposure. These findings directly implicate the IRS2-Akt signaling pathway as a critical regulator of dopamine cell morphology and opiate reward.

Animals↗
PubMed2006

Uranium, radium and radon measurements in the environs of Nurpur area, Himachal Himalayas, India.

LR-115 plastic track detectors have been used for the measurement of radon exhalation rate and radium concentration in soil and rock samples from Nurpur and its adjoining areas of Kangra district, Himachal Pradesh, India. Uranium concentration is also determined in these samples using fission track technique. The work is undertaken to explore the possibility of uranium prospection and health risk assessments due to uranium and radium in the study area. A positive correlation has been observed between uranium and radon exhalation rate in soil and rocks.

India↗
PubMed2006

Preparation and characterization of N-methylene phosphonic and quaternized chitosan composite membranes for electrolyte separations.

Chitosan was functionalized either by introducing a phosphonic acid group or by quaternization of existing primary ammonium groups in order to make it a water-soluble material. Functionalized chitosans and poly(vinyl alcohol) (PVA)-based nanoporous charged membranes were prepared in aqueous media and gelated in methanol at 10 degrees C to tailor their pore structure. These membranes were extensively characterized for their physicochemical, electrochemical, and permeation characteristics using FTIR, TGA, DSC, water content, ion-exchange capacity, ionic transport properties, and membrane permeability studies. N-Methylene phosphonic chitosan (NMPC)/PVA-based membranes exhibited mild cation selectivity and quaternized chitosan (QC)/PVA composite membranes had mild anion selectivity, while a blend of NMPC-QC/PVA membranes exhibited weak cation selectivity because of formation of zwitterionic structure. Viscosity measurements and interaction studies for individual and mixed solutions of NMPC and QC were carried out for the prediction of charge interactions between -PO3H2 and -N+(CH3)3 groups and effect on molecular weight due to functionalization. Elaborate electrochemical and permeation experiments were conducted in order to predict suitability of these membranes for the separation of mono- and bivalent electrolytes based on their hydrated ionic radius, and it was found that among all the synthesized membranes, PC/QC-30 had the highest relative permeability, which may extend its suitability for electrolyte separations. Observations were correlated with equivalent pore radius of the different membranes as estimated by membrane permeability measurements.

Calorimetry, Differential Scanning↗
PubMed2006

Induction of inducible cAMP early repressor expression in nucleus accumbens by stress or amphetamine increases behavioral responses to emotional stimuli.

Previous research has shown that cAMP response element (CRE)-mediated transcription is activated in the nucleus accumbens, a major brain reward region, by a variety of environmental stimuli and contributes to neuroadaptations to these stimuli. CRE-binding protein (CREB) is the most studied activator of CRE transcription and has been implicated in this brain region as a gating mechanism for behavioral responses to emotional stimuli. Little attention, however, has been given to naturally occurring inhibitors of CRE-mediated transcription, such as the inducible cAMP early repressor (ICER), an inhibitory product of the CRE modulator gene. In the present study, we investigated the extent to which ICER is induced in the nucleus accumbens by two types of environmental stimuli, stress and amphetamine, and characterized how induction of ICER in this region affects complex behavior. We show that stress and amphetamine each induces ICER expression and that overexpression of ICER in the nucleus accumbens, using viral-mediated gene transfer, increases behavioral responses to both rewarding and aversive emotional stimuli. For example, ICER overexpression increases sensitivity to amphetamine-stimulated locomotor activity as well as to natural rewards such as sucrose and social grooming. However, ICER overexpression also increases measures of anxiety in the elevated plus maze and neophobia to novel tastes. Finally, ICER produces an antidepressant-like effect in the forced swim test, further indication of an enhanced active response to stress. These results suggest that ICER is an important mechanism for modulating CRE-mediated transcription in the nucleus accumbens.

Amphetamine↗
PubMed2006

Trypanocidal activity of the phenyl-substituted analogue of furamidine DB569 against Trypanosoma cruzi infection in vivo.

OBJECTIVES: Aromatic diamidines have been successfully used to combat a wide range of parasites that cause important human infections. One such compound is furamidine (DB75) and we recently reported that one of its analogues, an N-phenyl analogue (DB569), exhibits higher trypanocidal dose and time-dependent effects against different forms of Trypanosoma cruzi as compared with DB75. Our present aim was to investigate the efficacy of DB569 in a T. cruzi mouse model. METHODS: The trypanocidal activity of the compound was evaluated by clinical, parasitological, histopathological and biochemical investigations. RESULTS: Treatment with DB569 significantly reduced cardiac parasitism, partially increased the survival rates of mice and lowered the levels of alanine aminotransferase and creatinine indicating a protective role against renal and hepatic lesions caused by the parasite infection. CONCLUSIONS: Altogether, the data support the potential effect of this class of compounds against T. cruzi and motivate the screening of new diamidines for efficacy against Chagas' disease.

Alanine Transaminase↗
PubMed2006

Intravenous immunoglobulin: striving for appropriate use.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the mainstay therapy in human immune deficiency states characterized by qualitative and quantitative reductions in B cells. In addition, however, there is widespread use of IVIG in a number of other areas, including neuroimmunologic, infectious, dermatologic, hematologic, autoimmune, inflammatory and idiopathic disorders. In many of these cases, there are little objective data to support the use. METHODS: We performed a review of more than 400 publications in PubMed using the key words 'intravenous immunoglobulin' and excluded publications that focused on immune deficiency, for which the indication for IVIG is already clear. RESULTS: For a number of off-label indications, there is significant evidence of efficacy and IVIG has become the standard of care for many clinical syndromes other than immune deficiency. In some conditions, however, the data have not been well controlled or randomized and are often limited to case reports that are difficult to interpret. Although the critical shortage of IVIG of the last decade is no longer an issue, IVIG is expensive and not without risk. The use of IVIG should be based not only on clinical data, but also, and especially, on the biological rationale for its use. CONCLUSIONS: The appropriate use of IVIG is an important issue that is difficult to resolve, and will continue to challenge clinicians based on expense and potentially limited supply, including the intrinsic limitations of donor plasma. The establishment of national and international voluntary registries to report use of IVIG in disorders for which evidence is lacking would be a first step toward facilitating randomized, controlled clinical trials.

Autoimmune Diseases of the Nervous System↗
PubMed2006

Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action.

To better understand the molecular mechanisms of depression and antidepressant action, we administered chronic social defeat stress followed by chronic imipramine (a tricyclic antidepressant) to mice and studied adaptations at the levels of gene expression and chromatin remodeling of five brain-derived neurotrophic factor (Bdnf) splice variant mRNAs (I-V) and their unique promoters in the hippocampus. Defeat stress induced lasting downregulation of Bdnf transcripts III and IV and robustly increased repressive histone methylation at their corresponding promoters. Chronic imipramine reversed this downregulation and increased histone acetylation at these promoters. This hyperacetylation by chronic imipramine was associated with a selective downregulation of histone deacetylase (Hdac) 5. Furthermore, viral-mediated HDAC5 overexpression in the hippocampus blocked imipramine's ability to reverse depression-like behavior. These experiments underscore an important role for histone remodeling in the pathophysiology and treatment of depression and highlight the therapeutic potential for histone methylation and deacetylation inhibitors in depression.

Acetylation↗
PubMed2006

An essential role for DeltaFosB in the nucleus accumbens in morphine action.

The transcription factor DeltaFosB is induced in the nucleus accumbens (NAc) and dorsal striatum by the repeated administration of drugs of abuse. Here, we investigated the role of DeltaFosB in the NAc in behavioral responses to opiates. We achieved overexpression of DeltaFosB by using a bitransgenic mouse line that inducibly expresses the protein in the NAc and dorsal striatum and by using viral-mediated gene transfer to specifically express the protein in the NAc. DeltaFosB overexpression in the NAc increased the sensitivity of the mice to the rewarding effects of morphine and led to exacerbated physical dependence, but also reduced their sensitivity to the analgesic effects of morphine and led to faster development of analgesic tolerance. The opioid peptide dynorphin seemed to be one target through which DeltaFosB produced this behavioral phenotype. Together, these experiments demonstrated that DeltaFosB in the NAc, partly through the repression of dynorphin expression, mediates several major features of opiate addiction.

Animals↗
PubMed2006

Liver abscess in children.

Liver abscesses are frequently observed in pediatric clinical practice in tropics and subtropics especially in developing countries. Children have unique set of predisposing factors which have been highlighted. Expected microbiology and setting for unusual organisms are mentioned. Clinical presentations', including importance of location and number of abscesses has been discussed. Role of each modality of treatment clarified. Importance and limitations of investigations and imaging explained and complications and mortality discussed.

Child↗
PubMed2006

Revision facial nerve surgery.

Transection of the facial nerve can result from blunt or penetrating trauma to the face or temporal bone. It can also occur accidentally during surgery, or as a planned surgical procedure carried out in the interest of eradicating disease. If transection is recognized at surgery, direct anastomosis or cable grafting is the procedure of choice. This article presents two cases with neither clinical nor electrical evidence of recovery. The authors review current understanding of the changes that occur in the neuron, axon, and muscle after injury to the nerve and the underlying pathology that led to graft failure in these cases. They also evaluate surgical options and diagnostic test results that help in selecting appropriate surgical procedures.

Cranial Nerve Neoplasms↗
PubMed2006

Should ossicular reconstruction be staged following tympanomastoidectomy.

OBJECTIVES: To determine whether ossicular reconstruction (OCR) performed concurrent with tympanomastoidectomy for cholesteatoma results in significantly different hearing results when compared to OCR performed in a separate, staged procedure. STUDY DESIGN: Retrospective. MATERIALS AND METHODS: Study subjects were patients undergoing OCR within a 2-year period. Intervention was OCR concurrent with tympanomastoidectomy for cholesteatoma (group 1) or staged following tympanomastoidectomy for cholesteatoma (group 2). Main outcome measures were mean postoperative air-bone gap (ABG), proportion achieving ABG closure to <20 dB and <30 dB for group 1 and group 2 overall and when controlling for type of mastoid cavity created (open or closed) and the status of the stapes suprastructure (TORP vs. PORP OCR). RESULTS: Eighty-three patients were identified. Forty underwent OCR concurrent with tympanomastoidectomy and 43 underwent a staged OCR after tympanomastoidectomy. Overall, similar hearing results were seen in the two groups. When considering the status of the stapes and mastoid cavity, concurrent OCR resulted in improved mean postoperative ABG in a closed mastoid cavity with an intact stapes suprastructure (P = .024). Furthermore, a greater proportion of patients who had concurrent OCR within this group achieved ABG <20 dB and ABG <30 dB, although this difference did not reach statistical significance (P = .092 and P = .078, respectively). By contrast, staged OCR resulted in improved mean postoperative ABG and ABG <30 dB in open mastoid cavities with an absent stapes suprastructure (P = .040, and P = .019, respectively). Similarly, a greater proportion achieved ABG <20 dB, approaching statistical significance (P = .055). CONCLUSIONS: Staged OCR is advantageous in those with most severe disease, whereas those with least severe disease may benefit from a concurrent OCR.

Adolescent↗
PubMed2006

Does co-infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children?

BACKGROUND: This study looked at the frequency of co-infection with multiple hepatotropic viruses and the effect of such infection on the course and outcome of acute sporadic viral hepatitis (AVH) and fulminant hepatic failure (FHF) in children. METHODS: Consecutive children up to 15 years of age presenting with AVH or FHF between January 1998 and July 2002 were evaluated prospectively. The following viral markers were assessed in all children: immunoglobulin M (IgM) anti-hepatitis A virus (HAV), IgM anti-hepatitis E virus (HEV), hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core (HBc), and anti-hepatitis C virus (HCV). RESULTS: A total of 149 children were included in the study, 122 with AVH and 27 with FHF. Co-infection with multiple viruses was detected in 30 (24.6%) AVH patients (A+E in 24, A+B in three, and E+B, A+C and A+E+B in one each) and seven (26%) FHF patients (A+E in five, and A+B and E+B in one each). The majority of single infections were due to HAV (AVH 70/92, FHF 14/20) followed by HEV (AVH 9/92, and FHF 5/20). HEV infection was associated with infection with another agent in 88% of patients with AVH (odds ratio 53, 95% confidence interval 15-186, P<0.0001). Frequency of anicteric state, prolonged cholestasis, relapsing hepatitis, ascites, hemolysis and mortality rates were similar in the single and multiple infection groups for both AVH and FHF patients. CONCLUSIONS: Co-infection with multiple viruses is observed in one-quarter of patients with sporadic AVH in childhood. Such infection does not produce a more severe disease. HEV positivity is a strong marker for multiple infections.

Adolescent↗
PubMed2006

Eosinophilic gastroenteritis and citrus-induced urticaria.

The immunological basis of eosinophilic gastroenteritis (EGE) is an interesting contrast between the enigma of urticaria and the increasing usage of molecular technology in clinical allergy. Little is known about the natural history of EGE. It has been known to spontaneously remit, but the typical course, especially in adults, is one of chronic and intermittent disease. Given the often chronic nature of this disease, it is important to use relatively benign treatments initially and limit the use of systemic corticosteroids. Also, given the fact that eosinophilic infiltration of the gastrointestinal tract may also be a manifestation of other potentially dangerous disease processes, such as malignancy or hypereosinophilic syndrome, which may be initially diagnosed as EGE, routine surveillance of the cardiopulmonary and gastrointestinal systems is important. We present a patient who demonstrates the variability of presentation and treatment response in this multifaceted disease. The fact that he has apparently entered remission also makes his an uncommon presentation of EGE.

Citrus paradisi↗
PubMed2005

Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum.

Given that cocaine induces neuroadaptations through regulation of gene expression, we investigated whether chromatin remodeling at specific gene promoters may be a key mechanism. We show that cocaine induces specific histone modifications at different gene promoters in striatum, a major neural substrate for cocaine's behavioral effects. At the cFos promoter, H4 hyperacetylation is seen within 30 min of a single cocaine injection, whereas no histone modifications were seen with chronic cocaine, consistent with cocaine's ability to induce cFos acutely, but not chronically. In contrast, at the BDNF and Cdk5 promoters, genes that are induced by chronic, but not acute, cocaine, H3 hyperacetylation was observed with chronic cocaine only. DeltaFosB, a cocaine-induced transcription factor, appears to mediate this regulation of the Cdk5 gene. Furthermore, modulating histone deacetylase activity alters locomotor and rewarding responses to cocaine. Thus, chromatin remodeling is an important regulatory mechanism underlying cocaine-induced neural and behavioral plasticity.

Acetylation↗