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1.  Thrombosed prosthetic mitral valve 
BMJ Case Reports  2012;2012:bcr1020115002.
doi:10.1136/bcr.10.2011.5002
PMCID: PMC3316824  PMID: 22605815
2.  Reconstruction of the chin using an expanded deltopectoral flap following multiple recurrences of oral cancer 
An important alternative to free tissue transfer in patients requiring correction of soft tissue chin defects are local and regional flaps, such as the pectoralis major myocutaneous flap and deltopectoral flap. With predictable vascular supply, potential for large size, and good aesthetic match for facial and cervical skin, the deltopectoral flap can offer the reconstructive surgeon additional options in patients who lack vessels suitable for free tissue transfer. The use of an expanded deltopectoral flap for a staged reconstruction of the chin in a patient with cancer recurrences, concomitant resections, radiation and multiple reconstructions is reported.
PMCID: PMC3433825  PMID: 23997595
Chin reconstruction; Deltopectoral
3.  Giant lipomas of the upper extremity: Case reports and a literature review 
Giant fibrolipomas involving the upper extremities are rare tumours. These large masses grow slowly and produce symptoms due to their size, location and compression of adjacent structures. Surgical excision usually leads to complete recovery from symptoms.
PMCID: PMC3433826  PMID: 23997596
Giant lipoma
4.  Intraneural lipoma of the ulnar nerve at the elbow: A case report and literature review 
Intraneural lipomas of the ulnar nerve or its branches are rare benign tumours. Although most intraneural lipomas present as asymptomatic tumours, some may present as compression neuropathies due to their location. In the majority of cases these tumours can be enucleated without damage to the nerve fibres.
PMCID: PMC3433827  PMID: 23997597
Intraneural lipoma; Ulnar nerve
5.  Acute carpal tunnel syndrome from burns of the hand and wrist 
Acute median nerve compression usually occurs from increased pressure within the carpal tunnel and forearm compartments. Although the hyperesthesia from burns may mimic symptoms of acute compression neuropathy, clinical diagnosis should be made from history, clinical signs and symptoms. Early recognition and decompression of the carpal tunnel either as part of the burn excision or along with escharotomy usually leads to full recovery.
PMCID: PMC2827286  PMID: 21119830
Burns of hands and wrist; Median nerve compression neuropathy
6.  Intraneural lipoma of the radial nerve presenting as Wartenberg syndrome: A case report and review of literature 
The superficial branch of the radial nerve is highly vulnerable to trauma, irritation and compression due to its anatomical location. Intraneural lipomas and fibrolipomas arising from the supporting tissues of this peripheral nerve can cause compression of the adjacent nerve leading to symptoms of neuritis of the radial nerve or Wartenberg syndrome.
PMCID: PMC2827289  PMID: 21119833
Intraneural lipoma; Wartenberg syndrome
7.  Faecal bifidobacteria in Indian neonates & the effect of asymptomatic rotavirus infection during the first month of life 
Background & Objectives:
Bifidobacteria colonize the gut after the first week of life and remain an important component of the gut microbiota in infancy. This study was carried out to characterize the diversity and number of bifidobacteria colonizing the gut in Indian neonates and to investigate whether asymptomatic infection with rotavirus in the first month of life affected gut colonization by bidifobacteria.
Methods:
DNA was isolated from faeces of 14 term-born neonates who were under surveillance for rotavirus infection. Bacterial and bifidobacterial diversity was evaluated by temporal temperature gradient electrophoresis (TTGE) of 16S rDNA amplified using total bacteria and bifidobacteria-specific primers. Real time PCR, targeting 16S rDNA, was used to quantitate faecal bifidobacteria and enterobacteria.
Results:
TTGE of conserved bacterial 16S rDNA showed 3 dominant bands of which Escherichia coli (family Enterobacteriaceae) and Bifidobacterium (family Bifidobacteriaceae) were constant. TTGE of Bifidobacterium genus-specific DNA showed a single band in all neonates identified by sequencing as Bifidobacterium longum subsp. infantis. Faecal bifidobacterial counts (log10 cfu/g faeces) ranged from 6.1 to 9.3 and enterobacterial counts from 6.3 to 9.5. Neonates without and with rotavirus infection in the first week of life did not show significant differences in the median count of bifidobacteria (log10 count 7.48 vs. 7.41) or enterobacteria (log10 count 8.79 vs. 7.92).
Interpretation & Conclusions:
B. longum subsp. infantis was the sole bifidobacterial species colonizing the gut of Indian neonates. Asymptomatic rotavirus infection in the first month of life was not associated with alteration in faecal bifidobacteria or enterobacteria.
PMCID: PMC3102461  PMID: 21245621
Bifidobacterium; colonization; gut; neonates; rotavirus
8.  Reconstruction of sacral defects following necrosis of buttocks due to embolization of internal iliac artery using a transverse lumbar flap 
Fractures of the pelvis associated with uncontrollable hypotension are managed by stabilization of fractures and arteriographic embolization of the bleeding vessels. Embolization of these arteries may result in necrosis of the buttocks. The use of a transverse lumbar artery-based flap can be used for repair of these defects.
PMCID: PMC2740608  PMID: 20808748
Transverse lumbar flap
9.  Reversed dorsal metatarsal artery flap for reconstruction of a soft tissue defect of the big toe 
Soft tissue defects of the great toe that include exposed tendon and bone present a reconstructive challenge for plastic surgeons. A distally based dorsalis pedis island flap based on the first dorsal metatarsal artery, which has been successfully used to cover the soft tissue defect following wide excision of melanoma of the big toe, is reported
PMCID: PMC2740609  PMID: 20808742
Dorsal metatarsal artery flap
10.  Acute carpal tunnel syndrome as a result of spontaneous bleeding 
Acute carpal tunnel syndrome is the most common compression neuropathy of the upper extremity following trauma. A rare occurence of spontaneous bleeding into the carpal tunnel, presenting as acute carpal tunnel syndrome, is presented.
PMCID: PMC2691013  PMID: 19721797
Carpal tunnel syndrome; Spontaneous bleeding
11.  Biodistribution of Fluorescently Labeled PAMAM Dendrimers in Neonatal Rabbits: Effect of Neuroinflammation 
Molecular pharmaceutics  2013;10(12):4560-4571.
Dendrimers are being explored in many preclinical studies as drug, gene, and imaging agent delivery systems. Understanding their detailed organ, tissue, cellular uptake, and retention can provide valuable insights into their effectiveness as delivery vehicles and the associated toxicity. This work explores a fluorescence-quantification based assay that enables simultaneous quantitative biodistribution and imaging of dendrimers with a single agent. We have labeled an ethylenediamine-core generation-4 hydroxyl-terminated poly(amidoamine) (PAMAM) dendrimer using the fluorescent photostable, near-IR cyanine dye (Cy5) and performed quantitative and qualitative biodistribution of the dendrimer-Cy5 conjugates (D-Cy5) in healthy neonatal rabbits and neonatal rabbits with cerebral palsy (CP). The biodistribution of D-Cy5 and free Cy5 dye was evaluated in newborn rabbits, based on the developed quantification methods using fluorescence spectroscopy, high-performance liquid chromatography (HPLC), and size exclusion chromatography (SEC) and supported by microscopic imaging. The uptake was assessed in the brain, heart, liver, lungs, kidneys, blood serum, and urine. Results obtained based on these three independent methods are in good agreement and indicate the fast renal clearance of D-Cy5 and free Cy5 with relatively higher organs accumulation of the D-Cy5 conjugate. Following systemic administration, the D-Cy5 mainly accumulated in kidneys and bladder at 24 h. The quantitative biodistribution is in good agreement with previous studies based on radiolabeling. These methods for dendrimers quantification are easier and more practical, provide excellent sensitivity (reaching 0.1 ng per gram of tissue), and allow for quantification of dendrimers in different organs over longer time periods without concerns for radioactive decay, while also enabling tissue and cellular imaging in the same animal. In kits with fetal-neuroinflammation induced CP, there was a significantly higher uptake of D-Cy5 in the brain, while biodistribution in other organs was similar to that of healthy kits.
doi:10.1021/mp400371r
PMCID: PMC3977004  PMID: 24116950
PAMAM dendrimer; biodistribution; brain uptake quantification; cellular imaging; pharmacokinetics; neuroinflammation; cerebral palsy
12.  Inducing Humoral and Cellular Responses to Multiple Sporozoite and Liver-Stage Malaria Antigens Using Exogenous Plasmid DNA 
Infection and Immunity  2013;81(10):3709-3720.
A vaccine candidate that elicits humoral and cellular responses to multiple sporozoite and liver-stage antigens may be able to confer protection against Plasmodium falciparum malaria; however, a technology for formulating and delivering such a vaccine has remained elusive. Here, we report the preclinical assessment of an optimized DNA vaccine approach that targets four P. falciparum antigens: circumsporozoite protein (CSP), liver stage antigen 1 (LSA1), thrombospondin-related anonymous protein (TRAP), and cell-traversal protein for ookinetes and sporozoites (CelTOS). Synthetic DNA sequences were designed for each antigen with modifications to improve expression and were delivered using in vivo electroporation (EP). Immunogenicity was evaluated in mice and nonhuman primates (NHPs) and assessed by enzyme-linked immunosorbent assay (ELISA), gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay, and flow cytometry. In mice, DNA with EP delivery induced antigen-specific IFN-γ production, as measured by ELISpot assay and IgG seroconversion against all antigens. Sustained production of IFN-γ, interleukin-2, and tumor necrosis factor alpha was elicited in both the CD4+ and CD8+ T cell compartments. Furthermore, hepatic CD8+ lymphocytes produced LSA1-specific IFN-γ. The immune responses conferred to mice by this approach translated to the NHP model, which showed cellular responses by ELISpot assay and intracellular cytokine staining. Notably, antigen-specific CD8+ granzyme B+ T cells were observed in NHPs. Collectively, the data demonstrate that delivery of gene sequences by DNA/EP encoding malaria parasite antigens is immunogenic in animal models and can harness both the humoral and cellular arms of the immune system.
doi:10.1128/IAI.00180-13
PMCID: PMC3811783  PMID: 23897618
13.  Purification, characterization and production optimization of a vibriocin produced by mangrove associated Vibrio parahaemolyticus 
Objective
To identify a potential bacterium which produces antimicrobial peptide (vibriocin), and its purification, characterization and production optimization. The bacteria subjected in the study were isolated from a highly competitive ecological niche of mangrove ecosystem.
Methods
The bacterium was characterized by phenotype besides 16S rRNA gene sequence analysis. The antibacterial activity was recognised by using agar well diffusion method. The vibriocin was purified using ammonium sulphate precipitation, butanol extraction, gel filtration chromatography, ion-exchange chromatography and subsequently, by HPLC. Molecular weight of the substance identified in SDS-PAGE. Production optimization performed according to Taguchi's mathematical model using 6 different nutritional parameters as variables.
Results
The objective bacterium was identified as Vibrio parahaemolyticus. The vibriocin showed 18 KDa of molecular mass with mono peptide in nature and highest activity against pathogenic Vibrio harveyi. The peptide act stable in a wide range of pH, temperature, UV radiation, solvents and chemicals utilized. An overall ∼20% of vibriocin production was improved, and was noticed that NaCl and agitation speed played a vital role in secretion of vibriocin.
Conclusion
The vibriocin identified here would be an effective alternative for chemically synthesized drugs for the management of Vibrio infections in mariculture industry.
doi:10.12980/APJTB.4.2014C947
PMCID: PMC3929786
Vibriocin; Vibrio parahaemolyticus; Vibrio harveyi; Mangrove rhizosphere; Antimicrobial peptide
14.  Clinical study to know the efficacy of Amlexanox 5% with other topical Antiseptic, Analgesic and Anesthetic agents in treating minor RAS 
Background: To evaluate the efficacy of topical antiinflammatory agent (amlexanox 5%), along with topical antiseptic, analgesic, and anesthetic agent (benzalkonium chloride 0.01%, choline salicylate 8.7% and lidocaine hydrochloride 2%), in promoting ulcer healing, decreasing ulcer size, erythema, pain and recurrence in minor RAS.
Materials & Methods: A randomized control trial was conducted on 100 patients of RAS who fulfilled the inclusion criteria. The number, size, erythema and pain with the ulcer were recorded. Visual analogue scale (VAS) and erythema scale were used to record pain and erythema. 50 patients comprising the study group received anti inflammatory paste (amlexanox 5%) applied four times daily and the control group of 50 patients received topical antiseptic, analgesic, and anesthetic agent (benzalkonium chloride 0.01%, choline salicylate 8.7% and lidocaine hydrochloride 2%) paste, patients were evaluated after 3rd, 6th, 9th and on 30th, 60th day for recurrence.
Results: The study group had reduction in ulcer number, size; erythema, pain and frequency of ulcers during follow up. The healing period and recurrence of ulceration reduced in both the groups but the study group had significant reduction in 30th and 60th day follow up for recurrence of ulcers.
Conclusion: Amlexanox 5% can reduce the frequency, duration and symptoms associated with the aphthous ulcers with no sideeffects attributed to the drug.
How to cite the article: Darshan DD, Kumar CN, Kumar AD, Manikantan NS, Balakrishnan D, Uthkal MP. Clinical study to know the efficacy of Amlexanox 5% with other topical Antiseptic, Analgesic and Anesthetic agents in treating minor RAS. J Int Oral Health 2014;6(1);5-11.
PMCID: PMC3959130  PMID: 24653596
Amlexanox; recurrent aphthous stomatitis (RAS); visual analogue scale (VAS)
15.  Wnt11 Is Required for Oriented Migration of Dermogenic Progenitor Cells from the Dorsomedial Lip of the Avian Dermomyotome 
PLoS ONE  2014;9(3):e92679.
The embryonic origin of the dermis in vertebrates can be traced back to the dermomyotome of the somites, the lateral plate mesoderm and the neural crest. The dermal precursors directly overlying the neural tube display a unique dense arrangement and are the first to induce skin appendage formation in vertebrate embryos. These dermal precursor cells have been shown to derive from the dorsomedial lip of the dermomyotome (DML). Based on its expression pattern in the DML, Wnt11 is a candidate regulator of dorsal dermis formation. Using EGFP-based cell labelling and time-lapse imaging, we show that the Wnt11 expressing DML is the source of the dense dorsal dermis. Loss-of-function studies in chicken embryos show that Wnt11 is indeed essential for the formation of dense dermis competent to support cutaneous appendage formation. Our findings show that dermogenic progenitors cannot leave the DML to form dense dorsal dermis following Wnt11 silencing. No alterations were noticeable in the patterning or in the epithelial state of the dermomyotome including the DML. Furthermore, we show that Wnt11 expression is regulated in a manner similar to the previously described early dermal marker cDermo-1. The analysis of Wnt11 mutant mice exhibits an underdeveloped dorsal dermis and strongly supports our gene silencing data in chicken embryos. We conclude that Wnt11 is required for dense dermis and subsequent cutaneous appendage formation, by influencing the cell fate decision of the cells in the DML.
doi:10.1371/journal.pone.0092679
PMCID: PMC3966816  PMID: 24671096
16.  Serological and molecular prevalence of selected canine vector borne pathogens in blood donor candidates, clinically healthy volunteers, and stray dogs in North Carolina 
Parasites & Vectors  2014;7:116.
Background
Canine vector borne diseases (CVBDs) comprise illnesses caused by a spectrum of pathogens that are transmitted by arthropod vectors. Some dogs have persistent infections without apparent clinical, hematological or biochemical abnormalities, whereas other dogs develop acute illnesses, persistent subclinical infections, or chronic debilitating diseases. The primary objective of this study was to screen healthy dogs for serological and molecular evidence of regionally important CVBDs.
Methods
Clinically healthy dogs (n = 118), comprising three different groups: Gp I blood donor candidates (n = 47), Gp II healthy dog volunteers (n = 50), and Gp III stray dogs (n = 21) were included in the study. Serum and ethylenediamine tetraacetic acid (EDTA) anti-coagulated blood specimens collected from each dog were tested for CVBD pathogens.
Results
Of the 118 dogs tested, 97 (82%) dogs had been exposed to or were infected with one or more CVBD pathogens. By IFA testing, 9% of Gp I, 42% of Gp II and 19% of Gp III dogs were seroreactive to one or more CVBD pathogens. Using the SNAP 4DX® assay, Gp I dogs were seronegative for Anaplasma spp., Ehrlichia spp., and B. burgdorferi (Lyme disease) antibodies and D. immitis antigen. In Gp II, 8 dogs were Ehrlichia spp. seroreactive, 2 were infected with D. immitis and 1 was B. burgdorferi (Lyme disease) seroreactive. In Gp III, 6 dogs were infected with D. immitis and 4 were Ehrlichia spp. seroreactive. Using the BAPGM diagnostic platform, Bartonella DNA was PCR amplified and sequenced from 19% of Gp I, 20% of Gp II and 10% of Gp III dogs. Using PCR and DNA sequencing, 6% of Gps I and II and 19% of Gp III dogs were infected with other CVBD pathogens.
Conclusion
The development and validation of specific diagnostic testing modalities has facilitated more accurate detection of CVBDs. Once identified, exposure to vectors should be limited and flea and tick prevention enforced.
doi:10.1186/1756-3305-7-116
PMCID: PMC3972993  PMID: 24655461
Healthy dogs; CVBDs; Co-infection; Blood donors
17.  Quantifying Vocal Mimicry in the Greater Racket-Tailed Drongo: A Comparison of Automated Methods and Human Assessment 
PLoS ONE  2014;9(3):e89540.
Objective identification and description of mimicked calls is a primary component of any study on avian vocal mimicry but few studies have adopted a quantitative approach. We used spectral feature representations commonly used in human speech analysis in combination with various distance metrics to distinguish between mimicked and non-mimicked calls of the greater racket-tailed drongo, Dicrurus paradiseus and cross-validated the results with human assessment of spectral similarity. We found that the automated method and human subjects performed similarly in terms of the overall number of correct matches of mimicked calls to putative model calls. However, the two methods also misclassified different subsets of calls and we achieved a maximum accuracy of ninety five per cent only when we combined the results of both the methods. This study is the first to use Mel-frequency Cepstral Coefficients and Relative Spectral Amplitude - filtered Linear Predictive Coding coefficients to quantify vocal mimicry. Our findings also suggest that in spite of several advances in automated methods of song analysis, corresponding cross-validation by humans remains essential.
doi:10.1371/journal.pone.0089540
PMCID: PMC3945749  PMID: 24603717
18.  Darunavir Is a Good Third-Line Antiretroviral Agent for HIV Type 1-Infected Patients Failing Second-Line Protease Inhibitor-Based Regimens in South India 
Abstract
Eleven protease mutations have been associated with reduced susceptibility to darunavir. In this study of 87 HIV-1-infected patients experiencing virological failure to second-line regimens containing protease inhibitors boosted with ritonavir (viral load >1,000 HIV RNA copies/ml), we observed a low prevalence (3%) of ≥3 darunavir resistance-associated mutations, indicating that this drug may be a good option for third-line antiretroviral therapy in southern India.
doi:10.1089/aid.2011.0334
PMCID: PMC3581023  PMID: 23045961
19.  TESTOSTERONE ALTERS MATERNAL VASCULAR ADAPTATIONS: ROLE OF THE ENDOTHELIAL NITRIC OXIDE SYSTEM 
Hypertension  2013;61(3):647-654.
Sex steroid hormones estradiol and progesterone play an important role in vascular adaptations during pregnancy. However, little is known about the role of androgens. Plasma testosterone (T) levels are elevated in preeclampsia, mothers with polycystic ovary, and pregnant African-American women, who have endothelial dysfunction and develop gestational hypertension. We tested whether elevated T alters vascular adaptations during pregnancy and if these alterations depend upon endothelium-derived factors such as prostacyclin, endothelium-derived hyperpolarizing factor (EDHF), and nitric oxide (NO). Pregnant Sprague Dawley rats were injected with vehicle (n=12) or T propionate [0.5 mg/Kg/day from gestation day (GD) 15–19;n=12] to increase plasma T levels 2-fold, similar to that observed in preeclampsia. Telemetric blood pressures and endothelium-dependent vascular reactivity were assessed with wire-myograph system. Phospho-eNOS and total-eNOS were examined in mesenteric arteries (MA). Mean arterial pressures were significantly higher starting from GD19 until delivery in T-treated dams. Endothelium-dependent relaxation responses to acetylcholine were significantly lower in MA of T-treated dams (pD2 (-log EC50)=7.05±0.06; Emax=89.4±1.89) compared to controls (pD2=7.38±0.04; Emax=99.9±0.97). Further assessment of endothelial factors showed NO-mediated relaxations were blunted in T-treated MA (Emax=45.4±5.48) compared to controls (Emax=76.49±5.06); however, prostacyclin- and EDHF-mediated relaxations were unaffected. Relaxation to sodium nitroprusside was unaffected with T-treatment. Phosphorylations of eNOS at Ser1177 were decreased and at Thr495 were increased in T-treated MA without changes in total-eNOS levels. In conclusion, elevated maternal T, at concentrations relevant to abnormal clinical conditions, cause hypertension associated with blunting of NO-mediated vasodilation. Testosterone may induce the increased vascular resistance associated with pregnancy-induced hypertension.
doi:10.1161/HYPERTENSIONAHA.111.00486
PMCID: PMC3596870  PMID: 23339170
blood pressure; eNOS phosphorylation; hypertension; vasodilation; mesenteric arteries; EDHF; prostacyclin
20.  Associations between Extreme Precipitation and Gastrointestinal-Related Hospital Admissions in Chennai, India 
Environmental Health Perspectives  2013;122(3):249-254.
Background: Understanding the potential links between extreme weather events and human health in India is important in the context of vulnerability and adaptation to climate change. Research exploring such linkages in India is sparse.
Objectives: We evaluated the association between extreme precipitation and gastrointestinal (GI) illness-related hospital admissions in Chennai, India, from 2004 to 2007.
Methods: Daily hospital admissions were extracted from two government hospitals in Chennai, India, and meteorological data were retrieved from the Chennai International Airport. We evaluated the association between extreme precipitation (≥ 90th percentile) and hospital admissions using generalized additive models. Both single-day and distributed lag models were explored over a 15-day period, controlling for apparent temperature, day of week, and long-term time trends. We used a stratified analysis to explore the association across age and season.
Results: Extreme precipitation was consistently associated with GI-related hospital admissions. The cumulative summary of risk ratios estimated for a 15-day period corresponding to an extreme event (relative to no precipitation) was 1.60 (95% CI: 1.29, 1.98) among all ages, 2.72 (95% CI: 1.25, 5.92) among the young (≤ 5 years of age), and 1.62 (95% CI: 0.97, 2.70) among the old (≥ 65 years of age). The association was stronger during the pre-monsoon season (March–May), with a cumulative risk ratio of 6.50 (95% CI: 2.22, 19.04) for all ages combined compared with other seasons.
Conclusions: Hospital admissions related to GI illness were positively associated with extreme precipitation in Chennai, India, with positive cumulative risk ratios for a 15-day period following an extreme event in all age groups. Projected changes in precipitation and extreme weather events suggest that climate change will have important implications for human health in India, where health disparities already exist.
Citation: Bush KF, O’Neill MS, Li S, Mukherjee B, Hu H, Ghosh S, Balakrishnan K. 2014. Associations between extreme precipitation and gastrointestinal-related hospital admissions in Chennai, India. Environ Health Perspect 122:249–254; http://dx.doi.org/10.1289/ehp.1306807
doi:10.1289/ehp.1306807
PMCID: PMC3948034  PMID: 24345350
21.  Stego on FPGA: An IWT Approach 
The Scientific World Journal  2014;2014:192512.
A reconfigurable hardware architecture for the implementation of integer wavelet transform (IWT) based adaptive random image steganography algorithm is proposed. The Haar-IWT was used to separate the subbands namely, LL, LH, HL, and HH, from 8 × 8 pixel blocks and the encrypted secret data is hidden in the LH, HL, and HH blocks using Moore and Hilbert space filling curve (SFC) scan patterns. Either Moore or Hilbert SFC was chosen for hiding the encrypted data in LH, HL, and HH coefficients, whichever produces the lowest mean square error (MSE) and the highest peak signal-to-noise ratio (PSNR). The fixated random walk's verdict of all blocks is registered which is nothing but the furtive key. Our system took 1.6 µs for embedding the data in coefficient blocks and consumed 34% of the logic elements, 22% of the dedicated logic register, and 2% of the embedded multiplier on Cyclone II field programmable gate array (FPGA).
doi:10.1155/2014/192512
PMCID: PMC3958694  PMID: 24723794
22.  Preferential inactivation of Scn1a in parvalbumin interneurons increases seizure susceptibility 
Neurobiology of disease  2012;0:10.1016/j.nbd.2012.08.012.
Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials in electrically excitable cells. Dominant mutations in SCN1A, which encodes the Nav1.1 VGSC α-subunit, underlie several forms of epilepsy, including Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS+). Electrophysiological analyses of DS and GEFS+ mouse models have led to the hypothesis that SCN1A mutations reduce the excitability of inhibitory cortical and hippocampal interneurons. To more directly examine the relative contribution of inhibitory interneurons and excitatory pyramidal cells to SCN1A-derived epilepsy, we first compared the expression of Nav1.1 in inhibitory parvalbumin (PV) interneurons and excitatory neurons from P22 mice using fluorescent immunohistochemistry. In the hippocampus and neocortex, 69% of Nav1.1 immunoreactive neurons were also positive for PV. In contrast, 13% and 5% of Nav1.1 positive cells in the hippocampus and neocortex, respectively, were found to co-localize with excitatory cells identified by CaMK2α immunoreactivity. Next, we reduced the expression of Scn1a in either a subset of interneurons (mainly PV interneurons) or excitatory cells by crossing mice heterozygous for a floxed Scn1a allele to either the Ppp1r2-Cre or EMX1-Cre transgenic lines, respectively. The inactivation of one Scn1a allele in interneurons of the neocortex and hippocampus was sufficient to reduce thresholds to flurothyl- and hyperthermia-induced seizures, whereas thresholds were unaltered following inactivation in excitatory cells. Reduced interneuron Scn1a expression also resulted in the generation of spontaneous seizures. These findings provide direct evidence for an important role of PV interneurons in the pathogenesis of Scn1a-derived epilepsies.
doi:10.1016/j.nbd.2012.08.012
PMCID: PMC3740063  PMID: 22926190
Epilepsy; SCN1A; ion channels; interneurons; pyramidal neurons
23.  Proteomic analysis of human osteoarthritis synovial fluid 
Clinical proteomics  2014;11(1):6.
Background
Osteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography.
Results
We identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples.
Conclusions
We present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.
doi:10.1186/1559-0275-11-6
PMCID: PMC3942106  PMID: 24533825
Body fluid; Cartilage; Joint destruction; Glycosylation
24.  Larvicidal Activity of Cassia occidentalis (Linn.) against the Larvae of Bancroftian Filariasis Vector Mosquito Culex quinquefasciatus 
Background & Objectives. The plan of this work was to study the larvicidal activity of Cassia occidentalis (Linn.) against the larvae of Culex quinquefasciatus. These larvae are the most significant vectors. They transmit the parasites and pathogens which cause a deadly disease like filariasis, dengue, yellow fever, malaria, Japanese encephalitis, chikungunya, and so forth, which are considered harmful towards the population in tropic and subtropical regions. Methods. The preliminary laboratory trail was undertaken to determine the efficacy of petroleum ether and N-butanol extract of dried whole plant of Cassia occidentalis (Linn.) belonging to the family Caesalpiniaceae at various concentrations against the late third instar larvae of Culex quinquefasciatus by following the WHO guidelines. Results. The results suggest that 100% mortality effect of petroleum ether and N-butanol extract of Cassia occidentalis (Linn.) was observed at 200 and 300 ppm (parts per million). The results obviously showed use of plants in insect control as an alternative method for minimizing the noxious effect of some pesticide compounds on the environment. Thus the extract of Cassia occidentalis (Linn.) is claimed as more selective and biodegradable agent. Conclusion. This study justified that plant Cassia occidentalis (Linn.) has a realistic mortality result for larvae of filarial vector. This is safe to individual and communities against mosquitoes. It is a natural weapon for mosquito control.
doi:10.1155/2014/236838
PMCID: PMC3943188
25.  Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents 
Neuropharmacology  2012;65:65-73.
Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether the NF-κB signal transduction pathway was mobilized by CNTF. Neurite outgrowth of sensory neurons derived from streptozotocin (STZ)-induced diabetic rats was reduced compared to neurons from control rats and exposure to CNTF for 24 h enhanced neurite outgrowth. CNTF also activated NF-κB, as assessed by Western blotting for the NF-κB p50 subunit and reporter assays for NF-κB promoter activity. Conversely, blockade of NF-κB signaling using SN50 peptide inhibited CNTF-mediated neurite outgrowth. Studies in mice with STZ-induced diabetes demonstrated that systemic therapy with CNTF prevented functional and structural indices of peripheral neuropathy along with deficiencies in dorsal root ganglion (DRG) NF-κB p50 expression and DNA binding activity. DRG neurons derived from STZ-diabetic mice also exhibited deficiencies in maximal oxygen consumption rate and associated spare respiratory capacity that were corrected by exposure to CNTF for 24 h in an NF-κB-dependent manner. We propose that the ability of CNTF to enhance axon regeneration and protect peripheral nerve from structural and functional indices of diabetic peripheral neuropathy is associated with targeting of mitochondrial function, in part via NF-κB activation, and improvement of cellular bioenergetics.
doi:10.1016/j.neuropharm.2012.09.015
PMCID: PMC3521091  PMID: 23022047
Axon regeneration; bioenergetics profile; dorsal root ganglia; CNTF; NF-κB; diabetes; diabetic neuropathy; oxidative phosphorylation; respiration

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