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1.
Magn Reson Med ; 91(1): 325-336, 2024 01.
Article in English | MEDLINE | ID: mdl-37799019

ABSTRACT

PURPOSE: Sodium MRI can be used to quantify tissue sodium concentration (TSC) in vivo; however, UTE sequences are required to capture the rapidly decaying signal. 2D MRI enables high in-plane resolution but typically has long TEs. Half-sinc excitation may enable UTE; however, twice as many readouts are necessary. Scan time can be minimized by reducing the number of signal averages (NSAs), but at a cost to SNR. We propose using compressed sensing (CS) to accelerate 2D half-sinc acquisitions while maintaining SNR and TSC. METHODS: Ex vivo and in vivo TSC were compared between 2D spiral sequences with full-sinc (TE = 0.73 ms, scan time ≈ 5 min) and half-sinc excitation (TE = 0.23 ms, scan time ≈ 10 min), with 150 NSAs. Ex vivo, these were compared to a reference 3D sequence (TE = 0.22 ms, scan time ≈ 24 min). To investigate shortening 2D scan times, half-sinc data was retrospectively reconstructed with fewer NSAs, comparing a nonuniform fast Fourier transform to CS. Resultant TSC and image quality were compared to reference 150 NSAs nonuniform fast Fourier transform images. RESULTS: TSC was significantly higher from half-sinc than from full-sinc acquisitions, ex vivo and in vivo. Ex vivo, half-sinc data more closely matched the reference 3D sequence, indicating improved accuracy. In silico modeling confirmed this was due to shorter TEs minimizing bias caused by relaxation differences between phantoms and tissue. CS was successfully applied to in vivo, half-sinc data, maintaining TSC and image quality (estimated SNR, edge sharpness, and qualitative metrics) with ≥50 NSAs. CONCLUSION: 2D sodium MRI with half-sinc excitation and CS was validated, enabling TSC quantification with 2.25 × 2.25 mm2 resolution and scan times of ≤5 mins.


Subject(s)
Magnetic Resonance Imaging , Sodium , Humans , Retrospective Studies , Magnetic Resonance Imaging/methods , Computer Simulation , Fourier Analysis , Imaging, Three-Dimensional/methods
2.
J Magn Reson Imaging ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37787109

ABSTRACT

BACKGROUND: 1 H-magnetic resonance spectroscopy (1 H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). PURPOSE: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1 H-MRS and their association with clinical disability in SPMS. STUDY-TYPE: Longitudinal. POPULATION: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. FIELD STRENGTH/SEQUENCE: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. ASSESSMENT: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. STATISTICAL TESTS: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. RESULTS: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (ß = -0.21); in the riluzole arm, GM Glx (ß = -0.25) and Glx/tCr (ß = -0.29) were reduced. Baseline tNAA(ß = 0.22) and tNAA/tCr (ß = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. DATA CONCLUSION: 1 H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

3.
Front Neuroinform ; 17: 1060511, 2023.
Article in English | MEDLINE | ID: mdl-37035717

ABSTRACT

Introduction: Conventional MRI is routinely used for the characterization of pathological changes in multiple sclerosis (MS), but due to its lack of specificity is unable to provide accurate prognoses, explain disease heterogeneity and reconcile the gap between observed clinical symptoms and radiological evidence. Quantitative MRI provides measures of physiological abnormalities, otherwise invisible to conventional MRI, that correlate with MS severity. Analyzing quantitative MRI measures through machine learning techniques has been shown to improve the understanding of the underlying disease by better delineating its alteration patterns. Methods: In this retrospective study, a cohort of healthy controls (HC) and MS patients with different subtypes, followed up 15 years from clinically isolated syndrome (CIS), was analyzed to produce a multi-modal set of quantitative MRI features encompassing relaxometry, microstructure, sodium ion concentration, and tissue volumetry. Random forest classifiers were used to train a model able to discriminate between HC, CIS, relapsing remitting (RR) and secondary progressive (SP) MS patients based on these features and, for each classification task, to identify the relative contribution of each MRI-derived tissue property to the classification task itself. Results and discussion: Average classification accuracy scores of 99 and 95% were obtained when discriminating HC and CIS vs. SP, respectively; 82 and 83% for HC and CIS vs. RR; 76% for RR vs. SP, and 79% for HC vs. CIS. Different patterns of alterations were observed for each classification task, offering key insights in the understanding of MS phenotypes pathophysiology: atrophy and relaxometry emerged particularly in the classification of HC and CIS vs. MS, relaxometry within lesions in RR vs. SP, sodium ion concentration in HC vs. CIS, and microstructural alterations were involved across all tasks.

4.
Ann Maxillofac Surg ; 12(1): 76-78, 2022.
Article in English | MEDLINE | ID: mdl-36199472

ABSTRACT

The Rationale: A 19-year-old female presented to the Otorhinolaryngology Department. Patient Concerns: Pain over the right side of the neck below the angle of the mandible following a fall on a pin cushion after a fight with her brother. She reported that the wound might have been caused by a sewing needle lodged in the pin cushion. Diagnosis: X-ray soft-tissue neck lateral view revealed a radiopaque linear shadow on the right side of the neck at the level of the C1-C2 vertebrae. On contrast-enhanced computed tomography, a linear (needle-like) foreign body at the level of C1-C2 was approximately 1.6 cm deep from the skin. The internal jugular vein seemed to be compressed between the needle and vertebrae. Treatment: Foreign body was explored and removed under general anaesthesia by an open lateral cervical approach. Outcomes: The patient's postoperative recovery was uneventful. Take-away Lesson: Due to early diagnosis, management, and a team of experienced surgeons, anaesthesiologists, and support staff, any morbidity or mortality was avoided.

5.
Appl Opt ; 60(26): 8145-8153, 2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34613078

ABSTRACT

One of the major science goals of the Visible Emission Line Coronagraph (VELC) payload aboard the Aditya-L1 mission is to map the coronal magnetic field topology and quantitative estimation of longitudinal magnetic field on a routine basis. The infrared channel of VELC is equipped with a polarimeter to carry out full Stokes spectropolarimetric observations in the Fe xiii line at 1074.7 nm. The polarimeter is in a dual-beam setup with a continuously rotating wave plate as the polarization modulator. Detection of circular polarization due to the Zeeman effect and depolarization of linear polarization in the presence of a magnetic field due to the saturated Hanle effect in the Fe xiii line require a high signal-to-noise ratio (SNR). Due to the limited number of photons, long integration times are expected to build the required SNR. In other words, signals from a large number of modulation cycles are to be averaged to achieve the required SNR. This poses several difficulties. One is the increase in data volume and the other is the change in the modulation matrix in successive modulation cycles. The latter effect arises due to a mismatch between the retarder's rotation period and the length of the signal detection time in the case of the VELC spectropolarimeter. It is shown in this paper that by appropriately choosing the number of samples per half rotation, the data volume can be optimized. A potential solution is suggested to account for modulation matrix variation from one cycle to another.

6.
Brain ; 144(5): 1409-1421, 2021 06 22.
Article in English | MEDLINE | ID: mdl-33903905

ABSTRACT

In early multiple sclerosis, a clearer understanding of normal-brain tissue microstructural and metabolic abnormalities will provide valuable insights into its pathophysiology. We used multi-parametric quantitative MRI to detect alterations in brain tissues of patients with their first demyelinating episode. We acquired neurite orientation dispersion and density imaging [to investigate morphology of neurites (dendrites and axons)] and 23Na MRI (to estimate total sodium concentration, a reflection of underlying changes in metabolic function). In this cross-sectional study, we enrolled 42 patients diagnosed with clinically isolated syndrome or multiple sclerosis within 3 months of their first demyelinating event and 16 healthy controls. Physical and cognitive scales were assessed. At 3 T, we acquired brain and spinal cord structural scans, and neurite orientation dispersion and density imaging. Thirty-two patients and 13 healthy controls also underwent brain 23Na MRI. We measured neurite density and orientation dispersion indices and total sodium concentration in brain normal-appearing white matter, white matter lesions, and grey matter. We used linear regression models (adjusting for brain parenchymal fraction and lesion load) and Spearman correlation tests (significance level P ≤ 0.01). Patients showed higher orientation dispersion index in normal-appearing white matter, including the corpus callosum, where they also showed lower neurite density index and higher total sodium concentration, compared with healthy controls. In grey matter, compared with healthy controls, patients demonstrated: lower orientation dispersion index in frontal, parietal and temporal cortices; lower neurite density index in parietal, temporal and occipital cortices; and higher total sodium concentration in limbic and frontal cortices. Brain volumes did not differ between patients and controls. In patients, higher orientation dispersion index in corpus callosum was associated with worse performance on timed walk test (P = 0.009, B = 0.01, 99% confidence interval = 0.0001 to 0.02), independent of brain and lesion volumes. Higher total sodium concentration in left frontal middle gyrus was associated with higher disability on Expanded Disability Status Scale (rs = 0.5, P = 0.005). Increased axonal dispersion was found in normal-appearing white matter, particularly corpus callosum, where there was also axonal degeneration and total sodium accumulation. The association between increased axonal dispersion in the corpus callosum and worse walking performance implies that morphological and metabolic alterations in this structure could mechanistically contribute to disability in multiple sclerosis. As brain volumes were neither altered nor related to disability in patients, our findings suggest that these two advanced MRI techniques are more sensitive at detecting clinically relevant pathology in early multiple sclerosis.


Subject(s)
Brain/diagnostic imaging , Demyelinating Diseases/diagnostic imaging , Multiple Sclerosis/diagnostic imaging , Neuroimaging/methods , Adult , Brain/metabolism , Brain/pathology , Cross-Sectional Studies , Demyelinating Diseases/metabolism , Demyelinating Diseases/pathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology
7.
J Ethnopharmacol ; 273: 114000, 2021 Jun 12.
Article in English | MEDLINE | ID: mdl-33705919

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In folk medicine, parts of Plumeria alba L. are used for the treatment of many diseases, with its latex being used for curing skin diseases and promoting wound healing. AIM OF THE STUDY: This study aimed to study the role of P. alba L. latex in hemostasis and platelet aggregation. MATERIALS AND METHODS: The latex of P. alba L. was processed to remove waxes and enrich protein content, and the final extract was named Plumeria alba L. natant latex (PaNL). PaNL was analyzed for protease activity against casein. The type of protease in PaNL was identified by using protease inhibitors such as E-64, phenylmethylsulfonyl fluoride, ethylenediaminetetraacetic acid, and pepstatin A. Human fibrinogen, fibrin, and collagen types I and IV were subjected to hydrolysis with different concentrations of PaNL. The thrombin-like activity of PaNL was determined by analyzing its fibrinogen-clotting and procoagulant activities. The role of PaNL in platelet aggregation was also investigated. Its hemorrhagic and edema-inducing activities were evaluated in a mouse model. Phytochemical compounds were identified by gas chromatography-mass spectroscopy. RESULTS: The findings of casein/gelatin zymography confirmed that PaNL possesses protease activity. The results of the protease inhibition study indicated the presence of a cysteine-type protease(s) in PaNL. PaNL hydrolyzed the subunits of fibrinogen, fibrin, and collagen types I and IV. Its fibrin-degradation activity indicated that PaNL possesses plasmin-like activity. PaNL induced clotting of citrated human plasma within 3 min of incubation in the absence of CaCl2, indicating the presence of thrombin-like activity, which was further confirmed by the results of the fibrinogen-clotting assay. PaNL induced platelet aggregation in the absence of agonists. There was no hemolytic activity. Mice injected with PaNL did not show edema/ hemorrhagic activity. CONCLUSION: PaNL possesses procoagulant, fibrino(geno)lytic, thrombin- and plasmin-like activities and induces platelet aggregation, which could explain its usage for wound treatment in folk medicine.


Subject(s)
Apocynaceae/chemistry , Cysteine Proteases/metabolism , Fibrinolysin , Latex/pharmacology , Platelet Aggregation/drug effects , Thrombin , Animals , Blood Coagulation/drug effects , Cysteine Proteases/genetics , Edema/chemically induced , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/pharmacology , Hemorrhage/chemically induced , Latex/adverse effects , Latex/chemistry , Male , Mice , Phytochemicals , Phytotherapy
8.
Proc Natl Acad Sci U S A ; 117(47): 29811-29822, 2020 11 24.
Article in English | MEDLINE | ID: mdl-33177235

ABSTRACT

Inflammasomes have been implicated in the detection and clearance of a variety of bacterial pathogens, but little is known about whether this innate sensing mechanism has any regulatory effect on the expression of stimulatory ligands by the pathogen. During infection with Salmonella and many other pathogens, flagellin is a major activator of NLRC4 inflammasome-mediated macrophage pyroptosis and pathogen eradication. Salmonella switches to a flagellin-low phenotype as infection progresses to avoid this mechanism of clearance by the host. However, the host cues that Salmonella perceives to undergo this switch remain unclear. Here, we report an unexpected role of the NLRC4 inflammasome in promoting expression of its microbial ligand, flagellin, and identify a role for type 1 IFN signaling in switching of Salmonella to a flagellin-low phenotype. Early in infection, activation of NLRC4 by flagellin initiates pyroptosis and concomitant release of lysophospholipids which in turn enhance expression of flagellin by Salmonella thereby amplifying its ability to elicit cell death. TRIF-dependent production of type 1 IFN, however, later represses NLRC4 and the lysophospholipid biosynthetic enzyme iPLA2, causing a decline in intracellular lysophospholipids that results in down-regulation of flagellin expression by Salmonella These findings reveal a previously unrecognized immune-modulating regulatory cross-talk between endosomal TLR signaling and cytosolic NLR activation with significant implications for the establishment of infection with Salmonella.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Calcium-Binding Proteins/metabolism , Flagellin/metabolism , Group VI Phospholipases A2/metabolism , Interferon Type I/metabolism , Salmonella Infections/immunology , Salmonella typhimurium/immunology , Adaptor Proteins, Vesicular Transport/genetics , Adaptor Proteins, Vesicular Transport/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Calcium-Binding Proteins/genetics , Cells, Cultured , Disease Models, Animal , Down-Regulation , Flagellin/immunology , Group VI Phospholipases A2/antagonists & inhibitors , Humans , Immunity, Innate , Inflammasomes/drug effects , Inflammasomes/immunology , Inflammasomes/metabolism , Ketones/administration & dosage , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/immunology , Lysophospholipids/metabolism , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Knockout , Naphthalenes/administration & dosage , Primary Cell Culture , Pyroptosis/immunology , Salmonella Infections/microbiology , Salmonella typhimurium/isolation & purification , Signal Transduction/drug effects , Signal Transduction/immunology
9.
J Magn Reson Imaging ; 52(5): 1429-1438, 2020 11.
Article in English | MEDLINE | ID: mdl-32476227

ABSTRACT

BACKGROUND: Associations between brain total sodium concentration, disability, and disease progression have recently been reported in multiple sclerosis. However, such measures in spinal cord have not been reported. PURPOSE: To measure total sodium concentration (TSC) alterations in the cervical spinal cord of people with relapsing-remitting multiple sclerosis (RRMS) and a control cohort using sodium MR spectroscopy (MRS). STUDY TYPE: Retrospective cohort. SUBJECTS: Nineteen people with RRMS and 21 healthy controls. FIELD STRENGTH/SEQUENCE: 3 T sodium MRS, diffusion tensor imaging, and 3D gradient echo. ASSESSMENT: Quantification of total sodium concentration in the cervical cord using a reference phantom. Measures of spinal cord cross-sectional area, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity from 1 H MRI. Clinical assessments of 9-Hole Peg Test, 25-Foot Timed walk test, Paced Auditory Serial Addition Test with 3-second intervals, grip strength, vibration sensitivity, and posturography were performed on the RRMS cohort as well as reporting lesions in the C2/3 area. STATISTICAL TESTS: Multiple linear regression models were run between sodium and clinical scores, cross-sectional area, and diffusion metrics to establish any correlations. RESULTS: A significant increase in spinal cord total sodium concentration was found in people with RRMS relative to healthy controls (57.6 ± 18 mmol and 38.0 ± 8.6 mmol, respectively, P < 0.001). Increased TSC correlated with reduced fractional anisotropy (P = 0.034) and clinically with decreased mediolateral stability assessed with posturography (P = 0.045). DATA CONCLUSION: Total sodium concentration in the cervical spinal cord is elevated in RRMS. This alteration is associated with reduced fractional anisotropy, which may be due to changes in tissue microstructure and, hence, in the integrity of spinal cord tissue. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Anisotropy , Diffusion Tensor Imaging , Humans , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Retrospective Studies , Sodium , Spinal Cord/diagnostic imaging
10.
J Oral Maxillofac Pathol ; 24(Suppl 1): S2-S6, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32189894

ABSTRACT

Ameloblastoma is the most common odontogenic tumor which presents with a variety of histopathological patterns. Among all, papilliferous keratoameloblastoma (PKA) is a very rare type which is characterized by multiple epithelial cysts of varying size, which are lined by non-keratinized papilliferous epithelium which is filled with necrotic desquamated epithelial cells. In this study, we reported PKA with characteristic ameloblastic features in a 65-year-old male patient who presented with a swelling in the right mandibular body region. This is the seventh case of PKA to be reported in the English literature till date. Present case showed multicystic areas in incision biopsy which lead to misdiagnosis as calcifying odontogenic cyst with adenomatoid odontogenic tumor, but in excision biopsy which turned out to be papilliferous keratoameloblastoma, further in this paper we had discussed all the areas which lead to misdiagnosis of calcifying odontogenic cyst with adenomatoid odontogenic tumor. In outlook, more cases will put an insight to the behavioral aspects of this rare histological type of ameloblastoma.

11.
J Family Med Prim Care ; 9(11): 5731-5735, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33532422

ABSTRACT

BACKGROUND AND OBJECTIVES: Social media offers a platform for its users to share information and spread awareness regarding various issues including mental health problems. In some previous studies it was found that people suffering from mental health issues benefited from social media. However, the use of social media is also significantly associated with increased depression, mood and anxiety disorders in adolescents. Furthermore, it was found that the prevalence of poor mental health was high in medical students. With this background, this study was taken up to contribute to the scarce literature about the impact social media has on the mental well-being of medical students. METHODS: The setting was a medical college and research centre, situated in the metropolitan city of Bengaluru in Karnataka. A pretested and predesigned questionnaire was self-administered anonymously by 318 students. The data was analyzed using appropriate statistics. RESULTS: A statistically significant relationship was found between the amount of time spent on social media and the mental well-being score, according to the Sell and Nagpal scale, of students. In participants with scores of < 90.8, (30.2%) of them used social media for 4 hrs or more, as opposed to those with scores ≥ to 90.8, (35.6%) of them spent between 1 and 2 hrs a day on social media, 90.8 being the mean well-being score in India. CONCLUSIONS: Students need to monitor their screen time. There is a need to go back to old times of establishing human connections and, families and friendships should be nurtured.

12.
Cureus ; 10(9): e3281, 2018 Sep 11.
Article in English | MEDLINE | ID: mdl-30443451

ABSTRACT

A poorly feeding neonate presents the clinician with a diagnostic challenge. Feeding difficulties and irritability may be due to sepsis, congenital heart disease, inborn errors of metabolism, non-accidental head trauma, as well as a vast variety of other pathologies. Teratomas are rare pediatric tumors that can occasionally present in the immediate neonatal period and can manifest in the infant's central nervous system (CNS) with non-specific symptoms of poor feeding, lethargy, and somnolence. Operative resection remains the cornerstone of treatment; however, there is no well-defined role for adjuvant chemotherapy or radiation in these treatments. We report a case of a four-week-old female presenting with progressive feeding intolerance secondary to a near holocord thoracic spinal teratoma. Her tumor was surgically resected and she was treated with adjuvant chemotherapy and radiation for 13 months and is now in clinical remission. While rare, intramedullary spinal cord lesions should be considered in the differential diagnosis of infants presenting with poor feeding and hypotonia.

13.
Bioconjug Chem ; 29(11): 3606-3613, 2018 11 21.
Article in English | MEDLINE | ID: mdl-30247899

ABSTRACT

The diagnosis and prognosis of the disease associated with lipid irregularity are areas of extreme significance. In this direction, fluoranthene based yellow fluorescent probes (FLUN-550, FLUN-552, FLUN-547) were designed and synthesized by conjugating the ethanolamine headgroup of the phospholipid phosphatidyl-ethanolamine present in biological membranes. Owing to unique photophysical properties and aqueous compatibility, these probes were successfully employed for staining lipid droplets (LDs) in preadipocytes and Leishmania donovani promastigotes. Furthermore, using the fluorescent probes FLUN-550 and FLUN-552 we successfully imaged and quantitatively detected the excess accumulation of lipids in a liver section of Plasmodium yoelii MDR infected mice (3- to 4-fold) and the tissue sections of third stage human cervical cancer patients (1.5- to 2-fold) compared to normal tissues. To the best of our knowledge, this is the first report of yellow fluorescent probes for imaging and quantitative detection of LDs in human cervical cancer tissues. These new yellow fluorescent lipid probes (FLUN-550 and FLUN-552) showed great potential for diagnosis of cervical cancer patients.


Subject(s)
Fluorescent Dyes/metabolism , Lipid Droplets/metabolism , Liver/metabolism , Liver/parasitology , Plasmodium yoelii/pathogenicity , Uterine Cervical Neoplasms/metabolism , 3T3-L1 Cells , Animals , Density Functional Theory , Female , Humans , Leishmania donovani/metabolism , Mice , Staining and Labeling
14.
Article in English | MEDLINE | ID: mdl-30094226

ABSTRACT

Although over the last 15 years, prevalence of malaria became reduced by over half but developing resistance against artemisinin derivatives and its combinations, which are only ray of hope to treat resistant malaria set back the control efforts and the key hinderence to achieve the goal of malaria elimination till 2030. In spite these artemisinins are precious antimalarials, their action mechanism is yet to be fully understood. Reactive oxygen species (ROS) produces by cleavage of endoperoxide bridge of artemisinin derivatives are known to be its antimalarial efficacy. Since ROS could induce apoptosis, here we had explored the effect of artemisinin derivatives on apoptotic machinery of malaria parasite, Plasmodium falciparum and its survival. We have studied the effect of a/ß arteether, artesunate and a synthetic 1, 2, 4 trioxane on mitochondria, caspase activity and DNA during asexual blood stages of Plasmodium falciparum 3D7. Results have shown that cleavage of peroxide bridge of artemisinin derivatives and 1,2,4 trioxane generate reactive oxygen species which depolarize mitochondrial membrane potential and make it permeable which further followed by activation of caspase like enzyme and DNA fragmentation, which are hallmark of apoptotic cell death. These findings suggest that artemisinin derivatives and synthetic trioxane induce apoptosis like phenomena in erythrocytic stage of malaria parasite; Plasmodium falciparum.


Subject(s)
Antimalarials/pharmacology , Apoptosis/drug effects , Artemisinins/pharmacology , Cell Survival/drug effects , Heterocyclic Compounds/pharmacology , Plasmodium falciparum/drug effects , Blood Cells/parasitology , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondrial Membranes/drug effects , Permeability/drug effects , Plasmodium falciparum/physiology , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/toxicity
15.
J Neurol ; 265(8): 1795-1802, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29846780

ABSTRACT

Proton magnetic resonance spectroscopy yields metabolic information and has proved to be a useful addition to structural imaging in neurological diseases. We applied short-echo time Spectroscopic Imaging in a cohort of 42 patients with secondary progressive multiple sclerosis (SPMS). Linear modelling with respect to brain tissue type yielded metabolite levels that were significantly different in white matter lesions compared with normal-appearing white matter, suggestive of higher myelin turnover (higher choline), higher metabolic rate (higher creatine) and increased glial activity (higher myo-inositol) within the lesions. These findings suggest that the lesions have ongoing cellular activity that is not consistent with the usual assumption of 'chronic' lesions in SPMS, and may represent a target for repair therapies.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Multiple Sclerosis, Chronic Progressive/diagnostic imaging , Multiple Sclerosis, Chronic Progressive/metabolism , Cohort Studies , Female , Humans , Linear Models , Male , Middle Aged , Proton Magnetic Resonance Spectroscopy
16.
NMR Biomed ; 31(5): e3899, 2018 05.
Article in English | MEDLINE | ID: mdl-29480533

ABSTRACT

The purpose of this study was to measure the sodium transverse relaxation time T2 * in the healthy human brain. Five healthy subjects were scanned with 18 echo times (TEs) as short as 0.17 ms. T2 * values were fitted on a voxel-by-voxel basis using a bi-exponential model. Data were also analysed using a continuous distribution fit with a region of interest-based inverse Laplace transform. Average T2 * values were 3.4 ± 0.2 ms and 23.5 ± 1.8 ms in white matter (WM) for the short and long components, respectively, and 3.9 ± 0.5 ms and 26.3 ± 2.6 ms in grey matter (GM) for the short and long components, respectively, using the bi-exponential model. Continuous distribution fits yielded results of 3.1 ± 0.3 ms and 18.8 ± 3.2 ms in WM for the short and long components, respectively, and 2.9 ± 0.4 ms and 17.2 ± 2 ms in GM for the short and long components, respectively. 23 Na T2 * values of the brain for the short and long components for various anatomical locations using ultra-short TEs are presented for the first time.


Subject(s)
Brain/diagnostic imaging , Magnetic Resonance Imaging , Sodium/chemistry , Adult , Female , Gray Matter/diagnostic imaging , Humans , Male , Phantoms, Imaging , Signal Processing, Computer-Assisted , White Matter/diagnostic imaging
17.
Eur J Med Chem ; 143: 632-645, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29216562

ABSTRACT

Sexually transmitted diseases like trichomoniasis along with opportunistic fungal infections like candidiasis are major global health burden in female reproductive health. In this context a novel non-nitroimidazole class of substituted carbamothioic amine-1-carbothioic thioanhydride series was designed, synthesized, evaluated for trichomonacidal and fungicidal activities, and was found to be more active than the standard drug Metronidazole (MTZ). Compounds were trichomonicidal in the MIC ranges of 4.77-294.1 µM and 32.46-735.20 µM against MTZ-susceptible and -resistant strains, respectively. Further, compounds inhibited the growth of at least two out of ten fungal strains tested at MIC of 7.50-240.38 µM. The most active compound (20) of this series was 3.8 and 9.5 fold more active than the MTZ against the two Trichomonas strains tested. Compound 20 also significantly inhibited the sulfhydryl groups present over Trichomonas vaginalis and was found to be more active than the MTZ in vivo. Further, a docking analysis carried out with cysteine proteases supported their thiol inhibiting ability and preliminary pharmacokinetic study has shown good distribution and systemic clearance.


Subject(s)
Carbonic Anhydrases/pharmacology , Drug Design , Fungicides, Industrial/pharmacology , Sulfhydryl Compounds/pharmacology , Trichomonas/drug effects , Carbonic Anhydrases/chemical synthesis , Carbonic Anhydrases/chemistry , Dose-Response Relationship, Drug , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Metronidazole/chemistry , Metronidazole/pharmacology , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity Relationship , Sulfhydryl Compounds/chemical synthesis , Sulfhydryl Compounds/chemistry , Trichomonas/growth & development
18.
Contemp Clin Dent ; 8(1): 175-178, 2017.
Article in English | MEDLINE | ID: mdl-28566875

ABSTRACT

Juvenile Paget's disease (JPD), a rare genetic skeletal disorder characterized by accelerated bone turnover with elevated levels of serum alkaline phosphatase, presents in early childhood. We report a female patient with typical features of JPD with dental finding who remained undiagnosed until 18 years of age. Scarcity of this disease in the Indian literature and need for timely diagnosis to avert progression of disease thus incited us to report this case.

19.
J Clin Diagn Res ; 11(5): ZC25-ZC28, 2017 May.
Article in English | MEDLINE | ID: mdl-28658902

ABSTRACT

INTRODUCTION: Angiogenesis is vital in the aetiology and pathogenesis of a number of pathological processes that include solid reactive lesions like pyogenic granuloma and chronic inflammatory disorders like periapical granuloma. Vascular Endothelial Growth Factor (VEGF) is a potent proangiogenic cytokine secreted by many cell types which present several pivotal functions in physiologic and pathologic angiogenesis. AIM: The aim of the present study was to evaluate and compare the expression of VEGF in oral Pyogenic Granuloma (PG) and Periapical Granuloma (PAG) and also to correlate with the inflammatory cell infiltrate. MATERIALS AND METHODS: Paraffin embedded tissue blocks of histologically diagnosed cases of PG and PAG, 20 of each were retrieved from the archives. The cases were selected randomly to evaluate the expression of VEGF marker and to assess the Mean Vascular Count (MVC) index and inflammation by Morphological Index (MI). The results were analysed using Unpaired t-test, Mann-Whitney U test and spearman correlation coefficient-test. RESULTS: The PG showed higher expression of VEGF when compared to PAG with no significant difference in inflammation. PG showed positive correlation and PAG showed negative correlation between inflammation and VEGF expression. CONCLUSION: Histologically similar PG and PAG are different not only by their clinical presentation but also by their mechanisms of formation and molecular sketch. Thereby raised expression of VEGF marker was established in PG emphasizing the fact that all histologically similar lesions need not have similar clinical course and molecular depiction.

20.
J Clin Diagn Res ; 11(1): ZD25-ZD27, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28274070

ABSTRACT

Ameloblastic Carcinoma (AC) is uncommon malignant epithelial odontogenic tumour of jaw, with characteristic histologic features and behavior. Clinically, it has aggressive, infiltrative growth pattern with a distinct predilection for mandible. It exhibits histologic features of ameloblastoma and gets dedifferentiated overtime to culminate in carcinoma. Majority of the cases arise denovo (primary) and only few cases arise from a pre-existing ameloblastoma (secondary). Spindle-cell differentiation in ameloblastic carcinoma is rare; Salter described it as a separate entity "low-grade spindle cell ameloblastic carcinoma. Here we report a case of 32-year-old female patient who presented with a swelling present for past six months. It was diagnosed as Spindle cell Ameloblastic Carcinoma (SpAC), after the hemimandibulectomy the patient was under regular follow up for 14 months, no sign of recurrence was seen.

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