scholarly journals Development of New Drugs to Treat Taenia solium Cysticercosis: Targeting 26 kDa Glutathione Transferase

2021 ◽  
Author(s):  
Rafael A. Zubillaga ◽  
Lucía Jiménez ◽  
Ponciano García-Gutiérrez ◽  
Abraham Landa
Keyword(s):  
Glutathione Transferase ◽  
Competitive Inhibition ◽  
Taenia Solium ◽  
Parasitic Infection ◽  
Docking Simulation ◽  
New Drugs ◽  
Inhibition Mechanism ◽  
Cytosolic Glutathione ◽  
The Central Nervous System ◽  
A Site

Taenia solium causes neurocysticercosis, a parasitic infection of the central nervous system in humans. The costs of management, treatment, and diagnosis of patients with neurocysticercosis are high, and some patients do not respond to the currently available treatments. Helminth cytosolic glutathione transferases (GSTs) are essential enzymes involved in the regulation of immune responses, transport, and detoxification. In T. solium, three cytosolic GSTs with molecular masses of 26.5 (Ts26GST), 25.5 (Ts25GST), and 24.3 kDa (TsMσGST), classified as mu-alpha, mu and sigma GST-classes, respectively, constitute the main detoxification system, and they may be immune targets for the development of vaccines and new anthelmintics. We performed a successful virtual screen, and identified I7, a novel selective inhibitor of Ts26GST that showed a non-competitive inhibition mechanism towards substrate glutathione with a Ki of 55.7 mM and mixed inhibition towards the electrophilic substrate 1-chloro-2,4-dinitrobenzene with a Ki of 8.64 mM. Docking simulation studies showed that I7 can bind to a site that is adjacent to the electrophilic site and the furthest from the glutathione site. This new inhibitor of Ts26GST will be used as a lead molecule to develop new effective and safe drugs against diseases caused by T. solium.

scholarly journals Uncommon Location of Common Parasite

2014 ◽  
Vol 4 (1) ◽  
pp. 63-66
Author(s):  
P Sherwani ◽  
S Tomer ◽  
L Pahuja ◽  
R Anand
Keyword(s):  
Rare Case ◽  
Cystic Lesion ◽  
Taenia Solium ◽  
Parasitic Infection ◽  
Cervical Region ◽  
Neck Stiffness ◽  
The Central Nervous System ◽  
Common Parasite ◽  
Uncommon Location ◽  
Ct And Mri

Neurocysticercosis is the most common parasitic infection of the Central Nervous System caused by Taenia solium. Spinal cysticercosis is an uncommon site of cysticercal infestation & intramedullary involvement is even rarer.1 We are reporting a rare case of intramedullary cysticercosis in the cervical region in an 11 year old girl who presented with headache & neck stiffness. CT and MRI of the cervical spine done revealed a cystic lesion with mural nodule (scolex) with cord edema in the cervical region. The child underwent treatment with antihelminthic drugs and showed marked clinico-radiological improvement.DOI: http://dx.doi.org/10.3126/njr.v4i1.11373 Nepalese Journal of Radiology, Vol.4(1) 2014: 63-66

Inhibitory Effect of Sesamolin on Melanogenesis in B16F10 Cells Determined by In Vitro and Molecular Docking Analyses

2020 ◽  
Vol 21 (2) ◽  
pp. 169-178
Author(s):  
Seung-Hwa Baek ◽  
Myung-Gyun Kang ◽  
Daeui Park
Keyword(s):  
Molecular Docking ◽  
Competitive Inhibition ◽  
Docking Simulation ◽  
Melanoma Cells ◽  
Inhibition Mechanism ◽  
Dual Function ◽  
Dependent Manner ◽  
Related Factors ◽  
Docking Simulations

Background: Melanin protects the skin against the harmful effects of ultraviolet irradiation. However, melanin overproduction can result in several aesthetic problems, including melasma, freckles, age spots and chloasma. Therefore, development of anti-melanogenic agents is important for the prevention of serious hyperpigmentation diseases. Sesamolin is a lignan compound isolated from sesame seeds with several beneficial properties, including potential for melanin inhibition. Objective: The aim of this study was to evaluate the anti-melanogenic effect of sesamolin in cell culture in vitro and the underlying mechanism of inhibition using molecular docking simulation. Methods: Melanogenesis was induced by 3-isobutyl-1-methylxanthine in B16F10 melanoma cells, and the inhibitory effects of sesamolin were evaluated using zymography, a tyrosinase inhibitory activity assay, western blotting, and real-time reverse transcription-polymerase chain reaction analysis. Docking simulations between sesamolin and tyrosinase were performed using Autodock vina. Results: Sesamolin significantly inhibited the expression of melanogenesis-related factors tyrosinase, and tyrosinase-related proteins 1 and 2 at the mRNA and protein levels. Treatment of melanoma cells with 50 µM sesamolin demonstrated the strongest inhibition against intercellular tyrosinase and melanin synthesis without exerting cytotoxic effects. Sesamolin significantly reduced mushroom tyrosinase activity in a dose-dependent manner via a competitive inhibition mechanism. Tyrosinase docking simulations supported that sesamolin (-6.5 kcal/mol) bound to the active site of tyrosinase more strongly than the positive control (arbutin, -5.7 kcal/mol). Conclusion: Sesamolin could be developed as a melanogenesis inhibiting agent owing to its dual function in blocking the generation of melanogenesis-related enzymes and inhibiting the enzymatic response of tyrosinase.

scholarly journals Cysticercosis Involving Muscle of Mastication: A Review and Report of Two Cases

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Sarbjeet Singh ◽  
V. Sreenivasan ◽  
Kanika Garg ◽  
Nikhel Dev Wazir ◽  
Jaspal Singh Rajput ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Taenia Solium ◽  
Parasitic Infection ◽  
Primary Site ◽  
Common Disease ◽  
Temporalis Muscle ◽  
Mri Findings ◽  
Larval Stages ◽  
The Central Nervous System

Cysticercosis is a parasitic infection caused by the larval stages of the parasitic cestode,Taenia solium. It is a common disease in developing countries where it is also endemic. The central nervous system (CNS) is the most important primary site of infection and the disease can present with solitary or multiple space occupying lesions. Cases of cysticercosis presenting as isolated muscle mass (pseudotumours) without involvement of the CNS have also been recently described in the literature. We present two cases who presented to us with pain, swelling, and tenderness involving the temporalis muscle along with trismus. Ultrasonography and MRI findings were suggestive of cysticercosis involving the temporalis muscle which resolved after the albendazole therapy.

scholarly journals Intradural spinal neurocysticercosis: case illustration

2017 ◽  
Vol 31 (4) ◽  
pp. 530-535
Author(s):  
Jorge Balderrama ◽  
Dania Elizabeth Trinidad Arevalo ◽  
Willem Guillermo Calderon-Mirada ◽  
Andrei F. Joaquim ◽  
Alfonso Pacheco-Hernandez ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Clinical Case ◽  
Neurological Diseases ◽  
Taenia Solium ◽  
Parasitic Infection ◽  
Clonic Convulsion ◽  
Recurrent Headache ◽  
Spatial Disorientation ◽  
History Of ◽  
The Central Nervous System

Abstract Introduction: Neurocysticercosis (NCC) is a common parasitic infection of the central nervous system caused by the larvae of the Taenia solium. Spinal cord involvement is very uncommon. Clinical case: A female patient with a history of NCC presented with chronic and recurrent headache associated with motor and sensory deficit, which develops tonic-clonic convulsion, with spatial disorientation. She also had intracranial hypertension syndrome, meningitis syndrome, and pyramidal sygns suggestive of spinal NCC. Conclusions: Neurocysticercosis usually occurs in developing countries and should be considered as a differential diagnosis of neurological diseases. Early diagnosis and treatment are mandatory, as well as education to the community to primary prevention.

scholarly journals Total IgE detection in paired cerebrospinal fluid and serum samples from patients with neurocysticercosis

2000 ◽  
Vol 42 (2) ◽  
pp. 67-70 ◽  
Author(s):  
Ednéia Casagranda BUENO ◽  
Adelaide José VAZ ◽  
Luís dos Ramos MACHADO ◽  
José Antônio LIVRAMENTO
Keyword(s):  
Cerebrospinal Fluid ◽  
Taenia Solium ◽  
Parasitic Infection ◽  
Control Group ◽  
Serum Samples ◽  
Total Ige ◽  
Normal Value ◽  
Significant Difference ◽  
Group A ◽  
The Central Nervous System

Neurocysticercosis (NC), the presence of Taenia solium metacestodes in tissues, is the most frequent and severe parasitic infection of the central nervous system. We investigated the presence of total IgE by an automated chemiluminescence assay in 53 paired cerebrospinal fluid (CSF) and serum samples from patients with NC (P) and in 40 CSF samples from individuals with other neurological disorders as the control group (C). Total IgE concentration ranged from 1.2 to 6.6 IU/ml (mean = 1.4 IU/ml, standard deviation-sd = 1.1 IU/ml) in 28.3% of CSF samples from the P group, a value significantly higher than for the C group (£1.0 IU/ml). The serum samples from the P group showed concentrations ranging from 1.0 to 2330.0 IU/ml (mean = 224.1 IU/ml, sd = 452.1 IU/ml), which were higher than the normal value cited by the manufacturer (<100.0 IU/ml) in 32.1% of the samples. A significant difference was observed in CSF samples from the P and C groups (p = 0.005) and in serum samples from the P group compared to the normal value (p = 0.005), with sera showing more frequent abnormal results.

scholarly journals Neurocysticercosis, unusual manifestations

2016 ◽  
Vol 64 (3) ◽  
pp. 561 ◽  
Author(s):  
David López-Valencia ◽  
Ángela Patricia Medina-Ortega ◽  
Janh Sebastián Saavedra-Torres ◽  
Luisa Fernanda Zúñiga-Cerón ◽  
Tomás Omar Zamora-Bastidas
Keyword(s):  
Central Nervous System ◽  
Taenia Solium ◽  
Parasitic Infection ◽  
Brain Parenchyma ◽  
Control Measures ◽  
Prevention Strategies ◽  
Initial Symptoms ◽  
The Central Nervous System ◽  
Epidemiological Profile ◽  
The Brain

Neurocysticercosis is the most common parasitic infection in the central nervous system. This disease is presented when a person ingests Taenia solium eggs excreted in feces from another individual infected with taeniasis. In 50% of the cases, neurocysticercosis takes place in the brain parenchyma, and its appearance is less frequent in the posterior fossa and the spinal cord.The case of a patient with an atypical location of the parasite at the medulla oblongata, between parenchymal and spinal areas, is presented. The initial symptoms were common but its subsequent manifestations were similar to those of Bruns syndrome. Furthermore, the epidemiological profile of neurocysticercosis in Colombia, its control measures and prevention strategies were reviewed in this study.

scholarly journals Serodiagnosis of Human Cysticercosis by Using Antigens from Vesicular Fluid of Taenia crassicepsCysticerci

2001 ◽  
Vol 8 (6) ◽  
pp. 1140-1144 ◽  
Author(s):  
Ednéia C. Bueno ◽  
Miriam Snege ◽  
Adelaide J. Vaz ◽  
Paulo G. Leser
Keyword(s):  
Complement Fixation Test ◽  
Taenia Solium ◽  
Screening Method ◽  
Parasitic Infection ◽  
Confirmatory Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
The Central Nervous System ◽  
Specific Reactivity ◽  
Standard Techniques

ABSTRACT Neurocysticercosis (NC), caused by the presence of Taenia solium metacestodes in tissues, is a severe parasitic infection of the central nervous system with universal distribution. To determine the efficiency of enzyme-linked immunosorbent assay (ELISA) and immunoblot with antigens of T. crassiceps vesicular fluid (Tcra) compared to standard techniques (indirect immunofluorescence test [IFT] and complement fixation test [CFT]) using T. solium cysticerci (Tso) for the serodiagnosis of NC, we studied serum samples from 24 patients with NC, 30 supposedly healthy individuals, 76 blood bank donors, 45 individuals with other non-NC parasitoses, and 97 samples from individuals screened for cysticercosis serology (SC). The sensitivity observed was 100% for ELISA-Tso and ELISA-Tcra, 91.7% for the IFT, and 87.5% for the CFT. The specificity was 90% for ELISA-Tso, 96.7% for ELISA-Tcra, 50% for IFT, and 63.3% for CFT. The efficiency was highest for ELISA-Tcra, followed by ELISA-Tso, IFT, and CFT. Of the 23 samples from SC group, which were reactive to ELISA-Tso and/or ELISA-Tcra, only 3 were positive to immunblot-Tcra (specific peptides of 14- and 18-kDa) and to glycoprotein peptides purified from Tcra antigen (gp-Tcra), showing the low predictive value of ELISA for screening. None of the samples from the remaining groups showed specific reactivity in immunoblot-Tcra. These results demonstrate that ELISA-Tcra can be used as a screening method for the serodiagnosis of NC and support the need for specific tests for confirmation of the results. The immunoblot can be used as a confirmatory test both with Tcra and gp-Tcra, with the latter having an advantage in terms of visualization of the results.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer&#039;s Disease (AD), Parkinson&#039;s Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

GABAA receptors: Various stoichiometrics of subunit arrangement in α1β3 and α1β3ε receptors

2018 ◽  
Vol 24 (17) ◽  
pp. 1839-1844 ◽  
Author(s):  
Ahmad Tarmizi Che Has ◽  
Mary Chebib
Keyword(s):  
Central Nervous System ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
New Drugs ◽  
Pharmacological Properties ◽  
Receptor Complex ◽  
The Third ◽  
Γ Subunit ◽  
Subunit Stoichiometry ◽  
The Central Nervous System

GABAA receptors are members of the Cys-loop family of ligand-gated ion channels which mediate most inhibitory neurotransmission in the central nervous system. These receptors are pentameric assemblies of individual subunits, including α1-6, β1-3, γ1-3, δ, ε, π, θ and ρ1-3. The majority of receptors are comprised of α, β and γ or δ subunits. Depending on the subunit composition, the receptors are located in either the synapses or extrasynaptic regions. The most abundant receptors are α1βγ2 receptors, which are activated and modulated by a variety of pharmacologically and clinically unrelated agents such as benzodiazepines, barbiturates, anaesthetics and neurosteroids, all of which bind at distinct binding sites located within the receptor complex. However, compared to αβγ, the binary αβ receptors lack a benzodiazepine α-γ2 interface. In pentameric αβ receptors, the third subunit is replaced with either an α1 or a β3 subunit leading to two distinct receptors that differ in subunit stoichiometry, 2α:3β or 3α:2β. The consequence of this is that 3α:2β receptors contain an α-α interface whereas 2α:3β receptors contain a β-β interface. Apart from the replacement of γ by α1 or β3 in binary receptors, the incorporation of ε subunit into GABAA receptors might be more complicated. As the ε subunit is not only capable of substituting the γ subunit, but also replacing the α/β subunits, receptors with altered stoichiometry and different pharmacological properties are produced. The different subunit arrangement of the receptors potentially constructs novel binding sites which may become new targets of the current or new drugs.

scholarly journals The Potency of Senggani (Melastoma malabathricum L) Leaves in Repair of Pancreatic Beta Cells for Diabetes Mellitus Patients: A Narrative Review

2020 ◽  
Vol 7 (2) ◽  
pp. 61-70
Author(s):  
Galuh Rizal Prayoga ◽  
Aziz Syamsul Huda ◽  
Syndilona Br Sitepu
Keyword(s):  
Diabetes Mellitus ◽  
Binding Site ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Docking Simulation ◽  
The Body ◽  
Inhibition Mechanism ◽  
Active Compounds ◽  
Glucose Levels ◽  
Melastoma Malabathricum

Diabetes mellitus is often caused by damage to pancreatic beta cells which play a role in secreting insulin in the body. Damage to pancreatic beta cells causes the body to lack insulin. Dipeptidyl peptidase-4 (DPP-4) is a peptidase enzyme complex located on the surface of the cell membrane. Inhibition of the DPP4 enzyme will increase blood GLP-1 levels and induce regeneration of pancreatic beta cells. Senggani leaf (Melastoma malabathricum) boiled water is believed by the people of the Ciamis area to be used as a diabetes medicine. There have been many studies and reviews related to Senggani (Melastoma malabathricum) and its potential. This review focuses on the discussion of Senggani as an antidiabetic by analyzing the reduction in glucose levels and the repair ability of pancreatic beta cells. The results of the literature study that show that senggani leaves have the ability to reduce blood glucose levels and repair activity of pancreatic beta cells through the DPP-4 enzyme inhibition mechanism supported by molecular docking simulation data. There are 12 active compounds that have a binding site similarity above 50% with the comparison compound vildagliptin. Rutin is the best active compound which has a 100% similarity of the binding site. Based on in vivo research and toxicity analysis on the admetsar database, senggani leaf extract and active compounds of senggani leaves have low toxicity, making it safe to be used as antidiabetic herbal preparations.

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