Category: 4730-54-5

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Design, expression, and evaluation of novel multiepitope chimeric antigen of Wuchereria bancrofti for the diagnosis of lymphatic filariasis ? A structure-based strategy

The Global Program for Elimination Lymphatic Filariasis (GPELF) is in an advanced stage and requires tools for diagnosing infection, assessing transmission and certification. This study was aimed at developing an antibody-based assay using a chiemric antigen containing multi-B-cell epitopes from antigens highly expressed in different stages of Wuchereria bancrofti to detect LF infection and its transmission. The antigen was express cloned and two indirect ELISA based (IgG1 & IgG4 based) antibody assays were developed using the recombinant antigen. The chimeric antigen displayed 1 and 3-fold reactivity with IgG1 and IgG4 antibodies, respectively in microfilaraial (mf) positive sera when compared to that in sera samples of Non-endemic normal sera (NEN) (O.D, 0.13 ¡À 0.20 and 0.18 ¡À 0.07), thus differentiating infected from uninfected individuals. In IgG1 and IgG4 antibody assays, the multiepitope antigen also showed reactivity (O.D, 0.27 ¡À 0.18 and 0.16 ¡À 0.03) in a small proportion (18 and 30, respectively out of 156) endemic normal individuals and in IgG1 antibody in a few (4) chronic patients (CP). The antigen did not react with IgG1 or IgG4 antibodies in the sera samples of malaria, scrub typhus, dengue, hookworm, and roundworm helminth cases (0.139 ¡À 0.018, 0.144 ¡À 0.007 0.17804 ¡À 0.007 and 0.162 ¡À 0.006), thus showing its high specificity. The sensitivity (%) and specificity (%) of the multi-epitope antigen-based IgG1 and IgG4 antibody assays are 100, 98.1 and 100, 99.52, respectively. Thus, the recombinant multiepitope antigen appears to have good potential in detecting active LF infection and in assessing its transmission in endemic communities.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Characterization and evaluation of nanoencapsulated diethylcarbamazine in model of acute hepatic inflammation

Previous studies from our laboratory have demonstrated that Diethylcarbamazine (DEC) is a potent anti-inflammatory drug. The aim of the present study was to characterize the nanoencapsulation of DEC and to evaluate its effectiveness in a model of inflammation for the first time. C57BL/6 mice were divided into six groups: 1) Control; 2) Carbon tetrachloride (CCl4); 3) DEC 25 mg/kg + CCl4; 4) DEC 50 mg/kg + CCl4; 5) DEC-NANO 05 mg/kg + CCl4 and 6) DEC-NANO 12.5 mg/kg + CCl4. Liver fragments were stained with hematoxylin-eosin, and processed for Western blot, ELISA and immunohistochemistry. Serum was also collected for biochemical measurements. Carbon tetrachloride induced hepatic injury, observed through increased inflammatory markers (TNF-alpha, IL-1beta, PGE2, COX-2 and iNOS), changes in liver morphology, and increased serum levels of total cholesterol, triglycerides, TGO and TGP, LDL, as well as reduced HDL levels. Nanoparticles containing DEC were characterized by diameter, polydispersity index and zeta potential. Treatment with 12.5 nanoencapsulated DEC exhibited a superior anti-inflammatory action to the DEC traditional dose (50 mg/kg) used in murine assays, restoring liver morphology, improving serological parameters and reducing the expression of inflammatory markers. The present formulation of nanoencapsulated DEC is therefore a potential therapeutic tool for the treatment of inflammatory hepatic disorders, permitting the use of smaller doses and reducing treatment time, while maintaining high efficacy.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Designing antifilarial drug trials using clinical trial simulators

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Filiarial chyluria with nephrotic-range proteinuria and associated hypoalbuminaemia and hypogammaglobulinaemia secondary to bilateral lymphorenal fistulae

A 55-year-old man of Indian descent, presented to the emergency department with a 2-year history of passing ? milky’ white urine, associated with dysuria, urinary retention, bilateral flank pain and 15 kg weight loss. He had migrated to Australia from India at the age of 16, with no overseas travel since, and denied having any fevers, rigours or chills. He was found to have chyluria and nephrotic-range proteinuria with marked hypoalbuminaemia and hypogammaglobulinaemia. Due to his ethnic origin and by diagnostic exclusion, a presumptive diagnosis of filariasis was made. With bilateral lymphorenal disconnection, as definitive management, the patient’s chyluria and proteinuria resolved with restoration of normal plasma protein and immunoglobulin levels.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Antiparasitic therapy

Parasitic diseases affect more than 2 billion people globally and cause substantial morbidity and mortality, particularly among the world’s poorest people. This overview focuses on the treatment of the major protozoan and helminth infections in humans. Recent developments in antiparasitic therapy include the expansion of artemisinin-based therapies for malaria, new drugs for soil-transmitted helminths and intestinal protozoa, expansion of the indications for antiparasitic drug treatment in patients with Chagas disease, and the use of combination therapy for leishmaniasis and human African trypanosomiasis.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Antifilarial actions of green tea extract and a synthetic heterocyclic thiazolidine derivative, Im8 compound in experimental mouse model

In spite of the advances in drug development and research against human lymphatic filariasis following the WHO mandate to address the disease-associated socioeconomic burden, diethylcarbamazine (DEC, N, N-diethyl-4-methyl-1-piperazine carboxamide) is the only available antifilarial drug to date. The major obstacle for further development of antifilarial drugs is the lack of validation of candidate drugs in the experimental animal models. Both, green tea extract and a synthetic heterocyclic thiazolidine derivative (Im8; 2-chloro-N-(4-phenylthiazol-2-yl), showed efficacy of antifilarial action in our earlier in vitro study and hence, they were screened in the present study for their antifilarial potential in the BALB/c mouse filariasis model. Mice were treated with 25 mg/kg dose of either Im8 or green tea extract or DEC or only with their respective vehicles. The untreated mice served as controls. Following insertion of the micropore chamber laden with microfilariae (Mf) of Brugia malayi, the drug or vehicle was administered s.c. in mice at 12 h intervals as 4 doses. After 12 h of administration of the last dose, the micropore chambers were removed to determine the action of the treatments as the loss of Mf motility. The green tea extract showed a significant antifilarial action and Im8 showed relatively less but significant antifilarial action as compared to the respective vehicle controls. Both the green tea extract and Im8 showed higher activity than that was exerted by DEC. These results revealed a greater efficacy of green tea and thiazolidine derivative, Im8 as the novelantifilarial agents in the experimental mouse model of filariasis.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Antifilarial activity in vitro and in vivo of some flavonoids tested against Brugia malayi

We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2mug/ml concentration, respectively. Microfilariae (mf) were killed at 250-500mug/ml. The half maximal inhibitory concentration (IC50) of naringenin for motility of adult females was 2.5mug/ml. Flavone immobilized female adult worms at 31.2mug/ml (MTT>80%) and microfilariae at 62.5mug/ml. Rutin killed microfilariae at 125mug/ml and inhibited MTT-reduction in female worms for >65% at 500mug/ml. Naringin had adulticidal effects at 125mug/ml while chrysin killed microfilariae at 250mug/ml. In vivo, 50mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Eosinophilic myositis and its medical management in a dog

A six-year male, mongrel dog weighing about 17 kg, presented with complaint of progressive atrophy of temporal, masseter muscles of left side since two months. Clinical examination revealed quidding while taking solid feed and change in voice but vital parameters were found within normal range. Muscle biopsy revealed striated muscle fibre with mild infiltration of polymorphonuclear cells; the inflammatory cells (mainly eosinophilic granulocytes) were distributed between the muscle cells. Based on the history, clinical evaluation and muscle biopsy, diagnosis was made for eosinophilic myositis and treatment was initiated with tab of multivitamin (Thiamine mononitrate 10 mg; riboflavine 10 mg; pyridoxine HCl 3 mg; cyanocobalamin triturate in gelatin eq to cyanocobalamin 15 mcg; nicotinamide 45 mg; calcium pantothenate 50 mg), ascorbic acid 500 mg/day, albendazole @ 400 mg stat, diethylcarbamazine @ 100 mg/day, p.o., for fourteen days along with topically lignocaine gel for application on affected area. After a gap of 7 days, a 14 days course of diethylcarbamazine was repeated with previous dose rate. Uneventful recovery was recorded.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Anterior chamber live Loa loa: Case report

We reported a case of unusual intraocular Loa loa in a 27-year-old patient who presented with painful red eye. Biomicroscopy revealed a living and active adult worm in the anterior chamber of the right eye. After surgical extraction under local anesthesia, parasitological identification confirmed L. loa filariasis.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Diethylcarbamazine inhibits NF-kappaB activation in acute lung injury induced by carrageenan in mice

Diethylcarbamazine citrate (DEC) is widely used to treat lymphatic filariasis and Tropical Pulmonary Eosinophilia. A number of studies have reported a possible role in the host immune system, but exactly how DEC exerts this effect is still unknown. The present study reports the effects of DEC pretreatment on NF-kappaB regulation using the pleurisy model induced by carrageenan. Swiss male mice (Mus musculus) were divided into four experimental groups: control (SAL); carrageenan (CAR); diethylcarbamazine (DEC) and curcumin (CUR). The animals were pretreated with DEC (50mg/kg, v.o), CUR (50mg/kg, i.p) or distilled water for three consecutive days before pleurisy. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test, and values were considered statistically significant when p<0.05. DEC pretreatment reduced tissue damage and the production of inflammatory markers, such as NO, iNOS, PGE2, COX-2, and PARP induced by carrageenan. Similarly, a known inhibitor of NF-kappaB pathway (curcumin) was also able to reduce these parameters. Like curcumin, DEC prevents NF-kappaB activation by reducing NF-kappaB p65 phosphorylation and IkappaBalpha degradation. DEC prevented NF-kappaB activation via p38 MAPK, but did not interfere in the ERK pathway in this experimental model. However, further studies should be developed to confirm this hypothesis. These findings suggest that DEC could be a promising drug for inflammatory disorders, especially in pulmonary diseases such as Acute Lung Inflammation, due its high anti-inflammatory potential which prevents NF-kappaB activation. I hope this article can help some friends in scientific research. I am very proud of our efforts over the past few months and hope to 4730-54-5, help many people in the next few years.category: catalyst-ligand

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI