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Gopinath P.M.,Sooriya Hospital | Kalra B.,Bharti Research Institute of Diabetes and Endocrinology BRIDE | Saxena A.,Menz Health Clinic | Malik S.,Holy Angels Hospital | And 3 more authors.
International Journal of Infertility and Fetal Medicine | Year: 2013

Introduction: To assess the effectiveness and safety of fixed dose combination (FDC) of antioxidants in treatment of idiopathic oligoasthenozoospermia. Materials and methods: Placebo-controlled, Double-blind, randomized, Parallel three arm, Multicentric trial. Setting: Fertility clinics of five centers across India. Patients: One hundred and thirty-eight male subjects, aged between 21 and 50 years and subfertile for 1 year or more with the following baseline sperm selection criteria: Concentration <15 million/ml and total sperm motility <40%. Intervention(s): Eligible subjects were randomized to either of the three arms in a double-blind manner, i.e. arm 1 was given 2 tablets twice daily of FDC of antioxidants (coenzyme-Q10: 50 mg, L-carnitine: 500 mg, lycopene: 2.5 mg and zinc: 12.5 mg); arm 2 was given 1 tablet of FDC of antioxidants and one tablet of placebo twice daily and arm 3 was two tablets twice daily of matching placebo all for 180 days. Main outcome measure(s): The primary outcome measures were improvement in sperm count and sperm motility, whereas pregnancy rate was the secondary efficacy outcome. Results: Compared to placebo, a statistically significant improvement was seen in sperm count (14.8-26.35 in arm 1 and 14.37-24.8 million/ml in arm 2, p < 0.0001), and sperm total motility (39.2-51.6% in arm 1 and 38.4-50.1% in arm 2, p < 0.0001), at 90 days, and treatment further improved these parameters at day 180. No intergroup difference was seen between arm 1 and arm 2. Mild adverse event of upper gastrointestinal discomfort by 8 subjects (three in arm 1; one in arm 2 and four subjects in arm 3) were reported. No serious adverse event was seen in the study. Conclusion: Exogenous administration of fixed dose combination of antioxidants is a safe and effective therapy in improving the male subfertility.


Mathew A.,Toyo University | Fukuda T.,Toyo University | Nagaoka Y.,Toyo University | Hasumura T.,Toyo University | And 5 more authors.
PLoS ONE | Year: 2012

Alzheimer's disease is a growing concern in the modern world. As the currently available medications are not very promising, there is an increased need for the fabrication of newer drugs. Curcumin is a plant derived compound which has potential activities beneficial for the treatment of Alzheimer's disease. Anti-amyloid activity and anti-oxidant activity of curcumin is highly beneficial for the treatment of Alzheimer's disease. The insolubility of curcumin in water restricts its use to a great extend, which can be overcome by the synthesis of curcumin nanoparticles. In our work, we have successfully synthesized water-soluble PLGA coated- curcumin nanoparticles and characterized it using different techniques. As drug targeting to diseases of cerebral origin are difficult due to the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet-1 peptide, which has the affinity to neurons and possess retrograde transportation properties. Our results suggest that curcumin encapsulated-PLGA nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can be used as a drug with multiple functions in treating Alzheimer's disease proving it to be a potential therapeutic tool against this dreaded disease. © 2012 Mathew et al.


Giri H.,Indian Institute of Technology Madras | Chandel S.,Indian Institute of Technology Madras | Dwarakanath L.S.,Sooriya Hospital | Sreekumar S.,Sooriya Hospital | Dixit M.,Indian Institute of Technology Madras
PLoS ONE | Year: 2013

Objective: The aim of this study was to determine subclinical inflammation in umbilical vein derived endothelial cells (HUVECs) obtained from Asian Indian subjects with gestational diabetes (GDM) and to determine levels of angiogenic factors and arginase activity in their cord blood. Methods: This case-control study included 38 control and 30 GDM subjects. Subjects were confirmed as GDM based on 75g oral glucose tolerance test (OGTT) conducted in the second trimester of pregnancy. Angiogenic markers and arginase activity were measured in cord blood by ELISA and colorimetric methods respectively. Endothelial inflammation was assessed through adhesion of PKH26-labelled leukocytes onto HUVEC monolayer obtained from the study groups. Gene and surface expression of adhesion molecules were confirmed via reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry respectively. Results: The study revealed increased adhesion of leukocytes to HUVECs isolated from GDM subjects compared to controls. HUVECs of babies born to GDM mothers had increased surface and mRNA expression of E-selectin. sTie2 levels were significantly higher in the cord blood for GDM subjects (3869 ± 370 ng/L) compared to controls (3045 ± 296 ng/L). Furthermore, arginase activity was higher in cord blood of GDM mothers as opposed to the control group (7.75 ± 2.4 μmoles of urea/ml/hour vs 2.88 ±0.49 μmoles of urea/ml/hour; p-value= 0.019). Spearman's correlation analysis revealed positive correlation of cord blood arginase activity with glucose intolerance (ρ=0.596, p=0.004) and post load glucose values (ρ=0.472, p=0.031) of mothers observed during the second trimester of pregnancy. Conclusions: HUVECs derived from Asian Indian GDM mothers, exhibit signs of sub-clinical endothelial inflammation along with increased levels of sTie2 and arginase activity in their cord blood serum. © 2013 Giri et al.


Mathew A.,Toyo University | Aravind A.,Toyo University | Brahatheeswaran D.,Toyo University | Fukuda T.,Toyo University | And 8 more authors.
BioNanoScience | Year: 2012

Alzheimer's disease is becoming a serious concern in the medical field due to its severity and prevalence. This multifactorial disease manifested by various genetic and nongenetic factors makes its treatment very difficult. Due to the inefficacy of the currently available drugs, newer therapeutic strategies are increasingly in demand. Most of the current drug discovery initiatives are pivoted around amyloid pathology which is considered to be central to the disease progression. In this work, we propose the use of amyloid-binding aptamer conjugated to poly(lactic-co-glycolic acid) (PLGA)-coated curcumin nanoparticles to bind to the amyloid plaques. Curcumin is a plant-derived compound with reported anti-amyloid activity. Recent reports reveal the importance of plasma amyloid in Alzheimer development. We propose that the amyloid-binding aptamer attached curcumin-PLGA nanoparticles can be used as a potential tool in targeting the plasma amyloid and thus helps in Alzheimer therapy. © Springer Science+Business Media, LLC 2012.


Shankar S.P.,Glenmark Pharmaceuticals Ltd | Shankar S.P.,Aarupadai Veedu Medical College and Hospital | Awad N.T.,Glenmark Pharmaceuticals Ltd | Chandrashekharan S.,Glenmark Pharmaceuticals Ltd | And 3 more authors.
Journal of the Indian Medical Association | Year: 2010

Patients with acute bronchitis, acute exacerbations of chronic bronchitis and asthmatic bronchitis suffer from cough with tenacious bronchial secretions requiring expectorants in addition to bronchodilating therapy. The present one-week, multicentric, prospective, randomised, double-blind study compared the efficacy and tolerability of three expectorant formulations in 426 patients with productive cough associated with varied aetiology after approval by the institutional review boards. Selected patients received 7 days' treatment with either fixed dose combination (FDC) of salbutamol 2mg + bromhexine HCl 8mg + guaiphenesin 100 mg (group A) or salbutamol 2mg+ guaiphenesin 100 mg expectorant (group B) or salbutamol 2mg + bromhexine 8mg (group C) thrice daily after obtaining their informed consent. In group A, there was improvement of symptoms in a larger number of patients and earlier onset of action in reducing cough frequency and severity and improving sputum characteristics as compared to the other two groups. More patients in group A reported excellent efficacy (44.4%) as compared to only 14.6% in Group B and 13% in Group C. Cough expectorant containing salbutamol + bromhexine +guaiphenesin could be the expectorant of choice in alleviating productive cough since it scored in terms of efficacy as well as tolerability over salbutamol with either bromhexine or guaiphenesin alone.


Balasubramanian S.,Toyo University | Ravindran Girija A.,Toyo University | Nagaoka Y.,Toyo University | Fukuda T.,Toyo University | And 5 more authors.
RSC Advances | Year: 2015

Nanoscience and nanotechnology utilize nanoparticles to provide several remarkable applications in biomedical fields such as bio imaging, diagnosis of several diseases, and efficient drug delivery. Multifunctional magnetic nanoparticles (MNPs) are a significant type of nanomaterials that are capable of developing therapeutic as well as diagnostic (theragnostic) applications. Multifunctional hybrid magnetic nanoparticles, as efficient theragnostic representatives, have been developed. The hybrid magnetic nanoparticles (HMNP)-Au-MNPs have been assimilated into PLGA NPs along with two potent chemotherapeutic agents (curcumin and gemcitabine). Delivering chemotherapeutics into cancer cells with multiple targeting moieties is an attractive area in cancer therapeutics. In this study, the nanoconjugates have been tailored to target the pancreatic and breast cancer cells by attaching three specific targeting ligands (folate, transferrin and AS1411 aptamer). Moreover, we report a nanoparticle-based delivery system that can deliver therapeutic cargos to the cancer cells and can exert its lethality by three distinctive modes (chemotherapeutic, photothermal and magnetic hyperthermia) either independently or by the synergistic action of drug and hyperthermia. Overall our results display an 'all in one' approach with the same nanoformulation for the combined destruction of cancer cells. The developed nanoformulation was highly versatile in terms of the choice of implementing lethality, depending on the cancer type. This journal is © The Royal Society of Chemistry.


Brahatheeswaran D.,Toyo University | Mathew A.,Toyo University | Aswathy R.G.,Toyo University | Nagaoka Y.,Toyo University | And 4 more authors.
Biomedical Materials | Year: 2012

Nanomedicine utilizes engineered nanodevices and nanostructures for monitoring, repair, construction and control of human biological systems at the molecular level. In this study, we investigated the feasibility and potential of zein nanofiber as a delivery vehicle for curcumin in biomedical applications. By optimizing the electrospinning parameters, ultrafine zein fluorescence nanofibers containing curcumin were developed with interconnected fibrous networks. We found that these nanofibers show an increase in fluorescence due to the incorporation of curcumin. The morphology and material properties of the resulting multifunctional nanofiber including the surface area were examined by a field emission-scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and confocal microscopy. The surface area and pore size were characterized by N2 adsorption-desorption isotherm. SEM and fluorescence images showed that the uniform fibers with smooth surface had an average diameter of about 310 nm. An in vitro degradation study showed significant morphological changes. The in vitro evaluations suggested that the curcumin incorporated zein nanofibers showed sustained release of curcumin and maintained its free radical scavenging ability. It provides an attractive structure for the attachment and growth of fibroblast as cell culture surfaces. The results demonstrate that the curcumin loaded zein nanofiber could be a good candidate for soft tissue engineering scaffolds and has the potential for further applications in drug delivery system. © 2012 IOP Publishing Ltd.


Balasubramanian S.,Toyo University | Ravindran Girija A.,Toyo University | Nagaoka Y.,Toyo University | Iwai S.,Toyo University | And 5 more authors.
International Journal of Nanomedicine | Year: 2014

The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU]) and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes) by initiating early and late apoptosis. © 2014 Sivakumar etal.


PubMed | Sooriya Hospital and Indian Institute of Technology Madras
Type: Journal Article | Journal: PloS one | Year: 2013

The aim of this study was to determine subclinical inflammation in umbilical vein derived endothelial cells (HUVECs) obtained from Asian Indian subjects with gestational diabetes (GDM) and to determine levels of angiogenic factors and arginase activity in their cord blood.This case-control study included 38 control and 30 GDM subjects. Subjects were confirmed as GDM based on 75g oral glucose tolerance test (OGTT) conducted in the second trimester of pregnancy. Angiogenic markers and arginase activity were measured in cord blood by ELISA and colorimetric methods respectively. Endothelial inflammation was assessed through adhesion of PKH26-labelled leukocytes onto HUVEC monolayer obtained from the study groups. Gene and surface expression of adhesion molecules were confirmed via reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry respectively.The study revealed increased adhesion of leukocytes to HUVECs isolated from GDM subjects compared to controls. HUVECs of babies born to GDM mothers had increased surface and mRNA expression of E-selectin. sTie2 levels were significantly higher in the cord blood for GDM subjects (3869 370 ng/L) compared to controls (3045 296 ng/L). Furthermore, arginase activity was higher in cord blood of GDM mothers as opposed to the control group (7.75 2.4 moles of urea/ml/hour vs 2.88 0.49 moles of urea/ml/hour; p-value= 0.019). Spearmans correlation analysis revealed positive correlation of cord blood arginase activity with glucose intolerance (=0.596, p=0.004) and post load glucose values (=0.472, p=0.031) of mothers observed during the second trimester of pregnancy.HUVECs derived from Asian Indian GDM mothers, exhibit signs of sub-clinical endothelial inflammation along with increased levels of sTie2 and arginase activity in their cord blood serum.


The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU]) and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes) by initiating early and late apoptosis.

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