Faisal Kunnathodi | Baylor University Medical Center (original) (raw)

Papers by Faisal Kunnathodi

American Journal of Biomedical Science & Research, 2021

This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.001984.

Transplantation, 2014

Background: Clinical application of islet transplantation to treat type-1 diabetes has been limit... more Background: Clinical application of islet transplantation to treat type-1 diabetes has been limited by islet allograft destruction by both allogeneic and autoimmune diabetogenic T-cell responses. The current study aims at determining whether an anti-T-cell receptor (TCR) monoclonal antibody (mAb) has potential as a novel and potent induction immunotherapy for islet transplantation. Methods: We have investigated the therapeutic effi cacy and mechanisms of action of anti-TCR therapy in four different murine models, which comprise either allo-or auto-immune responses alone or in combination. Results: The T-cell response to islet allografts was potently abrogated by a brief treatment with an anti-TCRβ mAb (clone H57-597), resulting in long-term survival (MST: 93.1±30.0 days compared to the untreated group: 15.6±1.7 days, p < 0.001) of BALB/c islet allografts in Streptozotocin-induced diabetic B6 mice. Moreover, transient anti-TCR treatment permanently prevented BALB/c skin allograft rejection on Rag1-/-B6 recipients that were reconstituted with Foxp3+ regulatory T-cell depleted B6 splenocytes, but did not impair the ability of the reconstituted cells to reject the later transplanted C3H skin allografts (transplanted at 120 days after BALB/c skin grafting). Transient anti-TCR treatment was also able to completely prevent diabetes onset in NOD.SCID.γc-/-mice that were transferred with lymphocytes from diabetic NOD mice. Next, transient anti-TCR treatment signifi cantly prolonged the survival of transplanted BALB/c islets in overtly diabetic NOD mice (MST: 28.0±7.7 days vs. untreated group: 8.7±0.6 days; p < 0.05), a model in which there are both allogeneic and autoimmune diabetogenic T-cell responses to the transplanted islets. Conclusions: Overall, anti-TCR mAb induced peripheral tolerance to specifi c alloantigens even in the absence of Foxp3-expressing natural regulatory T-cells. These fi ndings reveal the potential for using TCR-targeting mAbs as induction immunotherapy for islet transplantation.

Journal of Endocrinology and Reproduction, 2016

Quassia amara is a Brazilian medicinal plant traditionally used as an herbal remedy for a variety... more Quassia amara is a Brazilian medicinal plant traditionally used as an herbal remedy for a variety of diseases. Quassin is the major secondary chemical compound in it, which is under investigation as an anti-malarial compound. There are preliminary studies implicating Q. amara in male reproductive toxicity. Hence, this elaborate study was undertaken to find the male reproductive toxic effects of Q. amara and quassin. Methanolic extract of Q. amara bark and quassin were administered to male mice for 35 days. The cauda epididymidal sperm, testis and epididymis were subjected to analysis adopting light and transmission electron microscopy. Sperm counts, motility and viability decreased. The incidence of sperm with abnormal morphologies increased. There was premature loss of germ cells from the seminiferous tubules, which correlated with Sertoli cell pathology. The Leydig cells were vacuolated, suggesting a hypo-androgen status. The epididymis indicated severe histopathological changes, ...

Vaccines

Chikungunya virus (CHIKV) is an infectious agent spread by mosquitos, that has engendered endemic... more Chikungunya virus (CHIKV) is an infectious agent spread by mosquitos, that has engendered endemic or epidemic outbreaks of Chikungunya fever (CHIKF) in Africa, South-East Asia, America, and a few European countries. Like most tropical infections, CHIKV is frequently misdiagnosed, underreported, and underestimated; it primarily affects areas with limited resources, like developing nations. Due to its high transmission rate and lack of a preventive vaccine or effective treatments, this virus poses a serious threat to humanity. After a 32-year hiatus, CHIKV reemerged as the most significant epidemic ever reported, in India in 2006. Since then, CHIKV-related research was begun in India, and up to now, more than 800 peer-reviewed research papers have been published by Indian researchers and medical practitioners. This review gives an overview of the outbreak history and CHIKV-related research in India, to favor novel high-quality research works intending to promote effective treatment an...

Transplantation, 2014

Background: Although hypothermia attenuates renal injury induced by ischemiareperfusion (IR), pre... more Background: Although hypothermia attenuates renal injury induced by ischemiareperfusion (IR), precise molecular pathways have not been known yet. Our previous study showed ERK phosphrylation plays an important role in hypothermic protection in renal IR injury. Hypoxia-inducible factor-1(HIF-1) has been known as one of the potent protective proteins in IR injury. We evaluated the role of HIF-1 and interaction with ERK phosphorylation in hypothermic protection of renal IR injury. Methods: C57Bl/6 mice were divided into four groups; sham operated mice, cold IR mice(30°C), warmIR mice(37°C) and PD98059(MAP kinase kinase inhibitor) treated cold IR mice(IR injury; reperfusion 27 minutes after clamping of both renal artery and vein). Kidneys were harvested at 10min and 27min after both renal artery ischemia and 24hr after IR injury. Renal HIF-1, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC 1-alpha), AMP-activated protein kinase(AMPK), and 8-hydroxydeoxyguanosine(8-OHdG) were evaluated by western blot and immuohistochemical stain. BUN and serum creatinine(s-Cr) were measured 24 hrs after IR injury. TUNEL staining and light microscopic examination of kidneys was performed to evaluate the magnitude of renal injury. Results: Serum creatinine(s-Cr), tissue injury score, and 8-OHdG and TUNEL positive cells in cold IR mice were signifi cantly lower than those of warm IR mice (all, p<0.01).s-Cr, and tissue injury score,8-OHdG and TUNEL positive cells in kidneys of PD98059 treated cold IR mice were signifi cantly higher than those ofuntreated cold IR mice(all, p<0.05). Renal HIF-1, PGC 1-alpha, and AMPK expression were signifi cantly increased in the kidneys of cold ischemic mice at10min and 27min after both renal artery clamping compared to sham operated mice. PD98059 treatment in cold IR mice decreased renal HIF-1 signifi cantly (p<0.01). However, PGC-1 alpha and AMPK were not changed. Conclusions: In conclusion,HIF-1 preservation induced by ERK phosphorylation may be involved in hypothermic protection of renal ischemia-reperfusion injury.

Transplantation, 2014

without eupatilin. In vitro, islet viability and function were assessed. After treatment with a c... more without eupatilin. In vitro, islet viability and function were assessed. After treatment with a cytokine cocktail (TNF-α, INF-γ and IL-1β), cell viability, function and apoptosis were found with the islet cells. The GSH levels were measured in islet cells. Both HSP70 and proteins related to apoptosis were analyzed by Western blots. Viability and function was similar between the two groups. After treatment with a cytokine cocktail, viability were signifi cantly improved in eupatilin-treated islets compared with cytokine group. The GSH levels were signifi cantly elevated in the eupatilin-treated group. HSP70 expression in islets treated with eupatilin was markedly stronger compared with the control and cytokine group. Cytokine treated islets produced signifi cantly higher levels of PARP,caspase-3 than islets treated with eupatilin. The eupatilin-treated group showed attenuated cytokine-induced apoptosis. These results suggested that preoperative eupatilin administration induced HSP70 before islet transplantation, thus attenuating cytokine-induced apoptosis, which might be potential tool to mitigate the ischemic damage to islet cells and the early infl ammation at the site of implantation.

Journal of Endocrinology and Reproduction, 2006

In the background of the decreasing trend of male reproductive health in men and animals, the pre... more In the background of the decreasing trend of male reproductive health in men and animals, the present study was aimed at finding gravimetric, histopathologoical and histometric changes in the testis of Swiss mouse in response to treatment of aflatoxin B 1 (AFB 1 ) in a chronic toxicity testing over different periods of time and at finding recovery, if any, after cessation of the treatment. AFB 1 suspended in corn oil and ethanol, was administered through intraperitoneal route to 90 day old Swiss mouse at a daily dose of 50mg/kg body weight for 7, 15, 35, 45 days. In the recovery group the mice were kept, after cessation of the treatment, under observation for 35 or 70 days. The testicles and seminal vesicles of the animals were subjected to histopathological analysis adopting paraffin/resin embedding and light microscopy. Computer assisted histometric analysis of several parameters was also made. In general there was little impact of the treatment in the animals treated for 7 days. ...

Ubiquitination is believed to play a critical role in removal of dead and/or defective spermatozo... more Ubiquitination is believed to play a critical role in removal of dead and/or defective spermatozoa in normal and, more importantly, under circumstances when such spermatozoa are produced in large numbers due to genetic defects or toxic manifestations. Ubiquitination under such instances would involve specific gene expressions, many of which are not yet clearly understood. In an exhaustive study in Swiss mouse model to find the spermatotoxic effect of quassin, a diterpene compound isolated from Quassia amara , we found most of the spermatozoa to be abnormal in morphology and unviable. In the present study, we aimed at analysing the transcriptional profile of three selected genes, Ubb, Ube2c and Psmb8, involved in the ubiquitin proteolytic pathway in the testis and epididymal segments of Q. amara bark methanol extract treated mice adopting semi-quantitative RT-PCR and to study the level of DNA damage of the treated mouse spermatozoa. The results revealed that the treatment induced con...

Transplantation, 2014

Background: We have treated islet transplant recipients with thymoglobulin induction and maintena... more Background: We have treated islet transplant recipients with thymoglobulin induction and maintenance immunosuppression consisted of sirolimus or mycophenolate along with either efalizumab to block LFA-1. Dosing of sirolimus or mycophenolate was adjusted when efalizumab was withdrawn from the market. The immunological impact of Elalizumab was compared to belatacept in this study. Methods: Peripheral blood mononuclear cells were collected and cryopreserved beginning at enrollment before transplantation. Donor spleens were banked at the time of transplant. Percentages of regulatory T cells (Tregs) were determined using fl ow cytometry. Proliferative responses of CD4, CD8, and Tregs were measured in vitro using a CFSE dilution assay. Results: All patients on efalizumab showed dramatic increase of percentage of Tregs from 5 to 10% among CD4 + T cells pre-transplant to peaks of 15 to 67% between 1 and 3 months post transplant. Treg percentages remained elevated while patients were on the regimen. T cell proliferation to donor and polyclonal stimulations was markedly reduced in patients on efalizumab and returned to pre-transplant levels 5 months after the cessation of efalizumab (Figure 1). In contrast, percentages of Tregs and T cell proliferative responses remained stable in patients on the belatacept. Efalizumab led to profound changes of patients' immunological make-up when compared to belatacept. Particularly, one of the most severely immunosuppressed efalizumab patient experienced recurrent infections that necessitated complete withdrawal of immunosuppression. Her anti-donor and polyclonal responses rebounded from non-detectable levels to her pre-transplant baseline after efalizumab withdrawal. Remarkably, she has remained insulin independent despite receiving no immunosuppression in the past 16 months. Conclusion: Efalizumab increases percentages of circulating Tregs and profoundly suppresses T cell reactivity. Short-term efalizumab treatment may promote transplantation tolerance.

Transplantation, 2014

Introduction: We have shown that the autoimmune response to GAD65 peptide is a crucial cause of g... more Introduction: We have shown that the autoimmune response to GAD65 peptide is a crucial cause of graft dysfunction in clinical islet transplantation for type 1 diabetes and a signifi cant IFNγ release from CD4+ or CD8+ T cells which corresponded with the autoimmune response. In this study, the serum IFNγ levels in allogeneic islet recipients were assessed, in comparison with autologous recipients. Methods: Six allogeneic and 6 autologous islet recipients were included. Patients in both groups matched in basic characteristics. There was no difference in transplanted islet dose between both groups: 9,393±707 and 7,949±672 IEQ/kg of body weight, respectively (p=0.17). All recipients were administered with both etanercept and anakinra from Day 0 to 10. Autoimmune response was investigated with EpiMax assay after stimulation of peripheral blood mononuclear cells by GAD65 peptide clusters. Cytokine levels were measured using Luminex assay. Results: Signifi cant IFNγ production from both CD4+ and CD8+ T cells was observed at peri-transplant in allogeneic islet recipients (Fig. A). Signifi cant elevation of serum IFNγ levels were also seen immediately after islet infusion in allo-recipients and the elevation were sustained for 7 days (Fig. B). Autologous recipients, however, did not show signifi cant increase in IFNγ levels. Conclusions: Signifi cant difference in serum IFNγ levels was observed between allogeneic and autologous islet recipients even when similar dose of islets were transplanted. Further characterization of IFNγ production may help to determine the role of autoimmune response in clinical islet transplantation. Figure. An example of IFNγ production in EpiMax assay in an allogeneic recipient (A) and serum IFNγ levels in islet transplantation (B) are shown.

Mammalian Endocrinology and Male Reproductive Biology, 2015

Andrologia, 2021

Gross alterations in the morphology of spermatozoa, teratozoospermia, invariably render them inca... more Gross alterations in the morphology of spermatozoa, teratozoospermia, invariably render them incapable of fertilisation. One of the contributory factors to teratozoospermia is failure of spermatozoon to shed the cytoplasmic droplet even after their arrival at epididymis. Quassia amara and quassin are of medicinal value with special reference to malaria. Nevertheless, there are also reports implicating Quassia/quassin in male reproductive toxicity. We were interested in finding if its therapeutic application would jeopardise male fertility. So, we tested it for male reproductive toxicity by analysing, among other aspects, abnormal sperm morphologies, and made a systematic analysis of the spermatozoa of treated mice before they are spermiated and until they arrive at the cauda epididymis. The spermatozoa not only failed to shed the cytoplasmic droplet during epididymal transit but swell to a very large size and were angulated, resulting in Dag‐like defect or lasso shape. A link between cytoplasmic droplet that was retained and lasso shape of tail was indicated. This article traces the structural changes in spermatozoa that lead to angulation, flexion and coiling of the tail, caused due to retention of cytoplasmic droplet, and explains one of the mechanisms of toxicant‐induced teratozoospermia.

Andrologia, 2020

The epididymis responds to adverse conditions of misshapen spermatozoa resulting from pathologica... more The epididymis responds to adverse conditions of misshapen spermatozoa resulting from pathological changes or toxic insults by secretion of a dense matrix that segregates the latter for complete disintegration and dissolution. The objective of this study was to find the source of this matrix and the role‐player of disintegration and dissolution of misshapen spermatozoa. We chose Wistar strain male rat model to tackle this issue, and the rats were administered with aflatoxin B1 for 55 days so as to increase the incidence of misshapen spermatozoa. At the end of the treatment, different segments of epididymis were processed for microscopic observations. We found that parallel with abundant misshapen spermatozoa in the epididymis the principal cells of the initial segment secrete enormous membrane‐bound apical blebs called aposomes, which contain epididymosomes. The aposomes were found to coalesce so as for the content to merge and form a dense matrix that entangles the misshapen spermatozoa and segregates them from viable spermatozoa. The epididymosomes associate with the misshapen spermatozoa, and the latter is processed to disintegration and total dissolution. Therefore, we assign the role of segregation of misshapen spermatozoa from viable ones to the dense matrix of aposomes and their disintegration and dissolution to the epididymosomes.

Neurological Research, 2017

To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food ... more To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded. A separate batch of animals was used for the determination of serotonin (5HT) and 5 hydroxyindole acetic acid (5HIAA) levels in the brain. Harmaline treatment resulted in characteristic tremor that lasted for more than 2 hours and decreased the locomotor activity of rats. Pre-treatment with vanillin significantly reduced the duration, intensity, and tremor index of harmaline-treated animals. Vanillin treatment also significantly attenuated harmaline-induced decrease in the locomotor activity. An increase in 5HT levels and the changes in 5HIAA/5HT ratio observed in harmaline treated rats were significantly corrected in vanillin pretreated animals. Vanillin in low doses reduces harmaline-induced tremor in rats, probably through its modulating effect on serotonin levels in the brain. These findings suggest a beneficial effect of vanillin in essential tremor.

Aflatoxins, highly oxygenated, heterocyclic, difuranocoumarin compounds that could be present in ... more Aflatoxins, highly oxygenated, heterocyclic, difuranocoumarin compounds that could be present in human foods and animal feedstuffs, are an important group of mycotoxins produced by the fungi Aspergillus flavus, A. parasiticus and A. nomius (Diaz et al., 2008). Other species of Aspergillus such as A. bombycis, A. ochraceoroseus and A. pseudotamari may also produce aflatoxins (Bennett & Klich, 2003; Klich et al., 2000; Mishra & Das, 2003). On a worldwide scale, the aflatoxins are found in stored food commodities and oil seeds ...

Fragrances are generally synthetic, natural or a combination of both. Ittar or Attar is a natural... more Fragrances are generally synthetic, natural or a combination of both. Ittar or Attar is a natural fragrance material synthesized from plants which were majorly used by people worldwide as a matter of pride, deodorization and attractant. The effect and role of using Ittar on mammalian system is still not known at the behavioral and neurological level. This study was aimed to understand the constituents and the effect of Ittar on mice by measuring their behavioral and neurological changes upon exposure to Ittar. Batches of animals were exposed to ten different types of Ittar for 1, 2 and 3 weeks respectively. Behavior of the animals exposed to the Ittar perfumes were analyzed against the control animals behavior for physiological activities. Also, the expression level of neurotransmitter such as Dopamine, 5-HIAA, HVA and Serotonin were evaluated based on HPLC analysis. Based on this study it was found that all the ten Ittars were different for its different constituents with some basi...

Diabetes

discussion and reviewed and edited the manuscript. M.C.L. researched data and wrote the manuscrip... more discussion and reviewed and edited the manuscript. M.C.L. researched data and wrote the manuscript. M.C.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Journal of Neurology and Experimental Neuroscience, 2016

Background: Essential tremor (ET) is a common neurological disorder. Genetic, environmental and d... more Background: Essential tremor (ET) is a common neurological disorder. Genetic, environmental and dietary factors have been suggested to contribute to ET. The present study investigates the effect of vanillin, a polyphenol food additive with strong neuroprotective activity in harmaline induced tremors in rats. Methods: Seventy two male Sprague Dawley rats weighing 115 ± 5 g were divided into twelve groups of six animals each. Four groups were allotted to each study. Vanillin (50 mg, 100 mg, and 200 mg/kg) was administered ten minutes after the induction of tremor (therapeutic study) and before the induction of tremor (prophylactic study). In the acute prophylactic study, it was administered 30 m before and for sub-acute prophylactic study it was administered 7 days before the induction of tremor. Harmaline (10 mg/kg, IP.), was used for the induction of tremor. The latency of onset, duration, intensity of tremor and tremor index were recorded. Results: Harmaline treatment produced characteristic tremor that lasted for more than 2 hours. Vanillin both in therapeutic and prophylactic studies failed to produce any significant change in the latency of onset of tremor. The duration of tremor was significantly reduced in both therapeutic and acute prophylactic treatment, but the reduction was not significant in sub-acute prophylactic studies, while the intensity of tremor and tremor index were significantly reduced in both the therapeutic and prophylactic studies. Discussion: The present study suggests that vanillin ameliorates harmaline induced tremor in rats. Further detailed studies are warranted to understand the mechanism of this protection.

Journal of venom research, 2016

Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the ... more Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the host on envenomation and may also have a therapeutic potential. Scorpion venoms produced by the columnar cells of venom gland are complex mixture of mucopolysaccharides, neurotoxic peptides and other components. This study was aimed at cataloguing the elemental composition of venoms obtained from medically important scorpions found in the Arabian peninsula. The global elemental composition of the crude venom obtained from Androctonus bicolor, Androctonus crassicauda and Leiurus quinquestriatus scorpions were estimated using ICP-MS analyzer. The study catalogued several chemical elements present in the scorpion venom using ICP-MS total quant analysis and quantitation of nine elements exclusively using appropriate standards. Fifteen chemical elements including sodium, potassium and calcium were found abundantly in the scorpion venom at PPM concentrations. Thirty six chemical elements of di...

American Journal of Biomedical Science & Research, 2021

This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.001984.

Transplantation, 2014

Background: Clinical application of islet transplantation to treat type-1 diabetes has been limit... more Background: Clinical application of islet transplantation to treat type-1 diabetes has been limited by islet allograft destruction by both allogeneic and autoimmune diabetogenic T-cell responses. The current study aims at determining whether an anti-T-cell receptor (TCR) monoclonal antibody (mAb) has potential as a novel and potent induction immunotherapy for islet transplantation. Methods: We have investigated the therapeutic effi cacy and mechanisms of action of anti-TCR therapy in four different murine models, which comprise either allo-or auto-immune responses alone or in combination. Results: The T-cell response to islet allografts was potently abrogated by a brief treatment with an anti-TCRβ mAb (clone H57-597), resulting in long-term survival (MST: 93.1±30.0 days compared to the untreated group: 15.6±1.7 days, p < 0.001) of BALB/c islet allografts in Streptozotocin-induced diabetic B6 mice. Moreover, transient anti-TCR treatment permanently prevented BALB/c skin allograft rejection on Rag1-/-B6 recipients that were reconstituted with Foxp3+ regulatory T-cell depleted B6 splenocytes, but did not impair the ability of the reconstituted cells to reject the later transplanted C3H skin allografts (transplanted at 120 days after BALB/c skin grafting). Transient anti-TCR treatment was also able to completely prevent diabetes onset in NOD.SCID.γc-/-mice that were transferred with lymphocytes from diabetic NOD mice. Next, transient anti-TCR treatment signifi cantly prolonged the survival of transplanted BALB/c islets in overtly diabetic NOD mice (MST: 28.0±7.7 days vs. untreated group: 8.7±0.6 days; p < 0.05), a model in which there are both allogeneic and autoimmune diabetogenic T-cell responses to the transplanted islets. Conclusions: Overall, anti-TCR mAb induced peripheral tolerance to specifi c alloantigens even in the absence of Foxp3-expressing natural regulatory T-cells. These fi ndings reveal the potential for using TCR-targeting mAbs as induction immunotherapy for islet transplantation.

Journal of Endocrinology and Reproduction, 2016

Quassia amara is a Brazilian medicinal plant traditionally used as an herbal remedy for a variety... more Quassia amara is a Brazilian medicinal plant traditionally used as an herbal remedy for a variety of diseases. Quassin is the major secondary chemical compound in it, which is under investigation as an anti-malarial compound. There are preliminary studies implicating Q. amara in male reproductive toxicity. Hence, this elaborate study was undertaken to find the male reproductive toxic effects of Q. amara and quassin. Methanolic extract of Q. amara bark and quassin were administered to male mice for 35 days. The cauda epididymidal sperm, testis and epididymis were subjected to analysis adopting light and transmission electron microscopy. Sperm counts, motility and viability decreased. The incidence of sperm with abnormal morphologies increased. There was premature loss of germ cells from the seminiferous tubules, which correlated with Sertoli cell pathology. The Leydig cells were vacuolated, suggesting a hypo-androgen status. The epididymis indicated severe histopathological changes, ...

Vaccines

Chikungunya virus (CHIKV) is an infectious agent spread by mosquitos, that has engendered endemic... more Chikungunya virus (CHIKV) is an infectious agent spread by mosquitos, that has engendered endemic or epidemic outbreaks of Chikungunya fever (CHIKF) in Africa, South-East Asia, America, and a few European countries. Like most tropical infections, CHIKV is frequently misdiagnosed, underreported, and underestimated; it primarily affects areas with limited resources, like developing nations. Due to its high transmission rate and lack of a preventive vaccine or effective treatments, this virus poses a serious threat to humanity. After a 32-year hiatus, CHIKV reemerged as the most significant epidemic ever reported, in India in 2006. Since then, CHIKV-related research was begun in India, and up to now, more than 800 peer-reviewed research papers have been published by Indian researchers and medical practitioners. This review gives an overview of the outbreak history and CHIKV-related research in India, to favor novel high-quality research works intending to promote effective treatment an...

Transplantation, 2014

Background: Although hypothermia attenuates renal injury induced by ischemiareperfusion (IR), pre... more Background: Although hypothermia attenuates renal injury induced by ischemiareperfusion (IR), precise molecular pathways have not been known yet. Our previous study showed ERK phosphrylation plays an important role in hypothermic protection in renal IR injury. Hypoxia-inducible factor-1(HIF-1) has been known as one of the potent protective proteins in IR injury. We evaluated the role of HIF-1 and interaction with ERK phosphorylation in hypothermic protection of renal IR injury. Methods: C57Bl/6 mice were divided into four groups; sham operated mice, cold IR mice(30°C), warmIR mice(37°C) and PD98059(MAP kinase kinase inhibitor) treated cold IR mice(IR injury; reperfusion 27 minutes after clamping of both renal artery and vein). Kidneys were harvested at 10min and 27min after both renal artery ischemia and 24hr after IR injury. Renal HIF-1, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC 1-alpha), AMP-activated protein kinase(AMPK), and 8-hydroxydeoxyguanosine(8-OHdG) were evaluated by western blot and immuohistochemical stain. BUN and serum creatinine(s-Cr) were measured 24 hrs after IR injury. TUNEL staining and light microscopic examination of kidneys was performed to evaluate the magnitude of renal injury. Results: Serum creatinine(s-Cr), tissue injury score, and 8-OHdG and TUNEL positive cells in cold IR mice were signifi cantly lower than those of warm IR mice (all, p<0.01).s-Cr, and tissue injury score,8-OHdG and TUNEL positive cells in kidneys of PD98059 treated cold IR mice were signifi cantly higher than those ofuntreated cold IR mice(all, p<0.05). Renal HIF-1, PGC 1-alpha, and AMPK expression were signifi cantly increased in the kidneys of cold ischemic mice at10min and 27min after both renal artery clamping compared to sham operated mice. PD98059 treatment in cold IR mice decreased renal HIF-1 signifi cantly (p<0.01). However, PGC-1 alpha and AMPK were not changed. Conclusions: In conclusion,HIF-1 preservation induced by ERK phosphorylation may be involved in hypothermic protection of renal ischemia-reperfusion injury.

Transplantation, 2014

without eupatilin. In vitro, islet viability and function were assessed. After treatment with a c... more without eupatilin. In vitro, islet viability and function were assessed. After treatment with a cytokine cocktail (TNF-α, INF-γ and IL-1β), cell viability, function and apoptosis were found with the islet cells. The GSH levels were measured in islet cells. Both HSP70 and proteins related to apoptosis were analyzed by Western blots. Viability and function was similar between the two groups. After treatment with a cytokine cocktail, viability were signifi cantly improved in eupatilin-treated islets compared with cytokine group. The GSH levels were signifi cantly elevated in the eupatilin-treated group. HSP70 expression in islets treated with eupatilin was markedly stronger compared with the control and cytokine group. Cytokine treated islets produced signifi cantly higher levels of PARP,caspase-3 than islets treated with eupatilin. The eupatilin-treated group showed attenuated cytokine-induced apoptosis. These results suggested that preoperative eupatilin administration induced HSP70 before islet transplantation, thus attenuating cytokine-induced apoptosis, which might be potential tool to mitigate the ischemic damage to islet cells and the early infl ammation at the site of implantation.

Journal of Endocrinology and Reproduction, 2006

In the background of the decreasing trend of male reproductive health in men and animals, the pre... more In the background of the decreasing trend of male reproductive health in men and animals, the present study was aimed at finding gravimetric, histopathologoical and histometric changes in the testis of Swiss mouse in response to treatment of aflatoxin B 1 (AFB 1 ) in a chronic toxicity testing over different periods of time and at finding recovery, if any, after cessation of the treatment. AFB 1 suspended in corn oil and ethanol, was administered through intraperitoneal route to 90 day old Swiss mouse at a daily dose of 50mg/kg body weight for 7, 15, 35, 45 days. In the recovery group the mice were kept, after cessation of the treatment, under observation for 35 or 70 days. The testicles and seminal vesicles of the animals were subjected to histopathological analysis adopting paraffin/resin embedding and light microscopy. Computer assisted histometric analysis of several parameters was also made. In general there was little impact of the treatment in the animals treated for 7 days. ...

Ubiquitination is believed to play a critical role in removal of dead and/or defective spermatozo... more Ubiquitination is believed to play a critical role in removal of dead and/or defective spermatozoa in normal and, more importantly, under circumstances when such spermatozoa are produced in large numbers due to genetic defects or toxic manifestations. Ubiquitination under such instances would involve specific gene expressions, many of which are not yet clearly understood. In an exhaustive study in Swiss mouse model to find the spermatotoxic effect of quassin, a diterpene compound isolated from Quassia amara , we found most of the spermatozoa to be abnormal in morphology and unviable. In the present study, we aimed at analysing the transcriptional profile of three selected genes, Ubb, Ube2c and Psmb8, involved in the ubiquitin proteolytic pathway in the testis and epididymal segments of Q. amara bark methanol extract treated mice adopting semi-quantitative RT-PCR and to study the level of DNA damage of the treated mouse spermatozoa. The results revealed that the treatment induced con...

Transplantation, 2014

Background: We have treated islet transplant recipients with thymoglobulin induction and maintena... more Background: We have treated islet transplant recipients with thymoglobulin induction and maintenance immunosuppression consisted of sirolimus or mycophenolate along with either efalizumab to block LFA-1. Dosing of sirolimus or mycophenolate was adjusted when efalizumab was withdrawn from the market. The immunological impact of Elalizumab was compared to belatacept in this study. Methods: Peripheral blood mononuclear cells were collected and cryopreserved beginning at enrollment before transplantation. Donor spleens were banked at the time of transplant. Percentages of regulatory T cells (Tregs) were determined using fl ow cytometry. Proliferative responses of CD4, CD8, and Tregs were measured in vitro using a CFSE dilution assay. Results: All patients on efalizumab showed dramatic increase of percentage of Tregs from 5 to 10% among CD4 + T cells pre-transplant to peaks of 15 to 67% between 1 and 3 months post transplant. Treg percentages remained elevated while patients were on the regimen. T cell proliferation to donor and polyclonal stimulations was markedly reduced in patients on efalizumab and returned to pre-transplant levels 5 months after the cessation of efalizumab (Figure 1). In contrast, percentages of Tregs and T cell proliferative responses remained stable in patients on the belatacept. Efalizumab led to profound changes of patients' immunological make-up when compared to belatacept. Particularly, one of the most severely immunosuppressed efalizumab patient experienced recurrent infections that necessitated complete withdrawal of immunosuppression. Her anti-donor and polyclonal responses rebounded from non-detectable levels to her pre-transplant baseline after efalizumab withdrawal. Remarkably, she has remained insulin independent despite receiving no immunosuppression in the past 16 months. Conclusion: Efalizumab increases percentages of circulating Tregs and profoundly suppresses T cell reactivity. Short-term efalizumab treatment may promote transplantation tolerance.

Transplantation, 2014

Introduction: We have shown that the autoimmune response to GAD65 peptide is a crucial cause of g... more Introduction: We have shown that the autoimmune response to GAD65 peptide is a crucial cause of graft dysfunction in clinical islet transplantation for type 1 diabetes and a signifi cant IFNγ release from CD4+ or CD8+ T cells which corresponded with the autoimmune response. In this study, the serum IFNγ levels in allogeneic islet recipients were assessed, in comparison with autologous recipients. Methods: Six allogeneic and 6 autologous islet recipients were included. Patients in both groups matched in basic characteristics. There was no difference in transplanted islet dose between both groups: 9,393±707 and 7,949±672 IEQ/kg of body weight, respectively (p=0.17). All recipients were administered with both etanercept and anakinra from Day 0 to 10. Autoimmune response was investigated with EpiMax assay after stimulation of peripheral blood mononuclear cells by GAD65 peptide clusters. Cytokine levels were measured using Luminex assay. Results: Signifi cant IFNγ production from both CD4+ and CD8+ T cells was observed at peri-transplant in allogeneic islet recipients (Fig. A). Signifi cant elevation of serum IFNγ levels were also seen immediately after islet infusion in allo-recipients and the elevation were sustained for 7 days (Fig. B). Autologous recipients, however, did not show signifi cant increase in IFNγ levels. Conclusions: Signifi cant difference in serum IFNγ levels was observed between allogeneic and autologous islet recipients even when similar dose of islets were transplanted. Further characterization of IFNγ production may help to determine the role of autoimmune response in clinical islet transplantation. Figure. An example of IFNγ production in EpiMax assay in an allogeneic recipient (A) and serum IFNγ levels in islet transplantation (B) are shown.

Mammalian Endocrinology and Male Reproductive Biology, 2015

Andrologia, 2021

Gross alterations in the morphology of spermatozoa, teratozoospermia, invariably render them inca... more Gross alterations in the morphology of spermatozoa, teratozoospermia, invariably render them incapable of fertilisation. One of the contributory factors to teratozoospermia is failure of spermatozoon to shed the cytoplasmic droplet even after their arrival at epididymis. Quassia amara and quassin are of medicinal value with special reference to malaria. Nevertheless, there are also reports implicating Quassia/quassin in male reproductive toxicity. We were interested in finding if its therapeutic application would jeopardise male fertility. So, we tested it for male reproductive toxicity by analysing, among other aspects, abnormal sperm morphologies, and made a systematic analysis of the spermatozoa of treated mice before they are spermiated and until they arrive at the cauda epididymis. The spermatozoa not only failed to shed the cytoplasmic droplet during epididymal transit but swell to a very large size and were angulated, resulting in Dag‐like defect or lasso shape. A link between cytoplasmic droplet that was retained and lasso shape of tail was indicated. This article traces the structural changes in spermatozoa that lead to angulation, flexion and coiling of the tail, caused due to retention of cytoplasmic droplet, and explains one of the mechanisms of toxicant‐induced teratozoospermia.

Andrologia, 2020

The epididymis responds to adverse conditions of misshapen spermatozoa resulting from pathologica... more The epididymis responds to adverse conditions of misshapen spermatozoa resulting from pathological changes or toxic insults by secretion of a dense matrix that segregates the latter for complete disintegration and dissolution. The objective of this study was to find the source of this matrix and the role‐player of disintegration and dissolution of misshapen spermatozoa. We chose Wistar strain male rat model to tackle this issue, and the rats were administered with aflatoxin B1 for 55 days so as to increase the incidence of misshapen spermatozoa. At the end of the treatment, different segments of epididymis were processed for microscopic observations. We found that parallel with abundant misshapen spermatozoa in the epididymis the principal cells of the initial segment secrete enormous membrane‐bound apical blebs called aposomes, which contain epididymosomes. The aposomes were found to coalesce so as for the content to merge and form a dense matrix that entangles the misshapen spermatozoa and segregates them from viable spermatozoa. The epididymosomes associate with the misshapen spermatozoa, and the latter is processed to disintegration and total dissolution. Therefore, we assign the role of segregation of misshapen spermatozoa from viable ones to the dense matrix of aposomes and their disintegration and dissolution to the epididymosomes.

Neurological Research, 2017

To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food ... more To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded. A separate batch of animals was used for the determination of serotonin (5HT) and 5 hydroxyindole acetic acid (5HIAA) levels in the brain. Harmaline treatment resulted in characteristic tremor that lasted for more than 2 hours and decreased the locomotor activity of rats. Pre-treatment with vanillin significantly reduced the duration, intensity, and tremor index of harmaline-treated animals. Vanillin treatment also significantly attenuated harmaline-induced decrease in the locomotor activity. An increase in 5HT levels and the changes in 5HIAA/5HT ratio observed in harmaline treated rats were significantly corrected in vanillin pretreated animals. Vanillin in low doses reduces harmaline-induced tremor in rats, probably through its modulating effect on serotonin levels in the brain. These findings suggest a beneficial effect of vanillin in essential tremor.

Aflatoxins, highly oxygenated, heterocyclic, difuranocoumarin compounds that could be present in ... more Aflatoxins, highly oxygenated, heterocyclic, difuranocoumarin compounds that could be present in human foods and animal feedstuffs, are an important group of mycotoxins produced by the fungi Aspergillus flavus, A. parasiticus and A. nomius (Diaz et al., 2008). Other species of Aspergillus such as A. bombycis, A. ochraceoroseus and A. pseudotamari may also produce aflatoxins (Bennett & Klich, 2003; Klich et al., 2000; Mishra & Das, 2003). On a worldwide scale, the aflatoxins are found in stored food commodities and oil seeds ...

Fragrances are generally synthetic, natural or a combination of both. Ittar or Attar is a natural... more Fragrances are generally synthetic, natural or a combination of both. Ittar or Attar is a natural fragrance material synthesized from plants which were majorly used by people worldwide as a matter of pride, deodorization and attractant. The effect and role of using Ittar on mammalian system is still not known at the behavioral and neurological level. This study was aimed to understand the constituents and the effect of Ittar on mice by measuring their behavioral and neurological changes upon exposure to Ittar. Batches of animals were exposed to ten different types of Ittar for 1, 2 and 3 weeks respectively. Behavior of the animals exposed to the Ittar perfumes were analyzed against the control animals behavior for physiological activities. Also, the expression level of neurotransmitter such as Dopamine, 5-HIAA, HVA and Serotonin were evaluated based on HPLC analysis. Based on this study it was found that all the ten Ittars were different for its different constituents with some basi...

Diabetes

discussion and reviewed and edited the manuscript. M.C.L. researched data and wrote the manuscrip... more discussion and reviewed and edited the manuscript. M.C.L. researched data and wrote the manuscript. M.C.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Journal of Neurology and Experimental Neuroscience, 2016

Background: Essential tremor (ET) is a common neurological disorder. Genetic, environmental and d... more Background: Essential tremor (ET) is a common neurological disorder. Genetic, environmental and dietary factors have been suggested to contribute to ET. The present study investigates the effect of vanillin, a polyphenol food additive with strong neuroprotective activity in harmaline induced tremors in rats. Methods: Seventy two male Sprague Dawley rats weighing 115 ± 5 g were divided into twelve groups of six animals each. Four groups were allotted to each study. Vanillin (50 mg, 100 mg, and 200 mg/kg) was administered ten minutes after the induction of tremor (therapeutic study) and before the induction of tremor (prophylactic study). In the acute prophylactic study, it was administered 30 m before and for sub-acute prophylactic study it was administered 7 days before the induction of tremor. Harmaline (10 mg/kg, IP.), was used for the induction of tremor. The latency of onset, duration, intensity of tremor and tremor index were recorded. Results: Harmaline treatment produced characteristic tremor that lasted for more than 2 hours. Vanillin both in therapeutic and prophylactic studies failed to produce any significant change in the latency of onset of tremor. The duration of tremor was significantly reduced in both therapeutic and acute prophylactic treatment, but the reduction was not significant in sub-acute prophylactic studies, while the intensity of tremor and tremor index were significantly reduced in both the therapeutic and prophylactic studies. Discussion: The present study suggests that vanillin ameliorates harmaline induced tremor in rats. Further detailed studies are warranted to understand the mechanism of this protection.

Journal of venom research, 2016

Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the ... more Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the host on envenomation and may also have a therapeutic potential. Scorpion venoms produced by the columnar cells of venom gland are complex mixture of mucopolysaccharides, neurotoxic peptides and other components. This study was aimed at cataloguing the elemental composition of venoms obtained from medically important scorpions found in the Arabian peninsula. The global elemental composition of the crude venom obtained from Androctonus bicolor, Androctonus crassicauda and Leiurus quinquestriatus scorpions were estimated using ICP-MS analyzer. The study catalogued several chemical elements present in the scorpion venom using ICP-MS total quant analysis and quantitation of nine elements exclusively using appropriate standards. Fifteen chemical elements including sodium, potassium and calcium were found abundantly in the scorpion venom at PPM concentrations. Thirty six chemical elements of di...