Raj Raghupathy - Academia.edu (original) (raw)

Papers by Raj Raghupathy

European Journal of Pharmacology, Apr 1, 2010

Asthma is a chronic inflammatory disease of the airways. The treatment of asthma is far from opti... more Asthma is a chronic inflammatory disease of the airways. The treatment of asthma is far from optimal and hence the need for novel therapeutic agents exists. The purpose of this study was to assess the anti-asthma effects of an enaminone, E121, and also its effects on ...

Journal of Medical Microbiology, Feb 1, 2008

Campylobacter jejuni is a major cause of diarrhoea in humans. However, the pathogenesis of C. jej... more Campylobacter jejuni is a major cause of diarrhoea in humans. However, the pathogenesis of C. jejuni diarrhoea is poorly understood due to the lack of a good animal model of infection. Many animals have been tried with limited success, but a mouse lung model of infection has been found to be satisfactory previously; however, the lung pathology of this model has not been studied. For the purpose of characterizing the histopathological and ultrastructural lesions in the lung of the mouse pulmonary model of C. jejuni infection, C. jejuni strain 81-176 or sterile PBS was intranasally inoculated into BALB/c mice. The infection resulted in a mild illness only, and in an initial predominance of polymorphonuclear cells, followed by the accumulation of macrophages and later the prominence of epithelioid cells. Focal peribronchial pneumonia appeared on day 3, granuloma-like reaction on day 4 and bronchopneumonia on day 5 post-infection. These features developed until day 5 post-infection, but were less consistent afterwards when histopathology was monitored up to 9 days post-infection. Intracellular structures resembling bacteria were observed on days 3 and 5 post-infection, but not on day 7 post-infection. On days 3 and 5 post-infection, degenerative changes were also observed by transmission electron microscopy. The histological changes were not associated with acid-fast bacteria or any fungal elements. The infection was systemic as C. jejuni was isolated from blood and all organ homogenates (lung, spleen, liver, and small and large intestines) at 24 h post-infection. Thereafter, the organism was recovered from the intestine only, thus indicating its predilection for this location. This characterization of pathology should contribute to a better understanding of the animal model and pathogenesis of C. jejuni infection.

Journal of Immunology, Mar 15, 1992

Medical Principles and Practice, 2005

content in the renal cortex of diabetic rats recovered towards control values, especially after 1... more content in the renal cortex of diabetic rats recovered towards control values, especially after 10-day treatment. Ma londialdehyde content increased in diabetic rats and was reduced towards control value following 7-and 10day treatments. Treatment of diabetic rats with INS, VE or the combination of INS and VE decreased elevated TGF-␤ 1 in plasma, decreased excretion of TGF-␤ 1 in urine, and decreased renal cortex TGF-␤ 1 mRNA levels. Conclusions: Diabetes-induced overexpression of TGF-␤ 1 mRNA was suppressed by VE and INS after 5-, 7-and 10-day treatments. The results obtained with the antioxidant VE suggest that oxidative stress is involved in the development of diabetic nephropathy. Therefore, VE treatment may be effective in early stages of diabetic nephropathy to decrease or prevent pathological complications.

Kuwait Medical Journal, 2010

Current Science, May 25, 1991

Exploration of immunology, Jun 27, 2022

There is many a slip twist the cup and the lip" is a proverb that dates back to the 3rd century. ... more There is many a slip twist the cup and the lip" is a proverb that dates back to the 3rd century. This proverb comes to mind while writing a review on pregnancy loss; so many complications can occur between fertilization and development of the embryo through the long period of gestation until successful delivery of the baby. These include failure of implantation of the embryo, spontaneous miscarriage in the first trimester, pre-eclampsia in the second trimester, premature rupture of fetal membranes, pre-term labour, and pre-term delivery. The maternal immune system which does a phenomenal job of protecting the host from a daunting variety of infections, sometimes also mounts adverse reactions that complicate pregnancy and endanger the fetus. Maternal immune reactions that can adversely affect pregnancy have been shown to be mediated by lymphocytes, macrophages and natural killer cells, and by cytokines secreted by these cellular effectors. This review summarizes the deleterious effects of cytokines leading to recurrent spontaneous miscarriage, pre-eclampsia and pre-term delivery, which are the major complications of pregnancy. It then goes on to discuss the potential use of progesterone and dydrogesterone, an orally-administered progestogen, as immunomodulatory molecules that can be considered for the prevention and/or treatment of these complications.

Proceedings of Indian National Science Academy, 2015

Immunodystrophic Events in Spontaneous Abortions

Kuwait Medical Journal, 2010

World Academy of Science, Engineering and Technology, International Journal of Medical and Health Sciences, 2015

Experimental Parasitology, 2016

Toxoplasmosis is generally self-limiting in healthy adults but it may cause toxoplasmic retinocho... more Toxoplasmosis is generally self-limiting in healthy adults but it may cause toxoplasmic retinochoroiditis in cases of congenital infection leading to blindness. The importance of host genetics in determining disease severity in ocular toxoplasmosis has been shown in different inbred mouse strains using low-virulence toxoplasma strain. In this study, we studied intraocular immune response and tissue alterations in the genetically resistant BALB/c and susceptible MF1 mice infected with a virulent type I RH T. gondii strain by intravitreal route. We observed a significant up-regulation of IFN-γ and TNF-α to >2200 pg/ml and >300 pg/ml respectively in the blood of both BALB/c and MF1mice during the early stages of post intraocular infection (p<0.01) but the levels dropped sharply to normal during the late stages of the infection on day 26. The cytokine levels detected were higher in the MF1 mice compared with the BALB/c mice and a relatively higher levels were observed in the aqueous humour (AqH) than in the blood of both group of mice. The TGF-β1 level in the blood and AqH of BALB/c mice remained low throughout the infection period compared with MF1 mice which showed gradual increase to 50 pg/ml in the blood and AqH during the early stages of infection which then further increased 2fold to 132 pg/ml on day 11 (p<0.01) and remained high till the last day of observation on day 26 except that the TGF-β1 level in AqH dropped sharply to normal level. In summary, our results support that TGF-β1 may down-regulate the effector functions of anti-Toxoplasma cellular immunity during acute toxoplasmosis. We document that a mild Th1 proinflammatory response in the BALB/c mice with high IFN-γ and TNF-α and, low TGF-β1 levels during the early stages of infection may have contributed to an effective cellular immune response leading to lower morbidity, mortality and less ocular tissue damage. However in the MF1 mice, a significantly high TGF-β1 level in the blood as well as in the AqH during the acute

Immunology of Pregnancy 2013, 2013

Medical Principles and Practice, 2008

Objective: This study was aimed at detecting antibodies to the antigens which may contribute to p... more Objective: This study was aimed at detecting antibodies to the antigens which may contribute to protection against cytomegalovirus (CMV) infection after organ transplantation. Materials and Methods: A total of 203 kidney transplant patients were enrolled in the study. Based on CMV antigenemia assay, 23 patients were antigen-positive and of the remaining 180 antigen-negative patients, 46 were selected as controls matched for age, gender and source of kidney. The 69 kidney recipients (KR) had CMV antibody due to previous infection and were followed up for a period of 6 months after transplantation for the development of active CMV infections by the antigenemia assay. Antibody responses to five CMV-related peptide antigens (pp65, gB, pp150, pp28 and pp38) were investigated by enzyme immunoassay and their presence was correlated with the results of the CMV antigenemia assay. Results: Of the five CMV-related peptide antigens, only gB antigen showed response to the antibody in 10/23 (43.5...

Lupus, 2009

Tumour necrosis factor-α (TNF-α) plays a major role in propagating the inflammatory processes res... more Tumour necrosis factor-α (TNF-α) plays a major role in propagating the inflammatory processes responsible for tissue damage in systemic lupus erythematosus (SLE) and is overexpressed both systemically and locally in this disease. Hence, this pilot study was carried out to assess the safety and efficacy of TNF blockade in patients with active SLE. A total of 46 individuals (27 patients with active SLE and 19 healthy control volunteers) were the subjects of this study. Nine patients with SLE were allocated to treatment arm and 18 were allocated to control arm. In addition to conventional treatment, treatment arm received infliximab infusions 3 mg/kg body weight at 0, 2, 6 weeks and then q 8 weeks for a total of 24 weeks, that is, a total of five doses. Patients were closely monitored for infection. Clinical, laboratory and treatment data were entered into a pre-designed proforma. Health status (SF-36), patient global assessment (PGA) of disease activity, disease activity scores by SLE...

The Annals of Thoracic Surgery, 2002

ABSTRACT Cardiac operation produces substantial alterations within the immune system, which possi... more ABSTRACT Cardiac operation produces substantial alterations within the immune system, which possibly predispose postoperative complications. However, the interplay between proinflammatory and antiinflammatory reactions and the cells involved in this process are not completely clear. Therefore, we investigated serum levels, as well as synthesis patterns, of proinflammatory and antiinflammatory cytokines. Serum levels and production of interleukin (IL) IL-5, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma, using a mixed cell culture, (ie, monocytes, macrophages, and lymphocytes), as well as a purified lymphocyte culture were measured preoperatively (day 0), on postoperative day 1, on postoperative day 3, and on postoperative day 5 in 25 patients undergoing cardiac operations and were compared with 10 healthy volunteers. Serum level and mixed cell culture, production of IL-6, tumor necrosis factor-alpha, and IL-10 increased on postoperative day 1, but decreased in lymphocyte culture. Base line values were reached on postoperative day 5. Interferon-gamma serum levels remained unchanged, whereas IL-5 serum levels increased on postoperative days 3 and 5. Cell culture synthesis showed a significant suppression for both mediators in both cell cultures, which returned to baseline on postoperative day 3 in mixed cell culture. Interferon-gamma production by lymphocytes was suppressed until postoperative day 5, whereas IL-5 returned to preoperative values on postoperative day 5. Cardiac operation induces a biphasic immune response. The first phase (postoperative day 1) appears to represent the proinflammatory and antiinflammatory reaction of the innate immune system returning to base line on postoperative day 3. The second phase (postoperative day 5) may represent the response of the adaptive immune system and is characterized by an antiinflammatory type of reaction. This may explain why the systemic inflammatory response occurs immediately after cardiac operation, whereas infections occur later.

Journal of Immunology, May 1, 1995

CBA x DBA/2 placentae are quantitatively or qualitatively deficient in their production of the an... more CBA x DBA/2 placentae are quantitatively or qualitatively deficient in their production of the anti-inflammatory Th2-type cytokines IL-4 and IL-10 compared with the nonresorption-prone CBA x BALB/c mating combination. Wastage in this mating combination is accompanied by increased levels of local inflammatory cytokines. In addition, alloimmunization enhances the placental production of IL-4 and IL-10 in CBA x DBA/2 matings. Furthermore, rIL-10 by itself completely reverses the high incidence of fetal resorption after i.p. injection. Conversely, anti-IL-10 increases the resorption rate, but only in CBA x DBA/2 matings. On the other hand, injecting either anti-IFN-gamma or pentoxifillin (an anti-TNF agent) partially reduces the resorption. When given together, they produce a synergistic remission of fetal loss. Finally, we report that recombinant ovine trophoblast protein, an IFN-tau which is known to influence reproductive outcome in ruminants, can also counteract increased CBA x DBA/2 fetal resorption. It simultaneously induces increased placental IL-4 and IL-10 production in this mating combination. These results indicate that the placentally produced anti-inflammatory cytokines can play a vital role in the survival to term of the fetal allograft, by counteracting deleterious inflammatory cytokines.

PubMed, 1980

Optimistic evaluation of the safety of vasectomy in spite of apparent absence of deleterious side... more Optimistic evaluation of the safety of vasectomy in spite of apparent absence of deleterious side effects may have been premature. Numerous studies in a variety of vasectomized animal species show that antisperm antibodies develop following vasectomy. In addition 50% of vasectomized men have been found to have antisperm antibodies following vasectomy. By inference this would mean a chronic source of antigen-antibody complexes which might lead to extensive vascular pathology including endothelial damage with consequent acute vasculities and chronic atherosclerosis. A study by Alexander et al. of vasectomized monkeys suggests that the humoral immune response to antigens that often follow vasectomy could enhance diet-induced atherosclerosis. Long-term epidemiological studies of vasectomized men are needed to establish if vascular damage is a consequence of vasectomy. If so there is an obvious need to eliminate the chronic source of antigen in those already vasectomized.

European Journal of Pharmacology, Apr 1, 2010

Asthma is a chronic inflammatory disease of the airways. The treatment of asthma is far from opti... more Asthma is a chronic inflammatory disease of the airways. The treatment of asthma is far from optimal and hence the need for novel therapeutic agents exists. The purpose of this study was to assess the anti-asthma effects of an enaminone, E121, and also its effects on ...

Journal of Medical Microbiology, Feb 1, 2008

Campylobacter jejuni is a major cause of diarrhoea in humans. However, the pathogenesis of C. jej... more Campylobacter jejuni is a major cause of diarrhoea in humans. However, the pathogenesis of C. jejuni diarrhoea is poorly understood due to the lack of a good animal model of infection. Many animals have been tried with limited success, but a mouse lung model of infection has been found to be satisfactory previously; however, the lung pathology of this model has not been studied. For the purpose of characterizing the histopathological and ultrastructural lesions in the lung of the mouse pulmonary model of C. jejuni infection, C. jejuni strain 81-176 or sterile PBS was intranasally inoculated into BALB/c mice. The infection resulted in a mild illness only, and in an initial predominance of polymorphonuclear cells, followed by the accumulation of macrophages and later the prominence of epithelioid cells. Focal peribronchial pneumonia appeared on day 3, granuloma-like reaction on day 4 and bronchopneumonia on day 5 post-infection. These features developed until day 5 post-infection, but were less consistent afterwards when histopathology was monitored up to 9 days post-infection. Intracellular structures resembling bacteria were observed on days 3 and 5 post-infection, but not on day 7 post-infection. On days 3 and 5 post-infection, degenerative changes were also observed by transmission electron microscopy. The histological changes were not associated with acid-fast bacteria or any fungal elements. The infection was systemic as C. jejuni was isolated from blood and all organ homogenates (lung, spleen, liver, and small and large intestines) at 24 h post-infection. Thereafter, the organism was recovered from the intestine only, thus indicating its predilection for this location. This characterization of pathology should contribute to a better understanding of the animal model and pathogenesis of C. jejuni infection.

Journal of Immunology, Mar 15, 1992

Medical Principles and Practice, 2005

content in the renal cortex of diabetic rats recovered towards control values, especially after 1... more content in the renal cortex of diabetic rats recovered towards control values, especially after 10-day treatment. Ma londialdehyde content increased in diabetic rats and was reduced towards control value following 7-and 10day treatments. Treatment of diabetic rats with INS, VE or the combination of INS and VE decreased elevated TGF-␤ 1 in plasma, decreased excretion of TGF-␤ 1 in urine, and decreased renal cortex TGF-␤ 1 mRNA levels. Conclusions: Diabetes-induced overexpression of TGF-␤ 1 mRNA was suppressed by VE and INS after 5-, 7-and 10-day treatments. The results obtained with the antioxidant VE suggest that oxidative stress is involved in the development of diabetic nephropathy. Therefore, VE treatment may be effective in early stages of diabetic nephropathy to decrease or prevent pathological complications.

Kuwait Medical Journal, 2010

Current Science, May 25, 1991

Exploration of immunology, Jun 27, 2022

There is many a slip twist the cup and the lip" is a proverb that dates back to the 3rd century. ... more There is many a slip twist the cup and the lip" is a proverb that dates back to the 3rd century. This proverb comes to mind while writing a review on pregnancy loss; so many complications can occur between fertilization and development of the embryo through the long period of gestation until successful delivery of the baby. These include failure of implantation of the embryo, spontaneous miscarriage in the first trimester, pre-eclampsia in the second trimester, premature rupture of fetal membranes, pre-term labour, and pre-term delivery. The maternal immune system which does a phenomenal job of protecting the host from a daunting variety of infections, sometimes also mounts adverse reactions that complicate pregnancy and endanger the fetus. Maternal immune reactions that can adversely affect pregnancy have been shown to be mediated by lymphocytes, macrophages and natural killer cells, and by cytokines secreted by these cellular effectors. This review summarizes the deleterious effects of cytokines leading to recurrent spontaneous miscarriage, pre-eclampsia and pre-term delivery, which are the major complications of pregnancy. It then goes on to discuss the potential use of progesterone and dydrogesterone, an orally-administered progestogen, as immunomodulatory molecules that can be considered for the prevention and/or treatment of these complications.

Proceedings of Indian National Science Academy, 2015

Immunodystrophic Events in Spontaneous Abortions

Kuwait Medical Journal, 2010

World Academy of Science, Engineering and Technology, International Journal of Medical and Health Sciences, 2015

Experimental Parasitology, 2016

Toxoplasmosis is generally self-limiting in healthy adults but it may cause toxoplasmic retinocho... more Toxoplasmosis is generally self-limiting in healthy adults but it may cause toxoplasmic retinochoroiditis in cases of congenital infection leading to blindness. The importance of host genetics in determining disease severity in ocular toxoplasmosis has been shown in different inbred mouse strains using low-virulence toxoplasma strain. In this study, we studied intraocular immune response and tissue alterations in the genetically resistant BALB/c and susceptible MF1 mice infected with a virulent type I RH T. gondii strain by intravitreal route. We observed a significant up-regulation of IFN-γ and TNF-α to >2200 pg/ml and >300 pg/ml respectively in the blood of both BALB/c and MF1mice during the early stages of post intraocular infection (p<0.01) but the levels dropped sharply to normal during the late stages of the infection on day 26. The cytokine levels detected were higher in the MF1 mice compared with the BALB/c mice and a relatively higher levels were observed in the aqueous humour (AqH) than in the blood of both group of mice. The TGF-β1 level in the blood and AqH of BALB/c mice remained low throughout the infection period compared with MF1 mice which showed gradual increase to 50 pg/ml in the blood and AqH during the early stages of infection which then further increased 2fold to 132 pg/ml on day 11 (p<0.01) and remained high till the last day of observation on day 26 except that the TGF-β1 level in AqH dropped sharply to normal level. In summary, our results support that TGF-β1 may down-regulate the effector functions of anti-Toxoplasma cellular immunity during acute toxoplasmosis. We document that a mild Th1 proinflammatory response in the BALB/c mice with high IFN-γ and TNF-α and, low TGF-β1 levels during the early stages of infection may have contributed to an effective cellular immune response leading to lower morbidity, mortality and less ocular tissue damage. However in the MF1 mice, a significantly high TGF-β1 level in the blood as well as in the AqH during the acute

Immunology of Pregnancy 2013, 2013

Medical Principles and Practice, 2008

Objective: This study was aimed at detecting antibodies to the antigens which may contribute to p... more Objective: This study was aimed at detecting antibodies to the antigens which may contribute to protection against cytomegalovirus (CMV) infection after organ transplantation. Materials and Methods: A total of 203 kidney transplant patients were enrolled in the study. Based on CMV antigenemia assay, 23 patients were antigen-positive and of the remaining 180 antigen-negative patients, 46 were selected as controls matched for age, gender and source of kidney. The 69 kidney recipients (KR) had CMV antibody due to previous infection and were followed up for a period of 6 months after transplantation for the development of active CMV infections by the antigenemia assay. Antibody responses to five CMV-related peptide antigens (pp65, gB, pp150, pp28 and pp38) were investigated by enzyme immunoassay and their presence was correlated with the results of the CMV antigenemia assay. Results: Of the five CMV-related peptide antigens, only gB antigen showed response to the antibody in 10/23 (43.5...

Lupus, 2009

Tumour necrosis factor-α (TNF-α) plays a major role in propagating the inflammatory processes res... more Tumour necrosis factor-α (TNF-α) plays a major role in propagating the inflammatory processes responsible for tissue damage in systemic lupus erythematosus (SLE) and is overexpressed both systemically and locally in this disease. Hence, this pilot study was carried out to assess the safety and efficacy of TNF blockade in patients with active SLE. A total of 46 individuals (27 patients with active SLE and 19 healthy control volunteers) were the subjects of this study. Nine patients with SLE were allocated to treatment arm and 18 were allocated to control arm. In addition to conventional treatment, treatment arm received infliximab infusions 3 mg/kg body weight at 0, 2, 6 weeks and then q 8 weeks for a total of 24 weeks, that is, a total of five doses. Patients were closely monitored for infection. Clinical, laboratory and treatment data were entered into a pre-designed proforma. Health status (SF-36), patient global assessment (PGA) of disease activity, disease activity scores by SLE...

The Annals of Thoracic Surgery, 2002

ABSTRACT Cardiac operation produces substantial alterations within the immune system, which possi... more ABSTRACT Cardiac operation produces substantial alterations within the immune system, which possibly predispose postoperative complications. However, the interplay between proinflammatory and antiinflammatory reactions and the cells involved in this process are not completely clear. Therefore, we investigated serum levels, as well as synthesis patterns, of proinflammatory and antiinflammatory cytokines. Serum levels and production of interleukin (IL) IL-5, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma, using a mixed cell culture, (ie, monocytes, macrophages, and lymphocytes), as well as a purified lymphocyte culture were measured preoperatively (day 0), on postoperative day 1, on postoperative day 3, and on postoperative day 5 in 25 patients undergoing cardiac operations and were compared with 10 healthy volunteers. Serum level and mixed cell culture, production of IL-6, tumor necrosis factor-alpha, and IL-10 increased on postoperative day 1, but decreased in lymphocyte culture. Base line values were reached on postoperative day 5. Interferon-gamma serum levels remained unchanged, whereas IL-5 serum levels increased on postoperative days 3 and 5. Cell culture synthesis showed a significant suppression for both mediators in both cell cultures, which returned to baseline on postoperative day 3 in mixed cell culture. Interferon-gamma production by lymphocytes was suppressed until postoperative day 5, whereas IL-5 returned to preoperative values on postoperative day 5. Cardiac operation induces a biphasic immune response. The first phase (postoperative day 1) appears to represent the proinflammatory and antiinflammatory reaction of the innate immune system returning to base line on postoperative day 3. The second phase (postoperative day 5) may represent the response of the adaptive immune system and is characterized by an antiinflammatory type of reaction. This may explain why the systemic inflammatory response occurs immediately after cardiac operation, whereas infections occur later.

Journal of Immunology, May 1, 1995

CBA x DBA/2 placentae are quantitatively or qualitatively deficient in their production of the an... more CBA x DBA/2 placentae are quantitatively or qualitatively deficient in their production of the anti-inflammatory Th2-type cytokines IL-4 and IL-10 compared with the nonresorption-prone CBA x BALB/c mating combination. Wastage in this mating combination is accompanied by increased levels of local inflammatory cytokines. In addition, alloimmunization enhances the placental production of IL-4 and IL-10 in CBA x DBA/2 matings. Furthermore, rIL-10 by itself completely reverses the high incidence of fetal resorption after i.p. injection. Conversely, anti-IL-10 increases the resorption rate, but only in CBA x DBA/2 matings. On the other hand, injecting either anti-IFN-gamma or pentoxifillin (an anti-TNF agent) partially reduces the resorption. When given together, they produce a synergistic remission of fetal loss. Finally, we report that recombinant ovine trophoblast protein, an IFN-tau which is known to influence reproductive outcome in ruminants, can also counteract increased CBA x DBA/2 fetal resorption. It simultaneously induces increased placental IL-4 and IL-10 production in this mating combination. These results indicate that the placentally produced anti-inflammatory cytokines can play a vital role in the survival to term of the fetal allograft, by counteracting deleterious inflammatory cytokines.

PubMed, 1980

Optimistic evaluation of the safety of vasectomy in spite of apparent absence of deleterious side... more Optimistic evaluation of the safety of vasectomy in spite of apparent absence of deleterious side effects may have been premature. Numerous studies in a variety of vasectomized animal species show that antisperm antibodies develop following vasectomy. In addition 50% of vasectomized men have been found to have antisperm antibodies following vasectomy. By inference this would mean a chronic source of antigen-antibody complexes which might lead to extensive vascular pathology including endothelial damage with consequent acute vasculities and chronic atherosclerosis. A study by Alexander et al. of vasectomized monkeys suggests that the humoral immune response to antigens that often follow vasectomy could enhance diet-induced atherosclerosis. Long-term epidemiological studies of vasectomized men are needed to establish if vascular damage is a consequence of vasectomy. If so there is an obvious need to eliminate the chronic source of antigen in those already vasectomized.