Cancer is widely spread in Bathinda district of Punjab. Over usage of pesticides in agricultural ... more Cancer is widely spread in Bathinda district of Punjab. Over usage of pesticides in agricultural practices, concentration of uranium in water and use of tobacco and alcohol etc. are considered as important factors of it in this region. Cancer has a lot of socio-economic impact on the people of Bathinda district. Moreover, care cost of cancer is higher and it put negative impact not only over the patient but also on his/ her family members with negatively implication on credits. This impact can be seen more over the lowest and middle income group family. It has also impact on the people's ability to work which are further responsible for poverty. Therefore this present study is an attempt towards this. The study will try to find out the factors responsible and impacts of this disease on economy of different categories of Bathinda residents. By this, it will make an access the economic burden of cancer for different categories of people with various social and economic factors.
In this paper, I investigate the impact of secrecy, ownership dispersion and profitability on the... more In this paper, I investigate the impact of secrecy, ownership dispersion and profitability on the readability of annual reports of U.S.-listed Asian companies. This is perhaps the first paper to examine the effect on readability of cross-listed Asian companies. I use a measure of secrecy developed in Hope at al. (2008) to study its effect on readability. The sample of this paper consists of all 68 Asian companies from nine countries listed on NYSE/NASDAQ, that are registered and reporting with the SEC. The univariate and multivariate analyses show that companies whose domestic culture is more secretive are providing less readable financial statements. This result is robust to sensitivity tests. This is an interesting and important result in line with the efforts being made to have convergence in the International accounting area. This is despite the fact that a large number of these companies are using IFRS and U.S. GAAP to prepare their financial statements. The results also show that companies with higher ownership dispersion are providing more readable annual reports. The results fail to reject the hypothesis related to the effect of profitability. Finally, the results show that larger sample companies are providing more difficult to read financial statements. These results have important implications for international investors and global standard-setting bodies.
Liquidity is said to be the lifeblood of stock markets. It has prominent implications for traders... more Liquidity is said to be the lifeblood of stock markets. It has prominent implications for traders, regulators, stock exchanges and the listed firms. In recent years a huge amount of literature has emerged that deals with liquidity. This article classifies and organises the literature and provides a critical review of the frameworks currently available for modelling liquidity and its macroeconomic and firm specific drivers. Commonality and intraday behaviour of liquidity in various markets is discussed under the umbrella of market microstructures. Subsequently, liquidity risk as a factor in Asset pricing is analysed taking various models in to consideration. Finally, the study reviewed the impact of liquidity on corporate finance decisions viz. dividends, firm valuation, stock split, capital structure etc.
This paper has three objectives. First, we investigate the effects of perceived stress on the aca... more This paper has three objectives. First, we investigate the effects of perceived stress on the academic performance of accounting students. Second, we examine the association of Facebook use with perceived stress. Third, we investigate the effect of Facebook usage on accounting students' academic performance. To measure the perceived stress we used the Perceived Stress Scale developed in the prior research for the shorter version and used it to collect data from accounting students at two universities. We found that female accounting students reported higher stress scores than their male counterparts. In addition, the results indicated that this phenomenon affected their academic performance negatively. African American accounting students were more likely to report higher stress scores than their non-African American counterparts. Further investigation showed that African American students are more likely to live alone or to live in the dorm. They are also more likely to be working while going to school. Our analysis shows that higher Facebook use is associated with stress and the respondents in our sample, who used Facebook while studying, reported higher levels of stress and were less in control of things. Finally, our results show that accounting students who use Facebook while studying experienced lower academic performance after controlling for stress.
Aspergilloma infection in the lung can occur in preexisting cavities and is usually seen after tu... more Aspergilloma infection in the lung can occur in preexisting cavities and is usually seen after tuberculosis, pulmonary infarction and bronchestasis. Occassionally aspergilloma has been reported within a hydatid cyst. We describe a patient with aspergilloma formed within cyst hydatid. The primary symptom in this patient was recurrent hemoptysis. In this 42-year-old male, the diagnosis was established by HRCT chest. Treatment consisted of postero-lateral thoracotomy with a bilobectomy of lower and middle lobe. Aspergilloma is an unusual complication of hydatid cyst and results from the deterioration of local defence against opportunistic infections.
Introduction: Hallux valgus is the one of the commonest forefoot deformities. Apart from cosmetic... more Introduction: Hallux valgus is the one of the commonest forefoot deformities. Apart from cosmetic perspectives it can be problematic because of its pressure effects. Though common in the age group of 30-60s in females of shoe wearing population, It’s incidence in general population is also increasing. Many procedures have been documented in literature to correct such deformity. Mitchell’s osteotomy is one of the treatment options for such deformity. This osteotomy is actually two transverse osteotomies in which one is incomplete, forming a step cut. The distal fragment is displaced medially and planter-wards aiming to restore the function of the feet. Material and Methods: Thirty patients with ten bilateral feet’s of hallux valgus deformities were operated at Bone and Joints hospital between the years 2007-2012. We had 23 females and 7 male patients with all the bilateral cases being females. The age group was between 19 years to 35 years. The follow up period was between 2 years to 7 years. The pre-operative radiograph of Antero posterior view was taken and recorded. The indications for surgery included pain, difficulty in foot wear and cosmoses. Results: All patients were assessed according to a protocol based on the AOFAS (Smith et al 1984) and re-assessed at three-monthly intervals. Pain improved from 23 + 5.2 to 36 +5 on final follow up (max 40). Functional score improved from 31+ 4.1 to 42 +1.2 and alignment score from 3 + 2.3 to 16 +2.4 on final follow up. Overall AOFAS score improved from 58 +1.6 to 94 +8.6. Radiographic results of the procedure were also satisfactory. Preoperatively the Hallux valgus angle was 30.3 + 7.1 degrees which improved to 11.1 +4.9 degrees on final follow up. The Inter metatarsal angle also improved from a preoperative score of 15.7 + 2.9 to 7 + 2.0 Conclusion: Mitchell’s procedure is simple, cheap and can safely address the hallux valgus deformity with good postoperative function results, both clinical and radiological. Osteotomy is stable and avascular necrosis can be easily avoided by careful soft tissue handling.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India, 2002
Pseudoaneurysm of the facial artery has very characteristic clinical features and radiological fi... more Pseudoaneurysm of the facial artery has very characteristic clinical features and radiological findings and can be treated with successful catheter emholisation, thus decreasing the morbidity associated with surgical procedure. A rare case of pseudoaneurysm of the facial artery is presented here for clinical interest.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India, 2003
People working in mines, plating factories, cement industries are mainly exposed to chrome substa... more People working in mines, plating factories, cement industries are mainly exposed to chrome substances, IIexavalent chromium has been implicated for its toxic effect on the nasal mucosa. Hereby we present a rare study of 28 patients who attended out patient department of Otorhinolaryngology at SSG Hospital, Baroda from a nearby chromium industry. This study aims to present various nasal manifestations of toxic effects of prolonged chromium exposure.
Purpose To determine whether variable hepatic microwave ablation (MWA) can induce local inflammat... more Purpose To determine whether variable hepatic microwave ablation (MWA) can induce local inflammation and distant pro-oncogenic effects compared with hepatic radiofrequency ablation (RFA) in an animal model. Materials and Methods In this institutional Animal Care and Use Committee-approved study, F344 rats (150 gm, n = 96) with subcutaneous R3230 breast adenocarcinoma tumors had normal non-tumor-bearing liver treated with RFA (70°C × 5 minutes), rapid higher-power MWA (20 W × 15 seconds), slower lower-power MWA (5 W × 2 minutes), or a sham procedure (needle placement without energy) and were sacrificed at 6 hours to 7 days (four time points; six animals per arm per time point). Ablation settings produced 11.4 mm ± 0.8 of coagulation for all groups. Distant tumor growth rates were determined to 7 days after treatment. Liver heat shock protein (HSP) 70 levels (at 72 hours) and macrophages (CD68 at 7 days), tumor proliferative indexes (Ki-67 and CD34 at 7 days), and serum and tissue lev...
Purpose: Early life stress has enduring behavioral and neuroendocrine effects, particularly in hi... more Purpose: Early life stress has enduring behavioral and neuroendocrine effects, particularly in hippocampus and amygdala. This may be relevant to mesial temporal lobe epilepsy (MTLE) that arises from these structures. In rats, we tested the hypothesis that early postnatal stress, in the form of maternal separation (MS), creates vulnerability to limbic epileptogenesis in adult life. Methods: On postnatal days 2-14, we exposed male and female nonepileptic rats to either MS for 180 min/day, or early handling (EH) and brief separation (15 min/day). At 7 weeks of age, rats of both genders exposed to MS displayed significantly increased anxiety, as evidenced by reduced time spent in the open arms of the elevated plus maze compared with EH rats. For epileptogenesis experiments, separate cohorts of rats, similarly exposed to either early life MS or EH, were implanted with bipolar electrodes into the left amygdala and one week later rapid electrical kindling performed until fully kindled (five Class V seizures, Racine scale). Results: In females, fewer stimulations were required following MS than EH to reach the fully kindled state (39.6 ± 6.4 vs. 67.1 ± 9.4; p < 0.0001); no differences were observed in males (MS: 49.1 ± 5.1; EH: 53.7 ± 6.6 stimulations). Discussion: We conclude that, while postnatal MS stress increases anxiety in both genders, this early life stressor results in persisting vulnerability to limbic epileptogenesis only in females. This has implications for human MTLE and its psychiatric comorbidities, suggesting a common causation model and the involvement of gender-specific factors such as sex hormones.
International Journal of Innovation and Applied Studies, Jul 2, 2014
Crop residue left in the field after grain harvests have a large potential as a bioenergy feedsto... more Crop residue left in the field after grain harvests have a large potential as a bioenergy feedstock. Crop residues of interest for bioenergy include; wheat straw, soybean straw, and rice straw, paddy straw etc. Paddy straw and wheat straw are potential substrate which can be exploited in industries in future for bioethanol (biofuel) production as they are cheap, abundant and high cellulose content. In this study rice (paddy) and wheat straw had been given both acid (1%-2.5%) and heat treatment (100ºc for 1 hour) for better sugar extraction in media and different parameters were optimized for bioethanol production. Conc. of reducing sugar in the sample after heat treatment were 0.30µg/ml (wheat straw), 15µg/ml (paddy straw), 18µg/ml (mixed sample). After acid treatment total reducing sugar was 56µg/ml (wheat straw), 70 µg/ml (paddy straw), and 170µg/ml (mixed). The optimized parameters for bioethanol production were pH =5.5, Temp=37ºc, conc. of (NH4) 2 SO 4 = 0.6mg/ml and yield of ethanol was 5.4%. The concentration of bioethanol for acid treatment of 1%, 2%, 2.5% were 1.3%, 3.4%,5.4%.
Polymeric black tea polyphenols (PBPs) have been shown to possess anti-tumor-promoting effects in... more Polymeric black tea polyphenols (PBPs) have been shown to possess anti-tumor-promoting effects in two-stage skin carcinogenesis. However, their mechanisms of action are not fully elucidated. In this study, mechanisms of PBP-mediated antipromoting effects were investigated in a mouse model employing the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Compared to controls, a single topical application of TPA to mouse skin increased the translocation of protein kinase C (PKC) from cytosol to membrane. Pretreatment with PBPs 1-3 decreased TPA-induced translocation of PKC isozymes (a, b, Z, g, e) from cytosol to membrane, whereas PBPs 4 and 5 were less effective. The levels of PKCs d and z in cytosol/membrane were similar in all the treatment groups. Complementary confocal microscopic evaluation showed a decrease in TPA-induced PKCa fluorescence in PBP-3-pretreated membranes, whereas pretreatment with PBP-5 did not show a similar decrease. Based on the experiments with specific enzyme inhibitors and phosphospecific antibodies, both PBP-3 and PBP-5 were observed to decrease TPA-induced level and/or activity of phosphatidylinositol 3-kinase (PI3K) and AKT1 (pS473). An additional ability of PBP-3 to inhibit site-specific phosphorylation of PKCa at all three positions responsible for its activation [PKCa (pT497), PKC PAN (bII pS660), PKCa/bII (pT638/ 641)] and AKT1 at the Thr308 position, along with a decrease in TPA-induced PDK1 protein level, correlated with the inhibition of translocation of PKC, which may impart relatively stronger chemoprotective activity to PBP-3 than to PBP-5. Altogether, PBP-mediated decrease in TPA-induced PKC phosphorylation correlated well with decreased TPA-induced NF-kB phosphorylation and downstream target proteins associated with proliferation, apoptosis, and inflammation in mouse skin. Results suggest that the antipromoting effects of PBPs are due to modulation of TPA-induced PI3Kmediated signal transduction.
Immunophilins are abundantly present in the brain as compared to the immune system. Immunophilin-... more Immunophilins are abundantly present in the brain as compared to the immune system. Immunophilin-binding agents like FK506 are known to inactivate neuronal nitric oxide synthase (nNOS) by inhibiting calcineurin and decrease the production of nitric oxide. Nitric oxide is involved in the mediation of nociception at the spinal level. In the present study, the effect of FK506 on the tail flick response in mice and the possible involvement of NO-L-arginine pathway in this paradigm was evaluated. FK506 (0.5, 1 and 3 mg/kg, ip) produced a significant antinociception in the tail flick test. Nitric oxide synthase (NOS) inhibitor L-NAME significantly and dose dependently (10-40 mg/kg, ip) potentiated the FK506 (0.5 mg/kg)-induced antinociception. On the other hand, NOS substrate L-arginine (100, 200 and 400 mg/kg) inhibited the FK506-induced antinociception in a dose-dependent manner. Concomitant administration of L-NAME (20 and 40 mg/kg) with L-arginine (200 mg/kg) blocked the inhibition exerted by L-arginine on the FK506-induced antinociception. Thus, it was concluded that NO- L-arginine pathway may be involved in the FK506-induced antinociception in tail flick test.
Cancer is widely spread in Bathinda district of Punjab. Over usage of pesticides in agricultural ... more Cancer is widely spread in Bathinda district of Punjab. Over usage of pesticides in agricultural practices, concentration of uranium in water and use of tobacco and alcohol etc. are considered as important factors of it in this region. Cancer has a lot of socio-economic impact on the people of Bathinda district. Moreover, care cost of cancer is higher and it put negative impact not only over the patient but also on his/ her family members with negatively implication on credits. This impact can be seen more over the lowest and middle income group family. It has also impact on the people's ability to work which are further responsible for poverty. Therefore this present study is an attempt towards this. The study will try to find out the factors responsible and impacts of this disease on economy of different categories of Bathinda residents. By this, it will make an access the economic burden of cancer for different categories of people with various social and economic factors.
In this paper, I investigate the impact of secrecy, ownership dispersion and profitability on the... more In this paper, I investigate the impact of secrecy, ownership dispersion and profitability on the readability of annual reports of U.S.-listed Asian companies. This is perhaps the first paper to examine the effect on readability of cross-listed Asian companies. I use a measure of secrecy developed in Hope at al. (2008) to study its effect on readability. The sample of this paper consists of all 68 Asian companies from nine countries listed on NYSE/NASDAQ, that are registered and reporting with the SEC. The univariate and multivariate analyses show that companies whose domestic culture is more secretive are providing less readable financial statements. This result is robust to sensitivity tests. This is an interesting and important result in line with the efforts being made to have convergence in the International accounting area. This is despite the fact that a large number of these companies are using IFRS and U.S. GAAP to prepare their financial statements. The results also show that companies with higher ownership dispersion are providing more readable annual reports. The results fail to reject the hypothesis related to the effect of profitability. Finally, the results show that larger sample companies are providing more difficult to read financial statements. These results have important implications for international investors and global standard-setting bodies.
Liquidity is said to be the lifeblood of stock markets. It has prominent implications for traders... more Liquidity is said to be the lifeblood of stock markets. It has prominent implications for traders, regulators, stock exchanges and the listed firms. In recent years a huge amount of literature has emerged that deals with liquidity. This article classifies and organises the literature and provides a critical review of the frameworks currently available for modelling liquidity and its macroeconomic and firm specific drivers. Commonality and intraday behaviour of liquidity in various markets is discussed under the umbrella of market microstructures. Subsequently, liquidity risk as a factor in Asset pricing is analysed taking various models in to consideration. Finally, the study reviewed the impact of liquidity on corporate finance decisions viz. dividends, firm valuation, stock split, capital structure etc.
This paper has three objectives. First, we investigate the effects of perceived stress on the aca... more This paper has three objectives. First, we investigate the effects of perceived stress on the academic performance of accounting students. Second, we examine the association of Facebook use with perceived stress. Third, we investigate the effect of Facebook usage on accounting students' academic performance. To measure the perceived stress we used the Perceived Stress Scale developed in the prior research for the shorter version and used it to collect data from accounting students at two universities. We found that female accounting students reported higher stress scores than their male counterparts. In addition, the results indicated that this phenomenon affected their academic performance negatively. African American accounting students were more likely to report higher stress scores than their non-African American counterparts. Further investigation showed that African American students are more likely to live alone or to live in the dorm. They are also more likely to be working while going to school. Our analysis shows that higher Facebook use is associated with stress and the respondents in our sample, who used Facebook while studying, reported higher levels of stress and were less in control of things. Finally, our results show that accounting students who use Facebook while studying experienced lower academic performance after controlling for stress.
Aspergilloma infection in the lung can occur in preexisting cavities and is usually seen after tu... more Aspergilloma infection in the lung can occur in preexisting cavities and is usually seen after tuberculosis, pulmonary infarction and bronchestasis. Occassionally aspergilloma has been reported within a hydatid cyst. We describe a patient with aspergilloma formed within cyst hydatid. The primary symptom in this patient was recurrent hemoptysis. In this 42-year-old male, the diagnosis was established by HRCT chest. Treatment consisted of postero-lateral thoracotomy with a bilobectomy of lower and middle lobe. Aspergilloma is an unusual complication of hydatid cyst and results from the deterioration of local defence against opportunistic infections.
Introduction: Hallux valgus is the one of the commonest forefoot deformities. Apart from cosmetic... more Introduction: Hallux valgus is the one of the commonest forefoot deformities. Apart from cosmetic perspectives it can be problematic because of its pressure effects. Though common in the age group of 30-60s in females of shoe wearing population, It’s incidence in general population is also increasing. Many procedures have been documented in literature to correct such deformity. Mitchell’s osteotomy is one of the treatment options for such deformity. This osteotomy is actually two transverse osteotomies in which one is incomplete, forming a step cut. The distal fragment is displaced medially and planter-wards aiming to restore the function of the feet. Material and Methods: Thirty patients with ten bilateral feet’s of hallux valgus deformities were operated at Bone and Joints hospital between the years 2007-2012. We had 23 females and 7 male patients with all the bilateral cases being females. The age group was between 19 years to 35 years. The follow up period was between 2 years to 7 years. The pre-operative radiograph of Antero posterior view was taken and recorded. The indications for surgery included pain, difficulty in foot wear and cosmoses. Results: All patients were assessed according to a protocol based on the AOFAS (Smith et al 1984) and re-assessed at three-monthly intervals. Pain improved from 23 + 5.2 to 36 +5 on final follow up (max 40). Functional score improved from 31+ 4.1 to 42 +1.2 and alignment score from 3 + 2.3 to 16 +2.4 on final follow up. Overall AOFAS score improved from 58 +1.6 to 94 +8.6. Radiographic results of the procedure were also satisfactory. Preoperatively the Hallux valgus angle was 30.3 + 7.1 degrees which improved to 11.1 +4.9 degrees on final follow up. The Inter metatarsal angle also improved from a preoperative score of 15.7 + 2.9 to 7 + 2.0 Conclusion: Mitchell’s procedure is simple, cheap and can safely address the hallux valgus deformity with good postoperative function results, both clinical and radiological. Osteotomy is stable and avascular necrosis can be easily avoided by careful soft tissue handling.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India, 2002
Pseudoaneurysm of the facial artery has very characteristic clinical features and radiological fi... more Pseudoaneurysm of the facial artery has very characteristic clinical features and radiological findings and can be treated with successful catheter emholisation, thus decreasing the morbidity associated with surgical procedure. A rare case of pseudoaneurysm of the facial artery is presented here for clinical interest.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India, 2003
People working in mines, plating factories, cement industries are mainly exposed to chrome substa... more People working in mines, plating factories, cement industries are mainly exposed to chrome substances, IIexavalent chromium has been implicated for its toxic effect on the nasal mucosa. Hereby we present a rare study of 28 patients who attended out patient department of Otorhinolaryngology at SSG Hospital, Baroda from a nearby chromium industry. This study aims to present various nasal manifestations of toxic effects of prolonged chromium exposure.
Purpose To determine whether variable hepatic microwave ablation (MWA) can induce local inflammat... more Purpose To determine whether variable hepatic microwave ablation (MWA) can induce local inflammation and distant pro-oncogenic effects compared with hepatic radiofrequency ablation (RFA) in an animal model. Materials and Methods In this institutional Animal Care and Use Committee-approved study, F344 rats (150 gm, n = 96) with subcutaneous R3230 breast adenocarcinoma tumors had normal non-tumor-bearing liver treated with RFA (70°C × 5 minutes), rapid higher-power MWA (20 W × 15 seconds), slower lower-power MWA (5 W × 2 minutes), or a sham procedure (needle placement without energy) and were sacrificed at 6 hours to 7 days (four time points; six animals per arm per time point). Ablation settings produced 11.4 mm ± 0.8 of coagulation for all groups. Distant tumor growth rates were determined to 7 days after treatment. Liver heat shock protein (HSP) 70 levels (at 72 hours) and macrophages (CD68 at 7 days), tumor proliferative indexes (Ki-67 and CD34 at 7 days), and serum and tissue lev...
Purpose: Early life stress has enduring behavioral and neuroendocrine effects, particularly in hi... more Purpose: Early life stress has enduring behavioral and neuroendocrine effects, particularly in hippocampus and amygdala. This may be relevant to mesial temporal lobe epilepsy (MTLE) that arises from these structures. In rats, we tested the hypothesis that early postnatal stress, in the form of maternal separation (MS), creates vulnerability to limbic epileptogenesis in adult life. Methods: On postnatal days 2-14, we exposed male and female nonepileptic rats to either MS for 180 min/day, or early handling (EH) and brief separation (15 min/day). At 7 weeks of age, rats of both genders exposed to MS displayed significantly increased anxiety, as evidenced by reduced time spent in the open arms of the elevated plus maze compared with EH rats. For epileptogenesis experiments, separate cohorts of rats, similarly exposed to either early life MS or EH, were implanted with bipolar electrodes into the left amygdala and one week later rapid electrical kindling performed until fully kindled (five Class V seizures, Racine scale). Results: In females, fewer stimulations were required following MS than EH to reach the fully kindled state (39.6 ± 6.4 vs. 67.1 ± 9.4; p < 0.0001); no differences were observed in males (MS: 49.1 ± 5.1; EH: 53.7 ± 6.6 stimulations). Discussion: We conclude that, while postnatal MS stress increases anxiety in both genders, this early life stressor results in persisting vulnerability to limbic epileptogenesis only in females. This has implications for human MTLE and its psychiatric comorbidities, suggesting a common causation model and the involvement of gender-specific factors such as sex hormones.
International Journal of Innovation and Applied Studies, Jul 2, 2014
Crop residue left in the field after grain harvests have a large potential as a bioenergy feedsto... more Crop residue left in the field after grain harvests have a large potential as a bioenergy feedstock. Crop residues of interest for bioenergy include; wheat straw, soybean straw, and rice straw, paddy straw etc. Paddy straw and wheat straw are potential substrate which can be exploited in industries in future for bioethanol (biofuel) production as they are cheap, abundant and high cellulose content. In this study rice (paddy) and wheat straw had been given both acid (1%-2.5%) and heat treatment (100ºc for 1 hour) for better sugar extraction in media and different parameters were optimized for bioethanol production. Conc. of reducing sugar in the sample after heat treatment were 0.30µg/ml (wheat straw), 15µg/ml (paddy straw), 18µg/ml (mixed sample). After acid treatment total reducing sugar was 56µg/ml (wheat straw), 70 µg/ml (paddy straw), and 170µg/ml (mixed). The optimized parameters for bioethanol production were pH =5.5, Temp=37ºc, conc. of (NH4) 2 SO 4 = 0.6mg/ml and yield of ethanol was 5.4%. The concentration of bioethanol for acid treatment of 1%, 2%, 2.5% were 1.3%, 3.4%,5.4%.
Polymeric black tea polyphenols (PBPs) have been shown to possess anti-tumor-promoting effects in... more Polymeric black tea polyphenols (PBPs) have been shown to possess anti-tumor-promoting effects in two-stage skin carcinogenesis. However, their mechanisms of action are not fully elucidated. In this study, mechanisms of PBP-mediated antipromoting effects were investigated in a mouse model employing the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Compared to controls, a single topical application of TPA to mouse skin increased the translocation of protein kinase C (PKC) from cytosol to membrane. Pretreatment with PBPs 1-3 decreased TPA-induced translocation of PKC isozymes (a, b, Z, g, e) from cytosol to membrane, whereas PBPs 4 and 5 were less effective. The levels of PKCs d and z in cytosol/membrane were similar in all the treatment groups. Complementary confocal microscopic evaluation showed a decrease in TPA-induced PKCa fluorescence in PBP-3-pretreated membranes, whereas pretreatment with PBP-5 did not show a similar decrease. Based on the experiments with specific enzyme inhibitors and phosphospecific antibodies, both PBP-3 and PBP-5 were observed to decrease TPA-induced level and/or activity of phosphatidylinositol 3-kinase (PI3K) and AKT1 (pS473). An additional ability of PBP-3 to inhibit site-specific phosphorylation of PKCa at all three positions responsible for its activation [PKCa (pT497), PKC PAN (bII pS660), PKCa/bII (pT638/ 641)] and AKT1 at the Thr308 position, along with a decrease in TPA-induced PDK1 protein level, correlated with the inhibition of translocation of PKC, which may impart relatively stronger chemoprotective activity to PBP-3 than to PBP-5. Altogether, PBP-mediated decrease in TPA-induced PKC phosphorylation correlated well with decreased TPA-induced NF-kB phosphorylation and downstream target proteins associated with proliferation, apoptosis, and inflammation in mouse skin. Results suggest that the antipromoting effects of PBPs are due to modulation of TPA-induced PI3Kmediated signal transduction.
Immunophilins are abundantly present in the brain as compared to the immune system. Immunophilin-... more Immunophilins are abundantly present in the brain as compared to the immune system. Immunophilin-binding agents like FK506 are known to inactivate neuronal nitric oxide synthase (nNOS) by inhibiting calcineurin and decrease the production of nitric oxide. Nitric oxide is involved in the mediation of nociception at the spinal level. In the present study, the effect of FK506 on the tail flick response in mice and the possible involvement of NO-L-arginine pathway in this paradigm was evaluated. FK506 (0.5, 1 and 3 mg/kg, ip) produced a significant antinociception in the tail flick test. Nitric oxide synthase (NOS) inhibitor L-NAME significantly and dose dependently (10-40 mg/kg, ip) potentiated the FK506 (0.5 mg/kg)-induced antinociception. On the other hand, NOS substrate L-arginine (100, 200 and 400 mg/kg) inhibited the FK506-induced antinociception in a dose-dependent manner. Concomitant administration of L-NAME (20 and 40 mg/kg) with L-arginine (200 mg/kg) blocked the inhibition exerted by L-arginine on the FK506-induced antinociception. Thus, it was concluded that NO- L-arginine pathway may be involved in the FK506-induced antinociception in tail flick test.
Uploads
Papers by Gaurav Kumar