Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (... more Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP…
Journal of the American College of Clinical Pharmacy, 2021
Pharmacists play essential roles in the various aspects of nutrition support pharmacotherapy. Acc... more Pharmacists play essential roles in the various aspects of nutrition support pharmacotherapy. According to the available literature, deficiencies in pharmacists' knowledge and skills in nutrition support exist. Furthermore, postgraduate year two (PGY2) nutrition support training positions no longer exist in the United States. American Society of Health‐System Pharmacists (ASHP)‐accredited postgraduate year one (PGY1) residencies do not require nutrition support rotations, and pharmacy schools may not provide the foundation to prepare students to meet the challenges in clinical practice. This article discusses the roles of the pharmacists in nutrition support, the current climate of nutrition support education in pharmacy schools and postgraduate programs, and solutions to address the challenges associated with the inadequacy of learning experiences in nutrition support.
Just-In-Time Teaching (JiTT) is an active learning pedagogy that has been successfully adopted by... more Just-In-Time Teaching (JiTT) is an active learning pedagogy that has been successfully adopted by various disciplines. However, it is unclear if JiTT presents value to a pharmacy curriculum. The current study implemented JiTT as an active-learning tool for an Integrated Microbiology and Virology course offered during the first year of a PharmD program. At the end of the course, students were provided with a survey that included items about JiTT. Several items were aggregated into a single rating about the degree that students agreed with various statements purporting JiTT as helpful, with score choices ranging from 1 (I strongly disagree) to 4 (I strongly agree). Overall, students strongly endorsed JiTT as helpful ( M = 3.61, SD = 0.50), and even the lowest score, 2.50, was neutral in tone. Students were asked to endorse rationales for why JiTT questions were used in this course; 93.02% felt that JiTT helped them keep track with the material, and only 34.88% felt that JiTT gave them...
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2021
Recent studies have identified that reduced alternative intravenous insulin doses, such as 5 unit... more Recent studies have identified that reduced alternative intravenous insulin doses, such as 5 units or 0.1 units/kg, may reduce the risk of hypoglycemia compared to standard doses of 10 units in patients treated for hyperkalemia. However, some studies suggest that these alternative doses may reduce the ability to lower serum potassium. This study was performed to determine the impact of alternative insulin dosing on hypoglycemia and potassium reduction in patients with hyperkalemia.
Introduction: BK virus (BKV)-associated nephropathy (BKVAN) is currently the most challenging inf... more Introduction: BK virus (BKV)-associated nephropathy (BKVAN) is currently the most challenging infectious cause of renal graft dysfunction in kidney transplant patients, leading to graft loss in up to 10%. Several single nucleotide polymorphisms (SNPs) in the promoter of cytokines have been associated with parvovirus B19, hepatitis C virus, HIV-1/AIDS infection. Deregulated production of pro-or anti-inflammatory cytokines plays an important role in the disease susceptibility and progression. In the present study, we aimed at genotyping the SNPs of the promoter regions of tumor necrosis factor alpha (TNF-α) and the interferon gamma (IFN-γ) in a group of renal allograft recipients affected by BK virus infection, taking into account the role that these cytokines might play in the immune response against BK virus. Methods: The TNF-α −308G/A (rs1800629) and IFN-γ [(rs2069718, G/A) (intron3), (rs12369470, C/T) and (rs2870953, T/A) (3‘ untranslated region)] genotypes were determined in 70 kidney allograft recipients with BKVN and 182 without BKVN (control group). Distributions of genotypes were compared to the Hardy-Weinberg theoretical distribution using the chi-square test. A logistic regression model was used to evaluate the effect of the genetic polymorphisms on BKVN. Nongenetic and genetic characteristics were included in the multivariate risk model. A p value less than 0.05 was considered statistically significant. Results: BKVN developed at an average of 1.6 years post-transplantation (range from 38 days to 8 years). Analysis of the results showed that IFN-γ (rs12369470) C allele (p=0.002, OR=1.93) was more frequent, but IFN-γ (rs2069718) G allele (p=0.024, OR=0.61) was less frequent in BKVN group in comparison with control group. Using multiple logistic regression along with race, donor type, and recipient age showed that the GG genotype of the IFN-γ (rs2069718) may have a protective effect with regard to BKVN (p=0.034). The allelic as well as genotypic frequencies of -308G >A TNF-α gene polymorphism did not significantly differ between the BKVN and control groups (p>0.05). Of the nongenetic factors, the use of tacrolimus and mycophenolate mofetil was associated with increased risk for BKVN. Conclusion: The results suggest that IFN-γ (rs12369470 and rs2069718) gene polymorphisms has predictive values for the development of BKVN in renal allograft recipients. MONDAY MORNING MINI ORAL ABSTRACTS
The dimeric NF-κB transcription factors play critical roles in diverse cellular processes includi... more The dimeric NF-κB transcription factors play critical roles in diverse cellular processes including adaptive and innate immunity, cell differentiation, proliferation and apoptosis. It regulates the expression of numerous genes that play a key role in the inflammatory response during kidney allograft rejection. This study aims to determine the association of NF-κB gene polymorphisms with allograft outcomes in the Hispanic renal transplant recipients. A total of 607 Hispanic renal transplant recipients at St. Vincent Medical Center between 2001 and 2010 were included in this study. The NF-κB genotypes were studied along with clinical data. In the case of NF-κB genotypes, the following single nucleotide polymorphisms (SNPs) were included: NF-κB1 (rs3774959, rs3774932, rs3774937, rs230526, rs230519), NF-κB2 (rs1056890, rs7897947, rs12769316) and NF-κB inducing kinase (NIK) (rs9908330, rs7222094). The association of each genotype with renal allograft survival and acute rejection was evaluated. NF-κB1 (rs3774937) CC genotype showed protective association with allograft rejection (OR=0.66, 95% CI=0.44-0.99, p=0.04). There was a significant increase in allograft survival time associated with the NF-κB1 (rs3774959) A allele (OR=0.76, 95% CI=0.60-0.98, p=0.03) while GG genotype was associated with a higher risk of graft failure (OR=1.51, 95% CI=1.02-2.21, p=0.03). There were no associations between polymorphic markers in NF-κB2 and NIK genes with allograft survival or acute rejection. Among non-genetic factors, we found that the use of tacrolimus, a deceased donor, delayed graft function and acute rejection were associated with allograft failure. The result of present study suggests that NF-κB1 gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.
Mycophenolic acid (MPA), a widely used immunosuppressant, has a complex metabolism that involves ... more Mycophenolic acid (MPA), a widely used immunosuppressant, has a complex metabolism that involves a number of enzymes. Some of its metabolites are thought to be the cause of gastrointestinal (GI) side effects. In this study, we investigated whether polymorphisms of UDP-glucuronosyltransferases (UGT1) A8, 1A9, and hepatocyte nuclear factor (HNF1α) genes or pharmacokinetic parameters of mycophenolic acid (MPA) were associated with the severity of GI symptoms in patients receiving MPA therapy. A total of 109 kidney transplant patients taking mycophenolic acid (MPA) derivatives were genotyped for UGT1A8, 1A9 and HNF1α genes. Among these, a total of 15 patients were participants in the pharmacokinetic study. Severity of GI symptoms was assessed using a validated Gastrointestinal Symptom Rating Scale (GSRS). The overall and subscale GSRS scores were measured at 1 week (baseline), 2 weeks, 3 months and 6 months post-transplantation. In the case of the pharmacokinetic study, EC-MPS was administered and a total of nine blood samples were obtained at -1, 0, 0.5, 1, 2, 4, 6, 8, and 12h. Genotypes of UGT1A8 were significantly associated with the overall GSRS scores at week 1 (p=0.02) and week 2 (p=0.036). Subscales were only statistically significant for constipation at week 1 (p=0.002) and indigestion at week 2 (p=0.02), while UGT1A9 was only significant for the constipation at week 1 (p=0.04). HNF1α genotypes were significantly different at week 1 in the overall GSRS (p=0.004), and for abdominal pain (p=0.04), acid reflux (p=0.036) and constipation subscales (p=0.04). In addition, abdominal pain was statistically significantly different at 3 months and 6 months after transplantation (p=0.03 and 0.02, respectively). In the case of the pharmacokinetic study, we have found some correlations between MPAC0 and constipation (p=0.02) where MPAAUC was correlated with acid reflux (p=0.02) and constipation (p=0.012), MPAGCL/F was correlated to acid reflux, indigestion, constipation and the sum of the GSRS scores (p=0.037, p=0.032, p=0.033 and p=0.04, respectively). Multinomial regression analysis for MPAGCL/F showed a statistical significance for the subscale indigestion and the sum of the GSRS (p=0.033 and p=0.037, respectively). Our data suggests that among patients receiving MPA the UGT1A9 alleles might play a role in determining the severity of early GI side effects, while the HNF1α allele appears to be associated with a later effect as well as early side effects. Our data also showed that some kinetic parameters might predict MPA side effects.
Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (... more Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP…
Journal of the American College of Clinical Pharmacy, 2021
Pharmacists play essential roles in the various aspects of nutrition support pharmacotherapy. Acc... more Pharmacists play essential roles in the various aspects of nutrition support pharmacotherapy. According to the available literature, deficiencies in pharmacists' knowledge and skills in nutrition support exist. Furthermore, postgraduate year two (PGY2) nutrition support training positions no longer exist in the United States. American Society of Health‐System Pharmacists (ASHP)‐accredited postgraduate year one (PGY1) residencies do not require nutrition support rotations, and pharmacy schools may not provide the foundation to prepare students to meet the challenges in clinical practice. This article discusses the roles of the pharmacists in nutrition support, the current climate of nutrition support education in pharmacy schools and postgraduate programs, and solutions to address the challenges associated with the inadequacy of learning experiences in nutrition support.
Just-In-Time Teaching (JiTT) is an active learning pedagogy that has been successfully adopted by... more Just-In-Time Teaching (JiTT) is an active learning pedagogy that has been successfully adopted by various disciplines. However, it is unclear if JiTT presents value to a pharmacy curriculum. The current study implemented JiTT as an active-learning tool for an Integrated Microbiology and Virology course offered during the first year of a PharmD program. At the end of the course, students were provided with a survey that included items about JiTT. Several items were aggregated into a single rating about the degree that students agreed with various statements purporting JiTT as helpful, with score choices ranging from 1 (I strongly disagree) to 4 (I strongly agree). Overall, students strongly endorsed JiTT as helpful ( M = 3.61, SD = 0.50), and even the lowest score, 2.50, was neutral in tone. Students were asked to endorse rationales for why JiTT questions were used in this course; 93.02% felt that JiTT helped them keep track with the material, and only 34.88% felt that JiTT gave them...
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2021
Recent studies have identified that reduced alternative intravenous insulin doses, such as 5 unit... more Recent studies have identified that reduced alternative intravenous insulin doses, such as 5 units or 0.1 units/kg, may reduce the risk of hypoglycemia compared to standard doses of 10 units in patients treated for hyperkalemia. However, some studies suggest that these alternative doses may reduce the ability to lower serum potassium. This study was performed to determine the impact of alternative insulin dosing on hypoglycemia and potassium reduction in patients with hyperkalemia.
Introduction: BK virus (BKV)-associated nephropathy (BKVAN) is currently the most challenging inf... more Introduction: BK virus (BKV)-associated nephropathy (BKVAN) is currently the most challenging infectious cause of renal graft dysfunction in kidney transplant patients, leading to graft loss in up to 10%. Several single nucleotide polymorphisms (SNPs) in the promoter of cytokines have been associated with parvovirus B19, hepatitis C virus, HIV-1/AIDS infection. Deregulated production of pro-or anti-inflammatory cytokines plays an important role in the disease susceptibility and progression. In the present study, we aimed at genotyping the SNPs of the promoter regions of tumor necrosis factor alpha (TNF-α) and the interferon gamma (IFN-γ) in a group of renal allograft recipients affected by BK virus infection, taking into account the role that these cytokines might play in the immune response against BK virus. Methods: The TNF-α −308G/A (rs1800629) and IFN-γ [(rs2069718, G/A) (intron3), (rs12369470, C/T) and (rs2870953, T/A) (3‘ untranslated region)] genotypes were determined in 70 kidney allograft recipients with BKVN and 182 without BKVN (control group). Distributions of genotypes were compared to the Hardy-Weinberg theoretical distribution using the chi-square test. A logistic regression model was used to evaluate the effect of the genetic polymorphisms on BKVN. Nongenetic and genetic characteristics were included in the multivariate risk model. A p value less than 0.05 was considered statistically significant. Results: BKVN developed at an average of 1.6 years post-transplantation (range from 38 days to 8 years). Analysis of the results showed that IFN-γ (rs12369470) C allele (p=0.002, OR=1.93) was more frequent, but IFN-γ (rs2069718) G allele (p=0.024, OR=0.61) was less frequent in BKVN group in comparison with control group. Using multiple logistic regression along with race, donor type, and recipient age showed that the GG genotype of the IFN-γ (rs2069718) may have a protective effect with regard to BKVN (p=0.034). The allelic as well as genotypic frequencies of -308G >A TNF-α gene polymorphism did not significantly differ between the BKVN and control groups (p>0.05). Of the nongenetic factors, the use of tacrolimus and mycophenolate mofetil was associated with increased risk for BKVN. Conclusion: The results suggest that IFN-γ (rs12369470 and rs2069718) gene polymorphisms has predictive values for the development of BKVN in renal allograft recipients. MONDAY MORNING MINI ORAL ABSTRACTS
The dimeric NF-κB transcription factors play critical roles in diverse cellular processes includi... more The dimeric NF-κB transcription factors play critical roles in diverse cellular processes including adaptive and innate immunity, cell differentiation, proliferation and apoptosis. It regulates the expression of numerous genes that play a key role in the inflammatory response during kidney allograft rejection. This study aims to determine the association of NF-κB gene polymorphisms with allograft outcomes in the Hispanic renal transplant recipients. A total of 607 Hispanic renal transplant recipients at St. Vincent Medical Center between 2001 and 2010 were included in this study. The NF-κB genotypes were studied along with clinical data. In the case of NF-κB genotypes, the following single nucleotide polymorphisms (SNPs) were included: NF-κB1 (rs3774959, rs3774932, rs3774937, rs230526, rs230519), NF-κB2 (rs1056890, rs7897947, rs12769316) and NF-κB inducing kinase (NIK) (rs9908330, rs7222094). The association of each genotype with renal allograft survival and acute rejection was evaluated. NF-κB1 (rs3774937) CC genotype showed protective association with allograft rejection (OR=0.66, 95% CI=0.44-0.99, p=0.04). There was a significant increase in allograft survival time associated with the NF-κB1 (rs3774959) A allele (OR=0.76, 95% CI=0.60-0.98, p=0.03) while GG genotype was associated with a higher risk of graft failure (OR=1.51, 95% CI=1.02-2.21, p=0.03). There were no associations between polymorphic markers in NF-κB2 and NIK genes with allograft survival or acute rejection. Among non-genetic factors, we found that the use of tacrolimus, a deceased donor, delayed graft function and acute rejection were associated with allograft failure. The result of present study suggests that NF-κB1 gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.
Mycophenolic acid (MPA), a widely used immunosuppressant, has a complex metabolism that involves ... more Mycophenolic acid (MPA), a widely used immunosuppressant, has a complex metabolism that involves a number of enzymes. Some of its metabolites are thought to be the cause of gastrointestinal (GI) side effects. In this study, we investigated whether polymorphisms of UDP-glucuronosyltransferases (UGT1) A8, 1A9, and hepatocyte nuclear factor (HNF1α) genes or pharmacokinetic parameters of mycophenolic acid (MPA) were associated with the severity of GI symptoms in patients receiving MPA therapy. A total of 109 kidney transplant patients taking mycophenolic acid (MPA) derivatives were genotyped for UGT1A8, 1A9 and HNF1α genes. Among these, a total of 15 patients were participants in the pharmacokinetic study. Severity of GI symptoms was assessed using a validated Gastrointestinal Symptom Rating Scale (GSRS). The overall and subscale GSRS scores were measured at 1 week (baseline), 2 weeks, 3 months and 6 months post-transplantation. In the case of the pharmacokinetic study, EC-MPS was administered and a total of nine blood samples were obtained at -1, 0, 0.5, 1, 2, 4, 6, 8, and 12h. Genotypes of UGT1A8 were significantly associated with the overall GSRS scores at week 1 (p=0.02) and week 2 (p=0.036). Subscales were only statistically significant for constipation at week 1 (p=0.002) and indigestion at week 2 (p=0.02), while UGT1A9 was only significant for the constipation at week 1 (p=0.04). HNF1α genotypes were significantly different at week 1 in the overall GSRS (p=0.004), and for abdominal pain (p=0.04), acid reflux (p=0.036) and constipation subscales (p=0.04). In addition, abdominal pain was statistically significantly different at 3 months and 6 months after transplantation (p=0.03 and 0.02, respectively). In the case of the pharmacokinetic study, we have found some correlations between MPAC0 and constipation (p=0.02) where MPAAUC was correlated with acid reflux (p=0.02) and constipation (p=0.012), MPAGCL/F was correlated to acid reflux, indigestion, constipation and the sum of the GSRS scores (p=0.037, p=0.032, p=0.033 and p=0.04, respectively). Multinomial regression analysis for MPAGCL/F showed a statistical significance for the subscale indigestion and the sum of the GSRS (p=0.033 and p=0.037, respectively). Our data suggests that among patients receiving MPA the UGT1A9 alleles might play a role in determining the severity of early GI side effects, while the HNF1α allele appears to be associated with a later effect as well as early side effects. Our data also showed that some kinetic parameters might predict MPA side effects.
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