Wayne State Researching Effects of Tocotrienols From Palm Oil in End-Stage ... - Newswise (press release)
Newswise — DETROIT – End-stage renal disease (ERSD) is the last stage of chronic kidney disease where the kidneys function at under 10 to 15 percent of their normal capacity. At this stage, kidneys cannot effectively remove waste or excess fluid from the blood system, and dialysis or a kidney transplant is necessary to live.
A team of researchers led by Pramod Khosla, Ph.D., associate professor of nutrition and food science in the College of Liberal Arts and Sciences at Wayne State University, will study the effects of a daily supplement of a Tocotrienol-rich fraction from palm oil to see if it improves dyslipidemia, a disorder of lipoprotein metabolism that may be manifested by a decrease in the “good” high-density lipoprotein (HDL) cholesterol in patients with ESRD who are on hemodialysis. Tocotrienols are a form of Vitamin E and have been shown in recent years to have diverse health effects. In addition, Khosla’s team will explore the impact on symptoms such as inflammation and symptoms related to Restless Leg Syndrome in the same cohort of patients.
Khosla believes that the supplement will also act as an anti-inflammatory and antioxidant nutrient, leading to improved nutritional status, lipid profiles, and inflammatory and oxidative stress markers in the ESRD patients.
The three-year study, funded by a $2.4 million grant from the Malaysian Palm Oil Board, a premier government agency of Malaysia, will take place in multiple dialysis centers in the United States and Malaysia. The cross-collaboration will allow the investigators to evaluate differences in dietary patterns of 800 dialysis patients in the two countries. With the patient pool in Michigan of predominantly African Americans and Caucasians and the Malaysian cohort comprised of three distinct ethnicities – Malays, Chinese and Indians – the investigators hope to shed light on possible genetic and metabolic differences in the dialysis populations. Additionally, as a significant proportion of dialysis patients suffer from Restless Legs Syndrome — an unpleasant tingling or cramping sensation that impacts the quality of life — the investigators hope to shed some light on the underlying causes for the condition.
“End-stage renal disease patients undergoing chronic hemodialysis experience a higher risk of complications such as cardiovascular disease, dyslipidemia, Restless Leg Syndrome, insomnia and other health issues,” said Khosla. “In this study, we hope to see significant improvements in various biomarkers that should help decrease some of these complications.”
“Dialysis corrects many but not all of the symptoms and biochemical abnormalities that occur in kidney failure,” said Dr. James Sondheimer, associate professor of medicine and chief of the Division of Nephrology and Hypertension at WSU. “We hope to gain a better understanding of how tocotrienols, as substances with antioxidant and anti-inflammatory effects, affect clinical outcomes as well as metabolic parameters.”
Collaborators on the study who will be responsible for patient care include Smiti Gupta, Ph.D., associate professor of nutrition and food science in the College of Liberal Arts and Sciences at Wayne State University, and nephrologists James Sondheimer (WSU and Davita), Boniface Tubie (Great Lakes Dialysis) and Lalathaksha Kumbar (Henry Ford Health System). In addition, registered dietitians, nurses and technical personnel at each of the dialysis units will assist over the course of the study.
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About Wayne State University
Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit http://research.wayne.edu.
CRT-D benefits patients with mild HF, renal dysfunction - Healio
In patients with mild HF, renal dysfunction was associated with increased risk for HF and death, but the risk was attenuated in those who had a cardiac resynchronization therapy defibrillator, according to new findings.
Researchers assessed the impact of renal function on long-term outcomes with CRT-D in 1,820 patients with mild HF who participated in the MADIT-CRT study. Patients were stratified by QRS morphology based on the presence of left bundle branch block (LBBB). Within each strata, patients were further categorized by renal function: glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 or at least 60 mL/min/1.73 m2.
The primary endpoint was death. Secondary endpoints included HF or death and HF. Median follow-up was 5.6 years.
Usama A. Daimee, MD, and colleagues found that among the 1,274 patients with LBBB, 32% had GFR less than 60 mL/min/1.73 m2and 68% had GFR of at least 60 mL/min/1.73 m2.
Renal dysfunction confers higher risk
Compared with those with LBBB and no renal dysfunction, patients with LBBB and renal dysfunction had a higher risk for death (HR = 2.09; 95% CI, 1.53-2.86) and combined HF/death (HR = 1.46; 95% CI, 1.17-1.82). The researchers also observed a trend toward higher risk for HF (HR = 1.28; 95% CI, 1-1.66), according to the results.
In those with LBBB, CRT-D was associated with a reduction in the risk for HF or death, as well as HF alone, and a trend toward reduced risk for death, according to the researchers. This was observed in patients with impaired renal function (HR for death = 0.66; 95% CI, 0.44-1; HR for HF or death = 0.49; 95% CI, 0.36-0.67; HR for HF = 0.36; 95% CI, 0.25-0.54) and normal renal function (HR for death = 0.68; 95% CI, 0.44-1.05; HR for HF or death = 0.5; 95% CI, 0.38-0.66; HR for HF = 0.43; 95% CI, 0.32-0.59).
Compared with patients with high GFR, those with low GFR had a greater absolute reduction in risk for death (14% vs. 6%) and death or HF (25% vs. 15%).
In patients without LBBB, those with GFR less than 60 mL/min/1.73 m2 had higher risk for death (HR = 2.08; 95% CI, 1.37-3.15), HF or death (HR = 1.84; 95% CI, 1.35-2.51) and HF (HR = 2; 95% CI, 1.4-2.86) compared with those with GFR of at least 60 mL/min/1.73 m2.
However, CRT-D was not associated with reduced risk for death, HF or death or HF compared with implantable cardioverter defibrillator only in patients without LBBB, regardless of renal function.
Encouraging findings
“Our results have important clinical implications for patients with moderate renal dysfunction who are shown in this study to derive sustained benefit during long-term follow-up from CRT-D with greater absolute risk reductions in adverse outcomes,” Daimee, from the University of Rochester Medical Center, Rochester, New York, and colleagues wrote. “These findings are encouraging for patients with moderate renal dysfunction to be considered for implantation of a CRT-D.” – by Erik Swain
Disclosure: The MADIT-CRT trial was funded by an unrestricted research grant from Boston Scientific. Daimee reports no relevant financial disclosures. Four researchers report receiving grant support from Boston Scientific.
In patients with mild HF, renal dysfunction was associated with increased risk for HF and death, but the risk was attenuated in those who had a cardiac resynchronization therapy defibrillator, according to new findings.
Researchers assessed the impact of renal function on long-term outcomes with CRT-D in 1,820 patients with mild HF who participated in the MADIT-CRT study. Patients were stratified by QRS morphology based on the presence of left bundle branch block (LBBB). Within each strata, patients were further categorized by renal function: glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 or at least 60 mL/min/1.73 m2.
The primary endpoint was death. Secondary endpoints included HF or death and HF. Median follow-up was 5.6 years.
Usama A. Daimee, MD, and colleagues found that among the 1,274 patients with LBBB, 32% had GFR less than 60 mL/min/1.73 m2and 68% had GFR of at least 60 mL/min/1.73 m2.
Renal dysfunction confers higher risk
Compared with those with LBBB and no renal dysfunction, patients with LBBB and renal dysfunction had a higher risk for death (HR = 2.09; 95% CI, 1.53-2.86) and combined HF/death (HR = 1.46; 95% CI, 1.17-1.82). The researchers also observed a trend toward higher risk for HF (HR = 1.28; 95% CI, 1-1.66), according to the results.
In those with LBBB, CRT-D was associated with a reduction in the risk for HF or death, as well as HF alone, and a trend toward reduced risk for death, according to the researchers. This was observed in patients with impaired renal function (HR for death = 0.66; 95% CI, 0.44-1; HR for HF or death = 0.49; 95% CI, 0.36-0.67; HR for HF = 0.36; 95% CI, 0.25-0.54) and normal renal function (HR for death = 0.68; 95% CI, 0.44-1.05; HR for HF or death = 0.5; 95% CI, 0.38-0.66; HR for HF = 0.43; 95% CI, 0.32-0.59).
Compared with patients with high GFR, those with low GFR had a greater absolute reduction in risk for death (14% vs. 6%) and death or HF (25% vs. 15%).
In patients without LBBB, those with GFR less than 60 mL/min/1.73 m2 had higher risk for death (HR = 2.08; 95% CI, 1.37-3.15), HF or death (HR = 1.84; 95% CI, 1.35-2.51) and HF (HR = 2; 95% CI, 1.4-2.86) compared with those with GFR of at least 60 mL/min/1.73 m2.
However, CRT-D was not associated with reduced risk for death, HF or death or HF compared with implantable cardioverter defibrillator only in patients without LBBB, regardless of renal function.
Encouraging findings
“Our results have important clinical implications for patients with moderate renal dysfunction who are shown in this study to derive sustained benefit during long-term follow-up from CRT-D with greater absolute risk reductions in adverse outcomes,” Daimee, from the University of Rochester Medical Center, Rochester, New York, and colleagues wrote. “These findings are encouraging for patients with moderate renal dysfunction to be considered for implantation of a CRT-D.” – by Erik Swain
Disclosure: The MADIT-CRT trial was funded by an unrestricted research grant from Boston Scientific. Daimee reports no relevant financial disclosures. Four researchers report receiving grant support from Boston Scientific.
Renal cell carcinoma (RCC), normally considered an intrinsically chemotherapy-resistant cancer, is currently treated with targeted biologic therapies, including antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib.
The efficacy of these agents is limited by both intrinsic and acquired resistance. Death is almost always due to advanced metastatic disease, a treatment circumstance seldom modeled in preclinical (mouse) drug testing. Similarly, therapy results using postsurgical adjuvant therapy models of microscopic disease have not been reported. Using in vivo selection and transfection of established human RCC cell lines (786-0 and SN12-PM6), we derived clonal luciferase-expressing variants capable of spontaneous metastasis from an orthotopic primary tumor to organs typical of clinical RCC, including bone, lungs, and brain. The bioluminescence and consistent metastatic spread of von Hippel-Lindau-wild type SN12-PM6-1 cells allowed for the establishment of perioperative therapy models of RCC. We report that the combination of daily low-dose metronomic topotecan with pazopanib has highly potent antiprimary tumor as well as both postsurgical adjuvant and metastatic therapy efficacy despite lack of an antimetastatic effect of pazopanib monotherapy. The combination therapy resulted in sustained metastatic tumor cell dormancy, but tumor progression occurred upon treatment cessation. We also obtained evidence for a direct effect of pazopanib on RCC cells, resulting in increased intracellular concentration of topotecan. Our results suggest that this type of treatment combination should be considered for clinical evaluation in early- or late-stage metastatic disease, even for tumors seemingly intrinsically "resistant" to antiangiogenic TKIs or chemotherapy.
Written by:
Jedeszko C, Paez-Ribes M, Di Desidero T, Man S, Lee CR, Xu P, Bjarnason GA, Bocci G, Kerbel RS. Are you the author? Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada; Divisione di Farmacologia, Dipartimento di Medicina Clinica e Sperimentale, University of Pisa, Pisa 56126, Italy; Sunnybrook Odette Cancer Centre, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 2J7, Canada. This email address is being protected from spambots. You need JavaScript enabled to view it.
Pangasinan hospital's dialysis center resumes operation - Philippine Information Agency
SAN CARLOS CITY, Pangasinan, July 14 (PIA) –Patients in need of dialysis treatment can now go to the Mayor Julian V. Resuello Dialysis Center at the Pangasinan Provincial Hospital (PPH) here as operations have resumed on July 7.
PPH chief Dr. Policarpio Manuel said they are now ready to start dialysis operations again after five months of preventive maintenance that temporarily halted the center’s operation.
“The source of water being used in the clinic underwent repair and maintenance to ensure the safe and smooth procedure of the clinical operations being done at the center,” Manuel said.
He thanked the provincial government for acting fast on the repair of the water cleaner.
The center, which started providing its services six years ago, was established by the provincial government in partnership with the DaVita Corporation based in Los Angeles, California and the former San Carlos City Mayor Julier Resuello.
Da Vita donated the brand new dialysis machines and a water treatment plant for the center.
Dr. Anna Maria Teresa De Guzman, provincial health officer, said the center, during its normal operation, now serves 60 patients a day which is double the number of patients being served when the center has just started.
She said that the center has been of great help to dialysis patients especially those who do not have sufficient funds to finance their treatment.
De Guzman disclosed that seven new dialysis machines are expected to arrive during the last quarter of the year.
She said Da Vita is sending the new machines to replenish the old units nearing expiration.
In a report of the Provincial Information Office, Dr. Manuel said the center has 15 dialysis machines at present and the seven new machines set to replace the old ones will be arriving around October.
He added that the dialysis center has produced graduates from its training program that certifies nurses to work on a dialysis center.
Dr. Manuel said the Mayor Julian V. Resuello Dialysis Center has consistently become a top-rank dialysis training center and the biggest Dialysis Center among all local government units nationwide. (MCA/AMM/PIA-1, Pangasinan)
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