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Apolipoprotein B: A preferable measure to LDL-cholesterol in hypertriglyceridaemic patients undergoing lipoprotein apheresis
Abstracts / Atherosclerosis 218 (2011) e1–e12
Investigations revealed albumin 28 g/L, urea 8.0 mmol/L, creatinine 205 mol/L, normal thyroid profile and fasting glucose. Haemoglobin was 13.8 g/dL with platelets of 598 × 10−9 /L. Urinalysis revealed 4+ protein with a protein – creatinine index of 30,154. Serum and urine revealed monoclonal bands with urine lambda and kappa light chains 64.3 and 21.1 ng/L respectively. Discussion: Measurement of serum lipids is routinely performed in primary care as a prelude to starting statin therapy in high risk patients. A blanket approach to treating all patients with statins is clearly inappropriate as highlighted by this case. Secondary causes of hyperlipidaemia such as diabetes, hypothyroidism and nephrotic syndrome are recognized in primary care. There is a need to consider secondary causes in the event of refractory hyperlipidaemia. Thorough examination and relevant investigation is important to uncover this.
e7
Sociological study of familial hypercholesterolaemia cascade testing
was confirmed by the presence of a characteristic double doublet at ı 4 (dd, 2H, –CH2 of thiazolidinone ring) J = 14.3 Hz, and a singlet at ı 7.0 (s, 1H, Ar-CH-of thiazolidinone ring) in the 1 H NMR spectrum. The 13 C NMR signals at ı 176.47, 63.43, 170.8, & 32.96 corresponding to C-4 carbon of flavone, C-2, C-4, and C-5 carbons of thiazolidinone respectively were also in agreement with the structure. Molecular ion peaks in mass spectra supported the above findings in all the cases. The synthesized compounds were evaluated for their hypolipidaemic and hypoglycaemic activity in Swiss albino mice fed a high-fat diet along with fructose administered in drinking water. The newly synthesized analogues demonstrated a 5–10 times increase in the hypolipidaemic activity evidenced by the reduction in the elevated triglycerides and cholesterol levels in comparison to the parent compounds. Derivatives containing methoxy substitution in their structure were found to be most active. However the hypoglycaemic effects of these newly synthesized analogues were found to be not very promising. Further studies need to be carried out to confirm the hypolipidaemic activity and to establish the mechanism.
Jane Miller
doi:10.1016/j.atherosclerosis.2011.07.077
doi:10.1016/j.atherosclerosis.2011.07.075
Cesagen ESRC, Centre for Economic and Social Aspects of Genomics, Cardiff University, United Kingdom Cascade testing for Familial Hypercholesterolaemia (FH) was recommended in the 2008 NICE guidelines. The FH testing programme in Wales was launched last year and we are conducting a sociological study with FH patients and GPs. We are interviewing 30 patients across Wales to explore their experience of living with FH, their experience of diagnosis, their understanding of the genetic or familial nature of FH and their views on cascade testing through family tracing. We are also interviewing 30 GPs across Wales to ascertain their knowledge of FH itself, its genetic or familial nature, and their awareness of cascade testing. We are also exploring attitudes among both groups to the change in treatment age to 10 years. Preliminary findings from patient interviews will be presented with some emerging themes. These include powerful family histories, issues with insurance, experiences with GPs, successful and problematic family tracing, diagnosis and treatment of children and issues with FH and pregnancy. doi:10.1016/j.atherosclerosis.2011.07.076 Synthesis and evaluation of thiazolidinone analogues of flavones as hypolipidaemic agents Sudheer Moorkoth 1 , K.K. Srinivasan 1 , Gopalan Kutty 2 1
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India 2 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India Flavone heterocycle is a potential pharmacophore with low toxicity profile. There are several reports on the antiatherosclerotic effects, antithrombogenic effects, and hypolipidaemic effects of flavonoids. Thiazolidin-4-ones are another class of heterocycles which were evaluated by many earlier workers for their antidiabetic and hypolipidaemic effects. We aimed at combining the potential of these two heterocycles and investigating their hypolipidaemic and hypoglycaemic potential for a synergistic activity with less toxicity. Synthesis of thiazolidinone analogues of flavones was achieved by condensing 6-aminoflavone with aromatic aldehydes in the presence of thioglycollic acid. The cyclisation into thiazolidinone
Apolipoprotein B: A preferable measure to LDL-cholesterol in hypertriglyceridaemic patients undergoing lipoprotein apheresis E. Neves ∗ , B. Ussen, V. Kale, N. Bourdeaux, M. Calam, C. Huggett, E. Lee, A. Pottle, M. Barbir Harefield Hospital, Middlesex, United Kingdom Lipoprotein apheresis is an effective lipid-lowering treatment. Blood is withdrawn from the patient and passed through a treatment column which either filters or adsorbs Low Density Lipoprotein (LDL)-cholesterol, triglycerides, Lipoprotein(a) (Lp(a)) and Apolipoprotein B (Apo B). Once treated the blood is then returned to the patient. Apo B is the protein element of the LDL molecule. There are two types of Apo B: Apo B-100 is made in the liver and Apo B-48 is produced in the intestines and is responsible for the initial transfer of dietary lipids from the intestine to the liver for processing. It is believed that raised levels of Apo B-100 are associated with coronary heart disease (CHD) and are an even a better predictor of CHD than LDL-cholesterol. Over the last six months we have measured Apo B levels in thirteen patients receiving Lipoprotein Apheresis in our unit. Eleven patients were treated on a whole blood machine two patients were on a plasma system. Analysing data from six consecutive treatments, we have been able to demonstrate a consistent reduction in Apo B levels ranging from 35 to 70% (mean 52.7% (SD 10.6)). These results mirror the reductions achieved in LDL-cholesterol. When serum triglycerides exceed 4.5mmol/L, calculated LDLcholesterol levels are inaccurate and Apo-B can then be used as an accurate indicator of the efficacy of treatment. Apo B is a more reliable measure particularly in non-fasting samples, so in patients treated with apheresis, it may be a more accurate measure as they are non-fasting for the treatment. Apo B can be tested from routine plasma samples in usual laboratory conditions although there might be additional cost implications. In conclusion, Apo B measurements may be more accurate than those of LDL-cholesterol in patients treated with Lipoprotein Apheresis; particularly those with raised triglyceride levels.
doi:10.1016/j.atherosclerosis.2011.07.078
Investigations revealed albumin 28 g/L, urea 8.0 mmol/L, creatinine 205 mol/L, normal thyroid profile and fasting glucose. Haemoglobin was 13.8 g/dL with platelets of 598 × 10−9 /L. Urinalysis revealed 4+ protein with a protein – creatinine index of 30,154. Serum and urine revealed monoclonal bands with urine lambda and kappa light chains 64.3 and 21.1 ng/L respectively. Discussion: Measurement of serum lipids is routinely performed in primary care as a prelude to starting statin therapy in high risk patients. A blanket approach to treating all patients with statins is clearly inappropriate as highlighted by this case. Secondary causes of hyperlipidaemia such as diabetes, hypothyroidism and nephrotic syndrome are recognized in primary care. There is a need to consider secondary causes in the event of refractory hyperlipidaemia. Thorough examination and relevant investigation is important to uncover this.
e7
Sociological study of familial hypercholesterolaemia cascade testing
was confirmed by the presence of a characteristic double doublet at ı 4 (dd, 2H, –CH2 of thiazolidinone ring) J = 14.3 Hz, and a singlet at ı 7.0 (s, 1H, Ar-CH-of thiazolidinone ring) in the 1 H NMR spectrum. The 13 C NMR signals at ı 176.47, 63.43, 170.8, & 32.96 corresponding to C-4 carbon of flavone, C-2, C-4, and C-5 carbons of thiazolidinone respectively were also in agreement with the structure. Molecular ion peaks in mass spectra supported the above findings in all the cases. The synthesized compounds were evaluated for their hypolipidaemic and hypoglycaemic activity in Swiss albino mice fed a high-fat diet along with fructose administered in drinking water. The newly synthesized analogues demonstrated a 5–10 times increase in the hypolipidaemic activity evidenced by the reduction in the elevated triglycerides and cholesterol levels in comparison to the parent compounds. Derivatives containing methoxy substitution in their structure were found to be most active. However the hypoglycaemic effects of these newly synthesized analogues were found to be not very promising. Further studies need to be carried out to confirm the hypolipidaemic activity and to establish the mechanism.
Jane Miller
doi:10.1016/j.atherosclerosis.2011.07.077
doi:10.1016/j.atherosclerosis.2011.07.075
Cesagen ESRC, Centre for Economic and Social Aspects of Genomics, Cardiff University, United Kingdom Cascade testing for Familial Hypercholesterolaemia (FH) was recommended in the 2008 NICE guidelines. The FH testing programme in Wales was launched last year and we are conducting a sociological study with FH patients and GPs. We are interviewing 30 patients across Wales to explore their experience of living with FH, their experience of diagnosis, their understanding of the genetic or familial nature of FH and their views on cascade testing through family tracing. We are also interviewing 30 GPs across Wales to ascertain their knowledge of FH itself, its genetic or familial nature, and their awareness of cascade testing. We are also exploring attitudes among both groups to the change in treatment age to 10 years. Preliminary findings from patient interviews will be presented with some emerging themes. These include powerful family histories, issues with insurance, experiences with GPs, successful and problematic family tracing, diagnosis and treatment of children and issues with FH and pregnancy. doi:10.1016/j.atherosclerosis.2011.07.076 Synthesis and evaluation of thiazolidinone analogues of flavones as hypolipidaemic agents Sudheer Moorkoth 1 , K.K. Srinivasan 1 , Gopalan Kutty 2 1
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India 2 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India Flavone heterocycle is a potential pharmacophore with low toxicity profile. There are several reports on the antiatherosclerotic effects, antithrombogenic effects, and hypolipidaemic effects of flavonoids. Thiazolidin-4-ones are another class of heterocycles which were evaluated by many earlier workers for their antidiabetic and hypolipidaemic effects. We aimed at combining the potential of these two heterocycles and investigating their hypolipidaemic and hypoglycaemic potential for a synergistic activity with less toxicity. Synthesis of thiazolidinone analogues of flavones was achieved by condensing 6-aminoflavone with aromatic aldehydes in the presence of thioglycollic acid. The cyclisation into thiazolidinone
Apolipoprotein B: A preferable measure to LDL-cholesterol in hypertriglyceridaemic patients undergoing lipoprotein apheresis E. Neves ∗ , B. Ussen, V. Kale, N. Bourdeaux, M. Calam, C. Huggett, E. Lee, A. Pottle, M. Barbir Harefield Hospital, Middlesex, United Kingdom Lipoprotein apheresis is an effective lipid-lowering treatment. Blood is withdrawn from the patient and passed through a treatment column which either filters or adsorbs Low Density Lipoprotein (LDL)-cholesterol, triglycerides, Lipoprotein(a) (Lp(a)) and Apolipoprotein B (Apo B). Once treated the blood is then returned to the patient. Apo B is the protein element of the LDL molecule. There are two types of Apo B: Apo B-100 is made in the liver and Apo B-48 is produced in the intestines and is responsible for the initial transfer of dietary lipids from the intestine to the liver for processing. It is believed that raised levels of Apo B-100 are associated with coronary heart disease (CHD) and are an even a better predictor of CHD than LDL-cholesterol. Over the last six months we have measured Apo B levels in thirteen patients receiving Lipoprotein Apheresis in our unit. Eleven patients were treated on a whole blood machine two patients were on a plasma system. Analysing data from six consecutive treatments, we have been able to demonstrate a consistent reduction in Apo B levels ranging from 35 to 70% (mean 52.7% (SD 10.6)). These results mirror the reductions achieved in LDL-cholesterol. When serum triglycerides exceed 4.5mmol/L, calculated LDLcholesterol levels are inaccurate and Apo-B can then be used as an accurate indicator of the efficacy of treatment. Apo B is a more reliable measure particularly in non-fasting samples, so in patients treated with apheresis, it may be a more accurate measure as they are non-fasting for the treatment. Apo B can be tested from routine plasma samples in usual laboratory conditions although there might be additional cost implications. In conclusion, Apo B measurements may be more accurate than those of LDL-cholesterol in patients treated with Lipoprotein Apheresis; particularly those with raised triglyceride levels.
doi:10.1016/j.atherosclerosis.2011.07.078