Effects of feeding Pyrus malus (Apple) on serum lipid profile with special reference to high and low density lipoprotein cholesterol levels in normal albino rabbits

The effects of regular feeding ofPyrus malus whole fruit and its juice on total serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and phospholipids have been studied in normal albino rabbits. It was observed that the whole fruit as well as juice caused significant and progressive decrease in total serum cholesterol, LDL cholesterol and triglycerides within a period of 30 days. On the other hand, serum phospholipids and HDL cholesterol showed progressive and significant increase. Apparently, whole fruit appeared to bring about more per cent lowering in total cholesterol, LDL cholesterol and more increase in HDL cholesterol as compared to juice. Whole apple fruit also caused increase in body weight of rabbits on 30th day (p<0.05) while oral administration of juice showed insignificant change in body weight even on 30th day (p>0.05).     

Effect of herbal drug on serum lipid profile in albino rabbits

Abana, a herbal preparation of Himalaya Drug Co. significantly increases HDL—cholesterol and lowers LDL—cholesterol. Moreover, it antagonises the HDL lowering effect of metoprolol.     

Lipoprotein (a): a Unique Independent Risk Factor for Coronary Artery Disease

The current epidemic affecting Indians is coronary artery disease (CAD), and is currently one of the most common causes of mortality and morbidity in developed and developing countries. The higher rate of CAD in Indians, as compared to people of other ethnic origin, may indicate a possible genetic susceptibility. Hence, Lp(a), an independent genetic risk marker for atherosclerosis and cardiovascular disease assumes great importance. Lp(a), an atherogenic lipoprotein, contains a cholesterol rich LDL particle, one molecule of apolipoprotein B-100 and a unique protein, apolipoprotein (a) which distinguishes it from LDL. Apo(a) is highly polymorphic and an inverse relationship between Lp(a) concentration and apo(a) isoform size has been observed. This is genetically controlled suggesting a functional diversity among the apo(a) isoforms. The LPA gene codes for apo(a) whose genetic heterogeneity is due to variations in its number of kringles. The exact pathogenic mechanism of Lp(a) is still not completely elucidated, but the structural homology of Lp(a) with LDL and plasmin is possibly responsible for its acting as a link between atherosclerosis and thrombosis. Upper limits of normal Lp(a) levels have not been defined for the Indian population. A cut off limit of 20 mg/dL has been suggested while for the Caucasian population it is 30 mg/dL. Though a variety of assays are available for its measurement, standardization of the analytical method is highly complicated as a majority of the methods are affected by the heterogeneity in apo(a) size. No therapeutic drug selectively targets Lp(a) but recently, new modifiers of apo(a) synthesis are being considered.     

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

Understanding the mechanism behind cancer metastasis is a major challenge in cancer biology. Several in vitro models have been developed to mimic a cancer microenvironment by engineering cancer–endothelial cell (EC) and cancer-stromal cell interactions. It has been challenging to realistically mimic angiogenesis, intravasation, and extravasation using macro-scale approaches but recent progress in microfluidics technology has begun to yield promising results. We present a metastasis chip that produce microvessels, where EC and stromal cells can be patterned in close proximity to tumor cells. The vessels are formed following a natural morphogenic process and have smooth boundaries with proper cell-cell junctions. The engineered microvessels are perfusable and have well-defined openings toward inlet and outlet channels. The ability to introduce cancer cells into different locations bordering to the microvessel wall allowed generation and maintenance of appropriate spatial gradients of growth factors and attractants. Cancer angiogenesis and its inhibition by anti-vascular endothelial growth factor (bevacizumab) treatment were successfully reproduced in the metastasis chip. Cancer intravasation and its modulation by treatment of tumor necrosis factor-α were also modeled. Compared to other models, the unique design of the metastasis chip that engineers a clear EC-cancer interface allows precise imaging and quantification of angiogenic response as well as tumor cell trans-endothelial migration. The metastasis chip presented here has potential applications in the investigation of fundamental cancer biology as well as in drug screening.     

Oxidised LDL, HDL cholesterol, LDL cholesterol levels in patients of coronary artery disease

Coronary artery disease is a major cause of morbidity and has various risk factors. Lipid profile i.e. low HDL-cholesterol, high LDL cholesterol, high total cholesterol, high triglycerides playing important role in its causation. Recently interest has been shown in the oxidized fraction of LDL as one of the risk factors. In the present study 60 age and sex matched normal healthy individuals were taken as controls and 60 patients of CAD were taken. Cholesterol was measured by enzymatic method, HDL cholesterol by phosphotungstate precipitation method. Serum levels of LDL fraction of cholesterol was measured by a new and simpler method of precipitation. Result was expressed as mol/L of diene conjugates. It was observed that LDL cholesterol, VLDL cholesterol, total cholesterol, total cholesterol: HDL cholesterol, LDL cholesterol: HDL cholesterol were significantly raised and HDL cholesterol was significantly low in patients. (p<0.001). Though HDL cholesterol was significantly raised in females as compared to males in both the groups (p<0.001). Serum level of total cholesterol, oxidized LDL:HDL cholesterol were also raised significantly (p<0.05). The level of oxidized LDL showed an increasing trend in patients.     

Reference intervals for serum total cholesterol,HDL-cholesterol,LDL-cholesterol,triglycerides, Lp (a), apolipoprotein A-I,A-II,B, C-II,C-III,and E in healthy South Indians from Andhra Pradesh

The incidence of cardiovascular and cerebrovascular disease is steadily increasing in South East Asian countries including Indian sub continent. Many lipids, apolipoproteins and Lp (a) except HDL-C and apo A-I, A-II are implicated as risk factors for coronary artery disease and cerebrovascular disease. There is great need to have national guidelines for each country like the ATP III guidelines recommended for U.S. population. For recommending appropriate medical decision limits, it is mandatory that each country establishes reference intervals pertaining to their population due to dietary, genetic and environmental diversity. In the present study, reference intervals for serum lipids, apolipoproteins and Lp (a) were established in a total of 1923 healthy Indian reference individuals comprising 1161 healthy men and 762 healthy women from Andhra Pradesh. For each analyte viz., serum total cholesterol, HDL-C, LDL-C, triglycerides, Lp (a), Apo A-I, Apo A-II, B, C-II, C-III and E, mean, two SD, median, confidence limits of mean, different percentile values are presented. The study also includes decade wise changes in each analyte and comparison of lipids, lipoproteins and Lp (a) among few populations covering U.S., India, Japan, Sweden, Finland and China. Reference Intervals for all lipid and lipoprotein parameters will immensely help in assessing associated risk for cardiovascular and cerebrovascular diseases in India. Additionally, the results will be beneficial in formulating our own guidelines pertaining to Indian population.     

A Pilot clinical study to evaluate the effect of <Emphasis Type="Italic">Emblica officinalis</Emphasis> extract (Amlamax™) on markers of systemic inflammation and dyslipidemia

Emblica officinalis Gaertn., commonly known as the Indian gooseberry or “Amla”, has been used as health food for centuries in India and other Asian countries. The biological effects of amla have been attributed to the antioxidant properties of the low-molecular weight hydrolysable tannins present in the fruit. Amlamax™ is a purified, standardized, dried extract of amla containing about 35% galloellagi tannins along with other hydrolysable tannins. Our earlier studies on rabbits showed significant reduction in total cholesterol and triglycerides as well as increase in HDL. The present study extends these results to human volunteers. Two doses of the extract were evaluated — 500 mg and 1000 mg per day for 6 months. Blood samples were collected at the 3rd and 6th months showed reduction in total and LDL cholesterols and enhancement of beneficial HDL cholesterol. In addition, blood CRP levels, a marker for inflammation, were also significantly reduced. Since dyslipidemia and inflammation are the two major components of cardiovascular diseases, the present results must be considered encouraging and indicate the potential of Amlamax™ in the management of heart diseases.     

Inhibitory effect of metalloporphyrins in conjunction with cholesterol on hepatic phospholipase A2 activityin vivo in rats

We investigated the effect of cholesterol and the metalloporphyrins cobalt mesoporphyrin (CoMP) and chromium protoporphyrin (CrPP) on phospholipase A₂ (PLA₂) activity and the consequent hepatic mitochondrial stability as well as on lipid concentrations. Our studies revealed that on administration of cholesterol, CrPP, CoMP as well as simultaneous adminstration of cholesterol and CrPP, there was an inhibition of PLA₂ activity. These moieties may therefore, be agents for preventing destabilisation of the mitochondrial membrane and the consequent pathological conditions which may arise due to membrane lysis. Our results revealed that cholesterol administration increased phospholipid concentration, albeit by modest amounts. Although the independent administration of metalloporphyrins led only to minor elevations in phospholipid concentration, the simultaneous administration of cholesterol and CrPP generated a steep elevation in the concentration of total phospholipid. Since cholesterol inhibits PLA₂ activity it has the potential of being therapeutic agent for preventing the pathological conditions which may arise due to membrane lysis.     

Lipid profile in leukemia and Hodgkin's disease

A number of epidemiologic studies has been published in recent years showing an increase risk of death from cancer in subjects with low plasma cholesterol levels. Although several authors proposed that hypocholesterolemia is predisposing factor for cancer development, no causative relation has been established so far and that it may be that low plasma cholesterol is secondary to malignant disease. Hence, the present study was undertaken to examine the lipid profile in children patients with leukemia and Hodgkin's disease in comparison with age matched controls. The study included 52 normal healthy controls and 105 patients with leukemia and Hodgkin's disease. Lipid profile included serum cholesterol, HDL & LDL cholesterol and triglycerides. Serum cholesterol, HDL & LDL cholesterol were found to be inversely associated with incidence of cancer, whereas triglycerides were significantly elevated in cancer patients. The inverse association between cancer and serum cholesterol may reflect a physiological response to early undiagnosed stages of cancer.     

Study of serum lipid profile in pregnancy induced hypertension

Four groups of subjects: normal healthy normotensive nonpregnant women (Group A), normal normotensive pregnant women (Group B), women with preeclamptic toxaemia (Group C) and eclamptic women (Group D): with fifty subjects in each group, were investigated for serum lipid profile in the third trimester of pregnancy. There was significant increase in serum triglyceride and VLDL cholesterol leve as well as decrease in LDL cholesterol in normal pregnancy, while total cholesterol and HDL cholesterol levels did not show any statistically significant alteration. The preeclampsia (Group C) was associated with a significant rise in triglyceride and VLDL cholesterol and fall in HDL cholesterol concentration, while eclamptic women showed significant fall in HDL cholesterol and rise in LDL cholesterol as compared to normal pregnant women. However, interestingly, elevation of the ratios of total cholesterol: HDL cholesterol and triglyceride: HDL cholesterol as well as diminuition of the ratio of HDL cholesterol: VLDL cholesterol showed statistical significance in pregnancy induced hypertension in both Groups C and D, while eclamptic women showed significant elevation of LDL cholesterol: HDL cholesterol ratio in addition.     

Vitamin C in Disease Prevention and Cure: An Overview

The recognition of vitamin C is associated with a history of an unrelenting search for the cause of the ancient haemorrhagic disease scurvy. Isolated in 1928, vitamin C is essential for the development and maintenance of connective tissues. It plays an important role in bone formation, wound healing and the maintenance of healthy gums. Vitamin C plays an important role in a number of metabolic functions including the activation of the B vitamin, folic acid, the conversion of cholesterol to bile acids and the conversion of the amino acid, tryptophan, to the neurotransmitter, serotonin. It is an antioxidant that protects body from free radical damage. It is used as therapeutic agent in many diseases and disorders. Vitamin C protects the immune system, reduces the severity of allergic reactions and helps to fight off infections. However the significance and beneficial effect of vitamin C in respect to human disease such as cancer, atherosclerosis, diabetes, neurodegenerative disease and metal toxicity however remains equivocal. Thus further continuous uninterrupted efforts may open new vistas to understand its significance in disease management.     

力平脂调血脂作用的临床观察：附68例临床分析

观察了力平脂对高脂血症者的治疗作用和安全性．确诊高脂血症者６８例，力平脂，０．１，Ｔｉｄ，服一个月为一疗程后，血清总胆固醇（ＴＣ）平均降低２０．９８％，甘油三酯平均降低５１．８８％，ＨＤＬ－Ｃ平均升高１０．２６％，ＬＤＬ－Ｃ平均降低１２．５７％，ＡｐｏＡ１平均升高２．２４％，ＡｐｏＢ平均降低２１．１０％，从调血脂的个体疗效分析，力平脂降低ＴＣ的总有效率８４．６１％，降低ＴＧ的总有效率９５．２４％，升高ＨＤＬ－Ｃ的总有效率６１．７７％，降低ＬＤＬ－Ｃ的总有效率为５５．８８％，升高ＡｐｏＡ１的总有效率３８．２４％，降低ＡｐｏＢ的总有效率７７．９４％．提示：力平脂治疗高脂血症者，对降低ＴＣ，ＴＧ，ＬＤＬ－Ｃ，ＡｐｏＢ和升高ＨＤＬ－Ｃ，ＡｐｏＡ１均有明显效果，其中降低ＴＧ的疗效尤为突出，副作用轻微．临床实践表明：力平脂是一个疗效高、安全、服用方便的调血脂新药     

MicroRNAs: Potential biomarkers in cancer

microRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs, also known as micromanagers of gene expression. Polymorphisms in the miRNA pathway (miR-polymorphisms) are emerging as powerful tools to study the biology of a disease and have the potential to be used in disease prognosis and diagnosis. Advancements in the miRNA field also indicate a clear involvement of deregulated miRNA gene signatures in cancers, and several polymorphisms in pre-miRNA, miRNA binding sites or targets have been found to be associated with various cancers. The miRNA polymorphisms have also been reported to influence tumor aggressiveness as well as survival of cancer patients. miRNAs have a revolutionary impact on cancer research over recent years. They emerge as important players in tumorigenesis, leading to a paradigm shift in oncology. The extensive and comprehensive use of miRNA microarrays has enabled the identification of a number of miRNAs as potential biomarkers for cancer. Many miRNAs have been identified to act as oncogenes, tumor suppressors, or even modulators of cancer stem cells and metastasis. Some studies not only reported the identified miRNA biomarkers, but also deciphered their target genes and the underlying mechanisms. The rapid discovery of many miRNA targets and their relevant pathways has contributed to the development of miRNA-based therapeutics.     

Suppression of Type-II Diabetes with Dyslipidemia and Nephropathy by Peels of <Emphasis Type="Italic">Musa cavendish</Emphasis> Fruit

Musa cavendish, peels has local and traditional use to promote wound healing, hyperglycemia, ulceration etc. The present work investigated the lipid lowering; nephroprotective and glucose lowering properties of ethanolic extract of peels of Musa cavendish (EMC) in alloxan-induced diabetic rats. The EMC 250, 500 and 1000 mg/kg/day and the vehicle were administered orally to alloxan-induced diabetic rats (n = 6) for 3 weeks. Changes in plasma glucose, lipid profile along with kidney function before and after treatment with EMC were recorded. The ethanolic extract of peels of Musa cavendish reduced blood glucose, serum triglyceride, cholesterol, LDL cholesterol and creatinine levels and improvement in body weight, liver glycogen, serum HDL cholesterol, serum albumin and total protein level when compared with untreated rats. Musa cavendish has lipid lowering, nephroprotective and antidiabetic property by regulating glucose uptake in the liver and muscles by restoring the intracellular energy balance.     

Study of Common Genetic Variant S447X in Lipoprotein Lipase and Its Association with Lipids and Lipoproteins in Type 2 Diabetic Patients

Elevated plasma triglyceride and non-esterified fatty acid concentrations may cause insulin resistance and type 2 diabetes mellitus. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. A variant in the LPL gene has been identified which alters the penultimate amino acid Serine at 447 to a stop codon (S447X), and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser–Gly. The present study was designed to evaluate the frequency of S447X variant in the LPL gene and its effect on the lipid and lipoprotein levels in type 2 diabetic subjects. The genotype frequency distributions of type 2 diabetes patients and controls were in Hardy–Weinberg equilibrium. Comparison of the genotype and allelic frequencies of S447X in subjects with type 2 diabetics compared to controls demonstrated no significant difference. In subjects with type 2 diabetics having hypertriglyceridemia (TG ≥ 150 mg/dl) compared to diabetics with TG level <150 mg/dl, significant difference in genotype frequency was found among these groups, while allelic frequency of X was significantly differed. Logistic regression analysis showed the negative association of LPL S447X variant with TG and VLDL cholesterol, while no association with total cholesterol, HDL cholesterol and LDL cholesterol was found. The lipid levels except for HDL cholesterol were found to be significantly lower in carriers for S447X than wild type in diabetes group. The decreased level of TG and TG rich lipoprotein in subjects with SNP S447X in LPL, predicts anti-atherogenic activity of carriers for S447X variant in general population as well as type 2 diabetic patients.     

Lipid abnormalities,lipoprotein (a) and apoprotein pattern in non-dialyzed patients with chronic kidney disease

The present study was carried out to explore the altered lipid, lipoprotein and apoprotein abnormalities along with lipoprotein (a) in chronic kidney disease patients with stage I to V which were further divided into group 1 (stage I and II), group 2 (stage III and IV) and group 3 (stage V). 50 chronic kidney disease patients with stage I to V and 20 healthy normal subjects as controls were recruited for this study. Among the various parameters tested triglyceride levels were high in group 1 and 2, whereas VLDL cholesterol, Lp (a) and apo B levels were significantly high in all the groups when compared to controls (P<0.05). However, LDL cholesterol level was significantly low in group 3 only as compared to control group (P<0.05). Apoprotein AI values also showed significant decrease in all groups as compared to controls (P<0.05). Though total cholesterol levels in group 1 and LDL levels in group 1 and 2 were higher than controls, but the values attained not statistically significant (P>0.05). In conclusion high levels of VLDL cholesterol, Lp (a), apo B and low levels of apoprotein AI as reported in this study are the major lipid disorders in the development of cardiovascular complications at all the stages in these patients.     

Drug Delivery of Hydroxyurea to Breast Cancer Using Liposomes

It is clear that cancer is one of the most mortal diseases in the world and the most prevalent among women is breast cancer. As hydroxyurea (HU)—a drug which is used in chemotherapy—has many adverse effects in long-term despite of its therapeutic properties, we made use of nano drug delivery technology in order to reduce adverse effects and increase therapeutic index. Thus, liposomation is a novel way in drug delivery systems. In this study a mixture of phosphatidylcholine and cholesterol was mixed and HU was added to the resultant mixture. The mean diameter of the nanoliposomal HU measured with the Zeta Sizer device (equal to 402.5 nm) and its encapsulation efficiency was 70.8 %. Besides, using dialysis, the pattern of drug release from nanoliposomes has been studied and the results showed that the drug release of nanoliposomal drug within 28 h was equal to 25.85 %. This study showed that the cytotoxicity effect of nanoliposomal drug is more than that of the standard drug.     

Association of Single Nucleotide Polymorphisms of Adiponectin Gene with Type 2 Diabetes Mellitus,and Their Influence on Cardiovascular Risk Markers

Type 2 diabetes mellitus is a genetically heterogeneous condition, characterized by insulin deficiency and/or insulin resistance. The etiology of type 2 diabetes is complex, with involvement of genetic and environmental factors. The adipose tissue protein ‘adiponectin’ is known to increase insulin sensitivity with decreased risk of type 2 diabetes mellitus. The gene for adiponectin is present on chromosome 3q27, the association of number of single nucleotide polymorphisms of adiponectin gene with type 2 diabetes and its complications have been reported. In the present study the two most common SNPs +45T/G & +276G/T, and their association with type 2 diabetes mellitus and cardiovascular markers were studied. The significant difference in genotype frequencies of +45T/G & +276G/T was found in type 2 diabetic patients and controls, with odds ratio of 1.13 & 1.26 respectively. BMI, Fasting blood glucose, fasting insulin, HOMA IR, triglyceride and VLDL cholesterol levels were increased, and HDL cholesterol level was decreased in patients carrier for +45T/G SNP than the wild type. While only decrease in the HDL cholesterol was reported in carriers for SNP +276G/T than the wild type. The logistic regression analysis revealed the positive association of SNP +45T/G with total cholesterol & LDL cholesterol. And negative association of HDL cholesterol was found with SNPs +45T/G and +276G/T. The haplotype analysis shows the alterations in means of biochemical markers in the patients having haplotype (GG) for mutant allele of SNP +45T/G and wild allele for SNP +276G/T.     

Anti-Atherosclerotic and Anti-Inflammatory Effects of Curcumin on Hypercholesterolemic Male Rabbits

Curcumin has a potent antioxidant and anti-inflammatory properties that may suppress inflammatory component of atherosclerosis. It has been demonstrated that curcumin derivatives can reduce the formation of arterial fatty streaks in cholesterol-fed rabbits. Therefore in this study we evaluated the protective effects of Curcumin on the progression of atherosclerosis. 20 mature rabbits were included for this study; they were randomly divided into four groups each of 5. Group 1: (normal control) were fed corn pellets diet and tab water, group 2: (high cholesterol diet control) were kept on cholesterol rich diet (2% cholesterol) and tab water. Group 3: (cholesterol and rosuvastatin treated group) were kept on cholesterol rich diet (2% cholesterol) and 2.5 mg/kg/day Rosuvastatin dispersed in DW and given orally, group 4: (cholesterol and curcumin treated group) were kept on cholesterol rich diet (2% cholesterol) and 0.2% curcumin added with corn pellets. The study continued for 12 weeks then assessment of serum level of high sensitive C-reactive protein, ICAM1, VCAM1 and PCSK9 was carried out at the end of the study. Total antioxidant activity of curcumin was also determined. Histopathological examination of aortic tissues for atherosclerotic changes was also carried out. Atherogenic (cholesterol rich diet) induced an increment in serum level of TC, LDL, VLDL and TG with concomitant decrement in serum level of HDL and increased atherogenic index. Treatment with curcumin produced substantial reduction in serum TC, LDL, TG with no effect on HDL level thus decreased atherogenic index. Rabbits treated with curcumin showed a significant reduction in the serum level of high sensitive C-reactive protein, ICAM1, VCAM, PCSK9 serum expression and aortic total antioxidant capacity. Curcumin has a potent anti-inflammatory and anti- oxidant effects against atherosclerosis so exerts a protective role by decreasing lipid oxidation and inflammatory markers.