Downregulation of apolipoprotein A-IV in plasma & impaired reverse cholesterol transport in individuals with recent acts of deliberate self-harm

Background & objectives: The major limiting factor in the prevention of suicide is the limited knowledge on molecular insights in individuals at risk. Identification of peripheral protein markers which can classify individuals at high-risk of suicide might aid in early diagnosis and effective medical intervention. The aim of the present study was, therefore, to analyze the differential regulation of plasma proteins in individuals with deliberate self-harm compared to controls. Methods: Using two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption-ionization mass spectrometry, differentially expressed plasma proteins were identified in study participants with deliberate self-harm compared to age- and gender-matched controls. The finding was validated using mass spectrometry-based isotope-labelled relative quantification and Western blot analysis in a new set of individuals with deliberate self-harm and controls. Results: The plasma proteomic analysis showed that apolipoprotein A-IV (Apo A-IV ) was downregulated by 2.63-fold (confidence interval: 1.52-4.54) in individuals with deliberate self-harm (n=10) compared to matched controls, which was consistent in mass spectrometry-based relative quantification and Western blot analysis performed in an independent set of individuals with deliberate self-harm (n=18). In addition, plasma levels of total cholesterol, esterified cholesterol and high-density lipoprotein (HDL) were observed to be significantly lower individuals with deliberate self-harm compared to controls. Interpretation & conclusions: Apo A-IV, which plays a crucial role in the esterification of free cholesterol, was found to be downregulated with concomitantly decreased levels of HDL, esterified cholesterol and total cholesterol in individuals with deliberate self-harm compared to matched controls. The present findings might provide a link between the differential regulation of plasma proteins and the previously reported results on altered cholesterol levels in individuals with deliberate self-harm.

Elevated levels of glutathionyl haemoglobin as an oxidative stress marker in patients with major depressive disorder

Background & objectives: Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD), but biomarkers to assess oxidative stress in patients with MDD have yielded ambiguous results. Glutathionyl haemoglobin (GS-Hb) has been reported as a stable and potential biomarker for oxidative stress in various clinical conditions. The objective of the study was to evaluate GS-Hb as a potential biomarker of oxidative stress in patients with MDD through its quantification and to compare the levels of GS-Hb in age- and gender-matched healthy controls. Methods: The levels of GS-Hb were estimated using liquid chromatography coupled to electrospray ionization mass spectrometry in patients diagnosed with MDD and in a subset of patients after six weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Results: GS-Hb levels in drug-naïve patients with MDD (n=26) were significantly elevated compared to matched healthy controls (n=17). GS-Hb levels were not significantly different between MDD patients with and without co-morbid anxiety disorders. There were no significant differences in GS-Hb levels following six weeks of treatment with SSRIs compared to baseline. Interpretation & conclusions: Compared to controls, GS-Hb level in patients with MDD was significantly elevated, suggestive of increased oxidative stress associated with MDD. However, six weeks of antidepressant treatment was not sufficient to modify the alterations in antioxidant/oxidant system. Further studies need to be done with a large sample of MDD patients with a longer duration of antidepressant treatment.

Neuroprotective Effects of Garlic : A Review

Garlic has been investigated extensively for health benefits; resulting in more than one thousand publications over the last decade alone. It is considered one of the best disease preventive foods; based on its potent and varied effects. Midlife risk factors for cardiovascular diseases; such as high serum total cholesterol; raised LDL; increased LDL oxidation; increased platelet aggregation; impaired fibrinolysis; hypertension and homocystinemia are important risk factors for dementia in later years. These risk factors play a major role in the genesis of atherosclerosis of vital arteries causing both cardiovascular and cerebrovascular disease. Garlic is best known for its lipid lowering and anti-atherogenic effects. Possible mechanisms of action include inhibition of the hepatic activities of lipogenic and cholesterogenic enzymes that are thought to be the genesis for dyslipidemias; increased excretion of cholesterol and suppression of LDL-oxidation. Oxidative stress caused by increased accumulation of reactive oxygen species (ROS) in cells has been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease (AD). Several studies have demonstrated the antioxidant properties of garlic and its different preparations including Aged Garlic Extract (AGE). AGE and S-allyl-cysteines (SAC); a bioactive and bioavailable component in garlic preparations have been shown in a number of in vitro studies to protect neuronal cells against beta-amyloid (A ) toxicity and apoptosis. Thus the broad range of anti-atherogenic; antioxidant and anti-apoptotic protection afforded by garlic may be extended to its neuroprotective action; helping to reduce the risk of dementia; including vascular dementia and AD

Neuroprotective Effects of Garlic: A Review

Garlic has been investigated extensively for health benefits; resulting in more than one thousand publications over the last decade alone. It is considered one of the best disease preventive foods; based on its potent and varied effects. Midlife risk factors for cardiovascular diseases; such as high serum total cholesterol; raised LDL; increased LDL oxidation; increased platelet aggregation; impaired fibrinolysis; hypertension and homocystinemia are important risk factors for dementia in later years. These risk factors play a major role in the genesis of atherosclerosis of vital arteries causing both cardiovascular and cerebrovascular disease. Garlic is best known for its lipid lowering and anti-atherogenic effects. Possible mechanisms of action include inhibition of the hepatic activities of lipogenic and cholesterogenic enzymes that are thought to be the genesis for dyslipidemias; increased excretion of cholesterol and suppression of LDL-oxidation. Oxidative stress caused by increased accumulation of reactive oxygen species (ROS) in cells has been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease (AD). Several studies have demonstrated the antioxidant properties of garlic and its different preparations including Aged Garlic Extract (AGE). AGE and S-allyl-cysteines (SAC); a bioactive and bioavailable component in garlic preparations have been shown in a number of in vitro studies to protect neuronal cells against beta-amyloid (A ) toxicity and apoptosis. Thus the broad range of anti-atherogenic; antioxidant and anti-apoptotic protection afforded by garlic may be extended to its neuroprotective action; helping to reduce the risk of dementia; including vascular dementia and AD

A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent.

BACKGROUND: Therapeutic drug monitoring for mycophenolic acid (MPA) is increasingly being advocated. The present therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC).However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this sampling period? AIM: To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. SETTINGS AND DESIGN: Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paired data. MATERIALS AND METHODS: Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept were evaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the time after transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the 12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factor applied. These two AUCs were then compared. STATISTICAL ANALYSIS: Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were applied to the data. RESULTS: Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2) were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. No bias was seen with a Bland Altman plot or by calculation. CONCLUSION: For patients on Cellcept with prednisolone +/- cyclosporine the 6-hour corrected is an accurate measure of the full 12-hour AUC.

Cholesterol-lowering effect of organosulphur compounds from garlic: a possible mechanism of action.

OBJECTIVES: Hyperlipidemia constitutes a major etiopathological factor for atherosclerosis. The medicinal value of garlic is best known for its lipid lowering effects and antiatherogenic effects. The mechanism by which lipid soluble organosulphur compounds from garlic reduce plasma lipids has not been fully investigated. The author had previously shown that the hepatic activity of beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase, the rate limiting enzyme in cholesterol biosynthesis and the incorporation of radiolabeled (1, 2 14C), acetate into hepatic free and esterified cholesterol was significantly decreased in rat treated with garlic derived organosulphur compounds. We hypothesised that the antiatherogenic effect of the organosulphur compounds may be attributed to the formation of protein internal disulphide and thus inactivation of thiol (-SH) group enzymes such as HMG-CoA reductase and the multienzyme complex of fatty acid synthesis. The objective of the present study is to elucidate the inhibitory mechanism by in vitro studies. METHOD: Lipid soluble organosulphur compounds from garlic were treated in vitro with Luke's cysteine reagent (representing the thiol (-SH) group of enzymes) and the interaction products were separated by paper chromatography. RESULT: The result indicated that the organosulphur compounds were capable of interacting with the thiol (-SH) group of cysteine and thus forming cysteine derivatives. CONCLUSION: The antiatherogenic effects of these organosulphur compounds can be attributed to such reactions that inhibit HMG-CoA reductase and other lipogenic enzymes. The anticarcinogenic effects of these compounds may also be due to inhibitory reactions on enzymes that activate carcinogens.

Cryopreservation of mouse morulae through different methods: slow-freezing, vitrification and quick-freezing

The in vitro and in vivo development of mouse morulae after cryopreservation through different methods was examined. The slow-freezing involved an equilibration in 1.5M ethylene glycol (EG) and cooled at 0.5; 0.7; 1.0 or 1.2ºC/minute. The vitrification involved a 3 minutes equilibration in 20 percent EG and 60 seconds in solution containing 40 percent EG, 18 percent ficoll and 10.26 percent sucrose. The quick-freezing involved an equilibration in 3M EG + 0.3M sucrose for 5 minutes and 2 minutes in nitrogen vapor. In all three methods the straws were thawed in air for 10 seconds and in water at 25ºC for 20 seconds and the embryos cultured in vitro for 72 hours to estimate blastocyst rate. To assess viability in vivo, frozen morulae as well as fresh embryos were transferred into recipients. The in vitro development rates with 0.5, 0.7; 1.0 and 1.2ºC/minute were, respectively, 72.3; 79.6; 76.5 and 84.8 percent. There was no significant difference among the cooling rates of 0.7; 1.0 and 1.2ºC/minute (p > 0.01). The in vitro survival rates of vitrification and quick-freezing (84.5 and 74.3 percent, respectively) were similar to the slow-freezing. In vivo, the implantation rate and number of fetuses from embryos frozen through slow-freezing at 1.2ºC/minute, vitrification and quick-freezing were not significantly different

Primary choriocarcinoma of the ovary. Report of two cases.

Primary choriocarcinoma of the ovary (PCO) is rare. This can be gestational (GCO) or nongestational (NGCO) in origin. It is difficult to differentiate between CGO and NGCO. NGCO carries a worse prognosis than GCO. We present two cases of metastatic GCO who were treated successfully with combination chemotherapy and are alive and disease free at the time of reporting.

Antioxidant effect of two flavonoids from the bark of Ficus bengalensis Linn in hyperlipidemic rats.

Two flavonoid compounds, viz. 5,7-dimethyl ether of leucopelargonidin 3-0-alpha-L rhamnoside and 5,3'-dimethyl ether of leucocyanidin 3-0-alpha-D galactosyl cellobioside obtained from the bark of F. bengalensis were evaluated for their antioxidant action in hyperlipidemic rats. The results were compared with the activity of a structurally similar flavonoid, quercetin, a known antioxidant. The Ficus compounds showed significant antioxidant effects which may be attributed to their polyphenolic nature. The methylation of two hydrozyl groups in the Ficus flavonoids might have slowed down their antioxidant action as compared to quercetin.

Biochemical effects of garlic protein diet and garlic oil on glycosaminoglycan metabolism in cholesterol fed rats.

Garlic protein diet or daily administration of garlic oil to 2% cholesterol fed rats controlled significantly the increases in sulphated glycosaminoglycans in their heart and aorta. However hyaluronic acid level increased. UDPG dehydrogenase decreased and several degrading enzymes increased in the aorta on treatment. The effects of treatment were just the reverse in liver. The high percentage of cysteine in garlic protein and the reactive disulphide group in the oil may be responsible for their beneficial effects.

Hypolipidemic effect of garlic protein substituted for casein in diet of rats compared to those of garlic oil.

Garlic (Allium sativum Linn.) is ascribed with many therapeutic effects. For the present study, the water soluble proteins and the essential oil of garlic were investigated for their hypolipidemic effect on hyperlipidemia induced by cholesterol containing diet in albino rats. Both garlic protein (16% of diet) and garlic oil (100 mg/kg body weight/day) exhibited significant lipid lowering effects. The hypolipidemic action is primarily due to a decrease in hepatic cholesterogenesis in the treated rats. Even though garlic oil was found to be more effective, the garlic protein is more palatable and free from an obnoxious smell.

Antidiabetic and hypolipidemic effects of S-methyl cysteine sulfoxide isolated from Allium cepa Linn.

S-methyl cysteine sulphoxide (SMCS), a sulphur containing amino acid isolated from onion (Allium cepa Linn) showed antidiabetic and antihyperlipidemic effects. Oral administration of SMCS daily at a dose of 200 mg/kg body weight for a period of 45 days to alloxan diabetic rats controlled significantly their blood glucose and lipids in serum and tissues and altered the activities of liver hexokinase, glucose 6-phosphatase and HMG CoA reductase towards normal. The above effects of SMCS were comparable to those of glibenclamide and insulin.

Hypoglycemic effects of leucodelphinidin derivative isolated from Ficus bengalensis (Linn).

A Leucodelphinidin derivative isolated from the bark of Ficus bengalensis Linn demonstrated hypoglycemic action at a dosage of 250 mg/kg given both in normal and alloxan diabetic rats. It's action is closely similar to that of an effective dose of glibenclamide (2 mg/kg) tested under the same conditions. However, after a glucose load the plant product is only just significantly active but not as effective as the sulphonylurea. The efficacy of the plant product as a hydroglycemic agent adds to its other therapeutic effects, as it belongs to the class of flavonoids.

Prevention and early detection of oral, breast and cervical cancers: a practical approach in Indian context.

Cancer has emerged as a major killer disease in India. One-third of the total cancer load is constituted by oral, breast and uterine cervix cancers. Considerable knowledge is available on control strategies on these 3 major cancers and this can be transformed into the community through the individual health care practitioners. Oral cancer is preventable and both the precancerous and invasive lesions can be picked up easily by examination of the oral cavity. The occurrence of breast cancer in the country is on the increase. The poor survival rate indicates the impact of the major proportion of advanced cancer. An effective strategy comprising breast self-examination, examination by a physician and a mammography test, is described. Cancer of the uterine cervix is the commonest malignancy among females in several regions in India. An effective and definitive method is available in the form of Pap smear for the control of cervical cancer. An organised community screening programme is not economically viable at present. However, routine per speculum examination should be undertaken and this can result in clinical downstaging of cancer. Women above the age of 40 years should undergo regular Pap smear screening. Broad guidelines are presented for an opportunistic screening.