Biomedical subjects

S Ramasamy

Publications and source records attributed to S Ramasamy.

At least 19 recordsLinked to original sources

PubMed2003

Photodynamic effects of two hydroxyanthraquinones.

The aim of this work was to investigate the photodynamic action of electron-rich anthraquinones, viz., cynodontin (CYN) and cynodontin-5,8-dimethylether (CYNM). Both optical and EPR methods are used to detect the generation of singlet oxygen. Based on RNO bleaching, relative to rose bengal (RB), singlet oxygen generating efficiencies of CYN and CYNM are derived to be 0.055 and 0.254, respectively. The formation of superoxide anion via electron transfer to O2 was monitored by optical spectroscopy, using SOD-inhibitable cytochrome c reduction assay. The production of O2-* is enhanced in the presence of electron donors such as EDTA and NADH. Photolysis of CYN and CYNM in DMSO, in the presence of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), generates a multi-line EPR spectrum, characteristic of spin adduct mixture of O2-* and *OH. Both optical and ESR measurements indicate that O2-* (Type I) and 1O2 (Type II) paths are involved in CYN and CYNM photodynamic action.

Anthraquinones↗

PubMed2003

Exercise capability and myocardial perfusion in chronic angina patients treated with enhanced external counterpulsation.

BACKGROUND: Enhanced external counterpulsation (EECP) has been shown to improve treadmill times and myocardial perfusion. However, improvement in perfusion defects has been demonstrated only in patients exercised to the same cardiac workload on the post-EECP as the pre-EECP stress test. HYPOTHESIS: This study was to determine the effect of EECP on exercise capacity and myocardial perfusion by comparing results of maximal exercise radionuclide testing pre- and post-EECP treatment. METHODS: This prospective study included 25 patients with angina who had performed maximal symptom-limited exercise tolerance tests (ETT) with Bruce protocol and radionuclide perfusion single-photon emission computed tomography (SPECT) study prior to and at completion of EECP treatment. RESULTS: After 35 h of EECP, 23 patients (93%) improved by at least one functional angina class. There is a significant improvement in their total treadmill times (357 +/- 93 to 449 +/- 97 s, p < 0.001). There was a significant change in their peak double products, from 18,891 +/- 3,939 pre-EECP to 20,464 +/- 4,305 post-EECP ETT (p < 0.03). Pre EECP, 16 patients had ST-segment depression on their initial ETT. After EECP, 13 of these patients (80%) either no longer had ST depression or had a significant increase in their time to ST depression (229 +/- 52 to 315 +/- 60 s, p < 0.001). The radionuclide perfusion scores also showed a significant reduction in ischemic segments (16.36 +/- 10.52 to 14 +/- 10.9, p < 0.05). CONCLUSIONS: Patients treated with EECP demonstrated a reduction in angina symptoms, improvement in exercise capacity, increase in time to ST-segment depression, and decrease in perfusion defects despite performing at a higher workload.

Aged↗

PubMed2000

Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression by hydrogen peroxide.

Diverse stimuli, including shear stress, cyclic strain, oxidized LDL, hyperglycemia, and cell growth, modulate endothelial nitric oxide synthase (eNOS) expression. Although seemingly unrelated, these may all alter cellular redox state, suggesting that reactive oxygen intermediates might modulate eNOS expression. The present study was designed to test this hypothesis. Exposure of bovine aortic endothelial cells for 24 hours to paraquat, a superoxide (O(2)(-*))-generating compound, did not affect eNOS mRNA levels. However, cotreatment with paraquat and either Cu(2+)/Zn(2+) superoxide dismutase or the superoxide dismutase mimetic tetrakis(4-benzoic acid)porphyrin chloride increased eNOS mRNA by 2.3- and 2.2-fold, respectively, implicating a role for H(2)O(2). Direct addition of 100 and 150 micromol/L H(2)O(2) caused increases in bovine aortic endothelial cell eNOS mRNA that were dependent on concentration (ie, 3.1- and 5.2-fold increases) and time, and elevated eNOS protein expression and enzyme activity, accordingly. Nuclear run-on and 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole-chase studies showed that H(2)O(2) caused a 3.0-fold increase in eNOS gene transcription and a 2.8-fold increase in eNOS mRNA half-life. Induction of eNOS by H(2)O(2) was not affected by the hydroxyl radical scavenger DMSO, mannitol, or N-tert-butyl-alpha-phenylnitrone, but it was inhibited by the antioxidants N-acetylcysteine, ebselen, and exogenously added catalase. Unlike H(2)O(2), the 4.0-fold induction of eNOS by shear stress (15 dyne/cm(2) for 6 hours) was not inhibited by N-acetylcysteine or exogenous catalase. In conclusion, H(2)O(2) increases eNOS expression through transcriptional and post-transcriptional mechanisms. Although H(2)O(2) does not mediate shear-dependent eNOS regulation, it is likely to be involved in regulation of eNOS expression in response to other physiological and/or pathophysiological stimuli.

Animals↗

PubMed2000

Large Pericardial Effusions.

Pericardial effusions accompany a number of clinical conditions. The challenges facing the clinician when dealing with a pericardial effusion include assessing the urgency of draining the effusion, choosing the right approach for drainage, determining the mechanics of the effusion, and establishing a cause for the effusion. Currently available diagnostic methods, echocardiographic modalities in particular, greatly aid in the diagnostic assessment as well as in carrying out appropriate therapeutic strategies.

Journal Article↗

PubMed1999

Posttranscriptional regulation of endothelial nitric oxide synthase during cell growth.

The expression of the endothelial NO synthase (eNOS) is dramatically influenced by the state of cell growth. In proliferating cells, mRNA levels are increased 4-fold compared with postconfluent, nonproliferating cells. Nuclear run-on analysis indicated that there is no difference in the transcriptional rate of eNOS in proliferating versus postconfluent cells. The half-life of eNOS mRNA, measured after actinomycin D transcriptional arrest, was 3-fold greater in preconfluent compared with confluent endothelial cells. Using UV-cross-linking analysis, a cytoplasmic protein with an apparent molecular mass of 51 kDa was found to bind to terminal 545-nt eNOS mRNA 3-fold more in confluent cells than in proliferating cells. Further characterization of the eNOS mRNA indicated that a 43-nt sequence at the origin of the 3'-untranslated region (UTR) is critical in binding of this protein. Endothelial cells were stably transfected with a chimeric cDNA plasmid containing chloramphenicol acetyl transferase (CAT) ligated to the eNOS coding region and either the wild-type 3'-UTR (pcDNACAT/eNOS((wtUTR))) or a mutant 3'-UTR lacking the 43 nt found to bind the 51-kDa protein (pcDNACAT/eNOS((DeltaUTR))). The CAT/eNOS mRNA half-life was dramatically stabilized in these latter cells as compared with cells transfected with pcDNACAT/eNOS((wtUTR))). Thus, this 43-nt region plays a critical role in destabilizing eNOS mRNA. These studies demonstrate a mechanism for modulation of eNOS expression during cell growth via interactions between the proximal 3'-UTR and a novel approximately 51-kDa cytosolic protein.

3' Untranslated Regions↗

PubMed1999

Protein expression, vascular reactivity and soluble guanylate cyclase activity in mice lacking the endothelial cell nitric oxide synthase: contributions of NOS isoforms to blood pressure and heart rate control.

OBJECTIVE: Both disruption of the endothelial nitric oxide synthase (eNOS) gene and pharmacological inhibition of the NOS produce modest hypertension. It is unclear if and to what extent NOS isoforms other than eNOS contribute to this effect and how loss of one copy of the eNOS gene might impact on vascular reactivity or eNOS protein expression. METHODS: We examined protein expression, vascular reactivity, activity of soluble guanylate cyclase, blood pressure and heart rate in mice completely lacking the eNOS gene (eNOS-/-), wild-type mice (eNOS+/+) and mice heterozygotic for the eNOS gene (eNOS+/-). RESULTS: While eNOS-/- mice had mild hypertension and bradycardia, eNOS+/- mice were normotensive. In control mice, oral administration of L-NAME (approximately 100 mg/kg/day x 21 days) increased blood pressure to levels observed in eNOS-/- mice. In eNOS-/- mice, chronic oral administration of L-NAME had no effect on blood pressure, suggesting that inhibition of other NOS isoforms unlikely contribute to hypertension. L-NAME treatment induced bradycardia in both control and eNOS-/- mice, suggesting that both eNOS and other isoforms of NOS might be involved in heart rate control. Studies of aortic rings from eNOS-/- mice revealed a complete lack of endothelium-dependent vascular relaxation in response to acetylcholine and the calcium ionophore A23187 and an increase in sensitivity to phenylephrine, serotonin and nitroglycerin. Aortic rings from eNOS+/- mice demonstrated only minor alterations of responses to nitroglycerin and a normal relaxation to either acetylcholine or A23187 compared to vessels from eNOS-/+. Western analysis demonstrated that eNOS expression was virtually identical between eNOS+/+ and eNOS+/- mice and was absent in eNOS-/- mice. The activity of lung-isolated soluble guanylate cyclase was identical in the three strains of mice. CONCLUSIONS: We conclude that loss of one copy of the eNOS gene, as observed in heterozygotic animals, has no effect on vascular reactivity, blood pressure or eNOS protein expression. Isoforms of NOS, other than eNOS are unlikely involved in blood pressure regulation but may participate in heart rate control.

Animals↗

PubMed1999

Fourier transform Raman approach to structural correlation in hemoglobin derivatives.

In order to obtain information on the structural aspects of hemoglobin (Hb), Fourier transform Raman (FT-R) measurements on various ferrous, ferric derivatives and nickel reconstituted Hb (NiHb) has been made. FT-R spectra for these derivatives were obtained by laser excitation in the near infrared region (NIR) (1064 nm) whereby the wave-number region (600-1700 cm-1) related to both porphyrin ring modes and some globin modes were monitored. Comparison of various modes was made based on previous resonance Raman (RR) results. The wave-number shifts with respect to changes in oxidation state and spin state are very similar to those observed by RR. Additional bands at 1654, 1459, and 1003 cm-1 for deoxyHb and at 1656, 1454, and 1004 cm-1 for oxy Hb can be correlated to globin modes. The shift in the position of these bands for the binding of oxygen can be related to changes in conformation during the transformation. The presence of two distinct sites in NiHb could be monitored by the use of FT-R technique.

Carboxyhemoglobin↗

PubMed1999

Modulation of expression of endothelial nitric oxide synthase by nordihydroguaiaretic acid, a phenolic antioxidant in cultured endothelial cells.

Retrospective epidemiological studies have suggested that antioxidant therapy may decrease cardiovascular morbidity and mortality rates, although the mechanisms for this effect remain unclear. In the present study, we demonstrate that selective antioxidants can enhance expression of endothelial nitric oxide synthase (eNOS). We found that the antioxidants nordihydroguaiaretic acid (NDGA), catechol, glutaryl probucol, and N-acetylcysteine increased eNOS expression in cultured bovine aortic endothelial cells (BAECs). NDGA seemed to be the most potent of the phenolic antioxidants, producing a 3-fold increase in eNOS mRNA. This effect of NDGA was enhanced by nonphenolic antioxidants such as N-acetylcysteine and ascorbic acid. Nuclear run-on studies indicated that NDGA increased eNOS transcription. A similar increase in eNOS protein content was observed with Western blot analysis after treating BAECs or human aortic endothelial cells with NDGA. Exposure of BAECs to NDGA enhanced NO production, as measured by electron paramagnetic resonance spin trapping and eNOS activity, as measured by [14C]arginine-to-[14C]citrulline assay. Methylation of the phenolic hydroxyl groups completely inhibited the NDGA effect on eNOS mRNA levels. This effect of NDGA was not due to inhibition of lipoxygenase because cis-5,8,11,14-eicosatetraynoic acid did not alter eNOS expression. We conclude that antioxidants may not only increase the bioactivity of nitric oxide but also enhance expression of the eNOS enzyme. Such an effect may prove useful in conditions such as hypertension and atherosclerosis, in which nitric oxide production and/or biological activity is impaired.

Acetylcysteine↗

PubMed1998

Regulation of endothelial nitric oxide synthase gene expression by oxidized linoleic acid.

Hypercholesterolemia is associated with impairments in endothelium-dependent vascular relaxations. Paradoxically, endothelial production of nitrogen oxides is increased in early stages of hypercholesterolemia. Prior work has shown that oxidized low density lipoprotein (LDL) has both stimulatory and inhibitory effects on endothelial nitric oxide synthase expression (eNOS) and has focused on lysophosphatidyl choline (LPC) as a component of oxidized LDL which may modulate this effect. Another biologically active component of oxidized LDL is 13-hydroperoxyoctadecadienoic acid (13-HPODE), an oxidized form of linoleic acid. The purpose of this study was to determine the effect of HPODE on the expression of eNOS in bovine aortic endothelial cells (BAECs). Twenty four hour treatment of endothelial cells with HPODE caused a dose-dependent increase in eNOS mRNA levels as assessed by Northern analysis. The time response studies show that HPODE treatment significantly increased eNOS mRNA levels at 12 and 24 h. Concomitant with the increase in eNOS mRNA levels, 20 microM HPODE treatment significantly increased eNOS protein content and enzyme activity. Nuclear run-on studies indicated that the rate of transcription of eNOS gene was significantly elevated 4 h after HPODE treatment when compared to control cultures. Also, actinomycin D studies demonstrated that the half-life of eNOS mRNA was increased from 6 h to 12 h by HPODE treatment. Thus, HPODE-induced up-regulation of eNOS expression is mediated by both transcriptional and posttranscriptional mechanisms. These observations suggest that endothelial cells may attempt to compensate for oxidative injury by increasing expression of eNOS in early stages of hypercholesterolemia.

Animals↗

PubMed1997

Sociobiology and HLA genetic polymorphism in hill tribes, the Irula of the Nilgiri hills and the Malayali of the Shevroy hills, south India.

Two endogamous tribes of Tamil Nadu, South India, the Irula of the Nilgiri hills and the Malayali of the Shevroy hills, were studied for their sociobiology and HLA polymorphism. For sociobiological studies 166 marriages in the Irula and 368 marriages in the Malayali were recorded. The number and spatial distribution of patrilineal clans and their marriageable range (number of clans from which the brides came) were studied. Eight clans in the Irula and 16 clans in the Malayali were identified. Of these the Kuppar of the Irula and the Malayan of Malayali were the largest clans, and both of them had the greatest marriageable range. The numerical strength and the resultant spatial distribution correlated well with the marriageable range. HLA-A, B, and DR polymorphism was studied on 191 Irula and 42 Malayali following standard procedures. HLA typing revealed high frequencies (> 10%) of alleles HLA-A2, A9, A11, B17, B35, B40, DR2, and DR7 in both tribes, but the Irula had elevated HLA-A10, B8, and DR8 frequencies and the Malayali had elevated HLA-A31, B7, DR4, and DR5 frequencies. Two-locus haplotypes A10-B8 and A2-B5 were identified in both tribes, but A11-B40 and A2-B53 were present only in the Irula and A33-B44 and B15-DR6 were present only in the Malayali. The sociobiology of the Irula was correlated to the HLA genetic profile. The Irula sample was stratified based on clan and HLA data; The Kuppar clan was closer to the Kalkatti, the second largest clan, than to the Pungar and the Sambar clans. Thus the numerical strength and spatial distribution of various exogamous clans, presumably a result of migration during different periods of history, is reflected in the marriageable range and thus in the genetic distance. In studying HLA or any other genetic polymorphism of an endogamous tribe or caste, one needs to consider the social structure, spatial distribution, and marriageable range.

Emigration and Immigration↗

PubMed1996

Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability.

Vulnerable areas of atherosclerotic plaques often contain lipid-laden macrophages and display matrix metalloproteinase activity. We hypothesized that reactive oxygen species released by macrophage-derived foam cells could trigger activation of latent proforms of metalloproteinases in the vascular interstitium. We showed that in vivo generated macrophage foam cells produce superoxide, nitric oxide, and hydrogen peroxide after isolation from hypercholesterolemic rabbits. Effects of these reactive oxygens and that of peroxynitrite, likely to result from simultaneous production of nitric oxide and superoxide, were tested in vitro using metalloproteinases secreted by cultured human vascular smooth muscle cells. Enzymes in culture media or affinity-purified (pro-MMP-2 and MMP-9) were examined by SDS-PAGE zymography, Western blotting, and enzymatic assays. Under the conditions used, incubation with xanthine/xanthine oxidase increased the amount of active gelatinases, while nitric oxide donors had no noticeable effect. Incubation with peroxynitrite resulted in nitration of MMP-2 and endowed it with collagenolytic activity. Hydrogen peroxide treatment showed a catalase-reversible biphasic effect (gelatinase activation at concentrations of 4 microM, inhibition at > or = 10-50 microM). Thus, reactive oxygen species can modulate matrix degradation in areas of high oxidant stress and could therefore contribute to instability of atherosclerotic plaques.

Animals↗

PubMed1996

Oxidized lipid-mediated alterations in proteoglycan metabolism in cultured pulmonary endothelial cells.

Compared to cholesterol or linoleic acid (18:2), oxidized lipids such as cholestan-3 beta, 5 alpha, 6 beta-triol (triol) and hydroperoxy linoleic acid (HPODE) markedly impair endothelial barrier function in culture [Hennig and Boissonneault, 1987; Hennig et al. 1986]. Because proteoglycans contribute to vascular permeability properties, the effects of cholesterol and 18:2 and their oxidation products, triol and HPODE, on endothelial proteoglycan metabolism were determined. While cholesterol was without effect, a concentration-dependent decrease in cellular proteoglycans (measured by 35S incorporation) was observed after exposure to triol. Compared to control cultures, cholesterol reduced mRNA levels for the proteoglycans, perlecan and biglycan. Triol had a similar effect on biglycan but not an perlecan mRNA levels. Compared to 18:2, 1,3 and 5 microM HPODE depressed cellular proteoglycans. Perlecan mRNA levels were reduced more by HPODE when compared to 18:2. Biglycan mRNA levels were reduced by 3 microM, but not by 5 microM HPODE. These data demonstrate that oxidized lipids such as triol and HPODE can decrease cellular proteoglycan metabolism in endothelial monolayers and alter mRNA levels of major specific proteoglycans in a concentration-dependent manner. This may have implications in lipid-mediated disruption of endothelial barrier function and atherosclerosis.

Animals↗

PubMed1996

Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells.

A major determinant of the level of cellular superoxide anion (O2-.) is the dismutation of O2-. to hydrogen peroxide by the enzyme superoxide dismutase (SOD). Three forms of SOD exist, but in endothelial cells, the major form outside of the mitochondria is the cytosolic copper/zinc-containing superoxide dismutase (Cu/Zn SOD). Since fluid shear stress is an important determinant of the function and structure of endothelial cells in vivo, we examined the effect of laminar shear stress on the expression of Cu/Zn SOD in cultured human aortic endothelial cells. Laminar shear stress of 0.6 to 15 dyne/cm2 increased Cu/Zn SOD mRNA in a time- and dose-dependent manner in human aortic endothelial cells. Shear stress also increased both Cu/Zn SOD protein content and the enzyme activity. Nuclear runon assays showed that nuclei from human aortic endothelial cells exposed to laminar shear stress had a 1.6-fold greater transcriptional activity of the Cu/Zn SOD gene compared with cells not exposed to shear, indicating that an increase in Cu/Zn SOD mRNA induced by laminar shear stress is at least in part mediated by increased transcription. In contrast, shear stress had no effect on Cu/Zn SOD mRNA levels in human aortic smooth muscle cells. These findings show that physiological levels of shear stress increase expression of Cu/Zn SOD in the endothelium. This adaptation to shear stress might augment the effect of locally produced NO. and thereby promote the antiatherogenic and anti-inflammatory properties of the endothelial cell.

Aorta↗

PubMed1995

Tumor necrosis factor reduces proteoglycan synthesis in cultured endothelial cells.

Tumor necrosis factor (TNF)-induced disruption of vascular endothelial barrier function may be due in part to alterations in proteoglycan metabolism. To test this hypothesis, confluent endothelial cell monolayers were exposed for 24 h to 500 or 1,000 U of TNF per milliliter of culture medium together with 20 microCi Na2 35SO4. HPLC anion-exchange separation of proteoglycans secreted into media of control as well as TNF-treated cultures revealed one major peak (representing 95% of total radioactivity) and one minor peak (representing 5% of total radioactivity), which eluted at 0.6 and 0.9 M NaCl, respectively. One single peak was obtained from control as well as TNF-treated endothelial cell monolayers and eluted at 1.2 M NaCl. TNF treatment did not change the total quantity of radioactive proteoglycans secreted into the media but significantly decreased the amount of proteoglycans in endothelial cell monolayers. However, TNF treatment did not alter the size or glycosaminoglycan (GAG) composition of the proteoglycans either in the media or in the cell monolayers. In addition, mRNA levels of specific proteoglycans, perlecan and biglycan, were measured upon TNF treatment, using Northern analysis. TNF treatment caused a dose-dependent decrease in mRNA levels for the core proteins of perlecan, a major heparan sulfate proteoglycan (HSPG), and biglycan in endothelial cultures. These results suggest that TNF decreases production of proteoglycans and alters normal endothelial cell proteoglycan metabolism which may be sufficient to impair endothelial barrier function.

Animals↗

PubMed1995

Fumonisin B1 alters sphingolipid metabolism and disrupts the barrier function of endothelial cells in culture.

Fumonisins are responsible for at least two diseases of veterinary importance (equine leukoencephalomalacia and porcine pulmonary edema) and are carcinogenic for experimental animals and, perhaps, humans. They have been found to disrupt sphingolipid metabolism in many types of cells, including hepatocytes, neurons, and renal cells. In this study, endothelial cells form porcine pulmonary arteries were cultured on micropore filters as a model for the endothelial barrier, and barrier function was quantitated as the movement of albumin across the endothelial monolayers. Fumonisin B1 increased the amount of free sphinganine by 20- to 30-fold within 3 hr, as expected for inhibition of sphinganine (sphingosine) N-acyltransferase by this mycotoxin. At 30 to 50 microM, fumonisin B1 doubled the rate of albumin transfer across endothelial monolayers; however, there was no loss of cell viability based on morphology or trypan blue exclusion. When 15 microM D-erythro-sphinganine was added to the cells, the rate of albumin transfer also doubled (after 24 hr incubation) without a loss of viability; however, this treatment increased the cellular level of sphinganine by > 100-fold. Addition of 25 microM sphinganine caused even greater albumin transfer, but also resulted in significant cell death. These results establish that fumonisin B1 and D-erythro-sphinganine allow accelerated passage of macromolecules across the endothelium. Fumonisin B1 alters sphingolipid biosynthesis with an elevation of sphinganine in the cells which may, at least in part, explain the observed disruption of endothelial barrier function.

Albumins↗

PubMed1995

Role of fatty acids and eicosanoids in modulating proteoglycan metabolism in endothelial cells.

Endothelial cell dysfunction is considered to be a critical event in the etiology of atherosclerosis. Thus, the preservation of endothelial structure and function are a prerequisite for normal control of vascular permeability properties, mediation of both inflammatory and immunologic responses and the general 'communication' between blood-borne cells and abluminal tissues. Many of these properties can be influenced by proteoglycans present in vascular tissues. There is evidence that selected lipids can be atherogenic by altering endothelial proteoglycan metabolism. Little is known about the role of fatty acids in modulating proteoglycan composition in endothelial cells. Data suggest, however, that linoleic acid in particular can adversely alter proteoglycan metabolism, which may be related to an imbalance in eicosanoid synthesis patterns. These events could be sufficient to disrupt normal endothelial barrier function, initiate smooth muscle migration and proliferation, and result in other metabolic dysfunctions associated with the etiology of vascular diseases such as atherosclerosis. Thus, the focus of this review is on fatty acids and eicosanoids as they may alter proteoglycan metabolism of vascular tissues and in particular of the endothelium.

Animals↗

PubMed1994

Prevalence of sickle cells in Irula, Kurumba, Paniya & Mullukurumba tribes of Nilgiris (Tamil Nadu, India).

A total of 1377 tribals, comprising Irulas (536), Paniyas (196), Kurumbas (87), Mullukrurumbas (156) and Soligas (402), living in the Nilgiris, Tamil Nadu, India were studied for sickle cell trait between 1981-85. Patients attending various tribal clinics at Arayure, Kozhikarai, Kothagiri and Biligiri Rengan hills for various ailments were screened at random by solubility test and by acetate paper electrophoresis, if required. HbAS carrier frequency was 30-37.8 per cent in all the tribals studied except Kurumbas (19.5%). The frequency of carriers were more (37.8%) on the western part of Nilgiris (Nedungode, Kappala and adjoining regions) than the eastern part (30%). Further, the prevalence of carriers was higher (47-49%) in the 10-19 yr age group amongst Paniyas and Mullukurumbas living in the western part of Nilgiris. An episodic, epidemic of malaria so rampant during the early part of this century in the western parts of Nilgiris might have eliminated many children with HbAA and hence the higher frequency of HbAS in this particular age group.

Adolescent↗

PubMed1993

Proteoglycans and endothelial barrier function: effect of linoleic acid exposure to porcine pulmonary artery endothelial cells.

Certain fatty acids induce changes in endothelial barrier function which may be mediated by alterations in normal proteoglycan synthesis/metabolism. To test this hypothesis, pulmonary artery derived endothelial cells were treated with media supplemented with linoleic acid (18:2), and/or a known proteoglycan synthesis inhibitor, beta-D-xyloside. Independent exposure to 1 mM beta-D-xyloside or 90 microM 18:2 increased albumin transfer, i.e., decreased barrier function, when compared with control cultures. 18:2 and beta-D-xyloside increased albumin transfer additively, suggesting that the mechanisms by which 18:2 and beta-D-xyloside alter the proteoglycan metabolism are different. Compared with the control group, treatment with 18:2 inhibited proteoglycan synthesis, decreased anionic properties of heparan sulfate proteoglycans in the cell monolayers and caused the release of a unique chondroitin sulfate proteoglycan into the culture media. Treatment with beta-D-xyloside caused an increased incorporation of radioactive sulfate into glycosaminoglycans but inhibited proteoglycan synthesis. These results suggest that the fatty acid- and beta-D-xyloside-induced impairment in endothelial barrier function may involve changes in the synthesis, release and physicochemical properties of proteoglycans.

Albumins↗