Search PubMed⌕ Search

Biomedical subjects

N Sekar

Publications and source records attributed to N Sekar.

At least 19 recordsLinked to original sources
PubMed2004

Management of upper limb arterial injury without angiography--Chennai experience.

We present our experience and observations in the management of upper limb arterial injury in a tertiary trauma care centre of a University Hospital in a developing country from January 2000 to January 2002. In this retrospective study, we had treated 27 patients (identified from trauma register) with upper extremity vascular injuries. Clinical examination and Doppler pressure studies were our prime modalities of investigation. Angiography was not employed. Our immediate limb salvage rate was 100%. Two patients developed complications during a mean follow up of 70 days with one requiring amputation. We thereby emphasise the fact that good results can be obtained by thorough clinical examination and Doppler evaluation and prompt surgery without the need for angiography in upper limb vascular trauma.

Adult↗
PubMed2001

Concerted transcriptional activation of the low density lipoprotein receptor gene by insulin and luteinizing hormone in cultured porcine granulosa-luteal cells: possible convergence of protein kinase a, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase signaling pathways.

Insulin and insulin-like growth factor I (IGF-I) can amplify gonadotropin-stimulated steroidogenesis by augmenting the expression of key sterol regulatory genes in ovarian cells, viz. low density lipoprotein (LDL) receptor, steroidogenic acute regulatory protein, and P450 cholesterol side-chain cleavage enzyme (CYP11A). The mechanisms underlying the foregoing bihormonal interactions are not known. Accordingly, in relation to the LDL receptor gene, the present study tests the hypothesis that insulin/IGF-I and LH can act via concerted transcriptional control of promoter expression. To this end, we transiently transfected primary monolayer cultures of porcine granulosa-luteal cells with a reporter vector containing the putative 5'-upstream full-length (pLDLR1076/luc) regulatory region (-1076 to +11 bp) of the homologous LDL receptor gene driving firefly luciferase in the presence or absence of insulin (or IGF-I) and/or LH (each 100 ng/ml). Combined exposure to LH and insulin (or IGF-I) stimulated LDL receptor transcriptional activity maximally at 4 h by 8- to 20-fold, as normalized by coexpression of Renilla luciferase. Further analysis of multiple 5'-nested deletional constructs of the LDL receptor gene promoter showed that deletion of -139 bp upstream of the transcriptional start site virtually abolished basal expression and promoter responsiveness to LH and insulin/IGF-I. In contrast, full basal activity and 60-80% of maximal monohormonal and bihormonal drive were retained by the -255 to +11 bp fragment. As LDL receptor gene expression in other tissues is negatively regulated by the abundance of intracellular free cholesterol, we assessed the impact of concomitant pretreatment of granulosa-luteal cells with an exogenous soluble sterol (25-hydroxycholesterol, 1 and 10 microM). Excess sterol markedly (50-70%) attenuated bihormonally and, in lesser measure, LH-stimulated and basal LDL receptor promoter expression, thus affirming a feedback-sensitive sterol-repressive region in this gene. Non-LH receptor-dependent agonists of protein kinase A (PKA), 8-bromo-cAMP (1 mM), and forskolin (10 microM) with or without insulin/IGF-I costimulation likewise augmented LDL receptor promoter expression with similar strong dependency on the -255 to -139 bp 5'-upstream region. To assess more specific PKA-dependent mediation of LH's contribution to combined hormonal drive, the LDL receptor (-1076 to +11 bp) reporter plasmid was cotransfected with a full-sequence rabbit muscle protein kinase inhibitor (PKI) minigene driven constitutively by a Rous sarcoma virus promoter. Expression of the latter PKA antagonist blocked transcriptional stimulation by LH alone as well as that by LH combined with insulin (or IGF-I) by 70-85% without reducing basal transcriptional activity. Transfection of a mutant inactive (Arg to Gly) Rous sarcoma virus/PKI gene confirmed the specificity of the PKI effect. To investigate the convergent role of the insulin/IGF-I effector pathway mediating bihormonal stimulation of LDL receptor promoter expression, transfected granulosa-luteal cells were pretreated for 30 min with two specific inhibitors of phophatidylinositol 3-kinase, wortmannin (100 nM) and LY 294002 (10 microM), or of mitogen-activated protein kinase kinase, PD 98059 (50 microM), U0126 (10 microM), or the latter's inactive derivative, U0124 (10 microM). Both classes of antagonists impeded the ability of insulin or IGF-I to enhance LH-stimulated LDL receptor promoter expression by 60-80%. In conclusion, the present analyses indicate that LH and insulin (or IGF-I) can up-regulate LDL receptor transcriptional activity supraadditively in porcine granulosa-luteal cells 1) via one or more agonistic cis-acting DNA regions located between -255 and -139 bp 5'- upstream of the transcriptional start site, 2) without abrogating sterol-sensitive repressive of this promoter, and 3) by way of intracellular mechanisms that include the PKA, phophatidylinositol 3-kinase, and mitogen-activated protein kinase signaling pathways.

Animals↗
PubMed2000

Mechanisms underlying the steroidogenic synergy of insulin and luteinizing hormone in porcine granulosa cells: joint amplification of pivotal sterol-regulatory genes encoding the low-density lipoprotein (LDL) receptor, steroidogenic acute regulatory (stAR) protein and cytochrome P450 side-chain cleavage (P450scc) enzyme.

Growth of ovarian Graafian follicles and cytodifferentiation of granulosa and theca cells are regulated by gonadotropins, sex steroids and peptidyl growth factors. For example insulin and intraovarian insulin-like growth factor type I (IGF-I) may amplify the actions of both follicle stimulating hormone (FSH) and luteinizing hormone (LH) in promoting biochemical luteinization and enhancing steroidogenesis. To explore further the notion of interactions between insulinomimetic peptides and LH and to examine the associated mechanisms, we have established porcine granulosa cells in monolayer culture for 48 h in 3% serum with insulin (1 microg/ml), estradiol (0.5 microg/ml), and follicle stimulating hormone (FSH, 5 ng/ml) to allow cell anchorage, facilitate in vitro cytodifferentiation and confer LH responsiveness. To limit any carry-over effects of serum, granulosa cells were stabilized overnight in serum-free medium. Studies were then initiated to assess the impact of insulin on the dose-responsive actions of LH. A maximally effective concentration of insulin (1 microg/ml) synergistically augmented LH's dose-dependent ampilification of progesterone and cAMP accumulation; viz. by approximately twofold (progesterone) and approximately 2.5-fold (cAMP) above that observed in maximally LH-stimulated cultures (P < 0.001). Mechanistically, insulin significantly enhanced the sensitivity of granulosa cells to LH's drive of cAMP accumulation [ED50 for LH 61 +/- 14 ng/ml (control) vs. 10 +/- 1.0 ng/ml (insulin) (P < 0.01)]. Insulin also augmented the maximal stimulatory effect of LH; i.e. LH efficacy rose from 6.5 +/- 0.4 to 17 +/- 1.4 (pmole cAMP/microg DNA/48 h; P < 0.001). Insulin dose-response analysis showed that insulin alone minimally elevated basal, but significantly heightened LH's stimulation of progesterone and cAMP accumulation at (insulin) concentrations as low as 3-10 ng/ml. The molecular mechanisms underlying insulin and LH's synergy were assessed by RNase protection assays with (porcine) cRNA probes encoding the low density lipoprotein receptor (LDL-R), Steroidogenic Acute Regulatory Protein (StAR), P450 cholesterol sidechain cleavage enzyme (P450scc) and (as a possible negative control) Sterol Carrier Protein 2 (SCP-2) [data normalized to constitutive 18S rRNA]. Non linear least-squares analysis was applied to confirm or refute an hypothesis of interactive synergy between LH and insulin on gene expression. LH and insulin alone exerted no effect on StAR message accumulation, and LH alone minimally stimulated P450scc and LDL-R mRNA's accumulation at 48 h. In contrast, insulin in combination with LH augmented StAR mRNA concentrations by approximately 5-10-fold and stimulated LDL-R message levels by threefold above the respective maximally LH-driven values (P < 0.01). Maximal P450scc mRNA expression was enhanced twofold by cotreatment with LH and insulin compared with maximal LH-treated cultures. In contrast SCP-2 mRNA accumulation remained unaffected by any treatment. In summary, we have used a serum-free, in vitro differentiated porcine granulosa cell culture system to assess regulatory interactions between the disparate first messengers, LH and insulin. We observe marked LH-insulin steroidogenic synergy after 48 h of joint hormonal stimulation, and further clarify that the mechanism(s) of synergy include augmentation of cAMP production and increased steady-state concentrations of transcripts of key sterol-regulatory genes; namely, LDL-R, StAR, and P450scc, but not SCP-2. Since the encoded products of these genes variously control sterol substrate uptake, delivery to and utilization in mitochondrial steroidogenesis, we speculate that the concerted actions of insulin-like peptides and LH may contribute to steroidogenic differentiation during the later stages of follicular maturation and the granulosa-luteal cell transition.

Animals↗
PubMed2000

Vanadate restores glucose 6-phosphate in diabetic rats: a mechanism to enhance glucose metabolism.

Vanadate mimics the metabolic actions of insulin. In diabetic rodents, vanadate also sensitizes peripheral tissues to insulin. We have analyzed whether this latter effect is brought about by a mechanism other than the known insulinomimetic actions of vanadium in vitro. We report that the levels of glucose 6-phosphate (G-6-P) in adipose, liver, and muscle of streptozotocin-treated (STZ)-hyperglycemic rats are 77, 50, and 58% of those in healthy control rats, respectively. Normoglycemia was induced by vanadium or insulin therapy or by phlorizin. Vanadate fully restored G-6-P in all three insulin-responsive peripheral tissues. Insulin did not restore G-6-P in muscle, and phlorizin was ineffective in adipose and muscle. Incubation of diabetic adipose explants with glucose and vanadate in vitro increased lipogenic capacity three- to fourfold (half-maximally effective dose = 11 +/- 1 microM vanadate). Lipogenic capacity was elevated when a threshold level of approximately 7.5 +/- 0.3 nmol G-6-P/g tissue was reached. In summary, 1) chronic hyperglycemia largely reduces intracellular G-6-P in all three insulin-responsive tissues; 2) vanadate therapy restores this deficiency, but insulin therapy does not restore G-6-P in muscle tissue; 3) induction of normoglycemia per se (i.e., by phlorizin) restores G-6-P in liver only; and 4) glucose and vanadate together elevate G-6-P in adipose explants in vitro and significantly restore lipogenic capacity above the threshold of G-6-P level. We propose that hyperglycemia-associated decrease in peripheral G-6-P is a major factor responsible for peripheral resistance to insulin. The mechanism by which vanadate increases peripheral tissue capacity to metabolize glucose and to respond to the hormone involves elevation of this hexose phosphate metabolite and the cellular consequences of this elevated level of G-6-P.

Adipose Tissue↗
PubMed2000

Concerted regulation of steroidogenic acute regulatory gene expression by luteinizing hormone and insulin (or insulin-like growth factor I) in primary cultures of porcine granulosa-luteal cells.

The steroidogenic acute regulatory (StAR) protein is indispensable for maximal trophic hormone-stimulated steroidogenesis by the adrenal gland, testis, and ovary. Recently, our laboratory developed an in vitro primary culture system of porcine granulosa-luteal cells that retain responsiveness to LH and show LH and insulin [or insulin-like growth factor (IGF-I)] synergy in stimulating StAR messenger RNA accumulation. Here, we examine the mechanisms subserving this LH-insulin (IGF-I) augmentation. We corroborate LH's amplification of insulin as well as IGF-I-stimulated granulosa-luteal cell progesterone and cAMP accumulation (P < 0.001). Insulin or IGF-I elevated LH receptor transcript accumulation, and LH did not alter this effect. To determine the hormonal responsiveness of StAR promoter, truncated regions of the -1423 to +130 bp upstream sequence of the porcine gene were ligated into a firefly luciferase reporter plasmid. Transient transfection of the StAR plasmid containing the full-length porcine 5'-flanking region of StAR (pStAR1423/luc) showed superadditive stimulation by LH and insulin or IGF-I after 24 h. LH, but not insulin or IGF-I alone, stimulated pStAR1423/luc activity. Deletion of the proximal putative steroidogenic factor-1 (-48 to -41) site abolished hormonally driven StAR promoter activity. A stable cAMP analog, 8-bromo-cAMP (1 mM), and insulin/IGF-I also evoked supraadditive StAR promoter expression. To further explore the role of cAMP in LH-insulin (or IGF-I) actions, we cotransfected a Rous sarcoma virus (RSV)-driven minigene encoding the heat-stable inhibitor of the cAMP-dependent protein kinase (RSV/PKI) or a mutant plasmid (RSV/PKImut) along with the pStAR1423/luc promoter construct. Cotransfection of PKI, but not PKImut, with pStAR1423/luc significantly attenuated LH's stimulation of luciferase activity and also reduced the magnitude of the transcriptional amplification exerted by LH and insulin or IGF-I. In corollary analyses of the protein kinase A (PKA) pathway, cotransfection of full-length pStAR1423/luc and a complementary DNA encoding a constitutively activated PKA catalytic subunit elevated basal and insulin (or IGF-I)-stimulated StAR promoter expression. LH and insulin (or IGF-I) also augmented steady state StAR transcript levels, as assessed by homologous RT-PCR, and StAR protein concentrations, as evaluated by Western blotting. Together, these investigations document a significant role for insulin or IGF-I in enhancing LH-stimulated progesterone and cAMP biosynthesis and endogenous StAR message and protein accumulation and in augmenting cAMP-PKA-dependent transcriptional activation of the exogenous StAR promoter.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Independent signal-transduction pathways for vanadate and for insulin in the activation of glycogen synthase and glycogenesis in rat adipocytes.

The activating effect of vanadate on glycogenesis and on glycogen synthase (uridine diphosphate-glucose-glycogen glucosyl transferase) activity was studied in rat adipocytes and compared with that of insulin. Using several approaches and specific blockers, we found that vanadate and insulin resemble each other, in the activation of glycogen synthase, in several aspects: both require nonarrested protein phosphatase 1 activity; they are equally suppressed by conditions that elevate cAMP-levels; and both depend on the activation of phosphatidylinositol-3 kinase. The basic differences between them are as follows: 1) vanadate promotes glycogenesis through the activation of a cytosolic protein tyrosine kinase, in an insulin-receptor-independent manner; 2) vanadate elevates glucose-6-phosphate (G-6-P) to a higher level than insulin; 3) vanadate-activated glycogenesis is accompanied by an increase in the cellular content of immunoreactive glycogen synthase, an effect less noticeable with insulin; 4) adipose glucose-6-phosphatase is inhibited by vanadate (dose for 50% inhibition, IC50 = 7 +/- 0.7 microM) but not by insulin. We have concluded that insulin and vanadate activate glycogenesis through a phosphatidylinositol-3 kinase and dephosphorylation-dependent mechanism. Vanadate, however, uses a receptor-independent pathway and is superior to insulin in elevating the level of G-6-P, a key metabolite for activating glycogen synthase. This is attributed to the combined effect of vanadate in enhancing glucose entry and in inhibiting dephosphorylation of endogenously formed G-6-P. The latter effect is not exerted by insulin.

Adipocytes↗
PubMed1998

Vanadate elevates lipogenicity of starved rat adipose tissue: mechanism of action.

We have established an experimental system in rats in which the lipogenic capacity of adipose tissue was decreased in vivo by prolonged fasting, and restored in vitro by glucose together with insulin or vanadate. Incubation of fasted adipose explants for 5 h at 37 C with 2 mM glucose alone did not elevate lipogenic capacity. However, glucose with insulin (17 nM) or vanadate (100 microM), led, respectively, to 2.2- and 8- to 10-fold elevation. Actinomycin D (50 microM) completely blocked this increase, while low concentrations (ED50 = 4.0 +/- 0.4 microM) of vanadate potentiated it. Neither insulin nor vanadate elevated fasted adipose explants' lipogenic capacity in the absence of glucose, or in the presence of the nonmetabolizable glucose analog 3-O-methylglucose. Upon replacing glucose with 2-deoxyglucose (1 mM), a glucose analog that undergoes phosphorylation to 2-deoxyglucose-6-phosphate with no further metabolism, vanadate was nearly as potent as with glucose in elevating lipogenic capacity. Vanadate was superior to insulin in increasing glucose-6-phosphate level in fasted-adipose explants. Adipose glucose-6-phosphatase activity was inhibited by vanadate (IC50 = 7.0 +/- 0.4 microM). We have concluded that glucose-6-phosphate is the key metabolite of glucose involved in the transcriptionally regulated elevation of lipogenic capacity of fasted adipose explants. Vanadate has a more profound effect than insulin, as it elevates glucose-6-phosphate to higher levels and the subsequent increase in lipogenic capacity is four to five times greater than that induced by insulin. The mechanism involved is the combined action of vanadate in enhancing glucose entry and in inhibiting dephosphorylation of endogenously formed glucose-6-phosphate. The latter effect is not exerted by insulin.

3-O-Methylglucose↗
PubMed1997

A novel assay for evaluating glycogenolysis in rat adipocytes and the inability of insulin to antagonize glycogenolysis in this cell type.

We report here on a novel procedure for measuring glycogenolysis in rat adipocytes. In this procedure, cells are incubated for 30 min at 37 degrees C with insulin or vanadate, and with [U-14C]glucose to label the glycogen pool with radioactive glucose. The cells are washed and preincubated for an additional 1 h, before being assayed. The extent of glycogenolysis is determined by the decrease in radioactivity in precipitated glycogen, which was quite substantial under experimental conditions facilitating glycogenolysis. From the assay, we determined the following. (a) Glycogenolysis is activated in rat adipocytes in response to lipolytic hormones (i.e. catecholamines and adrenocorticotropic hormone). (b) Other agents and conditions elevating intracellular adenosine 3',5'-monophosphate levels (i.e. cholera toxin, dibutyryladenosine 3',5'-monophosphate, and isobutylmethylxanthine) also activate glycogenolysis. (c) Glycogenolysis (as opposed to lipolysis) is activated at concentrations of adrenocorticotropic hormone or isoproterenol 7-11-fold lower and at adenosine 3',5'-monophosphate concentrations 7-fold lower. (d) Calyculin A, a specific inhibitor of protein phosphatase 1, activates glycogenolysis as well. Calyculin A also activates lipolysis at an equimolar potency. (e) Insulin does not antagonize glycogenolysis in rat adipocytes. In conclusion, the assay allowed us to compare glycogenolysis to lipolysis within the same cell, and to find that the sensitivity to hormones and adenosine 3',5'-monophosphate was about 1 order of magnitude higher for glycogenolysis than for lipolysis. A more striking finding was the inability of insulin to antagonize glycogenolysis in the rat adipose cell, an effect which occurs readily in liver and muscle cells via protein phosphatase 1-activating machinery. This rules out a role for adipose protein phosphatase 1 activation in the mechanism by which insulin antagonizes lipolysis and supports the contention that the insulin effect in lowering adenosine 3',5'-monophosphate levels is the central mechanism by which insulin antagonizes lipolysis.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Clinical prediction rules. A review and suggested modifications of methodological standards.

BACKGROUND: Clinical prediction rules are decision-making tools for clinicians, containing variables from the history, physical examination, or simple diagnostic tests. OBJECTIVE: To review the quality of recently published clinical prediction rules and to suggest methodological standards for their development and evaluation. DATA SOURCES: Four general medical journals were manually searched for clinical prediction rules published from 1991 through 1994. STUDY SELECTION: Four hundred sixty potentially eligible reports were identified, of which 30 were clinical prediction rules eligible for study. Most methodological standards could only be evaluated in 29 studies. DATA ABSTRACTION: Two investigators independently evaluated the quality of each report using a standard data sheet. Disagreements were resolved by consensus. DATA SYNTHESIS: The mathematical technique was used to develop the rule, and the results of the rule were described in 100% (29/29) of the reports. All the rules but 1 (97% [28/29]) were felt to be clinically sensible. The outcomes and predictive variables were clearly defined in 83% (24/29) and 59% (17/29) of the reports, respectively. Blind assessment of outcomes and predictive variables occurred in 41% (12/29) and 79% (23/29) of the reports, respectively, and the rules were prospectively validated in 79% (11/14). Reproducibility of predictive variables was assessed in only 3% (1/29) of the reports, and the effect of the rule on clinical use was prospectively measured in only 3% (1/30). Forty-one percent (12/29) of the rules were felt to be easy to use. CONCLUSIONS: Although clinical prediction rules comply with some methodological criteria, for other criteria, better compliance is needed.

Decision Support Techniques↗
PubMed1997

Antilipolytic actions of vanadate and insulin in rat adipocytes mediated by distinctly different mechanisms.

Vanadate, which mimics the biological effects of insulin, also inhibits lipolysis in rat adipocytes. Here we demonstrate that the antilipolytic effect of vanadate differs from that of insulin at least by the five following criteria: 1) vanadate inhibits lipolysis mediated by high (supraphysiological) concentrations of catecholamines; 2) vanadate antagonizes (Bu)2cAMP-mediated lipolysis; 3) vanadate antagonizes isobutylmethylxanthine-dependent lipolysis, 4) vanadate inhibits lipolysis mediated by okadaic acid; and 5) wortmannin, which blocks the antilipolytic effect of insulin, fails to block vanadate-mediated antilipolysis. Vanadate does activate phosphoinositol 3-kinase, and wortmannin blocks this activation. Our working hypothesis assumes that all of the insulin-like effects of vanadate, including antilipolysis, are initiated by the inhibition of protein phosphotyrosine phosphatases (PTPases). Among documented PTPase inhibitors we found that VOSO4 (oxidation state +4), several organic vanadyl compounds (+4), zinc (Zn2+), tungstate (W), and molybdate (Mo) also had antilipolytic activity. The order of potency was vanadyl acetylacetonate > or = VOSO4 > or = NaVO3 > or = vanadyl-dipicolinate > Zn2+ >> W > Mo, and it correlated better with the inhibition of adipose membranal-PTPases in cell-free experiments. We have concluded that the antilipolytic effect of vanadate is 1) mechanistically distinct from that of insulin, 2) independent of phosphoinositol 3-kinase activation, and 3) independent of the lipolytic cascade. We also strongly suggest that the antilipolytic effect of vanadate emanates from inhibiting adipose membranal, rather than cytosolic PTPases, and present preliminary data showing distinct differences in catalysis between these two PTPase categories. Overall, the study indicates that antilipolysis can be manifested via alternative, insulin-independent, signal-transducing pathways.

Adipocytes↗
PubMed1997

Vanadate activates membranous nonreceptor protein tyrosine kinase in rat adipocytes.

The insulin-like effects of vanadate are independent of the insulin receptor and insulin receptor substrate 1 (IRS-1) phosphorylation. A cytosolic protein tyrosine kinase (CytPTK), sensitive to inhibition by nanomolar concentrations of staurosporine (concentration at which 50% inhibition occurs [IC50], 1-2 nmol/l), has been implicated in some (i.e., glucose oxidation, lipogenesis) but not all (i.e., hexose uptake, inhibition of lipolysis) of the insulin-like effects of vanadate. We report here the existence of another nonreceptor protein tyrosine kinase in rat adipocytes, located exclusively in the plasma membranes (MembPTK), which we suggest is associated with hexose uptake and the antilipolytic activity of vanadate. MembPTK is a nonglycoprotein with an estimated molecular weight of 55-60 kDa. In a cell-free experiment, vanadate activates MembPTK seven- to ninefold (median effective dose, 17 +/- 2 micromol/l). Vanadate-activated MembPTK is inhibited by staurosporine (IC50, 60 +/- 5 nmol/l). In intact adipocytes, staurosporine antagonized vanadate-induced hexose uptake (IC50, 6.0 +/- 0.3 micromol/l) and significantly reversed the antilipolytic effect of vanadate (IC50, 5.0 +/- 0.4 micromol/l). After vanadate treatment, a phosphorylated P55 protein is immunoprecipitated by antibodies to both phosphotyrosine and phosphatidylinositol (PI) 3-kinase. In conclusion, rat adipocytes contain an additional vanadate-activatable nonreceptor membranous protein tyrosine kinase that may participate in the effects of vanadate not carried out by CytPTK. We also suggest that after treatment with vanadate, MembPTK is activated by autophosphorylation and interacts with PI 3-kinase. This may explain how vanadate activates PI 3-kinase without involving receptor activation and IRS-1 phosphorylation.

Adipocytes↗
PubMed1996

Vanadium salts as insulin substitutes: mechanisms of action, a scientific and therapeutic tool in diabetes mellitus research.

Vanadium and its compounds exhibit a wide variety of insulin-like effects. In this review, these effects are discussed with respect to the treatment of type I and type II diabetes in animal models, in vitro actions, antineoplastic role, treatment of IDDM and NIDDM patients, toxicity, and the possible mechanism(s) involved. Newly established CytPTK plays a major role in the bioresponses of vanadium. It has a molecular weight of approximately 53 kDa and is active in the presence of Co2+ rather than Mn2+. Among the protein-tyrosine kinase blockers, staurosporine is found to be a potent inhibitor of CytPTK but a poor inhibitor of InsRTK. Vanadium inhibits PTPase activity, and this in turn enhances the activity of protein tyrosine kinases. Our data show that inhibition of PTPase and protein tyrosine kinase activation has a major role in the therapeutic efficacy of vanadium in treating diabetes mellitus.

Animals↗
PubMed1994

Chemopreventive potential of dietary bioflavonoids against 20-methylcholanthrene-induced tumorigenesis.

The effect of dietary supplementation of flavonoidal compounds such as quercetin, rutin, luteolin and (+)-catechin on the incidence of fibrosarcoma induced by 20-methylcholanthrene (20-MC) in male Swiss albino mice was observed. Subcutaneous injection of 20-MC produced 100% tumor incidence and the onset of tumor appeared within 7 weeks, while flavonoid-treated mice (1% quercetin- and luteolin-mixed diets) produced tumors in the 9th week, and the tumor incidences in mice treated with quercetin- and luteolin-mixed diets were 52% and 60%, respectively. Subcutaneous administration of 20-MC along with the flavonoidal compounds (quercetin, luteolin) was found to have significant effect on tumor expression. The compounds rutin and (+)-catechin did not influence tumor expression in both experiments. Elevated levels of lipid peroxides, cytochrome P450 and decreased activity of glutathione-S-transferase (GST) were observed in the tumor bearing animals. Test-diet-treated animals showed reduction in the lipid peroxides and cytochrome P450, and increased activity of GST (P < 0.001). In vitro [3H]thymidine incorporation showed the inhibition of DNA synthesis in fibrosarcoma cells by the flavonoids. The possible mode of action of the flavonoidal compounds may be through their influence on the initiation and promotion phases of the carcinogenic process coupled with enhancement of the detoxification process.

Animals↗
PubMed1994

Diagnostic and prognostic role of plasma and urinary sialic acid in human carcinoma of uterine cervix.

In different stages of carcinoma of uterine cervix, the plasma total sialic acid (TSA), lipid bound sialic acid (LSA) and urinary sialic acid levels were studied before and after radiation treatment. Glycocomponents of glycoproteins were found to be increased progressively as the disease advances. The increased levels of glycocomponents were found to be decreased to near normal levels after radiotherapy. This may be a better indicator of the disease in conjunction with the studies of cervical smear rather than the latter alone.

Adult↗
PubMed1993

Insulin-like effects of bis-glycinato oxovanadium (IV) complex on experimental diabetic rats.

The insulin-like activity of bis-glycinato oxovanadium (IV) complex on experimental diabetes has been studied. Rats made diabetic with streptozotocin, after one month, were fed ad libitum with bis-glycinato oxovanadium (IV) complex (30 mg/100 ml) for fifteen days. The altered blood glucose, urea, cholesterol, triglycerides, liver glycogen and the activities of liver enzymes such as hexokinase, lactate dehydrogenase and fructose-1, 6-bisphosphatase, were reverted to normal levels in bis-glycinato oxovanadium (IV) complex treated diabetic rats, thereby suggesting for the insulin-mimetic effect of bis-glycinato oxovanadium (IV) in experimental diabetes.

Animals↗
PubMed1991

Antitumor effect of echitamine chloride on methylcholonthrene induced fibrosarcoma in rats.

Echitamine chloride a plant alkaloid from Alstonia scholaris has been used to examine the anticancer effects on methylcholanthrene-induced fibrosarcoma. Echitamine chloride dissolved in saline (10 mg/kg body weight) and injected subcutaneously for 20 days in fibrosarcoma rats has exhibited significant regression in tumor growth. The altered activities of plasma and liver transaminases and gamma-glutamyl transpeptidase and lipid peroxidation in fibrosarcoma have been corrected to near normal after echitamine chloride treatment. The decreased liver glutathione content and the lowered activities of glutathione peroxidase, superoxide dismutase and catalase have also been reversed to near normals after echitamine chloride treatment.

Alkaloids↗
PubMed1991

Insulin mimetic role of vanadate on plasma membrane insulin-receptors.

Vanadate possesses insulin-mimetic effects, and has been reported to correct the metabolic imbalances in streptozotocin-induced diabetes. Rats were made diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight) in citrate buffer. After the onset of diabetes, the diabetic rats were treated with sodium orthovanadate (0.3 mg/ml) for 15 days. The increased percentage of 125 I insulin binding to the liver plasma membrane insulin receptors and increased plasma membrane phospholipids were found to be reduced significantly in vanadate treated diabetes. Hence the mode of action of vanadate may be similar to that insulin.

Animals↗