Adose-dependent Manner Research Articles

Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats.

The present study tested the hypothesis that Korean red ginseng (KRG) provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v) alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON), alcohol control (ET), and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively). Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK) signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

Effects of aqueous extract of turnip leaf (Brassica rapa) in alloxan-induced diabetic rats.

Turnip leaf has been used in folk medicine of Iran for the treatment of diabetes. However,so far no scientific study has been done to support its use in traditional medicine. The present study was carried out to evaluate the possible hypoglycemic efficacy of aqueous extract of turnip leaf (AETL) in diabetic rats. Alloxan-induced diabetic rats were orally treated with AETL at doses of 200 and 400 mg/kg body weight (bw) per day for 28 days. In order to evaluate the anti-diabetic activity, fasting blood glucose concentrations were determined on the 1(st), 14(th) and 29(th) days. Moreover,at the end of the study, plasma concentrations of total cholesterol, triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), aspartate amino transfarase (AST), and alanine amino transferase (ALT) were measured by the use of standard kits and auto-analyzer. Both doses of AETL significantly decreased (p<0.001) blood glucose and ALT levels in diabetic rats after 28 days of administration. AETL at both doses decreased (p<0.05) plasma total cholesterol and LDL-c in diabetic rats, but they significantly decreased (p<0.05) HDL-c and increased triglycerideand AST levels in a-dose dependent manner. The results showed that AETL has a dose- dependent decrease in the blood glucose in diabetic rats. However,we should not be unaware of adverse effects of AETL on lipid profiles and liver enzymes activity, especially decrease of HDL and increase of TG and AST.

Synergistic effects of loxoprofen and glycine on the micturition reflex in consciousrats

We examined the inhibitory effects of loxoprofen, a cyclooxygenase inhibitor, and glycine, a major inhibitory neurotransmitter, on the micturition reflex in conscious rats and hypothesized that these drugs would interact synergistically to inhibit micturition. Voiding behaviors were assessed using a metabolic cage. Oral loxoprofen decreased the urinary frequency, and only a high dose(10 mg/kg) significantly reduced the voided volume. With cystometry, intravenous loxoprofen(0.1-3 mg/kg) and glycine (30 and 100 mg/kg) prolonged the intercontraction intervals (ICI) in adose-dependent manner, but did not change the maximum voiding pressure (MVP) in conscious rats. The combination of loxoprofen (3 mg/kg) and glycine (100 mg/kg) strongly prolonged the ICI more than with either drug alone. The lowest dose of loxoprofen (0.1 mg/kg) and glycine(30 mg/kg) did not affect either the ICI or the MVP, but their combination resulted in a significant increase in the ICI. These results suggest that the combined administration of loxoprofen and glycine produced a synergistic inhibitory effect on the micturition reflex.

Some pharmacological studies on the methanolic extract of &amp;lt;i&amp;gt;Inula graveolense&amp;lt;/i&amp;gt; L.

Inula graveolens L. is widely used in Iraq for the treatment of rheumatic fever, infant convulsions, toothache, blood sugar, and also to dissolve internal blood clots, and to aid digestion. However, the efficacy and mechanisms of action of the plant remain unclear. Therefore, the objective of the present study was to investigate the pharmacological effects of the methanolic extract (MEIG) of this plant belonging to compositae family. Anti-diarrheal and antipyretic activities of the extract were examined in rats. Anti-inflammatory and antinociceptive were studied in mice. At the doses of 200 (P < 0.05) and 400 mg/kg body weight (P < 0.01), the extract displayed remarkable anti-diarrheal activity, evidence by a reduction in the rate of defecation as well as by retardation of intestinal transit of charcoal meal compared to normal saline control group, dose dependently similar to loperamide (5 mg/kg). The methanolic extract (400 mg/kg) showed a significant (P < 0.01) dose dependent anti-pyretic effect in yeast induced elevation of body temperature in experimental rats. The methanolic extract showed significant anti-inflammatory and antinociceptive activity at the dose of 400 mg/kg (P < 0.01) as compared to standard drug diclofenac sodium (50 mg/kg). The extract inhibited paw and ear edema in a dose-related manner. A dose-dependent analgesic action was obtained against chemical (writhing test) and thermal (hot-plate test) stimuli indicated that antinociceptive activity may involve inhibition of pain by peripheral and central mechanisms. Again, the methanolic extract (MEIG) was subjected for in vitro protein anti-denaturation using Bovine serum albumin and anti-platelet aggregation of human blood activity. It was observed that the extract showed greater percentage of inhibition of BSA (P < 0.01) at the highest concentration (400 μg/ml). The extract also showed potential platelet aggregation inhibitory activity in adose-dependent manner. The maximum inhibition was observed at the dose 400 μg/ml (P < 0.01) compared to standard drug commercial heparin (20 μg/ml).

Rapid purification and procoagulant and platelet aggregating activities of Rhombeobin: a thrombin-like/gyroxin-like enzyme from Lachesis muta rhombeata snake venom.

We report a rapid purification method using one-step chromatography of SVSP Rhombeobin (LMR-47) from Lachesis muta rhombeata venom and its procoagulant activities and effects on platelet aggregation. The venom was fractionated by a single chromatographic step in RP-HPLC on a C8 Discovery BIO Wide Pore, showing high degree of molecular homogeneity with molecular mass of 47035.49 Da. Rhombeobin showed amidolytic activity upon BAρNA, with a broad optimum pH (7–10) and was stable in solution up to 60°C. The amidolytic activity was inhibited by serine proteinase inhibitors and reducing agents, but not chelating agents. Rhombeobin showed high coagulant activity on mice plasma and bovine fibrinogen. The deduced amino acid sequence of Rhombeobin showed homology with other SVSPs, especially with LM-TL (L. m. muta) and Gyroxin (C. d. terrificus). Rhombeobin acts, in vitro, as a strong procoagulant enzyme on mice citrated plasma, shortening the APTT and PT tests in adose-dependent manner. The protein showed, “ex vivo”, a strong defibrinogenating effect with 1 µg/animal. Lower doses activated the intrinsic and extrinsic coagulation pathways and impaired the platelet aggregation induced by ADP. Thus, this is the first report of a venom component that produces a venom-induced consumptive coagulopathy (VICC).

ANTIOXIDANT POTENCY, pH AND HEAT STABILITY OF SELECTED PLANT EXTRACTS

The potential of methanolic extracts of six green leafy vegetables, viz. Punica granatum, Ipomoea batatas L., Beta vulgaris, Daucus carota, Amaranthus paniculatus and Peucedanum graveolens, as a natural antioxidant was assessed. Two experimental models, namely 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity and iron (III) reducing capacity,were used to evaluate the antioxidant activity (AOA) of green leafy vegetables. The stability of extracts to pH (4, 7 and 9) and temperature (100C) was investigated.All the extracts showed varying degrees of antioxidant efficacy in a dose-dependent manner. P. granatum had high glutathione and polyphenols, and D. carota had higher ascorbic acid and b-carotene. The AOA of D. carota leaves, A. paniculatus and P. graveolens almost remained the same at pH 7 and 9. The extracts of D. carota leaves, A. paniculatus and P. graveolens showed increasing AOA after heat treatment. P. granatum was more heat stable than other extracts.

Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy: Possible mechanisms of neurotoxic effects

Although there is still no ideal experimental model of hepatic encephalopathy, thioacetamide is widely used for the induction of acute and chronic liver failure. Thioacetamide exerts hepatotoxic effects through the formation of toxic metabolites in hepatocytes, oxidative stress and calcium mobilization. An ideal experimental model of hepatic encephalopathy should have similar behavioral and electroencephalographic manifestations as human encephalopathy. Thioacetamide induces motor manifestations in a dose-dependent manner. Milder forms of thioacetamide-induced encephalopathy are associated with an increase in relative alpha power, while more severe forms are followed by a flattening of the electroencephalogram. liver failure-induced hyperammonemia has a pivotal role in the neurotoxic effects of thioacetamide. Hyperammonemia induces brain edema, alterations in neurotransmission, oxidative stress, mitochondrial dysfunction and neuronal death. The aim of this article is to review the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy, as well as to summarize potential mechanisms involved in thioacetamide neurotoxicity.

BIK is a novel pro-apoptotic target gene for miR-125b in human monocytes

IntroductionThe high numbers of activated cells in rheumatoidarthritic (RA) joints critically contribute to the persis-tence of chronic disease and have been associated withtheir resistance to undergo apoptosis [1]. Activity ofpro- and anti-apoptotic Bcl-2 family members is con-strained by transcriptional and/or post-transcriptionalcontrols. As part of the post-transcriptional gene regula-tory network machinery, micro(mi)RNAs represent animportant class of endogenous, short, non-coding RNAthat decreases gene expression by pairing to target tran-scripts and inducing gene silencing. Among miRNAsthat have been assigned oncogenic and/or tumor sup-pressor-like functions, miR-125b is of particular interest.Among the dozen of genes that are identified so far asmiR-125b targets, three are directly involved in apopto-sis, all encoding for pro-apoptotic proteins: Bmf, BAK1and p53 [2-4].AimTo provide novel insight into the integrated genetic reg-ulatory network specifying cell fate, we have exploredother pro-apoptotic members of the Bcl-2 family in thecontext of miR-125b and analyzed their respectiveexpression levels in RA.MethodsmiRNA databases were usedto detect potential miR-125b responsive elements within the 3’-UTR mRNA ofpro- and anti-apoptotic genes. The human monocyticcell line THP-1 was co-transfected with the reporter sys-tem containing the BIK 3’-UTR down-stream of theluciferase together with either a synthetic miR-125bprecursor or antagonist. Inhibition of the luciferaseactivity was compared with cells transfected with themock construct. BIK expression and apoptosis weremonitored at mRNA and protein levels after transfectionof THP-1 monocytes with pre- or antago-miR-125b.Finally, miR-125b and BIK were quantified by RT-qPCRin blood samples from RA and healthy donors.ResultsWe identify miR-125b, whose expression was highly cor-related with patients with RA, as a post-transcriptionalregulator of the pro-apoptotic BH3-like protein BIK.Moreover, enforced expression of miR-125b in humanmonocytes promoted apoptosis by targeting BIK in adose-dependent manner, and broadly impacted apopto-sis-related genes as assessed by transcriptomic analysis.ConclusionUnderstanding the mechanisms that alter the balance ofanti- and pro-apoptotic proteins and identifying keymolecules able to re-establish tissue homeostasis willopen novel fundamental and therapeutic potentials.

Abstract 2513: Arsenic trioxide induces depolymerization of microtubules in an acute promyelocytic leukemia cell line

Abstract Arsenic trioxide (ATO) treatment has been used in recent decades to achieve clinical remission in patients with acute promyelocytic leukemia (APL). The biological basis for ATO treatment has been explained as being mediated through anti-proliferation, anti-angiogenesis, and apoptosis in both APL and solid tumor cells. Arsenic trioxide has been shown to affect microtubules such that dysfunction of the cellular cytoskeleton is induced, which ultimately leads to cell death. In this study, we reported that ATO disrupts tubulin assembly and results in microtubule dysfunction, inducing cell death in an APL cell line. ATO markedly enhanced the depolymerization of microtubules. Analysis of posttranslational modifications of microtubules also revealed that ATO decreased modified forms of the polymerized tubulin portion in adose-dependent manner. Immunocytochemical investigation showed that ATO changed the cellular microtubule network and inhibited the formation of polymerized microtubules. These alterations in microtubules suggest that ATO increases the depolymerized form of tubulin in the cells, potentially through its effect on the attenuation of spindle dynamics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2513.

Evaluation of the free radical scavenging activity and radioprotective efficacy of Grewiaasiatica fruit

The radioprotective effect of Grewia asiatica fruit (GAE) which contains anthocyanin-type cyanidin3-glucoside, vitamins C and A, minerals, carotenes and dietary fibre was studied. For the studySwiss albino mice were divided into five groups: (1) control (vehicle treated); (2) GAE treated (700 mg kg−1 day−1 for 15 days);(3) irradiated (5 Gy); (4) GAE+irradiated and (5) irradiated+GAE treated. The irradiation of animals resulted in a significant elevation of lipid peroxidationin terms of thiobarbituric acid reactive substances (TBARS) content and depletion inglutathione (GSH) and protein levels at all intervals studied, namely 1–30 days,in comparison to the control group. Treatment of mice with GAE before andafter irradiation caused a significant depletion in TBARS content followed by asignificant elevation in GSH and protein concentration in the intestine and testis ofmice at all post-irradiation autopsy intervals in comparison to irradiated mice.Significant protection of DNA and RNA in testis was also noticed. GAE wasfound to have strong radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH*)and O2− assays and also showed in vitro radioprotective activity in protein carbonyl assay in adose-dependent manner. The above results prove the radioprotective efficacy ofGAE.

PmRab7 Is a VP28-Binding Protein Involved in White Spot Syndrome Virus Infection inShrimp

Our aim was to isolate and characterize white spot syndrome virus (WSSV)-binding proteins from shrimp. After a blot of shrimp hemocyte membrane proteins was overlaid with a recombinant WSSV envelope protein (rVP28), the reactive bands on the blot were detected using anti-VP28 antibody. Among three membrane-associated molecules identified by liquid chromatography-tandem mass spectrometry, there was a 25-kDa protein that bound to both rVP28 and WSSV. Since it had a primary structure with high homology to the small GTP-binding protein Rab7, we named it Penaeus monodon Rab7 (PmRab7). The full-length PmRab7 cDNA was obtained, and results from a glutathione S-transferase pull-down assay confirmed specific binding to rVP28. Reverse transcriptase PCR analysis revealed PmRab7 expression in many tissues, and real-time PCR analysis revealed that expression was constitutive. Binding of PmRab7 to rVP28 or WSSV occurred in a dose-dependent manner and was inhibited by anti-Rab7 antibody. In an in vivo neutralization assay, the number of dead shrimp after challenge with WSSV plus PmRab7 (15%) or WSSV plus anti-Rab7 antibody (5%) was significantly lower than after challenge with WSSV alone (95%). In contrast to the WSSV-injected group, shrimp injected with WSSV plus PmRab7 or WSSV plus anti-Rab7 showed no WSSV-type histopathology. We conclude that PmRab7 is involved in WSSV infection in shrimp. This is the first study to identify a shrimp protein that binds directly to a major viral envelope protein of WSSV.

Growth Inhibition Effect of Parthenolide on Human Hepatocellular Carcinomacell Line BEL-7402

To study the effects of parthenolide on human hepatocellular carcinoma cell line BEL-7402 and explore its possible mechanism, human hepatocellular carcinoma cell line BEL-7402 was cultured in vitro and treated with parthenolide of different concentrations. Cells without addition of parthenolide were used as control. The growth of inhibition of cells induced by various concentrations was analyzed by using the MTT assay. The morphologic changes of apoptosis was observed under an inversion microscope by Giemsa staining. The expression levels of PCNA albumen were measured by means of immunohistochemical methods. Parthenolide can inhibit the proliferation of BEL-7402 cells in vitro in adose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage were found by means of inversion microscopy. Formation of apoptotic bodies was observed by Giemsa staining. The immunohistochemical results show that the expression of PCNA has been decreased. Parthenolide can inhibit the tumor growing of BEL-7402 cells, and induce the apoptosis of cells. The mechanisms of those functions may be via inhibiting the expression of PCNA.

Subchronic Toxicity of a Fluoroalkylethanol Mixture in Rats

The objective of this study was to evaluate the subchronic toxicity of a commercial fluoroalkylethanol mixture, which is an intermediate in the production of fluoroorganic compounds that are used as protectants and surfactants. The test substance was administered daily by gavage to Sprague–Dawley rats as a suspension in aqueous methylcellulose. The dosages were 0, 25, 100, or 250 mg kg− 1 day− 1. A 1- and 3-month recovery period was included to evaluate the reversibility of toxic effects. No test substance–related mortality or neurotoxicity occurred. Body weights and/or nutritional parameters were significantly reduced at 100 and 250 mg kg− 1 day− 1, and these effects were reversible. Broken and absent teeth were observed in rats dosed with 250 mg kg− 1 day− 1, and microscopic tooth lesions (ameloblast degeneration/disorganization) occurred at 100 and 250 mg kg− 1 day− 1 and persisted with decreased severity throughout recovery. Decreased red cell mass parameters occurred at 90 days in the 250 mg kg− 1 day− 1 group, but red cell counts were normal thereafter during recovery. A persistent elevation of liver weights was seen in groups given ≥ 100 mg kg− 1 day− 1. The increased weights correlated with microscopic hepatocellular hypertrophy only in males and females administered 250 mg kg− 1 day− 1. Hepatic β-oxidation was increased in a dose-dependent manner and persisted through 1 month of recovery at 250 mg kg− 1 day− 1. Increased kidney weights were observed at 25 (females only), 100, and 250 mg kg− 1 day− 1. These elevated weights persisted in the high dose after recovery and correlated with microscopic tubular hypertrophy (males only). Thyroid follicular hypertrophy was present at 100 and 250 mg kg− 1 day− 1 but was not present after recovery. Total fluorine in whole blood increased with continuous dosing and achieved steady state in approximately 42 days. Both plasma and urine fluoride levels were elevated in adose-dependent manner. Under the conditions of the study, the no-observed adverse effect level for this mixture was 25 mg kg− 1 day− 1 for subchronic toxicity.

Cytokinin-binding protein from Arabidopsis thaliana leaves participating in transcription regulation

The 67 kDa cytokinin-binding protein (CBP) has been isolated from old rosette leaves of 9-week-oldArabidopsis thaliana plants. The procedure of CBP isolation included the protein puri?cation by SephadexG-50, hydrophobic chromatography on phenyl-Sepharose and a?nity chromatography on zeatin riboside-Sepharose. Nuclear localization in leaves of 67 kDa CBP was demonstrated. The recognition of a naturalcytokinin trans-zeatin by 67 kDa CBP from Arabidopsis leaves was detected by a very speci?c and sensitiveassay based on trans-zeatin competition in ELISA with anti-idiotype antibodies (Aba-i) for complex formationwith CBP. Aba-i were raised against antibodies against zeatin. trans-Zeatin competed with Aba-i in adose-dependent manner, demonstrating a high a?nity for the protein. In combination with trans-zeatin,67 kDa protein activated RNA synthesis in vitro in the transcription elongation systems containingchromatin-bound RNA polymerase I from barley leaves (heterologous system) or from Arabidopsis leaves(homologous system). These data permit a suggestion that the 67 kDa CBPs from monocots and dicotsful?ll similar functions. A comparison of functional activity of 67 kDa CBP from young, growing rosetteleaves of 3-week-old Arabidopsis plants, from mature leaves of 7-week-old plants and from senescent leavesof 9-week-old plants demonstrated age-dependent changes of the protein properties. The data are discussedin context of recent advances in the study of transcription regulation in eukaryotic cells.

Involvement of P2 purinoceptors in the regulation ofdna synthesis in the neural retina of chick embryo

The activation of P2 purinoceptors induces Ca2 mobilization in the earlyembryonic chick neural retina. This purinergic Ca2 response declines parallel with thedecrease in mitotic activity during retinal development. To investigate the role of P2purinoceptors in the regulation of retinal cell proliferation, we studied the effects of the P2purinoceptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2fn2fn2triphosphate ; [Ca2]i, intracellular Ca2 concentration ;DMSO, dimethyl sulfoxide ; E, embryonic day ; EC50, concentration for half maximalexcitation ; F340, fluorescence excited at 340 nm ; F380, fluorescenceexcited at 380 nm ; F340/F380, the ratio of F340/F380 ;FCS, fetal calf serum ; fura-2 AM, fura-2 acetoxymethyl ester ; IC50, concentrationfor half maximal inhibition ; PPADS, pyridoxalphosphate-6-azophenyl-2,4-disulphonic acid ;UTP, uridine 5-triphosphate.,4-disulphonic acid (PPADS), and of the agonist ATP on DNA synthesis in retinal organcultures from embryonic day 3 (E3) chick. Suramin inhibited [3H]-thymidineincorporation in a dose-dependent manner (IC50 : ∼70 μM). PPADS alsoreduced [3H]-thymidine incorporation with maximum inhibition of 46% at 100 μM. Exogenous ATP enhanced [3H]-thymidine incorporation in adose-dependent manner to maximally 200% of control (EC50 : ∼70 μM). Indissociated retinal cultures from E7 chick, both antagonists showed similar inhibitory effects on [3H]-thymidine incorporation without affecting cell viability. In line with theseobservations, the presence of extracellular ATP was demonstrated both in vitro and in vivo. In the medium of E3 retinal organ cultures, the concentration of ATP increased25-fold within 1 h of incubation and this concentration was kept for at least 24 h. In the chickamniotic fluid, the ATP concentration was nearly 3 μM at E3 and declined to 0.15 μM at E7. The results indicate that P2 purinoceptors activated by autocrine or paracrinerelease of ATP are involved in the regulation of DNA synthesis in the neural retina at earlyembryonic stages.

Abscisic acid induces oscillations in guard-cell cytosolic free calcium that involve phosphoinositide-specific phospholipase C.

Oscillations in cytosolic free Ca2+ concentration ([Ca2+]cyt) are an important component of Ca2+-based signal transduction pathways. This fact has led us to investigate whether oscillations in [Ca2+]cyt are involved in the response of stomatal guard cells to the plant hormone abscisic acid (ABA). We show that ABA induces oscillations in guard-cell [Ca2+]cyt. The pattern of the oscillations depended on the ABA concentration and correlated with the final stomatal aperture. We examined the mechanism by which ABA generates oscillations in guard-cell [Ca2+]cyt by using 1-(6-[17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl]aminohexyl)-1H-pyrrole-2,5-dione (U-73122), an inhibitor of phosphoinositide-specific phospholipase C (PI-PLC)-dependent processes in animals. U-73122 inhibited the hydrolysis of phosphatidylinositol 4,5-bisphosphate by a recombinant PI-PLC, isolated from a guard-cell-enriched cDNA library, in a dose-dependent manner. This result confirms that U-73122 is an inhibitor of plant PI-PLC activity. U-73122 inhibited both ABA-induced oscillations in [Ca2+]cyt and stomatal closure. In contrast, U-73122 did not inhibit external Ca2+-induced oscillations in guard-cell [Ca2+]cyt and stomatal closure. Furthermore, there was no effect of the inactive analogue 1-(6-[17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl]aminohexyl)-2,5-pyrrolidinedione on recombinant PI-PLC activity or ABA-induced and external Ca2+-induced oscillations in [Ca2+]cyt and stomatal closure. This lack of effect suggests that the effects of U-73122 in guard cells are the result of inhibition of PI-PLC and not a consequence of nonspecific effects. Taken together, our data suggest a role for PI-PLC in the generation of ABA-induced oscillations in [Ca2+]cyt and point toward the involvement of oscillations in [Ca2+]cyt in the maintenance of stomatal aperture by ABA.

Scavenger receptor class B, type I (SR-BI) is the major route for the delivery of high density lipoprotein cholesterol to the steroidogenic pathway in cultured mouse adrenocortical cells.

The class B, type I scavenger receptor, SR-BI, binds high density lipoprotein (HDL) and mediates the selective uptake of HDL cholesteryl ester (CE) by cultured transfected cells. The high levels of SR-BI expression in steroidogenic cells in vivo and its regulation by tropic hormones provides support for the hypothesis that SR-BI is a physiologically relevant HDL receptor that supplies substrate cholesterol for steroid hormone synthesis. This hypothesis was tested by determining the ability of antibody directed against murine (m) SR-BI to inhibit the selective uptake of HDL CE in Y1-BS1 adrenocortical cells. Anti-mSR-BI IgG inhibited HDL CE-selective uptake by 70% and cell association of HDL particles by 50% in a dose-dependent manner. The secretion of [3H]steroids derived from HDL containing [3H]CE was inhibited by 78% by anti-mSR-BI IgG. These results establish mSR-BI as the major route for the selective uptake of HDL CE and the delivery of HDL cholesterol to the steroidogenic pathway in cultured mouse adrenal cells.

Safety and tolerance of dideoxycytidine as a single agent: Results of early-phase studies in patients with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex

Phase I and II clinical studies have been conducted to test the safety and potential activity of the reverse transcriptase inhibitor, dideoxycytidine (ddC), in treating human immunodeficiency virus-1-infected patients. Although ddC appears to be active in combating viral infection, as judged by its ability to decrease human immunodeficiency virus-1 p24 antigen titers and increase the number of CD4 + lymphocytes, it is also capable of causing severe peripheral neuropathy in adose-dependent manner. The studies discussed here indicate that low-dose ddC treatment regimens substantially reduce the toxic side effects of this drug, and yet retain the ability to affect p24 antigen and CD4 + lymphocyte levels. These studies also define the window of therapeutic usefulness for ddC, and suggest that both safety and activity can be maintained during long-term, low-dose use of ddC.