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PubMed2002

Role of ceramide in TNF-alpha-induced impairment of endothelium-dependent vasorelaxation in coronary arteries.

The present study tested the hypothesis that ceramide, a sphingomylinase metabolite, serves as an second messenger for tumor necrosis factor-alpha (TNF-alpha) to stimulate superoxide production, thereby decreasing endothelium-dependent vasorelaxation in coronary arteries. In isolated bovine small coronary arteries, TNF-alpha (1 ng/ml) markedly attenuated vasodilator responses to bradykinin and A-23187. In the presence of N(G)-nitro-L-arginine methyl ester, TNF-alpha produced no further inhibition on the vasorelaxation induced by these vasodilators. With the use of 4,5-diaminofluorescein diacetate fluorescence imaging analysis, bradykinin was found to increase nitric oxide (NO) concentrations in the endothelium of isolated bovine small coronary arteries, which was inhibited by TNF-alpha. Pretreatment of the arteries with desipramine (10 microM), an inhibitor of acidic sphingomyelinase, tiron (1 mM), a superoxide scavenger, and polyethylene glycol-superoxide dismutase (100 U/ml) largely restored the inhibitory effect of TNF-alpha on bradykinin- and A-23187-induced vasorelaxation. In addition, TNF-alpha activated acidic sphingomyelinase and increased ceramide levels in coronary endothelial cells. We conclude that TNF-alpha inhibits NO-mediated endothelium-dependent vasorelaxation in small coronary arteries via sphingomyelinase activation and consequent superoxide production in endothelial cells.

Animals↗
PubMed2002

Production of superoxide through NADH oxidase in thick ascending limb of Henle's loop in rat kidney.

We recently reported that NADH oxidase is one of the major enzymes responsible for superoxide (O(2)(-)*) production in the rat kidney. However, the functional significance of NADH oxidase-mediated O. production and the mechanisms regulating this enzyme activity are poorly understood. Using fluorescence microscopic imaging analysis, the present study demonstrated that thick ascending limbs of Henle's loop (TALHs) exhibited red fluorescence when incubated with dihydroethidium (DHE), suggesting that O(2)(-)* is produced in this tubular segment. Compared with other nephron segments, TALHs from both renal cortex and medulla showed the highest fluorescence intensity. By incubating cortical TALHs (cTALHs) with the substrates of NADH oxidase, xanthine oxidase, nitric oxide synthase, arachidonic acid-metabolizing enzymes, and intramitochondrial oxidases, NADH oxidase was found to be one of the most important enzymes for O(2)(-)* production in this tubular segment. The NADH oxidase inhibitor diphenyleneiodonium (DPI; 100 microM) completely blocked NADH-induced O(2)(-)* production in cTALHs. Exposure of cTALHs to low PO(2) (5-10 Torr) significantly increased O(2)(-)* production regardless of the absence or presence of NADH. Furthermore, angiotensin II (100 nM) increased NADH oxidase activity by 32%, which was completely blocked by DPI. These results suggest that NADH oxidase is a major enzyme responsible for O(2)(-)* production in the TALHs and that the production of O(2)(-)* via NADH oxidase may be regulated by renal tissue oxygenation and circulating hormones.

Angiotensin II↗
PubMed2004

Modular organization of the silkmoth antennal lobe macroglomerular complex revealed by voltage-sensitive dye imaging.

We succeeded in clarifying the functional synaptic organization of the macroglomerular complex (MGC) of the male silkmoth Bombyx mori by optical recording with a voltage-sensitive dye. Sensory neurons in the antennae send their axons down either the medial nerve (MN) or lateral nerve (LN), depending on whether they are located on the medial or lateral flagella. Pheromone-sensitive fibers in the MN are biased towards the medial MGC, and those in the LN are biased towards the lateral MGC in the antennal lobe. In our optical recording experiments, the postsynaptic activities in the MGC were characterized by pharmacological analysis. Postsynaptic activities in the MGC were separated from sensory activities under Ca(2+)-free conditions, and subsequently the inhibitory postsynaptic activities were separated by applying bicuculline. We found that the inhibitory postsynaptic responses always preceded the postsynaptic responses separated under Ca(2+)-free conditions. Moreover, the excitatory postsynaptic activities were calculated by subtracting the inhibitory potentials from the posysynaptic activities separated under Ca(2+)-free conditions. When the MN was stimulated, the amplitudes of the excitatory postsynaptic activities in the central toroid, the medial toroid and the medial cumulus were selectively higher than those in the other areas. By contrast, when the LN was stimulated, excitatory postsynaptic activities were evoked in areas in both the lateral toroid and the lateral cumulus. The inhibitory postsynaptic activities were equally distributed throughout the whole MGC. These data suggest that there is a modular organization to the MGC such that information from the two main branches of the antenna is segregated to different sub-regions of the MGC glomeruli.

Afferent Pathways↗
PubMed2002

A new method for counting of quail leukocytes by flow cytometry.

An automatic counting method was developed for fish blood cells using a fluorescent dye, 3, 3-dihexyloxacarbocyanine (DiOC (6)(3)), that selectively stain lipid bilayers in living cells. In the present study, the DiOC(6)(3) method was applied to quail (Cotumix cotumix japonica) blood cells. After quail blood cells were stained with DiOC(6)(3), absolute counts and relative proportions of erythrocytes, granulocytes, monocytes, and lymphocytes plus thrombocytes in whole blood were obtained by means of flow cytometry (FC). The number of each cell types by the FC was in good agreement with those counted microscopically. This method will offer new possibilities for routine blood cell counting for avian medicine.

Animals↗
PubMed2004

Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs.

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti-SARS-CoV activity. A drug-screening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, b-1b, a-n1, a-n3, and human leukocyte interferon a. These findings support clinical testing of approved interferons for the treatment of SARS.

Antiviral Agents↗
PubMed2005

Cholecystokinin octapeptide improves cardiac function by activating cholecystokinin octapeptide receptor in endotoxic shock rats.

AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats. METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the left ventricular pressure (LVP) and the maximal/minimum rate of LVP (+/-LVdp/dt(max))) were measured by using physiological record instrument in eight groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Low doses of sCCK-8 (0.4 microg/kg) caused tachycardia (441+/-27, normal control 391+/-22 s/min) and slight increase in MAP, LVP and +/-LVdp/dt(max) (16.96+/-1.79, 18.21+/-1.69 and +768.85+/-31.28/-565.04+/-27.71 kPa, respectively, all P<0.01), while medium doses (4.0 microg/kg) and high doses of sCCK-8 (40 microg/kg) elicited bradycardia and marked increase in MAP, LVP and +/-LVdp/dt(max) (17.29+/-1.63, 19.46+/-2.57 and +831.46+/-22.57/-606.08 +/-31.32; 17.46+/-1.08, 19.83+/-2.91 and +914.52+/-35.95/-639.15+/-30.23 kPa, respectively, all P<0.01). Proglumide (1.0 mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly inhibited the pressor effects of sCCK-8 (15.96+/-1.38, 17.36+/-0.66 and +748.18+/-19.29/-512.12+/-14.39 kPa, respectively, all P<0.01), whilst reversing the bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease in MAP, LVP and +/-LVdp/dt(max). (7.16+/-0.59, 7.6+/-0.68 and +298.01+/-25.52/-166.96+/-19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40 microg/kg) could reverse the decline of cardiac functions (10.71+/-0.45, 11.7+/-1.26 and +446.04+/-67.18/-347.90+/-36.98 kPa, respectively, all P<0.01), while proglumide could cause further decline of cardiac function in ES rats (4.71+/-0.67, 5.58+/-1.25 and +226.48+/-15.84/-142.83+/-20.23 kPa, respectively, all P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats. The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did not change at the first 0.5 h and was stable at a high level at 12 h. CONCLUSION: The above results indicate that endogenous and exogenous sCCK-8 may significantly improve cardiac function and intractable hypotension of ES rats, which was likely related to high expression of CCK-A/BR in myocardium induced by LPS.

Animals↗
PubMed2002

[Adriamycin thermotherapy through hepatic artery for model of VX2 carcinoma in rabbit liver].

BACKGROUND & OBJECTIVE: It was reported that heating can enhance sensitivity of rabbit VX2 cell to adriamycin and increase intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effects of interventional hyperthermia and interventional chemotheramotherapy on VX2 carcinoma in rabbit liver. METHODS: VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups(15 rabbits per group). To inject physiological saline(37 degrees C), adriamycin (37 degrees C), physiological saline(60 degrees C), and adriamycin (60 degrees C) in different groups via hepatic artery of the rabbits with liver cancer. One week later, to observe the volume of tumor, the serum level of aspartate transaminase(AST), and observe the survival period of VX2 rabbits. RESULTS: In group of ADM(60 degrees C), the tumor growth rate (0.53 +/- 0.21)% was significantly lower than group 2(1.09 +/- 0.26)%, group 3(3.32 +/- 1.28)%, and group 4(3.48 +/- 1.17)% (P < 0.05, P < 0.05, P < 0.01, respectively). The survival period of adriamycin (60 degrees C) group (50.0 +/- 2.0)d was significantly higher than the untreated control group (40.5 +/- 3.0)d, (P < 0.05). The serum level of AST of TNP-470 with lipiodol group was not higher than the other treated groups(P > 0.05), but being significantly higher than the untreated control group after treated(P < 0.05). CONCLUSION: Adriamycin (60 degrees C) greatly decreases the tumour growth rate, and prolongs the survival period.

Animals↗
PubMed2003

[Interaction of Helicobacter polyri and indomethacin in gastric mucosa injury of Balb/c mice].

OBJECTIVE: To investigate the interaction of Helicobacter pylori (Hp) and indomethacin in gastric mucosa injury of Balb/c mice. METHODS: Fifty specific pathogen free 6-week-old Balb/c mice were randomly divided into 5 groups: group A (n = 8, 25 mg/kg indomethacin was injected intraperitoneally every other day for 6 times, and 0.2 ml Hp culture containing 1 x 10(8) - 1 x 10(9) CFU/ml was inoculated intra-gastrically every other day for 6 times), B (n = 8, 1 x 10(8) - 1 x 10(9) CFU/ml Hp culture was inoculated intra-gastrically on the 1st, 2nd, and 3rd days, and since the 7th day 25 mg/kg indomethacin was injected intraperitoneally every other day for 6 tomes), group C (n = 9, 0.2 ml normal saline was inoculated intra-gastrically on the 1st, 2nd, and 3rd days and since the 7th day 25 mg/kg indomethacin was injected intraperitoneally every other day for 6 times), group D (n = 10, 1 x 10(8) - 1 x 10(9) CFU/ml Hp culture was inoculated intra-gastrically on the 1st, 2nd, and 3rd days, and since the 7th day 0.2 ml normal saline was injected intraperitoneally every other day for 6 times), and group E (n = 10, 0.2 ml normal saline was inoculated intra-gastrically on the 1st, 2nd, and 3rd days, then 0.2 ml normal saline was injected intraperitoneally since the 7th day every other day for 6 times). The mice were killed in the 4th week. The stomachs were observed morphologically. Tissues from gastric antrum underwent HE staining, silver staining, and urease examination. Rauws classification was used to grade the gastritis thus discovered. RESULTS: Two mice in group A, one mouse in group B and 2 mice in group C died. One mouse in group B was Hp silver staining negative. Twenty-six of the total 30 mice infected with Hp showed inflammation with an infection rate of 66.7%. Moderate to severe inflammatory reaction was seen in all 8 mice in group A with an average gastritis score of 6.38 and with Hp found in the epithelium. Two out of the 8 mice in group showed focal erosion. All mice in group B showed moderate inflammation and Hp in mucosa with an average gastritis score of 5.13. Focal erosion was seen in one mouse in group B. Light moderate inflammation was seen in all 9 mice in group C with an average gastritis score of 3.89. Mild inflammation was seen in all 10 mice in group D with an average gastritis score of 2.8. No erosion was found in groups C and D. No inflammation was seen in the mice in group E with an average gastritis score of 0.4. The differences between any 2 groups were all significant. CONCLUSION: Hp and indomethacin synergetically aggravate the gastric epithelial injury. Prior Hp infection may be a protective factor of indomethacin-induced gastritis to a certain degree.

Animals↗
PubMed2003

Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy.

We present a case report of a 10 years old boy with protein-losing enteropathy and eosinophilic gastroenteritis who had positive histamine release tests, increased allergen-specific IgE antibodies to some food items, and low levels of total serum protein and albumin. Upper gastrointestinal endoscopy revealed a number of polyps and diffuse gastritis. Biopsy specimens of the stomach and duodenum showed widespread eosinophilia and neutrophilia. Although a restricted diet was recommended, a diet which excluded foods with positive results to both histamine release test and allergen-specific IgE antibodies was poorly tolerated, and the patient rejected systemic administration of corticosteroids. Thus, we initiated an oral disodium cromoglycate (DSCG) and ketotifen therapy. After oral DSCG and ketotifen administration, the patient's condition improved gradually. Therefore, oral DSCG and ketotifen therapy might be considered as treatment option in patients with eosinophilic gastroenteritis and protein-losing enteropathy caused by food allergy.

Administration, Oral↗
PubMed2004

[Treatment of childhood leukemia with unrelated donor allogeneic bone marrow transplantation].

OBJECTIVE: Allogeneic bone marrow transplantation has been established as a standard method for the treatment of a range of malignant and non-malignant hematologic diseases in children. Unfortunately, fewer than 30% of patients have a human leukocyte antigen (HLA)-matched sibling. Advances in our understanding of the HLA system and the development of large international donor registries encourage the increasing use of unrelated donors as an alternative source of stem cells. The purpose of this study was to evaluate the clinical efficacy and safety of unrelated donor allogeneic bone marrow transplantation (URD-BMT) for the treatment of childhood leukemia. METHODS: Six patients with leukemia received URD-BMT. Two of them suffered from chronic myeloid leukemia (CML), 3 suffered from acute lymphocytic leukemia (ALL) and 1 suffered from acute promyelocytic leukemia (APL) (CR2). All cases were facilitated by Tzu Chi Marrow Donor Registry (TCTMDR). The high resolution DNA test for classIand II was carried out in HLA typing of all donor-receiver pairs. HLA allele matched in three cases, mismatched with one locus in two cases and with two loci in one case. All patients were prepared with cyclophosphamide (CY) 60 mg/kg/day for 2 days (total dose 120 mg/kg) and busulfan (Bu) 1 mg/kg x 4/day for 4 days (total dose 16 mg/kg). Mycophenolate mofetil (MMF), CsA and MTX were given to prevent acute graft-versus-host-disease (aGVHD). CsA of 3 mg/kg/d was continuously given by i.v. infusion, and then 6mg/kg/d by oral. The blood CsA concentration was 200 - 300 ng/ml. MTX was given at the dosage of 15 mg/m(2) on d 1 and 10 mg/m(2) on d 3, 6,9 or 11. MMF was given at the dosage of 0.25 - 0.5 g/d from day 0 to day 120. Prostaglandin E1 was given to prevent the hepatic veno-occlusive disease (VOD), Ganciclovir was used to prevent CMV infection until the CMV antigenemia became negative. RESULTS: Analysis of DNA short tandem repeats showed total engraftment of donor marrow after transplantation in all cases. The median time when granulocyte exceeded 0.5 x 10(9)/L was 14.5 (13 - 18) days, platelets exceeded 20 x 10(9)/L was 16 (14 - 23) days. The acute GVHD grade II-IV occurred in 2 of 6 (33.3%) patients. There were 3 cases with chronic GVHD and none of them developed with the extensive chronic GVHD. All patients were alive in disease-free situation now with median follow-up 412 (187 - 1338) days. CONCLUSION: URD-BMT is an effective method for the treatment of childhood leukemia.

Bone Marrow Transplantation↗
PubMed2004

Adsorption mechanism of phenolic compounds from aqueous solution on hypercrosslinked polymeric adsorbent.

The adsorption of two phenols, namely, phenol and salicylic acid(SA) onto a water-compatible hypercrosslinked polymeric resin (NJ-8) were studied in terms of pseudo-second-order and first order mechanisms for chemical sorption as well as an intraparticle diffusion mechanism process. Kinetic analysis showed that the intraparticle diffusion process was the essential rate-controlling step. The activation energies of sorption have also been evaluated with the pseudo-second-order and intraparticle diffusion constants, respectively. Adsorption equilibrium data were well fitted by the Langmuir, Freundlich and Redlich-Peterson isotherms. Adsorption was exothermic and basically of a type of transition between physical and chemical character. The sorption capacity was higher for SA due to its more hydrophobic. Phenol has a higher adsorption enthalpy since it could form stronger hydrogen bonding on NJ-8.

Adsorption↗
PubMed2006

[Pharmacodynamic study of Relinqing granules on bacterial pyelonephritis model in rats].

OBJECTIVE: To observe the effects of Relinqing granules (powder of Polygonum capitatum extract) on the bacterial pyelonephritis model in rats. METHOD: The rat bacterial pyelonephritis model was induced by injecting the escherichia coli ATCC-25922 into kidney parenchyma. The rats were divided ramdamly into Relinqing groups(52.32, 26.16 g x kg(-1)), norflorin group (0.03 g x kg(-1)), model group and normal control group, and were given experimental drugs by gastrogavage. The contents of leucocytes (WBC), occult bloo (BLD), glucose (GLU), protein (PRO), ketones, bilirubin and urobilinagen in urine were determined. RESULT: As compared with the model group, Relinqing granules 6.0 g x kg(-1) (crude drug 52.32 g x kg(-1)) could decrease significantly the contents of WBC and BLD in urine and, however, had no markedly effects on the other biochemical parameters of urine. CONCLUSION: Relinqqing granule has significant effects of decreasing urine WBC and BLD on the bacterial pyolonephritis in rats.

Animals↗
PubMed2006

[Dynamics of T lymphocyte subsets in HAART treated AIDS patients with successful suppression of HIV replication and different CD4 + T cell restoration].

OBJECTIVE: To study the dynamic changes of T lymphocyte subsets of AIDS patients during more than 24 months of highly active antiretrovirus therapy (HAART) with successful suppression of HIV replication and different CD4 + T cell restoration. METHODS: Totally 45 AIDS patients who had received HAART for more than 24 months were included. During HAART (including DO, M3, M6, M12, M18, and M24), the number of plasma HIV-1 RNA was measured quantitatively using the bDNA assay, and T lymphocyte subsets including CD3 + CD4 + cells, CD3 + CD8 + cells, naive CD4 + cells (CD4 + CD45RA + CD62L +), CD4 + CD28 + cells , and CD8 + CD38 + cells were detected with flow cytometer. RESULTS: Among 45 patients, 24 patients (53.3%) whose plasma viral load decreased to less than 500 copies/ml at M6 and maintained to M24 were classified into three groups according to the CD4 + T cell count increments on M24 (compared with DO): group A (< 100/mm3), group B (100-200/mm3), and group C (> 200/mm3). After the initiation of HAART, T lymphocyte response, including CD4 + T cell counts, naive CD4 + cell counts, percentages of CD4 + CD28 + cells in these patients were improved gradually, while CD8 + CD38 + percentage decreased. The improvement of T lymphocyte response in group C was most remarkable even with highest plasma viral load and lowest CD4 T cell count on DO. Compared with group A and B, group C had significantly better improvement not only in the quantities of CD4 + T cell, but also in the CD28 + expression and naive CD4 + T cell populations. CONCLUSIONS: T lymphocyte response of AIDS patients can be effectively reconstituted by HAART. Different dynamics of CD4 + CD28 + and naive CD4 + populations may considerably contribute to the quantity and cellular function restoration of CD4 + T lymphocyte.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Development of alginate-based slow release formulation of Bacillus sphaericus for controlling Culex quinquefasciatus.

Seven types of formulations were prepared as granules using the larvicidal factor of Bacillus sphaericus and different concentrations of calcium alginate which was used as matrix to immobilize and entrap the active ingredient (ai). All formulations were tested in disused wells against Culex quinquefasciatus at the rate of 15 kg ai per hectare. Among the seven types tested, the type 2 which contained 5% calcium alginate as immobilizing agent, exhibited the maximum larvicidal activity. Persistent control in breeding was noticed for 8 weeks with this formulation type.

Alginates↗
PubMed1998

Interaction of chicken anaemia virus and Cryptosporidium baileyi in experimentally infected chickens.

The natural occurrence of concomitant chicken anaemia virus (CAV) and Cryptosporidium baileyi infection was described earlier. In this experiment, 1-day-old chickens were infected with CAV alone (anaemia virus infected, AI) or followed by inoculation with 8 x 10(5) C. baileyi oocysts orally at 1 wk of age (anaemia virus and Cryptosporidium infected, ACI). Another group of chickens received the same dose of C. baileyi oocysts without previous virus infection (Cryptosporidium infected, CI), and two groups of uninfected chickens served as controls. Except one group (uninfected control, UC), all groups -- including the other control group (challenged control, CC) -- were challenged with an oral inoculum of 8 x 10(5) C. baileyi oocysts at the age of 4 wk. Haematological, serological, immunohistochemical and pathological findings confirmed the effect of the virus agent. The individual C. baileyi oocyst shedding did not show significant difference between group CI and ACI, however, after challenge infection the AI chickens shed approximately three times more C. baileyi oocysts than those in group CC. Mortality and the percentage of birds that developed anaemia was significantly higher among ACI than AI chickens, while haematocrit values at 2 wk of age and relative bursal weights at 4 wk of age were moderately lower in the ACI group. The results presented here suggest that concurrent CAV infection increases the reproductive potential of C. baileyi in chickens, and both pathogens have synergistic effect on each other.

Animals↗
PubMed1997

The potential transmission of infectious agents by semen packaging during storage for artificial insemination.

Plastic straws, of a type widely used for semen cryopreservation, sealed using three different methods, (PVA powder, plastic spheres and plasticine modelling clay) were tested for leakage of low molecular weight dye (methylene blue), bacteria (Escherichia coli) and virus (Newcastle disease virus). Leakage was found to be dependent on the method used to fill the straws. Straws filled using a traditional 'dip and wipe' method and sealed with PVA powder demonstrated a significant degree of methylene blue leakage (0.0269% of the total straw contents) probably associated with contamination of the powder sealing plug. Straws filled using an aseptic filling technique showed no detectable leakage of any agent with any of the sealing methods. This study highlights the need to establish good-practice guidelines for the packaging of semen collected for freezing and future AI from non-domestic livestock where disease-free status cannot be guaranteed and unsophisticated technology is used.

Animals↗
PubMed1987

Changes in lipoprotein kinetics during therapy with fenofibrate and other fibric acid derivatives.

The fibric acid derivatives, including fenofibrate, significantly reduce very low-density lipoprotein triglyceride concentrations by stimulating lipoprotein lipase activity, thereby increasing very low-density lipoprotein catabolism. These agents may also reduce the hepatic secretion of nascent very low-density lipoprotein, but this effect is less consistent. Effects on low-density lipoprotein metabolism appear to depend upon the lipid disorder present before therapy. If hypertriglyceridemia and normal or low low-density lipoprotein levels are present, fibrate therapy is associated with a rise in low-density lipoprotein levels. This is due to a decreased fractional catabolism of low-density lipoprotein from an unusually high clearance to a more normal value. Treating pre-existing hypercholesterolemia usually results in a significant decrease in low-density lipoprotein levels. In this disorder, there is a demonstrable increase in low-density lipoprotein receptor-mediated clearance. It is not known at which site these drugs act to increase low-density lipoprotein receptor function in the latter patients. Some studies suggest that fibrate therapy increases high-density lipoprotein apolipoprotein AI production, but how this occurs has not been defined.

Anticholesteremic Agents↗