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PubMed2006

Coexistence of megaloblastic anemia and iron deficiency anemia in a young woman with chronic lymphocytic thyroiditis.

Pernicious anemia is a megaloblastic anemia caused by vitamin B12 deficiency, and is the end-stage of autoimmune gastritis that typically affects persons older than 60 years. It is the most common cause of vitamin B12 deficiency. Pernicious anemia can also be diagnosed concurrently with other autoimmune diseases. We report the occurrence of megaloblastic anemia in a 22-year-old woman with chronic autoimmune thyroiditis for 10.5 years. Recently, she presented with microcytic anemia, and iron deficiency anemia was diagnosed initially. After administration of ferrous sulfate, macrocytic anemia was revealed and vitamin B12 deficiency was detected. Pernicious anemia was highly suspected because of the endoscopic finding of atrophic gastritis, and high titer of antigastric parietal cell antibody, as well as elevated serum gastrin level. After intramuscular injections of hydroxycobalamine 100 microg daily for 10 days, and monthly later, her blood counts returned to normal.

Adult↗

PubMed1997

Small molecule inhibition of tumor necrosis factor gene processing during acute pancreatitis prevents cytokine cascade progression and attenuates pancreatitis severity.

The morbidity and mortality associated with acute pancreatitis are primarily a result of pancreatic parenchymal necrosis and the development of marked pulmonary dysfunction. Recent evidence suggests that both of these conditions are propagated by interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha, which are produced in large quantities within these organs. Because the generation of these cytokines occurs in a predictable manner early in the development of acute pancreatitis, we aimed to determine whether cytokine gene processing could be inhibited in vivo and what effects this would have on pancreatitis severity. Mild [caerulein, 50 micrograms/kg/hour intraperitoneally (IP) x 4; n = 40] or severe (choline-deficient diet; n = 40) necrotizing pancreatitis was induced in NIH swiss mice. Animals were randomly given a novel small molecule (CNI-1493; 10 mg/kg IP) known to inhibit macrophage production of TNF and IL-1 in vitro by inhibiting translation of TNF mRNA into protein. Control animals received IP vehicle. All animals with acute pancreatitis showed dramatic up-regulation of the IL-1 beta and TNF-alpha genes. Those animals receiving CNI-1493 demonstrated attenuated production of both species of mRNA in pancreatic as well as pulmonary tissue (P < 0.01). Markers of pancreatitis severity such as serum amylase and lipase, as well as pancreatic necrosis, were decreased in animals treated with CNI-1493 (all P < 0.05). Posttranscriptional blockade of TNF production precludes induction of the proinflammatory cytokine cascade that normally occurs during acute pancreatitis. This lack of cytokine gene processing in the pancreas and lungs results in dramatic reductions in tissue damage and pancreatitis severity, which is not model dependent. This is the first time that a small molecule has been shown to influence this disease.

Amylases↗

PubMed1999

Erythropoietin hyporesponsiveness: from iron deficiency to iron overload.

Iron deficiency is the most frequently encountered cause of suboptimal response to recombinant human erythropoietin (rHuEPO). Carefully assessing iron status is of paramount importance in chronic renal failure patients prior to or during rHuEPO therapy. Because there is great need for iron in the EPO-stimulated erythroid progenitors, it is essential that serum ferritin and transferrin saturation levels should be maintained over 300 microg/liter and 30%, respectively. Investigators have shown that oral iron is unlikely to keep pace with the iron demand for an optimal rHuEPO response in uremics. Therefore, patients with iron deficiency will always require intravenous iron therapy. The early and prompt iron supplementation can lead to reductions in rHuEPO dose and hence cost. After the iron deficiency has been corrected or excluded, we must remember all of the possible causes of hyporesponsiveness in every rHuEPO-treated patient. As dose requirements vary, it is not clear which dose of rHuEPO causes this hyporesponsiveness. However, if the patient with iron repletion does not respond well after the induction period, the major causes blunting the response to rHuEPO should be investigated. Most factors are reversible and remediable, except resistant anemia associated with hemoglobinopathy or bone marrow fibrosis, which requires a further increase in the rHuEPO dose. By means of early detection and correction of the possible causes, the goal of increasing therapeutic efficacy can be achieved. Iron overload may lead to an enhanced risk for infection, cardiovascular complication, and cancer. Over-treatment with iron should be avoided in dialysis patients, despite the fact that the safe upper limit of serum ferritin to avoid iron overload is not clearly defined. On the other hand, functional iron deficiency may develop even when serum ferritin levels are increased. Controversy remains as to whether intravenous iron therapy can overcome this form of hyporesponsiveness in iron-overloaded patients. Moreover, a treatment option of iron supplementation is not warranted in these patients, as the potential hazards of iron overload will be worsened. We demonstrated that the mean hematocrit significantly increased from 25.1+/-0.9% to 31+/-1.2% after eight weeks of intravenous ascorbate therapy (300 mg three times a week) in 12 hemodialysis patients with serum ferritin levels of more than 500 microg/liter. The enhanced erythropoiesis paralleled with a rise in transferrin saturation (27.8+/-2.5% vs. 44.8+/-9.5%, P < 0.05) and reductions in erythrocyte zinc protoporphyrin (130+/-32 vs. 72+/-19 micromol/mol heme, P < 0.05) and monthly rHuEPO dose (24.2+/-4.5 vs. 16.8+/-3.4 x 10(3) units, P < 0.05) at the end of study. It is speculated that ascorbate supplementation not only facilitates the iron release from storage sites and its delivery to hematopoietic tissues, but also increases iron utilization in erythroid cells. Our study provides a more complete understanding of the pathogenesis of iron overload-related anemia and the development of an adjuvant therapy, intravenous ascorbic acid, to the existing treatments.

Aluminum↗

PubMed1988

Disruption of sustentacular (Sertoli) cell tight junctions and regression of spermatogenesis in vitamin-A-deficient rats.

The relationship between the intactness of sustentacular (Sertoli) cell tight junctions and the status of spermatogenesis was examined in rats fed a vitamin-A-deficient diet after weaning (VAD rats). Both serum and testicular retinol concentrations of the VAD rats declined to a nadir by 80 days of age. At this time, it was observed that Sertoli cell tight junctions of the VAD animals were intact and complete spermatogenesis was maintained. Leakage in Sertoli cell tight junctions, as demonstrated by the presence of lanthanum in the adluminal compartment of the seminiferous epithelium, was first observed in 90-day-old VAD rats. Severe regression of spermatogenic cells was noted in 100-day or older VAD animals. These results suggest that severe germ cell loss observed during chronic vitamin A deficiency may result from abnormal intratubular environment due to the disruption of the blood-testis barrier.

Animals↗

PubMed2006

Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset citrullinemia complicated with steatosis and hepatocellular carcinoma.

Citrullinemia is a metabolic disorder characterized by elevated plasma concentrations of citrulline and ammonia. Adult-onset citrullinemia (type II, CTLN2) has been attributed to citrin deficiency caused by mutations in the SLC25A13 gene. CTLN2 is associated with a high incidence of hepatocellular carcinoma (HCC) in Japanese. We report a 48-year-old Taiwanese man with citrullinemia, who was in good health until the age of 34 when he had repeated episodes of consciousness disturbance. Hyperammonia (201 micromol/L) was found during an episode of coma. Liver function and electrolyte levels were normal at that time. Serologic markers of viral hepatitis B and C were negative. Analysis of genomic DNA extracted from peripheral blood leukocytes showed homozygous 851del4 mutation in exon 9 of the SLC25A13 gene on chromosome 7q21.3. Fourteen years after disease onset, at the age of 48, he was admitted due to an episode of coma. Abdominal sonography and computed tomography showed a 2.5 cm tumor in the left lobe of the liver, without evidence of liver cirrhosis. Wedge resection of the tumor was performed and grade 2 HCC was diagnosed. The nontumor part of the resected specimen showed chronic persistent hepatitis with moderate steatosis. The results in this case support that both citrin deficiency and steatohepatitis may contribute to hepatocarcinogenesis.

Biopsy, Fine-Needle↗

PubMed2003

Microsatellite instability in esophageal squamous cell carcinoma is not associated with hMLH1 promoter hypermethylation.

To test whether a subset of esophageal squamous cell carcinomas (SCC) develop through a deficiency in DNA mismatch repair, we examined microsatellite instability (MSI) using 11 microsatellite markers including BAT-26, hMLH1 protein expression by immunohistochemistry, and methylation status of the hMLH1 promoter by methylation-specific polymerase chain reaction (MSP). p53 mutations were also investigated. Microsatellite instability at one or more loci was observed in 40% (12/30) of esophageal SCC tumor samples, although only one of these tumors was categorized as high-frequency MSI (MSI-H) and none showed BAT-26 instability. While immunohistochemistry revealed decreased hMLH1 protein expression in 27% (8/30) of the tumors, hMLH1 promoter hypermethylation was not observed. Absence of hMLH1 protein expression was relatively common in well-differentiated (keratinizing-type) esophageal SCC, but was not associated with hMLH1 promoter hypermethylation. p53 mutation was detected in 37% (11/30) and loss of heterozygosity (LOH) in 90% (27/30) of esophageal SCC samples. Our results suggested that most esophageal SCC develop through defects in tumor suppressor genes (i.e. the suppressor pathway), and that MSI in esophageal SCC probably represent random replication errors rather than being associated with DNA mismatch repair deficiency.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Differential expression of inducible nitric oxide synthase and IL-12 between peritoneal and splenic macrophages stimulated with LPS plus IFN-gamma is associated with the activation of extracellular signal-related kinase.

Resident peritoneal macrophages (pMphi) are found deficient in T cell-stimulating capacity compared with the competent splenic macrophages (sMphi). Macrophages (Mphi)-derived nitric oxide (NO) and IL-12 have been shown to play crucial roles in the interaction between Mphi and T cells. To further understand differential functions between pMphi and sMphi, we focused on the production of NO and IL-12 from LPS plus IFN-gamma-activated Mphi. We demonstrated the differential expression of inducible nitric oxide synthase (iNOS) and IL-12 in pMphi and sMphi with LPS plus IFN-gamma stimulation. pMphi produced high level of NO but low level of IL-12, whereas sMphi produced high level of IL-12 but no NO. Furthermore, we demonstrated that there were no differences in IFN-gamma-induced signal transducer and activator of transcription-1 activation and consequent interferon regulatory factor-1 and interferon consensus sequence-binding protein up-regulation between pMphi and sMphi. Likewise, p38 mitogen-activated protein kinase was activated by LPS with identical kinetics in both pMphi and sMphi. However, LPS-induced extracellular signal-regulated kinase (ERK) activation was prolonged in pMphi comparing with sMphi. Moreover, we demonstrated, using inhibitor selective for ERK cascade (PD98059), that the prolonged ERK activation contributed a positive signal for iNOS expression and a negative signal for IL-12p40 expression in resident pMphi. In addition, anti-IL-10-neutralizing antibody plus indomethacin could abrogate the inhibitory effects of endogenous IL-10 and prostaglandin E2 on the production of IL-12 by resident pMphi possibly through suppressing ERK activation. Taken together, profound difference in ERK activation may account for differential LPS plus IFN-gamma responsiveness between pMphi and sMphi. High production of NO and low production of IL-12 by pMphi may contribute to its deficiency in T cell-stimulating capacity.

Animals↗

PubMed1987

Alteration of pancreatic enzyme activities in small intestine of rats fed a high fructose, low copper diet.

This study describes the progressive effects on pancreatic enzyme activities from washings of the small intestine of rats fed diets containing either 62% starch (S) or fructose (F), with 0.6 mg copper/kg diet (-Cu) or 6.0 mg copper/kg diet (+Cu) from 21 to 61 d of age. Hepatic copper concentration of the copper-deficient groups was 50% of that of the copper-supplemented groups. Body and relative pancreatic weights were lower in the F-Cu dietary group than in any other group. Relative liver weight was significantly higher in the fructose dietary groups than in the starch dietary groups. There were significant carbohydrate (CHO) X week and Cu X week interactions for luminal amylase activities and the CHO X Cu X week interaction was significant for luminal lipase and trypsin activities. The lowest enzyme activities were observed in the F-Cu-fed rats. The CHO X week interaction was significant for chymotrypsin with the lowest enzyme activities in the fructose-fed rats. It appears that high dietary fructose and low dietary copper interact to produce greatly reduced pancreatic enzyme activities in small intestinal washings. We speculate that subsequent digestive and absorptive abnormalities during a period of rapid growth may account for the severe morbidity and mortality in copper-deficient, fructose-fed rats.

Amylases↗

PubMed1998

A murine skeletal muscle ischemia-reperfusion injury model: differential pathology in BALB/c and DBA/2N mice.

Ischemia-reperfusion injuries can occur with diseases such as myocardial infarction and stroke and during surgical procedures such as organ transplantation and correction of aortic aneurysms. We developed a murine model to mimic abdominal aortic aneurysm repair with cross-clamping of the aorta distal to the renal artery. After model development, we compared the normal complement BALB/c mouse with the C5-deficient DBA/2N mouse. To assess quantitative differences, we measured neuromuscular function up to 72 h after ischemia with a subjective clinical scoring system, as well as plasma chemistries, hematology, and histopathology. There were significant increases in clinical scores and creatine phosphokinase, lactate dehydrogenase, and muscle histopathology scores in BALB/c mice compared with those in DBA/2N mice and sham-surgery mice. Muscle histopathology scores of the cranial tibialis and quadriceps correlated well with clinical signs, creatine phosphokinase, and lactate dehydrogenase, and indicated the greatest pathology in these muscle groups. We developed a murine model of skeletal muscle ischemia-reperfusion injury that can utilize the benefits of murine genetic and transgenic models to assess therapeutic principles of this model. Additionally, we have shown a significant reduction in clinical signs, plasma muscle enzyme concentrations, and muscle pathology in the C5-deficient DBA/2N mouse in this model.

Animals↗

PubMed1998

Recombinant human acid alpha-glucosidase corrects acid alpha-glucosidase-deficient human fibroblasts, quail fibroblasts, and quail myoblasts.

Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists. We investigated the endocytic process in deficient cells of human recombinant GAA produced in Chinese hamster ovary cells, and the potential of GAA-deficient Japanese acid maltase-deficient quail as a model for evaluating the enzyme replacement therapy for Pompe disease. After 24-h incubation with a single dose of recombinant enzyme, intracellular GAA and glycogen levels in deficient human fibroblasts were normalized, and this correction lasted for 7 d. The 110-kD precursor recombinant enzyme was processed to the 76-kD mature form within 24 h after uptake. Intracellular GAA levels in deficient quail fibroblasts and myoblasts were similarly corrected to their average normal levels within 24 h. Differences existed in the efficiency of endocytosis among subfractions of the enzyme, and among different cell types. Fractions with a larger proportion of precursor GAA were endocytosed more efficiently. Quail fibroblasts required a higher dose, 4200 nmol.h-1.mL-1 to normalize intracellular GAA levels than human fibroblasts, 1290 nmol.h-1.mL-1, whereas primary quail myoblasts required 2800 nmol.h-1.mL-1. In all three cell lines, the endocytosed enzyme localized to the lysosomes on immunofluorescence staining, and the endocytosis was inhibited by mannose 6-phosphate (Man-6-P) added to the culture medium. Despite structural differences in Man-6-P receptors between birds and mammals, these studies illustrate that Man-6-P receptor mediated endocytosis is present in quail muscle cells, and demonstrate the potential of acid maltase-deficient quail to test receptor mediated enzyme replacement therapy for Pompe disease.

Animals↗

PubMed1999

Alteration of IGF system gene expression during the postnatal development of pcd mice.

IGF-I promotes growth during postnatal development via both endocrine and autocrine actions. In pcd mice (pcd/pcd), we previously found that IGF-I mRNA expression was decreased in cerebellar Purkinje cells as they underwent apoptosis. To investigate the endocrine function of IGF-I, we examined hepatic IGF-I mRNA by Northern hybridization, circulating IGF-I peptide by radioimmunoassay, and circulating IGFBP by Western ligand blot in pcd mice. At postnatal days (D) 17 and 24, hepatic IGF-I mRNA and circulating IGF-I and IGF-II concentrations were normal in pcd mice. From D45, both hepatic IGF-I mRNA and circulating IGF-I concentrations decreased. The decrease in circulating IGF-I concentrations was accompanied by a simultaneous increase in circulating IGF-II concentrations in both the D45 and adult pcd mice. An early decrease in the circulating IGFBP-3 levels and an increase in the IGFBP-2 levels were observed at D17 and were followed by decreases in both IGFBPs at D45 and in the adult. Therefore, after the cerebellar neurodegeneration, there was an overall decrease in IGF-I gene expression in pcd mice. Our results suggest that the decrease in IGF-I gene expression may contribute to growth deficiency and multiple system degeneration in pcd mice.

Animals↗

PubMed1996

Feeding of excessive cystine and cysteine enhances defects of dietary copper deficiency in rats by differential mechanisms involving altered iron status.

We have reported that excess cystine feeding exaggerates the defects of dietary copper deficiency in rats by a mechanism not involving oxidative stress and altered copper status. This study was conducted to examine whether this exacerbation is caused by a mechanism involving altered iron status and to compare the influences of cystine and cysteine feeding on the defects of copper deficiency. Male Wistar rats were fed copper-adequate or copper-deficient diet with supplementation of L-cystine or L-cysteine (2%) for 10 days or 21 days. Copper-deficient diet increased heart weight, caused anemia, reduced plasma iron and elevated liver iron. These defects were exacerbated by supplemental cystine. Cysteine feeding also exacerbated the defects of dietary copper deficiency including anemia, increased heart weight, and reduced plasma iron, although cysteine feeding had no influence on liver iron concentration. Supplemental cysteine reduced apparent absorption of iron, while supplemental cystine did not. These results suggest that cystine feeding enhances the defects of copper deficiency by a mechanism involving impaired mobilization of iron from liver into blood, and that cysteine feeding enhances the defects of copper deficiency by a mechanism involving reduced intestinal absorption of iron.

Anemia↗

PubMed2001

[Effect of cholesterol deficiency on the membrane fluidity of Jurkat T lymphocytes].

The mechanism of cholesterol deficiency on inhibiting the proliferation of T lymphocytes was investigated on cell membrane fluidity by using fluorescence polarization measurement, 3H-TdR incorporation test and flow cytometer analysis in Jurkat cells, in order to clarify the importance of cholesterol in maintaining the normal function of lymphocytes. The results showed that cell membrane fluidity was increased, cell proliferation was inhibited and blocked on G0/G1 phase in Jurkat cells after being cultured with lovastatin (an inhibitor of rate limiting enzyme for cholesterol synthesis) for 3 days. When the cells were treated with LDL. The changes could be partially buffered. These results suggest that the change of membrane fluidity may be caused by cholesterol deficiency on the proliferation of Jurkat cells.

Anticholesteremic Agents↗

PubMed2002

[Effect of excessive Zn2+ and deficient Zn2+ on the expression of wild type-p53 mRNA in rat glicoma cells].

RT-PCR is applied to observe the effects of excessive and deficient Zn2+ on the expression of wild type-p53 (wt-p53) in rat glicoma cells. Rat glicoma cells in garithmic growth phase is treated with 0.3 mmol/L Zn2+ and 5 mumol/L TPEN respectively for 24 hours. Results show that the expression of wt-p53 of rat glicoma cells increased obviously in the deficient zinc group but does not increased in the excessive zinc group. These indicate that the expression of wt-p53 mRNA of rat glicoma cells is up-regulated by deficient zinc and inhibited by excessive zinc.

Animals↗

PubMed2002

[The detection of cytokine and immunoglobulin in sera of children with respiratory papillomatosis].

OBJECTIVE: To investigate the levels and effects of cytokine and immunoglobulin on children with respiratory papillomatosis(RP). METHOD: The levels of cytokine and immunoglobulin in sera of 23 patients with RP were measured by ELISA and immunoassay and were compared with the normal data published by our department of Laboratory. RESULT: The levels of cytokine in RP group were significantly higher than that of normal group and the levels of immunoglobulin in RP group was significantly lower than that of normal group. CONCLUSION: The result shows that there are immune deficiency and abnormal immune reponse with cytokine in the RP patients.

Child↗

PubMed2003

[The relationship between hypoxia inducible factor-1 alpha expression and novoendotheliasis after autogenous vein grafting].

OBJECTIVE: To elucidate the relationship between the level of hypoxia inducible factor-1alpha (HIF-1alpha) expression and novoendotheliasis after autogenous vein grafting. METHODS: 40 Wistar rats underwent right internal jugular vein to common jugular artery interposition grafting. Twenty rats were killed 7 and 14 days after the grafting respectively and the grafted veins were harvested respectively. Twenty rats not undergoing grafting were used as controls. The expressions of HIF-1alpha mRNA and protein and vascular endothelial growth factor (VEGF) mRNA and protein were examined by using reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry. Electron microscope was used to observe the process of vascular novoendotheliasis. RESULTS: The percentage of HIF-1alpha positive cells 7 days after grafting was 20.5 +/- 6.2%, significantly higher than that 14 days after (12.3 +/- 3.7, P < 0.01) and that of the controls (0.5 +/- 0.1%, P < 0.01). The percentage of HIF-1alpha positive cells 14 days after grafting was significantly higher than that of the controls too (P < 0.01). The expression of HIF-1alphamRNA 7 days after grafting was 53.2 +/- 9.3, significantly higher than that 14 days after grafting (43.2 +/- 6.3, P < 0.01) and that in the control (29.4 +/- 5.6, P < 0.01). The expression of HIF-1alpha7 mRNA 14 days after grafting was significantly higher than that of the controls too (P < 0.01). The expression of HIF-1alpha protein 7 days after grafting was 5.6 +/- 0.4, significantly higher than that 14 days after grafting (3.5 +/- 0.2, P < 0.01) and that in the control (0.8 +/- 0.1, P < 0.01). The expression of VEGF protein 7 days after grafting was 2.2 +/- 0.1, significantly higher than that of the control (0.5 +/- 0.1, P < 0.01). Novoendotheliasis was seen 7 days after grafting and decreased 14 days after. The expression of HIF-1alpha was positively correlated with the expression of VEGF (r = 0.903, P < 0.01). CONCLUSION: HIF-1 alpha is closely related to novoendotheliasis. The deficiency of HIF-1 alpha expression plays an important role in intima hyperplasia.

Animals↗

PubMed1992

A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.

A G-to-A transition at nucleotide pair (np) 7444 in the mtDNA was found to correlate with Leber hereditary optic neuropathy (LHON). The mutation eliminates the termination codon of the cytochrome c oxidase subunit I (COI) gene, extending the COI polypeptide by three amino acids. The mutation was discovered as an XbaI restriction-endonuclease-site loss present in 2 (9.1%) of 22 LHON patients who lacked the np 11778 LHON mutation and in 6 (1.1%) of 545 unaffected controls. The mutant polypeptide has an altered mobility on SDS-PAGE, suggesting a structural alteration, and the cytochrome c oxidase enzyme activity of patient lymphocytes is reduced approximately 40% relative to that in controls. These data suggest that the np 7444 mutation results in partial respiratory deficiency and thus contributes to the onset of LHON.

Amino Acid Sequence↗

PubMed1992

Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with pressure-overload cardiac hypertrophy.

Evidence has been put forth that a number of human and experimental cardiomyopathies are associated with a lower myocardial carnitine content. This study was performed to test the hypothesis that the correction of carnitine derivative, propionyl-L-carnitine (PLC), may improve cardiac function. Repeated administration of PLC was compared to saline with respect to cardiac function in rats with pressure-overload cardiac hypertrophy and low myocardial carnitine levels. Cardiac hypertrophy was induced by abdominal aorta constriction in rats. Separate groups of rats were used for (a) determination of myocardial carnitine content, (b) evaluation of in vivo hemodynamics, and (c) evaluation of performance and metabolic state of Langendorff perfused hearts. Results showed the following: (i) The myocardial carnitine content was inversely correlated to cardiac hypertrophy (r = 0.68, p less than 0.05) and PLC treatment (50 mg/kg i.a. for 4 days) restored it to normal values (ii) The PLC effect on cardiac function was significantly and directly related to cardiac hypertrophy [correlations between heart weight and percent changes in cardiovascular parameters: cardiac output (CO), p less than 0.001; cardiac work (CW), p less than 0.01, stroke volume (SV) and stroke work (SW), p less than 0.02]. In animals with heart weight greater than 1,400 mg, the effect of PLC on CO, CW, SV, SW, and total peripheral resistance (TPR) was significantly different from that of saline (CO, CW, SV, and SW, p less than 0.005 each; TPR, p less than 0.05). The effect was observed 24 h after the first PLC administration and significantly diminished following a 4 day suspension of the treatment. (iii) Perfused hearts from PLC-treated rats displayed a significantly lower left ventricular end-diastolic pressure (p less than 0.01) and greater relaxation rate (p less than 0.05) than those from control rats. Moreover, in PLC-treated hearts, the content of creatine phosphate, ATP, and total adenine nucleotides (ATP+ADP+AMP; TAN) was significantly increased (CP, p less than 0.05; ATP and TAN, p less than 0.01 vs. control). These data show that PLC exerts a stimulatory activity on hearts with hypertrophy and low carnitine content, implying that carnitine deficiency may contribute to the depression of cardiac function in this model.

Adenine Nucleotides↗