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PubMed2006

Acute pulmonary edema in patients with decompensated heart failure. Role of underlying cardiopathy on the prognosis.

AIMS: To investigate the impact of acute pulmonary edema (APE) on the prognosis of patients hospitalized with congestive heart failure (CHF) and if the underlying cardiopathy influences the survival of these patients. METHOD AND RESULTS: All patients admitted to the cardiology department of a tertiary hospital with CHF between 1991 and 2002 were included in the present study. APE was diagnosed in 176 of 1659 patients. 60.2% of them were of ischaemic etiology, 48.6% and 42.9% of hypertensive and valvular origin, respectively. Survival analysis carried out in April 2003 has shown that APE patients have higher mortality rates, with a median survival of 3.1 years as against 4.8 years. This difference was due only to the behaviour of patients with ischaemic CHF as among patients with non-ischaemic CHF, the difference in median survival between patients with and without APE was insignificant. Within the APE group the survival of ischaemic patients was lower than that of non-ischaemic (median survival of 2.3 years vs 4.5 years, respectively). The difference was more pronounced between APE patients with CHF of ischaemic and hypertensive origin (median survival of 5.6 years for the latter). Among patients without APE, there was no significant difference between different etiological groups. CONCLUSION: In this study we found that the survival time of CHF patients is significantly shortened by the concurrence of APE and ischaemic etiology but not by either of these factors without the other.

Aged↗
PubMed2006

Antiangiogenic activity of Andrographis paniculata extract and andrographolide.

Inhibition of angiogenesis is currently perceived as one of the promising strategies in the treatment of cancer. In this study we analyzed the antiangiogenic activity of Andrographis paniculata extract (APE) and its major component andrographolide (ANDLE) using both in vitro and in vivo models. Intraperitoneal administration of APE and ANDLE significantly inhibited the B16F-10 melanoma cell line induced capillary formation in C57BL/6 mice. Analysis of serum cytokine profile showed a drastic elevation in the proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha and GM-CSF and the most potent angiogenic factor VEGF in angiogenesis induced animals. Treatment of APE and ANDLE significantly reduced this elevated levels. Moreover, VEGF mRNA level in B16F-10 cell line showed a reduced level of expression in the presence of APE and ANDLE. Serum NO level which was increased in B16F-10 melanoma injected control animals was also found to be significantly lowered by the administration of APE and ANDLE. Antiangiogenic factors such as TIMP-1 and IL-2 level was elevated in APE and ANDLE treated angiogenesis induced animals. In the rat aortic ring assay APE and ANDLE inhibited the microvessel outgrowth at non toxic concentrations. Taken together our results demonstrate that APE and ANDLE inhibit the tumor specific angiogenesis by regulating the production of various pro and antiangiogenic factors such as proinflammatory cytokine, nitric oxide, VEGF, IL-2 and TIMP-1.

Andrographis↗
PubMed2004

Apurinic/apyrimidinic endonuclease (APE/REF-1) haploinsufficient mice display tissue-specific differences in DNA polymerase beta-dependent base excision repair.

Apurinic/apyrimidinic (AP) endonuclease (APE) is a multifunctional protein possessing both DNA repair and redox regulatory activities. In base excision repair (BER), APE is responsible for processing spontaneous, chemical, or monofunctional DNA glycosylase-initiated AP sites via its 5'-endonuclease activity and 3'-"end-trimming" activity when processing residues produced as a consequence of bifunctional DNA glycosylases. In this study, we have fully characterized a mammalian model of APE haploinsufficiency by using a mouse containing a heterozygous gene-targeted deletion of the APE gene (Apex(+/-)). Our data indicate that Apex(+/-) mice are indeed APE-haploinsufficient, as exhibited by a 40-50% reduction (p < 0.05) in APE mRNA, protein, and 5'-endonuclease activity in all tissues studied. Based on gene dosage, we expected to see a concomitant reduction in BER activity; however, by using an in vitro G:U mismatch BER assay, we observed tissue-specific alterations in monofunctional glycosylase-initiated BER activity, e.g. liver (35% decrease, p < 0.05), testes (55% increase, p < 0.05), and brain (no significant difference). The observed changes in BER activity correlated tightly with changes in DNA polymerase beta and AP site DNA binding levels. We propose a mechanism of BER that may be influenced by the redox regulatory activity of APE, and we suggest that reduced APE may render a cell/tissue more susceptible to dysregulation of the polymerase beta-dependent BER response to cellular stress.

Animals↗
PubMed2001

Antiphosphatidylethanolamine antibodies contribute to the diagnosis of antiphospholipid syndrome in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the correlation between antiphosphatidylethanolamine antibodies (aPE) and some antiphospholipid antibodies (aPL)-related clinical manifestations in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n=217) were tested for the presence of aPE, anticardiolipin antibodies (aCL), and lupus anticoagulant (LA). The prospective aPL-related clinical manifestations studied were: thrombosis, thrombocytopenia, recurrent fetal losses, heart valvulopathies, hemolytic anemia, livedo reticularis, and pulmonary hypertension. RESULTS: A total of 109 SLE patients (50.23%) were IgG aPE-positive; 17.51% presented aPE as the sole autoantibody and had some clinical features of aPL-related clinical manifestations. IgG aPE were associated to the presence of heart valvulopathies (p=0.002). A statistical difference was also found when considering high levels of IgG aPE (O.D.>0.600) in patients with livedo reticularis (p=0.008). CONCLUSION: The evaluation of IgG aPE may allow us to detect some more patients with aPL-related clinical manifestations in the SLE population, aPE correlated particularly with valvulopathies and livedo reticularis.

Adolescent↗
PubMed2006

Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1.

Helicobacter pylori infection causes inflammation and increases the expression of IL-8 in human gastric epithelial cells. H. pylori activates NF-kappaB and AP-1, essential transcriptional factors in H. pylori-induced IL-8 gene transcription. Although colonization creates a local oxidative stress, the molecular basis for the transition from infection to the expression of redox-sensitive cytokine genes is unknown. We recently reported that the expression of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE-1/Ref-1), which repairs oxidative DNA damage and reductively activates transcription factors including AP-1 and NF-kappaB, is increased in human gastric epithelia during H. pylori infection. In this study, we examine whether APE-1/Ref-1 functions in the modulation of IL-8 gene expression in H. pylori-infected human gastric epithelial cells. Small interfering RNA-mediated silencing of APE-1/Ref-1 inhibited basal and H. pylori-induced AP-1 and NF-kappaB DNA-binding activity without affecting the nuclear translocation of these transcription factors and also reduced H. pylori-induced IL-8 mRNA and protein. In contrast, overexpression of APE-1/Ref-1 enhanced basal and H. pylori-induced IL-8 gene transcription, and the relative involvement of AP-1 in inducible IL-8 promoter activity was greater in APE-1/Ref-1 overexpressing cells than in cells with basal levels of APE-1/Ref-1. APE-1/Ref-1 inhibition also reduced other H. pylori-induced chemokine expression. By implicating APE-1/Ref-1 as an important regulator of gastric epithelial responses to H. pylori infection, these data elucidate a novel mechanism controlling transcription and gene expression in bacterial pathogenesis.

Cell Line↗
PubMedDate not supplied

Some in vitro and in vivo cardiovascular effects of Hypoxis hemerocallidea Fisch & CA Mey (Hypoxidaceae) corm (African potato) aqueous extract in experimental animal models.

This study was undertaken to investigate some cardiovascular effects of Hypoxis hemerocallidea Fisch & CA Mey (Hypoxidaceae) corm (African potato) aqueous extract in experimental animal paradigms. The effect of the corm aqueous extract (APE) on myocardial contractile performance was evaluated on guinea-pig isolated atrial muscle strips in vitro; whereas the antihypertensive (hypotensive) effect of the plant extract was examined in hypertensive Dahl salt-sensitive rats in vivo. APE (25-400 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001) negative inotropic and negative chronotropic effects on guinea-pig isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. Moreover, APE reduced or abolished, in a concentrationdependent manner, the positive inotropic and chronotropic responses of guinea-pig isolated atrial muscle strips induced by noradrenaline (NA, 1-100 microM) and calcium (Ca2+, 5-40 mM). The negative inotropic and chronotropic effects of APE on guinea-pig atrial muscle strips were not modified by exogenous administration of atropine (ATR, 7.5 x 10(-7)-2.5 - 10(-6) M) to the bath fluid. APE also significantly reduced (p < 0.05-0.001) or abolished in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from rats. Furthermore, APE caused dose-related transient but significant (p < 0.05-0.001) reductions in the systemic arterial blood pressure and heart rates of the hypertensive rats used. Although the exact mechanisms of the cardiodepressant and the transient hypotensive (antihypertensive) actions of APE could not be established in the present study, we exclude the involvement of the cholinergic system; since the extract's cardiovascular effects were resistant to atropine pretreatment. However, the results of this laboratory animal study indicated that APE caused bradycardia and brief hypotension in the mammalian experimental models used. These observations tend to suggest that the herb may be used as a natural supplementary remedy in some cases of cardiac dysfunctions and in essential hypertension. The findings of this experimental animal study lend pharmacological support to the folkloric, anecdotal uses of the African potato in the management and/or control of certain cardiac dysfunctions and essential hypertension in some rural communities of southern Africa.

Analysis of Variance↗
PubMed1995

Autoantibodies to phosphatidylethanolamine (PE) recognize a kininogen-PE complex.

Demonstration of autoimmune antiphospholipid antibodies (aPA) to negatively charged phospholipids (PL) in an enzyme-linked immunosorbent assay (ELISA) requires the presence of certain phospholipid-binding plasma proteins, eg, beta 2-glycoprotein I. We found a requirement for plasma against the electrically neutral or zwitterionic phospholipid, phosphatidylethanolamine (PE). Two of these PE-binding plasma proteins were identified as high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). We studied anti-PE antibody (aPE) seropositive plasma from 13 patients with SLE and/or recurrent spontaneous abortions by using partially purified kininogens and kininogen binding proteins from adult bovine serum isolated by carboxymethyl (CM)-papain affinity chromatography. Eleven of 13 sera recognized a kininogen-PE complex and/or a kininogen-binding protein-kininogen-PE complex. Some aPE-positive patient sera were shown to recognize highly purified HMWK and LMWK by ELISA only when the kininogens were presented on a PE substrate. These aPE sera did not recognize PE, HMWK, or LMWK when they were presented independently as the sole antigens on the ELISA plates. Other aPE-positive sera that did not react with PE-bound HMWK or LMWK reacted with the CM-papain column eluate when it was bound to PE, which suggests that these aPE recognize factor XI or prekallikrein, which normally bind to HMWK. The aPE ELISA reactivity of two patient sera were inhibited by preincubation of the CM-papain column eluate in the ELISA plate. These data show that most aPE are not specific for PE but require the presence of certain PL-binding plasma proteins that are kininogens or proteins in complex with kininogens. Our studies indicate that aPE bind to different plasma proteins than those implicated in anionic PL, aPA ELISA reactivity.

Abortion, Habitual↗
PubMed1996

Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies detected by ELISA. II. Kininogen reactivity.

OBJECTIVE: To study the requirement for serum and for low (LMWK) and high molecular weight kininogen (HMWK) and/or HMWK binding proteins to detect antiphosphatidylethanolamine antibodies (aPE) in ELISA. METHODS: Eighteen patients with aPE (9 IgG and 13 IgM) as the only antiphospholipid antibody (aPL) detected by ELISA were assigned to 4 groups: thromboembolic episodes (TEE) (Group I, n = 6); livedo reticularis (LR) without TEE, (Group II, n = 4); both LR and thrombosis (Group III, n = 4); and systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS) (Group IV, n = 4). All sera were analyzed in ELISA with and without bovine serum and with a purified chromatographic fraction containing LMWK, HMWK, and HMWK binding proteins. RESULTS: Eleven aPE were serum dependent: mostly IgG (7/9) and some IgM (4/13). Among the 11 serum dependent aPE, all the 7 IgG and 2 IgM were kininogen reactive. Some serum independent IgM were better detected in the absence than in the presence of serum in the ELISA. CONCLUSION: In the 18 patients, kininogens and/or HMWK binding proteins served as a "cofactor" significantly more often for aPE IgG than for aPE IgM (p = 0.007). Kininogen dependent aPE Ig were observed more often in patients with LR with or without TEE (6/8) than in those with SLE or primary APS (0/4) but this difference merely tended to significance (p = 0.06). In 2 patients, one with TEE, the other with primary APS, the IgM aPE was dependent on a serum "cofactor" that was not kininogen.

Antibodies, Antiphospholipid↗
PubMed2000

Factor V leiden and morbid obesity in fatal postoperative pulmonary embolism.

HYPOTHESIS: Currently, the risk for postoperative acute pulmonary embolism (APE) is assessed clinically. We hypothesize that the expensive screening for the most common genetic thrombophilic clotting defect (factor V Leiden; R(506)Q) after exclusion of established clinical risk factors does not offer additional benefit to surgical patients. DESIGN: We reviewed protocols and histories from 8249 consecutive autopsies performed at the Mayo Clinic, Rochester, Minn. All patients who died of APE after routine surgery and who lacked any other clinical risk factors for APE were included and compared with matched controls. Genomic DNA was extracted from archival tissues and examined for R(506)Q by polymerase chain reaction amplification, restriction enzyme digestion, and direct sequencing. RESULTS: Acute pulmonary embolism was the immediate cause of death in 454 patients (5.5%). Of those, 32 (7.0%) had undergone routine surgery. These patients represent less than 0.07% of all case-adjusted surgical procedures in the same period. The rate of postoperative death from APE was higher after neurosurgical procedures (0.3%) than all other procedures (0.04%). Sixteen patients (50.0%) were morbidly obese. Only 1 patient was heterozygous and none were homozygous for R(506)Q. CONCLUSIONS: (1) Fatal APE is uncommon in surgical patients lacking clinically apparent risk factors for venous thromboembolism. (2) Neurosurgical patients are at increased risk for postoperative APE. (3) Morbid obesity is a major independent risk factor in cases of sudden death from APE postoperatively. (4) Routine preoperative screening for R(506)Q in the factor V gene does not appear to offer additional benefit in surgical patients without clinically recognizable thromboembolic risk factor(s).

Activated Protein C Resistance↗
PubMed1995

Sex determination in miocene catarrhine primates.

Canines of fossil hominoids and primitive catarrhines from several early, middle, and late Miocene sites were analyzed according to the shape indices described in Kelley (1995) and compared to those of males and females of extant great apes. In bivariate plots of the fossil canines utilizing the indices, 90% of the upper canines and 85% of the lower canines fell within or just outside the exclusively male or exclusively female territories delimited by the extant great apes. The remainder fell in the male-female overlap zones. Sex assignments based on these distributions were nearly 100% concordant with classifications according to canine height, suggesting a high degree of accuracy. There were various taxon-specific shifts in bivariate space among fossil genera, reflecting subtle differences in canine shape between taxa within the overall pattern of similarity to extant great apes as a whole. In many cases these shifts are matched by particular extant-ape species and subspecies, while other fossil taxa have no exact analogue for canine shape among the extant great apes. However, the pattern of spatial segregation of canines identified as either male or female at each of the sites largely mirrors that of males and females within the extant-ape sample, indicating that Miocene catarrhines shared with extant great apes a common pattern of shape differences between male and female canines, regardless of taxon-specific morphologies. These observations demonstrate that the canines of fossil catarrhines can be sexed with a high degree of confidence based solely on intrinsic features of shape. This will permit more reliable characterizations of morphological sexual dimorphism among fossil species. It is also argued that canine shape is a more reliable indicator of sex in fossil taxa than are canine/molar size ratios.

Animals↗
PubMed1994

Sources of prediction error when using a Bayesian method to evaluate nortriptyline serum concentrations.

A Bayesian method was used to evaluate nortriptyline (NTP) serum concentrations (Cps) and predict future Cps in two populations: five simulated groups (n = 20 each) with known clearance (CL) and volume of distribution (Vd), and an actual inpatient group (n = 20). The effects of weight, CL, Vd, and magnitude of Cps on absolute prediction error (APE) were evaluated. In simulated groups, Cps after two doses of NTP and for steady-state were calculated for normal, increased, and decreased Vd and CL. In the actual patient group, Cps were measured in the first few days after starting NTP administration and again during maintenance therapy. The first Cps were used in the Bayesian program to estimate CL and Vd to predict the second Cps. In the simulated group, PE and APE differed significantly between normal and decreased values of CL. A large Vd resulted in less of a change in PE or APE in these subjects, but when combined with low CL led to the largest errors. In the actual patient group, PE was -5.9 +/- 19.2 ng/mL and APE was 15.4 +/- 12.6 ng/mL. In these patients, only body weight was correlated with the percent APE (r = 0.607, P = 0.005). The Bayesian method performs well clinically, but increased Vd and decreased CL can lead to higher PE. Clinically, the only factor that predicted higher APE was obesity. This may reflect an effect on Vd, and in these patients, a high APE may occur.

Adult↗
PubMed1987

Analysis of recurrence following curative low anterior resection and stapled anastomoses for carcinoma of the middle third and lower rectum.

In a series of 93 patients with middle and lower rectal cancer, who underwent potentially curative surgery by low anterior resection (LAR) with EEA stapled anastomosis or by abdominoperineal excision (APE) between January 1977 and December 1981, the incidence of recurrence and survival rate was compared. LAR with stapler was performed in 61 patients: 55 (90.2 percent) with tumors of the middle third and six (9.8 percent) for tumors of the lower third of the rectum. APE was performed in 32 patients: 13 (40.6 percent) with cancer of the midrectum and 19 (59.4 percent) of the lower rectum. Tumor site, Dukes' distribution, grade of malignancy, and extent of local spread were recorded. The tumor stages for LAR with stapler and for APE, respectively, were Dukes' A 7/1; Dukes' B 27/10; Dukes' C 25/18; Dukes' D 2/3. In a follow-up period of four years (range, 6 to 52 months) the overall recurrence rates were 20.4 percent in the LAR with stapled anastomosis group and 21 percent in the APE group. Local recurrence percentages were 9.8 percent after LAR and 14 percent after APE (P = N.S.). Distant recurrences were 12 percent and 14 percent, respectively. The four-year overall survival rates were 76.7 percent after LAR and 65.5 percent after APE (P = N.S.) The clinical and pathologic factors correlated with recurrence in low rectal carcinoma were reanalyzed and the controversial points of the surgical management for and against LAR with stapled anastomosis and APE were discussed. It is concluded that LAR with the EEA stapler can be carried out in the middle and lower rectum with the prospect of ultimate cure, when performed with proper technical skills in selected patients.

Adult↗
PubMed2006

Intracellular trafficking and regulation of mammalian AP-endonuclease 1 (APE1), an essential DNA repair protein.

AP endonuclease (APE), with dual activities as an endonuclease and a 3' exonuclease, is a central player in repair of oxidized and alkylated bases in the genome via the base excision repair (BER) pathway. APE acts as an endonuclease in repairing AP sites generated spontaneously or after base excision during BER. It also removes the 3' blocking groups in DNA generated directly by ROS or after AP lyase reaction. In contrast to E. coli and lower eukaryotes which express two distinct APEs of Xth and Nfo types, mammalian genomes encode only one APE, APE1, which is of the Xth type. However, while the APEs together are dispensable in the bacteria and simple eukaryotes, APE1 is essential for mammalian cells. We have shown that apoptosis of mouse embryo fibroblasts triggered by APE1 inactivation can be prevented by ectopic expression of repair competent but not repair-defective APE1. The mitochondrial APE (mtAPE) is an N-terminal truncation product of APE1. A significant fraction of APE1 is cytosolic, and oxidative stress induces its nuclear and mitochondrial translocation. Such age-dependent increase in APE activity in the nucleus and mitochondria is consistent with the hypothesis that aging is associated with chronic oxidative stress.

Animals↗
PubMed2004

Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators.

BACKGROUND: Eosinophil accumulation at sites of allergic inflammation is largely regulated by chemokines and lipid mediators released by a variety of cells of the local microenvironment. Recent studies have shown that pollen grains, apart from their function as allergen carriers, are a rich exogenous source of eicosanoid-like lipid mediators that are rapidly released on contact with the aqueous phase and thus may contribute to the generation of local inflammatory responses. OBJECTIVE: Here we analyze the biological activity of pollen-associated lipid mediators (PALMs) on peripheral human blood eosinophils. METHODS: Human eosinophils were coincubated with pollen grains and analyzed by electron microscopy. The lipid mediator composition of aqueous pollen extracts (APEs) was analyzed by HPLC. Human eosinophils were exposed to APEs or lipid fractions from pollen. Effects on eosinophils were tested by transwell migration and surface expression of CD11b. RESULTS: In vitro experiments showed adhesion of eosinophils to Phleum pratense pollen. In chemotaxis assays eosinophils displayed significant directed migration to APEs. HPLC analysis of APEs from Phleum pratense and Betula alba pollen demonstrated the occurrence of linoleic and alpha-linolenic acid as well as their monohydroxylated derivatives. Moreover, total lipid extracts from pollen and RP-HPLC fractions containing monohydroxylated derivatives of linoleic and alpha-linolenic acid induced similar migratory responses, although to a lesser degree than APEs. In addition, APEs and lipid extracts induced up-regulation of CD11b surface expression and secretion of eosinophil cationic protein. APE-induced chemotaxis was blocked by the leukotriene B(4) receptor antagonist LY293111, suggesting that PALMs may serve as ligands for LTB(4) receptors. CONCLUSION: Pollen grains release lipid mediators that recruit and activate eosinophils in vitro. Similar mechanisms may be effective under natural exposure conditions, in which PALMs may play a role in the recruitment of eosinophils to the site of allergic inflammation.

Benzoates↗
PubMed2005

Sildenafil selectively inhibits acute pulmonary embolism-induced pulmonary hypertension.

Selective pulmonary vasodilators attenuate acute pulmonary embolism (APE)-induced pulmonary hypertension. We examined the effects of intravenous sildenafil on the hemodynamic and respiratory changes caused by APE in anesthetized dogs. Sham operated animals (n=3) received only saline infusions. APE was induced by intravenous injections of microspheres in amounts adjusted to increase mean pulmonary artery pressures (MPAP) by 20 mmHg. Hemodynamic evaluation was performed and arterial blood samples were drawn for blood gas analysis at baseline, 15 and 30 min after APE was induced, and then 15, 30, and 45 min after the sildenafil infusion (1 mg kg(-1) infused intravenously in 15 min followed by 0.3 mg kg(-1) h(-1) for 30 min) started in the Sildenafil group (n=7), or saline infusion started in the control group (n=8). APE induced sustained pulmonary hypertension and 325% increase in pulmonary vascular resistance index (PVRI) without significant changes in the other hemodynamic parameters. While the animals in the control group showed no further changes in MPAP and PVRI, a significant decrease in MPAP and PVRI (-25 and -45%, respectively; P<0.05 both) was observed with sildenafil. No significant changes in the other hemodynamic parameters were observed in both groups. APE decreased PaO2, whereas sildenafil attenuated the decrease in PaO2 (P<0.05). We conclude that intravenous sildenafil can selectively attenuate the increases in MPAP and PVRI after APE.

Animals↗
PubMed2000

[IGM hyperimmunoglobulinemia anti-phosphatidylethanolamine antibodies of the IgM isotype: clinical and biological study of 72 patients with immune disorders].

PURPOSE: Antiphosphatidylethanolamine antibodies (aPE) are zwitterionic antiphospholipid antibodies that have been recently described in antiphospholipid syndrome. IgM is the most frequently observed isotype. We assessed the potential relationship between serum IgM levels and their presence. METHODS: Seventy-two patients (66 females, 6 males) positive for aPE of the IgM isotype were followed up for 2 years. They suffered from either an autoimmune disease or had clinical signs suggesting the existence of antiphospholipid syndrome or other immune disorders. Seventy-two control patients (58 females, 14 males) of similar age, with other immune disorders were also included in the study. For each of them, the IgM level was obtained and hyper-immunoglobulinemia M (hyper-IgM) was defined as a value upper than 2.5 g/L. Search for aPE of the IgM isotype was made using an in-house Elisa test. RESULTS: Half of the aPE-positive patients had serum hyper-IgM, whereas none of the aPE-negative patients had hyper-IgM. All IgMs were polyclonal. There was a positive correlation (r = 0.57, P = 0.001) between the level of IgM and the optical densities obtained by Elisa. The presence of a hyper-IgM did not modify the clinical manifestations (arterial and venous thromboses, recurrent fetal losses), nor the positivity of lupus anticoagulant, anticardiolipin and anti-beta-2-glycoprotein 1 antibodies. CONCLUSION: The positive correlation between the IgM level and aPE level is of value, as it suggests a possible relationship between lymphocytic activation and auto-antibodies production, which does not concern only aPE. Further studies regarding the antigenic specificity of IgM will probably provide further insights on IgM and phospholipid interactions.

Adult↗
PubMed2005

Effects of Hypoxis hemerocallidea (Fisch. & C.A. Mey.) [Hypoxidaceae] corm (African Potato) aqueous extract on renal electrolyte and fluid handling in the rat.

Current biomedical evidence suggests that Hypoxis hemerocallidea (Fisch. & C.A. Mey.) [Hypoxidaceae] (African Potato [AP]) corm extract may be useful in the management of type 2 diabetes mellitus. However, more recent reports have also indicated that certain herbal extracts attenuate the deterioration of kidney function in diabetes mellitus. Accordingly, this study investigated the effects of short- (acute) and long-term (chronic) administration of H. hemerocallidea corm aqueous extract (APE) on renal fluid and electrolyte handling in male Wistar rats. Acute effects of APE were investigated in separate groups of anesthetized rats challenged with a continuous jugular infusion of 0.077 M NaCl at 9 mL x h(- 1). After a 3.5-h equilibration period, consecutive 30-min urine collections were made over the subsequent 4 h of 1-h control, 1.5-h treatment, and 1.5-h recovery periods for measurements of urine flow, Na+, and K+ excretion rates. To establish the effects of acute APE, the extract was added to the infusate at doses of 90, 180, or 360 microg x h (-1) in separate groups of rats during the treatment period. For chronic studies, individually caged rats were administered twice with APE (30 mg x kg (-1) PO) every third consecutive day at 09h00 and 17h00 for 5 weeks. Control rats received distilled water (3 mL x kg(-1)). Urine volume and total urinary outputs of creatinine, Na+, and K+ were determined from 24-h samples. Acute infusion of APE produced a dose-dependent, significant (p < 0.01) decrease in urine flow, K+, and Na+ excretion rates. Chronic APE treatment significantly reduced urinary Na+ output between weeks 2 and 5, without affecting either urine flow or K+ excretion rates. When compared with control animals, APE significantly reduced GFR (2.54+/-0.09 mL x min (-1) vs. 1.52+/-0.02 mL x min (-1)) and increased plasma creatinine concentration (55 +/- 3 micromol x L(-1) vs. 68 +/-6 micromol x L(-1)). The results from this study suggest that the H. hemerocallidea corm aqueous extract may impair kidney function.

Analysis of Variance↗
PubMed2004

The major role of human AP-endonuclease homolog Apn2 in repair of abasic sites in Schizosaccharomyces pombe.

The abasic (AP) sites, the major mutagenic and cytotoxic genomic lesions, induced directly by oxidative stress and indirectly after excision of damaged bases by DNA glycosylases, are repaired by AP-endonucleases (APEs). Among two APEs in Saccharomyces cerevisiae, Apn1 provides the major APE activity, and Apn2, the ortholog of the mammalian APE, provides back-up activity. We have cloned apn1 and apn2 genes of Schizosaccharomyces pombe, and have shown that inactivation of Apn2 and not Apn1 sensitizes this fission yeast to alkylation and oxidative damage-inducing agents, which is further enhanced by Apn1 inactivation. We also show that Uve1, present in S.pombe but not in S.cerevisiae, provides the back-up APE activity together with Apn1. We confirmed the presence of APE activity in recombinant Apn2 and in crude cell extracts. Thus S.pombe is distinct from S.cerevisiae, and is similar to mammalian cells in having Apn2 as the major APE.

Alkylation↗