Biomedical subjects

J W Cheng

Publications and source records attributed to J W Cheng.

At least 37 records · Page 2Linked to original sources

PubMed2000

Molecular cloning of growth hormone-releasing hormone/pituitary adenylyl cyclase-activating polypeptide in the frog Xenopus laevis: brain distribution and regulation after castration.

Pituitary adenylyl cyclase-activating peptide (PACAP) appears to regulate several neuroendocrine functions in the frog, but its messenger RNA (mRNA) structure and brain distribution are unknown. To understand the potential role of PACAP in the male frog hypothalamic-pituitary-gonadal axis, we cloned the frog Xenopus laevis PACAP mRNA and determined its distribution in the brain. We then analyzed the castration-induced alterations of mRNA expression for PACAP and its selective type I receptor (PAC1) in the hypothalamic anterior preoptic area, a region known to regulate reproductive function. The PACAP mRNA encodes a peptide precursor predicted to give rise to both GH-releasing hormone and PACAP. The deduced peptide sequence of PACAP-38 was nearly identical to that of human PACAP with one amino acid substitution. Abundant PACAP mRNA was detected in the brain, but not several other tissues, including the testis. In situ hybridization revealed strong expression of the PACAP gene in the dorsal pallium, ventral hypothalamus, and nuclei of cerebellum. PACAP mRNA signals were weak to moderate in the hypothalamic anterior preoptic area and were absent in the pituitary. Castration induced an increase in the expression of PACAP and PAC1 receptor mRNAs in the hypothalamic anterior preoptic area after 3 days. Replacement with testosterone prevented the castration-induced changes. These results provide a molecular basis for studying the physiological functions of PACAP in frog brain and suggest that PACAP may be involved in the feedback regulation of hypothalamic-pituitary-gonadal axis.

Amino Acid Sequence↗

PubMed2000

Beneficial effects of statins in coronary artery disease--beyond lowering cholesterol.

OBJECTIVE: To review the benefits of statins in coronary artery disease management beyond their cholesterol-lowering effects. DATA SOURCES: A MEDLINE search (1966-May 2000) was conducted using the following terms: lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, cerivastatin, endothelium, plaque stabilization, antithrombotic effects. STUDY SELECTION: English-language human studies and case reports. DATA EXTRACTION: Studies published demonstrating other mechanisms of statins' clinical beneficial effects were evaluated and reviewed. DATA SYNTHESIS: The understanding of the pharmacologic effects of statins has led to the realization that the benefits of these agents extend beyond simply lowering cholesterol. These properties include beneficial effects on vessel endothelial tissue; decreased low-density lipoprotein oxidation and inflammation; ability to stabilize atherosclerotic plaques and perhaps promote regression; proliferative effects on smooth-muscle growths, possibly strengthening atherosclerotic plaques; antithrombotic effects by inhibiting platelet aggregation and stimulation of fibrinolytic factors; and improvement of blood viscosity and flow. With these actions, statins may benefit the situation of long-term atherosclerotic plaque formation and the setting of acute coronary syndrome. CONCLUSIONS: Further large-scale studies are needed to determine the clinical importance and validity of these postulated beneficial effects of statins.

Blood Coagulation↗

PubMed2000

The role of vasopressin in the treatment of vasodilation in shock states.

OBJECTIVE: To review the role of vasopressin in the treatment of vasodilatory shock. DATA SOURCES: A MEDLINE search on published reports (1966-April 1999) was conducted. STUDY SELECTION: English-language studies and case reports were selected and evaluated based on quality of review of vasopressin in the treatment of vasodilatory shock. DATA SYNTHESIS: In patients with end-stage vasodilatory shock, baroreceptor reflex is impaired and vasopressin stores are depleted. Persistent elevation of catecholamines may lead to down-regulation of beta-adrenergic receptors and reduces smooth-muscle response to catecholamines, leading to inability of maintaining organ perfusion. Small-scale studies and case reports have demonstrated vasopressin's efficacy in maintaining blood pressure in patients with septic shock, cardiac arrest, and end-stage heart failure, refractory to other vasopressor therapies. CONCLUSIONS: Vasopressin may be a reasonable alternative for patients in vasodilatory shock. However, larger-scale controlled dinical trials are warranted before its routine use can be recommended.

Humans↗

PubMed2000

The association of infection and coronary artery disease: an update.

Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections. This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (cytomegalovirus, Chlamydia pneumoniae and Helicobacter pylori) in atherogenesis and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease. The interactions of cytomegalovirus and the arterial wall have been extensively studied. However, despite the successful preliminary therapeutic trials with the use of macrolides in augmenting possible C. pneumoniae-induced cardiovascular events, the exact mechanisms of how C. pneumoniae enters the arterial wall remains unknown at this point. For H. pylori, regardless of the large number of studies performed to assess the association between H. pylori and coronary artery disease, no definitive conclusion could be made at this time, due to contradictory results. Before one can widely adopt the use of antibiotics or antiviral agents as treatment for atherosclerosis, further studies must be designed to address some important issues. In vivo animal models need to be established to further examine the various hypotheses regarding the interaction of infectious agents and atherosclerosis and restenosis. Large-scale prospective cohort studies should be designed to relate evidence of infection to future risk of cardiovascular diseases. Confounding variables, such as other cardiovascular risk factors and socio-economic status, should be controlled in order to strengthen the association. Further interventional studies are also required to establish the best antibiotic or antiviral regimen to maximise efficacy and minimise side effects.

Animals↗

PubMed1999

Solution structure and dynamics of G1TE, a nonphosphorylated cyclic peptide inhibitor for the Grb2 SH2 domain.

The solution structure and dynamics of G1TE, a nonphosphorylated cyclic peptide inhibitor for the Grb2 SH2 domain, was determined using two-dimensional NMR and simulated annealing methods. G1TE consists of 10 amino acids and a C-terminal Cys cyclized through its side-chain sulfur atom by a thioether linkage to its N terminus. The results indicate that G1TE assumes a circle-like shape in solution in which all the side chains are protruding outside, and none of the residues are involved in intramolecular hydrogen bonding. The average root-mean-square deviations were found to be 0.41 +/- 0.11 A for the backbone heavy atoms C, Calpha, and N, and 1.03 +/- 0.14 A for all heavy atoms in a family of 10 structures. (15)N relaxation measurements indicate that G1TE has rather restricted dynamics in the fast time scale within its backbone. However, residues Tyr3, Val6, and Gly7 may be involved in a possible conformational exchange. The structural comparison between G1TE in solution and the BCR-Abl phosphopeptide bound to Grb2 SH2 domain revealed that G1TE may form a larger circle-like binding surface than the BCR-Abl phosphopeptide in the bound form. Also, the restricted backbone dynamics of G1TE may result in a reduced loss of entropy and can compensate for the absence of a phosphate group at the Tyr3 position. These structural and dynamic properties of G1TE may provide a molecular basis for understanding its interactions with the Grb2 SH2 domain.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Solution structure and RNA-binding activity of the N-terminal leucine-repeat region of hepatitis delta antigen.

Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B virus (HBV) which provides the surface antigen for the viral coat. The RNA genome of HDV encodes two proteins: the small delta antigen and the large delta antigen. The two proteins resemble each other except for the presence of an additional 19 amino acids at the C terminus of the latter species. We have found that the N-terminal leucine-repeat region of hepatitis delta antigen (HDAg) binds to the autolytic domain of HDV genomic RNA and attenuates its autolytic activity. A 27-residue polypeptide corresponding to residues 24-50 of HDAg, designated dAg(24-50), was synthesized, and its solution structure was found to be an alpha-helix by circular dichroism and (1)H-nuclear magnetic resonance (NMR) techniques. Binding affinity of dAg(24-50) with HDV genomic RNA was found to increase with its alpha-helical content, and it was further confirmed by modifying its N- and C-terminal groups. Furthermore, the absence of RNA binding activity in the mutant peptides, dAgM(24-50am) and dAgM(Ac24-50am), in which Lys38, Lys39, and Lys40 were changed to Glu, indicates a possible involvement of these residues in their binding activity. Structural knowledge of the N-terminal leucine-repeat region of HDAg thus provides a molecular basis for the understanding of its role in the interaction with RNA. Proteins 1999;37:121-129.

Amino Acid Sequence↗

PubMed1999

Structural studies of symmetric DNA undecamers containing non-symmetrical sheared (PuGAPu):(PyGAPy) motifs.

Interstrand purine-purine stacks originate from tandem sheared purine.purine pairing and represent one of the most important motifs in both DNA and RNA structures. Several RNA and DNA structures, solved recently in both solution and the solid state, contain these special motifs, which greatly increase the structural diversity of nucleic acid molecules. The direct evidence for the sheared purine-purine pairing at neutral pH in solution remains, however, elusive. In this manuscript, we have used high resolution NMR methods to study a series of symmetrical DNA duplexes containing two non-symmetrical 5'-(PuGAPu)/(PyGAPy)-3' motifs. Many strong- and medium-strength NOEs across the G.A base pair were detected in the H2O-NOESY spectra collected at a relatively low temperature (-5 degrees C). These NOEs, especially those from A-6NH2 to G-H1', G-H4', and G-2NH2, clearly define the proposed side-by-side sheared G.A pairing nature. Another interesting feature is the strong NOEs exhibited by the unpaired G-imino proton in the G.A pair to its own G-2NH2, which implies that G-2NH2 is involved in H-bonding with a base in the minor groove edge. The finding that non-symmetrical (PuGAPu):(PyGAPy) motif also form similarly stable structures loosens the requirement for a more restricted (PyGAPu)2 motif in forming the interstrand purine-purine stacks.

Base Pairing↗

PubMed1998

Main-chain dynamics of cardiotoxin II from Taiwan cobra (Naja naja atra) as studied by carbon-13 NMR at natural abundance: delineation of the role of functionally important residues.

Cardiotoxin analogue II (CTX II) is an all beta-sheet, small molecular mass (6.8 kDa), basic protein possessing a wide array of biological properties. Nearly complete assignment of the protonated carbon resonances has been achieved by heteronuclear NMR experiments. The study shows that the correlation between the carbon-13 chemical shifts and CTX II structure is good in general, but interesting deviations are also noticed. To characterize the internal dynamics of CTX II, longitudinal, transverse relaxation rates and heteronuclear 13C{1H} NOEs were measured for alpha-carbons at natural abundance by two-dimensional NMR spectroscopy. Relaxation measurements were obtained in a 14.1 T spectrometer for 50 residues, which are evenly spread along the CTX II polypeptide chain. Except for five alpha-carbons, all data were analyzed from a simple two-parameter spectral density function using the model free approach of Lipari and Szabo. The microdynamical parameters (S2, taue, and Rex) were calculated with an overall rotational correlation time (taum) for the protein of 4.8 ns. For most residues, the alpha-carbons exhibit fast (taue < 30 ps) restricted libration motions (S2 = 0.79-0.89). The present study reveals that the functionally important residues located at the tips of the three loops are flexible, and the flexibility of residues in this region could be important in the binding of cardiotoxins to their putative "receptors" which are postulated to be located on the erythrocyte membrane. In addition, the results obtained in the present study support the earlier predictions on the relative role of the lysine residues in the erythrocyte lytic activity of cardiotoxins.

Amino Acid Sequence↗

PubMed1998

Local helix content and RNA-binding activity of the N-terminal leucine-repeat region of hepatitis delta antigen.

Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B virus (HBV) which provides the surface antigen for the viral coat. Our results show that the N-terminal leucine-repeat region of hepatitis delta antigen (HDAg), encompassing residues 24-50, binds to the autolytic domain of HDV genomic RNA and attenuates its autolytic activity. The solution conformation of a synthetic peptide corresponding to residues 24-50 of HDAg as determined by two-dimensional 1H NMR and circular dichroism techniques is found to be an alpha-helix. The local helix content of this peptide was analyzed by NOEs and coupling constants. Mutagenesis studies indicate that Lys38, Lys39, and Lys40 within this alpha-helical peptide may be directly involved in RNA binding. A structural knowledge of the N-terminal leucine-repeat region of HDAg thus provides a molecular basis for understanding its role in the interaction with RNA.

Amino Acid Sequence↗

PubMed1998

Infection and atherosclerosis--focus on cytomegalovirus and Chlamydia pneumoniae.

BACKGROUND AND OBJECTIVE: Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections. This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (i.e, cytomegalovirus and Chlamydia pneumoniae) in atherogenesis, and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to infectious agents and coronary atherosclerosis. STUDY SELECTION AND DATA EXTRACTION: Relevant seroepidemiologic and pathologic studies and animal models evaluating the role of cytomegalovirus or C. pneumoniae in coronary atherosclerosis. DATA SYNTHESIS: Studies evaluating the possible role of cytomegalovirus and C. pneumoniae in the pathogenesis of atherosclerosis, as well as studies examining the use of antimicrobial and antiviral agents for reduction of cardiovascular events, are reviewed and critiqued. CONCLUSIONS: Current data do not allow us to determine whether infection is a cause or a cofactor of atherosclerosis. These uncertainties can be resolved by larger scale seroepidemiologic, pathologic, and interventional studies. Such efforts will contribute to identifying populations that are appropriate for particular surveillance or specific interventions, such as antibiotics or antiviral therapy.

Animals↗

PubMed1997

SH3 domain of Bruton's tyrosine kinase can bind to proline-rich peptides of TH domain of the kinase and p120cbl.

X-linked agammaglobulinemia (XLA), an inherited disease, is caused by mutations in the Bruton's tyrosine kinase (BTK). The absence of functional BTK leads to failure of B-cell differentiation; this incapacitates antibody production in XLA patients, who suffer from recurrent, sometimes lethal, bacterial infections. BTK plays an important role in B-cell development; it interacts with several proteins in the context of signal transduction. Point mutation in the BTK gene that leads to deletion of C-terminal 14 aa residues of BTK SH3 domain was found in a patient family. To understand the role of BTK, we studied binding of BTK SH3 domain (aa 216-273, 58 residues) and truncated SH3 domain (216-259, 44 residues) with proline-rich peptides; the first peptide constitutes the SH3 domain of BTK, while the latter peptide lacks 14 amino acid residues of the C terminal. Proline-rich peptides selected from TH domain of BTK and p120cbl were studied. It is known that BTK TH domain binds to SH3 domains of various proteins. We found that BTK SH3 domain binds to peptides of BTK TH domain. This suggests that BTK SH3 and TH domains may associate in inter- or intramolecular fashion, which raises the possibility that the kinase may be regulating its own activity by restricting the availability of both its ligand-binding modules. We also found that truncated SH3 domain binds to BTK TH domain peptide less avidly than does normal SH3 domain. Also, we show that the SH3 and truncated SH3 domains bind to peptide of p120cbl, but the latter domain binds weakly. It is likely that the truncated SH3 domain fails to present to the ligand the crucial residues in the correct context, hence the weaker binding. These results delineate the importance of C-terminal in binding of SH3 domains and indicate also that improper folding and the altered binding behavior of mutant BTK SH3 domain likely leads to XLA.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed1997

Immunolocalization of the pseudorabies virus immediate-early protein IE180 by immunoperoxidase staining.

The immediate-early (1E) gene of pseudorabies virus (PRV) expresses immediately upon infection, a phosphorylated protein (immediate-early protein, IE180) that can transactivate viral other genes and plays an essential role in regulating viral gene expression. In order to detect and localize IE180 in infected cells early on, this gene was cloned for overexpression, and the expressed products were applied to generate specific antibodies against IE180 protein. Two recombinant expression plasmids pN and pNB were constructed by cloning the IE gene onto pET 30a(+) expression vector via NcoI and BamHI sites. Plasmid pN contains the 1.8-kb NcoI-NcoI fragment of IE gene coding for the N-terminus of 616 amino acid residues, while pNB contains the 2.8-kb NcoI-Bam HI fragment coding for the rest of the IE180 protein. Both pN and pNB were transformed, respectively, into E. coli cells and produced large amounts of IE protein products during induction with 1 mM IPTG. The expressed IE proteins for pN and pNB were 60 kDa and 100 kDa in size, respectively. These expression products were purified and then used as antigens to immunize mice for preparing specific antibodies against PRV IE180 protein. The specificities of the mice immune sera were confirmed by their abilities to react with IE180 protein present in the PRV infected cells in the Western immunoblotting assay. Furthermore, immunoperoxidase staining of PRV infected cells undertaken with these antisera revealed the subcellular distribution of the IE proteins in the infected cells and also demonstrated their transportation from the cytoplasm to the nucleus during infection.

Animals↗

PubMed1997

Current perspective on the use of angiotensin-converting enzyme inhibitors in the management of coronary (atherosclerotic) artery disease.

OBJECTIVE: To review the pathophysiology of atherosclerosis, the role of the renin-angiotensin system in atherogenesis, and studies supporting the potential beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular events with long-term use. BACKGROUND: Through its action in converting angiotensin I to angiotensin II and by degrading bradykinin, local tissue ACE exerts many effects that can contribute to the development of atherosclerosis. Therefore, the use of ACE inhibitors can possibly result in antiatherogenic effects. Possible mechanisms for antiatherogenic effects of ACE inhibitors include: (1) reduction of blood pressure; (2) antiproliferative and antimigratory effects on vascular smooth muscle cells, neutrophils, and monocytes; (3) restoration of endothelial function; (4) stabilization of fatty plaque by preventing vasoconstriction; (5) antiplatelet effects; and (6) enhancement of endogenous fibrinolysis. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to the use of ACE inhibitors and atherosclerosis. STUDY SELECTION AND DATA EXTRACTION: Relevant human studies examining the role of ACE inhibitors and atherosclerosis. DATA SYNTHESIS: Studies evaluating the possible beneficial effects of ACE inhibitors in the development of atherosclerosis are reviewed and critiqued. Design of ongoing studies with clinical and surrogate end points are discussed. CONCLUSIONS: Based on current published studies, recommendations are made regarding the use of ACE inhibitors in atherosclerosis. Therapeutic monitoring parameters for efficacy and adverse effects are also reviewed.

Angioplasty, Balloon, Coronary↗

PubMed1996

Hairpin loops consisting of single adenine residues closed by sheared A.A and G.G pairs formed by the DNA triplets AAA and GAG: solution structure of the d(GTACAAAGTAC) hairpin.

The DNA undecamers GTACAAAGTAC (AAA 11-mer) and GTACGAGGTAC (GAG 11-mer) have been studied in solution by high-resolution NMR spectroscopy. Both duplexes form stable hairpins containing single deoxyadenosine loops and stems containing five base-pairs that are closed at the loop end by sheared AxA and GxC pairs, respectively. These molecules thus contain new AAA and GAG loop turn motifs. All protons, including the chiral H5'/H5" protons of the loop residues, were assigned using NOESY, DQF-COSY and heteronuclear 1H-31P COSY experiments. The backbone torsion angles were constrained using experimental data from NOE crosspeaks, three-bond 1H-1H coupling constants and four-bond 1H-31P coupling constants and four-bond 1H-31P coupling constants. The AAA and GAG 11-mers form similar structures in solution. The detailed structure of the AAA 11-mer was determined by the combined use of NMR, distance geometry and energy minimization methods. This structure exhibits good stacking of the loop adenosine base on the closing 5Ax7A sheared pair, with the 6A base stacking on the 5A base and the 6A deoxyribose stacking with the 7A base. All sugars in the AAA 11-mer hairpin adopt the typical DNA C2'-endo conformation and a sharp backbone turn occurs between residues 6A and 7A. This loop turn is brought about mainly by a change in the backbone phosphate torsion angles from zeta(g-) alpha(g-) to zeta(g+) alphat(g+) at the turn. The gamma torsion angle of residue 7A in the closing sheared pair also changes from gauche+ to trans. In Pu1NPu2 loop turns of the GCA, AAA and GAG types, the chemical shift of the H4' proton of the loop deoxyribose depends on the nature of Pu2; this reflects the stacking of the loop sugar on the Pu2 base and the different ring current effects of A or G in this position.

Adenine↗

PubMed1996

Stability and folding of the SH3 domain of Bruton's tyrosine kinase.

Bruton's tyrosine kinase (BTK) plays an important role in B cell development. Deletion of C-terminal 14 amino acids of the SH3 domain of BTK results in X-linked agammaglobulinemia (XLA), an inherited disease. We report here on the stability and folding of SH3 domain of BTK. Peptides corresponding to residues 216-273 (58 residues) and 216-259 (44 residues) of BTK SH3 domain were synthesized by solid phase methods; the first peptide constitutes the entire SH3 domain of BTK while the latter peptide lacks 14 amino acid residues of the C-terminal. The 58 amino acid peptide forms mainly a beta-barrel type folding unit. Although small and lacking disulfide bonds, this peptide is extremely stable to thermal denaturation. Based on circular dichroism measurements, its melting temperature was found to be high, 82 degrees C at pH 6.0. However, the Gibbs free energy (delta GH2O) of the intrinsic stability and thermodynamic spontaneity of unfolding were found to be low, 2.6 kcal/mol by Gdn.HCl denaturation experiments, as compared to 12 kcal/mol obtained for larger single domain proteins, indicating poor stability of SH3 domain. Addition of 500 mM of Na2SO4 increased the free energy change delta GH2O to 4.0 kcal/mol, suggesting an ionic strength effect. The truncated peptide fails to fold correctly and adopts random coil conformation in contrast to 58 amino acid beta-barrel peptide, which exhibits high thermal stability but normal or low stability at ambient temperature. These results, to our knowledge the first to delineate the importance of C-terminal in structural integrity of SH3 domains, indicate also that improper folding and/or poor stability of mutant SH3 domain in BTK likely causes XLA.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed1995

Conformation of the propeptide domain of factor IX.

The propeptide domain in the precursor forms of blood clotting proteins contains the recognition sequences for gamma-carboxylase. In hemophilia B, several point mutations in this propeptide domain are responsible for the inherited disease. A peptide containing the propeptide sequence of factor IX was synthesized by solid phase methods. Two dimensional 1H-NMR and CD studies indicate that this peptide motif adopts an alpha-helical structure in a 40% trifluoroethanol-containing aqueous solution. The results suggest that the amphipathic alpha-helix within the propeptide domain of factor IX could create a recognition surface for gamma-carboxylase. The influences of mutations and their relationship with the alpha-helical structure are discussed.

1-Carboxyglutamic Acid↗

PubMed1995

Effects of renal function on recainam pharmacokinetics and pharmacodynamics.

OBJECTIVES: To investigate the pharmacokinetics and pharmacodynamics of recainam, an investigational class I antiarrhythmic agent, in subjects with various degrees of renal function. METHODS: This single-dose open-label study was carried out at the Clinical Research Center of the University of Pennsylvania Hospital. Twenty-six volunteers participated in the study (group 1, glomerular filtration rate [GFR] < 15 ml/min; group 2, GFR 15 to 50 ml/min; group 3, GFR > 50 ml/min). After a single 400 mg oral dose, plasma samples were collected for the following 48 hours. Recainam pharmacokinetic parameters of apparent volume of distribution (Varea/F), apparent clearance (CL/F), elimination rate constant (ke), absorption rate constant (ka), lag-time (tlag), time to peak (tmax), and maximum concentration (Cmax) were determined with a least-squares regression program. The relationship between recainam concentrations and electrocardiographic intervals were determined with the sigmoidal maximum effect model. Measured GFR was correlated to CL/F with regression analysis. RESULTS: There were no significant differences found among groups in ka, tlag, tmax, and Varea/F. Significant differences were found in CL/F (114.4 +/- 32.7, 319.4 +/- 129.2, and 795.9 +/- 341.8 ml/min, group 1 versus group 3 and group 2 versus group 3, p < 0.05), Cmax (3.54 +2- 0.81, 1.77 +/- 0.53, and 1.63 +/- 0.66 micrograms/ml, group 1 versus group 2 and group 1 versus group 3, p < 0.01), and ke (0.074 +/- 0.025, 0.137 +/- 0.124, and 0.352 +/- 0.300, group 1 versus group 3, p < 0.05). Recainam CL/F was highly correlated with GFR (r = 0.67, p = 0.001). Approximately 8.9% +/- 3.8% of a recainam dose was eliminated during a 4-hour hemodialysis period. There was a trend (but not statistically significant) of increasing maximum percentage change in PR interval and the effective recainam concentration that produces half of its maximum effect (EC50) in group 1. CONCLUSION: Recainam dosing adjustment is required in renal impairment. Recainam is not dialyzed to a significant extent. Further studies are required to fully characterize the pharmacodynamic profile of recainam.

Administration, Oral↗

PubMed1995

Possible inhibition of hepatic metabolism of quinidine by erythromycin.

OBJECTIVE: To present and analyze a patient case illustrating a possible drug interaction between quinidine and erythromycin. METHODS: This is a case report of one hospitalized patient. The setting for this analysis was a university hospital. Through a MEDLINE search of all English medical literature (1966 to 1994) documenting possible interactions between quinidine and erythromycin, retrospective patient chart review, and analysis of the relationship between serum quinidine concentrations and significant clinical events, deduce the possibility of a quinidine and erythromycin pharmacokinetic and pharmacodynamic interaction in this particular patient case. RESULTS: This case demonstrated a probable erythromycin-quinidine pharmacokinetic interaction that led to a decrease in quinidine apparent clearance, an increase in quinidine serum concentrations, and a possible quinidine toxicity. CONCLUSION: Serum quinidine concentrations, electrocardiograms, and other factors that may predispose patients to torsades de pointes, such as hypokalemia and hypomagnesemia, should be monitored closely if quinidine is coadministered with erythromycin.

Aged↗