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A Mandelbaum

Publications and source records attributed to A Mandelbaum.

At least 19 recordsLinked to original sources
PubMed2001

Structural assignment of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids by liquid chromatography electrospray and atmospheric pressure chemical ionization tandem mass spectrometry.

Positionally isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids give rise to similar electrospray ionization (ESI) and atmosphere pressure chemical ionization (APCI) mass spectra, which show very abundant MH(+) ions and negligible fragmentation. The MH(+) ions of these isomeric acids exhibit notably different behavior under collision-induced dissociation (CID) conditions. The acids with a sulfonic group at position 8' in the quinoline moiety, adjacent to the N-atom, exhibit highly abundant [MH - H(2)SO(3)](+) ions (m/z 272 for the mono- and m/z 352 for the disulfonic acids), which are of lower abundance in the CID spectra of isomers with the SO(3)H group at other positions, remote from the nitrogen atom. The latter isomers undergo efficient eliminations of SO(3) and HSO(3). The isomeric diacids with one SO(3)H group at position 4 of the indene-1,3(2H)-dione moiety, adjacent to one of the carbonyl groups, undergo highly efficient elimination of H(2)O. Mechanistic pathways, involving interactions between adjacent groups, are proposed for the above regiospecific fragmentations. Pronounced different behavior has been also observed in negative ion tandem mass spectrometric measurements of the sulfonic acids. The distinctive behavior of the isomeric acids was strongly pronounced when the measurements were performed with an ion trap mass spectrometer (LCQ), and much less so with a triple-stage quadrupole instrument (TSQ).

Coloring Agents↗
PubMed1999

Intramolecular proton transfers in stereoisomeric gas-phase ions and the kinetic nature of the protonation process upon chemical ionization

The isobutane chemical ionization (CI) mass spectra of cis- and trans-1-butyl-3- and -4-dimethylaminocyclohexanols and of their methyl ethers exhibit abundant [MH - H(2)O](+) and [MH - MeOH](+) ions respectively. On the other hand, only the MH(+) ions of the cis-isomers exhibit significant [MH - H(2)O](+) and [MH - MeOH](+) ions under collision-induced dissociation (CID) conditions. The non-occurrence of water and methanol elimination in the CID spectra of the trans-isomers indicates retention of the external proton at the dimethylamino group in the MH(+) ions that survive after leaving the ion source and the first quadrupole of the triple-stage quadrupole ion separating system, and the trans-orientation of the two basic sites does not allow proton transfer from the dimethylamino group to the hydroxyl or methoxyl. Such transfer is allowed in the cis-amino alcohols and amino ethers via internal hydrogen-bonded (proton-bridged) structures, resulting in the elimination of water and methanol from the surviving MH(+) ions of these particular stereoisomers upon CID. The abundant [MH - ROH](+) ions in the isobutane-CI mass spectra of the trans-isomers indicates protonation at both basic sites, affording two isomeric MH(+) ions in each case, one protonated at the dimethylamino group and the other at the less basic oxygen function. These results show that the isobutane-CI protonation of the amino ethers and amino alcohols is a kinetically controlled process, occurring competitively at both basic sites of the molecules, despite the large difference between their proton affinities ( approximately 25 and approximately 35 kcal mol(-1); 1 kcal = 4.184 kJ). Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1999

P-glycoprotein expression is not a useful predictor of acute or chronic kidney graft rejection.

Because of the role of P-glycoprotein (P-gp) in multidrug resistance (MDR), it has been suggested that P-gp might play a role in acute and chronic rejection after organ transplantation. The purpose of the present work was to investigate a possible relationship between graft outcome and P-gp expression on peripheral mononuclear cells of renal transplant recipients. We determined P-gp expression in 27 patients with long-term, stable graft function (ST) and in 15 patients with chronic deterioration of graft function (CR). In addition, 40 patients were studied prior to, and at intervals after, transplantation with 21 healthy individuals serving as controls. P-gp values were highest in healthy controls and in ST patients. We found no correlation between P-gp values and acute rejection. CR patients tended to have lower levels of P-gp expression. Our results contradict the opinion that an overexpression of P-gp induces acute or chronic rejection by inhibiting the efficacy of immunosuppressive treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Altered vascular reactivity following partial nephrectomy in the rat: a possible mechanism of the blood-pressure-lowering effect of heparin.

BACKGROUND: This study was designed to assess whether the antihypertensive effect of heparin in rats after renal mass reduction (RMR) is related to changes in nitric oxide activity, and to study in vitro the altered behaviour of resistance-sized arteries induced by chronic administration of heparin. METHODS: Male Wistar rats were assigned to one of two experimental protocols. In the first protocol, RMR rats received heparin (250 units/day s.c.) and tail systolic blood pressure (SBP) was measured weekly for 4 weeks. In a subgroup, urinary nitrate excretion (UNO3) and in vitro vascular reactivity of isolated perfused mesenteric arterial beds were measured 2 weeks after RMR. The second protocol assessed whether inhibition of NO synthesis with L-NAME (70 mg/l added to the drinking water) prevents the blood-pressure-lowering effect of heparin. RESULTS: In untreated RMR rats SBP increased from 111+/-3 mmHg to 127+/-5 mmHg at 2 weeks and 139+/-5 mmHg at 4 weeks. In contrast, in RMR rats treated with heparin, SBP was 114 +/-3 mmHg at 2 weeks and 115+/-4 mmHg at 4 weeks (P<0.05 for both). Treatment with L-NAME increased SBP both in untreated and heparin-treated RMR groups. Two weeks after nephrectomy daily urinary nitrate increased significantly more in RMR rats treated with heparin than in untreated RMR rats (22+/-2 vs 14.2+/-2.3 micromol/day, P<0.05). In vitro studies performed at 2 weeks showed that vessels of untreated RMR rats had a blunted vasodilator response to acetylcholine that was restored to levels similar to that of controls in the heparin-treated group. CONCLUSIONS: These results suggest that, in rats after renal ablation, heparin may exert its antihypertensive effect, at least in part, by affecting the altered behaviour of resistance vessels during the development phase of hypertension. Increased NO production may contribute to this effect.

Animals↗
PubMed1999

Role of thromboxane in the altered vascular reactivity of pregnant rats with adriamycin nephropathy.

BACKGROUND: Pregnant rats with adriamycin nephropathy (ADRP rats) develop hypertension and have an increased vascular reactivity to noradrenaline in the isolated mesenteric bed in vitro. We have shown previously that the administration of daltroban, a specific thromboxane receptor antagonist, prevented hypertension in ADRP rats. METHODS: We measured the effect of daltroban (10(-5) mol/l) on the vasoconstrictory response to noradrenaline (1-10 micromol/l) in the isolated mesenteric bed of ADRP rats at the end of pregnancy, as compared with normal pregnant and adriamycin-treated virgin rats. In further experiments, we measured the changes of flow induced by increasing concentrations of the thromboxane analogue, U46619 (10(-7)-10(-6) mol/l). Finally, changes of flow were assessed in arteries maximally constricted with U46619 (10(-6) mol/l), during perfusion in the presence of increasing concentrations of daltroban (10(-7)-10(-5) mol/l). RESULTS: Daltroban diminished the response to noradrenaline in all groups, shifting the concentration-effect curve to the right. However, at maximal concentrations of noradrenaline, daltroban was ineffective in all rats, except in ADRP animals. The vasoconstrictory response to U46619 was significantly reduced in all pregnant rats, both normal and adriamycin-treated. Daltroban progressively released the vasoconstriction induced by U46619 in all groups. However, this vasodilator response was attenuated in the adriamycin-treated rats, the slopes of their curves being smaller than those of the respective untreated groups (0.038 +/- 0.006 in virgin rats vs 0.063 +/- 0.011 in controls, P < 0.05; and 0.015 +/- 0.005 in ADRP vs 0.028 +/- 0.008 in normal pregnancy, P < 0.05). CONCLUSIONS: The findings could be explained by enhanced occupancy of thromboxane receptors by an endogenous agonist, possibly PGH2, as a consequence of either increased levels of the autacoid or increased number of affinity receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Hypertension in the transplanted patient.

Hypertension is a common finding after renal transplantation, and it has a variety of underlying mechanisms. One reason is the type of immunosuppressive therapy, with a higher prevalence of hypertension in cyclosporine-treated patients. Cyclosporine interferes with several humoral and neural systems which are involved in blood pressure regulation such as the renin-angiotensin system, endothelins, nitric oxide, prostaglandins and the sympathetic nervous system. Other pathomechanisms for posttransplant hypertension are uncontrolled renin secretion of the native kidneys, polycythemia, recurrence of renal disease in the graft and renal failure. Renal transplant artery stenosis is a potentially treatable cause of post-transplant hypertension and several techniques such MRT angiography, Doppler sonography and conventional angiography are available. The diagnosis and treatment of hypertension are of high importance in general for the transplanted patient, and especially for the long-term prognosis of graft function.

Female↗
PubMed1998

Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients.

Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares the pharmacokinetics of MPA and its major metabolite MPA glucuronide (MPAG) in pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those of adults on the currently recommended oral dose of 1 g of MMF twice a day. Concentration-time profiles of 18 children (age, 10.7+/-0.72 yr; range, 5.9 to 15.3 yr) and 10 adults were investigated 1 and 3 wk after transplantation. Plasma concentrations of MPA and MPAG were measured by reverse-phase HPLC. Because MPA is extensively bound to serum albumin and only the free fraction is presumed to be pharmacologically active, the MPA free fraction was also analyzed by HPLC after separation through ultrafiltration. The areas under the concentration-time curves (AUC0-12) of total and free MPA throughout the 12-h dosing interval in children were, in general, comparable to the corresponding data in adult patients. The mean AUC0-12 of MPA and free MPA did not change significantly over the first 3 wk after transplantation, but there was substantial intra- and interindividual variation. MPAG-AUC0-12 values in children with primary renal transplant dysfunction were threefold higher than in those with functioning transplants. Renal impairment had no consistent effect on total MPA-AUC0-12 values, but the MPA free fraction in children (median, 1.65%; range, 0.40 to 13.8%) was significantly (r2=0.46) modulated by renal transplant function and serum albumin levels. In conclusion, concentration-time profiles of pediatric renal transplant recipients administered 600 mg MMF/m2 body surface area twice a day are comparable to those in adults on 1 g MMF twice a day in the first 3 wk after transplantation. Renal impairment and decreased serum albumin levels led to an increase in the free fraction of MPA and the free MPA-AUC0-12 values. Because the pharmacologic activity of MPA is a function of unbound drug concentration, these findings might be relevant for the pharmacodynamic effects of MPA.

Adolescent↗
PubMed1996

Fragmentation of isomeric N-quinolinylphthalimides on electron impact ionization.

The isomeric 2-, 3-, 5-, 6- and 8-quinolinylphthalimides give rise to different electron impact ionization mass spectra, which permit easy distinction. The specific fragmentation process are rationalized in terms of proximity effects and stabilization of cyclic ion structures. Collision-induced dissociation spectra were used to support the proposed ion structures of major fragment ions.

Electrons↗
PubMed1996

Exercise activates renal dysfunction in hypertension.

A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance. Hypertensives with unilateral renovascular disease were studied in the continuing evaluation of the bilateral function disturbance. We examined 31 hypertensives with documented unilateral renovascular disease, all of whom had renography at rest and during 60 to 80 W ergometric exercise. An additional seven normotensives and 17 essential hypertensives served as controls, and had the same sequence of studies. All patients reported upon continued on to an infusion clearance with 131I-hippurate and 111In-diethylenetriamine pentaacetic acid to determine glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) at rest, and during 25 W ergometric exercise. Eighteen of 31 hypertensives with unilateral renovascular disease were found to have a bilateral-abnormal exercise renogram. Clearance examinations in these identified a prominent reduction of the GFR and a lesser decrease in the ERPF during exercise. Hypertensives with normal exercise renograms did not have the exercise mediated abnormal clearance pattern. Similar results were observed in the control population of essential hypertensives, 65% of whom developed the functional disturbance. The seven normotensives controls did not exhibit the exercise mediated function changes. We conclude that an exercise-mediated bilaterally occurring functional disturbance exists in certain hypertensives, who then have a bilateral-abnormal exercise renogram. Associated with this is a distinctly abnormal clearance during exercise which is characterized by a low filtration fraction.

Antihypertensive Agents↗
PubMed1996

Vena cava diameter measurement for estimation of dry weight in haemodialysis patients.

A correct estimation of volume status and so-called dry weight in dialysis patients remains a difficult clinical problem. Clinical status and chest X-ray are not sensitive enough, while invasively measured central venous pressures are not routinely available. Recently, the sonographic determination of the diameter and collapse of the inferior vena cava (IVC) has been proposed as a noninvasive method for estimating intravascular volume. We tried to evaluate the clinical relevance of this method in dialysis patients by comparing it with central venous pressures (CVP) and atrial natriuretic peptide (ANP). To establish a normal range and to control for confounding variables, we examined a large number of healthy controls. Furthermore, the influence of tricuspid insufficiency was examined echocardiographically. Measurements of the IVC diameters were well reproducible, with a coefficient of variation for interobserver error of 2.2%, and a coefficient of variation of 1.4% for intraobserver error. The collapse index was less well reproducible and therefore not used for further analysis. In 86 normal controls (age 18 to 76 years), IVC diameters showed a wide variation, and they were not correlated to age, height, weight, or body surface area. However, there was a significant correlation of IVCex to heart rate (r = 0.63, P < 0.001). Therefore, we calculated percentiles of the heart rate-IVCex relation in normals, and compared the results in patients to these. In 10 overhydrated haemodialysis patients, CVP was closely correlated to IVCex (r = 0.72, P < 0.001), but there was a wide interindividual variation of the slope of this relation. An IVCex above the 95th percentile of normal was a good predictor of an elevated CVP (i.e. > 12 cmH2O). In another 39 stable, chronic haemodialysis patients, there was a significant correlation of the intradialytic decrease of ANP and IVCex (r = 0.69, P < 0.001). However, this correlation existed only in patients without tricuspid insufficiency. In summary, sonography of the inferior vena cava is a valuable tool for estimating dry weight in dialysis patients, provided that some caveats are kept in mind: (i) there is a wide variation of IVC diameters in normals, and single measurements are not helpful in individual patients; (ii) there is a significant, inverse correlation between IVC diameters and heart rate, and the precision of intravascular volume assessment is enhanced by interpreting heart rate corrected diameters; (iii) the presence of tricuspid insufficiency leads to unreliable results, as it influences IVC diameters per se. Intravascular volume changes are reflected by IVC measurements, as shown by the correlation to other indices of intravascular volume, such as CVP and alpha-hANP. IVC sonography is noninvasive and easily available; serial measurements allow an estimation of changes of intravascular volume in patients without cardiac filling impairment. However, unlike with body impedance, interstitial volume is not reflected by IVC diameters.

Adolescent↗
PubMed1995

Repeat exercise renograms in hypertension identify persistent renal dysfunction.

BACKGROUND: Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology. OBJECTIVE: To determine whether bilateral-abnormal exercise renograms are spurious phenomena, or whether the results of exercise renography are reproducible. DESIGN: We reviewed the renographic examinations of 27 hypertensive patients, each of whom had undergone at least one resting and two [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine gamma-camera exercise renograms. The status of the renal artery at the time of scintigraphy was documented, using available arteriograms. The causes of vascular lesions were noted, as were revascularization procedures and the antihypertensive medication being taken at the time of scintigraphy. RESULTS: The average time between exercise renograms was 15.5 months, and 24 of the 27 hypertensive patients had comparable results in the first and the follow-up exercise renogram, divergent results being noted for the other three patients. Re-evaluation of the scintigrams of the three hypertensive patients with divergent results suggested that intermittent pelvic retention might have caused errors of interpretation in two. We found it notable that neither revascularization nor a change in antihypertensive drug therapy influenced the results of exercise renography. Exercise renograms were reproducible over long periods, and potential extraneous influences on blood flow, such as antihypertensive drugs or revascularization, failed to alter the results. CONCLUSION: The results are considered relevant, because a direct relationship appears probable between hypertension and the disturbance investigated. Reproducible results suggest that the exercise-mediated disturbance is fixed to the kidneys, that it can be reactivated repeatedly and that it may play a role in maintaining hypertension.

Antihypertensive Agents↗
PubMed1994

Preparative separation of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids by pH-zone-refining counter-current chromatography.

The application of pH-zone-refining counter-current chromatography (CCC) to the preparative separation of stereoisomeric acids is described. The separation was accomplished on the basis of the difference in acidity of the two stereoisomers. pH-Zone-refining CCC of 400 mg of a crude synthetic mixture of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids yielded 49.5 and 40 mg of the pure Z- and E-stereoisomers respectively. The two-phase solvent system consisted of hexane-ethyl acetate-methanol-water (1:1:1:1). Trifluoro acetic and octanoic acids were used as retainer acids. The eluent base was aqueous ammonia. The eluted fraction were monitored by gas chromatography-mass spectrometry.

Carboxylic Acids↗