N,N'-Bis(methoxycarbonylmethyl)terephthalamide.
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Journal Article↗
Biomedical subjects
E Escudero
Publications and source records attributed to E Escudero.
Structure of a cyclic dimer of amino undecanoic acid as a model of folding and hydration in polyamides, polypeptides, and related substances.
Aliphatic amides are often used in the synthesis of peptidomimetic compounds. Here we present the structure of two cyclic dimers of aminoundecanoic acid as determined by x-ray diffraction. Each dimer contains two peptide groups and twenty methylene units. In one of the crystal structures, water is associated with the peptide groups, forming a chain of hexagons similar to those found in crambin, and in other protein and nucleic acid crystals. The aminoundecanoic rings show a fold at the peptide group, similar to either beta-turn type III or V found in proteins. Such folds are an adequate model for the peptide bond structure in nylon crystallites and peptidomimetic compounds.
Amino Acids, Cyclic↗
Antiproteinuric effect of calcium antagonists on puromycin-induced experimental nephrosis.
Calcium antagonists have a potential for beneficial effects on kidney function unrelated to their antihypertensive action. In this study we have investigated the efficacy of calcium antagonists compounds (verapamil, nifedipine and diltiazem) on reversible acute renal insufficiency, proteinuria and interstitial nephritis induced by the puromycin ammonucleoside (PAN). An increase in blood pressure (BP) was detected on day 14, with no statistical differences in the response to calcium antagonists. Serum creatinine concentration increased to 1.2 mg/dL on day 7 after PAN and decreased to 0.7 mg/dL at 14 days, calcium antagonists shortened the time required to reach baseline or control levels. Calcium antagonists also reduced proteinuria in the PAN-treated animals, in both day 7 and day 14. Differential effects of the antagonists were observed. Verapamil caused a greater reduction (p < 0.01) in proteinuria than nifedipine or diltiazem in day 7. Moreover, verapamil (p < 0.01) and nifedipine (p < 0.01) reduced the total number of interstitial infiltrating leukocytes from 690 to 120 and 425 positive cells/20 high power fields (x63) respectively, by contrast, diltiazem had no effect. We conclude that in this model of PAN nephropathy verapamil is more effective in reducing both proteinuria and the severity of acute interstitial nephritis than either nifedipine or diltiazem. The possible clinical implications of these results remain to be elucidated.
Animals↗
Distinct patterns of glomerular disease in Lima, Peru.
AIM: We performed both a retrospective and prospective study to elucidate the types of glomerular diseases present in adults in Lima, Peru. MATERIAL AND METHODS: In the retrospective study, we analyzed 1,263 renal biopsies over a 10-year period (1985 -1995) that were processed at a central reference renal pathology laboratory in Lima. 101 cases were examined in the prospective study. RESULTS: The most common glomerular diseases observed were those due to systemic lupus erythematosus (30.2%), membranoproliferative glomerulonephritis (MPGN, 14.8%), and focal and segmental glomerulosclerosis (FSGS, 13.9%). Although mesangial-proliferative nephritis was observed in 9.5% of cases, IgA nephropathy was rare (0.9%). Examination of the year to year frequency showed that MPGN has tended to decrease in frequency with time whereas FSGS has been increasing. Although there is known to be a high frequency of infections in Peru, only 4.2% of the cases in the retrospective study were associated with infection. Furthermore, in the prospective study, only one case of hepatitis C and no cases of hepatitis B viral infection were detected, including in the 11 cases of MPGN observed. CONCLUSION: We conclude that the epidemiology of glomerular disease in Lima, Peru, is distinct from most areas of the world, but has similarities to certain regions in Africa, in that MPGN is common whereas IgA nephropathy appears to be rare. Further studies are necessary to elucidate the reasons why the patterns of glomerular disease are different from that observed in other parts of the world.
Adult↗
Biliary elimination kinetics and tissue concentrations of oxytetracycline after intravenous administration in hens.
The pharmacokinetics of the biliary elimination of oxytetracycline (OTC) and tissue concentrations in certain organs were studied in 10 Leghorn hens. The animals were anaesthetized using xylazine/ketamine administered by the intramuscular (i.m.) route and were immobilized for right laparotomy. Both bile ducts were cannulated and a dose of 20 mg/kg of oxytetracycline hydrochloride was administered intravenously (i.v.). Samples of bile excreted were taken at predetermined intervals during 6 h. At 6 h animals were slaughtered and tissue samples of blood, liver, kidney, pancreas, spleen, heart, lung and pectoral muscle were taken. The values for OTC biliary elimination rate times were best fitted to a one-exponential equation. The maximum value for OTC biliary excretion rate (3.69+/-0.6 microg/min/kg) was reached at approximately 17.5 min (time to maximum concentration (tmax)). The first-order rate constant for the biliary excretion (k) and the half-life (t1/2) were 6.7x10(-3) min(-1) and 110.55 min, respectively. The mean value of area under the biliary excretion rate time curve (AUC) indicated that 839.77 microg/kg body weight (b.w.) were eliminated by the biliary route. The cumulative biliary excretion data indicated that approximately 4.20% of the dose was eliminated by this route, 3.28% being eliminated during the first 6 h and 0.92% thereafter. The highest mean concentrations were found in the kidney (35.82 microg/kg) and liver (16.77 microg/g). Significant differences were found between the concentrations of the various tissues studied. Plasma concentration was lower than that of the other tissues (except lung).
Algorithms↗
Pharmacokinetics of moxidectin and doramectin in goats.
The pharmacokinetic behaviour of doramectin after a single subcutaneous administration and moxidectin following a single subcutaneous or oral drench were studied in goats at a dosage of 0.2 mg kg(-1). The drug plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. Maximum plasma concentrations of moxidectin were attained earlier and to a greater extent than doramectin (shorter t(max) and greater C(max) and AUC than doramectin). MRT of doramectin (4.91 +/- 0.07 days) was also significantly shorter than that of moxidectin (12.43 +/- 1.28 days). Then, the exposure of animals to doramectin in comparison with moxidectin was significantly shorter. The apparent absorption rate of moxidectin was not significantly different after oral and subcutaneous administration but the extent of absorption, reflected in the peak concentration (C(max)) and the area under the concentration-time curve (AUC), of the subcutaneous injection (24.27 +/- 1.99 ng ml(-1) and 136.72 +/- 7.35 ng d ml(-1) respectively) was significantly greater than that of the oral administration (15.53 +/- 1.27 ng ml(-1) and 36.72 +/- 4.05 ng d ml(-1) respectively). The mean residence time (MRT) of moxidectin didn't differ significantly when administered orally or subcutaneously. Therefore low oral bioavailability and the early emergence of resistance in this minor species may be related. These results deserve to be correlated with efficacy studies for refining dosage requirements of endectocides in this species.
Administration, Oral↗
Clinicopathologic correlations in lupus nephritis in Lima, Peru.
BACKGROUND: We assessed whether immunohistologic markers for glomerular or tubulointerstitial injury might provide better correlations with ongoing renal function and disease activity as compared with the WHO classification or the NIH activity and chronicity indices in lupus nephritis. METHODS: Thirty-three patients with clinically defined systemic lupus underwent renal biopsy over a 1-year period at Hospital Loayza in Lima, Peru. Biopsy specimens were evaluated for macrophages, proliferating cells, alpha-actin expression, and type IV collagen deposition in both glomeruli and the tubulointerstitium and the results compared with the current WHO and NIH classifications in relation to the clinical presentation. RESULTS: Patients with WHO class IV lupus nephritis were more likely to have lower serum complements, greater proteinuria and hematuria, and worse renal function. An elevated NIH activity index correlated with microhematuria, proteinuria, and impaired renal function, whereas an elevated chronicity index correlated with renal function, hypertension, and microhematuria, but not with proteinuria. The presence of glomerular macrophages correlated with both glomerular alpha-actin expression and type IV collagen deposition, but did not correlate with renal function or proteinuria. In contrast, interstitial macrophages correlated not only with interstitial collagen deposition and myofibroblast accumulation, but also correlated with both renal function and the presence of nephrotic syndrome. CONCLUSIONS: Both the WHO classification and the NIH activity/chronicity indices correlate with clinical manifestations of lupus nephritis. While glomerular macrophage accumulation correlates with mesangial cell activation (alpha-actin expression) and collagen deposition, and interstitial macrophage accumulation correlates with interstitial fibroblast activation and collagen deposition, only interstitial macrophages correlate with renal function. Of particular interest will be future studies to determine whether these markers correlate with the prognosis.
Actins↗
Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to sheep.
The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.32+/-0.06 L/kg and 0.42+/-0.04 L/kg, respectively and the total body clearances were 0.69+/-0.07 and 0.38+/-0.03 L/kg x h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.32+/-0.05 h and 0.75+/-0.27 h, respectively, whereas for sulbactam the half-lives were 0.74+/-0.10 h and 0.89+/-0.16 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (72.76+/-9.65% for ampicillin and 85.50+/-8.35% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.25+/-0.10 h and 0.24+/-0.08 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.01+/-7.36 mg/L of ampicillin and 10.39+/-3.95 mg/L of sulbactam). Both drugs had a similar pharmacokinetic behavior after intramuscular administration in sheep. Since the plasma concentrations of sulbactam where consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a higher than 2:1 ratio.
Adsorption↗
Differential effects of antibodies to vascular cell adhesion molecule-1 and distinct epitopes of the alpha4 integrin in HgCl2-induced nephritis in Brown Norway rats.
Four distinct epitopes (A, B1, B2, and C) have been functionally defined on the human alpha4 integrin. In this study, two cross-reactive antihuman alpha4 monoclonal antibodies (mAb) (HP2/1 and HP2/4 specific for epitopes B1 and B2, respectively) were used to functionally characterize the rat VLA-4 subunit and to define similar functional epitopes in this rodent species. It was found that B1 and B2 anti-alpha4 mAb completely block adhesion to fibronectin, but the inhibition of adhesion to vascular cell adhesion molecule-1 (VCAM-1) with HP2/1 mAb was lower than with HP2/4 mAb. It was also observed that epitope B2 HP2/4 mAb induced homotypic aggregation in rat lymphocytes, whereas epitope B1 HP2/1 mAb did not. Using the HgCl2 model of nephritis, this study shows the protective effect of both anti-alpha4 mAb against infiltration of the renal interstitium by leukocytes. Nevertheless, HP2/1 mAb, but not HP2/4 mAb, virtually abolished the anti-glomerular basement membrane antibody synthesis and glomerular deposits. These findings indicate the dual but independent role played by alpha4 integrins in both extravasation of leukocytes and in the production of antibodies. Finally, this study demonstrates that anti-rat VCAM-1 mAb showed a positive reactivity of the renal vascular endothelium and, most importantly, that administration of anti-VCAM-1 antibodies completely abrogated the interstitial cell infiltrates without affecting anti-glomerular basement membrane antibody production. These results confirm the important role played by VLA-4/VCAM-1 pathway in leukocyte infiltration, and further support the dual and independent role of alpha4 integrins in both renal infiltration and autoantibody synthesis in this model of renal disease.
Analysis of Variance↗
Role of leucocyte adhesion molecules in aminonucleoside of puromycin (PAN)-associated interstitial nephritis.
Rats receiving a single dose (10 mg/l00 g body wt) of PAN develop severe proteinuria and acute interstitial nephritis. To investigate the mechanisms involved in interstitial leucocyte accumulation, we examined the expression of adhesion molecules on kidney tissue sections as well as on endothelial cell cultures. We also performed in vivo treatments with antibodies against adhesion molecules. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) was found on day 7 of the disease, when interstitial nephritis was first detected. Also, rat endothelial cells in culture showed maximal expression of ICAM-1 in the presence of 10(-9) - 10(-11) M PAN. Adhesion of peripheral blood mononuclear cells (PBMC) on kidney sections from PAN-treated rats was highest on day 7 (3.05 +/- 0.7 (mean +/- s.e.m.); controls 0.75 +/- 0.5). Such increased adhesion was notably blocked after PAN-treated rat kidney sections were incubated with anti-ICAM-1 MoAb (0.9 +/- 0.4). In addition, adhesiveness of PBMC to PAN-stimulated endothelial cells in culture was enhanced (25 +/- 2.5%; non-stimulated cells 13 +/- 3.1%). The addition of specific MoAbs against ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) produced a high blockage of adhesiveness induced by exposure to PAN (inhibition 58 +/- 3%; non-stimulated cells 40 +/- 7%). Simultaneous administration to PAN-treated rats of anti-LFA-1 and anti-ICAM-1 MoAbs reduced the number of interstitial cells by 70% compared with the 30% of reduction obtained when anti-very late antigen-4 (VLA-4) MoAb and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies were used. Our results suggest that the LFA-1/ICAM-1 pathway plays a principal role in the interstitial nephritis occurring in rats with PAN-nephrosis.
Animals↗
Pharmacokinetics of amoxicillin/clavulanic acid combination and of both drugs alone after intravenous administration to goats.
The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination (25 mg kg-1), and both drugs alone (amoxicillin 20 mg kg-1), clavulanic acid 5 mg kg-1), was studied after intravenous (i.v.) administration of single doses of 10 goats. The objective was to determine whether there were differences in the plasma kinetics of these drugs when administered in combination or alone. The plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. The disposition curves for both drugs alone and in combination were best described by a biexponential equation (two-compartment open model). The elimination half-lives of amoxicillin were 1.05 +/- 0.09 h alone and 1.13 +/- 0.19 h in combination, and those of clavulanic acid were 0.87 +/- 0.07 h and 0.85 +/- 0.09 h, respectively. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two treatments. Body clearances of amoxicillin were 0.12 +/- 0.01 l h-1.kg alone and 0.11 +/- 0.01 l h-1.kg in combination, and of clavulanic acid were 0.12 +/- 0.02 l h-1.kg alone and 0.12 +/- 0.01 l h-1.kg in combination with amoxicillin. The half-lives and body clearances of amoxicillin and clavulanic acid did not differ significantly when administered alone and in combination. It was concluded that the i.v. administration of amoxicillin and clavulanic acid as a combination product did not alter the disposition kinetics of either drug.
Amoxicillin↗
Single-dose pharmacokinetics of ampicillin/sulbactam (2:1) combination after intravenous administration to sheep and goats.
The pharmacokinetic behaviour of a combination of ampicillin and sulbactam (2:1) in six sheep and six goats after single intravenous doses of 20 mg kg body weight-1 (13.33 mg kg-1 of ampicillin and 6.67 mg kg-1 of sulbactam) was investigated by using a high-performance liquid chromatographic method for determining plasma concentrations. The objective was to determine whether there are differences between sheep and goats in the disposition kinetics of ampicillin and sulbactam. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs were best described by a biexponential equation (two-compartment open model) in both sheep and goats. The mean (SD) elimination half-lives of ampicillin were 0.32 (0.05) h in sheep and 0.32 (0.04) h in goats, and the half-lives of sulbactam were 0.74 (0.10) h and 0.79 (0.18) h in sheep and goats, respectively. The apparent volumes of distribution of ampicillin and sulbactam were similar in the two species. Mean (SD) body clearances of ampicillin were 0.69 (0.07) litre h-1 kg-1 in sheep and 0.72 (0.11) litre h-1 kg-1 in goats, and the body clearances of sulbactam were 0.38 (0.03) and 0.38 (0.07) litre h-1 kg-1 in sheep and goats, respectively. There were no significant differences between any of the pharmacokinetic parameters of ampicillin and sulbactam in the sheep and goats.
Ampicillin↗
Some pharmacokinetic parameters of ampicillin/sulbactam combination after intravenous and intramuscular administration to goats.
Some pharmacokinetic parameters of an ampicillin/sulbactam (2:1) combination were studied in six goats, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open two-compartment model. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.34 +/- 0.04 l/kg and 0.45 +/- 0.15 l/kg, respectively, and the total body clearances were 0.72 +/- 0.11 and 0.38 +/- 0.07 l/kg.h. The half-lives of ampicillin after intravenous and intramuscular administration were 0.32 +/- 0.04 h and 0.71 +/- 0.14 h, respectively. For sulbactam the half-lives were 0.79 +/- 0.18 h and 1.13 +/- 0.21 h after administration by the same routes. The bioavailability after intramuscular injection was high and similar for both drugs (98.29% for ampicillin and 101.84% for sulbactam). The mean peak plasma levels of ampicillin (0.43 +/- 0.27 h) and sulbactam (0.34 +/- 0.14 h) were reached at a similar time, and peak concentrations were also similar and non-proportional to the dose of the products administered (11.02 +/- 3.11 mg/l of ampicillin and 9.5 +/- 0.98 mg/l of sulbactam).
Ampicillin↗
The pharmacokinetics of a long-acting formulation of oxytetracycline in sheep and goats.
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Absorption↗
Pharmacokinetics of oxytetracycline after intravenous administration at two dose levels to hens.
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Animals↗
Comparative pharmacokinetics of an ampicillin/sulbactam combination administered intramuscularly in lactating sheep and goats.
The pharmacokinetic behaviour of an ampicillin/sulbactam (2:1) combination was studied after intramuscular administration of a single dose (20 mg/kg body weight: 13.33 mg/kg of ampicillin and 6.67 mg/kg of sulbactam) to six sheep and six goats. The objective was to determine whether there were differences between sheep and goats in the disposition profiles of ampicillin and sulbactam. The disposition curves for both drugs were best described by a biexponential equation (one-compartment open model with first order absorption) in both sheep and goats. The maximum plasma concentrations of ampicillin and sulbactam were similar in both sheep (10.61 +/- 6.36 and 9.17 +/- 3.82 mg/L respectively) and goats (11.02 +/- 2.69 and 9.25 +/- 0.85 mg/L respectively), in spite of the fact that the ampicillin dose was twice that of sulbactam. The time of the peak plasma concentration for both drugs was also similar in both sheep and goats. The elimination half-life of ampicillin was 0.81 +/- 0.17 h in sheep and 0.71 +/- 0.12 h in goats, and that of sulbactam was 1.02 +/- 0.36 h in sheep and 1.13 +/- 0.18 h in goats. The rate of drug removal from the body was faster in sheep than in goats and consequently the area under the curve was greater for goats. It was concluded that the similarity in the disposition and elimination of both drugs in sheep and goats indicated that the combination preparation could be administered at the same dosing rate in both species.
Ampicillin↗
[Blood pressure levels in young students. Correlation between body mass and metabolic and hemodynamic factors].
Blood pressure (BP) levels were measured in 450 students (mean age 20.8 +/- .11 years old) and were correlated with different parameters. Prevalence of arterial hypertension was, according to the JNC-V, 13% in males and 3% in females. The correlations between Body Mass Index (BMI) and BP levels were statistically significant either in males and females. Mean BP (MBP) increased 1.17 mmHg per unit of increase of BMI in males and 0.97 mmHg in females. According to the BP levels proposed by the JNC-V the male individuals were classified in three groups: optimal BP (OBP), high normal BP (HNBP) and hypertensives stage 1 (Hypert.). These groups had different BMI; OBP: 22.74 +/- 2; HNBP 24.4 +/- 0.48; Hypert. 25.06 +/- 0.66 kg/m2 (P < 0.05 Hypert. and HNBP as regards PAO; HNBP and Hypert. were not statistically different). Samples of each of these groups were taken in order to analyze other parameters such as: cardiac index (CI), total peripheral resistance (TPR), plasma glucose, plasma insulin, glucose/insulin ratio and intracellular pH in platelets. No significant differences were found in the three groups as regards plasma glucose, plasma insulin and glucose/insulin ratio. The different BP levels among the groups were due to an increase in CI: OBP 3.25 +/- 0.13; HNBP 3.76 +/- 0.2; Hypert. 4.76 +/- 36 ml/min/m2 (P < 0.05) but with TPR numerically "normal": OBP: 2139 +/- 106; HNBP 2170 +/- 114; Hypert. 1858 +/- 146 dynes sec. cm-5 m2 (NS). The intracellular pH in platelets was: 7.15 +/- 0.07 in the OBP, 7.21 +/- 0.05 in the HNBP and 7.33 +/- 0.04 in the Hypert. (P < 0.05 in the Hypert. as regards the PAO). The increase of the pHi in the Hypert. suggests hyperactive Na+/H+ exchanger.
Adult↗
Left ventricular diastolic function in young men with high normal blood pressure.
OBJECTIVE: Abnormalities in left ventricular (LV) diastolic filling have been reported in hypertensive patients. This study was designed to compare LV diastolic filling between individuals with high normal blood pressure (HNBP) and optimal blood pressure (OBP). SUBJECTS AND DESIGN: From a survey of 219 young male individuals (age 21 +/- 0.1 years), two groups were selected according to their BP (group A: systolic BP [SBP] 120 mmHg and diastolic BP [DBP] 80 mmHg, n = 23 and group B: SBP 130 to 139 mmHg and/or DBP 85 to 89 mmHg, n = 21). Subjects habits, anthropometric characteristics, LV structure and systolic and diastolic function were compared. RESULTS: No differences were detected between the two groups in habits, systolic function or early diastole. LV mass index (LVMI) was higher in group B (103.6 +/- 4.58 g/m2 versus 90.49 +/- 3.27 g/m2 in group A, P < 0.05), though the values were not high enough to indicate LV hypertrophy. The pattern of LV late filling was different between the two groups. The peak late diastolic flow velocity (A) was 0.45 +/- 0.02 m/s in group B and 0.52 +/- 0.03 m/s in group A (P < 0.05). The early peak velocity (E):A ratio was 1.82 +/- 0.08 in group A and 1.59 +/- 0.08 in group B (P < 0.05). The early filling fraction also demonstrated a significant shift to more prominent late diastolic filling in group B (0.68 +/- 0.01% versus 0.73 +/- 0.01% in group A, P < 0.05). This pattern in LV filling did not correlate to inheritance, age, sex, heart rate, habits or body mass index. CONCLUSIONS: This shift in filling pattern to a late flow in young men with HNBP seemed to be an early indicator of an increased dependence of LV filling on atrial contraction and may reflect an impairment in LV relaxation.
Adult↗