Comparative serum prednisone and prednisolone concentrations following prednisone or prednisolone administration to beagle dogs

The relative serum prednisone and prednisolone concentrations were determined following the administration of prednisone or prednisolone as 5-mg tablets to male beagle dogs. Serum prednisone concentrations were significantly greater following prednisone administration than they were following prednisolone administration. Serum prednisolone concentrations were significantly greater following treatment with prednisolone than with prednisone. The combined prednisone and prednisolone areas under the serum concentration-time curves were similar for the two treatments.     

Development of radioimmunoassays for prednisone and prednisolone. Application to studies of hepatic metabolism of prednisone

Radioimmunoassays for measuring prednisone and prednisolone (delta1 corticosteroids) in serum have been developed. By using 6,7-3H-delta1 corticosteroids as tracer, rabbit antibodies against delta1 corticosteroid-21-hemisuccinate in bovine serum albumin, and ammonium sulfate precipitation, the assays detected less than 0.8 ng/ml of delta1 corticosteroid and interassay coefficients of variation were less than 8.5 %. The specificity of antibodies, tested against all drug metabolites and major endogenous steroids, showed that only 21-glucuronic acid esters of delta1 corticosteroids had cross-reactivity of possible clinical importance. Assays were validated by measuring levels in samples of fastingstate sera with or without adding known amounts of prednisolone. Measurements of serum concentrations of both prednisone and prednisolone in normal dogs and in those with hepatic vascular exclusion were made after intravenous administration of prednisone. Although high levels of prednisolone appeared rapidly in normal dogs, only slight amounts were measured in dogs with hepatic vascular exclusion, which emphasized the importance of the liver in the conversion of prednisone to prednisolone, its active metabolite.     

Molecular beacons: a new approach for semiautomated mutation analysis

IDDM is a polygenic and autoimmune disorder in which subsets of white blood cells (WBCs) are engaged in the destruction of beta-cells of the pancreas. The mechanisms that account for the abnormal behavior of these cells in IDDM are not fully understood. By measuring the mean length of telomeres of WBCs from patients with IDDM, we tested the concept that telomeres might play a role in IDDM. We examined the lengths of the terminal restriction fragments (TRFs) of DNA of WBCs from 234 white men comprising 54 patients with IDDM, 74 patients with NIDDM, and 106 control subjects. When adjusted for age, the TRF length from WBCs of patients with IDDM was significantly shorter than that of nondiabetic control subjects (mean +/- SE: 8.6 +/- 0.1 vs. 9.2 +/- 0.1, P = 0.002). No significant difference was observed between the TRF length from WBCs of patients with NIDDM versus nondiabetic subjects. Neither the duration nor the complications of IDDM (i.e., nephropathy and hypertension) had an effect on the TRF length of WBCs from patients with IDDM. The shortened TRF length of WBCs of patients with IDDM likely reflects a marked reduction in the TRF length of subsets of WBCs that play a role in the pathogenesis of IDDM.     

Collaborative study of a mineral oil method for the extraction of light filth from ground paprika

An official first action method for the extraction of light filth from spices, 44.A03--44.A05, was modified for the analyses of ground paprika. The sample is extracted with isopropanol and light filth is isolated from 40% isopropanol with mineral oil. Eight collaborators analyzed 4 paprika samples, 2 by the official method and 2 by the proposed method. Average recoveries of added elytral squares were 97 and 66%, respectively, for the proposed and official methods. Recoveries of added rodent hairs were 94 and 61%, respectively. The method has been adopted as official first action for the extraction of light filth from ground paprika.     

Effect of liquid diet on serum protein binding and prednisolone concentrations after oral prednisone

After prednisone (two 5 mg tablets) was given to each of six normal volunteers with water or with a liquid meal, standard pharmacokinetic parameters of prednisolone metabolism were similar, except that peak serum prednisolone concentrations occurred later after the meal. We conclude that prednisone can be given with a meal without significantly affecting the metabolism of prednisone or prednisolone.     

Reproducibility study of left ventricular measurements with breath-hold cine MRI using a semiautomated volumetric image analysis program

Measurement of exhaled nitric oxide (NO) may allow noninvasive assessment of inflammatory disease in the lung. We determined immediate and day-to-day reproducibility of single-breath NO measurements at different points on the exhaled test, and whether levels recorded reflect levels of NO in the lower airways. Using a rapid chemiluminescence analyser, 55 healthy control subjects performed three sequential tests on each of two days. NO levels were compared at the level corresponding with: 1) the time the mouth pressure fell below 4 cmH2O (MP); 2) the plateau of end-exhaled CO2 (CO2); and 3) the NO plateau (NOp). NO levels were measured directly from the lower airways of 15 lung transplant recipients and compared with NO levels from a single-breath test performed in the same cohort. For measurements performed at MP, CO2 and NOp, the mean +/- SD differences between the two closest levels performed on the same day were 0.11+/-0.18, 0.095+/-0.16 and 0.094+/-0.13 parts per billion (ppb), respectively, and between days were 0.18+/-0.76, 0.19+/-0.78 and 0.17+/-0.8 ppb, respectively. End-expiratory levels recorded at the mouth from a single-breath test and in the lower airways were highly correlated (mouth versus trachea r2=0.95, p<0.0001, mouth versus bronchus r2=0.92, p<0.0001). Single-breath exhaled nitric oxide levels are a simple, reproducible and valid measure of nitric oxide production from the lower respiratory tract.     

Retrospective analysis of alternate-day prednisone maintenance therapy for Crohn''s disease

INTRODUCTION: Clinical, microbiological, therapeutic and prognostic characteristics of brain abscesses were analyzed as well as the influence of CT in their evolution. MATERIALS AND METHODS: Retrospective study of 59 patients with the diagnosis of brain abscess of bacterial source before (group A) and after (group B) the introduction of CT (25 and 34 patients, respectively). RESULTS: The most common symptom was headache (76.3%) and the most common abnormality in physical examination was a decrease in the level of consciousness (61%) and this abnormality was associated with a higher mortality rate (13% versus 41.6%; p < 0.05) and also a higher proportion of neurologic sequelae (50% versus 85.7%; p < 0.05). The diagnosis was obtained earlier in group B. The hematogenous source predominated (32.2%); an adjacent source was identified in 28.8% and an apparent source was not recognized in 27.2% (40% in group A versus 17.6% in group B). Anaerobic and microaerophilic streptococci were the bacteria recovered most frequently. Gram-negative aerobic bacteria were the most common in otogenic abscesses. The use of corticosteroids had no influence upon mortality, but it was associated with a lower percentage of neurological sequelae (40% versus 14%; p < 0.05). The introduction of CT decreased mortality (40% in group A versus 23.5% in group B, although this difference was not significant) and also sequelae (86.6% in group A versus 57.6% in group B; p < 0.05). Leaving apart cases of bacterial endocarditis, in which death was due to the underlying heart disease and a systemic sepsis picture, mortality attributed to brain abscess was 20.3%. CONCLUSIONS: The introduction of CT has meant a significant breakthrough for the diagnosis, treatment and follow-up of these patients and has contributed to improvement in survival. In our series, the diagnosis of brain abscess was obtained earlier and the number of brain abscesses with no apparent source has decreased since the introduction of CT. Moreover, CT sensitivity is really good for locating multiple abscesses. Overall, the prognosis of these patients has improved since the introduction of this technique. Nevertheless, brain abscess is still associated with a relevant morbi-mortality rate.     

Robustness testing of a liquid chromatography method for the determination of vorozole and its related compounds in oral tablets

The robustness of a method for the determination of vorozole in oral tablets was examined by applying a two-level, seven factor Plackett-Burman statistical experimental design. Five method variables that are sensitive to variation, especially during method transfer, were evaluated for their influence on the system suitability criteria set in the method procedure and on the analysis time. The method variables were investigated in a specified range above and below the nominal method conditions. They included the concentration of an ion-pairing agent, the percentage organic modifier at the start of the linear gradient, the mobile phase flow rate, the percentage organic modifier at the end of the linear gradient and the pH of the mobile phase. Two dummy factors were included in the design to estimate the experimental error. It was found that none of the five studied variables affected significantly (t-test, alpha = 0.01) the capacity factor, the tailing factor or the analysis time. The resolution of the critical peak pair on the other hand, was significantly influenced by the factor pH. However, the responses for the resolution of all the experimental runs in the design were well above the system suitability limit stated in the normal assay procedure. Therefore, the method can overall be considered robust.     

Methylprednisolone versus prednisolone methylsulfobenzoate in pemphigoid: a comparative multicenter study

Bullous pemphigoid is a bullous skin disease associated with basal membrane antibodies. At present, the first treatment of these lesions is with corticosteroids. In this randomized study we compared the clinical results obtained with methylprednisolone (MePr) in 28 patients and with prednisolone methylsulfobenzoate (MsPr) in 29 patients. Both drugs were administered orally in daily doses of 1 to 1.5 mg/kg bodyweight. Three clinical data were examined: the number of bullous lesions, the intensity of pruritus and the extent of erythema after 5 then 10 days of treatment. After 10 days, the number of bullous lesions had decreased by 83 p. 100 with MePr and by 78 p. 100 with MsPr, and the decrease of pruritus had been significantly more pronounced in the MePr group than in the Ms group (p < 0.05). There had been no difference between treatments in the regression of erythema. Altogether, good results were obtained in 22/28 patients under MsPr (78.6 p. 100) and 18/29 patients under MePr (62.1 p. 100). This raises the question of the value of pharmacokinetic studies not only with these two corticosteroids, but also with prednisone which seems to be better absorbed.     

Automated analysis of warfarin sodium tablets

An automated procedure was developed for the determination of warfarin sodium by following the steps of the manual USP procedure. The automated procedure is applicable to single tablets and composites of 20 tablets at different tablet concentrations. Sensitivity, precision, accuracy, and reproducibility are equivalent to the manual USP procedure. Sensitivity was approximately 15 mug/ml, with a coefficient of variation of 0.711%.     

On the performance and cost-effectiveness of semiautomated Papanicolaou smear screening

The very rare case of leiomyoma sarcomatosum was presented and differentiated to "bizzare" leiomyoma at 39 years old woman, who was conservative preoperation diagnosis of uterine myoma. To get the after-operation prognosis the following elements of tumour have been studied: mitotic index, presence and type of necrosis, separation of the tumour and perivascular infiltration. A decision of conservative treatment was confirmed by shown world wide literature.     

Performance of a semiautomated Papanicolaou smear screening system: results of a population-based study conducted in Guanacaste, Costa Rica

Cardiovascular disease is one of the most common complications of dialysis and renal transplant patients, and high levels of AGE are present in end-stage renal failure. To address the potential involvement of AGE and growth factors in the pathophysiology of cardiovascular complications, we performed immunostaining using cardiac tissues from autopsy cases of patients on maintenance dialysis (10 cases), long-term surviving renal transplant patients with functioning grafts (8 cases), control subjects with normal renal function (7 cases) and non diabetic subjects with mild renal insufficiency (8 cases). We used two types of AGE-antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N epsilon-(carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CML-PA [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors and TGF beta. Positive 6D12 staining was observed in the coronary arterial walls and in macrophages. The accumulation of 6D12-reactive AGE in the coronary arterial walls of maintenance dialysis patients was significantly greater than that of control subjects (p < 0.05). Renal transplantation significantly reduced this accumulation (p < 0.05). On the other hand non-CML-PA mainly detected AGE in intracardiac arterioles and neural tissues. There was little difference in the accumulation of non-CML-AGE among the four groups. PDGFs and PDGF receptors were mainly detected in vascular endothelial cells and infiltrating cells of cardiac tissues of renal transplant patients, but not of maintenance dialysis patients. TGF beta was not detected in cardiovascular tissue of transplant patients. Our results indicated that the accumulation of oxidative AGE (CML-AGE) in the cardiac vascular tissue is one of the factors for cardiovascular complications of maintenance dialysis patients, and also that renal transplantation has a reducing effect on CML-AGE accumulation. PDGFs may be involved in the cardiovascular complications after renal transplantation.     

Antibiotic and prednisolone therapy of erysipelas: a randomized, double blind, placebo-controlled study

In the early eighties we found sex differences in the vomeronasal organ (VNO) and hypothesized that the vomeronasal system (VNS), a complex neural network involved in the control of reproductive behavior, might be sexually dimorphic. At that time sex differences had already been described for some structures that receive VNO input, such as the medial amygdala, the medial preoptic area, the ventromedial hypothalamic nucleus, and the ventral region of the premammillary nucleus. Since then, we have shown sex differences in the accessory olfactory bulb (AOB), the bed nucleus of the accessory olfactory tract (BAOT), and the bed nucleus of the stria terminalis (BST). When new VNS connections were found, all of them ended in nuclei that present sex differences. In general, sex differences in the olfactory system show two morphological patterns: one in which males present greater morphological measures than females, and just the opposite. To explain the morphometric measures of males in the latter, it has been hypothesized that androgens serve as inhibitors. Our work on the involvement of the GABA(A) receptor in the development of AOB and maternal behavior sex differences also suggests that neonatal changes in neuronal membrane permeability to the ion Cl- differences. This might be the first animal model to help us to understand the situation in which human genetic and gonadal sex do not agree with brain and behavioral sex. Finally, we stress that sex differences in the VNS constitute a neurofunctional model for understanding sex differences in reproductive behaviors.     

Collaborative study of a modified extraction procedure for lasalocid sodium in feeds by microbiological assay

A collaborative study was conducted on a modified extraction technique in the microbiological determination of lasalocid sodium in finished poultry feeds. The feed is warmed briefly with pH 4.7 buffer and the drug is extracted with ethyl acetate. The extract is washed with HCl and NaOH and evaporated to dryness, and the residue is dissolved in hexane, partitioned into methanol-water (3+1), and diluted to assay range at a final alcohol concentration of 25% (v/v). Seven laboratories participated in the study. Average recoveries of lasalocid sodium added at 0.01035, 0.00863, and 0.0069% ranged from 93 to 99% for mash feeds and from 86 to 95% for pellets. The coefficients of variation averaged 11.2% for mashes and 9.8% for pellets. The modified extraction technique has been adopted as official first action.     

Polyethylene glycol as a binder for tablets

Polyethylene glycol 6000 was evaluated as a binder for the direct compression of 11 tablet formulations. Six formulations compressed quite well, and the resulting tablets were satisfactory in all respects. To evaluate stability, actual shelflife studies were considered more appropriate than the accelerated studies. After a shelflife of 3 years, five of the six formulations were stable. The ascorbic acid formulation was stable for up to 18 months.