Effect of Mycophenolate Mofetil on Plasma Bioelements in Renal Transplant Recipients

The proper concentrations of plasma bioelements may favorably reduce the incidence of metabolic disorders, which often occur during immunosuppressive therapy. Mycophenolate mofetil (MMF) is currently one of the most frequently administered immunosuppressive agents; however, MMF treatment is often related to gastrointestinal side effects. The aim of this study was thus to verify whether the MMF treatment itself, or its metabolite pharmacokinetics, has an effect on the concentrations of plasma bioelements. To determine this, the effect of MMF on the levels of both major (sodium [Na], potassium [K], calcium [Ca], magnesium [Mg]), and trace (iron [Fe], zinc [Zn], copper [Cu]) plasma bioelements in 61 renal transplant recipients was assessed in comparison to a control group (n = 45). The pharmacokinetic parameters of mycophenolic acid were determined by the high-performance liquid chromatography method. All patients filled out a 24-h diet history questionnaire. The results showed high plasma concentrations of Fe and low plasma concentrations of Mg and Zn as compared with diagnostic norms. The patients treated with MMF had significantly lower plasma Na (P < 0.001) and significantly higher plasma Zn (P = 0.030) and Cu concentrations (P < 0.001). In conclusion, MMF treatment was found to affect plasma Fe, Zn, and Cu levels by increasing their concentrations while decreasing the plasma Na concentration. Mg and Zn deficiencies, as well as excessive Fe levels, are frequently observed irrespective of the immunosuppressive regimen applied, which suggests that monitoring of these bioelements may be favorable

Obesity and adiponectin after kidney transplantation

Obesity and hyperlipidaemia are found very frequently after kidney transplantation (Tx) and may represent independent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, a total of 68 obese transplant patients [body mass index (BMI)> 30 kg/m2] with dyslipidaemia over a period of 24 months. We compared the findings of a new therapeutic regimen 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with statins (atorvastatin 10–20 mg/day)) and followed-up for 2 years. All patients were on a regimen of cyclosporin A or tacrolimus and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (p<0.025) and an increase of the adiponectin level (p<0.01). Long-term therapy was associated with a significant decrease in serum leptin (p<0.01) and lipid metabolism parameters (p<0.01). Insulin clearance, mean systolic and diastolic blood pressure, proteinuria, lipoprotein(a) and apo-lipoprotein E isoforms did not differ significantly.Based on our results, we assume that obesity and hyperlipidaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), statins and long-term diet (IHHD). The increased level of adiponectin may be a marker of reducing atherosclerotic and chronic allograft nephropathy processes

Synthesis and biological activity of LH-RH antagonists modified in position 1

As part of our studies on the design of more potent antagonists of the LH-RH (luteinizing hormone-releasing hormone) decapeptide, twelve new highly soluble D-Arg 6-analogs have been synthesized. These peptides contain modifications in position 1 and are typified by the general formula (N-acetyl-X 1, D-p-Cl-Phe 2, D-Trp 3, D-Arg 6, D-Ala 10) LH-RH. We have found that a lypophilic, aromatic substituent is required in position 1 in order to elicit antiovulatory activity at a dose as low as 3 μg. The larger the hydrophobic amino acid (X: p-Br-Phe, β-Nal-2) in position 1, the higher is the antiovulatory activity that can be attained. Analogs with non-aromatic or hydrophilic amino acids (X: Gly, Leu, Arg, His, Glu) in position 1 generally have much lower activities in this series of LH-RH antagonists

ChemInform Abstract: SYNTHESIS OF D-PHE2, PHE3, D-PHE6-LH-RH, A POTENT INHIBITOR OF LH-RH

Die beiden Pentapeptide (I) und (II), deren Darstellung stufenweise unter Verwendung verschiedener Kupplungsmethoden erfolgt, werden nach der Azid‐Methode ko densiert

Distribution of 3H-α-MSH in rat brain

Radioactive synthetic α-MSH, prepared by selective tritiation of its dibromo-L-tyrosine 2-derivative, was injected into the carotid artery of intact, hypophysectomized or pinealectomized rats. More radioactivity was found in the occipital cortex, cerebellum, and pons-medulla than in most other brain parts of rats decapitated 15 sec and, to a less significant extent, 30 min after injection. Part of this radioactivity behaved like α-MSH in several identification procedures. After administration of 3H-tyrosine, the least radioactivity was consistently found in the pons-medulla. Large amounts of radioactivity after 3H-α-MSH were found in the pituitary and, particularly in the hypophysectomized rats, in the pineal. The half-time disappearance of the first component of radioactivity from the blood of each group of rats injected with tritiated-α-MSH was no more than 2.5 minutes, a time considerably shorter than the behavioral and EEG effects of this pituitary hormone on visual attention