Urinary cyclic AMP response to bovine parathyroid hormone during treatment with neuroleptics

The urinary cyclic AMP response to bovine parathyroid hormone and urinary concentrating ability (max Uosm) after des-amino-D -arginine vasopressin were studies in nine volunteers and seven patients receiving long-term neuroleptic treatment. Max Uosm was lower in the patient group (770 ± 70 mosmol/kg) compared with the controls (948 ± 152 mosmol/kg) but the trend to a lower cAMP response to bovine PTH was not statistically significant. These results suggest that, although adenylate cyclase inhibition may contribute, other mechanisms are also important in the genesis of reduced uring concentrating ability in patients treated with psychotropic drugs.     

Use of Fmoc-N-(2-hydroxy-4-methoxybenzyl) amino acids in peptide synthesis

The use of N, O-bisFmoc-N-(2-hydroxy-4-methoxybenzyl) amino acid derivatives in the synthesis of peptides with difficult sequences has already been described. With these amino acid derivatives the reversible protecting group 2-hydroxy-4-methoxybenzyl (Hmb) for the backbone amide bonds of peptide chains is introduced, and thus the aggregation due to hydrogen-bond interchain association is inhibited. This paper describes the synthesis and use of Fmoc-N-(2-hydroxy-4-methoxybenzyl)amino acid derivatives as an alternative means of introducing Hmb backbone protection. These new monoFmoc derivatives were obtained in higher yield than the bisFmoc derivatives. Coupling yields to the amino peptide resin were the same as those obtained with bisFmoc derivatives, under the TBTU/HOBt/DIEA conditions. We also compared different syntheses of a difficult peptide with the Fmoc approach [triple coupling, capping, use of chaotropic agents, backbone protection using monoFmoc (Hmb)Ala] and with optimized Boc chemistry. Both the backbone protection and optimized Boc chemistry approaches gave the desired product in excellent yield and purity. © Munksgaard 1997.     

A randomized placebo-controlled study of enalapril in the treatment of erythrocytosis after renal transplantation

BACKGROUND: Erythrocytosis is a common complication of renal transplantationwith an incidence of up to 17%. It is associated with an increasedrisk of complications due to thromboembolic events and has traditionallybeen treated by intermittent venesection. More recently, angiotensin-convertingenzyme inhibitors have been shown to cause a fall in haematocritin a number of groups of subjects and some uncontrolled studieshave shown these drugs to be of possible therapeutic benefitin post renal transplant erythrocytosis. METHODS: We performed a randomized double-blind placebo-controlled studyin 25 patients with post-transplant erythrocytosis. Subjectsreceived either 2.5 mg of enalapril daily or a placebo for 4months and all patients completed the study period without anyserious adverse effects. RESULTS: Haematocrit fell from 52.7 (±SEM 0.7) to 47.1 (±1.8) at 1 month and 46.1 (± 1.2) after 4 months in patientsreceiving enalapril, with no change in the placebo group (P=0.004).We did not demonstrate any change in serum erythropoietin ineither group. CONCLUSION: Angiotensin-converting enzyme inhibitors are a safe and effectiveform of treatment for erythrocytosis developing after renaltransplantation. The mechanism of action, however, is not mediatedby changes in erythropoietin production and remains uncertain.     

Phase II trial of Didemnin B in patients with advanced renal cell carcinoma

Summary Twenty-three patients with advanced renal cell cancer were treated with Didemnin B. One partial response was achieved (5%) in 21 evaluable patients. An allergic reaction was noted in four patients including one patient with anaphylaxis. Didemnin B is not recommended in the treatment of renal cell carcinoma.     

BIOCHEMICAL CORRECTION IN THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA BY SEVERE DIETARY SALT RESTRICTION SUGGESTS RENIN-ALDOSTERONE SUPPRESSION CRITICAL IN PATHOPHYSIOLOGY

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.     

The 2,4-dinitrophenyl group for protection of hydroxyl function of tyrosine during solid-phase peptide synthesis

The facile thiolytic cleavage of the O-2,4-dinitrophenyl (Dnp) tyrosine bond was applied to the solid-phase synthesis of the 22-amino acid residue peptide H-Asp-Ala-Val-Tyr -Thr-Gly-Leu-Asn-Thr-Arg-Asn-Gln-Glu-Thr-Tyr -Glu-Thr-Leu-Lys-His-Glu-Lys-OH, corresponding to positions 62-83 in the chain of the type 1 receptor for Fc_ε, domains expressed on the rat mucosal-type mast cells (line RBL-2H3). A method for the spectrophotometric determination of insoluble O-Dnp as well as of unprotected phenolic moieties of tyrosine was developed. It is based on monitoring S-Dnp-2-mercaptoethanol, produced upon O-Dnp thiolysis by 2-mercaptoethanol. © Munksgaard 1995. Dedicated to the memory of Dr. Susumu Funakoshi, a dear friend and a leader in peptide chemistry.     

Effects of carvedilol on renal function

A randomized, double-blind, placebo-controlled study was conducted to study the effects of acute and chronic administration of carvedilol in essential hypertension, with special emphasis on renal haemodynamics and function. Acute administration of a single dose of 50 mg carvedilol reduced systolic and diastolic blood pressure without inducing reflex tachycardia. Renal blood flow was preserved; accordingly, renal vascular resistance was significantly reduced. A significant reduction in the glomerular filtration rate and filtration fraction was observed. Plasma renin activity (PRA) and plasma aldosterone values were not changed. Chronic carvedilol treatment produced a significant fall in systolic and diastolic blood pressure, heart rate, PRA and plasma aldosterone. Renal blood flow, glomerular filtration rate and filtration fraction also remained unchanged; renal vascular resistance decreased significantly. It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties, both acutely and after chronic treatment.     

Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF-α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow-up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF-α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF-α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow-up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.     

冠心病患者CRP水平与肾动脉狭窄的关系

【论文特点介绍】本研究观察了CRP是否可以作为肾动脉粥样硬化狭窄（ARAs）的独立危险因子。通过对危险因素进行多变量Logistic回归分析，结果表明年龄、冠脉病变严重程度、外周血管疾病是ARAS的独立危险因素，而CRP水平、高血压、高脂血症、肾功能不全并非ARAS的独立危险因素。