Long tube implants in the management of glaucoma

The design, surgical insertion and results of a plastic draining implant for severe glaucoma are reported. The need for pharmacological control of bleb inflammation is stressed and the favourable long-term outlook for patients with such implants is discussed.     

Circadian variations of the urinary excretion of catecholamines and electrolytes

Concomitant measurements of circadian variations in the urinary excretion of dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), epinephrine (E) as well as of creatinine, sodium and potassium under controlled dietary conditions during relative physical and emotional rest in 13 volunteers have shown that maximum excretion of all these substances occurred in the afternoon period between 14:30h and 18:00h, and minimum excretion in the morning between 4:00h and 5:00h. The changes were in some cases progressive from one collection period to the other, and synchronized for NE and E. DA and HVA excretions fluctuated from subject to subject. Excretory rhythms of sodium and potassium were found to be similar to those of the catecholamines. This can be explained by diurnal changes in renal blood flow and different renal excretory mechanisms of catecholamines. None of the catecholamines correlated with the urinary volume but urinary NE and E positively correlated with urinary creatinine, urinary NE and E with urinary DA and urinary sodium with urinary E. There are some common patterns in the diurnal rhythms of catecholamines and electrolytes but their interrelationship is different for individual catecholamines.     

Activation of protein kinase C potentiates postsynaptic acetylcholine response at developing neuromuscular synapses

1. Phorbol 12-myristate 13-acetate (TPA, 1 microM) and phorbol 12,13-dibutyrate (PDBu, 2 microM), activators of protein kinase C (PKC), increased the mean amplitude and decay time of the spontaneous synaptic currents of Xenopus nerve-muscle coculture, whereas, 4 alpha-phorbol (2 microM) which is an inactive phorbol analogue had no effect. 2. Staurosporine (0.5 microM) and H-7 (10 microM), inhibitors of PKC, inhibited the potentiation effects of TPA on the spontaneous synaptic currents. 3. Effects of TPA on the postsynaptic acetylcholine (ACh) sensitivity were examined by iontophoresis of ACh to the surface of embryonic muscle cells of 1-day-old Xenopus cultures. TPA increased both the amplitude and decay time of ACh-induced whole-cell currents in isolated myocytes. 4. TPA concentration-dependently increased the mean open time of low-conductance ACh channels but did not affect those of high-conductance ACh channels. PDBu but not 4 alpha-phorbol exhibited similar effects to TPA. Staurosporine and H-7 inhibited the increasing effects of TPA. 5. These results suggest that activation of PKC might be involved in synaptogenesis at developing neuromuscular synapses by the postsynaptic potentiation of ACh sensitivity.     

A new series of imidazolones: highly specific and potent nonpeptide AT1 angiotensin II receptor antagonists

Starting from the structure of the novel nonpeptide AT1 receptor antagonist DuP 753 (losartan), a new series of potent antagonists was designed. In these compounds the central imidazole nucleus was replaced by the dihydroimidazol-4-one structure. The most active compounds had a spirocyclopentane or a spirocyclohexane ring in position 5. Like the imidazole series, the best substituents were the linear butyl chain in position 1 and the [2'-(tetrazol-5-yl)biphenylyl]methyl group in position 3. Antagonistic activity was assessed by the ability of the compounds to competitively inhibit [125I]AII binding to the AT1 subtype receptor and to antagonize AII-induced contractions in rabbit aorta rings. The most active compounds had IC50 values in the nanomolar range. In conscious rats, compounds 4 and 21 antagonized the AII pressor response when administered orally. Compound 21 (SR 47436) was the most active; it was recently shown to also be active in cynomolgus monkeys both intravenously and orally. This molecule is now undergoing clinical trials for the treatment of hypertension.     

Folliculitis in Down's syndrome

Twenty-two male and 20 female adults with Down's syndrome were examined. Ten of the men and two of the women had a follicular rash consistent with Malassezia folliculitis. Oral itraconazole treatment produced a significant improvement in the rash, accompanied by a decrease in the skin Malassezia count. Clinical relapse occurred when therapy was discontinued, and was accompanied by return of the Malassezia yeasts.     

Action potential characteristics of rabbit papillary muscle

The ionic components of the action potential (AP) in rabbit right papillary muscle (RRPM) were determined by simple methods such as changes in external concentrations of sodium and calcium ions and addition of MnCl2 ot the perfusion fluid. Two components (fast and slow) were clearly visible in the upstroke of AP in normal Tyrode solution. MnCl2 (5 mmol/l) eliminated the slow component which forms the overshoot (OS) leaving the fast one unaffected, indicating that the former was related to a slow inward current. Mn also drastically reduced AP duration without changing the slope of phase 3 of repolarization. Reduction of Na concentration to 90 mmol/l did not affect the peak voltage of the OS but shortened AP. This low-Na solution reduced both (Vmax)f and the amplitude of the fast component. Ca-free solution reduced OS and increased AP duration. In high-Ca Tyrode (7.2 mmol/l) OS was increased and AP shortened. The effects of MN were reversed in this solution. The results suggest that the upstroke of the RRPM action potential is determined by two different ionic currents: a fast Na current responsible for the fast component and a slow inward current carried mainly by Ca, this latter being responsible for the slow component in the upstroke and for the plateau phase. The existence of propagated, Ca-dependent slow responses was demonstrated. Emphasis is placed on the fact that the major determination of the repolarization process in this type of AP is probably the inactivation of the slow inward Ca current.