Inhibition of the endogenous volume-regulated anion channel (VRAC) in HEK293 cells by acidic di-aryl-ureas.

The endogenous volume-regulated anion channel (VRAC) from HEK293 cells was pharmacologically characterized using the whole-cell patch-clamp technique. Under isotonic conditions a small (1.3 nS), Ca(2+)-independent Cl conductance was measured. However, swelling at 75% tonicity activated a VRAC identified as an outward-rectifying anion current ( P(l) > P(Cl) > P(gluconate)), which was ATP-dependent and showed inactivation at positive potentials. Activation of this current followed a sigmoid time course, reaching a plateau conductance of 42.6 nS after 12-15 min ( t(1/2) = 7 min). The pharmacology of this VRAC was investigated using standard Cl(-)-channel blockers (NPPB, DIDS, and tamoxifen) as well as a new group (acidic di-aryl ureas) of Cl(-)-channel blockers (NS1652, NS3623, NS3749, and NS3728). The acidic di-aryl ureas were originally synthezised for inhibition of the human erythrocyte Cl(-) conductance in vivo. NS3728 was the most potent VRAC blocker in this series ( IC(50) = 0.40 micro M) and even more potent than tamoxifen (2.2 micro M). NS3728 accelerated channel inactivation at positive potentials. These results show that acidic di-aryl ureas constitute a promising starting point for the synthesis of potent inhibitors of VRAC.

Quality of the capsule in reconstructions with textured or smooth silicone implants after mastectomy.

Many women desire some kind of reconstruction after mastectomy for breast cancer to improve the cosmetic result. Since the introduction of silicone breast implants, capsular contracture has been the most common complication of breast augmentation or reconstruction. The aim of the present study was to evaluate the capsule quality in patients with breast cancer who had undergone reconstructions with either textured (rough) or smooth silicone implants after simple or modified radical mastectomy. Forty-three consecutive patients had reconstructions with textured silicone implants (49 implants) and were evaluated 32 months post-operatively in a prospective clinical trial. The last 43 consecutive patients who had reconstructions with bilumen smooth silicone implants (49 implants) acted as controls. The results were graded by Baker's classification. Among the patients with textured implants only 9% (4/47) was graded as having moderate or severe capsular contracture in contrast to 24% (11/46) in patients with bilumen smooth-surface implants (p < 0.05). These results confirm previous reports that favour textured silicone implants in breast augmentation and reconstruction.

[Extravasation of cytostatic agents--what is a good treatment?]. / Ekstravasering av cytostatika--hva er god behandling?

Extravasation of vesicant antitumour agents is a feared complication within oncologic therapy. The treatment is often meant to give palliation. Should extravasation occur it might further spoil the limited time many of these patients have left to live. The question is how to treat an extravasation injury without giving the patient an additional problem. The aim must be to remove the vesicant as soon as possible in a way that implies minimum morbidity and loss of function. At the Norwegian Radium Hospital, oncologists and plastic surgeons have cooperated on early surgical intervention, with good results. In our opinion, the problem arises when treatment is delayed. We present a retrospective study of 19 patients operated at the Norwegian Radium Hospital between 1986 and 1994, and discuss current methods of treatment.

[Partial gangrene of the scrotum and penis. A complication of sclerotherapy of testicular hydrocele]. / Partielt gangren av scrotum og penis. En komplikasjon til skleroserende behandling for hydrocele testis.

Localized gangrene of the scrotum and penis as a complication to tetracycline sclerotherapy for hydrocele has not been reported before. I describe the complication in a 56 year-old man who was admitted to our plastic surgery unit for excision and reconstruction four days after sclerotherapy. The procedure of tapping and injection, and how to avoid this type of complication, are discussed.

[Burns among the elderly. Occurrence, causes, local treatment]. / Brannskader hos eldre. Forekomst, årsker, lokalbehandling.

Burns in geriatric patients carry a grave prognosis. Reduced thickness of the skin and reduced mobility make older persons susceptible to deep burns. First-aid treatment is insufficient in most instances and generally, there is a delay in seeking medical treatment. Pre-existing degenerative diseases may account for numerous complications and a prolonged course. Accidents at home are most common. It is assumed that most of these could be prevented if proper precautions are taken. Our experiences from treatment of 85 geriatric burn patients at the Red Cross Clinic, Oslo, prompted the present study. We discuss various aspects of problems to geriatric patients.

[Large breasts--big problems?]. / Store bryster--store plager?

Hypertrophy of the breast often leads to pain in the neck and shoulders. This group of patients comprises mainly employed women who are otherwise in good health. For many of them, the problems cause long periods of absence from work. We wished to find out to what degree the main symptoms of these patients were caused by large and heavy mammae. We also wished to ascertain whether operative reduction of the breasts has the desired effect of alleviating the problems. A questionnaire was sent to 99 patients. The response was 69%. We discuss the interpretation of the answers, and conclude that the problems reported by patients were to a large extent real and that the vast majority of patients had been helped by operation.

Mechanistic studies on the phosphoramidite coupling reaction in oligonucleotide synthesis. I. Evidence for nucleophilic catalysis by tetrazole and rate variations with the phosphorus substituents.

Tetrazole catalyzed reactions of a series of phosphoramidites, 5'-O-DMTdT-3'-O-P(OR1)NR2(2) (1a-h), with 3'-O-SiButPh2-6-N-benzoyl-dA (2a) in acetonitrile solution have been studied. It is found that the coupling rate depends very much on whether tetrazole is added before or after 2a, and that dialkylammonium tetrazolide salts are inhibitors. These and other facts are evidence that the reactions are subjected to nucleophilic catalysis by tetrazole, in addition to acid catalysis. The rate variations with phosphorus substituents of 1a-h are NEt2 greater than NPri2 greater than N(CH2CH2)O greater than NMePh, and OMe greater than OCH2CH2CN greater than OCHMeCH2CN greater than OCMe2CH2CN much greater than OC6H4Cl. The inhibitor properties of dialkylammonium tetrazolides have practical consequences for the efficiency of DNA syntheses, when in situ prepared phosphoramidites are used; the same would apply for segmented, simultaneous syntheses or syntheses where recycling is performed.