Selective iNOS inhibition prevents hypotension in septic rats while preserving endothelium-dependent vasodilation.

UNLABELLED: Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) mediates hypotension and metabolic derangements in sepsis. We hypothesized that selective iNOS-inhibition would prevent hypotension in septic rats without inhibiting endothelium-dependent vasodilation caused by the physiologically important endothelial NOS. Rats were exposed to lipopolysaccharide (LPS) for 6 h and the selective iNOS-inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL), the nonselective NOS-inhibitor N:(G)-nitro-L-arginine methyl ester (L-NAME), or control. Mean arterial pressure (MAP) and vasodilation to acetylcholine (ACh, endothelium-dependent), sodium nitroprusside (SNP, endothelium-independent), and isoproterenol (ISO, endothelium-independent beta agonist) were determined. Exhaled NO, nitrate/nitrite-(NOx) levels, metabolic data, and immunohistochemical staining for nitrotyrosine, a tracer of peroxynitrite-formation were also determined. In control rats, L-NAME increased MAP, decreased the response to ACh, and increased the response to SNP, whereas L-NIL did not alter these variables. LPS decreased MAP by 18% +/- 1%, decreased vasodilation (ACh, SNP, and ISO), increased exhaled NO, NOx, nitrotyrosine staining, and caused acidosis and hypoglycemia. L-NIL restored MAP and vasodilation (ACh, SNP, and ISO) to baseline and prevented the changes in exhaled NO, NOx, pH, and glucose levels. In contrast, L-NAME restored MAP and SNP vasodilation, but did not alter the decreased response to ACh and ISO or prevent the changes in exhaled NO and glucose levels. Finally, L-NIL but not L-NAME decreased nitrotyrosine staining in LPS rats. In conclusion, L-NIL prevents hypotension and metabolic derangements in septic rats without affecting endothelium-dependent vasodilation whereas L-NAME does not. IMPLICATIONS: Sepsis causes hypotension and metabolic derangements partly because of increased nitric oxide. Selective inhibition of nitric oxide produced by the inducible nitric oxide synthase enzyme prevents hypotension and attenuates metabolic derangements while preserving the important vascular function associated with endothelium-dependent vasodilation in septic rats.

[Treatment of psoriasis using vitamin A, vitamin A acid and oral retinoids]. / Behandlung der Psoriasis mit Vitamin A, Vitamin-A-Säure und oralen Retinoiden.

Vitamin A, Vitamin A acid (retinoic acid) and their synthetic derivatives were variously applied in the management of psoriasis with different therapeutic results. Obviously, they influence the proliferation rate and the differentiation of human keratinizing epithelia and have beneficial effects on skin diseases with disturbances of keratinization, including psoriasis. Systemic application of Vitamin A has been yet largely abandonned since high dosages leading to clearing develop evident systemic toxicity. The anti-psoriatic effect of Vitamin A acid is either moderate or restricted, because of side effects. Only its combined local application with topical corticosteroids may be considered. Oral application of newly synthesized retinoids, however, was beneficial in psoriasis, particularly in erythrodermic or pustular types. With this group of retinoids new pathways were opened in dermatotherapy which may help to replace cytostatic drugs in these cases. Additionally, oral retinoid treatment may be introduced as an adjuvans in the management of widespread psoriasis, in order to enhance the effect of anthralin, PUVA or UVB treatments.

Oral treatment of keratosis follicularis with a new aromatic retinoid.

Four patients with extensive keratosis follicularis (Darler's disease) showed excellent clinical response to the oral administration of a new aromatic derivative of retinoic acid (RO 10-9359). Initial oral treatment with 50 to 75 mg of the drug was followed by substantial improvement in four to seven days and the lesions cleared completely after three to four weeks. Long-term treatment with 25 to 30 mg/day was sufficient to prevent recurrence. No serious side effects were seen with this dosage after several months. Some dryness of the lips and the nasal mucosa occurred and one patient experienced slight nausea. Histological investigations showed the gradual disappearance of acantholysis, dyskeratosis, and hyperkeratosis, in this order. The given therapeutic schedule is a reliable routine management for keratosis follicularis in adults.