The mechanism of the antagonism by naloxone of acute alcohol intoxication.

Naloxone lowers blood-ethanol concentration and causes a simultaneous reversal of the disturbances in the redox states of the hepatic nicotinamide-adenine dinucleotide (phosphate) couples in acutely-ethanol-intoxicated rats. It is suggested that these effects of naloxone form the basis of its antagonism of acute alcohol intoxication.     

Rapid reversal by naloxone of the chronic effects of morphine on rat liver and brain tryptophan metabolism.

The chronic morphine-induced inhibition of rat liver tryptophan pyrrolase activity and the resultant increases in tryptophan availability to the brain and brain 5-hydroxytryptamine (5-HT) synthesis are reversed within 10 min after naloxone administration. The possible involvement of hepatic tryptophan metabolism in morphine dependence is briefly discussed.     

The protective effect of melatonin against fumonisin-induced renal damage in rats

The present study was designed to investigate the potential protective effect of melatonin against the renal toxicity of fumonisin in female rats. Six groups of animals were used in this study. The first group served as control. The second group was given melatonin only at a dose level of 10 mg/kg. The third group was fed ration contaminated with fumonisin (100 mg/kg diet). The fourth group was fed ration contaminated with fumonisin (200 mg/kg diet). The fifth group was given daily interperitoneal injection (IP) 10 mg/kg melatonin and fed ration contaminated with fumonisin (100 mg/kg diet). The sixth group was given daily interperitoneal injection of 10 mg/kg melatonin and fed ration contaminated with fumonisin (200 mg/kg diet). The rats were treated for 1 month. Histopathological and histochemical changes in the kidney were investigated. In addition, DNA ploidy was measured in the kidney. Fumonisin administration (100 or 200 mg/Kg diet) to unpretreated control rats caused extensive renal damage as evaluated by histopathology, histochemistry, and/or DNA ploidy measurement. No apparent changes following administration of melatonin. Melatonin coadministration to the fumonisin-administered rats reduced kidney damage and the tissues appeared more or less like the normal. The present study indicates that melatonin has a protective effect in fumonisin-induced renal damage.     

Topical pimecrolimus for skin disease other than atopic dermatitis

Pimecrolimus is an ascomycin macrolactam. It is a specific calcineurin inhibitor that allows topical application. The highly lipophilic nature of this compound reduces the risk of systemic absorption through normal and inflammed skin. Pimecrolimus shows activity not only against T-cell activation, but also against mast cells and pruritus. Pimecrolimus 1% cream is approved for atopic dermatitis, and also has a great potential in other inflammatory skin diseases. Clinical trials have been performed in contact- and seborrhoeic dermatitis, genital lichen sclerosus, intertriginous psoriasis and cutaneous lupus erythematosus. In other diseases, the available data are limited to small case series, or individual cases of graft-versus-host disease or Netherton's disease. Although the use of calcineurin inhibitors in the treatment of vitiligo is promising, detailed studies with pimecrolimus and ultraviolet-irradiation are necessary and there is a need for prospective randomised, double-blind controlled trials.     

Cellular components in peritoneal fluid in infertile patients with and without endometriosis

Cellular components in peritoneal fluid of infertile patients with and without endometriosis were evaluated in 102 patients with Wright's-Giemsa and Papanicolaou stains. The secretory activity of these cells was studied indirectly by assaying acid phosphatase, prostaglandin (PG) F2 alpha and PGE2 and complement components C3c and C4. The results showed that macrophages and lymphocytes were the dominant cells in peritoneal fluid of these patients. These cells were significantly increased in endometriosis patients, as compared with control subjects. In addition, peritoneal fluid acid phosphatase, PGF2 alpha and PGE2, and complement components C3c and C4 were significantly increased in patients with endometriosis. These cellular changes and their activation in peritoneal fluid may explain infertility associated with endometriosis.     

Hepatocyte growth factor induces retinal vascular permeability via MAP-kinase and PI-3 kinase without altering retinal hemodynamics

PURPOSE: Although vascular endothelial growth factor (VEGF) is a key mediator of retinal vascular permeability (RVP), there may be additional humoral contributors. Hepatocyte growth factor (HGF) induces endothelial cell separation, regulates expression of cell adhesion molecules and is increased in the vitreous fluid of patients with proliferative diabetic retinopathy. The purpose of this study was to evaluate the in vivo effects of HGF on RVP and retinal hemodynamics and delineate the signaling pathways. METHODS: RVP was assessed by vitreous fluorescein fluorophotometry in rats. Time course and dose-response were determined after intravitreal HGF injection. MAP kinase (MAPK), phosphatidylinositol 3-kinase (PI-3 kinase), and protein kinase C (PKC) involvement were examined by using selective inhibitors. Retinal blood flow (RBF) and mean circulation time (MCT) were evaluated by video fluorescein angiography. RESULTS: HGF increased RVP in a time- and dose-dependent manner. HGF-induced RVP was evident 5 minutes after injection, and reached maximal levels after 25 minutes (+107% versus vehicle, P=0.002). This effect was comparable to that of maximum VEGF stimulation (134%+/-128% at 25 ng/mL). Selective inhibitors of MAPK (PD98059) and PI-3 kinase (LY294002) suppressed HGF-induced RVP by 86%+/-44% (P=0.015) and 97%+/-59% (P=0.021), respectively. Non-isoform-selective inhibition of PKC did not significantly decrease HGF-induced RVP. Although VEGF increases RBF and reduces MCT, HGF did not affect either. CONCLUSIONS: HGF increases RVP in a time- and dose-dependent manner at physiologically relevant concentrations with a magnitude and profile similar to that of VEGF, without affecting retinal hemodynamics. Thus, HGF may represent another clinically significant contributor to retinal edema distinct from the actions of VEGF.     

The dose-time relationship in the radiotherapy of carcinoma of the cervix uteri: an application of the CRE formalism.

A correlation could be obtained between the likelihood of control of central and nodal disease and the corresponding local CRE levels attained in a group of 79 cases of carcinoma of the cervix uteri treated according to a multistage protocol involving a combination of external telecobalt irradiation and intracavitary radium application. A nodal CRE level of 1700 reu and a central CRE value of 2900 reu seemed to be optimal for control of modal metastases and central disease respectively. These CRE levels seemed to be well tolerated even if salvage surgery had to be performed.     

Reversal by naloxone of the effects of chronic administration of drugs of dependence on rat liver and brain tryptophan metabolism.

1. Chronic administration of ethanol, morphine, nicotine or phenobarbitone has previously been shown to enhance rat brain 5-hydroxytryptamine (5-HT) synthesis by increasing the availability of circulating tryptophan to the brain secondarily to the NADPH-mediated inhibition of liver tryptophan pyrrolase activity. 2. Naloxone reverses the above enhancement of 5-HT synthesis and the accompanying increase in tryptophan availability to the brain and the inhibition of liver tryptophan pyrrolase activity. 3. It is suggested that naloxone exerts these effects by antagonizing the chronic drug-induced increase in liver [NADPH]. 4. Naloxone increases serum corticosterone concentration in rats chronically treated with the above four drugs of dependence. Possible explanations of this effect are discussed.