Corneal penetration of diclofenac from a fixed combination of diclofenac-gentamicin eyedrops

Recent studies suggest a dual role for nitric oxide (NO) in tumour biology. High concentrations of NO can mediate tumouricidal activity, whereas lower concentrations have been shown to promote tumour growth. In this study, NO synthase (NOS) activity was investigated in cells that were prepared from tissue from primary and metastatic sites and from malignant effusions in 41 cases of suspected ovarian cancer. NO biosynthesis, determined by nitrite + nitrate (NOx) accumulation in medium from cultured cells prepared from disaggregated tumours or effusions and indicative of the inducible NO synthase isoform, was detected in 37% of the cases investigated (range 10.2-114 microM). There was a significant relationship between NOx and tumour differentiation (P = 0.014), with NOx being significantly higher for the more differentiated tumours. NOS activity, determined by the conversion of radiolabelled L-arginine to citrulline by tissue or cell extracts, was detected in 29% of cases (range 0.9-6.9 pmol/min per mg of protein), with all samples tested being moderately or poorly differentiated. Seventy percent of this activity was calcium dependent, indicative of constitutive NOS isoforms. Morphological and immunohistochemical assessment of tumour samples indicated a significant relationship between high macrophage content and NOS activity (as NOx biosynthesis) (rs = 0.726, N = 16, P < 0.01). The relationship between NOS expression, immune response, and disease progression is complex and not simply dependent on the differentiation status of ovarian cancer.     

Effect of environmental temperature on the interactive developmental toxicity of radiofrequency radiation and 2-methoxyethanol in rats

OBJECTIVE: This research was conducted to determine if altered environmental temperatures would affect the interactive developmental toxicity of radiofrequency (RF) radiation and the industrial solvent, 2-methoxyethanol (2ME). This is important because RF radiation is used in a variety of workplaces that have poorly controlled environmental temperatures, and many workers are concurrently exposed to various chemicals. Furthermore, we have previously demonstrated that combined exposure to RF radiation (10 MHz) and 2ME produces enhanced teratogenicity in rats. METHODS: RF radiation sufficient to maintain colonic temperatures at the control value (38degrees ), 39.0degrees or 40.0 degrees C for 2 or 4 h combined with either 0 or 100 mg/ kg 2ME at environmental temperatures of 18 degrees , 24 degrees and 30 degrees C (65 degrees , 75 degrees , and 85 degrees F) were given on gestation day 13 to Sprague-Dawley rats. Dams were killed on gestation day 20, and the fetuses were examined for external malformations. RESULTS AND CONCLUSIONS: Environmental temperature does affect the specific absorption rate (SAR) necessary to maintain a specific colonic temperature but does not affect the interactive developmental toxicity of RF radiation and 2ME in rats. These results, consistent with the literature, add to the evidence that the developmental toxicity of RF radiation (combined or alone) is associated with colonic temperature, not with SAR.     

Electricity reform in the Republic of Macedonia

In contrast to some other countries in the South East European region, there has been privatization in the Macedonian electricity sector, and today the government has a majority stake in very few companies. After 2002, the focus of domestic policy shifted to compliance with the EU Energy Directives. The main obstacles to reform arise from low payment discipline, with state institutions among the problem customers, and the fact that prices do not match costs. In order to reduce the adverse effects of the inevitable electricity prices increase to more realistic levels, the paper suggests that sustainable social support mechanisms need to be developed, and proposes some options.     

Follicle selection in sheep with breed differences in ovulation rate

Genetic variations in ovulation rates which occur in different breeds of sheep provide useful models to explore the mechanisms underlying the antral of follicle development. Two principal strategies have evolved which enable these high fecundity breeds to over-ride the mechanisms which drastically restrict the number of ovulatory follicles. Firstly, Finnish Landrace involves reducing the sensitivity of the hypothalamic-pituitary unit to the feedback effects of ovarian hormones (inhibin and/or oestradiol) which normally suppress FSH. Treatment with oestrogens or immunisation against oestradiol or inhibin are pharmacological methods of manipulating the feedback system. The second mechanism as exemplified by the FecB gene results in an increased ovulation rate associated with the 'precocious' development of a large number of small antral follicles. The gene mutation responsible for this effect has not yet been identified. It is likely that the product will be a factor which enhances follicular development as well as affecting gonadotrophic function. Identification of the gene product should permit further research into the factors which regulate the orderly development of follicles within the ovary.     

Kawasaki disease: a dangerous acute childhood illness

Kawasaki disease is an acute febrile illness most commonly seen in children under the age of 5. It is characterized by fever, rash, cervical lymphadenopathy, bilateral nonexudative conjunctivitis, oropharyngeal mucosal changes, and erythema of the hands and feet followed by desquamation. However, a child with Kawasaki disease may not exhibit all of these symptoms. The disease resembles many other childhood illnesses, such as measles and scarlet fever, and misdiagnosis is common. Left untreated, Kawasaki disease has potential life-threatening consequences; 20% to 25% of children develop coronary artery aneurysms as a result. Although no specific laboratory tests exist that identify Kawasaki disease definitively, there are clinical and laboratory findings that guide diagnosis and treatment. Treatment includes the hospitalization of the child and subsequent administration of high doses of aspirin and intravenous immunoglobulin. With recovery, aspirin doses are reduced and the child may be monitored at home with outpatient follow-up. It is imperative that the health care provider be aware of the symptoms of Kawasaki disease in order to make the diagnosis and treat the child before cardiac sequelae ensue.     

Reproductive toxins and alligator abnormalities at Lake Apopka, Florida

The alligator population at Lake Apopka in central Florida declined dramatically between 1980 and 1987. Endocrine-disrupting chemicals and specifically DDT metabolites have been implicated in the alligators' reproductive failure. The DDT metabolite hypothesis is based largely on the observation of elevated concentrations of p,p-DDE and p,p-DDD in alligator eggs obtained from Lake Apopka in 1984 and 1985. In the following commentary, we draw attention to two nematocides that are established reproductive toxins in humans, dibromochloropropane (DBCP) and ethylene dibromide (EDB), which could also have played a role in the reproductive failure observed in alligators from Lake Apopka in the early 1980s.     

Cellular and molecular mechanisms of radiation inhibition of restenosis. Part I: role of the macrophage and platelet-derived growth factor

BACKGROUND: Desflurane, enflurane and isoflurane can be degraded to carbon monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane and halothane form negligible amounts of CO. Carbon monoxide formation is greater with drier absorbent, and with barium hydroxide, than with soda lime. The mechanism, role of absorbent composition and water, and anesthetic structures determining CO formation are unknown. This investigation examined sequential steps in anesthetic degradation to CO. METHODS: Carbon monoxide formation from anesthetics and desiccated barium hydroxide lime or soda lime was determined at equimole and equiMAC concentrations. Carbon monoxide formation from deuterium-substituted anesthetics was also quantified. Proton abstraction from anesthetics by strong base was determined by deuterium isotope exchange. A reactive chemical intermediate was trapped and identified by gas chromatography-mass spectrometry. The source of the oxygen in CO was identified by 18O incorporation. RESULTS: Desflurane,enflurane,andisoflurane(difluoromethylethyl ethers), but not sevoflurane (monofluoromethyl ether), methoxyflurane (methy-ethyl ether), or halothane (alkane) were degraded to CO. The amount of CO formed was desflurane > or = enflurane > isoflurane at equiMAC and enflurane > desflurane > isoflurane at equimole concentrations. Proton abstraction from the difluoromethoxy carbon was greater with potassium than with sodium hydroxide, but unmeasurable with barium hydroxide. Carbon monoxide formation was correlated (r = 0.95-1.00) with difluoromethoxy (enflurane > desflurane > isoflurane > or = methoxyflurane = sevoflurane = 0) but not ethyl carbon proton abstraction. Deuterium substitution on enflurane and desflurane diminished CO formation. Chemical trapping showed formation of a difluorocarbene intermediate from enflurane and desflurane. Incorporation of H2(18)O in barium hydroxide lime resulted in C18O formation from unlabeled enflurane and desflurane. CONCLUSIONS: A difluoromethoxy group is a structural requirement for haloether degradation to CO. Results are consistent with initial base-catalyzed difluoromethoxy proton abstraction (potassium > sodium hydroxide, thus greater CO formation with barium hydroxide lime vs. soda lime) forming a carbanion (reprotonated by water to regenerate the anesthetic, hence requirements for relatively dry absorbent), carbanion decomposition to a difluorocarbene, and subsequent difluorocarbene reaction to form CO.