Metabolic activation of N-hydroxy-4-acetylaminobiphenyl by cultured human breast epithelial cell line MCF 10A

Metabolism and nucleic acid binding of the mammary gland carcinogenN-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) was investigatedusing the human mammary epithelial cell line MCF 10A. Chromatographicanalysis of the ethyl acetate extract of the media from culturedMCF 1OA after 24 h exposure to N-OH-AABP revealed the formationof two metabolites, 4-aminobiphenyl (ABP) and 4-acetylamlnobi-phenyl (AABP). Incubation of [³H]N-OH-AABP with calf thymusDNA in the presence of the cytosols or microsomes revealed abinding of 0.21 and 2.36 nmol/mg DNA/mg protein respectively.In contrast to cytosol-mediated binding, the microsome-mediatedbinding of [³H]N-OH-AABP to DNA was inhibited by paraoxon. Furthermore,exogenous addition of non-labelled N-hydroxy-4-aminobiphenyl(N-OH-ABP) to the incubation mixture blocked the binding of[³H]N-OH-AABP to DNA, suggesting that the metabolic activationprocess involves inter-molecular transacetylation. Cytosolsfrom MCF 10A also catalyzed acetyl coenzyme A (AcCoA) dependentbinding of [³H]N-OH-ABP to DNA; the amount of binding was 0.51nmol/mg DNA/mg protein. HPLC of the DNA hydrolysate obtainedafter incubation of [³H]N-OH-AABP and [³H]N-OH-ABP with theMCF 10A microsomes and cytosols showed N-(deoxyguanosin-8-yl)-4-aminobiphenyl(dG-ABP) as the primary adduct, based on the mobility of theradioactive peak in comparison with the synthetic standard.³²P-postlabelllng of adducted DNA obtained on incubation withN-OH-ABP or N-OH-AABP showed similar adduct profiles, with themajor adduct corresponding with the bisphospho derivative ofdG-ABP and a minor adduct corresponding with N-(deoxyadenosin-8-yl)-4-aminobiphenyl(dA-ABP). Additionally, the cellular DNA isolated from MCF 10Afollowing exposure to N-OH-AABP also revealed a major spot correspondingwith the dG-ABP derivative. These results suggest that the mammarygland carcinogen N-OH-AABP is activated to reactive electrophilicspecies in the target human mammary tissues by acetyl transferase(s)enzyme systems.     

Superficial cervical plexus block for vocal cord surgery in an awake pediatric patient

Medialization thyroplasty is a surgical procedure that decreases the incidence of dysphonia and dysphagia in patients who have vocal cord paralysis. We report a case of a pediatric patient who underwent this procedure with minimal sedation and bilateral superficial cervical plexus blockade. The use of a regional technique provided analgesia while allowing the patient to phonate at the request of the surgeon. IMPLICATIONS: Medialization thyroplasty is a surgical procedure that decreases the incidence of dysphagia and dysphonia in patients with vocal cord paralysis. This procedure is best performed in a patient who maintains the ability to phonate. We report a case of medialization thyroplasty in a pediatric patient after bilateral superficial cervical plexus blocks with minimal sedation.     

The use of infraorbital nerve block for postoperative pain control after transsphenoidal hypophysectomy

OBJECTIVES: The transsphenoidal approach for pituitary resection is often used for a suprasellar tumor. The use of infraorbital nerve block for pain control in the postoperative period is described in this case report. CASE REPORT: An 11-year old male was scheduled for a transsphenoidal approach to a pituitary tumor. After induction of general anesthesia and placement of an endotracheal tube, bilateral infraorbital nerve blocks (maxillary division of the trigeminal nerve) were performed using an intraoral approach. This block was repeated at the conclusion of surgery. The patient was very comfortable in the postoperative period without need for additional analgesia. CONCLUSIONS: Bilateral infraorbital nerve blocks may provide adequate pain control following transsphenoidal hypophysectomy. The avoidance of opioids may allow better neurological examination following major neurosurgical procedures.     

Adapting the 'family wellbeing' empowerment program to the needs of remote indigenous school children

OBJECTIVE: To adapt the Family Wellbeing empowerment program, which was initially designed to support adults to take greater control and responsibility for their decisions and lives, to the needs of Indigenous school children living in remote communities. METHOD: At the request of two schools in remote Indigenous communities in far north Queensland, a pilot personal development and empowerment program based on the adult Family Wellbeing principles was developed, conducted and evaluated in the schools. The main aims of the program were to build personal identity and to encourage students to recognise their future potential and be more aware of their place in the community and wider society. RESULTS: Participation in the program resulted in significant social and emotional growth for the students. Outcomes described by participating students and teachers included increased analytical and reflective skills, greater ability to think for oneself and set goals, less teasing and bullying in the school environment, and an enhanced sense of identity, friendship and 'social relatedness'. CONCLUSION: This pilot implementation of the Family Wellbeing Program adapted for schools demonstrated the program's potential to enhance Indigenous young people's personal growth and development. Challenges remain in increasing parental/ family involvement and ensuring the program's sustainability and transferability. The team has been working with relevant stakeholders to further develop and package the School-based Family Wellbeing program for Education Queensland's New Basics curriculum framework.     

Ascorbate-mediated enhancement of reactive oxygen species generation from polymorphonuclear leukocytes: modulatory effect of nitric oxide

Recent studies from our laboratory have demonstrated that ascorbate potentiated enzymatic synthesis of nitric oxide (NO) from polymorphonuclear leukocytes (PMNs). NO is known to modulate various function of PMNs such as chemotaxis, adherence, aggregation, and generation of reactive oxygen species (ROS). The role of ascorbate in the PMN phagocytosis, ROS generation, and apoptosis was thus evaluated in the present study. Ascorbate and its oxidized and cell-permeable analog, dehydroascorbate (DHA), did not affect the phagocytosis but enhanced ROS generation and apoptosis following treatment with Escherichia coli or arachidonic acid. A detailed investigation on the DHA-mediated response indicated that inhibitors of DHA uptake, reduced nicotinamide adenine dinucleotide phosphate oxidase, NO synthase, or ROS scavengers attenuated ROS generation. In DHA-treated cells, enhanced generation of peroxynitrite was also observed; thus, ascorbate-mediated ROS and reactive nitrogen species generation might mediate cytotoxicity toward the ingested microbes and subsequently, augmented PMN apoptosis. Results of the present study have helped in delineating the role of ascorbate in the modulation of NO-mediated ROS generation from PMNs.     

Case series: IV regional anesthesia with ketorolac and lidocaine: is it effective for the management of complex regional pain syndrome 1 in children and adolescents?

IMPLICATIONS: We report our experience with ketorolac/lidocaine IV regional anesthesia (Bier block) (IVRA) in two adolescents with complex regional pain syndrome 1. IVRA resulted in complete resolution of symptoms.