Hospital-based management of acute asthmatic exacerbation: an assessment of physicians' behavior in Taiwan.

This retrospective study was conducted to assess Taiwanese emergency physicians for their preference in management and adherence to guidelines in treating patients with acute exacerbation of asthma. One hundred twenty patients from hospitals of three different levels were evaluated by reviewing their medical records. Our study revealed that physicians from medical centers and regional hospitals assessed patients more often with arterial blood gas or pulse oximetry; prescribed more doses of beta2-agonist nebulizers; administered more doses of beta2-agonist nebulizers before administering parenteral aminophylline; and prescribed ipratropium nebulizers more often as adjunctive therapy. On the other hand, physicians from district hospitals more frequently prescribed parenteral aminophylline as the first-line medication and more often prescribed only a single dose of beta2-agonist nebulizer. Most emergency physicians in Taiwan did not adhere to guidelines. Specifically, these included omission of peak expiratory flow as the means to assess the severity of asthma exacerbation and response to treatment; suboptimal use of inhaled bronchodilators, such as beta2-agonists and ipratropium; and inappropriate use of parenteral aminophylline as the first-line medication.

Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis.

Studies presented here show that cellular NAD, which we hypothesize to be the relevant biomarker of niacin status, is significantly lower in humans than in the commonly studied animal models of carcinogenesis. We show that nicotinamide and the resulting cellular NAD concentration modulate expression of the tumor suppressor protein, p53, in human breast, skin, and lung cells. Studies to determine the optimal NAD concentrations for responding to DNA damage in breast epithelial cells reveal that DNA damage appears to stimulate NAD biosynthesis and that recovery from DNA damage occurs several hours earlier in the presence of higher NAD or in cells undergoing active NAD biosynthesis. Finally, analyses of normal human skin tissue from individuals diagnosed with actinic keratoses or squamous cell carcinomas show that NAD content of the skin is inversely correlated with the malignant phenotype. Since NAD is important in modulating ADP-ribose polymer metabolism, cyclic ADP-ribose synthesis, and stress response proteins, such as p53, following DNA damage, understanding how NAD metabolism is regulated in the human has important implications in developing both prevention and treatment strategies in carcinogenesis.

Poly(ADP-ribose) polymerase null mouse cells synthesize ADP-ribose polymers.

Poly(ADP-ribose) polymerase (PARP) (EC 2.4.2.30), the only enzyme known to synthesize ADP-ribose polymers from NAD+, is activated in response to DNA strand breaks and functions in the maintenance of genomic integrity. Mice homozygous for a disrupted gene encoding PARP are viable but have severe sensitivity to gamma-radiation and alkylating agents. We demonstrate here that both 3T3 and primary embryo cells derived from PARP-/- mice synthesized ADP-ribose polymers following treatment with the DNA-damaging agent, N-methyl-N'-nitro-N-nitrosoguanidine, despite the fact that no PARP protein was detected in these cells. ADP-ribose polymers isolated from PARP-/- cells were indistinguishable from that of PARP+/+ cells by several criteria. First, they bound to a boronate resin selective for ADP-ribose polymers. Second, treatment of polymers with snake venom phosphodiesterase and alkaline phosphatase yielded ribosyladenosine, a nucleoside diagnostic for the unique ribosyl-ribosyl linkages of ADP-ribose polymers. Third, they were digested by treatment with recombinant poly(ADP-ribose) glycohydrolase, an enzyme highly specific for ADP-ribose polymers. Collectively, these data demonstrate that ADP-ribose polymers are formed in PARP-/- cells in a DNA damage-dependent manner. Because the PARP gene has been disrupted, these results suggest the presence of a previously unreported activity capable of synthesizing ADP-ribose polymers in PARP-/- cells.