Association between coronary heart disease risk factors and physical fitness in healthy adult women

We examined associations between physical fitness and risk factors for coronary heart disease in healthy women ages 18-65 years. Physical fitness was objectively determined by the duration of a maximal treadmill exercise test. Six physical fitness categories (very poor to superior), specific within 10-year age increments, were established. Mean risk factor levels varied across categories, but so did potential confounders such as age and weight. Multiple linear regression modeling was used to control for the effects of age, weight and year of exam on coronary risk factors. After adjustment, physical fitness was independently associated with triglycerides (p less than 0.001), high-density lipoprotein cholesterol (HDL-C) (p less than or equal to 0.001), total cholesterol/HDL-C ratio (p less than or equal to 0.001), blood pressure (p less than or equal to 0.001) and cigarette smoking (p less than or equal to 0.001).     

Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice

Loss-of-function mutations in the progranulin (GRN) gene are a common cause of autosomal dominant frontotemporal lobar degeneration, a fatal and progressive neurodegenerative disorder common in people less than 65 years of age. In the brain, progranulin is expressed in multiple regions at varying levels, and has been hypothesized to play a neuroprotective or neurotrophic role. Four neurotoxic agents were injected in vivo into constitutive progranulin knockout (Grn^−/−) mice and their wild-type (Grn^+/+) counterparts to assess neuronal sensitivity to toxic stress. Administration of 3-nitropropionic acid, quinolinic acid, kainic acid, and pilocarpine induced robust and measurable neuronal cell death in affected brain regions, but no differential cell death was observed between Grn^+/+ and Grn^−/− mice. Thus, constitutive progranulin knockout mice do not have increased sensitivity to neuronal cell death induced by the acute chemical models of neuronal injury used in this study.     

Risks of adverse events in patients with orthostatic intolerance undergoing surgery with general anesthesia

Clinical Autonomic Research - Orthostatic intolerance (OI) is a group of disorders characterized by symptoms that occur upon standing and resolve with recumbence. Although well established but not...     

Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults

STUDY OBJECTIVE: To determine the steady-state, extracellular, and intracellular pulmonary disposition of moxifloxacin (MXF), levofloxacin (LEVO), and azithromycin (AZI) relative to that of the plasma over a 24-h dosing interval. DESIGN: Randomized, multicenter, open-label investigation. PATIENTS: Forty-seven older adults (mean [+/- SD] age, 62 +/- 13 years) undergoing diagnostic bronchoscopy. INTERVENTIONS: Oral administration of MXF, 400 mg, LEVO, 500 mg daily for five doses, or AZI, 500 mg for one dose, then 250 mg daily for four doses. BAL and venipuncture were completed at 4, 8, 12, or 24 h following the administration of the last dose. MEASUREMENTS AND RESULTS: Steady-state MXF, LEVO, and AZI concentrations were determined in the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs). The concentrations of all three agents were greatest in the AMs followed by the ELF compared to the plasma. Plasma concentrations were similar to those previously reported with these agents. The mean ELF concentrations at 4, 8, 12, and 24 h were as follows: MXF, 11.7 +/- 11.9, 7.8 +/- 5.1, 10.5 +/- 3.7, and 5.7 +/- 6.3 micro g/mL, respectively; LEVO, 15.2 +/- 4.5, 10.2 +/- 6.7, 6.9 +/- 4.4, and 2.9 +/- 1.7 micro g/mL, respectively; and AZI, 0.6 +/- 0.4, 0.7 +/- 0.4, 0.9 +/- 0.5, and 0.9 +/- 0.7 micro g/mL, respectively. The AM concentrations at 4, 8, 12, and 24 h were as follows: MXF, 47.7 +/- 47.6, 123.3 +/- 126.4, 26.2 +/- 19.4, and 32.8 +/- 16.5 micro g/mL, respectively; LEVO, 28.5 +/- 30.2, 26.1 +/- 15.7, 28.3 +/- 12.6, and 8.2 +/- 6.1 micro g/mL, respectively; and AZI, 71.8 +/- 50.1, 73.8 +/- 75.3, 155.9 +/- 81.3, and 205.2 +/- 256.3 micro g/mL, respectively. CONCLUSIONS: The intrapulmonary concentrations of MXF, LEV, and AZI were superior to those obtained in the plasma. The AM concentrations of all agents studied were more than adequate relative to the minimum concentration required to inhibit 90% of the organism population (MIC(90)) of the common intracellular pathogens (< 1 micro g/mL). These data indicate that attainable extracellular concentrations of AZI are insufficient to reliably eradicate Streptococcus pneumoniae, based on the agent's current minimum inhibitory concentration profile, whereas the mean concentrations of MXF and LEVO in the ELF exceed the MIC(90) of the S pneumoniae population. Moreover, MXF concentrations exceeded the S pneumoniae susceptibility breakpoint (1.0 micro g/mL) at all time points, while 2 of 15 concentrations (13%) failed to maintain LEVO concentrations above the breakpoint (2.0 micro g/mL) throughout the dosing interval.     

Healing of mat mutations and control of mating type interconversion by the mating type locus in Saccharomyces cerevisiae

Homothallic yeasts switch cell types (mating types a and α) at high frequency by changing the alleles of the mating type locus, MATa and MATα. We have proposed in the cassette model that yeast cells contain silent MATa and MATα blocs (“cassettes”), copies of which can be substituted at the mating type locus for the resident information. The existence of silent cassettes was originally proposed to explain efficient switching of a defective MATα locus (matα) to a functional MATα locus. We report here that this “healing” of mat mutations is a general property of the mating type interconversion system and is not specific to the class of matα mutations studied earlier: a defective MATa (mata1) switches readily to MATa and various matα loci switch readily to MATα. These observations satisfy the prediction of the cassette model that all mutations within MATa and MATα be healed. These studies also identify MAT functions that control the switching process: the same functions known to promote sporulation and prevent mating in a/α cells also inhibit the switching system in a/α cells. Finally, we present additional characterization of a natural variant of MATα, MATα-inc [Takano, I., Kusumi, T. & Oshima, Y. (1973) Mol. Gen. Genet. 126, 19-28] that is insensitive to switching. Our observation that MATα-inc acts in cis suggests that it may be altered in a site concerned with excision of MATα-inc or its replacement by another cassette.     

Effects of angiotensin II on membrane current in cardiac Purkinje fibers

We studied the actions of the octapeptide hormone angiotensin II (AII) on isolated cardiac Purkinje fibers. AII (1 to 75 nm) increased the height and duration of the plateau phase of the action potential and increased the strength of contraction in these preparations. These effects were not blocked by propranolol (10^?6m). A two-microelectrode voltage clamp technique combined with simultaneous tension measurements was used to study the AII-induced changes in membrane current and contractile activation. AII enhanced peak tension and promoted an inward shift in the net membrane current-voltage relation at test voltages between ?40 and 0 mV. The inward shift in current was maintained for the duration of the 500 ms test voltage step. The AII-induced current shift was reduced or abolished when external calcium concentration was decreased from 5.4 mm to 1.8 mm, and was inhibited by the calcium antagonist D600.