Effects of selective alpha 1-adrenoceptor blockade in dogs with hypoxic pulmonary vasoconstriction

The acute effects of the selective alpha 1-blocker, E-643 (Bunazosine), on experimental pulmonary hypertension (PH) caused by hypoxic pulmonary vasoconstriction (HPV) in mongrel dogs were examined. Ninety second ventilation with 5% O2 and 95% N2 was used for hypoxic stimulation. The effects of E-643 were evaluated at doses of 1, 5, 10, 20 and 50 micrograms/kg in this order until the systemic arterial mean pressure (SAm) had decreased by 20 mmHg when compared with the control value during room air ventilation. PaO2 and PaCO2 decreased by 64.6 +/- 11.0 Torr and 2.4 +/- 2.5 Torr, respectively, and the pH increased by 0.031 +/- 0.012 during hypoxic ventilation. These blood gas changes affected during hypoxic stimulation were almost the same before E-643 administration. Progression of arterial blood hypoxemia due to E-643 administration during room air ventilation was not observed. SAm decreased by 8.0 +/- 11.9 mmHg after E-643 administration, while left atrial mean pressure (LAm) and cardiac output (CO) did not change significantly. Prior to E-643 administration, mean pulmonary arterial pressure (PAm) and pulmonary vascular resistance (PVR) increased by 6.4 +/- 3.3 mmHg and 6.2 +/- 3.8 HRU, respectively, during the 90 sec hypoxic ventilation period. After E-643 administration, the increases in PAm and PVR were 3.9 +/- 1.7 mmHg and 3.3 +/- 2.3 HRU, respectively. The suppression of increases in PAm and PVR was significant. The conclusion is that E-643, a selective alpha 1-blocker, is effective at restraining HPV in the dog model.     

Analysis of oral risk factors for ventilator-associated pneumonia in critically ill patients

Clinical Oral Investigations - This a cross-sectional study to evaluate the association between oral health findings and ventilator-associated pneumonia (VAP) among critically ill patients in...     

Clustered features of the metabolic syndrome and the risk for increased aortic pulse wave velocity in middle-aged Japanese men

The association between different features of the metabolic syndrome (MS) (obesity, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol level, hypertriglyceridemia, high fasting plasma glucose level, and hyperuricemia) and the risk for increased aortic pulse wave velocity (PWV) of > or = 8.0 m/sec was examined in 2431 Japanese men aged 35 to 54 years who were not taking antihypertensive medication. After controlling for age, cigarette smoking, and alcohol intake, the odds ratios for increased aortic PWV in subjects with 1, 2, 3, and > or = 4 features of the MS, compared with those without features of the MS, were 1.35 (95% CI, 0.86 to 2.11), 1.90 (95% CI, 1.18 to 3.06), 1.57 (95% CI, 0.89 to 2.76), and 2.38 (95% CI, 1.26 to 4.49), respectively (p for trend = 0.003). A 9-year longitudinal study was also performed to prospectively examine the association between clustered features of the MS and the development of increased aortic PWV in 2073 men without aortic stiffness with a PWV < 8.0 m/sec and without antihypertensive medication during the follow-up period. The multivariate-adjusted hazard ratios for the incidence of increased aortic PWV in subjects with 1, 2, 3, and > or = 4 features of the MS, compared with those without features of the MS, were 1.39 (95% CI, 1.10 to 1.77), 1.46 (95% CI, 1.1 1 to 1.92), 1.75 (95% CI, 1.27 to 2.40), and 2.22 (95% CI, 1.52 to 3.25), respectively (p for trend < 0.001). These results suggest that clustered features of the MS are closely associated with the risk for increased aortic PWV in middle-aged Japanese men.     

Effects of hypoglycaemia on early embryogenesis in rat embryo organ culture

Summary As congenital malformations may be caused by perturbations of glycolytic flux on early embryogenesis [16], effects of hypoglycaemia were investigated by using rat embryo organ culture. Nine and one-half day old rat embryos were grown in vitro for 48 h (day 9 1/2 to 11 1/2) in the presence of hypoglycaemic serum for different hours during the culture period. Hypoglycaemic serum was obtained from rats given insulin intraperitoneally. On exposure to hypoglycaemic serum during the first 24 h of culture (day 9 1/2 to 10 1/2), embryos showed marked growth retardation and had increased frequencies of neural lesions (42.7% versus 0%, p<0.01), in contrast to hypoglycaemic exposure during the second 24 h of culture (day 10 1/2 to 11 1/2), where only minor growth retardation and low frequencies of neural lesions (2.4% versus 0%, NS) were seen. Even exposure to hypoglycaemic serum for a relatively short period (8 h) during the first 24 h of culture resulted in neural lesions at the frequency of 9.3–13.3%. The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the principal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.     

A mitochondrial superoxide theory for oxidative stress diseases and aging

Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O₂^•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q₁₀) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.