Hospital-acquired acute kidney injury in medical, surgical, and intensive care unit: A comparative study.

Acute kidney injury (AKI) is a common complication in hospitalized patients. There are few comparative studies on hospital-acquired AKI (HAAKI) in medical, surgical, and ICU patients. This study was conducted to compare the epidemiological characteristics, clinical profiles, and outcomes of HAAKI among these three units. All adult patients (>18 years) of either gender who developed AKI based on RIFLE criteria (using serum creatinine), 48 h after hospitalization were included in the study. Patients of acute on chronic renal failure and AKI in pregnancy were excluded. Incidence of HAAKI in medical, surgical, and ICU wards were 0.54%, 0.72%, and 2.2% respectively (P < 0.0001). There was no difference in age distribution among the groups, but onset of HAAKI was earliest in the medical ward (P = 0.001). RIFLE-R was the most common AKI in medical (39.2%) and ICU (50%) wards but in the surgical ward, it was RIFLE-F that was most common (52.6%). Acute tubular necrosis was more common in ICU (P = 0.043). Most common etiology of HAAKI in medical unit was drug induced (39.2%), whereas in surgical and ICU, it was sepsis (34% and 35.2% respectively). Mortality in ICU, surgical and medical units were 73.5%, 43.42%, and 37.2%, respectively (P = 0.003). Length of hospital stay in surgical, ICU and medical units were different (P = 0.007). This study highlights that the characters of HAAKI are different in some aspects among different hospital settings.

Relationship between the depletion of O6-methylguanine-DNA methyltransferase by O6-methylguanine and the stimulation of DNA synthesis and growth of cultured chick hepatocytes.

O6-Methylguanine-DNA methyltransferase (O6-MT) has been described as a DNA repair enzyme that reverses alkylation damage at the O6 position of guanine in DNA. We demonstrate that the concentration of this protein decreases immediately prior to DNA synthesis in cultured chick hepatocytes. If intracellular levels are experimentally depleted by treatment of cultures with O6-methylguanine, DNA synthesis occurs as an associated resultant. This effect is dose dependent and can be followed by discernible morphological changes of organoids in culture. Increased and altered growth caused by O6-methylguanine was quantified and was also found to be dose dependent. Therefore, O6-MT may play a role in the regulation of DNA synthesis.

Cellular levels of O6-methylguanine-DNA methyltransferase in mammary epithelial cells and liver from virgin, pregnant and pituitary grafted mice.

O6-Methylguanine-DNA methyltransferase (O6-MT) is a DNA repair protein that reverses alkylation damage at the O6 position of guanine. In the process, O6-MT undergoes suicide inactivation. To determine if this enzyme might be regulated by pregnancy-associated hormones we measured changes in the level of O6-MT in isolated mouse mammary epithelial cell homogenates during different reproductive states. These were pregnancy, ectopic pituitary transplantation, proestrus/estrus and diestrus. O6-MT levels were found to be similar in mice in proestrus/estrus (0.95 fmol/micrograms DNA) as compared to diestrus (0.94 fmol/micrograms DNA) and also mixed populations of virgin mice (1.09 fmol/micrograms DNA). A mean for all virgin mice (0.97 fmol/micrograms DNA) was used as a comparative index. O6-MT decreased 2-fold during pregnancy in mammary epithelial cells to a mean value of 0.45 fmol/micrograms DNA (P less than 0.05). A smaller decrease (0.65 fmol/micrograms DNA; P less than 0.01) in mammary epithelial cells was found at 3 weeks following pituitary isograft. The repair capacity of mammary epithelial cells to liver was compared by measurements made in liver homogenates from the same mice and are approximately 3-fold higher in liver from virgin mice (3.2 fmol/micrograms DNA) than mammary gland. Liver levels of O6-MT increased in pregnant (5.3 fmol/micrograms DNA) and pituitary transplanted (3.9 fmol/micrograms DNA) mice, and were 5- and 4-fold higher than the concentration in virgin mammary epithelial cells respectively.

O6-methylguanine-DNA methyltransferase in human fetal tissues: fetal and maternal factors.

O6-Methylguanine methyltransferase (O6-MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race and of maternal smoking and drug usage. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin, and brain. Each fetal organ homogenate exhibited a 3- to 5-fold level of interindividual variation of O6-MT. There did not appear to be any significant differences of O6-MT as a function of fetal race and age and in the tissues obtained from mothers who smoked cigarettes during pregnancy. The fetal tissues obtained from an individual using phenobarbital exhibited 4-fold increases in O6-MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest a possible enhancement of human fetal O6-MT by certain xenobiotics, with little if any modulation by racial factors and maternal smoking habits.

Human erythrocyte acetylcholinesterase is an amphipathic protein whose short membrane-binding domain is removed by papain digestion.

Human erythrocyte acetylcholinesterase was shown to be an amphipathic protein in which proteases could cleave the hydrophobic domain from the enzymatically active hydrophilic domain. Papain and Pronase cleaved these domains with greatest efficiency, as measured by the disaggregation of purified acetylcholinesterase to disulfide-linked dimers (G2) on sucrose density gradients in the absence of detergent. Nonspecific proteolytic degradation was reduced both by the inclusion of edrophonium chloride, which protected acetylcholinesterase from inactivation, and by covalent attachment of papain to Sepharose CL-4B. In contrast to nondigested control acetylcholinesterase, the papain-disaggregated enzyme did not bind detergent according to hydrodynamic criteria and could not be reconstituted into liposomes. Thus, we conclude that the hydrophobic domain removed by papain digestion is in fact the membrane-binding domain in situ. This domain appeared largely inaccessible to proteases in intact erythrocytes, however, as less than 10% of the enzyme activity was solubilized by protease digestion. The hydrophobic domain removed by papain appeared very small, as nondigested control and disaggregated enzyme were identical in molecular weight and amino acid composition within experimental error. The fully reduced 75-kDa catalytic subunits of nondigested control enzyme appeared about 2 kDa larger than the corresponding subunits of disaggregated enzyme on polyacrylamide gel electrophoresis in sodium dodecyl sulfate, an indication that the hydrophobic domain was cleaved from the COOH or NH2 terminus of the catalytic subunit primary structure. Studies in which the NH-terminal amino acid was labeled by reductive methylation suggested that the hydrophobic domain is at the COOH terminus.