Aims To determine levels of microsomal protein (MPPGL) and hepatocellularity (HPGL) per gram of human liver and their interindividual variability. Methods Triplicate liver samples were used to determine values of MPPGL ( n = 20) and HPGL ( n = 7) after accounting for the fractional loss of microsomal protein or hepatocytes during processing. Repeated measurements from each liver sample allowed the estimation of true interindividual variability in MPPGL and HPGL using ANOVA . Results The value of MPPGL ranged from 26 to 54 mg g -1 (mean geo = 33 mg g -1 ). The value of HPGL ranged from 65 to 185 ¥ 10 6 cells g -1(mean geo = 107 ¥ 10 6 cells g -1 ). Conclusions There is significant interindividual variability in MPPGL, which has implications for the accurate extrapolation of in vitro data on drug metabolism to predict in vivo metabolic clearance.
The Big Potassium (BK) ion channel is commonly known by a variety of names (Maxi-K, KCNMA1, slo, Stretch-activated potassium channels, KCa1.1). Each name reflects a different physical property displayed by this single ion channel. This transmembrane channel is found on nearly every cell type of the body and has its own distinctive roles for that tissue type. The BKα channel contains the pore that releases potassium ions from intracellular stores. This ion channel is found on the cell membrane, endoplasmic reticulum, Golgi and mitochondria. Complex splicing pathways produce different isoforms. The BKα channels can be phosphorylated, palmitoylated and myristylated. BK is composed of a homo-tetramer that interacts with β and γ chains. These accessory proteins provide a further modulating effect on the functions of BKα channels. BK channels play important roles in cell division and migration. In this review, we will focus on the biology of BK channels, especially its role, and that it has in the immune response towards cancer. Recent proteomic studies have linked BK channels with various proteins. Some of these interactions offer further insight into the role that BK channels have with cancers, especially with brain tumors. This review shows that BK channels have a complex interplay with intracellular components of cancer cells and still have plenty of secrets to be discovered.
For the purpose of establishing a clearer age‐related profile of bone health our aim was to evaluate the ratio of osteoblastic marker bone‐specific alkaline phosphatase (ALP) to circulating parathyroid hormone (PTH) concentrations in 119 healthy women in two age groups (16–46, and 47–70 years of age) who were not on bisphosphonates or other osteoporosis therapies. The ALP increases from 8.5 mcg/l in younger women to 11.3 mcg/l (p<.0008). The PTH values also significantly increased (28.1 to 37.4 pg/ml, respectively; p<.020). The ALP:PTH ratio is unchanged (.30) for the two age groups. Our data holds promise for identifying an age‐related profile that can be used to illuminate the metabolic status of bone.
Biochemical markers of bone turnover have been shown to be useful as inexpensive and noninvasive tools for monitoring skeletal health. Because duel energy absorptiometry and other indicators of bone mineral density reflect changes to bone accumulated over months, we sought to assess bone health and to explore potential sex differences in bone metabolism. Bone‐specific alkaline phosphatase (ALP), 25‐hydroxy‐and 1, 25‐dihydroxyvitamin D, calcium, phosphate, and parathyroid hormone (PTH) in 359 men and women (n=77 and 282, respectively) between the ages of 18 and 80 years old. Subjects were placed in one of three age groups (20–50, 51–70 and >;71 years of age for men and 18–40, 41–60, and >;60 years of age for women, and into a self‐identified ethnicity category. As expected, we found a downward trend in bone densities as subjects got older. We also found that ALP values were significantly lower in the older cohort of males and significantly higher in the older cohort of females when compared to their respective younger cohort (p<0.01). We propose an index utilizing PTH and ALP ratios that may reflect the metabolic direction for bone health. Given the complexities of hormonal, nutrient and activity levels of elderly subjects, these data suggest that the mechanisms that contribute to bone remodeling may be different in males when compared to females. This research was funded by Irvine Health Foundation.
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