Identifying the energy gap: Magnitude and determinants of 5-year weight gain in midage women

Objective: The aims of this study were to estimate average yearly weight gain in midage women and to identify the determinants of weight gain and gaining weight at double the average rate. Research Methods and Procedures: The study sample comprised 8071 participants (45 to 55 years old) in the Australian Longitudinal Study on Women's Health who completed mailed surveys in 1996, 1998, and 2001. Results: On average, the women gained almost 0.5 kg per year [average 2.42 kg (95% confidence interval, 2.29 to 2.54) over 5 years]. In multivariate analyses, variables associated with energy balance (physical activity, sitting time, and energy intake), as well as quitting smoking, menopause/hysterectomy, and baseline BMI category were significantly associated with weight gain, but other behavioral and demographic characteristics were not. After adjustment for all of the other biological and behavioral variables, the odds of gaining weight at about twice the average rate (> 5 kg over 5 years) were highest for women who quit smoking (odds ratio = 2.94; 95% confidence interval, 2.17, 3.96). There were also independent relationships between the odds of gaining > 5 kg and lower levels of habitual physical activity, more time spent sitting, energy intake (but only in women with BMI > 25 at baseline), menopause transition, and hysterectomy. Discussion: The average weight gain equates with an energy imbalance of only about 10 kcal or 40 kJ per day, which suggests that small sustained changes in the modifiable behavioral variables could prevent further weight gain.

The role of group I metabotropic glutamate receptor's in neuronal excitotoxicity in Alzheimer's disease

Neurodegenerative diseases such as Huntington's disease, ischemia, and Alzheimer's disease (AD) are major causes of death. Recently, metabotropic glutamate receptors (mGluRs), a group of seven-transmembrane-domain proteins that couple to G-proteins, have become of interest for studies of pathogenesis. Group I mGluRs control the levels of second messengers such as inositol 1,4,5-triphosphate (IP3) Cal(2+) ions and cAMP. They elicit the release of arachidonic acid via intracellular Ca2+ mobilization from intracellular stores such as mitochondria and endoplasmic reticulum. This facilitates the release of glutamate and could trigger the formation of neurofibrillary tangles, a pathological hallmark of AD. mGluRs regulate neuronal injury and survival, possibly through a series of downstream protein kinase and cysteine protease signaling pathways that affect mitochondrially mediated programmed cell death. They may also play a role in glutamate-induced neuronal death by facilitating Cal(2+) mobilization. Hence, mGluRs have become a target for neuroprotective drug development. They represent a pharmacological path to a relatively subtle amelioration of neurotoxicity because they serve a modulatory rather than a direct role in excitatory glutamatergic transmission.

CIC-5: A chloride channel with multiple roles in renal tubular albumin uptake

CIC-5 is a chloride (Cl-) channel expressed in renal tubules and is critical for normal tubular function. Loss of function nonsense or missense mutations in CIC-5 are associated with Dent's disease, a condition in which patients present with low molecular weight (LMW) proteinuria (including albuminuria), hypercalciuria and nephrolithiasis. Several key studies in CIC-5 knockout mice have shown that the proteinuria results from defective tubular reabsorption of proteins. CIC-5 is typically regarded as an intracellular Cl- channel and thus the defect in this receptor-mediated uptake pathway was initially attributed to the failure of the early endosomes to acidify correctly. CIC-5 was postulated to play a key role in transporting the Cl- ions required to compensate for the movement of H+ during endosomal acidification. However, more recent studies suggest additional roles for CIC-5 in the endocytosis of albumin. CIC-5 is now known to be expressed at low levels at the cell surface and appears to be a key component in the assembly of the macromolecular complex involved in protein endocytosis. Furthermore, mutations in CIC-5 affect the trafficking of v-H+-ATPase and result in decreased expression of the albumin receptor megalin/cubulin. Thus, the expression of CIC-5 at the cell surface as well as its presence in endosomes appears to be essential for normal protein uptake by the renal proximal tubule. (c) 2005 Elsevier Ltd. All rights reserved.

Cell surface expression of urokinase receptor in normal mammary epithelial cells and breast cancer cell lines

Background: The urokinase receptor (uPAR) is important in the process of extracellular matrix degradation occurring during cancer cell invasion and metastasis. We wished to quantify uPAR on the surfaces of normal mammary epithelial cells (HMEC) and 6 well-known breast cancer cell lines using flow cytometry. Materials and Methods: Cell surface uPAR was labelled with a monoclonal antibody, and this was detected with a florescent-labelled second antibody and accurately measured using flow cytometry. The measured fluorescent signals of the stained cells were interpolated with those of Quantum Simply Cellular bead standards to determine the number of uPAR sites per cell. Results: The breast cancer cell lines ranged from 13,700 to 50,800 uPAR sites per cell, whilst HMEC cells had only 2,500 sites. Conclusions: This simple and reliable method showed that the expression of cell surface uPAR is higher in the breast cancer cell lines than in the normal mammary cells.