Renal redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and diabetic nephropathy: paying homage to the podocyte

Type 2 diabetes mellitus has reached epidemic proportions and diabetic nephropathy is the leading cause of end-stage renal disease. The metabolic syndrome constitutes a milieu conducive to tissue redox stress. This loss of redox homeostasis contributes to renal remodeling and parallels the concurrent increased vascular redox stress associated with the cardiometabolic syndrome. The multiple metabolic toxicities, redox stress and endothelial dysfunction combine to weave the complicated mosaic fabric of diabetic glomerulosclerosis and diabetic nephropathy. A better understanding may provide both the clinician and researcher tools to unravel this complicated disease process. Cellular remodeling of podocyte foot processes in the Ren-2 transgenic rat model of tissue angiotensin II overexpression (TG(mREN-2)27) and the Zucker diabetic fatty model of type 2 diabetes mellitus have been observed in preliminary studies. Importantly, angiotensin II receptor blockers have been shown to abrogate these ultrastructural changes in the foot processes of the podocyte in preliminary studies. An integrated, global risk reduction, approach in therapy addressing the multiple metabolic abnormalities combined with attempts to reach therapeutic goals at an earlier stage could have a profound effect on the development and progressive nature to end-stage renal disease and ultimately renal replacement therapy.     

Interventions for residents with dementia and their family and staff caregivers: evaluating the effectiveness of measures of outcomes in long-term care

This article describes six instruments developed for programs of research testing nursing interventions for individuals with dementia in Special Care Units and their family and staff caregivers. The Functional Abilities Checklist measures the functional abilities of residents with dementia. The Family Perceptions of Care Tool assesses family member satisfaction with care of the institutionalized relative with dementia. The Family Perceptions of Caregiving Role instrument evaluates stress experienced by family members of individuals with dementia related to their caregiving roles in long-term care settings. The Caregiver Stress Inventory and Staff Perceptions of Caregiving Role tools measure staff stress related to caring for residents with dementia. Finally, the Attitudes About Families Checklist assesses general staff attitudes about families of residents with dementia. Each instrument and its psychometric properties are described. The advantages of these instruments for research and clinical use with individuals with dementia are discussed.     

Rapid change in status: the case of William

In most geropsychiatric inpatient settings, the focus of care is reduction, management, or alleviation of psychiatric signs and symptoms through a combination of behavioral and pharmacologic interventions. However, unidentified or evolving medical conditions among frail older patients may precipitate rapid and unanticipated changes in status. The case of "William" illustrates how prompt adjustments in nursing care, collaboration within and between the geropsychiatric unit and other hospital services, and close working relationships with family may facilitate unexpected end-of-life decisions and promote quality of care.     

Cruciate ligament laxity and femoral intercondylar notch narrowing in early-stage knee osteoarthritis

OBJECTIVE: The influence of the cruciate ligaments in spontaneous osteoarthritis (OA) is not understood, although ligament rupture is known to cause secondary OA. Additionally, femoral notch narrowing at the anterior cruciate ligament (ACL) insertion site is associated with disease severity, but it is unknown whether ligament deterioration precedes or follows osteophyte formation. We examined cruciate ligament mechanics and metabolism and the intercondylar notch width in OA-prone Dunkin-Hartley (DH) guinea pigs at ages up to and including the age at OA onset (24 weeks), and compared the data with those in age-matched controls (Bristol strain 2 [BS2] guinea pigs). METHODS: Guinea pigs were assessed at 3, 6, 9, 12, 16, 20, 24, and 36 weeks of age. ACLs were mechanically tested, and the intercondylar notch width index (NWI) was determined. Cruciate ligament metabolism was determined by measuring the following markers of collagen turnover: matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinases 2, C-terminal type I procollagen propeptide (PICP), and the immature collagen-derived crosslink dihydroxylysinonorleucine (DHLNL). RESULTS: DH guinea pigs had significantly laxer ACLs than did BS2 guinea pigs, at 12, 16, and 24 weeks. We observed elevated levels of pro and active MMP-2, PICP, and DHLNL in the cruciate ligaments of DH animals at most ages, compared with BS2 guinea pigs. The NWI in DH animals was significantly lower than that in BS2 guinea pigs at 24 and 36 weeks. CONCLUSION: In DH guinea pigs, laxer ACLs, which are associated with increased collagen turnover, may cause joint instability and predispose these animals to the early onset of OA. Decreased intercondylar notch width in the DH animals indicates that bone remodeling at the ACL insertion site is a response to elevated ACL laxity.     

More frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women

In animals, ventral stroking for >5 days increases oxytocin (OT) activity and decreases blood pressure (BP), but related human studies are few. Thus, relationships between self-reported frequency of partner hugs, plasma OT and BP levels were examined in 59 premenopausal women before and after warm contact with their husbands/partners ending with hugs. Higher baseline OT before partner contact was associated with lower BP and heart rate, and met criteria to be a partial mediator of the lower resting BP shown by women reporting more frequent hugs (P<0.05). OT levels during post-contact stress were unrelated to hugs or BP. Menstrual cycle phase did not influence any OT measure. Thus, frequent hugs between spouses/partners are associated with lower BP and higher OT levels in premenopausal women; OT-mediated reduction in central adrenergic activity and peripheral effects of OT on the heart and vasculature are pathways to examine in future research.     

Psycho-educational strategies to promote fluid adherence in adult hemodialysis patients: a review of intervention studies

BACKGROUND: We reviewed psycho-educational intervention studies that were designed to reduce interdialytic weight gain (IDWG) in adult hemodialysis patients. Our goals were to critique research methods, describe the effectiveness of tested interventions, and make recommendations for future research. METHODS: Medline, PsychInfo, and the Cumulative Index to Nursing and Applied Health (CINAHL) databases were searched to identify empirical work. Each study was evaluated in terms of sample, design, theoretical framework, intervention delivery, and outcome. RESULTS: Nine studies were reviewed. Self-monitoring appears to be a promising strategy to be considered to reduce IDWG. Theory was not usually used to guide interventions, designs generally had control groups, interventions were delivered individually, more than one intervention was delivered at a time, the duration of the intervention varied greatly, there was no long-term follow-up, IDWG was the only outcome, and IDWG was operationalized in different ways. CONCLUSIONS: Theoretical models and methodological rigor are needed to guide future research. Specific recommendations on design, measurement, and conceptual issues are offered to enhance the effectiveness of future research.     

VPAC2 receptors mediate vasoactive intestinal peptide-induced neuroprotection against neonatal excitotoxic brain lesions in mice

Prepro-vasoactive intestinal peptide (VIP) mRNA codes for two neuropeptides: VIP and peptide histidine isoleucine (PHI). Two VIP receptors, shared with a similar affinity by pituitary adenylate cyclase-activating polypeptide (PACAP), have been cloned: VPAC(1) and VPAC(2). PHI binds to these receptors with a lower affinity. VPAC receptors are classically associated with a cAMP-dependent pathway, although other pathways, including calcium mobilization and protein kinase C activation have been described. We previously showed that intracerebral administration of the glutamate agonist ibotenate to postnatal day 5 mice induces white matter lesions mimicking human periventricular leukomalacia. In this model, coinjection of VIP protects against white matter lesions. This neuroprotection is independent from cAMP and is mediated by protein kinase C. Using this model, this study aimed to determine the receptor involved in VIP-induced neuroprotection. VIP effects were mimicked with a similar potency by VPAC(2) agonists and PHI but not by VPAC(1) agonists, PACAP 27, or PACAP 38. VIP neuroprotective effects were lost in mice lacking VPAC(2) receptor. In situ hybridization confirmed the presence of VPAC(2) mRNA in the postnatal day 5 white matter. When analyzed between embryonic life and adulthood, VIP-specific binding site density peaked at postnatal day 5. These data suggest that, in this model, VIP-induced neuroprotection is mediated by VPAC(2) receptors. The pharmacology of this VPAC(2) receptor seems unconventional because 1) PACAP does not mimic VIP effects, 2) PHI acts with a comparable potency, and 3) PACAP 27 modestly inhibited the VIP-specific binding, whereas for PHI or VIP, inhibition was complete.