• Preschoolers' knowledge of health and healthy behaviors

      Pearre, Rena C.; School of Nursing (1993-05)
      Children's knowledge and thoughts about health can influence their adult health behaviors, because behaviors learned in childhood are frequently carried throughout life. The purpose of this study was to explore preschoolers' knowledge of health. Twenty preschool children were interviewed using Flaherty's (1986) Preschool Health Picture Interview (PHPI). Data analyzed by t-tests revealed the age of the child to be a significant factor in the childs knowledge of health. The findings of this study suggest that preschoolers recognize pictures that indicate situations that could be hazardous to health as well as activities that promote health. Nurses need to work with preschoolers to promote health education so that these behaviors will continue in adulthood.
    • Prevalence and severity of hypertension in a dental hygiene clinic

      Thompon, Ana Luz; School of Graduate Studies (2004-07)
      This study assessed the prevalence and severity of hypertension in a dental hygiene clinic. Records of 615 patients, treated by dental hygiene students during 2003, were reviewed. Data collected included systolic and diastolic blood pressure, presence of \ I diabetes and renal' disease, non-modifiers (race, gender, age), and modifiers (marital status, smoking habits, and occupation). According to the JNC7 Classification, 154 (25%) of the subjects had Normal blood pressure readings, 374 (60.8%) had Prehypertension, and 87 (14.1 %) had Stag~ 1 Hypertension. Statistical analysis showed a significant difference in the JNC7 Classification between groups when considering the non-modifier, race (p = .02), and the modifiers, smoking habits· (p = .03) and occupation (p = .01). A statistically significant difference in the JNC7 Classification existed between groups with diabetes (p = .00). Several recommendations were made to align the dental hygiene clinic policy for assessing and diagnosing hypertension with the 2003 JNC7 Classification.
    • Primary Tumor-Induced Immunity Is Suppressed By Surgery-Induced Inflammation In The Presence Of Residual Tumor Cells

      Piranlioglu, Raziye; Department of Biochemistry and Molecular Biology (Augusta University, 2019-12)
      It is widely thought that tumor cells disseminate from a primary site into the circulation during the early stages of tumor development. However, the fate of these early disseminated tumor cells (DTCs) has been elusive. By utilizing the murine mammary tumors, 4T1 and EMT6, in a syngeneic mouse model, we show that both tumors disseminate into secondary organs but only 4T1 tumors are able to generate metastasis. In contrast, EMT6 primary tumors induce an anti-tumor response that leads to elimination of DTCs. This anti-tumor immunity is CD8+ T cell-dependent and provides long-term immunity. Furthermore, the mice are free of DTCs within a couple of days when primary tumors are completely resected and they reject subsequently injected tumors, whereas mice with residual tumors following surgery show enhanced local recurrence and outgrowth of DTCs at metastatic sites; this effect may be explained by elevated levels of granulocyte colony-stimulating factor (G-CSF). This increase is accompanied by an accumulation of immature myeloid-derived suppressor cells (MDSCs) in the spleen and lungs, the main target organ for metastasis. Moreover, the infiltration of a granulocytic subset of MDSCs (gMDSCs) leads to a decrease in a subset of T cells that have a role in long-term immunity. Our goal for this study is to elucidate how immune components of distant organs affect the fate of DTCs and the role of surgery induced-inflammation in generating a pre-metastatic niche. Our studies may also provide a molecular explanation of improved overall survival in breast cancer patients following complete resection of primary tumors with negative margins.
    • Primary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogs

      Hussein, Khaled A.; Department of Oral Biology (2012-12)
      Very often, delayed reconstruction becomes the setting of choice in the reconstruction of large segmental defects in the mandible. Our hypothesis is that rhBMP2 delivery would elicit endogenous expression of BMP2 and VEGF in the soft tissue bed of the defect. Such response is expected to be more pronounced in the immediate than the delayed reconstruction, which will correlate with the quantity and quality of bone formation in the two settings. We also hypothesized that vascular endothelial cells (ECs) of the surrounding soft tissue contribute to the endogenous production of BMP2. In this study we used a mandibular canine segmental defect model (35 mm), periosteum was excised and also the delayed reconstruction group was included in this study in addition to the control group. We investigated the effect of different reconstruction settings on the quantity and quality of bony regenerates; on the production of endogenous BMP2 from the soft tissue bed of the defects and finally we tried to explore the source of this rhBMP2- induced endogenous BMP2 production both in vivo and in vitro. This study demonstrated that rhBMP2 delivery is more effective in immediate reconstruction of large mandibular segmental defects. Immediate delivery of rhBMP2 yielded more adequate reconstruction of the defect after 12 weeks, evident by the quantity and quality of the bone regenerate. Only in the immediate reconstruction group, the advantageous bone parameters were associated with significant up-regulation of BMP2 mRNA and protein in the soft tissue bed of the defect. This suggests that endogenous-BMP2 is important in maintaining the short-acting effect of the delivered rhBMP2. Regarding the source of the endogenous-BMP2, protein co-localization with ECs marker suggested that these cells could be the source for the endogenous BMP2 secretion in response to rhBMP2 treatment. This was confirmed by the in-vitro results on both the mRNA and protein levels. The gradual increase in expression of BMP2 mRNA and the significant upregulation of secreted BMP2 protein upon stimulation of human umbilical vein endothelial cells with 100-ng/ml rhBMP2 recognized a new mechanism of positive feed back response of ECs in response to BMP2 treatment.
    • Proactive Readiness Among Parents of Children with Chronic Mental Health Conditions

      McKinnon, Caroline R.; Department of Physiological and Technological Nursing (2013-11)
      Childhood mental health conditions are prevalent, persistent, serious, and complex. Families are expected to be involved in their child’s care, but may vary in their readiness for taking an active role. Proactive readiness is a new concept encompassing role beliefs, knowledge, confidence, and self-efficacy. Understanding the relevance of proactive readiness is a critical first step in supporting family management for mentally ill children. The study purpose was to describe the extent for which mothers of mentally ill children discussed proactive readiness. Data from a social support intervention study for mothers of children with mental health conditions (Scharer et al., 2009) were used in a secondary analysis to examine the extent to which mothers participated in a web-based chat room intervention and the content of their posts. A step-wise quantitative content analysis was conducted using a census sample of transcript data. Trained coders categorized mothers’ posts into one of four proactive readiness categories or as other content. Relationships between content of mothers’ posts, chat room participation, and demographic and health variables were examined. Over 3 years, 24 of 39 mothers posted approximately 5,000 messages. Mothers posted proactive readiness content in an average of 20% of their sentences (n=1190). Knowledge was the dominant content category, followed by role belief and much less frequently confidence of self-efficacy. Mothers in the lowest income group posted significantly more proactive readiness, role belief, and confidence content. Maternal race was significantly associated with chat room attendance and total posts, but not with posts per session attended. Proactive readiness content and chat room participation were unrelated to any other child, maternal, or family demographic or health variable. based on the findings of this study, proactive readiness appears to be a relevant topic among mothers of children with chronic mental health conditions. Further data are needed to provide details about the nature of mothers’ proactive readiness. Future researchers should consider using this study’s coding scheme as well as research designs and statistical analyses that would expand on the limited generalizability of this exploratory study. Nursing practice implications include a particular concern for low-income families receiving child mental health services.
    • The production rate of estradiol in the stein-leventhal syndrome

      Puebla, Ruben A.; Department of Endocrinology (1964-06)
    • Progesterone Regulation of Proliferation and Regression of Rat Decidua Basalis

      Dai, Donghai; Department of Cellular Biology and Anatomy (1998-07)
      During implantation mesometrial cells o f the uterine stroma become decidualized under the coordinate actions of progesterone (P4 ) and estrogen (E) [1,2]. This process is characterized by transformation o f phenotype and stromal cell proliferation between Days 8-12 of gestation, resulting ultimately in the formation o f the decidua basalis (DB) [3,4], By Day 14. however, the DB begins to regress and a reduced layer o f stromal cells persists to the end of pregnancy [5.6]. The regression of DB is accompanied by development o f two other layers, namely junctional zone (JZ) and labyrinth zone (LZ), which are fetal parts of the placenta and morphologically become predominant at the end stages o f pregnancy. Although the morphological changes have been well documented and numerous functions have been revealed for DB [3-8], the mechanism and factors involved in the regulation of proliferation and regression o f DB have not been elucidated. The transition of DB from proliferation to regression occurs in such a delicate way that the morphological integrity and functional competence of the DB and placenta are maintained even though stromal cells are being lost. The objective o f this study was to identify the intracellular signals initially favoring proliferation and synthetic processes and those promoting remodeling and regression as pregnancy progresses.
    • Progesterone regulation of proliferation and regression of rat decidua basalis

      Dai, Donghai; Medical College of Georgia (Augusta University, 1998-07)
    • Proposal for coordination of care and discharge planning in a tertiary care facility

      Woodward, Elizabeth Scudder; School of Graduate Studies (1976-06)
    • Protection Against Colonic Inflammation and Colon Cancer by Commensal Bacterial Metabolites: An Obligatory Role for the Short- Chain Fatty Acid Transporter Slc5a8

      Gurav, Ashish; Georgia Cancer Center (2014-11)
      Dietary fiber consumption has long been known to protect against inflammatory bowel diseases and colorectal carcinogenesis. In mammals, large intestinal microorganisms ferment dietary fiber to generate energy, while releasing short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate. Interestingly, SCFAs are also known to protect against intestinal inflammation and colorectal carcinogenesis, although the molecular mechanisms behind these actions are still being investigated. For most of their biological effects, SCFAs must be transported from lumen into the intestinal tissue, where they activate multiple biological processes. We and others have reported Slc5a8 as a high affinity transport mechanism for SCFAs, which would remain fully functional, even when SCFA concentration drops to sub-millimolar range, whereas other transport mechanisms are rendered inefficient. The aim of the current study was to test protective role of Slc5a8 against intestinal inflammation and colorectal carcinogenesis during suboptimal intake of dietary fiber. We observed that Slc5a8 is obligatory for HDAC-inhibition in colonic epithelium and intestinal barrier function, only when the animals were fed a dietary fiber-free diet (FF diet), and not when the animals were fed diet containing optimal amounts of fibers (FC Diet). Compared to WT, Slc5a8-/- animals demonstrated higher susceptibility to AOMDSS- mediated intestinal inflammation and colorectal carcinogenesis under FF dietary conditions, but not under FC dietary conditions. At molecular level, we found that butyrate and propionate could induce potent immunosuppressive enzymes Indoleamine 2,3-dioxygenase and Aldehyde Dehydrogenase 1A2 in dendritic cells obtained from WT animals, but not from Slc5a8-/- animals. Butyrate, transported via Slc5a8 enabled DCs to suppress conversion of naïve T cells to interferon-γ secreting pro-inflammatory T cells and Slc5a8-/- animals harbored higher proportion of interferon-γ+ CD4+ T cells in vivo. Taken together, our data provide crucial evidence for critical role of Slc5a8 mediating protective effects of dietary fiber metabolites, SCFAs in protecting against intestinal inflammation and colorectal carcinogenesis.
    • Protein kinase C and contraction in rabbit iris smooth muscle

      Howe, Phillip H; Department of Cell and Molecular Biology (1988-03)
    • Protein Kinase D In Keratinocyte Maturation

      Dodd, M. Ernest; Department of Physiology (2004-08)
      The epidermis is important for the body's maintenance of water homeostasis and resistance to environmental stress, and the m ajor cell type of the epidermis is the keratinocyte. Keratinocyte maturation requires proliferation, followed by terminal differentiation, and diseases of the skin often exhibit deregulated epidermal maturation. Protein kinase D (PKD) expression correlates with proliferation in keratinocytes, and PKD activation occurs in response to mitogen stimulation in other cell types. W e have hypothesized that PKD functions as a pro-proliferative and/or anti-differentiative signal in primary mouse keratinocytes and have predicted that agents that stimulate differentiation might also initiate a reduction in PKD expression and/or activation to allow differentiation to proceed. Thus, changes in PKD levels, autophosphorylation and activity were analyzed upon treatment with differentiating agents and with 1 2 -0 - tetradecanoylphorbol-13-acetate, TPA, which stimulates differentiation acutely and proliferation chronically. 1,25-dihydroxyvitamin D3 -, elevated extracellular calcium-, and acute TPA-induced differentiation down-modulated PKD levels and autophosphorylation at serine 916. In addition, elevated extracellular calcium- and acute TPA-induced differentiation down-modulated PKD activity. Chronic TPA treatment stimulated proliferation and caused a recovery o f PKD levels, autophosphorylation and activity. In co-transfection experiments in keratinocytes, co-expression of PKD increased and decreased the promoter activities of keratin 5, a marker of proliferation, and involucrin, a marker of differentiation, respectively, and opposed the effects of elevated extracellular calcium on the expression of these markers. W hile cloning PKD for expression studies, we identified a splice variant of PKD, PKD{3, which is differentially spliced in a region important in activation and subcellular localization. Therefore, we hypothesized that this splice variant may have dissimilar activation properties and/or alternate roles in keratinocyte maturation. However, in vitro activation studies demonstrated equal activation of PK D a (full length) and PKDj3 by TPA and DAG. Co-transfection experiments showed that P K D a and PKDp affected marker expression to the same degree and similarly opposed the effects of elevated extracellular calcium-induced differentiation on marker expression. Our work represents the first demonstration of: 1) down-modulation o f PKD during differentiation, 2) pro-proliferative/anti-differentiative effects of PKD on keratinocyte marker expression and 3) existence of a splice variant of PKD.
    • Protein Kinase D Restrains Angiotensin II-Induced Aldosterone Secretion in Primary Adrenal Glomerulosa Cells

      Shapiro, Brian A.; Department of Physiology (2007-07)
      Misregulation of the renin-angiotensin II (Angll)-aldosterone (Aldo) system is a key feature of cardiovascular disease. A focus of study in this system is the Angll-elicited secretion of Aldo from the adrenocortical zona glomerulosa. An excellent model in which to study this phenomenon is primary cultures of bovine adrenal glomerulosa (AG) cells. These cells secrete detectable quantities of Aldo in response to secretagogues, such as Angll, elevated potassium (K+), adrenocorticotrophic hormone (ACTH) and phorbol 12-myristate 13-acetate (PMA), within 30 minutes. The serine (Ser)/threonine kinase protein kinase D (PKD) is reported to be activated by Angll in several systems, including the adrenocortical carcinoma cell line NCI H295R, and is thought to have a positive role in chronic (24 hours) Angll-evoked Aldo secretion. Because the role of PKD in acute Angll-elicited Aldo secretion has never been examined in a primary culture system, we undertook to study the role of PKD in acute (minutes to one hour) Aldo secretion. Thus, Angll (10 nM) and PMA (100 nM), but not elevated K+ (15 mM) and ACTH (10 nM), induced phosphorylation of PKD on Ser910, a marker of PKD activation, in primary bovine AG cells. This finding was confirmed by an in vitro kinase activity assay. Angll and PMA were also able to induce PKD activation in H295R cells. Furthermore, this activation was concentration dependent, and was rapidly induced (by 5 min). PKD activation was dependent on Angll type 1 (AT-1), but not AT-2 receptor, signaling, and was independent of tyrosine kinase signaling. Finally, we introduced, via adenovirus transduction, wild-type PKDwt and dominant negative PKDS738/742A constructs into primary AG cells and monitored Angll-evoked Aldo secretion. PKDwt -transduced AG cells exhibited decreased Angll-stimulated Aldo secretion, while in the PKDS738A742A - infected AG cells Angll-stimulated Aldo was enhanced. Thus, we hypothesize that PKD has an anti-secretory role in Angll-induced acute Aldo secretion.
    • Protein Kinase D restrains angiotensin II-induced aldosterone secretion in primary bovine adrenal glomerulosa cells

      Shapiro, Brian; Medical College of Georgia (Augusta University, 2007)
      Misregulation of the renin-angiotensin II (Angll)-aldosterone (Aldo) system is a key feature of cardiovascular disease. A focus of study in this system is the Angll-elicited secretion of Aldo from the adrenocortical zona glomerulosa. An excellent model in which to study this phenomenon is primary cultures of bovine adrenal glomerulosa (AG) cells. These cells secrete detectable quantities of Aldo in response to secretagogues, such as Angll, elevated potassium (K+), adrenocorticotrophic hormone (ACTH) and phorbol 12-myristate 13-acetate (PMA), within 30 minutes. The serine (Ser)/threonine kinase protein kinase D (PKD) is reported to be activated by Angll in several systems, including the adrenocortical carcinoma cell line NCI H295R, and is thought to have a positive role in chronic (24 hours) Angll-evoked Aldo secretion. Because the role ofPKD in acute Angll-elicited Aldo secretion has never been examined in a primary culture system, we undertook to study the role of PKD in acute (minutes to one hour) Aldo secretion. Thus, Angll (10 nM) and PMA (100 nM), but not elevated K+ (15 mM) and ACTH (10 nM), induced phosphorylation of PKD on Ser9l 0, a marker of PKD activation, in primary bovine AG cells. This finding was confirmed by an in vitro kinase activity assay. Angll and PMA were also able to induce PKD activation in H295R cells. Furthermore, this activation was concentration dependent, and was rapidly induced (by 5 min). PKD activation was dependent on Angll type 1 (AT-I), but not AT-2 receptor, signaling, and was independent of tyrosine kinase signaling. Finally, we introduced, via adenovirus transduction, wild-type PKDw' imd dominant negative PKDs738n4 zA constructs into primary AG cells and monitored Angll-evoked Aldo secretion. PKDw' -transduced AG cells exhibited decreased Angll-stimulated Aldo secretion, while in the PKDs738n42 Ainfected AG cells Angll-stimulated Aldo was enhanced. Thus, we hypothesize that PKD has an anti-secretory role in Angll-induced acute Aldo secretion.
    • Protein-Protein Interaction between G protein-coupled receptors and heterotrimeric G proteins

      Qin, Kou; Department of Pharmacology and Toxicology (2011-01)
      G protein-coupled receptors (GPCRs) interact directly with heterotrimeric G proteins to transduce physiological signals. Early studies of this interaction concluded that GPCRs (R) and G proteins (G) collide with each other randomly after receptor activation and that R-G complexes are transient (collision model). More recent studies have suggested that inactive R and G are preassembled as stable R-G complexes in cells (preassembly models). Using fluorescence recovery after photobleaching (FRAP) we examined the stability of complexes formed between cyan fluorescent protein-labeled a2Aadrenoreceptors (C-a2ARs) and G proteins in HEK293 cells. Labeled G proteins diffused in the plasma membrane with equal mobility in the absence and presence of immobile C- a2ARs. In contrast, a stable R-G interaction was detected when G proteins were deprived of nucleotides and C- a2ARs were active. Over-expression of regulator of G protein signaling 4 (RGS4) accelerated the onset of effector activation but did not alter the interaction between C- a2ARs and G proteins. At most a small fraction of C- a2ARs and G proteins exist as R-G complexes at any moment. However, applying similar technique and protocols, we demonstrated that immobilized M3R specifically decreases the mobility of Gaq heterotrimers on the plasma membranes of intact HEK293 cells, suggesting the existence of R-G preassembly. The C-terminus of M3R was determined to be both required and sufficient for preassembly. The M3R C-terminus contains a polybasic region (565KKKRRK570) located distal to the 8th a-helix domain. Substitution of this polybasic region with 6 electroneutral alanines (M3R6A) prevented preassembly. Permeabilization of cells with low ionic strength buffer resulted in enhanced R-G interaction, implicating electrostatic forces as a factor in the preassembly. We examined the functional properties of the mutant M3R6A, which showed decreases in acetylcholine potency compared with M3R. M3R6A produced active Gq at half the rate of M3R. Other Gq-coupled receptors, such as M1 and M5 muscarinic and a1a,a1b, aid adrenergic receptors, contain similar C-terminal polybasic regions. We found that both M5R and alb adrenoceptor (albAR) preassembled with Gq proteins. Our findings suggest that a polybasic regionmediated electrostatic mechanism could be a common mechanism of preassembly between Gq-coupled receptors and Gq proteins.
    • Psychiatric nurses' attitudes toward caring for suicide attempters

      Screene, Myrtis Delores; School of Nursing (1983-06)
      The two pu_rp ses of this study were 1 to develop an instrument to measure psychiatric nur es attitudes toward_ caring for suicide attempters and 2 to determine if there is a correlation between the perceived intention of the suic de attempter and psyihiatric nurses attitudes toward caring for these patients A descriptive correlational research approach was utilized using the Psychiatric Nurses Attitudes T ward Carin For Suicide Attempters Questionnaire A questionnaire consisting of 12 vignettes describing suicide attempters and a set of djectives on a semaritic differ ntial scale was develdped and admini tered to 15 psychiatric registered nurses employed at two hospitals The data collected were analyzed using descript ve statistics and the Spearman Rho Correlation Coefficients to determine if a relationship existed between perceived in tention of suicide attempters and psychiatric urses attitudes toward caring for_patients who have made suicide attempts The vignettes were sequentially ranked showing the overall means and standard deviations for the 12 vignettes intention check list nd set of adjectives The correlation of the summated score for each vignette with int nt was analyzed and these coefficients ranged from 18 to 35 Responses to the 12 vignett s sho ed n6 statistically_ iignificant differences p 25 Results of the data did not support the proposed hypothesis of the i nvesti gator
    • Pulmonary capillary endothelium -bound angiotensin -converting enzyme in acute thromboembolic pulmonary hypertension

      Theodorakis, Michael John; Department of Pharmacology and Toxicology (Medical College of Georgia, 2000-10)
      Pulmonary embolism (PE) imposes a significant hemodynamic burden upon the pulmonary circulation, compromising the functional integrity of pulmonary vascular endothelium. The relative contribution of mechanical occlusion alone or together with endothelial dysfunction in the lung vasculature is unclear. By indicator-dilution techniques we assessed relative changes in the activity and mass of pulmonary capillary endothelium-bound (PCEB)-angiotensin converting enzyme (ACE) in acute PE followed by thrombolysis with streptokinase in an autologous clot model of New Zealand White rabbits placed on heart by-pass and perfused with donor blood in Kreb's buffer at a constant flow. We estimated the percent metabolism (%M) and hydrolysis (v) of the ACE-specific substrate 3H-benzoyl-Phenylalanine-Alanine-Proline; 3H-BPAP, representing ACE activity within individual capillary groups. Changes in ACE mass, expressed as the Capillary Perfusion Index (CPI), reflected the dynamically perfused capillary surface area since ACE is uniformly distributed along the vascular endothelial surface. We evaluated the relationship between these parameters and effects of PE and thrombolysis on mean pulmonary arterial pressure (PAP) and employed on-line measurements of peak exhaled nitric oxide levels. Acute PE-induced increases in PAP 100% above baseline were immediately followed by significant decrease in all indices of PCEB-ACE activity. Without thrombolysis, they remained at low levels, while in the presence of thrombolysis, they significantly increased inversely proportionally to the decreasing PAP suggesting increasing recruitment of previously non-perfused capillary segments. Separate measurements of enzyme affinity constant and the product of enzyme mass with a kinetic constant ratio, showed stable enzyme function but suggested changing enzyme mass as the source of altered enzyme-substrate kinetics. Treating bovine aortic endothelial cells with either thrombin or perfusate from in vivo experiments with acute PE, failed to alter endothelial cell ACE activity. Streptokinase had no effect, both in vivo and in vitro. ETA-receptor blockade did not attenuate acute pressor responses to PE, but in the absence of thrombolysis, all enzyme-substrate kinetic parameters were significantly improved after the first hour of PE. Since this was abolished in the presence of immediate thrombolysis, ET-1-mediated endothelial dysfunction may be superimposed on the hemodynamic burden post-PE, later in the pathophysiological course. Animal pretreatment with superoxide dismutase, catalase and dimethylurea (known to ameliorate endothelial ACE dysfunction in vitro), did not have any effect. Exhaled NO gradually and steadily declined even in the absence of any intervention, but the decrease was more pronounced and immediate in the presence of acute PE. Thrombolysis, although partly reversing the post-thromboembolic decrease in ACE activity indices and lowering PAP, did not have any effect upon peak exNO levels. ETA-blockade transiently increased exNO levels 2.5 min post-PE and exNO remained in significantly higher levels compared to non-ET A-blocker pre-treated groups. This study demonstrates that acute PE followed by thrombolysis, decreases and subsequently increases and normalizes PCEB-ACE activity inversely proportionally to altered pulmonary hemodynamics. This phenomenon is due to mechanical occlusion rather than endothelial dysfunction, which, however, could complicate vascular luminal loss in the absence of thrombolysis, an effect which may be ET A-receptor mediated. ExNO significantly decreases immediately after PE—an effect reversed by ETA-receptor blockade—independently of restoration in hemodynamics or endothelial ACE activity.