bluuebunny/crossref_metadata_2025_split huggingface dataset:
KvLQT1 Function in Lung Physiology
Authors: Girault Alban , Chebli Jasmine , Prive Anik , Maille Emilie , Peloquin Fannie , Robichaud Annette , Brochiero Emmanuelle 
Published: June 2021

Acute lung injury and its more severe form, acute respiratory distress syndrome (ARDS), are characterized by extensive alveolar injury and lung edema. It has been established that the resolution of ARDS parameters is highly dependent on alveolar regeneration and edema resorption. Because we previously demonstrated that KvLQT1 potassium channels are involved in alveolar repair processes and in the control of ion and liquid transports in vitro, we now decided to investigate their role in lung function and in the resolution of ARDS parameters in vivo, using a KvLQT1 knockout (KO) mice model.We first noted an absence of morphological difference in airway structures (trachea, bronchus and alveolus) between control (wild type, WT) and KvLQT1 KO mice. We then evaluated the impact of KvLQT1 extinction on the mechanical properties of the respiratory system using the flexiVent system (SCIREQ Inc.). Our results showed a significant increase of tissue damping and dynamic resistance of the respiratory system in KvLQT1 KO mice compared to WT.The role of KvLQT1 was then evaluated in a model of lung edema induced by thiourea, disrupting the integrity of endothelial/alveolar barrier. We observed a significant increase in the wet/dry ratio (W/D, index of lung edema) in both WT and KO mice. Interestingly, the thiourea‐induced W/D increase was partially prevented by a treatment with R‐L3, a KvLQT1 activator, in WT mice. However, this beneficial effect of R‐L3 was lost in KO mice.Our results show that the activation of KvLQT1 K+ channels could play a role in the resolution of ARDS parameters, especially pulmonary edema resorption.Funded by CIHR, NSERC, FRQS.
Medical and Social Aspects of Termination of Pregnancy in Semey city in Kazakhstan
Authors: Yesbolatova Gulya , Kozhanova Saule , Sagimova Gulzira , Mekebaeva Alma , Temirtassova Zhanna , Musina Alya 
Published: June 2021

Formation of risk groups of abortion is an important part of the mother and child health program which is possible with a detailed analysis of epidemiological data.ObjectivesTo identify risk groups and critical periods for miscarriage based on the analysis of medical and social aspects of abortion in Semey, Eastern Kazakhstan.MethodsStudy was performed on 507 cases of miscarriage during 2011‐2012. Women were at age of 15‐45 years.Results20% of miscarriage cases were in age 21‐23 years, 28.8% were unmarried. With increasing age group the proportion of cases of miscarriage decreased from 16.8% in 24‐26 years to 3.7% for 42‐45 years. The proportion of unmarried women also reduced from 20.0% to 5.3% respectively. Miscarriage among girls of 15‐17 years was in 3.9% and girls of 18‐20 years in 13.0% of all cases, 80‐90% were unmarried. More than 65% of miscarriage occur in the first period of mature from 21 to 35 years. Among the medical and social aspects of abortion 65.8% are spontaneous abortion, 24.6% abortion for social and 9.6 % for medical reasons. These data did not differ in 2011 and 2012. Spontaneous abortion in 2011 occurred in 66.0% of cases, and in 2012 in 65.7 % of cases, for social reasons in in 25.1% and 23.9% respectively, for medical indications were at 9.6% and 10.3 % of cases respectively. The greatest number of cases of spontaneous abortion accounted on 16 and 20 weeks. On 16 weeks spontaneous abortion occurred in 16.9 % and on 20 weeks in 20.3% of all cases.ConclusionAmong the medico‐social aspects of miscarriage more than 65 % are spontaneous abortion. The risk group for miscarriage is the age group of 21‐23 years with the high percentage of unmarried women.
Long Term Probiotic Use Increases Bone Density in Female Mice
Authors: Collins Fraser , Quach Darin , Irwin Regina , Schaefer Laura , Britton Robert , Parameswaran Narayanan , McCabe Laura 
Published: June 2021

Probiotic bacteria are micro‐organisms that when taken in adequate amounts have beneficial effects on the host. A previously published study from our laboratory demonstrated that short term (4 week) treatment of male but not female mice, with Lactobacillus reuteri (ATCC 6475) lead to increased bone density. In the present study we investigate the long term (8 weeks) effects of L. reuteri treatment in female mice.Female Balb/c mice were treated by gavaging with L. reuteri (1x109cfu/ml) or vehicle control (MRS broth) three times per week. In addition, L. reuteri (1.5x108cfu/ml) or vehicle was added to the drinking water for the duration of the study. At 4 and 8 weeks femoral trabecular bone parameters were measured by µCT. Bone marrow (BM) cellular phenotype was analyzed by flow cytometry and RANKL, OPG and TGFβ gene expression evaluated by qPCR.Similar to our earlier studies in fertile female mice, we did not observe any effect of LR on bone parameters at 4 week treatment. Interestingly however, at 8 weeks a significant 30.3% increase in femoral trabecular bone volume fraction was identified in L. reuteri treated mice. Examination of BM cellular phenotype and gene expression demonstrated that L. reuteri increased numbers of CD4+ T cells and significantly reduced RANKL expression at 4 weeks but not at 8 weeks. OPG and TGFβ expression were found to be elevated at 4 weeks, with TGFβ expression significantly increased at 8 weeks in the L. reuteri cohort.Together our data indicates that long term L. reuteri treatment increases femoral trabecular bone in female mice via the regulation of immune cells and expression of key genes involved in osteoclastogenesis
Use of Vitamin A Supplementation to Enhance Neutrophil Function
Authors: Anderson Ericka , Corriden Ross , Dohrmann Simon , Nizet Victor 
Published: June 2021

Vitamin A is a micronutrient essential for growth, cellular differentiation, reproduction, vision, and immunity. Retinoic acid (RA), the active metabolite of Vitamin A, affects transcriptional activity by binding to its receptors, RARs (Retinoic Acid Receptors) and RXRs (Retinoid X Receptors). Vitamin A is essential for immunity in humans, and deficiency is associated with increased morbidity and mortality from infectious diseases. Vitamin A deficient (VAD) neutrophils and macrophages exhibit impaired phagocytosis and bacterial killing, and infectious diseases can cause VAD by decreasing intake, decreasing absorption, and increasing excretion of Vitamin A. Thus, VAD and infection are thought to exist in a “vicious cycle”.Here, we investigated whether RA treatment enhances neutrophil killing and has direct antibacterial activity. Human neutrophils were pretreated with RA and then tested for their ability to kill E. coli K1, S. aureus MRSA, and S. pyogenes. We found that RA induced production of both reactive oxygen species (ROS) and neutrophil extracellular traps (NETs), critical mediators of neutrophil bactericidal activity, and enhanced killing of all bacteria tested. RA was also found to have direct activity against S. pyogenes. These results suggest a potential for RA as a treatment for bacterial infections.This work was supported by the UNCF‐Merck Science Initiative Postdoctoral Fellowship (EA), and NIH grants AI096837 and AI077780 (VN).
Shortening Speed Dependence of Concentric Force Potentiation in the Absence of Myosin Phosphorylation
Authors: Bunda Jordan , Gittings Bill , Vandenboom Rene 
Published: June 2021

Contraction‐induced elevation of myoplasmic Ca2+ leads to sequential activation of skeletal muscle myosin light chain kinase (skMLCK), an enzyme responsible for phosphorylating the myosin regulatory light chain (RLC). In wildtype (WT) mouse skeletal muscle containing skMLCK, force potentiation correlates with RLC phosphate content; although, these muscles may contain an RLC phosphorylation‐independent component. In this study, extensor digitorum longus (EDL) muscles from knockout (KO) C57BL/6 mice, devoid of skMLCK, were activated in vitro (25°C) across a range of stimulation frequencies (10, 25, 45, 70 and 100 Hz) and subjected to shortening ramps at 0.1, 0.3 or 0.5 of maximal shortening velocity (Vmax). This was performed before and after a standard conditioning stimulus (CS) that potentiated mean concentric force at 0.3 and 0.5 Vmax to 1.20 ± 0.03 and 1.30 ± 0.02 of unpotentiated (pre‐CS) values, respectively; however, mean forces were depressed to 0.84 ± 0.03 of pre‐CS values at 0.1 Vmax (n = 3, P < 0.05). Increasing shortening speed augmented the frequency at which concentric force potentiation was maximal: 25 and 45 Hz at 0.3 and 0.5 Vmax, respectively. These results mirrored previous results from WT muscles (Gittings et al., 2012), except that concentric force potentiation was attenuated by ~50% across all frequencies at 0.3 and 0.5 Vmax, while force at 0.1 Vmax was reduced rather than unchanged. Thus, our data indicates the presence of an RLC phosphorylation‐independent mechanism for potentiation in skMLCK KO muscles that may complement the intact RLC phosphorylation mechanism in WT muscles.Supported by NSERC (2014‐05122).
Nandrolone Decanoate Changes The Natriuretic Peptide System in Femaile Rats
Authors: Brasil Girlandia , Lima Ewelyne , Nascimento Andrews , Caliman Izabela , dos Reis Adelina , Andrade Tadeu , Bissoli Nazaré 
Published: June 2021

IntroductionThe knowledge about the actions of androgenic‐anabolic steroid in females is poorly understood so the aim of the present study was evaluate the action of nandrolone decanoate (ND) and exercise on ANP system in young females.MethodsThe animals were divided in groups: S (sham surgery; vehicle), SD (sham surgery; ND, 20mg/kg/week), SE (sham surgery; resistive trainning) and SDE (sham surgery; ND, 20mg/kg/week and resistive trainning) the treatments started 21 days after surgery, and were made for 4 weeks. After that the animals were euthanized, the right atrium and left kidney were stored under refrigeration until the analysis. The ANP system evaluation were made looking for ANP gene on heart and ANP receptor on kidney (CEUA‐UFES: 031/2012). Two way ANOVA followed by bonferroni post‐test.ResultsThe treatment with ND was able to increase the gene expression on atrium (S:1.142±0.102; SD: 2.802±0.488; SE:1.000±0.030; SDE: 2.962±0.385 ANP/26s mRNA expression in arbitrary units; p<0.01 when compared to S group) and also decrease the expression of ANPimageA receptor on kidney (S:5.908±0.307, SD:1.050±0.243, SE:4.280±0.800, SDE:2.402±0.690 NPRA/26s mRNA expression in arbitrary units; p<0.01 when compared to S group). We also observed a cardiac hypertrophy and kidney hipertrophy after the treatmentsimageConclusionsSo these results suggest that the ND can promote an increase on ANP release on atrium and that can be the reason of the reduction on ANP receptor on kidney.
Effect of Salt Diet on Beat‐to‐Beat Blood Pressure Dynamics in Hypertensive and Non‐hypertensive Rats
Authors: Fares S , Habib J , Engoren M , Badr K , Habib R 
Published: June 2021

ObjectivesBlood pressure normally exhibits substantial short and long term variability (BPV). We assessed, in salt sensitive hypertensive (SS) and non‐hypertensive (SSBN13) Dahl rats, the impact of high (HS) versus low (LS) salt diet on beat‐to‐beat BPV indices including correlation properties (detrended fluctuation analysis scale coefficient α) and complexity (Sample Entropy; SpEn)MethodsBP data were analyzed from 9 SS [HTN] and 6 SSBN13 [No‐HTN] rats: 1) after 9 weeks of LS diet (0.4%), and 2) repeated after 2 weeks of HS diet (8%). Beat‐to‐beat systolic and diastolic BP series were derived from 2‐minute data epochs (Physionet.org). SpEn, coefficient α, standard deviation (SD) and coefficient of variation (CV, %) were comparedResultsMean systolic and diastolic BP increased on HS – particularly in SS rats (Table). SD and CV were similar across groups irrespective of diet. On LS, HTN and No‐HTN exhibited similar systolic and diastolic complexity and correlation indices. On HS, 1) HTN showed an increased α (smoother) for systolic (p=0.015) and diastolic (p=0.021) BP; 2) No‐HTN showed lower SpEn (less complex) for systolic and diastolic BP (p=0.046), while corresponding α were unchanged; and 3) HTN showed higher systolic (p=0.003) and diastolic (p=0.001) α compared to No‐HTN. Changes in α (ΔHS‐LS) were greater in HTN versus No‐HTN rats for diastolic (p=0.034) and systolic (p=0.099) BP seriesConclusionHypertensive rats are more susceptible to HS with a greater rise in mean BP and reduced complexity. Yet, the comparable mean pressures in HTN and No‐HTN rats when on LS diet coupled with similar BPV dynamics suggest a protective role of low salt diet in hypertensive ratsFunding: None

Study Group
SS rats (HTN)
SSBN13 rats (No‐HTN)

Teatment

LS
HS
ΔHS‐LS
LS
HS
ΔHS‐LS

Systolic BP
mmHg
137±2ab
195±7ab
57±5b
125±2ab
155±3ab
30±2b

α
0.94±0.04a
1.15±0.04ab
0.21±0.05
0.91±0.05
0.97±0.02b
0.07±0.04

SpEn
1.43±0.06
1.26±0.06
0.16±0.10
1.51±0.09a
1.24±0.08a
‐0.28±0.09

SD
4.40±0.30
5.73±0.46
1.33±0.57
4.30±1.30
5.19±0.49
0.89±0.59

CV(%)
3.2±0.2
2.9±0.2
0.26±0.34
3.5±0.4
3.4±0.4
‐0.07±0.48

Diastolic BP
mmHg
102±3a
153±7ab
51±6b
97±1a
123±3ab
26±3b

α
0.98±0.04a
1.17±0.04ab
0.18±0.06b
0.94±0.04
0.95±0.01b
0.01±0.04b

SpEn
1.27±0.04
1.03±0.09
0.24±0.14
1.37±0.06a
1.21±0.02a
‐0.16±0.06

SD
4.03±0.31
4.70±0.48
0.67±0.59
3.80±0.50
4.65±0.56
0.85±0.58

CV(%)
3.97±0.25
3.13±0.29
0.85±0.41
3.89±0.47
3.82±0.47
‐0.08±0.48

Nbeats: 626‐953; data shown as mean±std err; a = P<0.05 LS vs HS (within‐group); b = P<0.05 SS vs SSBN13 (between‐groups; same treatment); comparisons using the rank sum and the sign rank test as appropriate
AT1 Receptors Modulate Ca2+ Transient in Adult Cardiomyocytes Treated with T3
Authors: Taniguti Ana Paula , Nocchi Eduardo , Almeida Pedro , Guatimosim Silvia , Barreto‐Chaves Maria Luiza 
Published: June 2021

Increased thyroid hormone (TH) levels promote cardiac hypertrophy and arrhythmia by direct actions on myocardium and by interaction with other systems as local renin‐angiotensin system (RAS). Previous studies have confirmed that T3 rapidly increases AT1R and angiotensin II protein levels in cultured cardiomyocytes. In the present study, we evaluated the contribution of AT1R on Ca2+ transient cardiomyocytes treated with T3. Adult ventricular cardiomyocytes (n=07) were isolated and treated for 30 minutes with T3 (15nM, Sigma), T3 plus losartan (LOS, 1µM, Sigma) or LOS alone. Intracellular Ca2+ (Ca2+ i) imaging experiments were performed in Fluo‐4 AM (10µM; Invitrogen) loaded‐cardiomyocytes and electrically stimulated at 1 Hz.The confocal imaging was performed with a Zeiss LSM 510META microscope. The Ca2+ level was reported as F/F0, where F0 is the resting Ca2+ fluorescence. T3 treatment induced a significant increase on Ca2+i transient (3,53±0,88 in T3 vs. 2,89±0,69 in Control, ANOVA, p蠄0.05) in adult cardimyocytes, which was attenuated by concomitant LOS treatment (3,08±0,79 in T3+LOS vs. T3, ANOVA, p蠄0,05) demonstrating a possible contribution of AT1R in the action of T3 in inducing Ca2+i transient in adult cardiomyocytes.Supported by FAPESP #2012/18515‐4
Endocardial Prevalence of Coronary Collaterals Becomes Transmurally More Uniform in a Human Heart with Left Ventricular Hypertrophy
Authors: van Lier Monique , Oost Elco , van der Wal Allard , Spaan Jos , Siebes Maria , van den Wijngaard Jeroen 
Published: June 2021

AimTo quantify and characterize coronary collaterals (CC) in human hearts.MethodsWe obtained one heart with left ventricular hypertrophy (LVH), and an old inferior posterolateral infarction (64 years, 595 g) and one normal heart without prior coronary artery disease (84 years, 330 g). The coronary arteries were filled with fluorescent replica material. Hearts were frozen, alternately cut and block‐face imaged using an imaging cryomicrotome (voxel size 32 μm). Collateral transmural distribution, connectivity and diameter were determined.ResultsThree times more collaterals were detected in the normal (n=4308) compared to the LVH heart (n=1272). In the normal heart, collaterals were mainly in the LV free wall (endo: 78%, mid: 14%, epi: 5%), whereas a more uniform distribution over the LV free wall (endo: 25%, mid: 12%, epi: 21%) and septum (endo: 27%, mid: 10%, epi: 2%) was found in the LVH heart. More intraCC (within major branches) than interCC (between major branches) were detected in the normal (4191 vs. 117) and LVH (1187 vs. 85) heart. InterCC were most prevalent between LCX‐LAD (99%) in the normal and between LCX‐LAD (62%) and LAD‐RCA (33%) in the LVH heart. Most intraCC were within the LAD and LCX territories in both hearts. The median CC diameter was larger in the LVH compared to the normal heart for both interCC (92.3 vs. 71.6 μm, p<0.001) and intraCC (81.88 vs. 60.4 μm, p<0.001).ConclusionsAs in healthy canine hearts, human hearts have abundant intra‐ and interCC collaterals. Transmural distribution was more homogeneous in LVH, with fewer but larger collaterals.
Variability in IV Adenosine‐Induced Coronary Microvascular Resistance and Systemic Pressure Compromises FFR Determination despite Stable Stenosis Hemodynamics
Authors: Casadonte Lorena , Marques Koen , Spaan Jos , Siebes Maria 
Published: June 2021

AimTo investigate the effect of intracoronary (IC) and intravenous (IV) adenosine administration on variability in coronary and stenosis hemodynamics.MethodsIn 12 diseased coronary vessels (25‐56% DS), aortic pressure (Pa), distal pressure (Pd) and flow velocity (v) were simultaneously measured at baseline and hyperemia induced by IC (40 μg bolus) and IV adenosine administration (140 μg/kg/min). At baseline and throughout the hyperemic response we obtained cycle‐averaged pressure and velocity signals to derive microvascular resistance (MR = Pd/v) and FFR= Pd/Pa. From fitted stenosis pressure gradient‐velocity (ΔP‐v) relations, we determined ΔP at v= 30 cm/s (dPv30).ResultsMaximal v was similar for IC and IV adenosine (50 ± 4 vs. 54 ± 5 cm/s) with no difference in MR (1.73 ± 0.10 vs. 1.74 ± 0.13 mmHg/cm/s). However, MR during IV hyperemia rose between 9 and 135% in the post‐peak period, with concomitant fluctuations in v (13 to 61% decline) and pressures (up to 34% decline). Minimal FFR coincided with peak v for IC adenosine, but occurred 21 ± 8 s after peak v for IV adenosine, when Pa had decreased by 13% and HR increased by 25% vs. baseline. IV and IC derived stenosis ΔP‐v relations followed a stable common quadratic relationship, with no difference in dPv30.ConclusionIV adenosine caused persistent systemic and coronary hemodynamic variability. IC adenosine yielded comparable hyperemia with minor effects on systemic hemodynamics. Consistent ΔP‐v relations and dPv30 provide reliable means for stenosis evaluation free from maximal vasodilation.
Angiotensin AT2 Receptor Agonist Prevents Salt‐Sensitive Hypertension in Obese Zucker Rats
Authors: Ali Quaisar , Patel Sanket , Hussain Tahir 
Published: June 2021

High sodium intake is a risk factor for the pathogenesis of hypertension, especially in obesity. The present study was designed to investigate whether angiotensin type‐2 receptor (AT2R) activation with selective agonist C21 prevents high‐sodium diet (HSD)‐induced hypertension in obese animals. Male obese rats were treated with AT2R agonist C21 (1mg/kg/day, oral) while maintained on either normal‐sodium diet (NSD, 0.4%) or HSD (4%) for 2‐weeks. Radio‐telemetric recording showed a time dependent increase in systolic blood pressure in HSD‐fed obese rats, being maximal increase (~27 mmHg) at day 12 of the HSD regimen. C21 treatment completely prevented the increase in blood pressure in HSD‐fed rats. Compared to NSD controls, HSD‐fed obese rats had greater natriuresis/diuresis, which were further increased by C21 treatment. HSD‐fed rats expressed higher level of cortical Ang II, which was reduced to 50% by C21 treatment. HSD feeding and/or C21 treatment had no effects on cortical renin activity and the expression of ACE and chymase, both AngII producing enzymes. However, Ang(1‐7) concentration and ACE2 activity in the cortex were reduced by HSD feeding, but C21 treatment rescued both the parameters. Also, C21 treatment reduced the cortical expression of AT1R in HSD‐fed rats, but had no effect of AT2R expression. We conclude that chronic treatment with the AT2R agonist C21 prevents salt‐sensitive hypertension in obese animals and a reduction in the renal AngII/AT1R levels may play a potential role in this phenomenon.Acknowledgement: This study was supported by NIH R01grant DK61578 to TH.
Reactive Oxygen Species and NFkB Increase Peritoneal Filtration and Generate Ascites in Nephrotic Syndrome
Authors: Doucet Alain , Brideau Gaelle , Vogt Bruno , Udwan Khalil 
Published: June 2021

Clinical and experimental observations suggest that nephrotic ascites is not accounted for by hypoalbuminemia but by changes of the capillary endothelium permeability. We investigated the mechanism of these changes in puromycin aminonucleoside (PAN) nephrotic rats. The peritoneal filtration coefficient (Kf) was estimated by the slope of the regression line connecting the trans‐peritoneal gradient of osmotic pressure which was varied experimentally to the trans‐peritoneal water flux measured by osmotic dilution.Kf doubled and expression of aquaporin 1 (AQP1) increased in peritoneum of PAN rats. PAN rats displayed peritoneal oxidative stress attested by ROS accumulation and dysregulation of NADPH oxidase and ROS detoxifying enzymes expression. The ROS scavenger N‐acetyl cysteine (NAC) prevented the increase in Kf and in AQP1 expression. It also reduced by half the volume of ascites without changing renal sodium handling, albuminuria or hypoalbuminemia. PAN rats peritoneum also displayed activation of NFkB attested by increased nuclear labeling with anti‐p50 antibody. Activation of NFkB was blunted in NAC‐treated PAN rats. JSH‐23, an inhibitor of NFkB transcriptional activity, mimicked all the effects of NAC.These results show that nephrotic syndrome is associated with increased filtration coefficient of the peritoneal barrier which stems in part from increased expression of AQP1. These changes are triggered by oxidative stress and subsequent activation of NFkB. They account for at least half of increased filtration rate, the remaining stemming possibly from decreased plasma oncotic pressure.
ADF/COF Have Different Effects on Intestinal Brush Border Structure and NHE3 Activity
Authors: Gao Lucy , Sarker Rafiquel , Donowitz Mark 
Published: June 2021

The Na‐H exchanger 3 (NHE3) protein complex accounts for most Na absorption at the intestinal brush border. NHE3 expression/activity is acutely regulated by endocytosis/exocytosis. Cofilin‐1 (COF) and actin depolymerizing factor (ADF) are highly conserved isoforms of the cofilin family of actin severing proteins. COF/ADF are ubiquitously expressed though ADF has a stronger presence in intestinal tissue. We hypothesized that COF and/or ADF are necessary for basal and regulated NHE3 activity by remodeling the terminal web actin structure to allow endocytosis/exocytosis. COF and ADF knockdown (KD) cells were engineered with lentivirus/puromycin in Caco‐2 cells, a polarized intestinal Na‐absorptive cell line. COF‐KD reduced COF by 67±5% (p蠄0.01) without significantly altering ADF, while ADF‐KD cells reduced ADF by 60±7% (p蠄0.01) without altering COF. By transmission electron microscopy, COF‐KD cells had straighter and a greater number of microvilli (MV) than control and ADF‐KD cells had more bent MV. By immunofluorescence, neither COF nor ADF had a predominantly MV distribution. NHE3 activity was quantified by measuring pH change (BCECF/fluorometry) under basal and inhibited (forskolin (FSK), 2.5 uM) conditions. COF‐KD had 35±12% less activity than control cells (p蠄.05). ADF‐KD had 34±12% greater NHE3 activity than control cells (p蠄.05). FSK inhibited NHE3 similarly in all three conditions (approximately 49%).Conclusions1. Using KD studies we conclude that COF normally increases and ADF decreases basal NHE3 activity, but neither are involved in cAMP induced inhibition of NHE3. 2. COF normally reduces apical microvillar number while ADF is necessary for microvillar rigidity. The lack of ADF/COF in MV suggest that they affect the MV through intermediate proteins.