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IntroductionDevelopment of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period.MethodsPantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed via HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected via abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined via a bench top pH analyzer.ResultsFollowing Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3.DiscussionThe reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.

Background Screening for asymptomatic, undiagnosed atrial fibrillation (AF) has the potential to allow earlier treatment, possibly resulting in prevention of strokes, but also to increase medical resource utilization. Objective To compare healthcare utilization rates during the year following initiation of screening among participants screened for AF by electrocardiogram (ECG) sensor patch compared with a matched observational control group. Methods A total of 1718 participants recruited from a health care plan based on age and comorbidities who were screened with an ECG patch (actively monitored group) as part of a prospective, pragmatic research trial were matched by age, sex, and CHA2DS2-VASc score with 3371 members from the same health plan (observational control group). Healthcare utilization, including visits, prescriptions, procedures, and diagnoses, during the 1 year following screening was compared between the groups using health plan claims data. Results Overall, the actively monitored group had significantly higher rates of cardiology visits (adjusted incidence rate ratio [aIRR] [95% confidence interval (CI)]: 1.43 [1.27, 1.60]), no difference in primary care provider visits (aIRR [95% CI]: 1.0 [0.95, 1.05]), but lower rates of emergency department (ED) visits and hospitalizations (aIRR [95% CI]: 0.80 [0.69, 0.92]) compared with controls. Among those with newly diagnosed AF, the reduction in ED visits and hospitalizations was even greater (aIRR [95% CI]: 0.27 [0.17, 0.43]). Conclusion AF screening in an asymptomatic, moderate-risk population with an ECG patch was associated with an increase in cardiology outpatient visits but also significantly lower rates of ED visits and hospitalizations over the 1 year following screening.

In online environments, listening involves being able to pause or replay the recording as needed. Previous research indicates that control over the listening input could improve the measurement accuracy of listening assessment. Self-pacing also supports the second language (L2) comprehension processes of test-takers with specific learning difficulties (SpLDs) or, more specifically, of learners with reading-related learning difficulties who might have slower processing speed and limited working memory capacity. Our study examined how L1 literacy skills influence L2 listening performance in the standard single-listening and self-paced administration mode of the listening section of the Test of English as a Foreign Language (TOEFL) Junior Standard test. In a counterbalanced design, 139 Austrian learners of English completed 15 items in a standard single-listening condition and another 15 in a self-paced condition. L1 literacy skills were assessed via a standard reading, non-word reading, word-naming, and non-word repetition test. Generalized Linear Mixed-Effects Modelling revealed that self-pacing had no statistically significant effect on listening scores nor did it boost the performance of test-takers with lower L1 literacy scores indicative of reading-related SpLDs. The results indicate that young test-takers might require training in self-pacing or that self-paced conditions may need to be carefully implemented when they are offered to candidates with SpLDs.

Background Atrial fibrillation (AF) is common, often without symptoms, and is an independent risk factor for mortality, stroke and heart failure. It is unknown if screening asymptomatic individuals for AF can improve clinical outcomes. Methods mSToPS was a pragmatic, direct-to-participant trial that randomized individuals from a single US-wide health plan to either immediate or delayed screening using a continuous-recording ECG patch to be worn for two weeks and 2 occasions, ~3 months apart, to potentially detect undiagnosed AF. The 3-year outcomes component of the trial was designed to compare clinical outcomes in the combined cohort of 1718 individuals who underwent monitoring and 3371 matched observational controls. The prespecified primary outcome was the time to first event of the combined endpoint of death, stroke, systemic embolism, or myocardial infarction among individuals with a new AF diagnosis, which was hypothesized to be the same in the two cohorts but was not realized. Results Over the 3 years following the initiation of screening (mean follow-up 29 months), AF was newly diagnosed in 11.4% (n = 196) of screened participants versus 7.7% (n = 261) of observational controls (p Conclusions At 3 years, screening for AF was associated with a lower rate of clinical events and improved outcomes relative to a matched cohort, although the influence of earlier diagnosis of AF via screening on this finding is unclear. These observational data, including the high event rate surrounding a new clinical diagnosis of AF, support the need for randomized trials to determine whether screening for AF will yield a meaningful protection from strokes and other clinical events. Trail registration The mHealth Screening To Prevent Strokes (mSToPS) Trial is registered on ClinicalTrials.gov with the identifier NCT02506244.

This paper discusses the U.S. Environmental Agency’s potential improper expansion of its authority under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the federal pesticide statute, to regulate not only the registration, labeling, and use of wood preservatives, but also treated wood products. EPA’s oversight of wood preservatives under FIFRA is extensive. In recent years, despite EPA’s own Treated Articles Exemption, 40 C.F.R. § 152.25(a), EPA has moved toward utilizing wood preservative labeling in a way that could impose restrictions on the end use of treated wood. Wood preservative registrant and user groups should be concerned and vigilant about this trend toward regulation of treated wood. At the same time, they should continue to interact with EPA in a constructive manner, in part to ensure that EPA respects its own regulatory boundary between wood preservatives, such as creosote, and treated wood, such as creosote-treated railroad crossties, which are a key component of the nation’s transportation critical infrastructure.

To identify groups of heterogeneous HbAThe study comprised 6355 adults with newly diagnosed Type 2 diabetes (55% men, median age 62 years, baseline BMI 31 kg/mFour distinct longitudinal HbAFour subgroups with distinct HbA

Objectives: The advent of large databases, wearable technology, and novel communications methods has the potential to expand the pool of candidate research participants and offer them the flexibility and convenience of participating in remote research. However, reports of their effectiveness are sparse. We assessed the use of various forms of outreach within a nationwide randomized clinical trial being conducted entirely by remote means. Methods: Candidate participants at possibly higher risk for atrial fibrillation were identified by means of a large insurance claims database and invited to participate in the study by their insurance provider. Enrolled participants were randomly assigned to one of two groups testing a wearable sensor device for detection of the arrhythmia. Results: Over 10 months, the various outreach methods used resulted in enrollment of 2659 participants meeting eligibility criteria. Starting with a baseline enrollment rate of 0.8% in response to an email invitation, the recruitment campaign was iteratively optimized to ultimately include website changes and the use of a five-step outreach process (three short, personalized emails and two direct mailers) that highlighted the appeal of new technology used in the study, resulting in an enrollment rate of 9.4%. Messaging that highlighted access to new technology outperformed both appeals to altruism and appeals that highlighted accessing personal health information. Conclusions: Targeted outreach, enrollment, and management of large remote clinical trials is feasible and can be improved with an iterative approach, although more work is needed to learn how to best recruit and retain potential research participants. Trial registration: Clinicaltrials.gov NCT02506244. Registered 23 July 2015. Keywords: Clinical trials, Clinical research, Digital technology, Remote enrollment, Remote monitoring, Outreach

Toll-like receptor 2 (TLR2) recognizes bacterial derived- and synthetic-lipopeptides after dimerization with TLR1 or TLR6. Hyper-activation of TLR2 has been described in several inflammatory diseases and the discovery of inhibitors of its pro-inflammatory activity represent potential starting points to develop therapeutics in such pathologies. We designed peptides derived from the TLR2 sequence comprising amino acid residues involved in ligand binding (Pam3CSK4) or heterodimerization (TLR2/TLR1) as pointed out by structural data.2 We identified several peptides (P13, P13(LL), P16, P16(LL)) which inhibited TLR2/1 signaling in HEK293-TLR2 cells (MAPK activation and NF-kB activity). Moreover, P13L and P16L decreased TNFα release in human primary PBMCs and mouse macrophages. The peptides were selective for TLR2/1 as they did not inhibit the activity of other TLRs tested. P13L and P16L inhibited the internalization of Pam3CSK4 fluorescently labeled in macrophages and the heterodimerization of TLR2 with TLR1 as demonstrated by immunoprecipitation studies. Our data demonstrate that peptides derived from the region comprising the leucine-rich repeats (LRR) 11 and 13 in the extracellular domain of TLR2 are good starting points to develop more potent anti-inflammatory peptides with TLR2 inhibitory activity.

Cardiovascular disease remains the leading cause of death and disease worldwide. As demands on an already resource-constrained healthcare system intensify, disease prevention in the future will likely depend on out-of-office monitoring of cardiovascular risk factors. Mobile health tracking devices that can track blood pressure and heart rate, in addition to new cardiac vital signs, such as physical activity level and pulse wave velocity (PWV), offer a promising solution. An initial barrier is the development of accurate and easily-scalable platforms. In this study, we made a customized smartphone app and used mobile health devices to track PWV, blood pressure, heart rate, physical activity, sleep duration, and multiple lifestyle risk factors in ≈250 adults for 17 continual weeks. Eligible participants were identified by a company database and then were consented and enrolled using only a smartphone app, without any special training given. Study participants reported high overall satisfaction, and 73% of participants were able to measure blood pressure and PWV

Background Emergent therapies in anticancer vaccination use Toll-like receptors (TLRs) agonists as dendritic cell (DC) vaccine adjuvants. DCs from the patient are isolated, stimulated with TLR agonists and tumor antigens ex vivo and then infused back into the patient. Although some TLR ligands have been tested in clinical trials, novel TLR agonists with improved immunomodulatory properties are essential to optimize treatment success. We report on the discovery of small-molecule TLR2 agonists, with favorable properties as synthetic adjuvants. Methods We performed a shape- and featured-based similarity virtual screening against a commercially available compound library. The selected virtual hits were experimentally tested in TLR2-reporter cells and their activity in phagocytes and DCs was characterized. A binding model of the compounds to TLR2 (docking studies) was proposed. Results Through a virtual screening approach against a library of three million compounds four virtual hits (AG1, AG2, AG3, AG4) were found to synergistically augment the NF-kB activation induced by the lipopeptide ligand Pam 3 CSK 4 in luciferase reporter assays using HEK293-TLR2 cells. Biacore experiments indicated that AG1–AG4 are ago-allosteric modulators of TLR2 and AG2 bound TLR2 with high affinity (K D 0.8 μM). The compounds induced TNF-α production in human peripheral blood mononuclear cells (PBMCs) and they activated DCs as indicated by IL-12 production and upregulation of CD83/CD86. Conclusions Following a combined in silico / in vitro approach we have discovered TLR2-agonists (AG1–AG4) that activate human and mouse immune cells. General significance We introduce four novel TLR2 ago-allosteric modulators that stimulate myeloid cell activity and constitute promising candidates as synthetic adjuvants.

A wide range of personal wireless health-related sensor devices are being developed with hope of improving health management. Factors related to effective user engagement, however, are not well-known. We sought to identify factors associated with consistent long-term use of the Scanadu Scout multi-parameter vital sign monitor among individuals who invested in the device through a crowd-funding campaign. Email invitations to join the study were sent to 4525 crowd-funding participants from the US. Those completing a baseline survey were sent a device with follow-up surveys at 3, 12, and 18 months. Of 3872 participants receiving a device, 3473 used it during Week 1, decreasing to 1633 (47 percent) in Week 2. Median time from first use of the device to last use was 17 weeks (IQR: 5-51 weeks) and median uses per week was 1.0 (IQR: 0.6-2.0). Consistent long-term use (defined as remaining in the study at least 26 weeks with at least 3 recordings per week during at least 80% of weeks) was associated with older age, not having children in the household, and frequent use of other medical devices. In the subset of participants answering the 12-month survey (n = 1222), consistent long-term users were more likely to consider the device easy to use and to share results with a healthcare provider. Thirty percent of this subset overall reported improved diet or exercise habits and 25 percent considered medication changes in response to device results. The study shows that even among investors in a device, frequency of device usage fell off rapidly. Understanding how to improve the value of information from personal health-related sensors will be critical to their successful implementation in care.

Routine ECG screening for AF is not recommended due in part to a lack of healthcare utilization data. In the mSToPS trial asymptomatic individuals underwent screening with an ECG sensor patch. Healthcare utilization was evaluated following monitoring & compared to matched controls. 1738 Aetna

Importance Opportunistic screening for atrial fibrillation (AF) is recommended, and improved methods of early identification could allow for the initiation of appropriate therapies to prevent the adverse health outcomes associated with AF. Objective To determine the effect of a self-applied wearable electrocardiogram (ECG) patch in detecting AF and the clinical consequences associated with such a detection strategy. Design, Setting, and Participants A direct-to-participant randomized clinical trial and prospective matched observational cohort study were conducted among members of a large national health plan. Recruitment began November 17, 2015, and was completed on October 4, 2016, and 1-year claims-based follow-up concluded in January 2018. For the clinical trial, 2659 individuals were randomized to active home-based monitoring to start immediately or delayed by 4 months. For the observational study, 2 deidentified age-, sex- and CHA 2 DS 2 -VASc–matched controls were selected for each actively monitored individual. Interventions The actively monitored cohort wore a self-applied continuous ECG monitoring patch at home during routine activities for up to 4 weeks, initiated either immediately after enrolling (n = 1364) or delayed for 4 months after enrollment (n = 1291). Main Outcomes and Measures The primary end point was the incidence of a new diagnosis of AF at 4 months among those randomized to immediate monitoring vs delayed monitoring. A secondary end point was new AF diagnosis at 1 year in the combined actively monitored groups vs matched observational controls. Other outcomes included new prescriptions for anticoagulants and health care utilization (outpatient cardiology visits, primary care visits, or AF-related emergency department visits and hospitalizations) at 1 year. Results The randomized groups included 2659 participants (mean [SD] age, 72.4 [7.3] years; 38.6% women), of whom 1738 (65.4%) completed active monitoring. The observational study comprised 5214 (mean [SD] age, 73.7 [7.0] years; 40.5% women; median CHA 2 DS 2 -VASc score, 3.0), including 1738 actively monitored individuals from the randomized trial and 3476 matched controls. In the randomized study, new AF was identified by 4 months in 3.9% (53/1366) of the immediate group vs 0.9% (12/1293) in the delayed group (absolute difference, 3.0% [95% CI, 1.8%-4.1%]). At 1 year, AF was newly diagnosed in 109 monitored (6.7 per 100 person-years) and 81 unmonitored (2.6 per 100 person-years; difference, 4.1 [95% CI, 3.9-4.2]) individuals. Active monitoring was associated with increased initiation of anticoagulants (5.7 vs 3.7 per 100 person-years; difference, 2.0 [95% CI, 1.9-2.2]), outpatient cardiology visits (33.5 vs 26.0 per 100 person-years; difference, 7.5 [95% CI, 7.2-7.9), and primary care visits (83.5 vs 82.6 per 100 person-years; difference, 0.9 [95% CI, 0.4-1.5]). There was no difference in AF-related emergency department visits and hospitalizations (1.3 vs 1.4 per 100 person-years; difference, 0.1 [95% CI, −0.1 to 0]). Conclusions and Relevance Among individuals at high risk for AF, immediate monitoring with a home-based wearable ECG sensor patch, compared with delayed monitoring, resulted in a higher rate of AF diagnosis after 4 months. Monitored individuals, compared with nonmonitored controls, had higher rates of AF diagnosis, greater initiation of anticoagulants, but also increased health care resource utilization at 1 year. Trial Registration ClinicalTrials.gov Identifier:NCT02506244

Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed-monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF.

BACKGROUND: Debate and controversy remain concerning detection and management of common bile duct (CBD) stones in the era of laparoscopic cholecystectomy (LC). Since ERCP was introduced in the 1970s, therapeutic splitting with endoscopic sphincterotomy (ES) as a two-step procedure has become the most accepted strategy to remove CBD stones. This paper evaluates the one-step laparoscopic management of CBD stones during LC. METHODS: After economic clarification (anamnesis, clinical examination, laboratory tests, ultrasound) LC was performed even when CBD stones were suspected. During LC a cholangiography via the cystic duct was routinely performed. If bile duct stones were detected during cholangiography, retrieval via the cystic duct or via choledochotomy was intended using Dormia basket or Fogarty catheter. Exclusion criteria against laparoscopic CBD exploration were suspicion of malignancy, severe pancreatitis and/or cholangitis or unfitness for general anesthesia. RESULTS: From November 1991 to September 2005, 260 patients underwent laparoscopic therapy for bile duct stones. Retrieval was performed transcystically in 166 patients (64 %) and via choledochotomy in 94 patients (36 %). Laparoscopic CBD exploration was successful in 93 %. Conversion rate, complication rate and mortality were 1.5 % (n = 4), 6.6 % (n = 17), and 1.1 % (n = 3), respectively. CONCLUSIONS: Laparoscopic common bile duct exploration (LCBDE) as a one-step procedure is a safe alternative to therapeutic splitting, with comparable success rate. Regarding morbidity and mortality, the laparoscopic transcystic approach has clear advantages over therapeutic splitting. In more than 90 per cent of patients with CBD stones, LCBDE avoids diagnostic and therapeutic ERCP and preserves the papilla Vateri.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) activate cells of the innate immune system. Recent studies have shown that sole CpG-ODN administration induces resistance against infection and tumors. Effects of CpG-ODN administration are rapidly induced, and regarding infections only short-term protection was seen. One conceivable strategy to prolong protective effects is multiple administrations of CpG-ODN. However, inappropriate immune activation via CpG motifs has been implicated in septic shock and autoimmunity. To investigate effects of multiple CpG-ODN administrations, we analyzed Th1- and Th-2-associated Ig antibody levels, during and after multiple treatment with CpG-ODN. Our results show that multiple administrations of CpG-ODN lead to an increase in total IgG2c levels in CpG-ODN-treated mice in comparison to controls with distinct time and frequency correlation, in the absence of additional stimuli. This indicates a humoral Th1 bias based on stimulation of Th1-Ig isotype-producing B cells. These effects could account for observed anti-infection and anti-tumor properties of multiple CpG-ODN administrations; on the other hand, they might cause autoimmune disease.

Zusammenfassung Ziel: Die »Endoskopische Subfasziale Insufflations- Dissektion der Perforansvenen« (ESIDP) ist eine minimal- invasive chirurgische Methode zur Behandlung der Varikosis. Wir berichten über unsere Erfahrungen mit ESIDP. Methoden: Die für die Durchtrennung der Perforansvenen notwendige Entfaltung des subfaszialen Raumes erzielten wir mittels CO2-Insufflation (Pneumocavum subfasciale). Die präoperative Diagnostik (Lokalisation insuffizienter Perforans- und oberflächlicher Venen; Beurteilung der tiefen Beinvenen) erfolgte ausschließlich mittels farbkodierter Duplexsonographie. Ergebnisse: Die ESIDP wurde 150-mal bei 125 Patienten durchgeführt und in 117 Fällen (78%) mit Segmentstripping der Vena saphena magna und Phlebektomie, in 8 Fällen (5,4%) mit komplettem Stripping der Vena saphena magna und Phlebektomie, in 20 Fällen (12,6%) nur mit Phlebektomie und in 5 Fällen (4%) mit atypischem Stripping kombiniert. Wir beobachteten keine intraoperative und 13 postoperative Komplikationen: infiziertes Hämatom (n = 1), Thrombose (n = 1), Parästhesien (n = 9) und Schmerzen bis zu 6 Wochen postoperativ (n = 2). Schlussfolgerung: Wegen ausgezeichneter Sichtverhältnisse und der Möglichkeit zur selektiven Durchtrennung aller in Frage kommenden Perforansvenen, auch unter Hautulzerationen, stellt die ESIDP eine sinnvolle, minimal-invasive Methode in der Therapie der Varikosis und der transfaszial bedingten CVI dar.

Beneficial microbes enter the food supply primarily through fermented foods (largely milks) and addition of probiotics. Fermented milks are a significant component of the diet of some geographical regions, including Europe. The fermentation process serves to preserve safety, nutritional quality and palatability of milk. In addition, the microbes associated with fermented milks and probiotics are associated with human health benefits. However, in the area of health claims only one claim for beneficial microbes has been approved in the European Union, that is for yoghurt to improve lactose tolerance. We searched for health messages that include probiotics or fermented milks in nutrition guidelines and recommendations in thirteen countries of the EU plus Switzerland. Such messages are allowed when they are made by non-commercial government bodies. Our analysis revealed that five EU member states have national nutrition guidelines or recommendations that include either probiotics or fermented milks with live bacteria. This supports that some EU member states recognise health benefits associated with consumption of live microbes, even if commercial marketing claims are not authorised. Harmonisation between recommendations and approved health-claims would benefit consumers and public health.

Renal kallikrein is localized in the connecting tubule cells and secreted into the tubular fluid at late distal nephron segments. The present experiments were performed to further test the hypothesis that renal kallikrein reduces bicarbonate secretion of cortical collecting duct (CCD). The effect of orthograde injections of pig pancreatic kallikrein (1 or 3 μg/ml) into the renal tubular system was investigated. Urine fractions (Fr) were collected after a 2-min stop flow. Changes in the urine fraction with respect to those in free-flow urine samples (Ff) were related to the respective polyfructosan (Inutest) ratio. Renal kallikrein activity (Fr:Ff kallikrein/Fr:Ff polyfructosan) increased significantly in the first two urine fractions collected after glandular kallikrein administration (kallikrein, 1 μg/ml, P < 0.05; kallikrein, 3 μg/ml, P < 0.01).[Formula: see text] secretion of collecting ducts was significantly reduced dose dependently by orthograde and also reduced by retrograde pig pancreatic kallikrein administration. Release of kinins into the fractions was not affected by the retrograde kallikrein injection, even though the kallikrein activity increased considerably (2.26 ± 0.2 vs. 1.55 ± 0.2, P < 0.05). Adequacy of retrograde injections for delivering substances to the CCD was demonstrated by injecting colloidal mercury and detecting the appearance of this mercury in the renal cortex by transmission electron microscopy. The integrity of the renal tissue after a retrograde ureteral injection was confirmed by scanning electron microscopy. These results confirm and extend previous data (M. Marin-Grez and P. Vallés. Renal Physiol. Biochem. 17: 301–306, 1994; and M. Marin-Grez, P. Vallés, and P. Odigie. J. Physiol. 488: 163–170, 1995) showing that renal kallikrein reduces bicarbonate secretion at the CCD, probably by inhibiting [Formula: see text]transported by a mechanism unrelated to its kininogenase activity. Support for this assessment was obtained in experiments testing the effect of kallikrein on the luminal bicarbonate secretion of a subpopulation of Madin-Darby canine kidney cells capable of extruding the anion. Kallikrein inhibited[Formula: see text]/Cl−exchange, and the degree of inhibition was dose dependent. This inhibition occurred in the absence of kininogen in the bathing solution.

Our objective was to determine whether neonates adapt to protein malnutrition by preserving the relative growth and metabolism of gastrointestinal tissue at the expense of skeletal muscle. We measured gastrointestinal, liver, and carcass tissue masses and blood flow, oxygen consumption, and net glucose and amino acid fluxes in vivo of the portal-drained visceral tissues (PDV) in neonatal pigs fed isocaloric diets containing either 30% protein [control (C)] or 15% [low protein (LP)] for 14 days. Relative protein mass and fasting blood flow and oxygen consumption of PDV tissue in either group were not different. Relative protein mass of liver and carcass was lower in LP pigs. Net essential amino acid absorption and insulin concentration after feeding were lower in LP pigs. Results demonstrate that protein malnutrition in neonatal pigs differentially altered rates of tissue growth, such that the proportion of body protein partitioned into gastrointestinal tissue was preserved, while that of skeletal muscle was reduced. Chronic reduction in amino acid absorption in protein-malnourished pigs resulted in a reduced insulin response to feeding, which presumably limited substrate availability and the anabolic stimulus for skeletal muscle protein accretion.