In vitro pharmacological characterization of standard and new lysophosphatidic acid receptor antagonists using dynamic mass redistribution assay.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that acts as an agonist of six G protein-coupled receptors named LPA receptors (LPA1-6). LPA elicits diverse intracellular events and modulates several biological functions, including cell proliferation, migration, and invasion. Overactivation of the LPA-LPA receptor system is reported to be involved in several pathologies, including cancer, neuropathic pain, fibrotic diseases, atherosclerosis, and type 2 diabetes. Thus, LPA receptor modulators may be clinically relevant in numerous diseases, making the identification and pharmacodynamic characterization of new LPA receptor ligands of strong interest. In the present work, label-free dynamic mass redistribution (DMR) assay has been used to evaluate the pharmacological activity of some LPA1 and LPA2 standard antagonists at the recombinant human LPA1 and LPA2 receptors. These results are compared to those obtained in parallel experiments with the calcium mobilization assay. Additionally, the same experimental protocol has been used for the pharmacological characterization of the new compound CHI. KI 16425, RO 6842262, and BMS-986020 behaved as LPA1 inverse agonists in DMR experiments and as LPA1 antagonists in calcium mobilization assays. Amgen compound 35 behaved as an LPA2 antagonist, while Merck compound 20 from WO2012028243 was detected as an LPA2 inverse agonist using the DMR test. Of note, for all the compounds, similar potency values were estimated by DMR and calcium assay. The new compound CHI was found to be an LPA1 inverse agonist, but with potency lower than that of the standard compounds. In conclusion, we have demonstrated that DMR assay can be successfully used to characterize LPA1 and LPA2 ligands. Compared to the classical calcium mobilization assay, DMR offers some advantages, in particular allowing the identification of inverse agonists. Finally, in the frame of this study, a new LPA1 inverse agonist has been identified.

Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation of Staphylococcus epidermidis.

AIMS: The aim of this work was to investigate the possible effect of human cathelicidin antimicrobial peptide LL37 on biofilm formation of Staphylococcus epidermidis, a major causative agent of indwelling device-related infections. METHODS AND RESULTS: We performed initial attachment assay and biofilm formation solid surface assay in microtitre plates, as well as growth experiment in liquid medium using laboratory strain Staph. epidermidis ATCC35984. We found that already a low concentration of the peptide LL37 (1 mg l(-1)) significantly decreased both the attachment of bacteria to the surface and also the biofilm mass. No growth inhibition was observed even at 16 mg l(-1) concentration of LL37, indicating a direct effect of the peptide on biofilm production. CONCLUSIONS: As biofilm protects bacteria during infections in humans and allows their survival in a hostile environment, inhibition of biofilm formation by LL37 may have a key role to prevent bacterial colonization on indwelling devices. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings suggest that this host defence factor can be a potential candidate in prevention and treatment strategies of Staph. epidermidis infections in humans.

Maternal plasma level of antimicrobial peptide LL37 is a major determinant factor of neonatal plasma LL37 level.

AIM: To determine cathelicidin antimicrobial peptide LL37subcellular distribution in cord neutrophils and normal plasma LL37 levels in mothers and neonates, relate them to delivery mode and relevant biochemical markers, including 25-OHvitamin D [25(OH)D] as this molecules increases cathelicidin gene expression. METHODS: A total of 115 infants were included, n = 68 with normal delivery and n = 47 with elective Caesarean section (C-section), a subset of these being 50 mother-infant pairs. Biomarkers were determined in maternal and cord blood. Subcellular peptide LL37 distribution was analysed with immunoelectron microscopy. RESULTS: Cord plasma LL37 levels were three-times higher after normal delivery compared with C-section. A highly significant correlation was observed between maternal and cord plasma LL37 levels, regardless of delivery mode. No relationship was found between LL37 and 25(OH)D levels. Neutrophils from cord blood after normal delivery contained 10-times more cytoplasmatic cathelicidin peptide compared with corresponding cells after C-section where a strict granular localization was found. CONCLUSION: These data are consistent with a placental transfer of LL37 and identifies maternal stores as the critical factor determining neonatal plasma LL37 level. An additional enhancement of neonatal cathelicidin mobilization and release is connected to normal delivery stress.

[Nuchal translucency and combined test: what are the implications in clinical practice?]. / La translucenza nucale e il test combinato: quali risvolti nella pratica clinica?

AIM: The aim of this study was to evaluate the performance of the combined test (nuchal translucency, NT) and maternal serum free-beta human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), compared to the NT measurement alone, in fetal aneuploidy screening in the general population and in pregnant women aged 35 years and over. In addition, the association between increased NT and presence of cardiac defects in fetuses with normal karyotype was evaluated. METHODS: Screening at 11-14 weeks of gestation by NT measurement and combined test was carried out in 1521 pregnant women. The estimated risk for trisomy 21 and trisomy 13+18 was calculated (risk cut-off 1/300 and 1/750 respectively) and the outcomes was evaluated. RESULTS: Ten cases of trisomies (21 and 18) occurred, seven of which among the older group of pregnant women. The detection rate (DR) for the combined test was 80% in the general population and 85.7% in older pregnant women, which resulted higher rate than NT measurements alone. Detection rate of cardiac defects using NT measurements was 66.6%. CONCLUSION: The combined test is an effective screening for aneuploidies and reduces at 14% the need of invasive testing in the older obstetric population, detecting all the trisomies occurred in this group. The association between increased NT and cardiac defects is confirmed but it seems too weak to consider NT as a single screening strategy for these abnormalities.

The effect of pneumatic trabeculoplasty on intraocular pressure: the results of a 6-month, open-label, multicenter study.

PURPOSE: To evaluate the effects of pneumatic trabeculoplasty (PNT) in ocular hypertension and glaucoma subjects. METHODS: A total of 63 consecutive subjects, either treated (79%) or untreated (21%), with intraocular pressure (IOP) between 20 and 25 mmHg were enrolled; the eye with higher IOP (or, in case of identical IOP, worse visual field) was treated with PNT, with the fellow eye used as control. Subjects underwent a baseline evaluation the day before treatment, two PNT treatments at day 0 and 7, visits at day 1, 8, 14, and at each month until the end of the study, which lasted 6 months. Safety was addressed at all visits; an IOP curve (at 8 and 10 AM, 2 and 4 PM) was obtained at baseline and during monthly visits. RESULTS: In PNT eyes, baseline IOP was 22.2-/+1.6 mmHg. Following PNT a statistically significant reduction of IOP occurred at all visits (p<0.0001), with a mean decrease ranging from -2.7-/+2.5 (-11.9-/+10.8%) to -3.6-/+2.6 mmHg (-16.0-/+11.6%); mean reduction was 12.8-/+11.5%. Although IOP diminished also in the control eyes after baseline (p<0.05), the change in IOP was significantly higher in PNT group at each visit (p<0.05). Mild side effects were experienced by 76% of subjects and they all resolved without sequelae. CONCLUSIONS: The results suggest the effect of this procedure in reducing IOP in glaucoma and ocular hypertensive subjects.

Response of central serous chorioretinopathy evaluated by multimodal retinal imaging.

PurposeTo identify predictive biomarkers of treatment outcomes by multimodal retinal imaging in patients affected by central serous chorioretinopathy (CSC).Patients and methodsIn this interventional non-randomized clinical study, 27 treatment-naive CSC patients were prospectively enrolled and treated with oral eplerenone for 5-13 weeks. Primary outcomes included presence of pathological findings on indocyaine green angiography (ICGA), structural optical coherence tomography (OCT) and OCT-angiography (OCT-A) at baseline associated with different response to the treatment.ResultsA total of 29 eyes of 27 patients (2 females, 25 males) met the inclusion criteria and were included in the study (mean age was 45±7 years). Mean CSC duration at baseline was 13.5±4.4 weeks. After a mean of 10.5 weeks of treatment, mean central macular thickness significantly reduced (P<0.001), and mean best-corrected visual acuity improved (P<0.001). Seventeen eyes (61%) demonstrated total reabsorption of subretinal fluid on structural OCT, five eyes (18%) presented a partial response to eplerenone therapy and six eyes (21%) showed no response. The complete response to the treatment was associated with absence of CNV at OCT-A and the presence of hotspot at ICGA (P<0.001 and P=0.002, respectively). None of eight eyes with CNV in OCT-A imaging had a complete response to eplerenone and none of three eyes without hotspot at ICGA showed a complete response to the treatment.ConclusionsMultimodal retinal imaging allowed us to propose predictive biomarkers (ie, absence of CNV on OCT-A and presence of hotspot on ICGA) for treatment outcomes.

Simultaneous bilateral retinal detachment following coronary artery bypass graft: case report.

PURPOSE: To present an unusual case of simultaneous bilateral retinal detachment (RD) following a coronary artery bypass graft in a patient with acute myocardial infarction (AMI). METHODS: A 78-year-old man was first seen for bilateral sudden visual loss after surgical treatment of AMI. The patient underwent ultrasound biomicroscopy (UBM) and ocular B-scan echographic examination. RESULTS: The ocular assessment showed a bilateral seclusion of the pupil with bombe of the iris, an anterior chamber without cells or flare, and hypotonia. The evaluation of the visual acuity revealed no light perception in the right eye (RE) and uncertain light perception in the left eye (LE). The UBM analysis of the anterior segment confirmed the presence of bilateral pupillary block due to the seclusion of the pupil and a peripheral serous choroidal detachment involving the RE. The echographic B-scan analysis of the posterior segment showed a bilateral closed funnel-shaped RD and confirmed the presence of the peripheral flat serous choroidal detachment in RE. CONCLUSIONS: The cause for simultaneous bilateral RD remained unclear. It may have been a consequence of a persistent choroidal detachment with multiple swelling and 'kissing' of retinal surface. The increased venous pressure caused by congestive heart failure due to AMI could have caused a bilateral uveal effusion. Alternatively, the absence of retinal tears, the presence of a closed funnel-shaped morphology, and seclusion of the pupils allowed us to suspect an exudative pathogenetic mechanism due to a previous unrecognized ocular inflammatory state.

Efficacy of the symmetric, patient-oriented, rigid, three-dimensional, active (SPoRT) concept of bracing for scoliosis: a prospective study of the Sforzesco versus Lyon brace.

AIM: Bracing is considered to be effective in the treatment of adolescent idiopathic scoliosis. The concept prevailing today includes an asymmetrical construction, mainly using a mechanical three-point system. We developed the new Sforzesco brace, based on the SPoRT concept (Symmetric, Patient-oriented, Rigid, Three-dimensional, active). The aim of this study is to verify the results of this concept and brace, compared to three-point classical systems. METHODS: We performed a prospective, pair-controlled study. It was possible to match 15 patients, out of the first 18 consecutively treated with the Sforzesco brace (Group SPoRT), with previous patients treated with the Lyon brace (Group LY). SPoRT included 14.2+/-1.7 year old patients, with 47+/-7 degrees Cobb worst curves, and 11+/-4 degrees Bunnell; LY included 13.6+/-1.6 year old patients, with 43+/-7 degrees Cobb and 12+/-5 degrees Bunnell. The brace had to be worn 23 h per day and patients were evaluated after 6 months both clinically and radiographically (without the brace). Appropriate statistics were used. RESULTS: At the baseline there were slight differences between the groups, with SPoRT worse than LY. All radiographic and clinical parameters decreased significantly with treatment in both groups, apart from thoracic Cobb degrees in LY. SPoRT had better results than LY (P<0.05) radiographically (worst curve -10+/-5 degrees vs -5+/-7 degrees, all curves -8+/-7 degrees vs -6+/-7 degrees), for sagittal profile (distance from plumbline: T12 -6+/-9 mm vs +2+/-8 and L3 -7+/-12 vs 0+/-10) and aesthetics of the shoulders (9 improved and 6 unchanged vs 5 and 8) and waists (10 improved and 5 unchanged vs 5 and 8). Finally, clinical results in terms of patient recovery were better in SPoRT than LY (12 improved and 3 unchanged vs 8 and 5). CONCLUSION: When a new treatment is introduced, it is not possible to wait years (end of therapy) before verifying its utility, and in scoliosis bracing a short term study already gives very important clues. This study confirms the immediate efficacy of brace treatment (even in such high degree cases) whatever the brace concept used, with only 2 (out of 30) progressed curves. In SPoRT we had no progressions, and obtained a statistically significant 80% better radiographic results than LY in the worst scoliosis curve, and 40% in the average of all curves, as well as improved aesthetics and sagittal profile (that is crucial in scoliosis bracing). The Sforzesco brace should be used, and the SPoRT concept explored in the long term to verify if the classical three-point system should be totally (or partially) abandoned.

Influence of pancreas transplantation alone on native renal function.

Pancreas transplantation alone (PTA) has become an accepted treatment of nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus are greater than those of the surgical procedure and the posttransplant immunosuppression. As a decrease in native renal function is expected, we followed this parameter among patients who underwent PTA. From January 1997 through January 2005, we performed 69 PTA in 66 patients. All patients showed glucose hyperlability with hypoglycemic unawareness, or two or more diabetic complications as well as creatinine clearance (CrCl) > or = 45 mL/min. Immunosuppression was based on tacrolimus, mycophenolate mofetil and prednisone. Twenty-four hour CrCl were performed after all successful PTA. We divided patients in two groups according to the pretransplant CrCl: group 1, CrCl < or = 70 mL/min (n = 20) and group 2, CrCl > 70 mL/min (n = 25). The data were analyzed using Student's t-test (P < or = .05 was considered significant). Twenty-one patients were excluded from the analysis because of death (n = 5) or graft loss (n = 8) during the first year or follow-up shorter than 1 year (n = 8). The mean value of CrCl decreased 28.8% (85.0 +/- 31 versus 60.5 +/- 36 mL/min; P < .001). There was also a 39.3% reduction among group 1 subjects (P = .003), including 10 who displayed CrCl < or = 30 mL/min. There was also a 24.4% reduction among group 2 (P = .008), but no patient developed end-stage renal disease. In conclusion, native renal function decreased significantly after PTA, but was well tolerated among patients with CrCl > 70 mL/min. Patients with CrCl < 70 mL/min show a significant risk of worsened renal function.

[Hospital readmission after postpartum discharge of term newborns in two maternity wards in Stockholm and Marseille]. / Morbidité néonatale précoce après sortie de maternité : étude comparative entre deux maternités à Stockholm et Marseille.

The consequences of early postpartum discharge (EPPD, within 2 days after birth) on newborn health remain debated. Early discharge has been associated with increased neonatal morbidity. However, neonatal re-hospitalization can be prevented by careful follow-up during the 1st week after birth. We compared the early neonatal hospitalization of term newborns over 2 years in two hospitals: Karolinska University Hospital in Stockholm (n=7300 births), which allowed early discharge from 6h after birth with specific neonatal follow-up, and Marseille University Hospital (AP-HM) (n=4385) where postpartum discharge was more conventional after 72 h. During the study period, the EPPD rate was 41% vs. 2% in Stockholm and Marseille, respectively (P<0.001). Hospital readmission was comparable (5.6‰ vs. 7‰, P=0.2). The leading cause associated with hospitalization was icterus in Stockholm (76% vs. 26%, P<0.001) and feeding difficulties in Marseille (17% vs. 48%, P<0.001). In conclusion, close neonatal follow-up during the 1st week of life associated with restricted maternal and neonatal eligibility criteria for EPPD are required to prevent early neonatal re-hospitalization.

Discovery of a novel isoxazoline derivative of prednisolone endowed with a robust anti-inflammatory profile and suitable for topical pulmonary administration.

A novel glucocorticoids series of (GCs), 6α,9α-di-Fluoro 3-substituted C-16,17-isoxazolines was designed, synthesised and their structure-activity relationship was evaluated with glucocorticoid receptor (GR) binding studies together with GR nuclear translocation cell-based assays. This strategy, coupled with in silico modelling analysis, allowed for the identification of Cpd #15, an isoxazoline showing a sub-nanomolar inhibitory potency (IC50=0.84 nM) against TNFα-evoked IL-8 release in primary human airways smooth muscle cells. In Raw264.7 mouse macrophages, Cpd #15 inhibited LPS-induced NO release with a potency (IC50=6 nM)>10-fold higher with respect to Dexamethasone. Upon intratracheal (i.t.) administration, Cpd #15, at 0.1 µmol/kg significantly inhibited and at 1 µmol/kg fully counteracted eosinophilic infiltration in a model of allergen-induced pulmonary inflammation in rats. Moreover, Cpd #15 proved to be suitable for pulmonary topical administration given its sustained lung retention (t1/2=6.5h) and high pulmonary levels (>100-fold higher than plasma levels) upon intratracheal administration in rats. In summary, Cpd #15 displays a pharmacokinetic and pharmacodynamic profile suitable for topical treatment of conditions associated with pulmonary inflammation such as asthma and COPD.

Corneal transplantation activity over 7 years: changing trends for indications, patient demographics and surgical techniques from the Corneal Transplant Epidemiological Study (CORTES).

This study aims to examine evolving indications and changing trends for corneal transplantation in Italy. Corneal transplantations performed with donor tissues distributed by the Veneto Eye Bank Foundation between 2002 and 2008 were prospectively evaluated. Of the 13,173 keratoplasties performed on 11,337 patients, 10,742 (81.5%) were penetrating (PK), 1644 (12.5%) were anterior lamellar (ALK), and 787 (6.0%) were endothelial (EK). Keratoconus (42.5%), regraft (18.9%), and pseudophakic bullous keratopathy (PBK, 11.9%) were the leading indications for PK, with keratoconus (69.6%) and regraft (6.5%) showing higher indications for ALK, whereas pseudophakic bullous keratopathy (50.1%) and regraft (18.7%) were the major indications for EK. There was an overall decrease observed in corneal grafting for keratoconus (P = .0048) and an increase for PBK (P = .0653) and regrafting (P = .0137). These indications differed by age and gender. The number of keratoplasties over 7 years was stable (P = .2394), although the annual number of PKs declined by 34.0% (P = .0250), ALKs began to rise from 2005 (P = .0600), whereas EKs showed a huge growth, with their number tripling in 2007 and further doubling in 2008 (P = .0004). Leading indications for keratoplasty showed similar data that have been reported elsewhere for Western countries over the past few decades, albeit with a higher percentage of keratoconus. However, the overall number of keratoplasties for keratoconus was in decline, whereas regraft keratopathy and PKs increased due to the application of the newer surgical techniques for corneal grafting. This highlights an important shift in managing corneal diseases toward the application of selective and more conservative surgeries and changes in indications in corneal transplantation.

Plasma leptin in infants: relations to birth weight and weight loss.

BACKGROUND: The hormone leptin, produced in the adipose tissue, is involved in the regulation of body weight. The release of the hormone is increased in obese adults and decreased after fasting in human adults. This study investigated whether the plasma leptin level was related to the infant's birth weight and whether the level was reduced in connection with the physiological weight loss during the neonatal period. METHODS: We measured the plasma leptin level in cord blood from infants who were large for gestational age (LGA) (n = 15), small for gestational age (SGA) (n = 16), and appropriate for gestational age (AGA) (n = 38). AGA infants (n = 120), who were exclusively breastfed, were also studied during their first 4 postnatal days in a cross-sectional method. One blood sample was collected before breastfeeding from each infant. Plasma leptin concentrations were determined by radioimmunoassay. RESULTS: The median (range) concentration of leptin from cord blood was increased in LGA infants and decreased in SGA infants compared with the level in AGA infants. There was a positive correlation between the log of the plasma leptin level in cord blood and both the infant's birth weight (r = 0.76; n = 69) and the body mass index (r = 0.63; n = 69). The normal 3% to 6% weight reduction that occurs during the first 4 postnatal days was associated with a 26% decrease in the plasma leptin level in healthy breastfed infants. CONCLUSIONS: The plasma leptin level is highly correlated to the size of adipose tissue mass and decreases in connection with the initial physiological weight loss in newborn infants. These data provide evidence that leptin is highly related to the nutritional status already during the fetal and neonatal periods.

Choroidal calcification in Bartter syndrome.

PURPOSE: Bartter syndrome is characterized by hyperplasia of the renal juxtaglomerular apparatus, hyperaldosteronism, and hypokalemic alkalosis. We report a case of Bartter syndrome associated with normal serum calcium levels and posterior choroidal calcification. METHODS: Case report. A 59-year-old man with bilateral cataract and Bartter syndrome underwent a complete ophthalmic examination, including standardized echography before and after cataract surgery. RESULTS: Before cataract surgery, echography identified small, hyperreflective, multifocal, bilateral choroidal lesions with posterior shadowing. After surgery, these lesions appeared as yellow-white, barely elevated plaques with smooth edges and were diagnosed as choroidal calcification. CONCLUSIONS: Choroidal calcification may occur in patients with Bartter syndrome. This condition should be added to the differential diagnosis of posterior segment calcification.

Ultrasound biomicroscopy and intraocular-pressure-lowering mechanisms of deep sclerectomy with reticulated hyaluronic acid implant.

PURPOSE: To evaluate the anatomic characteristics and intraocular pressure (IOP) lowering mechanisms of deep sclerectomy with reticulated hyaluronic acid implant (DS with RHAI) using ultrasound biomicroscopy (UBM). SETTING: Eye Clinic, Department of Neurological and Vision Sciences, University of Verona, Verona, Italy. METHODS: Thirty patients with primary open-angle glaucoma not controlled by medical therapy had DS with RHAI in 1 eye. A complete ocular examination and UBM study were performed 1, 3, 6, and 12 months postoperatively and thereafter at 6 month intervals. Eleven parameters were evaluated, the most important of which were IOP, surgical success in lowering IOP to 21 mm Hg or less with or without additional medical therapy, UBM appearance of the site of DS with RHAI, size of the decompression space, presence of a filtering bleb and supraciliary hypoechoic area, and scleral reflectivity around the decompression space. RESULTS: After a mean follow-up of 11.4 months +/- 4.7 (SD), the mean percentage reduction in IOP compared to preoperatively was 38% (from 26 +/- 4.5 mm Hg to 16.2 +/- 3.8 mm Hg; P =.0001). Twenty-four patients (80%) had an IOP less than 21 mm Hg; however, 7 of these eyes (23%) required additional IOP-lowering medical therapy. The operation failed in 6 patients (20%) despite additional therapy. Ultrasound biomicroscopy revealed a reduction in the size of the decompression space from 6 months postoperatively and its disappearance in 2 cases. The difference in size at the last follow-up and at 1 month postoperatively (maximum length 2.41 +/- 1.02 mm versus 3.53 +/- 0.51 mm) was significant (P =.0001). At the last examination, a filtering bleb was present in 18 patients (60%), a supraciliary hypoechoic area in 18 (60%), and hyporeflectivity of the scleral tissue around the decompression space in 14 (47%). These 3 UBM characteristics were detected singly and in various combinations. The simultaneous presence of all 3 characteristics in the same eye correlated significantly with a higher surgical success rate (P =.004). CONCLUSIONS: Ultrasound biomicroscopy showed that filtering bleb formation was frequent in eyes having DS with RHAI but that it was not the only surgically induced IOP-lowering mechanism. Increased uveoscleral and transscleral filtration may be equally important.

Effects of intraocular dapiprazole in the rabbit eye.

Dapiprazole produces miosis by blocking the alpha 1 receptors in the radial muscle of the iris; its intraocular effect has not yet been investigated. In this preliminary experimental animal study, we investigated the intracameral use of 0.2 ml of 0.005%, 0.0075%, 0.01%, and 0.05% dapiprazole to reverse mydriasis by 10% phenylephrine plus 0.5% tropicamide. With the 0.05% dapiprazole concentration, the values (mean +/- S.E.) of pupillary diameter were as follows: prior to the experiment, 5.3 +/- 0.31 mm; after mydriatics, 8.7 +/- 0.22 mm; after intraocular dapiprazole, 5.6 mm +/- 0.29. The results showed a dose-related miotic effect of dapiprazole. No difference in the toxicity parameters (inflammatory score, corneal thickness, endothelial cell counting, aqueous humor protein concentration, and intraocular pressure) was found between dapiprazole-treated eyes and saline-solution-treated eyes. Intraocular 0.01% and 0.05% dapiprazole is an effective miotic agent that may be helpful during surgery when the reversal of sympathomimetic mydriasis is needed.

Metabolic correlates of behaviour in the newborn infant.

Twenty-four infants were submitted to behavioural observation 0.5 and 3.5 h after birth. Blood samples were collected from the umbilical cord and from the infant immediately following observation, for the determination of glucose, insulin, cholecystokinin (CCK), and free fatty acids (FFA). It was found that 88% of the infants were awake and 83% performed sucking movements 0.5 h after birth; these findings were associated to a decrease in the plasma glucose concentration (p = 0.05). Eighty-eight percent of the infants were asleep and only 12% exhibited sucking movements 3.5 h after birth; at this time point there was an increase in the plasma concentrations of both CCK (p = 0.05) and FFA (p = 0.01). The infants' plasma insulin concentrations remained unchanged during the time course. It is suggested that the initial behavioural pattern of the newborn, characterized by the appearance of sucking movements, may be due to the rapid decrease of the circulating glucose concentration. The successive increase in the blood concentrations of both CCK and FFA might be two of the factors contributing to the cessation of sucking and to the establishment of a sleeping state.

Pulsatile release of oxytocin in newborn infants.

Recently, a pulsatile, basal oxytocin blood level has been described in human adults. To investigate if such a hormone profile exists already during the neonatal period, we collected blood samples continuously with 20-s fractions for 4 min in 1-day-old infants (n = 26). Plasma oxytocin concentrations were determined by a specific radioimmunoassay. The values were further analysed by the pulse detection program PULSAR. We found that 42% of the infants presented one peak in the oxytocin level during a 4-min period. The peak constituted a 111 +/- 66% (mean +/- SD) increment of the baseline value. It is suggested that the release of oxytocin during basal conditions occurs in a pulsatile way in newborn infants and that these hormone pulses reflect fluctuations in the activity of the hypothalamic neurosecretory cells.

Fetal and maternal plasma levels of gastrin, somatostatin and oxytocin after vaginal delivery and elective cesarean section.

We measured the cord levels of gastrin, somatostatin and oxytocin with radioimmunoassay in plasma collected from the umbilical artery after vaginal delivery and after elective cesarean section. Maternal venous samples after the two labour modalities were also assayed for the same hormones. Fetal gastrin, somatostatin and oxytocin levels were significantly higher after vaginal delivery than after elective cesarean section. Independently of labour type, the fetal gastrin and somatostatin levels were always higher than the maternal levels. We suggest that the observed high levels of gastrin, somatostatin and oxytocin could be due to a stress-related stimulation of the oxytocin- as well as of the gastric gastrin- and somatostatin-producing cells, occurring particularly during vaginal delivery. The significant inverse correlation found between fetal pH and the recorded hormone levels is consistent with this hypothesis.

The relationship of plasma cholecystokinin levels to different feeding routines in newborn infants.

Plasma cholecystokinin concentrations were measured with radioimmunoassay in breast fed infants in Sweden (n = 101) and formula fed infants in Italy (n = 119). Blood samples were collected from the infants during the first five postnatal days, just before feeding in a cross-sectional way. We found no significant difference in the hormone concentration in relation to age, in breast fed or in formula fed infants. Breast fed infants had significantly higher plasma hormone concentrations than formula fed infants during the postnatal period 0-5 days: 2.8 pmol/l (1-10 pmol/l), median (range) versus 2.2 pmol/l (1-25 pmol/l), (P < 0.02). It cannot be excluded that the results were influenced by the circumstances that the samples were collected from two separate populations. However, the higher hormone levels in breast fed infants may also be the expression of the fact that natural feeding per se promotes cholecystokinin secretion in newborn infants.