bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Severe Ulcerative Colitis: Differences in Elderly Patients?
Authors: Vavricka Stephan R. , Rogler Gerhard
Published: September 2009

Almost as many as 10% of patients with ulcerative colitis have late onset with the first flare occurring at 60–70 years of age. The course of the disease and the basic principles of management in geriatric populations do not differ from those in younger patients. However, elderly patients pose distinct problems in therapy choice. In middle-aged patients untreated severe ulcerative colitis has been reduced to <1% in specialized centers at the present time but is still high in the elderly. In general, the management requires close collaboration between gastroenterologists and surgeons. In adult patients, current evidence supports initial treatment with intravenous steroids. However, only 40% of patients show complete response after corticosteroid therapy and almost 30% come to colectomy. Cyclosporine still has a first place as salvage therapy because of its short half-life and its established short-term efficacy in about 70% of patients who fail steroids. The drug should be avoided in frail or elderly patients (especially over 80 years old) with significant comorbidity, and also where colectomy is likely to be necessary in the short to medium term. The long-term benefit of this therapy remains unsatisfactory as colectomy is often only delayed. Infliximab is the choice for those patients with a less severe colitis and less likelihood of urgent colectomy. Tacrolimus has only been used in one randomized controlled trial with similar results to cyclosporine. Surgery is still the definitive procedure for the treatment of ulcerative colitis in adult patients, and its timing is of paramount importance.
Noncolorectal Malignancies in Inflammatory Bowel Disease: More than Meets the Eye
Authors: Beaugerie Laurent , Sokol Harry , Seksik Philippe
Published: September 2009

In patients with Crohn’s disease, the risk of small bowel adenocarcinoma is 20–40 times higher than the low background risk of the general population. In the subset of patients with longstanding small bowel lesions, the absolute risk of small bowel adenocarcinoma exceeds 1 per 100 patient-years after 25 years of follow-up and becomes equivalent to the risk of colorectal cancer. Growing evidence suggests that the pathogenesis of small bowel adenocarcinoma arising in inflammatory lesions of Crohn’s disease is similar to that of colorectal cancer complicating chronic colonic inflammation (inflammation-dysplasia-cancer sequence). However, contrasting with the established endoscopic detection of colonic advanced neoplasias in patients with longstanding extensive colitis, there is no consensus at this time how to face the excess-risk of small bowel adenocarcinoma in patients at high risk. There are no specific clinical or imaging alert signs and endoscopic surveillance of the totality of the inflamed small bowel mucosa would suppose to perform repeated enteroscopies, with the potential limiting factor of stenosis. Very preliminary data suggest that chemoprevention with salicylates could be an alternative way for reducing the risk. Data from referral centers and from the CESAME cohort suggest that intestinal lymphomas may arise in the chronically inflamed segments in patients with inflammatory bowel disease (IBD). Regarding nonintestinal lymphomas, it is now established that IBD patients treated with thiopurines have an excess risk of lymphomas, exhibiting in most cases pathological features of lymphomas associated with immunosuppression, including the frequent presence of EBV in neoplastic tissues. There is growing evidence that treatment with thiopurines is responsible by itself for this excess risk. IBD patients receiving immunomodulators, especially young men, are also at risk (0.4 for 10,000 patient-years in the CESAME study) for developing fatal early post-mononucleosis lymphomas, like in Purtilo’s syndrome, maybe in association with a background genetic susceptibility. Finally, patients receiving thiopurines and/or TNF-inhibitors are at risk for developing fatal hepatosplenic T cell lymphomas, but this risk is low (no case in the CESAME study). Whether patients receiving a monotherapy with methotrexate and/or TNF inhibitors are at increased risk of lymphomas is not known. Concordant data suggest that women receiving immunosuppressive therapy are at increased risk for developing uterine cervix dysplasia and require closer surveillance. But it is not established whether the risk of uterine cervix cancer and basal and squamous cell skin cancers (that may be associated with chronic human papillomavirus infection) is increased in patients receiving immunomodulators.
Technique and Results of the Anterior-to-Posterior-to-Anterior Approach in Revision Endoscopic Sinus Surgery
Authors: Ye Jing , Yu Hongmeng , Draf Wolfgang , Zheng Chunquan , Wang Dehui
Published: September 2009

Objective: To perform the anterior-to-posterior-to-anterior technique in revision endoscopic sinus surgery, and to assess the effects and safety of this technique in treating recurrent chronic sinusitis and nasal polyps. Methods: One hundred and thirteen patients with recurrent chronic sinusitis and nasal polyps received anterior-to-posterior-to-anterior revision endoscopic sinus surgery. This surgical technique has 5 important steps, including exposing the choana, enlarging the maxillary sinus ostium, opening the sphenoid sinus and posterior ethmoid sinus anteriorly to posteriorly, resecting the ethmoid sinus posteriorly to anteriorly, and opening the frontal sinus posteriorly to anteriorly. The choana, maxillary sinus ostium, middle turbinate remnant, and the roof and lateral wall of the sphenoid sinus are 4 stable anatomic reference points. Results: Twelve months postoperatively, the mean SNOT-22 score had improved by 18.48 and 100 (88.50%) patients had an improvement in nasal obstruction; thick nasal discharge, loss of smell or taste, and facial pain/pressure improvements were noted in 102 (90.27%), 64 (56.64%) and 76 (67.26%) patients, respectively. Postoperative endoscopic evaluation after 12 months indicated that 29 (25.66%), 12 (10.62%), 5 (4.42%), 6 (5.31%), and 2 (1.77%) patients had mucosal edema, nasal discharge, synechiae, polyps, and crusting, respectively. No severe complications were observed. Conclusion: The anterior-to-posterior-to-anterior technique is an effective and safe approach to revision endoscopic sinus surgery. The 4 stable anatomic reference points are helpful for preventing severe complications in total ethmoidectomy.
Stratum Corneum Damage and ex vivo Porcine Skin Water Absorption – A Pilot Study
Authors: Duch Lynggaard C. , Bang Knudsen D. , Jemec G.B.E.
Published: September 2009

A simple ex vivo screening technique would be of interest for mass screening of substances for potential barrier disruptive qualities. Ex vivo water absorption as a marker of skin barrier integrity was studied on pig ear skin. Skin water absorption was quantified by weighing and weight changes were found to reflect prehydration barrier damage. It is suggested that this simple model may be elaborated to provide a rapid, economical screening tool for potential skin irritants.
Interaction of Thiazolidinediones (Glitazones) with the ATP-Binding Cassette Transporters P-Glycoprotein and Breast Cancer Resistance Protein
Authors: Weiss Johanna , Sauer Alexandra , Herzog Melanie , Böger Rainer H. , Haefeli Walter E. , Benndorf Ralf A.
Published: September 2009

Aims: Thiazolidinediones (glitazones) are frequently prescribed antidiabetic drugs commonly used in combination drug regimens. To evaluate the risk of drug-drug interactions, we therefore aimed to systematically investigate the inhibitory and inductive effects of all glitazones on 2 of the most relevant drug transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), in vitro. Methods: The inhibition of P-gp and BCRP was assessed by fluorometric assays quantifying the increase in the intracellular concentration of fluorescent P-gp or BCRP substrates caused by their combination with the glitazones. The induction of mRNA expression was quantified by real-time RT-PCR after the treatment of HuH-7 cells with the respective compounds for 4 days. Results: Rosiglitazone and troglitazone significantly inhibited P-gp and BCRP function and induced mRNA expression of BCRP but not of P-gp. Pioglitazone, which exhibited very low solubility, could only be tested up to 0.5 μmol/l and did not provoke an effect in any of the assays. Conclusions: After comparison of the in vitro data and published clinical studies, it seems unlikely that the inhibition of BCRP and P-gp by rosiglitazone plays a role in the clinical situation. In contrast, BCRP induction by rosiglitazone might be of relevance in vivo, but has to be verified in dedicated clinical studies.
Effectiveness of Donepezil in Reducing Clinical Worsening in Patients with Mild-to-Moderate Alzheimer’s Disease
Authors: Wilkinson David , Schindler Rachel , Schwam Elias , Waldemar Gunhild , Jones Roy W. , Gauthier Serge , Lopez Oscar L. , Cummings Jeffrey , Xu Yikang , Feldman Howard H.
Published: September 2009

Background: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer’s disease (AD). Methods: Data from 906 patients (388 receiving placebo; 518 receiving donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10–27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician’s Interview-Based Impression of Change plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). Results: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds of declining were significantly reduced for donepezil-treated versus placebo patients (p < 0.0001; all definitions). Among patients meeting criteria for clinical worsening, mean declines in MMSE scores were greater for placebo than donepezil-treated patients. Conclusion: In this population, donepezil treatment was associated with reduced odds of clinical worsening of AD symptoms. Moreover, patients worsening on donepezil were likely to experience less cognitive decline than expected if left untreated. This suggests that AD patients showing clinical worsening on donepezil may still derive benefits compared with placebo/untreated patients.
Intervention with the Lidcombe Program for a Bilingual School-Age Child Who Stutters in Iran
Authors: Bakhtiar Mehdi , Packman Ann
Published: September 2009

Objective: In this study, the immediate and extended effects of the Lidcombe Program were investigated for the first time in Iran. Treatment in the Lidcombe Program is carried out by the child’s parent (or carer) in the child’s everyday environment. The program has been shown to be effective with preschool children who stutter (i.e. younger than 6 years) and to a lesser extent with older children. Participant and Method: The participant was a bilingual (Baluchi-Persian) boy aged 8 years 11 months. Treatment was conducted in both languages. Stuttering severity was measured in Baluchi with the parental rating scale, and in Persian with percentage of syllables stuttered (%SS). Results: The child completed stage 1 of the program in 13 weeks. %SS was less than 1 during the last 3 clinic visits and severity ratings made by the parent indicated no stuttering (severity rating = 1) for all days of the final week. Speech recordings made beyond the clinic in both languages also indicated stuttering at below 1%SS. The child met all criteria for stage 2 in both languages, over 10 months. Conclusion: This case report suggests that the Lidcombe Program could be suitable for bilingual Iranian children who stutter.
Immunological Reactivity against Neuronal and Non-Neuronal Antigens in Sporadic Adult-Onset Cerebellar Ataxia
Authors: Fancellu Roberto , Pareyson Davide , Corsini Elena , Salsano Ettore , Laurà Matilde , Bernardi Gaetano , Antozzi Carlo , Andreetta Francesca , Colecchia Maurizio , Di Donato Stefano , Mariotti Caterina
Published: September 2009

In recent years, the involvement of the immune system in acquired forms of cerebellar ataxia has been frequently demonstrated. In this study, we describe 6 out of 49 patients with subacute or chronic progressive cerebellar ataxia in whom antibodies against neuronal and non-neuronal antigens were identified. Two women had anti-Yo antibodies; two patients had anti-gliadin antibodies in the presence of celiac disease; one patient had a complex autoimmune disorder associated with anti-Ro-52/SS-A and anti-muscle-specific kinase antibodies, and a patient developed subacute cerebellar syndrome associated with the presence of a prostatic adenocarcinoma and atypical antibodies reacting both with cerebellar tissue and with the prostatic tumor. Our study confirms previous findings in paraneoplastic syndromes, and indicates that at least 10% of sporadic cerebellar ataxia may be related to immune-mediated mechanisms.
Carnitine and Carnitine Transferases in the Intestinal Mucosa of Suckling Rats
Authors: Hahn Peter , Chanez Claude , Hamilton Jennifer
Published: September 2009

Carnitine acetyltransferase and palmitoyltransferase activity in the mucosa of the small intestine of rats rises after birth and falls at the time of weaning. The carnitine contents of the mucosa (free, acetyl-, palmitoyl- and total) decrease postna tally, reaching adult levels at the time of weaning. Orally administered 14C-carnitine is only slowly absorbed so that radioactivity is still high in plasma and organs 6 h later, whereas label given subcutaneously disappears from the plasma and tissues more rapidly. The intestinal mucosa also takes up carnitine from 14C-carnitine administered subcutaneously. It is concluded that carnitine plays an important role in the gut of suckling rats.
Prenatal versus Neonatal Long-Term Effect of Phenobarbital on Mouse Microsomal Drug-Oxidizing System
Authors: Yanai Joseph , Wanich Ami
Published: September 2009

Mice were exposed to phenobarbital (PhB) prenatally or neonatally. Prenatal treatment (PreB) was accomplished by feeding the mother PhB, 3 g/kg milled food on gestation days 9–18. Neonates (NeoB mice) were injected daily with 50 mg/kg PhB. The activity of the hepatic microsomal drug-oxidizing system was assayed in the PreB mice (at ages 28 and 50 days), NeoB mice (22, 28 and 50 days) and controls. PreB had at day 28 only small increases in enzyme activity. However, on day 50 there was a 3-fold increase in PhB level compared to control. Among NeoB mice the enzyme activity was 3 times above control on day 22 but the increase was abolished on days 28 and 50. Thus, the long-term increase in the microsomal drug-oxidizing system takes place only after prenatal (and not neonatal) PhB exposure, and the increased enzyme activity occurs around maturity.
Reevaluation of Thyroid Function in Low Birth Weight Infants Based on Free Triiodothyronine and Triiodothyronine
Authors: Nagashima Kanji , Onoda Kimiyo , Suzuki Shigeyoshi , Sakaguchi Masao , Kuroume Takayoshi
Published: September 2009

We attempted to analyze the physiological meaning of abnormally low thyroid hormones in low birth weight (LBW) infants on the basis of cross-sectional data on free triiodothyronine (free T3) and T3 in addition to the other thyroid hormones. In LBW infants, the levels of free T3 and T3 were lower than those of normal infants, similar to the relation between free thyroxine (free T4) and T4. The ratio of free T3/T3 or free T4/T4, however, was not different between the groups. The levels of thyroid-stimulating hormone, thyroid hormone-binding globulin and reversed T3 in LBW infants were not significantly different from those of normal infants.
Allergenicity of Recombinant Troponin C from Tyrophagus putrescentiae
Authors: Jeong Kyoung Yong , Kim Chung-ryul , Un Sunjin , Yi Myung-hee , Lee In-Yong , Park Jung Won , Hong Chein-Soo , Yong Tai-Soon
Published: September 2009

Background: The storage mite, Tyrophagus putrescentiae, produces potent allergens, many of which have not been characterized. This study was undertaken to characterize the allergenicity of troponin C from T. putrescentiae.Methods: A cDNA encoding 17.7 kDa troponin C, with homology to cockroach allergen Bla g 6, was identified from T. putrescentiae-expressed sequence tags. Recombinant troponin C was expressed and IgE responses to the recombinant protein were assessed in the presence and absence of 10 mM CaCl2. Cross-reactivity between T. putrescentiae troponin C and Bla g 6 was tested using an inhibition ELISA. Results: Recombinant T. putrescentiae troponin C shares 62.7–85.5% homology with troponin C from various arthropods. Sera from 5 of 47 subjects in our study group (10.6%) showed IgE binding to the recombinant protein. Interestingly, addition of 10 mM CaCl2 increased the intensity of IgE binding approximately 2-fold. In an immune-inhibition ELISA with these sera, T. putrescetiae troponin C and Bla g 6 did not cross-react significantly. Conclusions: Troponin C is a new mite allergen with calcium-dependent IgE reactivity.
Effect of Acidosis and Hypoxia on Intestinal Blood Flow of Sheep Fetus
Authors: Younoszai M.K. , Kisker T. , Robillard J. , Nathan R.
Published: September 2009

In sheep fetuses 110–130 days of age acidosis (blood pH 6.95; produced by infusion with 1.1 M lactic acid) significantly lowered blood flow (ml/min/100 g) to the full thickness wall of the jejunum from 135 ± 11 to 93 ± 14 and in the full thickness wall of the ileum from 122 ± 13 to 95 ± 11. The decrease was mainly due to the decline in blood flow to mucosa of the segment, where flow decreased from 182 ± 20 to 83 ± 14 in the jejunum and from 130 ± 10 to 107 ± 9 in the ileum. Fetal hypoxemia (PaO2 of 14.9 mm Hg; induced by allowing ewes to breath 11.1% O2 and 88.9 % nitrogen) reduced blood flow only to the jejunal mucosa from 142 ± 14 to 99 ± 16. The reduction in blood flow to the full thickness wall of the jejunum and the ileum did not change significantly from the control period, when PaO2 was 25 mm Hg.
Unconjugated and Conjugated Bilirubin Pigments during Perinatal Development
Authors: Muraca Maurizio , Blanckaert Norbert , Rubaltelli Firmino F. , Fevery Johan
Published: September 2009

Unconjugated, mono- and diconjugated bilirubin was measured in rat plasma and intestine during perinatal development. Bilirubin monoconjugates were present in the intestines of 18-day-old fetuses, while diconjugates appeared on the 20th day. The concentration of conjugates increased rapidly, reaching 312 μmol/g of intestinal tissue 1 day after birth. The absolute concentration of unconjugated bilirubin increased in parallel. On the 18th day of fetal life, about 80% of the pigment in the intestine was unconjugated, while conjugates largely predominated from the 20th day onwards. Conjugation and/or excretion of bilirubin in the intestine seems therefore to develop rapidly during the last days of life. The plasma concentration of total bilirubin in 18-day-old fetuses was about 2–3 times higher than in adult serum, and it increased slightly during the following days. 2–7% of the pigment was conjugated. Transplacental clearance of bilirubin seems therefore to be deficient in this species. On the 1st day of extrauterine life, bilirubin concentration increased sharply in plasma, reaching 14.76 μmol/l, 38% in the conjugated form. This finding suggests that, unlike humans, an excretory defect is predominant in the neonatal rat.
Ontogenesis of the Kidney in the Congenital Hypothyroid Rat
Authors: Ali M. , Clos J.
Published: September 2009

The effect of congenital thyroid deficiency upon the postnatal development of the rat kidney has been studied by measuring the nucleic acid, protein and lipid contents, and the area and thickness of the different regions in the organ, i.e. cortex, outer and inner medulla. Thyroid deficiency, induced by daily propylthiouracil treatment, strongly affects the development of the renal cortex. The medulla, and still more its inner part which develops early and partly before the onset of thyroid function, is relatively preserved. These effects are completely corrected by daily thyroxine therapy, excluding a possible toxic effect of the antithyroid drug. Moreover, they are partly reversible after cessation of propylthiouracil treatment.
Qualitative and Quantitative Aspects of Human Fetal Liver Metallothioneins
Authors: Clough Stephen R. , Mitra Raj S. , Kulkarni Arun P.
Published: September 2009

This study examined the status of zinc, copper, and metallothionein (MT) in 31 second trimester (13–23 weeks) human fetal livers. In addition, the metal-binding capacities of concomitant and term placentas were investigated in the light of the role of this organ in transport and binding of the potentially toxic group lib elements, notably cadmium and mercury. Qualitative analyses indicate that human fetal liver contains three ‘isoforms’ of MT, with the second form (MT-1) being predominant. DEAE A-25 anion exchange chromatography revealed that human fetal hepatic MT-1 and MT-2 elute similarly to native newborn and cadmium-induced adult rat liver MT, MT-1 and MT-2. A significant quantity of a third isoform, which eluted in low-ionic-strength buffer, is also present in human fetal liver. The function of this isoform may be developmental in nature. Quantitative analyses show that MT levels are high (approximately 6.4% of the soluble protein) and correlate well with zinc in human fetal hepatic cytosol. In contrast, copper levels were low, and no significant correlation could be seen with MT. A slight, but significant positive correlation existed between gestational age (in weeks) versus zinc and MT levels (tissue weight basis); after normalizing for protein, no relationship could be observed. Both preterm and term placenta showed low levels of zinc and MT. It is suggested that the low level of cadmium-binding capacity seen in placenta may be one factor in the susceptibility of this organ to cadmium.
Serum Diamine Oxidase in the Neonate
Authors: Forget P. , De Curtis M. , Senterre J.
Published: September 2009

Serum diamine oxidase (DAO) activities were measured in 9 pregnant women and in 33 neonates during the 1st week of life. The radiometric method was used. Very high values were found in the mothers (mean ± SE: 720 ± 143 pmol ml-1 h-1) Neonates showed significantly elevated values (mean ± SE: 178 ± 54 pmol ml-1 h-1) on the 1st postnatal day when compared to the 7th day values (mean ± SE: 27 ± 5.7 pmol ml-1 h-1)·Serial determinations showed a progressive decline from day 1 to day 7 after birth. We suggest the high serum DAO levels in neonates during the first days of life are due to leakage of placental enzyme into the circulation either at birth or during fetal life. Consequently, serum DAO cannot be used as a marker of small bowel functional integrity in the 1 st postnatal week.
Free Fatty Acids of Human Meconium
Authors: Terasaka David , Clark David A. , Singh Bibhuti N. , Rokahr John
Published: September 2009

Meconium samples of 20 healthy full-term babies were analyzed for free fatty acid content. The total fatty acid content per net weight varied by as much as 9-fold between samples. Considerable variability was also observed in the individual fatty acids found in each sample. Palmitic, stearic and oleic acids were the most abundant fatty acids. Significant amounts of arachidonic and linoleic acids were found. Long-chain iso fatty acids, which are rare in mammalian tissue, were found. The source of these fatty acids is unknown, but intestinal lipases and transplacental origins may be important.
Indomethacin Metabolism in Liver Microsomes during Postnatal Development in the Rat
Authors: Clozel Martine , Beharry Kae , Aranda Jacob V.
Published: September 2009

Indomethacin is now widely used during the neonatal period, but few data exist concerning its metabolism during this period. Thus, we studied the maturational changes in the metabolism of indomethacin into desmethylindomethacin by isolated liver microsomes from 1- to 60-day-old rats. From 8 days of age on, there was a progressive increase in enzymatic activity which was inversely correlated with the change in Michaelis-Menten constant. However, the maximal velocity was not significantly affected by the age. These findings suggest that the deficient metabolism of indomethacin in the newborn rat is due to decreased affinity between enzyme and substrate, or presence of competitive inhibitors. To determine the substrate specificity of the monooxygenase-catalyzing inducers, sodium phenobarbital and β-naphthoflavone given during 3 days in neonatal rats were also studied. Although β-naphthoflavone did not exhibit any significant effect, phenobarbital significantly increased the activity and maximal velocity of indomethacin O-demethylation.
Changes of Acid and Alkaline Phosphatase Activities in the Developing Mouse Brain
Authors: Ng Tzi Bun , Tam Patrick P.L.
Published: September 2009

Acid and alkaline phosphatase activities in the mouse cerebrum, brainstem and cerebellum increased during the late fetal and perinatal period and reached a maximum on postnatal day 28 (P28). Myelination was most extensive on P28–P45 in the brainstem and in the cerebellum, and phosphatidic acid phosphatase activity concomitantly decreased to a low level after birth. The changes in acid and alkaline phosphatase activities correlate more with the extent of myelination than with the overall brain tissue growth.
Duration of Ventricular Ejection during Spontaneous Breathing and Positive Pressure Ventilation in Newborn Infants
Authors: Reller Mark , Kotagal Uma R. , Meyer Richard A. , Kaplan Samuel
Published: September 2009

Experimental manipulations of intrathoracic pressure at the investigational level have been shown to result in demonstrable changes in ventricular outputs. To assess whether these changes are detectable in the clinical setting of newborn infants, we evaluated changes in the duration of left and right ventricular ejection during spontaneous breathing and during positive pressure ventilation. This was accomplished by measuring left and right ventricular ejection times (VETs) using echocardiography. Values from cardiac cycles during peak inspiration were compared to cycles that occurred during expiration. In 6 infants breathing spontaneously, the mean duration of right VET increased by 4.0% at peak inspiration, while the concomitant mean left VET decreased by 3.3%. In 14 infants requiring positive pressure ventilation, the mean duration of right VET decreased by 7.2% at peak inspiration, while the left VET increased by 2.5%. We conclude that changes in intrathoracic pressure associated with spontaneous breathing and with positive pressure ventilation result in detectable changes in ventricular ejection in the newborn infant.
Effect of Endogenous Opioid Blockade on Fetal Cardiovascular and Sympathoadrenal Responses to Hypoxemia Induced by Umbilical Cord Constriction
Authors: Lewis Alan B. , Ferry David A.
Published: September 2009

The cardiovascular and plasma catecholamine responses to hypoxemia following endogenous opioid blockade were evaluated in 18 late gestation fetal lambs (0.75–0.83 gestation) in utero. Hypoxemia was produced by progressive constriction of the umbilical cord with an inflatable silicone rubber cuff while fetal heart rate, blood pressure, and arterial blood gases were monitored. Fetal arterial blood samples were obtained for plasma catecholamine analysis using a radioenzymatic method. The animals were divided into 4 experimental groups. Control animals during normoxemia and following hypoxemia are represented by groups I and III, respectively. During umbilical constriction, arterial oxygen tension declined from 21.4 ± 0.3 to 13.4 ± 0.3 torr (p < 0.001, mean ± SE) and was accompanied by an increase in blood pressure (44 ± 1 to 53 ± 1 torr), decrease in heart rate (176 ± 4 to 114 ± 4 beats/min) and rise in plasma norepinephrine (437 ± 90 to 3,410 ± 617 pg/ml) and epinephrine (53 ± 10 to 1,074 ± 325 pg/ml). Naloxone infusion had no significant effect on the fetus during either normoxemic (group II) or hypoxemic conditions (group IV). Plasma catecholamines rose less in group IV than in hypoxemic control fetuses (norepinephrine: 2,407 ± 406 vs. 3,410 ± 617 pg/ml; epinephrine: 966 ± 641 vs. 1,074 ± 305 pg/ml), but the differences were not significant (p > 0.2). It is concluded that endogenous opioids do not play a major role in the modulation of cardiovascular and sympathoadrenal adaptions to moderate hypoxemia in the fetus.
Prostaglandins in Human Milk
Authors: Alzina Valentin , Puig Myriam , de Echániz Luis , Villa Ignacio , da Cunha Ferreira Roque
Published: September 2009

Human milk contains many different components which interact locally in the gastrointestinal tract and stimulate some systemic functions. Among these substances are protaglandins. We obtained samples of foremilk and hindmilk in 8 lactating women by manual expression before and after 9 a.m. and 9 p.m. on the 3rd day post partum. The following values were found for prostaglandin E2: foremilk, 162 ± 135 pg/ml; hindmilk, 198 ± 148 pg/ml. The values for 6-ketoprostaglandin F1α were: foremilk, 818 ± 386 pg/ml, and hindmilk, 795 ± 487 pg/ml. The values for thromboxane B2 were: foremilk, 3,557 ± 2,770 pg/ml and hindmilk, 4,476 ± 4,053 pg/ml. The results showed a great variability without statistical differences between paired values of the four groups. This dispersion may be produced by the procedure for extraction and by individual basal levels.
Gluconeogenesis in Late Fetal and Early Neonatal Life
Authors: Girard Jean
Published: September 2009

Birth in most mammalian species represents an abrupt change from a high-carbohydrate and low-fat diet to a high-fat and low-carbohydrate diet. Gluconeogenesis is absent from the liver of the fetus of well fed mothers, but can be induced prematurely by prolonged fasting of the mother. Gluconeogenesis increases rapidly in the liver of newborn mammals in parallel with the appearance of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of this pathway. The rise in plasma glucagon and the fall in plasma insulin which occur immediately after birth are the main determinants of liver PEPCK induction. When liver PEPCK has reached its adult value, i.e. 24 h after birth, other factors are involved in the regulation of hepatic gluconeogenesis. In order to maintain a high gluconeogenic rate, the newborn liver must be supplied with sufficient amount of gluconeogenic substrates and free fatty acids. An active hepatic fatty acid oxidation is necessary to support hepatic gluconeogenesis by providing essential cofactors such as acetyl CoA and NADH. The relevance of animal studies for the understanding of neonatal glucose homeostasis in man is discussed.
Breast-Milk-Enhanced Intestinal and Somatic Growth in Neonatal Rats
Authors: Berseth Carol Lynn
Published: September 2009

Ten rat pups fed pooled rat milk and 9 pups fed artificial formula had significantly heavier stomachs and intestines that contained more DNA and RNA by 40 h of age than 12 pups sacrificed at birth. Breast-milk-fed animals had significantly heavier intestines, livers and kidneys than animals fed artificial formula. The intestines of pups fed breast milk contained more DNA and RNA with a lower RNA:DNA ratio than the intestines of pups fed artificial formula. Hence, when caloric intake and mode of feeding are controlled, natural milk enhances neonatal intestinal growth more than artificial formula.
Glucose Metabolism in Pregnancy
Authors: Leturque A. , Hauguel S. , Ferré P. , Girard J.
Published: September 2009

Pregnancy is characterized by a number of maternal metabolic modifications in order to meet the energy requirements of the growing fetus. A progressive alteration of maternal glucose homeostasis develops throughout gestation and becomes maximal during the last trimester. A relative hypoglycemia is observed during the postabsorptive period despite an elevated plasma insulin concentration and an enhanced hepatic glucose production. In addition, the glucose utilization rate by peripheral maternal tissues is lowered in late gestation indicating that the mother supplies glucose to the fetus at the expense of her own tissues. Concomitantly, an insulin-resistant state develops in the mother to help sparing glucose for the pregnant uterus. It involves both glucose-producing (liver) and glucose-utilizing tissues. So far, the factor(s) responsible for the development of pregnancy-induced insulin resistance has not been identified although a number of circulating hormones are known to counteract insulin effects.
Mechanisms of Congenital Malformations in Diabetic Pregnancy
Authors: Eriksson Ulf J. , Karlsson Mats-Göte , Styrud Johan
Published: September 2009

The reasons for the increased rate of congenital malformations in diabetic pregnancy are unclear. Several different teratological agents may be considered. In clinical investigations and animal experimentation hyperglycemia and hypoglycemia, hyperketonemia, altered trace metal metabolism, and a genetic predisposition have been suggested to be of significance in the teratogenic process of diabetic pregnancy. Studies of these possible etiological factors have so far failed to reveal a single agent or mechanism as the most important. The diabetic pregnancy, therefore, appears to be of multifactorial origin.
Pre- and Perinatal Clinical Characteristics of Infants Who Suffer Sudden Infant Death Syndrome
Authors: Stebbens V.A. , Alexander J.R. , Southall D.P.
Published: September 2009

In a population-based study, clinical and physiological data were collected in the neonatal period on 7,496 full-term (≥ 37 weeks) infants of birthweights > 2.50 kg born in 3 hospitals. The sample excluded a small number of infants who were born with severe illnesses from which there was no period of recovery before death in the neonatal period. Twenty-seven of the infants had died by the time all of the population had passed their third birthday. Twenty-one of these cases died suddenly and unexpectedly, and in 13 there was no adequate explanation for death (sudden infant death syndrome – SIDS). Pre- and early postnatal clinical data on the infants who had died were compared to a randomly selected sample of 478 survivors. This analysis showed that the infants who suffered SIDS showed similar clinical characteristics to those previously reported. Unlike the SIDS group, however, the prenatal histories of the non-SIDS deaths were similar to controls, showing no evidence of a sub-optimal intra-uterine environment.
Skinfold Thickness and Adiposity Index in Premature Infants
Authors: de Gamarra M.E. , Schutz Y. , Catzeflis C. , Freymond D. , Cauderay M. , Calame A. , Micheli J.L. , Jéquier E.
Published: September 2009

In order to assess the validity of the weight per square of length ratio as an index of adiposity during the neonatal period, 37 premature infants (gestational age, mean ± SD, = 31.5 ± 1.1 weeks, birthweight, mean ± SD, =1.448 ± 147 g) were studied for weight, length and skinfold thickness at 5 sites (biceps, triceps, subscapular, suprailiac and quadriceps) during their stay in the Neonatal Unit of the University Hospital in Lausanne. The results show a significant correlation between the adiposity index and the sum of 5 skinfold thickness sites in premature infants. The adiposity index gives a fair estimate of the body fat mass during the postnatal growth in premature infants.
Pedigree of the Major Histocompatibility Complex in a Family with a Neonatal Alloimmune Thrombocytopenia
Authors: Panzer S. , Kiefel V. , Mayr W.R. , Fielder A.H.L. , Lachmann D. , Mueller-Eckhardt C.
Published: September 2009

Immunization of a mother negative for the platelet-specific antigen P1A1 against the P1A1 antigen of her child induced neonatal alloimmune thrombocytopenia. This prompt immune response occurred in her first pregnancy and we were therefore interested to study whether there is an association with genes located within the major histocompatibility complex. We deduced haplotypes of HLA-A, B, C and DR as well as of complement C2, C4 and Bf in the maternal family members.
Net Sodium and Water Movements in the Newborn Rabbit Collecting Tubule: Lack of Modifications by Indomethacin
Authors: Reyes José-Luis , Roch-Ramel Françoise , Besseghir Kamel
Published: September 2009

In contrast to adult tubules, a bath-to-lumen sodium gradient was followed by net sodium entry in the lumen of in vitro isolated perfused newborn (3–5 days) rabbit collecting tubules. In addition, transepithelial voltage and electrical resistance were lower in newborn tubules. The sodium flux into the lumen was unaffected by indomethacin. These observations suggest that the newborn collecting tubule may be unable to maintain an adequate sodium gradient for the optimal function of the urinary concentrating mechanism, and that endogenous prostaglandins are not involved in this defect.
Enhancement of Lung Conditioning by Acetylcholine in the Prevention of Respiratory Distress Syndrome in the Preterm Fetal Lamb
Authors: Kolobow Theodor , Solca Maurizio , Chen Victor , Buckhold Delwin K. , Pierce Joseph E.
Published: September 2009

We exposed 128- to 130-day-gestation fetal lambs by cesarean section leaving the umbilical cord and placenta undisturbed, and we then treated the lungs with pulmonary conditioning (i.e., repeated prolonged inflations to 35 cm H2O, followed by a continuous positive airway pressure of 15 cm H2O). To investigate the added effect of pulmonary vasodilation upon the increase of total compliance and pulmonary oxygen uptake, we also administered acetylcholine intravenously at a rate of 80 μg min-1. Eleven of 13 lambs met the endpoint criteria of either compliance (0.5 ml [cm H2O]––1 kg––1; 1 animal), or pulmonary oxygen uptake (6 ml kg––1 min––1; 6 animals), or both (4 animals), and were delivered within 0.6 ± 0.3 h. This time was significantly (p < 0.05) shorter than previously seen in similar studies without the infusion of a vasodilator; all animals so delivered survived 24 h of mechanical ventilation in excellent health. We suggest that pharmacologic pulmonary vasodilation, in addition to deep sustained pulmonary insufflation and distension, is an effective and rapid means of transforming stiff immature lungs into lungs that can sustain normal ventilation and gas exchange.
Effect of Progesterone on the Testosterone and Estradiol Levels in the Hypothalamus of Neonatal Rats
Authors: Rhoda J. , Valens M. , Edwards D.A. , Roffi J.
Published: September 2009

Pregnant female rats were injected with progesterone or oil from 18.5 up to 21.5 days of gestation. Rat pups were delivered by caesarian section, and pups delivered from progesterone-treated mothers were injected with 100 μg of progesterone and pups from oil-treated mothers were injected with oil. Two hours after delivery, pups were killed and hypothalamic testosterone and estradiol were determined by RIA. Control males had substantially higher concentrations of testosterone and estradiol in hypothalamus than control females. Treatment with progesterone did not affect the accumulation of testosterone in the hypothalamic tissue of neonatal males, but completely prevented the formation of estradiol in hypothalamic tissue. This result suggests that progesterone can inhibit hypothalamic aromatase activity in the neonate and may explain why progesterone can protect against some of the neural defeminizing effects of neonatally administered androgens.
Developmental Pattern of Ornithine Decarboxylase Activity, S-Adenosylmethionine Decarboxylase, and Polyamines of Rat Adrenal Glands
Authors: Ekker Marc , Sourkes Theodore L.
Published: September 2009

The concentrations of polyamines and the activities of ornithine decarboxylase (ODC) and of S-adenosylmethionine decarboxylase (SAM-DC) were measured in the adrenal glands of rats during development. Adrenal spermine content increases gradually during the first month of life whereas spermidine and putrescine decrease. A low spermidine/spermine ratio is obtained. The developmental pattern of adrenal SAM-DC resembles that of spermine content. The activity of adrenal ornithine decarboxylase increases after birth and attains a peak at 17 days of age. It declines sharply thereafter. Induction of adrenal ODC following the stress of immobilization is already observed in the rat at 4 days of age but the induction caused by maternal deprivation or cold exposure is obtained only at 17 days. The results suggest that the developmental pattern of ODC activity is independent of its responsivity to various stressors.
Role of Catecholamines in the Control of Newborn Kidney Adenine Nucleotide Content
Authors: Sofack F. , Bastin J. , Boulekbache H. , Bismuth J. , Delaval E. , Geloso J.P.
Published: September 2009

During the 1 st h of extrauterine life, the adenine nucleotide content of the rat kidney is modified: the ATP level increases (+30%) while ADP and AMP are lowered (––30 and ––50%, respectively). This leads to a high value of energy charge in the newborn kidney (0.89 vs. 0.80 in the fetus). It was possible to obtain in utero a similar modification of ATP, ADP, AMP concentrations by injections to the fetuses of cAMP, dibutyryl cAMP, or isoprenaline. Conversely, the postnatal changes in adenine nucleotide content could be prevented by administration to the fetus, just before birth, of β- or β1-adrenoreceptor antagonists. Therefore the rise of kidney energy charge following parturition appears to be under hormonal control. Glucagon had no effect on kidney adenine nucleotide content. It is strongly suggested that the catecholamines released at the time of parturition are the triggering factor of this evolution.
Decreased Plasma Arachidonic Acid Binding Capacity in Neonates
Authors: Sadowitz David , Walenga Ronald W. , Clark David , Stuart Marie J.
Published: September 2009

Arachidonic acid (AA) metabolites have been implicated in neonatal pathologic states such as respiratory distress syndrome (RDS). Since free (nonprotein bound) AA is the substrate for synthesis of these compounds, a decreased capacity to bind AA in neonatal plasma could contribute to these disorders. AA binding was assayed by equilibrium dialysis in plasma samples from healthy adults and various infant groups. Plasma from these infant groups bound significantly less AA than adult plasma. Premature infants with RDS and premature infants receiving intralipid had the lowest capacity to bind AA. The increased availability of free AA may be important in neonatal pathophysiologic states involving arachidonate metabolites.
Effects of Maternal Caffeine Ingestion on the Perinatal Cerebrum
Authors: Tanaka Harumi , Nakazawa Kazuharu , Arima Masataka
Published: September 2009

The cerebra of fetal rats from dams given 0.04 or 0.02% caffeine in drinking water ad libitum before and/or during pregnancy were examined on gestational day 21. A low placental weight was induced by caffeine ingestion for a long time throughout premating and pregnancy. A greater reduction in the fetal weight of the cerebrum than that of the body was observed with caffeine ingestion during pregnancy of levels of 1.5–3.0 μg caffeine/ml or g wet weight in dams and fetuses. In the cerebra of offspring, the levels of caffeine and theophylline did not change for 4 h after birth, and theophylline was not detected at all after intraperitoneal injection of caffeine. Thus, maternal caffeine should be warned against the fetal cerebral function.
Development of Enzymes of Glycerol Metabolism in Human Fetal Liver
Authors: Sadava D. , Depper M. , Gilbert M. , Bernard B. , McCabe E.R.B.
Published: September 2009

The activities of three key enzymes of glycerol metabolism were measured in liver samples from 37 human fetuses ranging in gestational age from 18 weeks to term, from neonates (1–3 days) and from infants to 2 years. Glycerol kinase specific activity was constant throughout the period of fetal development examined, and was comparable to that measured in neonates and infants. owever, the subcellular distribution of the activity changed markedly, being predominantly particulate in fetal samples and cytoplasmic in postnatal samples. The particulate activity had an elevated Km for glycerol. Cytoplasmic glycerol-3-phosphate dehydrogenase activity was very low in the fetal period, and then rose to adult levels during infancy. There were no kinetic differences between the fetal and postnatal activities. Mitochondrial glycerol-3-phosphate dehydrogenase activity rose somewhat after birth to near adult levels. The data indicate that glycerol can be metabolized by human fetal, neonatal and infant liver.
Perinatal Hamster Gonadal Androgen and Estradiol Production in vitro and Response to hCG
Authors: Vomachka Archie J. , DiMario Karen B.
Published: September 2009

Testes or ovaries from fetal and neonatal hamsters (day 14 or 15 of gestation, the day of birth, or on day 1 or 2 of neonatal life) were incubated for 4 h in vitro with or without the addition of 10 IU human chorionic gonadotropin (hCG) to the medium. Release of androgen or estradiol into the medium at hourly intervals (testicular androgen) or after 4 h (all other groups) was estimated using radioimmunoassays. Fetal testes produced large amounts of androgen and were highly responsive to hCG. Androgen production and hCG sensitivity declined at birth and with increasing neonatal age. Testicular estradiol production and ovarian androgen and estradiol release followed the same pattern of a prenatal peak in basal release and hCH sensitivity. Release levels by the ovaries were exceedingly low when compared to testicular androgen release.
Postnatal Development of Uterine Abnormalities in Mice Exposed to DES in Utero
Authors: Iguchi Taisen , Takasugi Noboru
Published: September 2009

Postnatal development of uterine abnormalities was examined in the offspring of mice given 4 daily subcutaneous injections of 2,000 μg diethylstilbestrol (DES) and of oil vehicle alone from days 15 to 18 of gestation. The prenatally DES-exposed mice (DES mice) exhibited a disorganization of the inner circular musculature of the uterus as early as at 5 days of age. Invaginations of the luminal epithelium into the stroma which began to form in 5-day-old control and 10-day-old DES mice developed into uterine glands at 10 and 15 days, respectively. The number of glands per uterine section was significantly reduced in DES mice as compared with the controls at 10–30 days. Stratification with or without squamous metaplasia (ST) was found in the luminal epithelium of DES mice at 20 days. Five groups each of DES mice and the controls ovariectomized (OVX) at 10 days were given 5 daily subcutaneous injections of 10––4, 10––3, 10––2, 10––1, and 1 μg 17β-estradiol (E2) starting at 25 days. ST was never observed in OVX mice given prepubertal injections of any E2 dose, whereas in DES OVX mice aged 30 days, ST was produced by prepubertal injections of E2 doses higher than 10––2 μg/day. Uterine responsiveness, weight gain and gland formation were significantly reduced in DES mice given prepubertal E2 injections compared to the controls.