Photophysics of a copper phenanthroline elucidated by trajectory and wavepacket-based quantum dynamics: a synergetic approach.

On-the-fly excited state molecular dynamics is a valuable method for studying non-equilibrium processes in excited states and is beginning to emerge as a mature approach much like its ground state counterparts. In contrast to quantum wavepacket dynamics methods, it negates the need for modelling potential energy surfaces, which usually confine nuclear motion within a reduced number of vibrational modes. In addition, on-the-fly molecular dynamics techniques are easily combined with the atomistic description of the solvents (through the QM/MM approach) making it possible to explicitly address the effect of the environment. Herein, we study the nonadiabatic relaxation of photoexcited [Cu(dmp)2]+ (dmp = 2,9-dimethyl-1,10-phenanthroline) using QM/MM Trajectory Surface Hopping (TSH). We show that the decay of the initially excited singlet state into the lowest singlet (S1) state occurs within 100 fs, in agreement with previous experiments, and is slightly influenced by the solvent. Using a principal component analysis (PCA), we also identify the dominant normal modes activated during the excited state decay, which are then used to design the vibronic Hamiltonian for quantum wavepacket dynamics simulations.

Theoretical Rationalization of the Emission Properties of Prototypical Cu(I)-Phenanthroline Complexes.

The excited state properties of transition metal complexes have become a central focus of research owing to a wide range of possible applications that seek to exploit their luminescence properties. Herein, we use density functional theory (DFT), time-dependent DFT (TDDFT), classical and quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations to provide a full understanding on the role of the geometric and electronic structure, spin-orbit coupling, singlet-triplet gap and the solvent environment on the emission properties of nine prototypical copper(I)-phenanthroline complexes. Our calculations reveal clear trends in the electronic properties that are strongly correlated to the luminescence properties, allowing us to rationalize the role of specific structural modifications. The MD simulations show, in agreement with recent experimental observations, that the lifetime shortening of the excited triplet state in donor solvents (acetonitrile) is not due to the formation of an exciplex. Instead, the solute-solvent interaction is transient and arises from solvent structures that are similar to the ones already present in the ground state. These results based on a subset of the prototypical mononuclear Cu(I) complexes shed general insight into these complexes that may be exploited for development of mononuclear Cu(I) complexes for applications as, for example, emitters in third generation OLEDs.

A quantum dynamics study of the ultrafast relaxation in a prototypical Cu(I)-phenanthroline.

The ultrafast nonadiabatic dynamics of a prototypical Cu(I)-phenanthroline complex, [Cu(dmp)2](+) (dmp = 2,9-dimethyl-1,10-phenanthroline), initiated after photoexcitation into the optically bright metal-to-ligand charge-transfer (MLCT) state (S3) is investigated using quantum nuclear dynamics. In agreement with recent experimental conclusions, we find that the system undergoes rapid (∼100 fs) internal conversion from S3 into the S2 and S1 states at or near the Franck-Condon (FC) geometry. This is preceded by a dynamic component with a time constant of ∼400 fs, which corresponds to the flattening of the ligands associated with the pseudo Jahn-Teller distortion. Importantly, our simulations demonstrate that this latter aspect is in competition with subpicosecond intersystem crossing (ISC). The mechanism for ISC is shown to be a dynamic effect, in the sense that it arises from the system traversing the pseudo Jahn-Teller coordinate where the singlet and triplet states become degenerate, leading to efficient crossing. These first-principles quantum dynamics simulations, in conjunction with recent experiments, allow us to clearly resolve the mechanistic details of the ultrafast dynamics within [Cu(dmp)2](+), which have been disputed in the literature.

Solvent-induced luminescence quenching: static and time-resolved X-ray absorption spectroscopy of a copper(I) phenanthroline complex.

We present a static and picosecond X-ray absorption study at the Cu K-edge of bis(2,9-dimethyl-1,10-phenanthroline)copper(I) ([Cu(dmp)2](+); dmp = 2,9-dimethyl-1,10-phenanthroline) dissolved in acetonitrile and dichloromethane. The steady-state photoluminescence spectra in dichloromethane and acetonitrile are also presented and show a shift to longer wavelengths for the latter, which points to a stronger stabilization of the excited complex. The fine structure features of the static and transient X-ray spectra allow an unambiguous assignment of the electronic and geometric structure of the molecule in both its ground and excited (3)MLCT states. Importantly, the transient spectra are remarkably similar for both solvents, and the spectral changes can be rationalized using the optimized ground- and excited-state structures of the complex. The proposed assignment of the lifetime shortening of the excited state in donor solvents (acetonitrile) to a metal-centered exciplex is not corroborated here. Molecular dynamics simulations confirm the lack of complexation; however, in both solvents the molecules come close to the metal but undergo rapid exchange with the bulk. The shortening of the lifetime of the title complex and nine additional related complexes can be rationalized by the decrease in the (3)MLCT energy. Deviations from this trend may be explained by means of the effects of the dihedral angle between the ligand planes, the solvent, and the (3)MLCT-(1)MLCT energy gap.

Laparoscopic-assisted jejunostomy: an effective procedure for the treatment of neurologically impaired children with feeding problems and gastroesophageal reflux.

BACKGROUND: Feeding difficulties and gastroesophageal reflux (GER) are major problems in severely neurologically impaired children. Many patients are managed with a simple gastrostomy, with or without fundoplication. Unfortunately, fundoplication and gastrostomy are not devoid of complications, indicating the need for other options in the management of these patients. METHODS: Since January 2002, seven patients (age range, 5-14 years) have been treated by creating a jejunostomy with the laparoscopic-assisted procedure. The procedure was performed using two 10-mm trocars. The technique consists of identifying the first jejunal loop, grasping it 20-30 cm away from the Treitz ligament with fenestrated atraumatic forceps, and exteriorizing it to the trocar orifice under visual guide. The jejunostomy was created outside the abdominal cavity during open surgery. At the end of the jejunostomy, the correct positions of the intestinal loop and feeding tube were evaluated via laparoscopy. RESULTS: Surgery lasted 40 min on average, the laparoscopic portion only 5 min. There were no perioperative complications; hospital stay was 3 or 4 days for all patients. At the longest follow-up (18 months), all patients had experienced a significant weight gain, with a high level of parental satisfaction. One patient died 1 year after the procedure of unknown causes. All the others are well, without complications or problems, and their parents are extremely satisfied with the improved quality of life of their children. CONCLUSIONS: Laparoscopic-assisted jejunostomy is a safe and effective procedure to adopt in neurologically impaired children with feeding problems and GER. This procedure solves these patients' feeding problems even if the reflux is not completely eliminated. We advocate the use of this procedure in neurologically impaired patients with feeding problems and reflux due to its overall practicability and because there is minimal surgical trauma. This technique is extremely safe because the surgeon is able to verify, at the end of procedure, the status of the jejunostomy from outside and inside the abdominal cavity. The improvement in the quality of life of these children after the jejunostomy seems to be the major advantage of this procedure.

Stiffness of the aortic wall in hypercholesterolemic children.

Arterial stiffness may be an indicator of early vascular changes signaling the development of vascular disease, while hypercholesterolemia is a well-recognized promoter of atherogenesis. It has been shown that hypercholesterolemic children have a thicker intima-media in the carotid artery than children with normal cholesterol. The aim of this study was to assess the stiffness of the abdominal aorta in children with hypercholesterolemia. Noninvasive imaging evaluation of the aorta was performed in 85 outpatient children (age, 3 to 14 years) with and without high cholesterol levels ((and) 247 mg/dL [6.4 mmol/L], respectively). Ultrasound imaging of the abdominal aorta that allowed diameter measurements was available in 67 children. Using an image-processing workstation, the maximum and minimum internal diameter of the aorta was measured, and the following indices of elastic properties of the abdominal aorta were derived: arterial strain, pressure-strain elastic modulus, and stiffness. No statistical difference for aortic strain, stiffness, and elastic modulus was found in normocholesterolemic compared with hypercholesterolemic children. The effect of age on the elastic modulus was different in the two groups: in normal children, the elastic modulus increased linearly with age (y = -0.020+0.003 x age [months], P<.001), while the high-cholesterol group had a weak increase in this parameter with age (y = 0.118+0.0009 x age, P = .051). The slope of the regression equations (elastic modulus vage) was significantly different in the two groups (t = 2.45, P = .017). The behavior of arterial stiffness with respect to age was similar, y = 0.677+0.018 x age (P = .002) in normocholesterolemic children and y = 2.06+0.00198 x age (P = .66) in hypercholesterolemic children. The slope of the regression equations (stiffness v. age) was significantly different in the two groups (t = 2.37, P = .021). The present study demonstrates an influence of hypercholesterolemia on age-related modification in the elastic properties of the aorta. A remodeling of the aortic wall in hypercholesterolemic children (cholesterolemia >247 mg/dL) could explain the different age-dependent increase in aortic elastic modulus and stiffness.

Detection of clostridial toxins in stools from children with diarrhoea.

A cell-culture assay was used to detect toxins directly in stools from sporadic cases of infantile diarrhoea. Cytotoxins were revealed in 11 out of 58 samples from children with diarrhoea, nine of whom had no common enteric pathogens in their stools. A preliminary characterisation of the cytotoxins was obtained by neutralisation tests with clostridial antitoxins.

Gastrointestinal manifestations in children with cerebral palsy.

We describe the prevalence and nature of gastrointestinal (GI) symptoms in 58 children affected by cerebral palsy (range: from 6 months to 12 years of age) referred to a pediatric neurology outpatient clinic. In each patient we assessed (GI) symptoms and defined the associated GI functional or structural abnormalities. Furthermore, we tried to correlate the type of GI dysfunction with findings on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain. Our results showed that 92% of children with cerebral palsy had clinically significant gastrointestinal symptoms. Swallowing disorders were present in 60% of patients, regurgitation and/or vomiting in 32%, abdominal pain in 32%, episodes of chronic pulmonary aspiration in 41% and chronic constipation in 74%. Dysfunction of the oral and/or pharyngeal phase of swallowing was found in 28 of 30 (93%) patients with swallowing disorders. Of the 45 patients with symptoms suggesting gastroesophageal reflux, 41 (91%) had an abnormal pH-monitoring and/or esophagitis. Furthermore, a significant delay in the scintigraphic gastric emptying of liquids was found in 12 of 18 patients (67%) and an abnormal esophageal motility in 11 of the 18 (61%) investigated patients. In 25 patients with chronic constipation evaluation of colonic transit showed a delay at level of the proximal segments of the colon in 13 (52%), at level of the left colon and rectum in 9 (36%) and in 3 (12%) at level of the rectum only. Computed tomography and/or magnetic resonance imaging were normal in 5 (9%) and abnormal in 53 (91%) of the 58 children with cerebral palsy. No GI symptom was significantly associated with any kind of abnormal neuroimaging. In conclusion, children with cerebral palsy exhibited diffuse GI clinical manifestations, mostly due to disorders of GI motility. The GI symptoms seemed not to be related to any specific finding on CT or MRI of the brain.

Advances in infant nutrition.

Recent advances in the nutrition of low birth weight infants are discussed, with special emphasis on concepts and methods to establish parameters for the control of growth and nutrition. Furthermore, the recent developments of methods in the research on newborn nutrition, the problems related to the use of breast milk, the timing of feeding and the problems of the intravenous alimentation are discussed in some detail. Secondly, the effects of breast feeding on infant health are summarised, with particular emphasis on the long term consequences (occurrence of diseases later in life) and on the effects on some surgical diseases of infancy. Recent acquisitions in the field of enteral and parenteral nutrition are also mentioned, and the problems related to composition of the nutritive solutions and indications in pediatric age are covered in some detail. Finally, the dietary management of infant with cow's milk protein allergy or intolerance is discussed, with special regard to composition and indications of hydrolysed protein formulas (casein based, whey based, soy and collagen based), soy based formulas and aminoacid based formulas.

Production of Escherichia coli STa-like heat-stable enterotoxin by Citrobacter freundii isolated from humans.

Citrobacter species are often present in the stools of children and are generally considered a normal component of the intestinal microflora. Previous reports suggested that they might act as enteric pathogens. Aiming at defining the role of Citrobacter species in inducing diarrhea, we looked for their presence in the stools of 328 children with diarrhea and in 108 controls. Citrobacter strains were isolated from 46 patients (14%) and 7 controls (6.5%) (P less than 0.05). All isolates were tested for heat-stable (ST) and heat-labile (LT) enterotoxin. No LT-producing organisms were found. Three C. freundii strains, all isolated from children with diarrhea, elaborated an enterotoxin detected by the suckling mouse assay. A crude extract was prepared by acetone precipitation and a sequential ultrafiltration technique. The enterotoxin was heat stable, and its estimated molecular weight was between 2,000 and 10,000. Citrobacter enterotoxin was soluble in methanol and stable at acid and neutral pHs but not above pH 8, and its activity was destroyed by treatment with 2-mercaptoethanol. Citrobacter enterotoxin was inactive in the 18-h rabbit ileal loop test. All these characteristics closely resemble STa produced by Escherichia coli. The time course of Citrobacter enterotoxin-induced intestinal secretion in suckling mice was similar to that of E. coli STa. The enterotoxin produced by C. freundii cross-reacted with monoclonal antibodies raised against E. coli STa. These results suggest that C. freundii is capable of inducing diarrhea through the production of an E. coli-like STa, and its presence in the stools of patients with diarrhea should be considered as that of a possible etiologic agent.

Chronic diarrhea and failure to thrive in an infant with Campylobacter jejuni.

We report the case of an infant with chronic diarrhea and failure to thrive. Campylobacter jejuni was isolated from stools and treatment with erythromycin resulted in eradication of infection and prompt resolution of symptoms. A 22-month-old girl was referred to our University Hospital because of weight loss and chronic diarrhea, which did not respond to repeated dietetic trials that excluded milk, gluten, and other foodstuffs. Microscopic examination of the jejunal biopsy specimen revealed a mild degree of partial mucosal atrophy with inflammatory infiltrates in the lamina propria without any hallmarks of celiac disease. Repeated stool cultures on Butzler medium were positive for C. jejuni. This finding was associated with a high titer of specific serum antibodies. Erythromycin therapy without any other form of therapy led to prompt improvement, and the patient reached her "own" 50th centile as weight/height ratio. The aim of this report is to alert pediatric gastroenterologists of the possibility that Campylobacter may be associated with chronic diarrhea and failure to thrive.

Acute childhood diarrhoea in Naples: an aetiologic study.

A potential aetiologic agent was detected in the stools of 56% of 118 children hospitalized in Naples for acute diarrhoea. Rotavirus and Salmonella were the agents most commonly associated with disease, accounting for 23 and 17 percent of cases, respectively. Campylobacter jejuni, enterotoxigenic Escherichia coli, Yersinia and Shigella were less frequently isolated (total, 11% of cases). These findings fit well with the epidemiological picture described for other developed countries, except for the isolation rate of Salmonella which widely exceeds that reported in other investigations. Cytotoxic strains of E. coli and other Gram-negative bacilli were identified in the stools of 18 children; the possible pathogenic role of these strains is unknown and needs further investigation.

Influence of the polyamine, spermidine, on intestinal maturation and dietary antigen uptake in the neonatal rat.

Polyamines appear to have an important role in postnatal growth of the rat intestine. In the present study, we examined the effect of spermidine on the maturation of the intestine and on its ability to exclude macromolecules. Two litters of Sprague-Dawley rat pups were assigned to one of four experimental groups. These groups received, on Days 7, 8, and 9, either (a) saline by gavage; (b) spermidine, 0.9 mg (6 mumol) by gavage; (c) cortisone acetate, 3.5 mg i.p.; or (d) saline i.p. On Day 10, animals were fed by gavage with a mixture of bovine serum albumin (BSA; 2 mg/g) and the gamma-globulin fraction of mouse antiovalbumin (anti-OVA) antiserum (1 mg/g) and were bled 4 h later. Intestinal tissues were processed for histologic examination, sucrase determination, and identification of neonatal intestinal Fc receptor (FcRn) by Western blot. Serum immunoreactive BSA (iBSA) and mouse IgG1 and IgG2a anti-OVA antibodies were estimated by enzyme-linked immunosorbent assay. Sucrase activity was elevated in cortisone- and spermidine-treated compared to control rats. iBSA and anti-OVA were significantly reduced in cortisone-treated compared to control rats but were not diminished significantly in the spermidine-treated animals. A decrease in the neonatal intestinal Fc receptor was apparent in the spermidine-fed group; cortisone produced a large reduction in FcRn. Spermidine-fed animals showed morphologic evidence of maturation, with loss of giant vacuoles in the distal intestine; cortisone did not produce significant changes in morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics and mechanism of action of a heat-stable enterotoxin produced by Klebsiella pneumoniae from infants with secretory diarrhea.

Escherichia coli heat-stable enterotoxins (ST) are classified into STa and STb according to their physicochemical and biologic characteristics. STa induces diarrhea, activating the guanylate cyclase-cGMP system. ST-like enterotoxins can be produced by bacteria other than E. coli, including Klebsiella pneumoniae. A Klebsiella ST has previously been shown to share some chemical and immunologic characteristics with E. coli ST. Aiming to define better the nature of Klebsiella ST, we have screened 237 children with diarrhea and 179 controls for ST-producing Klebsiella, using the SMA. We detected 26 Klebsiella strains from patients, two of which were positive in the SMA, and 36 from controls, all negative for ST. A partial purification was performed using an acetone precipitation followed by ultrafiltration and gel filtration techniques. Klebsiella toxin was heat-stable, methanol-soluble, sensitive to mercaptoethanol, active at acid pH values, but not at pH greater than 8. The time course of Klebsiella toxin in the SMA resembled that of E. coli STa. Klebsiella ST caused reduced Na absorption and net Cl secretion in rabbit ileal mucosa mounted in Ussing chambers. It was found to increase the cGMP but not the cAMP concentration. Finally, Klebsiella ST did not react with anti-E. coli STa MAb in a competitive ELISA. We conclude that K. pneumoniae may induce diarrhea through the production of an STa similar but not identical to E. coli STa.

Polyamines in human and rat milk influence intestinal cell growth in vitro.

BACKGROUND: Polyamines are required for intestinal growth and development. In this study, we examined whether milk can supply the polyamines needed for growth of IEC-6 cells, a line on non-transformed rat intestinal crypt cells. METHODS: Human, bovine, and rat milk, and cow's milk-based infant formula were studied. Human, bovine, and rat milk were defatted and sterilized by filtration. IEC-6 cells were stabilized in Dulbecco's modified Eagle's medium (DMEM) containing 0.5% fetal bovine serum, 5 mM L-glutamine, 100 U/mL penicillin and 100 microg/mL streptomycin for 24 h at 37 degrees C. Thereafter, to initiate active growth, cells were placed in fresh DMEM containing 5% FBS (plus the other ingredients) supplemented with 5% (vol/vol) milk or infant formula. In some experiments, cells were also treated with difluoromethylornithine (2.5 mM) (DFMO), an inhibitor of polyamine synthesis, or dialyzed milk plus DFMO. After 44 hours of culture, cells were pulsed with 3H-thymidine (3H-TdR) for 4 hours, harvested and the radioactivity incorporated into DNA was measured. RESULTS: Human and rat milk stimulated proliferation of IEC-6 cells (p < 0.05 compared to controls); addition of DFMO did not reverse the stimulatory effect. Bovine milk and the infant formula did not stimulate proliferation or prevent the growth inhibition induced by DFMO. After dialysis, human milk had less ability to reverse the DFMO inhibition (p < 0.05). CONCLUSIONS: These experiments suggest that both human and rat milk, but neither bovine milk nor the infant formula, contain sufficient bioactive polyamines to sustain cell growth during inhibition of polyamine synthesis.

Etiology and risk factors of severe and protracted diarrhea.

Severe and protracted diarrhea (SPD) is the most severe form of diarrhea in infancy and has also been defined as intractable diarrhea. Its etiology is poorly defined. We have retrospectively evaluated the etiology, the outcome, and the risk factors of 38 children, admitted with protracted diarrhea and need for total parenteral nutrition (TPN) from 1977 to 1993. Children with anatomic abnormalities and/or primary immunodeficiency were excluded. There was an inverse relationship between the number of patients and the age of diarrheal onset (mean age, 2.9 +/- 3.5 months). Etiology of SPD was an enteric infection in 18 cases (eight Salmonella, three Staphylococcus, five rotavirus, one adenovirus, one Cryptosporidium), multiple alimentary intolerance (eight cases), familial microvillous atrophy (two), autoimmune enteropathy (two), celiac disease, lymphangectasia, eosinophilic enteropathy, intestinal pseudoobstruction, and intestinal neurodysplasia (1 case each). Etiology was not detected in three cases. Overall, 12 children died, five are presently being treated, and 21 had full remission. Comparative evaluation of risk factors between children with SPD and a control population of children with diarrhea but without the need for TPN showed that low birth weight, no breast feeding, history of fatal diarrhea in a relative, and early onset of diarrhea had a significantly higher incidence in the former. Social background was similar in the two populations. We conclude that a specific etiology can be identified in the majority of cases of SPD. The etiologic spectrum of SPD is broad, but an enteric infection is the most common cause of SPD. The severity of this condition is related, at least in part, to established risk factors.

Sigmoidoscopy, colonoscopy, and radiology in the evaluation of children with rectal bleeding.

The authors evaluated the diagnostic role of sigmoidoscopy, colonoscopy, and double contrast radiology in 103 children with rectal bleeding, with or without other gastrointestinal symptoms. The children's mean age was 44 months, with a range from 1 month to 12 years. In 74.5% of the subjects investigated, visual inspection of the anus and sigmoidoscopy with rectal biopsy disclosed a positive diagnosis. Of the remaining patients, a conclusive diagnosis was reached by either colonoscopy or double contrast radiology in all but six patients. These six, with mild painless hematochezia, remained without a diagnosis. The diagnostic procedure in pediatric patients with rectal bleeding should include an initial visual inspection of the anus, and sigmoidoscopy; air contrast enema and colonoscopy should be performed only in children whose sigmoidoscopy is negative, in diagnostic assessment of inflammatory bowel disease, and in cases of recurrent bleeding after removal of rectal polyps. Colonoscopy is important also in the follow-up examination of children with inflammatory bowel disease and allows the removal of polyps located in the proximal colon.

Enteric infections, cow's milk intolerance and parenteral infections in 118 consecutive cases of acute diarrhoea in children.

One hundred and eighteen consecutive cases of childhood acute diarrhoea (mean age: 10.5 months) were studied after admission to our Pediatric Unit in Naples over a 13-month period. A diagnosis was established in 92 patients (78%): 55% of patients were found to have an infectious enteritis (among them, 5 had ETEC infections and 1 had an ST-producing Klebsiella infection), 12% a parenteral infection, 11% cow's milk intolerance. The occurrence of gross blood (P less than 0.01), leukocytes, and reducing substances in the stools was more commonly associated with infectious enteritis than with diarrhoea due to all other causes. In 14 patients (8 of whom were malnourished), diarrhoea ran a prolonged course. In all, the eventual outcome was favourable. Our findings, while confirming that infectious enteritides account for most of acute diarrhoeas in children, stress the importance of parenteral infections and cow's milk intolerance in this condition. Also, the need for an accurate search for enterotoxigenicity of enterobacteria before ruling out their pathogenetic role is stressed.