Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study.

BACKGROUND: Congenital diaphragmatic hernia (CDH) accounts for 8% of all major congenital anomalies. Neonates who are small for gestational age (SGA) generally have a poorer prognosis. We sought to identify risk factors and variables associated with outcomes in neonates with CDH who are SGA in comparison to neonates who are appropriate for gestational age (AGA). METHODS: We used the multicenter Diaphragmatic Hernia Research & Exploration Advancing Molecular Science (DHREAMS) study to include neonates enrolled from 2005 to 2019. Chi-squared or Fisher's exact tests were used to compare categorical variables and t tests or Wilcoxon rank sum for continuous variables. Cox model analyzed time to event outcomes and logistic regression analyzed binary outcomes. RESULTS: 589 neonates were examined. Ninety were SGA (15.3%). SGA patients were more likely to be female (p = 0.003), have a left sided CDH (p = 0.05), have additional congenital anomalies and be diagnosed with a genetic syndrome (p < 0.001). On initial single-variable analysis, SGA correlated with higher frequency of death prior to discharge (p < 0.001) and supplemental oxygen requirement at 28 days (p = 0.005). Twice as many SGA patients died before repair (12.2% vs 6.4%, p = 0.04). Using unadjusted Cox model, the risk of death prior to discharge among SGA patients was 1.57 times the risk for AGA patients (p = 0.029). There was no correlation between SGA and need for ECMO, pulmonary hypertensive medication at discharge or oxygen at discharge. After adjusting for confounding variables, SGA no longer correlated with mortality prior to discharge or incidence of unrepaired defects but remained significant for oxygen requirement at 28 days (p = 0.03). CONCLUSION: Infants with CDH who are SGA have worse survival and poorer lung function than AGA infants. However, the outcome of SGA neonates is impacted by other factors including gestational age, genetic syndromes, and particularly congenital anomalies that contribute heavily to their poorer prognosis.

Dissociative electron attachment to 2,4,6-trichloroanisole and 2,4,6-tribromoanisole molecules.

2,4,6-trichloroanisole and 2,4,6-tribromoanisole were investigated by means of electron transmission spectroscopy and two different types of dissociative electron attachment spectrometers. The results obtained were interpreted with the support of density functional theory calculations. The dominant dissociative decay channels of the temporary molecular negative ions lead to the formation of Cl- and Br- in the low electron energy region. Formation of long-lived parent anions is observed at thermal electron energies. Their relative intensity depends on the experimental time window, ∼36 µs in the case of the static magnet mass analyzer and ∼200 µs for the quadrupole mass analyzer employed. The results obtained may be useful for rapid detection of these compounds in wine and pharmaceutical industries, as well as other branches connected to the food industry, e.g., packaging.

Spectral properties of ionic benzotristhiazole based donor-acceptor NLO-phores in polymer matrices and their one- and two-photon cellular imaging ability.

A series of ionic benzotristhiazolium (BTT) push-pull chromophores, with different nitrogen donor groups and different lengths of conjugated bridges, was successfully doped in polar polymer matrices (PVC and PSS). The spectral (photophysical) properties of their low concentration thin polymeric films are compared with those in solution and are discussed in terms of matrix polarity/viscosity influence, specific polymer-chromophore interaction, structure-spectral property relationship and Twisted Intramolecular Charge-Transfer (TICT) state formation. The elimination of a non-emissive phantom and TICT state formation by restricted intramolecular rotations in the polymer matrix or viscous solvent results in a relatively high ΦF of all the investigated NLO-phores; particularly for near-infrared NIR molecular rotors bearing diphenylamino and julolidine donor groups. Because of cationic characteristics, small molecular weight, calculated high second hyperpolarizability and significant emission efficiency dependence on surroundings' viscosity (rigidochromic effect), two dyes were chosen as candidates for potential fluorescent probes for one-photon (1P) and two photon (2P) cellular imaging. The selected BTT NLO-phore with a julolidine donor is promising as a mitochondria-specific fluorescent small molecular probe for live cell super-resolution imaging with low cytotoxicity and good photostability, and is also potentially suitable for super-resolution STED imaging.

Parenteral nutrition in childhood and consequences for dentition and gingivae.

AIM: Assessment of dentition in children under parenteral nutrition, risk factors for caries, and dental developmental abnormalities. MATERIALS AND METHODS: The study involved 63 patients (aged 2.25-16.6 years), i.e. 32 subjects receiving parenteral nutrition for a mean period of 5.6±2.94 years, and 31 healthy control subjects. Oral hygiene (OHI-S, PL-I), gingival (GI), and dentition status (caries, DMFT/dmft, enamel defects, shape alterations), frequency of oral meals and frequency of cariogenic snacks consumption were evaluated. Medical records provided information on parenteral meals per week, age parenteral nutrition started, birth body mass, Apgar score, weight deficiency, and antibiotic therapy until aged 1 year. The Mann-Whitney test, chi-squared test, and Spearman rank correlation coefficient were used (p≤0.05). RESULTS: Dental developmental abnormalities occurred more often in PN subjects (71.87% vs. 25.80%). The prevalence of caries in PN (56.25% vs. 90.32%) and dmft (2.00±3.30 vs. 4.21±3.33) and DMFT (2.47±4.08 vs. 3.33±3.50) were lower. Positive caries Spearman's rank correlation coefficients: frequency of oral meals and frequency of cariogenic snacks consumption, and GI. Negative correlation coefficients: low birth body mass, antibiotic therapy, and low body mass in the first year of life. Positive dental developmental abnormality Spearman's coefficients: low birth body mass, Apgar score < 7, parenteral nutrition duration, low body mass and antibiotic therapy in the first year of life. Beta- lactam, aminoglycoside, glycopeptide and nitroimidazole treatments were related to enamel hypoplasia. CONCLUSION: Parenteral nutrition in childhood is related to the risk of dental developmental abnormalities, promoted by malnutrition and antibiotic therapy in infancy. Limiting the number of meals and cariogenic snacks, and most probably administration of antibiotics, decreases the risk of caries.

Mechanochemically activated doxorubicin nanoparticles in combination with 40 MHz frequency irradiation on A-549 lung carcinoma cells.

Targeting of mechanochemically activated doxorubicin (MA DOXO) nanoparticles, conventional doxorubicin, and electromagnetic irradiation (EMI) at A-549 lung carcinoma cells in vitro was investigated. Conventional DOXO was micronized using an input energy of 20 W/g for 5 min resulting in positively charged MA DOXO particles 10 times smaller than conventional DOXO. Mechanochemical activation gives rise to additional free quinone radicals. High performance liquid chromatograph analyses demonstrate that conventional and MA DOXO are quantitatively similar. Tumor cells were exposed to 40 MHz electromagnetic irradiation at a power density of 2 W/cm2. The lethal dose LD50 values of MA DOXO were 5 times greater than conventional doxorubicin. MA DOXO in combination with EMI at 37 degrees C demonstrates improved drug delivery to A-549 human lung carcinoma and greater cell kill than does conventional DOXO.

Can optimal resource allocation models explain why ectotherms grow larger in cold?

Basically all organisms can be classified as determinate growers if their growth stops or almost stops at maturation, or indeterminate growers if growth is still intense after maturation. Adult size for determinate growers is relatively well defined, whereas in indeterminate growers usually two measures are used: size at maturation and asymptotic size. The latter term is in fact not a direct measure but a parameter of a specific growth equation, most often Bertalanffy's growth curve. At a given food level, the growth rate in determinate growers depends under given food level on physiological constraints as well as on investments in repair and other mechanisms that improve future survival. The growth rate in indeterminate growers consists of two phases: juvenile and adult. The mechanisms determining the juvenile growth rate are similar to those in determinate growers, whereas allocation to reproduction (dependent on external mortality rate) seems to be the main factor limiting adult growth. Optimal resource allocation models can explain the temperature-size rule (stating that usually ectotherms grow slower in cold but attain larger size) if the exponents of functions describing the size-dependence of the resource acquisition and metabolic rates change with temperature or mortality increases with temperature. Emerging data support both assumptions. The results obtained with the aid of optimization models represent just a rule and not a law: it is possible to find the ranges of production parameters and mortality rates for which the temperature-size rule does not hold.

Effects of mechanochemically activated doxorubicin and 40 MHz frequency irradiation on human A-549 lung carcinoma cells.

AIM: To study in vitro influence of mechanochemically activated (MA) doxorubicin (DOXO) and electromagnetic irradiation (EMI) on human lung carcinoma A-549 cells. METHODS: Solid state DOXO was MA by input energy 20 W/g during 5 min. Tumor cells were exposed to 40 MHz EMI with power density 2 W/cm(2) at temperature 37 degrees C. RESULTS: Particles of MA DOXO have sizes 10 time smaller than officinal DOXO, high performance liquid chromatography analysis showed that parameters of officinal and MA DOXO were quantitatively equal. Mechanochemical activation initiated in the drug formation of free radicals with g = 2.005, g = 2.003 and g = 1.97. LD(50) values of MA DOXO were 5 times lower than that of officinal drug. Cell survival decreased in the following way after effects EMI --> officinal DOXO --> MA DOXO --> officinal DOXO + EMI --> MA DOXO + EMI. CONCLUSION: Treatment by MA DOXO and drug with EMI at 37 degrees C showed better targeting of drug in human lung carcinoma A-549 cells outcomes than officinal DOXO.

Mechanoluminescence: lymphocyte analysis after exposure to ionizing radiation.

Lymphocyte mechanoluminescence (ML) develops as a result of mechanochemical activation of cells. This paper describes devices (tribogenerators) and techniques for lymphocyte mechanoluminescence analysis. At different stages of the cellular cycle the ML of non-irradiated peripheral blood lymphocytes (PBL) showed characteristic differences. After (60)Co gamma -irradiation of PBL in vitro at 0.25 Gy and 1 Gy an alteration of ML was observed with a relationship between ML values of lymphocytes, and also of mitochondria (MT), and the dose of ionizing radiation used. By using bioluminescence techniques it was shown that gamma-irradiation reduces the amount of ATP synthesized by PBL in the stationary phase.

[The effect of gamma irradiation on lymphocyte mechanical emission in rats at different stages of the cell cycle]. / Vliianie gamma-oblucheniia ba mekhanoémissiiu limfotsitov krys v razkykh stadiiakh kletochnogo tsikla.

Mechanoemission (ME) of rat peripheral blood lymphocytes (PBL) over the radio-frequency range has characteristic peculiarities in various stages of the cell cycle, both in unirradiated cells and in cells exposed to 0.25 or 1 Gy of gamma radiation. After 52 h incubation of irradiated and unirradiated lymphocytes, ME PBL indices take values equivalent to initial ones in the G0 phase. Increase of radiation dose from 0.25 to 1 Gy was followed by a decrease of the value of the ME PBL kinetic parameter after 24, 40 and maximum 48 h incubation.

Nonlinear relationship between V+max and h infinity in frog skeletal muscle.

The relationship between the maximum velocity of action potential upstroke (V+max) and steady-state Na+ channel inactivation (h infinity) was studied in frog skeletal muscle during repetitive discharges evoked in the presence of cevadine (1 mumol/l). Conventional microelectrodes and vaseline-gap voltage-clamp techniques were used. A severe degree of nonlinearity was found between (h infinity) and (V+max) especially when the Na+ conductance (gNa) was small. The observed nonlinearity could be explained as a property of the normal Na+ channel gating in skeletal muscle rather than that of cevadine-modified channels. Part of this work has been published in abstract form in Biophys. J. 57: 105A, 1990.

Repetitive electrical activity of the muscle membrane induced in chloride-free medium.

1. Superficial fibres of frog skeletal muscle were electrically stimulated in Ringer solution where the chloride content had been replaced by various weakly permeant anions. Changes of the membrane potential were recorded at three different time scales. The complex response was initiated by a volley of fast repetitive action potentials (10-20 ms cycle length) superimposed on the ascending phase of a transient depolarization to -35 mV. The transient depolarization was followed by a membrane potential oscillation (0.3-0.6 s cycle length). The parameters of the volley and membrane potential oscillation were not greatly affected by the substituent anion. 2. The transient depolarization was fully abolished by tetrodotoxin (3 mumol/L), but left unaffected by nifedipine (5 mumol/L), or by the replacement of extracellular Ca for Ni or Co. Tetraethylammonium (20-40 mmol/L) increased the duration and amplitude of the transient depolarization. The shape of transient depolarization was uniform in a given fibre, in spite of its marked variability under different experimental conditions. 3. Single outward current pulses applied in chloride-free solution containing tetraethylammonium (20-40 mmol/L) evoked prolonged depolarizations to positive membrane potentials accompanied by increases in the specific membrane conductance. This slow response, which was also frequently observed in the absence of TEA, was mediated by Ca ions, as it was insensitive to tetrodotoxin (3 mumol/L) but abolished by nifedipine (10 mumol/L). 4. Two populations of the muscle fibres were observed during the slow response. Some fibres repolarized completely, while others failed to produce complete repolarization but formed a plateau between -20 and -30 mV, lasting for several minutes. When the external K concentration was abruptly increased to 5 or 10 mmol/L during the plateau of the slow response, repolarization and increase in membrane conductance were observed. 5. In muscle fibres, having osmotically disrupted T-system, the duration of transient depolarization was in the range of minutes, in contrast to the range of seconds observed in intact fibres. The volley was preserved in glycerol treated fibres, however, the baseline of discharges was close to the resting potential and the rate of depolarization of the baseline was significantly less in glycerol treated than in intact fibres. 6. These results are consistent with the existence of a second stable membrane potential level in skeletal muscle between -40 and -30 mV. The depolarization and repolarization during the membrane potential oscillation and transient depolarization can be regarded as a partial or full transition, respectively, between these two stable membrane potential levels, possibly due to the conductance changes of the inward rectifier K channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Slow membrane potential changes in skeletal muscle induced in Cl(-)-free medium.

1. Conventional microelectrode techniques were used to measure simultaneous changes in membrane potential (Vm) and conductance (Gm) induced by single electrical stimuli in muscles bathed in Cl(-)-free solution containing 40 mM of tetraethylammonium (TEA+). 2. Stimulation induced slow transient depolarizations (slow response) accompanied by increased calcium conductance, while the potassium conductance was first elevated and later reduced. 3. Stepwise elevation of [K+]0 from 2.5 to 5 or 10 mM during the slow response evoked an abrupt repolarization of 42.3 +/- 8.9 mV (n = 4; p less than 0.001), and 24.8 +/- 3.5 +/- mV (n = 5; p less than 0.001), respectively, while Gm was increased to 1.45 +/- 0.25-fold (n = 5; p less than 0.05). Neither the slow response nor K(+)-induced changes in Vm or Gm were sensitive to tetrodotoxin (3 microM), however, nifedipine (10 microM) abolised the slow response. 4. It was concluded that beyond the increase of calcium conductance, the ionic conductance of the inward rectifier K+ channel was reduced during the slow response, which could be restored by the elevation of [K+]0. The results suggest the possible contribution of these mechanisms to the electrical instability of myotonic muscles. Potential therapeutic consequences are discussed.

Different actions of aconitine and veratrum alkaloids on frog skeletal muscle.

1. The electrophysiological effects of veratridine, cevadine and aconitine (10(-8)-2 x 10(-4), 2 x 10(-7)-2 x 10(-6) and 2 x 10(-6)-10(-4) mol/l, respectively) were compared on frog muscle membrane using conventional microelectrodes. 2. Veratridine and aconitine were equally effective in depolarizing the resting membrane with the threshold concentration of 5 x 10(-5) mol/l. 3. Volleys of repetitive discharges and slow transient depolarizations were observed when single electrical stimuli were applied in the presence of veratridine (5 x 10(-8)-2 x 10(-5) mol/l), but not aconitine. Volleys with aconitine could be evoked only by repetitive stimulation; however no tendency of repolarization was observed following these volleys. Two orders of magnitude more aconitine than veratridine was required to induce volleys with similar parameters. 4. The effects of cevadine were similar to those of the corresponding concentrations of veratridine. 5. The observed differences between the electrophysiological actions of aconitine and veratrum alkaloids may be explained in part with differences in Na+ channel inactivation produced by these toxins, in addition to differences in their use-dependent behavior.

Use-dependent action of antiarrhythmic drugs in frog skeletal muscle and canine cardiac Purkinje fiber.

1. Conventional microelectrode techniques were used to study the effect of quinidine (10 microM), lidocaine (20 microM), and verapamil (3-10 microM) on action potential upstroke (V+ max) in frog skeletal muscle and dog Purkinje fiber. 2. The frequency-dependent nature of V+ max depression induced by these drugs was similar in both preparations, however, quinidine was more potent in skeletal muscle while lidocaine was in Purkinje fibers. 3. In skeletal muscle tetrodotoxin (3 and 15 nM) and low concentrations of antiarrhythmic drugs proportionally reduced the maximum velocity of depolarization and repolarization (V+ max and V- max, respectively), whereas V- max was more depressed than V+ max by high concentrations (50-200 microM) of antiarrhythmics. Decreases in the overshoot potential were proportional to the V+ max block in the case of each drug. 4. These results indicate that therapeutically relevant concentrations of quinidine and lidocaine inhibit skeletal muscle Na+ channels in a use-dependent manner similar to heart, while at higher concentrations the K+ channels may also be blocked. Therapeutic implications of the results are discussed.

Effect of antiarrhythmic drugs, TTX, and 4-aminopyridine on repetitive electrical activity in frog skeletal muscle.

1. Conventional microelectrode techniques were used to study the effects of antiarrhythmic drugs (quinidine, 2-20 microM; lidocaine, 5-50 microM; verapamil, 2-20 microM), 4-aminopyridine (4-AP, 50-100 microM), and tetrodotoxin (TTX, 1.5-6 nM) on repetitive electrical discharges induced in the muscle membrane in the presence of 1 microM cevadine. 2. Antiarrhythmic drugs and 4-AP produced progressive reduction of the maximum upstroke velocity (V+ max) of the discharges, while the cycle length was prolonged by each drug except 4-AP. 3. The efficacy in depression of V+ max and prolongation of cycle length was not proportional in the case of individual drugs. 4. A simple model of the repetitive activity incorporating drug-effects was presented. The cevadine-modified Na+ channels could be blocked by antiarrhythmic agents, however, the efficacy of these drugs on the normal and cevadine-modified Na+ channels were found to be different.

Effects of bencyclane on normal and cevadine-modified Na channels in frog skeletal muscle.

The effect of 10(-5) mol/l bencyclane on the repetitive electrical activity of muscle membrane was studied with the conventional microelectrode technique. Electrical activity was induced by repetitive stimulation in normal Ringer solution (train) or by a single depolarizing current pulse in the presence of 10(-6) mol/l cevadine (volley). Bencyclane decreased, in a use-dependent manner, the maximum rates of depolarization and repolarization (Vmax+ and Vmax-, resp.) of the action potentials both of the train and the volley. The inhibition of Vmax+ and Vmax- was proportional; however, it was stronger for the volleys than for the trains. The cycle length (mean interspike interval) of the volley was increased by bencyclane; the prolongation was progressive during consecutive cycles. The dissociation of bencyclane from the Na channel was studied by applying trains of different durations with equal pulse numbers. Bencyclane at a higher concentration (5 x 10(-5) mol/l) caused a reversible tonic block: the overshoot potentials, Vmax+ and Vmax- were markedly reduced. The reduction of Vmax- was slightly stronger than that of Vmax+. Slow membrane potential oscillation (SMPO) was evoked by treating the muscle with 10(-4) mol/l of cevadine. The administration of 5 x 10(-6) mol/l bencyclane decreased the frequency of SMPO, while 10(-5) mol/l bencyclane terminated the slow oscillation activity without changing its baseline potential. The present results indicate that bencyclane induces use-dependent inhibition of Na channels in muscle, similarly as do class 1 antiarrhytnmic drugs. Inhibition was observed with both normal and cevadine-modified Na channels.

[Serum ferritin, its clinical significance and our personal experience]. / Sérový feritín, jeho klinický význam a nase skúsenosti.

The paper presents a survey of the information on serum ferritin and its clinical value along with the authors' own experience.

Paradox response of frog muscle membrane to changes in external potassium.

Applying conventional microelectrode technique the anomalous behaviour of membrane potential in response to changes in [K+]o was demonstrated in normal and cevadine-treated muscles bathed in Cl- -free medium. Partial repolarization of the cevadine-depolarized membrane and reappearance of the slow membrane potential oscillation (SMPO) were induced by elevating [K+]o from 2.5 mM to 10-20 mM. Both effects were reversed by return to 2.5 mM [K+]o. The K-induced repolarization was markedly reduced by 20 mM Cs+, but not by 0.1 mM ouabain, 1 mM 4-aminopyridine, or 1 mM diethyl-pyrocarbonate. The elevation of [K+]o failed to repolarize muscle fibers that had been depolarized only to a small extent. No K-induced repolarization has been observed in Cl- -containing fluid. In cevadine-free experiments the omission of potassium from the extracellular space in Cl- -free solution hyperpolarized some of the fibers, while depolarized others. Strong electrical stimuli applied in zero K-zero Cl solution turned all the fibers into depolarized state; on returning to 2.5 mM [K+]o complete repolarization was achieved in most of the fibers. It has been concluded that the paradox response of the muscle membrane to changes in [K+]o can be attributed to the K-dependent conductance changes of the inward rectifier K channel providing an explanation for the plateau-formation of SMPO and for the existence of two stable levels of membrane potential of the skeletal muscle bathed in Cl- -free medium.

[Structural dynamic properties of the cell membranes of Ehrlich ascites tumor associated with a polyamine deficiency caused by DL-difluoromethylornithine]. / Strukturno-dinamicheskie svoistva membran kletok astsitnogo raka Erhlikha pri defitsite poliaminov, vyzvannom DL-diftormetilornitinom.

The blocking of polyamine synthesis in cancer cell by a specific inhibitor (DFMO) results in an increase in membrane viscosity and in significant changes in cell deformability as determined by cell penetration through a nuclear filter with given porosity. Almost two-fold reduction of the penetration rate through the filter pores was registered for the DFMO-treated cells in spite of the fact that the cell size decreases after such a treatment. The number of cells penetrating through the filter after DFMO treatment is diminished due to an increasing resistance to penetration. The addition of putrescine to the incubation medium at physiological concentration restores all these parameters to the initial values. The possible association of these changes with differential sensitivity of cancer cells towards the inhibitor action depending on the stage of cell cycles is discussed.

[Effect of preparations of unsaturated fatty acids on the lipid component of the endoplasmic reticulum membranes of liver cells in rats following administration of N-nitrosodiethylamine]. / Vliianie preparatov nenasyshchennykh zhirnykh kislot na lipidnyi komponent membran éndoplazmaticheskogo retikuluma kletok pecheni krys pri vvedenii N-nitrozodiétilamina.

The effect of drugs, including unsaturated fatty acids and antioxidants, on the lipid composition of the endoplasmic reticulum membranes was studied at early stages of NDEA-induced hepatocarcinogenesis. The complexes containing oleic, linoleic, and arachidonic acids and biological antioxidants prevent changes in the fatty acid composition and the lipid bilayer organization of the both membrane fractions of endoplasmic reticulum which are observed after the injection of NDEA alone, and they inhibit the appearance and growth in the liver of gamma-glutamyltranspeptidase positive hyperplastic nodules.