Nitrogen and fat balances in very low birth weight infants fed human milk fortified with human milk or bovine milk protein

The study was designed to compare two different human milk fortifiers in a group of very low birth weight (VLBW) infants by analysing nitrogen and fat balances, serum concentrations of alpha-amino-nitrogen, urea, and prealbumin as well as growth rates when human milk enriched with one of the two studied fortifiers was fed to the infants. Fortifier A contained different bovine proteins, peptides and amino acids and had an amino acid composition comparable to that of the nutritional available proteins in human milk, with carbohydrates, and minerals. Fortifier B was composed of freeze-dried skimmed human milk and minerals to achieve a similar macronutrient composition in both fortifiers. Eleven infants were fed with human milk enriched with fortifier A and 13 with fortifier B. After a 10-day equilibration period, a 3-day metabolic balance was performed. On the 14th day of the study blood was obtained preprandially for serum analysis and growth rates were estimated. The nitrogen absorption rate (93.8% vs 93.5%) as well as the retention rate (80.8% vs 78.5%) were no different between the groups. The fat absorption rate (92.3% vs 91.5%) as well as the weight gain (32.1 vs 31.1 g/day) were similar and there were no differences in the serum parameters studied. The results indicate that feeding VLBW infants with human milk enriched with a well-balanced bovine fortifier fulfil their nutritional requirements as well as diets composed exclusively of human milk protein.     

Nitrogen utilization in pigs fed diets with soybean and rapeseed products leading to different ileal endogenous nitrogen losses

Nitrogen (N) balance was determined in 36 pigs (BW 24 to 30 kg) fed diets inducing different ileal endogenous N losses (ENL). We tested the hypothesis that enhanced ENL may be indicative of a higher recycling of endogenous proteins that will induce a greater urinary N loss and a lower efficiency of the dietary N utilization for retention. The cornstarch-based diets contained either soy concentrate (SC), soybean meal (SBM), a mixture of toasted and untoasted soybean meal (mSBM), dehulled-toasted rapeseed cake (RC1), non-dehulled-toasted rapeseed cake (RC2), or dehulled-untoasted rapeseed cake (RC3). The diets were balanced for their content of apparent ileal digestible (ID) CP (108 g/kg feed) and apparent ID of Lys, Thr, Met+Cys, Trp, and Ile. Feeding level was 2.7 times ME for maintenance per kilogram BWx75 and restricted to 88% of the requirements for ID Lys as the first-limiting amino acid. During a 5-d period, urine and feces were collected daily in metabolism cages. Compared with the SC diet (low ENL), the diets with SBM (medium ENL) and mSBM (high ENL) resulted in a greater (P < .05) urinary N excretion. Nitrogen retention tended to be less (P = .08) in pigs fed diets that caused greater ENL. The utilization of ID N for retention in pigs fed the mSBM diet was lower (P < .05) than for those fed the SC diet. There were no differences in urinary N excretion, N retention, and the utilization of ID N for retention in pigs fed the rapeseed diets of different fiber contents (hulls as the NDF source). We concluded that, at similar intakes of the first-limiting ID amino acid, N retention in pigs fed soybeans tended to be reduced by greater ENL as induced by antinutritional factors (e.g., trypsin inhibitors). Rapeseed hulls, as the predominant fiber source, do not affect N retention and the utilization of ID N for retention.     

Pharmacokinetics of antipyrine in calves at neonatal period fed with casein supplemented food

The purpose of the studies was to evaluate (on the basis of pharmacokinetics of antipyrine) hepatic biotransformation rate in calves in neonatal period, which received supplementary casein dose in their food. It was found that 25% increase in protein content in food ration of the examined animals significantly increased hepatic biotransformation rate (activity of monooxygenases dependent on cytochrome P-450). The results obtained also indicate that a protein-rich diet may significantly increase metabolism of other xenobiotics in MFO-P-450 enzymatic system, provided that they undergo the same biotransformation process as antipyrine.     

Comparison of the kinetics of pancreatic secretion and gut regulatory peptides in the plasma of preruminant calves fed milk or soybean protein

Exocrine secretion from the pancreas and concentrations of cholecystokinin, gastrin, secretin, and somatostatin in plasma were measured in relation to feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a soybean diet. Pancreatic fluid was continuously collected, measured, and reintroduced in catheterized calves. Blood samples were withdrawn for measurements of gut regulatory peptide concentrations in plasma. A slight increase in outflow of pancreatic fluid was observed 30 min before the milk diet was introduced but not before the soybean diet was fed. In contrast, concentrations and outflows of protein and trypsin immediately after feeding were higher when calves were fed the soybean diet. Overall, during the first 5 h postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet was fed than when the soybean diet was fed. No difference in outflow of protein was observed, but that of trypsin was 82% higher when the soybean diet was fed. This enhanced enzyme secretion could have been related to the increased plasma concentrations of gastrin and cholecystokinin after the soybean diet was fed. Secretin release was less in calves fed the milk diet that in calves fed the soybean diet during the first 2 h postfeeding, suggesting that this gut peptide along with gastrin and cholecystokinin, contributed to the stimulation of enzyme secretion. Plasma gut regulatory peptides could be influenced by the soybean diet, which does not coagulate in the stomach, inducing faster gastric emptying of protein and fat, and by the chemical form of protein from the soybean diet and the lower susceptibility of these proteins to protease compared with casein. However, the resulting enhancement of pancreatic trypsin secretion and activity seemed to be insufficient to increase the digestibility of soybean protein up to a level similar to that of milk.     

Responses of laying hens to a low-protein diet supplemented with essential amino acids, L-glutamic acid and/or intact protein

1. Three sequential experiments, each lasting 8 weeks, were carried out on 576 singly-caged light hybrids. 2. In experiment 1 egg production was 84% using a conventional control diet, 61% with a basal low-protein diet, and 79% with the basal diet supplemented with 10 essential amino acids+L-glutamic acid (GA). 3. In experiment 2 supplementation with lysine and methionine (L+M) alone increased egg production significantly from 54 to 72%, compared with 83% with the conventional diet. 4. In experiment 3 egg production was 55% with the basal diet, 71% with the basal diet+L+M, 75% with a diet containing 141 g protein/kg+L+M, and 73% with the conventional diet. 5. In all three experiments supplementation with GA alone either gave no significant response or a depression in production. 6. Daily intakes of 1-24 g nitrogen as non-essential amino acids and 13 to 14 g total crude protein per bird resulted in good egg production. Supplementation of the basal diet with L+M resulted in a daily intake of 413 mg methionine/bird day which was considered adequate, and a daily intake of 710 mg lysine which was considered slightly inadequate.     

Food intake is inversely correlated with central nervous system histamine receptor (H1) concentrations in male Sprague-Dawley rats fed normal, low protein, low energy or poor quality protein diets

The reported studies were designed to examine relationships between whole-brain histamine receptors (H1) and food intake in male Sprague-Dawley rats. Three different experiments were conducted. In each experiment, control rats were fed normal protein (25 g casein/100 g food) and normal metabolizable energy (16.21 kJ/100 g food) diets. Feeding low protein diets (1 g casein/100 g food) elevated central H1 receptor concentrations (P < 0.0027) and reduced voluntary food intake (P < 0.007) compared with normal diets. Feeding low energy diets lowered H1 receptor concentrations (P < 0.0089) and increased voluntary food intake (P < 0.0012). Low quality protein diets also affected the central nervous histaminergic system. Whole-brain H1 receptor concentrations were significantly higher for rats fed low quality protein (25 g gelatin/100 g food) compared with rats fed casein (P < 0.0001). Rats fed medium quality protein (25 g wheat gluten/100 g food) or low quality protein ate significantly less food (P < 0.0001). In all experiments, dietary manipulation affected central histamine receptors. Elevated concentrations of H1 receptors were associated with a decrease in food intake whereas lowered concentrations of H1 receptors were associated with an increase in food intake (P < 0.001). The results of these experiments support the hypothesis that central histamine H1 receptor concentrations in male rats are inversely correlated with voluntary food intake and affected by dietary composition.     

Energy metabolism and protein balance in growing rats housed in 18 degree C or 28 degree C environments and fed different levels of dietary protein

A study was performed to investigate the effect of environmental temperature and increasing levels of protein in the diet on visceral organ size, digestibility, protein balance and energy metabolism in rats. Thirty-six male Wistar rats, initial body weight 77-80 g, were used in a factorial design consisting of three levels of dietary protein and two environmental temperatures of either 18 or 28 degrees C. Three fish meal-based diets were prepared to contain 91, 171 and 262 g protein (N X 6.25/kg diet). Gas-exchange measurements were made and urine and feces were quantitatively collected. The weights of the visceral organs from rats housed at 18 degrees C were greater (P < 0.05) than those of rats housed at 28 degrees C. The digestibilities of dry matter and protein were not affected by environmental temperature, whereas fat and energy digestibilities were higher (P < 0.05) at 18 degrees C than at 28 degrees C. As the level of protein was increased, the digestibilities of protein, energy and fat increased (P < 0.05). Protein intake and protein retention were higher at 18 degrees C (P < 0.05) than at 28 degrees C and increased (P < 0.05) as dietary protein concentration increased. Apparent biological value was lower (P < 0.05) at 18 degrees C than at 28 degrees C and decreased (P < 0.05) as dietary protein level increased. Heat production as a percentage of metabolizable energy was higher (P < 0.05) for the low protein diet than for the medium and high protein diets. The efficiency of energy utilization was depressed (P < 0.05) for the high protein diet when rats were kept at 28 degrees C. The results suggest that thermogenesis was induced when low protein was fed. The increase in thermogenesis may have been important in regulating energy balance and maintaining a constant body temperature in a cold environment.     

Prostate cancer in African-American men: outcome following radiation therapy with or without adjuvant androgen ablation

It was recently demonstrated that capsaicin desensitization of the tongue can be temporarily reversed during bouts of recurrent or constant stimulation. The present study investigated whether this "stimulus-induced recovery" (SIR) also occurs on skin other than the oral mucosa. Twenty-two subjects received capsaicin treatments on the cheek and on the tongue tip at concentrations (330 and 33 microM) that produced approximately equal sensory irritation on the two sites. Desensitization and SIR occurred on both test sites, although the longer time course of irritation on the face changed the magnitude and form of SIR. There were large individual differences in the extent of desensitization and recovery, and the two phenomena were not correlated across sites, i.e., the capacity for SIR on the tongue was not a good predictor of an individual's capacity for SIR on the face. The results are discussed in terms of possible sources of regional and individual differences, and the implications they may have for the efficacy of topical analgesics that contain capsaicin.     

The central role of the mitochondrial megachannel in apoptosis: evidence obtained with intact cells, isolated mitochondria, and purified protein complexes

The mitochondrial megachannel (also called permeability transition pore) is a polyprotein complex formed in the contact site between the inner and the outer mitochondrial membranes and participates in the regulation of mitochondrial membrane permeability. We have obtained three independent lines of evidence suggesting the implication of the mitochondrial megachannel in apoptosis. First, in intact cells, apoptosis is accompanied by an early dissipation of the mitochondrial transmembrane potential (delta psi m). In several models of apoptosis, specific agents inhibiting the mitochondrial megachannels prevent this delta psi m dissipation and simultaneously abolish the manifestations of caspase- and endonuclease activation, indicating that megachannel opening is a critical event of the apoptotic process. Second, mitochondria are rate-limiting for caspase and nuclease activation in several cell-free systems of apoptosis. Isolated mitochondria release apoptogenic factors capable of activating pro-caspases or endonucleases upon opening of the mitochondrial megachannel in vitro. Third, opening of the purified megachannel reconstituted into liposomes is inhibited by recombinant Bcl-2 or Bcl-XL, two apoptosis-inhibitory proteins which also prevent megachannel opening in cells and isolated mitochondria. This indicates that the megachannel is under the direct regulatory control of anti-apoptotic members of the Bcl-2 family. Altogether, our results suggest that megachannel opening is sufficient and (mostly) necessary for triggering apoptosis.     

Plasma lipoprotein (a) levels in men and women consuming diets enriched in saturated, cis-, or trans-monounsaturated fatty acids

Studies that have shown adverse effects of trans-unsaturated fatty acids on plasma lipoprotein (a) [Lp(a)] levels have used levels of trans-fatty acid that are higher than those in the average U.S. diet. This study was conducted to clarify the effects on Lp(a) of trans-fatty acids levels commonly found in U.S. diets. Lp(a) levels were measured in a double-blind study of 29 men and 29 women who ate 4 controlled diets in random order for 6 weeks each. Fatty acids represented 39% to 40% of energy. The diets were: (1) Oleic (16.7% of energy as oleic acid); (2) Moderate trans (3.8% of energy as trans-monoenes, approximately the trans content of the U.S. diet); (3) High trans (6.6% of energy as trans-monoenes); (4) Saturated (16.2% of energy as lauric plus myristic plus palmitic acids). The Saturated diet lowered Lp(a) levels significantly (by 8% to 11%). Compared to the Oleic diet, the trans diets had no adverse effect on Lp(a) levels when all subjects were considered collectively. A subset with initially high levels of Lp(a) (> or = 30 mg/dL), however, responded to the High trans diet with a slight (5%) increase in Lp(a) levels relative to the Oleic and Moderate trans diets. Thus, in amounts commonly found in the typical U.S. diet, saturated fatty acids consistently decrease Lp(a) concentrations. The adverse effects of replacing cis- with trans-fatty acids are only suggestive and are restricted to high trans intakes in subjects with high Lp(a) levels.     

Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men

An acute load test was used to test the influence of dietary factors on urinary calcium excretion. In study 1, 10 fasting premenopausal women consumed test meals providing a moderate amount of protein (MP; 23 g), MP plus 23 mmol KHCO3 (MP+K), MP plus 23 mmol NaCl (MP+Na), and a high amount of protein (HP; 53 g), HP plus 70 mmol KHCO3 (HP+K), and HP plus 70 mmol NaCl (HP+Na). Protein was casein:lactalbumin (80:20), except for the treatments with added sodium chloride, to which only casein was added. In study 2, the effects of HP and HP plus 50 mmol KHCO3 (HP+K) were compared with those of MP or MP plus 7.5 mmol phosphate (MP+Pi), equaling the additional phosphate of HP, in 10 adult men. Subjects completed all treatments in random order. In study 1, the peak of calcium excretion was at 3 h for all treatments, except for HP+K, which indicated an acute hypocalciuric effect of potassium. Unexpectedly, there was no hypercalciuric effect of adding sodium chloride, nor was urine sodium increased. In study 2, calcium excretion was significantly higher with HP than with MP+Pi but not with MP at 3 h, indicating an acute hypercalciuric effect of protein alone. A hypocalciuric effect of potassium (HP+K compared with HP) but not of phosphate (MP compared with MP+Pi) was seen. An acute load test measuring changes 3 h postload was appropriate for examining the calciuric effects of protein and potassium bicarbonate, but not those of sodium chloride or phosphate in adults.     

Amination of tyrosine in liver cytosol protein of male F344 rats treated with 2-nitropropane, 2-nitrobutane, 3-nitropentane, or acetoxime

Previously, the secondary nitroalkane 2-nitropropane, a strong hepatocarcinogen in rats, had been shown to induce the formation of 8-aminoguanine in both DNA and RNA of rat liver through a sulfotransferase-mediated pathway. This pathway was postulated to convert the carcinogen into an aminating species [Sodum, R. S., et al. (1994) Chem. Res. Toxicol. 7, 344-351]. To submit this postulate to further test, we examined liver proteins of rats treated with 2-nitropropane, other carcinogenic secondary nitroalkanes, or the related rat liver tumorigen acetoxime for the presence of 3-aminotyrosine, the expected product of tyrosine amination. Using ion-pair and/or cation-exchange high-performance liquid chromatography with electrochemical detection, we found that the liver cytosolic proteins of these animals contained 0.1-1.5 mol of 3-aminotyrosine/10(3) mol of tyrosine. Treatment with the noncarcinogenic primary nitroalkane 1-nitropropane or with other primary nitroalkanes did not produce an analogous increase in the aminated amino acid (level of detection estimated at approximately 0.01 mol/10(3) mol of tyrosine). To our knowledge, this is the first report of the modification of protein tyrosine in vivo by a carcinogen. In vitro studies with acetoxime-O-sulfonate and hydroxylamine-O-sulfonate showed that these proposed intermediates in the activation pathway of 2-nitropropane react with guanosine to give 8-aminoguanosine, N1-aminoguanosine, and 8-oxoguanosine and also react with tyrosine to give 3-aminotyrosine and 3-hydroxytyrosine. The in vitro amination and oxidation of guanosine at C8 were also produced by acetophenoxime-O-sulfonate and 2-heptanoxime-O-sulfonate. These results provide additional evidence for the production of a reactive species capable of aminating nucleic acids and proteins from 2-nitropropane and other carcinogenic secondary nitroalkanes by a pathway involving oxime- and hydroxylamine-O-sulfonates as intermediates.     

Trends in HIV seroprevalence, AIDS and prevention policy among intravenous drug users and men who have sex with men, before and after 1990 in Austria

This study reports for the first time on secular trends in human immunodeficiency virus (HIV) infection and AIDS, and possible associations with prevention policy in Austria. We analysed HIV seroprevalence and AIDS cases among intravenous drug users (IDU) and men who have sex with men (MSM). In this study we found a diminished rate of increase in new cases of AIDS and a decline in HIV seroprevalence among IDU but not among MSM. Among clients visiting HIV counselling and testing centres in Austria between 1987 and 1990, seroprevalence among IDU was estimated at 27.9% as compared to 19.6% between 1990 and 1992 (odds ratio (OR): 0.62; 0.45-0.85). Among MSM corresponding prevalence for these two periods was 12.1% and 10.9%, respectively, which was not a significant decline. In the period 1990 to 1994, the increase in AIDS cases per half-year levelled off for IDU (incidence rate ratio (IRR) :1.00; 0.99-1.01) but to a lesser extent among MSM (IRR: 1.01; 1.01-1.02). The most effective prevention policy intervention was considered to be the national Methadone Maintenance Program (MMTP), started in 1987, and the provision of sterile injection equipment. We observed that in the recent period there was a decline in the frequency of attendance among young (less than 28 years of age) MSM at counselling centres (OR: 1.27; 95 % CI: 1.08-1.49), accompanied by the observation that the rate of seroprevalence among this group did not decline. This is in contrast to young IDU where attendance did not decline but seroprevalence did. Although inference is limited from cross sectional studies, we argue for a reoriented and effectively monitored HIV prevention policy focused on young MSM.     

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.     

Cross-resistance to antifolates in multidrug resistant cell lines with P-glycoprotein or multidrug resistance protein expression

Resistance to some (lipophilic) antifolates has been associated with P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). A possible relationship with non-P-gp MDR has not been established. We studied resistance to antifolates in SW-1573 human lung carcinoma cells, a P-gp overexpressing variant SW-1573/2R160 and a multidrug resistance protein (MRP) overexpressing variant SW-1573/2R120. In this study, thymidylate synthase (TS) inhibitors with different properties concerning the efficiency of membrane transport and the efficiency of polyglutamylation were tested for cross-resistance in SW-1573/2R120 and SW-1573/2R160 cells. Growth inhibition patterns in this cell line panel were measured by the Sulforhodamine B (SRB) assay. Resistance factors for TS inhibitors were: 2.4 and 0.4 for 5-fluorouracil (5FU), 18.8 and 8.8 for ZD1694, 17 and 0.7 for AG337, and 40 and 8.3 for BW1843U89 in SW-1573/2R160 and SW-1573/2R120, respectively. This study showed changes in the TS enzyme kinetics during the induction of doxorubicin resistance in both SW-1573 variants, resulting in 2-fold lower Km values for 2'-deoxyuridine-5'-monophosphate (dUMP) in both resistant variants compared to the parental cell line. TS activity, TS protein induction and TS mRNA expression all had 2-fold increased in the SW-1573/2R120 compared to the SW-1573/2R160. 3H-MTX influx was 2-fold lower in SW-1573/2R160 cells compared to SW-1573/2R120 and SW-1573 cells. In the SW-1573/2R160 cell line, an aberrant intracellular trafficking towards the target TS was observed, compared to SW-1573/2R120 and SW-1573 cells as measured by the TS in situ assay. The rate of TS inhibition by the TS inhibitors used in this study was similar in all cell lines. In conclusion, collateral sensitivity to 5FU and the lipophilic AG337 and cross-resistance to other antifolates were observed in non-P-gp MDR SW-1573/2R120 cells, as well as resistance to all antifolates in P-gp SW-1573/2R160 cells. The mechanism of resistance in SW-1573/2R160 cells possibly involves reduced influx and changes in intracellular trafficking routes. For the SW-1573/2R120 cell line, several changes related to the TS enzyme possibly play a role in the observed cross-resistance and collateral sensitivity pattern.     

Primary structure of a 120 kDa protein associated with the fucose sulfate glycoconjugate constituting the acrosome reaction-inducing substance of the sea urchin, Hemicentrotus pulcherrimus

This review provides an update on four areas of office practice: office laboratory procedures, office economics, patient and parent education, and urinary tract infection. Thomas Ball reviews physician office laboratories, with updates on the Clinical Laboratory Improvement Amendments, office proficiency testing, and office testing for streptococcal pharyngitis and Helicobacter pylori. Eve Shapiro reports on office economics, focusing on the influence of managed care on pediatric practice. Burris Duncan provides a review of the new National Institutes of Health asthma guidelines, and challenges us to become more involved in patient education. Richard Wahl reviews urinary tract infections, vesicoureteral reflux, dysfunctional voiding, and appropriate imaging studies. Our approach is to provide pediatricians with useful and practical information for their office practices.     

Activated protein C resistance and deficiencies of antithrombin III, protein C or protein S and the risk of thromboembolic disease in users of oral contraceptives

The congenital muscular dystrophies (CMDs) comprise a heterogeneous group of muscle disorders with onset in utero or during the first year of life. Several forms of CMD show various types of brain involvement in addition to a muscular dystrophy. Two forms are defined at the molecular level: merosin deficient-CMD caused by mutations in the LAMA2-gene on chromosome 6q2. Fukuyama congenital muscular dystrophy (FCMD) is prevalent in Japan and caused by an as yet unidentified gene on chromosome 9q31. At least two further forms of CMD with brain involvement are nosologically well defined: Walker--Warburg-CMD is characterized by lissencephaly type 11, eye dysgenesis and muscular dystrophy. This autosomal recessive disorder is fatal or results in complete lack of development. A similar but much milder phenotype with pachygyria of the brain, various degrees of eye changes and milder muscular dystrophy that is compatible with achievement of simple motor milestones has been described under the name of muscle-eye-brain disease (MEB) in Finland. A number of nosologically less distinct forms of muscular dystrophy have been outlined such as 'pure' CMD without brain involvement, CMD with cerebellar hypoplasia or CMD type Ullrich with hyperelasticity of the distal joints. Several other CMD phenotypes are known, some of which are suggestive of more distinctly separate nosological entities due to their occurrence in siblings or due to a characteristic pattern of clinical, histopathological and imaging features, and await further clarification.     

Biotransformation and elimination of 1-nitropyrene in the isolated perfused lung: effects of pretreating rats with phenobarbitone, beta-naphthoflavone, benz(A)anthracene or their mixtures

The isolated perfused rat lung (IPL) was perfused with 60 ml of recirculating Krebs-Ringer solution containing 150 micrograms of 1-nitropyrene (1-NP) for 1 h. The 1-NP was administered to the IPL by the intratracheal or intravascular route. At specific time points after 1-NP administration, perfusate samples were removed from the IPL and analysed for 1-NP and its metabolites by HPLC. Monohydroxynitropyrenes, dihydroxynitropyrenes and 1-NP were found to be present in the perfusate. The time course of 1-NP concentrations in the perfusate could be described by a one-compartment pharmacokinetic model. Pretreatment of rats with beta-naphthoflavone (BNF), benz(a) anthracene (BA) or a mixture of phenobarbitone (PB) and BNF (PB + BNF) significantly enhanced the metabolism of 1-NP and decreased the mean residence time (MRT) of 1-NP in the perfusate. Pretreatment of rats with these mixed-function oxidase inducers also increased significantly the absorption of 1-NP by the lung when it was administered intratracheally. In contrast, pretreatment of rats with PB did not appear to have any effect on the pharmacokinetics of 1-NP in the IPL.     

Palmitoylation of lung surfactant protein SP-C alters surface thermodynamics, but not protein secondary structure or orientation in 1,2-dipalmitoylphosphatidylcholine langmuir films

Pulmonary surfactant-specific protein, SP-C, isolated from porcine lung lavage, has been deacylated to investigate the role of the two thioester linked palmitoyl chains located near the N-terminus. Surface thermodynamic properties, secondary structure, and orientation of native and deacylated SP-C in 1, 2-dipalmitoylphosphatidylcholine (DPPC) monolayers has been characterized by combined surface pressure-molecular area (pi-A) isotherms and infrared reflection-absorption spectroscopy (IRRAS) measurements. The isotherms indicate that deacylation of SP-C produces more fluid monolayers at pressures less than 30 mN m-1. The helical secondary structure and tilt angle (70-80 degrees relative to the surface normal) of SP-C remained essentially unchanged upon deacylation in DPPC monolayers at a surface pressure approximately 30 mN m-1. The results are consistent with a model that acylation of SP-C may influence the rapid protein-aided spreading of a surface-associated surfactant reservoir, but not the structure of DPPC or SP-C in the monolayer at higher surface pressures.