Search

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

The objective of the current study was to determine if garlic-derived diallyl disulfide (DADS) and diallyl trisulfide (DATS) could mitigate oxidative and endotoxin stress, using an intestinal porcine epithelial cell (IPEC-J2) model. The experiment was arranged as a 2 × 2 × 2 factorial of DADS + DATS (0 or 18 µM), pro-oxidant stressor (hydrogen peroxide at 0 or 100 µM), and endotoxin stressor (lipopolysaccharide [LPS] at 0 or 10 µg/mL) with 8 replicates per treatment. Cells were incubated with DADS + DATS for 18 h, LPS for 6 h, then with hydrogen peroxide for 3 h. Gene expression was measured by RT-PCR for cytokines, interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α), and tight junction proteins, claudin 1 (CL-1), occludin (OC), and zonula occludens 1 (ZO-1). Trans-epithelial electrical resistance (TEER), the antioxidant enzyme catalase, and apical secretion of IL-8 protein into the incubation medium was also measured. There was an increase (P< 0.01) in TNF-α and IL-8 gene expression due to LPS, although there was no effect of hydrogen peroxide or DADS + DATS. Furthermore, there was a tendency for an increase (P= 0.08) in ZO-1 gene expression due to DADS + DATS. Treatment with DADS + DATS and hydrogen peroxide did not affect TEER, although there was a decrease (P= 0.02) in TEER with LPS incubation. Treatment of cells with hydrogen peroxide reduced catalase activity (P< 0.01), which was restored with pre-incubation of DADS + DATS (P< 0.10). There was an increase (P< 0.01) in IL-8 secretion due to LPS, which was further augmented (P< 0.01) by pre-incubation with DADS + DATS. Based on the results from the current study, DADS + DATS can ameliorate oxidative effects of hydrogen peroxide, as well as alter IL-8 secretion in LPS-treated IPEC-J2 cells.

Compounds in garlic have been shown to contain anti-inflammatory, antioxidant, and immune modulatory properties that may be able to mitigate the effects of nursery pig stressors. The objective of the current experiment was to determine if oral gavage of garlic-derived diallyl disulfide (DADS) and diallyl trisulfide (DATS) could mitigate the effects of a 24-h postweaning feed + water deprivation event in nursery pigs. Pigs (6.0 ± 0.05 kg and 21 d old) were allotted to 4 treatments in a randomized complete block design at weaning with 8 replicate pens per treatment that consisted of with or without a 24-h postweaning feed + water deprivation event and with or without an oral gavage containing 3.6 mg DADS + DATS/kg BW. Growth performance and morbidity were recorded throughout the experiment, and on 1, 6, and 21 d after weaning, 1 pig per pen was selected, blood was collected, the pig was euthanized, and a segment of the distal ileum was subsequently excised for morphological and gene and protein expression measurements. Mucosal gene expression was conducted by reverse transcription PCR for immune, antioxidant, and cellular integrity markers. Furthermore, activity of mucosal superoxide dismutase was measured by colorimetric assay. Immediately following the feed + water deprivation event, there was a decrease (P< 0.01) in growth performance and an increase (P= 0.01) in serum cortisol. The feed + water deprivation event tended (P= 0.10) to decrease ileal villus height and supplementation of DADS + DATS by oral gavage increased (P= 0.03) villus height 1 d after weaning. Supplementation of DADS + DATS by oral gavage decreased (P= 0.03) and tended to decrease (P= 0.08) gene expression of SODon 6 and 21 d after weaning, respectively. Furthermore, at 1 d after weaning, ileal mucosa SOD activity was decreased (P= 0.01) by the feed + water deprivation and increased (P= 0.04) by oral supplementation of DADS + DATS. Expression of the tight junction genes ZO-1and OCwere reduced (P≤ 0.05) due to the feed + water deprivation event 1 d after weaning. Results from the current study show that an acute feed + water deprivation event can impact growth performance, intestinal characteristics, and antioxidant status in nursery pigs, which can be partially mitigated by oral supplementation of garlic compounds DADS + DATS.

Bioactive components in garlic have anti-inflammatory, antioxidant, and immune modulatory properties that may improve gastrointestinal function in pigs. The current experiment was conducted to identify an effective dose of garlic-derived bioactive components diallyl disulfide (DADS) and diallyl trisulfide (DATS) and to evaluate the effect of graded doses of DADS and DATS on nursery pig performance and gastrointestinal function. Eight replicate pens of barrows were allotted on the basis of initial BW (12.45 kg ± 1.37) in a randomized complete block design to 1 of 6 treatments that consisted of administration of 0, 0.45, 0.90, 1.80, 3.60, or 7.20 mg DADS + DATS/kg BW. The DADS + DATS was administered daily by oral gavage to overnight-fasted pigs for a period of 6 d with soybean oil as the carrier and vehicle control. Growth performance and daily stool consistency scores were recorded. At the end of the experiment, pigs were euthanized and the mid ileum was excised for morphological and gene expression measurements. Mucosal gene expression was conducted by real-time PCR for mucin(MUC2), interleukin 8(IL-8), tumor necrosis factor(TNF-α), claudin 1(CL-1), occludin(OC), and zonula occludens 1(ZO-1). Supplementation with the oral gavage containing DADS + DATS did not affect growth performance or stool consistency, although there was a tendency (P= 0.06) for increased villus height. Expression of the IL-8gene was linearly increased (P= 0.01) and there was a tendency for a decrease (P= 0.07) in the ZO-1gene expression with oral DADS + DATS supplementation. There was no effect of the oral gavage on the expression of the MUC2, TNF-α, CL-1, and OCgenes. For the current experiment, the villus height plateaued at 381 μm, which was with daily oral supplementation of 1.71 mg DADS + DATS/kg BW. Furthermore, oral supplementation of DADS + DATS impacts IL-8and ZO-1gene expression, which may have implications on mucosal immune function and cellular integrity.

The current experiment was conducted to investigate the impact of acute feed and water deprivation (deprivation) at weaning and a subsequent heat stressor on growth performance and ileal morphology in nursery pigs. Mixed-sex pigs were allotted on the basis of individual birth weight (IBW; 7.0 ± 0.89 kg) in a randomized complete block design with treatments in a split-plot arrangement, consisting of the whole-plot factor of with or without a 24 h of deprivation at weaning and the subplot factor of with or without a cyclic 3-d heat stressor starting at d 27 post-weaning. Growth performance was measured throughout the experiment. On d 1, 27, and 30 post-weaning, 1 pig from each pen was selected, euthanized, and a segment of the mid ileum was excised for morphological measurements. Deprivation reduced (P< 0.01) ADG at d 1 post-weaning, and BW remained lower (P= 0.03) in pigs that were exposed to the deprivation up to d 27 post-weaning. When the heat stressor was imposed (d 27 to 30 post-weaning), heat stress and the combination of the 2 stressors reduced ADG and ADFI (P< 0.05). Furthermore, cumulatively (d 1 to 35 post-weaning), there was a tendency for an interactive effect (P= 0.10) on BW and ADG. The aforementioned interactive effect shows that pigs exposed to both stressors had the poorest performance. There was a reduction in villous height to crypt depth ratio (P= 0.05) due to the deprivation d 1 post-weaning and an interactive effect (P= 0.05) for crypt depth on d 30 post-weaning. Results from the current study show a link between feed and water deprivation at weaning and subsequent heat stress response with implications for growth and ileal morphology.

The impact of acute stressors (24-h feed or water deprivation) on growth performance, intestinal characteristics, and serum stress markers in weaned pigs was evaluated. Pigs (6.21 ± 0.29 kg) were allotted in a randomized complete block design to 4 treatments on the basis of BW at the time of weaning. There were 8 mixed-sex pigs in each of 12 pens per treatment. Treatments were arranged as a 2 × 2 factorial and consisted of a feed or water stressor that included a 0- or 24-h deprivation period postweaning, and pigs were subsequently allowed access to feed and water. Growth performance was measured 1, 7, 14, and 28 d postweaning. Serum and intestinal samples were taken 1 and 7 d postweaning. Serum was analyzed for cortisol and corticotrophin-releasing factor, and villus height, crypt depth, and mast cell density were measured in the jejunum and the ileum. Expression of mucin (MUC2), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), claudin 1 (CL-1), occludin (OC), and zonula occludens 1 (ZO-1) genes were measured on d 1 and 7 postweaning in the jejunum and ileum by real-time PCR. There was a decrease (P< 0.05) in ADG with the water stressor 1 d postweaning, although subsequently, there were improvements (P< 0.05) in ADG and feed efficiency. Furthermore, the water stressor reduced ADFI during the last 14 d of the trial and cumulatively (P< 0.05). Seven days postweaning there was an increase (P< 0.05) in jejunal villous height to depth ratio due to the feed stressor and a decrease (P< 0.05) in the ileal villous height to depth ratio due to the water stressor. There was an increase (P< 0.05) in serum cortisol levels due to the water stressor both 1 and 7 d postweaning. Furthermore, there was an increase in serum corticotrophin-releasing factor 1 d but not 7 d postweaning due to the water stressor (P< 0.05). The feed stressor reduced (P< 0.05) TNF-α gene expression, and the water stressor reduced (P< 0.05) OC gene expression in the jejunum 1 d postweaning. In the ileum, there was a reduction in CL-1 and ZO-1 gene expression (P< 0.05) due to the water stressor 7 d postweaning. The results from the current investigation showed that a 24-h feed or water deprivation at the time of weaning has negative impacts on growth performance, intestinal characteristics, and serum stress responses immediately following the stress event and throughout the nursery period.

In 2 experiments, a total of 184 pigs (PIC, initial BW of 10.3 and 9.7 kg for Exp. 1 and 2, respectively) were used to develop an available P (aP) release curve for commercially available Escherichia coli-derived phytases. In both experiments, pigs were fed a corn-soybean meal basal diet (0.06% aP) and 2 diets with added inorganic P (iP) from monocalcium phosphate (Exp. 1: 0.075 and 0.15% aP; Exp. 2: 0.07 and 0.14% aP) to develop a standard curve. In Exp. 1, 100, 175, 250, or 500 phytase units (FTU)/kg of OptiPhos 2000 or 200, 350, 500, or 1,000 FTU/kg of Phyzyme XP were added to the basal diet. In Exp. 2, 250, 500, 750, or 1,000 FTU/kg of OptiPhos 2000; 500, 1,000, or 1,500 FTU/kg of Phyzyme XP; or 1,850 or 3,700 FTU/kg of Ronozyme P were added to the basal diet. One FTU was defined as the amount of enzyme required to release 1 µmol of iP per minute from sodium phytate at 37°C. For all phytase products, the manufacturer-guaranteed phytase activities were used in diet formulation. All diets were analyzed for phytase activity using both the Phytex and AOAC methods. Pigs were blocked by sex and BW and allotted to individual pens with 8 pens per treatment. Pigs were killed on d 21, and fibulas were collected and analyzed for bone ash. In both experiments, increasing iP improved (linear, P< 0.01) G:F and percentage bone ash. Pigs fed increasing OptiPhos had improved (Exp. 1: linear, P< 0.001; Exp. 2: quadratic, P< 0.001) percentage bone ash, as did pigs fed increasing Phyzyme XP (linear, P< 0.001). In Exp. 2, increasing Ronozyme P improved (quadratic, P< 0.01) percentage bone ash. Using analyzed values from the AOAC method and percentage bone ash as the response variable, an aP release curve was developed for up to 1,000 FTU/kg of E. coli-derived phytases (OptiPhos 2000 and Phyzyme XP) in P-deficient diets. The prediction equation was Y = –0.000000125X2+ 0.000236X + 0.016, where Y = aP release (%) and X = analyzed phytase (FTU/kg) in the diet.

To report three unrelated infants with a distinctive phenotype of Leigh-like syndrome, neurogenic muscular atrophy, and hypertrophic obstructive cardiomyopathy. The patients all had a homozygous missense mutation in SCO2.

Abstract: The teleost gasbladder is believed to aid in fish audition by transferring pressure components of incoming sound to the inner ears. This idea is primarily based on both anatomical observations of the mechanical connection between the gasbladder and the ear, followed by physiological experiments by various researchers. The gasbladder movement has been modeled mathematically as a pulsating bubble. This study is extending the previous work on fish with a physical coupling of the gasbladder and ear by investigating hearing in two species (the blue gourami Trichogaster trichopterus, and the oyster toadfish Opsanus tau) without a mechanical linkage. An otophysan specialist (the goldfish Carassius auratus) with mechanical coupling, is used as the control. Audiograms were obtained with acoustically evoked potentials (e.g., auditory brainstem response) from intact fish and from the same individuals with their gasbladders deflated. In blue gourami and oyster toadfish, removal of gas did not significantly change thresholds, and evoked potentials had similar waveforms. In goldfish thresholds increased by 33–55 dB (frequency dependent) after deflation, and major changes in evoked potentials were observed. These results suggest that the gasbladder may not serve an auditory enhancement function in teleost fishes that lack mechanical coupling between the gasbladder and the inner ear.

Neurocognitive disorders are often the reason to call for an emergency physician. We report on a 71 year old male patient who showed a sudden sensorial clouding caused by an uremic encephalopathy. The patient was admitted to the intensive car unit. During the following two days he underwent three emergency hemodialysis sessions until renal function recovered. Further investigations revealed as hydronephrosis secondary to a benign prostatic hypertrophy as the cause of acute renal failure Unklare Bewußtseinsstörungen sind ein häufiger Alarmierungsgrund für den Notarzt. So wurde auch im vorliegenden Fall eines 71-jährigen Patienten mit einer plötzlichen Bewußtseinstrübung der Notarzt gerufen. Als Auslöser der Bewußtseinsstörung fand sich eine urämische Enzephalopathie bei akutem Nierenversagen. Der Patient wurde auf die internistische Intensivstation aufgenommen und in den folgenden zwei Tagen dreimal hämodialysiert. Danach stabilisierte sich die Nierenfunktion. Als Ursache des renalen Versagens fand sich eine Hydronephrose bei Prostataadenom, die drei Wochen später transurethral reseziert wurde. Die Kasuistik zeigt, daß bei unklaren Bewußtseinsstörungen im Notarztdienst auch seltene metabolische Krankheitsbilder differentialdiagnostisch zu berücksichtigen sind.

Menkes disease (MD) is an X-linked recessively inherited neurodegenerative disorder of copper (Cu) metabolism leading to death in early childhood. Symptoms are attributed to deficient activity of Cu-dependent enzymes. Limited experience has been reported concerning clinical and biochemical consequences of parenteral treatment with copper-(histidine)2-complex (Cu-His) in MD. Cu-His was administered in a 13-week-old boy with MD by daily intramuscular injections. After 6 weeks of therapy, Cu and caeruloplasmin in serum and Cu in CSF were normalized. The excessive dopamine level in CSF was corrected after 3 months of treatment. After 6 weeks of Cu supplementation, complete reduction of epileptic discharges, improved muscular tone and increased motor activities were observed. Developmental regression stopped and was replaced by a slight progression. Death at the age of 19 months was caused by septicaemia due to a fulminant urinary tract infection; there was no evidence of chronic Cu toxicity. These findings suggest that Cu-His supplementation may be a promising palliative treatment in MD.

Yield losses caused by chickpea chlorotic dwarf virus in chickpea were estimated by comparing uninfected and infected plants in the field at two locations in India. When infection was before flowering, yield losses of individual plants amounted to nearly 100% in the three cultivars studies. Plants that became infected during flowering had yield losses of 75–90%. Percentage of crop loss is likely to equal percentage of disease incidence, since plant densities in farmers' fields are probably too low to allow uninfected plants around infected ones to compensate the yield losses of infected plants.

During a survey of groundnut in 1986 and 1987 in South Sulawesi, West and East Java and West Sumatra a disease was frequently observed which is characterized by the presence of green blotches. These blotches were either randomly distributed over the entire leaflets or concentrated along the veins; sometimes they were surrounded by light green rings. On the basis of test plant studies, serology and electron microscopy it was concluded that the causal agent of the disease is peanut stripe virus (PStV). This virus has been described for the first time in the USA in 1984. Some potyviruses described earlier in Indonesia, viz. groundnut mottle-y and peanut mottle virus (PMV) probably are also PStV. The similarity of symptoms caused by PStV and peanut mottle virus was the reason why blotching on groundnut in Indonesia was ascribed for many years to PMV.

Fungicides which inhibit ergosterol biosynthesis have been in use for control of wheat powdery mildew (Erysiphe graminis f. sp.tritici) in the Netherlands since 1978. Mildew populations were tested for their variation in sensitivity to triadimefon from 1982 to 1984.

1. A significant proportion of plasma zinc exists complexed with amino acids. The effect of amino acids on the accumulation of radioactive zinc by rat erythrocytes was studied in vitro, to investigate the hypothesis that zinc might be transported into cells as an amino acid‐zinc complex. 2. L‐Histidine (500 microM‐10 mM) stimulated 65Zn uptake; 50 mM‐L‐histidine gave a slight inhibition of uptake. D‐Histidine (500 microM‐10 mM) inhibited uptake in a dose‐dependent manner. A non‐zinc‐binding amino acid, L‐alanine, did not affect 65Zn uptake. 3. The effect of L‐histidine was sodium dependent and temperature dependent, but was DIDS insensitive. These properties suggest that zinc is being transported as a zinc‐histidine complex, utilizing an amino acid carrier system. Uptake of zinc in the presence of L‐histidine differed from the previously described ionic mechanism, and may represent a physiological route of uptake. 4. L‐Histidine stimulated efflux of 65Zn from pre‐loaded cells. 5. The relevance of transport of a zinc‐histidine complex is discussed with reference to histidinaemia, and as a significant zinc transport system in the presence of the very low ionic zinc concentrations found in plasma.

1. The effect of histidine and cysteine on the initial rate of zinc influx into rat and human erythrocytes in the presence of bovine serum albumin has been investigated. 2. The L‐enantiomers of both amino acids promoted zinc influx into rat erythrocytes in a dose‐dependent manner. L‐Histidine, but not L‐cysteine, also promoted zinc uptake into human erythrocytes. D‐Histidine did not promote zinc uptake in either rat or human erythrocytes. In rat erythrocytes D‐cysteine was significantly less effective than L‐cysteine. 3. The stimulation of zinc influx into rat erythrocytes by 20 mM L‐histidine was approximately 4.1 times that seen with human erythrocytes. 4. The influx of zinc in the presence of varying concentrations of L‐histidine was linearly related to the calculated concentration of the zinc‐bis‐histidine complex but not to that of the zinc‐mono‐histidine complex or the free ionic zinc concentration. 5. These results are discussed in relation to the nature of the transport mechanisms involved.

1. Blood flow was measured in the renal cortex and medulla of anaesthetized rats by the hydrogen washout method. The effects of dopamine infusion were measured. 2. Low doses of dopamine (20 and 65 n‐mole.kg‐1.min‐1) caused only small increases in renal blood flow, and a higher dose (200 n‐mole.kg‐1.min‐1) caused vasoconstriction. After alpha‐blockade with phenoxybenzamine (9 mumole.kg‐1), all doses of dopamine caused vasodilatation in the cortex and medulla of the kidney. 3. This dopamine‐induced renal vasodilatation was almost abolished by sulpiride (0.7 mumole.kg‐1.min‐1), but was only slightly attenuated by propranolol (10 mumole.kg‐1). 4. Sulpiride did not significantly alter the renal blood flow responses to noradrenaline or isoprenaline, or the blood pressure responses to histamine, acetylcholine, 5HT, noradrenaline and isoprenaline. 5. In normal rats, infusion of sulpiride generally caused a reduction in renal cortical blood flow. This response showed a positive correlation with the initial blood pressure. 6. It is concluded that there are specific dopamine receptors in the renal vasculature of the rat, and that dopamine may play a role in the normal control of renal blood flow.

1. Blood flow through the inner cortex and outer medulla of the rat kidney was measured by the hydrogen wash‐out technique. 2. Renal nerve stimulation caused vasoconstriction in both cortex and medulla. This constriction was abolished or reduced by phenoxybenzamine (9 mumole/kg I.V.), phentolamine (100 n‐mole/kg) or prazosin (1.5 mumole/kg). 3. After prazosin (6 mumole/kg I.V.), renal nerve stimulation caused small but significant renal cortical vasodilatation. This vasodilatation was reversed by sulpiride (0.7 mumole kg‐1 min‐1), but was unaffected by propranolol (10 mumole/kg) or atropine (4.3 mumole/kg). 4. These results indicate the existence of dopaminergic vasodilator nerves to the renal cortex of the rat.

Increased64Cu uptake into cultured cells is a biochemical marker for mutant cells in Menkes' disease (McKusick 30940). Using this marker selective prenatal diagnosis has been carried out in more than 80 at-risk pregnancies. The64Cu uptake into cultures from affected male fetuses is, however, negatively correlated to the fetal age at amniocentesis. After the 18th week of gestation the risk of false negatives is significant.

Six patients with Menkes syndrome are described, who differ from patients with the classical form of Menkes syndrome because of their longer survival; some of them also exhibited a milder manifestation of symptoms. Based on the present data and a summary of seven case reports describing Menkes patients with long survival, it may be possible to divide these patients into two subgroups:one group of severely affected patients with long survival and another group of very mildly affected patients with late onset of symptoms. Perhaps only the latter represents a true subgroup of Menkes syndrome. The possible benefits of copper therapy are discussed.

105 patients with Menkes disease have been diagnosed from64Cu-uptake studies in fibroblasts. These results are presented together with chase results following removal of64Cu from the medium for 16 Menkes patients. Second-trimester prenatal diagnosis has been performed in 80 pregnancies with male karyotype. These64Cu-uptake results show some overlap between the upper end of the normal range and the lower end of the Menkes range. Results are presented to show that a combination of64Cu-uptake and chase results offers a better diagnostic potential than64Cu-uptakeper se. Chorionic villus copper values from 53 first-trimester prenatal diagnoses are presented. Maternal deciduum from some of these pregnancies contain similar high amounts of copper as found in the chorionic villus samples from affected fetuses.64Cu-uptake in cultured chorionic villi from affected fetuses and unaffected fetuses is not discriminatory. Chase results seem however to offer a better diagnostic potential.

During a systematic chromosomal survey of 167 unrelated boys with the X-linked recessive Menkes disease (MIM 309400), a unique rearrangement of the X chromosome was detected, involving an insertion of the long arm segment Xq13.3-q21.2 into the short arm at band Xp11.4, giving the karyotype 46,XY,ins(X) (p11.4q13.3q21.2). The same rearranged X chromosome was present de novo in the subject's phenotypically normal mother, where it was preferentially inactivated. The restriction fragment length polymorphism and methylation patterns at DXS255 indicated that the rearrangement originated from the maternal grandfather. Together with a previously described X;autosomal translocation in a female Menkes patient, the present finding supports the localization of the Menkes locus (MNK) to Xq13, with a suggested fine mapping to sub-band Xq13.3. This localization is compatible with linkage data in both man and mouse. The chromosomal bend associated with the X-inactivation center (XIC) was present on the proximal long arm of the rearranged X chromosome, in line with a location of XIC proximal to MNK. Combined data suggest the following order: Xcen-XIST(XIC), DXS128-DXS171, DXS56-MNK-PGK1-Xqter.

1. Histidine (2‐40 mM) stimulated cadmium uptake into human erythrocytes incubated in the presence of 1% bovine serum albumin to ensure that the free, ionic cadmium concentration was low. 2. The histidine‐stimulated cadmium uptake correlated with the calculated concentration of the cadmium‐bis‐histidine complex rather than the cadmium‐mono‐histidine complex or free ionic cadmium. 3. The histidine stimulation of cadmium uptake was saturable and stereospecific. D‐Histidine (10 mM) had no effect. 4. Cadmium and zinc were both able to inhibit 65Zn2+ uptake into erythrocytes incubated in the presence of 40 mM L‐histidine. The relationships between the percentage inhibition of 65Zn2+ uptake and the calculated concentrations of cadmium‐bis‐histidine and zinc‐bis‐histidine were very similar, which suggests that the metal histidine complexes compete for a common transport mechanism. 5. Pretreatment of the erythrocytes with N‐ethylmaleimide using a protocol which is known to inhibit the system y+ amino acid transport mechanism had no effect on the histidine stimulation of metal transport.

Mouse Interleukin 4 is a 20-kDa glycoprotein, synthesized by activated T lymphocytes and mast cells, which regulates the growth and/or differentiation of a broad spectrum of target cells of the immune system, including B and T lymphocytes, macrophages, and hematopoietic progenitor cells. Using an inducible recA promoter and the g10-L ribosome-binding site, recombinant non-glycosylated interleukin 4 (IL-4) was expressed as 17% of total cellular protein in Escherichia coli inclusion bodies, as a reduced, inactive 14.5-kDa polypeptide. The protein was refolded and aggregates dissociated when three disulfide bonds were reformed by slowly decreasing the concentration of guanidine hydrochloride and cysteine. The oxidized monomer was purified to homogeneity by sequential ion-exchange and size exclusion chromatography. When compared with native IL-4, E. coli-derived IL-4 displayed an identical specific activity of 4-7 x 10(7) units/mg. This recombinant IL-4 contained a three-amino-acid NH2-terminal extension, which did not affect its biological activity. Purified biologically active protein consisted of three isoforms as shown by two-dimensional gel electrophoresis, with a pI greater than 9.0. These data suggest that neither glycosylation nor the NH2 terminus of mouse IL-4 play a critical role in contributing to its in vitro biological activity.

The gene defective in Menkes disease, an X-linked recessive disturbance of copper metabolism, has been isolated and predicted to encode a copper-binding P-type ATPase. We determined the complete exon—intron structure of the Menkes disease gene, which spans about 150 kb of genomic DNA. The gene contains 23 exons, and the ATG start codon is in the second exon. All of the exon—intron boundaries were sequenced and conformed to the GT/AT rule, except for the 5′ splice site of intron 9. A preliminary comparison demonstrated a striking similarity between the exon structures of the Menkes and Wilson disease genes, giving insight into their evolution.

The authors report a 27-year-old man with B12-responsive muf-methylmalonic aciduria associated with pure muscle symptoms. Two mutations were found in the methylmalonyl-CoA mutase gene. An exercise test showed a reduced maximal workload and reduced oxygen uptake, and a muscle biopsy showed subsarcolemmal accumulation of mitochondria and normal respiratory chain enzyme activities. These findings may be caused by inhibition of mitochondrial energy metabolism by methylmalonate or its metabolites.

No abstract

“Gut health”, a catch-phrase used loosely across the animal nutrition industry, lacks a clear and simplistic definition, due to the complexity of the gastrointestinal tract in relation to physiological systems. The key to understanding the relationship between gastrointestinal function and animal health is a fundamental understanding of the integral role gastrointestinal organs play in regulating homeostatic functions, especially as related to protection from pathogens and immune tolerance. Contributing to the complexity of putting gastrointestinal health into tangible and descriptive terms is the dynamic relationship between dietary components and livestock management on the mucosal immune system, intestinal microflora, epithelial integrity, utilization of nutrients, and mucosal function. Further, recent literature reports that stress events impact short- and long-term functionality of gastrointestinal integrity and are linked to a depression in growth performance, thus showing the gut has a memory to stress events. Accurate measurement of gastrointestinal function is critical to valuation of health-promoting benefits of nutritional and management strategies. Unfortunately, assessment of the aforementioned strategies cannot always be conducted under commercial settings, therefore the strategic use of in-vitro and in-vivo research models is critical. Recent developments in the use of intestinal cell culture models, such as the secondary porcine cell culture line IPEC-J2 and porcine gut enteroids show promise in understanding the relationship between nutritional strategies, intestinal stressors, and epithelial integrity. Further, the use of in-vivo research models show that common in-field stress events can be partially mimicked to study gastrointestinal function. Additionally, assessment of the microbiome, metabolomics, and mucosal immune function can provide another piece of the puzzle in understanding gastrointestinal dynamics. However, in-vitro experimental models, molecular, and microbial measurements should be accompanied with classical systemic measurements, such as nutrient digestibility and utilization and growth performance, to allow for practical interpretation of results. Understanding “gut health” requires a fundamental understanding of the intestinal epithelium, the immune system, the intestinal microbiome, and the crosstalk that exists between these components. Further, measurement of “gut health” requires utilization of in-vitro and in-vivo research models coupled with novel and classical measurements.

We have calculated the incidence of Menkes disease for Denmark, France, The Netherlands, the United Kingdom and West Germany, based on known Menkes patients born during the time period 1976–87. Considering live-born Menkes patients, the combined incidence for these five countries is 1 Menkes patient per 298000 live-born babies. If the number of affected aborted fetuses are taken into account, the incidence is 1 Menkes per 254000 live-born babies. This incidence, which is 2–4 times lower than earlier published incidence figures, places Menkes disease as an extremely rare disease. The mutation rate for Menkes disease is estimated to be 1.96 × 10-6, based on the number of isolated Menkes cases born during the time period 1976–87 and the total number of newborn males during this time.

This study compared the intestinal goblet cell density of turkey poults at two different ages using Alcian blue-Periodic acid shiff (AB-PAS) and Mucicarmine stains. Neutral mucins are stained with PAS while acidic mucins are stained with AB. Mucicarmine is specific to the mucins of epithelial origin and it is currently used for human samples, Mucicarmine may have advantages for use in animals as a result of the methodological simplicity of staining as compared with AB-PAS. Jejunum samples were taken from 80 turkey poults at 21 and 28 d, and were assigned to two treatments which consisted of AB-PAS and Mucicarmine stains in a completely randomized design. A mid-section of jejunum from each bird was taken and placed in 10% buffered formalin for 48 h, dehydrated with ethanol, cleared with Sub-X and placed in a paraffin, prepared on two slides, and then tissues were briefly cleared and hydrated. Each slide was stained with either AB-PAS reagents or Mucicarmine reagents. Goblet cell counts were taken from four villi per slide and the villi height was measured and averaged. There was no difference in the goblet cell density between the staining methods AB-PAS and Mucicarmine at 21 or 28 d post-hatching. These results show that both staining methods are viable for assessment of goblet cell density in turkey poults.

Background. Circulatory response to hypoventilation is aimed at eliminating carbon dioxide and maintaining oxygen delivery (DO2) by increasing cardiac output (CO). The hypothesis that this increase is more pronounced with xenon than with isoflurane anaesthesia was tested in pigs. Methods. Twenty pigs received anaesthesia with xenon 0.55 MAC/remifentanil 0.5 µg kg−1 min−1 (group X, n=10) or isoflurane 0.55 MAC/remifentanil 0.5 µg kg−1min−1 (group I, n=10). CO, heart rate (HR), mean arterial pressure (MAP) and left ventricular fractional area change (FAC) were measured at baseline, after 5 and 15 min of hypoventilation and after 5, 15 and 30 min of restored ventilation. Results. CO increased by 10–20% with both anaesthetics, with an equivalent rise in HR, maintaining DO2 in spite of a 20% reduction in arterial oxygen content. Decreased left ventricular (LV) afterload during hypoventilation increased FAC, and this was more marked with xenon (0.60–0.66, P<0.05 compared with baseline and isoflurane). This difference is attributed to negative inotropic effects of isoflurane. Increased pulmonary vascular resistance during hypoventilation was found with both anaesthetics. Conclusion. The cardiovascular effects observed in this model of moderate hypoventilation were sufficient to maintain DO2. Although the haemodynamic response appeared more pronounced with xenon, differences were not clinically relevant. An increase in FAC with xenon is attributed to its lack of negative inotropic effects.

Background. It was hypothesized that xenon would stabilize mean arterial pressure (MAP) in haemorrhagic shock, recovery, and volume resuscitation, because a higher MAP has been observed with xenon, when compared with isoflurane anaesthesia. The responses to haemorrhage and subsequent volume replacement were therefore compared between xenon and isoflurane anaesthesia, in pigs. Methods. Pigs were randomized to anaesthesia with xenon 0.55 MAC (group Xe, n=9) or isoflurane 0.55 MAC (group Iso, n=9), each with remifentanil 0.5 µg kg−1 min−1. MAP, heart rate, cardiac output (CO), and left ventricular fractional area change (FAC) were collected at control (1), after haemorrhage (20 ml kg−1) (2), after 10 min of recovery (3), after volume replacement (4), and 30 min later (5). Data were analysed by two-way repeated measures anova. Results. Blood loss decreased MAP (Xe: 103 [21] to 53 [24] mm Hg; Iso: 92 [18] to 55 [14] mm Hg) and CO (Xe: 4.1 [0.8] to 2.6 [0.5] litre min−1; Iso: 5.1 [1.1] to 3.8 [1.2] litre min−1), in spite of significant tachycardia. MAP and CO recovered to about 75% of control, and subsequent volume replacement completely reversed symptoms in both groups, but increased FAC only with xenon. Conclusion. Haemodynamic response to acute haemorrhage appeared faster with xenon/remifentanil than with isoflurane/remifentanil anaesthesia. In particular MAP decrease and short-term recovery were more marked with xenon (P<0.02). In the xenon group, volume replacement increased FAC compared with control and isoflurane (P<0.02).

No Abstract

Background. The minimum alveolar concentration (MAC) is a traditional index of the hypnotic potency of an inhalational anaesthetic. To investigate the anaesthetic as well as the unwanted effects of xenon (Xe) in a swine model, it is useful to know MACXe. Methods. The study was performed using ten swine (weight 27.8–35.4 kg) anaesthetized with halothane and Xe 0, 15, 30, 40, 50 and 65% in oxygen. With each Xe concentration, various concentrations of halothane were administered in a step‐by‐step design. For each combination, a supramaximal pain stimulus (claw clamp) was applied and the appearance of a withdrawal reaction was recorded. The MACXe with halothane was calculated using a logistic regression model. Results. During stable ventilation, haemodynamics and temperature, MACXe value was determined as 119 vol. % (95% confidence limits 103–135). Conclusion. MACXe in swine was calculated by extrapolation of a logistic regression model. Its theoretical value is 119 vol. %. Br J Anaesth 2004; 92: 421–4