GH treatment in adults with chronic liver disease: A randomized, double-blind, placebo-controlled, cross-over study

Patients with chronic liver disease (CLD) are catabolic and GH-resistant. The effects of supraphysiological recombinant human GH (rhGH; 0.2 IU.kg(-1).d(-1)) treatment in adults with CLD were assessed in a randomized, double-blind, placebo-controlled cross-over trial (4-wk dietary run-in, 4-wk treatment, and 2-wk wash-out phases). Nine adults with mild- to moderate-severity CLD participated (median age, 49 yr; three males and six females; Child's classification A in six and B in three). Biopsy-proven etiologies were: alcohol (four patients), primary biliary cirrhosis (three patients), non-A, non-B, non-C hepatitis (one patient), and cryptogenic (one patient). Treatment with rhGH increased serum IGF-I (median increase over placebo, +93 mug.liter(-1); P = 0.004), IGF-binding protein-3 (+0.9 mg.liter(-1): P = 0.004), and acid labile subunit (+10.7 nM; P = 0.004). Total body potassium (+8.0 g; P = 0.023), body weight (+1.6 kg; P = 0.008), and total body water (by bioelectrical impedance; +4.9 kg; P = 0.004) increased. Resting metabolic rate (+313 ml.kg(-1).min(-1); P = 0.004) and lipid oxidation (+1072.0 kcal.d(-1); P = 0.032) increased. Metabolic changes included increased fasting plasma glucose (+1.2 mm; P = 0.008), insulin (+33.8 mU.liter(-1); P = 0.004), C-peptide (+0.7 nM; P = 0.004), and free-fatty acids (+0.1 mEq.liter(-1); P = 0.04). Clinical side effects included worsening edema and ascites. Hepatocellular function did not change. Therefore, rbGH treatment in CLD: 1) overcame hepatic GH resistance; 2) may have improved whole-body protein catabolism; 3) increased lipolysis and lipid oxidation; 4) increased insulin resistance; and 5) had potent antinatriuretic effects. Long-term safety and efficacy require further assessment.

Nutritional strategies for the prevention of hypocalcaemia at calving for dairy cows in pasture-based systems

This review considers the current literature on the macro-mineral nutrition of the soon-to-calve, or transition, dairy cow. Calcium is the main focus, since milk fever (clinical hypocalcaemia) appears to be the most common mineral-related problem faced by the transition cow Australia-wide. The importance of minimising calcium intake and optimising the balance of the key dietary electrolytes, sodium, potassium, sulfate, and chloride, in the weeks before calving is highlighted. Excess dietary potassium can, in some situations, induce milk fever, perhaps even more effectively than excess calcium. Excess sodium remains under suspicion. In contrast, excess dietary chlorine and, to a lesser extent, sulfur can improve the ability of the cow to maintain calcium homeostasis. Diets that promote either a hypomagnesaemia or hyperphosphataemia have also the potential to precipitate milk fever at calving. Current prevention strategies focus on the use of forages with moderate to low levels of calcium, potassium, and sodium, and also rely on or utilise addition of chloride and sulfate in the form of 'anionic' feeds. Anionic salts are one example of an anionic feed. However, legitimate questions remain as to the effectiveness of anionic salts in pasture-feeding systems. The causes and prevention of milk fever are considered from the perspective of the variety of Australian feedbases. Impediments to the use of anionic feeds in Australia feeding systems are outlined. The potential for improving maternal reserves of calcium around calving to reduce the risk of milk fever is also discussed.

On the effect of tracer density on axial dispersion in a batch oscillatory baffled column

In this paper, we report our modelling evaluation on the effect of tracer density on axial dispersion in a batch oscillatory baffled column (OBC). Tracer solution of potassium nitrite, its specific density ranged from 1.0 to 1.5, was used in the study, and was injected to the vertical column from either the top or bottom. Local concentration profiles are measured using conductivity probes at two locations along the height of the column. Using the experimental measured concentration profiles together with both 'Tank-in-Series' and 'Plug Flow with Axial Dispersion' models, axial dispersion coefficients were determined and used to describe the effect of specific tracer density on mixing in the OBC. The results showed that the axial dispersion coefficients evaluated by the two models are very similar in both magnitudes and trends, and the range of variations in such coefficients is generally larger for the bottom injection than for the top one. Empirical correlations linking the mechanical energy for mixing, the specific density of tracer and axial dispersion coefficient were established. Using these correlations, we identified the enhancements of up to 269% on axial dispersion for various specific tracer densities. (C) 2002 Elsevier Science B.V. All rights reserved.

Tree yield and fruit minerals concentrations influence 'Hass' avocado fruit quality

To investigate the variation in quality of 'Hass' avocado fruit within an orchard, fruit were harvested at commercial maturity from 15 'Hass' trees of similar appearance, growing in three adjacent rows on the same soil type, and receiving similar management. Fruit were harvested at commercial maturity, and either ripened at 22 degreesC or stored at 2 or 7 degreesC for 3 or 5 weeks and then ripened. Significant positive correlations (based, on the mean for each datum tree) were noted between fruit flesh calcium (Ca) and magnesium (Mg) concentrations and the (Ca + Mg)/potassium ratio, and the number of days for the fruit to reach the eating ripe stage (DTR). Negative correlations were also observed between these minerals and anthracnose and mesocarp discolouration (MD) severity. Negative correlations were observed between fruit potassium (K) and phosphorus (P) concentrations and DTR. Fruit from trees with high fruit yield were generally smaller, with lower anthracnose and MD severity, ripened more slowly, and had higher flesh Ca concentrations. It is likely that cultural practices that maintain moderate to high fruit yield and reduce variation in yield will improve avocado fruit quality and reduce variability in quality. Since the main differences between adjacent trees in this trial were the seedling rootstocks of unknown origin, it is suggested that rootstocks can have a significant impact on avocado yield and fruit quality. (C) 2002 Elsevier Science B.V. All rights reserved.

Identification of micronutrient deficiency of wheat in the Peshawar Valley, Pakistan

A field experiment was conducted to study the effect of micronutrients, zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), boron (13) and a commercial fritted micronutrient product called Zarzameen, on the yield and the yield components of wheat (Triticum aestivum L.), in the Peshawar valley, Pakistan. Different combinations of Zn, Cu. Fe. Mn, B, and Zarzameen were applied at the rate of 4.0, 2.0, 5.0, 2.0, 1.0 kg ha(-1) and 1.0 kg ha(-1), respectively, along with a basal dose of 100 kg ha(-1) nitrogen(N), 75 kg ha(-1) phosphorus (P) and 50 kg ha(-1) potassium (K). The fertilizer treatments (macro- and micronutrients) increased wheat dry matter, grain yield, and straw yield significantly over an unfertilized control. Soil tests for B and Zn were increased both at boot and harvesting stage, and Fe at boot stage, with the addition of micronutrients. Plants without B had showed classical B deficiency symptoms at grain formation stage, but not at vegetative stage. Boron concentration in the dry matter of wheat plants increased with the addition of the B fertilizer in the soil. Boron deficiency was not observed in plants containing >4 mg B kg(-1) at the boot stage, or in soils containing > 1.4 mg kg(-1) hot water soluble B.

The effect of sodium chloride supplementation on the milk production of grazing Holstein Friesian cows during summer and autumn in a humid sub-tropical environment

Two studies were conducted to examine the effects of including NaCl at various rates in grain-based supplements for Friesian cows grazing established, dominant (>90%), rainfed kikuyu (Pennisetum clandestinum cv. Common) pastures during summer and autumn in a humid sub-tropical environment. In study 1 (19 January-27 March 1998), 48 cows (36 multiparous, 12 primiparous; 27-96 days postpartum) were allocated to one of four groups based on genetic merit, milk production, liveweight (LW) and days postpartum. They were fed (2.7 kg dry matter (DM) per cow, twice-a-day) one of four isoenergetic and isonitrogenous barley grain-based concentrates containing NaCl at concentrations (% as-fed) of either 0 (SC1), 1.1 (SC2), 2.2 (SC3) or 3.3 (SC4). Maximum temperature humidity index (THImax) was greater than or equal to78 during 50% of the experimental period. Concentrate NaCl content had no effect (P>0.05) on daily milk yield or LW change but daily yields of 4% fat corrected milk (FCM), fat and protein were higher (P0.05) among treatments at 7.6+/-1.24 kg DM per cow. In study 2 (18 January 1999-1 March 1999), 48 cows (32 pluriparous, 16 primiparous: 32-160 days postpartum) were fed (2.7 kg DM per cow twice-a-day) one of two isoenergetic and isonitrogenous barley grain-based concentrates containing NaCl at concentrations (% as-fed) of 0 (control) or 2.2 (HSC). THImax was greater than or equal to78 during 34% of days in the experimental period. Yields of milk, FCM, fat and protein were lower (P0.05) by concentrate NaCl content. These studies indicate that NaCl supplementation can be beneficial in terms of milk production during warm, humid conditions as opposed to milder conditions. (C) 2002 Elsevier Science B.V. All rights reserved.

ATP-dependent K+ channels in renal ischemia reperfusion injury

ATP-dependent K+ channels (K-ATP) account for most of the recycling of K+ which enters the proximal tubules cell via Na, K-ATPase. In the mitochondrial membrane, opening of these channels preserves mitochondrial viability and matrix volume during ischemia. We examined KATP channel modulation in renal ischemia-reperfusion injury (IRI), using an isolated perfused rat kidney (IPRK) model, in control, IRI, IRI + 200 muM diazoxide (a K-ATP opener), IRI + 10 muM glibenclamide (a K-ATP blocker) and IRI + 200 muM diazoxide + 10 muM glibenclamide groups. IRI was induced by 2 periods of warm ischemia, followed by 45 min of reperfusion. IRI significantly decreased glomerular filtration rate (GFR) and increased fractional excretion of sodium (FENa) (p < 0.01). Neither diazoxide nor glibenclamide had an effect on control kidney function other than an increase in renal vascular resistance produced by glibenclamide. Pretreatment with 200 muM diazoxide reduced the postischemic increase in FENa (p < 0.05). Adding 10 muM glibenclamide inhibited the diazoxide effect on postischemic FENa (p < 0.01). Histology showed that kidneys pretreated with glibenclamide demonstrated an increase in injure in the thick ascending limb of outer medulla (p < 0.05). Glibenclamide significantly decreased post ischemic renal vascular resistance (p < 0.05). but had no significant effect on other renal function parameters. Our results suggest that sodium reabsorption is improved by K-ATP activation and blockade of K-ATP channels during IRI has an injury enhancing effect on renal epithelial function and histology. This may be mediated through K-ATP modulation in cell and or mitochondrial inner membrane.

Mineral uptake in tobacco leaf discs during different developmental stages of shoot organogenesis

Relationships between mineral uptake and tobacco shoot organogenesis were investigated during three morphogenic phases: phase 1, days 0-10, pre-meristem formation; phase 2, days 10-20, meristem initiation and formation; and phase 3, days 20-35, growth and differentiation of induced meristems into leafy shoots. The mineral content of both shoot-forming (SF) and non-shoot-forming (NSF) media was examined over the 35-day culture period. Both SF and NSF explants rapidly consumed iron during phase 1. Nitrate uptake in SF explants was high and independent of explant growth during phases 1 and 2, but greatest and strongly correlated with growth during phase 3. Phosphorus uptake was highest in SF explants during phases 2 and 3, and correlated with explant growth. Uptake of potassium, calcium and sulphur was strongly associated with explant growth during phase 3 whereas magnesium uptake was only poorly correlated with growth. Results from this study indicate that particular minerals may have an important role in regulating development as well as generally supporting growth.

Synthesis and complexation properties of some novel lariat-crown ethers

Several new lariat-crown ethers bearing either bridged bisdioxine or tetraoxaadamantane units as chiral substituents are prepared by reacting the corresponding amino-crown ether derivatives with the dimeric alpha-oxoketene, the latter obtained by flash vacuum pyrolysis of a furan-2,3-dione precursor. Complexation properties towards differently charged metal ions are investigated by H-1 NMR titration to obtain complexation constants (K-c-values for potassium/ sodium rhodanides: 480-1100 mol dm(-3)), as well as extraction experiments to explore the metal ion transportation abilities of the new lariat crown derivatives. In particular, a significantly increased ability to transport metal ions from water into chloroform was found with spherical tetraoxaadamantyl derivatives when compared with the free amino-benzocrown ethers.

Primary aldosteronism

Approaching the fiftieth year since its original description, primary aldosteronism is now thought to be the commonest potentially curable and specifically treatable form of hypertension. Correct identification of patients with primary aldosteronism requires that the effects of time of day, posture, dietary sodium intake, potassium levels and medications on levels of aldosterone and renin be carefully considered. Accurate elucidation of the subtype is essential for optimal treatment, and adrenal venous sampling is the only reliable means of differentiating aldosterone-producing adenoma from bilateral adrenal hyperplasia. With genetic testing already available for one inherited form, making more cumbersome biochemical testing for that subtype virtually obsolete and bringing about improvements in treatment approach, an intense search is underway for genetic mutations causing other, more common familial varieties of primary aldosteronism.

Solution structure of CnErg1 (Ergtoxin), a HERG specific scorpion toxin

The three-dimensional structure of chemically synthesized CnErg1 (Ergtoxin), which specifically blocks HERG (human ether-a-go-go-related gene) K+ channels, was determined by nuclear magnetic resonance spectroscopy. CnErg1 consists of a triple-stranded beta-sheet and an a-helix, as is typical of K+ channel scorpion toxins. The peptide structure differs from the canonical structures in that the first beta-strand is shorter and is nearer to the second beta-strand rather than to the third beta-strand on the C-terminus. There is also a large hydrophobic patch on the surface of the toxin, surrounding a central lysine residue, Lys13. We postulate that this hydrophobic patch is likely to form part of the binding surface of the toxin. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Structure of the HERG K+ channel S5P extracellular linker - Role of an amphipathic alpha-helix in C-type inactivation

The HERG K+ channel has very unusual kinetic behavior that includes slow activation but rapid inactivation. These features are critical for normal cardiac repolarization as well as in preventing lethal ventricular arrhythmias. Mutagenesis studies have shown that the extracellular peptide linker joining the fifth transmembrane domain to the pore helix is critical for rapid inactivation of the HERG K+ channel. This peptide linker is also considerably longer in HERG K+ channels, 40 amino acids, than in most other voltage-gated K+ channels. In this study we show that a synthetic 42-residue peptide corresponding to this linker region of the HERG K+ channel does not have defined structural elements in aqueous solution; however, it displays two well defined helical regions when in the presence of SDS micelles. The helices correspond to Trp(585)-Ile(593) and Gly(604)-Tyr(611) of the channel. The Trp(585)-Ile(593) helix has distinct hydrophilic and hydrophobic surfaces. The Gly(604)-Tyr(611) helix corresponds to an N-terminal extension of the pore helix. Electrophysiological studies of HERG currents following application of exogenous S5P peptides show that the amphipathic helix in the S5P linker interacts with the pore region of the channel in a voltage-dependent manner.

Therapeutic potential of venom peptides

Venomous animals have evolved a vast array of peptide toxins for prey capture and defence. These peptides are directed against a wide variety of pharmacological targets, making them an invaluable source of ligands for studying the properties of these targets in different experimental paradigms. A number of these peptides have been used in vivo for proof-of-concept studies, with several having undergone preclinical or clinical development for the treatment of pain, diabetes, multiple sclerosis and cardiovascular diseases. Here we survey the pharmacology of venom peptides and assess their therapeutic prospects.

Compositional changes of Australia-grown Western Schley pecans [Carya illinoinensis (Wangenh.) K. Koch] during maturation

Changes in composition during the maturation of Western Schley pecans [Carya illinoinensis (Wangenh.) K. Koch] grown in Australia were investigated. Pecans of different maturity levels were collected at monthly intervals between March and June in. 1999 and 2000 and analyzed for the concentrations of moisture, total lipid, sucrose, raffinose, protein, and the minerals aluminum, boron, calcium, copper, iron, potassium, magnesium, manganese, sodium, phosphorus, sulfur, and zinc. Moisture, total lipid, and calcium contents changed significantly (p < 0.05) with harvest time and maturity, whereas the other components did not. Western Schley pecans grown in Australia should be harvested after the shuck has opened and it is either green or brown in color to maximize total lipid content and quality. This occurred after May 11 in 1999 and after May 17 in 2000.

Muscarinic and nicotinic ACh receptor activation differentially mobilize Ca2+ in rat intracardiac ganglion neurons

The origin of intracellular Ca2+ concentration ([Ca2+](i)) transients stimulated by nicotinic ( nAChR) and muscarinic ( mAChR) receptor activation was investigated in fura-2-loaded neonatal rat intracardiac neurons. ACh evoked [Ca2+](i) increases that were reduced to similar to 60% of control in the presence of either atropine ( 1 muM) or mecamylamine ( 3 muM) and to < 20% in the presence of both antagonists. Removal of external Ca2+ reduced ACh-induced responses to 58% of control, which was unchanged in the presence of mecamylamine but reduced to 5% of control by atropine. The nAChR-induced [Ca2+](i) response was reduced to 50% by 10 μM ryanodine, whereas the mAChR-induced response was unaffected by ryanodine, suggesting that Ca2+ release from ryanodine-sensitive Ca2+ stores may only contribute to the nAChR-induced [Ca2+](i) responses. Perforated-patch whole cell recording at - 60 mV shows that the rise in [Ca2+](i) is concomitant with slow outward currents on mAChR activation and with rapid inward currents after nAChR activation. In conclusion, different signaling pathways mediate the rise in [Ca2+](i) and membrane currents evoked by ACh binding to nicotinic and muscarinic receptors in rat intracardiac neurons.