Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.     

Total content and dialyzable iron and zinc in foods from northern and Southern Mexico

Developing countries diets are based on a variety of plant foods that often are the main suppliers of important amounts of iron (Fe) and zinc (Zn). The objectives of this study were 1) to measure the total and dialyzable amounts of Fe and Zn in foods from Northern Mexico (Sonora) and from Southern Mexico (Oaxaca) and 2) to evaluate the effect of meat content of diets on the dialyzable amount of Fe and Zn. Methods to calculate the total dialyzable amount of Fe and Zn, were those of the AOAC and of Shen et al. Total Fe in e northern Mexican foods went from 0.78 +/- 0.0 to 11.59 +/- to 0.03 mg/ 100g (dry weight, DW); in southern Mexican foods the same micronutrient amounts were 0.86 +/- 0.18 to 8.8 +/- 0.57 mg/100 g (BS). Total Zn values were 0.91 +/- 0.00 to 13.58 +/- 0.05 mg/100 g (DW) in Sonora, and 0.64 +/- 0.18 to 20.80 +/- 0.33 mg/100 g (DW) in Oaxaca. In northern Mexico, foods dialyzable Fe had values from 0.1 +/- 0.04% to 10.6 +/- 0.36% and for Zn from 4.0 +/- 0.21% to 55.32 +/- 0.14%. Meanwhile, the range of values of dialyzable Fe for foods from Oaxaca were from 0.22 +/- 0.06% to 9.40 +/- 0.14% for and from 2.41 +/- 0.26% to 54.27 +/- 1.49% for dialyzable Zn. The average value for dialyzable Fe was higher in the foods that contained meat or meat products (p= 0.001).     

Synthesis of hyperbranched P poly(glycerol-diacid) oligomers

Novel oligomeric prepolymers were synthesized by acid-catalyzed condensation of glycerol with iminodiacetic, azelaic, or succinic acid. The prepolymers were obtained, on average, in 62% yield and were characterized by ¹³C NMR, ¹H NMR, matrix-assisted laser desorption ionization-time of flight-mass spectrometry, and gel permeation chromatography. The synthesized oligomers had an average M.W. of 1543 Daltons (average polydispersity (PD)=1.34, average degree of polymerization (DOP)=5.5). Hyperbranching was evident in the oligomers produced when using azelaic acid and succinic acid as co-monomers with glycerol, whereas the reaction between iminodiacetic acid and glycerol resulted in linear products bearing cyclic urethane structures.     

Potassium fertilization of broccoli transplants

Increased potassium fertilization may be important in broccoli transplant growth. Recommended amounts of water soluble 20N-8.7P-16.6K were supplemented with varying concentrations of K as KCl applied at intervals during broccoli transplant development. Transplant growth and subsequent broccoli yields were studied in greenhouse and field tests.Fertilization with supplemental K significantly increased broccoli transplant fresh and dry weight, leaf area, stem diameter and plant height over the control. Effect of number of applications was generally dependent on K concentration and age of the broccoli seedling at the first fertilization. High K concentrations (> 2098 ppm) applied two weeks after planting were detrimental to broccoli transplant growth.In two field tests, supplemental K applied to transplants had no effect on broccoli yield. No significant differences were found between supplementing fertilizer with K and hardening transplants in a cold frame for two weeks. Incidence of hollow stem was increased in one test by application of 1000ppm K. Two applications per week caused significant increases in yield, head diameter and hollow stem when compared with one application per week.     

Optimization of the in Situ Transesterification of Grain Sorghum (Milo) DDGS to Fatty Acid Methyl Esters and Fatty Acid Ethyl Esters

Distillers grains and solubles generated from the ethanol fermentation of grains contain acylglycerols (AG) that can be successfully converted to fatty acid methyl esters (FAME) and fatty acid ethyl esters (FAEE), commonly known as biodiesel. However, when grain sorghum (milo) DDGS were used as a feedstock for in situ transesterification (IST) under the previously established optimal conditions for other AG-bearing substrates, the yield plateaued at only 32.2% (corrected in this study to 24.2%). Several IST studies have reported significantly higher conversions of AG-bearing substrates to FAME. Therefore, the goal of this IST study was to improve the conversion of the AG in milo DDGS to FAME and FAEE by varying the temperature of reaction, the concentrations of the base (sodium methylate, NaOMe), volume of methanol and ethanol, and the amount of moisture in DDGS. Methyl tert-butyl ester was also evaluated as a co-solvent intended to improve miscibility and reaction rate. Among these variables, the most effective change was an increase in temperature from 40 to 65 °C. The most successful reaction used a AG:NaOMe:MeOH molar ratio of 1.0:2.6:168.9. Those reaction conditions used 4.8 mmol NaOMe dissolved in 12.6 mL MeOH and resulted in a 79.8% conversion of AG to FAME.     

L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide synthases

Nitric-oxide synthase (NOS) catalyzes the oxidation of L-arginine to citrulline and nitric oxide (NO). The enzyme is inhibited by a variety of N omega-monosubstituted L-arginine analogs, and some of these compounds are useful in reversing pathologies associated with the overproduction of NO (e.g. the hypotension of septic shock). We report here that L-thiocitrulline (gamma-thioureido-L-norvaline) is a potent, stereospecific inhibitor of the constitutive brain and endothelial isoforms of NOS as well as the isoform induced in vascular smooth muscle cells by lipopolysaccharide and interferon-gamma. Steady state kinetic studies show L-thiocitrulline inhibition is competitive with L-arginine (Ki approximately 4-20% of KArgm), indicating that initial binding is as a substrate/product analog. In contrast to L-arginine and N omega-methyl-L-arginine, the prototypic NOS inhibitor, L-thiocitrulline binding elicits a "Type II" difference spectrum, indicating a high spin to low spin transition of the iron in the heme cofactor. This finding suggests that L-thiocitrulline is contributing the sixth ligand to heme iron, probably through the thioureido sulfur. Such interaction with heme iron neither stimulates nor inhibits the direct flavin-mediated cytochrome c reduction activity of the enzyme, but it does inhibit heme-dependent superoxide formation. In vivo, L-thiocitrulline is a potent pressor agent in both normal and endotoxemic rats, the latter finding suggesting utility in treating the hypotension of septic shock.     

Severity of delayed (“secondary”) cerebral energy failure after acute hypoxia-ischemia is related to the time integral of acute ATP depletion

The aim of this study was to reproduce the delayed (secondary) cerebral energy failure previously described in birth-asphyxiated newborn infants and to investigate relationships between primary insult severity and the extent of the delayed energy failure. Phosphorus (³¹P) magnetic resonance spectroscopy (MRS) at 7 T was used to study the brains of 12 newborn piglets during an acute, reversible, cerebral hypoxic-ischemic episode which continued until nucleotide triphosphates (NTP) were depleted. After reperfusion and reoxygenation, spectroscopy was continued for 48 h. High-energy metabolite concentrations returned to near normal levels after the insult, but later they fell as delayed energy failure developed. The time integral of NTP depletion in the primary insult correlated strongly with the minimum [phosphocreatine (PCr)]/[inorganic orthophosphate (P_i)] observed 24–48 h after the insult. (Linear regression analysis gave slope –8.04 h^–1; ordinate intercept=1.23;r=0.92;P<0.0001.) This model is currently being used to investigate the therapeutic potential of various cerebroprotective strategies including hypothermia.     

Renal amyloidosis in a drug abuser

Drug abusers, particularly those who inject drugs s.c. ("skin popping"), may develop amyloidosis. Chronic infections are thought to play a pathogenetic role in this setting. A patient is presented who had a history of "skin popping" cocaine and heroin and developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. These observations suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis.     

Interfacial Connections between Organic Perovskite/n+ Silicon/Catalyst that Allow Integration of Solar Cell and Catalyst for Hydrogen Evolution from Water

The rapidly increasing solar conversion efficiency (PCE) of hybrid organic–inorganic perovskite (HOIP) thin-film semiconductors has triggered interest in their use for direct solar-driven water splitting to produce hydrogen. However, application of these low-cost, electronic-structure-tunable HOIP tandem photoabsorbers has been hindered by the instability of the photovoltaic-catalyst-electrolyte (PV+E) interfaces. Here, photolytic water splitting is demonstrated using an integrated configuration consisting of an HOIP/n⁺silicon single junction photoabsorber and a platinum (Pt) thin film catalyst. An extended electrochemical (EC) lifetime in alkaline media is achieved using titanium nitride on both sides of the Si support to eliminate formation of insulating silicon oxide, and as an effective diffusion barrier to allow high-temperature annealing of the catalyst/TiO₂-protected-n⁺silicon interface necessary to retard electrolytic corrosion. Halide composition is examined in the (FA_1-xCs_x)PbI₃ system with a bandgap suitable for tandem operation. A fill factor of 72.5% is achieved using a Spiro-OMeTAD-hole-transport-layer (HTL)-based HOIP/n⁺Si solar cell, and a high photocurrent density of −15.9 mA cm⁻² (at 0 V vs reversible hydrogen electrode) is attained for the HOIP/n⁺Si/Pt photocathode in 1 m NaOH under simulated 1-sun illumination. While this thin-film design creates stable interfaces, the intrinsic photo- and electro-degradation of the HOIP photoabsorber remains the main obstacle for future HOIP/Si tandem PEC devices.