Synthesis of alkali metal hexahydroaluminate complexes using dimethyl ether as a reaction medium

A novel method of preparation of hexahydroaluminate complexes M₃AlH₆ (M = Li, Na or K) from the corresponding alkali metal hydride and tetrahydroaluminate has been explored, using dimethyl ether (Me₂O) as a solvent at near-ambient temperatures. The results are compared with those obtained using a recently established mechanochemical approach. Characterization of the products by powder X-ray diffraction revealed M₃AlH₆ to be formed in high yield for M = Li and Na, but not for M = K. The attempted preparation of Li₂NaAlH₆ and Li₂KAlH₆ was unsuccessful.     

A cytotoxic substance produced by a wild culture of Lactobacillus casei D-34 against tumour cells

A wild lactic culture isolated from dahi (fermented milk) sample and characterised as L. casei D-34 was found to be significantly cytotoxic (34-36%) against three tumour cell lines, HeLa, HEp-2 and HFS-9. The cytotoxic substance (CS) was found to be in the culture supernatants, protein in nature, with a molecular weight ranging from 17,000-20,000. The crude culture supernatant was partially purified by dialysis and ion exchange chromatography as anionic, cationic and neutral fractions. Among the fractions, except for the anionic fraction, others were found to be highly cytotoxic against all three tumour cell lines. The cationic, neutral and pooled (anionic:cationic:neutral in 1:1:1 ratio) fractions showed 50, 70, 70% cytotoxicity against Hep-2 cells, 70, 88, 94% against HFS-9 cells and 50, 89, 90% against HeLa cells respectively. Pooled fraction was found to exhibit higher percent of cytotoxicity compared to individual fractions indicating a synergistic effect. (3H)-thymidine incorporation studies revealed that CS and its fractions inhibited DNA synthesis in tumour cells. The CS was stable towards heat and pH changes.     

Sleep patterns at an altitude of 3500 metres

Alterations in sleep pattern during acclimatisation at an altitude of 3500 m were studied on 27 healthy men (20–30 years of age). Of these, 15 were sojourners (SJ), 6 were acclimatised lowlanders (AL) and 6 were high altitude natives (HAN). Baseline sleep profile of SJ was electrophysiologically monitored, initially at Delhi (260 m) and later at 3500 m altitude in Western Himalayas for 2 weeks. At high altitude (HA) the sleep patterns of AL and HAN were also monitored for comparison. There were 4 cases of acute mountain sickness (AMS) among SJ, whose sleep profiles were also recorded. The state of autonomic arousal was assessed by a battery of indices, while the psychological arousal was measured by the anxiety scales. On completion of studies at HA, the SJ were flown back to the plains and re-tested within one week of return. SJ showed curtailment of slow wave sleep (SWS) and frequent short episodes of arousal during sleep at HA. AL and HAN also had lesser amounts of SWS; however, the arousals and awakenings during sleep were less frequent. Subjects who experienced AMS had normal amounts of SWS at HA. There was sympathetic hyperactivity and slight increase in anxiety level in SJ, while HAN and AL had relatively reduced level of sympathetic activity. The curtailment of SWS and frequent arousals observed in SJ during the initial phase of acclimatisation at HA, appear to be adaptive features to prevent the accentuation of arterial hypoxemia due to sleep hypoventilation.     

Metabolism of apolipoprotein E-containing human plasma lipoproteins by rat and human cells in culture.

Cultured preadipocytes from rat epididymal fat pads were able to bind, internalize, and degrade human plasma very-low-density lipoproteins (VLDL) more efficiently than low-density lipoproteins (LDL). VLDL, but not LDL, activated acyl-CoA: cholesterol acyltransferase (ACAT) and increased cholesterol accumulation in these cells. However, trypsin-treated VLDL (T-VLDL) lost the capacity to bind, activate ACAT, and increase cholesterol accumulation. After the treatment of VLDL with trypsin, SDS/polyacrylamide-gel electrophoresis and immunoblotting showed that apolipoprotein E (apo E) was completely degraded, whereas apolipoprotein CII (apo C-II) was preserved. ApoE complexed with dimyristoyl phosphatidylcholine (DMPC) was able to complete with VLDL for binding to the cells. Although T-VLDL did not bind to the preadipocytes, these cells accumulate triacylglycerols from T-VLDL, presumably after lipolysis, as efficiently as from native VLDL. Rat smooth muscle cells and skin fibroblasts also bind and metabolize human VLDL better than LDL. However, human skin fibroblasts and omental preadipocytes metabolized LDL better than VLDL. These studies indicate that rat tissues can recognize and metabolize apoE-containing human plasma VLDL although they cannot recognize human LDL.     

The metabolism of phenolic acids in the rat

Some of the enzyme systems in the formation of p-hydroxybenzoate from tyrosine have been studied in the rat liver in vitro. The conversion of p-hydroxycinnamate into p-hydroxybenzoate, which was found in rat liver mitochondria showed a number of differences when compared with the beta-oxidation of fatty acids. Studies with p-hydroxy[U-(14)C]cinnamate indicated that (14)CO(2) was released during the formation of p-hydroxybenzoate. The formation of p-hydroxycinnamate from tyrosine of p-hydroxyphenyl-lactate could not be demonstrated in vitro. The interconversion of p-hydroxycinnamate and p-hydroxyphenylpropionate was demonstrated in rat liver mitochondria.     

Comparison of phospho- and dephospho-ATP citrate lyase

The dephospho- form of rat liver citrate lyase has been prepared by treating purified [³²P]-ATP citrate lyase with a partially purified phosphatase. A comparison of the properties of the phospho- and dephosphoenzyme has been performed. The pH optima were the same for both forms of the enzyme in four different buffer systems although the optimum values varied identically for both enzyme forms with the buffer. Both the phospho- and dephosphoenzymes show the same kinetic properties except for the K_m observed for ATP in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer system where it was 54 μm for the phosphoenzyme and 292 μm for the dephosphoenzyme. The present study also indicates that both enzymes are cleaved by trypsin and lysosomal proteases in a similar manner. Both forms of the enzyme tend to associate with mitochondria to the same extent and both enzymes have identical temperature stability curves.     

Semaphorin 3A Is a New Early Diagnostic Biomarker of Experimental and Pediatric Acute Kidney Injury

Background

Semaphorin 3A is a secreted protein that regulates cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumor progression. However, nothing is known about its role in kidney pathophysiology. Here, we determined whether semaphorin3A is induced after acute kidney injury (AKI) and whether urinary semaphorin 3A can predict AKI in humans undergoing cardiopulmonary bypass (CPB).

Methods and Principal Findings

In animals, semaphorin 3A is localized in distal tubules of the kidney and excretion increased within 3 hr after reperfusion of the kidney whereas serum creatinine was significantly raised at 24 hr. In humans, using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine semaphorin increased at 2 hours after CPB, peaked at 6 hours (2596±591 pg/mg creatinine), and was no longer significantly elevated 12 hours after CPB. The predictive power of semaphorin 3A as demonstrated by area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.88, 0.81, and 0.74, respectively. The 2-hour urine semaphorin measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay. Adjusting for CPB time and gender, the 2-hour semaphorin remained an independent predictor of AKI, with an odds ratio of 2.19.

Conclusion

Our results suggest that semaphorin 3A is an early, predictive biomarker in experimental and pediatric AKI, and may allow for the reliable early diagnosis and prognosis of AKI after CPB, much before the rise in serum creatinine.     

2,4,6-Triphenylaniline nanoemulsion formulation,optimization, and its application in type 2 diabetes mellitus

The secondary metabolite 2,4,6-triphenylaniline (TPA) was isolated from an endophytic fungi Alternaria longipes strain VITN14G of mangrove plant Avicennia officinalis, that exhibited satisfactory in vitro antidiabetic activity for type 2 diabetes mellitus (T2DM). The TPA was encapsulated using nanoemulsion (NE) to overcome the problem of stability and permeability to increase its therapeutic applications. Response surface methodology (RSM) was used for the optimization of the variables given, such as hydrodynamic diameter, surface charge, and polydispersity index (PDI). TPA was encapsulated using an optimized ratio of olive oil and tween 80 (2:1) significantly affected the response variables including particle size (124.8 nm), ζ potential (−46.0 mV), and PDI (0.396), and the encapsulation efficiency was found to be 95.93%. The TPA-loaded NE after MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis showed nontoxic effects on L929 normal cell lines (areolar and adipose subcutaneous connective tissue of Mus musculus) with a viable percentage of 92%. In vitro release study revealed the slow and sustained release of the TPA over 48 hrs from NE under the Fickian diffusion mechanism and followed the Higuchi model for release kinetics. Further, the percentage of α-glucosidase and α-amylase inhibition rate of TPA-loaded NE was found to be 78.5 and 43.42%, respectively. The present study, therefore, can aid in the development of a novel drug delivery system as a therapeutic approach to T2DM.     

Construction and structure studies of DNA-bipyridine complexes as versatile scaffolds for site-specific incorporation of metal ions into DNA

The facile construction of metal–DNA complexes using ‘Click’ reactions is reported here. A series of 2′-propargyl-modified DNA oligonucleotides were initially synthesized as structure scaffolds and were then modified through ‘Click’ reaction to incorporate a bipyridine ligand equipped with an azido group. These metal chelating ligands can be placed in the DNA context in site-specific fashion to provide versatile templates for binding various metal ions, which are exchangeable using a simple EDTA washing-and-filtration step. The constructed metal–DNA complexes were found to be thermally stable. Their structures were explored by solving a crystal structure of a propargyl-modified DNA duplex and installing the bipyridine ligands by molecular modeling and simulation. These metal–DNA complexes could have wide applications as novel organometallic catalysts, artificial ribonucleases, and potential metal delivery systems.