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To determine the efficacy and safety profile of rhubarb and α-keto analogs of essential amino acids supplementation in patients of diabetic nephropathy (DN), we studied 96 patients of DN attending a tertiary care center of the North India. The patients were randomly divided into three equal interventional groups. Group I (control) that received conservative management along with placebo, Group II (rhubarb) that received conservative management along with rhubarb capsule (350 mg, thrice daily), and Group III [keto amino acid (KAA)] that received conservative management along with α-keto analogs of essential amino acids (600 mg, thrice daily). The treatment was continued for 12 weeks. Clinical and biochemical parameters were assessed at 0, 4, 8, and 12 weeks of treatment. A progressive improvement in clinical features and biochemical parameters was seen in all three groups after 12 weeks of treatment. The KAA group showed more marked improvement in clinical features as well as biochemical parameters compared to the rhubarb group. There was a reduction in blood glucose, blood urea, serum creatinine, and 24 h total urine protein. There was an increase in hemoglobin, 24 h total urine volume, and glomerular filtration rate. There was no statistical difference between the rhubarb and KAA groups with respect to side effects (P > 0.05). Our study suggests that KAA is more effective than rhubarb as add-on therapy with conservative management in patients of DN.

AIMS To investigate whether a fetal pathway of bile acid synthesis persists in neonates and infants. METHODS 3-oxo-Δ4 bile acids were determined qualitatively and quantitatively in the urine, meconium, and faeces of healthy neonates and infants, using gas chromatography–mass spectrometry. RESULTS The mean percentage of 3-oxo-Δ4 bile acids in total bile acids in urine at birth was significantly higher than that at 3 or 7 days, and at 1 or 3 months of age. The concentration of this component in meconium was significantly higher than that in faeces at 7 days and at 1 or 3 months of age. CONCLUSIONS The presence of large amounts of urinary 3-oxo-Δ4 bile acids may indicate immaturity in the activity of hepatic 3-oxo-Δ4-steroid 5β-reductase in the first week of postnatal life. Large amounts of this component in meconium may be due to the ingestion of amniotic fluid by the fetus during pregnancy.

Background The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Methods The study setting was on university hospital level with primary and secondary care functions in south-west Norway. Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n  = 25) or standard pre-operative fasting ( n  = 35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors ( n  = 18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group ( p  = 0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors ( r  = 0.680; p  = 0.002). In all tumors ( n  = 29), glutamate was increased in tumors with high proliferation (t-test; p  = 0.009), independent of intervention group. Moreover, there was a positive correlation between tumor size and proliferation markers in the carbohydrate group only. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Trial of registration ClinicalTrials.gov; NCT03886389 . Retrospectively registered March 22, 2019.

Biochemical studies of benzimidazole derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6·5 and 13 µ m of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.

Transforming waste materials into added-value products is critical for a sustainable and circular economy. Here, Mg/Fe layered double hydroxide (LDH) materials, with a Mg2+:Fe3+ ratio of 2, were successfully synthesized via the co-precipitation method from a dissolved acid mine drainage precipitate waste “ochre”, which is normally put to landfill. The prepared LDH materials were tested as a heterogeneous base catalyst to promote the production of the ketone, 12-tricosanone, from lauric acid, a component of plant oils, through a ketonic decarboxylation reaction, giving a circular economy route to catalysts for sustainable ketone production. The highest yield of the ketone observed was 80%.

A p-tert-octylcalix[4]arene derivative with four phenyl ketonic side arms has been synthesized as a solvent extraction reagent for precious metal ions in order to compare the extraction behavior with that of the corresponding methyl ketonic derivative of p-tert-octylcalix[4]arene in nitric acid media. The extraction efficiency of the phenyl ketonic derivative for palladium was superior to that of the methyl ketonic one over the whole nitric acid concentration range. Silver and platinum were also moderately extracted by the phenyl ketonic derivative in low nitric acid concentration. The results demonstrated that the extraction behavior of the ligands towards precious metals is related to several structural factors, such as the flexibility of the side arms, the electric charge on the carbonyl oxygen atoms and the lipophilic properties. This work also determined the extraction mechanism of palladium with the phenyl ketonic derivative of p-tert-octylcalix[4]arene based on slope analysis and the peak shift for the FT-IR spectra of the ligand before and after the metal loading. Stripping from the organic phase after forward extraction was performed to separate palladium and silver.

We report the isolation and characterization of a 1994-base-pair cDNA that encompasses the entire transcription unit of the mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase (EC4.1.3.5.) gene from rat. Analysis of the nucleotide sequence reveals that the cDNA encodes a polypeptide of 508 residues and 56,918-Da molecular mass. Identity of the cDNA clone isolated as mitochondrial HMG-CoA synthase was confirmed by the following criteria: (i) Amino acid residues are 65% homologous with hamster cytosolic HMG-CoA synthase. (ii) A 19-amino acid sequence probably corresponding to the catalytic site is highly homologous (90%) to that reported for chicken liver mitochondrial HMG-CoA synthase. (iii) The expression product of the cDNA in Escherichia coli has HMG-CoA synthase activity. (iv) The protein includes a sequence of 37 amino acid residues at the N terminus that is not present in the cytosolic enzyme. The predominantly basic, hydrophobic, and hydroxylated nature of the residues of this sequence suggests that it is a leader peptide to target HMG-CoA synthase inside mitochondria. These data plus the hybridization pattern in genomic Southern blot analysis, the different transcript size (2.0 kilobases versus 3.4 kilobases for the cytosolic enzyme), and the different expression pattern shown in RNA blot experiments suggest the presence of two HMG-CoA synthase genes, one for the cytosolic and another for the mitochondrial enzyme.

Porphyrins and chlorins containing acetylacetone residues in the peripheral substituents [-CH(Me)CHAc2] are converted under alkaline conditions into the corresponding deacetylated compounds with [-CH(Me)CH2Ac] residues. Reduction of the latter as acids using sodium borohydride gives the corresponding alcohols and, after esterification, their acetates with branched peripheral [-CH(Me)CH2CH(OAc)Me] substituents. Porphyrins and chlorins with such substituents in water-soluble form may hold interest as new photosensitizers in photodynamic cancer therapy.