Impact of recurrent lupus nephritis on lupus kidney transplantation

This study was conducted to delineate the frequency of recurrent lupus nephritis in a Chinese kidney transplant cohort and to estimate its impact on long-term transplant outcomes. A total of 32 lupus transplant patients were enrolled in this study, and the medical records were retrospectively reviewed. Patients with unexplained graft abnormalities were subjected to allograft biopsy. Recurrent lupus nephritis was diagnosed by light microscopy, immunofluorescence, and electron microscopy. In addition, to determine the clinical manifestations of recurrent lupus GN in these patients, serum original systemic lupus erythematosus disease activity index (SLEDAI) scores while undergoing allograft biopsy were evaluated. In total, six out of 32 patients (18.8%; mean age, 40.5 ± 9.1 years) were diagnosed as having recurrent lupus nephritis and the mean time at diagnosis was 5.1 ± 4.9 years post-transplantation. According to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 criteria, three of the six cases (50%) were defined as class I, one was class II, one was class IV, and one was class III + V. The graft and patient survival rates of recurrent lupus nephritis (n = 6) were not different from those of patients with other diagnostic entities. Although recurrent lupus nephritis was not uncommon, it did not appear to have a strong negative impact on long-term outcome in Chinese kidney transplant patients. The recurrence was potentially treatable and should not be precluded for receiving transplantation.     

Parameter control and property analysis in the preparation of platinum iodide nanocolloids through the electrical spark discharge method

This study employed the electrical spark discharge method to prepare platinum iodide nanocolloids at normal temperature and pressure. Wires composed of 99.5% platinum were applied as the electrodes, and 250 ppm liquid iodine was employed as the dielectric fluid. An electric discharge machine was applied to generate cyclic direct current pulse power between the electrodes. Five sets of turn-on and turn-off time (T_on–T_off) parameters, namely 10–10, 30–30, 50–50, 70–70, and 90–90 μs, were implemented to identify the optimal nanocolloid preparation conditions. An ultraviolet-visible spectroscope, a Zetasizer, and a transmission electron microscope were used to examine the nanocolloids'' properties. The results revealed that the T_on–T_off parameter set of 10–10 μs was the most ideal setting for platinum iodide nanocolloid preparation. With this parameter set, the characteristic wavelengths of the nanocolloid were 285 and 350 nm, respectively; its absorbance values were 0.481 and 0.425, respectively; and its zeta potential and particle size were −30.3 mV and 61.88 nm, respectively. This parameter set yielded maximized absorbance, satisfactory suspension stability, and minimized nanoparticle sizes for the nanocolloid.

This study employed the electrical spark discharge method to prepare platinum iodide nanocolloids at normal temperature and pressure.     

Design,synthesis, crystal structure,bioactivity, and molecular docking studies of novel sulfonylamidine-derived neonicotinoid analogs

Two novel series of sulfonylamidine-derived neonicotinoid analogues were designed and synthesized via a Cu-catalyzed one pot reaction. The structures of the target compounds were characterized by ¹H-NMR, ¹³C-NMR, HR-MS and the single-crystal structure of 14k was further determined by X-ray diffraction crystallography. In preliminary bioassays, many of the target compounds exhibited significant activity against Tetranychus cinnabarinus (carmine spider mite) and Brevicoryne brassicae (cabbage aphid). Some structural features important for potency were observed, and a model of the ligand–receptor complex was also generated with a molecular docking study using representative active analogues. The molecular binding mode observed at the active site of the nicotinic acetylcholine receptor model should provide useful information for future structure-based design of novel sulfonylamidine-derived neonicotinoid analogues.     

Identification and Synthesis of Quinolizidines with Anti-Influenza A Virus Activity

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Recent advances in the investigation of curcuminoids

More than 30 Curcuma species (Zingiberaceae) are found in Asia, where the rhizomes of these plants are used as both food and medicine, such as in traditional Chinese medicine. The plants are usually aromatic and carminative, and are used to treat indigestion, hepatitis, jaundice, diabetes, atherosclerosis and bacterial infections. Among the Curcuma species, C. longa, C. aromatica and C. xanthorrhiza are popular. The main constituents of Curcuma species are curcuminoids and bisabolane-type sesquiterpenes. Curcumin is the most important constituent among natural curcuminoids found in these plants. Published research has described the biological effects and chemistry of curcumin. Curcumin derivatives have been evaluated for bioactivity and structure-activity relationships (SAR). In this article, we review the literature between 1976 and mid-2008 on the anti-inflammatory, anti-oxidant, anti-HIV, chemopreventive and anti-prostate cancer effects of curcuminoids. Recent studies on curcuminoids, particularly on curcumin, have discovered not only much on the therapeutic activities, but also on mechanisms of molecular biological action and major genomic effects.     

Anti-HIV agents derived from the ent-kaurane diterpenoid linearol

Twenty-six semisynthetic ent-kaurane derivatives of linearol (1) have been investigated for their anti-HIV effects. Five compounds (4, 7, 11, 25, and 26) showed significant activity against HIV replication in H9 lymphocyte cells with EC(50) values in the range <0.1-3.11 microg/mL. With TI values of 163 and 184, compounds 4 and 25 are especially promising for further development as potential anti-HIV agents.     

Interiotherins C and D,two new lignans from Kadsura interior and antitumor-promoting effects of related neolignans on Epstein-Barr virus activation

Two new lignans, interiotherins C (1) and D (2), together with the known compounds interiorin (3), heteroclitin F (4), neokadsuranin (5), heteroclitin D (6), kadsurin (7), gomisin A (8), schisandrin C (9), interiotherin A (10), angeloylgomisin R (11), gomisin G (12), interiotherin B (13), and gomisin C (14), were isolated from the stems of Kadsura interior. The structures and stereochemistries of the new compounds were determined from mass, CD, and NMR spectral data. Fourteen neolignans were screened as potential antitumor promoters by examining their ability to inhibit Epstein-Barr virus early antigen (EBV-EA) activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. Neokadsuranin (5) and schisandrin C (9) were the most potent compounds. These data suggest that some neolignans might be valuable antitumor promoters or chemopreventors.     

Structural characterization of anti-HIV drug candidate PA-457 [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] and its acyl glucuronides in rat bile and evaluation of in vitro stability in human and animal liver microsomes and plasma.

PA-457 [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] represents a new class of anti-HIV drug candidates termed maturation inhibitors. After oral administration to rats, PA-457 was metabolized to several glucuronide conjugates and mainly eliminated into rat bile. Liquid chromatography-electrospray ionization-mass spectrometry analysis showed that the glucuronidation products of PA-457 were acyl glucuronides including one di-glucuronide, di-PA-457G, and two mono-glucuronides, referred to as mono-PA-457G (I) and mono-PA-457G (II), respectively. In-source fragmentation of MS spectra supported the conclusion that mono-PA-457G (I) was glucuronidated at the C-28 carboxyl of PA-457, whereas mono-PA-457G (II) was conjugated at the dimethylsuccinic acid side chain of the C-3 position. Quantification demonstrated that the predominant glucuronide of PA-457 in rat bile was mono-PA-457G (I) with lower amounts of mono-PA-457G (II) and di-PA-457G. In vitro stability indicated that the mono-acyl glucuronides of PA-457 were not degraded after incubation with 0.1 M phosphate buffer (pH 4, 7.4 and 9), plasma (human, rat, and mouse), and UDP-glucuronosyltransferase reaction media (without uridine 5'-diphosphoglucuronic acid) with microsomes (human, rat, and mouse liver microsomes), respectively, whereas the minor diglucuronide was unstable in rodent liver microsomes. All glucuronides of PA-457 could be hydrolyzed both by beta-glucuronidase and alkaline (1 M NaOH). Minor putative acyl migration products were slowly formed at pH 9, suggesting that the acyl glucuronides of PA-457 have relatively high in vitro stability.     

Multiple myeloma-associated cast nephropathy with crystal structure: case report and review of the literature

The causes of renal failure are diverse. Among them, monoclonal gammopathy is one important but easily-missed cause in aged people. Monoclonal gammopathy may produce a large number of abnormal immunoglobulins and/or fragments and produce different kinds of deposition in tissues, including cast, crystal, fibril and granules. Cast nephropathy is considered the hallmark of the renal disease in patients with multiple myeloma. Crystaglobulinemia syndrome and crystal nephropathy, on the other hand, have been rarely reported. Herein, we report a case of multiple myeloma presented with irreversible renal failure. The biopsy showed massive crystal deposition in bone marrow and kidneys.     

Plasma pyridoxal 5'-phosphate is a significant indicator of immune responses in the mechanically ventilated critically ill

OBJECTIVES: This study assessed the effect of vitamin B6 status on immune responses in mechanically ventilated, critically ill patients and compared the results with those of healthy controls. METHODS: This was designed as a cross-sectional observational study. Forty patients in the intensive care unit successfully completed this study. Vitamin B6 intake was recorded for 8 d. Severity of illness (Second Acute Physiology and Chronic Health Evaluation score) was recorded. Thirty-eighty healthy controls were recruited from the physical check unit of Taichung Veterans General Hospital (Taichung, Taiwan). All control subjects were given instruction on how to complete a 24-d diet recall. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5'-phosphate [PLP] and 4-pyridoxic acid) and indirect measures (erythrocyte alanine and aspartate aminotransferase activity coefficients). Levels of serum albumin, hemoglobin, hematocrit, high-sensitivity C-reactive protein, and immune responses (white blood cell, neutrophil, total lymphocytes, T lymphocytes [CD3], B lymphocytes [CD19], T-helper cells [CD4], and suppressor cells [CD8]) were determined. RESULTS: Critically ill patients had sufficient vitamin B6 intake but showed marginal PLP deficiency (20.9 +/- 1.5 nmol/L). In addition, critically ill patients had significantly lower and abnormal immune responses than did healthy controls. There was no significant correlation of vitamin B6 intake and erythrocyte alanine and aspartate aminotransaminase activity coefficients with immune indices. Plasma PLP concentration was strongly negatively correlated with high-sensitivity C-reactive protein level. However, plasma PLP was significantly associated with immune responses after adjustment for age, sex, high-sensitivity C-reactive protein, and the other four vitamin B6 indicators. CONCLUSIONS: Plasma PLP is a significant indicator of immune responses in human subjects. Further research is warranted to study whether vitamin B6 supplementation in critically ill patients improves their immune responses.