Sodium Carbonate-Promoted Formation of 5-Amino-1,2,4-thiadiazoles and 5-Amino-1,2,4-selenadiazoles with Elemental Sulfur and Selenium.

Sodium carbonate-promoted facile synthesis of 5-amino-1,2,4-thiadiazoles and 5-amino-1,2,4-selenadiazoles with elemental sulfur and selenium, respectively, was developed. This method was carried out with O2 in the air as the green oxidant, and it has several advantages, including low cost, low toxicity, and stable sulfur and selenium sources, good to excellent yields with water as the sole byproduct, simple operation, and a broad substrate scope. Preliminary mechanistic studies indicate that the formation of the 1,2,4-thiadiazole ring and the 1,2,4-selenadiazole ring undergoes different processes.

Three-Component Domino Reaction of Thioamide, Isonitriles, and Water: Selective Synthesis of 1,2,4-Thiadiazolidin-3-ones and (E)-N-(1,2-Diamino-2-thioxoethylidene)benzamides.

The three-component domino reaction of thioamides, benzyl isocyanide, and water in the presence of a catalytic amount of both Pd(dppf)Cl2 and Cu(OAc)2 afforded novel 1,2,4-thiadiazolidin-3-one cyclic compounds, whereas the same reaction with tertiary alkylisonitriles in the presence of rare earth metal salt [La(OTf)3] resulted in (E)-N-(1,2-diamino-2-thioxoethylidene)benzamide open-chain products. This divergent reaction enabled the one-pot construction of five (N-S, C-S, C-O, and two C-N) or four (C-S, C-N, C-O, and C-C) new chemical bonds. Mechanism studies indicate that the oxygen atom of the product was derived from H2O.

Aerobic Copper-Catalyzed Four-Component Reaction of O-Phenylenediamines, Isocyanides, and Selenium Powder for the Assembly of Benzo[4,5]imidazo[2,1-c][1,2,4]selenadiazol-3-imine Derivatives.

A convenient, four-component reaction of o-phenylenediamines, isocyanides, and selenium powder catalyzed by a natural abundant copper/air (O2) catalyst system has been developed, providing a highly step and atom economical protocol for the synthesis of benzo[4,5]imidazo[2,1-c][1,2,4]selenadiazol-3-imine derivatives with excellent yields and good functional group tolerance. This method enables the construction of an imidazo[2,1-c][1,2,4]selenadiazol ring, one N-Se bond, one C-Se bond, and three C-N bonds in a single step with only water as the byproduct. Preliminary mechanistic studies imply that the copper/air (O2)-catalyzed cyclization proceeds via a selenium-centered radical intermediate.

Palladium-catalyzed double coupling reaction of terminal alkynes with isocyanides: a direct approach to symmetrical N-aryl dialkynylimines.

A novel and efficient one-pot synthesis of symmetrical N-aryl dialkynylimines via palladium-catalyzed and copper-promoted isocyanide insertion, cross-coupling and elimination has been developed. This method features readily available starting materials, mild reaction conditions and high atom efficiency as well as simple one-pot operation, which make this strategy highly attractive. Moreover, 2-iodobenzo[f]quinoline derivatives can be obtained via electrophilic cyclization of N-aryl dialkynylimines.

Facile synthesis of 2-alkynyl oxazoles via a Ce(OTf)3-catalyzed cascade reaction of alkynyl carboxylic acids with tert-butyl isocyanide.

We developed an efficient and novel protocol to synthesize 2-alkynyl oxazoles from tert-butyl isocyanide and alkynyl carboxylic acids. This method allowed the synthesis of diversely functionalized oxazoles under mild reaction conditions, coupled with operational simplicity and these functionalized oxazoles showed a certain degree of biological activity. Moreover, compounds 2b, 2h, 2k, 2n, 2p and 2t exhibited good anticancer activities in human gastric cancer cells (MGC803) and human bladder tumor cells (T24), with IC50 below 20.0 µM.

Relationship Between Serum DNA Replication, Clinicopathological Characteristics and Prognosis of Hepatitis B Virus-associated Glomerulonephritis with Severe Proteinuria by Lamivudine Plus Adefovir Dipivoxil Combination Therapy.

OBJECTIVE: To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. METHODS: 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. RESULTS: Several findings were demonstrated with the increase of serum HBV DNA: 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly (P%lt;0.05), while the plasma level of albumin decreased significantly (P%lt;0.05); The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group (P%lt;0.01). CONCLUSION: With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

[Triptolide combined with irbesartan synergistically blocks podocyte injury in a type 2 diabetes rat model].

OBJECTIVE: To investigate the protective effect of combination of triptolide and irbesartan on the podocytes in a type 2 diabetic(T2DM) rat model, and evaluate its mechanism. METHODS: T2DM rats were induced by fed with high-sucrose-high-fat diet combined with a low dose of streptozocin. The rats were randomly divided into 5 groups: normal control group (NC, n = 10), diabetes group (DM, n = 11), triptolide treatment group (DT, n = 12), irbesartan treatment group (DI, n = 12) and triptolide combined with irbesartan treatment group (DTI, n = 13). Ultrastructure of podocytes was observed by electronic microscopy and urinary albumin (UAL) excretion by ELISA was determined after 8 weeks. The expression of nephrin and bone morphogenetic protein-7 (BMP-7), connective tissue growth factor (CTGF), transforming growth factor (TGF)ß(1) mRNA and proteins were detected by immunohistochemistry, real-time PCR and Western blot. RESULTS: Increased UAL was significantly attenuated in all treatment groups. Compared to NC group, UAL in DM group was increased significantly (0.45 ± 0.09 vs 6.36 ± 0.87, P < 0.01), while decreased in triptolide or irbesartan alone treatment group (2.48 ± 0.37 and 2.68 ± 0.42, both P < 0.01). Compared with those in control groups, kidney expression of nephrin, BMP-7 mRNA and proteins were downregulated while CTGF, TGFß(1) mRNA and proteins were significantly upregulated in T2DM rats. Triptolide or irbesartan each alone moderately ameliorated albuminuria and podocyte damage. However, their combined usage showed a dramatic therapeutic synergism, manifested by prevention of progressive albuminuria, restoration of the glomerular filtration barrier, reversal of the decline in slit diaphragm proteins, reduction expression of CTGF, TGFß(1), and upregulation of BMP-7. CONCLUSION: Our findings show that triptolide can increase the efficacy of irbesartan, leading to a more effective prevention of kidney disease in T2DM rat model, which may through upregulation of BMP-7 and inhibition the over-expression of CTGF and TGFß(1).

[Diagnosis and treatment of eye diseases associated with HIV infection and AIDS].

OBJECTIVE: To investigate the manifestations and treatment principles of ocular diseases associated with human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS). METHODS: It was a retrospective case series. One hundred and ten patients were recruited. Two hundred and twenty eyes underwent ophthalmologic examination that included vision acuity, anterior segment and fundus examinations with papillary dilation and fundus fluorescein angiography. CD(4)(+)T-lymphocyte was counted in peripheral blood of 110 patients. Intravitreal injection of ganciclovir 400 microg was performed in 4 eyes (2 patients) with cytomegalovirus (CMV) retinitis associated with AIDS. All statistical analyses were performed using SPSS 13.0 software. The association between the age, duration of HIV infection and HIV/AIDS related ocular manifestations was analyzed by Pearson Correlation Analysis. The association between the gender and HIV/AIDS related ocular manifestations was analyzed by Pearson Chi-Square test. For comparison of the CD(4)(+)T cells counts of the patients with normal fundus, HIV retinopathy, CMV retinitis, Kruskal-Wallis Test for Several Independent Samples was used. RESULTS: Baseline visual acuity: no light perception (NLP) 5 eyes; light perception (LP) to 0.04, 10 eyes; 0.05 to 0.2, 14 eyes; 0.3 to 0.7, 62 eyes and >/= 0.8, 129 eyes. Small grayish keratin precipitates or pigment keratin precipitates were present in 25 eyes, 22 eyes had positive aqueous flare, 4 eyes had posterior synechia of the iris, 28 eyes had cataract. HIV retinopathy was present in 34 eyes. Cotton-wool spots, retinal hemorrhages, and retinal microaneurysms were found in eyes with HIV retinopathy. CMV retinitis was present in 32 eyes. The fundus manifestations of CMV retinitis included retinal vasculitis; dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface in 26 eyes. Late stage retinopathy was demonstrated in 3 eyes characterized as atrophic retina, sclerotic and attenuated vessels, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The median of CD(4)(+)T-lymphocyte counts of the patients with normal fundus was 100.0/mm(3). The median of CD(4)(+)T-lymphocyte counts of the patients with HIV retinopathy was 41.0/mm(3). The median of CD(4)(+)T-lymphocyte counts of the patients with CMV retinitis was 18.0/mm(3). The difference of CD(4)(+)T-lymphocyte counts between patients with normal fundus and HIV retinopathy was statistically significant (chi(2) = 4.848, P = 0.028). The difference of CD(4)(+)T-lymphocyte counts between patients with normal fundus and CMV retinitis was statistically significant (chi(2) = 15.696, P = 0.000). The difference of CD(4)(+)T-lymphocyte counts between patients with CMV retinitis and HIV retinopathy was statistically significant (chi(2) = 4.860, P = 0.027). Four eyes (2 patients) with CMV retinitis underwent intravitreal injection of ganciclovir 400 microg. After intravitreal injection of ganciclovir, visual acuity was improved and fundus lesions disappeared in 4 eyes. CONCLUSIONS: HIV retinopathy is a common intraocular complication in HIV-infected patients. CMV retinitis is the severest intraocular complication in patients with AIDS. Highly active anti-retroviral therapy allows immune reconstitution. Intravitreal injection of ganciclovir can effectively control CMV retinitis and save the vision.

[Effect of content of hepatitis B virus DNA in the serum on the pathologic change in hepatitis B virus associated-glomerulonephritis].

OBJECTIVE: To investigate the correlation between the content of hepatitis B virus DNA(HBV-DNA) in the serum and the pathologic change in hepatitis B virus associated-glomerulonephritis (HBV-GN). METHODS: Forty one HBV-GN patients were divided into 3 groups by the content of HBV-DNA in the serum:low replicate group,midrange replicate group, and high replicate group. The relationship with the content of HBV-DNA in the serum and pathologic stage or change was analyzed in 35 membranous glomerulopathy patients; Effect of the content of hepatitis B virus DNA in the serum on HBVAg deposition in glomeruli of kidney was examined by immunohistochemistry; Effect of HBVAg deposition on pathologic change was observed in membranous glomerulopathy patients. RESULTS: With the multiplication of HBV-DNA in the serum, the pathologic lesion was aggravating from Stage I to Stage III in membranous glomerulopathy patients; the deposition of HBVAg in glomeruli of kidney was increasing; with the increasing of deposition of HBVAg in glomeruli of kidney, the pathologic lesion was aggravating in membranous glomerulopathy patients. CONCLUSION: With the multiplication of HBV-DNA in the serum, the deposition of HBVAg in glomeruli of kidney increases, and the pathologic lesion aggravates, which have significant correlation.