Synthesis and Anticonvulsant Activity of Some Cyclohexanone Derivatives – Knoevenagel Condensation Products

Pharmaceutical Chemistry Journal - Aseries of diethyl esters of 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylic acids (β-cycloketols) were synthesized by Knoevenagel condensation....     

Properties of cells with increased resistance to some picornaviruses

The resistance to picornaviral infection cells of susceptible lines has similar changes in the phenotype. They have decreased number of nucleoli and increased percentage of euploidy. Also the percentage of euploid cells those were resistant to the picornaviral infection increased in all highly transformed cultures. In resistant cells of all cultures has been found reduction of DNA. RNA amount also decreased both in nucleus and in cytoplasm. All these data correlated with the increased euploidy of the resistant population. The resistant cells had a less transformed phenotype, and decreased proliferative activity. Decreased nucleolar status became apparent by reduction of absolute and relative nucleolar indices. Consequently the reduction of viral titer (viral titters reduction) in resistant cells could be the direct result of diminished activity of the RNA synthesis machinery. It is important to note that the cells lose resistance while another type of virus, even from the same family, infects the culture once.     

Complement activation in leprosy: a retrospective study shows elevated circulating terminal complement complex in reactional leprosy

Mycobacterium leprae infection gives rise to the immunologically and histopathologically classified spectrum of leprosy. At present, several tools for the stratification of patients are based on acquired immunity markers. However, the role of innate immunity, particularly the complement system, is largely unexplored. The present retrospective study was undertaken to explore whether the systemic levels of complement activation components and regulators can stratify leprosy patients, particularly in reference to the reactional state of the disease. Serum samples from two cohorts were analysed. The cohort from Bangladesh included multi‐bacillary (MB) patients with (n = 12) or without (n = 46) reaction (R) at intake and endemic controls (n = 20). The cohort from Ethiopia included pauci‐bacillary (PB) (n = 7) and MB (n = 23) patients without reaction and MB (n = 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P ≤ 0·01), C4d (P ≤ 0·05) and iC3b (P ≤ 0·05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P ≤ 0·001 without R; P < 0·05 with R) were also elevated in MB patients, irrespective of a reaction. Similar analysis of the Ethiopian cohort confirmed that, irrespective of a reaction, serum TCC levels were increased significantly in patients with reactions compared to patients without reactions (P ≤ 0·05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions.     

Intraarticular factor IX protein or gene replacement protects against development of hemophilic synovitis in the absence of circulating factor IX

Hemophilic bleeding into joints causes synovial and microvascular proliferation and inflammation (hemophilic synovitis) that contribute to end-stage joint degeneration (hemophilic arthropathy), the major morbidity of hemophilia. New therapies are needed for joint deterioration that progresses despite standard intravenous (IV) clotting factor replacement. To test whether factor IX within the joint space can protect joints from hemophilic synovitis, we established a hemophilia B mouse model of synovitis. Factor IX knockout (FIX(-/-)) mice received a puncture of the knee joint capsule with a needle to induce hemarthrosis; human factor IX (hFIX) was either injected through the needle into the joint space (intraarticularly) or immediately delivered IV. FIX(-/-) mice receiving intraarticular FIX protein were protected from synovitis compared with mice receiving same or greater doses of hFIX IV. Next, adeno-associated virus (AAV) gene transfer vectors expressing hFIX were injected into knee joints of FIX(-/-) mice. Joints treated with 10(10) vector genomes (vg)/joint AAV2-, AAV5-, or AAV8-hFIX or 2.5 x 10(9) vg/joint AAV5-hFIX developed significantly fewer pathologic changes 2 weeks after injury compared with the pathology of control injured contralateral hind limbs. Extravascular factor activity and joint-directed gene transfer may ameliorate hemophilic joint destruction, even in the absence of circulating FIX.