Search

Fumiko Watanabe,1 Erika Hashizume,1 Gertrude P Chan,2 Ayako Kamimura11Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., Tsukuba, Ibaraki, Japan; 2Clinical Trial Management and Testing Associates, Inc., Filinvest Corporate City, Alabang, Muntinlupa City, PhilippinesPurpose: Glutathione is a tripeptide consisting of cysteine, glycine, and glutamate and functions as a major antioxidant. It is synthesized endogenously in humans. Glutathione protects thiol protein groups from oxidation and is involved in cellular detoxification for maintenance of the cell environment. Reduced glutathione (GSH) has a skin-whitening effect in humans through its tyrosinase inhibitory activity, but in the case of oxidized glutathione (GSSG) this effect is unclear. We examined the skin-whitening and skin-condition effects of topical GSSG in healthy women.Subjects and methods: The subjects were 30 healthy adult women aged 30 to 50 years. The study design was a randomized, double-blind, matched-pair, placebo-controlled clinical trial. Subjects applied GSSG 2% (weight/weight [w/w]) lotion to one side of the face and a placebo lotion to the other side twice daily for 10 weeks. We objectively measured changes in melanin index values, moisture content of the stratum corneum, smoothness, wrinkle formation, and elasticity of the skin. The principal investigator and each subject also used subjective scores to investigate skin whitening, wrinkle reduction, and smoothness. Analysis of variance was used to evaluate differences between groups.Results: The skin melanin index was significantly lower with GSSG treatment than with placebo from the early weeks after the start of the trial through to the end of the study period (at 10 weeks, P

Both lipoprotein glomerulopathy (LPG) and fibrillary glomerulonephritis (FGN) are rare causes of end-stage renal disease (ESRD), and the literature concerning the outcome of kidney transplant in patients with LPG or FGN is scarce. We report a patient who suffered from ESRD with coexisting FGN and LPG and received deceased kidney transplant >10 years ago did not reveal any clinical features of disease recurrence during follow-up. Our case shows that the prognosis of patients with LPG component who received kidney transplant can be good. Kidney transplantation remains a viable therapeutic option for patients with ESRD secondary to FGN with LPG.

Background: The FHIT tumor suppressor gene is arguably the most commonly altered gene in cancer since it is inactivated in about 60% of human tumors. The Fhit protein is a member of the ubiquitous histidine triad proteins which hydrolyze dinucleoside polyphosphates such as Ap3A. Despite the fact that Fhit functions as a tumor suppressor, the pathway through which Fhit inhibits growth of cancer cells remains largely unknown. Phosphorylation by Src tyrosine kinases provides a linkage between Fhit and growth factor signaling. Since many G proteins can regulate cell proliferation through multiple signaling components including Src, we explored the relationship between Gα subunits and Fhit., Results: Several members of the Gαq subfamily (Gα16, Gα14, and Gαq) were found to co-immunoprecipitate with Fhit in their GTP-bound active state in HEK293 cells. The binding of activated Gαq members to Fhit appeared to be direct and was detectable in native DLD-1 colon carcinoma cells. The use of Gα16/z chimeras further enabled the mapping of the Fhit-interacting domain to the α2-β4 region of Gα16. However, Gαq/Fhit did not affect either Ap3A binding and hydrolysis by Fhit, or the ability of Gαq/16 to regulate downstream effectors including phospholipase Cβ, Ras, ERK, STAT3, and IKK. Functional mutants of Fhit including the H96D, Y114F, L25W and L25W/I10W showed comparable abilities to associate with Gαq. Despite the lack of functional regulation of Gq signaling by Fhit, stimulation of Gq-coupled receptors in HEK293 and H1299 cells stably overexpressing Fhit led to reduced cell proliferation, as opposed to an enhanced cell proliferation typically seen with parental cells., Conclusions: Activated Gαq members interact with Fhit through their α2-β4 region which may result in enhancement of the growth inhibitory effect of Fhit, thus providing a possible avenue for G protein-coupled receptors to modulate tumor suppression.

Lipoprotein glomerulopathy is a rare kidney disease in which lipoprotein thrombi are seen in the glomerular capillaries. Most of these patients are found in Japan and East Asian countries. The presenting symptoms include proteinuria, an abnormal plasma lipoprotein profile that resembles type III hyperlipoproteinaemia, and a marked increase in serum apolipoprotein E concentration. Previous studies have suggested that lipoprotein glomerulopathy might be related to APOE gene mutation. No effective therapeutic regimen has been established for lipoprotein glomerulopathy. We report the first case of biopsy-proven lipoprotein glomerulopathy in Hong Kong in a patient who presented with nephrotic syndrome and dyslipidaemia. DNA analysis revealed apolipoprotein E Kyoto together with a novel apolipoprotein E mutation, apolipoprotein E (Asp230Tyr) Hong Kong. There was significant improvement in the clinical parameters and resolution of symptoms after the introduction of statins. Further studies will be needed to clarify the role of apolipoprotein E Hong Kong and its interaction with apolipoprotein E Kyoto in the pathogenesis of lipoprotein glomerulopathy.

Fusidic acid was assessed for antileprosy activity in nine lepromatous leprosy patients. Patients received fusidic acid at either 500 mg/day for 12 weeks or 750 mg/day for 4 weeks followed by 500 mg/day for 8 weeks. All patients showed time-dependent clinical improvement and decreases in bacillary morphological index, radiorespirometric activity and PCR signal, and in serum phenolic glycolipid I. Fusidic acid appears to be a weakly bactericidal antileprosy agent which may have a role in the multidrug treatment of leprosy pending an evaluation of lepra-reaction-suppressive activity.

Clarithromycin was administered to nine previously untreated lepromatous leprosy patients. Patients received two 1,500-mg doses on the first day, followed by 7 days of no treatment, in order to evaluate the potential efficacy of intermittent therapy. Patients then received 1,000 mg daily for 2 weeks followed by 500 mg daily for 9 weeks. The efficacy of therapy was monitored clinically, by changes in morphological index, mouse footpad infectivity, and radiorespirometric activity of Mycobacterium leprae obtained from serial biopsies and by serum levels of phenolic glycolipid I. Clarithromycin was well tolerated, with only minor side effects noted in two patients. Most patients showed reductions in morphological index and radiorespirometry 1 week after the first two doses. Within 3 weeks of starting treatment (total of 17 g of clarithromycin), biopsy-derived M. leprae specimens from all patients had a morphological index of zero, were noninfectious for mice, and had less than 1% of the radiorespirometric activity of pretreatment specimens. Reductions in serum phenolic glycolipid I levels were observed for most patients at 3 weeks. Significant clinical improvement was evident after 4 weeks of treatment. All analyses indicate that clarithromycin is rapidly bactericidal for M. leprae in humans.

Nine previously untreated patients with lepromatous leprosy were treated with 200 mg of sparfloxacin daily for 12 weeks to determine whether this drug is bactericidal for Mycobacterium leprae in humans. The efficacy of therapy was monitored both clinically and by measuring changes in morphological index, mouse footpad infectivity, and the radiorespirometric activity of M. leprae organisms obtained from serial biopsy specimens and also by determining titers of phenolic glycolipid-I in serum. Most patients showed clinical improvement within 2 weeks of treatment; this was accompanied by significant reductions in the morphological index, mouse footpad infectivity, and bacillary radiorespirometric activity. After 4 weeks of treatment, all patients had a morphological index of zero and specimens from most patients were noninfectious for mice, while the median decrease in radiorespirometric activity was > 99%. Overall results by the rapid radiorespirometric assay paralleled those of the mouse footpad and morphological index assays. Sparfloxacin given at 200 mg once daily appears to be rapidly bactericidal in humans, with activity similar to that observed in a previous clinical trial with 400 mg of ofloxacin.

The effects of standard fixatives (10% neutral buffered formalin, ethanol and mercury based) on the detection of Mycobacterium leprae DNA by the polymerase chain reaction (PCR) were studied. Mercury-based fixatives (Zenker's and Carnoy-Lebrun's fluids) strongly inhibited PCR amplification of M. leprae DNA. Ten percent neutral buffered formalin was inhibitory, but significant inhibition was observed only when fixation times exceeded 24 h. Ethanol-based fixatives provided the best medium for holding specimens for subsequent PCR with both free bacilli and skin biopsy specimens containing M. leprae. The M. leprae-specific, 360-bp region of the 18-kDa protein gene could be amplified from paraffin-embedded sections of formalin-fixed skin biopsy specimens from patients with either multibacillary or paucibacillary infections when proper fixation conditions were used. Results of the study demonstrate that tissues properly fixed with two standard fixatives (10% neutral buffered formalin and 50 or 70% ethanol) can be analyzed by PCR for the presence of M. leprae with no loss in specificity and only minimal diminution in sensitivity compared with the specificities and sensitivities obtained by use of freshly prepared, unfixed specimens.