| Background: Leprosy (Leprosy) characterized by skin and peripheral nerve chronicgranulomatous diseasesis caused by mycobacteria leprae which was discovered in1873by the Norwegian scientists Hansen, leprosy therefore also known as Hansen 'sdiseases. According to the amount of bacteria in patients with leprosy and the powerof cell-mediated immunity, leprosy can be divided into5types, including tuberculosisleprosy (TT), borderline tuberculoid (BT), borderline (BB), borderline lepromatous(BL) and lepromatous leprosy (LL). From TT to LL, the quantity of leprosy bacillusincreases gradually while infectioness also increases gradually. As the capital and theinternational metropolis, there is a large number of floating populations in Beijing.Beijing Tropical Medical Reaserch Institute at Beijing Friendship Hospital is the onlyprofessional unit in Beijing for leprosy diagnosis, differential diagnosis, treatment,rehabilitation, psychological treatment and follow-up.Objective: The present study aimed to analyze epidemiology of65new detectedcases from1990to2013in the Beijing.Results: Of65patients, the sex ratio was2.25:1(male:45, female:20);20to60yearsold patients accounted for87.7%of all patients (57/65). Among them,30patientswere the LL type,17of BL type,3of BB,9of BT and9of TT. Patients with BLand LL accounted for72.3%of the total number of cases (47/65). The cases wereoriginated from20provinces in which Henan, Shandong, Sichuan provinces are themost populous, while other provinces include Tianjin, Hebei, Jjilin, Heilongjiang,Gansu, Shaanxi, Yunnan, Guangxi, Hunan, Guizhou, Zhejiang, Jiangsu, Hubei,Jiangxi, Chongqing and Anhui. Additional, one patient came from India. The averageof delayed diagnosis was62.2months (3months to20years), particularly for patientswith LL.Among these patients,40cases first time visited as doctor at general hospitals,accounting for61.5%of the total patients. The majority of patients first visiteddermatology at these hospitals, but the final diagnosis was made by Beijing Tropical Medical Reaserch Institute at Beijing Friendship Hospital, in where treatment andfollow-up, monitoring, tracking and etc were also provided.It was noted that33cases were infected in contact within the families,accounting for30.8%of the total65patients, suggesting that the major infectious ruteof leprosy possibly is the direct ntact within family. Althernatively, patients'neighbors, relatives and so on who had leprosy accounted for20%while patients withno clear infection resource accounted for49.2%.Among the paitnes involved the study, level2disability caused by Leprosyaccounted for30.8%, diabilities at level1and level2were47.7%which was higherthan the national average (30%). There were50cases of multibacillary type, whichwas far more than that of paucibacillar patients (15cases). The average misdiagnosistimes from the onset of symptoms to the final diagnosis were181.5months,50.2months,53months and57.9months for TT, BT, BB and BL/or LL patients,respectively. Almost all patients belong to imported except one of them.Conclusion: There are still more than1000new cases detected every year in wholecountry although China has announced elimination of leprosyin2007. In view of thepatients' disability and social problems caused, it is necessary to increase publicity,strengthen the monitoring, improve the diagnostic level of laboratory, find and treatleprosy patients timely, cut off the source of infection, and strengthen prevention andcontrol, for an early realization the dream of a world without the leprosy. Leprosy (Leprosy) is an infectious disease casued by Leprosy mycobacteria, withcharacteriatics of skin and peripheral nerve chronic granulomatous. Leprosy bacilluswas found in1873by the Norwegian scientist Hansen, leprosy therefore was alsoknown as Hansen 's diseases. According to the bacteria amount and power of cellularimmunity, patients were divided as tuberculosis leprosy (TT), borderlinetumberculoid (BT), borderline (BB), borderline lepromatous (BL) and lepromatous(LL) types. From TT to LL, leprosy bacillus quantity increases gradually, cellularimmunity reduces gradually. As other mycobacteria, M.leprae cell membranescontain large amounts of lipid, such feature determines that leprosy bacterium havelongger “surviving time, incubatiing period (20to30years)?while patients need totake longer medication and complication time after treatment compared with otherinfections. From previous clinical observatious, it had been noted that leprosy patientshave lower levels of cholesterol and low density lipoprotein (LDL) compared withnormals, suggesting that leprosy patients' lipid metabolism might be different fromthat of normal people. However, the mechanism is still unclear. This study proposedto exlore the potential mechanisms of the peroxisome proliferator activated receptors-gamma, PPAR-? and adipose diffrentiation-related protein (ADRP) in leprosy lipidmetabolism through detecting the generation of such substances produced by byLeprosy mycobacteria infected cells.Materials and methods:(?) Using liquid chromatography-mass spectrometrymethod and metabonomics technology to analyze lipid metabolic patterns differencesbetween leprosy patients serum and normal serum for screening for leprosy patientsand normal serum lipid metabolism markers (n=5for each group);(?) Using mousefoot pad model to amplify leprosy bacillus isolated from damaged skin obtained froma LL patients. After18month incubation in mouse foot pad, homogenized infectedtissue to generate enough live bacteria (107/ml). After isolation of peripheral bloodmononuclear cell (PBMC) from a MB patient and a normal subject, PBMCs andhuman macrophage cell line (THP1) cells were stimulated with either live or dead leprosy bacillus. Immunofluorescence, Western blotting and rea-time PCR techniqueswere employeed to reveal expression of PPAR-? and ADRP by the leprosyinfected/or stimulated monocytes/macrophages.(?) Using immunohistochemistryand real time PCR to measure expression of expression of PPAR-? and ADRP in skinlesions of Leprosy patients. In addition, electron microscopy was used to detectwhether there are formation of lipid dropiest-like substance within the macrophagesof skin lesions of the patientsResults (?)?liquid chromatography-mass spectrometry method and metabonomicstechnology showed that the levels of arachidonic acid,12carbon olefine acid5,22carbon acid, linolenic acid, leukotriene6and22carbon olefine acid and otherunsaturated fatty acids are significantly higher in LL patients that of normals.In contrast, the levels of LDL and cholesterol were lower than that of normals.(?)?(1)Immunofluorescence showed that stimulation of normal human PBMC withviable leprosy bacterium for48h increased expression of PPAT-and ADRP, butdead bacterium or negative control did not; Both dead and viable bacterium inducedPPAT-and ADRP expression by PBMC from MB type patients. Again, only viable,but not dead bacterium induced PPAT-and ADRP expression by THP-1cells.Wester blotting showed the similar patterns of PPAT-and ADRP expression byPBMC. Highest expression of PPAT-and ADRP by THP-1cells was observed at48h after stimulation with viable bacterium, while dead bacterium did not induce suchexpression.(3) Real time PCR showed that48h after stimulation the levels ofexpression of PPAT-and ADRP in viable bacterium-treated normal human PBMCwere significantly higher than that of dead bacterial and negativel control groups.Similar to above, the levels of PPAT-and ADRP mRNA expression wassignificantly greater in viable bacterium-treated THP-1cells than that in deadbacterial and control groups.(?) Corresponding to in vitro observations, real timePCR showed ADRP, PPAR-? mRNA expression was significantly elevated in skinlesions from MB patients than that from PB patients. Immunohistochemistry furthersupported the observations of real time PCR. Furthermore, using electron microscope we observed exist of lipid droplet-like substances nearby leprosy bacillus within theskin lesions from leprosy patients.Conclusion?Our experiments show that leprosy bacillus infection might be accociatedwith formation of lipid droplets, possibly though promoting ADRP and PPAR-?expression. These results provide basic data for further investigation of releationshipsbetween leprosy bacillus and metablishms of fat and lipid. Whether production ofADRP and PPAR-?-induced by leprosy bacteria infection is associated with thechanges of lipid metabolism and increases in unsaturated fatty acids, and whetherthese changes are conducive to bacterial growth and inhibition of some immunefunctions need to be further clarified. |
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