Anestesia en una paciente con angioedema hereditario / Anesthesia in a patient with hereditary angioedema

El angioedema hereditario (AEH) es una enfermedad genética poco frecuente debida a una mutación de transmisión autosómica dominante que produce una alteración del gen que codifica la proteína inhibidora de la C1 esterasa activada (C1-INH), provoca un déficit o disfunción de la misma. Se caracteriza por episodios recurrentes y autolimitados con síntomas transitorios de hinchazón sin urticaria de tejidos subcutáneos, extremidades, pared intestinal, genitales y vías respiratorias superiores. La afectación de laringe y glotis puede ocasionar la muerte por asfixia. Se informa la conducción perioperatoria en una paciente portadora de AEH y un amplio historial de alergias donde las principales consideraciones están relacionadas con la prevención de una crisis aguda durante el perioperatorio. Para lograrlo se requirió de una preparación con plasma fresco congelado (PFC) y ácido tranexámico (ATX) con días de antelación a la cirugía que se continuó en el posoperatorio, además de un manejo cuidadoso durante el acto anestésico(AU)

Hereditary angioedema (HAE) is a rare genetic disease caused by an autosomal dominant mutation that results in an alteration of the gene encoding the activated C1 esterase inhibitor protein (C1-INH), causing deficiency or dysfunction of C1-INH. It is characterized by recurrent and self-limited episodes with transient symptoms of swelling without urticaria of subcutaneous tissues, extremities, intestinal wall, genitalia and upper respiratory tract. Involvement of the larynx and glottis may result in death by asphyxia. The perioperative managment is reported of a patient with HAE and a long history of allergies in which the main considerations are related to the prevention of an acute crisis during the perioperative period. This required a preparation with fresh frozen plasma and tranexamic acid days before surgery, which was continued postoperatively, in addition to careful management during the anesthetic procedure(AU)

Combination Of Momordica Charantia And Phyllanthus Amarus For Hepatoprotective Activity In Ethanol And Anti-Tubercular Drugs Induced Hepatotoxicity In Rats

Objective: To evaluate the synergistic protective effect of Momordica charantia and Phyllanthus amarus combination (MC+PA) of doses 200 and 400 mg/kg on the liver in different experimental models of hepatotoxicity. Methods: The hepatoprotective activity was evaluated in ethanol and anti-tubercular drugs (isoniazid-INH, rifampicin-RIF) induced hepatotoxicity models. Hepatotoxicity in both models was induced to all groups except the normal control. Intoxicated rats were treated with silymarin and various doses of MC+PA for 8 d in ethanol-induced and 21 d in INH+RIF induced hepatotoxicity models. At the completion of study, the biochemical markers and the anti-oxidant status (SOD and MDA) were measured and also the histopathological evaluation of the liver tissue was carried out. Results: Combination therapy remarkably reduced the elevated profile of the biochemical markers and thereby improved the anti-oxidant status, thus exhibiting the synergistic hepatoprotective effect when compared with the positive control group (p<0.001). Histopathological evaluation demonstrated that MC+PA decreased the liver damage significantly in comparison with the positive group. Conclusion: The current work suggests that the combined extract showed synergistic effects on ethanol and anti-tubercular drugs induced hepatotoxicity models by significantly decreasing the liver damage.

Isoniazid Preventive Chemotherapy in Children Contact with Adult Open Pulmonary Tuberculosis

Background: To investigate importance of INH preventivechemotherapy among the children age above 5 years whowere contacted with adults having open pulmonarytuberculosis, as well as the effectiveness of INH prophylaxisamong the children age under 5 years regarding Bangladeshicontext.Objectives: This prospective observational study was carriedout to detect the frequency of tuberculosis and also effect ofisoniazid preventive chemotherapy in children contact withadult open pulmonary tuberculosis.Methods: This study was conducted in the department ofPediatrics, Shaheed Suhrawardy Medical College andHospital, Dhaka for duration of three (3) years, from July 2015to July 2018. About 384 population under 12 years childrenwho were close contacted with adult open pulmonarytuberculosis patients, were taken as study sample. Thereprospectively document adherence to six months of INHchemoprophylaxis and outcome in children with householdexposure to an adult open pulmonary tuberculosis index caseon purposive sampling technique. All the children werefollowed up and evaluated after 6 and12 months with monthlymonitoring. Ethical issues were maintained accordingly.Results: In current study subjects, the mean age was6.27±3.08 years and gender distribution were near about equal(Male: 49.5% vs. Female: 50.5%).Among the ≤5 yearschildren, only 52.7% of them received INH prophylaxis andnobody developed TB. But TB was noticeably found in 21.3%of children aged ≤5 years those who didn’t take INHprophylaxis. The majority of tuberculosis patients was foundstayed in urban slum in comparison to LTBI and healthycontact (81.25% vs. 30.77% vs. 39.26%). More than 90% oftuberculosis patients were severe underweight in this study.Conclusion: INH preventive chemotherapy is an importantfactor in children contact of adult tuberculosis. It isrecommended to provide INH chemoprophylaxis in children upto 12 years age. So it should be consider in national policymaking of Bangladesh to reduce tubercular burden inchildhood age.

To Determine the Percentage of Isoniazid Monoresistant Tubercular Mutations Via Kat G V/S INH A Genes

Some important challenges for TB control strategies include the increasing prevalence and rapid distribution of drug-resistant TB. Recently, this concern has been further intensified by reports of multi drug resistant (MDR) and extensively drug resistant-TB (XDR-TB). Although resistance to first and second line drugs poses the important risk to patients, resistance to isoniazid (INH) alone is also important. INH is the most potent anti-TB drug and is the main part of any first-line treatment regimen for TB. Our objective is to determine the percentage of isoniazid monoresistance mutations via Kat G v/s Inh A gene. Methods: We conducted a retrospective record review of 100 INH monoresistant TB patients without rifampicin resistance registered during Feb 2017 - March 2018. Results: Of the 100 INH monoresistant patients taken in a year, 82% were found to be resistant via Kat G gene and only 18% were found to be resistant for Inh A gene. Conclusion: In conclusion, our study showed increased prevalence of isoniazid resistance via Kat G gene mutation than with Inh A gene.

Hereditary angioedema caused by C1-esterase inhibitor deficiency: a case report with literature-based analysis

Hereditary angioedema (HAE) caused by C1-esterase inhibitor deficiency is an autosomal-dominant disease caused by a mutation in the C1-inhibitor gene. It is a rare disease that is often worsened during pregnancy and childbirth. HAE, though uncommon but if untreated it may lead to maternal death.  The case report presents the successful management of a 24 years old, G2P1, with hereditary angioedema caused by C1-esterase inhibitor deficiency. This patient was managed with a multidisciplinary approach by an obstetrician, an immunologist, an anaesthesiologist and a pediatrician. She had an uneventful antenatal period, labor was induced. She had precipitate delivery and soon after delivery had a flare up of the disease. It was successfully managed with fresh frozen plasma and close observation.

Studies on characteristics of liver injury model induced by rifampicin and isoniazid in mice / 中国药理学通报

Aim: To establish an ideal anti-tuberculosis drug induced liver injury model and provide a suitable animal model for its pharmacodynamic evaluation. Methods To explore the contribution rate and interaction of isoniazid (INH) and rifampicin (RIF) on liver injury, mice received intragastric administration of RIF 100 nig · kg-1, 300 mg · kg-1 once, or RIF 300 mg · kg-1, INH 150 mg · kg-1, and RIF 300 mg · kg-1 + INH 150 mg · kg-1 for 1 -3 weeks. Then the biochemical and pathological indexes were determined and analyzed by factorial design ANOVA. Results After single intragastric administration of rifampicin, the serum bilirubin levels gradually increased, but no other indicators were affected in mice. Continuous intragastric administration of RIF 300 mg · kg-1, INH 150 mg · kg-1 or RIF 300 mg · kg-1 +INH 150 mg · kg-1 for 1 ∼3 weeks could significantly increase the liver index of mice. RIF alone or combined with isoniazid could significantly increase the level of ALT, AST and TBIL, resulting in vacuolar lesions in liver tissues in mice. The analysis of variance demonstrated that the combined use of RIF and INH for two weeks or three weeks showed significant antagonism in liver index and the level of ALT, and marked antagonism in TBIL at three weeks. The pathological results were basically consistent with the biochemical indicators. Conclusions RIF is the leading cause of liver injury in mice, and its hepatotoxicity is related to cholestasis. INH has a significant antagonistic effect on liver toxicity of RIF when they are combined, and the deep action mechanisms remains to be further explored.

A pilot study of the modulation of sirtuins on arylamine -acetyltransferase 1 and 2 enzymatic activity

Arylamine -acetyltransferase (NAT; E.C. 2.3.1.5) enzymes are responsible for the biotransformation of several arylamine and hydrazine drugs by acetylation. In this process, the acetyl group transferred to the acceptor substrate produces NAT deacetylation and, in consequence, it is susceptible of degradation. Sirtuins are protein deacetylases, dependent on nicotine adenine dinucleotide, which perform post-translational modifications on cytosolic proteins. To explore possible sirtuin participation in the enzymatic activity of arylamine NATs, the expression levels of NAT1, NAT2, SIRT1 and SIRT6 in peripheral blood mononuclear cells (PBMC) from healthy subjects were examined by flow cytometry and Western blot. The activity of the sirtuins on NAT enzymatic activity was analyzed by HPLC, in the presence or absence of an agonist (resveratrol) and inhibitor (nicotinamide) of sirtuins. We detected a higher percentage of positive cells for NAT2 in comparison with NAT1, and higher numbers of SIRT1+ cells compared to SIRT6 in lymphocytes. NAT2 activity in the presence of NAM inhibitors was higher than in the presence of its substrate, but not in the presence of resveratrol. In contrast, the activity of NAT1 was not affected by sirtuins. These results showed that NAT2 activity might be modified by sirtuins.

Drug Susceptibility Testing of M. tuberculosis to Isoniazid and Rifampicin- A Comparison between MTT Tube Method and LJ Proportion Method.

Aim: To evaluate the methodology of MTT tube assay and compare it with standard proportion method for detection of drug susceptibility of M. tuberculosis to rifampicin (RIF) and isoniazid (INH). Study Design: Prospective. Place and Duration of Study: Sher-i-Kashmir Institute of Medical Sciences, Kashmir, India. One year study. Methodology: MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay was performed on 60 clinical isolates of M. tuberculosis. An inoculum of 107CFU/ml prepared in Middlebrook 7H9 with OADC (Oleic acid, albumin, dextrose and catalase) was chosen as standard. For each drug three tubes were used, one drug containing (INH 0.2 μg/ml or RIF 1 μg/ml), second inoculum control and third blank control. The method was performed after incubating the tubes at 37°C for 4 days for RIF and 7 days for INH. Results were read visually and by spectrophotometer at 570 nm. Relative optical density units of 0.2, was taken as cutoff. Results of drug susceptibility were compared with those obtained by Lowenstein Jensen proportion method. Results: For RIF, sensitivity was 88.9% and 94.4%; specificity was 100% and 97.6% for visual MTT and MTT by RODU respectively. For INH similar sensitivity of 95.1% was seen while specificity was 97.0% and 95.0% by visual MTT and MTT by RODU respectively. There was almost perfect agreement between proportion and MTT method for both drugs. Turn-around time for MTT assay was 7 days. Conclusion: The MTT tube assay can be used for rapid drug susceptibility testing of M. tuberculosis to RIF and INH.

Immunogenicity of multi-epitope DNA vaccine of Mycobacterium tuberculosis and therapeutic effects of the vaccine combined with chemotherapy in a mouse model infected with multi-drug resistant Mycobacterium tuberculosis / 西安交通大学学报(医学版)

Objective To make a comparative study of the immunogenicity of multi-epitope DNA vaccine and BCG of Mycobacterium tuberculosis and therapeutic effects of the vaccines combined with chemotherapy in a mouse model infected with multi-drug resistant (MDR)Mycobacterium tuberculosis.Methods The BALB/c mice were randomly divided into Group A,Group B and Group C,which received subcutaneous immunization with PBS,BCG and multi-epitope DNA vaccine,respectively,once at weeks 1 ,3 and 5 .Specific IgG antibody,IL2 and IFN-γin mice serum were determined with ELISA after the final vaccination.At the same time,the splenic lymphocytes of mice were separated and the lymphocytes proliferation was determined by MTT method.To study the therapeutic effects of multi-epitope DNA vaccine,the mice were infected by intravenous injection in the tail vein with Mycobacterium tuberculosis clinical isolates that were resistant to isoniazid (INH)and rifampin (RFP).Four weeks later,the model mice were divided into Groups D,E and F.The mice in Group D and control group received saline injection. The mice in Group E were treated with RFP and INH.The mice in Group F were treated with multi-epitope DNA vaccine combined with INH and RFP for 10 weeks.The lungs,livers and spleens of mice were removed and weighed;the colony number of Mycobacterium tuberculosis in the lungs and spleens was counted.Results The antibody IgG,IL2 and IFN-γwere obviously higher in multi-epitope DNA vaccine group than in BCG group (P<0.05).Multi-epitope DNA vaccine combined with chemotherapy could obviously reduce the colony number of Mycobacterium tuberculosis in the lungs and spleens as well as indexes of the lungs,livers and spleens (P<0.05). Conclusion Mycobacterium tuberculosis Hsp70,Ag85A,and ESAT-6 multi-epitope DNA vaccine could induce strong specific immune response in mice that produced a high level of specific IgG antibody,IL2 and IFN-γ,specific lymphocyte proliferation,and significantly improve the efficacy of anti-tuberculosis drug resistant tuberculosis in mice.

Fast test for assessing the susceptibility of Mycobacterium tuberculosis to isoniazid and rifampin by real-time PCR

Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB), a leading cause of death from infectious disease worldwide. Rapid diagnosis of resistant strains is important for the control of TB. Real-time polymerase chain reaction (RT-PCR) assays may detect all of the mutations that occur in the M. tuberculosis 81-bp core region of the rpoB gene, which is responsible for resistance to rifampin (RIF) and codon 315 of the katG gene and the inhA ribosomal binding site, which are responsible for isoniazid (INH). The goal of this study was to assess the performance of RT-PCR compared to traditional culture-based methods for determining the drug susceptibility of M. tuberculosis. BACTEC TM MGIT TM 960 was used as the gold standard method for phenotypic drug susceptibility testing. Susceptibilities to INH and RIF were also determined by genotyping of katG, inhA and rpoB genes. RT-PCR based on molecular beacons probes was used to detect specific point mutations associated with resistance. The sensitivities of RT-PCR in detecting INH resistance using katG and inhA targets individually were 55% and 25%, respectively and 73% when combined. The sensitivity of the RT-PCR assay in detecting RIF resistance was 99%. The median time to complete the RT-PCR assay was three-four hours. The specificities for tests were both 100%. Our results confirm that RT-PCR can detect INH and RIF resistance in less than four hours with high sensitivity.

Seizures with single therapeutic dose of isoniazid.

Isoniazid (INH) is an integral component of treatment of tuberculosis. An acute overdose is potentially fatal and is characterised by the clinical triad of repetitive seizures unresponsive to the usual anticonvulsants, metabolic acidosis with a high anion gap and coma. A case of isoniazid induced seizures after therapeutic dose of 600 mg. as a part of CAT I thrice weekly intermittent anti-tuberculosis regimen for pulmonary tuberculosis is reported. The frequency of the usage of Isoniazid as antituberculosis therapy requires that physicians be aware of such toxicity.

N-acetyltransferase2 genotype and its association with hepatitis among Filipino children treated with first line anti-tuberculosis drugs

RATIONALE: Among the first line antituberculosis (anti-TB) drugs, the major drug incriminated in the development of hepatotoxicity is isoniazid (INH). The human N-acetyl transferase2 (NAT2) gene is mainly responsible for INH metabolism. This gene exhibits a hereditarily determined polymorphism. There is presently no study on the predominant NAT2 genotype among Filipinos. There are also no Filipino studies on the incidence of hepatitis and other adverse effects of first line anti-TB drugs. OBJECTIVES: To determine the predominant NAT2 genotype and its association with the development of hepatitis among Filipino children given first line anti-TB drugs (INH, rifampicin and pyrazinamide) and to determine the incidence of hepatitis and other serious adverse reactions to these drugs. STUDY DESIGN: Prospective cohort study SETTING: Tertiary government hospital in Metro Manila STUDY POPULATION: Children on to 18 years old with pulmonary tuberculosis and normal liver function test at baseline. METHODS: Total bilirubin (TB), direct bilirubin (DB) and liver transaminases (AST and ALT) were checked routinely at baseline and at thow, four, eight and 12 weeks after starting treatment. Within the first month of treatment, blood was also taken for NAT2 genotyping. The identification of the three NAT2 polymorphisms that are associated with a slow acetylator status - 481C to T (NAT2*5), 950G to A (NAT2*6) and 857G to A (NAT2*7) was carried out by polymerase chain reaction-restriction fragment length polymorphism. All patients were followed up for a total of six months. The presense of any adverse effects like gastroinstestinal symptoms, rash, hepatitis or drug fever was also monitored. RESULTS: A total of 24 children [mean age: 5 years; 11 males] were included. Majority (96%) were diagnosed by passive detection and mean Z score was - 1.38 (1 to -3). No patient developed hepatotoxicity or any side effects to anti-TB drugs. In 23 patients who had NAT2 genotyping, 39% and 22% were alleles homozygous for the NAT2*6 and NAT2*7, respectively. There was a combination of alleles in only three (13%) subjects. CONCLUSION: NAT2*6 and NAT2*7 alleles associated with a slow acetylator status were detected among our patients although the presence of these variants did not lead to any hepatotoxicity nor any treatment-related side effects. A larger study with broader genotype analysis is needed to confirm the present findings.

Results of molecular genetic study of m. Tuberculosis strains isolated from specimens of mdr-tb suspects in Ulaanbaatar, Mongolia in 2009-2010 / Монголын Анагаах Ухаан

Bacground: DST by conventional methods takes several weeks, while early diagnosis of the disease and the rapid identification of resistant strains are essential for efficient treatment and control of the MDR strains. Rapid molecular testing of detecting MDR-TB is needed.Objective: The aim of this study was to assess performance of molecular line probe assay, Genotype16 MTBDRp/us, for rapid detection of RIF and INH resistance for M.Tuberculosis in Mongolia. The sensitivity and specificity of Genotype® MTBDRp/us to detect RIF and INH resistance-associated mutations in culture specimens and directly in smear-positive clinical specimens was examined and compared with conventional culture and drug susceptibility testing on solid medium.Material and Methods: The subjects of this study were 218 MDR-TB suspects aged 14-75 years from 8 districts in Ulaanbaatar city. The study was conducted from July 2009 to May 2010. The Genotype M. Tuberculosis drug resistance first line (MTBDR plus) assay (Hain Life-science, Nehren, Germany) was tested on directly on 41 sputum specimens and 109 clinical isolates.Results: The high correlation of the results from Genotype® MTBDRp/us and conventional drug susceptibility testing was obtained from this study. The results clearly show high performance of Genotype® MTBDRp/us with almost 100% accuracy for all the important indicators, such as sensitivity, specificity, positive and negative predictive values of detection of RIF and INH resistance. Some minor discrepancies were obtained in comparison with DNA sequencing results.Our study found that among high proportion for detection of RIF resistance, S531L mutation (MUT3 band) occurred the most commonly, with 80.0% of all RIF-resistant strains (83.6% of MDR) having the mutation. Other mutation in the 530-533 regions was common, as detected by the lack of binding to the WT8 probe in the absence of S531L mutation.In this study we observed that mutations in the promoter region of inhA gene played a major role (67.6 % (63.9% of MDR strains and 90% of INH-mono-resistant strains) had a mutation in the inhA.Conclusion: The Genotype® MTBDRp/us assay was demonstrated as a rapid, reliable and highly accurate tool for early detection of MDR-TB through examining smear positive cases enabling early start of appropriate therapeutic and public health measures to control of the spread of drug resistant M.tuberculosis in the population.

Angioedema adquirido autoimune de difícil controle em paciente com lúpus eritematoso sistêmico / Intractable acquired autoimmune angioedema in a patient with systemic lupus erythematosus

O angioedema adquirido é causado por diferentes medicamentos e doenças linfoproliferativas, e tem sido raramente relacionado com a presença de doenças autoimunes. Descrevemos aqui uma paciente de 47 anos com lúpus eritematoso sistêmico (LES) com envolvimento cutâneo importante que desenvolveu angioedema recorrente localizado em face incluindo lábios e pálpebras, membros superiores e tórax, não acompanhado de urticária e com dosagem do inibidor de C1 esterase reduzida. A utilização de antimaláricos, glicocorticoides e pulsoterapia com metilprednisolona associada ao uso de azatioprina não determinou melhora. A paciente utilizou também danazol sem sucesso, e apresentou resposta clínica somente após ter sido submetida a múltiplas sessões de plasmaferese, ocorrendo inclusive resolução de extenso angioedema na mucosa do trato gastrointestinal.

Acquired angioedema is caused by different drugs and lymphoproliferative diseases, and rarely it has also been related to the presence of auto-immune disorders. We report the case of a 47 year old female with systemic lupus erythematosus (SLE) and severe cutaneous involvement who developed recurrent localized angioedema of the face, including lips and eye lids, upper limbs, and thorax, not associated with urticaria, and with reduced levels of C1 esterase inhibitor. Treatment with antimalarials, glucocorticoids, and pulse therapy with methylprednisolone associated with azathioprine did not improve her condition. The patient was also unsuccessfully treated with danazol, and she only showed clinical response after several sessions of plasmapheresis, including resolution of the extensive edema of the gastrointestinal tract.

Quick Detecting Mutation Site of 315 Codon in katG Gene of INH resistant MTB by Stem-ring Molecular Probe in Liquid / 中华医院感染学杂志

OBJECTIVE To detect 315 codon of mutation site in katG of isoniazid(INH)-resistant Mycobacterium tyberculosis(MTB) by stem-ring molecular probe quickly and detect out the fluorescence sign of hybridization between amplified products of katG 315 codon and probe in liquid by fluorescence spectrophotometer.The results were confirmed by sequencing.METHODS The software,Beacon designer,was used to design the katG 315 codon stem-ring molecular probe and the amplification system,and the relationship between the way and sequencing of the amplification products were compared.RESULTS The difference between PCR products from standard strain and INH-resistant one was significant in detecting the fluorescent light by use of fluorescence spectrophotometer.We detected fluorescent light signal between the 16 INH resistant strains and 10 H37RV standard strains.The resistant rate to INH detected was about 44%,and the rate of coincidence was about 97.5%.CONCLUSIONS The stem-ring molecular probe technology show high sensitivety in detecting mutation site of nucleic acid.The rate of coincidence is good between fluorescence spectrophotometer way and sequencing.

Mutations of katG and inhA in MDR M. tuberculosis / 결핵및호흡기질환

BACKGROUNDS: Mutations of katG and inhA (ORF and promoter) are known to be related to isoniazid (INH) resistance of Mycobacterium tuberculosis. Because reports on these mutations in Korean isolates are limited (i.e. only the frequency of katG codon 463 was evaluated.), we tried to know the kinds of mutations of two genes and their frequencies in INH resistant Korean M. tuberculosis strains. METHODS: PCR was performed to amplify katG (2,223 bp), inhA ORF (-77~897, 975 bp), and inhA promoter (-168~80, 248 bp) from 29 multidrug resistant M. tuberculosis (MDR-TB) DNAs prepared by bead beater-phenol method. Their sequences were determined and analyzed by ABI PRISM 3730 XL Analyzer and MegAlign package program, respectively. RESULTS: All of the isolates had more than one mutation in katG or inhA gene. Twenty seven (93%) of 29 tested strains had katG mutations, which suggests that katG is a critical gene determining INH resistance of M. tuberculosis. Amino acid substitutions, such as Arg463Leu and Ser315Thr, due to point mutations of the katG were the most frequent (62.1% and 55.2%) mutations. In addition, deletion of the katG gene was frequently observed (17.2%). Analyzed Korean MDR-TB isolates also had variable inhA mutations. Point mutation of inhA promoter region, such as -15 (C-->T) was frequently found. Substitution of amino acid (Lsy8Asn) due to point mutation (AAA-->AAC) of inhA ORF was found in 1 isolate. Interestingly, 14 point mutated types that were not previously reported were newly found. While four types resulted in amino acid change, the others were silent mutations. CONCLUSIONS: Although it is not clear that the relationship of these newly found mutations with INH resistance, they show marked diversity in Korean MDR-TB strains. It also suggests their feasibility as a molecular target to supplement determining the INH resistance of clinical isolates because of the possible existence of low-level INH resistant strains.

Mutations of katG and inhA in MDR M. tuberculosis / 결핵및호흡기질환

BACKGROUNDS: Mutations of katG and inhA (ORF and promoter) are known to be related to isoniazid (INH) resistance of Mycobacterium tuberculosis. Because reports on these mutations in Korean isolates are limited (i.e. only the frequency of katG codon 463 was evaluated.), we tried to know the kinds of mutations of two genes and their frequencies in INH resistant Korean M. tuberculosis strains. METHODS: PCR was performed to amplify katG (2,223 bp), inhA ORF (-77~897, 975 bp), and inhA promoter (-168~80, 248 bp) from 29 multidrug resistant M. tuberculosis (MDR-TB) DNAs prepared by bead beater-phenol method. Their sequences were determined and analyzed by ABI PRISM 3730 XL Analyzer and MegAlign package program, respectively. RESULTS: All of the isolates had more than one mutation in katG or inhA gene. Twenty seven (93%) of 29 tested strains had katG mutations, which suggests that katG is a critical gene determining INH resistance of M. tuberculosis. Amino acid substitutions, such as Arg463Leu and Ser315Thr, due to point mutations of the katG were the most frequent (62.1% and 55.2%) mutations. In addition, deletion of the katG gene was frequently observed (17.2%). Analyzed Korean MDR-TB isolates also had variable inhA mutations. Point mutation of inhA promoter region, such as -15 (C-->T) was frequently found. Substitution of amino acid (Lsy8Asn) due to point mutation (AAA-->AAC) of inhA ORF was found in 1 isolate. Interestingly, 14 point mutated types that were not previously reported were newly found. While four types resulted in amino acid change, the others were silent mutations. CONCLUSIONS: Although it is not clear that the relationship of these newly found mutations with INH resistance, they show marked diversity in Korean MDR-TB strains. It also suggests their feasibility as a molecular target to supplement determining the INH resistance of clinical isolates because of the possible existence of low-level INH resistant strains.

Expression of complement regulatory proteins C_1-INH and CD46 in nasal mucosa of allergic rhinitis rats / 第二军医大学学报

Objective:To determine the expression of complement regulatory proteins(CRPs) C_1-INH,MCP(CD46) in the nasal mucosa of allergic rhinitis rats and to study the role of CRPs in the pathogenesis of allergic rhinitis.Methods: Nine healthy SD rats were sensitized and intranasally challenged with ovalbumin and Al(OH)_3(as supplement) to establish allergic rhinitis models and another 9 SD rats treated with saline were taken as control.The nasal mucosa in respiratory area of both groups was obtained.Then Western blotting was performed to investigate the expression levels of C_1-INH and CD46.Results: Western blotting showed that both C_1-INH and CD46 had been detected in rat nasal mucosa.Expression level of CD46 in the nasal mucosa of allergic rhinitis was significantly higher than that in control rats(P

A case of acquired angioedema with C1 esterase inhibitor deficiency / 천식및알레르기

Angioedema is a well-demarcated localized edema involving the deeper layers of the skin, including the subcutaneous tissue. Angioedema occurs with Cl esterase inhibitor (Cl INH) deficiency that may be inborn as an autosomal dominant characteristic or may be acquired. Acquired angioedema (AAE) is a rare disorder characterized by adult onset and lack of evidence of inheritance of the disease. Two types of AAE are known today: type I in which there are lowering of functional Cl INH, an underlying disease such as a B-cell disease, and no detectable autoantibodies to Cl INH, type II with anti Cl INH autoantibodies in the circulation without detectable underlying disease and with depressed functional Cl INH levels. We experienced a case of angioedema in a 29-year old man. He had no family history of angioedema and laboratory data showed depressed Cl-INH levels. We diagnosed the case as acquired type of angioedema. Even though we could not measure anti-Cl INH auto-antibodies, we identified the case as type II because there was no evidence of underlying disease.

Effect of C1 esterase inhibitor on the cardiac dysfunction following ischemia and reperfusion in the isolated perfused rat heart

Complement-mediated neutrophil activation has been hypothesized to be an important mechanism of reperfusion injury. It has been proposed that C1 esterase inhibitor (C1 INH) may prevent the complement-dependent activation of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium. Therefore, The effect of C1 INH was examined in neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of C1 INH (5 mg/Kg) to I/R hearts in the presence of PMNs (100 X 106) and homologous plasma improved coronary flow and preserved cardiac contractile function (p<0.001) in comparison to those I/R hearts receiving only vehicle. In addition, C1 INH significantly (p<0.001) reduced PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective cardioprotective agent inhibits leukocyte-endothelial interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.