Idiopathic pulmonary fibrosis and mutation of TGF-beta gene, codon 10

Idiopathic pulmonary fibrosis [IPF] is associated with histological appearance of usual interstitial pneumonia. These fibrotic changes in lung interstitium are mostly attributed to cytokine production such as TGFbeta which stimulate migration and differentiation of fibroblast to myofibroblasts. The polymorphism of TGFbeta gene was found to be associated with development of IPF. We investigated whether TGFbeta1 gene polymorphism in codon 10 is associated with interstitial pulmonary fibrosis in Iranian population. The different genotypes of TGFbeta1 at [+ 870] position [in codon 10] was studied in41 cases and 83 control subjects. The allele specific PCR method was used for genotyping. In the patient group, the frequency of T allele [NO: 58] was 70.7% and C allele [NO: 24] was 29.3%. The frequency of TT genotype [NO: 20] was 48.8%, followed by T/C [NO: 18] 43.9% and CC [No. 3] 7.3% while in the control group, the frequency of T allele [N:117] was approximately 70.5% and C allele [NO: 49] was 29.5%. The frequency of TT genotype in control group [NO: 41] was 49.4%, followed by T/C [NO: 35] 42.2% and C/C [NO: 7]8.4% In comparison with the control group, there was no association between TGFbeta1 codon 10 T/C polymorphism in our cases with IPF

Expression of alpha-crystalline protein in the in- vitro model of hypoxically induced nonreplicating persistence of mycobacterium tuberculosis strains

Latent tuberculosis infection [LTBI] is caused by Mycobacterium tuberculosis [MTB] in a state of non-replicating persistence [NRP]. Recent evidence suggests that some very specific adaptations to oxygen depletion occur so that MTB undergoes hypoxic NRP state. In this study the modified slowly stirred, limited Head Space Ratio [0.5HSR] method was used to investigate the physiological response of MTB to different oxygen tension levels. For setting up the various NRP stages, some susceptible and drug resistant clinically isolated strains of MTB were cultivated in Dubos Tween-Albumin medium via hypoxically, slow stirring 0.5 HSR methods. Additionally, the effects of isoniazid, rifampin, pyrazinamide, ciprofloxacin and metronidazole against MTB were examined during NRP-1 and NRP-2 stages. The alpha-crystalline protein was detected during NRP-1 stage of the MTB cultures via performance of the suitable procedures for pellet preparation, washing and cell disruption and SDS-PAGE[Sodium dodecyl sulfate-polyacrylamide gel electrophoresis] technique. NRP-1 and NRP-2 stages of MTB were assessed. The first three of the four drugs mentioned above affected the MTB at actively replicating period and the rifampin effect was continued slightly during NRP-1 stage. Metronidazole affected the MTB at anaerobic NRP-2 stage. Alpha-crystalline protein was detected in NRP -1 stage but was not detected at aerated cultures. Induction of the alpha-crystalline protein during hypoxic shift-down of MTB metabolism, and its function as a chaperone, suggests a critical role for this protein in the ability of MTB to persist without replicating in the hostile regions of the host's tissues. Therefore, for an effective TB control program, it is critical to understand the mechanisms of factors induction associated with the hypoxic condition of tubercle bacilli and some strategies for the identification of new drug targets must be developed and the persistence states in human lesions should be prevented as well

Vitamin A supplementary effect on immunologic profiles in tuberculosis patients

The effects of vitamins on human immune system have been well studied. Vitamin A deficiency and its effects on immune system in pulmonary tuberculosis [TB] patients have been established. This study was carried out to evaluate vitamin A supplementary effect on immunologic profile of tuberculosis patients. In a double-blind clinical trial, thirty-five patients with confirmed pulmonary tuberculosis were included. The case group received vitamin A injection, 50000 lU, every 10 days for two months along with standard treatment of TB; the control group received only anti-TB drugs. Immunologic profiles including CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, HLA-DR, CD16+56+, and plasma vitamin A as well as nutritional status were assessed in both groups primarily and two months after above-mentioned treatments. Data were analysed using SPSS software version 10. The study showed that there were not significant differences in mean[ +/- SD] of age, body weight, height, body mass index [BMI], fat thickness and vitamin A plasma level between the vit A-receiving and control groups. The mean of peripheral blood CD3+ showed significant increase in patient-control group [71.8 +/- 7.9% lymphocytes [after supplementation] compared with 68.3 +/- 10.7% [before supplementation]; p= 0.014.]. This was also true about CD4+ [p= 0.001]. CD4+ to CD8+ ratio and the mean of CD19+ showed significant decrease in the patient control group and the vit A-receiving group, respectively [p= 0.002 and p= 0.04, respectively]. In contrast, there was an increased significant difference for CD+16+56+ mean in the above-mentioned groups which was more prominent in the vit A- receiving group [p=0.038]. The means of HLA-DR and CD8+ did not show significant differences in both groups before and after supplementation. It seems that vitamin A supplementary effects on the quality of lymphocytic markers are remarkable. However, further studies should be performed regarding immunologic response quality

Diagnostic value of Adenosine deaminase isoenzyme [ADA2] and total ADA in tuberculous pleural effusion

Determination of adenosine deaminase [ADA] activity is one of the most promising markers in diagnosing of tuberculous pleural effusion. ADA has two main isoenzymes: ADA1 and ADA2.The ADA2 is the predominant isoform in tuberculous pleural effusion, suggesting its important role as a diagnostic marker. This study was conducted to determine the diagnostic value of ADA and ADA2 measurement in tuberculous pleural effusion. Total ADA and ADA2 isoenzyme activities were measured in 93 case of pleural effusion, including tuberculosis [26males/5females], malignancy [22males/8females], empyema and para-pneumonic [11males/4females], transudate [6males/4females], rheumatoid arthritis and idiopathic [4males/3females]. ADA levels were determined by Giusti and Galanti methods. ADA2 was measured with a potent inhibitor of ADA1 isoenzyme. Total ADA and ADA2 activities in tuberculous exudates were 96.6 +/- 29.1 and 74.4 +/- 29 U/L, respectively. With diagnostic thresholds of 46 and 42 U/L, the sensitivities of ADA and ADA2 for tuberculous exudates were 100% and 97%; their specificities 82 and 88%; and their efficiencies 88% and 93.5%, respectively. All tuberculous exudates, 2 neoplastic, 8 para- infective [including 4 empyemas] and one rheumatoid arthritis had total ADA levels > 46 U/L; of these, only one lymphoma and one rheumatoid arthritis had ADA2/ADA activity ratio > 50%. Considering simultaneous criteria of total ADA more than 46U/L, ADA2 > 42 U/L and ADA2/ADA more than 50%, we had only two false positive results, rising the specificity up to 96%. 1. ADA2 is a more efficient diagnostic marker for Tuberculous pleural effusion compared with total ADA. 2. Overall, diagnostic value of ADA would be enhanced by the determination of its isoenzymes, especially for distinguishing between the tuberculous and para-infective effusions

Metabolomics in medicine

Genomic studies provide scientists with new techniques to quickly analyse genes and their products in mass. The post genomics era has brought ever increasing demands to observe and characterize variations within biological systems. These variations have been studied under Systems Biology. Systems biology is a multi disciplinary and multi-instrumental analysis of all molecules within the cell, tissue and organism. This technology includes studies regarding genomics [gene function], transcryptomics [mRNA function], proteomics [protein regulation] and the metabolomics [low molecular weight metabolites].The suffix " - omic " is added at the end of each part of the systems. Metabolomics/metabonomics has been labeled one of the new "- omics " joining genomics. It is rapidly becoming one of the platform sciences of the " omics ", with the majority of papers in this field having been published only in the past two years [Rochfort S, 2005]and the manufacture sale rose up to $230 million in 2005 [Lok C, 2005]. Metabolomics is concerned with the measurement of global sets of low-molecular weight metabolites. It is the study of metabolites and their roles in various disease states and is a novel methodology which arose in the last 3-5 years. The concept, characteristics, technologies and history of metabolomics are introduced. The techniques used in data acquisition and data analysis including NMR, GC/MS, LC/MS, and others, as well as the possibilities and the limitation of techniques are introduced. Metabolomics made on lab-on-a-chips techniques to provide earlier, faster, and more accurate diagnoses for many diseases. The major application of metabolomics is in toxicology, clinical trial testing, pharmacology and drug phenotyping,nutrient industry and food /beverage tests, cancer research, clinical pathology tests, and many others which have been tabulated in the text. Metabolomics developed mostly in plants, which are easier to study compared to mammals. Although use of metabolomics in medicine is in its infancy, this approach is considered to have the potential to revolutionize medical practice in prevention, predicting and personalizing health care

Detection of human papillomavirus in squamous cell carcinoma of the lung by semi-nested PCR

Background: Lung cancer is the second common malignancy in human. Human papillomavirus [HPV] has a well established association with squamous cell carcinoma of anogenital region. This study was performed in Massih Daneshvari hospital, between 1999 and 2003 to evaluate association of human papillomavirus type 16 and 18 in squamous cell carcinoma of the lung among Iranian patients

Materials and Methods: Paraffin embedded block of pathology archive of Massih Daneshvari hospital with diagnosis of SCC were selected for determination of HPV DNA by semi-nested PCR. For each specimen, all hematoxyline-eosin stained slides were reviewed by two pathologists; if the initial slide was inappropriate, a new slide was prepared. All inadequate specimens were excluded from the study

Results: 18 out of 45 paraffin- embedded specimens with diagnosis of squamous cell carcinoma were selected. Six specimens were positive for HPV type 16, and 2 were positive for HPV type 18. None of the specimens was shown to have concurrent positivity of HPV types 16 and 18

Conclusion: The present study showed that high risk HPV was associated with squamous cell carcinoma of the lung and more prevalent type was HPV 16. We suggest further investigations to evaluate this relationship

case of angiomyolipoma of the posterior upper mediastinum

Angiomyolipoma [AML] is uncommon outside the kidney, and it rarely occurs in mediastinum. This article presents a case of posterior upper mediastinal AML with a review of the literature on angiomyolipoma. A 56-year-old woman was referred to our hospital with 8-month history of cough and chest pain. Radiology showed a mass in the posterior upper mediastinum. Left thoracotomy was done for surgical removal of the tumor. Pathologic findings revealed an AML tumor in the left paravertebral and posterior upper mediastinal regions with massive infiltration of the intercostal nerves and subtle invasion of the adjacent thoracic spinal canal. This case is the third reported AML of posterior upper mediastinum. To prevent misdiagnosis, it is suggested that AML could be considered for the differential diagnosis of mediastinal tumors

Recovery of mycobacteria from clinical specimens and assessing drug susceptibility test of mycobacterium tuberculosis specimens by mycobacteria growth indicator tube [MGIT]

Tuberculosis is a disease of global importance. Indeed, the lack of sensitive methods for the diagnosis and inappropriate therapy may lead to increased multidrug-resistance [MDR] cases. However, early detection and identification of acid fast bacilli [AFB] in clinical specimens can lead to effective intervention. The sputum specimens from 156 clinically suspected tuberculosis patients and 40 non- tuberculosis patients were digested, examined microscopically for acid- fast bacilli, and inoculated into "Mycobacterium Growth Indicator Tube" [MGIT], BACTEC -12B vial and onto Lowenstein- Jensen slants by standard procedures. The result showed that smear was positive in 82 [52.5%] and negative in 74 [47.5%] of 156 clinically suspected tuberculosis patients. The culture positive rate with Lowenstein- Jensen, MGIT, and BACTEC-12B vial were 122 [78%], 136 [87%], and 143 [91%], respectively. Thereafter, MGIT indirect and direct susceptibility tests were performed on 15 sputum-positive specimens and the results were compared with proportional method. The results have revealed that accordance with proportional method was higher in MGIT indirect [83.5%] than direct [75%] susceptibility test, the difference was significant [p< 0.05]. In another set of experiments, the indirect MGIT drug susceptibility test in 25 mycobacterium tuberculosis isolates were performed and compared with proportional method. The results showed that MGIT could correctly detect susceptibility to streptomycin, ethambutol, rifampin and isoniazid for 77.8%, 33%, 77.2% and 80%, respectively. Also, the agreements with proportional method for resistance were 88% for streptomycin, 80% for ethambutol, 80% for rifampin and 89% for isoniazid. Furthermore, by combining MGIT technology with L.J media, the mean time required for culture to grow for identification test was reduced from 22-28 to 12-16 days [p<0.05]. MGIT is an efficient system to be used in center/ referral mycobacteriology laboratories of developing countries along with routine solid or liquid culture media

Thoracic CT-guided needle biopsy: a report of 150 cases

The purpose of this study is how to use CT-guided needle biopsy for the diagnosis of pulmonary, pleural, and mediastinal mass lesions. Meanwhile, the complications of the procedure were evaluated. The pathology results of 150 biopsy specimens, which were obtained from 145 patients aged from 9 to 87 years old [55.3 +/- 17.6] referred during a one-year period were reviewed, and the frequency of pneumothorax and hemoptysis were analyzed. Lesion size ranged 1-18 cm [mean [ +/- SD] 6.5 +/- 3.4 cm. 95 lesions were contacted to the chest wall. Pathological studies showed that 22 specimens were benign, 61 malignant, 28 nonspecifics, 17 suspicious for malignancy, and 22 insufficient for diagnosis. Risk for pneumothorax and hemoptysis was 6 and 2 percent respectively, which were much better results than previous reports. Although our low complication rate may be attributed to the large size of the lesions and their small distance from the chest wall, we still recommend CT-guided needle biopsy as a useful diagnostic method for thoracic mass lesions