Mesenchymal stem cells-derived extracellular vesicles for therapeutics of renal tuberculosis.

Extrapulmonary tuberculosis with a renal involvement can be a manifestation of a disseminated infection that requires therapeutic intervention, particularly with a decrease in efficacy of conventional regimens. In the present study, we investigated the therapeutic potency of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in the complex anti-tuberculosis treatment (ATT). A rabbit model of renal tuberculosis (rTB) was constructed by injecting of the standard strain Mycobacterium tuberculosis H37Rv into the cortical layer of the kidney parenchyma. Isolated rabbit MSC-EVs were intravenously administered once as an addition to standard ATT (isoniazid, pyrazinamide, and ethambutol). The therapeutic efficacy was assessed by analyzing changes of blood biochemical biomarkers and levels of anti- and pro-inflammatory cytokines as well as by renal computed tomography with subsequent histological and morphometric examination. The therapeutic effect of therapy with MSC-EVs was shown by ELISA method that confirmed a statistically significant increase of the anti-inflammatory and decrease of pro-inflammatory cytokines as compared to conventional treatment. In addition, there is a positive trend in increase of ALP level, animal weigh, and normalization of ADA activity that can indicate an improvement of kidney state. A significant reduction of the area of specific and interstitial inflammation indicated positive affect of MSC-EVs that suggests a shorter duration of ATT. The number of MSC-EVs proteins (as identified by mass-spectometry analysis) with anti-microbial, anti-inflammatory and immunoregulatory functions reduced the level of the inflammatory response and the severity of kidney damage (further proved by morphometric analysis). In conclusion, MSC-EVs can be a promising tool for the complex treatment of various infectious diseases, in particularly rTB.

Clinical Features and Drug-Resistance Profile of Urinary Tuberculosis in South-Western China: A Cross-sectional Study.

To investigate the epidemiology, clinical features, and drug-resistance profile of urinary tuberculosis (UTB) in south-western China to improve UTB diagnostics.After the screening of 1036 cases of suspected UTB, 193 patients with UTB were enrolled during 2009 to 2014. Urine samples were collected for routine urinalysis, smear, tuberculosis DNA (TB-DNA) detection, and drug-resistant analysis, whereas blood samples were collected for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and renal function evaluation. Clinical features (such as symptoms and outcome) and imageology results (such as B ultrasonic, computerized tomography, intravenous pyelography, and renography) were also collected and analyzed to investigate the epidemiology, clinical features, and drug-resistance profile.The most common presenting symptoms were urinary irritation (61.1%) and lumbago (49.2%). High proportions of microscopic hematuria (63.2%) and microscopic proteinuria (45.6%) were also observed. The positive rate for TB-DNA was 66.3%. The positive rate for culture was 13.1% and for smear it was 9.8%. The abnormal outcome rates of the computerized tomography, ultrasonography, intravenous pyelography, and the nephrogram were 76.9%, 70.1%, 29.8%, and 37.0%, respectively. The total rate of drug-resistant TB (resistant to at least 1 drug) was 39.7%, of which 20.7% was multidrug-resistance TB. The most prevalent mutation sites were katG S315T1, rpoB S531L, and gyrA D94G.We observed a serious epidemic of drug-resistant UTB and a substantial number of new UTB cases with multidrug resistance TB. Molecular diagnostics is crucial in the definite diagnosis of UTB, and our finding is a supplement and further confirmation of polymerase chain reaction usage for TB diagnosis. We recommend real-time polymerase chain reaction for TB-DNA identification instead of culture, and GenoType tests (MTBDRplus and MTBDRsl assay) for drug resistance as routine assays for patients with suspected UTB.

[Expression of lymphotactin in renal tuberculosis].

AIM: To study the expression of lymphotactin in normal kidney and renal tuberculosis and the arrangement of lymphotactin and infiltrating CD4(+) T cells and CD8(+) T cells in renal tuberculosis. METHODS: HLptn cDNA of tissues from six cases with normal kidneys and ten cases with tuberculous kidneys was amplified by RT-PCR. The RT-PCR products were separated with 2% of gel. The cDNA was cloned to vector pGM-T Easy and was completely sequenced. The immunohistochemical staining method was used to examine the expression of lymphotactin in normal kidneys and tuberculous kidneys and the expression of CD4 and CD8 in tuberculous kidneys. RESULTS: The sequence of cloned hLptn cDNA was confirmed and it was identical with the sequence of NO.U23772 published in GenBank. Both normal kidneys and tuberculous kidneys expressed hLptn mRNA. HLptn was detected not only in the cells of normal renal glomerulus and renal tubule but also in the cells of remaining renal glomerulus and renal tubule of tuberculous kidneys. The cells expressing surface antigens CD4 and CD8 scattered in granulomas. CONCLUSION: The constructive expression of hLptn is in the cells of renal glomerulus and renal tubule of normal kidney and tuberculous kidney. The accumulation of CD4(+) T cells and CD8(+) T cells in granulomas may not depend on hLptn.

Nodular lesions in renal tuberculosis.

We retrospectively studied the CT findings of renal tuberculosis in 27 cases (32 kidneys). As a characteristic CT finding, nodular lesions were recognized in 20 kidneys. Low density nodules were found in three kidneys, isodensity nodules in seven, and high density nodules in 10. In a case examined by follow-up five years later, the low and isodensity nodules changed to high density nodules with decreasing volume. Ultrasound demonstrated the high density nodules as low-echo mass lesions. These nodular lesions corresponded with the localized foci in the renal parencyma and/or pyocalyx. We consider that the density differences in nodular lesions reflect the process of water absorption from the caseous necrotizing materials of tuberculosis.

[Ectopic deposits of Tamm-Horsfall protein. A psuedo-tumoral lesion]. / Dépôts ectopiques de protéine de Tamm-Horsfall. Lésion pseudo-tumorale.

Three cases of unusual deposits of Tamm-Horsfall protein in peripelvic and perirenal fat tissue are reported. A renal tubular rupture leads to the deposition of this protein. In the first case, the association of the deposits with epithelial structures, raised the possibility of a bladder carcinoma infiltration. These deposits simulated on the X-ray examination, a pelvis neoplasm in our second patient and a tuberculosis in the third case. However the particular microscopic appearance of Tamm-Horsfall protein, its intense staining with the periodic-acid-Schiff, and its positivity with a specific antibody led to the diagnosis.

[Functional system of secretion in renal tuberculosis]. / Funktsional'naia sistema vydeleniia pri nefrotuberkuleze.

Data are given on the study of functional correlations of the pairs of organs (kidneys-liver and kidneys-lungs) that participate in provision of the functional system of secretion. The correlation of these pairs of organs contribution to the total secretion of metabolites as renal insufficiency grows is characterized by the S-shaped dependence, i.e. by a compensatory increase of the conjoined functions at the early stages and its depression at the graver stages of renal insufficiency. This approach makes it possible to determine the character, terms and significance of the participation of various organs in provision of metabolic homeostasis maintenance long before its failure and to reveal the main links in the pathogenesis of functional disorders of secretion.

[Clinico-experimental studies of therapy optimization in kidney tuberculosis]. / Klinisch-experimentelle Untersuchungen zur Therapieoptimierung der Nierentuberkulose.

The use of antituberculotic short-term chemotherapeutic methods did not yet make its way on a larger scale in the treatment of the extrapulmonary tuberculosis on account of supposed peculiarities of the terrain. Therefore, the present clinical and experimental study had the aim to investigate the distribution of INH and RMP in the kidney and the radiometrical determination of their concentration directly in the tuberculous focus of the kidney. For this purpose the tritium labelling of the two basis antituberculotics mentioned was carried out. Apart from the description of the applied working and measuring technique, questions of the distribution of medicaments are discussed. The results made evident that also in kidneys widely destroyed by tuberculosis both INH after an intravenous application of 300 mg and RMP after oral application of 600 mg even in large tuberculous caverns achieve antimycobacterially effective concentrations. Indeed, there are considerable differences, however, the values were always far above the minimum inhibition concentration. Thus there are no terrain-caused peculiarities for the tuberculous kidney and also no restrictions as to the use of an optimized antituberculotic chemotherapy. The same is probably also applied to all other forms of the extrapulmonary tuberculosis. The newly developed method distinguishes itself by a high measuring exactness and could analogously be used in questions of the chemotherapy of malignant tumours.