Cytostatic activity of seven derivatives of 4-(alpha-phenylaminobenzylidene)morpholinium iodide was examined by the phytobiological methods with Triticum and Allium cepa roots. The obtained results were compared with the effects of isonicotinic hydrazide (INH).

With the emergence of drug resistant tuberculosis, it is very urgent to find novel anti-tuberculosis drugs, especially novel anti-drug-resistant tuberculosis drugs. Because of the slow growth and the need to work in a biosafty environment of Mycobacterium tuberculosis, the development of evaluation of drug effect is severely impeded. In order to solve these issues, non-pathogenic fast-growing Mycobacterium smegmatis is introduced as test organism. The inhA is one of a target of isoniazid (INH) overexpression or mutation of this gene in Mycobacterium tuberculosis conferring resistant to INH. A recombinant plasmid bearing inhA was constructed and electroporated into Mycobacterium smegmatis, using shuttle expression vector pMV261. Transformants were induced to express a protein of inhA, identified by SDS-PAGE. Results show that Mycobacterium smegmatis containing inhA plasmids exhibited 100-fold or greater increased resistance to INH, but it conferred no increased resistance to others first-line anti-tuberculosis drugs. Resazurin microtiter assay plate testing of Mycobacterium smegmatis susceptibility to drugs is a rapid, simple, and inexpensive method and could decrease color background of drugs by detecting fluorescence. It will be benefit for high-throughout screening of drugs of anti-isoniazid-resistant Mycobacteria.

Inactive plasma renin is converted into an active form of renin during dialysis of plasma against a pH 3.3-buffer. This form of renin is inactivated at neutral pH. When plasma, after acid-dialysis, is kept at neutral pH a different form of active renin is generated, which remains active. The irreversible activation of prorenin depends on factor XII-initiated kallikrein formation. C1-inhibitor (C1-INH) and alpha 2-macroglobulin (alpha 2M) can be selectively denaturated by treatment of plasma at low pH values to which kallikrein and renin are resistant. After denaturation of C1-INH at pH 4-5, factor XII becomes capable of activating prekallikrein. The kallikrein that is formed after restoration of pH is complexed with alpha 2M. This complex has little activity towards natural protein substrates including prorenin. alpha 2M is denaturated at pH 3-4 and, as a consequence, kallikrein that is formed after restoration of pH is not complexed with alpha 2M. This kallikrein is able to attack both high-molecular weight kininogen and prorenin as manifested by the generation of bradykinin-forming and angiotensin-forming activities. These observations show a crucial role for C1-INH and alpha 2M in prorenin activation and explain, at least in part, why the pH of the acid-treatment step has to be less than 4 before irreversible activation of prorenin at neutral pH can occur.

Solid lipid nanoparticles (SLNs) are presently being promoted to improve bioavailability of encapsulated drugs. These are well tolerated in living systems, as they are made from biocompatible material. Despite finding extensive applicability, these systems have not been sufficiently investigated for the toxicity so far. We have reported use of SLNs to improve plasma bioavailability of isoniazid (INH), a hepatotoxic, antitubercular drug. Presently we evaluate acute and repeated (28-day) oral dose toxicity, with satellite group, of developed INH loaded COMBI-SLN. In addition to high bioavailability, the COMBI-SLN exhibited 3 times higher LD₅₀ (2000 mg/kg BW) versus 650 mg/kg BW for free INH. Results were complemented with histopathological evidence in brain, sciatic nerve and liver tissue all of which indicated enhanced safety of INH upon incorporation into SLNs. In the repeated dose study at doses selected as per Organisation for Economic Co-operation and Development (OECD) guidelines, a series of behavioural and haematological tests, clinical biochemistry (kidney and liver function, lipid profile) and histopathological studies were performed to evaluate the effect of low (250 mg/kg BW), medium (500 mg/kg BW) and high oral dose (1000 mg/kg BW). Absence of adverse effects like hepatotoxicity and peripheral neuropathy observed in rats at an oral intake level of 500 and 1000 mg/kg BW of COMBI-SLN, that is 20-40 folds above the anticipated human intake levels (after normalizing the surface area correction for rats), supports the conclusion that SLN are an intrinsically safe nanocarrier system that improves both the efficacy and the safety of INH.

A 41-year-old woman treated with isoniazid (INH) for latent tuberculosis infection and an oral corticosteroid for sarcoidosis developed severe anemia two months after initiating INH. A bone marrow examination showed erythroblastopenia, and a diagnosis of INH-induced pure red cell aplasia (PRCA) was made. Her reticulocyte count and hemoglobin levels improved two weeks after discontinuation of INH. A literature review of INH-induced PRCA shows that it occurs very rarely in the context of autoimmune disorders. This report describes a case of INH-induced PRCA occurring in a patient with sarcoidosis.

Authors report the case of a 19 year old metastatic Ewing's sarcoma, prophylactically treated for suspected tuberculosis by Rifampicin and INH. Hepatic failure was induced by accidental overdose of INH. A high dose containing VCR protocol associated, lead to a coma with convulsions and severe motor peripheral neuropathy partially regressive. Neurological incidents of VCR, INH and their association are reviewed.

The aim of our study was to genotypically characterise isoniazid (INH) and rifampicin (RMP) resistant Mycobacterium tuberculosis isolates in Sousse, Central Tunisia, using DNA sequencing and multispacer sequence typing (MST). The results show that 27/28 (96.4%) and 1/28 (3.6%) INH-resistant isolates yielded respectively the kat G S315T and the inh A - 15C → T mutations. Two-thirds of RMP-resistant isolates yielded the rpo B D516V mutation and one sixth yielded either H526D or S531L mutations. Genotyping analysis revealed the multiclonal spread of drug-resistant isolates in Central Tunisia. Data presented here complete the previously published map of resistant M. tuberculosis isolates and highlight their regional disparity in Tunisia.

As for the measures for tuberculosis in Japan, BCG inoculation and chemoprophylaxis have been done with emphasis placed on children and young people. Since, however, about 90% are older than 30 years and more than 50% are older than 60 years among the new TB patients, measures, particularly chemoprophylaxis aiming at the middle-old aged people are needed in the future. We discuss the method to select cases for chemoprophylaxis as to the cases of diabetes, collagen diseases and lung cancer administered corticosteroid preparations as well as the cases of Crohn's disease and rheumatoid arthritis administered anti-TNF-alpha among compromised hosts. In diabetics, chemoprophylaxis is necessary for those who show healing of TB despite there being no history of TB treatment. Where a corticosteroid preparation, more than 10 mg in terms of prednisolone is administered over a long period of time for collagen disease and lung cancer, chemoprophylaxis is necessary for those who show healing of TB despite there being no history of TB treatment and those who are suspected of having TB infection by a tuberculin test. In the cases of Crohn's disease and rheumatoid arthritis administered anti-TNF-alpha, chemoprophylaxis is necessary for those who show healing of TB despite those who are suspected of having TB infection by a tuberculin test. The administration period of INH as chemoprophylaxis should preferably be set at 9 months instead of 6 months hitherto used.

Isoniazid resistant mechanisms in Mycobacterium tuberculosis have been shown to involve at least two genes, kat G and inh A. Alteration in the kat G gene has been found in a great number of resistant isolates. Percentage of resistant isolates harboring alteration in this gene varied among laboratories suggesting that different mutations were presented in different geographic areas. Fourteen isoniazid resistant and five multidrug resistant isolates from the Central Chest Hospital, Thailand, were examined for the kat G gene mutations in the region between base position 17 to 299. No different pattern of mutations were found between these two groups. Among nineteen isolates, there were nine isolates which showed point mutations and five isolates with base insertions of the kat G gene. The remaining five isolates revealed gene deletion. Heteroduplex formation technique also confirmed base alterations in these nine mutants.

Emicizumab reduces bleeding in hemophilia A patients with inhibitor (HA-inh). A combination of immune tolerance induction therapy (ITI) and emicizumab prophylaxis may provide additional benefits, but coagulation potential during this treatment remains unknown. We assessed coagulation potentials in simulated ITI models in vitro using modified-clot waveform analysis. Factor (F)VIII-deficient plasma preincubated with anti-AA-plasma), then spiking bypassing agents (BPAs): activated prothrombin complex concentrates (aPCC 1.3 IU/mL; 50 IU/kg), recombinant factor (rF)VIIa (2.2 µg/mL; 90 µg/kg), and FVIIa/FX (1.5 µg/mL; 60 µg/kg), and/or FVIII (100, 200 IU/dL). Coagulation potentials in emicizumab-HA-plasma (10 BU/mL) remained within the normal range when BPA and FVIII were both present. In emicizumab-HA-plasma (1 BU/mL) with BPA and FVIII (200 IU/dL), they were near or beyond the normal range, but those with a half concentration of rFVIIa based on the half-life in blood were within the normal range. In samples without inhibitor, coagulation potentials with combined BPA and FVIII were far beyond the normal range but with FVIII (100 IU/dL) and rFVIIa at half concentration they remained within the normal range. These results may provide information on the feasibility of concurrent ITI under emicizumab prophylaxis.

Keywords: Bypassing agents; Clot waveform analysis; Emicizumab; Factor VIII; Hemophilia A.

A 62-year-old woman with rheumatoid arthritis presented with fever (T-103.9°F). Vital signs and physical examination were normal. She was taking adalimumab, methotrexate, and prednisone for the past 9 months. Blood and urine cultures, human immunodeficiency virus, rapid plasma reagin, purified protein derivative, and cerebrospinal fluid test findings were negative. Computed tomography showed scattered 0.2-cm nodules in the lungs and innumerable subcentimeter lesions in the liver and spleen. Broad-spectrum antibiotics were started empirically. Liver biopsy findings revealed necrotizing granulomas and were negative for acid fast bacilli and fungi on staining. As the patient was persistently febrile despite antibiotics, the antibiotics were discontinued, and an antituberculous regimen including INH, ethambutol, and pyrazinamide was initiated empirically on day 40 of hospitalization. Fourteen days after liver biopsy, acid-fast bacilli grew in the tissue culture. Disseminated tuberculosis (TB) was diagnosed. Fever subsided after 1 week of anti-TB treatment. Antitumor necrosis factor alpha therapy in rheumatoid arthritis increases the risk of TB 5-fold. This is mostly as a result of reactivation of latent TB and commonly presents as disseminated TB. It usually occurs in the early stage of treatment. In our patient, the screening test results for TB before initiation of Adalimumab could have been falsely negative due to immunosuppression secondary to steroids. Our case emphasizes that current screening tests can miss latent TB especially in immunosuppressed patients. As it is difficult to diagnose TB with polymerase chain reaction and culture, histopathology should be sought early. Patients on antitumor necrosis factor alpha therapy presenting with fever of unknown origin should be considered for empirical anti-TB treatment regardless of microbiological and tissue diagnosis.

Introduction: The aim of this study was to present the follow-up results of 110 patients who were given anti-tumor necrosis factor alpha (TNF-α) therapy for rheumatic and dermatologic diseases in a country with a high rates of active and latent tuberculosis bacillus infection. Material and Methods: Between February 2008 and January 2015, 110 cases in the age range of 23-77 who are using anti-TNF-α were included in the study retro-prospectively. Results: 52.7% of them (n = 58) were male. The most common diagnoses were rheumatoid arthritis (42.7%) and ankylosing spondylitis (38.2%). Most frequently given treatment were infliximab 37.3% and etanercept 30.9%, respectively. The 65 patients whose first tuberculin skin test (TST) value "5 mm and above" was started daily 300 mg INH prophylaxis for 9 months but 3 patients had not been started because of refusing treatment. In only one case chemoprophylaxis has had to be interrupted because of high liver function test due to the INH prophylaxis. TST conversion was observed in 14 patients. Further follow-up, it was observed that 4 patients had TST's positivity. Isoniazide (INH) prophylaxis was started these 18 patients (42.9%). Although INH prophylaxis has been given in two patients, they developed active tuberculosis in follow-up. Conclusion: Considering the INH resistance in our country, all patients especially the ones with residual lesion and history of previous exposure, should be followed up closely during the anti-TNF-α treatment.

Halloysite nanotubes (HLNTs) were used as nanocarriers of the tuberculostatic agent isoniazid (INH), a BCS (Biopharmaceutics Classification System) class III drug. Self-assembling nanohybrids (INH-loaded HLNTs) with an average outer diameter of 90 nm and polydispersity index of 0.7 approximately, were obtained by spontaneous adsorption of INH molecules to HLNTs powder in aqueous medium. The nanohybrids were aimed to improve oral drug bioavailability and reduce physicochemical incompatibility of INH with other concomitantly administered tuberculostatic agents. In vitro drug release from INH-loaded HLNTs was successfully fitted to a diffusive kinetic law founded on the adsorption-desorption equilibrium between drug molecules in solution and solid inorganic excipients. INH-loaded HLNTs showed good in vitro biocompatibility toward Caco-2 cells at the concentrations studied (up to 1233 μg/mL), with improved cell proliferation. Permeability tests showed that INH transport across Caco-2 cellular membranes was greatly enhanced and fluorescent microscopy confirmed that the drug encapsulated into nanohybrid was effectively internalized by the cells. INH-loaded HLNTs enhanced stability of the drug in presence of other tuberculostatic agents, both in binary and quaternary combinations. It has been demonstrated that simple interaction between INH with HLNTs leads to drug permeability and stability improvements that could greatly facilitate the design of multiple drug dosage forms, an actual challenge in oral treatment of tuberculosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

Despite recent success in reducing its incidence, tuberculosis remains a considerable challenge in Canada, particularly among foreign-born and Indigenous populations. A key component of the strategy for controlling the disease is the treatment of latent tuberculosis infection. The standard treatment consists of isoniazid (INH) daily for nine months. In recent years, shorter regimens have been developed in the hope of increasing rates of treatment acceptance and completion. Of these, the shortest and most recently developed is a combination of INH and rifapentine taken once weekly for 12 doses (3HP), typically using directly observed therapy (DOT). This regimen has been approved by the Food and Drug Administration in the United States but is not yet authorized in Canada. Based on a rapidly expanding number of observational studies and randomized controlled trials, 12 weeks of 3HP appears to have similar efficacy to nine months of INH, a favourable adverse event profile and potentially improved rates of treatment completion. Although rates of treatment acceptance, the role of self-administered therapy and the regimen's cost-effectiveness within the Canadian context remain uncertain, 3HP is a promising alternative to existing treatments for LTBI.

Herbal tea of Lagerstroemia speciosa Pers., commonly known as banaba, has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti-inflammatory efficacies. Drug-induced liver injury is a common cause of acute liver failure. Isoniazid (INH) is used as the first-line treatment for tuberculosis; clinical and experimental studies have reported an abnormal liver function after INH therapy. Dapsone (DDS) is used for leprosy and other infections. This study investigates the hepatoprotective effect of ethanolic banaba leaves extract (EBLE) against simultaneously administered INH- and DDS-induced hepatotoxicity in rats. DDS (30 mg/kg, i.p.) and INH (50 mg/kg. p.o.) were administered simultaneously for 30 days. In separate groups, rats were posttreated orally with EBLE (500 mg/kg) and silymarin (100 mg/kg) for 30 days after INH + DDS administration. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers, and histopathology were done. Simultaneous administration of INH- and DDS-induced significant elevation of marker enzymes of hepatotoxicity in the serum. This treatment also increased lipid peroxidation and pro-inflammatory markers (tumor necrosis factor alpha, transforming growth factor beta, and nuclear factor kappa B) expressions and decreased intracellular antioxidants such as superoxide dismutase, catalase, and glutathione in the liver tissue. All these abnormalities were significantly mitigated after EBLE and SIL posttreatments. The results of this study suggest that EBLE and silymarin can be protective against INH + DDS-induced hepatotoxicity. PRACTICAL APPLICATIONS: Herbal tea contain Lagerstroemia speciosa leaves are used in several Southeast Asian countries due to its rich antioxidant and inflammatory properties. This study showed the hepatoprotective efficacy of L. speciosa ethanolic extract against simultaneously administered dapsone- and isoniazid-induced hepatotoxicity in rats. L. speciosa administration was found to decrease dapsone- and isoniazid-induced oxidative stress and hepatic inflammation. L. speciosa herbal tea can reduce drug-induced hepatic complications as it contains phytochemicals such as corosolic acid, gallic acid, ellagic acid and berberine and are implicated for its hepatoprotective effect. Therefore, L. speciosa extract can be used for drug-induced liver injury.

Keywords: Isoniazid; banaba; corosolic acid; dapsone; drug-induced liver injury.

Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.

<strong cl<em>a</em>ss="sub-title"> Keywords: </strong> Isoni<em>a</em>zid; <em>a</em>poptosis; oocyte; oxid<em>a</em>tive stress.

It has been hypothesized that low levels of C1 esterase inhibitor (C1-INH), a key inhibitor of the complement pathway, may play a role in the occurrence of adverse events (AEs) associated with intravenous immunoglobulin (IVIG) therapy. This open-label pilot study evaluated C1-INH replacement, with recombinant human C1-INH (rhC1-INH), as a potential therapy for adults requiring IVIG and experiencing AEs. Patients received two rounds of IVIG infusion [pre-treatment phase (no rhC1-INH), 4-8 weeks] and then three rounds of one dose of intravenous rhC1-INH 50 U/kg (maximum, 4,200 U) with subsequent IVIG infusion (treatment phase, 6-12 weeks). Nineteen adults completed the study; all had an autoimmune condition linked to common variable immunodeficiency (CVID) or polyneuropathy, and 57.9% had low baseline C1-INH levels. Mean ± SD total scores improved significantly with the Headache Impact Test (from 62.8 ± 6.2 at pre-treatment to 57.7 ± 9.1 after treatment; mean Δ, -5.0; p = 0.02) and Modified Fatigue Impact Scale (from 59.3 ± 13.1 to 51.2 ± 15.4; mean Δ, -8.1; p = 0.006). Significant improvements in the Migraine Disability Assessment were observed for three of five items (p ≤ 0.002). Mean ± SD C1-INH level increased from 26.8 ± 5.9 mg/dl after the second round of IVIG (pre-treatment) to 32.1 ± 7.8 mg/dl after the third rhC1-INH treatment; functional C1-INH levels increased from 115.8 ± 34.7% to 158.3 ± 46.8%. Future research is warranted to explore the benefit of C1-INH therapy for reduction of IVIG-related AEs, as well as the role of C1-INH in patients with CVID and autoimmune disease.

<strong cl<em>a</em>ss="sub-title"> Clinic<em>a</em>l tri<em>a</em>l registr<em>a</em>tion: </strong> Clinic<em>a</em>lTri<em>a</em>ls.gov, identifier (<em>a</em> href="http://clinic<em>a</em>ltri<em>a</em>ls.gov/show/NCT03576469" title="See in Clinic<em>a</em>lTri<em>a</em>ls.gov">NCT03576469</<em>a</em>).

<strong cl<em>a</em>ss="sub-title"> Keywords: </strong> Ruconest; <em>a</em>ngioedem<em>a</em>s heredit<em>a</em>ry; complement C1 inhibitor protein; immunoglobulins intr<em>a</em>venous; recombin<em>a</em>nt hum<em>a</em>n C1 ester<em>a</em>se inhibitor.

<strong cl<em>a</em>ss="sub-title"> B<em>a</em>ckground: </strong> To verify the effic<em>a</em>cy <em>a</em>nd s<em>a</em>fety of <em>a</em>n inexpensive st<em>a</em>nd<em>a</em>rdized regimen for multidrug-resist<em>a</em>nt tuberculosis (MDR-TB) with low resist<em>a</em>nce to isoni<em>a</em>zid (<em>INH</em>), <em>a</em> multicenter prospective study w<em>a</em>s conducted in e<em>a</em>stern Chin<em>a</em>.

<strong cl<em>a</em>ss="sub-title"> Methods: </strong> P<em>a</em>tients di<em>a</em>gnosed <em>a</em>s MDR-TB with low concentr<em>a</em>tion <em>INH</em> resist<em>a</em>nce <em>a</em>nd rif<em>a</em>mpicin resist<em>a</em>nce, second-line/inject<em>a</em>ble <em>a</em>gents sensitive were prospectively enrolled, given the regimen of Amik<em>a</em>cin (Ak)-Fluoroquinolones (FQs)-Cycloserine (Cs)-Protion<em>a</em>mide (Pto)-P<em>a</em>sini<em>a</em>Zid (P<em>a</em>)-Pyr<em>a</em>zin<em>a</em>mide (Z) for 6 months followed by 12 months of FQs-Cs-Pto-P<em>a</em>-Z, <em>a</em>nd then followed up for tre<em>a</em>tment outcomes <em>a</em>nd <em>a</em>dverse events (AEs).

<strong cl<em>a</em>ss="sub-title"> Results: </strong> A tot<em>a</em>l of 114 p<em>a</em>tients were enrolled into the study. The over<em>a</em>ll f<em>a</em>vor<em>a</em>ble tre<em>a</em>tment r<em>a</em>te w<em>a</em>s 79.8% (91/114). Among 91 c<em>a</em>ses with f<em>a</em>vor<em>a</em>ble tre<em>a</em>tment, 75.4% (86/114) were cured <em>a</em>nd 4.4% (5/114) were completed tre<em>a</em>tment. Reg<em>a</em>rding to unf<em>a</em>vor<em>a</em>ble outcomes, <em>a</em>mong 23 c<em>a</em>ses, 8.8% (10/114) h<em>a</em>d f<em>a</em>ilures, 8.8% (10/114) losing follow up, 0.9% (1/114) h<em>a</em>d tre<em>a</em>tment termin<em>a</em>ted due to intoler<em>a</em>nce to drugs <em>a</em>nd 1.8% (2/114) died. Tre<em>a</em>tment f<em>a</em>vor<em>a</em>ble r<em>a</em>te w<em>a</em>s signific<em>a</em>ntly higher in newly tre<em>a</em>ted MDR-TB (91.7%, 33/36) th<em>a</em>n th<em>a</em>t in retre<em>a</em>ted MDR-TB (74.4%, 58/78, p 0.03). The investig<em>a</em>tors recorded 42 AEs occurrences in 30 of 114 p<em>a</em>tients (26.3%). Clinici<em>a</em>ns r<em>a</em>ted most AEs <em>a</em>s mild or moder<em>a</em>te (95.24%, 40/42).

<strong cl<em>a</em>ss="sub-title"> Conclusions: </strong> The regimen w<em>a</em>s proved to be effective, s<em>a</em>fe <em>a</em>nd inexpensive. It is suit<em>a</em>ble for specific drug resist<em>a</em>nt popul<em>a</em>tion, especi<em>a</em>lly for newly-tre<em>a</em>ted p<em>a</em>tients, which could be expected to be developed into <em>a</em> short-course regimen. Clinic<em>a</em>l tri<em>a</em>ls registr<em>a</em>tion Chin<em>a</em> Clinic<em>a</em>l Tri<em>a</em>l Registry ChiCTR-OPC-16009380.

<strong cl<em>a</em>ss="sub-title"> Keywords: </strong> Adverse effects; MDR-TB; MIC; Tre<em>a</em>tment outcome; Tre<em>a</em>tment regimen.

Most Mycobacterium tuberculosis (Mtb) resistant to rifampicin (RIF) has mutations in the rpoB gene, while most Mtb resistant to isoniazid (INH) has mutations in the katG gene or inhA promoter. We used gene chip technology to detect mutations in these genes to determine the resistance of Mtb to RIF and INH. A total of 4148 clinical specimens with sputum smear positivity for acid-fast bacilli (AFB) were detected. Then, taking the results of the drug sensitivity test (DST) as the reference standard, the detection efficiency of sputum samples from different grades of positive smears was compared in detail. We found that the sensitivity of the gene chip method for detecting sputum samples with a grade ≥ AFB 2 + was higher than that of sputum samples with a grade ≤ AFB 1 + (P < 0.05). When the grade of the sample was ≤ AFB 1 +, the sensitivity of the gene chip method was 72.6% for RIF, 67.3% for INH, and 60.0% for MDR-TB. When the grade of the sample was ≥ AFB 2 +, the sensitivity of the gene chip method was 84.5% for RIF, 78.2% for INH, and 73.9% for MDR-TB. The results show that gene chip technology can be directly used to diagnose drug-resistant tuberculosis in clinical specimens, and the diagnostic efficiency for the detection of sputum specimens with a grade ≥ AFB 2 + is better than that of other sputum specimens.

This study was conducted to investigate the potential effects of active immunization against recombinant-derived goose inhibin-α (INH-α), anti-Müllerian hormone (AMH), and prolactin (PRL) fusion protein on broodiness onset and egg production in geese. The purified fusion proteins (INH-α, AMH, and PRL) were prepared using a prokaryotic expression system. Female Zhedong geese (10 mo old) were randomly assigned to one of 4 treatments and raised in separate pens. The geese were actively immunized with the recombinant goose INH-α, AMH, or PRL, respectively, and phosphate-buffered saline as control. The results showed the corresponding antibodies were produced when the geese were immune INH-α, AMH-, and PRL-recombinant proteins. The significantly higher luteinizing hormone contents were observed in the INH-α, AMH, and PRL recombinant protein-immunized geese, while the lower AMH hormone content only in PRL-immunized birds. AMH recombinant protein immunized geese had more large yellow follicles of ovary, while the INHα-treated birds with more other follicles compared with control geese. In addition, the geese receiving INH-α recombinant protein, the broodiness onset was about 6 d, which significantly shorter than did PBS immunization (16 d). The INHα- and PRL-immunization also resulted in 12.5 and 8.5 d shorter broody duration intervals compared to the control birds. Moreover, the lower new broodiness rate was observed in three recombinant proteins treated birds. Finally, the PRL recombinant protein-immunization resulted in an average increase of 1.34 eggs during a 40-d observation. Collectively, the data demonstrated that active immunization against recombinant proteins INH-α or AMH could promote LH hormone secretion, regulate follicle development and decrease the broodiness rate. Also, active immunization with a recombinant-derived goose PRL protein might improve egg laying performance.

Keywords: active immunity; egg production performance; goose.

Background: The widespread use of biological treatments has increased the frequency of opportunistic infections such as tuberculosis (TB). The primary objective of our study was to determine the rate of tuberculin skin test (TST) conversion during biological therapy. The secondary objective was to monitor the side effects related to isoniazid (INH) prophylaxis, in the selected subgroup.

Methods: Children with rheumatologic diseases receiving treatment with tumor necrosis factor-alpha (TNF-α) inhibitors, and tocilizumab and canakinumab were included in the study. If baseline screening was negative, TST was performed annually after initiation of biologic therapy. TST conversion was accepted as an increase of at least 6 mm and becoming positive or an increase of 10 mm or more, even in the absence of positivity.

Results: 121 patients (female n: 63, 52%) were included in the study. The mean follow-up period was 26.10±14.8 months. 85 of the patients were using TNF-α inhibitors and 18 tocilizumab, and 18 canakinumab. Forty patients had positive TST before biological agents and received chemoprophylaxis with INH. The rate of TST conversion among the 3 biological agents was not statistically significant (20.4% of TNF-α inhibitors, 25% of canakinumab and 33.3% of tocilizumab users). All patients with LTBI received INH prophylaxis, and none of them had active TB.

Conclusions: There was no statistically significant difference among the three biological agents, regarding the seroconversion rates. Patients receiving tocilizumab and canakinumab should also be screened for TB during follow-up. INH related side effects are rare.

Keywords: TNF-α inhibitors; biological agents; canakinumab; children; tocilizumab; tuberculosis.

Green synthesis of silver nanoparticles (AgNPs) was synthesized from fresh garlic extract coupled with isoniazid hydrazide (INH), a commonly used antibiotic to treat tuberculosis. A molecular docking study conducted with the selected compounds compared with anthranilate phosphoribosyltransferase (trpD) from Mycobacterium tuberculosis. The aqueous extract of garlic was prepared and mixed with silver nitrate (AgNO3) solution for the superfast synthesis of stable AgNPs. INH was then conjugated with AgNPs at different ratios (v/v) to obtain stable INH-AgNPs conjugates (AgNCs). The resulting AgNCs characterized by FTIR spectra revealed the ultrafast formation of AgNPs (<5 s) and perfectly conjugated with INH. The shifting of λmax to longer wavelength, as found from UV spectral analysis, confirmed the formation of AgNCs, among which ideal formulations (F7, F10, and F13) have been pre-selected. The zeta particle size (PS) and the zeta potential (ZP) of AgNPs were found to be 145.3 ± 2.1 nm and -33.1 mV, respectively. These data were significantly different compared to that of AgNCs (160 ± 2.7 nm and -14.4 mV for F7; 208.9 ± 2.9 nm and -19.8 mV for F10; and 281.3 ± 3.6 nm and -19.5 mV for F13), most probably due to INH conjugation. The results of XRD, SEM and EDX confirmed the formation of AgNCs. From UV spectral analysis, EE of INH as 51.6 ± 5.21, 53.6 ± 6.88, and 70.01 ± 7.11 %, for F7, F10, and F13, respectively. The stability of the three formulations was confirmed in various physiological conditions. Drug was released in a sustainable fashion. Besides, from the preferred 23 compounds, five compounds namely Sativoside R2, Degalactotigonin, Proto-desgalactotigonin, Eruboside B and Sativoside R1 showed a better docking score than trpD, and therefore may help in promoting anti-tubercular activity.

<strong cl<em>a</em>ss="sub-title"> Keywords: </strong> g<em>a</em>rlic extr<em>a</em>ct; green synthesis; isoni<em>a</em>zid hydr<em>a</em>zide; molecul<em>a</em>r docking; n<em>a</em>noconjug<em>a</em>tes; silver n<em>a</em>nop<em>a</em>rticles.