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Ahmad Qasem, Mitra Safavikhasraghi, Saleh A Naser
BACKGROUND: Most recently we reported that RHB‑104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn's disease (CD)-associated with Mycobacterium avium subspecies paratuberculosis (MAP) (Alcedo et al. in Gut Pathog 14:32, 2016). The combination exhibited unique synergistic antimicrobial growth activity. The proprietary RHB-104 capsule formulation contains active ingredients (63.3 % Clarithromycin (CLA), 6.7 % Clofazimine (CLO) and 30 % Rifabutin (RIF))...
2016: Gut Pathogens
Nirupama Kasturi, Renuka Srinivasan
A 26-year-old male vitiliginous patient presented with decreased visual acuity because of a central scotoma in the left eye with no significant retinal changes on fundus examination. In this case report, a diagnosis of possible drug-induced premaculopathy was made, and the drugs were withdrawn. On the follow-up, after 3 months, the visual acuity in the left eye gradually improved. Early suspicion of drug-induced maculopathy and withdrawal of the drug may prevent the progression of maculopathy.
July 2016: Journal of Pharmacology & Pharmacotherapeutics
Onivola Raharolahy, Lala S Ramarozatovo, Irina M Ranaivo, Fandresena A Sendrasoa, Malalaniaina Andrianarison, Mala Rakoto Andrianarivelo, Emmanuelle Cambau, Fahafahantsoa Rapelanoro Rabenja
We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole...
2016: Case Reports in Infectious Diseases
Dhiraj Kumar Singh, Ved Prakash Dwivedi, Anand Ranganathan, William R Bishai, Luc Van Kaer, Gobardhan Das
Tuberculosis (TB) is the oldest known infectious disease, yet there is no effective vaccine against adult pulmonary TB. Emerging evidence indicates that T helper (Th)1 and Th17 cells play important roles in host protection against TB. However, TB vaccine efficacy in mice is critically dependent on the balance between antigen-specific central memory T (Tcm) to effector memory T (Tem) cells. Specifically, a high Tcm to Tem cell ratio is essential for optimal vaccine efficacy. Here, we show that pharmacological inhibition of Kv1...
August 28, 2016: Journal of Infectious Diseases
Z Ozturk, A Tatliparmak
Leprosy is a chronic disease which primarily affects the skin, mucous membranes and peripheral nerves due to Mycobacterium leprae. It is now infrequent in Europe and is rarely reported during pregnancy. Leprosy can be exacerbated during pregnancy, and without treatment it can permanently damage the skin, nerves, limbs and eyes. Therefore, it is important to treat leprosy during pregnancy. This article describes a patient with multibacillary lepromatous leprosy who was treated with multidrug therapy during pregnancy and breastfeeding...
August 23, 2016: Dermatologic Therapy
Angela Zaccagnino, Antonella Managò, Luigi Leanza, Artur Gontarewitz, Bernhard Linder, Michele Azzolini, Lucia Biasutto, Mario Zoratti, Roberta Peruzzo, Karen Legler, Anna Trauzold, Holger Kalthoff, Ildiko Szabo
Pancreatic ductal adenocarcinoma (PDAC) represents the most common form of pancreatic cancer with rising incidence in developing countries. Unfortunately, the overall 5-year survival rate is still less than 5%. The most frequent oncogenic mutations in PDAC are loss-of function mutations in p53 and gain-of-function mutations in KRAS. Here we show that clofazimine (Lamprene), a drug already used in the clinic for autoimmune diseases and leprosy, is able to efficiently kill in vitro five different PDAC cell lines harboring p53 mutations...
August 16, 2016: Oncotarget
Yu-Min Chuang, Noton K Dutta, Chien-Fu Hung, T-C Wu, Harvey Rubin, Petros C Karakousis
Mycobacterium tuberculosis (Mtb) remains a global health threat largely due to the lengthy duration of curative antibiotic treatment, contributing to medical nonadherence and the emergence of drug resistance. This prolonged therapy is likely due to the presence of Mtb persisters, which exhibit antibiotic tolerance. Inorganic polyphosphate (poly(P)) is a key regulatory molecule in the Mtb stringent response mediating antibiotic tolerance. The polyphosphate kinase PPK1 is responsible for poly(P) synthesis in Mtb, while the exopolyphosphatases PPX1 and PPX2, and the GTP synthase PPK2 are responsible for poly(P) hydrolysis...
August 15, 2016: Antimicrobial Agents and Chemotherapy
Dirk A Lamprecht, Peter M Finin, Md Aejazur Rahman, Bridgette M Cumming, Shannon L Russell, Surendranadha R Jonnala, John H Adamson, Adrie J C Steyn
The Mycobacterium tuberculosis (Mtb) electron transport chain (ETC) has received significant attention as a drug target, however its vulnerability may be affected by its flexibility in response to disruption. Here we determine the effect of the ETC inhibitors bedaquiline, Q203 and clofazimine on the Mtb ETC, and the value of the ETC as a drug target, by measuring Mtb's respiration using extracellular flux technology. We find that Mtb's ETC rapidly reroutes around inhibition by these drugs and increases total respiration to maintain ATP levels...
2016: Nature Communications
Petrease H Patton, Claire E Parker, John K MacDonald, Nilesh Chande
BACKGROUND: There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn's disease. A meta-analysis was performed to evaluate the use of anti-tuberculous therapy for the maintenance of remission in Crohn's disease. OBJECTIVES: To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease. SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015...
2016: Cochrane Database of Systematic Reviews
Shengke Li, Judy Yuet-Wa Chan, Yan Li, David Bardelang, Jun Zheng, Wing Wai Yew, Denise Pui-Chung Chan, Simon Ming Yuen Lee, Ruibing Wang
Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-tuberculosis drug, clofazimine (CFZ), that has poor water-solubility and inherent cardiotoxicity. In our study, CFZ was found to be complexed by CB[7], in a 1 : 1 binding mode with a relatively strong binding affinity (in the order of magnitude of 10(4)-10(5) M(-1)), as determined by the phase solubility method via HPLC-UV analysis and (1)H NMR titration, as well as UV-visible spectroscopic titration, and further confirmed by electrospray ionization mass spectrometry (ESI-MS)...
August 21, 2016: Organic & Biomolecular Chemistry
Kamal Ahmed, Holly V Shaw, Alexey Koval, Vladimir L Katanaev
Aberrant WNT signaling underlies cancerous transformation and growth in many tissues, such as the colon, breast, liver, and others. Downregulation of the WNT pathway is a desired mode of development of targeted therapies against these cancers. Despite the urgent need, no WNT signaling-directed drugs currently exist, and only very few candidates have reached early phase clinical trials. Among different strategies to develop WNT-targeting anti-cancer therapies, repositioning of existing drugs previously approved for other diseases is a promising approach...
2016: Cancers
Mohammad Rehan Ajmal, Sumit Kumar Chaturvedi, Nida Zaidi, Parvez Alam, Masihuz Zaman, Mohammad Khursheed Siddiqi, Saima Nusrat, Mohammad Sarwar Jamal, Mohamed H Mahmoud, Gamal Badr, Rizwan Hasan Khan
The present study details the binding process of clofazimine to hen egg white lysozyme (HEWL) using spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM) and molecular docking techniques. Clofazimine binds to the protein with binding constant (Kb) in the order of 1.57x10(4) at 298K. Binding process is spontaneous and exothermic. Molecular docking results suggested the involvement of hydrogen bonding and hydrophobic interactions in the binding process. Bacterial cell lytic activity in the presence of clofazimine was increased to more than 40% of the value obtained with HEWL only...
July 11, 2016: Journal of Biomolecular Structure & Dynamics
Arnold Mafukidze, Elizabeth Harausz, Jennifer Furin
INTRODUCTION: Drug-resistant forms of tuberculosis are a major public health problem with a serious global impact. Although there have recently been two new drugs introduced for the treatment of drug-resistant TB (bedaquiline and delamanid), the current therapeutic armamentarium is limited. Because treatment of drug-resistant TB requires the use of a multidrug-regimen, there has been growing interest in the use of antibiotics developed for other infectious pathogens but that have shown efficacy in the treatment of TB...
July 18, 2016: Expert Review of Clinical Pharmacology
Adam Heikal, Kiel Hards, Chen-Yi Cheung, Ayana Menorca, Mattie S M Timmer, Bridget L Stocker, Gregory M Cook
OBJECTIVES: Quinolinequinones (QQ) have been shown to inhibit the growth of mycobacterial species, but their mode(s) of action and molecular target(s) remain unknown. To facilitate further development of QQ as antimycobacterial drugs, we investigated the molecular mechanism and target of QQ in mycobacteria. METHODS: Cell viability of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin was determined in the presence of QQ8c, a representative QQ compound, and isoniazid, a frontline antitubercular drug...
October 2016: Journal of Antimicrobial Chemotherapy
Karel P Alcedo, Saisathya Thanigachalam, Saleh A Naser
BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated as an etiological agent of Crohn's disease (CD), a debilitating chronic inflammatory bowel disease. Clarithromycin (CLA), clofazimine (CLO), rifabutin (RIF) and other antibiotics have been used individually or in combinations with other drugs to treat mycobacterial diseases including CD. The treatment has varied by regimen, dosage, and duration, resulting in conflicting outcomes and additional suffering to the patients...
2016: Gut Pathogens
Thomas M Reeves, Patricia A Trimmer, Beverly S Colley, Linda L Phillips
Axonal injury is present in essentially all clinically significant cases of traumatic brain injury (TBI). While no effective treatment has been identified to date, experimental TBI models have shown promising axonal protection using immunosuppressants FK506 and Cyclosporine-A, with treatment benefits attributed to calcineurin inhibition or protection of mitochondrial function. However, growing evidence suggests neuroprotective efficacy of these compounds may also involve direct modulation of ion channels, and in particular Kv1...
September 2016: Experimental Neurology
Andrea Paradisi, Francesco Ricci, Paolo Sbano
Granuloma faciale (GF), also known as "eosinophilic granuloma," is a rare benign leukocytoclastic vasculitis which most commonly occurs on the face of middle-aged Caucasian males. Clinically, GF appears as single or multiple, slowly growing, reddish-brown papules, nodules or plaques which may be cosmetically unpleasant. Its pathogenesis is unknown and GF is notoriously resistant to treatments. Both medical (dapsone, colchicine, gold injections, isoniazid, clofazimine, corticosteroids, psoralen ultraviolet radiation, and topical tacrolimus) and surgical therapies (excision, graft, dermabrasion, argon laser, carbon dioxide laser, pulsed dye laser, cryotherapy, and electrosurgery) have been used for GF but no effective treatment has yet been found...
June 6, 2016: Dermatologic Therapy
Henning Trawinski, Jan-Hinnerk Brüning, Petra Baum, Mirjana Ziemer, Stefan Schubert, Christoph Lübbert
History and clinical findings | A 42-year-old migrant from Brazil presented with persistent sensory disturbances, skin discolorations and local alopecia in the upper limbs. Decisive for the presentation in our Tropical Medicine Clinic were new occurrences of severe pain and redness and swelling in the area of the lesions that had already been assessed by a number of medical specialists without a clear diagnosis could be made. Investigations and diagnosis | The histological analysis of skin biopsies showed perivascular, perineural, periadnexial lymphocytic and granulomatous dermatitis...
June 2016: Deutsche Medizinische Wochenschrift
Lauren C Fiske, Diane C Homeyer, Michael Zapor, Joshua Hartzell, Tyler Warkentien, Amy C Weintrob, Anuradha Ganesan, Timothy Burgess, Erik Snesrud, Paige Waterman, Lindsey Nielsen, Roseanne A Ressner
OBJECTIVES: Rapidly growing nontuberculous mycobacteria (RGNTM) have yet to be described in combat-related injuries. This study investigates the epidemiology, clinical findings, treatment, and outcomes of RGNTM infections among combat casualties wounded in Afghanistan from 2010 to 2012. METHODS: Patients with RGNTM were identified from the Department of Defense Trauma Registry through the Trauma Infectious Disease Outcomes Study. Trauma history, surgical management, and clinical data were collected...
June 2016: Military Medicine
Jie Feng, Wanliang Shi, Shuo Zhang, David Sullivan, Paul G Auwaerter, Ying Zhang
Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease...
2016: Frontiers in Microbiology
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