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This concise review navigates the intricate realm of Interleukin-6 (IL-6), an important member of the cytokine family. Beginning with an introduction to cytokines, this narrative review unfolds with the historical journey of IL-6, illuminating its evolving significance. A crucial section unravels the three distinct signaling modes employed by IL-6, providing a foundational understanding of its versatile interactions within cellular landscapes. Moving deeper, the review meticulously dissects IL-6's signaling mechanisms, unraveling the complexities of its pleiotropic effects in both physiological responses and pathological conditions. A significant focus is dedicated to the essential role IL-6 plays in inflammatory diseases, offering insights into its associations and implications for various health conditions. The review also takes a therapeutic turn by exploring the emergence of anti-IL-6 monoclonal inhibitors, marking a profound stride in treatment modalities. Diving into the molecular realm, the review explores small molecules as agents for IL-6 inhibition, providing a nuanced perspective on diverse intervention strategies. As the review embarks on the final chapters, it contemplates future aspects, offering glimpses into potential research trajectories and the evolving landscape of IL-6-related studies., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Protein electrophoresis is commonly used as an aid in the diagnosis of monoclonal gammopathies and is performed in many laboratories in Canada and throughout the world. However, unlike many other diagnostic tests, there is limited guidance for standardization and neither guidance nor specific recommendations for clinical reporting of serum (SPE) or urine (UPE) protein electrophoresis and immunotyping available in the literature. Therefore, a Canadian effort was undertaken to recommend standards that cover all aspects of clinical reporting with an ultimate goal towards reporting standardization. The Canadian Society of Clinical Chemists (CSCC) Monoclonal Gammopathy Interest Group (MGIG), which is composed of CSCC members with an interest in protein electrophoresis, has formed a Monoclonal Gammopathy Working Group (MGWG) to take initial steps towards standardization of SPE, UPE and immunotyping. Candidate standardization recommendations were developed, discussed and voted upon by the MGWG. Candidate recommendations that achieved 90% agreement are presented as consensus recommendations. Recommendations that did not achieve 90% consensus remain candidate recommendations and are presented with accompanying MGWG discussion. Eleven consensus recommendations along with candidate recommendations for nomenclature, protein fraction reporting, test utilization, interference handling and interpretive reporting options are presented., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The mycobacterial F0F1-ATP synthase (ATPase) is a validated target for the development of tuberculosis (TB) therapeutics. Therefore, a series of eighteen novel compounds has been designed, synthesized and evaluated against Mycobacterium smegmatis ATPase. The observed ATPase inhibitory activities (IC50) of these compounds range between 0.36 and 5.45μM. The lead compound 9d [N-(7-chloro-2-methylquinolin-4-yl)-N-(3-((diethylamino)methyl)-4-hydroxyphenyl)-2,3-dichlorobenzenesulfonamide] with null cytotoxicity (CC50>300μg/mL) and excellent anti-mycobacterial activity and selectivity (mycobacterium ATPase IC50=0.51μM, mammalian ATPase IC50>100μM, and selectivity >200) exhibited a complete growth inhibition of replicating Mycobacterium tuberculosis H37Rv at 3.12μg/mL. In addition, it also exhibited bactericidal effect (approximately 2.4log10 reductions in CFU) in the hypoxic culture of non-replicating M. tuberculosis at 100μg/mL (32-fold of its MIC) as compared to positive control isoniazid [approximately 0.2log10 reduction in CFU at 5μg/mL (50-fold of its MIC)]. The pharmacokinetics of 9d after p.o. and IV administration in male Sprague-Dawley rats indicated its quick absorption, distribution and slow elimination. It exhibited a high volume of distribution (Vss, 0.41L/kg), moderate clearance (0.06L/h/kg), long half-life (4.2h) and low absolute bioavailability (1.72%). In the murine model system of chronic TB, 9d showed 2.12log10 reductions in CFU in both lung and spleen at 173μmol/kg dose as compared to the growth of untreated control group of Balb/C male mice infected with replicating M. tuberculosis H37Rv. The in vivo efficacy of 9d is at least double of the control drug ethambutol. These results suggest 9d as a promising candidate molecule for further preclinical evaluation against resistant TB strains., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Medical errors are a prominent issue in health care. Numerous studies point at the high prevalence of adverse events, many of which are preventable. Although there is a range of severity in errors, they all cause harm, to the patient, to the system, or both. While errors have many causes, including human interactions and system inadequacies, the focus on individuals rather than the system has led to an unsuitable culture for improving patient safety. Important areas of focus are diagnostic procedures and clinical laboratories because their results play a major role in guiding clinical decisions in patient management. Proper disclosure of medical errors and adverse events is also a key area for improvement. Globally, system improvements are beginning to take place, however, in Canada, policies on disclosure, error reporting and protection for physicians remain non-uniform. Achieving a national standard with mandatory reporting, in addition to a non-punitive system is recommended to move forward., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The Institute of Medicine (IOM) report (1999) stated that the prevalence of medical errors is high in today's health care system. Some specialties in health care are more risky than others. A varying blunder/error rate of 0.1-9.3% in clinical diagnostic laboratories has been reported in the literature. Many of these errors occur in the preanalytical and postanalytical phases of testing. It has been suggested that the errors occurring in clinical diagnostic laboratories are smaller in number than those occurring elsewhere in a hospital setting. However, given the quantum of laboratory tests used in health care, even this small rate may reflect a large number of errors. The surgical specialties, emergency rooms, and intensive care units have been previously identified as areas of risk for patient safety. Though the nature of work in these specialties and their interdependence on clinical diagnostic laboratories presents abundant opportunities for error-generating behavior, many of these errors may be preventable. Appropriate attention to system factors involved in these errors and designing intelligent system approaches may help control and eliminate many of these errors in health care.

The issue of medical errors has received substantial attention in recent years. The Institute of Medicine (IOM) report released in 1999 has several implications for health care systems in all disciplines of medicine. Notwithstanding the plethora of available information on the subject, little, by way of substantive action, is done toward medical error reduction. A principal reason for this may be the stigma associated with medical errors. An educational program with a practical, informed, and longitudinal approach offers realistic solutions toward this end. Effective reporting systems need to be developed as a medium of learning from the errors and modifying behaviors appropriately. The presence of a strong leadership supported by organizational commitment is essential in driving these changes. A national, provincial or territorial quality care council dedicated solely for the purpose of enhancing patient safety and medical error reduction may be formed to oversee these efforts. The bioethical and emotional components associated with medical errors also deserve attention and focus.

The prevalence of medical errors in health care systems has generated immense interest in recent years. The research on adverse events in hospitalized populations has consistently revealed high rates of adverse events. Some of these adverse events result from medical errors and a majority of these errors may be preventable. These errors can occur anywhere and at anytime in health care processes. The consequences of these errors may vary from little or no harm to being ultimately fatal to the patients. It is important to recognize that a degree of error is inevitable in any human task and human fallibility in health care should be accepted. The underlying precursors for many of these human errors may primarily be attributed to latent systemic factors inherent in today's increasingly complex health care system. The focus of adverse event analyses on individual shortcomings without appropriate attention to system issues leads to ineffective solutions. The cognitive influence on medical decision-making and error generation is also significant and should not be discounted.

A precise and reproducible HPLC assay has been developed and validated for simultaneous determination of bulaquine (BQ) and its metabolite primaquine (PQ) in rabbit plasma. The method, applicable to 0.5 ml plasma, involves double extraction of samples with n-hexane: isopropanol (98:2, v/v) containing dimethyl octylamine (DMOA) (0.1%, v/ v). Separations were accomplished by reversed-phase liquid chromatography using a Spheri-5 cyano column with a low pressure gradient with mobile phase consisting of ammonium acetate buffer (50 mM, pH 6.0) and acetonitrile with DMOA. The method was sensitive with a limit of quantitation of 20 ng ml(-1) in rabbit plasma for both BQ and PQ and the recoveries were > 85 and > 45%, respectively. Excellent linear relationships (r > 0.99) were obtained between the measured and added concentration ratios of the plasma concentrations over a range of 20-1000 ng ml(-1) for both the analytes. Precision and accuracy were acceptable as indicated by relative standard deviations from 1.8 to 15.1%, bias values ranging from -14.2 to 15.7%. Moreover, BQ was stable in rabbit plasma for 15 days of storage at -60 degrees C and after being subjected to three freeze-thaw cycles. The method was applied to determine the levels and pharmacokinetics of BQ in rabbits following a single 2.5 mg kg(-1) oral and intravenous dose. The BQ levels declined and the PQ levels increased with time. The PQ/BQ ratio after oral dose at 1 and 1.5 h were higher than that after intravenous dose. In the pilot preclinical pharmacokinetic study after a single 2.5 mg kg(-1) oral dose, BQ levels were determined up to 6 h (post-prandial) and 8 h (fasting). The plasma concentration versus time data were best fitted to a two-compartment open model with first-order absorption and elimination processes without lag time. The AUC(0-infinity) and the elimination t1/2 in fasted rabbit was higher than that in post-prandial rabbit indicating the effect of food on BQ pharmacokinetics.

A high-performance liquid chromatographic (HPLC) method was developed for the analysis of N,N'-Dichlorobis (2,4,6-trichlorophenyl) urea (CC-2), a potent sulphur mustard decontaminant, in rat serum. The HPLC analysis, applicable to 0.5 ml volumes of serum, involved double extraction of serum samples with diethyl ether at alkaline pH followed by separation on a RP-18 column and the use of UV detector at 230 nm. The method was sensitive with a limit of quantitation of 10 ng ml(-1) in rat serum and the recovery was always >90%. Excellent linear relationships (r>0.99) were obtained between the measured and added concentration ratios of the serum concentrations over a range of 10-200 ng ml(-1). The precision and accuracy were acceptable as indicated by relative standard deviation ranging from 2.47 to 17.49%, bias values ranging from -4.35 to 13.21%. Moreover, CC-2 was found stable in rat serum even after 3 months of storage at -60 degrees C and being subjected to three freeze-thaw cycles. The assay was found to be sensitive, specific, accurate, precise, and reliable for use in pharmacokinetic studies.