Development and Use of Enzyme-Linked Immunosorbent Assays (ELISA) for the Detection of Protein Aggregates in Interferon-Alpha (IFN-α) Formulations

Purpose. Protein aggregates are thought to be involved in the immunogenicity of recombinant proteins in humans. To probe human IFN- formulations for the presence of soluble protein aggregates, enzyme-linked immunosorbent assays (ELISA) were developed. Methods. For the detection of IFN--IFN- and HSA-IFN- aggregates, sandwich ELISAs were developed using a monoclonal anti-IFN- antibody as a capture antibody and the same anti-IFN- antibody and an anti-human serum albumin (HSA) antibody (HRP-labeled), respectively. Results. Marketed freeze-dried, HSA-containing IFN- formulations tested in the ELISAs all contained IFN--IFN- and/or HSA-IFN- protein aggregates, although in varying amounts. These aggregates were predominantly IFN- dimers and 1:1 conjugates of HSA with IFN-. Test formulations revealed that aggregation of IFN- was strongly affected by the presence of pharmaceutical excipients, pH of the formulation, lyophilisation procedure, and storage temperature and time. Conclusions. The ELISAs are rapid, highly specific for aggregates in the presence of both IFN- and HSA monomers and allow the direct detection of both types of aggregates in formulations in the nanogram range. The new assays will assist the monitoring of the aggregate-inducing processes during IFN- formulation and storage in an early phase and the development of aggregate-free IFN- formulations.     

IFN-α-2a (Interferon) and ribavirin induced suicidal attempt in a patient of chronic HCV: A rare case report

Interferons (IFNs) are proteins produced by cells, fibroblasts and macrophages, in response to viral invasion, and mediates immune response. IFN-α and ribavirin are the approved treatment for HCV infection, but also carries a risk of neuropsychiatric adverse effects, viz. insomnia, irritability, mood changes, and depression.We present a case report of depression induced by IFN-α and ribavirin, leading to attempted suicide. Following the episode, antidepressant paroxetine (20 mg o.d.) and zolpidem (10 mg h.s) were added with psychotherapy. No significant improvement was observed. Patient was given a drug dechallenge (IFN-α and ribavirin). Dramatic improvement was seen over 1 month. Following rechallenge with combination, patient again experienced depressive symptoms with suicidal ideation. IFN-α and ribavirin were promptly stopped. Naranjo causality assessment scale revealed probable association with IFN-α and ribavirin. The report intends to improve awareness among clinicians to facilitate early diagnosis and intervention of similar cases.     

Pegylated IFN-α-2a and ribavirin in the treatment of hepatitis C infection in children

The epidemiology, natural history and efficacy of treatment for chronic hepatitis C in children are presented. An increase in the number of vertical infections of this etiology is suggested. In children, especially in those vertically infected, spontaneous elimination of hepatitis C virus (HCV) is observed more often than it is in adults. The most common HCV genotype detected in children is genotype 1, but Italian researchers have described an increase of infection with genotypes 3 and 4 HCV in children in recent years. In the context of recent opinions suggesting a more rapid progression of HCV 3 genotype infection, treatment of these children should begin immediately. The high efficacy (sustained viral response > 50%), safety (few adverse events with less intensity as compared to adults) and good tolerance of therapy with pegylated IFN α-2a and ribavirin have been revealed in children. The differences in the efficacy and tolerability of HCV treatment between children and adults are described. A recommendation for inclusion and monitoring parameters of children’s physical and mental development during HCV treatment is presented. Regarding new anti-HCV therapies with very high efficacy, including IFN-free treatment, the introduction of these therapies to children is recommended.     

Role of the Breast Cancer Resistance Protein (BCRP/ABCG2) in Drug Transport—an Update

The human breast cancer resistance protein (BCRP, gene symbol ABCG2) is an ATP-binding cassette (ABC) efflux transporter. It was so named because it was initially cloned from a multidrug-resistant breast cancer cell line where it was found to confer resistance to chemotherapeutic agents such as mitoxantrone and topotecan. Since its discovery in 1998, the substrates of BCRP have been rapidly expanding to include not only therapeutic agents but also physiological substances such as estrone-3-sulfate, 17β-estradiol 17-(β-d-glucuronide) and uric acid. Likewise, at least hundreds of BCRP inhibitors have been identified. Among normal human tissues, BCRP is highly expressed on the apical membranes of the placental syncytiotrophoblasts, the intestinal epithelium, the liver hepatocytes, the endothelial cells of brain microvessels, and the renal proximal tubular cells, contributing to the absorption, distribution, and elimination of drugs and endogenous compounds as well as tissue protection against xenobiotic exposure. As a result, BCRP has now been recognized by the FDA to be one of the key drug transporters involved in clinically relevant drug disposition. We published a highly-accessed review article on BCRP in 2005, and much progress has been made since then. In this review, we provide an update of current knowledge on basic biochemistry and pharmacological functions of BCRP as well as its relevance to drug resistance and drug disposition.KEY WORDS: ABCG2, ATP-binding cassette, BCRP, drug transport, transporter     

Incidence of Healthcare-Associated Infections (HAIs) and the adherence to the HAIs’ prevention strategies in a military hospital in Alkharj

BackgroundHealthcare-associated infections (HAI) are considered one of the most common adverse events in health care service provision. In order to prevent the occurrence of HAIs, it is important to implement several prevention strategies.ObjectivesThis study aims to determine the incidence of healthcare-associated infections in a military hospital in Alkharj and the adherence to the HAIs’ prevention strategies.MethodsThis study included exporting data for all infected cases confirmed by the infection disease specialists in 2019. The data were collected from the reports that were written by infection control unit and infectious disease department.ResultsThe rate of healthcare associated infections (HAIs) in 2019 was 0.43% of total patient admissions. The rate of central line associated bloodstream infections in 2019 was 1.15 per 1000 central line days. The rate of catheter associated urinary tract infections in 2019 was 1.00 per 1000 catheter days. The rate of ventilator associated pneumonia in 2019 was 2.11 per 1000 ventilator days and the rate of surgical site infections in 2019 was 0.41 %.ConclusionThe rate of overall healthcare-associated infections (HAI) was low. The compliance rate of health care workers to preventive measures that control HAIs was generally high but there was a need for more awareness particularly regarding personal protective equipment and hand hygiene. So it is important to attend more awareness activities and workshops particularly regarding personal protective equipment and hand hygiene. Furthermore, infection control unit and infectious disease department in the hospital should support the robust HAI prevention programs.     

Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes

The topoisomerase-IIα inhibition and antiproliferative activity of α-heterocyclic thiosemicarbazones and their corresponding copper(II) complexes have been investigated. The Cu(II)(thiosemicarbazonato)Cl complexes were shown to catalytically inhibit topoisomerase-IIα at concentrations (0.3-7.2 μM) over an order of magnitude lower than their corresponding thiosemicarbazone ligands alone. The copper complexes were also shown to inhibit the proliferation of breast cancer cells expressing high levels of topoisomerase-IIα (SK-BR-3) at lower concentrations than cells expressing lower levels of the enzyme (MCF-7).     

Characterization of ligand binding to the σ(1) receptor in a human tumor cell line (RPMI 8226) and establishment of a competitive receptor binding assay

The standard assay for the determination of σ(1) receptor affinities of novel compounds is a competitive binding assay using [(3)H]-(+)-pentazocine as radioligand and membrane preparations from guinea pig brain. Herein, a novel competitive binding assay was developed employing the hematopoietic cell line of human multiple myeloma (RPMI 8226), which expresses a large amount of the human σ(1) receptor. Membrane fragments of RPMI 8226 cells were prepared and characterized. A Western blot analysis confirmed the high density of σ(1) receptors in this cell line. Assay conditions were carefully optimized leading to an incubation period of 120 min, an incubation temperature of 37°C, and receptor material for each well was prepared from 300,000 cells. It was shown that a large excess (10 μM) of (+)-pentazocine, haloperidol, and di-o-tolylguanidine provided the same results during determination of the nonspecific binding. Saturation experiments with the radioligand [(3)H]-(+)-pentazocine led to a K(d)-value of 36±0.3 nM and a B(max)-value of 477±7 fmol/mg protein. These data resulted in approximately 122,000 σ(1) binding sites per cell. The assay was validated by using six known σ(1) ligands and eight σ(1) ligands prepared in our lab. The K(i)-values determined with RPMI 8226-derived receptor material are in good accordance with the K(i)-values obtained with guinea pig brain membrane preparations. Compared with guinea pig brain preparations, the RPMI 8226-derived receptor material represents a better standardized receptor material with a high density of human σ(1) receptors.     

Effects of (R)-α-methylhistamine and scopolamine on spatial learning in the rat assessed using a water maze

The effects of (R)--methylhistamine ((R)--MeHA, a selective H₃-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)--MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)--MeHA and SCOP, (R)--MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)--MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.     

Role of tumor necrosis factor and nitric oxide in the protection of N-methyl-N-(3,4-methylenedioxybenzoyl) methyl-acetamide against immunological liver injury in mice

研究了Ｎ－甲基－Ｎ－（３，４－亚甲二氧基苯甲酰）甲基－乙酰胺（ＳＹ－６４０）的保肝作用及其机理．给小鼠ｉｖ活卡介苗（ＢＣＧ）１２ｄ后再ｉｖ脂多糖（ＬＰＳ）诱导小鼠血浆一氧化氮（ＮＯ），肿瘤坏死因子（ＴＮＦ），谷丙转氨酶（ＧＰＴ），谷草转氨酶（ＧＯＴ）剧烈升高及严重的肝损伤．以ＳＹ－６４０给小鼠ｉｇ（每日一次，连续１０ｄ），显著降低ＢＣＧ＋ＬＰＳ诱导的肝损伤小鼠血浆ＧＰＴ，ＧＯＴ和ＴＮＦ水平的升高，血浆ＮＯ水平的升高更加显著，肝损伤减轻．以单甲基精氨酸抑制ＮＯ的生成，ＳＹ－６４０的上述作用被抵消．ＳＹ－６４０对正常小鼠血浆ＮＯ，ＧＰＴ，ＧＯＴ水平无影响．可见，ＳＹ－６４０的保肝作用与其升高血浆ＮＯ，降低血浆ＴＮＦ水平有关．     

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1-4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1-4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including gamma-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and L: -lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose.     

Characterization of the self assembly of methoxy poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) for the solubilization and in vivo delivery of valspodar

The aim of this study was to characterize the nanostructures formed from assembly of poly(ethylene oxide)-bpoly( α-benzyl carboxylate ε-caprolactone) (PEO-b-PBCL) in water, determine the effect of weight fraction of the hydrophilic block( fEO) on their morphology, and to investigate their potential for solubilization and delivery of P-glycoprotein (P-gp) inhibitor, valspodar. Three PEO-b-PBCL block copolymers having fEO ranging from 0.18-0.40 were synthesized. Assembly of PEO-b-PBCL was triggered through a co-solvent evaporation method. The average critical aggregation concentration (CAC) for PEO114-b-PBCL??, PEO???-b-PBCL??, and PEO???-b-PBCL?? was found to be 62, 41, and 23 nM, respectively. A lower rigidity of the hydrophobic domain in nanostructures formed from the assembly of PEO???-b- PBCL?? and PEO???-b-PBCL?? in comparison to PEO???-b-PBCL?? was observed. The morphology of the assembled structures was characterized by transmission electron microscopy (TEM). The TEM images of PEO???-b-PBCL?? (fEO = 0.40) showed the formation of spherical micelles with high polydispersity, whereas the assembly of PEO???-b-PBCL?? (fEO = 0.25) and PEO???-b-PBCL95 (fEO = 0.18) resulted in a mixed population of spherical micelles and vesicles. Valspodar achieved high loading in all the three PEO-b-PBCL nanocarriers reaching aqueous solubility of nearly 2 mg/mL. The morphology of PEO-b-PBCL carrier did not seem to influence the pharmacokinetics of the encapsulated valspodar in rats following intravenous administration. In conclusion, the results show a potential for PEO-b-PBCL nanocarriers as efficient solubilizing agents for delivery of valspodar.     

A general practice study to compare the efficacy and tolerability of a spray (‘Otomize’) versus a standard drop formulation(‘Sofradex’) in the treatment of patients with Otitis externa

Summary

In an open, multi-centre study in general practice, a comparison was made of the efficacy, tolerability and acceptability of a neomycin/ dexamethasone preparation administered by metered-dose spray (‘Otomize’) and a framycetin/gramicidin/ dexamethasone preparation (‘Sofradex’) administered as drops in 60patients with otitis externa. Patients were allocated at random to receive one or other preparations 3-times daily for 10 days and were followed-up again 14 days after cessation of therapy. Clinical assessments were carried out under observer blind conditions on entry (Day 0) and on Days 10 and 24 of the severity of erythema, swelling and debris in the affected ear(s). A global assessment of clinical outcome was made by the doctor on Day 10. There were no significant differences in the two groups at the start of treatment. Significant improvement occurred in both groups from Day 0 to Day 10 and from Day 10 to Day 24 in all symptoms, with the proportion symptom-free in the ‘Otomize’ group significantly greater than in the ‘Sofradex’ group at 24 days, and approaching significance at 10 days. Significantly more patients in the ‘Otomize’ group were rated as having a good clinical outcome by the physician, and fewer patients experienced discomfort on application. Few side-effects were reported by either treatment group, none necessitating discontinuation of therapy.     

Distinct periods of developmental sensitivity to the effects of 3,4-(±)-methylenedioxymethamphetamine (MDMA) on behaviour and monoamines in rats

Previous findings showed allocentric and egocentric learning deficits in rats after MDMA treatment from postnatal days (PD) 11-20 but not after treatment from PD 1-10. Shorter treatment periods (PD 1-5, 6-10, 11-15, or 16-20) resulted in allocentric learning deficits averaged across intervals but not for any interval individually and no egocentric learning deficits individually or collectively. Whether this difference was attributable to treatment length or age at the start of treatment was unclear. In the present experiment rat litters were treated on PD 1-10, 6-15, or 11-20 with 0, 10, or 15 mg/kg MDMA q.i.d. at 2-h intervals. Two male/female pairs/litter received each treatment. One pair/litter received acoustic startle with prepulse inhibition, straight channel swimming, Cincinnati water maze (CWM), and conditioned fear in a latent inhibition paradigm. The other pair/litter received locomotor activity, straight channel swimming, Morris water maze (MWM), and locomotor activity retest with MK-801 challenge. MDMA impaired CWM learning following PD 6-15 or 11-20 exposure. In MWM acquisition, all MDMA-treated groups showed impairment. During reversal and shift, the PD 6-15 and PD 11-20 MDMA-treated groups were significantly impaired. Reductions in locomotor activity were most evident after PD 6-15 treatment while increases in acoustic startle were most evident after PD 1-10 treatment. After MK-801 challenge, MDMA-treated offspring showed less locomotion compared to controls. Region-specific changes in brain monoamines were also observed but were not significantly correlated with behavioural changes. The results show that PD 11-20 exposure to MDMA caused the largest long-term cognitive deficits followed by PD 6-15 exposure with PD 1-10 exposure least affected. Other effects, such as those upon MK-801-stimulated locomotion showed greatest effects after PD 1-10 MDMA exposure. Hence, each effect has a different window of developmental susceptibility.     

Sexual disruption in zebrafish (Danio rerio) exposed to mixtures of 17α-ethinylestradiol and 17β-trenbolone

Environmental estrogens and androgens can be present simultaneously in aquatic environments and thereby interact to disturb multiple physiological systems in organisms. Studies on interaction effects in fish of androgenic and estrogenic chemicals are limited. Therefore, the aim of the present study was to evaluate feminization and masculinization effects in zebrafish (Danio rerio) exposed to combinations of two synthetic steroid hormones detected in environmental waters: the androgen 17β-trenbolone (Tb) and the oestrogen 17α-ethinylestradiol (EE2). Juvenile zebrafish were exposed between days 20 and 60 post-hatch to different binary mixtures of Tb (1, 10, and 50 ng/L) and EE2 (2 and 5 ng/L). The endpoints studied were whole-body homogenate vitellogenin concentration at 40 days post-hatch, and sex ratio including gonad maturation at 60 days post-hatch. The feminizing potency of 5 ng/L of EE2, alone as well as in combination with Tb, was clear in the present study, with exposures resulting in almost all-female populations and females being sexually immature. Masculinization effects with male-biased sex ratios were observed when fish were exposed to 2 ng/L of EE2 in combination with Tb concentrations. Intersex fish were observed after exposure to mixtures of 2 ng/L EE2 with 50 ng/L Tb. Sexual maturity generally increased among males at increasing concentrations of Tb. The results of the present study show that exposure to environmentally relevant mixtures of an oestrogen and androgen affects the process of gonad differentiation in zebrafish and lead to sexual disruption.     

Sensitization to MDMA locomotor effects and changes in the functionality of 5-HT(2A) and D₂ receptors in mice

The behavioral and neurochemical adaptations related to chronic 3,4-methylenedioxymethamphetamine (MDMA) treatment are largely unknown. In this study, we assessed whether repeated administration of MDMA would induce (a) context-dependent locomotor sensitization in mice and (b) changes in serotonin 5-HT(2A) and dopamine D? receptor functionality as measured by [3?S]GTPγS binding. Mice were treated with MDMA (10 mg/kg, intraperitoneally) or saline every other day for 11 days either in their home cages or in the environment where locomotor activity was measured. After a 10-day withdrawal period, mice were challenged with MDMA (5 and 10 mg/kg) and saline before locomotor activity measurements. During repeated MDMA treatment, locomotion was progressively enhanced, indicating the development of behavioral sensitization. The MDMA challenge at a dose of 5 mg/kg increased locomotor activity to a greater extent in mice pretreated with MDMA in the testing apparatus than in mice pretreated in the home cages, revealing that contextual cues paired with repeated drug exposure can enhance the expression of behavioral sensitization to MDMA. In contrast, a challenge administration of MDMA at 10 mg/kg induced similar locomotor sensitization in mice pretreated in both environments. An increase in the functionality of cortical 5-HT(2A) receptors was observed in mice pretreated with MDMA compared with mice pretreated with saline, but this activation was significantly greater in mice pretreated in the locomotor environment. In contrast, the functional activity of striatal D? receptors was significantly decreased only in mice pretreated with MDMA in the testing apparatus. These results reveal neuroadaptations in cortical 5-HT(2A) and striatal D? receptors after MDMA-induced behavioral sensitization in mice.     

Progress in acetylcholinesterase reactivators and in the treatment of organophosphorus intoxication: a patent review (2006–2016)

Introduction: organophosphorus compounds act as irreversible inhibitors of the vital enzyme acetylcholinesterase (AChE). this leads in the accumulation of acetylcholine (ACh) leading to cholinergic crisis and death. The main therapeutic approach is based on immediate administration of an ache reactivator as an antidote enabling recovery of the ache function.

Areas covered: This review covers the development of AChE reactivators in order to introduce a new efficient drug that will overcome significant failures of common antidotes. Further options together with methods of detection are also discussed in order to assure a complete insight into the treatment of intoxication.

Expert opinion: Since organophosphates belong to the most toxic chemical warfare agents, efficient antidotes are a matter of importance. The solution of how to limit the basic drawbacks of clinically used reactivators remained a spotlight for many researches worldwide. Recent strategies of the treatment of OP exposure bring us new possibilities which may overcome classic antidotes. The importance of detection of OP also has to be taken into consideration. Especially, with the fast spreading toxic effect when death can occur within minutes.     

Identifying “Hitting Bottom” Among Individuals with Alcohol Problems: Development and Evaluation of the Noteworthy Aspects of Drinking Important to Recovery (NADIR)

Background: Alcohol use disorder (AUD) is a costly public health concern; yet, many individuals with AUD never receive formal treatment. Prior studies have identified that “hitting bottom” may be an important factor in seeking treatment for AUD) and the notion that “hitting bottom” is necessary for recovery is commonly portrayed in the popular media. Yet, “hitting bottom” has never been formally operationalized. Objectives: The present article aimed to operationalize “hitting bottom.” Methods: A multiphase process was used to develop a measure of hitting bottom among individuals experiencing alcohol problems: The Noteworthy Aspects of Drinking Important to Recovery (NADIR). Psychometric evaluation of the measure was conducted using online data collected from individuals who identified as moderate to heavy drinkers (N = 597). Results: The NADIR included five lower-order dimensions and one higher-order dimension (“hitting bottom”), had strong concurrent validity with measures of alcohol use severity and alcohol-related problems, and was found to have excellent internal consistency reliability (α > 0.90). An overall summary score on the NADIR of 50+ (factor scores>0) differentiated individuals who had previously sought treatment for AUD and reported more excessive alcohol use compared to those with no treatment history and lower levels of alcohol use. Thus, the NADIR with a cutoff of 50 may be a good starting point for future researchers to test as a method to identify individuals who have hit bottom. Conclusions/Importance: The NADIR provides a viable operational definition of hitting bottom. Future research should evaluate the predictive validity of the NADIR.     

3,4-Methylenedioxymethamphetamine (MDMA – Ecstasy) Decreases Neutrophil Activity Through the Glucocorticoid Pathway and Impairs Host Resistance to Listeria Monocytogenes Infection in Mice

Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg^?1) administration decreases NFκB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NFκB expression, while 6-OHDA or ICI-118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro-inflammatory cytokine (IL-12p70, TNF, IFN-γ, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NFκB signaling, being mediated by HPA axis activity and corticosterone.     

Innovative strategies in the diagnosis and treatment of tuberculosis: a patent review (2014–2017)

Introduction: Tuberculosis (TB) is a disease caused due to an infection of Mycobacterium tuberculosis (M TB) bacilli affecting millions of people worldwide. It is the ninth leading cause of death and ranks above the HIV/AIDS. The unique intracellular life cycle, more dangerous drug-resistant forms of bacilli, and insufficient investments in the TB research and development hindered the occurrence of optimum diagnostic, preventive, and treatment strategy against this disease.

Areas covered: The aim of this review is to provide an update and overview of the current trends in the diagnosis, prevention, and treatment of the disease. It summarizes a recent patent literature (2014–2017) available on the same.

Expert opinion: Some questions like ‘why most of these inventions do not reach up to the market for public use? Are these inventions being explored only to get a financial return to a particular industry or do they have any societal benefit?’ emphatically come to mind. Together with the efforts taken by various governmental and nongovernmental organizations, a public awareness about the recent advancements in the diagnosis and treatment of the disease is of the highest importance to make ‘the end of TB’ from the universe.