Synthesis of 6H-Chromeno[4,3-b]quinolin-7-ylphosphonates through Three Component Phosphonylation of Coumarin Carbaldehyde and Their Antimicrobial and Photophysical Properties.

Organophosphorylated coumarin derivatives were synthesized by a three-component reaction of 4-chloro-3-formylcoumarin, aromatic amines, and dialkyl phosphite in the presence of ZnCl2. This process includes the formation of C(sp3)-P and C(sp2)-N bonds in one pot. The modular scope of the reaction allowed rapid access to a variety of 6H-chromeno[4,3-b]quinolin-7-ylphosphonate derivatives in good yields. Furthermore, photophysical studies of the products revealed their stimulating fluorescence properties.

Risk Factors Of Idiopathic Pulmonary Fibrosis In Pakistani Population: A Matched Case-Control Studyy.

OBJECTIVE: To evaluate the factors associated with idiopathic pulmonary fibrosisrisk. Methods: The case-controlstudywas conductedfromJanuary 5, 2017,toSeptember 4, 2018, attheprivate-sectorAga Khan University Hospital and the public-sector Jinnah Postgraduate Medical Centre, two large tertiary care centres in Karachi, andcomprisedadultpatientsof eithergenderwithdiagnosedidiopathicpulmonary fibrosis, asdefinedby the IndianChest Registry. Subjects without idiopathic pulmonary fibrosis but registered with the department of pulmonology of the two hospitalswere enrolledas controls.Datawas collectedusinga structuredquestionnaire, andanthropometricmeasurements were noted for each subject. Gastroesophageal reflux disease was assessed using GerdQ. This wasfollowed by serological evaluations and spirometry. Data was analysed using SPSS 21. RESULTS: Of the 459 subjects, 154(33.6%)were cases and305(66.4%)were controls.Amongthe cases, 81(52.6%)were females and 73(47.4%) were males with mean age 66.1±10.9 years. Among the controls, 162(53.1%) were females and 143(46.9%) were males with mean age 64.6±11.1 years(p>0.05.)The most common ethnicity wasUrdu-speaking; 89(58%) among the cases and 150(49%) among the controls (p<0.05). Ethnicity, number of persons in the household per room, and type of house were significantly associated with the risk of developing idiopathic pulmonary fibrosis(p<0.05). CONCLUSIONS: Ethnicity,type of house and the number of personsin a household perroom were found to be the significant risk factorsfor idiopathic pulmonary fibrosisIPF.

Sarcoidosis: An experience from a tertiary care center in Karachi Pakistan.

OBJECTIVE: To assess the demographic and clinical characteristics and treatment of patients with sarcoidosis in tertiary care settings. METHODS: The descriptive retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from 2017 to 2019 of patients with established diagnosis of sarcoidosis. Data was collected on a predesigned proforma and it was analysed using SPSS 23. RESULTS: Of the 974 patients evaluated, sarcoidosis was established in 108(11.1%); 58(53.7%) of them being females. The overall mean age was 50.9±12.9 years. Hypertension 49(45.4%) and diabetes mellitus 37(34.3%) were the most frequent co-morbidities. Extra-pulmonary manifestations were found in 27(25%) patients; ophthalmic 9(33.3%), musculoskeletal 8(29.6%) and skin 7(25.9%). Prednisolone was the mainstay of treatment in 93(86.1%) patients. CONCLUSIONS: Sarcoidosis was not found to be rare in Pakistan.

Comparative analysis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis from a tertiary care centre in Pakistan.

OBJECTIVE: To compare the characteristics of connective tissue disease-associated interstitial lung disease with idiopathic pulmonary fibrosis at a tertiary care hospital. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised demographical, clinical and radiological data of patients with interstitial lung disease between October 2016 and October 2017 accessed through the outpatient data registry. Data was compared in terms of characteristics and key features of patients with connective tissue disease-associated interstitial lung disease with those of idiopathic pulmonary fibrosis. Statistical analysis was done using STATA 12. RESULTS: Of the 184 patients, 52(29.3%) had connective tissue disease-associated interstitial lung disease and 62(35%) had idiopathic pulmonary fibrosis. The most prevalent conditions among connective tissue disease-associated interstitial lung disease patients were rheumatoid arthritis 22(42.3%) and scleroderma 13(25%). Compared to patients with idiopathic pulmonary fibrosis, those with connective tissue disease-associated interstitial lung disease were predominantly younger (p<0.001) and female (p<0.001). History of gastroesophageal reflux disease was also significantly lower in connective tissue disease-associated interstitial lung disease (p=0.05). CONCLUSIONS: Connective tissue disease-associated interstitial lung disease patients were found to be younger and predominantly female compared to patients of idiopathic pulmonary fibrosis.

Spectrum of interstitial lung disease from a tertiary care hospital in Karachi.

OBJECTIVE: To determine the clinical features and patterns of interstitial lung disease. METHODS: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised record of patients diagnosed with interstitial lung disease from January 2005 to December 2015. All patients aged 16 years and above diagnosed with interstitial lung disease on the basis of clinical features, radiological features on high-resolution computed tomography of the chest, and lung biopsies were included. SPSS 19 was used for data analysis. RESULTS: Of the 537 patients, 324(60.3%) of the participants were females. The overall mean age was 60.5±14.9 years. The most common co-morbid condition was diabetes mellitus in 72(13.4%) patients, followed by hypertension in 48(8.9%) and ischaemic heart disease in 21(3.9%). The most common interstitial lung disease was idiopathic pulmonary fibrosis in 217(40.4%) patients, followed by non-specific interstitial pneumonia in 106(19.7%), sarcoidosis in 82(15.3%) and connective tissue disease-related interstitial lung disease in 56(10.4%) patients. CONCLUSIONS: Idiopathic pulmonary fibrosis was found to be the most common interstitial lung disease subtype followed by non-specific interstitial pneumonia, sarcoidosis and connective tissue disease-related-interstitial lung disease.

Behaviour change intervention for smokeless tobacco cessation: its development, feasibility and fidelity testing in Pakistan and in the UK.

BACKGROUND: People of South Asian-origin are responsible for more than three-quarters of all the smokeless tobacco (SLT) consumption worldwide; yet there is little evidence on the effect of SLT cessation interventions in this population. South Asians use highly addictive and hazardous SLT products that have a strong socio-cultural dimension. We designed a bespoke behaviour change intervention (BCI) to support South Asians in quitting SLT and then evaluated its feasibility in Pakistan and in the UK. METHODS: We conducted two literature reviews to identify determinants of SLT use among South Asians and behaviour change techniques (BCTs) likely to modify these, respectively. Iterative consensus development workshops helped in selecting potent BCTs for BCI and designing activities and materials to deliver these. We piloted the BCI in 32 SLT users. All BCI sessions were audiotaped and analysed for adherence to intervention content and the quality of interaction (fidelity index). In-depth interviews with16 participants and five advisors assessed acceptability and feasibility of delivering the BCI, respectively. Quit success was assessed at 6 months by saliva/urine cotinine. RESULTS: The BCI included 23 activities and an interactive pictorial resource that supported these. Activities included raising awareness of the harms of SLT use and benefits of quitting, boosting clients' motivation and self-efficacy, and developing strategies to manage their triggers, withdrawal symptoms, and relapse should that occur. Betel quid and Guthka were the common forms of SLT used. Pakistani clients were more SLT dependent than those in the UK. Out of 32, four participants had undetectable cotinine at 6 months. Fidelity scores for each site varied between 11.2 and 42.6 for adherence to content - maximum score achievable 44; and between 1.4 and 14 for the quality of interaction - maximum score achievable was 14. Interviews with advisors highlighted the need for additional training on BCTs, integrating nicotine replacement and reducing duration of the pre-quit session. Clients were receptive to health messages but most reported SLT reduction rather than complete cessation. CONCLUSION: We developed a theory-based BCI that was also acceptable and feasible to deliver with moderate fidelity scores. It now needs to be evaluated in an effectiveness trial.

Prevalence of bacteriocin activities and bacteriocin-encoding genes in enterococcal clinical isolates in Iran.

The aim of the project was to isolate and characterize bacteriocin-producing enterococci, as well as determine the prevalence of enterocin structural genes in 187 enterococcal clinical isolates from the northwest of Iran. The isolates were screened for antibacterial activity against 15 different indicator strains. The proteinaceous nature of the antimicrobial substances was confirmed by sensitivity to proteinase K; their stability to heat treatment was tested at 60 °C and 100 °C for 20 and 10 min, respectively. The PCR method was applied to detect previously identified enterocin genes. Our results showed that 38 (20.3%) of the enterococcal isolates were considered to be potential bacteriocinogenic strains. Furthermore, genes encoding diverse bacteriocin are highly distributed among clinical enterococci, and the strains with multi-bacteriocin genes displayed high antimicrobial activity. Enterocin A, enterolysin A, and enterocin L50A/B were the most abundant structural genes detected in bacteriocinogenic strains. This work is the first survey on the prevalence of bacteriocin genes among clinical enterococci in Iran that has isolated a strain with high antimicrobial activity and sensitivity to clinically relevant antibiotics.

Evaluation of antibacterial and wound-healing activities of alcoholic extract of Boswellia carterii, in vitro and in vivo study.

BACKGROUND: Today, despite the existence of various chemical and physical treatments for wound healing, the use of traditional medicine including herbal medicine is still widely used in most developed and developing countries. OBJECTIVES: To investigate the antimicrobial and wound-healing activities of alcoholic extract of Boswellia carterii (BC) plant. METHODS: The BC extract was prepared using alcohol 70%. The chemical groups and extract compounds were determined using Fourier transform infrared spectroscopy (FTIR) and high-performance liquid chromatography (HPLC) analysis, respectively. The antimicrobial and wound-healing activities of different concentrations of BC extract and its combination with penicillin-streptomycin were assessed by agar well diffusion and infected wound model in albino rabbits, respectively. RESULTS: FTIR revealed the presence of hydroxyl, amide, carboxyl, alkyl C-H stretches, aromatic C=C bends, and aromatic C-H bends in the BC extract. The HPLC revealed 14 different compounds including thujene (48.0%) as the most abundant ingredient. All BC concentrations showed antibacterial and wound-healing activities. The 10% concentration of BC extract had the strongest antibacterial effect. Also, the combination of penicillin-streptomycin with BC extract showed synergistic antibacterial effect. The 5% concentration of BC was the best wound-healing compound which healed the wound in 6 days and decreased the wound size 10 mm each day. CONCLUSIONS: This study demonstrated the potential abilities of BC as an antibacterial and wound-healing medicinal plant. Further studies are required to justify the in vivo use of this plant.

Emerging evidence implicating a role for neurexins in neurodegenerative and neuropsychiatric disorders.

Synaptopathies are brain disorders characterized by dysfunctional synapses, which are specialized junctions between neurons that are essential for the transmission of information. Synaptic dysfunction can occur due to mutations that alter the structure and function of synaptic components or abnormal expression levels of a synaptic protein. One class of synaptic proteins that are essential to their biology are cell adhesion proteins that connect the pre- and post-synaptic compartments. Neurexins are one type of synaptic cell adhesion molecule that have, recently, gained more pathological interest. Variants in both neurexins and their common binding partners, neuroligins, have been associated with several neuropsychiatric disorders. In this review, we summarize some of the key physiological functions of the neurexin protein family and the protein networks they are involved in. Furthermore, examination of published literature has implicated neurexins in both neuropsychiatric and neurodegenerative disorders. There is a clear link between neurexins and neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia. However, multiple expression studies have also shown changes in neurexin expression in several neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Therefore, this review highlights the potential importance of neurexins in brain disorders and the importance of doing more targeted studies on these genes and proteins.

GC/MS analysis of Juniperus procera extract and its activity with silver nanoparticles against Aspergillus flavus growth and aflatoxins production.

From ancient to currently, it has been hard to prevent the exposure to mycotoxigenic fungi, due to these fungi occurs naturally in the environment. This paper reports the antifungal activities of the Juniperus procera stem extract with silver nanoparticles (AgNPs) against Aspergillus flavus growth and aflatoxins production. Numerous constituents of J. procera extract were detected by GC/MS analysis. Methanolic extract at 30, 60 and 90 mg/mL inhibited the growth of A. flavus, where the inhibition reached to 50.86, 51.60 and 52.58 %. respectively while weak inhibition was observed using the aqueous extract. Growth of A. flavus was reduced using AgNPs, the highest inhibition 39.31 % was recorded at 100 ppm AgNPs. Synergistic activity was observed by applying 50 ppm of AgNPs with aqueous and methanolic extracts of J. procera . A reduction in aflatoxin B2 and G2 synthesis was observed using different concentrations of methanolic stems extract of J. procera particularly with AgNPs.

Discovery of novel isatin-based thiosemicarbazones: synthesis, antibacterial, antifungal, and antimycobacterial screening.

BACKGROUND AND PURPOSE: A group of thiosemicarbazones were prepared and their structures were confirmed by spectroscopic methods such as IR and H-NMR, mass spectrometry and also analytical method like elemental analysis. The synthesized semicarbazones were then assessed for their inhibitory activity against bacterial strains including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Bacillus cereus, Salmonella species, Enterobacter faecalis, methicillin-resistant Staphylococcus aureus, and fungi such as Candida albicans and Aspergillus niger. EXPERIMENTAL APPROACH: The schiff bases of isatin (2a-j) were prepared by a condensation reaction between thiosemicarbazide and substituted N-aryl isatins leading to the desired thiosemicarbazones with exquisite purity. FINDINGS / RESULTS: The results disclosed that all compounds have noticeable inhibitory activity. Compounds 2a, 2b, 2c, 2g, and 2h were among the most potent derivatives against Gram negative bacteria and fungi. Besides, the activity of theses compounds were tested against Mycobacterium bovis bacillus Calmette-Guerin (M. bovis BCG). The antimycobacterial activity indicated compounds 2e and 2j are highly active against M. bovis BCG (minimum inhibitory concentration < 3.9 µg/mL). Among fluorinated structures, compounds 2a and 2j showed the best activities against M. bovis BCG. CONCLUSION AND IMPLICATIONS: To sum up, amongst the 10 synthesized compounds, fluorinated derivatives exhibited remarkable activities against both gram negative strains and candida albicans microorganism. Therefore, they should be considered as a clue for further modifications in next investigations. Furthermore, inserting a small/medium size halogen atom with electron-withdrawing and lipophilic properties increases anti- salmonella activity of these compounds and moreover 2-halogenated semithiocarbazones presented promising antimycobacterial activity.

Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin, a marinobufagenin antagonist.

Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats. Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 µg/kg/day of leptin (LEP), or 120 µg/kg/day of leptin+30 µg/kg/day of resibufogenin (L + RBG) or 30 µg/kg/day of resibufogenin (RBG) from Day 1-20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum. SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups. The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.

Photocatalytic degradation and kinetic modeling of azo dye using bimetallic photocatalysts: effect of synthesis and operational parameters.

Industrial wastewaters are the major source polluting the surface and ground water resources. Pollutants released along with the untreated textile industry wastewaters are responsible for the great damage to the natural resources like water. Considering the hazardous effects of the azo dyes (textile coloring agents) and their byproducts, there is a need to develop cost-effective and efficient treatment method for the textile wastewaters as such dyes have been reported as toxic, mutagenic, and carcinogenic and can cause direct demolition of aquatic communities. One of the possible and effective treatment methods is the use of TiO2 photocatalysis due to its chemical stability, low cost, and non-toxic nature. The present study explored the photocatalytic potential of anatase-type of bimetallic Cu-Ni/TiO2 photocatalysts under visible light irradiation for possible photocatalytic degradation and mineralization of Methyl Orange (MO), as model azo dye. The focus was to correlate the synthesis (different calcination temperatures, phase composition of TiO2 either anatase or rutile, and metal ion loading in terms of concentration and composition (Cu:Ni)) and operational parameters (photocatalyst loading, pollutant concentration, and irradiation time) that were believed responsible for the enhanced photocatalytic performance. Blank experiments were carried out to check the effect of metal loading in comparison to bare TiO2 and effect of absence or presence of light and photocatalysts on MO photodegradation. Results obtained using bimetallic photocatalysts are promising as compared to bare TiO2 as 100% MO removal and ~ 90% %COD removal were obtained in 90 min of irradiation, obeying a pseudo-first-order kinetics with photocatalytic reaction via the Langmuir-Hinshelwood mechanism with a good linear fit. Photocatalysts synthesized using anatase TiO2 were reported with improved performance compared to rutile phase. It is evident that synthesis parameters influence photocatalyst performance directly. The higher rate constant (> 1) that proves the excellent adsorption capacity of the tested photocatalysts for tested pollutants on the surface may have a great prospective for photocatalytic water purification at neutral pH.

Assessment of left ventricular systolic function after VSD transcatheter device closure using speckle tracking echocardiography.

BACKGROUND: This is a case-control study conducted on 30 children, 15 with VSD who performed VSD transcatheter device closure (group A) and 15 controls of matching age and gender (group B), in the period between September 2015 and February 2018. We aimed to assess the global left ventricular (LV) systolic function by 2D speckle tracking before and after ventricular septal defect (VSD) transcatheter closure, in comparison to normal controls. All patients were subjected to full history taking; general and cardiac examination; ECG; CXR; full transthoracic echocardiographic examination, including VSD number, size, and site; LV dimensions and volumes; estimated pulmonary artery pressure; right ventricular size and function; left ventricular circumferential; and radial strain imaging by 2D speckle tracking. Patients who had ventricular septal defect closed were reassessed by transthoracic echocardiography after 3 months. RESULTS: The study included 15 children with VSD: 3 males and 12 females; their age ranged from 2 to 13 years; all had subaortic VSD except for 1 who had apical muscular VSD: VSD size ranged from 3 to 8 mm; PFM coil was used to close defect in all patients except for 2 patients who had an Amplatzer duct occlude I (ADOI) device, and 1 patient needed an additional vascular plug after significant hemolysis. Pre-procedurally, group A had a significantly higher LVEDD, LVESD, and LVEDV than group B. Mean circumferential strain was significantly higher (more negative) in group A than that in group B either pre- or post-procedure. Post-procedurally, there was a significant decrease in circumferential strain (less negative) and a significant increase in radial strain (more positive). CONCLUSION: Following transcatheter VSD closure, there is a significant decrease in LV circumferential strain and a significant increase in LV radial strain, which conclude a decrease in LV volume overload with the improvement of its contractility.

Protective Effect of Matricaria chamomilla Ethanolic Extract on Hippocampal Neuron Damage in Rats Exposed to Formaldehyde.

Formaldehyde, as a frequently used compound in many applications, crosses the blood-brain barrier and leads to hippocampal cell death and memory impairment. This study investigates the effects of ethanolic extract of Matricaria chamomilla (MC) on passive avoidance learning induced by damaged hippocampal cells and evaluates the antioxidant traits of MC. The male Wistar rats were divided into six (6 in each) groups: control (10 mg/kg normal saline), 200 (200 mg/kg MC extract), 500 (500 mg/kg MC extract), F (10 mg/kg formaldehyde), F200 (10 mg/kg formaldehyde and 200 mg/kg MC extract), and F500 (10 mg/kg formaldehyde and 500 mg/kg MC extract). Shuttle box assay was used for evaluation of passive avoidance learning. The apoptosis rate of hippocampal tissue, malondialdehyde (MDA) free radicals, and total antioxidant capacity was evaluated to determine the positive effect of the ethanolic extract of MC. We found that the ethanolic extract of MC reduced the cell death, time spent in a dark room, and MDA free radicals in the hippocampus, leading to increased total antioxidant capacity in this region. In conclusion, the ethanolic extract of MC could ameliorate formaldehyde-induced memory damage through decreasing cell death and MDA activity of the hippocampal region and increasing total antioxidant capacity.

Clinical characteristics and factors associated with mortality in idiopathic pulmonary fibrosis: An experience from a tertiary care center in Pakistan.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) that predominantly affects older adults. IPF has the highest mortality burden of all ILDs. Data on mortality in patients with IPF is limited in developing countries. OBJECTIVES: To identify factors associated with mortality in patients with IPF at a tertiary care center in Pakistan. METHODS: A retrospective chart review was conducted at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan from January 2005 to December 2015. Patients were assessed for smoking status, clinical onset of disease, pulmonary hypertension, disease severity based on spirometry and hypoxemia. RESULTS: A total of 239 cases were reviewed, of which 103 were non-survivors. A total of 45 (18%) were current smokers and 71 (29.7%) were ex-smokers. Smoking was more common in non-survivors (56.3% P ≤ .01). Pulmonary hypertension was present in 18.8% of patients. 95.4% of patients who had received pirfenidone treatment were alive at the time of study. On multivariate analysis, pirfenidone treatment (OR 0.03; 95% CI 0.01-0.08), current smoking (OR 2.60; 95% CI 1.04-6.58), age older than 60 years (OR 2.63; 95% CI 1.04-6.58) and hypoxemia (OR 3.29; 95% CI 1.58-6.84) were the factors associated with mortality. CONCLUSION: Smoking, age greater than 60 years and hypoxemia were identified as factors that increased the odds of mortality in IPF patients, whereas pirfenidone was found to lower the odds of mortality.

Nanoliposome-based antibacterial drug delivery.

Although most bacterial infectious diseases can be treated successfully with the remarkable array of antibiotics, the microbial pathogens continue to be one of the most critical health challenges worldwide. One of the common efforts in addressing this issue lies in improving the existing antibacterial delivery systems since inefficient delivery can lead to poor therapeutic outcome of the administered drug. Recently, nanoliposomal systems have been widely used as promising strategies to overcome these challenges due to their unique set of properties. This article tries to briefly summarize the current studies that have taken advantage of liposomal nanoparticles as carriers to deliver antibacterial agents. The reviewed investigations demonstrate the immense potential of liposomal nanoparticles as carriers for antibiotic delivery and highlight the latent promise in this class of vehicles for treatment of bacterial infections. The future of these promising approaches lies in the development of more efficient techniques for preparing liposomal nanoparticles with great potential in effective and selective targeting of antibiotics to bacterial cells for eradication as well as the highest safety for human host.

A rare cause of recurrent wheeze and seizures.

A 34-year-old woman presented with recurrent attacks of breathlessness and seizures. The patient's condition worsened during the course of her hospital stay, as a result of which she had to be intubated twice. Radiological studies showed a mass in the trachea and the subsequent biopsy of the mass revealed an infiltrating carcinoma with morphological features of adenoid cystic carcinoma.

Efficient Inactivation of Multi-Antibiotics Resistant Nosocomial Enterococci by Purified Hiracin Bacteriocin.

PURPOSE: Because of the emergence of multi-antibiotic resistant bacteria, a number of infectious diseases have become a major concern to treat in health care services worldwide. This situation is worsened by the fact that very limited progress has been made in developing new and potent antibiotics in recent years. In this context antimicrobial peptides (AMPs) represent new potential therapeutic compounds with bactericidal or bacteriostatic activity against closely related bacterial strains. METHODS: In this study, a collection of enterococci (n=170) from clinical sources were investigated for their potential to inhibit multiresistant nosocomial enterococci from Iranian hospitals. RESULTS: Four isolates produced antimicrobial peptides that inhibited all the antibiotic resistant enterococci. This included three Enterococcus faecium isolates producing combinations of enterocin A, B and L50 AB. The most potent antagonism was produced by E. faecalis HO91. Purification and subsequent characterization by MALDI-TOF MS, Edman degradation and DNA-sequencing revealed that the antimicrobial compound was Hiracin. The purified Hiracin was evaluated for antibacterial activity against 12 multiresistant enterococcal isolates from clinical samples. The results demonstrated that Hiracin is highly effective towards enterococci which were resistant even to antibiotics from four distinct classes. CONCLUSION: The present research addresses Hiracin as a promising alternative to conventional antibiotics in treatment of multiresistant enterococcal infections.

Dissemination of aminoglycoside-modifying enzymes and 16S rRNA methylases among acinetobacter baumannii and Pseudomonas aeruginosa isolates.

AIMS: The purpose of the present study was to investigate the diversity of the genes encoding aminoglycoside-modifying enzymes (AMEs) and their associations with resistance phenotypes and clonality in Acinetobacter baumannii and Pseudomonas aeruginosa isolates. METHODS: Seventy six P. aeruginosa and 75 A. baumannii isolates were collected from three University affiliated hospitals in Tehran. MIC determination of amikacin and gentamicin as well as the disk diffusion method for tobramycin, netilmicin, and kanamycin were carried out. Nine AMEs genes and three RNA methylases were investigated in all isolates using the PCR method. Clonality for A. baumannii and P. aeruginosa was investigated using repetitive extragenic palindromic and enterobacterial repetitive intergenic consensus PCR, respectively. RESULTS: aph(3')-VIa (90.6%) and aph(3')-IIb (61.8%) were the most prevalent AME genes in A. baumannii and P. aeruginosa, respectively. Eight (26%) amikacin highly resistant A. baumannii isolates were positive for armA methylase. Phenotypes and clonality did not link to the genetic determinants of resistance to aminoglycosides in our isolates. CONCLUSIONS: AMEs genes are disseminated in different clones of A. baumannii and P. aeruginosa isolates in Iran. Other than AMEs, there are more complex and multifactorial mechanisms that result in aminoglycoside-resistant phenotypes.