Anxiolytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: a review

Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.

El significado del capital social "individual" en diabéticos receptores de cuidado en un contexto urbano colombiano / The meaning of "individual" social capital for diabetics receiving care in a Colombian city / O significado do capital social "individual" em diabéticos que precisam de cuidados dentro de um contexto urbano colombiano

Comprender el significado del capital social de la diabetes tipo 2 según género, dentro un contexto urbano colombiano. Investigación cualitativa del interaccionismo simbólico. 25 mujeres y 16 hombres, diabéticos, familiares, vecinos y personal asistencial participaron en seis grupos focales. Emergieron 850 códigos que se integraron en un set de 142 códigos de códigos para el ego, el alter y alter ego. Tres categorías y veinte subcategorías fueron identificadas para el diseño del "paradigma de la codificación". El significado no es igual para hombres y mujeres. Los vínculos sociales de las redes sociales, creados cotidianamente por la confianza y la solidaridad para el cuidado, son valorados de manera diferente, debido a experiencias y hechos sociales resultantes de la autoconfianza, la autoeficacia para el apoyo social principalmente y, la autoestima frente al manejo y control de la enfermedad. Los recursos sociales de un individuo son reificados para el manejo y cuidado de la enfermedad como estrategia para disminuir las inequidades en salud.

The aim of this study was to understand the meaning of social capital in relation to type 2 diabetes according to gender, within an urban setting in Colombia, based on a qualitative design for symbolic interactionism. Twenty-four women and 16 men with diabetes, family members, and healthcare personnel participated in six focus groups. A total of 850 codes emerged that comprised a set of 142 codes for ego, alter, and alter ego. Three categories and 20 subcategories were identified for the "coding paradigm design". The meaning differed between men and women. Social ties in social networks, created daily through trust and solidarity for care, were valued differently due to the social experiences and events resulting from self-confidence, self-efficacy for social support, and mainly self-esteem vis-à-vis management and control of the disease. An individual's social resources are reified for the management and care of the disease as a strategy to mitigate health inequalities. .

Compreender o significado do capital social, diabetes tipo 2 por sexo, um contexto urbano da Colômbia. pesquisa qualitativa do interacionismo simbólico. 25 mulheres e 16 homens, diabéticos, familiares, vizinhos e cuidadores participaram seis grupos focais. 850 códigos se que foram integrados em um conjunto de 142 codes para o ego, o alter e alter ego. Três categorias e vinte subcategorias foram identificados para o projeto de "codificação de paradigma". O significado não é o mesmo para homens e mulheres. Laços sociais das redes sociais criadas diariamente pela confiança e solidariedade são valorizados cuidado diferente, porque as experiências sociais e fatos resultantes da auto-confiança, auto-eficácia e de apoio social, principalmente, auto-gestão e controle em relação a doença. Os recursos sociais de um indivíduo são reificadas para a gestão o cuidado da doença como uma estratégia para reduzir as desigualdades na saúde.

In vitro susceptibility to methicillin, vancomycin and linezolid of staphylococci isolated from bloodstream infections in eastern Turkey

Staphylococcus species are one of the major causes of bacterial bloodstream infections. Multi-resistant staphylococci infections are major therapeutic problems. This study was aimed to detect methicillin, linezolid and vancomycin susceptibilities of Staphylococcus isolates. A total of 870 Staphylococcus strains isolated from blood cultures of hospitalized patients with BSI. Antimicrobial susceptibilities of methicillin, linezolid and vancomycin were detected according to the Clinical and Laboratory Standards Institute (CLSI). A total of 771 (88.6%) isolates were coagulase-negative staphylococci (CoNS). 700 (80.5%) isolates were methicillin-resistant (MR) and 170 (19.5%) were methicillin-susceptible (MS). All the MS isolates were also susceptible to linezolid. However 15 (1.7%) of MR strains were resistant to linezolid. The minimum inhibitory concentration range for the linezolid-resistant isolates by Etest was 6-32 µg/mL. The difference between linezolid susceptibilities for MS and MR staphylococci was not quite statistically significant (p = 0.052). There was no statistically significant difference between S. aureus and CoNS isolates for linezolid susceptibility. All of the isolates were susceptible to vancomycin. In conclusion, linezolid is currently an efficient option for the treatment of methicillin-resistant staphylococci infections.

Colistin and anti-Gram-positive bacterial agents against Acinetobacter baumannii

Introduction Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii. Methods The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin. Results The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fluid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis. Conclusions Subinhibitory doses of colistin significantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii. .

Sensibilidad antimicrobiana in vitro en aislamientos de Enterococcus faecalis y Enterococcus faecium obtenidos de pacientes hospitalizados / In vitro antimicrobial susceptibility in Enterococcus faecalis and Enterococcus faecium isolated from hospitalized patients

Introducción. Actualmente se considera a Enterococcus spp. como uno de los agentes de infección hospitalaria más importantes, siendo su resistencia a los antibióticos un problema importante en los centros de salud. Objetivos. Caracterizar la resistencia antimicrobiana en 50 cepas de Enterococcus spp. aisladas de muestras clínicas de pacientes hospitalizados . Materiales y métodos. Se llevó a cabo un estudio de tipo descriptivo observacional de corte transversal en 50 aislamientos clínicos de estas especies microbianas. Se trabajó un aislamiento por paciente. La identificación y la sensibilidad a los antibióticos se realizaron por métodos automatizados y convencionales. El análisis fenotípico de los mecanismos de resistencia a glucopéptidos se hizo según las recomendaciones de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Resultados. De 50 aislamientos, 30 (60,0 %) y 20 (40,0 %) pertenecían a las especies de Enterococcus faecalis y Enterococcus faecium, respectivamente. La resistencia global expresada por este género fue de 38/50 (76,0 %) para ampicilina; 33/50 (66,0 %) para gentamicina de alto nivel; 34/50 (68,0 %) para estreptomicina de alto nivel; 26/50 (52,0 %) para ciprofloxacina; 4/50 (8,0 %) para linezolid; 17/50 (34,0 %) para teicoplanina; 25/50 (50,0 %) para vancomicina; 31/50 (62,0 %) para minociclina; 34/50 (68,0 %) para tetraciclina y 9/50 (18,0 %) para nitrofurantoina. Frente a los glucopéptidos, 25/50 (50,0 %) y 10/50 (20,0 %) de los aislamientos presentaron los mecanismos Van A y Van B, respectivamente. Conclusiones. Podemos concluir que la mayoría de las veces, las cepas aisladas en el Hospital Hermanos Ameijeiras mostraron porcentajes de resistencia por encima de lo reportado en la literatura científica consultada. El alto porcentaje de cepas con resistencia a la vancomicina podría influir en la aparición de otros gérmenes Gram positivos con resistencia a este fármaco. Se reporta por primera vez en un hospital cubano resistencia de E. faecium a linezolid.

Introduction: Enterococcus spp is currently considered as one of the most important nosocomial pathogens . The antibiotic resistance of this group of bacteria is a particularly important problem in health centers. Objective: To characterize the antibiotic resistance of 50 Enterococcus spp strains isolated from hospitalized patients clinical samples. Materials and methods: We conducted a cross-sectional descriptive observational study in 50 clinical isolates of Enterococcus spp. Only one isolate per patient was analyzed . The identification and antibiotic susceptibility were studied by conventional and automated methods . The phenotypic analysis of glycopeptide resistance mechanisms was performed as recommended by the Spanish Society of Clinical Microbiology and Infectious Diseases . Results: Of 50 isolates obtained from clinical samples, 30 ( 60.0%) belonged to Enterococcus faecalis and 20 (40.0 %) to Enterococcus faecium . The global resistance expressed by this genre was as follows: Ampicillin, 38/50 ( 76.0%); high-level gentamicin, 33/50 ( 66.0%); high-level streptomycin, 34/50 (68.0 %) ; ciprofloxacin, 26/50 (52.0 %); linezolid, 4/50 (8.0 %); teicoplanin, 17/50 ( 34.0%); vancomycin, 25/50 (50.0 %); minocycline, 31/50 ( 62.0%); tetracycline, 34/50 (68.0 %); nitrofurantoin, 9/50 ( 18.0%). As regards glycopeptides, 25/50 (50.0%) showed a Van A mechanism and 10/50 (20.0 %) a Van B mechanism . Conclusions: The isolates obtained at Hospital Hermanos Ameijeiras showed higher resistance rates than those reported in the consulted literature. The high percentage of vancomycin-resistant strains might have influenced the development of other Gram-positive bacteria resistant to this drug. This is the first report on Enterococcus faecium resistant to linezolid in a Cuban hospital.

Synthesis, characterization and biological screening of N-substituted derivatives of 5-benzyl-1,3,4-oxadiazole-2yl-2''-sulfanyl acetamide

A series of new N-substituted derivatives of 5-benzyl-1, 3, 4-oxadiazole-2yl-2''-sulfanyl acetamide [6a-n] were synthesized in three phases. The first phase involved the sequentially converting phenyl acetic acid into ester, hydrazide and finally cyclized in the presence of CS[2] to afford 5-benzyl-1, 3, 4-oxadiazole-2-thiol. In the second phase N-substituted-2-bromoacetamides were prepared by reacting substituted amines with bromoacetyl bromide in basic media. In the third phase, 5-benzyl-1,3,4-oxadiazole-2-thiol was stirred with N-substituted-2-bromoacetamides in the presence of N,N-dimethyl formamide [DMF] and sodium hydride [NaH] to get the target compounds. Spectral techniques were used to confirm the structures of synthesized compounds. Synthesized compounds were screened against butyrylcho linesterase [BChE], acetylcholinesterase [AChE], and lipoxygenase enzymes [LOX] and were found to be relatively more active against acetylcholinesterase

Detection of resistance to linezolid in Staphylococcus aureus infecting orthopedic patients.

Context: In today's medical scenario, the human race is battling the most intelligent enemy who has unending alternatives to combat with the potent elements they have produced against it. Aim: To study the resistance to linezolid among Staphylococcus aureus isolated from pus samples of orthopedic patients. Settings and Design: Pus samples were collected from dirty wounds of orthopedic patients undergoing long antimicrobial treatment programs. The sampling period was from July 2010 to June 2011. The samples were collected from different orthopedic hospitals of Nagpur (central India) representing a mixed sample of patients. Materials and Methods: One hundred pus samples were screened for S. aureus, by growth on mannitol salt agar (MSA), Baird-Parker agar (BPA), deoxyribonuclease test, tube coagulase test, and HiStaph latex agglutination test. Fifty-one S. aureus isolates were obtained which were further subjected to antimicrobial susceptibility testing by Kirby-Bauer disc diffusion method (DDM). Minimal inhibitory concentrations (MICs) were determined by an automated system, the VITEK 2 system. Also, Ezy MIC strip method was carried out in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. Results and Conclusion: Twelve linezolid-resistant S. aureus (LRSA) isolates were recovered from 51 S. aureus cultures tested for susceptibility to linezolid using the DDM, VITEK 2 system, and Ezy MIC strip method. The emergence of resistance suggests nosocomial spread and abuse of antibiotic.

Sepsis due to linezolid resistant Staphylococcus cohnii and Staphylococcus kloosii: First reports of linezolid resistance in coagulase negative staphylococci from India.

Linezolid, a viable alternative to vancomycin against methicillin resistant staphylococcal isolates, has been in use for a decade around the globe. However, resistance against staphylococci remains extremely rare and unreported from most of the Asian countries. Herein, we report two cases of linezolid resistant, coagulase negative staphylococcal sepsis for the first time from India. The first case was an 18-year-old burn patient, who, after a major graft surgery, landed in sepsis, and linezolid resistant Staphylococcus cohnii with an minimum inhibitory concentration (MIC) of >256 μg/ml by both broth microdilution and Etest, was isolated from multiple blood cultures. The second patient was a 60-year-old male with an intracranial bleed and sepsis, from whose blood cultures, linezolid resistant Staphylococcus kloosii was repeatedly isolated. Linezolid MIC was >32 μg/ml by broth microdilution and >16 μg/ml by Etest.

Lacosamide, a newer antiepileptic

Lacosamide [LCM] is a newer antiepileptic drug with a dual mode of action. It selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation, and modulates collapsing response mediator protein 2 [CRMP-2]. It has a high oral bioavailability of approximately 100%. It has shown potent and broad neuroprotective effects in vitro and in vivo animal models making it a potential candidate for long term treatment of epilepsy. In addition to this, it has demonstrated analgesic activity in various animal models. Apart from this, LCM has demonstrated potent effects in animal models for a variety of CNS disorders like schizophrenia and stress induced anxiety. Various safety pharmacology and toxicology studies have shown that LCM is well tolerated. Clinical trials have also suggested that LCM is a safe, effective, and well tolerated adjunctive treatment for reduction of seizure frequency in patients with highly refractory, partial seizures. Other potential indications of LCM are being investigated

Linezolid vancomycin resistant Enterococcus isolated from clinical samples in Tehran hospitals.

Background: Vancomycin-resistant enterococci pose an emerging health risk. The limitation in therapeutic options has resulted in the development of new drugs such as quinupristin/ dalfopristin and linezolid. Aim, Setting and Design: This study investigated the species prevalence and antibacterial resistance among enterococci isolated in selected Tehran hospitals. Materials and Methods: Between March 2006 and August 2007, 200 enterococcal isolates from urine, blood, stool and wound were recovered in 2 teaching hospitals of Tehran province. Susceptibility of all isolates was tested against vancomycin, teicoplanin and linezolid antibiotics by disk diffusion and agar dilution method. Results and Conclusion: Seventeen (8.5%), 6 (3%) and 4 (2%) of the isolates were resistant to vancomycin, teicoplanin and linezolid, respectively. Within the vancomycin-resistant isolates, 6 (35.2%), 4 (25%) and 1 (5.88%) showed vanA, vanB and vanC genotype patterns, respectively. Four (23.5%) of VRE isolates were resistant to linezolid with minimum inhibitory concentrations between 16 and 32 µg/mL. Two linezolid vancomycin resistant enterococci were E. faecium.

In vitro activity of antimicrobial agents against oxacillin resistant staphylococci with special reference to Staphylococcus haemolyticus.

One hundred and sixty seven isolates of staphylococci isolated from the inpatients of a tertiary care referral hospital in South India were speciated and activity of oxacillin, glycopeptides, linezolid and quinupristin/dalfopristin against these isolates was tested by broth microdilution method. Of the 114 coagulase negative staphylococci (CoNS), 49.1 % were S. haemolyticus, isolated predominantly from urine (64.6%), while the rest belonged to 11 other species. More than half the isolates of S. aureus (52.8%) and 68.4% of the CoNS were oxacillin resistant. All the strains were uniformly susceptible to vancomycin, linezolid and quinupristin/dalfopristin; but 25.6% isolates of S. haemolyticus showed reduced susceptibility to teicoplanin (MIC: 8-16 mg/L). Our study demonstrates the high prevalence of oxacillin resistance among hospital isolates of S. aureus and CoNS in India. Vancomycin, along with the newer agents like linezolid and quinupristin/dalfopristin remains the drug of choice for treating multi drug resistant staphylococcal infections.

In vitro activity of linezolid & quinupristin/dalfopristin against Gram-positive cocci.

BACKGROUND & OBJECTIVES: Since the incidence of vancomycin- and methicillin-resistant Gram-positive infections continue to increase, novel antimicrobials such as linezolid and streptogramin may provide new options to treat patients. The aim of this study was to investigate in vitro susceptibility of Enterococcus faecium resistant to glycopeptides, coagulase negative staphylococci and S. aureus resistant to methicillin isolated mainly from blood and also rectal swab cultures of patients against quinupristin/dalfopristin and linezolid. METHODS: The in vitro susceptibility to linezolid and quinupristin/dalfopristin for a total of 332 isolates of Gram-positive cocci [127 methicillin-resistant Staphylococcus aureus, 109 methicillin-resistant coagulase negative staphylococci (71 S. epidermidis, 38 S. haemolyticus) and 96 vanA genotype vancomycin-resistant Enterococcus faecium] was investigated by E test. RESULTS: All MRSA and MRCoNS isolates were susceptible to linezolid (MICs < 4.0 mg/l). Ninety per cent of VRE isolates were inhibited by linezolid at concentration of 2.0 mg/l and presented similar activities to quinupristin/dalfopristin. MICs for quinupristin/dalfopristin against staphylococci were also low (MIC(90) = 1.0 mg/l for both MRSA and MRCoNS isolates). INTERPRETATION & CONCLUSION: The results of the present study demonstrated that quinupristin/ dalfopristin and linezolid, have good in vitro activity against MRSA, MRCoNS and vancomycin resistant E. faecium in Turkey. These drugs could be promising therapeutic options in an era of rapidly growing antibiotic resistance in all parts of world.

Effects of manipulation of N-methyl-D-aspartate receptors on imipenem/cilastatin-induced seizures in rats.

BACKGROUND & OBJECTIVES: Epileptic seizures have been reported in patients on imipenem/cilastatin (Imi/Cil) therapy. To investigate contribution of N-methyl-D-aspartate (NMDA) receptors in inducing imipenem/cilastatin (Imi/Cil) seizures, the effects of competitive NMDA antagonist, APV [(+/-)-2-amino-5-phosphonovaleric acid], non-competitive NMDA antagonist remacemide [(+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)-acetamidel, and glycine receptor partial agonist HA-966 [(+/-)-(3-amino-1-hydroxypyrrolid-2-one)] on electroencephalographic (EEG) activity and behaviour were studied in rats. METHODS: Adult male Wistar albino rats were implanted with electrodes and cannulae were placed into the right lateral ventricle. Animals were divided into five groups: (i) saline (icv)+Imi/Cil (ii) APV (0.2 micromol)+Imi/Cil, (iii) APV (0.4 micromol)+Imi/Cil, (iv) remacemide (100 mg/kg, ip)+Imi/Cil, and (v) HA-966 (200 microg, icv)+Imi/Cil. The drugs were administered 30 min before icv injection of Imi/Cil (100/100 microg), and their effects on incidence of seizures, latencies to EEG changes and convulsions, severity, lethality and time to lethal outcome were studied. RESULTS: Imi/Cil provoked complete seizure response in all rats and all animals died within 10-18 min after the injection. EEG epileptiform activity preceded behavioral seizures. Clonic-tonic seizures were characterized by continuous bursts of high frequency high amplitude spikes in the EEG. The dose of 0.2 micromol of APV prolonged only the latency to the first EEG changes, while 0.4 micromol dose significantly influenced all seizure parameters. HA-966 increased only the latency to Imi/Cil-induced convulsions, while remacemide had no significant effect on seizure parameters. INTERPRETATION & CONCLUSION: The results suggested that excitatory neurotransmission contributed to the generation and/or propagation of Imi/Cil-induced seizures in rats, and that the effects of NMDA antagonists depended on a particular binding site within the NMDA receptor complex, and affinity to that site.

Relative efficacy of DEPA and neem oil for repellent activity against Phlebotomus papatasi, the vector of leishmaniasis.

The insect repellent N, N-diethylphenyl acetamide (DEPA) was compared with neem oil, a commercial preparation, for protection against 3 day old un-fed female of the sandfly, Phlebotomus papatasi, (Diptera: Psychodidae) under laboratory conditions on mouse. The percentage protection against sandfly bite provided by neem oil was significantly higher than DEPA when applied at 1% and 2% concentrations (p = 0.000, t = 21.474; df = 6 and p = 0.001, t = 5.960; df = 6 respectively). However, neem oil did not show any significant difference with DEPA at 5% (p = 0.1682, t = 0.15667; df = 6). This clearly indicates that at higher concentration (5%) both neem oil and DEPA exhibited similar repellent action against P. papatasi.

Espectro de acción antiepiléptica de la DL-4-hidroxi, 4-etil,4-fenil butiramida y sus homólogos inferiores / Profile of the antiepileptic action of DL-4-hydroxy, 4-ethyl, 4-phenyl butiramide and its inferior homologues

Se estudio la actividad farmacológica en animales de una serie nueva de compuestos anticonvulsionantes, la DL-4-hidroxil, 4-etil, 4-fenil butiramida (HEPB) y sus homólogos inferiores propionamida (HEPP) y acetamida (HEPA). La neurotoxidad fue determinada con un rotarod y se indujeron cuadros convulsivos con electrochoque supramáximo (MES), pentilentetrazol (TSC), estricnina (STR) y picrotoxina (PIC). HEPP es menos neurotóxica que HEPB y HEPA y altera el comportamiento de los ratones solamente a dosis altas. Los tres compuestos presentaron un amplio espectro de acción anticonvulsionante. Ellos son muy potentes para inhibir cuadros convulsivos inducidos con 4-AP, BIC, TSC y PTZ en dosis no tóxicas administradas ip, pero son inefectivas contra convulsiones inducidas con pic y STR. Los índices terapéuticos (IT = DT 50/D 50) fueron más elevados para HEPP. En consecuencia los resultados indican que los tres compuestos probados pueden servir para el tratamiento de convulsiones generalizadas tipo ausencias. Puesto que HEPP es el compuesto menos neurotóxico se ha seleccionado para los estudios toxicológicos y neuroquímicos

Persistence of leech repellents on cloth.

Trials on persistence of repellent properties of N, N-diethyl phenyl acetamide (DEPA), N,N-diethyl-m-toluamide (DEET), 3acetyl2(2-6-dimethyl-5-heptenyl)oxazolidine(Citronyl) , dimethyl phthalate (DMP) and N-benzoyl piperidine (NBP) on cloth were conducted against land leeches in evergreen rain and deciduous forests of Assam. Results obtained were compared with volatile oil of Zanthoxylum armatum DC. syn. Z. alatum Roxb (Timur) to evaluate its efficacy as leech repellent. DEPA and DEET were found to be the best. Timur oil was at par with Citronyl and exhibited better results than DMP and NBP.