RESUMO
Although deep learning networks applied to digital images have shown impressive results for many pathology-related tasks, their black-box approach and limitation in terms of interpretability are significant obstacles for their widespread clinical utility. This study investigates the visualization of deep features (DFs) to characterize two lung cancer subtypes, adenocarcinoma and squamous cell carcinoma. It demonstrates that a subset of DFs, called prominent DFs, can accurately distinguish these two cancer subtypes. Visualization of such individual DFs allows for a better understanding of histopathologic patterns at both the whole-slide and patch levels, and discrimination of these cancer types. These DFs were visualized at the whole slide image level through DF-specific heatmaps and at tissue patch level through the generation of activation maps. In addition, these prominent DFs can distinguish carcinomas of organs other than the lung. This framework may serve as a platform for evaluating the interpretability of any deep network for diagnostic decision making.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Aprendizado Profundo , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma de Pulmão/patologia , Carcinoma de Células Escamosas/patologia , Conjuntos de Dados como Assunto , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/patologia , Masculino , Redes Neurais de Computação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of Zanthoxylum rhetsa, together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction of the isolated compounds with the main protease of SARS-CoV-2 (Mpro) was evaluated using molecular docking followed by MD simulations. The result suggests that 2,11-didemethoxy-vepridimerine A, the new compound, has the highest negative binding affinity against the Mpro with a free energy of binding of -8.5 Kcal/mol, indicating interaction with the Mpro. This interaction was further validated by 100 ns MD simulation. This implies that the isolated new compound, which can be employed as a lead compound for an Mpro-targeting drug discovery program, may be able to block the action of Mpro.
Assuntos
Alcaloides , Antineoplásicos , COVID-19 , Quinolonas , Zanthoxylum , SARS-CoV-2 , Simulação de Acoplamento Molecular , Alcaloides/farmacologia , Polímeros , Inibidores de Proteases , Simulação de Dinâmica MolecularRESUMO
BACKGROUND: There is a paucity of data on the burden of insurance limitations for patients undergoing patch testing. OBJECTIVE: To characterize the burden of insurance limitations and its impact on differences in management and execution of patch testing. METHODS: A retrospective chart review was performed on patients with a diagnosis of contact dermatitis (International Classification of Disease [ICD], Ninth Edition, code ICD 692) who received patch testing (Current Procedural Terminology code 95044) at the George Washington Medical Faculty Associates Dermatology Clinic between January 1, 2015 and June 30, 2017. Variables including allergen limitations were compared between government-sponsored insurance and private insurance providers (eg, Insurers A, B, C, and D). RESULTS: A total of 371 records were identified. Government-sponsored insurance patients encountered allergen limitations more frequently than private insurance patients (86.8% vs 14.2%, P < .0001). Insurer C and D patients were least likely to encounter allergen limitations (1.2% vs 0%, P < .0001) and were tested to the most allergens (mean = 146 vs 152, P < .0001). Insurer A patients had the least allergens tested among those privately insured. CONCLUSION: Considering modification of insurance policies to allow patch testing with a larger number of allergens without restrictions is needed, with the goal of improving quality of life of these patients while saving costs from chronic use of topical corticosteroids.
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Alérgenos/administração & dosagem , Dermatite Alérgica de Contato/diagnóstico , Gastos em Saúde/estatística & dados numéricos , Cobertura do Seguro/estatística & dados numéricos , Testes do Emplastro/economia , Adulto , Dermatite Alérgica de Contato/economia , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Estudos Retrospectivos , Pele/efeitos dos fármacos , Pele/imunologia , Pele/fisiopatologiaRESUMO
Prurigo nodularis is a chronic dermatologic condition involving the development of multiple cutaneous nodules in the setting of intractable pruritus. Given emerging treatment options for this difficult-to-treat condition, a current review of therapeutics is needed. A systematic review was performed for clinical studies investigating prurigo nodularis treatment published from 1990 to present including ≥5 subjects. A total of 35 articles were assigned a level of evidence according to the Oxford Center for Evidence-based Medicine. All 5 studies investigating topical agents, including corticosteroids, calcineurin inhibitors, calcipotriol, and capsaicin, conveyed some beneficial effect with level of evidence 2b or higher. Six of 8 reports investigating photo- and photochemotherapy achieved levels of evidence 2b or greater and showed good partial response rates. Thalidomide was studied by 6 reports providing evidence of good symptom response, only 2 of which were rated level 2b or greater. Cyclosporine and methotrexate have demonstrated benefit in 4 combined studies, albeit with level 4 evidence. Pregabalin, amitriptyline, paroxetine, fluvoxamine, and neurokinin-1 receptor antagonists have demonstrated promising evidence in 5 level 2b studies. Higher-powered studies and additional randomized controlled trials are needed for the evaluation of safe and efficacious systemic treatment options for prurigo nodularis.
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Antipruriginosos/uso terapêutico , Fotoquimioterapia , Prurigo/terapia , Talidomida/uso terapêutico , Corticosteroides/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Calcitriol/análogos & derivados , Calcitriol/uso terapêutico , Capsaicina/uso terapêutico , Ciclosporina/uso terapêutico , Medicina Baseada em Evidências , Humanos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Terapia PUVARESUMO
Since the first reported cases in 2007, idiopathic mast cell activation syndrome has been increasingly recognized. Understanding of the cutaneous manifestations of this condition is imperative for dermatologists given the substantial clinical heterogeneity in its presentation and high estimated prevalence. A review of PubMed® and SCOPUS® databases was performed in order to investigate the most common dermatologic manifestations of idiopathic mast cell activation syndrome. Evidence to date suggests that flushing, pruritus, and clotting dysfunction or bleeding disorder are the most frequently observed dermatologic symptoms in idiopathic mast cell activation syndrome, while dermatographism has been identified as a common finding in patients as well. Mast cell activation syndromes have also been linked to connective tissue disorders, including an Ehlers-Danlos Syndrome-like phenotype possibly mediated by matrix metalloproteinases and tryptase released by mast cells. Current literature regarding dermatologic manifestations of idiopathic mast cell activation syndrome is limited by the heterogeneity of studies including clinical descriptions, inconsistency of diagnostic criteria implemented, and a paucity of literature available. This work provides a guide for dermatologists to strengthen diagnostic acuity for idiopathic mast cell activation syndrome, therefore contributing toward a goal of helping patients to receive timely, effective, and targeted therapy. J Drugs Dermatol. 2019;18(2):162-168.
Assuntos
Mastócitos/patologia , Mastocitose/diagnóstico , Mastocitose/epidemiologia , Dermatopatias/diagnóstico , Dermatopatias/epidemiologia , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/epidemiologia , Síndrome de Ehlers-Danlos/imunologia , Humanos , Mastócitos/imunologia , Mastocitose/imunologia , Prurido/diagnóstico , Prurido/epidemiologia , Prurido/imunologia , Dermatopatias/imunologiaRESUMO
BACKGROUND: The quality of cryopreserved buffalo semen is low due to high susceptibility of sperm membranes to cold shock. OBJECTIVE: The present study was designed to investigate the effect of recombinant type-III antifreeze protein from the eel pout Macrozoarces americanus (rAFPIII) on freezability of buffalo semen. MATERIALS AND METHODS: Semen was collected from three buffalo bulls for three weeks (replicates). Qualified ejaculates (N=18) were split into four aliquots and diluted in Tris-citric acid extender containing 0.0, 0.1, 1 and 10 µg mL-1 of rAFPIII. Semen was cooled to 4 C, evaluated for sperm motility and PMI, cryopreserved and assessed for post-thaw quality. RESULTS: Supplementation of the extender with rAFPIII didn't affect motility and PMI of chilled semen. Post-thaw sperm motility and PMI were higher in extender supplemented with rAFPIII (10µg mL-1) compared to control. Sperm viability and acrosome integrity remained the same. CONCLUSION: Addition of rAFPIII in extender improved motility and PMI of cryopreserved buffalo semen.
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Reflex sympathetic dystrophy is a subtype of complex regional pain syndrome, a condition characterized by persistent post-injury extremity pain. Temperature and sweating changes, edema, mobility changes, and a variety of hair, nail, and skin sequelae have been described. Only 23 articles published since 1990 describe dermatologic changes in CRPS. Given this paucity of literature, we present a case to further elucidate cutaneous manifestations of CRPS. Our patient is a 52-year-old Caucasian woman with a 19-year history of reflex sympathetic dystrophy who has presented with several dermatologic complaints. She was first referred to the clinic due to episodic, mildly tender, clustered, non-blanching, and non-palpable petechiae on the legs bilaterally, which was histologically consistent with leukocytoclastic vasculitis. No systemic involvement was identified and symptoms resolved with topical steroids. The patient was also noted to have severe ten toenail dystrophy without any evidence of onychomycosis based on multiple cultures and PAS staining of clipped nails. Avulsion of the great toenail was performed to provide symptomatic relief. Incidentally, the patient was found to have lower extremity and facial hypotrichosis on physical exam. Further, she required increased lidocaine administration in addition to pre and post-procedure lidocaine and prilocaine 5% emulsion cream for various office procedures, suggestive of lidocaine insensitivity. This case captures previously described cutaneous manifestations of CRPS such as vasculitis, nail dystrophy, extremity hypotrichosis, and telangiectasia, along with newly described potential manifestations about which dermatologists should be aware, including facial hypotrichosis and lidocaine insensitivity. J Drugs Dermatol. 2018;17(5):532-536.
Assuntos
Síndromes da Dor Regional Complexa , Doenças da Unha/diagnóstico , Vasculite/diagnóstico , Administração Cutânea , Diagnóstico Diferencial , Feminino , Humanos , Perna (Membro) , Lidocaína/administração & dosagem , Pessoa de Meia-Idade , Doenças da Unha/complicações , Vasculite/complicaçõesRESUMO
The free radical scavenging activity (RSA) of Nigella sativa extract and its efficiency for cryopreservation of buffalo spermatozoa was investigated. In experiment 1, Nigella sativa extract was prepared and evaluated for RSA using 2,2-diphenyl-1-picrylhydrazyl assay. The results showed increased pattern of RSA at 1%-5% of Nigella sativa extract. In experiment 2, buffalo semen from three bulls (24 ejaculates) was incubated at 0%, 0.1%, 0.3%, 0.5%, 1%, 1.5%, 2%, 3%, 4%, 5% and 6% extract to assess in vitro tolerability to Nigella sativa in terms of progressive motility (PM). Buffalo spermatozoa showed tolerance to all levels; rather, sperm PM was increased at 1%-4% extract. In experiment 3, semen from three bulls (24 ejaculates) was cryopreserved with 0%, 1%, 2%, 3%, 4% and 5% of Nigella sativa extract. Sperm PM and plasma membrane integrity (PMI) were evaluated after dilution and cooling, while PM, PMI, viability and DNA integrity were evaluated after thawing. Nigella sativa extract at 4% in extender improved (p < .05) post-dilution, post-cooling and post-thaw sperm quality. In conclusion, Nigella sativa extract at all concentrations (1%-6%) showed antioxidant activity and its supplementation at 4% in extender improved buffalo sperm quality at all stages of cryopreservation.
Assuntos
Búfalos , Criopreservação/métodos , Nigella sativa , Extratos Vegetais/farmacologia , Preservação do Sêmen/métodos , Espermatozoides/efeitos dos fármacos , Animais , Crioprotetores/farmacologia , Sequestradores de Radicais Livres/farmacologia , MasculinoRESUMO
Routinely, swim-up method is used to separate high-quality sperm; however, long processing time and close cell-to-cell contact during the centrifugation step are inevitable elements of oxidative stress to sperm. The objective was to evaluate Sephadex™ and glass wool filtration to separate motile, intact and viable sperm for in vitro fertilization in buffalo. The cumulus-oocyte complexes (COCs) were collected from ovaries of slaughtered buffaloes by aspiration and matured for 24 hr in CO2 incubator at 38.5°C and 5% CO2 . Matured COCs were rinsed twice in fertilization TALP and placed in the pre-warmed fertilization medium without sperm. Cryopreserved buffalo semen was thawed at 37°C for 30 s and processed through Sephadex™ , glass wool filtration and swim-up (control). Total and motile sperm recovery rates were assessed, resuspended in fertilization TALP and incubated for 15-20 min in CO2 incubator. Samples prepared by each method were divided into two aliquots: one aliquot was studied for sperm quality (progressive motility, membrane integrity, viability, liveability), while the other was subjected to co-incubation with sets of 10-15 in vitro matured oocytes. Data on sperm quality were analysed by ANOVA, while in vitro fertilizing rates were compared by chi-squared test using SPSS-20. Least significant difference (LSD) test was used to compare treatment means. Glass wool filtration yielded higher total and motile sperm recovery rate, while Sephadex™ filtration improved (p < .05) sperm quality (progressive motility, membrane integrity, viability, liveability). Sperm preparation through Sephadex filtration yielded higher in vitro fertilization rate in terms of cleavage rate compared to glass wool filtration and swim-up (control). In conclusion, cryopreserved Nili-Ravi buffalo sperm selected through Sephadex filtration showed improved quality and yielded better fertilization rates (cleavage rate) of in vitro matured/fertilized oocytes. Sephadex filtration could be a promising technique for use in in vitro fertilization in buffalo.
Assuntos
Búfalos , Separação Celular/veterinária , Filtração/veterinária , Espermatozoides/fisiologia , Animais , Separação Celular/métodos , Criopreservação/veterinária , Feminino , Fertilização in vitro/veterinária , Filtração/métodos , Vidro , Técnicas de Maturação in Vitro de Oócitos/veterinária , Masculino , Oócitos , Preservação do Sêmen/veterinária , Motilidade dos EspermatozoidesRESUMO
Obesity is a common comorbidity of chronic obstructive pulmonary disease (COPD) and has been associated with worse outcomes. However, it is unknown whether the interaction between obesity and COPD modulates diaphragm shape and consequently its function. The body mass index (BMI) has been used as a correlate of obesity. We tested the hypothesis that the shape of the diaphragm muscle and size of the ring of its insertion in non-COPD and COPD subjects are modulated by BMI. We recruited 48 COPD patients with postbronchiodilator forced expiratory volume in 1 s (FEV1)-to-forced vital capacity (FVC) < 0.7 and 29 age-matched smoker/exsmoker control (non-COPD) subjects, who underwent chest computed tomography (CT) at lung volumes ranging from functional residual capacity (FRC) to total lung capacity (TLC). We then computed maximum principal diaphragm curvature in the midcostal region of the left hemidiaphragm at the end of inspiration during quiet breathing (EI) and at TLC. The radius of maximum curvature of diaphragm muscle increased with BMI in both COPD and non-COPD subjects. The size of diaphragm ring of insertion on the chest wall also increased significantly with increasing BMI. Surprisingly, COPD severity did not appear to cause significant alteration in diaphragm shape except in normal-weight subjects at TLC. Our data uncovered important factors such as BMI, the size of the diaphragm ring of insertion, and disease severity that modulate the structure of the ventilatory pump in non-COPD and COPD subjects.
Assuntos
Diafragma/fisiopatologia , Pulmão/fisiopatologia , Obesidade/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Mecânica Respiratória , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Diafragma/diagnóstico por imagem , Feminino , Volume Expiratório Forçado , Capacidade Residual Funcional , Humanos , Iowa , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Obesidade/diagnóstico , Obesidade/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Texas , Tomografia Computadorizada por Raios X , Capacidade Pulmonar Total , Capacidade VitalRESUMO
BACKGROUND: Semen from the Nili-Ravi buffalo bull, Bubalus bubalis, shows poor survival after freeze storage compared to bovine (Bos taurus and Bos indicus) semen. Freeze-susceptibility distinctions in these two genera have been attributed to differences in sperm membranes. MATERIALS AND METHODS: We measured the impact of protein preparations derived from a frost-resistant perennial grass, Lolium perenne, with ice recrystallization inhibition activity on the low temperature storage of B. bubalis semen. RESULTS: When the L. perenne preparations (0.1, 1, 10 µg/mL) were added to buffalo semen [2 ejaculates per bull (N=3) per replicate (r=3)] in Tris-citrate extender (50×106sperm mL-1), there was no impact on semen quality, as measured by sperm motility and plasma membrane integrity, after storage at 4 degree C (P>0.05). However, when semen supplemented with the grass proteins (0.1 and 1 µg mL-1) was evaluated after freezing and storage in liquid nitrogen for 24 h, post-thaw sperm progressive motility and plasma membrane integrity was higher (P<0.05) than in control samples. Post-thaw sperm viability and sperm acrosome integrity was similar (P > 0.05) to controls. CONCLUSION: The improvement in cryopreserved buffalo sperm progressive motility and plasma membrane integrity suggests that the use of these easily-made preparations may improve fertility after cryopreservation and offers the prospect of improved conception rates after artificial insemination with cryopreservation.
Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Lolium , Extratos Vegetais/farmacologia , Preservação do Sêmen/métodos , Animais , Búfalos , Bovinos , Crioprotetores/química , Lolium/química , Masculino , Proteínas de Plantas/farmacologia , Espermatozoides/efeitos dos fármacosRESUMO
Benign prostatic hyperplasia and carcinoma of the prostate are the most common disorders of Bangladeshi male in recent years. Volume of the prostate is necessary to estimate the amount of BPH adenoma to determine the appropriate therapy or to select the surgical approach. Transurethral resection of prostate (TURP) is preferred for small glands and open prostatectomy for larger ones. Decrease in prostatic mass after hormonal manipulation or radiation therapy can be used as an indicator of therapeutic efficacy. The effect of prostate volume on biopsy outcome was assessed and was noted that there was an inverse relationship in between size of the gland and prostate cancer. A cross sectional descriptive study was conducted in Department of Anatomy, Mymensingh Medical College, Mymensingh, Bangladesh to find out the difference in volume of the prostate gland of Bangladeshi people in relation to age. The present study was performed on 67 postmortem human prostate gland collected from the morgue in the Department of Forensic Medicine, Mymensingh Medical College by non random purposive sampling technique. The specimens were collected from Bangladeshi cadaver of age ranging from 10 to 80 years. All the specimens were grouped into three categories: Group A (upto 18 years), Group B (19 to 45 years) and Group C (above 45 years) according to age. Dissection was performed according to standard autopsy techniques. The volume of the prostate gland were measured and recorded. The mean volume of the prostate gland was 13.75ml in Group A, 24.44ml in Group B and 29.72ml in Group C. Variance analysis shows that mean differences of volume of the prostate were highly significant among all age groups. The volume of prostate gland was found to be increased with increasing age. For statistical analysis, differences between age groups were analyzed by using students unpaired 't' test. The present study will help to increase the information pool on the volume of prostate gland of Bangladeshi people.
Assuntos
Próstata , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bangladesh , Cadáver , Criança , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Adulto JovemRESUMO
OBJECT: Cases of postoperative psychosis in Parkinson's disease patients receiving deep brain stimulation (DBS) treatment have previously been published. However, the magnitude of symptom incidence and the clinical risk factors are currently unknown. This retrospective study sheds light on these issues by investigating psychosis in a group of 128 Parkinson's disease patients who received DBS implants. METHODS: A retrospective chart review was performed to obtain surgery dates, follow-up clinic visit dates, and associated stimulation parameter settings (contacts in use and the polarity of each along with stimulation voltage, frequency, and pulse width) for each patient. Unified Parkinson's Disease Rating Scale II Thought Disorder scores, used as a clinical assessment tool to evaluate the presence of psychosis at each visit, were also collected. The data were compiled into a database and analyzed. RESULTS: The lifetime incidence of psychosis in this cohort of patients was 28.1%. The data suggest that risk of psychosis remains fairly constant throughout the first 5 years after implantation of a DBS system and that patients older at the time of receiving the first DBS implant are not only more likely to develop psychosis, but also to develop symptoms sooner than their younger counterparts. Further analysis provides evidence that psychosis is largely independent of the clinically used electrode contact and of stimulation parameters prior to psychosis onset. CONCLUSIONS: Although symptoms of psychosis are widely seen in patients with Parkinson's disease in the years following stimulator placement, results of the present suggest that most psychoses occurring postoperatively are likely independent of implantation and stimulation settings.
Assuntos
Estimulação Encefálica Profunda/efeitos adversos , Globo Pálido/fisiologia , Doença de Parkinson/terapia , Complicações Pós-Operatórias/etiologia , Transtornos Psicóticos/etiologia , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Recently, hypothalamic RFRP-3 (a mammalian ortholog of avian GnIH) signaling has been proposed as an important negative modulator of the reproductive axis. The current study examined whether repression of reproductive hormonal expression during short-term fasting conditions in higher-order primate is influenced by altered RFRP-3 signaling. Eight intact postpubertal male macaques (Macaca mulatta) were administered a single intravenous bolus of RF-9 (n = 4), a potent and putative RFRP-3 receptor antagonist, or vehicle (n = 4) following a 48-h fasting condition. Intermittent blood samples were collected every 30 min during the 4-h post-bolus period, and blood glucose, plasma cortisol, and testosterone concentrations were measured. Relative to fed conditions, fasting reduced glucose and testosterone levels (p < 0.005) and increased cortisol levels (p < 0.05). Relative to baseline, mean testosterone levels were elevated 150 min after RF-9 (p < 0.05) but not vehicle administration. In addition, elevated mean plasma testosterone levels following RF-9 administration were equivalent to levels observed in normal fed monkeys. These results suggest an important role for RFRP-3 signaling in conveying metabolic state information to the reproductive axis in higher primates.
Assuntos
Adamantano/análogos & derivados , Dipeptídeos/administração & dosagem , Dipeptídeos/farmacologia , Jejum/fisiologia , Gônadas/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Adamantano/administração & dosagem , Adamantano/farmacologia , Administração Intravenosa , Animais , Glicemia/metabolismo , Jejum/sangue , Comportamento Alimentar , Gônadas/efeitos dos fármacos , Hidrocortisona/sangue , Macaca , Masculino , Testosterona/sangueRESUMO
OBJECTIVE: Aqueous extracts of four medicinal plants including Ferula gummosa, Echinophora orientalis, Nasturtium microphyllum and Verbascum thapsus were used to determine their antibacterial activities and minimum inhibitory concentration (MIC). The aim of this study was to assess antibacterial activity of extracts of four medicinal plants against a Gram-positive and a Gram-negative bacteria (Staphylococcus aureus PTCC1431, and Escherichia coli HP101BA 7601c). METHODS: Radial diffusion assay was used to assess the antibacterial activity of extracted samples. Haemolysis assay was also used to examine their nontoxic effects on human red blood cells (RBCs). RESULTS: This study showed that all the mentioned plants have satisfactory antibacterial effects against both Gram-positive and Gram-negative bacteria. Minimum inhibitory concentration values of these samples were less than 750 µg/mL. In addition, no significant haemolytic activity was observed at their MIC values. CONCLUSION: The results of this study showed that all these studied plants have good potential for further studies for drug discovery.
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Given the widespread and established use of Jasminum scandens (Retz) Vahl, a member of the Oleacea family, this study aimed to identify and characterise secondary metabolites derived from the plant, with the objective of evaluating their potential biological activities. Using chromatographic separations techniques based on molecular weight and polarity, various VLC fractions of the plant were purified. These fractions yielded seven compounds- 2-(4-hydroxyphenyl)-ethanol (1), 2-(4-hydroxy-3-methoxy-phenyl)-ethanol (2), 1-(4-hydroxy-3-methoxy-phenyl)-1,2,3-propanetriol (3), 1-(4-hydroxy-3,5-dimethoxy-phenyl)-1,2,3-propanetriol (4), lupeol (5), ß-sitosterol (6), and methyl linoleate (7), which have never been previously reported in this plant. Out of the seven identified compounds, compounds 3 and 4 had the greatest capacity to scavenge free radicals with IC50 values of 3.81 µg/ml and 4.08 µg/ml, respectively when compared to the standard Butylated Hydroxy Toluene (BHT) with IC50 value of 6.54 µg/ml.
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Many antibiotic-resistant bacteria carry resistance genes on conjugative plasmids that are transferable to commensals and pathogens. We determined the ability of multiple enteric bacteria to acquire and retransfer a broad-host-range plasmid RP4. We used human-derived commensal Escherichia coli LM715-1 carrying a chromosomal red fluorescent protein gene and green fluorescent protein (GFP)-labeled broad-host-range RP4 plasmid with ampR, tetR, and kanR in in vitro matings to rifampicin-resistant recipients, including Escherichia coli MG1655, Dec5α, Vibrio cholerae, Pseudomonas putida, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter rodentium, and Salmonella Typhimurium. Transconjugants were quantified on selective media and confirmed using fluorescence microscopy and PCR for the GFP gene. The plasmid was transferred from E. coli LM715-1 to all tested recipients except P. aeruginosa. Transfer frequencies differed between specific donor-recipient pairings (10-2 to 10-8). Secondary retransfer of plasmid from transconjugants to E. coli LM715-1 occurred at frequencies from 10-2 to 10-7. A serial passage plasmid persistence assay showed plasmid loss over time in the absence of antibiotics, indicating that the plasmid imposed a fitness cost to its host, although some plasmid-bearing cells persisted for at least ten transfers. Thus, the RP4 plasmid can transfer to multiple clinically relevant bacterial species without antibiotic selection pressure.
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Novel modified cytosine analogs bearing phosphodiester/thiophosphodiester functionality were synthesized. The interactions between different metal ions and modified cytosine-cytosine base-pairs in DNA duplexes were investigated by UV-melting experiments. The thiophosphodiester modification binds to the Ag(I) ions strongly compared to the phosphodiester counterpart as examined in ESI-MS spectra as well.
Assuntos
Citosina , Prata , Nucleotídeos , DNA/genética , Íons , OrganofosfatosRESUMO
Two types of anthraquinone conjugates were synthesized as non-nucleosidic oligonucleotide components. These include an anthraquinone derivative conjugated with 2,2-bis(hydroxymethyl)propionic acid and an anthraquinone--polyamine derivative conjugated with 2,2-bis(hydroxymethyl)propionic acid. The conjugates were successfully incorporated into the "linking-region" of the α-ß chimeric oligonucleotides via phosphoramidite method as non-nucleosidic backbone units. The resultant novel α-ß chimeric oligonucleotides possessed two diastereomers that were generated by the introduction of the anthraquinone conjugate with a stereogenic carbon atom. The isomers were successfully separated by a reversed-phase HPLC. UV-melting experiments revealed that both stereoisomers formed a substantially stable alternate-strand triple helix, irrespective of the stereochemistry of the incorporated non-nucleosidic backbone unit. However, the enhancing effect on thermal stability depended on the length of the alkyl linker connecting anthraquinone moiety and the propionic acid moiety. The sequence discrimination ability of the chimeric oligonucleotides toward mismatch target duplex was also examined. The T(m) values of the triplexes containing the mismatch target were substantially lower than the T(m) values of those containing the full-match target. The thermodynamic parameters (ΔH°, ΔS°, and ΔG°) required for the dissociation of the triplexes into the third strand and target duplex were also measured.
Assuntos
Antraquinonas/química , DNA/química , Oligonucleotídeos/química , Poliaminas/química , Propionatos/química , Antraquinonas/farmacologia , Concentração de Íons de Hidrogênio , Conformação Molecular/efeitos dos fármacos , Estrutura Molecular , Oligonucleotídeos/síntese química , Oligonucleotídeos/isolamento & purificação , Poliaminas/farmacologia , Estereoisomerismo , TermodinâmicaRESUMO
COVID-19 is reported as an extremely contagious disease with common symptoms of fever, dry cough, sore throat, and tiredness. The published literature on incidence and gender-wise prevalence of COVID-19 is scarce in Pakistan. Therefore, the present study was designed to compare the distribution, incubation period and mortality rate of COVID-19 among the male and female population of district Attock. The data were collected between 01 April 2020 and 07 December 2020 from the population of district Attock, Pakistan. A total of 22,962 individuals were screened and 843 were found positive for RT-qPCR for SARS-CoV-2. The confirmed positive cases were monitored carefully. Among the positive cases, the incidence of COVID-19 was 61.7% among males and 38.2% among females. The average recovery period of males was 18.89±7.75 days and females were 19±8.40 days from SARS-CoV-2. The overall mortality rate was 8.06%. The death rate of male patients was significantly higher (P<0.05) compared to female patients. Also, the mortality rate was higher (P<0.05) in male patients of 40-60 years of age compared to female patients of the same age group. Moreover, the mortality rate significantly increased (P<0.05) with the increase of age irrespective of gender. In conclusion, the incidence and mortality rate of COVID-19 is higher in males compared to the female population. Moreover, irrespective of gender the mortality rate was significantly lower among patients aged <40 years.