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1.
Emerg Radiol ; 31(1): 83-96, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37978126

RESUMEN

Gastrointestinal hemorrhage remains one of the most common causes of morbidity and mortality among patients with liver cirrhosis. Mostly, these patients bleed from the gastroesophageal varices. However, nonvariceal bleeding is also more likely to occur in these patients. Because of frequent co-existing coagulopathy, cirrhotics are more prone to bleed from a minor vascular injury while performing percutaneous interventions. Ultrasound-guided bedside vascular access is an essential procedure in liver critical care units. Transjugular portosystemic shunts (TIPS) with/without variceal embolization is a life-saving measure in patients with refractory variceal bleeding. Whenever feasible, balloon-assisted retrograde transvenous obliteration (BRTO) is an alternative to TIPS in managing gastric variceal bleeding, but without a risk of hepatic encephalopathy. In cases of failed or unfeasible endotherapy, transarterial embolization using various embolic agents remains the cornerstone therapy in patients with nonvariceal bleeding such as ruptured hepatocellular carcinoma, gastroduodenal ulcer bleeding, and procedure-related hemorrhagic complications. Among various embolic agents, N-butyl cyanoacrylate (NBCA) enables better vascular occlusion in cirrhotics, even in coagulopathy, making it a more suitable embolic agent in an expert hand. This article briefly entails the different interventional radiological procedures in vascular emergencies among patients with liver cirrhosis.


Asunto(s)
Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Humanos , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/terapia , Várices Esofágicas y Gástricas/complicaciones , Urgencias Médicas , Radiología Intervencionista , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Derivación Portosistémica Intrahepática Transyugular/métodos , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/terapia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Resultado del Tratamiento
2.
Emerg Radiol ; 31(3): 359-365, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38664278

RESUMEN

BACKGROUND: Vascular plug-assisted retrograde transvenous obliteration (PARTO) obliterates the gastric varices and portosystemic shunt, thus resulting in a lower rebleeding rate than endoscopic glue/sclerotherapy. AIMS: To evaluate the safety and efficacy of PARTO as salvage therapy in liver cirrhosis with gastric variceal bleed (GVB) after failed endotherapy. We assessed the clinical success rate and changes in liver function at 6- months. MATERIALS AND METHODS: Patients who underwent salvage PARTO after failed endotherapy for GVB (between December 2021 and November 2022) were searched and analyzed from the hospital database. Clinical success rate and rebleed rate were obtained at six months. Child-Pugh score (CTP) and Model for end-stage liver disease (MELD) score were calculated and compared between baseline and 6-month follow-up. RESULTS: Fourteen patients (n = 14, Child-Pugh class A/B) underwent salvage PARTO. Nine had GOV-2, and five had IGV-1 varices. The mean shunt diameter was 11.6 ± 1.6 mm. The clinical success rate of PARTO was 100% (no recurrent gastric variceal hemorrhage within six months). No significant deterioration in CTP (6.79 ± 0.98 vs. 6.21 ± 1.52; p = 0.12) and MELD scores (11.5 ± 4.05 vs. 10.21 ± 3.19; p = 0.36) was noted at 6 months. All patients were alive at 6 months. One patient (n = 1, 7.1%) bled from esophageal varices after three days of PARTO and was managed with variceal banding. 21.4% (3/14) patients had progression of esophageal varices at 6 months requiring prophylactic band ligation. Three patients (21.4%) had new onset or worsening ascites and responded to low-dose diuretics therapy. CONCLUSIONS: PARTO is a safe and effective procedure for bleeding gastric varices without any deterioration in liver function even after six months. Patient selection is critical to prevent complications. Further prospective studies with larger sample size are required to validate our findings.


Asunto(s)
Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Terapia Recuperativa , Humanos , Várices Esofágicas y Gástricas/terapia , Masculino , Femenino , Terapia Recuperativa/métodos , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Cirrosis Hepática/complicaciones , Adulto , Embolización Terapéutica/métodos , Resultado del Tratamiento
3.
Mycopathologia ; 188(6): 1027-1040, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37924426

RESUMEN

BACKGROUND: Cladosporium halotolerans is a saprobic fungus, rarely implicated in human infections. The identification is challenging due to non-specific phenotypic features. OBJECTIVE: To decipher clinical spectrum, microbiological and susceptibility profile of clinical and environmental isolates of Cladosporium halotolerans. METHOD: All the isolates identified as Cladosporium halotolerans deposited in National Culture Collection for Pathogenic Fungi (NCCPF), Postgraduate Institute of Medical Education and Research, Chandigarh, India were revived. Phenotypic and molecular characterization targeting internal transcribed spacer (ITS) region of ribosomal DNA, large subunit of ribosomal DNA (LSU; NL1 and NL4), actin (ACT) and beta-tubulin (TUB) was done. Scanning electron microscopy (SEM) was performed to determine any phenotypic variations. Antifungal susceptibility testing (AFST) was carried out for eight antifungal agents as per CLSI M38 Ed3 guidelines. We also performed systematic literature review of all the cases of Cladosporium halotolerans reported till date. RESULTS: A total of four isolates (clinical, n = 3; soil, n = 1) identified as Cladosporium halotolerans were included in the study. The clinical sites were skin, maxillary tissue and nail. All patients were apparently immunocompetent, and history of trauma was recorded in one patient. All patients improved on antifungal therapy. The cultures revealed growth of black mycelial fungus and microscopic examination demonstrated dematiaceous septate hyphae with erect conidiophores and conidia in branched acropetal chains. Based on molecular methods, all the four isolates were identified as C. halotolerans. SEM revealed no variation in length and width of the conidia, conidiophores, ramoconidium and hyphae among the isolates. All molecular targets, such as ITS region, LSU (partially sequenced), ACT and TUB were able to differentiate the isolates. Minimum inhibitory concentrations for antifungals were: triazoles (0.12-2 µg/ml), amphotericin B (4 µg/ml) and echinocandins (2-8 µg/ml). CONCLUSION: We report role of the rarely isolated dematiaceous fungus, C. halotolerans, in causing human infections. The study emphasizes the role of molecular methods in precisely identifying these species. Triazoles are more active against these black fungi compared to polyenes or echinocandins.


Asunto(s)
Antifúngicos , Hongos , Humanos , Antifúngicos/farmacología , Hongos/genética , Equinocandinas/farmacología , ADN Ribosómico/genética , Triazoles , Microscopía Electrónica de Rastreo , Esporas Fúngicas
4.
Lasers Med Sci ; 37(3): 2063-2070, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34853932

RESUMEN

This randomized clinical trial aimed to compare the efficacy of topical aloe vera with low-level laser therapy in patients with oral lichen planus (OLP). A randomized, parallel arm, single-blind study comprising of 60 patients with OLP was randomly divided into two groups. Group A was given topical aloe vera extract gel applied thrice daily for 2 months, and group B was given low-level laser therapy (LLLT) at 980 nm twice weekly for 2 months. Both groups were followed up for 9 months. Patients were assessed for various parameters according to the Escudier scale at baseline, after treatment at 9 months. Results were assessed using the McNemar-Bowker test and the Mann-Whitney U test. Both individual groups showed significant (p < 0.05) results at the end of the treatment period (0-2 months) and the follow-up period (2-7 months). Intergroup comparison showed significant results in the laser group (reduction of VAS by 44.1%, site score by 24.6%, and activity score by 50%) as compared with the aloe vera group (reduction of VAS by 26.7%, site score by 9.2%, and the activity score by 26%) in the treatment period. In the follow-up period, both groups showed insignificant differences in comparison to each other. Within the limitations of the study, LLLT was more effective as compared with topical aloe vera in managing oral lichen planus during the active treatment time, while both were equally effective during the follow-up period. The clinical study was registered under the Clinical Trials Registry India with the registration number CTRI/2018/04/013147.


Asunto(s)
Aloe , Liquen Plano Oral , Terapia por Luz de Baja Intensidad , Humanos , Liquen Plano Oral/tratamiento farmacológico , Liquen Plano Oral/radioterapia , Terapia por Luz de Baja Intensidad/métodos , Método Simple Ciego
5.
Int J Mol Sci ; 23(5)2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35269980

RESUMEN

Heat stress (HS) is one of the major abiotic stresses affecting the production and quality of wheat. Rising temperatures are particularly threatening to wheat production. A detailed overview of morpho-physio-biochemical responses of wheat to HS is critical to identify various tolerance mechanisms and their use in identifying strategies to safeguard wheat production under changing climates. The development of thermotolerant wheat cultivars using conventional or molecular breeding and transgenic approaches is promising. Over the last decade, different omics approaches have revolutionized the way plant breeders and biotechnologists investigate underlying stress tolerance mechanisms and cellular homeostasis. Therefore, developing genomics, transcriptomics, proteomics, and metabolomics data sets and a deeper understanding of HS tolerance mechanisms of different wheat cultivars are needed. The most reliable method to improve plant resilience to HS must include agronomic management strategies, such as the adoption of climate-smart cultivation practices and use of osmoprotectants and cultured soil microbes. However, looking at the complex nature of HS, the adoption of a holistic approach integrating outcomes of breeding, physiological, agronomical, and biotechnological options is required. Our review aims to provide insights concerning morpho-physiological and molecular impacts, tolerance mechanisms, and adaptation strategies of HS in wheat. This review will help scientific communities in the identification, development, and promotion of thermotolerant wheat cultivars and management strategies to minimize negative impacts of HS.


Asunto(s)
Fitomejoramiento , Triticum , Aclimatación , Adaptación Fisiológica , Respuesta al Choque Térmico
6.
Indian J Crit Care Med ; 26(3): 276-281, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35519933

RESUMEN

Background: The acute physiology and chronic health evaluation (APACHE) II severity score has shown a good calibration and discriminatory value across a range of disease processes and remains the most widely used source of prognostic information on the risk for death in patients admitted to intensive care units (ICUs). Objectives: To study APACHE II scores in patients of acute kidney injury (AKI) admitted in the ICU and to find its association with outcome. Materials and methods: One hundred patients with AKI aged 18 years or above were admitted in the ICU, department of general medicine, of a tertiary care institute in Haryana, North India, from October 2019 to September 2020, were studied. Patients who had known causes of chronic kidney disease (CKD), on maintenance hemodialysis, and those who underwent renal replacement therapy (RRT) or nephrectomy were excluded. All required investigations were performed, and data were collected. The patients were followed till discharge or in-hospital mortality. Results: The mean age of the patients was 55.92 ± 18.18 years. Male-female ratio was 1.5:1. Thirty-five percent of the admitted patients had an in-hospital mortality. Sepsis (47%) was the most common cause of AKI, and 83% of the patients had underlying comorbid conditions. The mean APACHE II score of the expired patients on admission, i.e., 24.80 ± 13.65, was found to be significantly higher compared to the mean APACHE II score (17.25 ± 10.12) of the discharged patients (p-value <0.001). APACHE II score was found to have 57.14% sensitivity, 86.15% specificity, 69% PPV, 78.9% NPV, and 76% diagnostic accuracy to predict mortality among the AKI patients. Conclusion: APACHE II scoring system has a good discrimination and calibration when applied to ICU-admitted AKI patients and is a good predictor of prognosis in them. How to cite this article: Patel P, Gupta S, Patel H, Bashar MDA. Assessment of APACHE II Score to Predict ICU Outcomes of Patients with AKI: A Single-center Experience from Haryana, North India. Indian J Crit Care Med 2022;26(3):276-281.

7.
Int J Mol Sci ; 22(22)2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34830037

RESUMEN

Two genes, HvSAP8 and HvSAP16, encoding Zinc-finger proteins, were identified earlier as active in barley plants. Based on bioinformatics and sequencing analysis, six SNPs were found in the promoter regions of HvSAP8 and one in HvSAP16, among parents of two barley segregating populations, Granal × Baisheshek and Natali × Auksiniai-2. ASQ and Amplifluor markers were developed for HvSAP8 and HvSAP16, one SNP in each gene, and in each of two populations, showing simple Mendelian segregation. Plants of F6 selected breeding lines and parents were evaluated in a soil-based drought screen, revealing differential expression of HvSAP8 and HvSAP16 corresponding with the stress. After almost doubling expression during the early stages of stress, HvSAP8 returned to pre-stress level or was strongly down-regulated in plants with Granal or Baisheshek genotypes, respectively. For HvSAP16 under drought conditions, a high expression level was followed by either a return to original levels or strong down-regulation in plants with Natali or Auksiniai-2 genotypes, respectively. Grain yield in the same breeding lines and parents grown under moderate drought was strongly associated with their HvSAP8 and HvSAP16 genotypes. Additionally, Granal and Natali genotypes with specific alleles at HvSAP8 and HvSAP16 were associated with improved performance under drought via higher 1000 grain weight and more shoots per plant, respectively.


Asunto(s)
Alelos , Regulación de la Expresión Génica de las Plantas , Hordeum , Proteínas de Plantas , Polimorfismo de Nucleótido Simple , Estrés Fisiológico/genética , Factores de Transcripción , Deshidratación , Hordeum/genética , Hordeum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Dedos de Zinc
8.
Med Mycol ; 58(4): 425-433, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-31342074

RESUMEN

Apophysomyces elegans species complex is an important cause of cutaneous mucormycosis in India. However, majority of those cases are reported as case reports only. We desired to analyze our patients with Apophysomyces infection reported over 25 years (1992-2017) to understand the epidemiology, management, and outcome of the disease. During the study period 24 cases were reported, and the majority (95.8%) of them presented with necrotizing fasciitis following accidental/surgical/iatrogenic trauma. One patient presented with continuous ambulatory peritoneal dialysis (CAPD) related peritonitis. Healthcare related Apophysomyces infection was noted in 29.2% patients. In addition to trauma, comorbidities were noted in 37.5% patients (type 2diabetes mellitus-6, chronic alcoholism-2, and chronic kidney disease-1). Of the 24 isolates, 11 isolates starting from year 2014 were identified as Apophysomyces variabilis by molecular methods. Majority (95.8%) of the patients were managed surgically with or without amphotericin B deoxycholate therapy, while one patient was treated with amphotericin B deoxycholate alone. Among 24 patients, seven (29.1%) recovered, six (25%) patients could not afford antifungal management and left the hospital against medical advice, and 11 (45.9%) patients died.The present case series highlights that necrotizing fasciitis caused by A. variabilis is prevalent in India, and the disease may be healthcare related. Although diagnosis is not difficult, awareness among surgeons is still limited about the infection, leading to a delay in sending samples to the mycology laboratory. Apophysomyces infection must be considered in the differential diagnosis in apatient with progressive necrosis of a wound who is not responding to antibacterial therapy.


Asunto(s)
Mucorales/patogenicidad , Mucormicosis/epidemiología , Adolescente , Adulto , Anciano , Antifúngicos/uso terapéutico , Comorbilidad , Fascitis Necrotizante/tratamiento farmacológico , Fascitis Necrotizante/microbiología , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Mucorales/clasificación , Mucormicosis/tratamiento farmacológico , Mucormicosis/mortalidad , Estudios Retrospectivos , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven
9.
Int J Mol Sci ; 21(21)2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33167455

RESUMEN

Down-regulator associated protein, DrAp1, acts as a negative cofactor (NC2α) in a transcription repressor complex together with another subunit, down-regulator Dr1 (NC2ß). In binding to promotors and regulating the initiation of transcription of various genes, DrAp1 plays a key role in plant transition to flowering and ultimately in seed production. TaDrAp1 and TaDrAp2 genes were identified, and their expression and genetic polymorphism were studied using bioinformatics, qPCR analyses, a 40K Single nucleotide polymorphism (SNP) microarray, and Amplifluor-like SNP genotyping in cultivars of bread wheat (Triticum aestivum L.) and breeding lines developed from a cross between spelt (T. spelta L.) and bread wheat. TaDrAp1 was highly expressed under non-stressed conditions, and at flowering, TaDrAp1 expression was negatively correlated with yield capacity. TaDrAp2 showed a consistently low level of mRNA production. Drought caused changes in the expression of both TaDrAp1 and TaDrAp2 genes in opposite directions, effectively increasing expression in lower yielding cultivars. The microarray 40K SNP assay and Amplifluor-like SNP marker, revealed clear scores and allele discriminations for TaDrAp1 and TaDrAp2 and TaRht-B1 genes. Alleles of two particular homeologs, TaDrAp1-B4 and TaDrAp2-B1, co-segregated with grain yield in nine selected breeding lines. This indicated an important regulatory role for both TaDrAp1 and TaDrAp2 genes in plant growth, ontogenesis, and drought tolerance in bread and spelt wheat.


Asunto(s)
Regulación de la Expresión Génica de las Plantas/genética , Fosfoproteínas/genética , Factores de Transcripción/genética , Triticum/genética , Alelos , Sequías , Genes de Plantas/genética , Fosfoproteínas/metabolismo , Fitomejoramiento/métodos , Desarrollo de la Planta/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Semillas , Estrés Fisiológico/genética , Factores de Transcripción/metabolismo , Triticum/metabolismo
10.
Oral Dis ; 25(1): 73-79, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30059188

RESUMEN

OBJECTIVES: To evaluate and compare the therapeutic response of lycopene and curcumin with placebo in patients suffering from oral submucous fibrosis (OSMF) and to correlate the habit variables of smoked and smokeless tobacco products in OSMF. METHODS: A randomized placebo-controlled parallel clinical study was conducted on ninety OSMF patients, who were divided into three treatment groups using computer-generated randomization. Group A patients (n = 30) were given curcumin tablet (300 mg) twice daily, Group B patients (n = 30) received lycopene capsules (8 mg) twice daily, and for Group C (n = 30), placebo capsules were given once daily for a period of six months. Both the participant and outcome assessor were blinded. Pre- and post-treatment comparison of mouth opening, burning sensation, tongue protrusion, and cheek flexibility was analyzed at periodic follow-up of 9 months. RESULTS: The overall improvement in mouth opening, burning sensation, tongue protrusion, and cheek flexibility was 3.9 ± 4.9 mm, 4.8 ± 2.6, 5.0 ± 7.2 mm, & 0.36 ± 0.71 mm, respectively, for curcumin and 4.1 ± 4.2 mm, 5.0 ± 2.3, 2.4 ± 3.5 mm, & 0.66 ± 0.80 mm, respectively, for lycopene with the p value <0.05. CONCLUSION: Statistically significant improvement in clinical findings was observed in both curcumin and lycopene treatment groups in comparison with placebo. However, the therapeutic efficacy of curcumin and lycopene was found to be almost equal in OSMF patients.


Asunto(s)
Curcumina/uso terapéutico , Licopeno/uso terapéutico , Fibrosis de la Submucosa Bucal/tratamiento farmacológico , Adolescente , Adulto , Areca , Mejilla , Femenino , Humanos , Masculino , Persona de Mediana Edad , Boca , Fumar , Tabaco sin Humo , Lengua , Adulto Joven
11.
Lasers Med Sci ; 33(8): 1739-1745, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29948450

RESUMEN

To evaluate the efficacy of laser fibrotomy in patients with oral submucous fibrosis (OSMF) and also to correlate the habit variables causing OSMF. Thirty patients diagnosed clinically and histopathologically with OSMF were included in the study. Laser fibrotomy was done under local anesthesia using Zolar diode laser (980 nm frequency) at 2-W power in contact mode with fibro-optic cutting tip. The patients were advised to practice mouth-opening exercises rigorously, and topical corticosteroid was given for burning sensation and pain for 6 months. Pre- and post-treatment comparison of mouth opening, burning sensation, tongue protrusion, and cheek flexibility was analyzed after a follow-up period of 9 months. After a follow-up period of 9 months from the surgical intervention, the mean value of difference in pre- and post-treatment of VAS score, mouth opening, and tongue protrusion was found to be 3.3 ± 2.1, 7.7 ± 5.1, 1.6 ± 2.7, and 0.38 ± 0.61 respectively. Using the Wilcoxon signed rank test, all the above difference in mean was found to be significant with p value < 0.05. With above suggested significant results, lasers can provide an alternative and better means for surgical fibrotomy, relieving trismus in moderate OSMF as they are minimally invasive, cause less hemorrhage, and have faster healing and minimal surgical site scaring and relapse.


Asunto(s)
Hábitos , Láseres de Semiconductores/uso terapéutico , Fibrosis de la Submucosa Bucal/cirugía , Adulto , Mejilla , Femenino , Estudios de Seguimiento , Humanos , Láseres de Semiconductores/efectos adversos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Resultado del Tratamiento , Escala Visual Analógica , Adulto Joven
12.
Biochemistry ; 56(3): 534-542, 2017 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-27478903

RESUMEN

Charged, solvent-exposed residues at the entrance to the substrate binding site (gatekeeper residues) produce electrostatic dipole interactions with approaching substrates, and control their access by a novel mechanism called "electrostatic gatekeeper effect". This proof-of-concept study demonstrates that the nucleotide specificity can be engineered by altering the electrostatic properties of the gatekeeper residues outside the binding site. Using Blastocystis succinyl-CoA synthetase (SCS, EC 6.2.1.5), we demonstrated that the gatekeeper mutant (ED) resulted in ATP-specific SCS to show high GTP specificity. Moreover, nucleotide binding site mutant (LF) had no effect on GTP specificity and remained ATP-specific. However, via combination of the gatekeeper mutant with the nucleotide binding site mutant (ED+LF), a complete reversal of nucleotide specificity was obtained with GTP, but no detectable activity was obtained with ATP. This striking result of the combined mutant (ED+LF) was due to two changes; negatively charged gatekeeper residues (ED) favored GTP access, and nucleotide binding site residues (LF) altered ATP binding, which was consistent with the hypothesis of the "electrostatic gatekeeper effect". These results were further supported by molecular modeling and simulation studies. Hence, it is imperative to extend the strategy of the gatekeeper effect in a different range of crucial enzymes (synthetases, kinases, and transferases) to engineer substrate specificity for various industrial applications and substrate-based drug design.


Asunto(s)
Adenosina Trifosfato/química , Blastocystis/genética , Guanosina Trifosfato/química , Ingeniería de Proteínas , Proteínas Protozoarias/química , Succinato-CoA Ligasas/química , Adenosina Trifosfato/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Blastocystis/enzimología , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Guanosina Trifosfato/metabolismo , Cinética , Simulación de Dinámica Molecular , Mutación , Unión Proteica , Estructura Secundaria de Proteína , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Electricidad Estática , Especificidad por Sustrato , Succinato-CoA Ligasas/genética , Succinato-CoA Ligasas/metabolismo , Porcinos
13.
Biochim Biophys Acta ; 1862(6): 1228-35, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26912411

RESUMEN

HIV protease inhibitors are key components of HIV antiretroviral therapies, which are fundamental in the treatment of HIV infection. However, the protease inhibitors are well-known to induce metabolic dysfunction which can in turn escalate the complications of HIV, including HIV associated neurocognitive disorders. As experimental and epidemiological data support a therapeutic role for adiponectin in both metabolic and neurologic homeostasis, this study was designed to determine if increased adiponectin could prevent the detrimental effects of protease inhibitors in mice. Adult male wild type (WT) and adiponectin-overexpressing (ADTg) mice were thus subjected to a 4-week regimen of lopinavir/ritonavir, followed by comprehensive metabolic, neurobehavioral, and neurochemical analyses. Data show that lopinavir/ritonavir-induced lipodystrophy, hypoadiponectinemia, hyperglycemia, hyperinsulinemia, and hypertriglyceridemia were attenuated in ADTg mice. Furthermore, cognitive function and blood-brain barrier integrity were preserved, while loss of cerebrovascular markers and white matter injury were prevented in ADTg mice. Finally, lopinavir/ritonavir caused significant increases in expression of markers of brain inflammation and decreases in synaptic markers in WT, but not in ADTg mice. Collectively, these data reinforce the pathophysiologic link from metabolic dysfunction to loss of cerebrovascular and cognitive homeostasis; and suggest that preservation and/or replacement of adiponectin could prevent these key aspects of HIV protease inhibitor-induced toxicity in clinical settings.


Asunto(s)
Adiponectina/metabolismo , Lesiones Encefálicas/inducido químicamente , Encéfalo/irrigación sanguínea , Inhibidores de la Proteasa del VIH/efectos adversos , Lopinavir/efectos adversos , Ritonavir/efectos adversos , Adiponectina/genética , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Cognición/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Homeostasis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Regulación hacia Arriba
14.
Biochem Biophys Res Commun ; 469(2): 306-12, 2016 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-26631965

RESUMEN

The YacK gene from Yersinia enterocolitica strain 7, cloned in pET28a vector and expressed in Escherichia coli BL21 (DE3), showed laccase activity when oxidized with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and guaiacol. The recombinant laccase protein was purified and characterized biochemically with a molecular mass of ≈58 KDa on SDS-PAGE and showed positive zymogram with ABTS. The protein was highly robust with optimum pH 9.0 and stable at 70 °C upto 12 h with residual activity of 70%. Kinetic constants, Km values, for ABTS and guaiacol were 675 µM and 2070 µM, respectively, with corresponding Vmax values of 0.125 µmol/ml/min and 6500 µmol/ml/min. It also possess antioxidative property against BSA and Cu(2+)/H2O2 model system. Constant pH MD simulation studies at different protonation states of the system showed ABTS to be most stable at acidic pH, whereas, diclofenac at neutral pH. Interestingly, aspirin drifted out of the binding pocket at acidic and neutral pH, but showed stable binding at alkaline pH. The biotransformation of diclofenac and aspirin by laccase also corroborated the in silico results. This is the first report on biotransformation of non-steroidal anti-inflammatory drugs (NSAIDs) using recombinant laccase from gut bacteria, supported by in silico simulation studies.


Asunto(s)
Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Lacasa/química , Lacasa/metabolismo , Simulación del Acoplamiento Molecular , Yersinia enterocolitica/enzimología , Sitios de Unión , Biotransformación , Simulación por Computador , Activación Enzimática , Estabilidad de Enzimas , Escherichia coli/fisiología , Lacasa/genética , Modelos Químicos , Unión Proteica , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/ultraestructura , Yersinia enterocolitica/genética
15.
Med Mycol ; 54(2): 103-10, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26483432

RESUMEN

Magnusiomyces capitatus is an emerging opportunistic yeast in the Mediterranean region. We report from Nepal one case of M. capitatus infection and six other cases of colonization/probable infection due to M. capitatus at a tertiary care center. Majority of the patients were immunocompromised, at extreme age, associated with comorbidities, and had history of close contact with livestock and poultry. The isolates were identified by phenotypic and genotypic (ITS and D1/D2 region of 26S rDNA sequence) methods. Molecular typing of the isolates was carried out by amplified fragment length polymorphism. Minimum inhibitory concentration (MIC) of the isolates for amphotericin B, caspofungin, fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, and micafungin were 2, 0.1-4, 2, 0.12-0.5, 0.12-0.5, 0.25, 1-4, and 1-4 µg/ml, respectively. Presence of M. capitatus infection was not known in Nepal, and the study should alert the clinicians and infectious disease specialists.


Asunto(s)
Micosis/epidemiología , Micosis/microbiología , Saccharomycetales/clasificación , Saccharomycetales/aislamiento & purificación , Adolescente , Anciano , Anciano de 80 o más Años , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Antifúngicos/farmacología , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Datos de Secuencia Molecular , Tipificación Molecular , Técnicas de Tipificación Micológica , Nepal/epidemiología , Filogenia , ARN Ribosómico/genética , Saccharomycetales/genética , Saccharomycetales/fisiología , Análisis de Secuencia de ADN , Centros de Atención Terciaria
16.
Med Mycol ; 54(6): 567-75, 2016 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-27118802

RESUMEN

The rare mucoraceous fungus, Apophysomyces species complex ranks second after Rhizopus arrhizus causing mucormycosis in India. The source of this agent in the environment is not clearly known. We conducted an environmental study to find its presence in Indian soil. The soil samples from different geographical locations were analyzed for isolation of Mucorales. Rhizopus arrhizus (24.6%) was most commonly isolated from soil, followed by Lichtheimia spp. (23.2%), Cunninghamella spp. (21.7%), Rhizopus microsporus (14%) and Apophysomyces spp. (4.5%). The isolation of Apophysomyces species complex was significantly associated with low nitrogen content of the soil. Based on sequencing of internal transcribed spacer (ITS) and 28S (D1/D2) regions of ribosomal DNA, the Apophysomyces isolates were identified as Apophysomyces variabilis with 98 to 100% similarity to type strain A. variabilis (CBS658.93). The analysis of amplified fragment length polymorphism (AFLP) fingerprinting data demonstrated genomic diversity of A. variabilis isolates with multiple clades (similarity 40-90%). The minimum inhibitory concentrations (MIC), MIC50 and MIC90 for A. variabilis isolates were 1 and 4 µg/ml for amphotericin B, 0.25 and 0.5 µg/ml for itraconazole, 0.125 and 0.25 µg/ml for posaconazole, 0.06 and 0.12 µg/ml for terbinafine, respectively. The present study revealed abundant presence of A. variabilis in Indian soil with low nitrogen content, its genetic heterogeneity and relatively high MICs for amphotericin B.


Asunto(s)
Mucorales/clasificación , Mucorales/aislamiento & purificación , Mucormicosis/etiología , Microbiología del Suelo , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Antifúngicos/farmacología , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Variación Genética , Genotipo , India , Pruebas de Sensibilidad Microbiana , Mucorales/efectos de los fármacos , Mucorales/genética , Nitrógeno/análisis , Filogenia , ARN Ribosómico 28S/genética , Análisis de Secuencia de ADN , Suelo/química
19.
Mycoses ; 59(3): 186-93, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26691935

RESUMEN

In this case, the authors report Chaetomium globosum as a cause of invasive pulmonary infection in a patient with Wegener's granulomatosis. Fungal hyphae (KOH and Calcofluor) were seen on direct microscopy of lung biopsy sample and bronchoalveolar lavage (BAL) sample. C. globosum isolated on culture clinched the diagnosis of invasive pulmonary infection by Chaetomium spp. A positive galactomannan of serum and BAL was repeatedly seen and was utilised for follow-up and as prognostic marker in patient management. The patient was successfully treated with liposomal amphotericin B followed by voriconazole. All the Chaetomium infections reported till date since 1980 are reviewed. Chaetomium spp. with its unique ecology has a hidden clinical potential to cause invasive mould infections.


Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Chaetomium , Granulomatosis con Poliangitis/complicaciones , Enfermedades Pulmonares Fúngicas/microbiología , Mananos/análisis , Chaetomium/clasificación , Chaetomium/crecimiento & desarrollo , Chaetomium/aislamiento & purificación , Reacciones Falso Positivas , Femenino , Galactosa/análogos & derivados , Humanos , Pulmón/microbiología , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Mananos/sangre , Persona de Mediana Edad , Senos Paranasales/cirugía , Sinusitis/complicaciones , Sinusitis/diagnóstico , Sinusitis/cirugía
20.
Mycoses ; 59(2): 127-32, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26647904

RESUMEN

We report here the first case of disseminated Emmonsia pasteuriana infection in a patient with AIDS in India. The patient presented with weight loss, dyspnoea, left-sided chest pain and multiple non-tender skin lesions over face and body for 3 months. Disseminated emmonsiosis was diagnosed on microscopic examination and fungal culture of skin biopsy and needle aspirate of lung consolidation. It was confirmed by sequencing internal transcribed spacer region of rDNA, beta tubulin, actin, and intein PRP8. The patient responded to amphotericin B and itraconazole therapy.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Chrysosporium/aislamiento & purificación , Micosis/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Biopsia con Aguja , Dolor en el Pecho/microbiología , Chrysosporium/clasificación , Chrysosporium/genética , ADN de Hongos/aislamiento & purificación , ADN Ribosómico/aislamiento & purificación , Errores Diagnósticos , Disnea/microbiología , Femenino , Humanos , India/epidemiología , Itraconazol/uso terapéutico , Micosis/tratamiento farmacológico , Micosis/microbiología , Filogenia , Pérdida de Peso
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