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1.
Environ Microbiol ; 24(6): 2797-2816, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34347343

RESUMEN

Pseudomonas sp. CSV86, an Indian soil isolate, degrades wide range of aromatic compounds like naphthalene, benzoate and phenylpropanoids, amongst others. Isolate displays the unique and novel property of preferential utilization of aromatics over glucose and co-metabolizes them with organic acids. Interestingly, as compared to other Pseudomonads, strain CSV86 harbours only high-affinity glucokinase pathway (and absence of low-affinity oxidative route) for glucose metabolism. Such lack of gluconate loop might be responsible for the novel phenotype of preferential utilization of aromatics. The genome analysis and comparative functional mining indicated a large genome (6.79 Mb) with significant enrichment of regulators, transporters as well as presence of various secondary metabolite production clusters, suggesting its eco-physiological and metabolic versatility. Strain harbours various integrative conjugative elements (ICEs) and genomic islands, probably acquired through horizontal gene transfer events, leading to genome mosaicity and plasticity. Naphthalene degradation genes are arranged as regulonic clusters and found to be part of ICECSV86nah . Various eco-physiological properties and absence of major pathogenicity and virulence factors (risk group-1) in CSV86 suggest it to be an ideal candidate for bioremediation. Further, strain can serve as an ideal chassis for metabolic engineering to degrade various xenobiotics preferentially over simple carbon sources for efficient remediation.


Asunto(s)
Pseudomonas putida , Pseudomonas , Biodegradación Ambiental , Ingeniería Metabólica , Naftalenos/metabolismo , Pseudomonas/genética , Pseudomonas/metabolismo , Pseudomonas putida/genética
2.
Natl Med J India ; 35(4): 201-205, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36715043

RESUMEN

Background Most individuals with Covid-19 infection develop antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the dynamics of these antibodies is variable and not well-studied. We aimed to determine the titres of naturally acquired antibodies over a 12-week follow-up. Methods We recruited healthcare workers who had tested positive on a specific quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for SARS-CoV-2, and then tested for the presence of immunoglobulin G (IgG) antibody against the same virus at baseline and again at 6 and 12 weeks. The antibody titre was determined by a semi-quantitative assay based on signal/cut-off ratio. Healthcare workers with antibody positivity were divided into those with high titre (ratio ≥12) and low titre (<12). Their demographic details and risk factors were surveyed through a Google form and analysed in relation to the antibody titres at three time-points. Results Of the 286 healthcare workers, 10.48% had high antibody titres. Healthcare workers who had tested positive by qRT-PCR and those who had received the Bacille Calmette-Guérin (BCG) vaccination or other immune-boosters had a higher frequency of high antibody titres. While there was a significant decline in antibody titres at 6 and 12 weeks, 87.46% of individuals positive for IgG antibody persisted to have the antibody even at 12 weeks. Conclusion Healthcare workers who tested positive for SARS-CoV-2 on qRT-PCR had a high positivity for the specific antibody, which continued to express in them even at 12 weeks. Further follow-up is likely to enhance our understanding of antibody kinetics following SARS-CoV-2 infection.


Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios Longitudinales , SARS-CoV-2 , Personal de Salud , Factores de Riesgo , Anticuerpos Antivirales
3.
Adv Appl Microbiol ; 112: 1-65, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32762865

RESUMEN

As a result of anthropogenic activity, large number of recalcitrant aromatic compounds have been released into the environment. Consequently, microbial communities have adapted and evolved to utilize these compounds as sole carbon source, under both aerobic and anaerobic conditions. The constitutive expression of enzymes necessary for metabolism imposes a heavy energy load on the microbe which is overcome by arrangement of degradative genes as operons which are induced by specific inducers. The segmentation of pathways into upper, middle and/or lower operons has allowed microbes to funnel multiple compounds into common key aromatic intermediates which are further metabolized through central carbon pathway. Various proteins belonging to diverse families have evolved to regulate the transcription of individual operons participating in aromatic catabolism. These proteins, complemented with global regulatory mechanisms, carry out the regulation of aromatic compound metabolic pathways in a concerted manner. Additionally, characteristics like chemotaxis, preferential utilization, pathway compartmentalization and biosurfactant production confer an advantage to the microbe, thus making bioremediation of the aromatic pollutants more efficient and effective.


Asunto(s)
Bacterias/metabolismo , Regulación Bacteriana de la Expresión Génica , Hidrocarburos Aromáticos/metabolismo , Redes y Vías Metabólicas/fisiología , Bacterias/clasificación , Bacterias/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biodegradación Ambiental , Evolución Biológica , Carbono/metabolismo , Compartimento Celular , Quimiotaxis , Variación Genética , Hidrocarburos Aromáticos/química , Redes y Vías Metabólicas/genética , Tensoactivos/metabolismo
4.
Nature ; 507(7491): 238-42, 2014 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-24487620

RESUMEN

Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.


Asunto(s)
Proteína Relacionada con Agouti/metabolismo , Hambre/fisiología , Vías Nerviosas/fisiología , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/fisiología , Proteína Relacionada con Agouti/deficiencia , Animales , Apetito/efectos de los fármacos , Apetito/fisiología , Núcleo Arqueado del Hipotálamo/citología , Núcleo Arqueado del Hipotálamo/metabolismo , Mapeo Encefálico , Rastreo Celular , Clozapina/análogos & derivados , Clozapina/farmacología , Dependovirus/genética , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Femenino , Privación de Alimentos , Hambre/efectos de los fármacos , Integrasas/metabolismo , Masculino , Ratones , Vías Nerviosas/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Neuronas/efectos de los fármacos , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/metabolismo , Núcleo Hipotalámico Paraventricular/citología , Fragmentos de Péptidos/deficiencia , Fragmentos de Péptidos/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Virus de la Rabia/genética , Respuesta de Saciedad/fisiología , Hormona Liberadora de Tirotropina/metabolismo
5.
J Assoc Physicians India ; 68(11): 14-19, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33187030

RESUMEN

BACKGROUND: Seroprevalence studies for COVID-19 evaluate the extent of undetected transmission in a defined community, with special significance among health care workers (HCW) owing to their greater exposure and potential to transmit. METHODS: A total of 1122 HCW (approximately 25% of the employees) of a large tertiary care hospital in India were recruited for this cross-sectional study. COVID PCR-positive HCW were excluded. Based on their risk-assessment, participants were grouped into three categories. A questionnaire was administered and they were tested for SARS-CoV-2-IgG antibodies using the chemiluminescence. RESULTS: The overall seroprevalence among workers was 11.94%, which included 19.85% in COVID units, 11.09% in non-COVID units, and 8% in administrative workers (p=0.007). Antibody prevalence was highest in the department of gastroenterology (11.94%), followed by oncology (10.53%), pathology (10.26%), emergency medicine (7.84%) and critical care medicine (7%). Housekeeping staff, food and beverage staff, lab assistants and technicians had higher seroprevalence rate than doctors and nurses (p < 0.0001). HCW with a history of BCG vaccination in childhood and those who received an adequate prophylactic dose of hydroxychloroquine (HCQ) had a lower seroprevalence as compared to those who did not (7.31% vs. 16.8% and 1.30% vs. 11.25% respectively). CONCLUSION: BCG vaccination, HCQ prophylaxis, and the job profile influence the seroprevalence rate in HCW. Seroprevalence rate and follow-up evaluation of its durability may help hospitals to triage their staff at risk, rationalize their placement, prioritize the use of PPE, thereby potentially reducing the risk.


Asunto(s)
Infecciones por Coronavirus , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Niño , Estudios Transversales , Personal de Salud , Humanos , India/epidemiología , SARS-CoV-2 , Estudios Seroepidemiológicos , Centros de Atención Terciaria
6.
J Urol ; 202(2): 406-412, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30840542

RESUMEN

PURPOSE: We determined the safety and efficacy of intraoperative magnetic resonance imaging guided surgical reconstruction of bladder exstrophy for the identification of the urogenital diaphragm fibers and the thickened muscular attachments between the posterior urethra, bladder plate and pubic rami. MATERIALS AND METHODS: Institutional review board and U.S. Food and Drug Administration approval was obtained for the use of Brainlab (Munich, Germany) intraoperative magnetic resonance imaging guided navigation of the pelvic floor anatomy during closure of classic bladder exstrophy and cloacal exstrophy at our institution. Preoperative pelvic 3-dimensional magnetic resonance imaging was obtained 1 day before closure in patients undergoing pelvic osteotomies. Intraoperative registration was performed after preoperative planning with a pediatric radiologist using 5 anatomical landmarks immediately before initiation of surgery. Accuracy of pelvic anatomy identification was assessed by 2 pediatric urological surgeons and 1 pediatric radiologist. RESULTS: In 43 patients with classic bladder exstrophy and 4 patients with cloacal exstrophy closed at our institution, Brainlab technology was used successfully to navigate and guide the dissection of the pelvic floor intraoperatively. In all patients there was 100% accuracy in the correlation of gross anatomical landmarks with 3-dimensional magnetic resonance imaging identified landmarks intraoperatively, and all patients had successful closure without any major complications. CONCLUSIONS: Brainlab intraoperative 3-dimensional magnetic resonance imaging guided pelvic floor navigation and dissection is an effective way to accurately identify pelvic anatomy during classic bladder exstrophy and cloacal exstrophy closure. This technology offers a unique opportunity for surgical skill education in this complex reconstructive operation.


Asunto(s)
Extrofia de la Vejiga/diagnóstico por imagen , Extrofia de la Vejiga/cirugía , Imagenología Tridimensional , Imagen por Resonancia Magnética , Diafragma Pélvico/diagnóstico por imagen , Diafragma Pélvico/cirugía , Cirugía Asistida por Computador , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos/efectos adversos , Procedimientos Quirúrgicos Urológicos/métodos
7.
J Sex Med ; 16(2): 333-337, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30692027

RESUMEN

INTRODUCTION: Many men suffering from erectile dysfunction are overweight with generous suprapubic fat pads, which often contribute to a decrease in visible exophytic phallic length. AIM: To present a novel surgical concept of suprapubic fat pad excision with a concomitant placement of inflatable penile prosthesis. METHODS: A transverse incision begins slightly medial to the anterior superior iliac spine, with the superior edge crossing transversely to the contralateral anterior superior iliac spine. The inferior border is incised in a curvilinear fashion, with the medial apex being approximately 1 cm above the base of the penis. Dissection is carried down to the lower abdominal anterior fascia, which leads to excision of the suprapubic fat pad. Using this same exposure, the inflatable penile prosthesis (IPP) is placed via an infrapubic approach. The wound is reapproximated in multiple layers, and 2 drains are placed, 1 subcutaneous in the area of the fat pad excision and the other in the scrotum around the pump. MAIN OUTCOME MEASURES: Primary outcomes included penile implant functionality, ability to engage in sexual activity, and cosmetic satisfaction. RESULTS: A total of 8 patients have undergone suprapubic fat pad excision with simultaneous placement of IPP at our institution. Average body mass index of our patient cohort was 36.6. 1 patient developed prosthetic infection after inadvertent removal of his drains in the immediate postoperative period. At last follow-up, all other patients have excellent cosmetic and functional outcomes. CLINICAL IMPLICATIONS: This technique can lead to higher patient satisfaction with their penile implant, enhanced sexual performance, and improved quality of life for patients with concurrent erectile dysfunction and significant suprapubic fat pad. STRENGTHS & LIMITATIONS: This unique technique has never been previously described. It allows placement of IPP in the setting of fat pad excision without any additional incisions. Limitations include the small patient population and relatively short follow-up. CONCLUSIONS: Suprapubic fat pad excision is a safe and reproducible technique that can be performed simultaneously with the placement of an IPP in appropriately selected patients. Patients must be counseled appropriately on the expectations of surgeries and the theoretical increased risk of postoperative complications, such as infection. Baumgarten AS, Beilan JA, Shah BB, et al. Suprapubic Fat Pad Excision with Simultaneous Placement of Inflatable Penile Prosthesis J Sex Med 2019;16:333-337.


Asunto(s)
Tejido Adiposo/cirugía , Disfunción Eréctil/cirugía , Prótesis de Pene , Pene/cirugía , Humanos , Masculino , Persona de Mediana Edad , Implantación de Pene , Complicaciones Posoperatorias , Diseño de Prótesis , Hueso Púbico , Calidad de Vida , Resultado del Tratamiento
8.
Molecules ; 24(10)2019 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-31100979

RESUMEN

In this work we summarize our understanding of melanocortin 4 receptor (MC4R) pathway activation, aiming to define a safe and effective therapeutic targeting strategy for the MC4R. Delineation of cellular MC4R pathways has provided evidence for distinct MC4R signaling events characterized by unique receptor activation kinetics. While these studies remain narrow in scope, and have largely been explored with peptidic agonists, the results provide a possible correlation between distinct ligand groups and differential MC4R activation kinetics. In addition, when a set of small-molecule and peptide MC4R agonists are compared, evidence of biased signaling has been reported. The results of such mechanistic studies are discussed.


Asunto(s)
Péptidos/farmacocinética , Receptor de Melanocortina Tipo 4/agonistas , Receptor de Melanocortina Tipo 4/metabolismo , Transducción de Señal , Animales , Peso Corporal , Sistema Cardiovascular/efectos de los fármacos , AMP Cíclico/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Humanos , Cinética , Ligandos , Péptidos/química , Péptidos/farmacología , Primates , Unión Proteica , Transporte de Proteínas , Roedores , Transducción de Señal/efectos de los fármacos , alfa-MSH/análogos & derivados , alfa-MSH/farmacología
11.
J Sex Med ; 14(7): 870-875, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28546066

RESUMEN

BACKGROUND: Infra-pubic placement of an inflatable penile prosthesis (IPP) has a well-known configuration deformity from contralateral tubing that crosses the corporal bodies, resulting in tubing visibility and irritation under the penile skin. AIM: To present a novel step to eliminate this tubing crossover deformity. METHODS: The V-neck technique was applied to five patients, two of whom underwent suprapubic fat pad excision with simultaneous infra-pubic IPP placement and three patients who underwent only infra-pubic IPP placement. The technique added an additional 1 minute of procedure time. The reservoir was placed on one (ipsilateral) side into the space of Retzius. OUTCOMES: Primary outcome measurements were esthetic appeal at follow-up, immediate postoperative complications, and difficulty of implementation of the technique. RESULTS: The technique included the following steps. (i) The standard infra-pubic approach, as popularized by Perito (J Sex Med 2008;5:27-30), was used to place the reservoir and cylinders. The ipsilateral and contralateral cylinders and the reservoir were clamped and unconnected. (ii) Finger dissection was used to create a sub-phallic window and a U-shaped aortic clamp was used to pass the contralateral tubing. (iii) After passing the green tubing through the window, all connections were performed in the usual fashion. Tubing crossover was eliminated, as was passage of the right and left cylinder tubes down their respective gutters. Postoperative follow-up at 2 weeks showed no visible tubing. CLINICAL IMPLICATIONS: This simple maneuver could help prevent the discomfort of tubing crossover deformity commonly seen after infra-pubic placement of an IPP. STRENGTHS AND LIMITATIONS: This unique maneuver can be applied to all infra-pubically placed IPPs. Limitations include the small patient population and short follow-up. Whether this maneuver will make revision surgery more difficult is unclear. CONCLUSION: This technique is a novel step to infra-pubic IPP placement that adds minimal operative time and could eliminate visible tubing. Shah BB, Baumgarten AS, Morgan K, et al. V-Neck Technique: A Novel Improvement to the Infra-Pubic Placement of an Inflatable Penile Implant. J Sex Med 2017;14:870-875.


Asunto(s)
Enfermedades del Pene/cirugía , Implantación de Pene/métodos , Pene/cirugía , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Implantación de Pene/instrumentación , Prótesis de Pene , Pene/anomalías , Reoperación
12.
Proc Natl Acad Sci U S A ; 111(36): 13193-8, 2014 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-25157144

RESUMEN

Activation of melanocortin-4 receptors (MC4Rs) restrains feeding and prevents obesity; however, the identity, location, and axonal projections of the neurons bearing MC4Rs that control feeding remain unknown. Reexpression of MC4Rs on single-minded 1 (SIM1)(+) neurons in mice otherwise lacking MC4Rs is sufficient to abolish hyperphagia. Thus, MC4Rs on SIM1(+) neurons, possibly in the paraventricular hypothalamus (PVH) and/or amygdala, regulate food intake. It is unknown, however, whether they are also necessary, a distinction required for excluding redundant sites of action. Hence, the location and nature of obesity-preventing MC4R-expressing neurons are unknown. Here, by deleting and reexpressing MC4Rs from cre-expressing neurons, establishing both necessity and sufficiency, we demonstrate that the MC4R-expressing neurons regulating feeding are SIM1(+), located in the PVH, glutamatergic and not GABAergic, and do not express oxytocin, corticotropin-releasing hormone, vasopressin, or prodynorphin. Importantly, these excitatory MC4R-expressing PVH neurons are synaptically connected to neurons in the parabrachial nucleus, which relays visceral information to the forebrain. This suggests a basis for the feeding-regulating effects of MC4Rs.


Asunto(s)
Conducta Alimentaria , Glutamatos/metabolismo , Neuronas/metabolismo , Núcleos Parabraquiales/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Receptor de Melanocortina Tipo 4/metabolismo , Sinapsis/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Peso Corporal , Dependovirus/metabolismo , Metabolismo Energético , Neuronas GABAérgicas/metabolismo , Eliminación de Gen , Inyecciones , Integrasas/metabolismo , Ratones , Neuropéptidos/metabolismo , Proteínas Represoras/metabolismo , Reproducibilidad de los Resultados , Técnicas Estereotáxicas , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo
13.
Catheter Cardiovasc Interv ; 88(3): E99-E102, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24510603

RESUMEN

Intra-aortic balloon pump (IABP) is used in cardiogenic shock of different etiologies. Routinely, it is inserted through the transfemoral access, but in the patients with severe peripheral artery obstruction disease (PAOD), use of alternative approach is needed. In this case report, IABP insertion through the right subclavian artery with the help of cardiothoracic surgeon in a patient of anterior wall myocardial infarction (AWMI) with severe PAOD has been described. A 60-years-old male patient, with the history of chronic smoking, presented with progressing chest pain for last 3 days. On the basis of clinical examination and radiological findings, he was diagnosed with AWMI along with the ventricular septal rupture and PAOD. The patient was advised to undergo coronary artery bypass graft with VSR repair, but to stabilize the patient, it was necessary to put him on IABP. Because of the severe PAOD, femoral access was not suitable to insert the IABP, and hence, the right subclavian route was accessed. Then, the patient was operated and no other complications were encountered. Subclavian arterial IABP insertion under local anesthesia is easier and safer to perform and allows increased patient mobility. Other routes, such as, ascending aorta and axillary artery have also been discussed in other literatures, but subclavian arterial IABP insertion was found to be the best in the patients with severe PAOD. Trans-subclavian route is an effective approach in extended IABP utilization even in patients with severe PAOD. © 2014 Wiley Periodicals, Inc.


Asunto(s)
Infarto de la Pared Anterior del Miocardio/terapia , Contrapulsador Intraaórtico/métodos , Enfermedad Arterial Periférica/complicaciones , Arteria Subclavia , Rotura Septal Ventricular/terapia , Infarto de la Pared Anterior del Miocardio/complicaciones , Infarto de la Pared Anterior del Miocardio/diagnóstico por imagen , Infarto de la Pared Anterior del Miocardio/fisiopatología , Angiografía Coronaria , Puente de Arteria Coronaria , Hemodinámica , Humanos , Contrapulsador Intraaórtico/instrumentación , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Índice de Severidad de la Enfermedad , Arteria Subclavia/diagnóstico por imagen , Resultado del Tratamiento , Rotura Septal Ventricular/diagnóstico por imagen , Rotura Septal Ventricular/etiología , Rotura Septal Ventricular/fisiopatología
14.
Ann Pharmacother ; 50(11): 942-952, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27465879

RESUMEN

OBJECTIVE: To review the pharmacology, efficacy, safety, and place in therapy for tenofovir alafenamide (TAF). DATA SOURCES: A search using PubMed was conducted (2004 to May 2016) using the following keywords: tenofovir alafenamide, TAF, and GS-7340. Articles were evaluated for content, and bibliographies were reviewed. Data available exclusively as abstracts from major infectious diseases and HIV conferences were also evaluated for inclusion. STUDY SELECTION AND DATA EXTRACTION: Studies included were in vitro investigations; phase I, II, and III clinical trials; and pharmacokinetic and pharmacodynamic evaluations. DATA SYNTHESIS: Similar to tenofovir disoproxil fumarate (TDF), TAF is a prodrug of tenofovir but results in significantly higher intracellular tenofovir concentrations and lower serum levels. As a result, TAF is expected to have efficacy similar to that of TDF while reducing tenofovir-associated nephrotoxicity and bone mineral density losses. Clinical trials evaluating the safety and efficacy of TAF-containing antiretroviral regimens have confirmed these expectations, consistently demonstrating similar virological suppression compared with TDF-containing regimens as well as significant improvements in markers of kidney function and bone health. Three combination products containing TAF were approved by the United States Food and Drug Administration for the management of HIV-1 infection. The first of these was a single tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF which is now a recommended regimen in clinical practice guidelines for initial treatment in antiretroviral-naïve patients. CONCLUSIONS: TAF is a novel nucleotide reverse transcriptase inhibitor for the treatment of HIV-1 infection that has efficacy similar to that of TDF and improved safety compared with TDF.


Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Adenina/uso terapéutico , Adulto , Alanina , Densidad Ósea/efectos de los fármacos , Femenino , VIH-1/efectos de los fármacos , Humanos , Profármacos/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Comprimidos , Tenofovir/análogos & derivados
15.
Pharm Dev Technol ; 19(7): 868-80, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24079361

RESUMEN

Butorphanol is potent analgesic useful in pain management. However, because of high first-pass metabolism butorphanol is not available in market as oral dosage form. Drugs that undergo extensive first-pass metabolism can be delivered orally if protected in the stomach, and proximal small intestine. An oral controlled porosity osmotic pump (CPOP) was designed to deliver butorphanol tartrate that can maintain therapeutic blood concentration up to 24 h. The target release profile for extended release formulation was calculated by Wagner Nelson de-convolution using published immediate release blood concentration data for oral route. Composition of the core and coating were optimized using USFDA approved ingredients by evaluation of the drug release. Drug release from the developed system was inversely proportional to the weight gain and directly related to the level of pore former. Scanning electron microscopy (SEM) confirmed the formation of pores in the coating membrane on contact with water which lead to drug to release. Kinetic models were applied to drug release data to establish the drug release mechanism. The developed osmotic system effectively delivers selected drug at a predetermined rate for extended period.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Butorfanol/administración & dosificación , Preparaciones de Acción Retardada/química , Administración Oral , Analgésicos Opioides/sangre , Butorfanol/sangre , Humanos , Presión Osmótica , Porosidad , Solubilidad
16.
BMJ Case Rep ; 17(2)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38331445

RESUMEN

A South Asian male in his early 60s presented with acute-onset dyspnoea on postoperative day 4 after undergoing middle hepatic vein sacrificing partial liver resection for epithelioid angiomyolipoma. The patient's SpO2 on presentation was 65% in standing position which improved to 90% in left lateral decubitus. He was suspected of having platypnea-orthodeoxia syndrome (POS) which was confirmed on echocardiogram with microbubble contrast showing a large intracardiac right-to-left shunt. The patient was taken up for transcatheter closure of patent foramen ovale (PFO). A 30 mm Amplatzer PFO Occluder was deployed across the PFO which reduced the intracardiac shunt resulting in an improved arterial saturation as well as immediate relief of patient's symptoms. This case illustrates the importance of suspecting and recognising POS clinically as well as the efficacy of transcatheter closure of PFO in such cases leading to resolution of hypoxaemia in a short span of time.


Asunto(s)
Foramen Oval Permeable , Dispositivo Oclusor Septal , Humanos , Masculino , Persona de Mediana Edad , Disnea/diagnóstico , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/diagnóstico por imagen , Foramen Oval Permeable/cirugía , Hipoxia/etiología , Hipoxia/terapia , Hipoxia/diagnóstico , Hígado , Síndrome de Platipnea Ortodesoxia
17.
Indian Heart J ; 76(1): 57-59, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38199561

RESUMEN

This single-center, prospective, observational study was conducted at a tertiary-care center over a span of two years. Patients presenting with acute Anterior-Wall STEMI were included as a study population. The subgroups included qRBBB pattern on ECG and non-qRBBB group. Among 1128 patients included in the study, 100 (11.28 %) patients presented with qRBBB pattern. Increased risk of cardiogenic shock, increased hospital-stay, a higher Killip class on presentation, high incidence of recanalized IRA, remarkably depressed LVEF were significantly associated with qRBBB-MI, which is a menacing form of ACS that leads not only to a high mortality but also to a long-term morbidity.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Estudios Prospectivos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/complicaciones , Choque Cardiogénico/etiología , Tiempo de Internación , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/complicaciones , Mortalidad Hospitalaria , Factores de Riesgo , Intervención Coronaria Percutánea/efectos adversos
18.
J Bone Miner Res ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38590263

RESUMEN

Achondroplasia, the most common form of disproportionate short stature, is caused by gain-of-function point mutations in fibroblast growth factor receptor 3 (FGFR3). Abnormally elevated activation of FGFR3 modulates chondrocyte proliferation and differentiation via multiple signaling pathways, such as the MAPK pathway. Using a mouse model mimicking achondroplasia (Fgfr3Y367C/+), we have previously shown that daily treatment with infigratinib (BGJ398), a selective and orally bioavailable FGFR1-3 inhibitor, at a dose of 2 mg/kg, significantly increased bone growth. In this study, we investigated the activity of infigratinib administered at substantially lower doses (0.2 and 0.5 mg/kg, given once daily) and using an intermittent dosing regimen (1 mg/kg every 3 days). Following a 15-day treatment period, these low dosages were sufficient to observe significant improvement of clinical hallmarks of achondroplasia such as growth of the axial and appendicular skeleton and skull development. Immunohistological labeling demonstrated the positive impact of infigratinib on chondrocyte differentiation in the cartilage growth plate and the cartilage end plate of the vertebrae. Macroscopic and microcomputed analyses showed enlargement of the foramen magnum area at the skull base, thus improving foramen magnum stenosis, a well-recognized complication in achondroplasia. No changes in FGF23 or phosphorus levels were observed, indicating that the treatment did not modify phosphate homeostasis. This proof-of-concept study demonstrates that infigratinib administered at low doses has the potential to be a safe and effective therapeutic option for children with achondroplasia.

19.
Ther Adv Urol ; 16: 17562872241241858, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38571490

RESUMEN

Background: The increasing popularity of the silicone sleeve penile implant has been accompanied by concerns over potential risks and adverse events. Objectives: To provide multi-institutional data on safety outcomes in patients undergoing silicone sleeve penile implant surgery across high-volume implant surgeons. In addition, we discuss preventative techniques to minimize postoperative complications and the management of these events. Design and methods: We performed a retrospective analysis of men undergoing penile silicone sleeve implants between November 2020 and November 2022 with four surgeons, each from a separate institution. Perioperative and postoperative adverse events, including unsatisfactory cosmetic outcomes requiring revision, were determined by physician follow-up. Flaccid penile length and girth were measured preoperatively and postoperatively. Results: A total of 299 male patients underwent silicone sleeve implant surgery, with an average age of 42.5 ± 10.5 years and an average body mass index of 28.5 ± 4.0. The patient cohort exhibited minimal comorbidities, with 5% having hyperlipidemia, 2% being smokers, 2% having cardiovascular disease, and 1% having diabetes. Patients experienced an average increase of 4.1 ± 1.5 cm in their flaccid penile length (a 50% increase) and an average increase of 3.4 ± 1.5 cm in their flaccid girth (a 37% increase) (p < 0.01). Complication rates included new-onset postoperative erectile dysfunction (0%), infection (1.3%), seroma (2.0%), and erosion (5.0%). The average follow-up time was 11.6 months. Notably, our rates of infection and seroma were lower than those reported in a previous single-center review, while erosion rates were higher. Conclusion: This is the largest study to characterize the safety of the penile silicone sleeve implant across multiple institutions. In men who desire cosmetic size augmentation, silicone sleeve implant surgery is associated with significantly increased flaccid penile length and girth. Complications are mainly cosmetic and may be corrected; however, patients should be appropriately counseled on the risk of erosion, which appears to be higher than previously reported.


Outcomes for penile silicone sleeve surgery This is the largest study to characterize the safety of the penile silicone sleeve implant across multiple institutions. In men who desire cosmetic penile size improvement, the silicone sleeve implant surgery is associated with significantly increased flaccid penile length and girth. Complications are mainly cosmetic and may be corrected, however, patients should be appropriately counseled on the risk of erosion, which appears to be higher than previously reported.

20.
Curr Urol Rep ; 14(4): 359-65, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23686356

RESUMEN

The exstrophy-epispadias complex is a rare congenital malformation of the genitourinary system, abdominal wall musculature, and pelvic bones. Historically, surgical outcomes in patients with classic bladder exstrophy, the most common presentation of the exstrophy-epispadias complex, were poor. However, modern techniques have increased the success of achieving urinary continence, satisfactory cosmesis, and improved quality of life. Still, recent studies recognize complications that may occur during management of these patients. This review provides readers with an overview of the exstrophy-epispadias complex, the modern management of bladder exstrophy, and potential surgical complications.


Asunto(s)
Extrofia de la Vejiga/cirugía , Epispadias/cirugía , Extrofia de la Vejiga/complicaciones , Epispadias/complicaciones , Humanos , Procedimientos de Cirugía Plástica
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