RESUMEN
Plumbagin and other naphthoquinone derivatives from the Plumbago zeylanica L. (Plumbaginaceae) are known for their anticancer and other medicinal properties. Previous reports suggest that 3-methyl-1,8-naphthalene-diol is an intermediate of the plumbagin biosynthetic pathway and is synthesized from hexaketide backbone; a reaction catalyzed by type III polyketide synthase (PKS) along with certain accessory enzymes. Our earlier transcriptomic and metabolomic studies suggest that along with PKS, putative cyclase and aldo-keto reductase might be involved in the formation of 3-methyl-1,8-naphthalene-diol. The present study probed young leaf transcriptome and identified cyclase and aldo-keto reductase like transcripts that might be involved in the intramolecular aldol condensation of hexaketide intermediate and decarboxylation, carbonyl reduction and hydroxyl elimination of keto or enol forms of hexaketide intermediates respectively. Moreover, sequence alignment of identified cyclase1 possesses signature ß-α-ß-ß-α-α-ß topology, which belongs to the dimeric α + ß barrel (DABB) protein family and is involved in the C2-C11 and C4-C9 intramolecular aldol condensation of hexaketide intermediates. Along with cyclase1, we further identified and characterized P. zeylanica specific aldo-keto reductase1 (AKR1) which is a novel member of the aldo-keto reductase (AKR) multi-gene family that possesses the conserved Asp60, Tyr65, Lys91, and His132 residues and is proposed to be involved in the C1 decarboxylation, C3 carbonyl reduction and C7 hydroxyl elimination of keto or enol form of hexaketide intermediate to form 3-methyl-1,8-naphthalene-diol. Further, the functional characterization using the artificial microRNA mediated transient silencing approach confirmed the involvement of cyclase1 and AKR1 in the plumbagin biosynthetic pathway. This is the first study reporting the identification and functional characterization of cyclase1 and AKR1 genes involved in the plumbagin biosynthetic pathway and general plant polyketide biosynthesis.
Asunto(s)
MicroARNs , Naftoquinonas , Aldo-Ceto Reductasas/genética , Aldo-Ceto Reductasas/química , Aldo-Ceto Reductasas/metabolismo , MicroARNs/metabolismo , Vías Biosintéticas/genéticaRESUMEN
The tuberculin skin test, used to detect latent systemic tuberculosis (TB), has its limitations. The utility of interferon-gamma assays, found useful in the diagnosis of latent TB, is still unestablished in tubercular uveitis. We present the results of QuantiFERON(®)-TB Gold (QFT-G) test and its relevance in the diagnosis and management of suspected tubercular uveitis in India. All suspected tubercular uveitis patients seen at our uveitis clinic between October 2006 and June 2008 who underwent relevant blood investigations, chest X-rays, Mantoux tests and QFT-G tests were included. Clinical profile, systemic correlation and outcome with treatment were analysed. Fifty suspected tubercular uveitis patients underwent QFT-G testing. The age range of the patients was 6-55 years (mean 32.66 years). Seven patients presented with active and three with a past history of systemic TB. The QFT-G test was positive in 29 patients. Radiological findings of TB were seen in four patients with a positive QFT-G and one patient with a negative QFT-G test. In 11 patients both QFT-G and Mantoux tests were positive. Eighteen Mantoux-negative patients were QFT-G-positive. Significantly, no patient with a positive Mantoux had a negative QFT-G test. Of the 32 patients with posterior uveitis, 17 patients had serpiginous choroiditis, four patients had a choroidal granuloma, six patients had multifocal choroiditis, four patients had retinal vasculitis, and one patient had a subretinal abscess. All QFT-G-positive patients were treated with anti-tuberculosis therapy as well as systemic steroids with a favorable clinical outcome. Our study shows that the QFT-G test is very useful in the diagnosis and management of suspected ocular TB. It was found to be very sensitive in identifying latent TB patients who, upon treatment, had a significantly reduced frequency of recurrences. It was more sensitive than the Mantoux test and is not significantly affected by previous treatment with systemic steroids or immunosuppressives. A negative QFT-G test can also be used as an adjunct before initiation of systemic steroids or immunosuppressives in uveitic patients particularly in an endemic setting like India.
Asunto(s)
Técnicas de Diagnóstico Oftalmológico , Interferón gamma/sangre , Tuberculosis Ocular/diagnóstico , Uveítis/diagnóstico , Adolescente , Adulto , Antituberculosos/uso terapéutico , Niño , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Humanos , India , Masculino , Persona de Mediana Edad , Radiografía Torácica , Prueba de Tuberculina , Tuberculosis Ocular/sangre , Tuberculosis Ocular/tratamiento farmacológico , Tuberculosis Pulmonar/diagnóstico por imagen , Uveítis/sangre , Uveítis/tratamiento farmacológico , Adulto JovenRESUMEN
STUDY DESIGN: A prospective, criterion-based validity study. OBJECTIVES: To assess the diagnostic properties of the carpal compression test (CCT) when performed with the Durkan carpal tunnel syndrome (CTS) gauge, and to determine the measurement validity of the gauge. BACKGROUND: The CCT has been reported to be highly sensitive (.87-.89) and specific (.93-1.0) in the diagnosis of CTS when it is done with thumb pressure. The accuracy of measurements with the Durkan CTS gauge, however, has not been established and the diagnostic sensitivity and specificity of the CCT when the gauge is used has not been independently confirmed. METHODS AND MEASURES: The study sample included 33 women and 19 men, aged 18 to 85 years (45.7 +/- 13.5 years). The accuracy of the gauge was determined with a force dynamometer and holding frame. Standard nerve conduction studies (NCS) and the CCT were performed on the symptomatic extremity of all subjects. A compatible history and the NCS results were used to confirm CTS. RESULTS: The Durkan gauge registered pressures of 11.94 psi and 15.25 psi at the 12 and 15 psi gauge marks, respectively. Test sensitivity and specificity were .36 (95% CI = .17-.54) and .57 (95% CI = .39-.74), respectively. CONCLUSIONS: Pressure measurements obtained with the Durkan CTS gauge were accurate. The CCT when performed with the Durkan gauge, however, was neither sensitive or specific for the diagnosis of CTS.
Asunto(s)
Síndrome del Túnel Carpiano/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Ortóptica/instrumentación , Presión , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Vecuronium bromide (Norcuron, Organon, Inc., West Orange, NJ) is a common neuromuscular blocking agent used to facilitate mechanical ventilation. Cases have been reported in which prolonged use of vecuronium resulted in severe motor neuropathy, with or without myopathy. However, the time course of recovery, the functional prognosis, and the use of inpatient rehabilitation is not well-established. We are reporting the functional recovery of two cases with the diagnosis of severe vecuronium motor neuropathy and/or myopathy. The patients presented with pneumonia and meningococcemia, respectively, and received vecuronium during ventilatory support, which lead to quadriparesis. In one patient, vecuronium toxicity occurred while neuromuscular junction monitoring was in place. Significant improvement was noted during an average of 3 to 4 wk in a comprehensive inpatient rehabilitation program, documented by the improvement in total motor Functional Independence Measure scores for patient 1 (from 15 to 71) and for patient 2 (from 65 to 84). In addition, the distal compound motor amplitudes showed a 4-fold increase for the ulnar, a 7-fold increase for the median, an 11-fold increase for the peroneal, and a 3-fold increase for the tibial nerves on follow-up nerve conduction studies correlating with neurologic recovery. In summary, even when patients present with quadriparesis, the recovery after vecuronium toxicity appears to be favorable.
Asunto(s)
Fármacos Neuromusculares no Despolarizantes/efectos adversos , Cuadriplejía/inducido químicamente , Cuadriplejía/rehabilitación , Bromuro de Vecuronio/efectos adversos , Actividades Cotidianas , Adulto , Femenino , Humanos , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacosRESUMEN
Musculoskeletal abnormalities have rarely been reported after major organ transplantation. We recorded five cases of elbow complications after orthotopic liver and bilateral lung transplantation. Three patients (four elbows) developed heterotopic ossification at the elbow, leading to decreased range of motion, pain and difficulty performing self-feeding and perineal hygiene. Two patients (three elbows) had electrodiagnostic evidence of ulnar mononeuropathy at the elbow, whereas one patient had bilateral median mononeuropathies caused by compression at the level of the ligament of Struthers. Surgical resection of ectopic bone with postoperative radiation was required in two patients (two elbows), and nerve decompression was used in three patients (four elbows). Common factors noted in all patients with either heterotopic ossification or ulnar mononeuropathy at the elbow included prolonged encephalopathy and the use of wrist restraints with the presentation of symptoms occurring weeks after surgery. In the patient with bilateral median nerve entrapment, symptoms occurred immediately after surgery suggesting perioperative limb compression. Elbow complications after organ transplantation should be recognized to minimize long-term disability through preventive measures and appropriate treatment.