Lanosterol 14α-demethylase. Similarity of the enzyme system from yeast and rat liver

The chemical synthesis of 24,25-dihydro[32-¹⁴C]lanosterol is described. The incubation of this material with a cell-free system from $\text{Saccharomvoes cerevisiae}$ or with a microsomal preparation from rat liver resulted in both cases in the release of [¹⁴C]formic acid. This result suggests that in the biosynthesis of ergosterol in yeast, as well as in that of cholesterol in higher animals, the 14α-methyl group of lanosterol is removed as formic acid. In both systems, the measurement of the rate of release of [¹⁴C]formic acid from 24,25-dihydro[32-¹⁴C]lanosterol provides a simple and direct assay of lanosterol 14α-demethylase. Carbon monoxide inhibited both yeast and liver 14α-demethylase.     

Purification,properties, and mode of action of hemicellulase I produced by Ceratocystis paradoxa

A culture isolate (CP₂) of the fungal plant pathogen Ceratocystis paradoxa produces at least five extra-cellular hemicellulases when grown on a medium containing a commercial hemicellulose as inducer. One of the five enzymes, hemicellulase I (HC-I), was purified by ammonium sulphate precipitation, ion-exchange chromatography (DEAE-Sephadex and then Cellex-CM), and iso-electric focusing at pH 3–10 and 8–10. HC-I behaves as a single protein on electrophoresis at pH 6.0 and 8.4. The enzyme degrades hemicellulose B (an arabino-4-O-methylglucuronoxylan) and arabinoxylan to arabinose, xylose, xylobiose (Xyl₂; β-D-Xylp-(1→4)-D-Xyl), and a mixture of arabinose-xylose and xylose oligosaccharides (AraXyl_n and Xyl_n, where n  3, 4, or 5). The enzyme is deduced to be an endo-enzyme. Xylotetraose (Xyl₄) was the lowest homologue of the xylose oligosaccharides attacked, yielding xylobiose and xylotriose (Xyl₃) only. A mechanism is postulated for this reaction. AraXyl₂AraXyl₅ were slowly hydrolysed to arabinose and the respective xylose saccharide (Xyl₂Xyl₅), and thence to Xyl₂ and Xyl₃. Hydrolysis of the arabinofuranosyl linkage probably does not occur at the same active site as for the xylose oligosaccharides. Hemicellulose B fractions from different sources appeared to be degraded by HC-I. The enzyme showed optimum activity at pH 5.5 and 40°, and K_m was 4.24 mg of hemicellulose/ml.     

A cutin acid in Pinus sylvestris microspores

Nonacosan-10-ol (0.7%) and the cutin acid, 9,16-dihydroxyhexadecanoic acid (0.3%) are present in Pinus sylvestris microspores. The pollen coat hence has some features in common with leaf cuticles.     

Genetic control of susceptibility of mice to Rous sarcoma virus tumorigenesis

Studies with congenic resistant strains of mice indicate that susceptibility to Rous sarcoma virus tumorigenesis is influenced by a gene or genes associated with the major histocompatibility complex (H-2). These genes manifest dominant relative susceptibility. Preliminary studies indicate that the CBA/J strain harbors a gene or genes for relative susceptibility, which are recessive. These results are compared with other studies onH-2-associated genes affecting murine viral oncogenesis.     

Intrathecal Morphine Use in Adolescent Idiopathic Scoliosis Surgery is Associated with Decreased Opioid Use and Decreased Length of Stay

BackgroundLength of stay (LOS) in the hospital following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has decreased over the past decade due to well-defined postoperative clinical pathways, earlier mobilization, and improved pain control methods. Historically, liberal use of parenteral and oral opioids for pain control caused side effects, resulting in delayed discharge. Intraoperative intrathecal morphine (ITM) has been posited to reduce the need for postoperative opioids and to expedite the discharge process. This study examines the relationship between the use of ITM with average required postoperative opioid usage and with average LOS.MethodsThis IRB-approved retrospective cohort study examined 105 patients with AIS who received PSF with instrumentation split into two cohorts. One cohort underwent PSF via standard surgical protocol (n=40) while the other cohort received intraoperative ITM with the standard surgical protocol (n=65). Power analysis demonstrated a study power of 0.8. LOS and total postoperative opioid analgesic medication (morphine milligram equivalent, MME) data were collected. Age at surgery, gender, number of spinal levels fused, estimated intraoperative blood loss (EBL), preoperative Cobb angle, and any complications related to the use of ITM were also recorded. Continuous variables were analyzed with Student’s t-test and categorical variables were analyzed with chi-square independent-sample tests using SAS 9.4 (α = 0.05).ResultsPatients who were treated with ITM displayed shorter LOS (p<0.0001) and reduced postoperative analgesic requirement (p<0.0001). Patients who received ITM spent an average of 1.8 fewer midnights in the hospital and received an average of 221.2 MME less than patients who received standard protocol (57% decrease). There were no significant differences between the two groups for any other variable.ConclusionIntraoperative ITM is a simple and effective treatment for scoliosis surgeons to better control postoperative pain in patients, reduce the risk of dependency, and achieve earlier discharge from the hospital. Shortened LOS reduces the overall cost of care, benefitting patients, hospitals, and insurance companies. Based on the results of this study and several earlier studies, the authors recommended that scoliosis surgeons consider incorporating use of ITM into their standard operative protocols. Level of Evidence: IV     

Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance

Imaging modalities play an important role in the clinical management of cancer, including screening, diagnosis, treatment planning and therapy monitoring. Owing to increased research efforts during the past two decades, photoacoustic imaging (a non-ionizing, noninvasive technique capable of visualizing optical absorption properties of tissue at reasonable depth, with the spatial resolution of ultrasound) has emerged. Ultrasound-guided photoacoustics is noted for its ability to provide in vivo morphological and functional information about the tumor within the surrounding tissue. With the recent advent of targeted contrast agents, photoacoustics is now also capable of in vivo molecular imaging, thus facilitating further molecular and cellular characterization of cancer. This review examines the role of photoacoustics and photoacoustic-augmented imaging techniques in comprehensive cancer detection, diagnosis and treatment guidance.     

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Dyslipidemia is an important risk factor for cardiovascular disease (CVD) and atherosclerosis. When dyslipidemia coincides with other metabolic disorders such as obesity, hypertension, and glucose intolerance, defined as the metabolic syndrome (MS), individuals present an elevated risk to develop type 2 diabetes (T2D) as well as CVD. Because the MS epidemic represents a growing public health problem worldwide, the development of therapies remains a major challenge. Alterations of bile acid pool regulation in T2D have revealed a link between bile acid and metabolic homeostasis. The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS.