ABSTRACT
Historically, pregnancy in females with spinal muscular atrophy was contraindicated due to the great risk to the parturient, but with improved management and increased survival more patients are becoming pregnant. We describe the management of a pregnant patient with spinal muscular atrophy type-2, who had severe restrictive lung disease, extensive spinal fusion that precluded neuraxial anesthesia, and chronic respiratory failure on nocturnal Bilevel Positive Airway Pressure. Airway management was further complicated by limited mouth opening and cervical spine ankylosis.
Subject(s)
Airway Management/methods , Conscious Sedation/methods , Dexmedetomidine , Hypnotics and Sedatives , Pregnancy Complications/therapy , Spinal Muscular Atrophies of Childhood/complications , Adult , Cesarean Section , Emergency Medical Services , Fatal Outcome , Female , Humans , Muscle Weakness/etiology , Muscle Weakness/therapy , Pregnancy , Spinal Muscular Atrophies of Childhood/therapy , TracheostomyABSTRACT
BACKGROUND: MDR1 or MRP1 drug resistance mechanisms seriously limit the efficacy of anthracyclines such as doxorubicin, in the treatment of acute myeloid leukemia (AML). Our studies indicated that reducing basicity, increasing steric hindrance at C-4', and/or lipophilicity may help circumvent P-glycoprotein (P-gp)-mediated anthracycline efflux and thus increase drug retention in MDR-positive cells. From a series of 4'-substituted analogs, 4'-O-benzylated doxorubicin (WP744) was selected for a comparison with the classic anthracycline doxorubicin for their cytotoxic and pro-apoptotic properties. WP744 retains cytotoxic activity against P-gp and MRP-positive cells. METHODS AND RESULTS: In three AML cell lines (K562, KBM-3, and OCIM2) WP744 was markedly more potent (IC50 values of 0.18, <0.05, and <0.05 microg/ml, respectively) than doxorubicin (IC50 values of >0.5, 0.07, and 0.09 microg/ml, respectively). Likewise, WP744 inhibited the colony formation by AML-CFU cells from fresh bone marrow of three AML patients more strongly than doxorubicin. Cell growth inhibition by WP744 is accompanied by apoptosis induction as shown by TUNEL assay in OCIM2 cells. WP744-induced apoptosis appears to be mediated by caspase-3 as apoptotic changes were abrogated in the presence of the caspase 3 inhibitor Z-DEVD-FMK. Accordingly, caspase 3 activity was elevated in the lysates from drug-treated cells. WP744 induced also cleavage of apoptotic marker poly(ADP-ribose)polymerase (PARP). Finally, WP744 at 0.05 microM and greater was a potent inducer of apoptosis (by quantitative DNA fragmentation) in cultured human acute lymphoblastic leukemia (ALL) CEM cells, compared to 0.5 microM doxorubicin needed for a similar effect. CONCLUSION: The novel anthracycline WP744 was found to be an antileukemic agent with proapoptotic activity superior to that of doxorubicin.
Subject(s)
Anthracyclines , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/pharmacokinetics , Apoptosis/drug effects , Doxorubicin/analogs & derivatives , Leukemia, Monocytic, Acute/drug therapy , Leukemia, Myeloid, Acute/drug therapy , Adult , Aged , Caspase 3 , Caspases/metabolism , Cell Division/drug effects , DNA Fragmentation , Doxorubicin/pharmacology , Female , Growth Inhibitors/pharmacology , Humans , K562 Cells/drug effects , K562 Cells/pathology , Leukemia, Monocytic, Acute/enzymology , Leukemia, Monocytic, Acute/pathology , Leukemia, Myeloid, Acute/enzymology , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Poly(ADP-ribose) Polymerases/metabolism , Tumor Cells, CulturedABSTRACT
The aim of the study was to assess the structure of perception in people with bruxism. 50 people with a diagnosis of bruxism (B), in whom primary evidence of oclusal disharmony and temporomandibular disorders were excluded, were included in the study. The control group (C) consisted of 50 people with no evidence of parafunctional abnormalities of the chewing mechanism. Shalit's diagram was used to assess the structure of perception. The primary indices: discriminability (D), articulation (A), affective load+ (AL+) and affective load- (AL-) and secondary indices: reduction (R), emotionality (E), intensity (I) were derived from Shalit's diagram. A significant reduction in the mean value of the primary indices D and AL+ was noted, as well as in the secondary indices E and I in people with bruxism, in comparison to the control group. Assessment of the structure of perception in people with bruxism through the analysis of the primary and secondary indices, makes it possible to predict behavior which has a negative effect on the individual's own health and provides the opportunity for changing such behavior to be more pro-health oriented.
Subject(s)
Bruxism/psychology , Perception , Adult , Female , Health Behavior , Humans , Male , Middle AgedABSTRACT
The aim of the present study was to determine whether the liver cytosol detoxication enzymes, glutathione S-transferases (GSTases) as well as gamma-glutamyl transpeptidase (GGT) foci induced by aflatoxin B1 (AFB) were changed by feeding weanling rats diets containing brussels sprouts, a glucosinolate fraction of brussels sprouts (extract), or a non-glucosinolate fraction (residue). All 3 of these diets induced high levels of hepatic GSTase specific activity as compared to purified-basal diet fed control rats. The brussels sprouts and the extract treatments, but not the residue dietary treatment, inhibited hepatic GGT foci induced by AFB. Thus, glucosinolates and non-glucosinolate fractions of brussels sprouts induce hepatic enzymes involved in detoxication mechanisms but the non-glucosinolate compound(s) apparently are not involved in all chemical carcinogen metabolic processes.
