ABSTRACT
The prevalence of osteoporosis is about three times greater in people living with HIV than in the general population. Bisphosphonates are the only class of antiresorptive drugs which have proved to be safe and effective in HIV patients. However, bisphosphonates are not recommended in women of childbearing age due to an increased rate of associated neonatal complications. To the best of our knowledge no reports on the use of denosumab in HIV-infected individuals have been published so far. We describe a 38 year-old woman with HIV, osteoporosis and vertebral fractures treated with denosumab, a monoclonal antibody targeting RANKL. After four years of treatment, bone mineral density improved, no new fractures occurred, and neither HIV reactivation nor opportunistic infections were observed. We show that denosumab could be a safe and effective approach for osteoporosis in patients with HIV and could be considered in women of childbearing age.
Subject(s)
Bone Density Conservation Agents , HIV Infections , Osteoporosis, Postmenopausal , Osteoporosis , Adult , Bone Density Conservation Agents/therapeutic use , Denosumab/therapeutic use , Female , HIV Infections/complications , HIV Infections/drug therapy , Humans , Infant, Newborn , Osteoporosis/drug therapyABSTRACT
BACKGROUND: Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ). METHODS: Using MassARRAY high-throughput DNA analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we genotyped patients with sAPL (n=20) developed after treatment of MS (18 out 20 treated with MTZ) for the presence of 210 SNPs of 22 genes mostly involved in DNA repair and drug detoxification. Patients with MS who did not develop sAPL including 41 treated with MTZ (n=253 and 41, respectively) and healthy blood donors (n=310) were also genotyped as controls. RESULTS: We observed risk allele frequency between MS and sAPL for BRCA2 (rs1801406): 6% and 26%, p=0.007; XRCC5 (rs207906): 2.5% and 15%, p=0.016; CYP3A4 (rs2740574): 4.5% and 25%, p=0.0035. The association of homozygous variants of BRCA2 and XRCC5 yielded higher risk of sAPL (MS vs sAPL: 0.4% and 18%, p=0.001). We also observed a significant association between a SNP in the promoter region (rs2740574) of CYP3A4, an enzyme involved in the metabolism of chemotherapeutic agents and development of sAPL. CONCLUSIONS: Increased susceptibility to develop sAPL in patients with MS receiving MTZ may be linked to genetic variants in DNA repair and drug-metabolizing enzymes that result in impaired detoxification of chemotherapy or inefficient repair of drug-induced genetic damage.
Subject(s)
DNA Repair Enzymes/genetics , Genetic Predisposition to Disease , Leukemia, Promyelocytic, Acute/genetics , Multiple Sclerosis/genetics , Adult , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Humans , Leukemia, Promyelocytic, Acute/chemically induced , Leukemia, Promyelocytic, Acute/complications , Male , Mitoxantrone/adverse effects , Mitoxantrone/therapeutic use , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
The high activity of the rrnB P1 promoter in Escherichia coli results from a cis-acting DNA sequence, the UP element, and a trans-acting transcription factor, FIS. In this study, we examine the effects of FIS and the UP element at the other six rrn P1 promoters. We find that UP elements are present at all of the rrn P1 promoters, but they make different relative contributions to promoter activity. Similarly, FIS binds upstream of, and activates, all seven rrn P1 promoters but to different extents. The total number of FIS binding sites, as well as their positions relative to the transcription start site, differ at each rrn P1 promoter. Surprisingly, the FIS sites upstream of site I play a much larger role in transcription from most rrn P1 promoters compared to rrnB P1. Our studies indicate that the overall activities of the seven rrn P1 promoters are similar, and the same contributors are responsible for these high activities, but these inputs make different relative contributions and may act through slightly different mechanisms at each promoter. These studies have implications for the control of gene expression of unlinked multigene families.
Subject(s)
Carrier Proteins/physiology , Escherichia coli Proteins , Escherichia coli/genetics , Gene Expression Regulation, Bacterial , Promoter Regions, Genetic , RNA, Ribosomal/biosynthesis , rRNA Operon , Base Sequence , Binding Sites , Factor For Inversion Stimulation Protein , Integration Host Factors , Molecular Sequence Data , RNA, Bacterial/biosynthesis , Response Elements , Sequence Homology, Nucleic Acid , Transcription Factors/physiology , Transcriptional ActivationSubject(s)
Femur/surgery , Knee Joint , Osteochondritis Dissecans/surgery , Osteochondritis/surgery , Osteotomy/methods , Adult , Female , Femur/transplantation , Follow-Up Studies , Humans , MaleSubject(s)
Osteosarcoma/diagnosis , Spinal Neoplasms/diagnosis , Thoracic Neoplasms , Adult , Humans , Male , Osteosarcoma/pathology , Osteosarcoma/surgery , Radionuclide Imaging , Spinal Neoplasms/pathology , Spinal Neoplasms/surgery , Thoracic Neoplasms/diagnostic imaging , Thoracic Neoplasms/pathology , Tomography, X-Ray ComputedSubject(s)
Femur/transplantation , Osteochondritis Dissecans/surgery , Osteochondritis/surgery , Adult , Female , Humans , Knee/surgery , MaleSubject(s)
Femur Head/surgery , Hip Joint , Joint Prosthesis , Osteoarthritis/surgery , Aged , Female , Hip Dislocation, Congenital/complications , Humans , Male , Methods , Middle Aged , Osteoarthritis/etiologyABSTRACT
The treatment of three cases of aneurysmal bone cyst by selective arterial embolism is described. Two cases had involvement of the pelvis and one of the knee. The 2-year follow up has been promising. Radiologically the lesion has been arrested with increased density of the cyst wall and intra-cystic trabecular new bone formation. Pain relief has been complete and up to now no surgical treatment has been required.
Subject(s)
Bone Cysts/therapy , Embolization, Therapeutic , Hip Joint , Knee Joint , Pelvic Neoplasms/therapy , Adult , Child , Female , Follow-Up Studies , Humans , Ilium , Ischium , Male , Pelvic Bones , Sacroiliac JointSubject(s)
Bone Cysts/therapy , Embolization, Therapeutic/methods , Pelvic Bones , Adult , Child , Female , Humans , MaleABSTRACT
Norepinephrine (NE) concentrations were measured in the olfactory bulbs and olfactory cortex of male albino rats and golden hamsters sacrificed 13-16 days after castration or sham surgery. Castration significantly decreased NE concentrations in the olfactory bulbs of rats but not hamsters. Castration had no significant influence on NE levels in the olfactory cortex of either species. Regional brain weights were not influenced by surgery, and previous olfactory exposure had no significant effect on any variable measured. The decrease in rat olfactory bulb NE levels may be involved in castration-induced changes in preferences for conspecific odors.
Subject(s)
Castration , Norepinephrine/metabolism , Olfactory Bulb/metabolism , Animals , Cricetinae , Hydroxydopamines/pharmacology , Male , Mesocricetus , Rats , Smell/drug effects , Species SpecificitySubject(s)
Discrimination Learning , Nesting Behavior , Social Environment , Animals , Animals, Newborn , Choice Behavior , Cues , Exploratory Behavior , Female , Male , RatsSubject(s)
Arthrodesis , Foot Diseases/surgery , Ankle Joint , Humans , Paralysis/surgery , Tarsal JointsABSTRACT
Rat pups injected subcutaneously with 6-hydroxydopamine (6-OHDA) showed reduced preference for a familiar combination of conspecific and botanical odors when subsequently tested in a two-choice situation. However, drug treatment did not influence preference for the simple botanical odor. 6-OHDA also reduced norepinephrine (NE) concentrations in the forebrain and the olfactory bulbs. The data implicate NE in the ontogeny of the acquired responses to conspecific odors.
Subject(s)
Choice Behavior/drug effects , Hydroxydopamines/pharmacology , Odorants , Aging , Animals , Brain Chemistry/drug effects , Epinephrine/analysis , RatsABSTRACT
In order to learn more about their ability to recognize one another via olfaction, domestic male rats were given a series of preference tests in which pairs of odors from male conspecifics were presented. Both immature and mature males prefer (p less than .05) the odor from immature strangers over that from immature cage mates but are indifferent to the ordors from mature strangers versus cage mates. Both immature and mature males prefer (p less than .05) the odor from mature novel cage mates over that from mature cage mates to which they are temporarily habituated but are indifferent to the odors from immature novel versus familial cage mates. Mature males prefer (p less than .08) the odor from a cage mate over the subject's own odor, and they prefer (p less than .01) their own odor over no odor. Under certain conditions, male rats can discriminate between the odors from (a) strangers versus cage mates, (b) two cage mates, and (c) their own body versus a cage mate.