- AAV-8 and AAV-9 Vectors Cooperate with Serum Proteins Differently Than AAV-1 and AAV-6. [Journal Article]
- MTMol Ther Methods Clin Dev 2018 Sep 21; 10:291-302
- Under intravenous delivery, recombinant adeno-associated vectors (rAAVs) interact with blood-borne components in ways that can critically alter their therapeutic efficiencies. We have previously show...
Under intravenous delivery, recombinant adeno-associated vectors (rAAVs) interact with blood-borne components in ways that can critically alter their therapeutic efficiencies. We have previously shown that interaction with human galectin 3 binding protein dramatically reduces rAAV-6 efficacy, whereas binding of mouse C-reactive protein improves rAAV-1 and rAAV-6 transduction effectiveness. Herein we have assessed, through qualitative and quantitative studies, the proteins from mouse and human sera that bind with rAAV-8 and rAAV-9, two vectors that are being considered for clinical trials for patients with neuromuscular disorders. We show that, in contrast to rAAV-1 and rAAV-6, there was a substantial similarity in protein binding patterns between mouse and human sera for these vector serotypes. To establish an in vivo role for the vector binding of these sera proteins, we chose to study platelet factor 4 (PF4), which interacts with both vectors in both mouse and human sera. Experiments using PF4-knockout mice showed that a complete lack of PF4 did not alter skeletal muscle transduction for these vectors, whereas heart transduction was moderately improved. Our results strongly support our position that the impact of serum proteins on the transduction properties of rAAV-8 and rAAV-9, already observed in mouse models, should be similar in human preclinical trials.
- Experimental morphologic study of reparative processes in erosive lesions of the oral mucosa. [Journal Article]
- GDGen Dent 2018 Jul-Aug; 66(4):e5-e9
- The goal of this preclinical study was to substantiate the effectiveness of using autologous platelet-rich plasma (PRP) to heal erosive lesions in the oral cavity. This study employed analyses of qua...
The goal of this preclinical study was to substantiate the effectiveness of using autologous platelet-rich plasma (PRP) to heal erosive lesions in the oral cavity. This study employed analyses of qualitative and semiquantitative morphologic parameters, including histologic assessment of biopsy specimens. The most favorable results were observed in a group of 16 dogs receiving 2-mL injections of autologous PRP 3 times: day 1 of the experiment and after 7 and 14 days of observation; in this group, no traces of inflammatory symptoms were found at the end of the observation period (14 days). At the end of the same time period, a control group of 16 dogs receiving conventional therapy-which consisted of twice daily applications of an anesthetic agent, proteolytic enzymes, an antiseptic agent, and a wound healing preparation-exhibited signs of nonspecific chronic inflammation in certain zones of the oral mucosa. These results suggest that autologous PRP may be useful in the treatment of various inflammatory disorders in the maxillofacial area.
- A 43-year-old woman with unexplained elevation of hCG. [Case Reports]
- CBClin Biochem 2018; 55:86-88
- CONCLUSIONS: In plasma recipients with unexplained hCG elevation, passive transfer of hCG from plasma should be considered in the differential diagnosis. Retrospective measurement of hCG in remnant samples obtained prior to plasma exchange can assist in confirming the source.
- Platelet Dysfunction and Intracerebral Hemorrhage in a Patient Treated with Empiric Piperacillin-Tazobactam in the Neurocritical Care Unit. [Case Reports]
- WNWorld Neurosurg 2018; 114:204-210
- CONCLUSIONS: This is unique in that the significant bleeding that occurred was attributable to platelet dysfunction rather than thrombocytopenia. This is the first reported case of intracranial (periprocedural) hemorrhage potentially related to piperacillin-tazobactam; further research into this drug's impact upon qualitative platelet function is needed.
- Pilot study of novel lab methodology and testing of platelet function in adolescent women with heavy menstrual bleeding. [Journal Article]
- PRPediatr Res 2018; 83(3):693-701
- BackgroundApproximately 40% of adolescent women experience heavy menstrual bleeding (HMB), and 10-62% of them have an underlying bleeding disorder (BD). Diagnosing a BD remains challenging because of...
BackgroundApproximately 40% of adolescent women experience heavy menstrual bleeding (HMB), and 10-62% of them have an underlying bleeding disorder (BD). Diagnosing a BD remains challenging because of limitations of available clinical platelet function assays. The aim of this study was to characterize platelet function in a population of adolescent women with HMB using small-volume whole-blood assays.MethodsAnticoagulated whole blood was used to assess platelet GPIIbIIIa activation, α-granule secretion, and aggregation in response to multiple agonists. Platelet adhesion on collagen or von Willebrand Factor (VWF) under static and shear flow was also assessed.ResultsFifteen participants with HMB were included in the study, of which eight were diagnosed with a clinically identifiable BD. Platelet activation was blunted in response to calcium ionophore in participants without a BD diagnosis compared with that in all other participants. Impaired GPIIbIIIa activation was observed in response to all GPCR agonists, except adenosine diphosphate (ADP), in participants with qualitative platelet disorders. Our assays detected platelet aggregation in the majority of participants with a BD in response to ADP, collagen-related peptide (CRP), thrombin receptor activator 6 (TRAP-6), or U46619. Platelet adhesion and aggregation on collagen and VWF was decreased for participants with VWD.ConclusionParticipants with and without BD exhibited aberrant platelet function in several assays in response to select agonists.
- A Retrospective Study of the Effects of Oncology Pharmacist Participation in Treatment on Therapeutic Outcomes and Medical Costs. [Journal Article]
- BPBiol Pharm Bull 2017; 40(11):1956-1962
- Specialist oncology pharmacists are being trained in Japan to assist cancer treatment teams. These specialized pharmacists address patients' physical and mental problems in pharmacist-managed cancer ...
Specialist oncology pharmacists are being trained in Japan to assist cancer treatment teams. These specialized pharmacists address patients' physical and mental problems in pharmacist-managed cancer care clinics, actively participate in formulating treatment policies, and are beneficial in offering qualitative improvements to patient services and team medical care. However, the effect of outpatient treatment by oncology pharmacists on therapeutic outcomes and medical costs is still unknown. A retroactive comparative analysis of the treatment details and clinical course was conducted among three groups of patients: patients who underwent adjuvant chemotherapy managed by a gynecologic oncologist only (S arm), patients managed by a non-oncologist (general practice gynecologist) only (NS arm), and patients managed by both a non-oncologist and a specialist oncology pharmacist (NS+Ph arm). The medical cost per course was significantly lower for patients in the NS+Ph arm than for those in the other two arms. Surprisingly, the outpatient treatment rate in the NS+Ph arm was overwhelmingly high. The involvement of an oncology pharmacist did not make a significant difference in therapeutic outcomes such as recurrence rate and survival. The participation of oncology pharmacists in the management of cancer patients undergoing chemotherapy enables safe outpatient treatment and also reduces medical costs.
- Molecular characterization of Glanzmann's thrombasthenia in Iran: identification of three novel mutations. [Journal Article]
- BCBlood Coagul Fibrinolysis 2017; 28(8):681-686
- : Quantitative and/or qualitative defects of the platelet membrane glycoprotein IIb/IIIa complex lead to the clinical entity of Glanzmann's thrombasthenia. A large variety of mutations and polymorphi...
: Quantitative and/or qualitative defects of the platelet membrane glycoprotein IIb/IIIa complex lead to the clinical entity of Glanzmann's thrombasthenia. A large variety of mutations and polymorphisms are responsible for the aberrant expression and defective activity of this heterodimeric complex. The current study aimed to determine the pattern of mutations among Iranian population with Glanzmann's thrombasthenia. A total of 20 patients with Glanzmann's thrombasthenia have been evaluated. All exons and splice sites of ITGA2B and ITGB3 genes were amplified using touchdown PCR. Mutation screening was analyzed using conformation sensitive gel electrophoresis heteroduplex PCR, and DNA sequencing. In addition to finding one previously identified mutation and polymorphism, the experimenters explored 3 and 2 novel mutations and polymorphisms, respectively. One substitution mutation, two deletions of a single nucleotide, one insertion of a single nucleotide, two synonymous polymorphisms, and one missense polymorphism were found using Sanger sequencing method. All detected mutations were homozygous which will most likely contribute to the pathogenesis of Glanzmann's thrombasthenia. Furthermore, it suggested ITGB3 as the mainly affected gene impaired in the patients with Glanzmann's thrombasthenia. As expected, the molecular results were consistent with the phenotypic findings so that GPIIb/IIIa complex was disrupted due to mutations in all type-I Glanzmann's thrombasthenia patients. It is concluded that intronic alterations or epigenetic regulations could be responsible for aberrant expression and/or defective activity of GPIIb/IIIa complex among other patients.
- A rare case of bleeding disorder: Glanzmann's thrombasthenia. [Case Reports]
- AAAnn Afr Med 2017 Oct-Dec; 16(4):196-198
- CONCLUSIONS: GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.
- Flow cytometric immunobead assay for quantitative detection of platelet autoantibodies in immune thrombocytopenia patients. [Journal Article]
- JTJ Transl Med 2017 Oct 23; 15(1):214
- CONCLUSIONS: A quantitative FCIA assay was established. Reduced levels of platelet autoantibodies could be confirmed by our quantitative FCIA in ITP patients after corticosteroid treatment. Our quantitative assay is not only good for ITP diagnosis but also for ITP treatment monitoring.
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- Evaluation of platelet surface glycoproteins in patients with Glanzmann thrombasthenia: Association with bleeding symptoms. [Journal Article]
- IJIndian J Med Res 2017; 145(5):629-634
- CONCLUSIONS: Type I GT was found most common in our patients and with lowered mean CD41 expression in comparison with CD61. Type III GT patients had significantly lower numbers of severe bleeders, but the severity of bleeding did not vary significantly in type I and II GT patients.