Paget von Schroetter Syndrome Secondary to Exotic Dancing: A Case Study

Axillary vein thrombosis, or Paget von Schroetter syndrome, is a rare clinical condition. It is associated with several thrombogenic states and numerous sporting activities involving excessive use of the arm. We report one such case associated with exotic dancing. In societies where dancing involves excessive arm movement, the physician must be aware of this condition to permit early diagnosis and effective treatment.     

Gene-Directed Enzyme Prodrug Therapy

As one targeting strategy of prodrug delivery, gene-directed enzyme prodrug therapy (GDEPT) promises to realize the targeting through its three key features in cancer therapy—cell-specific gene delivery and expression, controlled conversion of prodrugs to drugs in target cells, and expanded toxicity to the target cells’ neighbors through bystander effects. After over 20 years of development, multiple GDEPT systems have advanced into clinical trials. However, no GDEPT product is currently marketed as a drug, suggesting that there are still barriers to overcome before GDEPT becomes a standard therapy. In this review, we first provide a general introduction of this prodrug targeting strategy. Then, we utilize the four most thoroughly studied systems to illustrate components, mechanisms, preclinical and clinical results, and further development directions of GDEPT. These four systems are herpes simplex virus thymidine kinase/ganciclovir, cytosine deaminase/5-fluorocytosine, cytochrome P450/oxazaphosphorines, and nitroreductase/CB1954 system. Later, we focus our discussion on bystander effects including local and distant bystander effects. Lastly, we discuss carriers that are used to deliver genes for GDEPT including virus carriers and non-virus carriers. Among these carriers, the stem cell-based gene delivery system represents one of the newest carriers under development, and may brought about a breakthrough to the gene delivery issue of GDEPT.KEY WORDS: bystander effects, gene delivery, gene-directed enzyme, prodrug, stem cell-based targeting     

A Critical Review of Alcohol Administration Guidelines in Laboratory Medication Screening Research: Is It Time to Include Treatment Seekers?

Human laboratory studies play an important role in alcohol use disorder (AUD) medication development. Medications that are found to be safe and effective during human laboratory screening will then move to more expensive clinical trials in patient populations. Given the gatekeeping role of human laboratory studies in the medication development pipeline, it is critical that these studies accurately forecast how pharmacotherapies will perform under true-to-life clinical conditions. On the other hand, the design of these studies also must adhere to ethical guidelines: certain aspects of clinical reality cannot be incorporated into screening studies because doing so might place the participant at risk for harm or breach other ethical guidelines. Conventions exist that guide the resolution of these conflicting ideals. This article considers the practice of recruiting non–treatment-seeking heavy drinkers to participate in laboratory screening studies. By convention, volunteers are excluded from laboratory screening studies that involve alcohol administration if they are deemed “treatment seeking,” meaning that they recently stopped drinking or are motivated to do so. Although this common practice may reduce risk to participants, findings may not accurately predict medication effects on treatment seekers. Indeed, there is empirical evidence that treatment seekers differ from nontreatment seekers in their responses to medications (Neuropsychopharmacology 2017a; 42: 1776; Am J Drug Alcohol Abuse 2017b; 43: 703; J Psychiatr Res 2006; 40: 383). Here, we argue for the importance of recruiting treatment seekers for this research due to their qualitative difference from nontreatment seekers. We argue that these individuals should be the default population in human laboratory medication screening studies. We conclude by discussing 2 case examples of medication experiments led by our research groups that involved administering medications to treatment seekers.     

De novo development of antibodies to kidney‐associated self‐antigens angiotensin II receptor type I,collagen IV,and fibronectin occurs at early time points after kidney transplantation in children

Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self‐antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney‐associated self‐antigens develop following pediatric renal transplantation. We investigated post‐transplant development of Abs to kidney‐associated self‐antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney‐associated self‐antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post‐transplant. No samples had Abs to kidney‐associated self‐antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney‐associated self‐antigen post‐transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney‐associated self‐antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation—a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes.     

First living‐related liver transplant to cure factor VII deficiency

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first‐ever youngest baby reported worldwide. A six‐month‐old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life‐threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre‐, intra‐ and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency.     

Enhanced electron transfer mediated detection of hydrogen peroxide using a silver nanoparticle–reduced graphene oxide–polyaniline fabricated electrochemical sensor

The current study aims at the development of an electrochemical sensor based on a silver nanoparticle–reduced graphene oxide–polyaniline (AgNPs–rGO–PANI) nanocomposite for the sensitive and selective detection of hydrogen peroxide (H₂O₂). The nanocomposite was fabricated by simple in situ synthesis of PANI at the surface of rGO sheet which was followed by stirring with AEC biosynthesized AgNPs to form a nanocomposite. The AgNPs, GO, rGO, PANI, rGO–PANI, and AgNPs–rGO–PANI nanocomposite and their interaction were studied by UV-vis, FTIR, XRD, SEM, EDX and XPS analysis. AgNPs–rGO–PANI nanocomposite was loaded (0.5 mg cm⁻²) on a glassy carbon electrode (GCE) where the active surface area was maintained at 0.2 cm² for investigation of the electrochemical properties. It was found that AgNPs–rGO–PANI–GCE had high sensitivity towards the reduction of H₂O₂ than AgNPs–rGO which occurred at −0.4 V vs. SCE due to the presence of PANI (AgNPs have direct electronic interaction with N atom of the PANI backbone) which enhanced the rate of transfer of electron during the electrochemical reduction of H₂O₂. The calibration plots of H₂O₂ electrochemical detection was established in the range of 0.01 μM to 1000 μM (R² = 0.99) with a detection limit of 50 nM, the response time of about 5 s at a signal-to-noise ratio (S/N = 3). The sensitivity was calculated as 14.7 μA mM⁻¹ cm⁻² which indicated a significant potential as a non-enzymatic H₂O₂ sensor.

The current study aims at the development of an electrochemical sensor based on a silver nanoparticle–reduced graphene oxide–polyaniline (AgNPs–rGO–PANI) nanocomposite for the sensitive and selective detection of hydrogen peroxide (H₂O₂).     

Investigation of rotameric conformations of substituted imidazo-[1,2-a]pyrazine: experimental and theoretical approaches

The different rotameric conformations of imidazo-[1,2-a]pyrazine have been synthesized and characterized by means of different experimental techniques, such as NMR, FTIR, and absorption spectroscopy and quantum chemical calculations. The different conformations were stabilized by hydrogen bonds, such as OH⋯N, ArH⋯N and ArH⋯ArH. The ground state optimizations and potential energy surface (PES) scanning profiles produced using density functional theory (DFT) show two stable rotameric forms for each molecule. The relative population of the conformations is affected by the strength of the hydrogen bonds. The calculated absorption spectra and isotopic shielding constants were acquired by time-dependent density functional theory (TD-DFT) and gauge invariant atomic orbitals (GIAO)-DFT, respectively. The strength of the hydrogen bonding interactions that resulted in the different conformations was studied by quantum theory of atoms in molecules (QTAIM).

The different rotameric conformations of imidazo-[1,2-a]pyrazine have been synthesized and characterized by means of different experimental techniques, such as NMR, FTIR, and absorption spectroscopy and quantum chemical calculations.