Dopamine Gene Polymorphism, Biochemical and Oxidative Stress Parameters in Geriatric Population with and Without Depression: A Pilot Study.

Dopamine transporter takes released dopamine back into presynaptic terminals and has been implicated in several aging disorders including depression. The present study was designed to demonstrate dopamine gene polymorphism, its circulatory levels, biochemical and oxidative stress parameters in geriatric population with and without depression. Thirty geriatric patients with depression and thirty age and sex matched normal controls were genotyped for Dopamine Active Transporter (DAT TaqA1 and DAT VNTR) gene polymorphisms using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. The frequency of genotypes and alleles were compared in study groups. Biochemical markers, oxidative stress parameters, and dopamine levels were also measured using standard protocols and compared between patients and controls. The frequency distribution of DAT TaqA1 and DAT VNTR genotypes and alleles in patients were not statistically significant as compared to controls. At DAT TaqA1 gene polymorphism we found that the levels of dopamine were significantly high in genotypes A1A2 as compared to A2A2 (p ≤ 0.01). The present study demonstrated elevated levels of Catalase, Lipid Peroxide, and Glutathione Reductase, whereas decreased levels of Superoxide Dismutase, Dehydroepiandrosterone, Glutathione Peroxidase and Melatonin, in depressive patients as compared to controls. Our results clearly suggested that elevated mean levels of Catalase, Lipid Peroxides and Glutathione Reductase and decreased levels of Dehydroepiandrosterone, Superoxide Dismutase, Glutathione Peroxidase and Melatonin in depressed individuals may be a consequence of depression. Moreover, DAT TaqA1 allele A1 has a protective effect with high dopamine levels and DAT VNTR genotype 10R/10R has the highest protective effect followed by 9R/10R and 10R/11R.

Annular Rupture Due to Calcified Nodule Located in Left Ventricular Outflow Tract (LVOT) During Transcatheter Aortic Valve Replacement (TAVR) Managed by Protamine Sulfate.

Annular rupture is a rare yet fatal complication of transcatheter aortic valve replacement (TAVR). The likelihood of annular rupture is increased by the presence of extensive subannular calcification, excessive balloon dilatation for valve expansion or aggressive valve oversizing to prevent paravalvular leakage during TAVR. Although extensive annular or aortic root calcification increases the likelihood of annular rupture, rupture due to the presence of a calcified nodule in the left ventricular outflow tract (LVOT) is not commonly reported. We present the case of an 84-year-old man who developed an annular rupture during TAVR, likely due to the presence of a calcified nodule located in LVOT, which was noted on a pre-procedural computed tomography (CT) scan. The rupture was identified early and was successfully reversed with the administration of protamine sulfate during the procedure.

eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes.

We have developed a transgenic mouse model of Type 1 Diabetes (T1D) in which human GAD65 is expressed in pancreatic ß-cells, and human MHC-II is expressed on antigen presenting cells. Induced GAD65 antigen presentation activates T-cells, which initiates the downstream events leading to diabetes. In our humanized mice, we have shown downregulation of eukaryotic translation initiation factor 5 A (elF5A), expressed only in actively dividing mammalian cells. In-vivo inhibition of elF5A hypusination by deoxyhypusine synthase (DHS) inhibitor "GC7" was studied; DHS inhibitor alters the pathophysiology in our mouse model by catalyzing the crucial hypusination and the rate-limiting step of elF5A activation. In our mouse model, we have shown that inhibition of eIF5A resets the pro-inflammatory bias in the pancreatic microenvironment. There was: (a) reduction of Th1/Th17 response, (b) an increase in Treg numbers, (c) debase in IL17 and IL21 cytokines levels in serum, (d) lowering of anti-GAD65 antibodies, and (e) ablation of the ER stress that improved functionality of the ß-cells, but minimal effect on the cytotoxic CD8 T-cell (CTL) mediated response. Conclusively, immune modulation, in the case of T1D, may help to manipulate inflammatory responses, decreasing disease severity, and may help manage T1D in early stages of disease. Our study also demonstrates that without manipulating the CTLs mediated response extensively, it is difficult to treat T1D.

Ceftaroline Fosamil as an Alternative for a Severe Methicillin-resistant Staphylococcus aureus Infection: A Case Report.

Bacteremia secondary to methicillin-resistant Staphylococcus aureus (MRSA) is a dreaded medical condition that is not only associated with a significant medical cost but also carries high morbidity and mortality. The poor clinical outcomes seen in MRSA patients and the nephrotoxic effects of high-doses of vancomycin are challenging its current status as the first-line treatment for MRSA. Fortunately, vancomycin-intermediate-staphylococcus aureus (VISA) and vancomycin-resistant-staphylococcus aureus (VRSA) are not common in the United States. However, MRSA still presents different treatment challenges. Elevated vancomycin minimum inhibitory concentrations (MICs) commonly result in decreased efficacy and an increased probability of treatment failure, prompting the use of alternative agents. Although daptomycin is an alternative, adverse effects (i.e., elevations in serum creatine phosphokinase (CPK), drug-induced myopathy, peripheral neuropathy, and eosinophilic pneumonia) may limit its use in some patients. In the search for a suitable replacement for vancomycin, great promise has been shown by anti-MRSA cephalosporins. We present a case of MRSA bacteremia and endocarditis requiring a different approach to treatment as compared to traditional treatment with vancomycin alone. This case report describes the successful treatment of MRSA bacteremia with ceftaroline fosamil in a patient who responded poorly to conventional therapy, specifically vancomycin, due to an elevated MIC (2 µg/mL).

Venous Thrombosis Secondary to Acute Cytomegalovirus Infection in an Immunocompetent Host: Consideration for New Screening Guidelines.

Serious thrombotic complications associated with an acute cytomegalovirus (CMV) infection in immunocompromised and immunocompetent patients are becoming increasingly recognized. While typically asymptomatic and self-limiting, an acute CMV infection appears to demonstrate a rare propensity for a vascular thrombosis, such as deep vein thrombosis (DVT), thrombophlebitis, and pulmonary embolism (PE). It remains unclear whether other predisposing factors play a role in its pathogenesis. We report the case of a young, immunocompetent male with extensive lower extremity DVT who was coincidentally found to be CMV-immunoglobulin M (IgM) seropositive. In light of the increasing prevalence of CMV-associated thrombotic events, we reviewed the current literature on its incidence, pathophysiology, clinical features, and thrombophilia screening to consider the possibility of CMV seropositivity as an independent risk factor for vascular events. This may have repercussions for screening guidelines and preventive strategies in those with active CMV infection.