Angiotensin-converting enzyme inhibition and angiotensin II subtype-1 receptor blockade during the progression of left ventricular dysfunction: differential effects on myocyte contractile processes

Inhibition of the angiotensin-converting enzyme (ACE) in the setting of chronic left ventricular (LV) dysfunction has been demonstrated to have beneficial effects on survival and symptoms. However, whether ACE inhibition has direct effects on myocyte contractile processes and if these effects are mediated primarily through the AT1 angiotensin-II receptor subtype remains unclear. The present project examined the relationship between changes in LV and myocyte function and beta adrenergic receptor transduction in four groups of six dogs each: (1) Rapid Pace: LV failure induced by chronic rapid pacing (4 weeks; 216 +/- 2 bpm); (2) Rapid Pace/ACEI: concomitant ACE inhibition (ACEI: fosinopril 30 mg/kg b.i.d.) with chronic pacing; (3) Rapid Pace/AT1 Block: concomitant AT1 Ang-II receptor blockade [Irbesartan: SR 47436(BMS-186295) 30 mg/kg b.i.d.] with chronic pacing; and (4) Control: sham controls. With Rapid Pace, the LV end-diastolic volume increased by 62% and the ejection fraction decreased by 53% from control. With Rapid Pace/ACEI, the LV end-diastolic volume was reduced by 24% and the ejection fraction increased by 26% from Rapid Pace only values. Rapid Pace/AT1 Block did not improve LV geometry or function from Rapid Pace values. Myocyte contractile function decreased by 40% with Rapid Pace and increased from this value by 32% with Rapid Pace/ACEI. Rapid Pace/AT1 Block had no effect on myocyte function when compared with Rapid Pace values. With Rapid Pace/ACEI, beta receptor density and cyclic AMP production were normalized and associated with an improvement in myocyte beta adrenergic response compared with Rapid Pace only. Although Rapid Pace/AT1 also normalized beta receptor density, cyclic AMP production was unchanged and myocyte beta adrenergic response was reduced by 15% compared with Rapid Pace only. ACE inhibition with chronic rapid pacing improved LV and myocyte geometry and function, and normalized beta receptor density and cyclic AMP production. However, AT1 Ang-II receptor blockade with chronic rapid pacing failed to provide similar protective effects on LV and myocyte geometry and function. These unique findings suggest that the effects of ACE inhibition on LV geometry and myocyte contractile processes in the setting of developing LV failure are not primarily caused by modulation of AT1 Ang-II receptor activation.     

Enhancing Planar Inverted Perovskite Solar Cells with Innovative Dumbbell-Shaped HTMs: A Study of Hexabenzocoronene and Pyrene-BODIPY-Triarylamine Derivatives

Dumbbell-shaped systems based on PAHs-BODIPY-triarylamine hybrids TM-(01-04) are designed as novel and highly efficient hole-transporting materials for usage in planar inverted perovskite solar cells. BODIPY is employed as a bridge between the PAH units, and the effects of the conjugated π-system's covalent attachment and size are investigated. Fluorescence quenching, 3D fluorescence heat maps, and theoretical studies support energy transfer within the moieties. The systems are extremely resistant to UVC 254 nm germicidal light sources and present remarkable thermal stability at degradation temperatures exceeding 350 °C. Integrating these systems into perovskite solar cells results in outstanding power conversion efficiency (PCE), with TM-02-based devices exhibiting a PCE of 20.26%. The devices base on TM-01, TM-03, and TM-04 achieve PCE values of 16.98%, 17.58%, and 18.80%, respectively. The long-term stability of these devices is measured for 600 h, with initial efficiency retention between 94% and 86%. The TM-04-based device presents noticeable stability of 94%, better than the reference polymer PTAA with 91%. These findings highlight the exciting potential of dumbbell-shaped systems based on PAHs-BODIPY-triarylamine derivatives for next-generation photovoltaics.     

HCV/HGV coinfection and cryoglobulinemia

OBJECTIVE: To determine the rates of spontaneous pregnancies among women whose infertile male partners had sperm surface antibodies. DESIGN: Retrospective analysis. SETTING: Infertility clinic of a university referral center. PATIENT(S): One hundred fifty-seven infertile couples; the male partner had IgA and/or IgG sperm surface antibody concentrations of >10%. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Spontaneous pregnancy rates (PRs) over 6 years. RESULT(S): Spontaneous PRs correlated negatively with antibody concentrations. CONCLUSION(S): Although the chance of spontaneous pregnancy among women whose partners had sperm antibody concentrations of <50% was good, intracytoplasmic sperm injection should be recommended to patients with concentrations of >90%.     

Nationwide survey of fluoroscopy: radiation dose and image quality

PURPOSE: To determine the average abdominal entrance air kerma, low-contrast sensitivity, and spatial resolution in upper gastrointestinal tract fluoroscopy in the United States. MATERIALS AND METHODS: A random sample of fluoroscopic facilities was selected to be surveyed for the Nationwide Evaluation of X-ray Trends program. Measurements were performed by using a newly developed fluoroscopic phantom. The surveys were conducted by state radiation control personnel. RESULTS: Average air kerma rates 1 cm above the tabletop, free in air, were 43 mGy/min (n = 340). The rate increased to 64 mGy/min when a 1.6-mm-thick copper filter, which simulated the use of barium contrast medium, was added to increase attenuation. The average entrance air kerma, free in air, for radiographs was 3.4 mGy, and an average of 12 radiographs were obtained per examination. Of 352 facilities surveyed, 306 (87%) were able to resolve wire mesh with 20 or more lines per inch. Of 339 facilities for which percentage contrast could be calculated, 192 (57%) had minimum percentage contrast values of 4% or more. CONCLUSION: Spatial resolution for fluoroscopy is adequate for most of the facilities surveyed, but a substantial proportion of facilities could not visualize low-contrast test objects, which strongly suggests image quality problems.     

Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma

Urocanic acid (UCA) is a major chromophore for ultraviolet (UV) radiation in the skin. On UV exposure, the naturally occurring trans-isomer converts to the cis-isomer in a dose-dependent manner. Accumulating evidence indicates that cis-UCA acts as an initiator of the UV-induced suppression of certain skin immune functions. This immunomodulation is recognized as an important factor in the development of skin cancer. In this study, pigmentation and UCA isomers were measured in 29 patients with previous basal cell carcinoma (BCC), 23 patients with previous cutaneous malignant melanoma (MM), and 32 healthy controls. Measurements were performed on UV-exposed (forehead, upper back) and UV non-exposed (buttock) skin. No significant differences in pigmentation percentage, total UCA concentration, relative (%) or absolute (nmol/cm2) cis-UCA concentration were observed between the groups in any of the body sites studied. The net production of cis-UCA after irradiation with a single test UV dose was evaluated. The relative production of cis-UCA following irradiation was significantly higher in both cancer groups when compared with the control group, while no significant difference was found between the BCC and the MM patients.     

Retinal degeneration in the rd mouse in the absence of c-fos

PURPOSE: Apoptosis is the final common death pathway of photoreceptors in light-induced retinal degeneration and in several animal models for retinal dystrophy. To date, little is known about gene regulation of apoptosis in the retina. The expression of the immediate early gene c-fos is upregulated concomitant with apoptosis in light-induced photoreceptor degeneration and in the rd mouse, an animal model for inherited retinal degeneration. In a recent study it was shown that c-Fos is essential for light-induced apoptosis of photoreceptors in vivo. To determine whether c-Fos is also involved in the apoptotic pathway of inherited retinal degeneration, rd/rd, c-fos -/- double-mutant mice have been generated. METHODS: Double-mutant mice (rd/rd, c-fos -/-) were crossbred from c-fos+/- mice and rd/rd mice. Their genotype was determined by polymerase chain reaction analysis of genomic DNA. Wild-type control mice and homozygous rd mice were killed at 2-day intervals from postnatal day (P)9 through P21. Double-mutant mice were killed at postnatal days P9, P11, P13, P15, and P21. To determine levels of apoptosis in the retina, eyes were enucleated and processed for light microscopy and in situ nick-end labeling. Total retinal DNA was extracted from isolated retinas for DNA fragmentation analysis. RESULTS: Morphologic, histochemical, and biochemical analyses showed that the time course of apoptosis and the outcome of photoreceptor degeneration in rd/rd, c-fos-/- double-mutant mice was indistinguishable from that in rd mice carrying functional c-fos. CONCLUSIONS: These data suggest that in contrast to its role in light-induced photoreceptor degeneration, c-Fos is not essential for apoptosis in the rd mouse.     

Cytosolic enzymes with a mitochondrial ancestry from the anaerobic chytrid Piromyces sp. E2

The anaerobic chytrid Piromyces sp. E2 lacks mitochondria, but contains hydrogen-producing organelles, the hydrogenosomes. We are interested in how the adaptation to anaerobiosis influenced enzyme compartmentalization in this organism. Random sequencing of a cDNA library from Piromyces sp. E2 resulted in the isolation of cDNAs encoding malate dehydrogenase, aconitase and acetohydroxyacid reductoisomerase. Phylogenetic analysis of the deduced amino acid sequences revealed that they are closely related to their mitochondrial homologues from aerobic eukaryotes. However, the deduced sequences lack N-terminal extensions, which function as mitochondrial leader sequences in the corresponding mitochondrial enzymes from aerobic eukaryotes. Subcellular fractionation and enzyme assays confirmed that the corresponding enzymes are located in the cytosol. As anaerobic chytrids evolved from aerobic, mitochondria-bearing ancestors, we suggest that, in the course of the adaptation from an aerobic to an anaerobic lifestyle, mitochondrial enzymes were retargeted to the cytosol with the concomitant loss of their N-terminal leader sequences.