Purpose We evaluated the efficacy and safety of 2 doses of silodosin vs placebo in men with moderate to severe abacterial chronic prostatitis/chronic pelvic pain syndrome who had not been treated ...previously with α-blockers for chronic prostatitis/chronic pelvic pain syndrome. Materials and Methods In this multicenter, randomized, double-blind, phase II study, men 18 years old or older with chronic prostatitis/chronic pelvic pain syndrome, a total National Institutes of Health Chronic Prostatitis Symptom Index score of 15 or greater and a National Institutes of Health Chronic Prostatitis Symptom Index pain score of 8 or greater received 4 or 8 mg silodosin, or placebo once daily for 12 weeks. The primary efficacy end point was change from baseline to week 12 in National Institutes of Health Chronic Prostatitis Symptom Index total score. Results Of 151 patients (mean age 48 years) 52 received 4 mg silodosin, 45 received 8 mg silodosin and 54 received placebo. Silodosin 4 mg was associated with a significant decrease in total National Institutes of Health Chronic Prostatitis Symptom Index score (mean ± SD change –12.1 ± 9.3) vs placebo (–8.5 ± 7.2, p = 0.0224), including a decrease in urinary symptom (−2.2 ± 2.7, placebo −1.3 ± 3.0, p = 0.0102) and quality of life (−4.1 ± 3.1, placebo −2.7 ± 2.5, p = 0.0099) subscores. The 4 mg dose of silodosin also significantly increased Medical Outcomes Study Short Form 12 physical component scores (4.2 ± 8.1, placebo 1.7 ± 9.0, p = 0.0492). During global response assessment 56% of patients receiving 4 mg silodosin vs 29% receiving placebo reported moderate or marked improvement (p = 0.0069). Increasing the dose of silodosin to 8 mg resulted in no incremental treatment effects. Conclusions Silodosin 4 mg relieved symptoms and improved quality of life in men with chronic prostatitis/chronic pelvic pain syndrome but its efficacy requires confirmation in additional studies.
A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification ...system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques. The isolated metabolites recovered from the NMR experiments were then submitted directly to an in vitro FIXa enzymatic assay. The order of the metabolites’ binding affinity to the Factor IXa protein from the ALIS assay was completely consistent with the enzymatic assay results. This work showcases an innovative and efficient approach to uncover structure–activity relationships (SARs) and guide drug design via microisolation–structural characterization and ALIS capabilities.
Although the number of U.S. hospitals offering an acute pain service (APS) is increasing, the typical structure remains unknown. This survey was undertaken to describe the structure and function of ...the APS in U.S. hospitals only. We contacted 200 non-teaching and 101 teaching U.S. hospitals. The person in charge of postoperative pain management completed and returned the survey. Seventy-four percent of responding hospitals had an organized APS. An APS was significantly more formally organized in academic/teaching hospitals when compared to non-teaching hospitals. Pain assessments included “pain at rest” (97%), “pain on activity” (63%), and reassessment after pain therapy intervention (88.8%). Responding hospitals utilized postoperative pain protocols significantly more commonly in teaching hospitals when compared to non-teaching and VA hospitals. Intravenous patient controlled analgesia (IV-PCA) was managed most commonly by surgeons (75%), while epidural analgesia and peripheral nerve block infusions were exclusively managed by anesthesiologists. For improved analgesia, 62% allowed RNs to adjust the IV-PCA settings within set parameters, 43% allowed RN adjustment of epidural infusion rates, and 21% allowed RN adjustment of peripheral nerve catheter local anesthetic infusion rates.
Recent publications suggest that target end-tidal carbon dioxide concentrations should be higher than values currently considered as acceptable. This paper presents evidence that end-tidal carbon ...dioxide values higher than concentrations that are currently targeted result in improved patient outcomes and are associated with a reduced incidence of postoperative complications.
In this study cauda epididymal spermatozoa of rats maintained on a selenium-deficient diet for 5 and 7 months exhibited an array of flagellar defects. Spermatids and spermatozoa were analyzed by ...light and electron microscopy to define the appearance of flagellar abnormalities during spermiogenesis and post-testicular sperm development. Late spermatids of selenium-deficient rats displayed normal structural organization of the flagellar plasma membrane, axoneme, outer dense fibers, fibrous sheath and annulus, but they exhibited a premature termination of the mitochondrial sheath. A comparison of late spermatids and caput epididymal spermatozoa revealed that a late step in flagellar differentiation was the structural remodeling of the annulus and its accompanying fusion with both the fibrous sheath and the mitochondrial sheath. In selenium-deficient animals, however, the annulus failed to fuse with the mitochondrial sheath, generating an apparent weak point in the flagellum. After epididymal passage, cauda epididymal spermatozoa of selenium-deficient animals also exhibited extensive flagellar disorganization resulting from the apparent sliding and extrusion of specific outer dense fiber-doublet microtubule complexes from the proximal and the distal ends of the mitochondrial sheath and the accompanying loss of the midpiece plasma membrane. Only fiber complex number 4 was extruded proximally, whereas fibers 4, 5, 6 and 7 were extruded from the mitochondrial sheath-deficient posterior midpiece. Axonemal fibers 8, 9, 1, 2 and 3 retained their normal geometric relationships. These data suggest that the known loss of male fertility in selenium deficiency results from the sequential development of sperm defects expressed during both spermiogenesis and maturation in the epididymis.
Cardiopulmonary bypass induces an inflammatory state characterized by tumor necrosis factor-α release. Integrin CD11b is a neutrophil surface adhesive glycoprotein integrin that is rapidly and ...permanently unregulated by tumor necrosis factor-α exposure. The CD11b integrin is known to be the primary neutrophil integrin responsible for neutrophil lung and myocardial entrapment after cardiopulmonary bypass and subsequent reperfusion injury. Twenty-four adults admitted to the hospital for myocardial revascularization were equally randomized to one of three groups: group A (control), group B (methylprednisolone before cardiopulmonary bypass), and group C (low-dose aprotinin protocol). Blood was collected at three times: (1) baseline, (2) 50 minutes of cardiopulmonary bypass duration, and (3) 30 minutes after cardiopulmonary bypass termination. Neutrophil CD11b integrin expression was measured by fluorescence-activated cell sorter analysis and plasma tumor necrosis factor-αlevels measured by enzyme-linked immunosorbent assay. Group A demonstrated significant (
p < 0.05) increases in CD11b expression at times 2 and 3 when results were compared with those of the same group baseline and with those of groups B and C at similar times. No significant changes were noted between groups B and C at any time. Group A demonstrated a significant (
p < 0.05) increase in levels of tumor necrosis factor-α at time 3 when results were compared with those of the same group baseline and of groups B and C at the same time. No significant changes were noted between groups B and C at any time. These results demonstrate low-dose aprotinin has a similar antiinflammatory effect to that of methylprednisolone in blunting cardiopulmonary bypass–induced systemic tumor necrosis factor-α release and neutrophil integrin CD11b upregulation. (J T
HORAC C
ARDIOVASC S
URG 1995;110:1658-62)
Organ toxicity caused by poisons or drug therapy is diverse and may not be commonly encountered clinically. In general, commonly encountered conditions caused by drug/toxin pharmacology can be ...classified into 7 categories by shared mechanisms of organ injury. This review of drug/toxin-induced injury discusses drug or toxin-induced pathology that the clinician may encounter and therapeutic approaches to these syndromes.
Living mulch (LM) production systems are gaining traction as an alternative to the use of annual cover crops in the southeastern United States, warranting research on the viability and functionality ...of this system. Our objective was to evaluate the benefits of LM in corn silage and grain production and to evaluate the potential of LM grazing during the corn (Zea Mays L.) growing season. The experiment was conducted in Spring Hill, TN in 2020 and 2021 and consisted of two mulch species, white clover (WC) (Trifolium repens L.) and a mixture of crimson clover (Trifolium incarnatum L.) and cereal rye (CCCR) (Secale cereale L.). Cull cows were used for the grazing periods (4 weeks before planting and after the harvest of corn). The study evaluated the botanical composition, mulch mass, nutritive value, corn silage and grain production, and cow average daily weight gain (ADG). The WC treatment had a greater weed control than CCCR. In 2020, when differences in mulch mass were observed, CCCR had greater mass than WC mass due to the weed presence. Meanwhile, in 2021, the mulch mass did not differ between WC and CCCR, with both treatments showing less mass in spring and early summer. Grain production was 30% less than silage in 2020 and 90% less in 2021. The ADG was only observed for WC (0.5 kg−1) paddocks. It was concluded that WC as LM has greater corn production than CCCR treatments. The LM for grazing is a beneficial strategy if feeding costs are greater than $2.22 head day−1.
Core Ideas
White clover living mulch improves corn production systems.
White clover living mulch promotes weed suppression in corn production.
White clover enhances the average daily weight gain of cows.
Core Ideas
Cowpea is well‐adapted for organic systems but cultivar differences are not well explored.
Cultivars differed widely in biomass, stand density/seedling disease, and quality.
Cowpea ...cultivars examined did not respond to P fertilizer in low soil P status soils.
Cowpea (Vigna unguiculata Walp.) is a warm‐season legume with many traits that make it an attractive forage or cover crop for organic systems. Eight cowpea cultivars were evaluated under organic management at two locations for stand establishment, forage yield and quality, and weed biomass. The experiment was arranged in a strip‐plot design with two P fertilization rates, amended (45 kg P ha−1) and unamended, to evaluate responsiveness to P fertilization in low native soil P status (Mehlich‐1 P < 10 mg P kg−1). Cowpea was seeded at 209,000 seeds ha−1. Stand density at 4 wk indicated the highest plant populations from cultivar Iron & Clay (166,000 plants ha−1), intermediate populations from Speckled Purple Hull, IT82E‐18, and IT85‐867‐5F (143,000 to 138,000 plants ha−1), and lowest populations from IAR7/8‐5‐4‐1, Coronet, KV×396, and IT97K‐556‐4 (128,000 to 118,000 plants ha−1) primarily due to presence of seedling diseases caused by Fusarium spp. Speckled Purple Hull and Iron & Clay had the highest total yield (4922 and 4623 kg ha−1, respectively). Yield was lowest from IT82E‐18, Coronet and IAR7/8‐5‐4‐1 (1958–2585 kg ha−1), likely due to low plant populations (IAR7/8‐5‐4‐1, Coronet) and higher weed biomass than cowpea biomass (IAR7/8‐5‐4‐1, Coronet, IT82E‐18). There was no statistical difference in cowpea biomass between unamended (3422 kg ha−1) and P‐amended plots (3150 kg ha−1), or differences in cowpea tissue P concentration. High forage quality values of top‐performing cultivars suggest that they are well adapted to address low summer forage quality in applicable forage systems.
Atheroscierosis is a vascular injury characterized by elevated tissue levels of tumor necrosis factor-
α (TNF-
α), increased expression of endothelial cell adhesion molecules, and vascular wall ...inflammatory cell infiltration. Foam cells are associated with atherosclerotic plaque material, and low density lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde (MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MDA-modified LDL, are present in atherosclerotic human vascular tissue. Acetaldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to produce an antigenically distinct protein adduct, termed the MAA adduct. This study demonstrates that proteins modified in the presence of high concentrations of MDA can produce MAA-modified proteins in vitro. In addition, MAA adducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-
α, and cause rHEC upregulation of endothelial adhesion molecule expression, including ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-
α concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atherosclerosis. These data further suggest that previous studies demonstrating MDA modified protein in atherosclerotic plaque may in fact have MAA modified proteins associated with them.
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