β1- and β3-adrenoceptors mediate relaxation in ovine trachealis smooth muscle

1 Isoprenaline (non-selective) and noradrenaline (β₁-selective) concentration-dependently relaxed ovine tracheal strips precontracted with carbachol. The pD₂ values were 7.07 ± 0.08 and 6.13 ± 0.10 for isoprenaline and noradrenaline, respectively. In the same preparation, salbutamol either produced weak relaxation or in some cases, contractile responses indicating the presence of very little or no β₂-adrenoceptors in this preparation. 2 Isoprenaline-and noradrenaline-induced relaxations were antagonized by propranolol and atenolol with pA₂ values in the range reported in the literature for an action on β₁-adrenoceptors. ICI 118551 also antagonized isoprenaline- and noradrenaline-induced relaxation but at concentrations much higher than are required to block β₂-adrenoceptors, confirming that β₂-adrenoceptors do not contribute significantly to these responses. 3 The selective β₃-adrenoceptor agonist, BRL 37344A produced concentration-dependent relaxation of tracheal strips. BRL 37344A was a full agonist producing 100% relaxation of carbachol-induced tone. BRL 37344A-induced relaxation was weakly antagonized by propranolol confirming an action, mainly, on β₃-adrenoceptors. Cyanopindolol antagonized isoprenaline-induced relaxation (in the presence of propranolol, 10^??7 m ) with a pA₂ value of 8.06 ± 0.24. 4 It was therefore concluded that β₁- and β₃-adrenoceptors mediated agonist-induced relaxation in sheep tracheal strips.     

CHANGES IN THE CONTENT OF DOPAMINE AND ITS METABOLITES IN THE BASAL GANGLIA FOLLOWING RIGHT MIDDLE CEREBRAL ARTERY OCCLUSION AND REFLOW IN MONKEYS

Focal ischaemia was produced experimentally in Macaca radiata monkeys by occlusion of middle cerebral artery (MCA). There was a lowering of the dopamine (DA) content of basal ganglia after 4 and 12 h of occlusion. DA content was restored to normal in basal ganglia after restoration of blood flow. With the progress of time the DA content was increased above that of sham controls. Changes were also observed in the non-occluded left basal ganglia. The homovanillic acid (HVA) content was decreased significantly at 12 h after occlusion. After the onset of reflow, the HVA content of the right basal ganglia was higher than that of sham controls. The 3,4 dihydroxyphenylacetic acid (DOPAC) content of right basal ganglia was significantly decreased after 12 h occlusion. Reflow restored the level of DOPAC to normal within 1 h after removal of clip. Discrete changes were also observed in the left basal ganglia at some of the time intervals.     

Metallothionein levels in liver and kidney of Canadians--a potential indicator of environmental exposure to cadmium

Liver and kidney cortex samples were obtained from 89 human autopsies for the determination of metallothionein (MT), cadmium (Cd), zinc (Zn), and copper (Cu). An age-dependent increase of Cd, Zn, and Cd/Zn was observed in the kidney; increases peaked at mid-age and were followed by a decline. Cadmium was present at a low constant level in the liver at all ages. The mean concentrations of Cd and Zn were 18.0 and 40.1 micrograms/g wet weight, respectively, in the kidney, and for the liver the values for Cd and Zn were 2.0 and 79.0 micrograms/g wet weight, respectively. A positive linear relationship was observed between Cd or Zn and MT in the kidney and between Zn and MT in the liver. No other correlation was found between Cu and MT in either organs. Similar values were obtained for MT when estimated by Ag-hem and Cd-hem methods.     

Urapidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension

Urapidil is a postsynaptic alpha 1-adrenoceptor antagonist with a pharmacodynamic profile similar to prazosin. Unlike prazosin, however, urapidil also has some central activity which may explain the apparent improved tolerability of urapidil, including the absence of first-dose syncope. In clinical trials urapidil therapy resulted in significant reductions in blood pressure in patients with mild to severe essential hypertension, with little influence on heart rate. It is an effective antihypertensive when administered as monotherapy or in combination with beta-blockers and thiazide diuretics. In the few patients with cardiac dysfunction who have been studied to date, urapidil has improved myocardial oxygen consumption, systemic vascular resistance, left ventricular function, cardiac output and pulmonary capillary wedge pressure; however, further study is needed to assess the full therapeutic potential of urapidil in these patients. Urapidil has also been used successfully in the treatment of hypertensive emergencies, including eclampsia and pre-eclampsia, hypertensive crisis and hypertension occurring during general and cardiac surgery, rapidly lowering blood pressure without altering heart rate. Urapidil does not affect lipid or glucose metabolism, nor does it impair renal function. In addition, urapidil may be beneficial to patients with pulmonary hypertension, in whom it dilates pulmonary vascular beds to a greater extent than systemic vasculature, although therapeutic trials have not examined this effect. The most common adverse effects associated with urapidil therapy are dizziness, nausea, headache, fatigue and palpitations; however, these tend to be mild and transient and usually do not require discontinuation of treatment. Thus, urapidil offers a useful alternative to currently available drugs for the treatment of mild to severe hypertension, either as monotherapy or in combination with other antihypertensive drugs.     

Acid glycosidase and arylsulfatase activities of human cerebrospinal fluid as measured by concanavalin A-sepharose affinity chromatography.

An affinity chromatographic method using concanavalin A-Sepharose is described for the determination of N-acetyl-beta-D-glucosaminidase, arylsulfatase. alpha-L-Fucosidase and alpha-D-mannosidase activities in the human cerebrospinal fluid. By this method (starting with 12 to 20 ml samples of cerebrospinal fluid) the above enzymes could be obtained in a concentrated form and their activities could be determined within incubation periods of 30 min to 1 h under the assay conditions described. The pH optima of the enzymes were in the range of pH 4 to 5. About 80% of the total cerebrospinal fluid N-acetyl-beta-D-glucosaminidase was found to be the A form by DEAE-Sephadex A-50 chromatography. About 60% of the total arylsulfatase was also found to be the A form. Determination of these enzyme activities in a few samples of human cerebrospinal fluid indicated a rough proportionality between the enzyme activities and the protein concentration in the cerebrospinal fluid.     

Global Budget Revenue on a Single Institution's Costs and Outcomes in Patients Undergoing Total Hip Arthroplasty

Background

The state of Maryland was granted a waiver by the Center for Medicare and Medicaid Services to implement a Global Budget Revenue (GBR) reimbursement model. This study aims to compare (1) costs of inpatient hospital stays; (2) postacute care costs; (3) lengths of stay (LOS); and (4) discharge disposition who underwent primary total hip arthroplasty at a single Maryland-based orthopedic institution before and after the implementation of GBR.

Most patients are eligible for an alternative to conventional whole breast irradiation for early‐stage breast cancer: A National Cancer Database Analysis

We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast‐conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I‐III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET‐alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET‐alone based on the CALGB 9343/PRIME‐II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC‐ESTRO trial/ASTRO guidelines/ABS guidelines/GEC‐ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET‐alone. This analysis shows that a large proportion of patients with node‐negative breast cancer are eligible for HFRT, APBI and/or ET‐alone after breast‐conserving surgery.     

Evaluation of Different Screening Tools for Predicting Femoral Neck Osteoporosis in Rural South Indian Postmenopausal Women

The measurement of bone mineral density by dual-energy X-ray absorptiometry scan is the “gold standard” for the diagnosis of osteoporosis, which has limited availability in many parts of India. This study was done to assess the diagnostic performance of 6 internationally validated tools (Simple Calculated Osteoporosis Risk Estimation [SCORE], age, bulk, one or never estrogen [ABONE], Osteoporosis Risk Assessment Instrument [ORAI] and Osteoporosis Self-Assessment Tool for Asians [OSTA], Fracture Risk Assessment Tool [FRAX®], and calcaneal quantitative ultrasound [QUS]) for the diagnosis of osteoporosis at the femoral neck (FN). This was a cross-sectional study conducted in 2108 ambulatory South Indian rural postmenopausal women who were assessed with SCORE, ABONE, ORAI, OSTA, and FRAX® tools. QUS was performed in 850 subjects. Bone mineral density was estimated by dual-energy X-ray absorptiometry scan at the FN, and sensitivity and specificity were calculated for all tools for predicting FN osteoporosis. The receiver operating characteristic curve was constructed for each tool and the area under the curve (AUC) was calculated. FN osteoporosis was seen in 27%. The sensitivities of SCORE, ABONE, OSTA, ORAI, FRAX®, and QUS were 91.3%, 91.0%, 88.5%, 81.0%, 72.7%, and 81.9%, and the specificities were 36.0%, 33.5%, 41.7%, 52.0%, 60.5%, and 50.3%, respectively, for the FN osteoporosis. When the receiver operating characteristics were constructed, the AUC was good only for SCORE (0.806), and the performance of the rest was under fair category (0.713–0.766). In our large cohort of rural postmenopausal women, the SCORE screening tool was found to be useful with good sensitivity and good AUC for predicting FN osteoporosis. Thus, this tool may be used in resource-limited countries to screen the population at risk and to enable treating physicians to make appropriate management decisions.     

Properties of IncP-2 plasmids of Pseudomonas spp.

Thirty IncP-2 R plasmids from isolates of Pseudomonas spp. of diverse geographical origins were examined for the production of resistance properties. All the plasmids determined resistance to tellurite and all inhibited the propagation of certain DNA phages, although several patterns of phage inhibition were detected. Of the 30 plasmids, 29 determined resistance to streptomycin, 28 determined resistance to mercuric ion, and 24 determined resistance to sulfonamide. Resistance to other antibiotics, to compounds of arsenic, boron, or chromium, and to UV irradiation was less common. The degradative plasmid CAM also belonged to this group. When CAM was introduced into recipients carrying an IncP-2 R plasmid, recombinant plasmids were often formed in which antibiotic resistance and the ability to grow on camphor were transferred together to further recipients or were lost together in a strain in which IncP-2 plasmids were unstable. Such hybrid plasmid formation was rec dependent. CAM and other IncP-2 plasmids that determine UV light resistance demonstrated UV-enhanced, nonpolarized transfer of the Pseudomonas aeruginosa chromosome. By agarose gel electrophoresis, all IncP-2 R plasmids and CAM were ca. 300 X 10(6) in molecular weight.