Effect of triiodothyronine administration in experimental myocardial injury

Twelve healthy pigs were subjected to a 20-min, period of regional myocardial ischemia by snaring the left anterior descending coronary artery (LAD) between its first and second diagonal branches. The resulting myocardial injury caused significant acute hemodynamic impairments. Cardiac index declined significantly during reperfusion interval and returned to preischemic level by postoperative day 7. Plasma total triiodothyronine (TT3), free triiodothyronine (FT3) and free fatty acid (FFA) decreased gradually and reached the nadir at 6 h after LAD occlusion. In contrast, plasma reverse triiodothyronine (rT3) increased progressively after LAD occlusion and reperfusion. To investigate the effect of T3 on ischemic myocardium, T3 (0.2 microgram/kg/dose; n = 5) or saline (placebo; n = 6) was administered immediately, 30 min, 60 min, 90 min, and 120 min after reperfusion. Plasma TT3 and FT3 increased dramatically after triiodothyronine supplement but declined to presichemic level at six h after LAD occlusion. The pigs treated with T3 demonstrated a rapid improvement in cardiac index over the reperfusion interval, whereas cardiac index in the placebo group remained depressed. Myocardial oxygen consumption estimated by rate pressure product showed no difference between placebo and T3-treated groups. Oxygen extraction as O2 saturation difference between aorta and coronary sinus was less in T3-treated group. Nine pigs (four in the T3-treated group and five in the placebo group) were subjected to euthanasia with hypertonic KCl solution on postoperative day 7. Myocardial infarct size determined by triphenyltetrazolium chloride (TTC) tissue enzyme staining technique was not significantly different between T3-treated and placebo groups. We concluded that this animal model is a useful model of myocardial injury simulating "euthyroid sick syndrome" as seen in patients with cardiopulmonary bypass, and T3 supplementation after reperfusion significantly enhanced postischemic left ventricular functional recovery but did not affect myocardial oxygen consumption and myocardial infarct size.     

Maternal and neonatal plasma inorganic fluoride levels after methoxyflurane analgesia for labor and delivery

At the time of the experiment, lean animals weighed 226-235 gm and the fatty rats 330-440 gm. On Day 5 after castration, rats received injections of estradiol-17beta (E2) for a 3-day period. Doses were .01-100 mcg/100 gm of body weight. Radioiodine uptake was determined by injecting 50 microCi of iodine-125 ip 24 hours before sacrifice. Beginning 12 hours after the last dose of E2, pairs of rats including a fatty and lean rat were sacrificed until all had been killed. Ovaries (at castration or autopsy), pituitary, and thyroid were removed and weighed. Uteri in obese rats were significantly smaller than in lean rats. There was a close dose-response relationship between E2 and the weight of the uteri; this was more marked in the obese rats. The radioactivity of the thyroid was increased more in the lean rats. Fatty rats ate more food than lean rats. The highest dose of E2 did not increase the food intake of obese rats but did increase that of the lean animals. It is concluded that the small uteri in the fatty rats may be due to decreased estrogenization and that this may also partly account for the small pituitary and low thyroid uptake of radioiodine.     

Heteroaromatic analogs of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909) as high-affinity dopamine reuptake inhibitors

A new series of heteroaromatic GBR 12935 [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine] (I) and GBR 12909 [1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine] (2) analogs was synthesized and evaluated as dopamine transporter (DAT) ligands. Analogs 5-16, in which the benzene ring in the phenylpropyl side chain of the GBR molecule had been replaced with a thiophene, furan, or pyridine ring, exhibited high affinity and selectivity for the DAT vs serotonin transporter (SERT) and stimulated locomotor activity in rats in a manner similar to the parent compound 2. In cocaine and food self-administration studies in rhesus monkeys, both thiophene-containing (6 and 8) and pyridine-containing (14 and 16) derivatives displayed potency comparable to 2 in decreasing the cocaine-maintained responding at the doses tested (0.8, 1.7, and 3 mg/kg). However, these compounds did not produce the degree of separation between food- and cocaine-maintained responding that was seen with 2. Among the bicyclic fused-ring congeners 17-38, the indole-containing analog of 2, 22, showed the greatest affinity for binding to the DAT, with IC50 = 0.7 nM, whereas the corresponding indole-containing derivative of 1, 21, displayed the highest selectivity (over 600-fold) at this site vs the SERT site.     

The Gag domain of the Gag-Pol fusion protein directs incorporation into the L-A double-stranded RNA viral particles in Saccharomyces cerevisiae

The L-A double-stranded RNA virus of yeast encodes its major coat protein, Gag, and a Gag-Pol fusion protein made by a -1 ribosomal frameshift, a coding strategy used by many retroviruses. We find that cells expressing only Gag from one plasmid and only Gag-Pol (in frame) from a separate plasmid can support the propagation of M1 double-stranded RNA, encoding the killer toxin. We use this system to separately investigate the functions of Gag and the Gag part of Gag-Pol. L-A contains two fusion protein molecules per particle, and although N-terminal acetylation of Gag is essential for viral assembly, it is completely dispensable for function of Gag-Pol. In general, the requirements on Gag for viral assembly and propagation are more stringent than on the Gag part of Gag-Pol. Finally, we directly show that it is Gag that instructs the incorporation of Gag-Pol into the viral particles.     

Conversion from phacoemulsification to extracapsular cataract extraction: incidence, risk factors, and visual outcome

PURPOSE: To evaluate the incidence, risk factors, and visual outcome in cases converted from phacoemulsification to routine extracapsular cataract extraction (ECCE). SETTING: Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. METHODS: A retrospective study was performed in 540 eyes that had clear corneal phacoemulsification performed by an experienced phacoemulsification surgeon. The cases in which phacoemulsification was initiated and then converted to ECCE were studied. The main parameters evaluated were the factors responsible for the conversion, corneal endothelial cell loss, and visual outcome. RESULTS: Twenty eyes (3.7%) required conversion to ECCE during phacoemulsification. Pupillary miosis (6 cases), posterior capsule rupture (5 cases), prolonged phaco time (4 cases), posterior extension of the capsulorhexis (2 cases), corneal thermal burn (1 case), subluxation of the lens (1 case), and malfunctioning of the ultrasonic handpiece (1 case) were the reasons for the conversion. The mean percentage of endothelial cell loss was 11.06% +/- 2.3 (SD); 18 cases (90.0%) achieved a visual acuity of 20/40 or better at 6 weeks. CONCLUSIONS: Intraoperative pupillary miosis, posterior capsule rupture, and very hard nuclear cataract causing prolonged phacoemulsification were the major risk factors for conversion to ECCE. Optimal preoperative preparation and prompt recognition of complications during phacoemulsification can lead to timely conversion to ECCE to achieve a good visual outcome.