Serine and d-serine position-1 substituted angiotensin II analogues Synthesis using new 2,3,5,6-tetrafluorophenyl active esters and biological activities

[Ser¹], ( 32 ), [d -Ser¹]- ( 29 ), [Ser¹, Leu⁸]- ( 31 ), and [d -Ser¹, Leu⁸] angiotensin II ( 30 ) were synthesized by a repetitive method in solution using new protected amino acid 2,3,5,6-tetrafluorophenyl active esters. 32 and 29 were agonists, and 31 and 30 were specific antagonists to angiotensin II (AII) receptors determined by the rabbit aortic strip (RAS) and rat blood pressure (RBP) assays. It was found that the hydroxymethyl side chains of serine and D-serine in position-l has an important influence on the agonistic activity of the analogues. The pressor activities of 32 and 29 were 129 and 314%, respectively, as potent as AII. On the other hand, 31 and 30 were effective in antagonizing the AII-induced contraction of RAS and rise in RBP.     

Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats

Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats.KATZ, G. V., RENNER, E. R., JR., AND TERHAAR, C. J. (1986).Fundam. Appl. Toxicol. 6, 498–505. Rats were exposed byinhalation, 6 hr/day, 5 days/week, to target vapor concentrationsof 2000, 1000, or 0 ppm of methyl isoamyl ketone (MIAK) for12 exposures spanning 16 days, and 2000, 1000, 200, or 0 ppmfor 69 exposures spanning 96 days. Body weights, hematology,and serum clinical chemistry determinations were comparableto controls in both inhalation studies. Clinical signs of toxicitywere lethargy and decreased aural response (2000 ppm, 2-weekstudy; 2000 and 1000 ppm, 90-day study) and nasal and eye irritation(2000 and 1000 ppm, 90-day study). In addition, the excretionof gel-like casts in seminal fluid was seen in males exposedto 2000 and 1000 ppm in both studies. increases in absoluteand relative liver and kidney weights were observed in bothsexes following exposure to 2000 and 1000 ppm in the 2-weekand 90-day studies. Liver weight increases were exposure dependentand in the 90-day study reflected hepatocyte hypertrophy observedon microscopic examination. Microscopic kidney changes werehyalin degeneration or hyalin droplet formation in males inthe 2-week (2000 and 1000 ppm) and 90-day (2000 ppm) studies;and minor to moderate regeneration of tubular epithelium (2000and 1000 ppm) in both studies. Minor tubular epithelium regenerationwas seen in females exposed to 2000 ppm for 90 days. The toxicityof MIAK following inhalation exposure was not as extensive orsevere as that resulting from a prior study in which male ratswere dosed orally with 2000 mg/kg/day (a dose comparable to2000 ppm) for 13 weeks. The 90-day inhalation exposure no-observed-effectlevel for toxicity was 200 ppm MIAK.     

The Effects of Coherin on Patients with Idiopathic Delayed Gastric Emptying

Ten patients with idiopathic delayed gastric emptying were studied in a randomized double-blind fashion to examine the effects of coherin versus placebo upon their symptoms and objective measurements of gastric emptying. The results showed no significant effect of coherin on either symptom scores or gamma camera ⁹⁹Technetium gastric emptying studies in this group of patients. There is a need to develop other agents in treatment of this poorly understood condition.     

Radiology of Skiing Injuries

Skiing is the fastest growing winter sport in Australia. This paper describes the radiological features of the common skiing injuries. It is based on the author's experience of having treated 6,050 such injuries. With the further expansion of skiing, it is important that medical practitioners at both the primary and specialist levels be familiar with the radiological features of this popular sport.     

Mitotic Indices of Human Bone Marrow Cells. I. Number and Cytologic Distribution of Mitoses

1. The diurnal variation of mitotic index of human bone marrow has beenstudied. A diurnal variation has not been demonstrated but remains subjectfor further study.

2. Data on the distribution of hone marrow mitoses on cell lines and maturation stages are presented. From this and the gross mitotic index of thebone marrow, the mitotic indices of various cell types are computed.

Submitted on December 12, 1961 Accepted on February 12, 1962     

Atrial Fibrosis Helps Select the Appropriate Patient and Strategy in Catheter Ablation of Atrial Fibrillation: A DE‐MRI Guided Approach

MRI for AF Patient Selection and Ablation Approach. Introduction: Left atrial (LA) fibrosis and ablation related scarring are major predictors of success in rhythm control of atrial fibrillation (AF). We used delayed enhancement MRI (DE‐MRI) to stratify AF patients based on pre‐ablation fibrosis and also to evaluate ablation‐induced scarring in order to identify predictors of a successful ablation. Methods and Results: One hundred and forty‐four patients were staged by percent of fibrosis quantified with DE‐MRI, relative to the LA wall volume: minimal or Utah stage 1; <5%, mild or Utah stage 2; 5–20%, moderate or Utah stage 3; 20–35%, and extensive or Utah stage 4; >35%. All patients underwent pulmonary vein (PV) isolation and posterior wall and septal debulking. Overall, LA scarring was quantified and PV antra were evaluated for circumferential scarring 3 months post ablation. LA scarring post ablation was comparable across the 4 stages. Most patients had either no (36.8%) or 1 PV (32.6%) antrum circumferentially scarred. Forty‐two patients (29%) had recurrent AF over 283 ± 167 days. No recurrences were noted in Utah stage 1. Recurrence was 28% in Utah stage 2, 35% in Utah stage 3, and 56% in Utah stage 4. Recurrence was predicted by circumferential PV scarring in Utah stage 2 and by overall LA wall scarring in Utah stage 3. No recurrence predictors were identified in Utah stage 4. Conclusions: Circumferential PV antral scarring predicts ablation success in mild LA fibrosis, while posterior wall and septal scarring is needed for moderate fibrosis. This may help select the proper candidate and strategy in catheter ablation of AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 16‐22, January 2011)