The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Mesenteric and omental cysts: An ultrasonographic and clinical study of 15 patients

The clinical and ultrasonographic (US) features of 15 cases of mesenteric or omental cyst are herein described. This series included seven male and eight female patients, whose age ranged from 2–89 years. Correct clinical diagnosis was made in two children only, but preoperative US examination accurately demonstrated the lesion in 11 of 13 patients (85%). These cystic lesions usually had a thin wall, internal septations, and fluid content with sedimentation. Enteric duplication cysts had a relatively thick wall merging with the muscle layer of bowel loop, and multiloculation was noted mainly with cystic lymphangiomas or pseudocysts. The diagnostic and surgical management of these lesions are briefly reviewed and their US appearance is illustrated.     

Correlation between amount of retinal afferents to the pretectal nucleus of the optic tract and dorsal terminal accessory optic nucleus and performance of horizontal optokinetic reflex in rat.

Intraocular kainic acid injection in Long-Evans rats induces loss of retinal afferents to subcortical visual centers as assessed by the axoplasmic transport of [14C]valine. The optical terminal fields of the pretectal nucleus of the optic tract (NOT), superior colliculus and accessory optic system (AOS) nuclei appear particularly affected. Since NOT and the AOS dorsal terminal nucleus (DTN) represent the first relay station of the visuomotor pathway mediating horizontal optokinetic nystagmus (HOKR), we have studied the characteristics of HOKR after various degrees of retinal deafferentation of these nuclei induced by intraocular KA injection. Taking advantage of the arrangement of the primary optic projections to NOT-DTN, that in rats are almost entirely crossed, in each animal, monocular HOKR induced by stimulation of the injected eye was compared to monocular HOKR elicited by stimulation of the intact, ipsilateral eye. Following NOT-DTN optic denervation, HOKR gain always worsened, and in a way, that the greater the deficits of retinal afferents, the greater the HOKR inability to compensate for visual motion. Furthermore, for any given retinal denervation the higher the stimulus velocity, the greater the HOKR deficit. While the correlation between HOKR gain and the amount of retinal afferents to NOT-DTN would seem to indicate a functional homogeneity of the retinal ganglion cells sending axons to these nuclei, the finding that the extent of HOKR impairment also varied with velocity might not support the above view.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Cardiokymograph system with a capacitance transducer and its preliminary application in the measurement of heart wall movement

A novel cardiokymograph system is introduced. The new system features a capacitance transducer with increased sensitivity and can be used in multichannel measurements. The novelty of this technique is the injection of a current into the patient coupled with the use of a capacitive displacement transducer and the possibility of multichannel monitoring. It provides for the possibility of removing breath noise when some signal processing technique, such as adaptive filtering, is used. Further investigation is needed to demonstrate clinical significance and pathologies.     

Features of head injury in a developing country--Taiwan (1977-1987)

Certain features of head-injured patients admitted to the Chang Gung Memorial Hospital in Taiwan during the period 1977 to 1987 were reviewed. The most common causes of injury were motorcycle accidents (56.3%) and street accidents with pedestrian injury (29.47%). The age groups with the greatest incidence of injury were aged 16-20 years, 21-25 years, and 25-30 years. The pedestrian group involving the highest incidence of injury was less than 10 years of age. Overall mortality was 17.26%. The injured pedestrian group had the highest mortality (19.1%). Initial clinical assessment was recorded using the Glasgow Coma Scale. Head-injured patients with a GCS less than 8 had a mortality in the injured pedestrian group of 46%, whereas the mortality rate in the motorcycle accident group was 41%. Additional features studied were time of occurrence of injury and pattern of injury. Information gathered from this study would suggest the need to establish a Head Injury Prevention Program in Taiwan. This of course implies major cooperation among the providers of health care delivery, the medical profession, legislators, and the government at all levels.     

Intraoperative Remifentanil Infusion Does Not Increase Postoperative Opioid Consumption Compared with 70% Nitrous Oxide

Background: Remifentanil is commonly used to replace nitrous oxide in general anesthesia to avoid the side effects of the latter. However, there are reports that intraoperative remifentanil infusion can lead to acute opioid tolerance. In this study, the authors tried to determine the dose of remifentanil comparable in efficacy to 70% nitrous oxide and to evaluate its effect on postoperative pain and morphine consumption after colorectal surgery using isoflurane anesthesia.

Methods: Sixty adult patients undergoing open colorectal surgery were randomly assigned to receive either remifentanil or 70% nitrous oxide along with isoflurane anesthesia. After morphine analgesia titration in the postanesthesia care unit, patient-controlled analgesia was commenced. Morphine consumption and pain were scored at rest and during cough or movement for 24 h.

Results: The mean remifentanil infusion rate was 0.17 [mu]g [middle dot] kg-1 [middle dot] min-1. The median visual analog pain score on arrival in the postanesthesia care unit was 1 (0-10) in the nitrous oxide group and 3 (0-9) in the remifentanil group (P < 0.05). Otherwise, there was no difference in pain scores at 5, 10, and 15 min and no difference in the total morphine consumption during the stay in the postanesthesia care unit. The two groups had similar total morphine consumption in the first 24 h and pain scores at rest and during movement. The incidence of postoperative nausea and vomiting was 10% in both groups. There was no difference in the sedation scores.     

Application of a radiotelemetric system to evaluate the performance of enteric coated and plain aspirin tablets

The bioavailability of enteric coated and plain aspirin tablets was studied in four beagle dogs. Blood sampling for enteric coated tablets was planned with the aid of a radiotelemetric system. The release of aspirin from its dosage form was detected by monitoring the change in intestinal pH. Aspirin and salicylic acid levels in plasma obtained from the enteric coated dosage form exhibited familiar concentration versus time absorption profiles. Variation in the plasma concentrations of these two compounds within each dog studied (four runs each) was relatively small when time zero was adjusted to the commencement of tablet dissolution. The plasma levels obtained from plain aspirin (three runs each), however, show atypical absorption. The estimated absolute bioavailability was 0.432 +/- 0.0213 and 0.527 +/- 0.0260 for enteric coated and plain aspirin, respectively. Other pharmacokinetic parameters for these two dosage forms such as the highest observed plasma concentration (Cmax) (10.9 +/- 0.535 microgram/mL versus 13.6 +/- 1.88 micrograms/mL) and the time to reach Cmax (tmax) (26.6 +/- 1.94 min versus 31.0 +/- 7.04 min) agree well. The mean values for gastric emptying time, in vivo coating dissolution time, and in vivo disintegration/dissolution time of the tablet core for enteric coated aspirin are 48.7 +/- 7.23 min, 44.3 +/- 3.80 min, and 34.7 +/- 2.04 min, respectively.