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Day-old White Leghorn cockerels were fed graded levels (10, 50, 100, and 1000 ppm) of pentachloronitrobenzene (PCNB) containing pentachlorobenzene (PCB), tetrachloronitrobenzene (TCNB), and hexachlorobenzene (HCB) at trace contaminants, for 12 weeks. Bioaccumulation of PCNB and its metabolites in tissues does not appear to occur to any major extent. The contaminants of PCNB, HCB, and PCB were found to accumulate to a greater degree in adipose tissue than does PCNB itself. TCNB was also detected in adipose tissue and in trace amounts in other tissues. PCNB accumulated to the highest concentration in body fat followed by gizzard and kidney. Only traces of PCNB were found in heart, liver, leg, and heart muscle. Metabolites, pentachloroaniline (PCA), and pentachlorphenylmethylsulfide (PCMS) were found in only trace quantities following the feeding of 1000 ppm PCNB. Half-life values for the depletion of the contaminants of PCNB, PCB, and HCB were determined in adipose tissue of cockerels; values as high as 53 and 95 days were found for PCB and HCB, respectively.

Exercise to exhaustion was associated with the appearance in plasma of plasminogen activator (PA) in several mol wt forms, as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with zymography. A number of active bands, all immunologically identified as tissue-type PA (t-PA), were observed. The major form had an apparent mol wt of approximately 60,000 and is due to free t-PA. The other strong bands had apparent mol wts of approximately 110,000 and 180,000. The 110,000 band, also present in pre-exercise samples, represents t-PA complexed with its major inhibitor (PAI-1), and the 180,000 band is due to t-PA complexed with C1 inhibitor. The released forms of t-PA were cleared rapidly after cessation of exercise at exhaustion. Urokinase-type PA (u-PA) activity was also identified in pre- and postexercise samples at an apparent mol wt of approximately 50,000. This is consistent with its being free u-PA; no complexed forms of u-PA were observed. Qualitatively similar changes in plasma PA were observed after venous occlusion. Small quantities of plasmin were generated after strenuous exercise, as observed by detection of plasmin-alpha 2-antiplasmin complex by two-dimensional immunoelectrophoresis in three of five subjects. This complex was cleared rapidly after cessation of exercise. Plasmin-alpha 2-antiplasmin complex was not detected in any of the subjects after venous occlusion.

A life-long bleeding disorder is described, characterized by hemorrhage occurring after surgery, injury, or dental extraction, and finally by spontaneous intracerebral bleeding. No abnormality of platelet function or plasma coagulation was demonstrable, but grossly enhanced overall fibrinolytic activity was present. The patient had, additionally, a hyperlipidemia with gross arterial atheroma and a family history of myocardial infarction but not of any hemorrhagic disorder. Laboratory studies led to the conclusion that the enhanced fibrinolysis was due to consistently greatly raised levels of a plasma plasminogen activator physically and immunologically related to that in human tissues and blood vessel endothelium. No deficiency of any known inhibitor of fibrinolysis was detected. Free plasmin was not detectable in functional assays but continuous intravascular plasmin generation clearly occurred as evidenced by presence of plasmin-alpha 2-antiplasmin complexes and of fibrin/fibrinogen-related antigens. Excessive production of plasminogen activator appeared to have occurred throughout life and to be independent of the hyperlipidemia. The pathologically increased fibrinolytic activity may have accounted for the complete absence of detectable thrombotic vascular occlusion at autopsy despite extensive arterial disease with severe narrowing of coronary and cerebral arteries.

Measurements of the principal protease inhibitors were carried out in patients with two types of chronic liver disease: alcoholic cirrhosis and primary biliary cirrhosis. Measurement of the two major protease inhibitors operative in the haemostatic mechanism--that is, antithrombin III and alpha 2-antiplasmin--showed significantly reduced levels in the alcoholic cirrhosis group, who satisfied clinical and biochemical criteria of impaired hepatocellular function, but not in the primary biliary cirrhosis group, who had relatively good preservation of hepatocellular function. Significant correlation of levels of both these major protease inhibitors with the serum albumin concentration was also found. No evidence of disseminated intravascular coagulation was detected, and therefore failure of synthesis by the liver is the likely explanation of the low levels noted.

Groups of fentanyl-droperidol-pentobarbital-anesthetized dogs (n = 6 dogs/group) were given IV saline solution (control group), graded doses of naloxone (0.01, 0.1, 1.0, 10.0 mg/kg) or fixed doses of 4-aminopyridine (0.5 mg/kg), yohimbine (0.4 mg/kg), or doxapram (5.0 mg/kg) alone or in combination with a fixed dose of naloxone (1.0 mg/kg). The purpose was to determine which drug or drug combination would produce arousal most quickly without producing obvious undesirable side effects. Control group mean arousal time, mean walk time and mean duration of postarousal sedation were 66.1 minutes, 112.4 minutes and 5.6 hours, respectively. Naloxone (1.0 mg/kg) decreased mean arousal time to 10.8 minutes without significantly decreasing mean walk time or mean duration of postarousal sedation. The combination of naloxone + doxapram decreased mean arousal time and mean walk time to 1.0 minute and 57.1 minutes, respectively, without decreasing mean duration of postarousal sedation. In all groups, emergence from anesthesia was smooth. Relapses or undesirable side effects were not observed. Naloxone + doxapram is superior to naloxone alone for arousal of fentanyl-droperidol-pentobarbital-anesthetized dogs.

Twenty-four crossbred steers (4 groups of 6 steers each) were injected IM with a standard dosage range of xylazine hydrochloride (0.2 to 0.3 mg/kg of body weight). When the steers were maximally sedated, group I (control group) were given isotonic saline solution (1 ml, IV), group II were given 4-aminopyridine (4-AP, 0.3 mg/kg) IV, group III were given yohimbine hydrochloride (0.125 mg/kg) IV, and group IV were given 4-AP (0.3 mg/kg) plus yohimbine hydrochloride (0.125 mg/kg) IV. The 4-AP decreased mean standing time (MST; time until animal could stand unaided) from 94.3 minutes (control) to 13.4 minutes. Yohimbine decreased MST to 27 minutes. The combination of 4-AP + yohimbine decreased MST to 7.4 minutes. Mean total recovery time (MTRT; time from xylazine injection until normal behavior, including eating and drinking) was not significantly (P = greater than 0.05) decreased from control values by any of the antagonists tested. The combination of 4-AP + yohimbine decreased MST in animals given a 3X overdose of xylazine (0.6 mg/kg) from 124 minutes (control) to 30.3 min. The MTRT was not significantly (P greater than 0.05) decreased from control values. Two animals given a 5X overdose of xylazine (1 mg/kg) and then given 4-AP + yohimbine had a MST of 32.5 minutes and a MTRT of 3.7 hours. The combination of 4-AP + yohimbine produced marked antagonism of xylazine sedation in cattle. The combination of antagonists may prove to be useful for the arousal of animals sedated with xylazine alone or with a combination of sedatives including xylazine.

The alpha 2-adrenergic agonist clonidine hydrochloride, the serotonin agonist quipazine maleate, and the serotonin (5-HT2) antagonist LY 53857 were tested alone and in various combinations for their capabilities to increase mean serum prolactin (MSP) concentrations in rats given the synthetic ergot alkaloid CB-154 (2-bromo-alpha-ergocriptine), a known prolactin suppressor. The LY 53857 and the combination of clonidine, quipazine, and LY 53857 significantly decreased MSP concentrations. Quipazine given alone (10 mg/kg of body weight) was best able to increase MSP concentration and has potential to antagonize prolactin-depressant effects of ergot alkaloids.

Documentation in the literature indicates that death is as painless following the induction of hypoxia by rapid decompression as by other methods that lead to hypoxia, such as exposure to high altitude, carbon monoxide, and inert gases (nitrogen, xenon, and krypton). Many of the signs and symptoms of hypoxia are the same as those for alcoholic intoxication and inert gas narcosis. Moreover, there is good evidence that analogous relationships or mechanisms may exist for hypoxia, inert gas narcosis, and anesthesia.