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Objective: To evaluate circulating HER-2/neu in cervical cancer patients prior to and following treatment., Methods: Controls, and patients with either cervical dysplasia or cancer taken from an active gynecologic oncology service were evaluated for the expression of HER-2/neu in serum by ELISA before and following surgery, radiation, chemotherapy or combinations thereof. The resulant data was then evaluated for significance by either ANOVA or non-parametric testing., Results: Mean differences were noted for patients with cervical cancer compared to controls. Patients with a good response to the chemotherapy indicated an increase in the serum oncogene, while those not responding either had no marked change or decreased the level of serum HER-2/neu., Conclusions: As serum HER-2/neu is a membrane bound portion of the intact molecule, these results suggest that due to the induction of cell death and breakdown, the liberation of this fraction (increased levels in the serum), is a viable indicator of response to treatment in some patients. A more detailed examination of this possibility along with expanded correlation with tissue expression is required.

The authors have previously documented that appropriate chemical and pharmacologic modification of the hemoglobin molecule are required to attenuate certain pathophysiologic reactions of the reticuloendothelium. The current study further investigates the molecular responses of human coronary artery endothelial cells to a high concentration (0.4 mmol) of 1) unmodified bovine hemoglobin; and 2) an improved blood substitute that comprises hemoglobin cross-linked intramolecularly with o-adenosine triphosphate and intermolecularly with o-adenosine, and conjugated with reduced glutathione. In this study, the scavenging effect of hemoglobins toward nitric oxide (NO) was evaluated by the measurement of nitrite (NO2-) and nitrate (NO3-) formation. The pro-oxidant effect of hemoglobin on endothelial cells was examined by the measurement of intracellular reduced glutathione, and by monitoring the formation of lipid hydroperoxides and 8-iso prostaglandin F2alpha, a novel potent vasoconstrictor, which is produced by a noncyclooxygenase mechanism involving free radical catalyzed peroxidation of arachidonic acid. The inflammatory reactions of endothelial cells were evaluated by the expression of the adhesion molecule, intracellular adhesion molecule-1, and the activation of nuclear transcription factor, nuclear factor kappaB. In additional, endothelial cell responses were investigated by analysis of intracellular ionized calcium concentrations. Results indicate that unmodified hemoglobin in a concentration of 0.4 mmol/L can aggravate endothelial cell oxidative and inflammatory responses. This hemoglobin produced a significant (p < 0.01) depletion of reduced glutathione, acceleration of lipid peroxidation, and a greater influx of Ca2+. The formation of 8-iso prostaglandin F2alpha increased compared with the control cells (p < 0.01). Unmodified hemoglobin was found to be a potent scavenger of NO, great activator of nuclear factor kappaB, and a stimulator of intracellular adhesion molecule-1 expression. Contrarily, the improved blood substitute did not appear to induce oxidative stress nor to increase the intracellular Ca2+. The concentration of 8-iso prostaglandin F2alpha was similar to that in the control cells, whereas the formation of NO2-/NO3- was much lower (p < 0.05) than in the unmodified hemoglobin group. The effect of an improved blood substitute can be linked with the anti-inflammatory and cytoprotective properties of adenosine, which is used as a cross-linker and surface modifier, and the type of the chemical modification procedure that lowers hemoglobin pro-oxidant potential.

Previous studies have established a linkage between free Hb molecules and the production of inflammatory mediators by the reticuloendothelial cells. An important aspect of the endothelial response to the inflammatory stimuli is the expression of adhesion molecules on the luminal surface. Therefore, the present study was designed to investigate the effects of various free-Hb based oxygen carrying solutions on the intracellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and also von Willebrand factor (vWF) expression by human endothelium. Human coronary artery endothelial cells (HCAEC) were cultured on glass coverslips until they reached confluence, then incubated for 18 hours with endothelial basal medium (EBM) supplemented with 5% FBS and a 0.1 mmol or 0.2 mmol of the bovine Hb solutions: 1) pure unmodified bovine Hb (UHb); 2) modified bovine Hb solution (Hb-PP-GSH) prepared according to our newly developed procedure (U.S. Patent No. 5,439,882); and 3) modified bovine Hb solution polymerized with glutaraldehyde (GLUT-Hb). The HCAECs were also incubated with EBM (negative control) and EBM containing bacterial endotoxins in a concentration of 50 EU/ml (positive control). After treatment, cells were exposed to primary antibodies; anti-human ICAM-1, anti-human VCAM-1 or anti-human vWF, and consequently to the secondary antibody (fluorescein isothiocyanate-conjugated F(ab)2). Immunofluorescence analysis revealed different expressions of ICAM-1 and VCAM-1 on the surface membranes of variously treated cells. Although negative control cells had an undetectable level of adhesion molecules, the positive control cells, activated by endotoxin, exhibited high immunoreactivity for ICAM-1 and VCAM-1. The Hb's treated cells demonstrated differing degrees of activation. An insignificant expression of ICAM-1 was observed in HCAEC, following treatment with a 0.1 or 0.2 mmol of Hb-PP-GSH and 0.1 mmol of UHb. Cell treated with 0.2 mmol of UHb and both concentrations of GLUT-Hb demonstrated a massive expression of this adhesion molecule. A similar effects was observed during induction of VCAM-1. While a lack of expression was noted with both concentrations of Hb-PP-GSH and 0.1 mmol of UHb, the GLUT-Hb stimulated significant VCAM-1 induction at all tested concentrations. Immunofluorescence analysis confirmed the expression of vWF uniformly in HCAEC from the different experimental groups. The data suggest, vWF expression was unaffected by all but the GLUT-Hb treatment. In conclusion, the Hb stimulatory activity toward ICAM-1 and VCAM-1 inductions were related with the type of Hb chemical modification method. Although modification of Hb with glutaraldehyde potentiates adhesion molecules expression, our novel Hb modification procedure, which comprises intramolecular cross-linking with o-adenosine triphosphate and intermolecular with o-adenosine, and combined with reduced glutathione, apparently prevents these inflammatory events.

The aim of the present study was to evaluate the role of hemoglobin (Hb) and the contribution of chemically modified Hb solutions on the activation of nuclear transcription factor. NF-kappa B, and propagation of oxidative stress within human vascular endothelial cells. The activation of an oxidative stress-sensitive NF-kappa B can be linked with the propagation of an inflammatory state via rapid induction of genes for several pro-inflammatory mediators. Human coronary artery endothelial cells (HCAEC) were cultured on glass coverslips or cell culture plates to confluence. Then, the cells were incubated for up to 18 hours with endothelial basal medium (EBM) supplemented with 5% FBS and test agents in a concentration of 0.1 and 0.2 mmol: 1) unmodified bovine Hb (UHb): 2) modified Hb solution polymerized with glutaraldehyde (GLUT-Hb), and 3) a novel modified Hb solution (Hb-PP-GSH) prepared according to our patented procedure (U.S. Patent No. 5,439,882). The positive control for the NF-kappa B activation study included a treatment of the cells with: I) endotoxin: IL-1; TNF; and H2O2. Results indicate that Hb's pro-oxidant potential was influenced by the type of chemical modification procedure. The GLUT-Hb autoxidation rate, peroxidase-like activity and reactivity with H2O2/ferryl species formation were higher as compared to UHb, by 15%, 35% and 30%, respectively. However, pro-oxidant potential of Hb-PP-GSH was significantly lower than that of UHb (by 22%, 12% and 28%, respectively). The extent of oxidative stress of the HCAECs was found to be the Hb modification-type and concentration dependent. Although the highest endothelial lipid peroxidation and the largest depletion of intracellular GSH was associated with 0.2 mmol of GLUT-Hb, the Hb-PP-GSH did not produce significant changes when compared to the control cells. The UHb generated a moderate oxidative stress to the endothelium. The immunofluorescent and EMSA results indicate a correlation between the type of Hb chemical modification and the induction of NF-kappa B nuclear translocation. We found that GLUT-Hb rapidly activated NF-kappa B and induced nuclear translocation. Treatment of the cells with an increasing amount of UHb leads to the partial nuclear induction of NF-kappa B. However, Hb-PP-GSH did not activate NF-kappa B directly. In this study, the positive control cells treated with endotoxin, IL-1 or TNF demonstrated full nuclear translocations, whereas H2O2 caused only partial induction. In conclusion, nuclear translocation of NF-kappa B by Hb solutions might be dependent on Hb's pro-oxidant potential and extent of Hb-mediated endothelial oxidative stress. Besides the low oxidative potential of Hb-PP-GSH, the observed lack of NF-kappa B activation by this Hb solution can be also related to the anti-inflammatory properties of adenosine which is used in our novel modification procedure. In this study, only the Hb-PP-GSH, cross-linked intramolecularly with o-adenosine triphosphate and intermolecularly with o-adenosine, and combined with reduced glutathiore, was shown to be non-toxic to the endothelium and promises to be an effective free-Hb based blood substitute.

1. This study was designed to see if propranolol hydrochloride alone or in conjunction with ethanol had any marked effect on blood coagulation. 2. Rats were given the compounds for 7 days and clotting activity measured. 3. Propranolol induced changes in coagulation, both alone and in conjunction with ethanol. 4. The data suggest that propranolol plus ethanol induce changes that could be detrimental to hemostasis to a greater degree than propranolol alone.

1. Thirty-nine nonsmoking women, 14 who had never used oral contraceptives and 25 who had a prior history of contraceptive use were placed on a 1-year regimen of oral triphasic contraception containing a new progestin. 2. Biochemical determinations of 21 different variables were made at baseline, 3 months, 6 months, and 12 months of exposure. 3. Most of the significant changes were in those women with no prior exposure to contraceptives. 4. Thyroxine increased and T3 decreased, as did urinary cortisol. No changes were noted in the CBC, hematocrit, or platelet count. Slight increases in cholesterol and triglycerides resulted, with small nonsignificant increases in LDL also occurring; this increase was also noted for HDL. 5. The experimental contraceptive seems to have a very minimal influence on chemistry profiles, suggesting a favorable biochemical response to the progestin.

1. Coagulation variables were determined in 14 contraceptive nonusers and 25 prior contraceptive users at 3, 6, and 12 months' exposure to a new oral form of progestin. 2. Overall hemostasis was unaffected, as was the intrinsic pathway. 3. Changes were noted in several vitamin-K dependent factors along with a marked decrease in fibrinogen. 4. Protein C antigen (a coagulation inhibitor), was elevated. 5. This new triphasic contraceptive appears to have a minimal influence on thrombosis while activating antithrombotic protein C. The data suggest a favorable hematologic response to this contraceptive.

The actual hemoglobin (Hb) contribution to endothelin-1 (ET-1) production in human umbilical vein endothelial cells (EC) was investigated. Cells were incubated with 0.1 mmol or 0.3 mmol of bovine: 1) unmodified (U) ferrous-Hb; 2) U-ferric-Hb; 3) U-ferryl-Hb; 4) polymerized low molecular weight (m.w.) Hb with chemically modified surface (< 400 kDa); and 5) glutaraldehyde polymerized, high m.w. Hb (< 1020 kDa). The incubation medium was tested at 6 and 24 hr for lactate dehydrogenase (index of cellular injury), and for ET-1 release by the cells. Before radioimmunoassay, the ET-1 was extracted from cell culture medium by a two-step purification procedure: 1) ultrafiltration, and 2) column extraction with C18 cartridges. The data suggested that the oxidation status of Hb and its concentration play an important role in causing EC injury. The highest toxicity was observed when EC were incubated with 0.1 mmol of ferryl-Hb, and there was no toxicity with 0.3 mmol of ferric-Hb. These results indicate that the ferric-Hb and low m.w. polymerized Hb at a concentration of 0.1 mmol did not alter ET-1 synthesis and produced a level similar to that of the control. However, it was found that ferryl-Hb and ferrous-Hb in a concentration of 0.1 mmol significantly reduced ET-1 release. All Hbs at a concentration of 0.3 mmol markedly inhibited the production of ET-1. The greatest decrease in ET-1 levels was produced by ferryl-Hb, and the lowest by ferric-Hb and low m.w. polymerized Hb. The Hb's inhibitory effect was more pronounced at 24 hr of incubation. It was also found that although Hb molecules showed a high degree of cross-reactivity with polyclonal anti ET-1 antibodies, the presence of different Hb solutions in the EC culture medium did not change the immunologic properties of ET-1 peptide. In conclusion, Hb inhibitory activity toward ET-1 production might be related to Hb mediated endothelial oxidative injury.

Monocytes [M] were isolated from venous blood of healthy volunteers and activated macrophage-leukocytes (Mø-L] were obtained from peritoneal fluid of patients with mild endometriosis. The M were incubated with pyrogen free CELLGRO culture medium [Control], and with 0.2 mM of [A] unmodified bovine hemoglobin (UHb), [B] Hb crosslinked to form polymers with M.W. < 400 kDa (LMWHb), [C] Hb crosslinked to form large polymers (< 1,020 kDa) (HMWHb), and Mø-L additionally with [D] UHb contaminated with endotoxin (Hb+E) (2.5 EU/mL), and [E] UHb contaminated with phospholipids (Hb+PLs). The Mø-L medium of incubation was tested for TNF alpha, IL-1 alpha, IL-6, GM-CSF and PAF after 6 and 24 hours, but M for TNF alpha and GM-CSF at 12, 24 and 36 hours. Mø-L were found more responsive than M colonies. The strongest reaction of Mø-L was to Hb+E, which produced levels of cytokines and PAF higher than Controls (p < 0.001). Hb+PLs induced smaller increases of TNF and IL-6, and a decrease in the levels of IL-1 and GM-CSF. However, the release of PAF was much greater with this Hb than with Hb+E. UHb caused an increase in TNF, as compared to control (p < 0.01). LMWHb generated a similar increase in TNF, but also a decrease in IL-1. Both polymerized Hb forms inhibited expression of GM-CSF. HMWHb induced high levels of TNF, IL-1 and PAF. UHb, LMWHb and HMWHb significantly increase levels of TNF in M cultures after 36 hours of incubation.

Human umbilical vein endothelial cells (HUVEC) were incubated for 24 hours with 0.1 mM or 0.3 mM of: [A] unmodified (U) Hb-FeIIO2; [B] UHb-FeIII; [C] UHb-FeIV-OH; [D] polymerized low molecular weight Hb (< 400 kDa); [E] polymerized high molecular weight Hb (< 1,020 kDa); [F] polymerized low molecular weight Hb + Endotoxin (2.5 EU/mL); [G] rTNF alpha 100 pg/mL; [H] rTNF alpha 400 pg/mL; [I] rTNF alpha 800 pg/mL. The medium of the incubation was tested for LDH (index of cell injury), and for cytokines GM-CSF and IL-1 alpha released by the cells. The data suggests that oxidation status of the iron in the Hb molecule and concentration of Hb play an important role in causing EC injury. The highest toxicity was observed when EC were incubated with 0.1 mM of UHb-FeIV-OH (ferryl-Hb) and no toxicity with 0.3 mM of Hb-FeIII (ferric-Hb). The direct stimulation of EC by Hb for the production of IL-1 was limited, related only to high molecular weight Hb polymers or to Hb+E, however GM-CSF expression was increased by almost all Hb forms. TNF induced dose-related injury (R2 = 0.986), and dose-related release of IL-1 (R2 = 0.977). A different EC reaction was observed on the release of GM-CSF. Intermediate levels of TNF (400 pg/mL) increased the expression of this cytokine, while high levels (800 pg/mL) blocked its release.

1. Plasma levels of beta-endorphin were not significantly different in women with normal plasma prolactin or women with hyperprolactinemia. 2. A bromocriptine induced decrease in plasma prolactin was not accompanied by a decrease in beta-endorphin. 3. This study suggests that no direct link exists between plasma prolactin levels and endogenous beta-endorphin.

Coagulation factor activity was evaluated in female rats treated with danazol. Following 30 days of treatment, slight decreases in factor VII and X activities were noted. After 60 days, a prolongation of the prothrombin time, as well as a decrease in factor VII, was noted. The data suggest that in the rodent, danazol has minimal effects on coagulation activity.

In this study, sperm motility, velocity, and progression were compared with the total and Ca++ concentrations in the SF from men with normal and decreased motility (less than 60%). No significant difference in SF total calcium content was observed in men with normal and hypomotility. However, a statistically significant decrease in seminal Ca++ was observed in those men with decreased motility, when compared with that of men with normal motility.

1. This study was undertaken to evaluate the effects of low dose ingestion of omega-3 fatty acids on clotting profiles in healthy men ingesting 3 g of MaxEPA (900 mg omega-3 fatty acids) daily for 30 days. 2. No effect was noted on either platelet aggregation or circulating prostaglandin levels. 3. Significant decreases were noted for total cholesterol and low density lipoprotein. 4. Clotting factor decreases were noted for factors primarily of the intrinsic pathway and several factors which promote fibrinolysis. 5. The data suggests that low level ingestion of marine fish oil has a beneficial effect on lipids and possibly the clotting profiles in healthy men.

1. Cycling women both taking or not taking oral contraceptives and menopausal women on replacement estrogen ingested 3 g daily of marine fish oil for 30 days. 2. Triglycerides decreased in the contraceptive users, cholesterol and LDL increased in the non-contraceptive user; while LDL decreased in the menopausal women. 3. After 14 days removal of the fish oil, lipid profiles generally returned to a pattern generally thought to be harmful. 4. Fish oil appears to alter lipids favorably in women receiving exogenous estrogens compared to natural circulating estrogen.

A practical and accurate method of determining ovulation using cervical mucus is described. Ovulatory cycles from 32 healthy women were assessed using hormonal and nonhormonal methods. Cervical mucus extractable immunoglobulins were assayed for the complete cycles of nine women and randomly collected from 23 additional women with normal cycles. All normal ovulatory women showed a minimum concentration present at midcycle when optimum conditions for fertilization existed. Using newer laser nephelometry techniques, the content of extractable immunoglobulin G and immunoglobulin A per sample weight confirmed the cyclic nature of the concentration of immunoglobulin in cervical mucus, and correlated well with previously defined biophysical properties of cervical mucus. Nephelometry proved to be rapid, accurate, and an inexpensive technique for determining ovulation and has potential for clinical use.

Male Sprague-Dawley rats were injected with either a single subcutaneous dose of 75 mg of secobarbital, or once daily injections of 20 mg of secobarbital for 7 days. Plasma was collected prior to treatment and 18 hours later (75 mg) or 8 and 15 days later (20 mg). Plasma was analyzed for the platelet count (PLT), prothrombin time (PT), fibrinogen (FIB), and coagulation factor activities for factors II, V, VII, IX, and X. Treatment with a single subcutaneous injection of 75 mg of secobarbital caused statistically significant alterations in every clotting activity measured whereas 7 days of treatment with 20 mg once daily resulted in only 2 clotting factors being abnormal. These two factors returned to pretreatment levels following 7 days of withdrawal of secobarbital. The data indicates that a single larger dose of secobarbital is more influential on hepatic synthesized clotting factor activity than is longer treatment with a lesser dose.

Female Sprague-Dawley rats were placed on a drinking solution of 1 ppm Diazinon or malathion dissolved in water for 6 months. At the conclusion of the experiment liver tissue and plasma were examined. Clotting studies included the prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen, and factors II, V, VII, X, plus the platelet count. Hepatic morphology, basically hepatocyte degeneration, was altered by malathion while diazinon had no notable effect. Likewise, malathion prolonged both the PT and APTT, the only changes in clotting activity.

Patients with documented pre-eclampsia of pregnancy were utilized on this study. Various clotting factor activities were measured and these included the prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen (FIB), and clotting factors II, V, VII, VIII, X and XII plus the platelets. Statistical analysis of the data indicates that the activity of many clotting factors was significantly changed due to pre-eclampsia, in general, being elevated over normal pregnant controls. This was primarily reflected in the common pathway portion of the clotting cascade.

The toxic effects of hemolysed RBCs have been studied for more than 100 years, but the specific factors involved have not been identified. This study focused on phosphatidylethanolamine (PE) and phosphatidylserine (PS), two aminophospholipids that normally reside on the cytoplasmic side of the red cell membrane. An in vitro experiment with murine peritoneal exudate macrophages showed that PE and PS: a) stimulated the production of H2O2, complement factor C3a, prostacyclin, and thromboxane at a dose of 5 micrograms/ml; b) produced cell injury, evidenced by release of lipid peroxides, LDH, and by morphologic changes on phase-contrast and electron microscopy at a dose of 50 micrograms/ml; and c) caused cell death in 50-66% of cells at a dose of 100 micrograms/ml. An in vivo experiment showed that PE and PS injected intravenously into various groups of rabbits: a) caused only transient hypotension at a dose of 0.05 mg/kg body weight; b) caused significant hypotension, cardiac arrhythmias, bronchospasm, activation of intravascular coagulation, complement, platelets, and leukocytes with release of histamine, serotonin, and thromboxane at a dose of 0.10 mg/kg; and c) caused cardiac arrest and death at a dose of 0.30 mg/kg. In contrast, the phospholipids of the outer cell membrane (phosphatidylcholine and phosphatidylinositol) caused minimal toxicity in vitro and none in vivo.

1. Female rats were placed on water, 5% ethanol (ET), or 20% ET drinking solutions for 8 weeks. The last 2 weeks, the rats received orally either ethinyl estradiol (EE), norethindrone acetete (NED), or a combination of both. 2. Luteinizing hormone decreased due to ET drinking and was undetectable subsequent to the steroidal treatment. 3. Prolactin increased after steroid treatment and alcohol drinking in the controls. 4. Ethanol (5%) plus EE increased prolactin as did the steroidal combination, whereas ET (20%) likewise increased prolactin in conjunction with NED over water controls. 5. Hepatic alcohol dehydrogenase was inhibited due to EE when compared to water-controls in the 5% ET drinking animal, whereas aldehyde dehydrogenase was induced in combination with NED in both the 5% and 20% ET drinking rats.

Adult male and female rats were subjected to gonadectomy by means of surgical removal of the gonads. In the male, castration resulted in a significant decrease in both body and liver weights compared to intact controls, which persisted for at least 3 weeks. Conversely, ovariectomy was associated with a significant enhancement in both growth rate and liver weight from intact controls. Castration of male rats resulted in induction of hepatic L-ADH (cytosolic alcohol dehydrogenase) and L-ALDH (cytosolic aldehyde dehydrogenase) as contrasted with inhibition of mitochondrial ALDH which was evident in the enzyme with the apparent high Km. Kinetic studies indicate that there was an increase in apparent Km of L-ADH, and hence reduced affinity to hepatic metabolism of ethanol as a consequence of castration in the male rat. This is compared with few changes occurring in the apparent Km value of L-ALDH. Ovariectomy did not alter endogenous L-ADH or L-ALDH. Short-term administration of a synthetic estrogenic steroid ethinyl estradiol, inhibited liver mitochondrial ALDH in the intact female rat but not in the ovariectomized female. Short-term administration of the same dose of an androgen, testosterone, did not alter specific activities of the liver enzymes measured in the intact or in the castrated male rat. Administration of both components of OCs (oral contraceptives) combined or the estrogen alone in behavioral experiments profoundly reduced ethanol drinking by voluntary intake of diluted ethanol solution by the intact female rat. These results suggest a hepatic-gonadal link may exist and that a toxic interaction between the OCs and alcohol drinking is definitely possible.

Male Sprague-Dawley rats were placed on a drinking solution containing either 10 parts per million (ppm) carbaryl or water for 30 days. Plasma was analyzed for the prothrombin time, partial thromboplastin time, fibrinogen, and clotting factor activity for coagulation factors II, V, VII, VIII, IX, X, XII and the platelet count. Only two hematological parameters measured were statistically different from the controls; these parameters were the platelet count and factor VII activity, both of which were reduced. Histological examination of the hepatic tissue illustrated that a number of pathological changes were occurring.

Plasminogen activity and antigen, tissue-type plasminogen activator (tPA) activity and antigen, plasminogen activator inhibitor (PAI) activity, and plasmin generation rates were determined in 32 normal newborn plasmas and 25 normal adult plasmas. The newborns showed reduced levels of plasminogen activity and antigen and tPA antigen, and activity, normal levels of PAI activity, and slower plasmin generation rates. The slower generation was shown to be due to the hypoplasminogenemia. The in vitro plasmin generation studies also showed that the newborn needed 11 times the usual concentration of urokinase and 5 times the usual concentration of tPA to achieve the minimal activation rate of the adult.

A 21 year old caucasian male, who was admitted to the medicine service for respiratory problems and hematemesis was ultimately diagnosed as having metastatic choriocarcinoma. Plasma samples were analyzed for prothrombin time (PT), activated partial thromboplastin time (APTT), platelets, and clot activation time for fibrinogen (FIB), and coagulation factors II, V, VII, VIII, X and XII. Abnormal clotting parameters included thrombocytopenia, PT, APTT, FIB, factors II, V, VII, and X. The coagulation abnormalities indicate the patient was in a state of consumption coagulopathy possibly induced by hepatic metastasis of the primary tumor.

Female rats were exposed to a drinking solution containing either 650 or 1950 parts per million (ppm) of the organophosphate insecticide malathion for 14 days. Plasma samples were assayed for prothrombin time (PT), partial thromboplastin time (APTT), hematocrit (HCT), platelet count (PLT) and clot activation time for fibrinogen and coagulation factors, II, V, VII, VIII, X, and XII. Significant changes following 650 ppm malathion were noted for the fibrinogen, factors VII and XII. Drinking 1950 ppm malathion causes significant differences in factors II, VII, X and XII. The data strongly suggest that in the rat, malathion ingestion has a potent effect on blood coagulation.

Our previous findings that the degree of endotoxin-induced hypotension in the dog is inversely related to ambient temperature (19 degrees through 30 degrees C) and that only increased doses of naloxone are effective at 19 degrees C suggested that opioid activity is also influenced by ambient temperature, increasing in the cold and decreasing in the warm. Others have reported increases in plasma beta-endorphin in rats with acute exposure to both 5 degrees and 36 degrees C. In this study we measured changes in pain thresholds after both acute and chronic exposures to lesser alterations in ambient temperature as a potentially more sensitive index of changes in central opioid activity. Compared to 24 degrees C there was a marked increase in pain threshold with acute exposure to 10 degrees C and marked decreases at 30 degrees and 35 degrees C. A slight decrease occurred after 30 minutes but not 60 or 120 minutes at 19 degrees C. All acute changes disappeared three hours after the animals had been returned from the altered ambient temperature to 24 degrees C. No changes were observed after six days chronic exposure to 10 degrees or 30 degrees C. These findings suggest that moderate, acute changes in ambient temperature can produce inversely related, adaptable alterations in central opioid activity.

1. Female Sprague-Dawley rats were placed on water (controls) or 10% ethanol (ETOH) for 14 days. A second group of ETOH treated rats were removed from ETOH and placed on water for 7 days. 2. Plasma samples were assayed for various coagulation factors following treatment. 3. Following 2 weeks of ETOH, significant differences were noted for fibrinogen, the platelet count and factors V, VII, VIII, X and XII. After 1 weeks' removal from ETOH, differences were still noted for the platelet count, fibrinogen and factors VII, VIII and XII.

Male Sprague-Dawley rats were treated with 1 ml of diazinon or malathion, 1750 ppm given orally by gavage. Clotting determinations included the prothrombin time, partial thromboplastin time, fibrinogen, and coagulation factors II, V, VII, and X, plus the hematocrit and platelet count. The results suggest that insecticides influence the clotting times of rats ingesting these insecticides even after as short a time span as 2 hr.

Anolis carolinensis were used as experimental models to study the short-term effects of the fertility drug, clomiphene citrate, on male squamate reproductive function. Daily injections of 10.0 micrograms of clomiphene induced an increase in plasma testosterone over a 5 day period. No change in testis mass or morphology was elicited over this time.

Male Sprague-Dawley rats were treated with 0.5 ml of 46% ETOH, 2.8 mg/kg of secobarbital or 14.3 mg/kg secobarbital or combinations thereof. Twenty-four hours following treatment, blood clotting data was determined. The data indicated that either ethanol or secobarbital alone is just as detrimental to hemostasis as is the combined abuse of both. Likewise, a lesser concentration of alcohol was just as disruptive on hemostasis as was the greater concentration of ethanol.

Female rats were given either ethinyl estradiol or norethindrone in conjunction with water or 5% ethanol. Hematological parameters measured included the prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen (FIB), factors II, V, VII, VIII, X, and XII activity; plus the platelet count (PLT) and hematocrit (HCT). The data indicates that norethindrone together with water produces the greatest number of changes in clotting activity.

Circulating plasma levels of human prothrombin antigen and activity were determined in normal pregnancy and in pregnancies complicated by hypertension, eclampsia, or preeclampsia. The ratio of prothrombin antigen to activity (Ag/Act) was within normal limits for all hypertensive patients. However, every untreated preeclamptic patient, as well as 2 eclamptic patients, had abnormal prothrombin antigen to activity ratios.

The reproductive biology of the bat Macrotus waterhousii was investigated anatomically and physiologically several times monthly throughout the year. The male spermatogenic cycle is initiated in June; sperm are available in August. Testicular hypertrophy is accompanied by increased levels of testicular ascorbic acid and circulating plasma testosterone. Sperm are present in the seminiferous tubules and later the epididymides from August to early December. Regression in testicular size begins in late September and testes are involuted by early December. Levels of testicular ascorbic acid and plasma testosterone decline at this time, although detectable amounts of both are present year-round. Mature sperm are absent from the male tract after late November or early December. The accessory sex gland complex and Cowper's glands undergo an annual cycle in synchrony with the testicular cycle. The accessory complex contains fructose, the concentration of which varies seasonally in direct proportion to glandular hypertrophy. Only trace levels of fructose are elaborated by Cowper's glands undergo an annual cycle in synchrony with the testicular cycle. The accessory complex contains fructose, the concentration of which varies seasonally in direct proportion to glandular hypertrophy. Only trace levels of fructose are elaborated by Cowper's glands. In contrast to vespertilionid bats, where the accessory glands remain enlarged and active when testes involute, those in Macrotus regress. The penis differs structurally from that of other temperate North American bats, primarily by lacking a bony baculum and specialized erectile accessory corpus cavernosus bodies. Males are not reproductively active in their first autumn.

This study was undertaken to evaluate the effect of preeclampsia on maternal and cord blood clotting parameters. Pregnant controls and preeclamptics plus their offspring had plasma analyzed for prothrombin time, partial thromboplastin time, fibrinogen, and clotting activity for factors II, V, VII, VIII, IX, X, XII, plus factor II antigen. Maternal data was consistent with that previously reported by numerous authors. The cord blood data showed that neonates of the preeclamptic mother had elevated fibrinogen and decreased II, V and VII activity, plus decreased II antigen. The data indicates that abnormal clotting parameters seen in the neonates from preeclampic mothers may result from impaired liver function and not as previously thought, from a deficiency in neonatal vitamin K.

Adult male rats were subjected to intraperitoneal (i.p.) saline (controls) or barbiturates (20 mg/rat) as a single injection. Seventeen hours later the rats were sacrificed and plasma collected. Hematocrit (HCT), Platelet count (PLT), prothrombin time (PT), partial thromboplastin time (APTT), and coagulant activity for factors II, V, VII, VIII, X and XII, plus fibrinogen were determined. The data indicates that a single injection of phenobarbital and secobarbital had a greater effect on clotting activity than did barbital or amobarbital. This was primarily reflected in the hepatic synthesized clotting factors, plus the platelets.

Female rats were exposed to a drinking solution containing 157 parts per million (ppm) of the organophosphate insecticide diazinon for 14 days. Plasma samples were assayed for prothrombin time (PT), partial thromboplastin time (APTT), hematocrit (HCT), platelet count (PLT) and clotting times for coagulation factors I (Fibrinogen), II, V, VII, VIII, X and XII. Significant change following ingestion of diazinon were noted for the PT, APTT, Fibrinogen, factors II, VII, VIII, X, XII and hematocrit. The data suggest that in the rat, diazinon ingestion has a direct effect on the clotting activity of various blood coagulation parameters.