Push-pull perfusion and microdialysis studies of central oxytocin and vasopressin release in freely moving rats during pregnancy, parturition, and lactation.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J A Russell
Publications and source records attributed to J A Russell.
Pregnancy alters the density of opioid binding sites in the supraoptic nucleus and posterior pituitary gland of rats.
Opioid receptor binding was measured in cryostat sections of supraoptic nucleus (SON) and posterior pituitary of virgin and pregnant rats by quantitative receptor autoradiography after in vitro incubation with [3H]etorphine or [3H](-)-bremazocine in the presence of unlabelled sub-type-selective agonists. Mu-selective [3H]etorphine-binding in the SON was reduced on the last day (21) of pregnancy vs. virgin controls (9.9 +/- 2.2 vs. 31.7 +/- 6.5 fmol/mg). Kappa-selective [3H](-)-bremazocine binding to the SON was not altered by pregnancy. Kappa-selective [3H](-)-bremazocine-binding to the posterior pituitary was less on day 16 of pregnancy vs. virgin females (19.1 +2- 5.2 vs. 74.4 +/- 16.2 fmol/mg). The results suggest mechanisms for the changes in actions of opioids on oxytocin neurones in pregnancy.
Analgesics↗
Allogeneic bone-marrow transplantation without protective isolation in adults with malignant disease.
Bone-marrow transplant (BMT) patients are severely immunocompromised immediately after the procedure and they are commonly nursed in strict protective isolation to reduce the risk of both infection and graft-versus-host disease (GvHD). We have studied a consecutive series of patients to see whether protective isolation is of benefit as prophylaxis against infectious complications of BMT. 50 consecutive patients who had malignant disease and received their first BMT from siblings or unrelated donors were nursed in standard single rooms with visitors instructed to wash their hands. A subset of 20 patients living locally spent a median of 25 days in hospital after BMT; they also spent some time at home on a median of 8 days before engraftment and 3 patients went home on more than 90% of their hospital days. 16 patients (32%) had positive bacterial cultures and/or focal infection. Gram-positive bacteraemia was found in 12 subjects (24%) but there were no gram-negative or deep fungal infections. Grade II or III acute GvHD developed in 17 patients (34%). There were no deaths from infection or acute GvHD. Transplant-related mortality was 6% in the first 100 days and 18% overall with a median follow-up of 22 months. Our mortality data compare favourably with those from institutions with strict isolation procedures. We conclude that BMT may be safely completed in some institutions without either protective isolation or the need to confine patients continuously in hospital.
Acute Disease↗
Plasma ionized calcium and blood lactate concentrations are inversely associated in human lactic acidosis.
Plasma ionized calcium [Ca++] concentrations are decreased in patients having lactic acidosis. To further investigate this observation, we prospectively studied nine critically ill patients who had lactic acidosis and measured arterial pH, PCO2, [Ca++], lactate, and albumin concentrations. We found a strong association between decreased [Ca++] and increased plasma lactate concentrations (r2 = 0.78, p less than or equal to 0.001). This unexpected association--[Ca++] usually increases with increasing acidosis--might be clinically important and the mechanism deserves further investigation.
Acidosis, Lactic↗
Naloxone prevents interruption of parturition and increases plasma oxytocin following environmental disturbance in parturient sows.
Experiments in rodents have suggested that environmental disturbance can disrupt parturition through an opioid-mediated inhibition of oxytocin secretion. To test this hypothesis in a large animal model, 14 primiparous female pigs were allowed to commence parturition in a strawed pen. Five of these gilts were allowed to continue parturition undisturbed in this pen, while the remainder were moved to a farrowing crate immediately after the birth of the first piglet. At this time, pigs were injected subcutaneously with either the opioid antagonist naloxone (n = 4; dose 1 mg/kg body weight) or saline (n = 5). Whereas the undisturbed pigs all gave birth to a second piglet within 53 min, in three of the five disturbed and saline-treated pigs no further births occurred for 2 h, at which time oxytocin was administered subcutaneously to restart parturition. By contrast, all of the naloxone-treated pigs gave birth spontaneously within 2 h, although mean interbirth intervals were still prolonged compared to undisturbed pigs. In a second experiment, nine primiparous female pigs with chronic catheters preplaced in the external jugular vein were similarly moved after the birth of their first piglet and either injected with naloxone (n = 5) or saline (n = 4). Again, parturition was interrupted in three out of four saline-treated animals for at least 2.5 h, but resumed promptly when exogenous oxytocin was administered. Plasma concentrations of oxytocin in these pigs were significantly lower than in naloxone-treated pigs, five out of six of which gave birth spontaneously to one or more piglets within 2.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Transfer of [3H]leucine across the blood-brain barrier at high blood-side oxytocin concentrations in normal and morphine-dependent rats.
The effects of circulating oxytocin on permeability of the blood-brain barrier (BBB) to L-[3H]leucine were studied in anaesthetized rats using the intracarotid, single pass, bolus injection technique. After bolus intracarotid oxytocin injection (10(-9) M), there were no differences in [3H]leucine uptake, compared with controls, in any of eight brain regions with a 'tight' BBB (olfactory bulb, frontal cortex, visual cortex, corpus striatum, hippocampus, thalamus, hypothalamus and colliculi) or in BBB-free, 'leaky' structures (pineal gland, choroid plexus, neuro-intermediate pituitary, anterior pituitary). [3H]leucine uptake by the 'leaky' structures was 2.4x and 2.6x uptake by 'tight' regions in the oxytocin and control groups respectively. In morphine-dependent rats, naloxone increased oxytocin secretion 28-fold within 5 min, but did not affect [3H]leucine uptake for any BBB-protected brain region or BBB-free 'leaky' structure. Accumulation of [3H]leucine was 8.3x and 7.0x greater in the 'leaky' structures than in the 'tight' regions in the naloxone and control groups respectively; [14C]inulin accumulation by each 'tight' region (measured simultaneously with [3H]leucine to determine the vascular space) was not affected by naloxone. It is concluded that even very high blood plasma concentrations of oxytocin do not affect BBB permeability for leucine. It is unlikely that altered BBB permeability, at least for amino acids, contributes to CNS changes during naloxone-provoked morphine withdrawal.
Animals↗
Pregnancy and opioid interactions with the anterior perithird ventricular input to magnocellular oxytocin neurones.
Explore the source record for details and available documents.
Animals↗
Endogenous opioids regulate intracerebral oxytocin release during parturition in a region-specific manner.
Explore the source record for details and available documents.
Animals↗
Contribution of the region anterior and ventral to the third ventricle to opiate withdrawal excitation of oxytocin secretion.
Virgin female or lactating rats were given infusion into a lateral cerebral ventricle (i.c.v.) of either morphine to produce tolerance and dependence or vehicle from a subcutaneous osmotic minipump for 5 days, then they were anaesthetized with urethane. In virgins either an electrolytic or sham lesion of the region anterior and ventral to the third ventricle (AV3V region) was made. Initial blood plasma concentrations of oxytocin, measured by radioimmunoassay were similar in i.c.v. morphine- and i.c.v. vehicle-infused rats (20.6 +/- 2.7 and 19.0 +/- 4.3 pg/ml, respectively). Naloxone (5 mg/kg i.v.) significantly increased oxytocin secretion in all groups for at least 60 min; oxytocin concentration at 6 min after naloxone was in the order: sham-lesioned i.c.v. morphine group (mean 1,839 +/- 809 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. morphine group (326 +/- 65 pg/ml, n = 6), = sham-lesioned i.c.v. vehicle group (251 +/- 66 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. vehicle group (47.2 +/- 12.4 pg/ml, n = 6). Thus in both intact and lesioned rats naloxone increased oxytocin secretion much more in morphine-dependent rats than in the respective controls; in both morphine-naive and morphine-dependent rats, the AV3V lesion reduced the effect of naloxone with respect to plasma oxytocin concentration, but not with respect to the increase relative to the lower prenaloxone concentrations in the lesioned rats (prenaloxone values in the lesioned rats were: i.c.v. vehicle group, 15.8 +/- 6.8 pg/ml; i.c.v. morphine group, 24.3 +/- 7.8 pg/ml; and in the sham-lesioned rats: i.c.v. vehicle group, 67.3 +/- 31.2 pg/ml, i.c.v. morphine group, 65.5 +/- 15.0 pg/ml). Thus the AV3V region is not essential for withdrawal excitation of oxytocin secretion in morphine-dependent rats. In lactating morphine-dependent rats, i.c.v. infusion of the angiotension II antagonist saralasin (2.5 micrograms/min) decreased plasma oxytocin concentration after 10 min (5.7 +/- 1.1 pg/ml, n = 7 vs. 13.2 +/- 3.2 pg/ml, n = 8), but did not prevent naloxone-provoked excitation of oxytocin secretion, measured by radioimmunoassay (6 min after naloxone in the i.c.v. saralasin group 402.8 +/- 124.5 pg/ml, n = 7 vs, in controls, 1,009 +/- 382 pg/ml, n = 7) or assessed by continuous recording of intramammary pressure. These results indicate that centrally acting angiotensin II is not an important mediator of naloxone-induced oxytocin hypersecretion in morphine-dependent rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Angiotensin II↗
Prolonged lobar hypoxia in vivo enhances the responsivity of isolated pulmonary veins to hypoxia.
The hypoxic response of pulmonary vessels isolated from eight sheep whose right apical lobes (RAL) had inspired 100% N2 for 20 h was studied. The RAL of these conscious sheep inspired hypoxic gas and the remainder of the lung inspired air. During hypoxia, RAL perfusion was 33 +/- 3% of its air value, carotid arterial PO2 averaged 86 +/- 3 mm Hg and pulmonary perfusion pressure was not significantly different from the initial control period when the RAL inspired air. At the end of the hypoxic exposure, the sheep were killed, and pulmonary artery and vein rings (0.5 to 2 mm inner diameter) were isolated from both the RAL and the right cardiac lobe, which served as the control lobe (CL). Arteries from the RAL and CL did not contract in response to 6% O2/6% CO2/88% N2 (hypoxia). In contrast, RAL veins did contract vigorously in response to hypoxia, whereas CL veins did not contract or contracted only minimally. Rubbing of the endothelium or prior incubation of RAL veins with catalase (1,200 units/ml), indomethacin (10(-5) M), or the thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptor antagonist, SQ 29,548 (3 X 10(-6) M) each significantly reduced the response to hypoxia. RAL veins were also found to be more reactive than CL veins to the prostaglandin endoperoxide analogue U46619. We conclude that prolonged lobar hypoxia in vivo increases the responsivity of isolated pulmonary veins to hypoxia. These contractions may result from an increase in reactive O2 species, which in turn modify production of, metabolism of, and/or tissue responsivity to TxA2/PGH2.
Animals↗
Multisystem organ failure predicts mortality of ICU patients with acute respiratory failure secondary to AIDS-related PCP.
OBJECTIVE: To evaluate the ability of a variety of scoring systems to predict mortality of patients admitted to an intensive care unit (ICU) with acute respiratory failure (ARF) secondary to AIDS-related Pneumocystis carinii pneumonia (PCP). METHODS: All patients with AIDS-related PCP admitted to ICU at St. Paul's Hospital between January 1, 1985 and April 1, 1991 were reviewed. For each case, the following scores were calculated from data obtained within 24 h of ICU admission: acute physiology and chronic health evaluation II (APACHE II); acute lung injury score; AIDS score as described by Justice and Feinstein; and modified multisystem organ failure (MSOF) score. The serum lactate dehydrogenase (LDH) level was also recorded when obtained within 24 h of ICU admission. RESULTS: A total of 52 ICU admissions in 51 patients were studied. Overall mortality was 65 percent. Mortality increased with increasing MSOF (p < 0.05) score and LDH (p < 0.05). Based on receiver operating characteristic (ROC) curves, the MSOF score and the LDH were found to be good predictors of mortality. Multivariate logistic regression showed that the MSOF score was the only independent predictor of mortality (p < 0.05). The AIDS score, APACHE II, and the acute lung injury score were not significantly associated with mortality. Addition of the serum LDH level improved the performance of both the MSOF and AIDS scores, though the AIDS score plus LDH performed no better than the LDH alone. Of all the scores tested, the MSOF plus LDH level was the best (p < 0.005) predictor of mortality. CONCLUSIONS: The modified MSOF score and the serum LDH level are the best predictors of mortality of patients admitted to ICU with ARF secondary to AIDS-related PCP. The performance of the MSOF score was enhanced when the LDH level was added. The AIDS score, APACHE II, and the acute lung injury score were not found to be useful in this group of critically ill patients.
AIDS-Related Opportunistic Infections↗
Oxytocin and vasopressin release in discrete brain areas after naloxone in morphine-tolerant and -dependent anesthetized rats: push-pull perfusion study.
The effects of naloxone on the release of oxytocin and vasopressin in discrete brain areas were investigated in control and morphine-tolerant/dependent female rats anesthetized with urethane. Two or three consecutive push-pull perfusates were collected for 30-40 min each and the peptide contents measured by radioimmunoassay; naloxone (5 mg/kg, i.v.) was given after the first perfusion. In control rats, naloxone did not increase oxytocin release from any of the regions studied: mediolateral septum, dorsal hippocampus, nucleus of tractus solitarius, or supraoptic nucleus. After naloxone, vasopressin release was approximately doubled in the nucleus of tractus solitarius (p less than 0.05), indicating endogenous opioid inhibition of vasopressin release. Naloxone increased oxytocin concentration in the circulation 3.7-fold (p less than 0.001) but did not affect vasopressin secretion. In rats made morphine tolerant/dependent by intracerebroventricular infusion of morphine for 5 d, oxytocin and vasopressin release in the perfused brain was initially similar to that in control rats, indicating tolerance to any initial morphine effects. In these rats, naloxone increased oxytocin release in the septum threefold relative to control rats (p less than 0.02) but did not alter oxytocin release in hippocampus or nucleus of tractus solitarius. Thus, the oxytocin neurons projecting to septum can develop morphine dependence and may be inhibited acutely by opioids acting via mu-receptors. The results indicate morphine acts selectively on oxytocin neurons projecting to mediolateral septum compared with other central projection areas and compared with centrally projecting vasopressin neurons. In the supraoptic nucleus, naloxone increased oxytocin release 2.3-fold (from 9.2 +/- 3.1 pg/30 min) and increased oxytocin release from axons of these neurons fivefold (from 7.8 +/- 3.2 pg/30 min). Naloxone had no significant effect on vasopressin release from any of the central sites, or on vasopressin secretion into blood, although oxytocin secretion was increased 36-fold (from 17.2 +/- 2.6 pg/ml; p less than 0.001), confirming dependence of magnocellular oxytocin neurons. The central processes of magnocellular supraoptic neurons may be a major source of central oxytocin released during morphine withdrawal.
Anesthesia↗
Linkage of manchette microtubules to the nuclear envelope and observations of the role of the manchette in nuclear shaping during spermiogenesis in rodents.
Structural features of the mouse and rat manchette and the role of the manchette in shaping the spermatid nucleus were investigated. Rod-like elements about 10 nm in diameter and 40-70 nm in length were seen linking the innermost microtubules of the manchette and the outer leaflet of the nuclear envelope in step 8 through step 11 rat and mouse spermatids that either had been routinely fixed for electron microscopy or had been isolated and detergent extracted. Rod-like linkers were also seen joining the nuclear ring to the plasma membrane and nuclear envelope. These linkers may ensure that under normal conditions the manchette remains in a defined position relative to these membranous components. A variety of compounds (taxol, cytoxan, and 5-fluorouracil) were found to perturb the manchette and to affect nuclear shaping. In addition, sys and azh mutant mice were used to determine the consequences of defective manchette formation. These genetic conditions and chemical treatments either produced manchettes that were not in their normal position (azh, sys, and taxol) and/or caused the manchette to appear abnormal (azh, sys, cytoxan, 5-fluorouracil, and taxol), and all resulted in a deformation of the step 9-11 spermatid nucleus. In all instances where the manchette was present, either in normal or ectopic locations, the sectioned nuclear envelope was parallel to the long axis of the microtubules of the manchette. In general, areas of the nuclear envelope where the manchette was not present, or where it was expected to be present but was not, were rounded (normal animals, sys, cytoxan). In addition, there are indications using certain compounds (cytoxan and 5-fluorouracil) as well as in the azh and sys mouse that the manchette may exert pressure to deform the nucleus. It is suggested that the rod-like linkages of the manchette ensure that the nuclear envelope remains at a constant distance from the manchette microtubules and that this is a major factor acting to impart nuclear shape changes on a region of the head caudal to the acrosome during the early elongation phase of spermiogenesis. The manchette microtubules, which are also known to be linked together, may act as a scaffold to deform this part of the nucleus from its spherical shape, perhaps in concert with forces initiated by other structural elements. Evidence from sys animals indicates that structural elements, such as the acrosomal complex over the anterior head (acrosome-actin-nuclear envelope), may affect nuclear shaping over the acrosome-covered portion of the spermatid head.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Short-term morphological response of the rat testis to administration of five chemotherapeutic agents.
As cancer survival rates improve, there is increasing concern about the adverse effects of chemotherapeutic agents on male fertility. Five chemotherapeutic agents (amethopterin, AP or methotrexate; doxorubicin, DX; cytoxan or cyclophosphamide, CP; cisplatinum, CDDP; and 5-fluorouracil, 5-FU) which belong to three different categories of chemotherapeutic agents (antimetabolite, antibiotic, alkylating agent, alkylating agent, antimetabolite, respectively) were given systemically to adult rats to determine the short-term morphological patterns of response in the testis, and the testes were examined by light microscopy. Morphological patterns of response were found to be highly characteristic for each agent, and some shared morphological responses were evident. All except one chemotherapeutic agent (5-FU) caused spermatogonial damage. Among the defects seen were probable degenerating meiotic spermatocytes (CDDP), presence of micronuclei (DX), "arrested" spermatid development (5-FU), and abnormally shaped step 15 spermatids (5-FU). Damage that could be due to the effect of an agent on the Sertoli cell was failure of sperm release (5-FU, CDDP, DX, and AP), increase in the Sertoli cell lipid (5-FU), and malorientation of step 8 spermatids (5-FU, DX). The varied patterns of damage observed are a possible explanation of why the reproductive recovery potential in cancer patients undergoing chemotherapy is variable and drug-specific.
Animals↗
Rapid changes in the content of proenkephalin A and corticotrophin releasing hormone mRNAs in the paraventricular nucleus during morphine withdrawal in urethane-anaesthetized rats.
Quantitative in situ hybridization was used to measure corticotrophin-releasing hormone (CRH) and proenkephalin A mRNA in the medial parvocellular paraventricular nucleus (PVN) 4 h after test procedures. Urethane anaesthesia alone resulted in a significant increase in both CRH and proenkephalin transcripts. The additional stimulus of i.p. hypertonic saline, however, resulted in a further significant increase in both mRNA species. Female rats were given intracerebroventricular (i.c.v.) infusion for 5 days of either morphine sulphate to induce tolerance and dependence, or vehicle, via a subcutaneous osmotic minipump implanted under ether anaesthesia. The rats were then anaesthetized with urethane, fitted with an intravenous cannula for injections and 65 min later either naloxone (5 mg/kg) or vehicle was injected. Naloxone alone in the i.c.v. vehicle rats had no effect on CRH or proenkephalin A mRNA. In i.c.v. morphine-infused rats proenkephalin a mRNA in the PVN was significantly less than in controls. Naloxone given to i.c.v. morphine-infused rats resulted in a doubling of hybridization to proenkephalin mRNA in the PVN which was significantly greater than that seen in the i.c.v. vehicle group. CRH mRNA in the PVN was not altered either by naloxone in control rats, or by chronic i.c.v. morphine infusion. By contrast, naloxone did increase CRH mRNA by ca. 40% in morphine-infused rats. The results show that stress-induced increases in CRH and enkephalin mRNAs in the PVN do not require conscious appreciation of the stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, General↗
Functional antagonism in rabbit pulmonary veins contracted by endothelin.
An endothelium-derived 21-residue peptide, endothelin, has been shown to be a constrictor of arteriolar smooth muscle. This study investigated the effect of endothelin on isolated pulmonary veins and arteries using tissue bath techniques. Endothelin elicited concentration-dependent contractions and maximal responses were equal in magnitude to those of phenylephrine (PE) or norepinephrine (NE). Responses to endothelin were long lasting and persisted despite repeated washing. The following agents had no significant effect on endothelin-induced contractions: FPL 55712 (1 microM), indomethacin (10 microM), methysergide (3 microM), phentolamine (3 microM), pyrilamine (3 microM) and the putative thromboxane A2 receptor antagonist SQ 29,548 (3 microM). Moreover, removal of the endothelium did not alter responses to endothelin. Isoproterenol, forskolin, and 8-bromo-cAMP had a differential inhibitory effect on matched contractions induced by endothelin and the putative thromboxane A2 receptor agonist U-46619. Isoproterenol (0.1 microM) relaxed endothelin and U-46619 contractions by 2 +/- 1% and 74 +/- 5%, respectively; forskolin (3 microM) by 12 +/- 3% and 84 +/- 9%, respectively and 8-bromo-cAMP (10 mM) by 23 +/- 8% and 82 +/- 9%, respectively. Likewise, 10 microM sodium nitroprusside relaxed endothelin contractions by 32 +/- 4% and PE contractions by 80 +/- 9%. Endothelin is a very potent pulmonary vasoconstrictor that appears to have a direct effect on vascular smooth muscle. Compared to U-46619 or PE, endothelin-induced contractions are highly resistant to relaxing agents that increase either cAMP or cGMP. Moreover, resistance to cAMP does not appear to involve inhibition of adenylate cyclase.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Culture and the categorization of emotions.
Some writers assume--and others deny--that all human beings distinguish emotions from nonemotions and divide the emotions into happiness, anger, fear, and so on. A review of ethnographic and cross-cultural studies on (a) emotion lexicons, (b) the emotions inferred from facial expressions, and (c) dimensions implicit in comparative judgments of emotions indicated both similarities and differences in how the emotions are categorized in different languages and cultures. Five hypotheses are reviewed: (a) Basic categories of emotion are pancultural, subordinate categories culture specific; (b) emotional focal points are pancultural, boundaries culture specific; (c) emotion categories evolved from a single primitive category of physiological arousal; (d) most emotion categories are culture specific but can be defined by pancultural semantic primitives; and (e) an emotion category is a script with both culture-specific and pancultural components.
Cross-Cultural Comparison↗
Compliance with follow-up of patients treated for non-seminomatous testicular cancer.
Many patients with Stage 1 non-seminomas are now treated by orchidectomy and close follow-up along. Chart review indicated that a group of such patients, compared with patients treated with chemotherapy, tended to be less compliant with follow-up. A questionnaire given to a second sample of patients confirmed that surgical patients underestimated the dangers of the disease and chances of relapse, and doubted the value of follow-up.
Adult↗