Enhancing biogas production from caribbean pelagic Sargassum utilising hydrothermal pretreatment and anaerobic co-digestion with food waste.

The recurring inundation of beaches in the tropical North Atlantic by pelagic Sargassum and the associated social, ecological and economic challenges, have aroused great interest in its potential use as a marine energy crop. However, to date, the seasonal availability and low experimental methane potential of these invasive brown seaweeds have hindered their commercial exploitation as feedstock for sustainable energy production. This novel study evaluated Caribbean pelagic Sargassum and the synergistic interactions of hydrothermal pretreatment and co-digestion with food waste at different mixture ratios, on biogas production enhancement and bio-fertiliser recovery. Batch testing revealed that hydrothermal pretreatment promoted the hydrolysis of organics in pelagic Sargassum and food waste, thus increasing methane recovery from mono-substrate digestion by 212.57% and 10.16%, respectively, in comparison to the untreated samples. Co-digestion of pelagic Sargassum and food waste redistributed metal elements and raised the buffering capacity of the digester, facilitating high organic loadings without pH control. Food waste also provided lipids to the seaweed feed which augmented the digestion performance. The maximum cumulative methane yield of 292.18 ± 8.70 mL/gVS was obtained from a blend of co-pretreated pelagic Sargassum and food waste at the weight ratio 25:75. Screening of the whole digestate from co-digestion indicated bio-fertiliser potential. However, the solid fraction necessitates arsenic remediation to meet international soil standard guidelines. The findings of this study are promising and suggest opportunity for the design, scale up and optimisation of biogas systems, equipped with hydrothermal pretreatment for utilisation of Sargassum seaweeds during influx.

Grey's Anatomy effect: television portrayal of patients with trauma may cultivate unrealistic patient and family expectations after injury.

BACKGROUND: Expectations of the healthcare experience may be influenced by television dramas set in the hospital workplace. It is our perception that the fictional television portrayal of hospitalization after injury in such dramas is misrepresentative. The purpose of this study was to compare trauma outcomes on television dramas versus reality. METHODS: We screened 269 episodes of Grey's Anatomy, a popular medical drama. A television (TV) registry was constructed by collecting data for each fictional trauma portrayed in the television series. Comparison data for a genuine patient cohort were obtained from the 2012 National Trauma Databank (NTDB) National Program Sample. RESULTS: 290 patients composed of the TV registry versus 4812 patients from NTDB. Mortality was higher on TV (22% vs 7%, P<0.0001). Most TV patients went straight from emergency department (ED) to operating room (OR) (71% vs 25%, P<0.0001). Among TV survivors, a relative minority were transferred to long-term care (6% vs 22%, P<0.0001). For severely injured (Injury Severity Score ≥25) survivors, hospital length of stay was less than 1 week for 50% of TV patients versus 20% in NTDB (P<0.0001). CONCLUSIONS: Trauma patients as depicted on television dramas typically go from ED to OR, and survivors usually return home. Television portrayal of rapid functional recovery after major injury may cultivate false expectations among patients and their families. LEVEL OF EVIDENCE: Level III.

Health literacy and quality of physician-trauma patient communication: Opportunity for improvement.

BACKGROUND: Although physician-patient communication and health literacy (HL) have been studied in diverse patient groups, there has been little focus on trauma patients. A quality improvement project was undertaken at our Level I trauma center to improve patient perception of physician-patient communication, with consideration of the effect of HL. We report the first phase of this project, namely the reference level of satisfaction with physician-patient communication as measured by levels of interpersonal care among patients at an urban Level I trauma center. METHODS: Level I trauma center patients were interviewed during hospitalization (August 2016 to January 2017). Short Assessment of Health Literacy tool was used to stratify subjects by deficient versus adequate HL. Interpersonal Processes of Care survey was administered to assess perception of physician-patient communication. This survey allowed patients to rate physician-patient interaction across six domains: "clarity," "elicited concerns," "explained results," "worked together (on decision making)," "compassion and respect," and "lack of discrimination by race/ethnicity." Each is scored on a five-point scale. Frequencies of "top-box" (5/5) scores were compared for significance (p < 0.05) between HL-deficient and HL-adequate patients. RESULTS: One hundred ninety-nine patients participated. Average age was 42 years, 33% female. Forty-nine (25%) patients had deficient HL. The majority of patients in both groups rated communication below 5/5 across all domains except "compassion and respect" and "lack of discrimination by race/ethnicity." Health literacy-deficient patients were consistently less likely to give physicians top-box scores, most notably in the "elicited concerns" domain (35% vs. 54%, p = 0.012). CONCLUSION: Health literacy-deficient patients appear relatively less satisfied with physician communication, particularly with respect to perceiving that their concerns are being heard. Overall, however, the majority of patients in both groups were unlikely to score physician communication in the "top box." Efforts to improve physician-trauma patient communication are warranted, with attention directed toward meeting the needs of HL-deficient patients. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, level I.

The anatomy of the musculocutaneous latissimus dorsi flap for neophalloplasty.

In transgender surgery, the ideal neophallus is one that: (a) is constructed using a reproducible procedure, (b) possesses tactile and erogenous sensation, (c) is large and rigid enough (naturally, or using a prosthesis) to permit penetrative intercourse, (d) leaves acceptable donor site morbidity, (e) results in esthetically satisfactory appearance, and (f) allows for voiding while standing. The musculocutaneous latissimus dorsi (MLD) flap has favorable results in the area of neophalloplasty. Among its advantages are acceptable donor site appearance, stiffness sufficient for intercourse, and esthetically satisfactory genital appearance. The anatomy of the MLD flap supports the creation of a neophallus for transsexual anatomy revision. Herein, we give an overview of the advantages and disadvantages of the procedure, and the anatomical details and surgical steps involved. Novel illustrations were created from standard surgical text descriptions to clarify this topic for surgical training and patient understanding and decision making. A review of the relevant literature regarding the anatomy, procedure development, and outcomes is presented. The MLD flap uses part of the latissimus dorsi muscle with branches of the thoracodorsal vessels and nerve to construct a neophallus. A thin strip of muscle around the pedicle is harvested, resulting in a slightly curvilinear scar. The blood supply is connected to the femoral artery and saphenous vein or the deep inferior epigastric artery and vein, while the nerve is connected to the ilioinguinal nerve or the obturator nerve. The MLD flap for neophalloplasty is a reliable graft with a well concealed scar and low donor site morbidity. Clin. Anat. 31:152-159, 2018. © 2017 Wiley Periodicals, Inc.

The anatomy of forearm free flap phalloplasty for transgender surgery.

Transgender surgeries are becoming more frequent and visual interpretation of anatomy is essential for both surgeons and patients. Since the forearm free flap phalloplasty was introduced in 1984, it has been known to provide reliable cosmetic and functional results for transitioning men compared with phalloplasty by different flaps. Surgical text descriptions were enhanced by the creation of new anatomic illustrations. The forearm free flap consists of the anterior forearm skin, subcutaneous tissue, fascia containing the radial artery as the perforator and its venae comitantes, cephalic and basilic veins, and lateral and medial antebrachial cutaneous nerves are demonstrated in relation to the surgically derived flap. Song's forearm free flap phalloplasty requires two surgical stages with a three-month interval between the stages: prelamination of a neourethra and construction of a neophallus. The neophallus created by forearm flap phalloplasty is reported to achieve acceptable aesthetical and psychological satisfaction, appropriate size and shape, and satisfying sexual intercourse. Despite increasing experiences in gender confirming surgery with modifications made by many authors, urethral complications including fistula and/or stricture formation are the leading causes of reoperation. The poor esthetic outcome of the forearm donor site and a decrease in rigidity of the neophallus are the main limitations. Illustrations of anatomy help inform surgical choice and understanding of risks and benefits by patients. The anatomy of the free forearm flap phalloplasty supports creation of a neophallus for transsexual anatomy revision. Clin. Anat. 31:145-151, 2018. © 2017 Wiley Periodicals, Inc.

Risk factors for extubation failure at a level I trauma center: does the specialty of the intensivist matter?

INTRODUCTION: Extubation failure in critically ill patients is associated with higher morbidity and mortality. Although predictors of failed extubation have been previously determined in intensive care unit (ICU) cohorts, relatively less attention has been directed toward this issue in patients with trauma. The aim of this study was to identify predictors of extubation failure among patients with trauma in a multidisciplinary ICU setting. METHODS: A prospective observational study of extubation failures (EF) was conducted at an American College of Surgeons level I trauma center over 3 years (2011-2013). Case-control patients (CC) were then compared with the study group (EF) with respect to demographic/clinical characteristics and outcomes. Failure of extubation was defined as reintubation within 72 hours following planned extubation. RESULTS: 7830 patients were admitted to the trauma service and 1098 (14%) underwent mechanical ventilation. 63 patients met inclusion criteria for the EF group and 63 comprised the CC group. The overall rate of extubation failure was 5.7% and mean time to reintubation was 13.0 hours. Groups (EF vs CC) were similar for Injury Severity Score (21 vs 21), Glasgow Coma Scale at extubation (11 vs 10), number of comorbidities (1.5 vs 1.7), injury mechanism (blunt 79% vs 74%), and body mass index (27.9 vs 27.2). In addition, groups were similar with respect to weaning protocol compliance (84% vs 89%, p=0.57). EF group had significantly increased ICU length of stay (LOS) (15.7 vs 7.4 days, p<0.001), ventilator days (13.3 vs 4.8, p<0.001), and mortality (9.5% vs 0%, p=0.03). Multiple regression analysis identified that EF was associated with increased odds of: (1) temperature >38°C at time of extubation (OR 5.9, 95% CI 1.7 to 20.8), and (2) non-surgeon intensivist consultation (OR 24.2, 95% CI 5.5 to 105.9). CONCLUSIONS: Extubation failure is associated with increased LOS, ventilator days, and mortality in patients with trauma. Fever at time of extubation is associated with extubation failure, and the presence of such should give pause in the decision to extubate. Non-surgeon intensivist involvement increases risk of extubation failure, and a surgical critical care service may be most appropriate for the management of ventilated patients with trauma. LEVEL OF EVIDENCE: III, Prognostic and epidemiological.

Structural basis for thermostability in aporubredoxins from Pyrococcus furiosus and Clostridium pasteurianum.

The structures of apo- and holorubredoxins from Pyrococcus furiosus (PfRd) and Clostridium pasteurianum (CpRd) have been investigated and compared using residual dipolar couplings to probe the origin of thermostability. In the native, metal (Fe or Zn) containing form, both proteins can maintain native structure at very high temperatures (>70 degrees C) for extended periods of time. Significant changes in either structure or backbone dynamics between 25 and 70 degrees C are not apparent for either protein. A kinetic difference with respect to metal loss is observed as in previous studies, but the extreme stability of both proteins in the presence of metal makes thermodynamic differences difficult to monitor. In the absence of metal, however, a largely reversible thermal denaturation can be monitored, and a comparison of the two apoproteins can offer insights into the origin of stability. Below denaturation temperatures apo-PfRd is found to have a structure nearly identical to that of the native holo form, except immediately adjacent to the metal binding site. In contrast, apo-CpRd is found to have a structure distinctly different from that of its holo form at low temperatures. This structure is rapidly lost upon heating, unfolding at approximately 40 degrees C. A PfRd mutant with the hydrophobic core mutated to match that of CpRd shows no change in thermostability in the metal-free state. A metal-free chimera with residues 1-15 of CpRd and the remaining 38 residues of PfRd is severely destabilized and is unfolded at 25 degrees C. Hence, the hydrophobic core does not seem to be the key determinant of thermostability; instead, data point to the hydrogen bond network centered on the first 15 residues or the interaction of these 15 residues with other parts of the protein as a possible contributor to the thermostability.

Central interactions between angiotensin II and PGD(2) in the regulation of vasopressin and oxytocin secretion in dehydrated rats.

Brain-derived angiotensin II (ANG II) and prostaglandins have important roles in the regulation of body fluid and blood pressure homeostasis. In the present studies we investigated the central interactions between these two neurochemical products in regulating the hypothalamo-neurohypophysial system during dehydration. Intracerebroventricular (icv) administration of prostaglandin D(2) (PGD(2); 20 microg/5 microl) to conscious adult male Sprague-Dawley rats deprived of water for 24 h did not alter significantly the already elevated plasma levels of vasopressin or oxytocin. When PGD(2) was administered in combination with losartan, an antagonist of ANG II AT(1)-receptor subtype, however, concentrations of both hormones in plasma became further elevated. Icv administration of ANG II (50 ng/5 microl) increased further the enhanced plasma levels of vasopressin and oxytocin, as expected. Pretreatment with indomethacin (200 microg/5 microl; icv), an inhibitor of cyclo-oxygenase, significantly attenuated the ANG II-induced increase in oxytocin secretion only. Independent of the presence of ANG II, however, indomethacin decreased plasma levels of vasopressin, but not oxytocin. These results indicate that a prostaglandin is required for the stimulated release of vasopressin during dehydration and that the elevation of oxytocin secretion in response to ANG II depends largely on activation of cyclo-oxygenase and production of prostaglandins. The oxytocin response to exogenously administered PGD(2), however, can be negatively modulated by a mechanism dependent upon ANG II AT(1) receptors.

Indomethacin prevents the L-NAME-induced increase in plasma levels of oxytocin in dehydrated rats.

Inhibiting NO synthase (NOS) with N(G)-nitro-L-arginine methyl ester (L-NAME, 250 microg/5 microl of artificial cerebrospinal fluid (aCSF)) injected intracerebroventricularly (i.c.v.) increased already enhanced levels of oxytocin, but not vasopressin, in conscious adult male Sprague-Dawley rats dehydrated for 24 h. Intracerebroventricular pretreatment with indomethacin (200 microg/5 microl aCSF), an inhibitor of cyclo-oxygenase, but not with losartan (25 microg/5 microl aCSF), an antagonist of angiotensin II (ANG II) AT(1)-receptor subtype, nearly prevented the elevation in oxytocin levels after L-NAME. Thus, NO inhibits prostaglandin (but not ANG II) mediated the modulatory actions of NO on oxytocin secretion from the hypothalamo-neurohypophysial system (HNS) during water deprivation.

Variation of molecular alignment as a means of resolving orientational ambiguities in protein structures from dipolar couplings.

Residual dipolar couplings for pairs of proximate magnetic nuclei in macromolecules can easily be measured using high-resolution NMR methods when the molecules are dissolved in dilute liquid crystalline media. The resulting couplings can in principle be used to constrain the relative orientation of molecular fragments in macromolecular systems to build a complete structure. However, determination of relative fragment orientations based on a single set of residual dipolar couplings is inherently hindered by the multi-valued nature of the angular dependence of the dipolar interaction. Even with unlimited dipolar data, this gives rise to a fourfold degeneracy in fragment orientations. In this Communication, we demonstrate a procedure based on an order tensor analysis that completely removes this degeneracy by combining residual dipolar coupling measurements from two alignment media. Application is demonstrated on (15)N-(1)H residual dipolar coupling data acquired on the protein zinc rubredoxin from Clostridium pasteurianum dissolved in two different bicelle media.

The effect of mass, stiffness and geometry on injury outcome in side impacts - a parametric study.

This paper reports on a cooperative research project between the Australian Department of Transport and Regional Services and Transport Canada. This project was a parametric study aimed at better understanding the effects on side impact injury risk of: * Trolley mass * Barrier stiffness * Barrier stiffness distribution * Barrier face height above ground * Crabbed or perpendicular impact * Impact Speed The following observations on injury risk can be made from the tests: * The 2 largest effects for the driver are increasing the height of the barrier face (mainly thoracic) and test speed (all body regions). * Increasing the trolley mass, with a bullet / target mass ratio less than 1, has the effect of increasing only the pubic force. * Doubling the barrier stiffness increases injury risk in only the pelvic area. * The custom high and stiff element (attempting to replicate an SUV) increases both pelvic and abdominal loading.

Angiotensin II does not mediate the pressor response to PGD2 (icv).

The objective of the present studies was to examine the interaction between brain-derived angiotensin II (Ang II) and prostaglandins in order to identify the mechanisms mediating the pressor response produced by these neuroregulators. Inhibiting synthesis of prostaglandins with indomethacin [indocin, 200 microg/ 5 microl artificial cerebrospinal fluid (aCSF)], administered intracerebroventricularly (icv) to conscious adult male Sprague-Dawley rats, reduced blood pressure to values below basal levels. When injected prior to Ang II (50 ng/5 microl aCSF; icv), indomethacin completely abolished the pressor response induced by the octapeptide. The increase in blood pressure produced by prostaglandin D(2) (PGD(2), 20 microg/5 microl; icv), the most prominent prostaglandin in the rat brain, however, was not prevented by losartan (25 microg/5 microl; icv), an Ang II AT(1)-receptor antagonist. Collectively, these results indicate that prostaglandins produced tonically in the brain maintain resting arterial blood pressure and that the pressor action of Ang II is dependent on de novo synthesis of a prostaglandin.

Intraventricular infusion of nerve growth factor as the cause of sympathetic fiber sprouting in sensory ganglia.

OBJECT: The results of previous clinical trials have indicated that intraventricular infusion of nerve growth factor (NGF) in patients with Alzheimer's disease is frustrated by the appearance of weight loss and diffuse back pain. The present study tested whether NGF induces sympathetic sprouting in sensory ganglia. Such sprouting has been implicated in previous studies as a possible mechanism of sympathetically maintained pain in neuropathic animals. METHODS: Nineteen Long-Evans rats underwent intraventricular infusion of either artificial cerebrospinal fluid (ACSF; seven animals) or NGF (12 animals). After 14 days of infusion, the sensory ganglia of the trigeminal nerve and the C-2, C-8, T-1, L-4, and L-5 dorsal roots were examined for sympathetic sprouting by using tyrosine hydroxylase immunohistochemical analysis. CONCLUSIONS: In the animals receiving NGF, 52 of 144 ganglia showed sympathetic fiber sprouting. In the control animals receiving ACSF, only two of 72 ganglia showed minor sympathetic fiber sprouting. A preferential sprouting of sympathetic fibers was demonstrated at lower lumbar ganglia compared with the cervical and thoracic ganglia. The data presented here demonstrate that in the rat intraventricular NGF infusion caused sympathetic sprouting in dorsal root ganglia (p < 0.01). These findings may have importance both for the treatment of Alzheimer's disease and the understanding of neuropathic pain.

Brain ANG II and prostaglandins mediate the pressor response after central blockade of nitric oxide synthase.

Central inhibition of nitric oxide synthase (NOS) by intracerebroventricular (i.c.v.) administration of NG-nitro-l-arginine methyl ester (L-NAME; 150 microg/5 microl) to conscious rats produced a biphasic pressor response characterized by an initial transient increase within 5 min, and a delayed response starting between 60-90 min. The effect was stereospecific, as D-NAME (250 microg/5 microl) did not modify the resting arterial blood pressure, nor did L-arginine (323 microg/5 microl, i.c.v.), indicating the substrate for NOS is not rate-limiting. Intracerebroventricular pretreatment with losartan (25 microg/5 microl), a non-peptide antagonist of the angiotensin II AT1 receptor subtype, or indomethacin (100 microg/5 microl), a blocker of cyclooxygenase, however, prevented the initial increase in blood pressure without affecting the delayed pressor response. In contrast, neither intravenous losartan (10 mg/kg b.wt) nor prazosin, an alpha1 adrenergic receptor antagonist, at doses of 5 microg/5 microl (i.c.v.) or 0.3 mg/kg b.wt (i.v.) were effective in altering the pressor responses. These results indicate that centrally produced NO maintains the resting arterial blood pressure at least partially through modulation of the brain angiotensin system and prostaglandins.

Nitric oxide control of drinking, vasopressin and oxytocin release and blood pressure in dehydrated rats.

Intracerebroventricular (i.c.v.) injection of the inhibitor of NO synthase (NOS), N(G)-nitro-L-arginine methyl ester (L-NAME) (250 microg/5 microL) attenuated the drinking response in rats deprived of water for 24 h. Moreover, oxytocin (OT) levels in plasma increased after 2 min, whereas both oxytocin and vasopressin levels were elevated at 120 min after intracerebroventricular injection. The delayed effect of L-NAME on both hormones was not observed in dehydrated animals allowed to drink water. Blood pressure remained stable after injection of artificial cerebrospinal fluid (aCSF) in dehydrated rats not allowed to drink. In rats having access to water, however, there was an immediate but transient pressor response (0-5 min) with a delayed hypotension from 45 to 120 min. L-NAME consistently increased blood pressure in a biphasic mode, whether the animals drank or not, with an early peak at 5 min that decayed after 15-30 min and a second pressor response beginning at 30-45 min and remaining elevated at 120 min when the experiment ended. These pressor responses were independent of the adrenal glands. Thus, centrally produced nitric oxide facilitates drinking, inhibits release of vasopressin and oxytocin from the magnocellular system, and maintains resting arterial blood pressure in normally hydrated and dehydrated rats.

Effects of L-NAME on cerebral metabolic, vasopressin, oxytocin, and blood pressure responses in hemorrhaged rats.

NG-nitro-L-arginine methyl ester (L-NAME; 250 micrograms/5 microliters), an inhibitor of NO synthase, or the vehicle artificial cerebrospinal fluid (aCSF; 5 microliters) was administered intracerebroventricularly to conscious rats hemorrhaged (0.7 ml/min) to a 20% volume depletion. Hypotension was maximal 5 min after hemorrhage ended, with compensatory recovery to basal levels 20 min later, regardless of drug treatment. L-NAME, however, elevated (P < 0.05) blood pressure (vs. aCSF controls) 40-45 min after intracerebroventricular administration. In normovolemic rats, L-NAME produced a significant pressor response and increased plasma levels of vasopressin (VP) and oxytocin (OT). After hemorrhage, both hormone levels increased, but only OT was further enhanced by L-NAME. Thus centrally produced NO tonically inhibits OT and VP secretion under basal normovolemic conditions and selectively inhibits OT release during hypovolemia. Hemorrhage increased the rates of glucose utilization in the neural lobe, indicative of enhanced efferent neural functional activity. L-NAME further enhanced the metabolic activity in the entire hypothalamoneurohypophysial system of hemorrhaged animals. Several other brain structures involved in the regulation of blood pressure and the stress response were also metabolically affected by the hemorrhage and L-NAME.

Effects of central injection of kyotorphin and L-arginine on oxytocin and vasopressin release and blood pressure in conscious rats.

Intracerebroventricular (I.C.V.) administration of an inhibitor of nitric oxide synthase (NOS) increases oxytocin but not vasopressin secretion, in dehydrated rats [38]. Surprisingly, central injection of L-arginine, the substrate for NOS, caused a similar effect. Kyotorphin (L-tyrosyl-L-arginine), a dipeptide formed from L-arginine by kyotorphin synthetase in the brain may mediate this magnocellular response. Therefore, the dose and time responses of hormone release were compared following I.C.V. injection of kyotorphin and L-arginine to conscious rats that were normally hydrated or deprived of water for 24 h. In water-sated rats, both L-arginine and kyotorphin increased blood pressure and plasma glucose levels coincident with elevating circulating levels of oxytocin, but not vasopressin. In dehydrated animals, both L-arginine and kyotorphin increased plasma oxytocin levels with a similar time course but only kyotorphin decreased vasopressin release. D-arginine, like L-arginine, stimulated secretion of oxytocin, indicating a nonstereospecific effect. A kyotorphin receptor antagonist (L-leucyl-L-arginine) given I.C.V. to dehydrated animals elevated plasma oxytocin and prevented the decrease in vasopressin levels after kyotorphin. Thus, kyotorphin, but not L-arginine, appears to attenuate release of vasopressin either directly from magnocellular neurons or indirectly via modulating compensatory reflexes activated by the pressor response. On the other hand, an excess of L-arginine and kyotorphin within the CNS may mimic the stress response by augmenting release of oxytocin and activating the sympathetic nervous system to increase blood pressure and plasma glucose levels.

Role of NO on vasopressin and oxytocin release and blood pressure responses during osmotic stimulation in rats.

NG-nitro-L-arginine methyl ester (L-NAME, 250 micrograms/5 microliters), an inhibitor of nitric oxide (NO) synthase, or artificial cerebrospinal fluid (5 microliters) was administered intracerebroventricularly to conscious naive rats or to rats treated subcutaneously (15 microliters/kg) with NaCl (0.15, 0.45, or 1.0 M) or given a needle prick only. Intracerebroventricular injection of L-NAME increased plasma concentration of vasopressin (VP) and oxytocin (OT) in control naive rats, indicating that NO tonically inhibits basal secretion of both hormones during isosmotic isovolemic conditions. Osmotic stimulation with hypertonic saline (0.45 and 1.0 M NaCl) elevated plasma levels of both hormones as expected. Central blockade of NO synthase further enhanced secretion of OT during mild, but not strong, osmotic stimulation, whereas the high levels of VP remained unaffected by L-NAME. In animals treated with the needle prick or 0.15 M NaCl, only OT levels were increased after L-NAME. Therefore, NO selectively inhibits OT release in response to a painful stimulus (needle prick) and moderate osmotic stimulation to promote a preferential release of VP. A transient pressor response was observed after subcutaneous injection of 0.15 and 0.45 M NaCl, but a sustained response was obtained after 1.0 M NaCl. Regardless of whether the animals received NaCl solutions, however, treatment with L-NAME elevated blood pressure in all animals. Thus NO-induced vasodilation maintains basal arterial blood pressure and limits the pressor response to osmotic stimulation.

NO and angiotensin II effects on blood pressure and fluid homeostasis.

Angiotensin II (50 ng/5 microl) and L-NAME (250 microg/5 microl), an inhibitor of NO synthase (NOS), were administered intracerebroventricularly alone or in combination to conscious rats. Mean arterial blood pressure (MABP) increased reaching a peak within 5 min in all groups compared to controls treated with the vehicle, artificial CSF (5 microl). MABP returned to basal levels at 30 min after angiotensin II and remained stable for the following 90 min. In animals treated with L-NAME alone, after the initial pressor response, MABP declined but began to increase progressively from 30 min until the end of the experiment at 120 min. When administered with angiotensin II, however, the initial pressor response was prolonged. Angiotensin II-induced drinking was significantly attenuated by L-NAME. In control rats, inhibiting NOS elevated plasma levels of oxytocin and vasopressin but in angiotensin II-stimulated animals, only oxytocin was further elevated after L-NAME. Thus, NO formed centrally inhibits basal secretion of oxytocin and vasopressin as well as the resting blood pressure. During stimulation with angiotensin II, NO facilitates drinking, limits the pressor response and selectively inhibits oxytocin release.

Osmoregulation of the magnocellular neuroendocrine system during lactation.

Glucose utilization and Fos expression were used to compare responses of cerebral structures involved in osmoregulation in virgin and lactating rats given 0.15, 0.85, or 1.5 M NaCl subcutaneously. In virgin animals, glucose utilization increased (P < 0.05) in the supraoptic nuclei (SON), paraventricular nuclei (PVN), and neural lobe (NL) proportionally to the osmotic stimulus (0.15 M NaCl < 0.85 M NaCl < 1.5 M NaCl), whereas metabolism in the median preoptic nucleus (MPO) and median eminence (ME) increased only after 1.5 M NaCl. In lactating rats, enhanced utilization of glucose in response to osmotic stimulation was absent in the PVN (0.85 M NaCl), MPO, and ME or significantly (P < 0.01) reduced (SON, PVN, NL) compared with virgin animals. Glucose utilization in each structure correlated linearly with plasma osmolality but with a lower slope (P < 0.05) in lactating animals. Magnocellular neurons expressing Fos in the SON increased linearly with plasma osmolality and were more numerous (P < 0.05) in control lactating animals but increased less (P < 0.05) than in virgin rats after 0.85 M NaCl. The attenuated magnocellular response during lactation results from reduced afferent activation from osmosensitive forebrain sites.