The effect of changes in arterial PCO2 on neuroendocrine function in man

There is evidence that changes in arterial P(CO(2)) (P(a,CO(2))), as well as P(O(2)), influence neuroendocrine function. The hyponatraemia and fluid retention (cor pumonale) seen in chronic obstructive pulmonary disease (COPD) and type II respiratory failure is associated with increased vasopressin release. This study examines the specific effects of altered P(a,CO(2)) on hormone release from the posterior and anterior pituitary. The study was performed in 20 ventilated ICU patients in the late recovery phase of their illness. None had primary respiratory disease. Control blood samples were taken and the alveolar ventilation was then adjusted to allow the P(a,CO(2)) increase or decrease for a period of 3 h, during which time further blood samples were taken for the determination, by radioimmmunoassy of vasopressin, oxytocin, growth hormone and cortisol. Urine output and electrolyte concentrations were also measured. Circulating concentrations of growth hormone and oxytocin increased with increasing P(a,CO(2)). Vasopressin release showed a similar pattern up to a P(a,CO(2)) of approximately 6.0 kPa, above which vasopressin concentrations were inversely related to P(a,CO(2)). There was no significant effect on cortisol concentrations. No significant effects were established in urinary parameters during the short period of this study. Thus an increase in CO(2) is associated with stimulated pituitary hormone release. The effect on the neurohypophysial hormones may account for the fluid retention and hyponatraemia seen in COPD and hence provide a rationale for treatment.     

Hyponatraemia aggravates cardiac susceptibility to ischaemia/reperfusion injury

Hyponatraemia is defined as a serum sodium concentration of <135 mEql/L and is the most common electrolyte disturbance in patients with chronic heart failure. We hypothesize that hyponatraemia may induce Ca²⁺ overload and enhance reactive oxygen species (ROS) production, which will exacerbate myocardial injury more than normonatraemia. We investigated the effect of hyponatraemia on the ability of the heart to recover from ischaemia/reperfusion episodes. Cardiomyocytes were obtained from 1‐ to 3‐day‐old Sprague Dawley rats. After isolation, cardiomyocytes were placed in Dulbecco's modified Eagle's medium (DMEM) containing low sodium concentration (110, 120, or 130 mEq/L) or normal sodium concentration (140 mEq/L) for 72 hours. Exposure of cardiomyocytes to each of the low‐sodium medium significantly increased both ROS and intracellular Ca²⁺ levels compared with the exposure to the normal‐sodium medium. In vivo, 8‐week‐old male Sprague Dawley rats were divided into four groups: control group (Con), furosemide group (Fur), low‐sodium diet group (Lsd) and both furosemide and low‐sodium diet group (Fur + Lsd). The hearts subjected to global ischaemia exhibited considerable decrease in left ventricular developed pressure during reperfusion, and the size of infarcts induced by ischaemia/reperfusion significantly increased in the Fur, Lsd and Fur + Lsd compared with that in the Con. Hyponatraemia aggravates cardiac susceptibility to ischaemia/reperfusion injury by Ca²⁺ overload and increasing in ROS levels.     

Relative adrenal insufficiency in post-transplant lymphoproliferative disorder

Post-transplant lymphoproliferative disorder is treated with rapid decrement of immunosuppressive therapy. This cannot be achieved with ease in patients on long-term glucocorticoid therapy, as chronically suppressed adrenal glands may not be capable of mounting adequate response to stress. A 52-year-old Caucasian male presented with fever, orthostatic hypotension, lymphadenopathy and hyponatraemia. Serum cortisol levels were within normal levels with a sub optimal response to stimulation by ACTH. Hyponatraemia and orthostasis responded poorly to fluid restriction, saline and salt repletion but corrected after increasing the steroid dose. The normal baseline cortisol levels represented a stimulated adrenal gland, however, the ACTH stimulation had inadequate response. This sub optimal stimulation and a good response to increased steroids suggest the presence of relative or occult adrenal insufficiency. Relative adrenal insufficiency must be considered in patients who have received prolonged glucocorticoid therapy and have symptoms such as hypotension and/or hyponatraemia.     

Experimental water intoxication induced by dDAVP in rat, and its prevention with the vasopressin antagonist d(CH2)5Tyr(Et)VAVP

A new rat model of the Schwartz--Bartter syndrome was created by the administration of 1-deamino-8-D-arginine vasopressin together with a forced water intake. The treatment led to water retention, hypernatriuria, marked hyponatraemia (in 4-5 days) and severe cerebral oedema. These changes could be prevented by the simultaneous administration of [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid)- 2-o-ethyltyrosine-4-valine] arginine vasopressin. The observations indicate that this vasopressin antagonist analogue might be of use in the future as an effective drug against the Schwartz--Bartter syndrome.     

Severe hyponatraemia: investigation and management in a district general hospital

AIMS: To study the incidence, investigation, and management of severe hyponatraemia (serum sodium < 120 mmol/litre) over a period of six months in a district general hospital. METHODS: The laboratory computer was used to identify all inpatients who had a serum sodium concentration of less than 120 mmol/litre over a six month period. The records of these patients were reviewed for the relevant demographic, clinical, and laboratory data, in addition to diagnosis, treatment, and outcome of hospitalisation. RESULTS: Forty two patients were studied, with a female to male ratio of 2 : 1. Nine patients had central nervous system symptoms, and four of these patients died in hospital. Only 14 patients had their urinary electrolytes and/or osmolality checked. A diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was mentioned in eight patients, sometimes without checking their urinary electrolytes or osmolality. Twenty one patients died in hospital. The patients who died did not have lower serum sodium values or a higher rate of correction of hyponatraemia, but they all suffered from advanced medical conditions. CONCLUSIONS: The possible cause of hyponatraemia should always be sought and that will require an accurate drug history, clinical examination, and assessment of fluid volume, plus the measurement of urinary electrolytes and osmolality in a spot urine sample. The diagnosis of SIADH should not be confirmed without the essential criteria being satisfied. The current or recent use of diuretics is a possible pitfall in the diagnosis of SIADH. The rate of serum sodium correction of less than 10 mmol/day is probably the safest option in most cases.     

Intracellular calcium signalling in magnocellular neurones of the rat supraoptic nucleus: understanding the autoregulatory mechanisms

Oxytocin and vasopressin, released at the soma and dendrites of neurones, bind to specific autoreceptors and induce an increase in [Ca²⁺]₁. In oxytocin cells, the increase results from a mobilisation of Ca²⁺ from intracellular stores, whereas in vasopressin cells, it results mainly from an influx of Ca²⁺ through voltage-dependent channels. The response to vasopressin is coupled to phospholipase C and adenylyl-cyclase pathways which are activated by V₁ (V_1a and V_1b)- and V₂-type receptors respectively. Measurements of [Ca²⁺]₁ in response to V_1a and V₂ agonists and antagonists suggest the functional expression of these two types of receptors in vasopressin neurones. The intracellular mechanisms involved are similar to those observed for the action of the pituitary adenylyl-cyclase-activating peptide (PACAP). Isolated vasopressin neurones exhibit spontaneous [Ca²⁺]₁ oscillations and these are synchronised with phasic bursts of electrical activity. Vasopressin modulates these spontaneous [Ca²⁺]₁ oscillations in a manner that depends on the initial state of the neurone, and such varied effects of vasopressin may be related to those observed on the electrical activity of vasopressin neurones in vivo.     

Vasopressin receptor antagonism — a therapeutic option in heart failure and hypertension

The precise role of vasopressin in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is important for several reasons. Firstly, circulating concentrations of vasopressin are elevated in heart failure and some forms of hypertension. Secondly, there is evidence that vasopressin is synthesized not only in the hypophysial-pituitary axis but also in peripheral tissues including the heart where it acts as a paracrine hormone. Thirdly, vasopressin has vasoconstrictor, mitogenic, hyperplastic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Finally, the availability of orally active non-peptide vasopressin receptor antagonists allows vasopressin receptor antagonism to be considered as a therapeutic option in cardiovascular disease.     

Hyponatraemia in cases of children with pneumonia

Introduction

Hyponatraemia is the most common electrolyte imbalance seen in clinical practice, and a common laboratory finding in children with community-acquired pneumonia (CAP). This study aimed to identify the incidence of hyponatraemia in cases of CAP, to find predictive tools in order to classify the severity and outcome of CAP and to explore possible differences of clinical importance between the two sexes.

Material and methods

The medical files of 54 children (66.4% males), 4.67 ±2.88 years old, were retro-prospectively reviewed.

Results

35/54 (64.8%) children with pneumonia had normal values of sodium at admission, 18/54 (33.3%) had mild hyponatraemia and 1 child (1.9%) moderate hyponatraemia. Increased heart rhythm and tachypnoea at admission were correlated with lower values of sodium (z= −2.664, p = 0.007 and z = −1.705, p = 0.089 respectively). No differences were found between the two sexes concerning the characteristics of pneumonia or the range of sodium in serum at admission. A correlation was found between sodium admission values and: a) C-reactive protein (p = 0.000), and b) leukocyte count (p = 0.006). Sedimentation rate (p = 0.021) was also considered as a possible risk factor affecting the value of sodium at admission to hospital. Finally, a negative association was also observed between the degree of hyponatraemia and the duration of hospitalization (z = −3.398, p = 0.001).

Conclusions

Although studies in larger population groups are needed, in our study increased heart rhythm, tachypnoea, leucocyte count, C-reactive protein, and also erythrocyte sedimentation rate could be considered as possible risk factors influencing the degree of hyponatraemia, and thus the outcome of hospitalized children with CAP.     

Intracellular calcium and hormone release from nerve endings of the neurohypophysis in the presence of opioid agonists and antagonists

Summary Rat neural lobes and isolated nerve terminals from the neurohypophysis were stimulated in the presence of different opioid agonists and antagonists. The secretion of arginine vasopressin and oxytocin and rise in cytoplasmic calcium induced by depolarization were analyzed by radioimmunoassay and the fluorescent probe fura-2, respectively. The kappa-agonists dynorphin A_{1 -13} and dynorphin A_{1 -8} did not affect electrically evoked release of vasopressin, although oxytocin release was slightly reduced. U-50 488, a relatively specific kappa-receptor agonist, had no effect on the amount of vasopressin or oxytocin secreted, although it significantly reduced K⁺-evoked changes in [Ca²⁺]_i in isolated nerve endings. Two kappa-receptor antagonists, MR 2266 and diprenorphin, alone had no effect on vasopressin and oxytocin secretion from isolated nerve endings depolarized with potassium. Opioid agonists less selective for the kappa receptors, etorphin and ethylketocyclazocin, were found to inhibit the release of both vasopressin and oxytocin significantly. Naloxone, a nonselective opiate receptor antagonist, alone had no effect on vasopressin release but potentiated the electrically evoked release of oxytocin. Naloxone also could overcome the inhibitory effect of etorphin on oxytocin and vasopressin release observed after electrical stimulation of the neural lobe. A number of inconsistencies therefore exist between the effects of opioid agonists and antagonists on neuropeptide release and on the evoked changes in [Ca²⁺]_i. In view of these inconsistencies and the high concentrations of opioid agonists and antagonists necessary to modify release, we conclude that it is doubtful that opioid molecules have a physiological role in controlling neurohypophysial secretion.     

Natriferic and hydrosmotic effects of neurohypophysial peptides and their analogues in augmenting fluid uptake by Bufo melanostictus

1. The effect of intramuscular injection of 8-arginine vasotocin, 8-arginine vasopressin, 8-lysine vasopressin, oxytocin, 8-ornithine oxytocin and 8-ornithine vasopressin on fluid uptake across the skin was studied in the live toad, Bufo melanostictus, bathed either in distilled water or in NaCl solution (0.1 g/100 ml.).2. When the bathing solution was distilled water, 8-arginine vasotocin was the most potent, 0.14 nmole/kg augmenting the rate of fluid uptake by 50%. Compared with it the others had relative potencies of: 8-arginine vasopressin 0.8, 8-lysine vasopressin 0.8 x 10(-3), oxytocin 0.8 x 10(-3), 8-ornithine oxytocin 0.8 x 10(-2), 8-ornithine vasopressin < 1.4 x 10(-4).3. When the bathing solution contained 0.1% NaCl, 8-arginine vasotocin was again the most potent, 0.06 nmole/kg augmenting the rate of fluid uptake by 50%. Compared with it the others had relative potencies of: 8-arginine vasopressin 0.3, 8-lysine vasopressin 0.3 x 10(-3), oxytocin 0.3 x 10(-2), 8-ornithine oxytocin 0.8 x 10(-2), 8-ornithine vasopressin < 0.6 x 10(-4).4. Dose-response curves for each peptide showed that in the case of 8-arginine vasopressin, 8-lysine vasopressin and 8-ornithine vasopressin the augmentation of rate of fluid uptake did not differ in the absence or in the presence of NaCl in the bathing solution; whereas in the case of 8-arginine vasotocin, oxytocin, and 8-ornithine oxytocin the augmentation was greater in the presence of sodium chloride.5. Support has been found for the postulate of a binary action of some neurohypophysial peptides on amphibian skin, arginine in position 8 being correlated with hydrosmotic effect, and isoleucine in position 3 with natriferic effect.     

Management of rhinitis: allergic and non-allergic

RHINITIS IS A GLOBAL PROBLEM AND IS DEFINED AS THE PRESENCE OF AT LEAST ONE OF THE FOLLOWING: congestion, rhinorrhea, sneezing, nasal itching, and nasal obstruction. The two major classifications are allergic and nonallergic rhinitis (NAR). Allergic rhinitis occurs when an allergen is the trigger for the nasal symptoms. NAR is when obstruction and rhinorrhea occurs in relation to nonallergic, noninfectious triggers such as change in the weather, exposure to caustic odors or cigarette smoke, barometric pressure differences, etc. There is a lack of concomitant allergic disease, determined by negative skin prick test for relevant allergens and/or negative allergen-specific antibody tests. Both are highly prevalent diseases that have a significant economic burden on society and negative impact on patient quality of life. Treatment of allergic rhinitis includes allergen avoidance, antihistamines (oral and intranasal), intranasal corticosteroids, intranasal cromones, leukotriene receptor antagonists, and immunotherapy. Occasional systemic corticosteroids and decongestants (oral and topical) are also used. NAR has 8 major subtypes which includes nonallergic rhinopathy (previously known as vasomotor rhinitis), nonallergic rhinitis with eosinophilia, atrophic rhinitis, senile rhinitis, gustatory rhinitis, drug-induced rhinitis, hormonal-induced rhinitis, and cerebral spinal fluid leak. The mainstay of treatment for NAR are intranasal corticosteroids. Topical antihistamines have also been found to be efficacious. Topical anticholinergics such as ipratropium bromide (0.03%) nasal spray are effective in treating rhinorrhea symptoms. Adjunct therapy includes decongestants and nasal saline. Investigational therapies in the treatment of NAR discussed include capsaicin, silver nitrate, and acupuncture.     

Psychopharmacotherapy of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that develops after a psychological trauma usually caused by a situation perceived as deeply threatening to a person’s life or integrity. Complex neurobiological changes triggered by such a traumatic and stressful experience may explain a wide range of PTSD symptoms and provide the rationale for psychopharmacological treatment. Selective serotonin-reuptake inhibitors make the first-line treatment of PTSD. Clinical experience has shown that they are more effective than noradrenalin-reuptake inhibitors or tricyclic antidepressants. Antipsychotic drugs, especially atypical ones, have been shown effective in PTSD patients with psychotic characteristics or refractoriness to other treatments. Mood stabilizers seem to reduce mostly autonomous overreactions to stress, whereas the evidence for effectiveness of monoamine oxidase inhibitors is largely inconclusive. Other groups of medications, such as serotonin agonists and antagonists, new antidepressants, dual inhibitors of serotonin- and noradrenalin-reuptake, anticonvulsants, and opiate antagonists are also sometimes used in PTSD treatment. However, as shown in the present review, most clinical studies performed to date to investigate the effectiveness of different psychopharmacological agents in the therapy of PTSD have serious limitations in terms of small sample size, lack of blinding and randomization, and small effect size. More rigorously designed, comparative studies are needed to determine the usefulness, efficacy, tolerability, and safety of particular psychopharmaceutical drugs in the treatment of this therapeutically and functionally challenging disorder.     

The So-Called Borderline Patient: Aetiology,Diagnosis, and Treatment

This short paper examines the relationship between borderline psychopathology and various theories regarding the aetiology of this disorder. In the formation of borderline personality organization, distinct structural alterations in personality development are thought to arise from both genetic/neurobiological and environmental/trauma factors. We concur that these variables are instrumental in the formation of borderline personality organization. However, we believe that genetic/neurobiological variables are more closely related to developmental deficits, whereas environmental/trauma factors are primarily associated with either arrested development or regressive phenomenon. Regardless of aetiology, the resultant borderline personality organization disorders may present with comparable symptoms. Further, we hypothesize that the prognosis for response to treatment is related primarily to whether the borderline disorder arises from developmental deficits, arrested development, or regressive phenomena. Diagnostic indicators and treatment considerations for each of the borderline aetiologies are presented.     

Sertraline, a selective serotonin reuptake inhibitor, affects thirst, salt appetite and plasma levels of oxytocin and vasopressin in rats

We investigated the effects of chronic administration of sertraline (SERT; approximately 20 mg kg(-1) day(-1) in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT-treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.7 +/- 0.5 versus 20.0 +/- 0.9 ml, respectively, at 300 min after water presentation, P < 0.0001). Subcutaneous injection of 2 m NaCl or isoproterenol evoked a lower dipsogenic response in rats treated with SERT for 21 days. Fluid and food deprivation also induced a weaker dipsogenic response in SERT-treated rats (1.6 +/- 0.5 versus 10.2 +/- 1.2 ml, at 300 min, P < 0.0001) but had no effect on saline intake. Sodium depletion induced a higher natriorexigenic response in the SERT group (5.6 +/- 1.3 versus 1.2 +/- 0.3 ml, at 300 min, P < 0.0002). Higher urinary density and lower plasma sodium levels were observed after SERT treatment. Sertraline also increased plasma levels of vasopressin and oxytocin (AVP, 2.65 +/- 0.36 versus 1.31 +/- 0.16 pg ml(-1), P < 0.005; OT, 17.16 +/- 1.06 versus 11.3 +/- 1.03 pg ml(-1), P < 0.0009, at the third week post-treatment). These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT.     

Neuropharmacologic control of cerebral capillary permeability: current implications for therapy of vasogenic brain edema

Vasogenic brain edema occurs as a result of a diverse spectrum of central nervous system pathology. The fundamental physiologic abnormality of vasogenic brain edema is an increase in cerebral capillary permeability. It is hypothesized that the recent development of new, potent, synthetic vasopressin antagonists will make it possible to impede the formation of vasogenic brain edema by the intraventricular administration of such agents with the subsequent inhibition of the neural control of brain capillary permeability by the locus ceruleus. The action of the vasopressin antagonists should be synergistic with the anti-edema effects of central alpha-adrenergic blockade produced by phentolamine. The combination of these two modes of therapy is expected to produce an increase in intracranial pressure which will require additional forms of medical therapy to control, in spite of the overall decrease of brain parenchymal water content.     

Primary Sellar Neuroblastoma Presenting with Syndrome of Inappropriate Secretion of Anti-diuretic Hormone

A 29-year-old Ethiopian man presented with marked bilateral visual loss, headache, hypopituitarism and significant hyponatraemia (115 mmol/L). A brain MRI scan demonstrated a large, lobulated, sellar and suprasellar mass, elevating the floor of the 3rd ventricle and compressing the optic chiasm. The patient underwent a transphenoidal resection of the mass followed by a craniotomy 10 days later. Histological examination demonstrated a Hyams’ grade III neuroblastoma with ectopic expression of vasopressin. He underwent fractionated radiotherapy at a dose of 60 Gy in 30 fractions. Fourteen months after the onset, he is well with no neuroimaging evidence of tumour recurrence. His serum and urine sodium are completely normalised.     

Attachment insecurity,mentalization and their relation to symptoms in eating disorder patients

Objective: To investigate the relationships of attachment security and mentalization with core and co-morbid symptoms in eating disorder patients. Method: We compared 51 eating disorder patients at the start of intensive treatment and 20 healthy controls on attachment, mentalization, eating disorder symptoms, depression, anxiety, personality disorders, psycho-neuroticism, autonomy problems and self-injurious behavior, using the Adult Attachment Interview, the SCID-I and II and several questionnaires. Results: Compared with the controls, the eating disorder patients showed a higher prevalence of insecure attachment; eating disorder patients more often than controls received the AAI classification Unresolved for loss or abuse. They also had a lower level of mentalization and more autonomy problems. In the patient group eating disorder symptoms, depression, anxiety, psycho-neuroticism and autonomy problems were neither related to attachment security nor to mentalization; self-injurious behavior was associated with lesser attachment security and lower mentalization; borderline personality disorder was related to lower mentalization. In the control group no relations were found between attachment, mentalization and psychopathologic variables. Discussion: Eating disorder patients’ low level of mentalization suggests the usefulness of Mentalization Based Treatment techniques for eating disorder treatment, especially in case of self-injurious behavior and/or co-morbid borderline personality disorder.     

The role of steroid hormones in the regulation of vasopressin and oxytocin release and mRNA expression in hypothalamo neurohypophysial explants from the rat

Vasopressin and oxytocin release from the neural lobe, and the vasopressin and oxytocin mRNA contents of the supraoptic and paraventricular nuclei are increased by hypertonicity of the extracellular fluid. The factors regulating these parameters can be conveniently studied in perifused explants of the hypothalamo-neurohypophysial system that include the supraoptic nucleus (but not the paraventricular nucleus) with its axonal projections to the neural lobe. Vasopressin and oxytocin release and the mRNA content of these explants respond appropriately to increases in the osmolality of the perifusate. This requires synaptic input from the region of the organum vasculosum of the lamina terminalis. Glutamate is a likely candidate for transmitting osmotic information from the organum vasculosum of the lamina terminalis to the magnocellular neurones, because agonists for excitatory amino acid receptors stimulate vasopressin and oxytocin release, and because increased vasopressin release and mRNA content induced in hypothalamo-neurohypophysial explants by a ramp increase in osmolality are blocked by antagonists of both NMDA ( N -methyl-D-aspartate) and non-NMDA glutamate receptors. Osmotically stimulated vasopressin release is also blocked by testosterone, dihydrotestosterone, oestradiol and corticosterone. Both oestrogen and dihydrotestosterone block NMDA stimulation of vasopressin release, and in preliminary studies oestradiol blocked AMPA stimulation of vasopressin release. Thus, steroid inhibition of osmotically stimulated vasopressin secretion may reflect inhibition of mechanisms mediated by excitatory amino acids. Recent studies have demonstrated numerous mechanisms by which steroid hormones may impact upon neuronal function. Therefore, additional work is warranted to understand these effects of the steroid hormones on vasopressin and oxytocin secretion and to elucidate the potential contribution of these mechanisms to regulation of hormone release in vivo.     

Examining Insomnia and PTSD Over Time in Veterans in Residential Treatment for Substance Use Disorders and PTSD

Objective/Background: Insomnia occurs in 66–90% of individuals with posttraumatic stress disorder (PTSD) and 36–72% of individuals with substance use disorder (SUD). Individuals with both PTSD and SUD are more likely to have insomnia than individuals with only one disorder. Insomnia is associated with poorer treatment outcomes for both PTSD and SUD, increased daytime symptomology for PTSD, and increased relapse for SUDs. As such, it is important to understand how sleep affects PTSD treatment among patients dually diagnosed with SUD and how sleep changes over time in a residential unit for SUDs. Participants: Participants were 40 veterans with comorbid PTSD and SUD in a 28-day Substance Abuse Residential Rehabilitation Treatment Program (SARRTP) PTSD track. Methods: Analyses used mixed models with Time (baseline, posttreatment, 3-month follow-up) to examine PTSD and insomnia severity over time. Results: Results of the longitudinal mixed model showed that PTSD symptoms improved over time but that insomnia symptoms did not. Although baseline insomnia did not affect follow-up PTSD symptoms, individuals with greater insomnia severity at the start of treatment had more severe baseline PTSD symptomatology. However, there was not an interaction of insomnia and PTSD severity over time such that baseline insomnia did not affect PTSD trajectories. Conclusions: These findings are consistent with the PTSD outpatient treatment findings and further adds evidence that insomnia is unremitting without direct intervention. Given the relationship insomnia has with PTSD severity, SUD, and relapse, directly targeting insomnia may further help improve both PTSD and SUD treatment outcomes.     

Role of vasopressin in rat distal colon function

The specific role of vasopressin in colonic crypt function and its possible synergistic action with aldosterone were studied. Sprague-Dawley rats fed a high-Na⁺ (HS; 150 m m NaCl) or a low-Na⁺ (LS; 150 μ m NaCl) diet were deprived of water or infused with vasopressin, and some animals were treated with specific vasopressin receptor subtype V₁ and V₂ antagonists. The expression of the epithelial Na⁺ channel (ENaC), α-smooth muscle actin (α-SMA) and aquaporin-2 (AQP-2) were determined by immunolocalization in distal colonic mucosa. The pericryptal Na⁺ concentration was determined by confocal microscopy, using a low-affinity Na⁺-sensitive fluorescent dye (sodium red) and crypt permeability was measured by the rate of escape of fluorescein isothiocyanate-labelled dextran (10 kDa) from the crypt lumen into the pericryptal space in isolated rat distal colonic mucosa. A high plasma concentration of vasopressin raised α-SMA expression in the pericryptal sheath ( P < 0.05), increased the pericryptal Na⁺ accumulation in this space ( P < 0.01) and caused a reduction of crypt wall permeability ( P < 0.01). All these effects were reversed by selective blockade of V₁ and V₂ receptors. No synergistic effects with aldosterone were observed. Dehydration and vasopressin infusion increased AQP-2 expression in distal colonic mucosa ( P < 0.05). This action of vasopressin was prevented by tolvaptan, a specific V₂ receptor antagonist ( P < 0.05). It is concluded that vasopressin has trophic effects in the rat distal colon, increasing pericryptal myofibroblast growth which affects crypt absorption, and these effects are independent of the presence of aldosterone.