Globe and adnexal trauma at Australian trauma centres.

INTRODUCTION: In multisystem trauma, the assessment and management of globe and adnexal trauma is often complex. Ophthalmology input may assist managing such patients. To understand the role of ophthalmology in tertiary trauma centres we report on the management of globe and adnexal trauma at two tertiary trauma centres in Sydney, Australia. METHOD: A retrospective case series was completed at Royal North Shore Hospital (RNSH) and Royal Prince Alfred Hospital (RPAH) on patients admitted between January 2015 and December 2019. International Classification of Disease, Tenth Revision codes, diagnostic and procedural coding data were used to identify patients admitted with globe and/or adnexal trauma. Data extracted from medical records included demographics, mechanism of injury, ocular examination and specialist ophthalmic referral. RESULTS: Over 5-years, 773 patients, average age of 53.2years and 62% male, were admitted to RNSH and RPAH with globe and/or adnexal trauma. Most patients (83%) first presented to RNSH or RPAH. The most common mechanism of injury was falls (45%) followed by burns (13%). Two-hundred and thirty-five patients had multisystem trauma, of these patients, 121 (51%) suffered globe trauma with 49 (21%) classified as severe. Three patients were not diagnosed initially due to delayed ophthalmology referral. CONCLUSION: Falls followed by burns were common causes of globe and adnexal trauma in Sydney, Australia. The presence of orbital/mid-facial injury may indicate a patient has globe trauma. In multisystem trauma, globe trauma may be diagnosed late or not identified. Ophthalmology review has an important role in diagnosing and managing globe trauma in multisystem trauma.

The First Case Report of Schnitzler Syndrome Presenting with Eye Pain.

Schnitzler syndrome is a rare, auto inflammatory condition known to manifest with bone pain, urticarial rash, fevers, relapsing arthralgia, and fatigue. In this case report, we describe a patient who was diagnosed with Schnitzler Syndrome that had initially presented with a unilateral pressure-type headache with a sensation of a 'dagger' stabbing into the back of the eye. He also had an associated ipsilateral redness of the conjunctiva, eyelid swelling, subtle optic disc elevations bilaterally and facial flushing - but with no visual acuity, pupillary, or lacrimatory changes. Anterior segment, fundoscopy, intraocular pressures and extraocular muscle movements were otherwise normal.

Monitoring of optic nerve function in Neurofibromatosis 2 children with optic nerve sheath meningiomas using multifocal visual evoked potentials.

Monitoring optic nerve sheath meningiomas (ONSM) in Neurofibromatosis type 2 (NF2) patients remains difficult. Other ocular manifestations of NF2 may obscure ophthalmic assessment of optic nerve function in these patients. Serial magnetic resonance imaging (MRI) used to assess the optic nerve is not without limitations, being expensive and often requiring general anaesthetic in children, with associated risks. This study was undertaken to describe the use of multifocal visual evoked potentials (multifocal VEP, mfVEP) in the regular monitoring of NF2 patients with ONSM. This study involved three NF2 patients with ONSM who undertook mfVEP testing at an academic ophthalmic centre. Same day mfVEP and routine ophthalmic testing were undertaken. Topographical function of the optic nerve was assessed, utilising tools such as asymmetry deviation and accumap severity index. Results were assessed alongside MRI and visual acuity (VA). From the three patients, five eyes had ONSMs, of which two caused unilateral blindness. The remaining three affected eyes had initial VAs 6/6, 6/24, and 6/18. Over follow up, ranging from 5 to 12 years, all tumours progressed, and VA declined for all patients. Multifocal VEP detected optic nerve functional loss corresponding with visual decline. This case series suggests mfVEP is effective in the objective topographic monitoring of optic nerve function in NF2 patients with ONSM. Due also to its safety in a paediatric population, the test may be considered in the routine monitoring of these patients, to be used to assist regular ophthalmic review and MRI scans.

Adult Horner's syndrome: a combined clinical, pharmacological, and imaging algorithm.

The diagnosis of Horner's syndrome (HS) can be difficult, as patients rarely present with the classic triad of ptosis, miosis, and anhydrosis. Frequently, there are no associated symptoms to help determine or localise the underlying pathology. The onset of anisocoria may also be uncertain, with many cases referred after incidental discovery on routine optometric assessment. Although the textbooks discuss the use of cocaine, apraclonidine, and hydroxyamphetamine to diagnose and localise HS, in addition to reported false positive and negative results, these pharmacological agents are rarely available during acute assessment or in general ophthalmic departments. Typically, a week is required between using cocaine or apraclonidine for diagnosis and localisation of HS with hydroxyamphetamine, leaving the clinician with the decision of which investigations to request and with what urgency. Modern imaging modalities have advanced significantly and become more readily available since many of the established management algorithms were written. We thus propose a practical and safe combined clinical and radiological diagnostic protocol for HS that can be applied in most clinical settings.

Biocompatible polyester macroligands: new subunits for the assembly of star-shaped polymers with luminescent and cleavable metal cores.

The synthesis of a series of star-shaped, biocompatible polyesters--polylactides (PLAs), polycaprolactones (PCLs), and various copolymer analogues--with either labile iron(II) tris-bipyridyl or luminescent ruthenium(II) tris-bipyridyl cores is described. These polymers were readily assembled by a convergent, metal-template-assisted approach that entailed the synthesis of bipyridine (bpy) ligands incorporating PLA- and PCL-containing arms and subsequent chelation of the "macroligands" to iron(II) or ruthenium(II). Specifically, the polyester macroligands bpyPLA(2) and bpyPCL(2) were prepared by a stannous octoate catalyzed ring-opening polymerization of DL- or L-lactide and epsilon-caprolactone, using bis(hydroxymethyl)-2,2'-bipyridine as the initiator. Copolymers bpy(PCL-PLA)(2) and bpy(PLA-PCL)(2) were generated in an analogous manner using bpyPLA(2) and bpyPCL(2) as macroinitiators. Polymers with narrow molecular weight distributions and with molecular weights close to values expected based upon monomer/initiator loading were produced. The macroligands were subsequently chelated to iron(II) to afford six-armed, iron-core star polymers, which were characterized by UV-vis and (1)H NMR spectroscopy. Estimated chelation efficiencies for formation of the star polymers (M(n) calcd: 20-240 kDa) were high, as determined by UV-vis spectral analysis. Within the molecular weight range investigated, differential scanning calorimetry and thermogravimetric analysis revealed that the small amounts of metal in the polyester stars and differences in polymer architecture had little effect on the thermal properties of the PLA/PCL materials. However, thin films of the red-violet colored iron-core stars exhibited reversible, thermochromic bleaching. Solutions and films of the polymers also responded (with color loss) to a variety of chemical stimuli (e.g., acid, base, peroxides, ammonia), thus revealing potential for use in diverse sensing applications. Likewise, the polyester macroligands were chelated to ruthenium(II) to produce both linear and star-shaped polymers, which were characterized by UV-vis and (1)H NMR spectral analysis. Molecular weights of the polymers were determined by gel permeation chromatography (M(n)(MALLS): 6-30 kDa) with in-line, UV-vis diode-array detection, confirming the presence of the [Ru(bpy)(3)](2+) core in the eluting polymer fractions. As was the case with the corresponding iron-core polyesters, estimated chelation efficiencies were high.

Na-K-ATPase activity decreases with aging in female rat brain synaptosomes.

To understand why elderly females are better able to tolerate hyponatremia, we measured brain Na-K-ATPase activity to determine whether this adaptive mechanism was affected by age. Using synaptosomes from 2-, 12-, and 19-mo-old female rats, we show in our results that Na-K-ATPase activity changes with age in female rats. Enzyme activity was significantly (P = 0.0026) reduced (17%) from 0.416 +/- 0.01 at 2 mo to 0.345 +/- 0.01 at 12 mo and reduced (P = 0.0001) (34%) to 0.274 +/- 0.02 micromol. min(-1). mg protein(-1) at 19 mo. To determine whether this decrease was due to reduced transport function of the Na-K-ATPase pump, we performed potassium transport using rubidium ((86)Rb+) as tracer. Ouabain-sensitive potassium uptake at 2 mo was 16.18 +/- 1.31 nmol/mg protein, was significantly (P = 0.0063) reduced (39%) to 9.79 +/- 1.44 nmol/mg at 12 mo, and was significantly (P = 0.0003) reduced (62%) to 6.12 +/- 1.05 nmol/mg protein at 19 mo. On the contrary, Na-K-ATPase activity remained elevated in males during aging. These data suggest that the Na-K-ATPase pump in female rat brain synaptosomes is decreased with increased age, and that this decrease is probably due in part to decreased potassium transport by the Na-K-ATPase pump.

The use of e-mail by doctors in the West Midlands.

We surveyed the use of e-mail by doctors in the West Midlands. In addition to 224 questionnaires distributed to doctors at three large hospitals, 300 general practitioners (GPs) selected randomly from a list of 711 were also sent questionnaires. There was a 60% response rate. Overall, 65% of the 314 respondents used e-mail, but 84% of hospital doctors used email compared with 55% of GPs. E-mail was used mainly for communication with friends and family (92%) and work colleagues (61%), with only 7% using e-mail for transmitting clinical data and 3% to send or receive referrals. E-mail usage showed a significant trend with respect to age, being highest in the 20-29-year age group and lowest among those aged over 60 years. Over 60% of respondents felt that e-mail was not secure for the transfer of patient data. However, 90% felt that they would be using e-mail in a clinical setting in five years' time. Despite the relatively high use of e-mail for social communication, work-related use by doctors was low.

Effects of arginine vasopressin on cell volume regulation in brain astrocyte in culture.

Astrocytes initially swell when exposed to hypotonic medium but rapidly return to normal volume by the process of regulatory volume decrease (RVD). The role that arginine vasopressin (AVP) plays in hypotonically mediated RVD in astrocytes is unknown. This study was therefore designed to determine whether AVP might play a role in astrocyte RVD. With the use of 3-O-[3H]methyl-D-glucose to determine water space, AVP treatment resulted in significantly increased 3-O-methyl-D-glucose water space within 30 s of hypotonic exposure (P = 0.0001) and remained significantly elevated above baseline (1. 75 microliter/mg protein) at 5 min (P < 0.021). In contrast, in untreated cells, complete RVD was achieved by 5 min. At 30 s, cell volume with AVP treatment was 37% greater than in cells that received no treatment (2.9 vs. 2.26 microliter/mg protein, respectively; P < 0.006). The rate of cell volume increase (dV/dt) over 30 s was highly significant (0.038 vs. 0.019 microliter. mg protein-1. s-1 in the AVP-treated vs. untreated group; P = 0.0004 by regression analysis). Additionally, the rate of cell volume decrease over the next 4.5 min was also significantly greater with vasopressin treatment (-dV/dt = 0.0027 vs. 0.0013 microliter. mg protein-1. s-1; P = 0.0306). The effect of AVP was concentration dependent with EC50 = 3.5 nM. To determine whether AVP action was receptor mediated, we performed RVD studies in the presence of the V1-receptor antagonists benzamil and ethylisopropryl amiloride and the V2-receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP). Both V1-receptor antagonists significantly inhibited AVP-mediated volume increase by 40-47% (P < 0.005), whereas DDAVP had no stimulatory effects above control. Taken together, these data suggest that AVP treatment of brain astrocytes in culture appears to increase 3-O-methyl-D-glucose water space during RVD through V1 receptor-mediated mechanisms. The significance of these findings is presently unclear.

Epidemiology, pathophysiology, and management of hyponatremic encephalopathy.

Hyponatremia is the most common electrolyte abnormality among hospitalized patients. Death or brain damage associated with hyponatremia has been described since 1935, and it is now evident that hyponatremia can lead to death in otherwise healthy individuals. In the past, it had been assumed that the likelihood of brain damage from hyponatremia was directly related to either a rapid decline in plasma sodium or a particularly low level of plasma sodium. Recent studies have demonstrated that other factors may be more important. These factors include the age and gender of the individual, with children and menstruant women the most susceptible. Although many clinical settings are associated with hyponatremia, those most often associated with brain damage are postoperative, polydipsia, pharmacological agents, and heart failure. Morbidity and mortality associated with hyponatremia are primarily a result of brain edema, hypoxemia, and associated hormonal factors. Management of hyponatremia is largely determined by symptomatology. If the patient is asymptomatic, discontinuation of drugs plus water restriction is often sufficient. If the patient is symptomatic, active therapy to increase the plasma sodium with hypertonic NaCl is usually indicated. Although inappropriate therapy of hyponatremia can lead to brain damage, such an occurrence is rare. Thus, the risk of not treating a symptomatic patient for exceeds that of improper therapy.

Metabolic encephalopathy as a complication of renal failure: mechanisms and mediators.

Among patients with end-stage renal disease, nervous system dysfunction remains a major cause of disability. Patients with chronic renal failure who have not yet received dialysis may develop symptoms ranging from mild sensorial clouding to delirium and coma. Dialysis itself is associated with at least three distinct disorders of the CNS: dialysis disequilibrium syndrome; dialysis dementia; and progressive intellectual dysfunction. Peripheral neuropathy is also a major cause of disability in uremic subjects. It is believed that aluminum contributes to the pathogenesis of dialysis dementia. Biochemically, brain calcium is elevated in patients with renal failure, probably because of actions of parathyroid hormone on the brain. The diagnosis of dialysis disequilibrium syndrome, intellectual dysfunction, dialysis dementia, and uremic neuropathy can be made by the characteristic clinical pictures of these syndromes and the exclusion of other causes of nervous system dysfunction.

Female sex hormones inhibit volume regulation in rat brain astrocyte culture.

To determine whether sex steroids play any role in the increased morbidity associated with acute symptomatic hyponatremia in menstruant females, we studied the actions of estradiol, progesterone, and testosterone on regulatory volume decrease (RVD) of brain astrocytes in culture. To determine intracellular space with the use of 3-O-[methyl-D-3H] glucose, cells were cultured in media containing either estradiol or progesterone. Those treated with ouabain were unable to regulate volume normally, whereas testosterone-treated cells displayed normal RVD. After 15 s of hypotonic exposure, control cell volume and 100 nM testosterone-treated cell volume increased by 26 and 31%, respectively. Cell volume in control cells changed from 1.74 +/- 0.24 to 2.41 +/- 0.28 microliters/mg protein. At the same time, cells treated with either 10 nM estradiol or 10 nM progesterone significantly (P < 0.01) increased their volume by 129 and 90%, respectively. Both the antiestrogen agent tamoxifen and the antiprogesterone agent mifepristone (RU-486) blocked the effects of estradiol and progesterone. The Na-K-ATPase pump, which plays an important role in cell RVD, was significantly (P < 0.03) inhibited by 32 and 21% in estradiol- and progesterone-treated cells, but significantly (P < 0.001) stimulated (49%) by testosterone treatment. Taken together, these results provide a possible explanation for the increased morbidity associated with acute symptomatic hyponatremia in menstruant females.

Inhibition of Na+/Ca2+ exchange in renal BLMV by IP3 depends on site of action and direction of Ca2+ flux.

It has previously been shown in synaptosomes that inositol 1,4,5-trisphosphate (1,4,5-IP3) inhibits Ca2+ transport by the plasma membrane-bound Na+/Ca2+ exchanger. The present study was therefore designed to determine if the effect of 1,4,5-IP3 was dependent on its site of action at the plasma membrane or on the direction of Ca2+ flux. To investigate this possibility, studies were performed in basolateral membrane vesicles (BLMV) isolated from rat renal cortex. As with synaptosomes, Ca2+ transport was inhibited by 1,4,5-IP3 in a concentration-dependent manner. At a concentration of 10(-6) M, 1,4,5-IP3 significantly (P < 0.005) inhibited Ca2+ transport by 36%. When Ca2+ transport was carried out in inside-out vesicles, 10(-6) M 1,4,5-IP3 significantly (P < 0.002) increased the degree of inhibition by an additional 75% (63 vs. 36%). However, 1,4,5-IP3 had no significant effect on Ca2+ transport in inside-out vesicles when Ca2+ flux was reversed (i.e., Ca2+ efflux). These data in renal BLMV confirm the novel action of 1,4,5-IP3 on the Na+/Ca2+ exchanger previously described in brain synaptosomes. These results also suggest that the action of 1,4,5-IP3 depends on both its site of action at the plasma membrane and on the direction of Ca2+ flux.

Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic encephalopathy in laboratory animals.

Hypoxemia is a major comorbid factor for permanent brain damage in several metabolic encephalopathies. To determine whether hypoxia impairs brain adaptation to hyponatremia, worsening brain edema, we performed in vitro and in vivo studies in cats and rats with hyponatremia plus either ischemic or hypoxic hypoxia. Mortality with hypoxic hypoxia was 0%; with hyponatremia, 22%; and with hyponatremia+hypoxia, 100%. Hyponatremia in cats produced brain edema, with a compensatory decrease of brain sodium. Ischemic hypoxia also resulted in brain edema, but with elevation of brain sodium. However, when ischemic hypoxia was superimposed upon hyponatremia, there was elevation of brain sodium with further elevation of water. Outward sodium transport in cat cerebral cortex synaptosomes was measured via three major pathways through which brain osmolality can be decreased. After hyponatremia, sodium transport was significantly altered such that brain cell osmolality would decrease: 44% increase in Na(+)-K(+)-ATPase transport activity (ouabain inhibitable); 26% decrease in amiloride-sensitive sodium uptake. The change in veratridine-stimulated sodium uptake was not significant (P > 0.05). When ischemic hypoxia was superimposed upon hyponatremia, all of the cerebral adaptive changes induced by hyponatremia alone were eliminated. Thus, hypoxia combined with hyponatremia produces a major increase in brain edema and mortality, probably by eliminating the compensatory mechanisms of sodium transport initiated by hyponatremia that tend to minimize brain swelling.

Hyponatraemia and death or permanent brain damage in healthy children.

OBJECTIVE: To determine if hyponatraemia causes permanent brain damage in healthy children and, if so, if the disorder is primarily limited to females, as occurs in adults. DESIGN: Prospective clinical case study of 16 affected children and a review of 24,412 consecutive surgical admissions at one medical centre. PATIENTS: 16 children (nine male, seven female; age 7 (SD 5) years) with generally minor illness were electively hospitalised for primary care. Consultation was obtained for the combination of respiratory arrest with symptomatic hyponatraemia (serum sodium concentration less than or equal to 128 mmol/l). MAIN OUTCOME MEASURES: Presence, gender distribution, and classification of permanent brain damage in children with symptomatic hyponatraemia in both prospective and retrospective studies. RESULTS: By retrospective evaluation the incidence of postoperative hyponatraemia among 24,412 patients was 0.34% (83 cases) and mortality of those afflicted was 8.4% (seven deaths). In the prospective population the serum sodium concentration on admission was 138 (SD 2) mmol/l. From three to 120 inpatient hours after hypotonic fluid administration patients developed progressive lethargy, headache, nausea, and emesis with an explosive onset of respiratory arrest. At the time serum sodium concentration was 115 (7) mmol/l and arterial oxygen tension 6 (1.5) kPa. The hyponatraemia was primarily caused by extrarenal loss of electrolytes with replacement by hypotonic fluids. All 16 patients had cerebral oedema detected at either radiological or postmortem examination. All 15 patients not treated for their hyponatraemia in a timely manner either died or were permanently incapacitated by brain damage. The only patient treated in a timely manner was alive but mentally retarded. CONCLUSIONS: Symptomatic hyponatraemia can result in high morbidity in children of both genders, which is due in large part to inadequate brain adaptation and lack of timely treatment.

Regulation of plasma membrane-bound Ca(2+)-ATPase pump by inositol phosphates in rat brain.

We have previously shown that inositol 1,4,5-trisphosphate (1,4,5-IP3) may participate in signal transduction in brain by inhibiting plasma membrane-bound Na(+)-Ca2+ exchanger. This study was therefore designed to determine whether 1,4,5-IP3 and/or inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4) might also affect Ca2+ transport by the plasma membrane Ca(2+)-ATPase pump. Our data show that 1,4,5-IP3 significantly (P less than 0.005) stimulates Ca2+ transport, whereas 1,3,4,5-IP4 significantly (P less than 0.006) inhibits transport by the pump. However, in the presence of both 1,4,5-IP3 and 1,3,4,5-IP4, the stimulatory effect of 1,4,5-IP3 is dominant. Thus Ca2+ transport was significantly stimulated as though 1,4,5-IP3 alone was present. We also observed that 1,3,4-IP3, which had no effect on Ca2+ transport by itself, antagonizes the stimulatory action of 1,4,5-IP3 and potentiates the inhibition of Ca2+ transport by 1,3,4,5-IP4. Half-maximal activities were observed at 10(-8) M. Our data suggest that 1,3,4,5-IP4, 1,4,5-IP3, and 1,3,4-IP3 may participate in signal transduction in brain by regulating the plasma membrane-bound Ca(2+)-ATPase pump.

Inositol 1,4,5-trisphosphate may regulate rat brain Cai++ by inhibiting membrane bound Na(+)-Ca++ exchanger.

The role of inositol 1,4,5-trisphosphate (1,4,5-IP3) in regulating cytosolic Ca++ by stimulating Ca++ release from intracellular organelles is well established. However, other modes of intracellular Ca++ regulation by 1,4,5-IP3 have not been determined. To determine if 1,4,5-IP3 may regulate cell cytosolic Ca++ by acting on plasma membrane bound Na(+)-Ca++ exchanger, we investigated Ca++ transport in synaptosomes using 45Ca++ as tracer. In the presence of either an inhibitor of voltage gated Na+ channels (tetrodotoxin) or the K+ ionophore (valinomycin), Ca++ uptake was significantly inhibited (P less than 0.05) by 1,4,5-IP3 in a concentration dependent manner, with half-maximal inhibition occurring at submicromolar concentrations between 10(-9) M and 10(-10) M 1,4,5-IP3. Similarly, Ca++ efflux by the exchanger was significantly inhibited 40% by 1,4,5-IP3. The inhibitory effect of 1,4,5-IP3 on the Na(+)-Ca++ exchanger was observed in the presence of Ca++ channel blockers, and in vesicles pretreated with caffeine to deplete the 1,4,5-IP3-sensitive stores of Ca++. These results suggest that during signal transduction in brain, 1,4,5-IP3 may increase cytosolic [Ca++] in part by inhibiting the Na(+)-Ca++ exchanger and thus, Ca++ efflux from cell.

Hyponatraemia in patients with cirrhosis.

Hyponatraemia occurs in nearly half of patients in hospital with cirrhosis and ascites, and is due to the excessive retention of free water which results from the kidney's inability to excrete it normally. The morbidity and mortality associated with hyponatraemia is largely attributable to central nervous system disturbances. The degree to which brain water content increases depends on the duration of hyponatraemia and on compensatory mechanisms. Altered steroid and peptide hormones in cirrhotic patients may contribute to the development of hyponatraemic encephalopathy, symptoms of which overlap with hepatic encephalopathy and uraemia. The occurrence of central pontine myelinolysis is unrelated to the rate of correction of hyponatraemia. The appearance of hyponatraemia in cirrhotic patients, long regarded as a poor prognostic sign, may be a function of unrecognized underlying impaired renal function. Therapy for hyponatraemia remains suboptimal.

Fatal central diabetes mellitus and insipidus resulting from untreated hyponatremia: a new syndrome.

After elective hospitalization, eleven healthy young women developed symptomatic hyponatremia that was rapidly followed by polyuria, hypernatremia, hyperglycemia, and death. The patients were 30 +/- 2 years old (+/- SE) with initial serum sodium of 140 +/- 1 mmol/L. They all awoke from analgesia but, 32 hours after completion of the procedure, they went from alertness to respiratory arrest in less than 1 hour. At this time, serum sodium was 116 +/- 2 mmol/L and blood glucose was 6.7 +/- 0.7 mmol/L. Without treatment for the hyponatremia, urine output spontaneously increased from 38 to 689 mL/h and urine osmolality fell from 546 to 83 mmol/kg body weight. Over the next 51 hours, blood glucose rose to a high of 24.1 +/- 2.5 mmol/L while serum sodium rose to a high of 167 +/- 2 mmol/L. None of the patients regained consciousness. At autopsy, all patients had cerebral edema with herniation along with hypoxic brain damage. The pituitary showed infarction of both anterior and posterior lobes in 7 of 7 patients examined, while 8 of 11 had necrosis of the medulla and 8 of 8 patients examined had hypothalamic necrosis. All had normal pancreas and kidneys at autopsy. Soon after respiratory arrest, all of the patients developed fixed, dilated pupils that often led to the diagnosis of brain death. Autopsy showed compression of the third cranial nerve (oculomotor) because of cerebral herniation. Thus, all of the patients were diagnosed as being brain dead when some may have been saved. These data suggest that in otherwise healthy young women, untreated symptomatic hyponatremia may lead to brain edema, cerebral herniation, and infarction of pituitary and hypothalamus, resulting in central diabetes insipidus and mellitus.

Na+-K+-ATPase pump function in rat brain synaptosomes is different in males and females.

To understand the increased morbidity and mortality associated with acute hyponatremia in young women, we characterized the Na+-K+-adenosinetriphosphtase (ATPase) pump in rat brain synaptosomes to determine if this adaptive mechanism was different between the sexes. Veratridine-stimulated sodium (Na+) uptake was significantly greater (P less than 0.001) in females than in males (8.08 +/- 0.3 vs. 5.56 +/- 0.4 nmol/mg protein), suggesting either an increased rate of Na+ uptake and/or decreased extrusion of Na+ by the Na+-K+-ATPase pump in females. Uptake rate was determined by measuring Na+ transport at 5 s, and it was found to be twice as large in females as in males (1.01 +/- 0.2 vs. 0.46 +/- 0.1 nmol/mg protein). However, in the presence of 2.5 mM ouabain, uptake in both groups were similar, suggesting that the difference was probably due to decreased function of the Na+-K+-ATPase pump in females. Transport evaluation of the Na+-K+-ATPase pump showed ouabain-sensitive K+ uptake in males to be significantly greater (P less than 0.001) than in females (10.53 vs. 4.97 nmol/mg protein), and ouabain-sensitive Na+ uptake in inverted synaptosomes was 70% greater in males (4.00 vs. 2.37 nmol/mg protein). [3H]ouabain binding studies showed maximum binding capacity in males and females to be similar (103 +/- 12 vs. 110 +/- 15 pmol/mg protein), whereas the dissociation constant was significantly (P less than 0.005) greater in males (109 +/- 8 vs. 82 +/- 6 nM).(ABSTRACT TRUNCATED AT 250 WORDS)