Investigation and management of hypotonic polyura is a common challenge in clinical endocrinology. The three main causes, recently renamed to arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus), AVP-resistance (AVP-R, formerly nephrogenic diabetes insipidus), and primary polydipsia (PP) require accurate diagnosis as management differs for each. This new nomenclature more accurately reflects pathophysiology, and has now been adopted by the Systemised Nomenclature of Medicine (SNOMED). Advances in diagnosis over the last few years have centered around the use of copeptin measurement. Here, we use three patient case histories to highlight the use of this approach, and to demonstrate how it can succeed where other approaches, such as the water deprivation test, sometimes fail. We discuss the overall approach to each type of patient and the strengths and limitations of diagnostic strategies, illustrating the use of the new nomenclature.

Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable in vitro. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimated glomerular filtration rate and a greater risk of new-onset chronic kidney disease. Furthermore, copeptin is associated with disease severity in patients with autosomal dominant polycystic kidney disease. Copeptin predicts the development of coronary artery disease and cardiovascular mortality in the older population. Moreover, the predictive value of copeptin was found to be comparable with that of N-terminal pro-brain natriuretic peptide for all-cause mortality in patients with heart failure. Whether the measurement of copeptin in these conditions alters clinical management remains to be demonstrated in future studies.

Az újszülött- és csecsemőkori hypernatraemia lázat okozó hatására 100 évvel ezelőtt Heim Pál is felhívta a figyelmet. Az évszázados ismeret ellenére ritkán gondolunk ennek lehetőségére. Egy négynapos, láz miatt felvett fiú újszülött esete kapcsán mutatjuk be az újszülöttkori hypernatraemia elkülönítő kórisméjét. A hypernatraemia ebben a korban az esetek döntő részében elégtelen anyatejes táplálás, 10%-ot meghaladó súlyvesztés következménye. A súlyvesztés mértéke arányos a hypernatraemia fokával. A lázért azonban nem a folyadékhiány, hanem a hypernatraemia a felelős, ahogy azt csecsemők sómérgezéssel járó esetei mutatják. Mind a dehidráció, mind a sómérgezés következtében fellépő hypernatraemia fokozott vizeletozmolalitással jár, a frakcionális nátriumkiválasztás azonban csak sómérgezésben magas. A felvett újszülött vizeletozmolalitása azonban alacsony, 100 mOsm/kg alatti, fajsúlya 1005 g/l volt. A hypernatraemia és a hipozmoláris vizelet együttes fennállása diabetes insipidusra utal. Ennek leggyakoribb, X-hez kötött, renalis formáját igazolta a genetikai vizsgálat, az AVPR2 öröklött variánsának kimutatásával. A gyermek polyuriája hipotiazid- és indometacinkezelés hatására jelentősen csökkent, a folyadékbevitel ad libitum biztosításával nem alakult ki a következő hónapokban hypernatraemia. Orv Hetil. 2024; 165(29): 1107–1111.

OBJECTIVE: Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis.
METHODS: UTI was induced in 8-10 w female BALB/cJ-mice by surgically injecting Escherichia coli (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. In vitro bacterial growth (OD600) was determined in urine from mice or from human volunteers.
RESULTS: Gel feeding increased urine output (1.40 ± 0.77 μL min-1, p < 0.01) and diluted the urine (668.7 ± 177 mOsmol kg-1, p < 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min-1, osmolality: 1439 ± 473.5 mOsmol kg-1). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg-1 tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg-1, p < 0.01). Correspondingly, the growth of E. coli was markedly reduced at osmolalities above 1200 mOsmol kg-1 compared to 600 mOsmol kg-1 and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL-1, p < 0.01) compared to controls (24.65 ± 2.70 μg mL-1).
CONCLUSIONS: Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for E. coli. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake.

BACKGROUND: Hyponatremia is a well-documented adverse effect of oxcarbazepine treatment, but no clinical trial has yet been conducted to explore any intervention for reducing the incidence of hyponatremia.
METHODS: This open-label trial evaluated the efficacy of add-on daily oral sodium chloride supplementation of 1-2 g/day for 12 weeks in reducing the incidence of hyponatremia in children receiving oxcarbazepine monotherapy aged 1-18 years. Apart from comparing the incidence of symptomatic and severe hyponatremia, serum and urine sodium levels, serum and urine osmolality, changes in behavior and cognition, and the number of participants with recurrence of seizures and requiring additional antiseizure medication (ASM) were also compared.
RESULTS: A total of 120 children (60 in each group) were enrolled. The serum sodium level at 12 weeks in the intervention group was higher than that of the control group (136.5 ± 2.6 vs 135.4 ± 2.5 mEq/L, p = 0.01). The number of patients with hyponatremia was significantly lower in the intervention group (4/60vs14/60, p = 0.01). However, the incidence of symptomatic and severe hyponatremia (0/60vs1/60, p = 0.67 for both), changes in social quotient and child behavior checklist total score (0.6 ± 0.8 vs 0.7 ± 0.5, p = 0.41 and 0.9 ± 1.2 vs 1.1 ± 0.9, p = 0.30 respectively), the number of patients with breakthrough seizures (9/60vs10/60, p = 0.89), and the number of patients requiring additional ASMs (8/60vs10/60, p = 0.79) were comparable in both groups.
CONCLUSIONS: Daily oral sodium chloride supplementation is safe and efficacious in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy. However, sodium chloride supplementation does not significantly reduce more clinically meaningful outcome measures like symptomatic and severe hyponatremia. Trial registry No. CTRI/2021/12/038388.

Embryoid bodies (EB) are sensitive to changes in the culture conditions. Recent studies show that the addition of PEG 300 to culture medium affects cell growth and differentiation; however, its effect on the embryoid body is unclear. This study aims to understand the role of PEG 300 in the process of EB formation and germ layer differentiation. EBs formed more efficiently and differentiated toward the mesoderm when cultured in a medium supplemented with appropriate concentrations of PEG 300. The expression of T/Bry, a marker of mesodermal differentiation, increases in EBs in the PEG group, and the expression of TUBB3 generally decreases, showing a quantitative relationship with PEG. Furthermore, further differentiation of PEG-pretreated EB into vascular smooth muscle cells (VSMCs) by directional induction shows that PEG 300-pretreated induced VSMCs have higher expression of phenotypic markers and greater secretory and contractile functions. This study highlights the role of PEG 300 in the culture medium during EB differentiation, which can significantly enhance mesodermal gene expression and the efficiency of subsequent differentiation into smooth muscle cells and other target cells.

UNASSIGNED: To investigate the physical properties of commercially available multipurpose soft contact lens solutions in Ghana.
UNASSIGNED: pH (Kelilong ICL-099 pH meter, China), osmolality (OSMOMAT 3000, GONOTEC, Germany), surface tension (Sigma 700 Tensiometer, Sweden), and viscosity (CFOC-200 Viscometer, Cannon Company, USA) of various soft contact lens multipurpose solutions (MPS) were measured in triplicates at room temperature. Viscosity measurements were also taken at 34 °C ocular surface temperature. The solutions examined were Opti-Free Replenish (OFR), Trufresh (TF), Avizor (AV), Freshlook (FL), and Refresh (RF).
UNASSIGNED: Several solutions were largely hypo-osmotic in the range of 108-231 mOsm/kg, the exception being Avizor, which had osmolality values that were closer to human tears (301 ± 0.58 mOsm/kg). The range of pH values of the solutions (6.33-8.24, mean (SD) = 7.53 ± 0.18) fell within the reported tolerable range for the ocular surface (6.20-9.00). Surface tension values ranged from 35.86 to 42.27 mNm with a mean of 38.49 ± 2.32 mNm. The average viscosity of most solutions at room temperature (25 °C) was 1.44 ± 0.49 cP with a range of 1.04-2.15 cP. Significantly lower values ranging from 0.79 to 1.58 cP were obtained at ocular surface temperature (34 °C), p = 0.0001).
UNASSIGNED: The physical properties of many of the solutions used as MPS in Ghana are markedly variable. Nevertheless, pH, surface tension, and viscosity fall within the acceptable limits of ocular physiological tolerance; except for osmolality, which majority were outside the reported tolerable range for the ocular surface. This information may partly explain the reason some patients exhibit strong preferences for certain care systems and should aid clinical decision-making when prescribing eye care systems to patients.

Water regulation is an important physiological challenge for insects due to their small body sizes and large surface area to volume ratios. Adaptations for decreasing cuticular water loss, the largest avenue of loss, are especially important. The melanin desiccation hypothesis states that melanin molecules in the cuticle may help prevent water loss, thus offering protection from desiccation. This hypothesis has much empirical support in Drosophila species, but remains mostly untested in other taxa, including Lepidoptera. Because melanin has many other important functions in insects, its potential role in desiccation prevention is not always clear. In this study we investigated the role of melanin in desiccation prevention in the white-lined Sphinx moth, Hyles lineata (Lepidoptera, Sphingidae), which shows high plasticity in the degree of melanin pigmentation during the late larval instars. We took advantage of this plasticity and used density treatments to induce a wide range of cuticular melanization; solitary conditions induced low melanin pigmentation while crowded conditions induced high melanin pigmentation. We tested whether more melanic larvae from the crowded treatment were better protected from desiccation in three relevant responses: i) total water loss over a desiccation period, ii) change in hemolymph osmolality over a desiccation period, and iii) evaporation rate of water through the cuticle. We did not find support for the melanin desiccation hypothesis in this species. Although treatment influenced total water loss, this effect did not occur via degree of melanization. Interestingly, this implies that crowding, which was used to induce high melanin phenotypes, may have other physiological effects that influence water regulation. There were no differences between treatments in cuticular evaporative water loss or change in hemolymph osmolality. However, we conclude that osmolality may not sufficiently reflect water loss in this case. This study emphasizes the context dependency of melanin\'s role in desiccation prevention and the importance of considering how it may vary across taxa. In lepidopteran larvae that are constantly feeding phytophagous insects with soft cuticles, melanin may not be necessary for preventing cuticular water loss.

This study investigates the influence of four culture media pre-equilibration methods on embryo development and clinical pregnancy outcomes. The methods are as follows: Method A involved covering media with fresh mineral oil in humid-type incubators for 24 h. Method B replicated Method A in dry-type incubators. Method C utilized pre-equilibrated (humidified) mineral oil to cover the media, also in humid-type incubators for 24 h. Method D followed the same process as Method C but in dry-type incubators. Subsequently, media from all groups were transferred to dry-type incubators for 72 h. Osmolality was measured at 24, 48, 72, and 96 h. For G1 PLUS, no significant differences were observed among groups at 24, 48, and 72 h. However, at 96 h, Groups B and D exhibited significantly higher osmolality than Groups A and C (A vs B, p = 0.043; A vs D: p = 0.046; B vs C, p = 0.043; C vs D, p = 0.046). No significant variations were found between Groups A and C or B and D. Similar results were obtained for G2 PLUS. A retrospective analysis of embryo development and clinical outcomes using Methods A revealed significant improvements in good blastocysts and available embryos compared with Method B for all (p = 0.005 and 0.004) and IVF cycles (p = 0.025 and 0.017). Method A also enhanced blastocyst formation in ICSI cycles (p = 0.017). However, clinical pregnancy outcomes did not significantly differ between Methods A and B. Pre-equilibrating culture media overnight in humid-type incubators, even when covered with fresh mineral oil, significantly mitigates osmolality rise and improves embryo development potential during embryo culture in dry-type incubators.

This study aimed to measure and compare the osmolality and tonicity of isotonic beverages that can be bought on the Slovenian market. The main goal was to examine how good is the agreement between the measured osmolalities of the beverages and the requirements for isotonic beverages set up by EFSA. Osmolalities were measured with an osmometer using the freezing point depression method. Afterwards, two complementary methods for the observation of tonicity were developed. Erythrocytes were exposed to standard NaCl solutions of different osmolalities to observe their influence on the volume and shape of cells following the turbidity of the solution and the morphology of erythrocytes. These two methods enabled us to determine whether standard solutions were hypo-, iso-, or hypertonic. In this way, we found that the osmolality of 12 out of the 18 investigated isotonic beverages was in the range of 270-330 mOsm/kg, as required by EFSA. However, six samples did not meet this criterion and should therefore not have the label \"isotonic\" or be described as such. The measurements of turbidity of solutions indicated that most isotonic beverages exhibit a lower tonicity than standard NaCl solutions of identical osmolality. However, examination of the erythrocytes in isotonic beverages showed that the measurements were additionally complicated by the low pH values of these beverages. Finally, by demonstrating how different components of isotonic beverages pass through the erythrocyte membranes, we found that even isoosmolal beverages are often not isotonic, as the concentration of actively transported sugars in these beverages is relatively high.