Metabolic Compensation Research Articles

Human Physiologic Thermogenic Response to Resting Cold-Water Immersion: A Thorough Calorimetric Inquiry

PURPOSE: Navy Diver thermal protection, a primary concern in attempting or completing cold-water tasks, remains inadequate. Optimal heat distribution with minimal energy input is sought. Therefore, heating requirements that support thermal balance (TB) in various cold-water scenarios were quantified. METHODS: Nine active duty Navy personnel underwent four resting immersion scenarios in a temperature-controlled 4900-gallon water tank after donning the same full-body tubesuit calorimeter (for diver heat delivery and measurement), undergarments, and a dry suit (total 1.2 Clo). Each subject achieved TB (<2hrs immersion). TB was defined as temperature equilibrium where core and mean skin temperatures varied < 0.2°F over 20 minutes time. The four scenarios were combinations of the independent variables: 1) inlet tubesuit water temperature (89 and 102°F), and 2) immersion tank temperature (35 or 50°F). RESULTS: Metabolic compensation continuously increased over time (Fig 1a) in the 89°F tubesuit/35°F immersion temperature water group. At the fourth quartile time point (during achievement of thermal balance, Fig 1a - Fourth), subjects in the groups of greater tubesuit heat delivery (102°F) required significantly less metabolic activity than did the coldest scenario (89°F/35°F). Distal anatomical sites showed much lower temperatures than proximal sites (data not shown). Tubesuit heat delivery (Wattage) increased significantly (Fig 1b) with both greater tubesuit temperature (102°F vs 89°F) and in colder water immersion (35°F vs 50°F). Thermal balance was achieved in all scenarios thereby allowing steady-state assessment of heat input/extraction parameters. All * indicate p<0.05. CONCLUSIONS: Given that thermal balance was achieved over the course of each ≤ 2-hr exposure, results suggest that using a lower tubesuit perfusion temperature (89°F vs 102°F) requires less Wattage provided a sufficient metabolic response is activated during the immersion.Figure 1

A discussion of new-onset extrapyramidal syndrome without tremor and neuroimaging signs of encephalopathy following hepatic cirrhosis

Liver cirrhosis can cause neurological, extrapyramidal-type disorders, such as stiffness, bradykinesia, tremor, confusion, depression. Cirrhotic extrapyramidal syndrome can worsen clinically, leading to encephalopathy, which in the most severe cases leads to coma. Brain MRI is able to highlight the extrapyramidal signs, through the presence of hyperintensity areas at the basal ganglia. In addition, extrapyramidal symptoms appear already in the metabolic compensation phase. We describe the case of a 50-year-old male, suffering from new-onset extrapyramidal syndrome, secondary to alcoholic hepatic cirrhosis, diagnosed seven years before. The case is singular for some features: the late-onset of the extrapyramidal syndrome, the absence of tremor, and especially the lack of neuroimaging findings such as MRI hyperintense areas along the basal ganglia.We hypothesize a mechanism of metabolic compensation, which would be responsible for the late appearance of the extrapyramidal syndrome and the lack of signs of encephalopathy in brain MRI.The lack of tremor is less clear, because it is a constant symptom of extrapyramidal pathology, and it is unusual that it is lacking as a symptom, after so many years.

Dynamics of clinical and laboratory indices in children with glycogen storage disease type I on comprehensive therapy

Treatment of the glycogen storage disease (GSD) type I with uncooked cornstarch (UCS) allows to maintain long-term normoglycemia, however, the efficacy of the treatment declines due to the insufficient compliance of children patients and their parents. There were determined clinical and laboratory features of the course of GSD type I in children on the long-term comprehensive therapy. There was performed a retrospective analysis of case histories data on 19 GSD children, including 8 patients with subtype Ia and 11 cases - with subtype Ib. All children received the treatment with both UCS and hepatoprotectors. It was established that during the treatment liver sizes did not change significantly, the fasting blood glucose concentration increased by 2.8 times to 4.21 mmol/l, lactate content decreased by 1.9 times to 5.1 mmol/L, ALT activity decreased by 2.5 times, AST - by 3.3 times, and GGT - by 1.8 times if compared to the level before the treatment. In children with GSD subtype Ib blood concentrations of triglycerides prior to the treatment were 2 times higher than baseline values andfailed to change on the comprehensive therapy. Blood levels of cholesterol and uric acid after the treatment also were not significantly dependent on the duration of the therapy. The authors suggest that comprehensive course therapy of GSD type I by means of prescription to children UCS in combination with hepatoprotectors contributes to the compensation of carbohydrate metabolism and provides the relief of cytolysis and cholestasis, but disturbances of the purine and lipid metabolism in patients persist.

Features of carbohydrate metabolism in a patient with type 1 diabetes mellitus in subclinical hypothyroidism in the outcome of chronic autoimmune thyroiditis

Diabetes mellitus and primary hypothyroidism, in the outcome of chronic autoimmune thyroiditis, the two most common diseases in endocrinology and the practicing doctor are important not to forget about the possible association of these pathologies. This applies to patients with diabetes mellitus, both 1 and 2 types. However, the combination of these two pathologies is more common in type 1 diabetes, which is due to the autoimmune nature of these diseases. A clinical case of a patient with type 1 diabetes mellitus, which is on pump insulin therapy, is presented, which, in the background of previously selected therapy, during the last 2 months, episodes of hypoglycemia increased. In the course of the survey, primary subclinical hypothyroidism was identified, in the outcome of chronic autoimmune thyroiditis. Against the background of the achievement of euthyroidism, it was possible to achieve compensation of carbohydrate metabolism without correction of previously selected insulin therapy. The high incidence of thyroid dysfunction in patients with diabetes mellitus, and as a consequence, the deterioration in the compensation of carbohydrate metabolism, requires a systematic screening of thyroid disorders in the presence of diabetes mellitus.

Predictors of effectiveness of glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes and obesity

Background: Type 2 diabetes mellitus (DM2), which mainly develops from visceral obesity, is a socially significant disease. Reduction of losses from DM2 is a priority in modern medicine development. Glucagon-like peptide-1 receptor agonists (aGLP-1) present one of few groups of antidiabetic drugs that allows to reduce not only glycemia, but also weight in DM2. Taking into account predictors of response to the therapy will allow to reach trearment targets with the highest probability, maintaining a safety of treatment, to optimize recommendations for administration of aGPP-1 as much as possible.&#x0D; Aims: To assess dynamics of metabolic parameters, to identify predictors of reduction in blood glucose, body weight and other metabolic parameters on aGLP-1 therapy in patients with DM2 with body mass index (BMI) 35 kg/m2.&#x0D; Materials and methods: The study involved 33 patients (10 men, 23 women), who had been treated with aGLP-1, the observation period for 24 weeks was planned. 3 patients terminated the participation before the appointed time (1 due to pancreatitis development 2 due to the lack of financial opportunity to purchase the drug). So, 30 patients (10 men, 20 women) were included in the final analysis. Examination consisted of the survey, physical examination with measurement of anthropometric, clinical parameters, filling questionnaires. Data were evaluated at baseline and after 24 weeks of treatment.&#x0D; Results: The study found that patients who achieved weight loss 5% initially had higher BMI (p = 0.028), lower GLP-1 (p = 0.036), had lower level of ghrelin after standard breakfast test (p = 0.022). There was trend (p = 0.071) to greater decrease in BMI in patients with restrictive type of eating behavior compared to patients who had a mixed type. More pronounced decrease in glycemia was noted in patients who had higher fasting plasma glucose level at inclusion (p = 0.001). Dynamics of HbA1c was better in patients with initially higher GLP-1 (p = 0.016) and higher levels of glycemia (p = 0.001). Also, we revealed the statistically significant decrease in triglycerides level, blood pressure by end of the treatment period.&#x0D; Conclusions: Results indicate the different predictors for reduction in weight, glycemia and blood pressure on aGLP-1 therapy. In addition to the metabolic parameters, level of orexigenic and anorexigenic hormones and psycho-social characteristics of patients help to estimate an expected effect of aGLP-1 therapy. When being identifying, the predictors of weight loss and the predictors of carbohydrate metabolism compensation should be studied separately. Identification of response predictors is necessary to optimize indications for this group of drugs administration in DM2.

Carbohydrate Metabolic Compensation Coupled to High Tolerance to Oxidative Stress in Ticks

Reactive oxygen species (ROS) are natural byproducts of metabolism that have toxic effects well documented in mammals. In hematophagous arthropods, however, these processes are not largely understood. Here, we describe that Rhipicephalus microplus ticks and embryonic cell line (BME26) employ an adaptive metabolic compensation mechanism that confers tolerance to hydrogen peroxide (H2O2) at concentrations too high for others organisms. Tick survival and reproduction are not affected by H2O2 exposure, while BME26 cells morphology was only mildly altered by the treatment. Furthermore, H2O2-tolerant BME26 cells maintained their proliferative capacity unchanged. We evaluated several genes involved in gluconeogenesis, glycolysis, and pentose phosphate pathway, major pathways for carbohydrate catabolism and anabolism, describing a metabolic mechanism that explains such tolerance. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by glucose uptake and energy resource availability. Transient increase in ROS levels, oxygen consumption, and ROS-scavenger enzymes, as well as decreased mitochondrial superoxide levels, were indicative of cell adaptation to high H2O2 exposure, and suggested a tolerance strategy developed by BME26 cells to cope with oxidative stress. Moreover, NADPH levels increased upon H2O2 challenge, and this phenomenon was sustained mainly by G6PDH activity. Interestingly, G6PDH knockdown in BME26 cells did not impair H2O2 tolerance, but generated an increase in NADP-ICDH transcription. In agreement with the hypothesis of a compensatory NADPH production in these cells, NADP-ICDH knockdown increased G6PDH relative transcript level. The present study unveils the first metabolic evidence of an adaptive mechanism to cope with high H2O2 exposure and maintain redox balance in ticks.

COMPLE X TRE ATMENT OF OSTEOPOROSIS IN PATIENTS WITH 2 T YPE DIABETES MELLITUS IN COMBINATION WITH NON-ALCOHOLIC FATTY LIVER DISEASE

An actual problem of modernity is the relationship between type 2 diabetes mellitus (DM) and osteoporosis(OP), as well as type 2 DM with non-alcoholic fatty liver disease (NAFLD), which are actively considered by scientists.There are different data on the development and course of OP, depending on gender, age and race. So theaim of the study was to determine the tactics of treatment of OP in patients with type 2 DM with NAFLD. 37patients with type 2 DM with OP and NAFLD (15 men and 22 women) were examined and treated. When examiningpatients with type 2 DM with OP and NAFLD before treatment, there was a deficiency of vitamin D, thatis, none of the patients had an adequate supply of vitamin D, while the indicators of the level of CA were in thenormal range, and the indicators of Ca++ were reduced, so they were prescribed therapy with magnesium, vitaminD, calcium in daily doses, depending on gender, age, revealed pathology and laboratory abnormalities, andall patients received individually selected therapy with sugar-lowering. To assess the degree of compensationof carbohydrate metabolism was carried out to study the level of glycosylated hemoglobin (HbA1c) and furthercorrection zakreslajac therapy. According to the results of the study, the expediency of prescribing drugs that affectthe improvement of bone structure in patients with type 2 DM with OP in daily doses depending on gender,age, degree of detected violations and deviations of laboratory parameters was proved, and it was determinedthat the improvement of bone tissue has a positive effect on the compensation of carbohydrate metabolism in theexamined patients. It was found that patients with type 2 DM with OP and NAFLD require monitoring withdensitometry and laboratory diagnosis in dynamics against the background of treatment.

Rapid metabolic compensation in response to temperature change in the intertidal copepod, Tigriopus californicus

Animals living in the intertidal zone must adapt to thermal variability, including adjustments in metabolism. We examined metabolic responses to temperature in the copepod, Tigriopus californicus, which inhabits supratidal splash pools along the Pacific coast of North America. We maintained three populations of T. californicus at 20 °C, one from southern California (San Diego, “SD”) and two from Oregon (Fogarty Creek, “FCN”, Boiler Bay, “BOB”) and examined possible geographic patterns in metabolism. We measured oxygen consumption rate (V̇o2) at 20 °C and following 48 h (chronic) acclimation to 25, 27.5 and 30 °C. V̇o2 was temperature-independent, with temperature quotients (Q10) values ≤1 in all populations, indicative of metabolic compensation. We detected no variation in V̇o2 or survival between populations. To explore the time course of metabolic compensation, we performed an acute acclimation experiment in which V̇o2 was measured at 20 °C, following immediate exposure to 25 °C, and following 2 h, 4 h and 6 h exposure to 25 °C. This acute acclimation experiment revealed that V̇o2 increased immediately in SD and FCN, but was no longer different than 20 °C levels by 2 h and 4 h at 25 °C, respectively. BOB showed no significant change in V̇o2, which may indicate complete temperature-independent metabolism or different mechanisms of compensation between populations. This study demonstrates a time course of rapid metabolic compensation in response to temperature that occurs in a small intertidal animal, and suggests intertidal invertebrates can thermally acclimate within a few hours of a significant temperature change.

Does the combination of resistance training and stretching increase cardiac overload?

OBJECTIVES:To compare the effects of combinations of resistance training (RT) and static stretching (SS) on heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP), rate pressure product (RPP), oxygen saturation (SpO2), rating of perceived effort (RPE), and heart rate variability (HRV) in men.METHODS:Twelve normotensive healthy men participated in four protocols: a) SS+RT, b) RT+SS, c) RT, and d) SS. Variables were measured before, immediately after, and 15, 30, and 45 min after the sessions.RESULTS:The combination of SS and RT increased (p<0.001) HR when compared to the effects of the noncombined protocols (from 2.38 to 11.02%), and this result indicated metabolic compensation. Regarding DBP, there were differences (p<0.001) between the RT and SS groups (53.93±8.59 vs. 67.00±7.01 mmHg). SS has been shown to be able to reduce (p<0.001) SpO2 (4.67%) due to the occlusion caused by a reduction in the caliber of the blood vessels during SS compared to during rest. The increase in RPP (6.88% between RT and SS+RT) along with the HR results indicated higher metabolic stress than that reflected by the RPE (combined protocols increased RPE from 21.63 to 43.25%). The HRV analysis confirmed these results, showing increases (p<0.01) in the LF index between the combined and noncombined protocols. Compared to the effect of RT, the combination of SS and RT promoted a vagal suppression root mean square of the successive differences (RMSSD) index (from 9.51 to 21.52%) between the RT and SS+RT groups (p<0.01) and between the RT and RT+SS groups (p<0.001).CONCLUSION:Static stretching increases cardiac overload and RPE, reducing oxygen supply, especially when performed in combination with RT.

Chum salmon migrating upriver adjust to environmental temperatures through metabolic compensation.

Ectotherms adjust their thermal performance to various thermal ranges by altering their metabolic rates. These metabolic adjustments involve plastic and/or genetic traits and pathways depend on species-specific ecological contexts. Chum salmon (Oncorhynchus keta) are ecologically unique among the Pacific salmonids as early-run and late-run populations are commonly observed in every part of their range. In the Sanriku coastal area, Japan, early-run adults experience high water temperatures (12-24°C) during their migration, compared with those of the late-run adults (4-15°C), suggesting that the two populations might have different thermal performance. Here, we found population-specific differences in the thermal sensitivities of metabolic rates [resting metabolic rate, RMR, and maximum (aerobic) metabolic rate, MMR] and critical temperature maxima. Using these parameters, we estimated thermal performance curves of absolute aerobic scope (AAS). The populations had different thermal performance curves of AAS, and in both populations high values of AAS were maintained throughout the range of ecologically relevant temperatures. However, the populations did not vary substantially in the peak (AAS at optimal temperature, ToptAAS) or breadth (width of sub-optimal temperature range) of the performance curves. The AAS curve of early-run fish was shifted approximately 3°C higher than that of late-run fish. Furthermore, when the data for RMR and MMR were aligned to the thermal differences from ToptAAS, it became clear that the populations did not differ in the temperature dependence of their metabolic traits. Our results indicate that chum salmon thermally accommodate through compensatory alterations in metabolic rates. Our results imply that metabolic plasticity and/or the effect of genetic variance on plasticity might play a pivotal role in their thermal accommodation.

Assessment of selected food intake frequency in patients with type 1 diabetes treated with personal insulin pumps

It has been established that in Type 1 Diabetes Mellitus (T1DM), regardless of the insulin therapy model used, diet and proper eating habits are still important in the treatment of the disease. The dietary intervention in these patients is aimed at maintaining proper body weight, obtaining target fasting and post meal blood glucose levels, optimizing lipid profiles. The aim of the study was to assess dietary habits in a homogeneous group of adults with T1DM treated with personal insulin pumps. The study included 141 adult patients (57% women) with type 1 diabetes treated with personal insulin pumps. The surveyed population was characterized by an average age of 25.8 ± 6.2 years, an average duration of diabetes 13.9 ± 6.9 years, and treatment with a personal pump for 8.2 ± 4.1 years and mean BMI 23.0 ± 2.8 g/m2. All were dwellers of south-eastern Poland. The validated KomPAN questionnaire was used to assess the frequency of consumption of individual food products. The mean percentage of HbA1c in the study group was 7.3% [56 mmol/mol]. The mean total cholesterol level was 4.4 mmol/l, HDL - 1.7 mmol/l, LDL - 2.3 mmol/l and triglycerides - 0.8 mmol/l. In the multivariate regression model, no correlation was found between dietary quality parameters and metabolic compensation measured with HbA1c or lipidogram and the place of residence (village, small town, big city). However, there were differences in the quality of the diet depending on the sex. Women were characterized by higher index of a healthy diet (pHDI-10) (26.3 vs 21.4, p=0.005) and lower index of unhealthy diet (nHDI-14) (13.3 vs 18.6, p <0.001) than men. The results of this study clearly suggest, that despite good metabolic control, patients require more education on the choice of healthy product groups.

Barriers of the initiation of insulin treatment in type 2 diabetic patients - conquering the "psychological insulin resistance"

Type 2 diabetes is a progressive disease and its consequence is the gradual decrease of endogenous insulin secretion to a very low level. Beyond this point, without insulin it is not possible to achieve proper metabolic compensation. The authors are trying to explain why the insulin therapy is often delayed in type 2 diabetic patients despite existing guidelines about its initiation and continuation. The causes of delay can be divided into two groups. One is the fear and disagreement of the patients (psychological insulin resistance - PIR) arising from different cognitive, emotional and other reasons. The second is the "clinical inertia", when the physicians are not able to explain in an effective and persuasive way the rationale and necessity of insulin treatment to their patients. The common background of both causes is the lack of sufficient knowledge about the pathogenesis of type 2 diabetes and the rationale of insulin treatment together with an insufficient level of communication between doctor and patient. The authors see the solution in the improvement of pre- and postgradual education of doctors and other health care providers (nurses, educators, psychologists), in their mutual cooperation and the translation of their knowledge towards a system of successful patient education. Orv Hetil. 2019; 160(3): 93-97.

Impact of celiac disease and symptomatic hypothyroidism on progression of type 1 diabetes in children: literature review and researchers’ own observation

It is not uncommon for type 1 diabetes to run concurrently with endocrine and non-endocrine immunopathological diseases. The most prevalent of those are thyroid gland diseases and celiac disease. A combination of several autoimmune diseases significantly affects indices of long-term metabolic control of diabetes. Presented in the article is literature review on impact that celiac disease and autoimmune pathology of thyroid gland have on carbohydrate metabolism compensation in children with type 1 diabetes. We have provided our own observation on combination of these diseases in a child.

Predictors of effectiveness of glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes and obesity.

Diabetes type 2 (CD2), which develops mainly against visceral obesity, is socially significant disease, reduction of losses from which is priority in development of modern medicine. Glucagon-like peptide-1 receptor agonists (aGPP-1) is one of few groups of antidiabetic drugs that allows to reduce not only glycemia, but also weight with CD2. Taking into account predictors of response to therapy will allow highest probability to reach targets while maintaining safety of treatment, optimize recommendations for appointment of aGPP-1 as much as possible. Aims: to assess dynamics of metabolic parameters, to determine predictors of reduction in blood glucose, body weight and other metabolic parameters in AGPP-1 therapy in patients with type 2 diabetes with body mass index (BMI) &gt;35 kg/m. Material and methods. Study involved 33 patients (10 men, 23 women) who had been treated with aGPP-1, planned period of observation for 24 weeks. Early termination ofparticipation of 3 patients (1 - due to development ofpancreatitis, 2 - due to lack of financial opportunity to purchase the drug). Accordingly, 30 patients (10 men, 20 women) were included in final analysis. Examination consisted of survey, physical examination with measurement of anthropometric, clinical parameters, filling questionnaires. Data were evaluated initially and after 24 weeks of treatment. Results. Study found that patients who achieved weight loss &gt; 5% initially had higher BMI (p = 0.028), lower GLP-1 (p = 0.036), had lower level of ghrelin after sample with standard breakfast (p = 0.022). There was trend (p = 0.071) to greater decrease in BMI in patients with restrictive type of eating behavior compared to patients who had mixed type. More pronounced decrease in glycemia was noted in patients who had higher fasting plasma glucose level at inclusion (p = 0.001). Dynamics of HbA1C was better in patients with initially higher GLP-1 (p = 0.016) and higher levels of glycemia (p = 0.001). Also, in examined patients, there was statistically significant decrease in level of triglycerides, blood pressure by end of treatment period. Conclusions. Results indicate that there are different predictors for weight loss, glycemia and blood pressure in aGPP-1 therapy. In addition to metabolic parameters, level of orexigenic and anorexigenic hormones and psycho-social characteristics ofpatients help to estimate expected effect of therapy for ARP1. When predictors are identified, predictors of weight loss and carbohydrate metabolism compensation should be studied separately. Identification of response predictors is necessary to optimize indications for prescribing this group of drugs with CD2.

El Niño-Related Thermal Stress Coupled With Upwelling-Related Ocean Acidification Negatively Impacts Cellular to Population-Level Responses in Pteropods Along the California Current System With Implications for Increased Bioenergetic Costs

Understanding the interactive effects of multiple stressors on pelagic mollusks associated with global climate change is especially important in highly productive coastal ecosystems of the upwelling regime, such as the California Current System (CCS). Due to temporal overlap between a marine heatwave, an El Nino event, and springtime intensification of the upwelling, pteropods of the CCS were exposed to co-occurring increased temperature, low Ωar and pH, and deoxygenation. The variability in the natural gradients during NOAA’s WCOA 2016 cruise provided a unique opportunity for synoptic study of chemical and biological interactions. We investigated the effects of in situ multiple drivers and their interactions across cellular, physiological, and population levels. Oxidative stress biomarkers were used to assess pteropods’ cellular status and antioxidant defenses. Ocean acidification (OA) stress induced significant activation of oxidative stress biomarkers, as indicated by increased levels of lipid peroxidation (LPX), but the antioxidative activity defense might be insufficient against cellular stress. Thermal stress in combination with low Ωar additively increases the level of LPX toxicity, while food availability can mediate the negative effect. On the physiological level, we found synergistic interaction between low Ωar and deoxygenation and thermal stress (Ωar: T, O2:T). On the population level, temperature was the main driver of abundance distribution, with low Ωar being a strong driver of secondary importance. The additive effects of thermal stress and low Ωar on abundance suggest a negative effect of El Nino at the population level. Our study clearly demonstrates Ωar and temperature are master variables in explaining biological responses, cautioning the use of a single parameter in the statistical analyses. High quantities of polyunsaturated fatty acids are susceptible to oxidative stress because of lipid peroxidation, resulting in the loss of lipid reserves and structural damage to cell membranes, a potential mechanism explaining extreme pteropod sensitivity to OA. Accumulation of oxidative damage requires metabolic compensation, implying energetic trade-offs under combined thermal and OA stress. Oxidative stress biomarkers can be used as early-warning signal of multiple stressors on the cellular level, thereby providing important new insights into factors that set limits to species’ tolerance to in situ multiple drivers.

Comparison of blood carbonic anhydrase activity of athletes performing interval and continuous running exercise at high altitude

The effects of high-intensity interval and continuous exercise on erythrocytes carbonic anhydrase (CA, EC 4.2.1.1) activity levels were scarcely investigated up until now. Here we present a study focused on the CA activity from erythrocytes of athletes experiencing interval and continuous training for 6 weeks, during cold weather and at high altitude (> 1600 m). We observed a 50% increase in the blood CA activity at the second week after initiation of the training in both interval and continuos running groups, whereas the control group did not experience any variation in the enzyme activity levels. In the trained individuals a mild decrease in their body mass, BMI and an increased were also observed. The CA activity returned at the basal values after 4–6 weeks after the training started, probably proving that a metabolic compensation occurred without the need of an enhanced enzyme activity. The unexpected 50% rise of activity for an enzyme which acts as a very efficient catalyst for CO2 hydration/bicarbonate dehydration, such as the blood CA, deserves further investigations for better understanding the physiologic basis of this phenomenon.

Measurement of corneal thickness, optic nerve sheath diameter and retinal nerve fiber layer as potential new non-invasive methods in assessing a risk of cerebral edema in type 1 diabetes in children

AimsSome patients with diabetic ketoacidosis develop cerebral edema (CE) in the course of type 1 diabetes mellitus (T1D), which may result in central nervous system disorders and high mortality. The imperfection of existing neuroimaging techniques for early recognition of CE forces us to search for the new and non-invasive methods. The aim of the study was to assess the usefulness of new methods (pachymetry, transorbital ultrasonography—USG, optical coherence tomography—OCT study) in the assessment of the risk of CE occurrence in children with newly diagnosed T1D.MethodsThe study group included 50 children with newly diagnosed T1D, 54 patients with long-term T1D as a reference group and 40 children without glucose tolerance disorders as controls. In all subjects, a corneal thickness (CCT) index with pachymeter, optic nerve sheath diameter (ONSD) using transorbital USG and retinal nerve fiber layer (RNFL) during OCT study were measured and compared with selected clinical parameters of T1D.ResultsIn patients from a study group at onset of T1D, the higher CCT (p < 0.001) and ONSD (p < 0.001) values were observed as compared to the results obtained after 48 h of metabolic compensation. The ONSD correlated negatively with pH value (r = − 0.64; p < 0.001), BE (r = − 0.54, p < 0.001) and HCO3− (r = − 0.50; p < 0.001). A positive correlation between RNFL and Na+ levels (r = 0.47; p < 0.005) was also observed.ConclusionsTransorbital USG and pachymetry may serve as the potential promising methods for the non-invasive assessment of the increased risk of development of CE in patients with T1D.

ATF4-amino acid circuits: a recipe for resistance in melanoma.

Lactate dehydrogenase A (LDHA) has appropriately received attention as a therapeutic target for the treatment of a broad spectrum of tumor types, yet little is known regarding intrinsic resistance to LDHA inhibitors. Pathria et al (2018) now establish that ATF4‐dependent control of enzymes that direct amino acid metabolism confers resistance to LDHA inhibitors in melanoma and identify chokepoints that can be exploited to overcome metabolic compensation, setting the stage for trials with such combinations.

Environmentally induced phenotypic plasticity explains hatching synchrony in the freshwater turtle Chrysemys picta.

Environmentally cued hatching allows embryos to alter the time of hatching in relation to environment through phenotypic plasticity. Spatially variable temperatures within shallow nests of many freshwater turtles cause asynchronous development of embryos within clutches, yet neonates still hatch synchronously either by hatching early or via metabolic compensation. Metabolic compensation and changes in circadian rhythms presumably enable embryos to adjust their developmental rates to catch up to more advanced embryos within the nest. Hatchlings of the North American freshwater turtle Chrysemys picta usually overwinter within the nest and emerge the following spring, but still hatch synchronously via hatching early. Here, we used rates of oxygen consumption and heart rate profiles to investigate the metabolic rates of clutches of C. picta developing in conditions that result in asynchronous development to determine if compensatory changes in metabolism occur during incubation. Embryos hatched synchronously and displayed circadian rhythms throughout incubation, but exhibited no evidence of metabolic compensation. Phenotypic traits of hatchlings, including body size and righting performance, were also not affected by asynchronous development. We conclude that less developed embryos of C. picta hatch synchronously with their clutch-mates by hatching early, which does not appear to inflict a fitness cost to individuals. The ultimate mechanism for synchronous hatching in C. picta could be for hatchlings to ensure an optimal overwintering position within the center of the nest. Consequently, immediate fitness costs will not hinder hatchling survival. The geographic location, as well as environmental and genetic factors unique to populations, can all influence hatching behavior in turtles through phenotypic plasticity. Hence, synchronous hatching is an adaptive bet-hedging strategy in turtles, but the mechanisms to achieve it are diverse.

Low Molecular Weight Proteinuria in Children with Distal Renal Tubular Acidosis

Abstract Distal renal tubular acidosis (dRTA) (MIM #267300, #602722 and #179800) is a rare inherited tubulopathy characterized by the inability of the distal tubule to acidify the urine with consecutive systemic acidosis. The clinical features include polyuria, polydipsia, poor appetite, failure to thrive, short stature and rickets. Prominent biochemical features are hypokalemia, hypercalciuria and hypocitraturia. There are reports on patients who presented with unusual biochemical features such as low molecular proteinuria, hypophosphatemia, hypouricemia, generalized hyperaminioaciduria, hyperoxaluria and other making diagnostic confusion to the clinicians. In this work, we report on a series of 8 children with clinically, biochemically and genetically proven dRTA who present with low molecular proteinuria at the disease onset. With metabolic compensation of the disease, there was complete resolution of the low molecular weight protenuria and other proximal tubular abnormalities in all children. Late recognition of the disease with long standing hypokalemia and acidosis may result in abnormal expression and function of the transporters in the proximal tubules. Sodium dodecyl sulphate polyacrylamide gel electrophoeresis is an accurate method for detection and follow up of patients with low molecular weight proteinuria.