The first experience of using beta-hydroxybutyrate analysis of capillary blood in the diagnosis of non-diabetic hypoglycemia in adults

Background: The diagnostic threshold of β-hydroxybutyrate (BHB) at the moment of hypoglycemia in insulinoma was developed for venous blood many years ago, when there were no alternative ways to measure ketones. Number of works, mainly on patients with diabetes mellitus, found differences in the measurement of this indicator in venous and capillary blood, but the results were contradictory. Moreover, this study was not previously used in the diagnosis of non-diabetic hypoglycemia (NDH) in adults on the territory of the Russian Federation.Aim: To estimate the effectiveness of the method for determining BHB in capillary blood and its place in the diagnosis of NDH.Materials and methods: We conducted an experimental, cross-sectional, comparative study and included patients with suspected NDH who underwent a standard fast test. The BHB level in capillary blood was determined every 6 hours during the fast test and at its completion.Results: Based on the results of the fast test, the participants (n=154) were divided into groups: with hyperinsulinemic variant of NDH and IFRoma (n=98; group 1), with hypoinsulinemic variant of NDH /absence of NDH (n=56; group 2). When comparing the level of BHB at the moment of fasting completion, significant differences were obtained between groups 1 and 2 (p<0.001). According to the ROC analysis, the determination of BHB for differentiation the hyper- and hypoinsulinemic variants of hypoglycemia is characterized by excellent quality of model (AUC=99,1% [98,0%; 100,0%]). The BHB determination in capillary blood has the maximum diagnostic accuracy at a cut-off point of ≤ 1.4 mmol/L (Se 98.0%, Sp 96.4%, PPV 98.0%, NPV 96.4%, Ac 97.4%). Exceeding the diagnostic threshold of BHB was first recorded after 24h of fasting; at the same point, a significant difference was determined when comparing BHB indicators between two consecutive measurements (between 18h and 24h).Conclusion: The BHB determination in capillary blood is a highly sensitive and highly specific additional method for the differential diagnosis of NDH variants. The diagnostic threshold for BHB of capillary blood, which allows differentiating hyper- and hypoketonemic variants of NDH, is ≤1.4 mmol / L. It is advisable to initiate control of BHB in the blood no earlier than 18 hours after the start of the fast test

Effect of glucocorticoids on bone metabolism in replacement therapy of adrenal insufficiency. Literature review

Adrenal insufficiency (AI) is a syndrome caused by disturbance in the synthesis and secretion of hormones of the adrenal cortex, which ensure the vital activity, energy and water-salt homeostasis. The widest hormonal deficiency is observed in primary hypocorticism, when the synthesis of not only glucocorticoids (GC) and adrenal androgens, but also mineralocorticoids is disrupted. Lifelong replacement therapy with GCs for this pathology may be associated with a risk of bone loss and osteoporosis. However, at present, there are no clear guidelines for diagnosis of bone condition, including and bone mineral density (BMD) monitoring during treatment with GCs in patients with AI. This review summarizes collected data on the key pathogenetic links of glucocorticoid-induced osteoporosis, incidence of decreased BMD and fractures in patients with AI. In this review factors that influence bone metabolism in this cohort of patients are considered: the type and the dose of prescribed GCs, the type (primary, secondary, HH in congenital adrenal cortex dysfunction) and the duration of AI, age, gender, and the presence of concomitant endocrine disorders (hypogonadism, growth hormone (GH) deficiency). In addition, the review presents data on the effect of adrenal androgen replacement therapy and recombinant GH therapy on bone metabolism in secondary AI

MADNESS: A Multiresolution, Adaptive Numerical Environment for Scientific Simulation

MADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics

ПОСЛЕОПЕРАЦИОННАЯ КОГНИТИВНАЯ ДИСФУНКЦИЯ – ЧТО МЫ ЗНАЕМ И КУДА ДВИГАТЬСЯ ДАЛЕЕ

The authors reviewed the literature and presented results of their own research of post-operative cognitive dysfunction confirming its social importance. The development of post-operative cognitive dysfunction is to be perceived as a real fact despite the differences in the published epidemiological data. Currently, there are no grounds to correlate it directly with the general anesthesia given to patients, and there is no evidence that a certain method of anesthesia or a certain drug can reduce the frequency of post-operative clinical decline. There are numerous factors within genesis of post-operative cognitive decline and they are not studied well. All suspected mechanisms (neurotoxicity of the used agents, and other factors of anesthesia and surgery; impairment of information neuro-transmission mechanisms; neuroinflammation developing as a response to trauma) can initiate the complex neuro-physiological reactions causing cognitive dysfunction.The authors presented experimental data about morphofunctional changes in neurons and cerebellar cortex microglia after laparotomy and anesthesia with sevoflurane followed by the exposure to it in a special box for 6 hours (induction of 8 vol. % with the air flow of 2 l/min., maintaining 2 vol. % of sevoflurane with the air flow of 1 l/min.). They demonstrated that neuroinflammation was not the key factor of the detected neuronal damage. Purkinje neurons were damaged the most, since they were fairy sensitive to energy metabolic disorders, promoting the death of other neurons of the molecular layer. Neurons of the granular layer with the low level of energy metabolism were the most resistant to the impact provided by surgery/anesthesia. These data confirmed the importance of multifactorial approach when assessing the genesis of cognitive dysfunction. This research is to be continued and aimed to find out predictors of post-operative cognitive decline and to optimize anaesthesiologic support of surgery and other invasive interventions to provide a balance between their aggressiveness and effectiveness of protection, especially in senile patients who already have some cognitive dysfunctions. Авторы представили итоги анализа литературы и результатов некоторых собственных исследований по проблеме послеоперационной когнитивной дисфункции (ПОКД) и подтвердили ее социальную значимость. Факт развития послеоперационных когнитивных нарушений следует воспринимать как реальность, несмотря на различие в публикуемых эпидемиологических данных. Однако на сегодня нет оснований связывать их исключительно с влиянием проводимой пациенту общей анестезии, так же как нет и четких доказательств способности того или иного метода анестезии и лекарственного препарата снизить частоту возникновения ПОКД. Генез ПОКД многофакторный и до конца не изучен. Все предполагаемые механизмы (нейротоксичность используемых средств, а также иных факторов анестезии и операции; нарушение нейротрансмиссионных механизмов передачи информации; развивающееся в ответ на травму нейровоспаление) могут быть ответственны за инициацию сложных нейрофизиологических процессов, приводящих к когнитивной дисфункции.Представлены полученные авторами в эксперименте данные о морфофункциональных изменениях нейронов и микроглии коры мозжечка после лапаротомии с использованием анестезии севофлураном и последующей его экспозиции в специальном боксе в течение 6 ч (индукция 8 об. % в потоке воздуха 2 л/мин, поддержание ‒ 2 об. % севофлурана и поток воздуха 1 л/мин). Они показали, что нейровоспаление не явилось ключевым фактором выявленного повреждения нейронов. В большей степени страдали клетки Пуркинье, весьма чувствительные к нарушению энергетического обмена, которые вовлекали в процесс гибели другие нейроны молекулярного слоя. Нейроны зернистого слоя с низким уровнем энергетического обмена оказались более устойчивы по отношению к действию факторов операции/анестезии. Эти данные подтвердили важность многофакторного подхода к оценке генеза когнитивных нарушений. Следует продолжать исследования, направляя их на выявление предикторов развития ПОКД и на оптимизацию анестезиологического сопровождения операций и иных инвазивных вмешательств для обеспечения соответствия между степенью их агрессивности и эффективности защиты, особенно у пожилых пациентов с имеющимися когнитивными нарушениями.

СТРУКТУРНО-ФУНКЦИОНАЛЬНАЯ ПЕРЕСТРОЙКА НЕЙРОНОВ ГИППОКАМПА ПОСЛЕ ОПЕРАЦИИ ПОД АНЕСТЕЗИЕЙ СЕВОФЛУРАНОМ (экспериментальное исследование)

Hippocampus plays an important role in the cognitive mnestic functions. It coordinates emotional process, defines the intensity and specificity of behavioral, neuron and hormone reactions. Structural changes in hippocampus neurons can result in learning and memory disorders. The objective: to investigate morphometric parameters of hippocampus fields in rats after abdomen surgery with exposure to sevoflurane. Subjects and methods. The experimental research was performed using Wistar rats (n = 15). Rats from the experimental group (n = 7) had abdomen surgery with anesthesia with sevoflurane with the consequent continuous exposure to it (6 hours, 2 vol. % of sevoflurane, air flow – 1 l/min.). During 21 days rats from both groups had a number of behavioral tests. In 12 hours after the last behavioral test (on the 22-th day after the start of the experiment) the rats were decapitated with consequent brain extraction. The obtained materials were fixed in 10% neutral formalin on phosphate buffer (pH 7.4) for 24 hours minimum. Preparations of CA1, Ca2, Ca3, and Ca4 fields were studied under light microscope DM-750 (Leica, Germany) using the computer image analysis software of ImageScope M with 400-fold magnification. Results. The tests showed that cytoarchitectonics of hippocampus field was intact, pyramidal neurons had a large rounded nucleus with one, two or more distinct nucleoli. No pericellular and perivascular edema was detected. In the experimental group, all fields of the hippocampus had structural and functional changes. It manifested through both quantitative and qualitative signs of neuronal damage, especially in the Ca1 field. Segments of pyramidal neurons were disorganized, morphologically modified neurons were found: hyperchromatic shriveled neurons with no nucleus or poorly visible nucleus of the irregular shape. The appearance of morphologically changed neurons and disorganization of hippocampal layers led to changes in the width of pyramidal neurons segments. Conclusion. Morphological changes of hippocampal structures of rats after surgery and anesthesia may be the cause of cognitive functions decline during the postoperative period. Гиппокамп играет важную роль в реализации когнитивно-мнестических функций. Он координирует эмоциональные процессы, определяет величину и специфику поведенческих, нейрональных и гормональных реакций. Структурные изменения нейронов гиппокампа могут приводить к нарушениям процессов обучения и памяти. Цель: изучение морфометрических показателей полей гиппокампа крыс после операции на органах брюшной полости на фоне экспозиции севофлурана. Материал и методы. Проведено экспериментальное исследование на крысах стока Вистар (n = 15). Крысы экспериментальной группы (n = 7) подвергались операции на органах брюшной полости на фоне анестезии севофлураном с последующей его длительной экспозицией (6 ч, 2 об. % севофлурана, поток воздуха 1 л/мин). В течение 21 сут у крыс обеих групп выполняли ряд поведенческих тестов. Через 12 ч после проведения последнего поведенческого теста (22-е сут после начала эксперимента) крыс декапитировали и извлекали головной мозг. Материал фиксировали в 10%-ном нейтральном формалине на фосфатном буфере (рН 7,4) не менее 24 ч. Препараты полей СА1, СА2, СА3 и СА4 изучали под световым микроскопом ДМ-750 (Leica, Германия) с помощью компьютерной программы анализа изображений ImageScope M при увеличении в 400 раз. Результаты. В контроле цитоархитектоника полей гиппокампа не нарушена, пирамидные нейроны имели крупное округлое ядро с одним, двумя и более четкими ядрышками. Перицеллюлярного и периваскулярного отека не выявлено. В экспериментальной группе структурно-функциональная перестройка затронула все поля гиппокампа. Это проявилось появлением как количественных, так и качественных признаков повреждения нейронов, в особенности в поле СА1. Отмечена дезорганизация слоев пирамидных нейронов, определены морфологически измененные нейроны: гиперхромные сморщенные без ядер или с плохо различимым ядром неправильной формы. Появление морфологически измененных нейронов и дезорганизация слоев гиппокампа приводили к изменению ширины слоя пирамидных нейронов. Вывод. Морфологическая перестройка гиппокампальных структур крыс после операции и анестезии может лежать в основе ухудшения когнитивных функций в послеоперационном периоде.

ВЛИЯНИЕ ГЛОБАЛЬНОЙ ИШЕМИИ-РЕПЕРФУЗИИ ГОЛОВНОГО МОЗГА НА АКТИВНОСТЬ СУКЦИНАТДЕГИДРОГЕНАЗЫ В НЕЙРОНАХ РАЗЛИЧНЫХ СЛОЕВ НЕОКОРТЕКСА

The aim of the study was to investigate changes in activity of succinate dehydrogenase (SDH) in cytoplasm of neurons of different cortical layers in early and late reperfusion period after global cerebral ischemia in rats. Reversible global cerebral ischemia was modeled by occlusion of the brachiocephalic trunk, left subclavian artery and left common carotid artery for 10 minutes and following reperfusion during 2 or 7 days. The SDH activity in cytoplasm of neurons of II, III and V cortical layers was determined histoenzymatically. It is shown that the SDH activity in neurons of the studied cortical layers was characterized by the increased reperfusion period to the 2 days with a subsequent increased activity of the reperfusion period to the 7 days. The change in the SDH activity in cytoplasm of cortical neurons depends on the particular cerebral layer and duration of postischemic reperfusion.Целью исследования являлось изучение изменения активности сукцинатдегидрогеназы (СДГ) в цитоплазме нейронов различных слоев коры головного мозга (ГМ) в раннем и отдаленном реперфузионном периоде после глобальной ишемии ГМ у крыс. Обратимую полную глобальную ишемию ГМ моделировали окклюзией плечеголовного ствола, левой подключичной артерии и левой общей сонной артерии на 10 минут, с последующей реперфузией, длительность которой составляла 2 либо 7 суток. Гистоэнзимологически определяли активность СДГ в цитоплазме нейронов II, III и V слоев коры ГМ. Показано, что активность СДГ в нейронах изученных слоев коры ГМ характеризовалась повышением ко 2-м суткам реперфузионного периода с последующим нарастанием активности к 7-м суткам периода реперфузии. Изменение активности СДГ в цитоплазме нейронов коры ГМ зависит от принадлежности к слою коры и продолжительности постишемической реперфузии

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

SECONDARY (ENDOCRINE) HYPERTENSION: LECTURE

Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation

POSTOPERATIVE COGNITIVE DYSFUNCTION – WHAT WE KNOW AND WHERE WE GO

The authors reviewed the literature and presented results of their own research of post-operative cognitive dysfunction confirming its social importance. The development of post-operative cognitive dysfunction is to be perceived as a real fact despite the differences in the published epidemiological data. Currently, there are no grounds to correlate it directly with the general anesthesia given to patients, and there is no evidence that a certain method of anesthesia or a certain drug can reduce the frequency of post-operative clinical decline. There are numerous factors within genesis of post-operative cognitive decline and they are not studied well. All suspected mechanisms (neurotoxicity of the used agents, and other factors of anesthesia and surgery; impairment of information neuro-transmission mechanisms; neuroinflammation developing as a response to trauma) can initiate the complex neuro-physiological reactions causing cognitive dysfunction.The authors presented experimental data about morphofunctional changes in neurons and cerebellar cortex microglia after laparotomy and anesthesia with sevoflurane followed by the exposure to it in a special box for 6 hours (induction of 8 vol. % with the air flow of 2 l/min., maintaining 2 vol. % of sevoflurane with the air flow of 1 l/min.). They demonstrated that neuroinflammation was not the key factor of the detected neuronal damage. Purkinje neurons were damaged the most, since they were fairy sensitive to energy metabolic disorders, promoting the death of other neurons of the molecular layer. Neurons of the granular layer with the low level of energy metabolism were the most resistant to the impact provided by surgery/anesthesia. These data confirmed the importance of multifactorial approach when assessing the genesis of cognitive dysfunction. This research is to be continued and aimed to find out predictors of post-operative cognitive decline and to optimize anaesthesiologic support of surgery and other invasive interventions to provide a balance between their aggressiveness and effectiveness of protection, especially in senile patients who already have some cognitive dysfunctions