Сенсорные фенотипы хронической боли у пациентов, переживших критическое состояние: проспективное наблюдательное исследование

АКТУАЛЬНОСТЬ: Определение сенсорных фенотипов, которые отражают лежащие в их основе болевые механизмы, актуально для пациентов с хронической болью, переживших критическое состояние. ЦЕЛЬ ИССЛЕДОВАНИЯ: Оценить интенсивность, локализацию и сенсорные фенотипы хронической боли у пациентов, перенесших критическое состояние. МАТЕРИАЛЫ И МЕТОДЫ: В исследование было включено 99 пациентов, перенесших критическое состояние. Критериями включения являлись: возраст 18–75 лет, длительность пребывания в отделении реанимации и интенсивной терапии (ОРИТ) > 3 дней, длительность искусственной вентиляции легких (ИВЛ) > 48 ч, оценка на момент поступления по шкале Acute Physiology And Chronic Health Evaluation II (APACHE II) ≥ 7 баллов, получение информированного согласия. Локализацию, интенсивность и качественные характеристики длительной (6 мес.) боли, связанной с пребыванием в ОРИТ, оценивали при помощи краткого опросника боли, опросника PainDetect, выраженность тревоги и депрессии — по шкале Hospital Anxiety and Depression Scale (HADS). Всем пациентам перед выпиской выполнено термальное количественное сенсорное тестирование (КСТ) с оценкой порогов обнаружения холода и обнаружения тепла, парадоксальных тепловых ощущений, порогов холодовой и тепловой боли, условной модуляции боли. РЕЗУЛЬТАТЫ: Через 6 мес. хронический болевой синдром сформировался у 59 % пациентов. Были получены данные об интенсивности, о локализации, степени выраженности нейропатического и дисфункционального компонента боли. При оценке термальных показателей КСТ с помощью иерархического кластерного анализа выявлены статистически достоверная связь изменений статических и динамических показателей термального сенсорного тестирования, формирование «раздраженного» и «деафферентационного» сенсорного фенотипа в зависимости от длительности ИВЛ, пребывания в отделении интенсивной терапии и оценки по шкале Sequential Organ Failure Assessment (SOFA). ВЫВОДЫ: Выявление сенсорных фенотипов позволяет определить пациентов с дисфункцией волокон малого диаметра, нарушением эндогенных механизмов контроля боли, что позволит подобрать индивидуальную программу облегчения боли

INDEX OF ANALGESIA-NOCICEPTION: OPPORTUNITIES AND LIMITS

The review includes clinical opportunities of the new technique for evaluation balance of nociception/anti-nociception with help of medication of ANI-Monitor (MetroDoloris®, France), used abroad, with the calculation of original index of analgesia/nociception of ANI (Analgesia Nociception Index). Objective and non-invasive technique is based on the evaluation of changes in variability of cardiac rhythm under nociception effect. Basing on literature the further investigation is required to identify specificity and sensitivity of ANI index in various clinical situations

LIPOPROTEIN(A) MEANING AS AN ADDITIONAL MARKER OF CARDIOVASCULAR RISK IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA

Aim. To analyze the relation of Lp(a) and atherosclerosis development in familial hypercholesterolemia (FHCE).Material and methods. Totally, 81 patient with definite FHCE studied, mean age 39,1±0,4 y. o. The participants were selected to two groups: first — with increased level of Lp(a) >0,3 g/L (n=34); mean age — 44,5±0,3; second — with normal Lp(a) <0,3 g/L (n=47, 58,1%); mean age — 37,5±0,3 y. o.Results. Mean level of Lp(a) in various age persons did not differ significantly. In both subgroups in about a half of all participants there was arterial hypertension (AH) revealed (50,8% and 42,6%, respectively), obesity was diagnosed in one third of both groups, number of smokers was higher in higher Lp(а) group (11,8% and 8,5%). IHD had 25,9% of participants. Revalence of IHD in IHD group was 44, 4%, in non-smoker group — 25,8% (RR 1,72 (0,75; 3,99)), acute myocardial infarction prevalence (MI) in smoking subgroup was — 44,6% versus 13,5% (RR 3,26 (1,26; 8,43)). Among lipid profile parameters LDL level was definitive for IHD development (p=0,012). Presence of obesity increased MI risk 2,54 times in FHCE (OR 2,4 (1,05; 5,63)). With increase of Lp(a) IHD was diagnosed more commonly: 32,4% versus 19%, non-significant (p=0,47). Prevalence of MI in the first group was higher than in the second: 8 (23,5%) and 4 (8,5%), respectively, (OR 3,3 (1,1; 9,8), р=0,03).Conclusion. In FHCE, the risk of IHD was influenced by traditional RF (smoking, obesity, LDL level)

The new hybrid method for measuring transpiration sap flows in trees

Sap flow measurements have become relevant in many physiological and ecological investigations. A variety of methods are used to estimate sap flow in trees in modern studies. However the determination of accuracy of commonly used techniques often presents a challenge. We analyzed advantages, pitfalls and restrictions of up-to-date methods that were implemented in commercially available devices. We proposed a new hybrid method for measuring linear sap flow velocity, which was designed on the base of different variants of heat-pulse velocity (HPV) technique and thermal dissipation (TD) technique developed by Granier. The method was created in order to increase accuracy and precision of sap flow velocity measurements. The mathematical model of the proposed method was developed. It allows to determine accuracy of measurements and potential limits of applying the new technique in the field studies. The model is based on the description of heat process dynamics in the volume of 1 cubic decimeter of sap tissue. The obtained relationships were used in developed software that allows to model reverse heat pulses distribution under the condition of shortened interval between their generations. The proposed algorithm enables verification of zero sap flow velocity measurement in tree trunk with given accuracy. The computer program was developed. It allows to define maximum acceptable time interval for a given accuracy of determined values when the velocity is close to zero as well as to demonstrate the shape of the heat signal depending of time in the given point of trunk. The model calculations showed that the new method improves the accuracy of sap flow velocity measurements at low and high flow rates when conventional techniques suffer from significant errors. The applying of the new method allows to detect zero sap flow without using any additional measuring procedures and devices

ANALYSIS OF THE TRADITIONAL RISK FACTORS INFLUENCE ON DEVELOPMENT OF ISCHEMIC HEART DISEASE IN FAMILIAL HYPERCHOLESTEROLEMIA

Familial hypercholesterolemia (FH) is inherited pathology with increased level of cholesterol, and predisposes for early development of atherosclerosis, but prevalence of cardiovascular pathology in FH patients varies, and demands for more precise definition of additional factors of risk of ischemic heart disease (IHD).Aim. To evaluate in FH patients an association of IHD and classical risk factors (sex, age, arterial hypertension (AH), smoking, obesity, cholesterol of low density lipoproteides (LDL-C) and high density (HDL-C), complicated heredity for cardiovascular disorders), mutation of LDL receptors.Material and methods. Totally, 253 patients studied, age 18 and older, with heterozygous FCHE, diagnoses according to Dutch Lipid Clinic Network, (mean age — 51±3,4 y. o.). 109 patients (43%) underwent genetic test. IHD was diagnosed in 106 (41,8%), anamnesis of acute myocardial infarction (MI) had 63 (24,9%) patients.Results. In FH, IHD was associated with the following risk factors: AH, age older 40 y., complicated inheritance for cardiovascular pathology. An increase of LDL-C level by every1 mM increased the prevalence of CHD in heterozygous FCHE patients by 4,5% up to LDL-C 8,5 mM/L. In higher LDL-C values IHD prevalence increases by 1-2%. In patients with mutation of LDL receptor, IHD develops 5 years earlier. There was no association revealed for the type of mutation and IHD.Conclusion. The main risk factors associated with CHD in heterozygous FH are AH, age more than 40 y. o., complicated inheritance for cardiovascular diseases. The relation of LDL-C and IHD prevalence in FH patients is not linear

ИНДЕКС АНАЛЬГЕЗИИ-НОЦИЦЕПЦИИ: ВОЗМОЖНОСТИ И ПРЕДЕЛЫ

The review includes clinical opportunities of the new technique for evaluation balance of nociception/anti-nociception with help of medication of ANI-Monitor (MetroDoloris®, France), used abroad, with the calculation of original index of analgesia/nociception of ANI (Analgesia Nociception Index). Objective and non-invasive technique is based on the evaluation of changes in variability of cardiac rhythm under nociception effect. Basing on literature the further investigation is required to identify specificity and sensitivity of ANI index in various clinical situations. В обзоре рассмотрены клинические возможности используемого в зарубежной практике нового метода оценки баланса ноцицепции/антиноцицепции с помощью аппарата ANI-Monitor (MetroDoloris®, Франция) с расчётом оригинального индекса анальгезии/ноцицепции ANI (Analgesia Nociception Index). Объективный и неинвазивный метод основан на оценке изменения вариабельности сердечного ритма при ноцицептивном воздействии. Судя по данным литературы, требуются дальнейшие исследования для установления специфичности и чувствительности индекса ANI в различных клинических ситуациях

Carbocyclic functionalization of quinoxalines, their chalcogen congeners 2,1,3-benzothia/selenadiazoles, and related 1,2-diaminobenzenes based on nucleophilic substitution of fluorine

Previously unknown mono-, di- and in some cases tri- and tetra- carbocycle-substituted quinoxalines (2–8), 2,1,3-benzothiadiazoles (11, 12, 14–17) and 2,1,3-benzoselenadiazoles (20-25) were synthesized by nucleophilic substitution of fluorine in 5,6,7,8-tetrafluoroquinoxaline (1) and 4,5,6,7-tetrafluoro-2,1,3-benzothia/selenadiazoles (10 and 19, respectively) with methoxide and dimethylamine. In the 1:1 reactions, the nucleophiles attacked selectively the position 6 of 1 or the position 5 of 10 and 19. The regioselective nature of the 1:1 reactions was confirmed by the DFT calculations at the M06-2X/6-31+G(d,p) level of theory. Disubstituted quinoxaline (28), thia- (29) and selena- (30) diazoles bearing two different substituents, i.e. MeO- and Me2N-, were synthesized in a similar way. New substituted 1,2-diaminobenzenes (31–33) were prepared by reduction of corresponding thiadiazoles (12, 14, 15) and isolated in the form of hydrochlorides. Compound 33 was converted into a new quinoxaline (34) by reaction with (PhCO)2. Compounds 5, 7 and 14 were studied for cytotoxicity toward the human cancer cells and effects on the cytochrome P450 mRNA expression. They did not cause any significant modulations in the expression of several cytochrome P450 genes, and 7 was weakly toxic for the Hep2 (carcinoma) and U937 (leukemia) cells, particularly, apoptosis was observed

Carbocyclic functionalization of quinoxalines, their chalcogen congeners 2,1,3-benzothia/selenadiazoles, and related 1,2-diaminobenzenes based on nucleophilic substitution of fluorine

Previously unknown mono-, di- and in some cases tri- and tetra- carbocycle-substituted quinoxalines (2–8), 2,1,3-benzothiadiazoles (11, 12, 14–17) and 2,1,3-benzoselenadiazoles (20-25) were synthesized by nucleophilic substitution of fluorine in 5,6,7,8-tetrafluoroquinoxaline (1) and 4,5,6,7-tetrafluoro-2,1,3-benzothia/selenadiazoles (10 and 19, respectively) with methoxide and dimethylamine. In the 1:1 reactions, the nucleophiles attacked selectively the position 6 of 1 or the position 5 of 10 and 19. The regioselective nature of the 1:1 reactions was confirmed by the DFT calculations at the M06-2X/6-31+G(d,p) level of theory. Disubstituted quinoxaline (28), thia- (29) and selena- (30) diazoles bearing two different substituents, i.e. MeO- and Me2N-, were synthesized in a similar way. New substituted 1,2-diaminobenzenes (31–33) were prepared by reduction of corresponding thiadiazoles (12, 14, 15) and isolated in the form of hydrochlorides. Compound 33 was converted into a new quinoxaline (34) by reaction with (PhCO)2. Compounds 5, 7 and 14 were studied for cytotoxicity toward the human cancer cells and effects on the cytochrome P450 mRNA expression. They did not cause any significant modulations in the expression of several cytochrome P450 genes, and 7 was weakly toxic for the Hep2 (carcinoma) and U937 (leukemia) cells, particularly, apoptosis was observed