Pharmacognostic study of complex phytotherapeutic composition "Detox composition"

We realized pharmacognostic study of 6-component composition recommended as a therapeutic and prophylactic agent at the hepatic and bile passages disorders, for the accelerated elimination of products of kidneys' nitrogen metabolism and for normalization of lipid metabolism. The norms of indices defining composition's quality and also significant macro- and microscopic characteristics are determined. As the result of phytochemical research we identified main groups of biologically active substances

Use of grape polyphenols in complex therapy of overweight patients with type 2 diabetes mellitus

Проведен анализ эффективности естественного фармацевтика «Вин-Вита» в комплексной терапии пациентов с сахарным диабетом 2 типа на фоне избыточной массы тела. Введение препарата в комплекс терапии в сочетании с модификацией питания, дифференцированной дозированной контролированной физической нагрузкой, а также сахароснижающими препаратами улучшает показатели липидного обмена, что является особенно важным у пациентов с сахарным диабетом 2 типа и избыточной массой тела, которые входят в группу риска развития кардиоваскулярных заболеваний.The article focuses on efficacy of a natural farmaceutic “Vin-Vita” in the management of overweight patients with type 2 diabetes mellitus. Introduction of the product into the course of treatment including eating behavior modification, differential dosed controlled physical activity as well as hypoglycemic agents, improves blood lipid parameters, which is especially important in overweight patients with type 2 diabetes who are at major risk of developing cardiovascular disease

Long-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortex

Objective: Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under longterm continuous glucocorticoid exposure has not been elucidated. Material and Methods: We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. Results: We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. Conclusions: The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecula

Localization of Mineralocorticoid Receptors at Mammalian Synapses

In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids

Vitamin D3 (Cholecalciferol) and Pelvic Pain Caused by Ovarian Endometriosis

Статья посвящена изучению взаимосвязи концентрации витамина D с наличием и интенсивностью тазовой боли у женщин, страдающих эндометриозом яичников. Цель исследования: установить взаимосвязь уровня витамина D и интенсивности тазовой боли у женщин, страдающих эндометриозом яичников. В исследование были включены 190 женщин репродуктивного возраста с верифицированным диагнозом эндометриоз яичников, в возрасте от 20 до 41 года (средний возраст – 29,1±3,3 года). Для определения интенсивности тазовой боли использовали визуальную аналоговую шкалу (ВАШ). Всем пациенткам (n=190) исходно оценку уровня витамина D проводили путем определения уровня общего 25(ОН)D в сыворотке крови методом масс-спектрометрии, адаптированным к клинической практике, согласно международным стандартам, на тандемном масс-спектрометре AB SCIEX QTRAP 5500.The article studies the relation between vitamin D concentration and the presence and intensity of pelvic pain in women suffering from ovarian endometriosis. The aim of the study is to examine the relation between vitamin D levels and intensity of pelvic pain in women with ovarian endometriosis. Study design: cohort, prospective, non-comparative study. The study included 190 women of reproductive age suffering from ovarian endometriosis (OE), aged 20 to 41 years (mean age 29.1±3.3 years). Visual analogue scale (VAS) was used to determine the intensity of pelvic pain.The evaluation of vitamin D level in all patients (n=190) was initially performed by determining the level of total 25 (OH) D in blood serum by the method of mass spectrometry. Study Results: The average vitamin D level in the study was 23.98±6.82 ng/ml. The average concentration of vitamin D in the blood of the patients with low-intensity pelvic pain was 26.7±5.92 ng/ml, with moderate-intensity – 23.06±of 5.55 ng/ml, with high pain intensity – 19.26±6,01 ng/ml. The content of vitamin D in the blood of the patients in the control group was 28.83±6.15 ng/ml, which met the criteria of insufficiency. Аn inverse correlation between the severity of pain based on VAS and vitamin D in women with endometriosis of the main group was established in the study, it amounted to 0.502 (p<0.001)

Overexpression of Mineralocorticoid Receptors in the Mouse Forebrain Partly Alleviates the Effects of Chronic Early Life Stress on Spatial Memory, Neurogenesis and Synaptic Function in the Dentate Gyrus

Evidence from human studies suggests that high expression of brain mineralocorticoid receptors (MR) may promote resilience against negative consequences of stress exposure, including childhood trauma. We examined, in mice, whether brain MR overexpression can alleviate the effects of chronic early life stress (ELS) on contextual memory formation under low and high stress conditions, and neurogenesis and synaptic function of dentate gyrus granular cells. Male mice were exposed to ELS by housing the dam with limited nesting and bedding material from postnatal day (PND) 2 to 9. We investigated the moderating role of MRs by using forebrain-specific transgenic MR overexpression (MR-tg) mice. Low-stress contextual (i.e., object relocation) memory formation was hampered by ELS in wildtype but not MR-tg mice. Anxiety like behavior and high-stress contextual (i.e., fear) memory formation were unaffected by ELS and/or MR expression level. At the cellular level, an interaction effect was observed between ELS and MR overexpression on the number of doublecortin-positive cells, with a significant difference between the wildtype ELS and MR-tg ELS groups. No interaction was found regarding Ki-67 and BrdU staining. A significant interaction between ELS and MR expression was further observed with regard to mEPSCs and mIPSC frequency. The ratio of evoked EPSC/IPSC or NMDA/AMPA responses was unaffected. Overall, these results suggest that ELS affects contextual memory formation under low stress conditions as well as neurogenesis and synaptic transmission in dentate granule cells, an effect that can be alleviated by MR-overexpression

Noradrenergic activation of the basolateral amygdala modulates the consolidation of object-in-context recognition memory

Contains fulltext : 135989.pdf (publisher's version ) (Open Access)Noradrenergic activation of the basolateral complex of the amygdala (BLA) is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic activation of the BLA also influences the consolidation of object-in-context recognition memory, a low-arousing training task assessing episodic-like memory. Male Sprague-Dawley rats were exposed to two identical objects in one context for either 3 or 10 min, immediately followed by exposure to two other identical objects in a distinctly different context. Immediately after the training they received bilateral intra-BLA infusions of norepinephrine (0.3, 1.0, or 3.0 mu g) or the beta-adrenoceptor antagonist propranolol (0.1, 0.3, or 1.0 mu g). On the 24-h retention test, rats were placed back into one of the training contexts with one copy of each of the two training objects. Thus, although both objects were familiar, one of the objects had not previously been encountered in this particular test context. Hence, if the animal generated a long-term memory for the association between an object and its context, it would spend significantly more time exploring the object that was not previously experienced in this context. Saline-infused control rats exhibited poor 24-h retention when given 3 min of training and good retention when given 10 min of training. Norepinephrine administered after 3 min of object-in-context training induced a dose-dependent memory enhancement, whereas propranolol administered after 10 min of training produced memory impairment. These findings provide evidence that post-training noradrenergic activation of the BLA also enhances the consolidation of memory of object-in-context recognition training, enabling accuracy of episodic-like memories

Noradrenergic activation of the basolateral amygdala enhances object recognition memory and induces chromatin remodeling in the insular cortex

Contains fulltext : 149204.pdf (publisher's version ) (Open Access)It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA) and modulatory influences on information storage processes in its many target regions. While this concept is well accepted, the molecular basis of such BLA effects on neural plasticity changes within other brain regions remains to be elucidated. The present study investigated whether noradrenergic activation of the BLA after object recognition training induces chromatin remodeling through histone post-translational modifications in the insular cortex (IC), a brain region that is importantly involved in object recognition memory. Male Sprague-Dawley rats were trained on an object recognition task, followed immediately by bilateral microinfusions of norepinephrine (1.0 mug) or saline administered into the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas norepinephrine treatment induced robust 24-h object recognition memory. Most importantly, this memory-enhancing dose of norepinephrine induced a global reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine administered into the BLA of non-trained control rats did not induce any changes in the histone marks investigated in this study. These findings indicate that noradrenergic activation of the BLA induces training-specific effects on chromatin remodeling mechanisms, and presumably gene transcription, in its target regions, which may contribute to the understanding of the molecular mechanisms of stress and emotional arousal effects on memory consolidation