[Study of the effect of Unifuzol on cognitive impairment and damage to the hippocampus and cerebral cortex during course administration to rats with bilateral stenosis of the common carotid arteries, causing chronic circulatory failure]. / Vliyanie preparata Unifuzol na sostoyanie kognitivnykh funktsii v usloviyakh eksperimental'nogo khronicheskogo narusheniya mozgovogo krovoobrashcheniya.

OBJECTIVE: To study the effect of Unifuzol (L-arginine sodium succinate) on cognitive impairment, cerebral blood flow, and damage to the tissues of the hippocampus and cerebral cortex during a 10-day course of administration to rats with chronic cerebral ischemia (CCI) caused by bilateral stenosis of the common carotid arteries (CCA). MATERIAL AND METHODS: The study was conducted on male rats with CCI caused by bilateral stenosis of the CCA by 60%. 40 days after surgery, rats received Unifusol (21, 42 and 84 ml/kg), nicergoline (10 mg/kg), citicoline (500 mg/kg) or placebo (0.9% NaCl) for 10 days. Next, cognitive impairments were assessed in the Morris Water Maze and the New Object Recognition (NOR) test, as well as the level of motor and exploratory activity in the Open Field test. The level of cerebral blood flow was determined immediately after the CCA stenosis and at the end of the experiment. Animals were euthanized in a CO2 incubator, after which the brain was removed and subjected to morphometric analysis. RESULTS: In animals that were modeled with CCA stenosis, pronounced behavioral and cognitive impairments occurred as a result of a decrease in blood flow in the vessels of the brain and subsequent changes in the tissues of the hippocampus and the cerebral cortex. Intravenous course administration of Unifuzol at doses of 42 and 84 ml/kg to animals with CCI was comparable in efficiency to nicergoline and citicoline, which was expressed in greater preservation of the cognitive abilities of animals in the Morris Water Maze and NOR tests. In the Open Field test, animals injected with Unifusol at doses of 42 and 84 ml/kg performed more acts of motor and exploratory activity than animals from the placebo group, and had a higher level of cerebral blood flow (compared to animals that were injected with citicoline). Based on the results of a morphological study, it was found that the most significant neuroprotective effect was provided by nicergoline and Unifuzol (at doses of 42 and 84 ml/kg). CONCLUSION: Unifuzol at a course of administration at doses of 42 and 84 ml/kg, comparable to the reference drugs nicergoline and citicoline, reduces the severity of psychoneurological deficit in animals with CCI, comparable to them improves the microcirculation of brain tissues, preventing damage to brain tissues.

Concomitant Bandage Contact Lens, Oral Nicergoline, and Topical Autologous Serum for Severe Neurotrophic Keratitis.

BACKGROUND: To report the outcomes of using the combination of oral nicergoline, autologous serum, and contact lens to enhance corneal epithelization in neurotrophic keratitis and to discuss the clinical potential of this management. METHODS: This was a prospective consecutive case series study of eight patients treated for neurotrophic keratitis at the "Conde de Valenciana" Institute of Ophthalmology. Oral nicergoline, autologous serum, and bandage contact lens were initiated at the same time, immediately after stage 3 diagnosis keratitis was confirmed clinically, and until corneal epithelialization was achieved or eminent corneal perforation was seen. In patients where diabetes was a cause, glycosylate hemoglobin was measured to asses metabolic control. Corneal esthesiometry and corrected distance visual acuity were assessed before and after treatment. RESULTS: This study included eight eyes of eight patients (5 men [62.5%], average age 57±17.9 years). All patients completed at least 1 month of follow-up after nicergoline and contact lens suspension. Of the eight eyes, no one had positive culture growth and complete epithelial healing was achieved in all cases. Half of patients had diabetes and had a poor metabolic control. Corneal sensitivity improved in all eyes almost 2 centimeters in Cochet-Bonnet esthesiometry ( P= 0.01). In addition, final visual acuity gains were obtained ( P= 0.100). CONCLUSIONS: The combination of oral nicergoline, autologous serum, and bandage contact lens simultaneously could be an alternative in the management of stage 3 neurotrophic keratitis when conventional medical treatment has no improvement of corneal epithelization.

[Vascular cognitive impairment]. / Sosudistye kognitivnye narusheniya.

Vascular cognitive impairment is considered the second most common cause of dementia after Alzheimer's disease. One of the most significant factors leading to vascular dementia is stroke, which increases the risk of developing dementia by about 2 times. Delayed-onset post-stroke dementia is mainly due to severe small vessel disease, recurrent stroke, or concomitant Alzheimer's disease. Among the many mechanisms involved in the development of vascular cognitive impairment, cerebral small vessel disease is perhaps the most common, contributing to cognitive impairment independent of stroke. An important feature of small vessel disease is its steady progression. The cognitive decline in cerebrovascular disease, including small vessel disease, is also usually gradual and gradual, progresses slowly, and the underlying defect extends to processing speed, complex attention, and fronto-executive functions. Vascular cognitive impairments are quite heterogeneous in nature, while having a negative impact on all major cognitive domains. Patient management should include the earliest possible diagnosis of cognitive impairment and the appointment of timely therapy. One of the drugs that has been successfully used to treat vascular cognitive impairment is nicergoline (Sermion). The clinical efficacy of the drug is achieved due to the improvement of cerebral blood flow, a positive effect on cholinergic neurotransmission and neuroprotective action.

[Combined chemoreflexes of the vertebral arteries zone on the systemic arterial pressure, cerebral and infra-aural blood circulation in the experiment]. / Sochetannye khemorefleksy zony pozvonochnykh arterii na sistemnoe arterial'noe davlenie, tserebral'noe i vnutriushnoe krovoobrashchenie v eksperimente.

OBJECTIVE: To study reflexes coming from the chemoreceptors in the humoral-isolated vertebral artery zone on systemic arterial pressure, cerebral and intra-ear hemodynamics in separate stimulation with angioprotectors. RESULTS: A more pronounced reflex depression of the above-described effectors was caused by Nicergoline, it was less pronounced when using Vinpocetine and Pentoxifylline. Correlation analysis in doing so of the dynamics of arterio-venular coefficient of bulbar conjunctiva vessels and the membrane of the ears labyrinth round window revealed a direct relationship. CONCLUSION: These studies objectivize the therapy of ear labyrinth discirculation with angioprotectives.

Use of Nicergoline as Adjunctive Treatment of Neurotrophic Keratitis in Routine Clinical Practice: A Case Series.

PURPOSE: To describe the effectiveness and safety of nicergoline in patients with epithelial corneal defect or corneal ulcer due to neurotrophic keratitis (NK). METHODS: A prospective case series review was performed in 14 patients with NK who started treatment with nicergoline as an off-label prescription from January to November 2020. Patients with a epithelial defect or corneal ulcer due to NK were treated with oral nicergoline. RESULTS/SERIAL CASES: Complete corneal healing was observed in 10 (71.4%) of the 14 patients after 25.6 ± 26.60 days (range 7-90) with nicergoline. In three (21.5%) patients wound healing was not achieved, and one patient (7.1%) was lost to follow-up. The mean time between diagnosis and the starting of nicergoline was 10.92 ± 8.85 days (0-28). No adverse effects of nicergoline were observed. CONCLUSION: Nicergoline as an adjunctive treatment for NK showed a potential use in the healing of epithelial defect in real-life clinical practice.

[Efficacy of Sermion in the treatment of tinnitus noise in patients with chronic cerebrovascular pathology]. / Effektivnost' Sermiona v lechenii shuma v ushakh u patsientov s khronicheskoi tserebrovaskulyarnoi patologiei.

Noise in the ears or tinnitus is one of the earliest and most frequent non-cognitive manifestations of chronic cerebral ischemia (CCI) and is the most difficult clinical phenomenon for therapeutic intervention. OBJECTIVE: Of an open observational noncomparative clinical study was to study in patients with CCI and tinnitus and/or head the efficacy and tolerability of Sermion in a daily dose of 30 mg for 6 months. MATERIAL AND METHODS: 56 patients (51.1±8.7 years) were clinically and neurologically examined using standard questionnaires to analyze the severity of tinnitus and its impact on daily life and the level of patient distress associated with noise, and to study the quality of life using the SF-36 questionnaire. All patients independently assessed the therapy satisfaction index. RESULTS AND CONCLUSION: The safety, good tolerance and obvious clinical effect were shown when using the drug Sermion. The best results were obtained with the use of Sermion for 6 months in relation to the severity of tinnitus, the degree of its influence on daily activity, the level of distress and an increase in the quality of life of patients, as well as a significant improvement in well-being and cognitive functions in almost all subjects. It has been shown that after an adequate course of therapy and after 3 months, the therapeutic efficacy of Sermion is preserved, and the patients themselves were more satisfied with this remedy after 6 months of treatment. The data obtained suggest a wider use of Sermion in patients with cerebrovascular diseases and tinnitus and/or head, the use of which allows a safe, effective and pathogenetically reasonable effect on the existing disorders in these patients.

Role of nicergoline in corneal wound healing in diabetic rats.

BACKGROUND: To investigate the effect of nicergoline on the rate of complete corneal ulcer reepithelialization (CCUR) in diabetic rats with diabetic keratopathy. METHODS: Forty-eight streptozotocin-induced diabetic rats were randomly divided into two groups. The experimental group (n = 24) received nicergoline (10 mg.kg- 1.day- 1), while the control group (n = 24) received a placebo. A corneal epithelial defect was induced using a corneal diamond burr, and defect area was compared at time points of 0, 12, 24, 48 and 72 h after the injury using image analysis software. The probability of CCUR within 72 h was assessed using the Kaplan-Meier survival analysis log-rank test. RESULTS: When compared, 4 of the 24 rats (17%) in the placebo group and 12 of the 24 rats (50%) in the nicergoline group were found to have CCUR within 72 h (log-rank = 0.027). Cox regression analysis found no effect of the covariates blood glucose (P = 0.601) or weight (P = 0.322) on the corneal reepithelialization (survival) curve. CONCLUSIONS: Nicergoline increased wound healing rates relative to placebo and may therefore be investigated as a treatment option in diabetic keratopathy.

Human platelets use a cytosolic Ca2+ nanodomain to activate Ca2+-dependent shape change independently of platelet aggregation.

Human platelets use a rise in cytosolic Ca2+ concentration to activate all stages of thrombus formation, however, how they are able to decode cytosolic Ca2+ signals to trigger each of these independently is unknown. Other cells create local Ca2+ signals to activate Ca2+-sensitive effectors specifically localised to these subcellular regions. However, no previous study has demonstrated that agonist-stimulated human platelets can generate a local cytosolic Ca2+ signal. Platelets possess a structure called the membrane complex (MC) where the main intracellular calcium store, the dense tubular system (DTS), is coupled tightly to an invaginated portion of the plasma membrane called the open canalicular system (OCS). Here we hypothesised that human platelets use a Ca2+ nanodomain created within the MC to control the earliest phases of platelet activation. Dimethyl-BAPTA-loaded human platelets were stimulated with thrombin in the absence of extracellular Ca2+ to isolate a cytosolic Ca2+ nanodomain created by Ca2+ release from the DTS. In the absence of any detectable rise in global cytosolic Ca2+ concentration, thrombin stimulation triggered Na+/Ca2+ exchanger (NCX)-dependent Ca2+ removal into the extracellular space, as well as Ca2+-dependent shape change in the absence of platelet aggregation. The NCX-mediated Ca2+ removal was dependent on the normal localisation of the DTS, and immunofluorescent staining of NCX3 demonstrated its localisation to the OCS, consistent with this Ca2+ nanodomain being formed within the MC. These results demonstrated that human platelets possess a functional Ca2+ nanodomain contained within the MC that can control shape change independently of platelet aggregation.

The Efficacy of Sertraline, Escitalopram, and Nicergoline in the Treatment of Depression and Apathy in Alzheimer's Disease: The Okayama Depression and Apathy Project (ODAP).

BACKGROUND: Neuropsychiatric symptoms of dementia such as depression and apathy in patients with Alzheimer's disease (AD) are associated with a lower quality of life. OBJECTIVE: We aimed to determine the efficacy of two antidepressants and one antipathy drug in the treatment of depression and apathy in AD patients. METHODS: In the present study, we evaluated the efficacy of sertraline (n = 11; average dose = 31.8 mg), escitalopram (n = 13; average dose = 7.3 mg), and nicergoline (n = 9; average dose = 14.5 mg) in treating depression and apathy over a period of 3 months (M).The 33 patients with AD demonstrated high Geriatric Depression Scale (GDS) (>5) or a high Apathy Scale (AS) (>16) scores. RESULTS: The patients receiving escitalopram treatment showed a significant improvement in GDS score from baseline (8.2±3.5) to 3 M (5.7±2.6, p = 0.04), and the patients receiving sertraline treatment showed a significant improvement in AS score from baseline (20.8±5.2) to 3 M (16.8±6.1, p = 0.05); however, no significant changes were noted in patients receiving nicergoline. CONCLUSION: These results provide novel information on the efficacy of sertraline and escitalopram in the treatment of apathy and depression, respectively, in patients with AD.

Clinical efficacy and safety of nicergoline combined with oxiracetam in the treatment of vascular cognitive impairment.

As a α1-adrenergic receptor antagonist, nicergoline can induce vasodilation and increase arterial blood flow. Its clinical application can effectively prevent and treat cognitive impairment and reduce cognitive decline and comprehensively improve patients' daily living ability and social function. The clinical efficacy of nicergoline combined with oxiracetam in the treatment of vascular cognitive impairment after stroke was analyzed. 120 patients with cognitive impairment after stroke were randomly divided into nicergoline group and Experience group. They were treated with nicergoline and nicergoline combined with oxiracetam respectively. Both groups were treated for one month. Montreal Cognitive Assessment Scale (MoCA) was used to evaluate the cognitive function of the two groups before and after treatment, and the clinical efficacy was compared. The results showed that the average score of MoCA in the combined group was (5.97±2.06), higher than that in the nicergoline group (3.53±1.44). The change of MoCA score was the most significant. There was significant difference between the nicergoline group and the combined group (t=4.21, P<0.01). The combined group had the highest effective rate and the total effective rate was 93.3%. Conclusion: Nicergoline and oxiracetam are effective drugs in the treatment of vascular cognitive impairment (VCI). The combined use of nicergoline and oxiracetam is better than that of nicergoline alone. The combined use of nicergoline and oxiracetam can significantly improve the severity of symptoms and quality of life in patients with vascular cognitive impairment after stroke. The clinical effect is definite.

Nerve growth factor in dogs: Assessment of two immunoassays and selected ocular parameters following a nicergoline challenge per os.

Impairment of corneal nerves can result in the development of ocular surface diseases such as aqueous tear deficiency and neurotrophic keratopathy. This study investigates oral nicergoline, an α-adrenoceptor antagonist shown to enhance endogenous secretion of nerve growth factor (NGF) by the lacrimal gland, as a potential therapy for these conditions. Five female spayed Beagle dogs received a 2-week course of oral nicergoline (10 mg twice daily). Drug safety was evaluated with ophthalmic and physical examinations, blood pressure monitoring, bloodwork, and urinalysis. The effect of nicergoline on the ocular surface was assessed with corneal esthesiometry, Schirmer tear test-1, and tear film breakup time. Drug effect on NGF levels was assessed by collecting tears and blood at baseline and completion of therapy using a bead-based immunoassay and an enzyme-linked immunosorbent assay. Although nicergoline was well tolerated in all dogs, it did not have a significant impact on corneal sensitivity, tear production, or tear stability. Of note, NGF was below the limit of quantification in all tear samples and was only detected in 8/20 serum samples with no significant difference between levels at baseline (189.4 ± 145.1 pg/mL) and completion of therapy (149.4 ± 79.4 pg/mL). Further validation of NGF analytical assays is warranted before nicergoline is investigated in clinical patients.

Efficacy of nicergoline treatment in Parkinson's disease associated with dementia.

Parkinson's disease (PD) has a variable spectrum of cognitive impairment. However, there are no clear evident-based management guidelines for PD with dementia (PDD). Alternative treatments for PDD are therefore required. We conducted this longitudinal study to evaluate the efficacy of nicergoline in treating PDD by analyzing changes in regional cerebral blood flow (rCBF) and neuropsychological tests before and after nicergoline administration. A total of nine PDD patients who received nicergoline therapy (PDD + N) and 14 PD patients who did not receive nicergoline therapy (PDD - N) underwent single photon emission computed tomography (SPECT) and clinical assessments at baseline and 12-month follow-up visits. The PDD + N received nicergoline at 30 mg twice per day. Changes in rCBF were compared between the groups, and correlation analysis was performed to determine possible relationship between rCBF and clinical characteristics. There were no significant differences in rCBF between the two groups at baseline. Although changes in cognitive test scores and the motor severity scale were not significantly different between baseline and the 12-month follow-up within groups, rCBF was lower in both the temporal and inferior frontal restricted areas in the PDD - N group than the PDD + N at the 12-month follow-up visit. In conclusions, nicergoline appears to delay the speed of deterioration of cognitive function in patients with PDD based on our observation of decreased rCBF in the temporal regions and inferior frontal regions of PDD - N patients compared to PDD + N patients after 12-month of nicergoline therapy. Therefore, we cautiously suggest that nicergoline administration in PDD patients may slow progression of cognitive impairment in affected brain regions.

Dihydrogen Bond in the Aminoborane Complex of a Nicergoline Intermediate.

An aminoborane side product from the nicergoline manufacture process was identified by single-crystal X-ray diffraction. As boranes of pharmaceutical molecules are quite rare, the binding potential of the BH3 group was investigated and compared with similar compounds using Cambridge Structural Database (CSD). Surprisingly, the packing was stabilized by a dihydrogen bond, which triggered a false alert for too-short contact of hydrogen atoms in IUCR checkCIF. As the dihydrogen bond concept is not widely known, such an alert might mislead crystallographers to force -CH3 optimal geometry to -BH3 groups. The B-H distances equal to or less than 1.0 Å (17% of the CSD structures) are substantially biased when analyzing the structures of aminoborane complexes in CSD. To conduct proper searching, B-H bond length normalization should be applied in the CSD search.

Changes in the Solid State of Nicergoline, a Poorly Soluble Drug, Under Different Grinding and Environmental Conditions: Effect on Polymorphism and Dissolution.

Nicergoline native crystals (Form I) were subjected to different grinding methods for 15, 30, 45, and 60 min: Method A, grinding at 20°C under air atmosphere; Method B, grinding in presence of liquid nitrogen under air atmosphere; Method C, grinding at 20°C under nitrogen atmosphere; and Method D, grinding in presence of liquid nitrogen under nitrogen atmosphere. Scanning electron microscopy, differential scanning calorimetry, X-ray powder diffractometry, thermogravimetry, and infrared spectroscopy were used to follow changes in the particle size and in crystalline structures. Batches from Methods A and C underwent partial amorphization immediately after grinding; Form II was obtained by heating these partially amorphous forms or after spontaneous crystallization after 1 and 5 months storage. Method B promoted the hydration of nicergoline to a monohydrate form. Batch D was stable under grinding and neither amorphization nor hydration were observed. The best intrinsic dissolution rate was that of metastable Form II, followed by Form I, while the worst was that of the Method B monohydrate form. The slowest particle dissolution was observed for hydrated particles, because of the lowest IDR, while the most rapid was exhibited by batch D, because of the very small particle size.

Ameliorative effect of nicergoline on cognitive function through the PI3K/AKT signaling pathway in mouse models of Alzheimer's disease.

Alzheimer's disease is one of the most common age­associated diseases that frequently leads to memory disorders, cognitive decline and dementia. Evidence suggests that nicergoline serves an important role in the apoptosis of hippocampal cells, memory recovery, cognitive function and neuronal survival. However, the signaling pathway affected by nicergoline treatment remains to be elucidated. The purpose of the present study was to investigate the role of nicergoline in the cognitive competence of a mouse model of Alzheimer's disease. The apoptosis rates of hippocampal cells were studied in mice with Alzheimer's disease treated with nicergoline compared with the negative control. Apoptosis­associated gene expression levels in hippocampal cells, and hippocampus area, were analyzed in the experimental mice. Visual attention and inhibitory control were assessed and neural counting was performed in brain regions of interest. The phosphatidylinositol 3­kinase (PI3K)/RAC­α serine/threonine­protein kinase (AKT) signaling pathway was additionally analyzed in hippocampal cells following treatment with nicergoline. The results of the present study demonstrated that nicergoline ameliorated apoptosis in hippocampal cells and hippocampus tissue in 3xTg­AD mice with Alzheimer's disease. The data indicated that apoptosis­associated genes, including caspase­3, BCL2 associated X, BH3 interacting domain death agonist and caspase­9, were downregulated in hippocampal cells isolated from nicergoline-treated experimental mice. In addition, the expression levels of inflammatory factors, in addition to oxidative stress, were decreased in hippocampal cells treated with nicergoline. Additionally, amyloid precursor protein accumulation was cleared in the hippocampal area in nicergoline­treated mice. Nicergoline inhibited neuronal loss and prevented cognitive impairment through the restoration of learning/memory ability. It was additionally demonstrated in the present study that nicergoline improved motor attention impairment and cognitive competence in hippocampal cells by acting on the PI3K/AKT signaling pathway. Therefore, memory recovery, cognitive function and neuronal survival were repaired by nicergoline via inhibition of the PI3K/AKT signaling pathway, suggesting that nicergoline may be an efficient drug for the clinical treatment of patients with Alzheimer's disease.

A unique and promising combination of medications for the treatment of Alzheimer's disease.

At present there is no therapy for Alzheimer's Disease which completely stops the progressive dementia effecting late onset Alzheimer's Disease (AD) patients. It is felt that the main reason for this failure is that AD appears to be a disease caused by four major pathological processes. To date, efforts to develop treatments have addressed only one or another of these four etiologies. However, even a partially effective therapy against one cause allows the others, untreated, to continue their inexorable destruction of the neurons of the brain. It is suggested that a therapy is required which inhibits all four causes of the disease. Just such a therapy is proposed here with four specific drugs and a vitomer together in a combination treatment. The four major pathologic processes causing AD are: I. vascular hypoperfusion of the brain with associated mitochondrial dysfunction. II. destructive protein occlusions. III. uncontrolled oxidate stress and IV: pro-inflammatory immune processes secondary to microglial and astrocytic dysfunction in the brain. A detailed literature search has provided four drugs and a B6 vitomer which together provide an ideal combination to treat the four etiologies of AD. All four drugs are used clinically for various indications and would be used "off label" in combination to treat AD. The drugs have been used in preliminary studies to treat dementia with favorable indications in all of them inhibiting dementia with only modest side effects. In in vitro studies all five of the combination have been shown effective in inhibiting one or more of the four disease etiologies and together they are effective against all four. The four drugs are Trental, Nicergoline, Nilotinib, and Methylene blue. The vitamer is B6 pyridoxamine. The cumulative benefits of this combination should provide an effective treatment to completely stop the progressive dementia of AD, measured in 12-18months. The use of an endpoint of complete cessation of progressive dementia rather than the standard of a statistical determination of the slowing of progressive dementia allows the study to be conducted with a cohort of only 15 patients (no statistics and no placebo patients) as every AD patient would otherwise show progressive dementia without the effective treatment.

[The use nicergoline in the treatment of diabetes mellitus]. / Ispol'zovanie nitsergolina v terapii oslozhnenii sakharnogo diabeta.

Presented herein is a literature review aimed at investigating the appropriateness and possibility of using nicergoline (sermion) for treatment of patients suffering from diabetes mellitus. The analysis includes the most clinically significant results of scientific studies. The material to be reviewed was retrieved using the following key words: 'nicergoline', 'sermion', and 'diabetes mellitus' (with their respective Russian equivalents) in such databases as Medline, PubMed, ScienceDirect, PMC, Cochrane, as well as archives of both Russian and foreign journals, guidelines (clinical guidelines on rendering medical care for patients with diabetes mellitus, selected lectures on endocrinology). A broad spectrum of action and no significant side effects have made it possible to use this drug in various pathological conditions. At the same time, because of limited experience of using nicergoline for vascular diseases and an insufficient number of the carried out studies the precise role of this therapeutic agent in clinical practice has not yet been conclusively defined. Special attention is given to the analysis of efficacy of nicergoline in atherosclerosis and diabetes mellitus.

The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria.

The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO4. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAßN (Phe-Arg-ß-naphthylamide) was investigated. The impacts of PAßN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100-800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine) tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAßN to the studied clinical strains of five groups of species.

[Pathogenesis of chronic disorders of cerebral circulation]. / Patogenez khronicheskikh rasstroistv mozgovogo krovoobrashcheniia.

Chronic disorders of cerebral circulation are a common syndrome, in the pathogenesis of which the important role play structural and functional alterations in large and small arteries, autoregulation of cerebral circulation and the level of systemic arterial pressure. Drugs that increase cerebral blood flow and restore the ability to its autoregulation are used, among others, in treatment of patients with CRMC. The possibility of using nicergoline (sermion) for the treatment of patients with CRMK is considered.

Microwave-assisted digestion using nitric acid for heavy metals and sulfated ash testing in active pharmaceutical ingredients.

The monitoring of inorganic impurities in active pharmaceutical ingredients plays a crucial role in the quality control of the pharmaceutical production. The heavy metals and residue on ignition/sulfated ash methods employing microwave-assisted digestion with concentrated nitric acid have been demonstrated as alternatives to inappropriate compendial methods recommended in United States Pharmacopoeia (USP) and European Pharmacopoeia (Ph. Eur.). The recoveries using the heavy metals method ranged between 89% and 122% for nearly all USP and Ph. Eur. restricted elements as well as the recoveries of sodium sulfate spikes were around 100% in all tested matrices. The proposed microwave-assisted digestion method allowed simultaneous decomposition of 15 different active pharmaceutical ingredients with sample weigh up to 1 g. The heavy metals and sulfated ash procedures were successfully applied to the determination of heavy metals and residue on ignition/sulfated ash content in mycophenolate mofetil, nicergoline and silymarin.