Glucocorticoid Deflazacort Normalizes the Ultrastructure of Skeletal Muscles and the State of the Colon Microbiota in Dystrophin-Deficient Mice.

We studied the effect of enteral administration of the glucocorticoid deflazacort (DFC, 1.2 mg/kg per day, 28 days) on the state of skeletal muscles and tissue ultrastructure, as well as the composition of the colon microbiota in dystrophin-deficient mdx mice. DFC has been shown to reduce the intensity of degeneration/regeneration cycles in muscle fibers of mdx mice. This effect of DFC was accompanied by normalization of the size of sarcomeres of skeletal muscles of mdx mice, improvement of the ultrastructure of the subsarcolemmal population of mitochondria, and an increase in the number of organelles, as well as normalization of the number of contact interactions between the sarcoplasmic reticulum and mitochondria. In addition, DFC had a corrective effect on the colon microbiota of mdx mice, which manifested in an increase in the number of the Bifidobacterium genus microorganisms and a decrease in the level of E. coli with reduced enzymatic activity.

[First experience of applying domestic video fluorescent equipment for visualization and blood flow evaluation of the parathyroid glands]. / Pervyi opyt primeneniya otechestvennoi videoflyuorestsentnoi ustanovki dlya vizualizatsii i otsenki krovotoka okoloshchitovidnykh zhelez.

In recent years, predictive methods for assessing the preservation of the parathyroid glands have been actively implemented. The article describes the first experience of evaluating the blood supply of the parathyroid glands by quantitative determination of the indocyanine green (ICG) accumulation index in real time in 6 patients before and after a thyroidectomy with central neck lymph node dissection for papillary thyroid cancer. Intraoperative fluorescent angiography was performed by using domestic equipment with a fluorescent module, as well as by using a domestic medication of ICG. Intraoperative values of the ICG accumulation index were compared with the levels of ionized calcium and parathyroid hormone perioperatively. No clinical manifestations of hypocalcemia were detected in the postoperative period. The obtained results showed the informativeness of the numerical assessment of the intensity of ICG fluorescence. The evaluation of the distribution (accumulation) of ICG has prospects for practical application in thyroid surgery in the formation of tactics for preserving the parathyroid glands and predicting postoperative hypoparathyreosis.

Proteins of the Vesicular Cycle as a Marker of Neuroplasticity of Dopaminergic Neurons in the Substantia Nigra of the Brain.

Nigrostriatal dopaminergic neurons (DNs), involved in the regulation of motor function, are characterized by a high plasticity. Indeed, at the death of up to 50% of DNs in Parkinson's disease, the survived neurons provide normal regulation. This study was aimed to determine whether the vesicle cycle proteins, syntaxin Ia (Syn Ia), synaptotagmin I (Syt I), Rab5a, and complexins I and II (Cmpx I and II) are involved in the mechanisms of neuroplasticity in the substantia nigra, which mainly contains cell bodies and processes of the DNs. In the neurotoxic models of Parkinson's disease in mice, it was shown that, at the degeneration of up to 50% of DNs, the content of Syt I, Syn Ia, and Cmpх I and II, involved in vesicle exocytosis, does not change in the substantia nigra as a whole but is compensatorily increased in individual survived DNs. Thus, the data obtained in this study suggest that the impairment of motor behavior, which occurs at the death of half of the nigrostriatal DNs, is not caused by the impairment of the production of vesicle cycle proteins in the survived DNs.

[ABERRANT RIGHT SUBCLAVIAN ARTERY (ARSA)--A NEW ULTRASOUND MARKER FOR CHROMOSOMAL FETAL ABNORMALITIES].

UNLABELLED: The development of the fetal aorta ends with the formation of the aortic arch which normally branches into three blood vessels: 1) a. brachiocephalica (a. innominata), which divides into the right subclavian artery (RSA) and the right carotid artery; 2) the left carotid artery; and 3) the left subclavian artery. Occasionally, RSA originates as a separate fourth branch of the aortic arch, passing behind the trachea with an oblique course to the right shoulder. This rare variant is called an aberrant right subclavian artery (ARSA) and is observed in approximately 2% of normal individuals. On the other hand, the reported incidence of ARSA varies between 25 and 37% in cases with Down syndrome and other chromosomal abnormalities. OBJECTIVE: To evaluate the success rate of ultrasound visualization of the fetal RSA between 18 and 23 weeks of gestation and to establish the importance of the prenatal diagnosis of ARSA in the risk assessment for fetal chromosomal abnormalities in the second trimester. RESULTS: Three experienced sonographers scanned 992 fetuses in MC "Markovs", Sofia between 01.09.2013-01.06.2014 with Voluson 730 Expert (GE Healthcare) ultrasound equipment. Visualization of RSA was successful in 92.7% of cases. Overall, 17 cases with ARSA were diagnosed in the study period. ARSA was an isolated sonographic finding in 13 of them. The remaining 4 cases had additional pathology. In the first case ARSA was associated with a short femurand humerus, short nasal bone and borderline nuchal thickness without any other soft markers or structural abnormalities. Trisomy 21 was diagnosed after amniocentesis and the pregnancy was terminated at patient's request. In the second case ARSA was associated with severe polymalformation syndrome. Trisomy 18 was diagnosed by DNA analysis post abortem. In the third case ARSA was associated with an unilateral cleft lip and cleft palate. Abnormalities of the fetal karyotype and Di George syndrome were excluded by amniocentesis. The fourth case was associated with a single umbilical artery without any structural and chromosomal abnormalities. The pregnancy had a favourable perinatal outcome at term. CONCLUSION: Visualization of RSA and prenatal diagnosis of ARSA in the second trimester is relatively easy in experienced hands. The examination slightly prolongs the fetal morphology scan. Since there is an obvious association between ARSA and chromosomal fetal abnormalities, implementation of its sonographic evaluation in the protocol of fetal echocardiography in the second trimester is strongly recommended.

[THE IMPACT OF 3D ULTRASOUND ON MATERNAL-FETAL BONDING DURING THE FETAL ANOMALY SCAN IN THE FIRST AND SECOND TRIMESTER].

OBJECTIVES: To assess the role of prenatal conventional (2D) and volume (3D/4D) ultrasound on maternal-fetal bonding and to investigate its emotional impact on women's perceptions. METHODS: Overall 133 pregnant women with a mean maternal age 29.81 ± 5.56 years presented for a routine first and second trimester scan in MC "Markovs" and University hospital of Obstetrics and Gynecology "Maichin dom", Sofia, Bulgaria. All participants had uncomplicated singleton pregnancies with no fetal abnormalities. The women were asked to complete a questionnaire in two parts. The first part assessed the patient's understanding and knowledge about the different imaging modalities (2D and 3D), the level of maternal-fetal attachment and the overall expectations about the scan. The second part of the questionnaire was completed after the examination and assessed the expectations of the mode of visualization, the emotional perceptions of the fetus and the maternal-fetal attachment. RESULTS: Maternal-fetal bonding increased after both the 2D and 3D/4D ultrasound examination. However, almost half of the pregnant women did not understand the difference between the two imaging modalities. There was no accumulative effect of prenatal ultrasound on maternal-fetal bonding in late gestation. Most of the patients declared that the scan had improved their overall perception of the fetus. Maternal age, educational status and gestational age had no significant impact on understanding and improving womens' emotional perceptions. CONCLUSIONS: Prenatal 2D and 3D/4D ultrasound has a positive impact on antenatal emotional maternal-fetal bonding, particularly when performed in the first trimester.

[THE FETAL MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY AS A PEDICTOR OF FETAL ANEMIA IN RH-ALLOIMMUNIZED PREGNANCY].

UNLABELLED: Rh-isoimmunization is a pathological condition in which the fetal red blood cells of a Rh (+) fetus are destroyed by the isoantibodies of a Rh (-) woman sensitized in a previous event. Despite of the wide spread implementation of anti D-gammaglobolin prophylaxis this is still the most common cause for fetal anemia. Recently, sonographic measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV) has been shown to be an accurate non-invasive test to predict low fetal hemoglobin levels. We present a case report of Rh-alloimmunized pregnancy with moderate fetal anemia, followed-up by weekly MCA-PSV measurements. CASE REPORT: A 37-year-old Rh (-) negative gravida 3, para 1, without anti-D gammaglobolin prophylaxis in her previous pregnancies, presented at 27+0 weeks of gestation (w.g.) for a routine third trimester scan. Subsequent ultrasound measurements of MCA-PSV confirmed a progressive increase of the peak systolic velocities from 40 to 80 cm/sec, as well as a gradual rise in the anti-D titers. The evidence of developing fetal anemia necessitated elective Caesarean section performed at 35 wg. The neonate was admitted in the intensive care unit and required resuscitation, one exchange blood transfusion and several courses of phototherapy. The patient was discharged two weeks post partum. CONCLUSIONS: There is a strong correlation between the high peak systolic velocities in the middle cerebral artery (MCA-PSV) and the low levels of fetal hemoglobin. The high sensitivity and positive predictive value concerning the development of fetal anemia, as well as its good repeatability, makes this non-invasive test a valuable asset in the management of all pregnancies complicated by severe Rh-alloimmunization.

B cell lymphoma and myeloma in murine Gaucher's disease.

Multiple myeloma and B cell lymphoma are leading causes of death in Gaucher's disease but the nature of the stimulus driving the often noted clonal expansion of immunoglobulin-secreting B cells and cognate lymphoid malignancy is unknown. We investigated the long-term development of B cell malignancies in an authentic model of non-neuronopathic Gaucher's disease in mice: selective deficiency of ß-glucocerebrosidase in haematopoietic cells [Gba(tm1Karl/tm1Karl)Tg(Mx1-cre)1Cgn/0, with excision of exons 9-11 of the murine GBA1 gene, is induced by poly[I:C]. Mice with Gaucher's disease showed visceral storage of ß-glucosylceramide and greatly elevated plasma ß-glucosylsphingosine [median 57.9 (range 19.8-159) nm; n = 39] compared with control mice from the same strain [median 0.56 (range 0.04-1.38) nm; n = 29] (p < 0.0001). Sporadic fatal B cell lymphomas developed in 11 of 21 GD mice (6-24 months) but only two of eight control animals developed tumours by age 24 months. Unexpectedly, most mice with overt lymphoma had absent or few Gaucher cells but local inflammatory macrophages were present. Eleven of 39 of Gaucher mice developed monoclonal gammopathy, but in the control group only one animal of 25 had clonal immunoglobulin abnormalities. Seven of 10 of the B cell lymphomas were found to secrete a monoclonal paraprotein and the lymphomas stained intensely for pan-B cell markers; reactive T lymphocytes were also present in tumour tissue. In the Gaucher mouse strain, it was notable that, as in patients with this disease, CD138(+) plasma cells frequently surrounded splenic macrophages engorged with glycosphingolipid. Our strain of mice, with inducible deficiency of ß-glucocerebrosidase in haematopoietic cells and a high frequency of sporadic lethal B cell malignancies, faithfully recapitulates human Gaucher's disease: it serves as a tractable model to investigate the putative role of bioactive sphingolipids in the control of B cell proliferation and the pathogenesis of myelomatosis-the most prevalent human cancer associated with this disorder.

Singlet-triplet fission of carotenoid excitation in light-harvesting LH2 complexes of purple phototrophic bacteria.

The current generally accepted structure of light-harvesting LH2 complexes from purple phototrophic bacteria conflicts with the observation of singlet-triplet carotenoid excitation fission in these complexes. In LH2 complexes from the purple bacterium Allochromatium minutissimum, a drop in the efficiency of carotenoid triplet generation is demonstrated, which correlates with the extent of selective photooxidation of bacteriochlorophylls absorbing at ~850 nm. We conclude that singlet-triplet fission of carotenoid excitation proceeds with participation of these excitonically coupled bacteriochlorophylls. In the framework of the proposed mechanism, the contradiction between LH2 structure and photophysical properties of carotenoids is eliminated. The possibility of singlet-triplet excitation fission involving a third mediator molecule was not considered earlier.

[Three- and four-dimensional (3D/4D) ultrasound in obstetric practice: review].

Three-dimensional (3D) ultrasound is following the natural development of the imaging technology. This review of the technical applications and clinical aspects of the three-dimensional ultrasound is focused on vizualiztion of the fetal anatomy and the possibilities of this new technology and to increase awareness of its present clinical usefulness. Consulting specialists understand fetal pathology better and can better plan postnatal interventions. 3D ultrasound is a promising imaging method to image the fetus. Here are presented the methods for visualization in obstetrics, and the place of the ultrasound imaging in prenatal diagnosis. The role and value of this method will be in the focus of further studies.

[Three-dimensional (3D) ultrasound in evaluation of fetal brain anatomy].

OBJECTIVES: The objective of this study is to evaluate the potential of three-dimensional (3D) ultrasound identifying the fetal brain structures during second trimester and the time of offline analysis of brain volumes to perform a basic and a detailed fetal neurosonogram. METHODS: 140 pregnant women were included in this study presented for a second trimester routine ultrasound scan in Medical Centre "Markovs", Sofia and the University Hospital in Obstetrics and Gynecology, Maichin dom, Sofia, Bulgaria. All pregnancies were singleton with no diagnosed fetal anomalies. 3D fetal brain volumes were obtained by transabdominal aquisition in the most suitable plane and analyzed later offline by two trained ultrasonologists with special software. RESULTS: A standart systematic volume orientation was used to identify a list of brain structures and to complete basic evaluation, intracranial biometry and elected structures for detailed fetal neurosonogram. Diagnostic visualization was possible with excellent visualization rate in 91-100% in all brain structures for basic evaluation and in 76-100% for detailed targeted neurosonogram. An average number of 7 volumes was used to complete the examination by the two specialists. In this study a few limitation of the method are presented. CONCLUSION: 3D volume ultrasound is useful method for identification of fetal brain structures in second trimester. There are advantages in storage the digital information and for education.

[Targeting NMDAR/AMPAR: a promising pharmacotherapeutic approach for depressive disorders]. / Targetirovanie NMDAR/AMPAR ­ perspektivnyi podkhod farmakokorrektsii depressivnykh rasstroistv.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

[Evolution of insulin therapy: past, present, future].

2021 marks the 100th anniversary of the discovery of insulin, an event that forever changed the lives of people with diabetes mellitus. At present patients around the world experience the miracle of insulin therapy every day. A disease that used to kill children and teenagers in 2 years in 1920 has become a disease that can be controlled with a possibility to lead a long productive life. Over the past century, the great discovery of Banting, Best and Collip has forever changed the world and saved millions of lives. This review is devoted to the history of the development of insulin and its further improvement: from the moment of discovery to the present days. Various generations of insulin are considered: from animals to modern ultrashort and basal analogues. The article ends with a brief review of current trends in the development of new delivery methods and the development of new insulin molecules. Over the past century, insulin therapy has come a long way, which has significantly improved the quality of life of our patients. But research is actively continuing, including in the field of alternative methods of insulin delivery, which are more convenient for the patient, as well as in the development of «smart¼ molecules that will have a glucose-dependent effect.

[Potential bioeffects in interaction between ultrasound and tissue--safety of diagnostic ultrasound].

Diagnostic ultrasound has an incredible impact in medicine, especially in obstetrics and gynecology practice. Due to wide clinical practice the knowledge about potential bioeffects in tissues are mandatory. Safety assurance for diagnostic ultrasound in obstetrics is interesting topic, there is a lack of proven harmful effects in fetuses. Technical developments in imaging suggest higher energy exposition levels. For this reason education and responsibility play important role in safety use of the ultrasound.

[Bilateral hydrocephalus due to fetal intracranial hemorrhage in third trimester].

Antenatal diagnosis of intracranial hemorrhage (ICH) has been widely published. Hemorrhages may occur either within the cerebral ventricles, subdural space or infratentorial fossa. Differential diagnosis is clinical challenge. Usually the outcome is poor. In this case report we present a case of antenatal diagnosis of severe intracranial hemorrhage in third trimester, opted for termination. We discussed etiology, pathophysiology of this condition, classification and the prognosis.

[Cesarean scar ectopic pregnancy: diagnosis with 2D, three-dimensional (3D) ultrasound and 3D power doppler of a case and review of the literature].

Cesarean scar pregnancy is rare type of ectopic pregnancy. It is associated with severe complication if it is not diagnosed early in pregnancy. We present a case of difficult first-trimester diagnosis of Cesarean scar pregnancy. In this paper we discuss the incidence of this condition, the antenatal diagnosis, the prognosis and management and the importance of 2D and 3D ultrasound technique as a diagnostic tool.

[Giant orofacial teratoma of the fetus (epignathus) - prenatal 2d and three-dimensional 3D ultrasound detection of this rare condition].

An epignathus is an extremely rare form of oropharyngeal teratoma that arises from the oral cavity, most commonly from the palate and is associated with a high mortality secondary to airway obstruction in the neonatal period. We present a case of prenatal diagnosis in 29 w.g. preterm baby with a giant epignathus, preterm birth and fetal death. We discuss the incidence of these tumors, the antenatal diagnosis and the prognosis and management of this condition.

["High" and "low" gastric ulcers in posthelicobacterial era--is this division vital?].

AIM OF INVESTIGATION: To specify etiopathogenetical characteristics of the disease in case of "high" and "low" gastric ulcers. MATERIALS AND METHODS: 96 patients with relapse of gastric ulcer disease (GUD) were examined, median age 41 +/- 3.1 years, 71.9% of male patients, 28.1% of female patients. The first group included 58 patients with "high" ulcer, the second included 38 patients with pyloroantral ulcer. All patients underwent esophagogastroduodenoscopy and 24-hour intragastric pH-metry prior to the prescription of antisecretory therapy. The results of the examination were compared with data of 100 healthy subjects. RESULTS: Intragastric acidity in case of "high" ulcers, by value of fundal and antral pH and its circadian dynamics, was comparable to that of the healthy people. By the frequency of duodenogastral reflux (DGR) close to normal the total duration was significantly higher because of considerable increase of portion of long and high refluxes. High acidity in corpus and antral region, absence of the normal daily variations, significant increase of night acidity, decrease of DGR frequency and duration were noted by "low" gastric ulcers. CONCLUSIONS: In case of "high" localization of gastric ulcer normal acidity production and unusual high and enduring duodenogastral refluxes are revealed more often; combination of high hyperacidity and pronounced depression of duodenogastral reflux are seen in case of pyloroantral ulcer.

Combining branched copolymers with additives generates stable thermoresponsive emulsions with in situ gelation upon exposure to body temperature.

Branched copolymer surfactants (BCS) containing thermoresponsive polymer components, hydrophilic components, and hydrophobic termini allow the formation of emulsions which switch from liquid at room temperature to a gel state upon heating. These materials have great potential as in situ gel-forming dosage forms for administration to external and internal body sites, where the emulsion system also allows effective solubilisation of a range of drugs with different chemistries. These systems have been reported previously, however there are many challenges to translation into pharmaceutical excipients. To transition towards this application, this manuscript describes the evaluation of a range of pharmaceutically-relevant oils in the BCS system as well as evaluation of surfactants and polymeric/oligomeric additives to enhance stability. Key endpoints for this study are macroscopic stability of the emulsions and rheological response to temperature. The effect of an optimal additive (methylcellulose) on the nanoscale processes occurring in the BCS-stabilised emulsions is probed by small-angle neutron scattering (SANS) to better comprehend the system. Overall, the study reports an optimal BCS/methylcellulose system exhibiting sol-gel transition at a physiologically-relevant temperature without macroscopic evidence of instability as an in situ gelling dosage form.

Transcranial direct current stimulation of the premotor cortex aimed to improve hand motor function in chronic stroke patients.

OBJECTIVE: To investigate the effects of single-session premotor and primary motor tDCS in chronic stroke patients with relation to possible inter-hemispheric interactions. METHODS: Anodal tDCS of either M1 or premotor cortex of the side contralateral to the paretic hand, cathodal tDCS of the premotor cortex of the side ipsilateral to the paretic hand and sham stimulation were performed in 12 chronic stroke patients with mild hand paresis in a balanced cross-over design. The Jebsen-Taylor Hand Function test, evaluating the time required for performance of everyday motor tasks, was employed. RESULTS: The repeated-measure ANOVA with Greenhouse-Geisser correction showed significant influence of the stimulation type (factor SESSION; F(2.6, 28.4) = 47.3, p < 0.001), the test performance time relative to stimulation (during or after tDCS; factor TIME, F(1.0, 11.0) = 234.5, p < 0.001) with higher effect after the stimulation and the interaction SESSION*TIME (F(1.7, 1.2) = 30.5, p < 0.001). All active conditions were effective for the modulation of JTT performance, though the highest effect was observed after anodal tDCS of M1, followed by effects after anodal stimulation of the premotor cortex contralateral to the paretic hand. Based on the correlation patterns, the inhibitory input to M1 from premotor cortex of another hemisphere and an excitatory input from the ipsilesional premotor cortex were suggested. CONCLUSION: The premotor cortex is a promising candidate area for transcranial non-invasive stimulation of chronic stroke patients.