Direct electrical stimulation enhances osteogenesis by inducing Bmp2 and Spp1 expressions from macrophages and preosteoblasts

The capability of electrical stimulation (ES) in promoting bone regeneration has already been addressed in clinical studies. However, its mechanism is still being investigated and discussed. This study aims to investigate the responses of macrophages (J774A.1) and preosteoblasts (MC3T3-E1) to ES and the faradic by-products from ES. It is found that pH of the culture media was not significantly changed, whereas the average hydrogen peroxide concentration was increased by 3.6 and 5.4 µM after 1 and 2 hr of ES, respectively. The upregulation of Bmp2 and Spp1 messenger RNAs was observed after 3 days of stimulation, which is consistent among two cell types. It is also found that Spp1 expression of macrophages was partially enhanced by faradic by-products. Osteogenic differentiation of preosteoblasts was not observed during the early stage of ES as the level of Runx2 expression remains unchanged. However, cell proliferation was impaired by the excessive current density from the electrodes, and also faradic by-products in the case of macrophages. This study shows that macrophages could respond to ES and potentially contribute to the bone formation alongside preosteoblasts. The upregulation of Bmp2 and Spp1 expressions induced by ES could be one of the mechanisms behind the electrically stimulated osteogenesis.Biotechnology and Biological Sciences Research Council (BBSRC) grant (BB/M013545/1). It also receives funding from The Royal Thai Government scholarship (ST 4729

Neocortical hyperexcitability in a genetic model of absence seizures and its reduction by levetiracetam

PURPOSE: To study the effect of the antiepileptic drug levetiracetam (LEV) on the patterns of intrinsic optical signals (IOSs) generated by slices of the somatosensory cortex obtained from 3- and 6-month-old WAG/Rij and age-matched, nonepileptic control (NEC) rats. METHODS: WAG/Rij and NEC animals were anesthetized with enfluorane and decapitated. Brains were quickly removed, and neocortical slices were cut coronally with a vibratome, transferred to a submerged tissue chamber, and superfused with oxygenated artificial cerebrospinal fluid (aCSF). Slices were illuminated with a dark-field condensor and examined with a x2.5 objective; images were processed with a real time digital video image-enhancement system. Images were acquired before (background) and during electrical stimulation with a temporal resolution of 10 images/s and were displayed in pseudocolors. Extracellular stimuli (200 micros; <4 V) were delivered through bipolar stainless steel electrodes placed in the white matter. RESULTS: IOSs recorded in NEC slices bathed in control aCSF became less intense and of reduced size with age (p < 0.05); this trend was not seen in WAG/Rij slices. Age-dependent decreases in IOS intensity and area size were also seen in NEC slices superfused with aCSF containing the convulsant 4-aminopyridine (4-AP, 5 microM); in contrast, significant increases in both parameters occurred with age in 4-AP-treated WAG/Rij slices (p < 0.05). Under any of these conditions, the IOS intensity and area size slices were larger in WAG/Rij than in NEC slices. LEV (50-500 microM) application to WAG/Rij slices caused dose-dependent IOS reductions that were evident both in control and in 4-AP-containing aCSF and were more pronounced in 6-month-old tissue. CONCLUSIONS: These data demonstrate age-dependent IOS modifications in NEC and WAG/Rij rat slices and identify a clear pattern of hyperexcitability that occurs in 6-month-old WAG/Rij neocortical tissue, an age when absence seizures occur in all animals. The ability of LEV to reduce these patterns of network hyperexcitability supports the potential use of this new antiepileptic drug in primary generalized epileptic disorders

Uneven focal shoe deterioration in Tourette syndrome.

A 31-year-old single man (AB) sought neuropsychiatric consultation for treatment-resistant motor and vocal tics. He described himself expressing a total of 24 different tics, mainly facial twitches (eye blinking, raising eyebrows, mouth opening, lips licking, stereotyped grimacing) and inappropriate utterances (grunting, throat clearing, sniffing), since the age of 7. There appeared to be no family history of tic disorder. He reported occasional utterance of swear words in contextually inappropriate situations (coprolalia), and the urge to copy other people’s movements (echopraxia). Other tic-associated symptoms included self-injurious behaviours and forced touching of objects. A.B. met both DSM-IV-tr and ICD-10 criteria for Tourette syndrome, and also DSM-IV-tr criteria for attention deficit hyperactivity disorder (combined type) in childhood

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective.

Benzodiazepines represent the first-line treatment for the acute management of epileptic seizures and status epilepticus. The emergency use of benzodiazepines must be timely, and because most seizures occur outside of the hospital environment, there is a significant need for delivery methods that are easy for nonclinical caregivers to use and administer quickly and safely. In addition, the ideal route of administration should be reliable in terms of absorption. Rectal diazepam is the only licensed formulation in the USA, whereas rectal diazepam and buccal midazolam are currently licensed in the EU. However, the sometimes unpredictable absorption with rectal and buccal administration means they are not ideal routes. Several alternative routes are currently being explored. This is a narrative review of data about delivery methods for benzodiazepines alternative to the intravenous and oral routes for the acute treatment of seizures. Unconventional delivery options such as direct delivery to the central nervous system or inhalers are reported. Data show that intranasal diazepam or midazolam and the intramuscular auto-injector for midazolam are as effective as rectal or intravenous diazepam. Head-to-head comparisons with buccal midazolam are urgently needed. In addition, the majority of trials focused on children and adolescents, and further trials in adults are warranted

АКТУАЛЬНЫЕ ПРИРОДНО-ОЧАГОВЫЕ ИНФЕКЦИИ, ПЕРЕДАВАЕМЫЕ КЛЕЩАМИ, В САНКТ-ПЕТЕРБУРГЕ

Purpose: to conduct a comparative analysis and to identify the epidemiological and clinical features of tick-borne encephalitis (TBE) and Lyme borreliosis as a mono- and coinfections in St. Petersburg. Materials and methods. 718 cases of TBE, 4353 cases of Lyme borreliosis and 127 combined diseases registered by the St. Petersburg epidemiological bureau in 2006-2017 were studied. Identification of combined diseases was carried out by a special software that allows to identify co-morbid diseases from the array of monoinfections. To identify clinical and epidemiological features, 144 cases of TBE, 286 Lyme borreliosis, and 43 cases of co-infection were studied. Age and sex characteristics, places of human contagion, infection rates of ticks, clinical forms of mono- and associated diseases, morbidity dynamics changes and patients’ IgM seropositivity were studied. Results. The long-term dynamics of TBE and Lyme borreliosis incidence had did not have significant upward or downward trends, it was characterized by synchronous fluctuations. The priority of the incidence of men over women is revealed. 61–69% cases of TBE and Lyme borreliosis occurred in Leningrad region, 19–30% – in the adjacent territories of Russia, 5,7–6,7% of cases were imported from other countries. High tick infection rates of TBE virus and Borrelia was revealed. Borrelia аnd virus of TBE and were detected in 81,6–87,5% of the examined ticks removed from patients with a later established diagnosis. Seasonal distribution of Lyme borreliosis was shifted by a month to the right in comparison with TBE. The clinical forms of both diseases did not differ in their structure from the country data, however after 2012 subclinical forms were more common in women. The proportion of non-erythematous forms of Lyme borreliosis in 2011–2015 compared with the 2006–2010 observation period increased almost 1,5-fold mainly forms, including those with co-infection. The IgM seropositivity rate in the dynamics of the disease testifies to the incomplete rehabilitation of patients. Conclusion. The clinical and epidemiological characteristics of TBE, Lyme borreliosis and combined infection in the North-West region of Russia, with the example of St. Petersburg, have certain distinctive features. The reasons for the revealed features need further study.Цель: провести сравнительный эпидемиологический анализ и выявить эпидемиологические и клинические особенности клещевого энцефалита и боррелиоза как моно- , так и одновременного сочетания этих инфекций у больных в Санкт-Петербурге. Материалы и методы: ретроспективно изучено 718 случаев клещевого энцефалита, 4353 случая клещевого боррелиоза и 127 сочетанных заболеваний, зарегистрированных в отделе учета и регистрации инфекционных и паразитарных заболеваний Центра гигиены и эпидемиологии Санкт-Петербурга за 2006–2017 гг. Идентификация сочетанных заболеваний происходила с помощью специальной программы, позволяющей выявлять сочетанные заболевания из массива моноинфекций. Для выявления клинико-эпидемиологических особенностей изучено 144 истории болезни клещевым энцефалитом, 286 – клещевым боррелиозом и 43 истории болезни в случаях сочетания этих инфекций. Проанализированы возрастно-половые характеристики, места заражения людей, вирусо- и борелиафорность клещей, клинические формы моно- и сочетанных заболеваний, изменения, происходящие во времени. Коэффициент серопозитивности IgM у больных оценивался в динамике обследования пациентов. Результаты: многолетняя динамика заболеваемости клещевым энцефалитом и клещевым боррелиозом не имела выраженных тенденций к росту или снижению и характеризовалась синхронными колебаниями. Выявлен приоритет заболеваемости мужчин над женщинами. Заражения клещевым энцефалитом и боррелиозами в 61–69% случаев происходили в Ленинградской области, в 19–30% – на сопредельных территориях России, в 5,7–6,7% – в странах ближнего и дальнего зарубежья. Выявлена высокая инфицированность клещей вирусом клещевого энцефалита и боррелиями. Боррелии и вирус клещевого энцефалита выявлены у 81,6 и 87,5% исследованных переносчиков, снятых с больных с позднее установленным диагнозом. Сезонное распределение заболеваний боррелиозом было сдвинуто на месяц вправо по сравнению с клещевым энцефалитом. Клинические формы как клещевого энцефалита, так и боррелиоза по своей структуре не отличались от литературных данных по стране, однако субклинические формы чаще встречались у женщин в период после 2012 г. Доля безэритемных форм боррелиоза в 2011–2015 гг. по сравнению с 2006–2010 гг. наблюдения увеличилась почти в 1,5 раза, в том числе и при сочетанной инфекции. Коэффициент серопозитивности IgM в динамике болезни свидетельствует о неполном выздоровлении больных. Заключение: клинико-эпидемиологическая картина клещевого энцефалита, клещевого боррелиоза и сочетания этих инфекций в Северо-Западном регионе России на примере Санкт-Петербурга имеет определенные отличительные особенности. Причины выявленных особенностей нуждаются в дальнейшем изучении

Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis

Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis