TMS by double-cone coil prefrontal stimulation for medication resistant chronic depression: A case report

A double-cone coil with large angled windings has been developed to modulate deeper brain areas such as the anterior cingulate cortex (ACC). Abnormal resting state activity in the pregenual ACC (pgACC), dorsal ACC (dACC) and subgenual ACC (sgACC) has been observed in depression. A patient with medication resistant chronic depression received ten sessions of transcranial magnetic stimulation (TMS) (10 Hz, 2000 stimuli/session) using a double-cone coil placed over the supplementary motor area, targeting the anterior cingulate. Source localized EEG recordings were conducted pre- and post-TMS. The Beck Depression Inventory (BDI-II) improved by 27%, and the two subscales of the Hospital Anxiety Depression Scale (HADS), namely depression (40%) and anxiety (33%) improved as well. Along with the clinical improvement eletrophysiological resting state activity changed in the dACC and sgACC in this patient in comparison to a normative group. The results of this case report further support the involvement of pgACC, dACC and sgACC activity in the pathophysiology of depression and indicate that modulation of neural activity in this area by high frequency TMS with a double-cone coil might represent a new promising approach in the treatment of medication resistant chronic depression.     

Submandibular myofibroma: a case report

Purpose

Myofibroma is a rare benign spindle cell neoplasm, and the aim of the present study was to carry out a literature review and present a clinical case of a patient with a myofibroma in the submandibular region and its management.

Conclusions

Diagnosis of myofibroma can be reached by a histopathologic and immunohistochemical analysis and surgical excision is the treatment of choice.     

Isolation of myelinoid Marchi-positive bodies from normal rabbit spinal cord

Normal rabbit spinal cord was homogenized in sucrose and fractionated by centrifugation in a sucrose density gradient system slightly modified after the Norton-Poduslo method for the isolation of myelin. The following fractions were recovered: the fraction floating on 0.32 M sucrose, the myelin fraction at the 0.32 M/0.85 M interface and the pellet. After fixation in glutaraldehyde the fractions were subjected to Marchi staining, a histochemical method used for the demonstration of degenerating myelin. The floating fraction was enriched in Marchi-positive bodies as compared to the homogenate while the myelin fraction and the pellet contained low amounts. No esterified cholesterol was found in the floating fraction. Since histochemical and electron microscopical studies have shown that Marchi-positive myelinoid bodies in the normal CNS are associated with node-paranode regions our results indicate a possibility to isolate and biochemically characterize a presumably closely myelin-related fraction of known anatomical origin. The absence of esterified cholesterol in the floating fraction shows that biochemical or biophysical properties other than a content of esterified cholesterol may give rise to a positive Marchi reaction.     

Ueber die histologischen Vorgänge in durchschnittenen Nerven

Ohne Zusammenfassung     

不同性别青年人体重指数对血压升高的影响研究

高血压是全球主要的公共健康问题,包括高血压在内的心血管疾病已成为我国首要的死亡原因,高血压和高血压前期是主要的危险因素,它们显著增加了心血管疾病的病死率[1-2]。体重指数(body mass index,BMI)的升高增加了高血压、脑中风和心肌梗死等心血管疾病发病的风险,BMI与血压升高所致的心血管疾病发病风险不尽相     

How to Regulate Nonbiological Complex Drugs (NBCD) and Their Follow-on Versions: Points to Consider

The aim of this critical review is to reach a global consensus regarding the introduction of follow-on versions of nonbiological complex drugs (NBCD). A nonbiological complex drug is a medicinal product, not being a biological medicine, where the active substance is not a homo-molecular structure, but consists of different (closely related and often nanoparticulate) structures that cannot be isolated and fully quantitated, characterized and/or described by state of the art physicochemical analytical means and where the clinical meaning of the differences is not known. The composition, quality and in vivo performance of NBCD are highly dependent on manufacturing processes of both the active ingredient as well as in most cases the formulation. The challenges posed by the development of follow-on versions of NBCD are illustrated in this paper by discussing the ‘families’ of liposomes, iron–carbohydrate (‘iron–sugar’) drugs and glatiramoids. It is proposed that the same principles for the marketing authorization of copies of NBCD as for biosimilars be used: the need for animal and/or clinical data and the need to show similarity in quality, safety and efficacy. The regulatory approach of NBCD will have to take into consideration the specific characteristics of the drugs, their formulation and manufacturing process and the resulting critical attributes to achieve their desired quality, safety and efficacy. As with the biosimilars, for the NBCD product, family-specific methods should be evaluated and applied where scientifically proven, including sophisticated quality methods, pharmacodynamic markers and animal models. Concerning substitution and interchangeability of NBCD, it is also advisable to take biosimilars as an example, i.e. (1) substitution without the involvement of a healthcare professional should be discouraged to ensure traceability of the treatment of individual patients, (2) keep an individual patient on a specific treatment if the patient is doing well and only switch if unavoidable and (3) monitor the safety and efficacy of the new product if switching occurs.     

Saliva-mediated aggregation of Enterococcus faecalis transformed with a Streptococcus sanguis gene encoding the SSP-5 surface antigen.

The interaction of a high-molecular-weight salivary glycoprotein (agglutinin) with Streptococcus sanguis M5 leads to the formation of bacterial aggregates. We have previously shown that the SSP-5 surface antigen from S. sanguis M5 binds the salivary agglutinin and therefore may be involved in the aggregation process. Here we report the transformation of a nonaggregating Enterococcus faecalis strain with the SSP-5 gene and show that the protein is expressed on the cell surface and confers an aggregation-positive phenotype. E. faecalis S161 protoplasts were transformed with pAM401 EB-5, a shuttle vector containing the S. sanguis SSP-5 gene, resulting in the isolation of E. faecalis S161EB-5. Crude cell extracts from this transformant and from S. sanguis M5 were analyzed by Western blotting. Extracts from S. sanguis M5 possessed peptides of 190 and 205 kilodaltons that reacted strongly with polyclonal antibodies against the recombinant SSP-5 antigen. E. faecalis S161EB-5 contained only the 190-kilodalton immunoreactive protein, suggesting that the antigen may be processed differently in E. faecalis S161EB-5. The parent strain, E. faecalis S161, did not react with this antibody preparation. Immunogold labeling of intact E. faecalis S161EB-5 and S. sanguis M5 with anti-SSP-5 immunoglobulin G showed that both organisms expressed similar levels of the antigen. Both organisms formed visible aggregates upon incubation with salivary agglutinin. These results suggest that the SSP-5 antigen may mediate both the binding of agglutinin to S. sanguis M5 and the subsequent formation of bacterial aggregates.